Tribofilm Formation of Zinc Dialkyldithiophosphate as Oil Additives Impregnated in Porous Polyimide under Different Contacts.

To improve the tribological properties of porous polyimide (PPI), ZDDP-mixed PAO4 was impregnated in PPI (denoted as ZPPI), and the tribological properties of ZPPI under single- and double-contacts were investigated. In the single-contact of ZPPI-steel, a rough and thick tribofilm was formed on the steel ball, which could protect the steel surface but resulted in large fluctuations in the friction coefficient. In the double-contact of ZPPI-steel-steel, ZDDP formed a uniform and thinner tribofilm on steel surfaces, leading to a lower friction. ZDDP could inhibit the formation of iron oxides significantly in the double-contact, while the antioxidant effect of ZDDP in the single-contact of ZPPI-steel was not obvious. ZnS and ZnO generated from ZDDP were adsorbed in the ZPPI pores, which aggravated the blackening of the ZPPI worn surface.

Prediction of hot spots in protein-DNA binding interfaces based on discrete wavelet transform and wavelet packet transform.

BACKGROUND: Identification of hot spots in protein-DNA binding interfaces is extremely important for understanding the underlying mechanisms of protein-DNA interactions and drug design. Since experimental methods for identifying hot spots are time-consuming and expensive, and most of the existing computational methods are based on traditional protein-DNA features to predict hot spots, unable to make full use of the effective information in the features. RESULTS: In this work, a method named WTL-PDH is proposed for hot spots prediction. To deal with the unbalanced dataset, we used the Synthetic Minority Over-sampling Technique to generate minority class samples to achieve the balance of dataset. First, we extracted the solvent accessible surface area features and structural features, and then processed the traditional features using discrete wavelet transform and wavelet packet transform to extract the wavelet energy information and wavelet entropy information, and obtained a total of 175 dimensional features. In order to obtain the best feature subset, we systematically evaluate these features in various feature selection strategies. Finally, light gradient boosting machine (LightGBM) was used to establish the model. CONCLUSIONS: Our method achieved good results on independent test set with AUC, MCC and F1 scores of 0.838, 0.533 and 0.750, respectively. WTL-PDH can achieve generally better performance in predicting hot spots when compared with state-of-the-art methods. The dataset and source code are available at https://github.com/chase2555/WTL-PDH .

Correlation Analysis of the Pneumatization of the Supraorbital Ethmoid Cell and the Position of the Anterior Ethmoidal Artery.

OBJECTIVES: This study aimed to measure the supraorbital ethmoid cell (SOEC) and characterize the relationship between the degree of SOEC pneumatization and the position of the anterior ethmoidal artery (AEA) in relation to the skull base. METHODS: Computed tomography (CT) scans of 100 patients were analyzed. The correlation between the pneumatization of SOEC and the distance of the AEA from the skull base was explored by Spearman's correlation rho efficient test. RESULTS: The distance of the AEA from skull base was 3.10 (2.60,3.60) mm in patients with SOEC compared with 0.6(0.40,2.10)mm in those without(P < .001). In 50.5% of the patients, the AEA was located below the skull base; the incidence of this localization was significantly higher in those with SOEC than in those without (78.79%vs22.77%, P < .001). Compared to female patients, male patients owned greater SOEC height (9.65vs8.20mm, P = .007). The SOECs volume (r = 0.45, P < .001), height (r = .30, P = .003), and transverse diameter (r = 0.28, P = .005) were all significantly correlated with the distance of the AEA from the skull base. CONCLUSIONS: The pneumatization of SOEC critically impact the distance between the AEA and skull base. The higher the degree of pneumatization, the farther from the skull base the AEA will be, increasing the risk of complications during nasal endoscopic surgery. These results provide an important reference for protecting the AEA during nasal endoscopic surgery.

A sequentially responsive cascade nanoplatform for increasing chemo-chemodynamic therapy.

Poly(lactide-co-glycolide) (PLGA) is promising carrier material for drugs delivery in cancer therapy. However, the slow degradation and lack of targeting have greatly limited the clinical effectiveness of PLGA-based nanomedicines. Herein, we fabricated a hybrid nanosystem (3 P @ He/Pt-NPs) comprising of acid-sensitive polymer (mPOE-PLGA), active-targeting polymer (PBA-PLGA) and therapeutic agents (hemin+cisplatin) to combat these problems. In neutral environment, PEGylation can effectively improve the blood stability and circulation time of hybrid nanosystem. After reaching tumor regions, this nanosystem efficiently increased cellular uptake by dePEGylation and PBA-mediated active-targeting. Furthermore, encapsulated hemin could catalyze the oxygen bubbles generation, which remarkably increasing the drugs release rate. Subsequently, hybrid particles produced a higher cell-killing effect to lung cancer cells (A549) by the combination therapy (chemotherapy and chemodynamic therapy (CDT)). Importantly, cisplatin further amplified CDT effect by inducing H2O2 regeneration owing to the cascade enzymatic reactions, while hemin decreased intracellular glutathione (GSH) level, resulting in a low detoxification effect to cisplatin. Thus, hybrid particles could efficiently inhibit drug-resistant tumor growth and the inhibition rate reached 83.2%. Overall, this hybrid polymer nanosystem improve the drawbacks of PLGA-based nanocarriers, and can realize a cascading enhanced tumor treatment.

Short-term exposure of HFD depresses intestinal cholinergic anti-inflammatory activity through hypothalamic inflammation in mice.

High-fat diet (HFD) exposure has been proven to impair vagus nerve function. However, it is not yet known whether the HFD challenge impacts vagal efferent-based intestinal cholinergic anti-inflammation activity. This investigation aims to evaluate the effect of HFD on intestinal cholinergic anti-inflammatory activity in mice. Mice with or without intracerebroventricular treatment with an antibody against toll-like receptor 4 (TLR4) were fed with HFD or standard chow for 2 weeks. Vagus nerve-based anti-inflammatory activity was analyzed by heart rate variability. Acetylcholine (ACh) content, nicotinic acetylcholine receptor α7 subtype (α7nAChR), and pro-inflammatory cytokines were analyzed by biochemical kits or qRT-PCR. HFD feeding mice exhibit a significant increase in high frequency (HF) and a decrease in the ratio of low frequency/HF, which were accompanied by lower ACh levels and α7nAChR mRNA expression in the intestinal segments. However, anti-TLR4 antibody-treated HFD mice showed normal ACh levels and α7nAChR mRNA expression in the intestinal segments. Moreover, TNF-α production in small intestine was significantly reduced in HFD + antibody group compared with HFD + vehicle group. Collectively, our present results reveal that HFD challenge depresses intestinal cholinergic anti-inflammatory activity, which is mediated by hypothalamic inflammation. Impairment of intestinal cholinergic anti-inflammatory pathway is the cause of intestinal low-grade inflammation by HFD consumption.

Long-Term Effect of Pancreaticoduodenectomy Combined with Revascularization for Resectable Pancreatic Carcinoma in Elderly Patients.

BACKGROUND Pancreaticoduodenectomy combined with revascularization (PDR) is the main surgical procedure for resectable pancreatic ductal adenocarcinoma (PDAC) with venous system invasion, but this procedure is discouraged in elderly patients because of physical complexity. Our aim was to explore the differences of perioperative and survival in patients of different ages who underwent PDR. MATERIAL AND METHODS We reviewed data from PDAC patients undergoing PDR from 2007 to 2018. Patients were subdivided into 3 groups according to age: <60 years, 60-70 years, and ≥70 years. Postoperative complications and long-term survival were compared among the 3 groups. RESULTS From 626 patients, 185 had en bloc venous resection who underwent PDR (103, 55, and 27 patients from young to elderly). Increasing age was linked to a higher prevalence of ICU management (P=0.035) and more serious complications (grade ≥III, P=0.043); overall mortality was 8.1% and did not significantly differ among age-matched groups. Further, there was no difference in overall survival (OS) or progression-free survival (PFS) based on age (<60, 60-70, ≥70, median OS were 9.7, 8.4 vs 9.1 months, respectively, P=0.787; median PFS were 6.9, 6.1 vs 8.4 months, respectively, P=0.603). However, patients <60 years whose tumors invaded the superior mesenteric vascular had better survival outcomes when compared with the other 2 groups (11.5 vs 8.4, 9.1 months, P=0.049). CONCLUSIONS The results show that age should not be considered an absolute contraindication for PDR, as elderly patients can achieve the same surgical efficacy and long-term survival prognosis.

Elevated Serum Uric Acid/Albumin Ratio as a Predictor of Post-Contrast Acute Kidney Injury After Percutaneous Coronary Intervention in Patients with ST-Segment Elevation Myocardial Infarction.

Background: The serum uric acid/albumin ratio (sUAR), a novel inflammatory marker, effectively predicts acute kidney injury (AKI) and cardiovascular outcomes. However, whether the sUAR predicts post-contrast acute kidney injury (PC-AKI) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) remains uncertain. In this study, we evaluated the association between the sUAR and PC-AKI in patients with STEMI undergoing PCI. Methods: We consecutively recruited patients with STEMI who underwent PCI and stratified them into three groups according to the terciles of the sUAR. The primary outcome was the incidence of PC-AKI. The association between the sUAR and PC-AKI was assessed by multivariate logistic regression analysis. Results: A total of 2861 patients with STEMI were included in this study. The incidence of PC-AKI increased stepwise with increasing sUAR tercile (2.6% vs 4.0% vs 11.6%, p < 0.001), and the incidence of in-hospital major adverse clinical events (MACEs) was highest among patients in the Q3 group. Multivariate logistic regression analysis revealed that the sUAR was also an independent predictor of PC-AKI (continuous sUAR, per 1-unit increase, odds ratio [OR] [95% confidence interval (CI)]: 1.06 [1.02-1.10], p = 0.005; tercile of sUAR, OR [95% CI] for Q2 and Q3: 1.18 [0.69-2.01] and 1.85 [1.12-3.06], respectively, with Q1 as a reference) but not in-hospital MACEs. In the receiver operating characteristic (ROC) analysis, the area under the curve (AUC) of the sUAR for predicting PC-AKI was 0.708 (95% CI: 0.666-0.751), and ROC analysis also showed that the sUAR was superior to uric acid and albumin alone in predicting PC-AKI. Conclusion: Increasing sUAR was significantly associated with a higher risk of PC-AKI but not in-hospital MACEs in patients with STEMI who underwent PCI, suggesting that sUAR had a predictive value for PC-AKI after PCI in patients with STEMI. Further studies are required to confirm this finding.

Flexible endoscopy in the visualization of 3D-printed maxillary sinus and clinical application.

BACKGROUND: During postoperative follow-up, the visible range of maxillary sinus (MS) is limited, even combining 0° and 70° rigid endoscopes together. Flexible endoscope has been used in larynx examinations for a long time, but rarely in nasal cavity and sinus. We aimed to evaluate the application values of rigid and flexible endoscopes for visualization of MS. METHODS: We followed up 70 patients with lesions in MS via both rigid and flexible endoscopes. In addition, we used thin-slice CT image of the sinus to create a MS model and divided it into two parts for 3D printing. The inner surface of the 3D-printed sinus was marked with grid papers of the same size (5 mm × 5 mm), then the visual range under rigid endoscopes with different angle and flexible endoscopes was calculated and analyzed. RESULTS: In clinical follow-up, we found that flexible endoscopy can reach where rigid endoscopy cannot, which is more sensitive than medical imaging. Endoscopes showed the largest observation range of the posterolateral wall, more than half of which can be visualized by 0° endoscope. Almost all of the posterolateral wall can be revealed under 45° endoscope, 70° endoscope and flexible endoscope. The visual range of each wall under flexible endoscope is generally greater than that under rigid endoscopes, especially of the anterior wall, medial wall and inferior wall. CONCLUSION: There was obviously overall advantage of using flexible endoscope in postoperative follow-up of MS lesions. Flexible endoscopy can expand the range of observation, and improve the early detection of the recurrent lesion. We recommend flexible endoscope as a routine application.

Risk Estimation for Infection in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention: Development and Validation of a Predictive Score.

Background: Infection during hospitalization is a serious complication among patients who suffered from acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI); however, there are no suitable and accurate means to assess risk. This study aimed to develop and validate a simple scoring system to predict post-AMI infection in such patients. Methods: All patients with ST-segment elevation myocardial infarction (STEMI) undergoing PCI consecutively enrolled from January 2010 to May 2016 were served as derivation cohort, and those from June 2016 to May 2018 as validation cohort, respectively. The primary endpoint was post-AMI infection during hospitalization, and all-cause death and major adverse cardiovascular events (MACE) were considered as secondary endpoints. The simplified risk model was established using logistic regression. The area under the receiver operating curve and calibration of predicted and observed infection risk were calculated. Results: A 24-point risk score was developed, with infection risk ranging from 0.7 to 99.6% for patients with the lowest and highest score. Seven variables including age, Killip classification, insulin use, white blood cell count, serum albumin, diuretic use, and transfemoral approach were included. This model achieved the same high discrimination in the development and validation cohort (C-statistic:0.851) and revealed adequate calibration in both datasets. The incidences of post-AMI infection increased steadily across risk score groups in both development (1.3, 5.1, 26.3, and 69.1%; P < 0.001) and validation (1.8, 5.9, 27.2, and 79.2%; P < 0.001) cohort. Moreover, the risk score demonstrated good performance for infection, in-hospital all-cause death, and MACE among these patients, as well as in patients with the non-ST-elevation acute coronary syndrome. Conclusion: This present risk score established a simple bedside tool to estimate the risk of developing infection and other in-hospital outcomes in patients with STEMI undergoing PCI. Clinicians can use this risk score to evaluate the infection risk and subsequently make evidence-based decisions.

Two entry tunnels in mouse TAAR9 suggest the possibility of multi-entry tunnels in olfactory receptors.

Orthosteric binding sites of olfactory receptors have been well understood for ligand-receptor interactions. However, a lack of explanation for subtle differences in ligand profile of olfactory receptors even with similar orthosteric binding sites promotes more exploration into the entry tunnels of the receptors. An important question regarding entry tunnels is the number of entry tunnels, which was previously believed to be one. Here, we used TAAR9 that recognizes important biogenic amines such as cadaverine, spermine, and spermidine as a model for entry tunnel study. We identified two entry tunnels in TAAR9 and described the residues that form the tunnels. In addition, we found two vestibular binding pockets, each located in one tunnel. We further confirmed the function of two tunnels through site-directed mutagenesis. Our study challenged the existing views regarding the number of entry tunnels in the subfamily of olfactory receptors and demonstrated the possible mechanism how the entry tunnels function in odorant recognition.

Evolution of Brain-Expressed Biogenic Amine Receptors into Olfactory Trace Amine-Associated Receptors.

The family of trace amine-associated receptors (TAARs) is distantly related to G protein-coupled biogenic aminergic receptors. TAARs are found in the brain as well as in the olfactory epithelium where they detect biogenic amines. However, the functional relationship of receptors from distinct TAAR subfamilies and in different species is still uncertain. Here, we perform a thorough phylogenetic analysis of 702 TAAR-like (TARL) and TAAR sequences from 48 species. We show that a clade of Tarl genes has greatly expanded in lampreys, whereas the other Tarl clade consists of only one or two orthologs in jawed vertebrates and is lost in amniotes. We also identify two small clades of Taar genes in sharks related to the remaining Taar genes in bony vertebrates, which are divided into four major clades. We further identify ligands for 61 orphan TARLs and TAARs from sea lamprey, shark, ray-finned fishes, and mammals, as well as novel ligands for two 5-hydroxytryptamine receptor 4 orthologs, a serotonin receptor subtype closely related to TAARs. Our results reveal a pattern of functional convergence and segregation: TARLs from sea lamprey and bony vertebrate olfactory TAARs underwent independent expansions to function as chemosensory receptors, whereas TARLs from jawed vertebrates retain ancestral response profiles and may have similar functions to TAAR1 in the brain. Overall, our data provide a comprehensive understanding of the evolution and ligand recognition profiles of TAARs and TARLs.

Restrictive vs. Liberal Red Blood Cell Transfusion Strategy in Patients With Acute Myocardial Infarction and Anemia: A Systematic Review and Meta-Analysis.

Objective: Anemia is frequent in patients with acute myocardial infarction (AMI), and the optimal red blood cell transfusion strategy for AMI patients with anemia is still controversial. We aimed to compare the efficacy of restrictive and liberal red cell transfusion strategies in AMI patients with anemia. Methods: We systematically searched PubMed, EMBASE, Web of Science, Cochrane Library, and Clinicaltrials.gov, from their inception until March 2021. Studies designed to compare the efficacy between restrictive and liberal red blood cell transfusion strategies in patients with AMI were included. The primary outcome was all-cause mortality, including overall mortality, in-hospital or follow-up mortality. Risk ratios (RR) with 95% confidence intervals (CI) were presented and pooled by random-effects models. Results: The search yielded a total of 6,630 participants in six studies. A total of 2,008 patients received restrictive red blood cell transfusion while 4,622 patients were given liberal red blood cell transfusion. No difference was found in overall mortality and follow-up mortality between restrictive and liberal transfusion groups (RR = 1.07, 95% CI = 0.82-1.40, P = 0.62; RR = 0.89, 95% CI = 0.56-1.42, P = 0.62). However, restrictive transfusion tended to have a higher risk of in-hospital mortality compared with liberal transfusion (RR = 1.22, 95% CI = 1.00-1.50, P = 0.05). No secondary outcomes, including follow-up reinfarction, stroke, and acute heart failure, differed significantly between the two groups. In addition, subgroup analysis showed no differences in overall mortality between the two groups based on sample size and design. Conclusion: Restrictive and liberal red blood cell transfusion have a similar effect on overall mortality and follow-up mortality in AMI patients with anemia. However, restrictive transfusion tended to have a higher risk of in-hospital mortality compared with liberal transfusion. The findings suggest that transfusion strategy should be further evaluated in future studies.

Clinical application of collagen membrane with umbilical cord-derived mesenchymal stem cells to repair nasal septal perforation.

Objective. We aimed to investigate the clinical efficacy of collagen membrane with umbilical cord-derived mesenchymal stem cells in the endoscopic repair of nasal septal perforation.Methods.We performed a prospective clinical trial between March 2017 and October 2019. Nasal septal perforations were repaired by the endoscopic sandwich technique with the collagen membrane and umbilical cord-derived mesenchymal stem cells. These patients were followed up postoperatively. Their outcomes were comprehensively evaluated by assessing the healing process of the perforations, the visual analog scale (VAS) for nasal discomfort, and the nasal mucociliary transit time (MTT) for the regenerated nasal mucosa.Results. Our study included a total of eight patients with nasal septal perforation (six males and two females, age 36.6 ± 12.8 years, diameter of perforation 1.0 ± 0.2 cm). Seven patients successfully underwent surgical repair. These patients had significantly improved VAS scores 1 month after the operations (1.1 ± 0.4) compared with the preoperative period (5.9 ± 0.7) (P< 0.05). Although the nasal MTT in the nasal septum and the inferior turbinate surface were within the normal limits before the operation and at 1 month after the operation, the postoperative transit time (11.1 ± 2.0 m) was significantly shorter than the preoperative transit time (12.1 ± 2.4 m) (P< 0.05). There were no recurrences of perforation, scab formations, or epistaxis after the operation.Conclusions. The application of the collagen membrane with umbilical cord-derived mesenchymal stem cells is a simple and feasible endoscopic procedure to repair perforated nasal septa and restore satisfactory functional mucosa.

Convergent olfactory trace amine-associated receptors detect biogenic polyamines with distinct motifs via a conserved binding site.

Biogenic amines activate G-protein-coupled receptors (GPCRs) in the central nervous system in vertebrate animals. Several biogenic amines, when excreted, stimulate trace amine-associated receptors (TAARs), a group of GPCRs in the main olfactory epithelium, and elicit innate behaviors. How TAARs recognize amines with varying numbers of amino groups is largely unknown. We reasoned that a comparison between lamprey and mammalian olfactory TAARs, which are thought to have evolved independently but show convergent responses to polyamines, may reveal structural determinants of amine recognition. Here, we demonstrate that sea lamprey TAAR365 (sTAAR365) responds strongly to biogenic polyamines cadaverine, putrescine, and spermine, and shares a similar response profile as a mammalian TAAR (mTAAR9). Docking and site-directed mutagenesis analyses show that both sTAAR365 and mTAAR9 recognize the two amino groups of cadaverine with the conserved Asp3.32 and Tyr6.51 residues. sTAAR365, which has remarkable sensitivity for cadaverine (EC50 = 4 nM), uses an extra residue, Thr7.42, to stabilize ligand binding. These cadaverine recognition sites also interact with amines with four and three amino groups (spermine and spermidine, respectively). Glu7.36 of sTAAR365 cooperates with Asp3.32 and Thr7.42 to recognize spermine, whereas mTAAR9 recognizes spermidine through an additional aromatic residue, Tyr7.43. These results suggest a conserved mechanism whereby independently evolved TAAR receptors recognize amines with two, three, or four amino groups using the same recognition sites, at which sTAAR365 and mTAAR9 evolved distinct motifs. These motifs interact directly with the amino groups of the polyamines, a class of potent and ecologically important odorants, mediating olfactory signaling.

Development and Validation of a Risk Score for Predicting Post-acute Myocardial Infarction Infection in Patients Undergoing Percutaneous Coronary Intervention: Study Protocol for an Observational Study.

Background: Post-acute myocardial infarction (post-AMI) infection is an infrequent but important and serious complication in patients with ST-segment elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI). Predicting its occurrence is essential for future prevention. However, little is known about the prediction of post-AMI infection in such patients to date. This study aims to develop and validate a new risk score based on risk factors for early prediction of infection in STEMI patients undergoing PCI. Methods: This prospective, multi-center and observational study assesses the predictive value of risk score for post-AMI infection among a cohort of patients hospitalized due to STEMI. The STEMI patients undergoing PCI enrolled between January 1st 2010 and May 31st 2016 were served as a development cohort while those enrolled from June 1st 2016 to May 31st 2018 were served as validation cohort. The primary endpoint was post-AMI infection during hospitalization, defined as infection requiring antibiotics (reflecting the clinical influence of infection compatible with the necessity for additional treatment), and all-cause death and major adverse cardiovascular events (MACE) including all-cause death, recurrent myocardial infarction, target vessel revascularization, and stroke were considered as secondary endpoints. The risk score model based on risk factors was established using stepwise logistic regression, and will be validated in other centers and external patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). Results: This study will provide evidence on prognostic property, reliability of scoring, comparative performance, and suitability of the novel model for screening purpose in order to be recommended for clinical practice. Discussion: Our study is designed to develop and validate a clinical risk score for predicting infection in participants with STEMI who have undergone PCI. This simple tool may therefore improve evaluation of post-AMI infection and enhance future researches into the best practices to prevent or reduce infection in such patients. Clinical Trial Registration: www.chictr.org.cn, identifier: ChiCTR1900028278.

Coordination of two enhancers drives expression of olfactory trace amine-associated receptors.

Olfactory sensory neurons (OSNs) are functionally defined by their expression of a unique odorant receptor (OR). Mechanisms underlying singular OR expression are well studied, and involve a massive cross-chromosomal enhancer interaction network. Trace amine-associated receptors (TAARs) form a distinct family of olfactory receptors, and here we find that mechanisms regulating Taar gene choice display many unique features. The epigenetic signature of Taar genes in TAAR OSNs is different from that in OR OSNs. We further identify that two TAAR enhancers conserved across placental mammals are absolutely required for expression of the entire Taar gene repertoire. Deletion of either enhancer dramatically decreases the expression probabilities of different Taar genes, while deletion of both enhancers completely eliminates the TAAR OSN populations. In addition, both of the enhancers are sufficient to drive transgene expression in the partially overlapped TAAR OSNs. We also show that the TAAR enhancers operate in cis to regulate Taar gene expression. Our findings reveal a coordinated control of Taar gene choice in OSNs by two remote enhancers, and provide an excellent model to study molecular mechanisms underlying formation of an olfactory subsystem.

Machine-learning radiomics to predict early recurrence in perihilar cholangiocarcinoma after curative resection.

BACKGROUND AND AIMS: Up to 40%-65% of patients with perihilar cholangiocarcinoma (PHC) rapidly progress to early recurrence (ER) even after curative resection. Quantification of ER risk is difficult and a reliable prognostic prediction tool is absent. We developed and validated a multilevel model, integrating clinicopathology, molecular pathology and radiology, especially radiomics coupled with machine-learning algorithms, to predict the ER of patients after curative resection in PHC. METHODS: In total, 274 patients who underwent contrast-enhanced CT (CECT) and curative resection at 2 institutions were retrospectively identified and randomly divided into training (n = 167), internal validation (n = 70) and external validation (n = 37) sets. A machine-learning analysis of 18,120 radiomic features based on multiphase CECT and 48 clinico-radiologic characteristics was performed for the multilevel model. RESULTS: Comprehensively, 7 independent factors (tumour differentiation, lymph node metastasis, pre-operative CA19-9 level, enhancement pattern, A-Shrink score, V-Shrink score and P-Shrink score) were built to the multilevel model and quantified the risk of ER. We benchmarked the gain in discrimination with the area under the curve (AUC) of 0.883, superior to the rival clinical and radiomic models (AUCs 0.792-0.805). The accuracy (ACC) of the multilevel model was 0.826, which was significantly higher than those of the conventional staging systems (AJCC 8th (0.641), MSKCC (0.617) and Gazzaniga (0.581)). CONCLUSION: The radiomics-based multilevel model demonstrated superior performance to rival models and conventional staging systems, and could serve as a visual prognostic tool to plan surveillance of ER and guide post-operative individualized management in PHC.

TAAR Agonists.

Trace amine-associated receptors (TAARs) are a family of G protein-coupled receptors (GPCRs) that are evolutionarily conserved in vertebrates. The first discovered TAAR1 is mainly expressed in the brain, and is able to detect low abundant trace amines. TAAR1 is also activated by several synthetic compounds and psychostimulant drugs like amphetamine. Activation of TAAR1 by specific agonists can regulate the classical monoaminergic systems in the brain. Further studies have revealed that other TAAR family members are highly expressed in the olfactory system which are termed olfactory TAARs. In vertebrates, olfactory TAARs can specifically recognize volatile or water-soluble amines. Some of these TAAR agonists are produced by decarboxylation of amino acids. In addition, some TAAR agonists are ethological odors that mediate animal innate behaviors. In this study, we provide a comprehensive review of TAAR agonists, including their structures, biosynthesis pathways, and functions.

The predictive value of the renal resistive index for contrast-induced nephropathy in patients with acute coronary syndrome.

BACKGROUND: Percutaneous coronary intervention (PCI) has been associated with contrast-induced nephropathy (CIN) at a rate that varies depending on the patient's risk factors. This study was conducted to evaluate the predictive value of the renal resistive index (RRI) for CIN in patients with acute coronary syndrome (ACS) undergoing PCI. METHODS: This prospective study enrolled 146 consecutive patients with ACS. Renal Doppler ultrasound examinations to measure RRI were performed pre-PCI and at 1 h and 24 h after PCI. The primary endpoint was CIN, defined as a relative (≥25%) or absolute (≥0.5 mg/dL; 44 µmol/L) increase in serum creatinine from baseline within 48 h after contrast exposure. RESULTS: CIN was identified in 31 patients (21.2%); however, none of the patients required haemodialysis. Compared to patients without CIN, higher RRIs were observed at 1 h (0.71 ± 0.05 vs. 0.65 ± 0.06, p < 0.05) and 24 h (0.70 ± 0.05 vs. 0.66 ± 0.06, p < 0.05) post-procedure in patients with CIN. The RRI rose transiently from baseline (0.68 ± 0.05) to 1 h (0.71 ± 0.05) and then tended to decline at 24 h (0.70 ± 0.05). A receiver operating characteristic curve analysis showed that the pre-procedure RRI was a powerful predictive indicator of CIN (area under the curve = 0.661, p = 0.006). The best cutoff value was 0.69 with 67.7% sensitivity and 67% specificity. Besides hyperuricemia and chronic kidney disease, the multivariate logistic regression analysis revealed that a high baseline RRI (≥0.69) was a significant predictor of CIN (odds ratio = 4.445; 95% confidence interval: 1.806-10.937; p = 0.001). CONCLUSIONS: A high pre-procedural RRI appears to be independently predictive of CIN in patients with ACS undergoing PCI.

Loss of ARHGEF6 Causes Hair Cell Stereocilia Deficits and Hearing Loss in Mice.

ARHGEF6 belongs to the family of guanine nucleotide exchange factors (GEFs) for Rho GTPases, and it specifically activates Rho GTPases CDC42 and RAC1. Arhgef6 is the X-linked intellectual disability gene also known as XLID46, and clinical features of patients carrying Arhgef6 mutations include intellectual disability and, in some cases, sensorineural hearing loss. Rho GTPases act as molecular switches in many cellular processes. Their activities are regulated by binding or hydrolysis of GTP, which is facilitated by GEFs and GTPase-activating proteins, respectively. RAC1 and CDC42 have been shown to play important roles in hair cell (HC) stereocilia development. However, the role of ARHGEF6 in inner ear development and hearing function has not yet been investigated. Here, we found that ARHGEF6 is expressed in mouse cochlear HCs, including the HC stereocilia. We established Arhgef6 knockdown mice using the clustered regularly interspaced short palindromic repeat-associated Cas9 nuclease (CRISPR-Cas9) genome editing technique. We showed that ARHGEF6 was indispensable for the maintenance of outer hair cell (OHC) stereocilia, and loss of ARHGEF6 in mice caused HC stereocilia deficits that eventually led to progressive HC loss and hearing loss. However, the loss of ARHGEF6 did not affect the synapse density and did not affect the mechanoelectrical transduction currents in OHCs at postnatal day 3. At the molecular level, the levels of active CDC42 and RAC1 were dramatically decreased in the Arhgef6 knockdown mice, suggesting that ARHGEF6 regulates stereocilia maintenance through RAC1/CDC42.