Calreticulin regulates hepatic stellate cell activation through modulating TGF-beta-induced Smad signaling.

Liver fibrosis is characterized by excessive deposition of extracellular matrix (ECM) as a wound healing process. Activated hepatic stellate cells (HpSCs) are the major producer of the ECM and play a central role in liver fibrogenesis. It has been widely accepted that elimination of activated HpSCs or reversion to a quiescent state can be a feasible strategy for resolving the disease, further highlighting the urgent need for novel therapeutic targets. Calreticulin (CRT) is a molecular chaperone that normally resides in the endoplasmic reticulum (ER), important in protein folding and trafficking through the secretory pathway. CRT also plays a critical role in calcium (Ca2+) homeostasis, with its Ca2+ storage capacity. In the current study, we aimed to demonstrate its function in directing HpSC activation. In a mouse liver injury model, CRT was up-regulated in HpSCs. In cellular experiments, we further showed that this activation was through modulating the canonical TGF-ß signaling. As down-regulation of CRT in HpSCs elevated intracellular Ca2+ levels through a form of Ca2+ influx, named store-operated Ca2+ entry (SOCE), we examined whether moderating SOCE affected TGF-ß signaling. Interestingly, blocking SOCE had little effect on TGF-ß-induced gene expression. In contrast, inhibition of ER Ca2+ release using the inositol trisphosphate receptor inhibitor 2-APB increased TGF-ß signaling. Treatment with 2-APB did not alter SOCE but decreased intracellular Ca2+ at the basal level. Indeed, adjusting Ca2+ concentrations by EGTA or BAPTA-AM chelation further enhanced TGF-ß-induced signaling. Our results suggest a crucial role of CRT in the liver fibrogenic process through modulating Ca2+ concentrations and TGF-ß signaling in HpSCs, which may provide new information and help advance the current discoveries for liver fibrosis.

CgPHB2 involved in the haemocyte mitophagy in response to Vibrio splendidus stimulation in Pacific oyster Crassostrea gigas.

Prohibitin2 (PHB2) is recently identified as a novel inner membrane mitophagy receptor to mediate mitophagy. In the present study, the function of CgPHB2 in mediating mitophagy in response to Vibrio splendidus stimulation was investigated in Crassostrea gigas. CgPHB2 protein was mainly distributed in the cytoplasm of three subpopulations of haemocytes. After V. splendidus stimulation, the expressions of CgPHB2 mRNA in haemocytes were up-regulated significantly at 6, 12 and 24 h, and the abundance of CgPHB2 protein was also enhanced at 12-24 h compared to control group. Furthermore, the green signals of CgPHB2 were colocalized respectively with the red signals of mitochondria and CgLC3 in the haemocytes at 12 h after V. splendidus stimulation, and the co-localization value of CgPHB2 and mtphagy Dye was significantly increased. The direct interaction between CgPHB2 and CgLC3 was simulated by molecular docking. In PHB2-inhibitor Fluorizoline-treated oysters, the mRNA expressions of mitophagy-related genes and the ratio of mitophagy were significantly decreased in haemocytes of oysters after V. splendidus stimulation. All the results collectively suggested that CgPHB2 participated in mediating the haemocyte mitophagy in the antibacterial immune response of oysters.

Efficacy of esketamine for the treatment of postpartum depression and pain control following cesarean section: a randomized, double-blind, controlled clinical trial.

BACKGROUND: Postpartum depression (PPD) following a cesarean delivery is a frequently seen complication. Despite the prophylactic effects of ketamine, the impact of esketamine on PPD in women undergoing cesarean section remains uncertain. This study aimed to assess the effectiveness of esketamine as an adjunct to patient-controlled intravenous analgesia (PCIA) in preventing PPD in women undergoing caesarean section. METHODS: A total of 275 parturients undergoing caesarean section and subsequent patient-controlled intravenous analgesia (PCIA) were randomly assigned to receive either the control treatment (sufentanil 2 µg/kg + tropisetron 10 mg) or the experimental treatment with additional esketamine (1.5 mg/kg). The primary outcome measured was the incidence of postpartum depression (PPD), classified by Edinburgh Postnatal Depression Scale (EPDS) scores equal to or greater than 13 indicating PPD. Secondary outcomes included cumulative sufentanil consumption during specific time periods (0-24 h, 24-48 h, and 0-48 h) after the surgical procedure and numerical rating scale (NRS) scores at rest and during movements. RESULTS: The final analysis included a total of 246 postpartum women who had undergone caesarean delivery. On postoperative day 42, the incidence of depression among the control group was 17.6%, which was significantly higher compared to the esketamine group with a rate of 8.2% (P = 0.02). The EPDS scores also showed a significant difference between the two groups, with a mean score of 9.02 ± 2.21 in the control group and 6.87 ± 2.14 in the esketamine group (p < 0.0001). In terms of pain management, the esketamine group showed lower sufentanil consumption in the 0-24 h (42.5 ± 4.58 µg vs. 50.15 ± 5.47 µg, P = 0.04) and 0-48 h (87.40 ± 9.51 µg vs. 95.10 ± 9.36 µg, P = 0.04) postoperative periods compared to the control group. Differences in movement were also observed between the two groups at 24 and 48 h after the cesarean Sect. (3.39 ± 1.57 vs. 4.50 ± 0.80, P = 0.02; 2.43 ± 0.87 vs. 3.56 ± 0.76, P = 0.02). It is worth noting that the frequency of side effects observed in both groups was comparable. CONCLUSIONS: Esketamine at a dose of 1.5 mg/kg, when used as a supplement in PCIA, has been shown to significantly reduce the occurrence of PPD within 42 days. Additionally, it has been found to decrease cumulative consumption of sufentanil over a 48-hour period following cesarean operation, all without increasing the rate of adverse effects. TRIAL REGISTRATION: Registered in the Chinese Clinical Trial Registry (ChiCTR2200067054) on December 26, 2022.

Curcumin inhibits propofol-induced autophagy of MN9D cells via Akt/mTOR/p70S6K signaling pathway.

The rapid rise in propofol dependency and abuse has highlighted limited resources for addressing substance abuse-related cognitive impairment, prompting the development of novel therapies. Dysregulated autophagy flow accelerates neuronal cell death, and interventions countering this dysregulation offer an appealing strategy for neuronal protection. Curcumin, a potent natural polyphenol derived from turmeric rhizomes, is renowned for its robust antineurotoxic properties and enhanced cognitive function. Utilizing CCK-8 and Ki67 fluorescent staining, our study revealed that curcumin treatment increased cell viability and proliferative potential in MN9D cells exposed to propofol-induced neurotoxicity. Furthermore, enzyme-linked immunosorbent assay and western blot analysis demonstrated the partial restoration of dopamine synthesis, secretion levels, and TH expression in damaged MN9D cells treated with curcumin. Scanning electrode microscope images displayed reduced autolysosomes and phagosomes in curcumin-treated cells compared to the propofol group. Immunoblotting revealed that curcumin mitigated the degradation of LC3I to LC3II and p62 induced by propofol stimulation, with green fluorescence expression of LC3 postcurcumin treatment resembling that following autophagy inhibitor HCQ treatment, indicating that modulating autophagy flow can alleviate propofol's toxic effects. Moreover, curcumin treatment upregulated the Akt/mTOR/p70S6K signaling pathway, suggesting that curcumin potentially curtails autophagy dysregulation in nerve cells by activating Akt/mTOR/p70S6K. In conclusion, our findings suggest that curcumin can ameliorate propofol abuse-induced neurotoxicity, partially through autophagy regulation and Akt/mTOR/p70S6K signaling activation.

A novel multimodal prediction model based on DNA methylation biomarkers and low-dose computed tomography images for identifying early-stage lung cancer.

Objective: DNA methylation alterations are early events in carcinogenesis and immune signalling in lung cancer. This study aimed to develop a model based on short stature homeobox 2 gene (SHOX2)/prostaglandin E receptor 4 gene (PTGER4) DNA methylation in plasma, appearance subtype of pulmonary nodules (PNs) and low-dose computed tomography (LDCT) images to distinguish early-stage lung cancers. Methods: We developed a multimodal prediction model with a training set of 257 individuals. The performance of the multimodal prediction model was further validated in an independent validation set of 42 subjects. In addition, we explored the association between SHOX2/PTGER4 DNA methylation and driver gene mutations in lung cancer based on data from The Cancer Genome Atlas (TCGA) portal. Results: There were significant differences between the early-stage lung cancers and benign groups in the methylation levels. The area under a receiver operator characteristic curve (AUC) of SHOX2 in patients with solid nodules, mixed ground-glass opacity nodules and pure ground-glass opacity nodules were 0.693, 0.497 and 0.864, respectively, while the AUCs of PTGER4 were 0.559, 0.739 and 0.619, respectively. With the highest AUC of 0.894, the novel multimodal prediction model outperformed the Mayo Clinic model (0.519) and LDCT-based deep learning model (0.842) in the independent validation set. Database analysis demonstrated that patients with SHOX2/PTGER4 DNA hypermethylation were enriched in TP53 mutations. Conclusions: The present multimodal prediction model could more efficiently distinguish early-stage lung cancer from benign PNs. A prognostic index based on DNA methylation and lung cancer driver gene alterations may separate the patients into groups with good or poor prognosis.

A Comprehensive Review on Combinatorial Film via High-Throughput Techniques.

Numerous technological advancements in the 21st century depend on the creation of novel materials possessing enhanced properties; there is a growing reliance on materials that can be optimized to serve multiple functions. To efficiently save time and meet the requirements of diverse applications, high-throughput and combinatorial approaches are increasingly employed to explore and design superior materials. Among them, gradient thin-film deposition is one of the most mature and widely used technologies for high-throughput preparation of material libraries. This review summarizes recent progress in gradient thin-film deposition fabricated by magnetron sputtering, multi-arc ion plating, e-beam evaporation, additive manufacturing, and chemical bath deposition, providing readers with a fundamental understanding of this research field. First, high-throughput synthesis methods for gradient thin films are emphasized. Subsequently, we present the characteristics of combinatorial films, including microstructure, oxidation, corrosion tests, and mechanical properties. Next, the screening methods employed for evaluating these properties are discussed. Furthermore, we delve into the limitations of high-throughput preparation and characterization techniques for combinatorial films. Finally, we provide a summary and offer our perspectives.

Development and external validation of the multichannel deep learning model based on unenhanced CT for differentiating fat-poor angiomyolipoma from renal cell carcinoma: a two-center retrospective study.

PURPOSE: There are undetectable levels of fat in fat-poor angiomyolipoma. Thus, it is often misdiagnosed as renal cell carcinoma. We aimed to develop and evaluate a multichannel deep learning model for differentiating fat-poor angiomyolipoma (fp-AML) from renal cell carcinoma (RCC). METHODS: This two-center retrospective study included 320 patients from the First Affiliated Hospital of Sun Yat-Sen University (FAHSYSU) and 132 patients from the Sun Yat-Sen University Cancer Center (SYSUCC). Data from patients at FAHSYSU were divided into a development dataset (n = 267) and a hold-out dataset (n = 53). The development dataset was used to obtain the optimal combination of CT modality and input channel. The hold-out dataset and SYSUCC dataset were used for independent internal and external validation, respectively. RESULTS: In the development phase, models trained on unenhanced CT images performed significantly better than those trained on enhanced CT images based on the fivefold cross-validation. The best patient-level performance, with an average area under the receiver operating characteristic curve (AUC) of 0.951 ± 0.026 (mean ± SD), was achieved using the "unenhanced CT and 7-channel" model, which was finally selected as the optimal model. In the independent internal and external validation, AUCs of 0.966 (95% CI 0.919-1.000) and 0.898 (95% CI 0.824-0.972), respectively, were obtained using the optimal model. In addition, the performance of this model was better on large tumors (≥ 40 mm) in both internal and external validation. CONCLUSION: The promising results suggest that our multichannel deep learning classifier based on unenhanced whole-tumor CT images is a highly useful tool for differentiating fp-AML from RCC.

Comparison of non-radiomics imaging features and radiomics models based on contrast-enhanced ultrasound and Gd-EOB-DTPA-enhanced MRI for predicting microvascular invasion in hepatocellular carcinoma within 5 cm.

OBJECTIVES: The purpose of this study is to establish microvascular invasion (MVI) prediction models based on preoperative contrast-enhanced ultrasound (CEUS) and ethoxybenzyl-enhanced magnetic resonance imaging (EOB-MRI) in patients with a single hepatocellular carcinoma (HCC) ≤ 5 cm. METHODS: Patients with a single HCC ≤ 5 cm and accepting CEUS and EOB-MRI before surgery were enrolled in this study. Totally, 85 patients were randomly divided into the training and validation cohorts in a ratio of 7:3. Non-radiomics imaging features, the CEUS and EOB-MRI radiomics scores were extracted from the arterial phase, portal phase and delayed phase images of CEUS and the hepatobiliary phase images of EOB-MRI. Different MVI predicting models based on CEUS and EOB-MRI were constructed and their predictive values were evaluated. RESULTS: Since univariate analysis revealed that arterial peritumoral enhancement on the CEUS image, CEUS radiomics score, and EOB-MRI radiomics score were significantly associated with MVI, three prediction models, namely the CEUS model, the EOB-MRI model, and the CEUS-EOB model, were developed. In the validation cohort, the areas under the receiver operating characteristic curve of the CEUS model, the EOB-MRI model, and the CEUS-EOB model were 0.73, 0.79, and 0.86, respectively. CONCLUSIONS: Radiomics scores based on CEUS and EOB-MRI, combined with arterial peritumoral enhancement on CEUS, show a satisfying performance of MVI predicting. There was no significant difference in the efficacy of MVI risk evaluation between radiomics models based on CEUS and EOB-MRI in patients with a single HCC ≤ 5 cm. CLINICAL RELEVANCE STATEMENT: Radiomics models based on CEUS and EOB-MRI are effective for MVI predicting and conducive to pretreatment decision-making in patients with a single HCC within 5 cm. KEY POINTS: • Radiomics scores based on CEUS and EOB-MRI, combined with arterial peritumoral enhancement on CEUS, show a satisfying performance of MVI predicting. • There was no significant difference in the efficacy of MVI risk evaluation between radiomics models based on CEUS and EOB-MRI in patients with a single HCC ≤ 5 cm.

Anticancer efficacy of hirsuteine against colorectal cancer by opposite modulation of wild-type and mutant p53.

PURPOSE: The present study aimed to explore the anticancer activity of hirsuteine (HST), an indole alkaloid from the traditional Chinese herbal medicine Uncaria rhynchophylla, against colorectal cancer (CRC) and the underlining mechanism. METHODS: MTT, colony formation, flow cytometry and MDC staining were conducted to confirm the antiproliferative effect of HST on human CRC cells harboring different p53 status. Protein expressions were evaluated by the Western blot analysis. p53 protein half-life and the interaction between p53 and MDM2 were investigated using cycloheximide (CHX)-chase assay and Co-immunoprecipitation (Co-IP), respectively. Transcriptional activity of p53 was examined by qRT-PCR and Chromatin immunoprecipitation (ChIP). Xenograft tumor in nude mice was created to evaluate in vivo anticancer effect of HST against CRC. RESULTS: HST inhibited cell growth, arrested cell cycle and induced autophagy, showing efficient anticancer effects on CRC cells independent of p53 status. In HCT-8 cells, HST prolonged wtp53 half-life, and upregulated mRNA level of p21, suggesting that HST activated the p53 pathway through enhancement of wtp53 stability and transcriptional activity. Meanwhile in SW620 cells, HST induced MDM2-mediated proteasomal degradation of mutp53R273H, increased the DNA-binding ability of mutp53R273H at the p21 promoter, and upregulated mRNA levels of p21 and MDM2, demonstrating the depletion of mutp53R273H and restoration of its wild-type-like properties by HST. p53 knockdown by siRNA significantly impaired the growth inhibition of HST on HCT-8 and SW620 cells. Moreover, HST showed anticancer effects in xenograft tumors, accompanied with an opposite regulation of wtp53 and mutp53 R273H in mechanism. CONCLUSION: This study revealed the anticancer efficacy of HST against CRC via opposite modulation of wtp53 and mutp53 R273H, indicating the potential of HST to be a CRC drug candidate targeting p53 signaling.

Why can poorly conductive Bi@UiO-MOF catalyze CO2 electroreduction?

Metal NP @ metal-organic frameworks (MOFs) are widely used in electrocatalysis. However, many of the MOFs are poorly conductive. Here, we loaded bismuth (Bi) into a Zr-based MOF of the UiO structure that is active for CO2 reduction to formate and found that a moderate conductivity of the nanosized MOFs is sufficient to support a reasonably high catalytic current density. This finding allows simpler catalyst design and quantitative rationalization of MOF electrocatalysis.

Enhancement in the physicochemical properties, antioxidant activity, volatile compounds, and non-volatile compounds of watermelon juices through Lactobacillus plantarum JHT78 fermentation.

In this study, the influences of Lactobacillus plantarum JHT78 fermentation on the physiological properties, antioxidant activities, and volatile/non-volatile metabolites of watermelon juices were comprehensively investigated. The results indicated that total polyphenols flavonoids and anthocyanin in the watermelon juices remarkably increased through L. plantarum JHT78 fermentation. L. plantarum JHT78 fermentation enhanced the antioxidant activities, lipase inhibition, and α-glucosidase activities of watermelon juices. A total of 62 volatile compounds were detected using HS-SPME-GC-MS, mainly including 11 acids, 8 aldehydes, 7 ketones, and 7 alcohols. The abundance of 19 volatile compounds especially for acids remarkably increased for the fermentated watermelon juice. Furthermore, non-volatile compounds detected by UHPLC-QTOF-MS revealed that L. plantarum JHT78 significantly altered the non-volatile compounds of watermelon juices, especially increased indole-3-lactic acid. The results confirmed that L. plantarum JHT78 enhanced the functionality of watermelon juices thus providing a theoretical basis for the development of LAB on plant-based beverages.

Vessels That Encapsulate Tumor Clusters (VETC) Predict cTACE Response in Hepatocellular Carcinoma.

Background: To investigate the correlation between hepatocellular carcinoma (HCC) pathological types and conventional transarterial chemoembolization (cTACE), and to evaluate the predictive value of the pathological types for efficacy of cTACE. Methods: We investigated 186 naive HCC patients from 2 hospitals, including 63 patients with recurrence after surgical resection, and 123 unresectable cases, who underwent at least one cTACE procedure as the first treatment. All patients were histologically diagnosed with HCC by surgical resection and/or liver biopsy. Lipiodol deposition rate, ORR (objective response rate), PFS (progression-free survival), OS (overall survival) were compared among different HCC pathological types. Results: This study evaluated 186 naive HCC patients and 189 tumor nodules. Vessels that encapsulate tumor clusters (VETC), macrotrabecular-massive (MTM), CK19-positive types were identified in 38% (72/189), 40% (76/189), and 28% (53/189) of the whole cohort, respectively. VETC, MTM and CK19-negative HCCs derived significantly better lipiodol deposition rate and ORR. cTACE prolonged the PFS of VETC and CK19-negative HCCs compared with non-VETC and CK19-positive HCCs in the recurrence, liver biopsy and combining whole cohorts, whereas the OSs of different pathological types were not significantly different. Multivariate analysis showed that VETC (OR, 4.671, 95% CI [1.954, 11.166], P<0.001) and CK19-positive type (OR, 0.127, 95% CI [0.044, 0.362], P<0.001) were independent predictive factors for the first cTACE response. However, only VETC type was significantly associated with the second cTACE response in multivariate analysis (OR, 3.31, 95% CI [1.24, 8.83], P=0.017), suggesting that VETC might be a more useful predictor of cTACE response. Conclusion: Our study suggests that VETC is an effective predictor of cTACE response in patients with HCC.

A Polymer Network Layer Containing Dually Anchored Ionic Liquids for Stable Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries with high sulfur utilization, long-cycle life, and dendrite-free features hold great promise for the development of next-generation energy storage devices of high energy density. Considerable efforts have been committed to solving the polysulfide shuttle problem toward highly stable Li-S batteries. Here, a unique polymer network containing dually anchored ionic liquids (DA-PIL) is devolped to improve the cycling performance and coulombic efficiency of Li-S batteries. This DA-PIL electrolyte incorporates the amphiphilicity of both the polysulfides anion and lithium cation, creating an ionic function layer on polypropylene separator. Noteworthily, the DA-PIL network is "clean" in the sense that no free ionic specifies are introduced to the electrolyte system. The DA-PIL layer not only enables strong supression against polysulfide shuttling but simultaneously allows fast lithium transportation owing to cooperate electrostatic interaction among anchored cations and anions. The DA-PIL layer functionalized on a polypropylene separator can boost excellent stability of Li-S battery with >1600 h cycling test at 0.25 mA cm-2 . The Li-S cell with DA-PIL layer delivers a higher discharge capacity of 827.4 mAh g-1 at 1C. A discharge capacity of 630.6 mAh g-1 is retained after 1000 cycles.

Recent advances in development of functional magnetic adsorbents for selective separation of proteins/peptides.

Nowadays, proteins separation has attracted great attention in proteomics research. Because the proteins separation is helpful for making an early diagnosis of many diseases. Magnetic nanoparticles are an interesting and useful functional material, and have attracted extensive research interest during the past decades. Because of the excellent properties such as easy surface functionalization, tunable biocompatibility, high saturation magnetization etc, magnetic microspheres have been widely used in isolation of proteins/peptides. Notably, with the rapid development of surface decoration strategies, more and more functional magnetic adsorbents have been designed and fabricated to meet the growing demands of biological separation. In this review, we have collected recent information about magnetic adsorbents applications in selective separation of proteins/peptides. Furthermore, we present a comprehensive prospects and challenges in the field of protein separation relying on magnetic nanoparticles.

Comprehensive analysis of HHV-6 and HHV-7-related gene signature in prognosis and response to temozolomide of glioma.

Human herpesvirus (HHV)-6 and HHV-7 have been detected in central nervous system and glioma tissue, while their exact role in glioma remains uncertain. Omics profiles and clinical information were downloaded from public databases, including The Cancer Genome Atlas cohort for training set and the Chinese Glioma Genome Atlas cohorts for validation sets. Differentially expressed genes between HHV-6 and HHV-7 infected or noninfected glioma patients were screened for establishing the HHV-6 and HHV-7 infection (HI) model through Lasso regression analysis. Bioinformatics methods were used to analyze the correlation between HI scores and prognosis, metastasis in glioma patients. Predictable efficacy of HI in temozolomide-resistance and HI-related genetic signatures were also explored. The HI model was constructed as: Risk score = (0.014709*DIRAS3) + (0.029787*TEX26) + (0.223492*FBXO39) + (0.074951*MYBL1) + (0.060202*HILS1). The five gene signature showed good performance in predicting survival time for glioma patients, while higher HI score is correlated with malignant features. Moreover, DNA mismatch repair genes were augmented in glioma patients with higher HI score as well as nonresponse to temozolomide treatment, which was in parallel with the transcriptomic result of temozolomide-resistant glioma cell. Targeting the five gene signature is beneficial for prognosis of glioma patients, especially in glioma patients underwent temozolomide treatment.

Melatonin reduces myocardial cell damage in myocardial ischemia/reperfusion rats by inhibiting NLRP3 activation.

Melatonin (Mel) is an endogenous hormone with many pharmacological effects, such as sedation, hypnosis, antidepressant, blood pressure regulation, anti-inflammatory and anti-tumor. It is mainly synthesized by pineal gland in vivo. Mel can regulate the function of cardiovascular system and effectively reduce myocardial cell injury, thus playing a role in myocardial protection, but its specific mechanism is unclear. Ischemia-reperfusion injury (IRI) often leads to poor prognosis and complications in patients with cardiovascular diseases, and inflammatory reaction mediated by nod-like receptor thermoprotein domain-related protein 3(NLRP3) is an important reason for the further aggravation of subsequent injury after IRI. Rats were intervened with Mel or NLRP3 inhibitor MCC950 for 10 days, and then the IRI rat model was established. After that, rats were anesthetized and killed, and myocardial tissues were collected for experiments. The experimental results showed that Mel reduced the myocardial infarction area, decreased aspartate aminotransferase (AST), creatine kinase myocardial band (CK-MB), lactate dehydrogenase (LDH) and malondialdehyde (MDA), and significantly inhibited the expression of reactive oxygen species (ROS), NLRP3, caspase-1 and apoptosis-associated speck-like protein containing a CARD (ASC), but its effect on superoxide dismutase (SOD) was opposite. Therefore, Mel may improve autophagy and inflammation during myocardial ischemia/reperfusion and may decrease myocardial cell damage by inhibiting NLRP3.

Saturated Nonsingular Fast Sliding Mode Control for the Crane-Form Pipeline System.

The crane-form pipeline (CFP) system is a kind of petrochemical mechanical equipment composed of multiple rotating joints and rigid pipelines. It is often used to transport chemical fluid products in the factory to tank trucks. In order to realize the automatic alignment of the CFP and the tank mouth, the trajectory tracking control problem of the CFP must be solved. Therefore, a saturated nonsingular fast terminal sliding mode (SNFTSM) algorithm is proposed in this paper. The new sliding mode manifold is constructed by the nonsingular fast terminal sliding mode (NFTSM) manifold, saturation functions and signum functions. Further, according to the sliding mode control algorithm and the dynamic model of the CFP system, the SNFTSM controller is designed. Owing to the existence of saturation functions in the controller, the stability analysis using the Lyapunov equation needs to be discussed in different cases. The results show that the system states can converge to the equilibrium point in finite time no matter where they are on the state's phase plane. However, due to the existence of signum functions, the control signal will produce chattering. In order to eliminate the chattering problem, the form of the controller is improved by using the boundary layer function. Finally, the control effect of the algorithm is verified by simulation and compared with the NTSM, NFTSM and SNTSM algorithms. From the comparison results, it is obvious that the controller based on the SNFTSM algorithm can effectively reduce the amplitude of the control torque while guaranteeing the fast convergence of the CFP system state error. Specifically, compared with the NFTSM algorithm, the maximum input torque can even be reduced by more than half.

Structures of UBA6 explain its dual specificity for ubiquitin and FAT10.

The covalent modification of target proteins with ubiquitin or ubiquitin-like modifiers is initiated by E1 activating enzymes, which typically transfer a single modifier onto cognate conjugating enzymes. UBA6 is an unusual E1 since it activates two highly distinct modifiers, ubiquitin and FAT10. Here, we report crystal structures of UBA6 in complex with either ATP or FAT10. In the UBA6-FAT10 complex, the C-terminal domain of FAT10 binds to where ubiquitin resides in the UBA1-ubiquitin complex, however, a switch element ensures the alternate recruitment of either modifier. Simultaneously, the N-terminal domain of FAT10 interacts with the 3-helix bundle of UBA6. Site-directed mutagenesis identifies residues permitting the selective activation of either ubiquitin or FAT10. These results pave the way for studies investigating the activation of either modifier by UBA6 in physiological and pathophysiological settings.

In situ forming injectable γ-poly(glutamic acid)/PEG adhesive hydrogels for hemorrhage control.

Rapidly in situ forming adhesive hydrogels are promising candidates for efficient hemostasis due to their easy administration and minimal invasion. However, development of biocompatible and high-performance hemostatic hydrogels without any additional toxic agents remains a challenge. Herein, a series of novel injectable adhesive hydrogels based on N-hydroxysuccinimide (NHS) modified γ-poly(glutamic acid) (γPGA-NHS) and tetra-armed poly(ethylene glycol) amine (Tetra-PEG-NH2) were developed. Among all samples, PGA10-PEG15 and PGA10-PEG20 hydrogels with higher PEG contents exhibited rapid gelation time (<20 s), strong mechanical strength (compression modulus up to ∼75 kPa), good adhesive properties (∼15 kPa), and satisfactory burst pressure (∼18-20 kPa). As a result, PGA10-PEG15 and PGA10-PEG20 hydrogels showed a remarkable reduction in hemostasis time and blood loss compared with gauze and fibrin glue. More importantly, the PGA10-PEG20 hydrogel was also successfully used to seal femoral arterial trauma. Subcutaneous implantation experiments indicated a good biocompatibility of the hydrogels in vivo. All these results strongly support that the developed PGA-PEG hydrogels could serve as promising hemostatic agents in emergency and clinical situations.

The Novel Role of Cytomorphology from Ultrasound-Guided Fine Needle Aspiration Cytology in Evaluating the Status of Prognostic Factors including Estrogen Receptor, Progesterone Receptor and HER2 in Breast Cancer.

It is well established that estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2) could be regarded as prognostic factors in breast cancer. Ultrasound-guided fine needle aspiration cytology (FNAC) has revolutionized the management of cancers, providing less invasive and quick diagnostic method. There are hardly any studies on the correlation between cytomorphology and prognostic biomarkers. We retrospectively analyzed the immunohistochemistry and the fluorescence in situ hybridization of breast cancer specimens from 252 patients, who have been diagnosed as breast cancer at our hospital. Morphological features of cytology smears were scored. The relationship between cytological features and three biomarkers were analyzed. Based on this, we developed a system to predict the status of biomarkers. The results indicated that some cytological parameters, especially the features of nucleoli, were distinctively related to the makers' expression. In the novel scoring system, a cutoff of 12.0 provided a statistical discrimination for cytological grading. We concluded that cytomorphological features were associated with prognostic factors. The HR+ neoplasms showed scattered micronucleoli, while HER2+ neoplasms demonstrated centered macronucleoli. We summarized a scoring system to predict the status of three factors. This may help us to broaden the application of breast cancer cytology.