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Objective To investigate the predictive value of serum actinin-4, trefoil factor 1 (TFF1), and transforming growth factor-β-induced protein (TGFBI) for the prognosis of patients with primary hepatocellular carcinoma (PHC) after transarterial chemoembolization (TACE). Methods From January 2020 to May 2023, 312 patients with PHC who underwent TACE in Shijiazhuang People's Hospital were collected as the study subjects (PHC group), patients with PHC were separated into a group with good prognosis (n=252) and a group with poor prognosis (n=60) based on their postoperative conditions. And 312 subjects who underwent health examinations were selected as the control group. Serum levels of actinin-4, TFF1, and TGFBI were detected by ELISA. Logistic regression was applied to analyze the influencing factors of poor prognosis in patients with PHC after TACE. Receiver operating characteristic curve (ROC) was applied to analyze the predictive value of serum actinin-4, TFF1, and TGFBI for poor prognosis after TACE in patients with PHC. Results There was no significant difference in gender, age, Child-Pugh grade, and clinical stage between the group with good prognosis and the group with poor prognosis (P＞0.05), but there were statistically differences in tumor size and portal vein tumor thrombus (P＜0.05). Compared with control group, the serum levels of actinin-4 ［(45.67±10.23) pg/mL vs (28.25±6.96) pg/mL, t=24.868, P＜0.01］, TFF1 ［(5.04±1.53) ng/mL vs (2.32±0.64) ng/mL, t=28.969, P＜0.01］, TGFBI ［(19.16±4.36)ng/mL vs (10.25±2.43) ng/mL, t=31.530, P＜0.01］ were obviously higher in PHC group. Compared with the group with good prognosis, the serum levels of actinin-4, TFF1, and TGFBI in the group with poor prognosis were obviously increased (P＜0.01). The results of multivariate logistic regression analysis showed that tumor size, portal vein tumor thrombus, serum actinin-4, TFF1, and TGFBI were all influencing factors for poor prognosis of PHC patients after TACE (P＜0.05). ROC curve results showed that the combined prediction of serum actinin-4, TFF1, and TGFBI for poor prognosis after TACE in PHC patients had an AUC of 0.926, a sensitivity of 81.3%, and a specificity of 76.8%. Conclusion The serum levels of actinin-4, TFF1, and TGFBI in patients with poor prognosis after TACE for PHC are obviously increased, and the combined determination of the three has good predictive value for prognosis of patients.

Abstract AAA+ proteases degrade intracellular proteins in a highly specific manner. E. coli ClpXP, for example, relies on a C-terminal ssrA tag or other terminal degron sequences to recognize proteins, which are then unfolded by ClpX and subsequently translocated through its axial channel and into the degradation chamber of ClpP for proteolysis. Prior cryo-EM structures reveal that the ssrA tag initially binds to a ClpX conformation in which the axial channel is closed by a pore-2 loop. Here, we show that substrate-free ClpXP has a nearly identical closed-channel conformation. We destabilize this closed-channel conformation by deleting residues from the ClpX pore-2 loop. Strikingly, open-channel ClpXP variants degrade non-native proteins lacking degrons faster than the parental enzymes in vitro but degraded GFP-ssrA more slowly. When expressed in E. coli, these open channel variants behave similarly to the wild-type enzyme in assays of filamentation and phage-Mu plating but resulted in reduced growth phenotypes at elevated temperatures or when cells were exposed to sub-lethal antibiotic concentrations. Thus, channel closure is an important determinant of ClpXP degradation specificity.

High alkaline environment can lead to respiratory alkalosis and ammonia toxification to freshwater fish. However, the Amur ide (Leuciscus waleckii), which inhabits an extremely alkaline lake in China with titratable alkalinity up to 53.57 mM (pH 9.6) has developed special physiological and molecular mechanisms to adapt to such an environment. Nevertheless, how the Amur ide can maintain acid-base balance and perform ammonia detoxification effectively remains unclear. Therefore, this study was designed to study the ammonia excretion rate (Tamm), total nitrogen accumulation in blood and tissues, including identification, expression, and localization of ammonia-related transporters in gills of both the alkali and freshwater forms of the Amur ide. The results showed that the freshwater form Amur ide does not have a perfect ammonia excretion mechanism exposed to high-alkaline condition. Nevertheless, the alkali form of Amur ide was able to excrete ammonia better than freshwater from Amur ide, which was facilitated by the ionocytes transporters (Rhbg, Rhcg1, Na+/H+ exchanger 2 (NHE2), and V-type H+ ATPase (VHA)) in the gills. Converting ammonia into urea served as an ammonia detoxication strategy to reduced endogenous ammonia accumulation under high-alkaline environment.

The effect of hold time with 0, 20, and 40 s on in-phase thermomechanical fatigue (TMF) behavior and life of P92 steel is investigated in this study. TMF tests are carried out under mechanical strain control with strain amplitudes of 0.40.4, 0.60.6, and 0.8%0.8\text{\%}, and temperature range of 550–650°C which is closely relevant to the operating condition in power plant. TMF tests are performed in a mechanical strain ratio of R=−1R=-1 and cycle time of 120 s. The fatigue life variation follows the sequence of Nf0s

By experiment at a low-speed large-scale axial contra-rotating compressor, the near stall points of 19 speed configurations were captured and the stall characteristics under different speed ratios were obtained successfully. The results show that the compressor with speed ratio greater than 1 are more likely to stall than the compressor with speed ratio less than 1 and the flow rate at the starting point of stall is at least 18% earlier, the pressurization capacity is at least 5.5% higher when speed values of the front and rear rotors are interchanged. At the same speed ratio, the dimensionless characteristic lines of pressure rise coefficient-flow coefficient almost coincide. With the decrease of speed ratio, the dimensionless characteristic line of contra-compressor moves upward. Through summing up all speed configurations' stall types and stall initial disturbance frequency, it can be found that: there is a critical speed ratio between 1.125 and 1.167 in the contra-rotating compressor studied in this paper. When the speed ratio is less than the critical value, the stall disturbance has the characteristic like spike stall. At this time, the initial stall disturbance frequency is higher with the speed ratio is smaller. And at the same speed ratio, the initial stall disturbance frequency increases with the increase of the average speed of the front and rear rotors. When the speed ratio is greater than the critical value, the stall disturbance doesn't rotate circumferentially.

The thermal transient load of the primary loop nuclear pipeline will cause fatigue damage at sensitive locations.And cumulative fatigue damage factors of these sensitive locations need to be monitored during the life extension of the nuclear power plant,and thermal transient stresses need to be calculated rapidly during online monitoring. Taking the thermal shock of the spray nozzle of pressurizer as an example,the double temperature boundary Green’s function method is discussed. By the volume integration of Green’s function,the transient thermal stress under the heat-up condition is calculated. The accuracy of the two temperature boundary Green’s function is verified by comparing with the direct calculation results of finite element method.Studies have shown that the Green’s function should be established separately for subdivisions which are divided according to the differences of the flow heat transfer boundary（ such as the convection heat transfer coefficient） and the width of the temperature range. While in a certain temperature range,it is feasible to establish the Green’s function based on the average temperature of the temperature range with large enough step temperature.

The Amur ide (Leuciscus waleckii) is a fish in the Cyprinidae family. Compared with other Amur ide living in freshwater ecosystems, the Amur ide population in Lake Dali Nor of China is famous for its high tolerance to the alkaline conditions of 54 mM (pH 9.6). Yet, surprisingly, the ionoregulatory mechanism responsible for this remarkable alkaline adaptation remains unclear. Therefore, this study sought to investigate how bicarbonate affects the acid-base balancing and ionoregulatory responses of this animal. Here, using a comparative approach, the alkali form of Amur ide and its ancestral freshwater form living in other freshwater basins were each exposed to 50 mM (pH 9.59 ± 0.09), a level close to the alkalinity of Lake Dali Nor, and their physiological (AE1) adjustment of ions and acid-base regulation were investigated. This study highlighted differences in blood pH and serum ions (e.g., Na+, K+, Cl−, and Ca2+), Na+/K+ ATPase (NKA) activity and its mRNA level, and mRNA expression of gill transporters (Na+/H+ exchanger member 2 and/or 3, Na+/HCO3- cotransporter (NBC1), Cl−/HCO3- exchanger, Na+/Cl− cotransporter (NCC), Na+/K+/2Cl− (NKCC1), SLC26A5, and SLC26A6) for alkalinity adaptation between the two forms of Amur ide differing in alkalinity tolerance. Specifically, close relationships among the serum Na+ and mRNA levels of NCC, NKCC1, and NHE, and also NKA and NBC1, in addition to serum Cl− and bicarbonate transporters (e.g., SLC26A5 and SLC26A6), characterized the alkali form of Amur ide. We propose that this ecotype can ensure its transepithelial Cl− and Na+ uptake/base secretions are highly functional, by its basolateral NKA with NBC1 and apical ionic transporters, and especially NCC incorporated with other transporters (e.g., SLC26). This suggests an evolved strong ability to maintain an ion osmotic and acid-base balance for more effectively facilitating its adaptability to the high alkaline environment. This study provides new insights into the physiological responses of the alkaline form of the Amur ide fish for adapting to extreme alkaline conditions. This information could be used as a reference to cultivating alkaline-tolerant fish species in abandoned alkaline waters.

Leuciscus waleckii is a freshwater fish that is known to inhabit the Dali Nor Lake, Inner Mongolia, China. The water in this lake has an HCO3–/CO32– concentration of 54 mM (pH 9.6) and a salinity of 0.6‰. The physiological mechanisms that allow this fish to tolerate these saline/alkaline conditions have yet to be elucidated. Transcriptional component analysis has shown that the expression levels of a large number of genes involved in the pathways responsible for osmo-ionoregulation and arachidonic acid metabolism pathway expression change significantly (p < 0.05) during the regulation of acid–base balance under high alkaline stress. In this study, we investigated the role of long non-coding RNAs (lncRNAs) during adaptation to high alkaline conditions. Fish were challenged to an NaHCO3-adjusted alkalinity of 0 mM, 30 mM (pH 9.44 ± 0.08), and 50 mM (pH 9.55 ± 0.06) for 20 days in the laboratory. Gill and kidney tissues were then collected for high-throughput sequencing assays. A total of 159 million clean reads were obtained by high-throughput sequencing, and 41,248 lncRNA transcripts were identified. Of these, the mean number of exons and the mean length of the lncRNA transcripts were 4.8 and 2,079 bp, respectively. Based on the analysis of differential lncRNA transcript expression, a total of 5,244 and 6,571 lncRNA transcripts were found to be differentially expressed in the gills and kidneys, respectively. Results derived from Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the coding genes were correlated with the lncRNA expression profiles. GO analysis showed that many lncRNAs were enriched in the following processes: “transporter activity,” “response to stimulus,” and “binding.” KEGG analysis further revealed that metabolic pathways were significantly enriched. A random selection of 16 lncRNA transcripts was tested by RT-qPCR; these results were consistent with our sequencing results. We found that a large number of genes, with the same expression profiles as those with differentially expressed lncRNAs, were associated with the regulation of acid–base balance, ion transport, and the excretion of ammonia and nitrogen. Collectively, our data indicate that lncRNA-regulated gene expression plays an important role in the process of adaptation to high alkaline conditions in L. waleckii.

Firstly, the experimental J-R curve and the predicting curves by the three models of 400℃ thermally aged Z3 CN20-09 M pipe and elbow were compared. The results showed that ANL model and H3 T model aren’t suitable for the prediction of low toughness CASS components, however the EDF model is better for low toughness CASS components prediction. All the three models present non-conservative prediction for the early crack propagation, but it doesn’t affect the threshold judgment. According to the comparison between experimental J-R curves and the predicting curves, the ANL model and H3 T model are more suitable for the thermal aging assessment of CASS Z3 CN20-09 M.

When ribosomes fail to complete normal translation, all cells have mechanisms to ensure degradation of the resulting partial proteins to safeguard proteome integrity. In Escherichia coli and other eubacteria, the tmRNA system rescues stalled ribosomes and adds an ssrA tag or degron to the C-terminus of the incomplete protein, which directs degradation by the AAA+ ClpXP protease. Here, we present cryo-EM structures of ClpXP bound to the ssrA degron. C-terminal residues of the ssrA degron initially bind in the top of an otherwise closed ClpX axial channel and subsequently move deeper into an open channel. For short-degron protein substrates, we show that unfolding can occur directly from the initial closed-channel complex. For longer degron substrates, our studies illuminate how ClpXP transitions from specific recognition into a nonspecific unfolding and translocation machine. Many AAA+ proteases and protein-remodeling motors are likely to employ similar multistep recognition and engagement strategies.

ClpXP is an ATP-dependent protease in which the ClpX AAA+ motor binds, unfolds, and translocates specific protein substrates into the degradation chamber of ClpP. We present cryo-EM studies of the E. coli enzyme that show how asymmetric hexameric rings of ClpX bind symmetric heptameric rings of ClpP and interact with protein substrates. Subunits in the ClpX hexamer assume a spiral conformation and interact with two-residue segments of substrate in the axial channel, as observed for other AAA+ proteases and protein-remodeling machines. Strictly sequential models of ATP hydrolysis and a power stroke that moves two residues of the substrate per translocation step have been inferred from these structural features for other AAA+ unfoldases, but biochemical and single-molecule biophysical studies indicate that ClpXP operates by a probabilistic mechanism in which five to eight residues are translocated for each ATP hydrolyzed. We propose structure-based models that could account for the functional results.

BackgroundNon-alcoholic fatty liver disease (NAFLD) is increasingly widespread with an overall global estimated prevalence of 25%. Type 2 diabetes Mellitus (T2DM) is a key contributor to NAFLD progression and predicts moderate-severe liver fibrosis and mortality. However, there is currently no uniform consensus on routine NAFLD screening among T2DM patients, and the risk factors of NAFLD and advanced fibrosis among T2DM patients remain to be clarified fully.AimWe explored the prevalence, clinical spectrum, and risk factors of NAFLD and liver fibrosis among T2DM patients.MethodsThis is a cross-sectional study that enrolled subjects from a primary care clinic and a diabetes centre in Singapore. Subjects aged 21 to 70 years of all ethnic groups with an established T2DM diagnosis were included. Subjects with chronic liver diseases of other aetiologies were excluded. All subjects underwent transient elastography for hepatic steatosis and fibrosis assessment. Their demographics, anthropometric measurements and clinical parameters were collected. Statistical analysis was performed using STATA/SE16.0 software.ResultsAmong 449 enrolled T2DM subjects, 436 with complete data and valid transient elastography results were analysed. Overall, 78.72% (344/436) of the T2DM subjects had NAFLD, of which 13.08% (45/344) had increased liver stiffness. Higher ALT level (OR = 1.08; 95% CI: 1.03-1.14; p = 0.004), obesity (BMI ≥ 27.5 kg/m2, OR = 2.64; 95% CI: 1.28-5.44; p = 0.008) and metabolic syndrome (OR = 4.36; 95% CI 1.40-13.58; p = 0.011) were independent factors associated with increased CAP (NAFLD). Higher AST level (OR = 1.06; 95% CI: 1.02-1.11; p = 0.008), CAP value (OR = 1.02; 95% CI: 1.00-1.03; p = 0.003), lower platelet count (OR = 0.99; 95% CI: 0.98-1.00; p = 0.009) and concomitant hypertension (OR = 4.56; 95% CI: 1.18-17.62; p = 0.028) were independent factors associated with increased liver stiffness.ConclusionsOur study demonstrated a considerably high prevalence of NAFLD among T2DM patients, with the proportion of advanced liver fibrosis among T2DM NAFLD patients much higher than the general population. Given that NAFLD is largely asymptomatic, increased awareness and vigilance for identifying NAFLD and increased liver stiffness among T2DM patients should be advocated.

Abstract P2X receptors, a subfamily of ligand-gated ion channels activated by extracellular ATP, are implicated in various physiopathological processes, including inflammation, pain perception, and immune and respiratory regulations. Structural determinations using crystallography and cryo-EM have revealed that the extracellular three-dimensional architectures of different P2X subtypes across various species are remarkably identical, greatly advancing our understanding of P2X activation mechanisms. However, structural studies yield paradoxical architectures of the intracellular domain (ICD) of different subtypes (e.g., P2X3 and P2X7) at the apo state, and the role of the ICD in P2X functional regulation remains unclear. Here, we propose that the P2X3 receptor’s ICD has an apo state conformation similar to the open state but with a less tense architecture, containing allosteric sites that influence P2X3’s physiological and pathological roles. Using covalent occupancy, engineered disulfide bonds and voltage-clamp fluorometry, we suggested that the ICD can undergo coordinated motions with the transmembrane domain of P2X3, thereby facilitating channel activation. Additionally, we identified a novel P2X3 enhancer, PSFL77, and uncovered its potential allosteric site located in the 1α3β domain of the ICD. PSFL77 modulated pain perception in P2rx3 +/+, but not in P2rx3 −/−, mice, indicating that the 1α3β, a “tunable” region implicated in the regulation of P2X3 functions. Thus, when P2X3 is in its apo state, its ICD architecture is fairly ordered rather than an unstructured outward folding, enabling allosteric modulation of the signaling of P2X3 receptors.

AIM: To observe early clinical outcome with lens position adjustment following the implantable collamer lens (ICL) surgery. METHODS: Sixty patients were selected for this retrospective study. One eye from each patient received Toric ICL for astigmatism correction, and the other received non-astigmatic ICL surgery using horizontal position. Patients with higher postoperative arch height were selected, and their non-astigmatic eye clinical outcome were observed after ICL surgery at 1wk, 1, and 3mo. The clinical measurements included uncorrected visual acuity (UCVA), intraocular pressure (IOP), refractive state, corneal endothelium cell count, and arch height. Three months later, the ICL in each patient's non-astigmatic eye was adjusted to the vertical from the horizontal position. The results were compared before and 1wk, 1, and 3mo after adjustment. RESULTS: UCVA and IOP were significantly reduced 1wk after position adjustment compared to 1wk after ICL implantation (P0.05). CONCLUSION: Early positioning adjustment post-phakic ICL implantation can benefit patients with adjusted arch height or higher IOP. Despite the good clinical effects, the doctors should pay attention to the potential for adverse effects on UCVA and corneal endothelium cells following early position adjustment after posterior chamber phakic ICL implantation.

The proliferation of information and communication technologies (ICTs) within smart cities has not only enhanced the capabilities and efficiencies of urban energy systems but has also introduced significant cyber threats that can compromise these systems. To mitigate the financial risks associated with cyber intrusions in smart city infrastructures, this study introduces a two-stage hierarchical planning model for ICT-integrated multi-energy systems, emphasizing the economic role of cyber insurance. By adopting cyber insurance, smart city operators can mitigate the financial impact of unforeseen cyber incidents, transferring these economic risks to the insurance provider. The proposed two-stage optimization model strategically balances the economic implications of urban energy system operations with cyber insurance coverage. This approach allows city managers to make economically informed decisions about insurance procurement in the first stage and implement cost-effective defense strategies against potential cyberattacks in the second stage. Utilizing a distributionally robust approach, the study captures the emergent and uncertain nature of cyberattacks through a moment-based ambiguity set and resolves the reformulated linear problem using a dynamic cutting plane method. This work offers a distinct perspective on managing the economic risks of cyber incidents in smart cities and provides a valuable framework for decision making regarding cyber insurance procurement, ultimately aiming to enhance the financial stability of smart city energy operations.

An untargeted metabolomic analysis of five Eucalyptus species was used to compare their chemical profiles. Gas chromatography-mass spectrometry (GC-MS) along with multivariate analyses including principal component analysis (PCA) and hierarchical cluster analysis (HCA) were applied to assess variations in the leaf chemical profiles of E. maidenii F. Muell, E. robusta Smith, E. citriodora Hook (syn Corymbia citriodora), E. tereticornis Smith and E. camaldulensis Dehnh. In total, 299 relevant metabolites were identified and subjected to statistical analyses in order to detect either the major common metabolites of the genus or the specific compounds contributing to the characteristic chemical composition of each species. Organic acids, nitrogenous compounds, and phenolic constituents were the main discriminatory groups between the investigated eucalypts. The cluster analysis revealed that fatty acids and fatty alcohols were more concentrated in the leaves of E. citriodora and distinguished it from other species, whereas sugars, polyols, and glycosides were characteristic to E. camaldulensis.