An integrated multi-omics approach reveals polymethoxylated flavonoid biosynthesis in Citrus reticulata cv. Chachiensis.

Citrus reticulata cv. Chachiensis (CRC) is an important medicinal plant, its dried mature peels named "Guangchenpi", has been used as a traditional Chinese medicine to treat cough, indigestion, and lung diseases for several hundred years. However, the biosynthesis of the crucial natural products polymethoxylated flavonoids (PMFs) in CRC remains unclear. Here, we report a chromosome-scale genome assembly of CRC with the size of 314.96 Mb and a contig N50 of 16.22 Mb. Using multi-omics resources, we discover a putative caffeic acid O-methyltransferase (CcOMT1) that can transfer a methyl group to the 3-hydroxyl of natsudaidain to form 3,5,6,7,8,3',4'-heptamethoxyflavone (HPMF). Based on transient overexpression and virus-induced gene silencing experiments, we propose that CcOMT1 is a candidate enzyme in HPMF biosynthesis. In addition, a potential gene regulatory network associated with PMF biosynthesis is identified. This study provides insights into PMF biosynthesis and may assist future research on mining genes for the biosynthesis of plant-based medicines.

Impact of AML1/ETO Fusion on the Efficacy of Venetoclax Plus Hypomethylating Agents in Newly Diagnosed Acute Myeloid Leukemia.

BACKGROUND: AML1/ETO fusion confers favorable prognosis in acute myeloid leukemia (AML) treated with intensive chemotherapy (IC). However, the impact of AML1/ETO fusion on the efficacy of venetoclax in the treatment of AML is unclear. OBJECTIVE: The aim of this study was to evaluate the efficacy of venetoclax plus hypomethylating agents (VEN/HMAs) in patients with AML1/ETO-positive AML. PATIENTS AND METHODS: Patients with newly diagnosed AML in two centers were reviewed and divided into three cohorts: AML1/ETO-positive AML treated with frontline VEN/HMA (Cohort A), AML1/ETO-negative AML treated with frontline VEN/HMA (Cohort B), or AML1/ETO-positive AML treated with frontline IC (Cohort C). The response and survival were compared between the cohorts. RESULTS: A total of 260 patients were included in the study. Patients in Cohort A had a significantly lower overall response rate (ORR) than patients in Cohort B (40.9% vs 71.2%, p = 0.005). The median event-free survival (EFS) in Cohort A and Cohort B was 2.7 months and 7.7 months, respectively, with no significant difference. The ORR and median EFS in Cohort C were 80.8% and 14.9 months, respectively, which were significantly superior to those in Cohort A, and the advantages remained significant after propensity score matching. ORR and EFS in KIT-mutated patients with AML1/ETO-positive AML receiving VEN/HMA were much inferior to those in KIT wild-type patients (ORR 0.0% vs 81.8%, p = 0.001; EFS 1.2 months vs not reached, p < 0.001). CONCLUSIONS: Newly diagnosed AML patients with AML1/ETO fusion had a poor response to frontline VEN/HMA treatment. When determining induction therapy for patients with AML1/ETO-positive AML, IC should be preferred over VEN/HM.

Data Imputation of Soil Pressure on Shield Tunnel Lining Based on Random Forest Model.

With the advancement of engineering techniques, underground shield tunneling projects have also started incorporating emerging technologies to monitor the forces and displacements during the construction and operation phases of shield tunnels. Monitoring devices installed on the tunnel segment components generate a large amount of data. However, due to various factors, data may be missing. Hence, the completion of the incomplete data is imperative to ensure the utmost safety of the engineering project. In this research, a missing data imputation technique utilizing Random Forest (RF) is introduced. The optimal combination of the number of decision trees, maximum depth, and number of features in the RF is determined by minimizing the Mean Squared Error (MSE). Subsequently, complete soil pressure data are artificially manipulated to create incomplete datasets with missing rates of 20%, 40%, and 60%. A comparative analysis of the imputation results using three methods-median, mean, and RF-reveals that this proposed method has the smallest imputation error. As the missing rate increases, the mean squared error of the Random Forest method and the other two methods also increases, with a maximum difference of about 70%. This indicates that the random forest method is suitable for imputing monitoring data.

Confining Pressure Forecasting of Shield Tunnel Lining Based on GRU Model and RNN Model.

The confining pressure has a great effect on the internal force of the tunnel. During construction, the confining pressure which has a crucial impact on tunnel construction changes due to the variation of groundwater level and applied load. Therefore, the safety of tunnels must have the magnitude of confining pressure accurately estimated. In this study, a complete tunnel confining pressure time axis was obtained through high-frequency field monitoring, the data are segmented into a training set and a testing set. Using GRU and RNN models, a confining pressure prediction model was established, and the prediction results were analyzed. The results indicate that the GRU model has a fast-training speed and higher accuracy. On the other hand, the training speed of the RNN model is slow, with lower accuracy. The dynamic characteristics of soil pressure during tunnel construction require accurate prediction models to maintain the safety of the tunnel. The comparison between GRU and RNN models not only highlights the advantages of the GRU model but also emphasizes the necessity of balancing speed accuracy in tunnel construction confining pressure prediction modeling. This study is helpful in improving the understanding of soil pressure dynamics and developing effective prediction tools to promote safer and more reliable tunnel construction practices.

Outcomes of COVID-19 in multiple myeloma patients treated with daratumumab.

Despite concerns about an increased risk of adverse outcomes following coronavirus disease (COVID-19) in multiple myeloma patients treated with anti-CD38 Abs, the impact of COVID-19 on this group of patients is unclear. We tried to evaluate the clinical outcomes of these patients. We collected data from 1036 patients with multiple myeloma and enrolled 509 cases with COVID-19. We divided enrolled patients into daratumumab or nondaratumumab cohorts based on whether they had received daratumumab-based treatment within 6 months of COVID-19 infection. We applied a propensity score matching method to reduce the bias of baseline characteristics, and then compared the incidence of adverse outcomes between these two cohorts. A total of 117 patients were enrolled in the daratumumab cohort, and 392 patients in the nondaratumumab cohort. After propensity score matching, 204 patients were matched. The proportions of patients who developed COVID-19 pneumonia (59.8% vs. 34.3%, p < 0.001), were hospitalized (33.3% vs. 11.8%, p < 0.001) and developed severe disease (23.5% vs. 6.9%, p = 0.001) were higher in the matched daratumumab cohort. By multivariate analysis, daratumumab exposure was an independent risk factor for severe disease. An ECOG performance status >2 and history of chronic kidney disease were independent risk factors for COVID-19-related mortality among patients who received daratumumab-based therapy. This study suggested that multiple myeloma patients exposed to daratumumab were at a higher risk of adverse outcomes from COVID-19.

Pneumocystis jirovecii with high probability detected in bronchoalveolar lavage fluid of chemotherapy-related interstitial pneumonia in patients with lymphoma using metagenomic next-generation sequencing technology.

BACKGROUND: Previous studies achieved low microbial detection rates in lymphoma patients with interstitial pneumonia (IP) after chemotherapy. However, the metagenomic next-generation sequencing (mNGS) is a comprehensive approach that is expected to improve the pathogen identification rate. Thus far, reports on the use of mNGS in lymphoma patients with chemotherapy-related IP remain scarce. In this study, we summarized the microbial detection outcomes of lymphoma patients with chemotherapy-related IP through mNGS testing of bronchoalveolar lavage fluid (BALF). METHODS: Fifteen lymphoma patients with chemotherapy-related IP were tested for traditional laboratory microbiology, along with the mNGS of BALF. Then, the results of mNGS and traditional laboratory microbiology were compared. RESULTS: Of the 15 enrolled patients, 11 received rituximab and 8 were administered doxorubicin hydrochloride liposome. The overall microbial yield was 93.3% (14/15) for mNGS versus 13.3% (2/15) for traditional culture methods (P ≤ 0.05). The most frequently detected pathogens were Pneumocystis jirovecii (12/15, 80%), Cytomegalovirus (4/15, 26.7%), and Epstein-Barr virus (3/15, 20%). Mixed infections were detected in 10 cases. Five patients recovered after the treatment with antibiotics alone without glucocorticoids. CONCLUSION: Our findings obtained through mNGS testing of BALF suggested a high microbial detection rate in lymphoma patients with IP after chemotherapy. Notably, there was an especially high detection rate of Pneumocystis jirovecii. The application of mNGS in patients with chemotherapy-related IP was more sensitive.

Anatomical investigation of the pelvic urogenital fascia in 10 formalin-fixed female cadavers: novel insights into the laparoscopic total mesometrial resection.

PURPOSE: Previous anatomical studies of the urogenital fascia (UGF) have focused on males, and there is a lack of relevant anatomical studies on the distribution of the extraperitoneal UGF in females. METHODS: In this investigation, guided by the embryonic development of the female urogenital system, the ventral pelvic fascia structure of 10 female cadavers was dissected, and the distribution and morphology of female extraperitoneal UGF were observed, recorded in text, photographs and video, and 3D modeling was performed. RESULTS: We find that in the female extraperitoneal space there is a migratory fascial structure, the UGF, which surrounds the urogenital system and extends from the perinephric region to the pelvis along with the development of the urogenital organs. The two layers of the UGF are composed of loose connective tissue rich in fat that surrounds the urogenital organs, their accessory vascular structures, and the nerves of the abdominopelvic cavity. In the pelvis, it participates in the formation of the ligamentous structures around the rectum and uterus. Finally, it surrounds the bladder and gradually moves into the loose connective tissue of the medial umbilical fold. CONCLUSIONS: Sorting out the distribution characteristics of UGF has some reference value for studying the metastasis of gynecological tumors, the biomechanical structure of the female pelvis, and the surgical methods of gynecology, colorectal surgery, and hernia surgery.

Effect of intra-knee injection of autologous adipose stem cells or mesenchymal vascular components on short-term outcomes in patients with knee osteoarthritis: an updated meta-analysis of randomized controlled trials.

OBJECTIVE: Assess the efficacy of single and multiple intra-articular injections of autologous adipose-derived stem cells (ASCs) and adipose-derived stromal vascular fraction (ADSVF) for the treatment of knee osteoarthritis (OA). METHODS: We conducted a thorough and systematic search of several databases, including PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov, to identify relevant studies. The included studies were randomized controlled trials (RCTs) that involved single or multiple intra-articular injections of autologous ASCs or ADSVF for the treatment of patients with knee osteoarthritis, without any additional treatment, and compared to either placebo or hyaluronic acid. RESULTS: A total of seven RCTs were analyzed in this study. The results of the meta-analysis show that compared to the control group, both single and multiple intra-articular injections of ASCs or ADSVF demonstrated superior pain relief in the short term (Z = 3.10; P < 0.0001 and Z = 4.66; P < 0.00001) and significantly improved function (Z = 2.61; P < 0.009 and Z = 2.80; P = 0.005). Furthermore, MRI assessment showed a significant improvement in cartilage condition compared to the control group. (Z = 8.14; P < 0.000001 and Z = 5.58; P < 0.00001). CONCLUSIONS: In conclusion, in osteoarthritis of the knee, single or multiple intra-articular injections of autologous ASCs or ADSVF have shown significant pain improvement and safety in the short term in the absence of adjuvant therapy. Significant improvements in cartilage status were also shown. A larger sample size of randomized controlled trials is needed for direct comparison of the difference in effect between single and multiple injections.

Geoenvironmental properties of a Cr(VI)-contaminated soil treated by alkali-activated GGBS under freeze-thaw cycles: Insights into Cr species transformation and microscopic mechanism.

Stabilization/solidification is the most frequently used method for treating soils contaminated by heavy metals; however, degradation of the treatment will occur under freeze-thaw (F-T) cycles. In this paper, a low-carbon emission by-product, ground granulated blast furnace slag (GGBS), was adopted as a binder to treat Cr(VI)-contaminated soil after alkali excitation. Built on the usage scenarios of subgrade materials, the impact of F-T cycles and initial water content on the geoenvironmental properties of the treated soils, including leaching toxicity, unconfined compressive strength (UCS), pH, Eh, and permeability, were discussed. To investigate the mechanisms of the changing properties, this study analyzed the chemical morphology of Cr, the micromorphology of the reaction products, and the pore characteristics. The results demonstrated that negative impact of F-T cycles on treatment effectiveness was low at the optimal water content. After 28 F-T cycles, the Cr(VI) component increased by 6.4 %, and the leached Cr concentration showed a significant increase, especially for specimens with low water content. A new solid phase with mixed valence Mn(III/IV), mainly composed of birnessite and manganite, was observed via microscopic analysis. During the first 3 F-T cycles, the content of hydration gel increased by 0.18 %, and the cumulative pore volume decreased such that the UCS increased by an average of 1.2 MPa. This study demonstrated that a few F-T cycles would result in a secondary alkali-activated GGBS reaction, enhancing the treatment effect. However, additional F-T cycles would create an oxidizing environment under which the initially precipitated Cr(III) would react with manganese oxide, resulting in more Cr(VI) released. The degree of reoxidation was closely related to the initial water content of the solidified soil.

Hepatotoxic mechanism of cantharidin: insights and strategies for therapeutic intervention.

Cantharidin (CTD), a natural compound derived from Mylabris, is widely used in traditional Oriental medicine for its potent anticancer properties. However, its clinical application is restricted due to its high toxicity, particularly towards the liver. This review provides a concise understanding of the hepatotoxic mechanisms of CTD and highlights novel therapeutic strategies to mitigate its toxicity while enhancing its anticancer efficacy. We systematically explore the molecular mechanisms underlying CTD-induced hepatotoxicity, focusing on the involvement of apoptotic and autophagic processes in hepatocyte injury. We further discuss the endogenous and exogenous pathways implicated in CTD-induced liver damage and potential therapeutic targets. This review also summarizes the structural modifications of CTD derivatives and their impact on anticancer activity. Additionally, we delve into the advancements in nanoparticle-based drug delivery systems that hold promise in overcoming the limitations of CTD derivatives. By offering valuable insights into the hepatotoxic mechanisms of CTD and outlining potential avenues for future research, this review contributes to the ongoing efforts to develop safer and more effective CTD-based therapies.

Mining attention distribution paradigm: Discover gaze patterns and their association rules behind the visual image.

BACKGROUND AND OBJECTIVE: Attention allocation reflects the way of humans filtering and organizing the information. On one hand, different task scenarios seriously affect human's rule of attention distribution, on the other hand, visual attention reflecting the cognitive and psychological process. Most of the previous studies on visual attention allocation are based on cognitive models, predicted models, or statistical analysis of eye movement data or visual images, however, these methods are inadequate to provide an inside view of gaze behavior to reveal the attention distribution pattern within scenario context. Moreover, they seldom study the association rules of these patterns. Therefore, we adopted the big data mining approach to discover the paradigm of visual attention distribution. METHODS: We applied the data mining method to extract the gaze patterns to discover the regularities of attention distribution behavior within the scenario context. The proposed method consists of three components, tasks scenario segmented and clustered, gaze pattern mining, and association rule of frequent pattern mining. RESULTS: The proposed approach is tested on the operation platform. The complex operation task is simultaneously segmented and clustered with the TICC-based method and evaluated by the BCI index. The operator's eye movement frequent patterns and their association rule are discovered. The results demonstrate that our method can associate the eye-tracking data with the task-oriented scene data. DISCUSSION: The proposed method provides the benefits of being able to explicitly express and quantitatively analyze people's visual attention patterns. The proposed method can not only be applied in the field of aerospace medicine and aviation psychology, but also can likely be applied to computer-aided diagnosis and follow-up tool for neurological disease and cognitive impairment related disease, such as ADHD (Attention Deficit Hyperactivity Disorder), neglect syndrome, social attention differences in ASD (Autism spectrum disorder).

Towards pilot's situation awareness enhancement: A framework of adaptive interaction system and its realization.

Adaptive interaction system in flight control always aims to enhance the pilot's situation awareness (SA) to achieve human-in-the-loop control. Most adaptive interaction systems are always activated according to the pilot's current workload state. However, the pilot may already lose important information during a high workload, and thus the corresponding reaction of the adaptive interaction system would lag. Moreover, most adaptive interaction systems adopt the expert's knowledge as a reference to generate information. Still, the tacit knowledge that reveals the information interrelationship is seldom studied, despite being the foundation of the interactive information display. To solve the above problems, we proposed an adaptive interaction system architecture with three subsystems. Firstly, we developed a workload level prediction subsystem, where physiological parameters are used to predict future workload levels, thus avoiding interaction system lag; Secondly, we developed a tacit expert knowledge mining subsystem to discover the interrelationship hidden in the expert's perceived information, which will guide the interactive information interface. Thirdly, we developed a tips information inference subsystem to provide the lost SA information based on expert knowledge and the pilot's online perceived information. The effectiveness of the proposed system is verified via a comparative experiment utilizing the control interface of a remotely piloted aircraft.

Towards tacit knowledge mining within context: Visual cognitive graph model and eye movement image interpretation.

Visual attention is one of the most important brain cognitive functions, which filters the rich information of the outside world to ensure the efficient operation of limited cognitive resources. The underlying knowledge, i.e., tacit knowledge, hidden in the human attention allocation performances, is context-related and is hard to be expressed by experts, but it is essential for novice operator training and interaction system design. Traditional models of visual attention allocation and corresponding analysis methods seldomly involve task contextual information or present the tacit knowledge in an explicit and quantified way. Thus, it is challenging to pass on the expert's tacit knowledge to the novice or utilize it to construct an interaction system by employing traditional methods. Therefore, this paper first proposes a new model called the visual cognitive graph model based on graph theory to model the visual attention allocation associated with the task context. Then, based on this graph model, utilize the data mining method to reveal attention patterns within context to quantitatively analyze the operator's tacit knowledge during operation tasks. We introduced three physical quantities derived from graph theory to describe the tacit knowledge, which can be used directly to construct an interaction system or operator training. For example, discover the essential information within the task context, the relevant information affecting critical information, and the bridge information revealing the decision-making process. We tested the proposed method in the example of flight operation, the comparison results with the traditional eye movement graph model demonstrate that the proposed visual cognitive model can compromise the task context. The comparison results with the statistical analysis method demonstrate that our tacit knowledge mining method can reveal the underlying knowledge hidden in the visual information. Finally, we give practical applications in the examples of operator training guidance and adaptive interaction system. Our proposed method can explore more in-depth knowledge of visual information, such as the correlations of different obtained information and the way operator obtains information, most of which are even not noticed by operators themselves.

LINC00536 knockdown inhibits breast cancer cells proliferation, invasion, and migration through regulation of the miR-4282/centromere protein F axis.

Breast cancer (BC) poses a huge threat to women's health. Growing evidence has shown lncRNAs play critical roles in BC progression. However, the effect of LINC00536 in BC remains unknown. LINC00536, miR-4282, and centromere protein F (CENPF) expressions in BC cells were determined using qPCR assay. Colony formation assay was employed to evaluate the cell proliferation of BC cells. Besides, cell migration and invasion were evaluated using the transwell assay. FISH assay was employed to analyze LINC00536 and miR-4282 locations in BC cells. Additionally, dual luciferase reporter gene assay was performed to verify the binding relationships between LINC00536 and miR-4282, miR-4282 and CENPF. Here, our results displayed that LINC00536 and CENPF were overexpressed in BC cells, while miR-4282 was downregulated. LINC00536 could negatively regulate miR-4282 expression via directly binding to miR-4282. LINC00536 silence suppressed the proliferation, migration, and invasion of BC cells, which was abolished by miR-4282 inhibition. Additionally, miR-4282 could negatively regulate CENPF expression via directly binding to CENPF. MiR-4282 overexpression suppressed BC development, which was abolished by CENPF overexpression. Finally, we proved that LINC00536 silencing suppressed BC growth via regulating the miR-4282/CENPF axis in vivo. Our research displayed that LINC00536 acted as an oncogene in BC. LINC00536-enhanced BC cell proliferation, migration, and invasion. Moreover, LINC00536 functioned as a ceRNA to exert malignant characteristics in BC via the miR-4282-CENPF axis. Collectively, our results demonstrated that the LINC00536-miR-4282-CENPF axis was a critical player in BC development and was a promising target for BC therapy.

Reduction, stabilization, and solidification of Cr(VI) in contaminated soils with a sustainable by-product-based binder.

This study evaluated the use of a sustainable GFD binder for the stabilization/solidification (S/S) of chromium VI (Cr(VI))-contaminated soil. The GFD binder was composed of ground granulated blast furnace slag (GGBFS), fly ash and desulfurization ash, named after the initials of the three materials. The effects of curing time and binder dosage on soil unconfined compressive strength (UCS), Cr leachability, soil pH, and reduction ratio of Cr (VI) were tested. The immobilization mechanisms of Cr(VI) in contaminated soil were further explored using X-ray diffraction (XRD), scanning electron microscopy (SEM), and sequential extraction procedure (SEP). The results showed that the UCS and pH of the soil increased substantially after the GFD binder was added. After 28 days of curing with a 20% binder dosage, the leached total Cr concentration decreased from 34.4 mg/L in the contaminated soil to 1.44 mg/L in the treated soil, and the leached Cr(VI) concentration decreased from 28.0 mg/L to 0.45 mg/L. A Cr(VI) reduction ratio of 96.2% was achieved, indicating the strong reducibility of GGBFS. XRD revealed that the main hydration products of the GFD binder were hydrated calcium silicate (C-S-H) and ettringite. SEM results showed that the formation of hydration products and Cr-bearing precipitates filled the soil pores, resulting in a dense soil structure. The SEP results demonstrated that the levels of the unstable fraction F1 decreased considerably, and that the levels of the stable fractions F3 and F5 increased after treatment. Encapsulation by C-S-H, reduction by sulfides, adsorption of C-S-H, and precipitation of Cr-bearing hydroxides were the main mechanisms involved in Cr immobilization using the GFD binder.

Long noncoding RNA HCP5 promotes osteosarcoma cell proliferation, invasion, and migration via the miR-29b-3p-LOXL2 axis.

Osteosarcoma (OS) is the second most common primary malignant bone tumors in adolescents that causes cancer-related deaths. Previous studies have confirmed the promoting role of lncRNA HCP5 in the development of OS, but the specific mechanism is still not well understood. MiRNA levels were measured via RT-qPCR and protein expression was detected via western blotting. Cell proliferation was analyzed by CCK-8 assays and colony formations assay were conducted to measure colony formation ability. Dual-luciferase reporter assay was performed to detect the targeting relationship between HCP5 and miR-29b-3p, and between miR-29b-3p and LOXL2. Wound healing assays and Transwell assays were conducted to verify the migration and invasion abilities of OS cells. Correlations between the levels of HCP5 and miR-29b-3p, and between miR-29b-3p and LOXL2 were determined by Pearson correlation coefficient analysis. MiR-29b-3p expression was decreased and HCP5 and LOXL2 levels were increased in OS tissues and cell lines. MiR-29b-3p could directly act on LOXL2 and knockdown of LOXL2 restrained the proliferation, migration, and invasion of OS cells. Moreover, transfection with sh-HCP5-1 and sh-HCP5-2 suppressed the malignant biological behavior of OS cells. HCP5 directly targeted miR-29b-3p, and promoted OS proliferation, migration, and invasion via the miR-29b-3p/LOXL2 axis. The lncRNA HCP5 may upregulate LOXL2 expression by targeting miR-29b-3p, thereby promoting OS proliferation, migration, and invasion.

Fibroblasts Drive Metabolic Reprogramming in Pacemaker Cardiomyocytes.

BACKGROUND: The sino atrial node (SAN) is characterized by the microenvironment of pacemaker cardiomyocytes (PCs) encased with fibroblasts. An altered microenvironment leads to rhythm failure. Operable cell or tissue models are either generally lacking or difficult to handle. The biological process behind the milieu of SANs to evoke pacemaker rhythm is unknown. We explored how fibroblasts interact with PCs and regulate metabolic reprogramming and rhythmic activity in the SAN. METHODS: Tbx18 (T-box transcription factor 18)-induced PCs and fibroblasts were used for cocultures and engineered tissues, which were used as the in vitro models to explore how fibroblasts regulate the functional integrity of SANs. RNA-sequencing, metabolomics, and cellular and molecular techniques were applied to characterize the molecular signals underlying metabolic reprogramming and identify its critical regulators. These pathways were further validated in vivo in rodents and induced human pluripotent stem cell-derived cardiomyocytes. RESULTS: We observed that rhythmicity in Tbx18-induced PCs was regulated by aerobic glycolysis. Fibroblasts critically activated metabolic reprogramming and aerobic glycolysis within PCs, and, therefore, regulated pacemaker activity in PCs. The metabolic reprogramming was attributed to the exclusive induction of Aldoc (aldolase c) within PCs after fibroblast-PC integration. Fibroblasts activated the integrin-dependent mitogen-activated protein kinase-E2F1 signal through cell-cell contact and turned on Aldoc expression in PCs. Interruption of fibroblast-PC interaction or Aldoc knockdown nullified electrical activity. Engineered Tbx18-PC tissue sheets were generated to recapitulate the microenvironment within SANs. Aldoc-driven rhythmic machinery could be replicated within tissue sheets. Similar machinery was faithfully validated in de novo PCs of adult mice and rats, and in human PCs derived from induced pluripotent stem cells. CONCLUSIONS: Fibroblasts drive Aldoc-mediated metabolic reprogramming and rhythmic regulation in SANs. This work details the cellular machinery behind the complex milieu of vertebrate SANs and opens a new direction for future therapy.

Performance Index Based on Predicted Auditory Reaction Time Analysis for the Evaluation of Human-Machine Interface in Flight Control.

With the rapid development of complex equipment, such as airplanes, the appropriate design of the human-machine interface is often upgraded, thus emerged many methods to evaluate whether such an upgrade is effective. Most researches focus on the time accumulation effect of the human state during the interaction to evaluate the interface. However, in the aviation application, the performance of the pilot's instantaneous reactions also reveals the design efficiency of the interface, since the difficulty level of obtaining the useful information would severely influence the reaction time in some voice command tasks or emergency situations. Besides, there are so many flight scenarios that are impossible to be simulated in experiments or in a laboratory environment. Also, voice commands are too numerous to be traversed simulated. This paper introduced predicted auditory reaction time as an index to evaluate human-machine interface design. The proposed method has two advantages. On the one hand, it effectively measures the pilot's auditory reaction time based on the eye movement tracking; thus, the data can be taken in flight task scenarios, and the experiment would not cause interference to the subjects. On the other hand, a prediction model is proposed, in which the pilot's reaction time under more generalized voice command can be estimated based on a small-size sample set.

The Effect of Carbon Emission Taxes on Environmental and Economic Systems.

Carbon dioxide is believed widely to be the major contributor to global warming. Policymakers worldwide are turning to tax policies in an effort to abate carbon emissions. China is the largest emitter of carbon emissions on our planet. The central government, as well as the local official, has introduced a series of environmental regulations, such as environmental protection tax and emissions trading system, to reduce carbon emissions and improve environmental quality. In the near future, the carbon emission tax is also expected to be implemented by the Chinese government. In order to analyze and predict the effect of the carbon emission tax on environmental and economic systems, we developed a four department dynamic stochastic general equilibrium model, which includes households, enterprises, the government, and the environment. The dynamic parameters were obtained using maximum likelihood estimation. In the comparative static-s analysis, we found that after the introduction of carbon emission tax, the level in environmental quality was substantially improved, whereas most economic variables were significantly reduced. Moreover, we used impulse responses functions to evaluate how one shock to the carbon emission tax affects the steady static values for these endogenous variables in our model. We found that the carbon emission tax shock has an instantaneous effect on the majority of economic variables, but it does not affect the environmental quality immediately. In addition, we tested the Porter hypothesis and found no evidence suggesting the statement regarding this hypothesis. Finally, we applied Bayesian estimation to assure our findings in this study, again.

Biomaterial-induced conversion of quiescent cardiomyocytes into pacemaker cells in rats.

Pacemaker cells can be differentiated from stem cells or transdifferentiated from quiescent mature cardiac cells via genetic manipulation. Here we show that the exposure of rat quiescent ventricular cardiomyocytes to a silk-fibroin hydrogel activates the direct conversion of the quiescent cardiomyocytes to pacemaker cardiomyocytes by inducing the ectopic expression of the vascular endothelial cell-adhesion glycoprotein cadherin. The silk-fibroin-induced pacemaker cells exhibited functional and morphological features of genuine sinoatrial-node cardiomyocytes in vitro, and pacemaker cells generated via the injection of silk fibroin in the left ventricles of rats functioned as a surrogate in situ sinoatrial node. Biomaterials with suitable surface structure, mechanics and biochemistry could facilitate the scalable production of biological pacemakers for human use.