FLT3-Selective PROTAC: Enhanced Safety and Increased Synergy with Venetoclax in FLT3-ITD Mutated Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) patients carrying Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutations often face a poor prognosis. While some FLT3 inhibitors have been used clinically, challenges such as short efficacy and poor specificity persist. Proteolytic targeting chimera (PROTAC), with its lower ligand affinity requirement for target proteins, offers higher and rapid targeting capability. Gilteritinib, used as the ligand for the target protein, was connected with different E3 ligase ligands to synthesize several series of PROTAC targeting FLT3-ITD. Through screening and structural optimization, the optimal lead compound PROTAC Z29 showed better specificity than Gilteritinib. Z29 induced FLT3 degradation through the proteasome pathway and inhibited tumor growth in subcutaneous xenograft mice. We verified Z29's minimal impact on platelets in a patient-derived xenografts (PDX) model compared to Gilteritinib. The combination of Z29 and Venetoclax showed better anti-tumor effects, lower platelet toxicity, and lower hepatic toxicity in FLT3-ITD+ models. The FLT3-selective PROTAC can mitigate the platelet toxicity of small molecule inhibitors, ensuring safety and efficacy in monotherapy and combination therapy with Venetoclax. It is a promising strategy for FLT3-ITD+ patients, especially those with platelet deficiency or liver damage.

Development of a risk assessment model for cardiac injury in patients newly diagnosed with acute myeloid leukemia based on a multicenter, real-world analysis in China.

BACKGROUND: Studies have revealed that acute myeloid leukemia (AML) patients are prone to combined cardiac injury. We aimed to identify hematological risk factors associated with cardiac injury in newly diagnosed AML patients before chemotherapy and develop a personalized predictive model. METHODS: The population baseline, blood test, electrocardiogram, echocardiograph, and genetic and cytogenetic data were collected from newly diagnosed AML patients. The data were subdivided into training and validation cohorts. The independent risk factors were explored by univariate and multivariate logistic regression analysis respectively, and data dimension reduction and variable selection were performed using the least absolute shrinkage and selection operator (LASSO) regression models. The nomogram was generated and the reliability and generalizability were verified by receiver operating characteristic (ROC) curves, the area under the curve (AUC) and calibration curves in an external validation cohort. RESULTS: Finally, 499 AML patients were included. After univariate logistic regression, LASSO regression and multivariate logistic regression analysis, abnormal NT-proBNP, NPM1 mutation, WBC, and RBC were independent risk factors for cardiac injury in AML patients (all P < 0.05). The nomogram was constructed based on the above four variables with high accuracy. The area under the curve was 0.742, 0.750, and 0.706 in the training, internal validation, and external validation cohort, respectively. The calibration curve indicated that the model has good testing capability. The Kaplan-Meier curve showed that the higher the risk of combined cardiac injury in AML patients, the lower their probability of survival. CONCLUSIONS: This prediction nomogram identifies hematological risk factors associated with cardiac injury in newly diagnosed AML patients and can help hematologists identify the risk and provide precise treatment options.

Development of the Panic Response Scale and the Predicting Factors of Panic Response During the COVID-19 Pandemic.

Introduction: During emergencies, individuals and communities often react in a variety of ways, including panic response. However, the study of panic response is limited due to narrow assessment tools that measure only one or two dimensions of human response (eg, physiology, cognition, emotion, and behavior). To address this limitation and to explore the risk and protective factors of panic response during the global spread of the Coronavirus Disease 2019 (COVID-19), the current study developed and evaluated the Panic Response Scale (PRS). Methods: Four samples were recruited for the following purposes: interview analysis (n = 26); item analysis and exploratory factor analysis (n = 604); confirmatory factor analysis and reliability analysis (n = 603); and retest reliability, validity analysis, and regression analysis (n = 349). Results: The PRS consists of 21 items with four subscales: Physical Discomfort, Anxious Fluster, Sensitive Depression, and Excessive Prevention. Each of these subscales demonstrated good internal consistency (rs > 0.73), test-retest reliability (rs > 0.77), criterion validity (r = 0.69, p < 0.01), and convergent validity (rs = 0.31-0.65, p < 0.01). Regression analysis revealed significant predicting effects of COVID-19 knowledge and neuroticism on panic response. Additionally, cognitive reappraisal moderated the association between neuroticism and panic response. Discussion: Following a traumatic event, the PRS offers a potential tool for identifying individuals in need of mental health services. Moreover, during the COVID-19 pandemic, knowledge and neuroticism served as risk factors for heightened panic response, while cognitive reappraisal served as a protective factor for coping with panic response.

Comprehensive analysis of clinical prognostic features and tumor microenvironment landscape of CD11b+CD64+ patients with acute myeloid leukemia.

BACKGROUND: Immunophenotyping surface molecules detected in the clinic are mainly applied in diagnostic confirmation and subtyping. However, the immunomodulatory molecules CD11b and CD64, are highly associated with leukemogenesis. Hence, the prognostic value of them and their potential biological functions merit further investigation. METHODS: Flow cytometry was operated to detect immunophenotypic molecules from AML bone marrow samples. Multivariate cox regression, Kaplan-Meier analyses, and nomogram were conducted to predict survival. Transcriptomic data, lymphocyte subsets, and immunohistochemical staining were incorporated to identify potential biological functions of prognostic immunophenotype in acute myeloid leukemia (AML). RESULTS: We classified 315 newly diagnosed AML patients of our center based on the expression of CD11b and CD64. The CD11b+CD64+ populations were identified as independent risk factors for overall survival and event-free survival of AML, exhibiting specific clinicopathological features. The predictive models based on CD11b+CD64+ showed high classification performance. In addition, the CD11b+CD64+ subset, characterized by high inhibitory immune checkpoints, M2-macrophage infiltration, low anti-tumor effector cells infiltration, as well as abnormal somatic mutation landscape, presented a distinctive tumor microenvironmental landscape. The CD11b+CD64+ population showd a higher expression of BCL2, and the drug sensitivity indicated that they presented a lower half-maximal inhibitory concentration value for BCL2 inhibitor, and could benefit more from the above medicine. CONCLUSIONS: This work might be of benefit to enhanced understanding of CD11b+CD64+ in the prognosis and leukemogenesis, and yielded novel biomarkers to guide immunotherapy and targeted therapy for AML.

Subsidy or not? How much government subsidy can improve performance level of energy-saving service company?

Contract energy management model is a new energy-saving mode based on single market mechanism. Due to its externality, the energy efficiency market cannot realize the optimal allocation of resources. Government energy-saving subsidy can solve the market failure of energy-saving service market and improve the performance level of energy-saving service company. However, due to the unbalanced support fields and single incentive tools in the government incentive policy, the incentive effect of the government subsidy policies for contract energy management projects is not satisfactory. Based on a two-stage dynamic decision-making model, this article analyzes the impact of different forms of government subsidy policies on the performance-level decision-making of energy service company, and draws the following conclusions: (1) The effect of the government's variable subsidy policy with payment conditions is better than the fixed subsidy policy without payment conditions. (2) Government incentive policy for contract energy management needs to be directed against different energy-saving fields. (3) The government should adopt different forms of incentive policies for energy-saving service companies with different energy-saving levels in the same energy-saving field. (4) When the government implements the variable subsidy policy with preset energy-saving target, each within a reasonable range, with the increase of which, the incentive effect on energy-saving service companies with lower energy-saving level decreases. When the subsidy policy has no incentive effect, it is more unfavorable for the energy-saving service companies which are below the average level of the industry.

Intergenerational effects of childhood maltreatment: The relationships among parental childhood emotional neglect, emotional expressiveness and children's problem behaviors.

BACKGROUND: Childhood maltreatment has a severe impact on both the health and parenting styles of abused individuals in adulthood, and it even has a negative impact on the offspring of abused individuals. Although studies have confirmed the intergenerational effects of childhood maltreatment, relatively few have emphasized emotional neglect and its mechanism of intergenerational effects. Additionally, few studies have examined the unique role of fathers and how mothers and fathers interact with one another. OBJECTIVE: The current study aimed to employ the actor-partner interdependence mediation model to investigate the relationship between parental childhood emotional neglect and children's problem behaviors, as well as whether parents' positive and negative emotional expressiveness plays a mediating role. METHODS, PARTICIPANTS, AND SETTING: In total, 397 dyads of mothers and fathers of children aged 6-9 were recruited and reported their childhood emotional neglect experience and emotional expressiveness, and mothers also rated their children's problem behaviors. RESULTS: The findings revealed that (a) maternal childhood emotional neglect was associated solely with mothers' own negative emotional expressiveness, followed by their children's problem behavior and (b) paternal childhood emotional neglect showed no effect on children's problem behavior through fathers' own or their spouses' positive and negative emotional expressiveness. CONCLUSIONS: The findings of this study suggest that childhood emotional neglect has intergenerational effects and that mothers' parenting behaviors are relatively important in preventing adverse effects on their children.

Identification and validation of immunohistochemical marker panels to predict the prognosis of muscle invasive bladder cancer.

Background: Currently, the treatment regimen of bladder cancer depends on the stage and grade. Yet, patients with similar histopathological characteristics may have distinct prognosis. Luminal/basal subtyping had proved to be a satisfactory subtyping method. Here we intended to evaluate immunohistochemistry, a more clinically-practical method, in luminal/basal classification and further risk-stratification. Methods: Patients diagnosed with urothelial carcinoma of the bladder in Changhai Hospital were retrospectively recruited and corresponding formalin-fixed paraffin embedded blocks were acquired. Tissue microarrays (TMAs) of these patients were established followed by immunohistochemical (IHC) staining of 14 markers. Patients were classified into luminal or basal subtype according to CK5/6, CK14, CK20 and GATA3 expression. Further subtyping of luminal and basal tumors was performed according to the expression of other markers. Results: A total of 236 patients were included: 163 and 73 patients were assigned to training and validation cohorts, respectively. Patients with basal tumor were related with poorer prognosis compared to those with luminal tumor (P=0.025 and 0.008 in training and validation cohorts, respectively). We further revealed luminal muscle invasive bladder cancer (MIBC) patients could be further categorized into subgroups with different risks. Cytoplasmic YAP1 and CCNB1 were selected as classifier, patients with low expression of cytoplasmic YAP1 or CCNB1 were independent risk factor for poorer prognosis (hazard ratio =2.19, P=0.04). Conclusions: Molecular subtyping into luminal/basal subtype and risk stratification method using a 2-marker method by immunohistochemistry can be an economical, clinically practical method to predict patient prognosis and could help to develop treatment strategy and follow-up schedule in clinical practice.

The Double-Edged Impact of the COVID-19 Pandemic on Chinese Family Relationships.

To comprehensively understand the Chinese family relationships (i.e., marital relationship, parent-child relationship, sibling relationship, and grandparent-grandchild relationship) during the COVID-19 pandemic, this study investigated the changes of family relationships and the individual differences related to knowledge of the COVID-19, personality traits (i.e., neuroticism and optimism), and emotional characteristics (i.e., emotion regulation and negative emotional reactions). From March 1 to April 5, 2020, 8821 participants were involved, including 3995 teenagers, 1146 unmarried young adults, 3571 married adults, and 109 grandparents. Results revealed a double-edged pattern that people experienced both positive changes and negative changes during the pandemic. Teenagers reported significant negative changes in the relationships with their parents. Peoples' knowledge of the COVID-19, neuroticism, optimism, emotion regulation, and negative emotional reactions were in varying extents to which accounted for the individual differences in the changes of family relationships. These findings help recognize the overall Chinese family relationships during the hard period.

dSTORM-Based Single-Cell Protein Quantitative Analysis Can Effectively Evaluate the Degradation Ability of PROTACs.

As an emerging therapeutic strategy, proteolysis-targeting chimeras (PROTACs) have been proven to be superior to traditional drugs in many aspects. However, due to their unique mechanism of action, existing methods for evaluating the degradation still have many limitations, which seriously restricts the development of PROTACs. In this methodological study, using direct stochastic optical reconstruction microscopy (dSTORM)-based single-cell protein quantitative analysis, we systematically investigated the dynamic degradation characteristics of FLT3 protein during PROTACs treatment. We found that the distribution of FLT3 varies between FLT3-ITD mutation and FLT3-WT cells. PROTACs had an obvious time-course effect on protein degradation and present two distinct phases; this provided a basis for deciding when to evaluate protein degradation. High concentrations of PROTACs were more effective than long-time administration because a higher Dmax was achieved. Two-color dSTORM-based colocalization analysis efficiently detected the proportion of ternary complexes, making it very useful in screening PROTACs. Taken together, our findings show that the dSTORM method is an ideal tool for evaluating PROTACs and will accelerate the development of new PROTACs.

The effect of short-form video addiction on undergraduates' academic procrastination: a moderated mediation model.

Background: Short-form videos have become one of the most popular ways for people to entertain and relax. However, the intense interest in short-form videos has given rise to short-video addiction, which poses risks to both physical and mental health of individuals. Undergraduates are one of the important users for short-form videos, and the influence of short-form video addiction calls for more attention. This study aimed to investigate the association between short-form video addiction and academic procrastination among undergraduates, exploring the role of executive functions (i.e., attentional control) and personality traits (i.e., boredom proneness) in the association. Methods: Using stratified random cluster sampling method, the data of 1,047 college students were used in the study. All variables were measured by empirical instruments, and all instruments were highly reliable. Mediation and moderation analysis was conducted using Model 4 and 7 in PROCESS macro powered by SPSS. Results: Results revealed that short-form video addiction not only directly impacted academic procrastination but also placed indirect effect on academic procrastination through attentional control. Furthermore, the mediating effect of attentional control was contingent upon individuals' boredom proneness. Higher levels of boredom proneness weakened the impact of short-form video addiction on attentional control. Conclusion: The findings expand our knowledge of the negative effects of short-form video addiction and the underlying mechanisms, providing implications for mitigating undergraduates' academic procrastination.

Reaction N(2D) + CH2CCH2 (Allene): An Experimental and Theoretical Investigation and Implications for the Photochemical Models of Titan.

We report on a combined experimental and theoretical investigation of the N(2D) + CH2CCH2 (allene) reaction of relevance in the atmospheric chemistry of Titan. Experimentally, the reaction was investigated (i) under single-collision conditions by the crossed molecular beams (CMB) scattering method with mass spectrometric detection and time-of-flight analysis at the collision energy (E c) of 33 kJ/mol to determine the primary products and the reaction micromechanism and (ii) in a continuous supersonic flow reactor to determine the rate constant as a function of temperature from 50 to 296 K. Theoretically, electronic structure calculations of the doublet C3H4N potential energy surface (PES) were performed to assist the interpretation of the experimental results and characterize the overall reaction mechanism. The reaction is found to proceed via barrierless addition of N(2D) to one of the two equivalent carbon-carbon double bonds of CH2CCH2, followed by the formation of several cyclic and linear isomeric C3H4N intermediates that can undergo unimolecular decomposition to bimolecular products with elimination of H, CH3, HCN, HNC, and CN. The kinetic experiments confirm the barrierless nature of the reaction through the measurement of rate constants close to the gas-kinetic rate at all temperatures. Statistical estimates of product branching fractions (BFs) on the theoretical PES were carried out under the conditions of the CMB experiments at room temperature and at temperatures (94 and 175 K) relevant for Titan. Up to 14 competing product channels were statistically predicted with the main ones at E c = 33 kJ/mol being formation of cyclic-CH2C(N)CH + H (BF = 87.0%) followed by CHCCHNH + H (BF = 10.5%) and CH2CCNH + H (BF = 1.4%) the other 11 possible channels being negligible (BFs ranging from 0 to 0.5%). BFs under the other conditions are essentially unchanged. Experimental dynamical information could only be obtained on the overall H-displacement channel, while other possible channels could not be confirmed within the sensitivity of the method. This is also in line with theoretical predictions as the other possible channels are predicted to be negligible, including the HCN/HNC + C2H3 (vinyl) channels (overall BF < 1%). The dynamics and product distributions are dramatically different with respect to those observed in the isomeric reaction N(2D) + CH3CCH (propyne), where at a similar E c the main product channels are CH2NH (methanimine) + C2H (BF = 41%), c-C(N)CH + CH3 (BF = 32%), and CH2CHCN (vinyl cyanide) + H (BF = 12%). Rate coefficients (the recommended value is 1.7 (±0.2) × 10-10 cm3 s-1 over the 50-300 K range) and BFs have been used in a photochemical model of Titan's atmosphere to simulate the effect of the title reaction on the species abundance (including any new products formed) as a function of the altitude.

The N(2D) + CH2CHCN (Vinyl Cyanide) Reaction: A Combined Crossed Molecular Beam and Theoretical Study and Implications for the Atmosphere of Titan.

The reaction of electronically excited nitrogen atoms, N(2D), with vinyl cyanide, CH2CHCN, has been investigated under single-collision conditions by the crossed molecular beam (CMB) scattering method with mass spectrometric detection and time-of-flight (TOF) analysis at the collision energy, Ec, of 31.4 kJ/mol. Synergistic electronic structure calculations of the doublet potential energy surface (PES) have been performed to assist in the interpretation of the experimental results and characterize the overall reaction micromechanism. Statistical (Rice-Ramsperger-Kassel-Marcus, RRKM) calculations of product branching fractions (BFs) on the theoretical PES have been carried out at different values of temperature, including the one corresponding to the temperature (175 K) of Titan's stratosphere and at a total energy corresponding to the Ec of the CMB experiment. According to our theoretical calculations, the reaction is found to proceed via barrierless addition of N(2D) to the carbon-carbon double bond of CH2═CH-CN, followed by the formation of cyclic and linear intermediates that can undergo H, CN, and HCN elimination. In competition, the N(2D) addition to the CN group is also possible via a submerged barrier, leading ultimately to N2 + C3H3 formation, the most exothermic of all possible channels. Product angular and TOF distributions have been recorded for the H-displacement channels leading to the formation of a variety of possible C3H2N2 isomeric products. Experimentally, no evidence of CN, HCN, and N2 forming channels was observed. These findings were corroborated by the theory, which predicts a variety of competing product channels, following N(2D) addition to the double bond, with the main ones, at Ec = 31.4 kJ/mol, being six isomeric H forming channels: c-CH(N)CHCN + H (BF = 35.0%), c-CHNCHCN + H (BF = 28.1%), CH2NCCN + H (BF = 26.3%), c-CH2(N)CCN(cyano-azirine) + H (BF = 7.4%), trans-HNCCHCN + H (BF = 1.6%), and cis-HNCCHCN + H (BF = 1.3%), while C-C bond breaking channels leading to c-CH2(N)CH(2H-azirine) + CN and c-CH2(N)C + HCN are predicted to be negligible (0.02% and 0.2%, respectively). The highly exothermic N2 + CH2CCH (propargyl) channel is also predicted to be negligible because of the very high isomerization barrier from the initial addition intermediate to the precursor intermediate able to lead to products. The predicted product BFs are found to have, in general, a very weak energy dependence. The above cyclic and linear products containing an additional C-N bond could be potential precursors of more complex, N-rich organic molecules that contribute to the formation of the aerosols on Titan's upper atmosphere. Overall, the results are expected to have a significant impact on the gas-phase chemistry of Titan's atmosphere and should be properly included in the photochemical models.

Observation of Competitive Nonadiabatic Photodissociation Dynamics of H2S+ Cations.

A comprehensive understanding of dissociation mechanisms is of fundamental importance in the photochemistry of small molecules. Here, we investigated the detailed photodissociation dynamics of H2S+ near 337 nm by using the velocity map ion imaging technique together with the theoretical characterizations by developing global full-dimensional potential energy surfaces (PESs). Rotational state resolved images were acquired for the S+(4S) + H2 product channel. Significant changes in product total kinetic energy release distributions and angular distributions have been observed within a small excitation photon energy range of 5 wavenumbers. Analysis based on the full-dimensional PESs reveals that two nonadiabatic pathways determined by the transition state connecting two minima on the 12A' state are responsible for the dramatic variation of observed product distributions. The current study has directly witnessed the competitive photodissociation mechanisms controlled by a critical energy point on the PES, thereby providing in-depth insight into the nonadiabatic dynamics in photochemistry.

Crossed Molecular Beam Study of the H + HD → H2 + D Reaction at 0.60 and 1.26 eV Using the Near-Threshold Ionization Velocity Map Ion Imaging.

By using the 1 + 1' near-threshold ionization velocity map ion imaging technique, state-to-state reactive differential cross sections have been measured for the H + HD → H2 + D reaction. High-resolution images of the D products, with the rotational states of the H2 co-products clearly resolved, were acquired at the collision energies of 0.60 and 1.26 eV, respectively. It is found that the angular distribution is predominantly backward-scattering at the collision energy of 0.60 eV. However, at 1.26 eV, where the collision energy is higher, the angular distribution becomes forward-backward-scattering. Notably, at both collision energies, the main peaks of backward-scattered products gradually shift from backward toward sideways direction as the rotational quantum number of H2 increases. Moreover, in the forward direction, fast angular oscillations, which are induced by specific partial waves have also been observed at 1.26 eV. These features show a strong correlation between the product states and angular distributions and also indicate the unique role of partial waves in quantum reactive scattering.

Preparation of Y2O3/TiO2-Loaded Polyester Fabric and Its Photocatalytic Properties under Visible Light Irradiation.

In this study, Y2O3/TiO2-loaded polyester fabric was prepared to improve the catalytic activity of the TiO2 and to increase its reuse efficiency. The samples were systematically characterized by scanning electron microscopy (SEM), X-ray diffractometry (XRD), X-ray photoelectron spectroscopy (XPS), and infrared spectroscopy (FT-IR). Furthermore, the degradation performance of methyl orange in the presence of simulated visible light irradiation was also investigated. The results showed that the TiO2 in the Y2O3/TiO2 composite photocatalyst was suitably anatase. In addition, Y2O3/TiO2-loaded polyester fabric had higher photocatalytic performance than that of pure polyester fabric under visible light and the degradation rate reached 83% after 120 min of light exposure but remained above 50% after repeated exposure (three times). Compared to the pure polyester fabric, Y2O3/TiO2-loaded polyester fabric had self-cleaning effects in methyl blue and soy sauce solutions under visible light.

Cardiac-Related Lesions in Newly Diagnosed Patients With Acute Leukemia: A Chinese Population-Based Real-World Study.

The relationship between newly diagnosed acute leukemia (AL) and heart-related lesions remains unclear. This study aimed to investigate baseline cardiac function and risk of cardiovascular diseases (CVDs) in patients with new-onset AL, and provide data on cardiac management strategies for patients with AL. We retrospectively collected data on baseline characteristics, echocardiography, and biochemical blood indicators (e.g., myocardial enzymes) from 408 patients, 200 with newly diagnosed AL, 103 with coronary artery disease (CAD), and 105 controls from January 1, 2015 to August 31, 2019. The creatine kinase isoenzyme myocardial band, lactate dehydrogenase, highly sensitive troponin-I, and B-type natriuretic peptide levels and left ventricular internal diameter (LVID) were significantly higher in patients with newly diagnosed AL than in the control group. The degree of cardiac damage was lower in newly diagnosed AL patients than in CAD patients. The best predictor of heart damage was LVID (AUC [area under the curve] = 0.709; 95% CI [confidence interval]: 0.637-0.781; p < 0.001), and independent prognostic risk factors were age and ejection fraction (HR [hazard ratio] = 1.636; 95% CI: 1.039-2.575; p = 0.033). The ratio of leukemia blasts among patients with AL was positively correlated with cardiac damage. Our data indicated that newly diagnosed AL patients had certain myocardial damage before treatment. Clinicians need to pay attention to these manifestations, which may be related to the prognosis.

The empathy questionnaire for children and adolescents (EmQue-CA) in Chinese: Psychometric properties and measurement invariance.

The current study aimed to evaluate the reliability and validity of the Chinese version of the EmQue-CA, as well as the measurement invariance across gender. A sample of 1107 students (498 boys and 609 girls) enrolled in fourth grade to twelfth grade (Mage = 13.29; SD = 2.22) participated in the current study. Results indicated that the Chinese version had a similar three-factor model with two items deleted from the original form. The reliability, including internal consistency and test-retest reliability, of the Chinese version of the EmQue-CA was acceptable. Concurrent validity was assessed by examining the correlations of the EmQue-CA with the Basic Empathy Scale and the prosocial behavior subscale of the Strengths and Difficulties Questionnaire, with significant associations delivered. The results of convergent validity demonstrated strong correlations of the EmQue-CA subscales with callous unemotional traits and bullying. For the measurement invariance across gender, configural invariance and metric invariance were supported by the data, while scalar invariance failed. Overall, the EmQue-CA is a valuable tool for assessing empathy in Chinese children and adolescents.

Icariin, Formononetin and Caffeic Acid Phenethyl Ester Inhibit Feline Calicivirus Replication In Vitro.

Cats infected with feline calicivirus (FCV) often display oral ulcers and inflammation of the upper respiratory tract, which can lead to death in severe cases. Antiviral therapy is one of the most effective ways to control FCV infection. Natural compounds in Chinese herbal medicines and medicinal plants provide abundant resources for research on antiviral drugs. In this study, we found that icariin (ICA), formononetin (FMN) and caffeic acid phenethyl ester (CPAE) show low cytotoxicity towards F81 cells, that the three natural compounds have apparent antiviral effects on FCV in vitro, and that they can inhibit different FCV strains. Then, we found that ICA and FMN mainly function in the early stage of FCV infection, while CAPE can function in both the early and late stages of FCV infection. Finally, we found that ICA has an antagonistic effect on FMN and CAPE in FCV infection, and FMN has a synergistic effect with CAPE against FCV infection. Our results showed that ICA, FMN and CAPE may be potential drug candidates for FCV-induced diseases.

Shengxuening Extracted from Silkworm Excrement Mitigates Myelosuppression via SCF-Mediated JAK2/STAT3 Signaling.

Shengxuening (SXN) is a Chinese patent medicine with main ingredients (including chlorophyll derivatives and sodium iron chlorophyllin) extracted from silkworm excrement. SXN exhibited efficacy in clinical trials of renal anemia and iron deficiency anemia; however, the specific mechanisms remain unclear. This study found that SXN increased the number of peripheral blood cells and improved the bone marrow morphology in myelosuppressed mouse model, reversed the reduction in body weight and spleen indices, and increased the serum levels of erythropoietin and granulocyte-macrophage colony-stimulating factor. Quantitative real-time PCR array and Western blot analysis showed the enhanced expression of stem cell factor (SCF), JAK2, and STAT3 in the liver. These results suggested that SXN promoted the recovery of hemopoietic function in myelosuppressed models by increasing the secretion of hematopoietic factors and activating the JAK2/STAT3 pathway. Therefore, this medicine may be applied as therapeutic pharmaceutical drug to mitigate myelosuppression.

Vacuum ultraviolet photodissociation dynamics of OCS + hv → CO(1Σ+) + S(1S0) via the E and F Rydberg states.

The state-resolved photodissociation of the CO(1Σ+) + S(1S0) photoproduct channel, formed by vacuum ultraviolet photoexcitation of OCS to a progression of the symmetric stretching vibration (ν1') in the E and F states, has been investigated by using the time-sliced velocity map ion imaging technique. The total kinetic energy release spectra and the vibrational state specific anisotropy parameters (ß) were obtained based on the raw images of S(1S0) photoproducts detected in the wavelength ranges of 134.40-140.98 nm, respectively. Except for vibrational band origins, the CO(1Σ+) photoproducts are found to have more significant populations at highly vibrationally excited states as the symmetric stretching vibrational excitation of the E and F states increases. Furthermore, the vibrational-state specific ß values for the CO(1Σ+) + S(1S0) channel via the E and F states both show a sudden change from negative to positive in the vicinity of moderately vibronic levels of the E and F states. This anomalous phenomenon suggests that multiple excited states with different symmetries are involved in the photoexcitation process at relatively short photolysis wavelengths due to the strong vibronic couplings existing in the higher vibronic levels of the E and F states, and the formation of CO(1Σ+) + S(1S0) photoproducts may proceed by different nonadiabatic interactions from the prepared excited states to the lower dissociative state 1Σ+, with strong dependence of the initially symmetric stretching excitation in the Rydberg-type transitions.