Selective Vulnerability of GABAergic Inhibitory Interneurons to Bilirubin Neurotoxicity in the Neonatal Brain.

Hyperbilirubinemia (HB) is a key risk factor for hearing loss in neonates, particularly premature infants. Here we report that bilirubin (BIL)-dependent cell death in auditory brainstem of neonatal mice of both sexes is significantly attenuated by ZD7288, a blocker for hyperpolarization-activated cyclic nucleotide-gated (HCN) channel mediated current (Ih), or by genetic deletion of HCN1. GABAergic inhibitory interneurons predominantly express HCN1, on which BIL selectively acts to increase their intrinsic excitability and mortality by enhancing HCN1 activity and Ca2+-dependent membrane targeting. Chronic BIL elevation in neonatal mice in vivo increases the fraction of spontaneously active interneurons and their firing frequency, Ih and death, compromising audition at young adult stage in HCN1+/+, but not in HCN1-/- genotype. We conclude that HB preferentially targets HCN1 to injure inhibitory interneurons, fueling a feedforward loop in which lessening inhibition cascades hyperexcitability, Ca2+ overload, neuronal death and auditory impairments. These findings rationalize HCN1 as a potential target for managing HB encephalopathy.Significance Statement This study demonstrated that bilirubin preferentially targets GABAergic interneurons where it facilitates not only gating of HCN1 channels but also targeting of intracellular HCN1 to plasma membrane in calcium-dependent manner, resulting in neuronal hyperexcitability, injury and sensory dysfunction. These findings implicate HCN1 channel not only as a potential driver for auditory abnormalities in neonatal patients with bilirubin encephalopathy, but also potential intervention target for clinical management of neurological impairments associated with severe jaundice. Selective vulnerability of interneurons to neurotoxicity may be of general significance for understanding other forms of brain injury.

SPRDA: a link prediction approach based on the structural perturbation to infer disease-associated Piwi-interacting RNAs.

piRNA and PIWI proteins have been confirmed for disease diagnosis and treatment as novel biomarkers due to its abnormal expression in various cancers. However, the current research is not strong enough to further clarify the functions of piRNA in cancer and its underlying mechanism. Therefore, how to provide large-scale and serious piRNA candidates for biological research has grown up to be a pressing issue. In this study, a novel computational model based on the structural perturbation method is proposed to predict potential disease-associated piRNAs, called SPRDA. Notably, SPRDA belongs to positive-unlabeled learning, which is unaffected by negative examples in contrast to previous approaches. In the 5-fold cross-validation, SPRDA shows high performance on the benchmark dataset piRDisease, with an AUC of 0.9529. Furthermore, the predictive performance of SPRDA for 10 diseases shows the robustness of the proposed method. Overall, the proposed approach can provide unique insights into the pathogenesis of the disease and will advance the field of oncology diagnosis and treatment.

Origins of High Air Sensitivity and Treatment Strategies in O3-Type NaMn1/3 Fe1/3Ni1/3O2.

Sodium-ion layered oxides are one of the most highly regarded sodium-ion cathode materials and are expected to be used in electric vehicles and large-scale grid-level energy storage systems. However, highly air-sensitive issues limit sodium-ion layered oxide cathode materials to maximize cost advantages. Industrial and scientific researchers have been developing cost-effective air sensitivity treatment strategies with little success because the impurity formation mechanism is still unclear. Using density functional theory calculations and ab initio molecular dynamics simulations, this work shows that the poor air stability of O3-type NaMn1/3Fe1/3Ni1/3O2 (NMFNO) may be as follows: (1) low percentage of nonreactive (003) surface; (2) strong surface adsorption capacity and high surface reactivity; and (3) instability of the surface sodium ions. Our physical images point out that the high reactivity of the NMFNO surface originates from the increase in electron loss and unpaired electrons (magnetic moments) of the surface oxygen active site as well as the enhanced metal coactivation effect due to the large radius of the sodium ion. We also found that the hydrolysis reaction requires a higher reactivity of the surface oxygen active site, while the carbon hybridization mode transformation in carbonate formation depends mainly on metal activation and does not even require the involvement of surface oxygen active sites. Based on the calculation results and our proposed physical images, we discuss the feasibility of these treatment strategies (including surface morphology modulation, cation/anion substitution, and surface configuration design) for air-sensitive issues.

Line graph attention networks for predicting disease-associated Piwi-interacting RNAs.

PIWI proteins and Piwi-Interacting RNAs (piRNAs) are commonly detected in human cancers, especially in germline and somatic tissues, and correlate with poorer clinical outcomes, suggesting that they play a functional role in cancer. As the problem of combinatorial explosions between ncRNA and disease exposes gradually, new bioinformatics methods for large-scale identification and prioritization of potential associations are therefore of interest. However, in the real world, the network of interactions between molecules is enormously intricate and noisy, which poses a problem for efficient graph mining. Line graphs can extend many heterogeneous networks to replace dichotomous networks. In this study, we present a new graph neural network framework, line graph attention networks (LGAT). And we apply it to predict PiRNA disease association (GAPDA). In the experiment, GAPDA performs excellently in 5-fold cross-validation with an AUC of 0.9038. Not only that, it still has superior performance compared with methods based on collaborative filtering and attribute features. The experimental results show that GAPDA ensures the prospect of the graph neural network on such problems and can be an excellent supplement for future biomedical research.

Cyclin B2 impairs the p53 signaling in nasopharyngeal carcinoma.

BACKGROUND: Cyclin B2 (CCNB2), a member of the cyclin family, is an oncogene in multiple cancers, including nasopharyngeal carcinoma (NPC). However, the epigenetics mechanism for CCNB2 overexpression in NPC remains unclear. This study dissects the regulatory role of CCNB2 in NPC and the molecular mechanism. METHODS: Differentially methylated genes (DMG) and differentially expressed genes (DEG) were screened out in GSE52068 and GSE13597 databases, respectively, and candidate targets were identified by the Venn diagram. GO annotation and pathway enrichment analyses were performed on selected DMG and DEG, and a PPI network was constructed to pinpoint hub genes. PCR and qMSP were conducted to detect the expression and methylation of CCNB2 in cells. The siRNA targeting CCNB2 was transfected into NPC cells, and the migration, proliferation, cell cycle, epithelial-mesenchymal transition (EMT), tumorigenesis, and metastasis were examined. The upstream factor responsible for CCNB2 overexpression in NPC was explored. The p53 activity in NPC cells was assessed using western blot analysis. RESULTS: CCNB2 showed hypomethylation and overexpression in NPC. CCNB2 silencing inhibited cell migration, proliferation, cell cycle entry, and EMT. JMJD6 was overexpressed in NPC and upregulated CCNB2 through demethylation. JMJD6 reversed the effects of CCNB2 downregulation, resulting in elevated cellular activity in vitro and tumorigenic and metastatic activities in vivo. CCNB2 blocked the p53 pathway, while the p53 pathway inhibitor reversed the effect of CCNB2 silencing to increase the activity of NPC cells. CONCLUSIONS: JMJD6 enhanced CCNB2 transcription by demethylating CCNB2, thereby repressing the p53 pathway and promoting NPC progression.

Exhaustive State-to-State Cross Sections and Rate Coefficients for Inelastic N2-N2 Collisions using QCT Combined with Neural Network Models.

Using the quasi-classical trajectory method, we systematically studied the state-to-state vibrational relaxation process of N2(v1) + N2(v2) collisions over a wide temperature range (5000-30,000 K). Different temperature dependencies of the single- and multiquantum VV and VT events in various (v1,v2) collisions are captured, with the dominant channel being related to the initial vibrational energy levels (vmax = 50). At a specified relative translational energy, there is a monotonic relationship of the VT cross sections with the vibrational energy level, particularly in high-energy collisions. Additionally, we constructed well-trained neural network models (R-values reaching 0.99) using limited quasi-classical trajectory (QCT) data sets, which can be used to predict the state-to-state cross sections and rate coefficients of the VV processes N2(v1) + N2(v2) → N2(v1 - Δv) + N2(v2 + Δv) and VT processes N2(v1) + N2(v2) → N2(v1 - Δv) + N2(v2) (Δv = ±1, ±2, ±3) for collisions with arbitrary initial vibrational states. This work not only significantly reduces computational resources but also serves as a reference for the study of the state-to-state dynamics of all four-atom collision systems in hypersonic flows.

Occurrence and seasonal variation of Perkinsus sp. Infection in wild mollusk populations from coastal waters of Qingdao, northern China.

Perkinsosis has been recognized as one of the major threats to natural and farmed bivalve populations, many of which are of commercial as well as environmental significance. Three Perkinsus species have been identified in China, and the Manila clam (Ruditapes philippinarum) was the most frequently infected species in northern China. Although the occurrence and seasonal variation of Perkinsus spp. have previously been examined, the pathological characteristics of these infections in wild Manila clams and sympatric species in China have seldom been reported. In the present study, the prevalence and intensity of Perkinsus infection in wild populations of Manila clams and 10 sympatric species from three sites were investigated by Ray's fluid thioglycolate medium (RFTM) assay seasonally across a single year. Perkinsus infection was only identified in Manila clams, with a high prevalence (274/284 = 96.48 %) and low intensity (89.8 % with a Mackin value ≤ 2, suggesting generally low-intensity infections) throughout the year. Heavily infected clams were mainly identified in Tianheng in January, which displayed no macroscopic signs of disease. An overview of the whole visceral mass section showed that the trophozoites mostly aggregated in gills and connective tissue of the digestive tract, to a lesser extent in the mantle and foot, and even less frequently in adductor muscle and connective tissues of the gonad. PCR and ITS-5.8S rRNA sequencing of 93 representative RFTM-positive samples revealed a 99.69 to 100 % DNA sequence identity to Perkinsus olseni. Unexpectedly, significantly higher infection intensities were usually identified in January and April when the Condition Index (CI) was relatively high. We propose that factors associated with the anthropogenic harvesting pressure and irregular disturbances should be responsible for the uncommon seasonal infection dynamics of perkinsosis observed in the present study.

Unveiling the potential of machine learning in schizophrenia diagnosis: A meta-analytic study of task-based neuroimaging data.

The emergence of machine learning (ML) techniques has opened up new avenues for identifying biomarkers associated with schizophrenia (SCZ) using task-related fMRI (t-fMRI) designs. To evaluate the effectiveness of this approach, we conducted a comprehensive meta-analysis of 31 t-fMRI studies using a bivariate model. Our findings revealed a high overall sensitivity of 0.83 and specificity of 0.82 for t-fMRI studies. Notably, neuropsychological domains modulated the classification performance, with selective attention demonstrating a significantly higher specificity than working memory (ß = 0.98, z = 2.11, P = 0.04). Studies involving older, chronic patients with SCZ reported higher sensitivity (P <0.015) and specificity (P <0.001) than those involving younger, first-episode patients or high-risk individuals for psychosis. Additionally, we found that the severity of negative symptoms was positively associated with the specificity of the classification model (ß = 7.19, z = 2.20, P = 0.03). Taken together, these results support the potential of using task-based fMRI data in combination with machine learning techniques to identify biomarkers related to symptom outcomes in SCZ, providing a promising avenue for improving diagnostic accuracy and treatment efficacy. Future attempts to deploy ML classification should consider the factors of algorithm choice, data quality and quantity, as well as issues related to generalization.

Cross-cultural adaptation and clinical application of the Perth Empathy Scale.

OBJECTIVE: Alterations of empathy have been observed in patients with various mental disorders. The Perth Empathy Scale (PES) was recently developed to measure a multidimensional construct of empathy across positive and negative emotions. However, its psychometric properties and clinical applications have not been examined in the Chinese context. METHODS: The Chinese version of the PES was developed and administered to a large Chinese sample (n = 1090). Factor structure, internal consistency, test-retest reliability, and convergent, discriminant, as well as concurrent validity were examined. Moreover, 50 patients with major depressive disorder (MDD) and 50 healthy controls were recruited to explore the clinical utility of the PES. RESULTS: Confirmatory factor analyses supported a theoretically congruent three-factor structure of empathy, namely Cognitive Empathy, Negative Affective Empathy and Positive Affective Empathy. The PES showed good to excellent internal consistency reliability, good convergent and discriminant validity, acceptable concurrent validity, and moderate to high test-retest reliability. Patients with MDD had significantly lower PES scores compared to healthy controls. Linear discriminant function comprised of the three factors correctly differentiated 71% of participants, which further verified the clinical utility of the PES. CONCLUSIONS: Our findings indicated that the Chinese version of the PES is a reliable and valid instrument to measure cognitive and affective empathy across negative and positive emotions, and could therefore be used in both research and clinical practice.

[Network Meta-analysis of Chinese patent medicines in treatment of chronic pulmonary heart disease].

Network Meta-analysis was performed to compare the efficacy and safety of Chinese patent medicines in treating chronic pulmonary heart disease. CNKI, VIP, Wanfang, SinoMed, PubMed, Web of Science, EMbase, and Cochrane Library were searched for randomized controlled trial(RCT) of treating chronic pulmonary heart disease with Chinese patent medicines with the time interval from inception to December 2023. The Cochrane risk-of-bias tool was used for quality assessment of the included articles. RevMan 5.4 and Stata 17.0 were employed to establish the risk of bias map and perform the network Meta-analysis, respectively. Ultimately, a total of 95 RCTs involving 8 787 cases and 11 different Chinese patent medicines were included. Network Meta-analysis yielded the following results based on the surface under the cumulative ranking curve(SUCRA).(1)In terms of cardiac function improves clinical total effective rate, SUCRA the top three were Wenxin Granules + conventional western medicine, Tongxinluo Capsules + conventional western medicine, and Qishen Yiqi Dropping Pills + conventional western medicine.(2)For improving forced expiratory volume in the first se-cond(FEV1), SUCRA the top three were Danting Feixin Granules + conventional western medicine, Tongxinluo Capsules + conventional western medicine, and Bufei Huoxue Capsules + conventional western medicine.(3)Regarding increasing the FEV1/forced vital capacity(FVC%) value, SUCRA the top three were Qili Qiangxin Capsules + conventional western medicine, Shexiang Baoxin Pills + conventional western medicine, and Qishen Yiqi Dropping Pills + conventional western medicine.(4)In terms of increasing the partial pressure of oxygen(PaO_2), SUCRA the top three were Qili Qiangxin Capsules + conventional western medicine, Qishen Yiqi Dropping Pills + conventional western medicine, and Shexiang Baoxin Pills + conventional western medicine.(5)In terms of reducing the partial pressure of carbon dioxide(PaCO_2), SUCRA the top three were Tongxinluo Capsules + conventional western medicine, Qishen Yiqi Dropping Pills + conventional western medicine, and Shexiang Baoxin Pills + conventional western medicine.(6)In terms of increasing left ventricular ejection fraction(LVEF), SUCRA the top three were Bufei Huoxue Capsules + conventional western medicine, Qishen Yiqi Dropping Pills + conventional western medicine, and Shexiang Baoxin Pills + conventional western medicine.(7)In terms of decreasing brain natriu-retic peptide(BNP), SUCRA the top three were Compound Danshen Dropping Pills + conventional western medicine, Qili Qiangxin Capsules + conventional western medicine, and Tongxinluo Capsules + conventional western medicine.(8)In terms of improving the hematocrit level, SUCRA the top three were Qishen Yiqi Dropping Pills + conventional western medicine, Compound Danshen Dropping Pills + conventional western medicine, and Tongxinluo Capsules + conventional western medicine. In terms of safety, 26 RCTs reported adverse reactions, which primarily involved the circulatory and digestive systems. The combination of Chinese patent medicines with conventional western medicine has demonstrated enhanced therapeutic effects on chronic pulmonary heart disease. However, due to the varying quality and sample sizes of included studies and the absence of direct comparisons between Chinese patent medicines, the conclusions should be further validated by multicenter studies with larger sample sizes and higher methodological rigor.

Anterior cingulate glutamate levels associate with functional activation and connectivity during sensory integration in schizophrenia: a multimodal 1H-MRS and fMRI study.

BACKGROUND: Glutamatergic dysfunction has been implicated in sensory integration deficits in schizophrenia, yet how glutamatergic function contributes to behavioural impairments and neural activities of sensory integration remains unknown. METHODS: Fifty schizophrenia patients and 43 healthy controls completed behavioural assessments for sensory integration and underwent magnetic resonance spectroscopy (MRS) for measuring the anterior cingulate cortex (ACC) glutamate levels. The correlation between glutamate levels and behavioural sensory integration deficits was examined in each group. A subsample of 20 pairs of patients and controls further completed an audiovisual sensory integration functional magnetic resonance imaging (fMRI) task. Blood Oxygenation Level Dependent (BOLD) activation and task-dependent functional connectivity (FC) were assessed based on fMRI data. Full factorial analyses were performed to examine the Group-by-Glutamate Level interaction effects on fMRI measurements (group differences in correlation between glutamate levels and fMRI measurements) and the correlation between glutamate levels and fMRI measurements within each group. RESULTS: We found that schizophrenia patients exhibited impaired sensory integration which was positively correlated with ACC glutamate levels. Multimodal analyses showed significantly Group-by-Glutamate Level interaction effects on BOLD activation as well as task-dependent FC in a 'cortico-subcortical-cortical' network (including medial frontal gyrus, precuneus, ACC, middle cingulate gyrus, thalamus and caudate) with positive correlations in patients and negative in controls. CONCLUSIONS: Our findings indicate that ACC glutamate influences neural activities in a large-scale network during sensory integration, but the effects have opposite directionality between schizophrenia patients and healthy people. This implicates the crucial role of glutamatergic system in sensory integration processing in schizophrenia.

Bismuth, esomeprazole, metronidazole and amoxicillin or tetracycline as a first-line regimen for Helicobacter pylori eradication: A randomized controlled trial.

BACKGROUND: Due to general unavailability and common side effects of tetracycline, the clinical application of bismuth quadruple therapy (BQT) is greatly limited. Whether amoxicillin can replace tetracycline in BQT remains unknown. This study aimed to compare the eradication rate, safety and compliance between amoxicillin-containing and tetracycline-containing BQT as a first-line regimen for Helicobacter pylori eradication. METHODS: This randomized trial was conducted on 404 naïve patients for H. pylori eradication. The participants were randomly assigned to 14-day amoxicillin-containing (bismuth potassium citrate 110 mg four times/day, esomeprazole 20 mg twice daily, metronidazole 400 mg four times/day and amoxicillin 500 mg four times/day) and tetracycline-containing (tetracycline 500 mg four times/day and the other three drugs used as above) BQT. Safety and compliance were assessed within 3 days after eradication. Urea breath test was performed 4-8 weeks after eradication to evaluate outcome. RESULTS: As for the eradication rates of amoxicillin-containing and tetracycline-containing BQT, the results of both intention-to-treat and per-protocol analyses showed that the difference rate of the lower limit of 95% confidence interval was above -10.0% (intention-to-treat analysis: 81.7% vs. 83.2%, with a rate difference of -1.5% [-6.3% to 9.3%]; per-protocol analysis: 89.0% vs. 91.6%, -2.6% [-4.1% to 9.3%]). The incidence of adverse events in amoxicillin-containing BQT was significantly lower than tetracycline-containing BQT (29.5% vs. 39.7%). Both groups achieved relatively good compliance (92.0% vs. 89.9%). CONCLUSION: The eradication efficacy of amoxicillin-containing BQT was non-inferior to tetracycline-containing BQT as a first-line regimen for H. pylori eradication with better safety and similar compliance.

A novel l-rhamnose-binding lectin participates in defending against bacterial infection in zebrafish.

l-rhamnose-binding lectin (RBL), which is a class of animal lectins independent of Ca2+, can specifically bind l-rhamnose or d-galactose. Although several lectins in zebrafish have been reported, their functional mechanisms have not been fully uncovered. In this study, we discovered a novel l-rhamnose binding lectin (DrRBL) and studied its innate immune function. The DrRBL protein contains only one carbohydrate-recognition domain (CRD), which includes two strictly conserved motifs, "YGR" and "DPC". DrRBL was detected in all tested tissues and was present at high levels in the spleen, hepatopancreas and skin. After Aeromonas hydrophila challenge, the DrRBL mRNA level was significantly upregulated. Additionally, DrRBL was secreted into the extracellular matrix. Recombinant DrRBL (rDrRBL) could significantly inhibit the growth of gram-positive/negative bacteria, bind to several bacteria and cause obvious agglutination. The rDrRBL protein could combine with polysaccharides, such as PGN and LPS, rather than LTA. A more detailed study showed that rDrRBL could combine with monosaccharides, such as mannose, rhamnose and glucose, which are important components of PGN and LPS. However, rDrRBL could not bind to ribitol, which is an important component of LTA. The DrRBL deletion mutants, DrRBLΔ144-150 and DrRBLΔ198-200, were also constructed. DrRBLΔ144-150 ("ANYGRTD" deficient) showed weak bacterial inhibiting ability. However, DrRBLΔ198-200 ("DPC" deficient) showed weak agglutination ability. These results suggest that the "DPC" domain is important for agglutination. The conserved domain "ANYGRTD" is essential for inhibiting bacterial growth.

The role of the sextet potential energy surface in O2 + N inelastic collision processes.

We have performed molecular dynamics simulations of inelastic collisions between molecular oxygen and atomic nitrogen, employing the quasi-classical trajectory method on the new doublet, quartet, and sextet analytical potential energy surfaces of NO2. A complete database of vibrationally detailed rate coefficients is constructed in a wide temperature range for high vibrational states up to ν = 25. In particular, the present work shows that the sextet potential energy surface plays a crucial role in the rovibrational relaxation process of O2 + N collisions. The state-to-state rate coefficients increase by a factor of 2 to 6 when we consider the contribution of this sextet potential energy surface according to the corresponding weight factor, especially for vibrational energy transfer processes in single quantum jumps and/or high-temperature regimes. Furthermore, we also provide Arrhenius-type accurate fits for the vibrational state-specific rate coefficients of this collision system to achieve the flexible application of rate coefficients in numerical codes concerning air kinetics. Our results have implications for understanding the relaxation mechanism of the collision system with degenerate electronic states.

Real-time dynamic simulation of laser-induced N2 dissociation on two-dimensional graphene sheets.

Due to its relatively high inertness, nitrogen dissociation at ambient temperature and pressure has always been a challenging task. Plasmon driven photocatalysis has proved to be an effective method. Owing to their unique physical, chemical, and electronic properties, two-dimensional planar materials have become the most promising candidates to replace noble metal catalytic nitrogen reduction. In this study, real-time dynamics of N2 dissociation on graphene sheets under femtosecond laser irradiation was studied by using time-dependent density functional theory. We confirm that electrons generated by plasmon excitation of graphene transfer to the N2 molecular antibonding orbital and activate the N-N bond. The threshold of laser intensity of N2 dissociation can be effectively reduced by mixing CO molecules. This work provides basic insights for understanding the plasmon induced N2 activation process at the atomic scale and proves that graphene can be used as one of the candidate materials for N2 reduction photocatalysts with excellent performance.

Dissociation cross sections and rates in O2 + N collisions: molecular dynamics simulations combined with machine learning.

The collision-induced dissociation reaction of O2 (v, j) + N, a fundamental process in nonequilibrium air flows around reentry vehicles, has been studied systematically by applying molecular dynamics simulations on the 2A', 4A' and 6A' potential energy surfaces of NO2 in a wide temperature range. In particular, we have directly investigated the role of the 6A' surface in this process and discussed the applicability of the simplified approximate rate models proposed by Esposito et al. and Andrienko et al. based on the lowest two surfaces. The present work indicates that the state-selected dissociation of O2 + N is dominated by the 6A' surface for all except for the low-lying O2 states. Furthermore, a complete database of rovibrationally detailed cross sections and rate coefficients is a prerequisite for modeling the relevant nonequilibrium air flows in spacecraft reentry. Here, the combination of the quasi-classical trajectory (QCT) and the neural network (NN) has been proposed to predict all state-selected dissociation cross sections and further construct dissociation parameter sets. All NN-based models established in this work accurately reproduce the results calculated from QCT simulations over a wide range of rovibrational quantum numbers with R2 > 0.99. Compared with the explicit QCT simulations, the computational requirement for predicting cross sections and rates based on the NN models significantly reduces. Finally, thermal equilibrium rate coefficients computed from NN models match remarkably well the available theoretical and experimental results in the whole temperature range explored.

Exhaustive state-specific dissociation study of the N2(Σg+1)+N(S4) system using QCT combined with a neural network method.

This work studies the exhaustive rovibrational state-specific collision-induced dissociation properties of the N2+N system by QCT (quasi-classical trajectory) combined with a neural network method based on the ab initio PES recently published by Varga et al. [Phys. Chem. Chem. Phys. 23, 26273 (2021)]. The QCT combined with a neural network for state-specific dissociation (QCT-NN-SSD) model is developed and used to predict the dissociation cross sections and their energy dependence on the thermal range from a sparsely sampled noisy dataset. It is conservatively estimated that using this method can reduce the cost of the calculation by 96.5%. The rate coefficient of thermal non-equilibrium between different energy modes is obtained by combining the QCT-NN-SSD model with the multi-temperature model. The results show that, for the equilibrium state, dissociation mainly occurs at high vibrational and moderately low rotational levels. When the system is in non-equilibrium, there is no obvious vibrational level preference and highly rotationally excited molecules play a major role in promoting the dissociation by compensating for the lack of vibrational energy. The use of neural network training to generate complete datasets based on limited and discrete data provides an economical and reliable way to obtain a complete kinetic database needed to accurately simulate non-equilibrium flows.

Myocardial Work for Dynamic Monitoring of Myocardial Injury in Neonatal Asphyxia.

To assess the value of parameters of myocardial work for dynamic monitoring of myocardial injury after neonatal asphyxia. Fifty-three neonates with asphyxia admitted within 24 h after delivery were divided into a mild asphyxia group (n = 40) and severe asphyxia group (n = 13). Echocardiography was performed within 24 h post-birth, within 72 h post-birth (48 h after first echo), and during recovery. The left ventricular ejection fraction on M-mode echocardiography and by Simpson's biplane method (LVEF and Bi-EF, respectively), stroke volume (SV), cardiac output (CO), cardiac index (CI), global longitudinal strain (GLS), global work index (GWI), global constructive work (GCW), and other parameters were measured. Echocardiographic indicators were compared between groups and over time. GWI was significantly increased at 72 h in the mild asphyxia group (P < 0.05) but showed no significant change over time in the severe asphyxia group (P > 0.05). While GCW increased significantly over time in both groups (P < 0.05), it increased earlier in the mild asphyxia group. Time and grouping factors had independent effects on GWI and GCW (P > 0.05). The characteristics of differences in GWI and GCW between the two groups were different from those for LVEF, Bi-EF, SV, CO, CI, and GLS and their change characteristics with improvement from treatment. GWI and GCW changed significantly during recovery from neonatal asphyxia, and their change characteristics differed between mild and severe asphyxia cases. Myocardial work parameters can be used as valuable supplements to traditional indicators of left ventricular function to dynamically monitor the recovery from myocardial injury after neonatal asphyxia.

Exploration of the mechanism of NORAD activation of TGF-ß1/Smad3 through miR-136-5p and promotion of tacrolimus-induced renal fibrosis.

BACKGROUND: Tacrolimus is a potent immunosuppressant, but has various side effects, with nephrotoxicity being the most common. Renal fibrosis is an important process of tacrolimus nephrotoxicity. Therefore, it is important to identify the factors that contribute to renal fibrosis after tacrolimus nephrotoxicity, and control its development. METHODS: The present study aims to determine whether tacrolimus may speed up the course of renal fibrosis by upregulating noncoding RNA activated by DNA damage (NORAD) to compete with miR-136-5p, and activating the TGF-ß1/Smad3 pathway. Furthermore, in vivo rat models and in vitro cell models were established. Then, the expression levels of NORAD and miR-136-5p were determined by RT-qPCR, while the expression of the TGF-ß1/Smad3 pathway was determined by western blot and RT-qPCR. In order to investigate the interaction between NORAD and miR-136-5p, as well as miR-136-5p and SYK, two luciferase reporters were employed. The renal fibrosis of mice was observed using Masson and PAS staining. The expression of inflammatory factors IL-1, IL-6, MCP-1 and TNF-α was detected by ELISA. RESULTS: In the in vitro experiments, NORAD was upregulated, while miR-136-5p was downregulated after tacrolimus induction. The expression of the TGF-ß1/Smad3 pathway correspondingly changed after the induction by tacrolimus. In the in vivo experiments, the expression of NORAD and miR-136-5p, and the trend for renal fibrosis were consistent with the results in the in vitro experiments. Furthermore, the inflammatory factors correspondingly changed with the severity of renal fibrosis. Moreover, the expression trend of the TGF-ß1/Smad3 pathway in tacrolimus-induced rats was consistent with that in the in vitro experiments. CONCLUSION: Through in vitro and in vivo experiments, the present study was able to successfully prove that tacrolimus upregulates NORAD to compete with miR-136-5p, resulting in a decrease in miR-136-5p expression, which in turn activates the TGF-ß1/smad3 pathway, and finally induces the aggravation of renal fibrosis.

Sexually dimorphic age-related molecular differences in the entorhinal cortex of cognitively intact elderly: Relation to early Alzheimer's changes.

INTRODUCTION: Women are more vulnerable to Alzheimer's disease (AD) than men. The entorhinal cortex (EC) is one of the earliest structures affected in AD. We identified in cognitively intact elderly different molecular changes in the EC in relation to age. METHODS: Changes in 12 characteristic molecules in relation to age were determined by quantitative immunohistochemistry or in situ hybridization in the EC. They were arbitrarily grouped into sex steroid-related molecules, markers of neuronal activity, neurotransmitter-related molecules, and cholinergic activity-related molecules. RESULTS: The changes in molecules indicated increasing local estrogenic and neuronal activity accompanied by a higher and faster hyperphosphorylated tau accumulation in women's EC in relation to age, versus a mainly stable local estrogenic/androgenic and neuronal activity in men's EC. DISCUSSION: EC employs a different neurobiological strategy in women and men to maintain cognitive function, which seems to be accompanied by an earlier start of AD in women. HIGHLIGHTS: Local estrogen system is activated with age only in women's entorhinal cortex (EC). EC neuronal activity increased with age only in elderly women with intact cognition. Men and women have different molecular strategies to retain cognition with aging. P-tau accumulation in the EC was higher and faster in cognitively intact elderly women.