Gene redundancy and gene compensation of insulin-like peptides in the oocyte development of bean beetle.

Bean beetle (Callosobruchus maculatus) exhibits clear phenotypic plasticity depending on population density; However, the underlying molecular mechanism remains unknown. Compared to low-density individuals, high-density individuals showed a faster terminal oocyte maturity rate. Four insulin-like peptide (ILP) genes were identified in the bean beetle, which had higher expression levels in the head than in the thorax and abdomen. The population density could regulate the expression levels of CmILP1-3, CmILP2-3, and CmILP1 as well as CmILP3 in the head, thorax, and abdomen, respectively. RNA interference results showed that each CmILP could regulate terminal oocyte maturity rate, indicating that there was functional redundancy among CmILPs. Silencing each CmILP could lead to down-regulation of some other CmILPs, however, CmILP3 was up-regulated in the abdomen after silencing CmILP1 or CmILP2. Compared to single gene silencing, silencing CmILP3 with CmILP1 or CmILP2 at the same time led to more serious retardation in oocyte development, suggesting CmILP3 could be up-regulated to functionally compensate for the down-regulation of CmILP1 and CmILP2. In conclusion, population density-dependent plasticity in terminal oocyte maturity rate of bean beetle was regulated by CmILPs, which exhibited gene redundancy and gene compensation.

Combination of hyperoxygenation and targeted temperature management improves functional outcomes of post cardiac arrest syndrome irrespective of causes of arrest in rats.

BACKGROUND: The high mortality rates of patients who are resuscitated from cardiac arrest (CA) are attributed to post cardiac arrest syndrome (PCAS). This study evaluated the effect of hyperoxygenation and targeted temperature management (TTM) on PCAS in rats with different causes of CA. METHODS AND RESULTS: One hundred and sixty-eight Sprague-Dawley rats were equally divided into asphyxial and dysrhythmic groups. Animals were further randomized into four subgroups immediately after resuscitation: 1) Normoxia-normothermia (NO-NT): ventilated with 21% oxygen under normothermia; 2) Hyperoxia-normothermia (HO-NT): ventilated with 100% oxygen for 3 h under normothermia; 3) Normoxia-hypothermia (NO-HT): ventilated with 21% oxygen for 3 h under hypothermia; 4) Hyperoxia-hypothermia (HO-HT): ventilated with 100% oxygen for 3 h under hypothermia. Post resuscitation cardiac dysfunction, neurological recovery, and pathological analysis were assessed.For asphyxial CA, HO-NT and HO-HT (68.8% and 75.0%) had significantly higher survival than NO-NT and NO-HT (31.3% and 31.3%). For dysrhythmic CA, NO-HT and HO-HT (81.3% and 87.5%) had significantly higher survival than NO-NT and HO-NT (44.0% and 50.0%). When all of the rats were considered, the survival rate was much higher in HO-HT (81.3%). Compared with NO-NT (57.7 ± 14.9% and 40.3 ± 7.8%), the collagen volume fraction and the proportion of fluoro-jade B-positive area in HO-HT (14.0 ± 5.7% and 28.0 ± 13.3%) were significantly reduced. CONCLUSIONS: The beneficial effects of hyperoxygenation and TTM are dependent on the cause of arrest: hyperoxygenation benefits asphyxial whereas TTM benefits dysrhythmic CA. The combination of hyperoxygenation and TTM could effectively improve the functional outcome of PCAS regardless of the cause of CA.

Evaluation of functional and electrical features of automatic external defibrillators in extreme altitude and temperature environments.

Aims: Human exposure to high-altitude and/or low-temperature areas is increasing and cardiac arrest in these circumstances represents an increasing proportion of all treated cardiac arrests. However, little is known about the performance of automated external defibrillators (AED) in these circumstances. The objective of this study is to assess the functional and electrical features of 6 commercially available AEDs in extreme environments. Methods: Accuracy of shockable rhythm detection, the time required for self-test, rhythm analysis, and capacitor charging, together with total energy, peak voltage, peak current, and phasic duration of defibrillation waveform measured after placing the AEDs in simulated high-altitude, simulated low-temperature, and natural composite high-altitude and low-temperature environment for 30 min, were compared to those measured in the standard environment. Results: All of the shockable rhythms were correctly detected and all of the defibrillation shocks were successfully delivered by the AEDs. However, the time required for self-test, rhythm detection, and capacitor charging was shortened by 1.2% (3 AEDs, maximum 12.4%) in the simulated high-altitude environment, was prolonged by 3.6% (4 AEDs, maximum 40.8%) in the simulated low-temperature environment, and was prolonged by 4.1% (5 AEDs, maximum 52.1%) in the natural environment. Additionally, the total delivered energy was decreased by 2.5% (2 AEDs, maximum 6.8%) in the natural environment. Conclusion: All of the investigated AEDs functioned properly in simulated and natural environments, but a large variation in the functional and electrical feature change was observed. When performing cardiopulmonary resuscitation in extreme environments, the impact of environmental factors may need consideration.

[Development of Human Vital Signs and Body Posture Monitoring and Positioning Alarm Systems].

In view of the high incidence of malignant diseases such as malignant arrhythmias in the elderly population, accidental injuries such as falls, and the problem of no witnesses when danger occurs, the study developed a human vital signs and body posture monitoring and positioning alarm system. Through the collection and analysis of electrocardiogram (ECG), respiration (RESP) and acceleration (ACC) signals, the system monitors human vital signs and body posture in real time, automatically judges critical states such as malignant arrhythmias and accidental falls on the local device side, and then issues alarm information, opens the positioning function, and uploads physiological information and patient location information through 4G communication. Experiments have shown that the system can accurately determine the occurrence of ventricular fibrillation and falls, and issue position and alarm information.

Mitogenome of the stink bug Aelia fieberi (Hemiptera: Pentatomidae) and a comparative genomic analysis between phytophagous and predatory members of Pentatomidae.

Aelia fieberi Scott, 1874 is a pest of crops. The mitogenome of A. fieberi (OL631608) was decoded by next-generation sequencing. The mitogenome, with 41.89% A, 31.70% T, 15.44% C and 10.97% G, is 15,471 bp in size. The phylogenetic tree showed that Asopinae and Phyllocephalinae were monophyletic; however, Pentatominae and Podopinae were not monophyletic, suggesting that the phylogenetic relationships of Pentatomoidae are complex and need revaluation and revision. Phytophagous bugs had a ~20-nucleotide longer in nad2 than predatory bugs. There were differences in amino acid sequence at six sites between phytophagous bugs and predatory bugs. The codon usage analysis indicated that frequently used codons used either A or T at the third position of the codon. The analysis of amino acid usage showed that leucine, isoleucine, serine, methionine, and phenylalanine were the most abundant in 53 species of Pentatomoidae. Thirteen protein-coding genes were evolving under purifying selection, cox1, and atp8 had the strongest and weakest purifying selection stress, respectively. Phytophagous bugs and predatory bugs had different evolutionary rates for eight genes. The mitogenomic information of A. fieberi could fill the knowledge gap for this important crop pest. The differences between phytophagous bugs and predatory bugs deepen our understanding of the effect of feeding habit on mitogenome.

Evaluation of three approaches used for respiratory measurement in healthy subjects.

Objective. Respiration is one of the critical vital signs of human health status, and accurate respiratory monitoring has important clinical significance. There is substantial evidence that alterations in key respiratory parameters can be used to determine a patient's health status, aid in the selection of appropriate treatments, predict potentially serious clinical events and control respiratory activity. Although various approaches have been developed for respiration monitoring, no definitive conclusions have been drawn regarding the accuracy of these approaches because each has different advantages and limitations. In the present study, we evaluated the performance of three non-invasive respiratory measurement approaches, including transthoracic impedance (IMP), surface diaphragm electromyography-derived respiration (EMGDR) and electrocardiogram-derived respiration (ECGDR), and compared them with the direct measurement of airflow (FLW) in 33 male and 38 female healthy subjects in the resting state.Approach. The accuracy of six key respiratory parameters, including onset of inspiration (Ion), onset of expiration (Eon), inspiratory time (It), expiratory time (Et), respiratory rate (RR) and inspiratory-expiratory ratio (I:E), measured from the IMP, EMGDR and ECGDR, were compared with those annotated from the reference FLW.Main results. The correlation coefficients between the estimated inspiratory volume and reference value were 0.72 ± 0.20 for IMP, 0.62 ± 0.23 for EMGDR and 0.46 ± 0.21 for ECGDR (p< 0.01 among groups). The positive predictive value and sensitivity for respiration detection were 100% and 100%, respectively, for IMP, which were significantly higher than those of the EMGDR (97.2% and 95.5%,p< 0.001) and the ECGDR (96.9% and 90.0%,p< 0.001). Additionally, the mean error (ME) forIon,Eon,It,EtandRRdetection were markedly lower for IMP than for EMGDR and ECGDR (p< 0.001).Significance. Compared with EMGDR and ECGDR, the IMP signal had a higher positive predictive value, higher sensitivity and lower ME for respiratory parameter detection. This suggests that IMP is more suitable for dedicated respiratory monitoring and parameter evaluation.

Accessing indole-isoindole derivatives via palladium-catalyzed [3+2] cyclization of isocyanides with alkynyl imines.

A facile protocol for the preparation of indole-isoindole derivatives was developed and proceeds via a palladium-catalyzed [3+2] cyclization of isocyanides with alkynyl imines. In this transformation, the palladium catalyst has a triple role, serving simultaneously as a π acid, a transition-metal catalyst and a hydride ion donor, thus enabling the dual function of isocyanide both as a C1 synthon for cyanation and a C1N1 synthon for imidoylation. Significantly, the reaction is the sole successful example for accessing indole-isoindole derivatives, and will open up new avenues to assemble unique N-heterocycle frameworks. Furthermore, the synthetic value of this protocol is demonstrated in the late-stage modification of physiologically active molecules and in the construction of aggregation-induced emission compounds.

Characterization and Discrimination of Volatile Compounds in Chilled Tan Mutton Meat during Storage Using HiSorb-TD-GC-MS and E-Nose.

Chilled Tan mutton is currently the mainstream of Tan mutton production and consumption in China, but the reports on chilled meat quality evaluation and shelf-life discrimination by volatiles are limited. This study aimed to investigate the changes of volatile compounds in chilled Tan mutton at four storage stages (1d, 3d, 5d, 7d) in order to differentiate the various storage stages. An analysis protocol was established for the characterization and discrimination of the volatiles in chilled Tan mutton based on high capacity sorptive extraction-thermal desorption-gas coupled with chromatography-mass spectrometry (HiSorb-TD-GC-MS), electronic nose (E-nose), and multivariate statistical analysis. A total of 96 volatile compounds were identified by HiSorb-TD-GC-MS, in which six compounds with relative odor activity value >1 were screened as the key characteristic volatiles in chilled Tan mutton. Four storage stages were discriminated by partial least squares discriminant analysis, and nine differential volatile compounds showed a variable importance for the projection score >1, including octanoic acid, methyl ester, decanoic acid, methyl ester, acetic acid, heptanoic acid, methyl ester, propanoic acid, 2-hydroxy-, methyl ester, (ñ)-, hexanoic acid, propanoic acid, butanoic acid, and nonanoic acid. With the volcano plot analysis, hexadecanoic acid, methyl ester, was the common volatile marker candidate to discriminate chilled stages of Tan mutton. Meanwhile, E-nose could discriminate chilled Tan mutton at different storage stages rapidly and efficiently using linear discriminant analysis. Furthermore, E-nose sensors could obtain comprehensive volatile profile information, especially in esters, acids, and alcohols, which could confirm the potential of E-nose for meat odor recognition. Thus, this analysis protocol could characterize and discriminate the volatiles in chilled Tan mutton during storage.

Real-time amplitude spectrum area estimation during chest compression from the ECG waveform using a 1D convolutional neural network.

Introduction: Amplitude spectrum area (AMSA) is a well-established measure than can predict defibrillation outcome and guiding individualized resuscitation of ventricular fibrillation (VF) patients. However, accurate AMSA can only be calculated during cardiopulmonary resuscitation (CPR) pause due to artifacts produced by chest compression (CC). In this study, we developed a real-time AMSA estimation algorithm using a convolutional neural network (CNN). Methods: Data were collected from 698 patients, and the AMSA calculated from the uncorrupted signals served as the true value for both uncorrupted and the adjacent corrupted signals. An architecture consisting of a 6-layer 1D CNN and 3 fully connected layers was developed for AMSA estimation. A 5-fold cross-validation procedure was used to train, validate and optimize the algorithm. An independent testing set comprised of simulated data, real-life CC corrupted data, and preshock data was used to evaluate the performance. Results: The mean absolute error, root mean square error, percentage root mean square difference and correlation coefficient were 2.182/1.951 mVHz, 2.957/2.574 mVHz, 22.887/28.649% and 0.804/0.888 for simulated and real-life testing data, respectively. The area under the receiver operating characteristic curve regarding predicting defibrillation success was 0.835, which was comparable to that of 0.849 using the true value of the AMSA. Conclusions: AMSA can be accurately estimated during uninterrupted CPR using the proposed method.

Modulation of WNT, Activin/Nodal, and MAPK Signaling Pathways Increases Arterial Hemogenic Endothelium and Hematopoietic Stem/Progenitor Cell Formation During Human iPSC Differentiation.

Several differentiation protocols enable the emergence of hematopoietic stem and progenitor cells (HSPCs) from human-induced pluripotent stem cells (iPSCs), yet optimized schemes to promote the development of HSPCs with self-renewal, multilineage differentiation, and engraftment potential are lacking. To improve human iPSC differentiation methods, we modulated WNT, Activin/Nodal, and MAPK signaling pathways by stage-specific addition of small-molecule regulators CHIR99021, SB431542, and LY294002, respectively, and measured the impact on hematoendothelial formation in culture. Manipulation of these pathways provided a synergy sufficient to enhance formation of arterial hemogenic endothelium (HE) relative to control culture conditions. Importantly, this approach significantly increased production of human HSPCs with self-renewal and multilineage differentiation properties, as well as phenotypic and molecular evidence of progressive maturation in culture. Together, these findings provide a stepwise improvement in human iPSC differentiation protocols and offer a framework for manipulating intrinsic cellular cues to enable de novo generation of human HSPCs with functionality in vivo.

Modulation of WNT, Activin/Nodal and MAPK Signaling Pathways Increases Arterial Hemogenic Endothelium and Hematopoietic Stem/Progenitor Cell Formation During Human iPSC Differentiation.

Several differentiation protocols enable the emergence of hematopoietic stem and progenitor cells (HSPCs) from human induced pluripotent stem cells (iPSCs), yet optimized schemes to promote the development of HSPCs with self-renewal, multilineage differentiation and engraftment potential are lacking. To improve human iPSC differentiation methods, we modulated WNT, Activin/Nodal and MAPK signaling pathways by stage-specific addition of small molecule regulators CHIR99021, SB431542 and LY294002, respectively, and measured the impact on hematoendothelial formation in culture. Manipulation of these pathways provided a synergy sufficient to enhance formation of arterial hemogenic endothelium (HE) relative to control culture conditions. Importantly, this approach significantly increased production of human HSPCs with self-renewal and multilineage differentiation properties, as well as phenotypic and molecular evidence of progressive maturation in culture. Together, these findings provide a stepwise improvement in human iPSC differentiation protocols and offer a framework for manipulating intrinsic cellular cues to enable de novo generation of human HSPCs with functionality in vivo . Significance Statement: The ability to produce functional HSPCs by differentiation of human iPSCs ex vivo holds enormous potential for cellular therapy of human blood disorders. However, obstacles still thwart translation of this approach to the clinic. In keeping with the prevailing arterial-specification model, we demonstrate that concurrent modulation of WNT, Activin/Nodal and MAPK signaling pathways by stage-specific addition of small molecules during human iPSC differentiation provides a synergy sufficient to promote arterialization of HE and production of HSPCs with features of definitive hematopoiesis. This simple differentiation scheme provides a unique tool for disease modeling, in vitro drug screening and eventual cell therapies.

Amplitude Spectrum Area of ventricular fibrillation to guide defibrillation: a small open-label, pseudo-randomized controlled multicenter trial.

BACKGROUND: Ventricular fibrillation (VF) waveform analysis has been proposed as a potential non-invasive guide to optimize timing of defibrillation. METHODS: The AMplitude Spectrum Area (AMSA) trial is an open-label, multicenter randomized controlled study reporting the first in-human use of AMSA analysis in out-of-hospital cardiac arrest (OHCA). The primary efficacy endpoint was the termination of VF for an AMSA ≥ 15.5 mV-Hz. Adult shockable OHCAs randomly received either an AMSA-guided cardiopulmonary resuscitation (CPR) or a standard-CPR. Randomization and allocation to trial group were carried out centrally. In the AMSA-guided CPR, an initial AMSA ≥ 15.5 mV-Hz prompted for immediate defibrillation, while lower values favored chest compression (CC). After completion of the first 2-min CPR cycle, an AMSA < 6.5 mV-Hz deferred defibrillation in favor of an additional 2-min CPR cycle. AMSA was measured and displayed in real-time during CC pauses for ventilation with a modified defibrillator. FINDINGS: The trial was early discontinued for low recruitment due to the COVID-19 pandemics. A total of 31 patients were recruited in 3 Italian cities, 19 in AMSA-CPR and 12 in standard-CPR, and included in the data analysis. No difference in primary outcome was observed between the two groups. Termination of VF occurred in 74% of patients in the AMSA-CPR compared to 75% in the standard CPR (OR 0.93 [95% CI 0.18-4.90]). No adverse events were reported. INTERPRETATION: AMSA was used prospectively in human patients during ongoing CPR. In this small trial, an AMSA-guided defibrillation provided no evidence of an improvement in termination of VF. TRIAL REGISTRATION: NCT03237910. FUNDING: European Commission - Horizon 2020; ZOLL Medical Corp., Chelmsford, USA (unrestricted grant); Italian Ministry of Health - Current research IRCCS.

Performance of heart rate adjusted heart rate variability for risk stratification of sudden cardiac death.

PURPOSE: As a non-invasive tool for the assessment of cardiovascular autonomic function, the predictive value of heart rate variability (HRV) for sudden cardiac death (SCD) risk stratification remains unclear. In this study, we investigated the performance of the individualized heart rate (HR) adjusted HRV (HRVI) for SCD risk stratification in subjects with diverse risks. METHODS: A total of 11 commonly used HRV metrics were analyzed in 192 subjects, including 88 healthy controls (low risk group), 82 hypertrophic cardiomyopathy (HCM) patients (medium risk group), and 22 SCD victims (high risk group). The relationship between HRV metrics and HR was examined with long-term and short-term analysis. The performance HRVI was evaluated by area under the receiver operating characteristic curve (AUC) and covariance of variation (CV). RESULTS: Most of the HRV metrics were exponentially decayed with the increase of HR, while the exponential power coefficients were significantly different among groups. The HRVI metrics discriminated low, medium and high risk subjects with a median AUC of 0.72[0.11], which was considerably higher than that of the traditional long-term (0.63[0.04]) and short-term (0.58[0.05]) HRV without adjustment. The average CV of the HRVI metrics was also significantly lower than traditional short-term HRV metrics (0.09 ± 0.02 vs. 0.24 ± 0.13, p < 0.01). CONCLUSIONS: Subjects with diverse risks of SCD had similar exponential decay relationship between HRV metrics and HR, but with different decaying rates. HRVI provides reliable and robust estimation for risk stratification of SCD.

Mitogenome of the leaf-footed bug Notobitus montanus (Hemiptera: Coreidae) and a phylogenetic analysis of Coreoidea.

Notobitus montanus Hsiao, 1963 is a major pest of bamboos. The mitogenome of N. montanus (ON052831) was decoded using next-generation sequencing. The mitogenome, with 42.26% A, 30.54% T, 16.54% C, and 10.65% G, is 16,209 bp in size. Codon usage analysis indicated that high frequently used codons used either A or T at the third position of the codon. Amino acid usage analysis showed that leucine 2, phenylalanine, isoleucine and tyrosine were the most abundant in 31 Coreoidea species. Thirteen protein-coding genes (PCGs) were evolving under purifying selection, nad5 and cox1 had the lowest and strongest purifying selection stress, respectively. Correlation analysis showed that evolutionary rate had positive correlation with A+T content. No tandem repeat was detected in the non-coding region of N. montanus. The phylogenetic tree showed that Alydidae and Coreidae were not monophyletic. However, the topology of phylogenetic trees, based on 13 PCGs, was in accordance with that of tree based on both mitochondrial and nuclear genes but not ultraconserved element loci or combination of 13 PCGs and two rRNAs. It seems that their relationships are complex, which need revaluation and revision. The mitogenomic information of N. montanus could shed light on the evolution of Coreoidea.

De Novo Generation of Human Hematopoietic Stem Cells from Pluripotent Stem Cells for Cellular Therapy.

The ability to manufacture human hematopoietic stem cells (HSCs) in the laboratory holds enormous promise for cellular therapy of human blood diseases. Several differentiation protocols have been developed to facilitate the emergence of HSCs from human pluripotent stem cells (PSCs). Most approaches employ a stepwise addition of cytokines and morphogens to recapitulate the natural developmental process. However, these protocols globally lack clinical relevance and uniformly induce PSCs to produce hematopoietic progenitors with embryonic features and limited engraftment and differentiation capabilities. This review examines how key intrinsic cues and extrinsic environmental inputs have been integrated within human PSC differentiation protocols to enhance the emergence of definitive hematopoiesis and how advances in genomics set the stage for imminent breakthroughs in this field.

Influence of oxygen concentration on the neuroprotective effect of hydrogen inhalation in a rat model of cardiac arrest.

Background: Post-cardiac arrest (CA) brain injury is the main cause of death in patients resuscitated from CA. Previous studies demonstrated that hydrogen inhalation mitigates post-CA brain injury. However, factors affecting the efficacy of hydrogen remain unknown. In the present study, we investigated the influence of oxygen concentration and targeted temperature on neuroprotective effect in a CA rat model of ventricular fibrillation (VF). Methods: Cardiopulmonary resuscitation (CPR) was initiated after 7 min of untreated VF in adult male Sprague-Dawley rats. Immediately following successful resuscitation, animals were randomized to be ventilated with 21% oxygen and 79% nitrogen (21%O2); 2% hydrogen, 21% oxygen, and 77% nitrogen (2%H2 + 21%O2); 2% hydrogen, 50% oxygen, and 48% nitrogen (2%H2 + 50%O2); or 2% hydrogen and 98% oxygen (2%H2 + 98%O2) for 3 h. For each group, the target temperature was 37.5°C for half of the animals and 35.0°C for the other half. Results: No statistical differences in baseline measurements and CPR characteristics were observed among groups. For animals with normothermia, 2%H2 + 50%O2 (123 [369] vs. 500 [393], p = 0.041) and 2%H2 + 98%O2 (73 [66] vs. 500 [393], p = 0.002) groups had significantly lower neurological deficit scores (NDSs) at 96 h and significantly higher survival (75.0 vs. 37.5%, p = 0.033 and 81.3 vs. 37.5%, p = 0.012) than 21%O2 group. For animals with hypothermia, no statistical difference in NDS among groups but 2%H2 + 98%O2 has significantly higher survival than the 21%O2 group (93.8 vs. 56.3%, p = 0.014). Conclusion: In this CA rat model, inhaling 2% hydrogen combined with a high concentration of oxygen improved 96-h survival, either under normothermia or under hypothermia.

Genetic characterization of a novel HIV­1 CRF01_AE/ CRF07_BC recombinant form found among men who have sex with men in Baoding City, Hebei Province, China.

Large numbers of unique recombinant forms (URF) of human immunodeficiency virus (HIV-1) have been found among sexual transmission populations in China. Here, we report a novel second-generation URF of HIV-1 named BD201AQ that was isolated from an HIV-1-positive man who was infected through homosexual transmission in Baoding City, Hebei Province, China. Phylogenetic analysis based on the near-full-length genome (NFLG) sequence indicated that BD201AQ formed a monophyletic branch that did not cluster with other HIV-1 subtypes. Recombination analysis showed that the NFLG of BD201AQ had 12 segments, six CRF07_BC and six CRF01_AE segments, with CRF07_BC as the main framework. These findings indicate that the constant emergence of novel recombinant forms should receive more attention and that more measures should be taken to monitor the molecular epidemiological characteristics of HIV-1 and to prevent the spread of HIV-1 infections.

Complete mitochondrial genome of Liorhyssus hyalinus (Hemiptera: Rhopalidae).

The mitogenome of Liorhyssus hyalinus (Fabricius, 1794), decoded using next-generation sequencing, is the first report of Liorhyssus. The mitogenomic size was 16,355 bp with 41.99% A, 33.44% T, 14.53% C, and 10.05% G (OM328158). The phylogenetic tree, constructed with the amino acid sequences of 13 protein-coding genes, showed that L. hyalinus clustered together with other species in Rhopalidae, which supported the monophyly of each family in Pentatomomorpha.

Large-scale multiplexed mosaic CRISPR perturbation in the whole organism.

Here, we report inducible mosaic animal for perturbation (iMAP), a transgenic platform enabling in situ CRISPR targeting of at least 100 genes in parallel throughout the mouse body. iMAP combines Cre-loxP and CRISPR-Cas9 technologies and utilizes a germline-transmitted transgene carrying a large array of individually floxed, tandemly linked gRNA-coding units. Cre-mediated recombination triggers expression of all the gRNAs in the array but only one of them per cell, converting the mice to mosaic organisms suitable for phenotypic characterization and also for high-throughput derivation of conventional single-gene perturbation lines via breeding. Using gRNA representation as a readout, we mapped a miniature Perturb-Atlas cataloging the perturbations of 90 genes across 39 tissues, which yields rich insights into context-dependent gene functions and provides a glimpse of the potential of iMAP in genome decoding.

Trimetazidine Alleviates Postresuscitation Myocardial Dysfunction and Improves 96-Hour Survival in a Ventricular Fibrillation Rat Model.

Background Myocardial dysfunction is a critical cause of post-cardiac arrest hemodynamic instability and circulatory failure that may lead to early mortality after resuscitation. Trimetazidine is a metabolic agent that has been demonstrated to provide protective effects in myocardial ischemia. However, whether trimetazidine protects against postresuscitation myocardial dysfunction is unknown. Methods and Results Cardiopulmonary resuscitation was initiated after 8 minutes of untreated ventricular fibrillation in Sprague-Dawley rats. Animals were randomized to 4 groups immediately after resuscitation (n=15/group): (1) normothermia control (NTC); (2) targeted temperature management; (3) trimetazidine-normothermia; (4) trimetazidine-targeted temperature management. TMZ was administered at a single dose of 10 mg/kg in rats with trimetazidine. The body temperature was maintained at 34.0°C for 2 hours and then rewarmed to 37.5°C in rats with targeted temperature management. Postresuscitation hemodynamics, 96-hours survival, and pathological analysis were assessed. Heart tissues and blood samples of additional rats (n=6/group) undergoing the same experimental procedure were collected to measure myocardial injury, inflammation and oxidative stress-related biomarkers with ELISA-based quantification assays. Compared with normothermia control, tumor necrosis factor-α, and cardiac troponin-I were significantly reduced, whereas the left ventricular ejection fraction and 96-hours survival rates were significantly improved in the 3 experimental groups. Furthermore, inflammation and oxidative stress-related biomarkers together with collagen volume fraction were significantly decreased in rats undergoing postresuscitation interventions. Conclusions Trimetazidine significantly alleviates postresuscitation myocardial dysfunction and improves survival by decreasing oxidative stress and inflammation in a ventricular fibrillation rat model. A single dose of trimetazidine administrated immediately after resuscitation can effectively improve cardiac function, whether used alone or combined with targeted temperature management.