5-HT Neurons Integrate GABA and Dopamine Inputs to Regulate Meal Initiation.

Obesity is a growing global health epidemic with limited effective therapeutics. Serotonin (5-HT) is one major neurotransmitter which remains an excellent target for new weight-loss therapies, but there remains a gap in knowledge on the mechanisms involved in 5-HT produced in the dorsal Raphe nucleus (DRN) and its involvement in meal initiation. Using a closed-loop optogenetic feeding paradigm, we showed that the 5-HTDRN→arcuate nucleus (ARH) circuit plays an important role in regulating meal initiation. Incorporating electrophysiology and ChannelRhodopsin-2-Assisted Circuit Mapping, we demonstrated that 5-HTDRN neurons receive inhibitory input partially from GABAergic neurons in the DRN, and the 5-HT response to GABAergic inputs can be enhanced by hunger. Additionally, deletion of the GABAA receptor subunit in 5-HT neurons inhibits meal initiation with no effect on the satiation process. Finally, we identified the instrumental role of dopaminergic inputs via dopamine receptor D2 in 5-HTDRN neurons in enhancing the response to GABA-induced feeding. Thus, our results indicate that 5-HTDRN neurons are inhibited by synergistic inhibitory actions of GABA and dopamine, which allows for the initiation of a meal.

Quantitative assessment of left ventricular myocardial work in patients with different types of atrial fibrillation by non-invasive pressure-strain loop technique.

OBJECTIVE: This study aimed to analyze myocardial work in patients with atrial fibrillation (AF) using a noninvasive pressure strain loop (PSL) technique to provide a basis for the quantitative assessment of left ventricular (LV) systolic function. METHODS: LV myocardial work of 107 AF patients (56 with paroxysmal atrial fibrillation and 51 with persistent atrial fibrillation) and 55 healthy individuals were assessed by the noninvasive PSL and then compared. RESULTS: Global longitudinal strain (GLS) in absolute values, global work index (GWI), global constructive work (GCW), and global work efficiency (GWE) were significantly lower in the AF group than control group, whereas peak strain dispersion (PSD) and global wasted work (GWW) were significantly higher (P < .05). Further subdivision according to the AF type revealed that, compared with the controls, GLS in absolute values and GWE decreased significantly; PSD and GWW increased significantly in the paroxysmal AF group (P < .05). Nevertheless, GWI and GCW were not significantly different between paroxysmal AF and control groups (P > .05). Compared to paroxysmal AF, persistent AF induced a further decrease in absolute GLS and GWE and a further increase in GWW (P < .05), but PSD did not increase further (P > .05). Multiple linear regression analysis showed that GWI and GCW were independently associated with systolic blood pressure. GWW was associated with types of AF and left atrial volume index (LAVI). GWE was correlated with age, types of AF, disease duration, and LAVI. Receiver operating characteristic curve analysis showed that the area under the curve predicting myocardial injury was higher for GWE and GWW than for GLS (area under the curve:  .880,  .846, and  .821, respectively). CONCLUSIONS: Non-invasive PSL can quantitatively assess LV systolic function in patients with different kinds of AF and detect early subclinical myocardial injury in patients with paroxysmal AF. GWE and GWW outperform GLS and LV ejection fraction when assessing myocardial injury. Systolic blood pressure, type of AF, LVAI, disease duration, and age may be associated with myocardial injury in patients with AF.

Multi-slice computed tomographic analysis and identification of remarkable anatomical types of segmental bronchi in bilateral inferior lobes: based on extensive data.

Background: The progress of interventional respiratory medicine necessitates a comprehensive knowledge of the segmental bronchi because of their complexity in branching patterns. Therefore, based on extensive research data, we aimed to examine the anatomical diversity and sex-related variations of the segmental bronchial branching patterns in the bilateral inferior lobes. Methods: Following the exclusion and inclusion criteria, a total of 10,000 participants who underwent multi-slice computed tomography (MSCT) scans from September 2019 to December 2021 at Cheeloo College of Medicine, Shandong University were enrolled in this retrospective study. The computed tomography (CT) data were utilized to generate three-dimensional (3D) and virtual bronchoscopy (VB) simulations of a bronchial tree using the syngo.via post-processing workstation. The distinct bronchial patterns in the bilateral inferior lobes were then found and categorized using the reconstructed images. The proportions of different types of bronchial branches and their sex-related correlations were analyzed by cross-tabulation and chi-square analysis. Results: Our findings primarily identified four types of bronchial branching patterns in the right inferior lobe (RIL), i.e., (B6, B7, B8, B9+10), 71.44%; (B6, B7, B8+9, B10), 16.06%; (B6, B7+8, B9+10), 7.40%; (B6, B7, B8+9+10), 5.10%; and four types in the left inferior lobe (LIL), i.e., (B6, B7+8, B9+10), 82.89%; (B6, B7+8, B9, B10), 13.53%; (B6, B7, B8+9, B10), 2.88%; (B6, B7, B8+9+10), 0.70%. Besides various research methods and outcomes, this study has revealed the types of bronchial branches that were not seen in previous studies. In addition, the proportion of bronchial branches in the LIL did not differ significantly between males and females (P>0.05). However, there was a significant difference in the proportion of bronchial branches in the RIL between sexes (P<0.05). Conclusions: The current study has validated the segmental bronchial variations in the bilateral inferior lobes. The diagnosis of symptomatic patients as well as the performance of interventions like bronchoscopies, endotracheal intubation, and lung resections may be significantly influenced by our findings in the clinical setting.

Leptin signaling and its central role in energy homeostasis.

Leptin plays a critical role in regulating appetite, energy expenditure and body weight, making it a key factor in maintaining a healthy balance. Despite numerous efforts to develop therapeutic interventions targeting leptin signaling, their effectiveness has been limited, underscoring the importance of gaining a better understanding of the mechanisms through which leptin exerts its functions. While the hypothalamus is widely recognized as the primary site responsible for the appetite-suppressing and weight-reducing effects of leptin, other brain regions have also been increasingly investigated for their involvement in mediating leptin's action. In this review, we summarize leptin signaling pathways and the neural networks that mediate the effects of leptin, with a specific emphasis on energy homeostasis.

Evaluation of Left Atrial Function in Patients with Paroxysmal Atrial Fibrillation Using Left Atrial Automatic Myocardial Functional Imaging Ultrasonography.

Aim: To evaluate volume and strain of the left atrium (LA) in people suffering from paroxysmal atrial fibrillation which is not valvular (NVPAF) using the new technology of left atrial automatic myocardial function imaging (AFILA) and to analyze prognostic factors in patients with NVPAF by follow-up. Methods: Between August 2019 and August 2022, a total of 80 NVPAF patients and 60 normal control patients who were hospitalized in the Department of Cardiology were included in the study. The LA volume and strain parameters of the two groups were analyzed. The differences in LA function (LAF) parameters were compared between the two groups to generate the receiver operating characteristic curve (ROC) and calculate the area under the curve (AUC), sensitivity, and specificity of each parameter. Follow-up was conducted on the 80 NVPAF patients included, their treatment methods after admission and their rehospitalization due to heart events were recorded, and independent risk factors influencing the prognosis of NVPAF were obtained. Results: A total of 140 patients participated in the study, including 80 in the NVPAF group and 60 in the normal control group. There was no statistically significant difference in age and sex between the two groups. Compared to the normal group, the LA minimum volume (LAVmin), LA maximum volume (LAVmax), and volume at onset of LA contraction (LAVpreA) in the NVPAF group were significantly increased. The LA emptying fraction (LAEF) was significantly decreased, and LA reservoir strain (S_R), LA conduit strain (S_CD), and LA contractile strain (S_CT) were significantly compromised (P < 0.05). There was no significant difference in LA evacuation volume (LAEV) reduction (P > 0.05). Logistic regression analysis of LAF parameters in NVPAF patients showed that LAEF and S_R were independently correlated with NVPAF (odds ratio values: 0.883 (0.827-0.943), P < 0.001; 0.916 (0.569-1.474), P = 0.047). The ROC curve results showed that LAEF had a high efficiency in the diagnosis of NVPAF, with P < 0.001, AUC of 0.843, sensitivity of 0.788, and specificity of 0.867. For the LA strain parameters, the S_R test efficiency was higher, with P < 0.001, AUC of 0.762, sensitivity of 0.713, and specificity of 0.783. There was a strong correlation between S_R and LAEF in patients with no end event and those with end event. The ROC curve revealed that the S_R was better than LAEF in predicting prognosis of patients with AF (AUC = 0.914, P < 0.0001 vs. AUC = 0.876, P < 0.0001). S_R of 10.5 and LAEF of 21 were the cut-off values for endpoint events in NVPAF patients, with sensitivity of 0.909 and 0.727 and specificity of 0.904 and 0.901, respectively. Conclusions: AFILA ultrasound technology comprehensively evaluated the LA size and function in patients with NVPAF. The LAEF and S_R were independently correlated with NVPAF and can determine the prognosis of patients with NVPAF.

A dimensionality-reduction genomic prediction method without direct inverse of the genomic relationship matrix for large genomic data.

KEY MESSAGE: A new genomic prediction method (RHPP) was developed via combining randomized Haseman-Elston regression (RHE-reg), PCR based on genomic information of core population, and preconditioned conjugate gradient (PCG) algorithm. Computational efficiency is becoming a hot issue in the practical application of genomic prediction due to the large number of data generated by the high-throughput genotyping technology. In this study, we developed a fast genomic prediction method RHPP via combining randomized Haseman-Elston regression (RHE-reg), PCR based on genomic information of core population, and preconditioned conjugate gradient (PCG) algorithm. The simulation results demonstrated similar prediction accuracy between RHPP and GBLUP, and significantly higher computational efficiency of the former with the increase of individuals. The results of real datasets of both bread wheat and loblolly pine demonstrated that RHPP had a similar or better predictive accuracy in most cases compared with GBLUP. In the future, RHPP may be an attractive choice for analyzing large-scale and high-dimensional data.

Genome-Wide Identification and Characterization of the PP2C Family from Zea mays and Its Role in Long-Distance Signaling.

The protein phosphatase 2C (PP2C) constitutes a large gene family that plays crucial roles in regulating stress responses and plant development. A recent study has shown the involvement of an AtPP2C family member in long-distance nitrogen signaling in Arabidopsis. However, it remains unclear whether maize adopts a similar mechanism. In this study, we conducted a genome-wide survey and expression analysis of the PP2C family in maize. We identified 103 ZmPP2C genes distributed across 10 chromosomes, which were further classified into 11 subgroups based on an evolutionary tree. Notably, cis-acting element analysis revealed the presence of abundant hormone and stress-related, as well as nitrogen-related, cis-elements in the promoter regions of ZmPP2Cs. Expression analysis demonstrated the distinct expression patterns of nine genes under two nitrogen treatments. Notably, the expression of ZmPP2C54 and ZmPP2C85 in the roots was found to be regulated by long-distance signals from the shoots. These findings provide valuable insights into understanding the roles of ZmPP2Cs in long-distance nitrogen signaling in maize.

Use of left atrial automated functional myocardial imaging to identify patients with paroxysmal atrial fibrillation at high risk of stroke.

Background: Left atrial automated functional myocardial imaging (AFILA) is a new software program for analyzing the structure and function of the left atrium (LA). The present study sought to analyze the correlation between the LA function parameters as measured by AFILA echocardiography and the risk of cerebral ischemic stroke (CIS) in patients with non-valvular paroxysmal atrial fibrillation (NVPAF) to explore the diagnostic value of LA strain in patients with congestive heart failure, hypertension, age of ≥75 years (doubled), diabetes mellitus, stroke or transient ischemic attack (TIA) (doubled), age of 65-74 years, and sex category (female) (CHA2DS2-VASc) scores of <2. Methods: A total of 205 patients with NVPAF were included in the study and divided into the no-CIS group (154 patients) and the CIS group (51 patients). The baseline clinical data for the 2 groups were analyzed, and routine echocardiography examinations were performed. AFILA was used to evaluate the LA function of all the patients. Results: Compared to the no-CIS group, the LA emptying fraction and the LA reservoir strain were decreased, the LA contractile strain (S_CT) was increased, and the S_CT value changed from negative to positive in the CIS group, and the difference between the 2 groups were statistically significant (P<0.001). However, there were no significant differences in the volume at the onset of LA contraction, LA evacuation volume, LA minimum volume, LA maximum volume, and LA conduit strain between the 2 groups. The multifactorial regression analysis showed that age, hypertension, and the S_CT were independently associated risk factors for patients with CIS. After correcting for the clinical factors included in the CHA2DS2-VASc score, the S_CT was shown to predict to NVPAF with stroke [odds ratio (OR): 1.234, 95% confidence interval (CI): 1.101-1.383, P=0.000]. In addition, we included the CHA2DS2-VASc score (instead of age, diabetes, coronary artery disease, and hypertension) in a multiple regression analysis, and found that the S_CT was still significant (OR: 1.252, 95% CI: 1.118-1.402, P=0.000). The difference between the 2 groups in the CHA2DS2-VASc score for the S_CT was statistically significant, especially when the CHA2DS2-VASc score was <2. The S_CT equaled -4.5% was the cut-off value for the presence or absence of CIS in the NVPAF patients, with an area under the curve (AUC) of 0.866, sensitivity of 0.80, and specificity of 0.75 (P<0.0001). Conclusions: Comparison with LA volume parameter, measuring LA strain by AFILA provides a better index for the dynamic assessment of impaired LA function in patients with NVPAF combined with CIS, especially in those with a CHA2DS2-VASc score of <2. In addition, a LA S_CT of >-4.5% is a valuable cut-off for patients with NVPAF. The results of the current study may form the basis for a large prospective multicenter interventional study in which patients with impaired LA S_CT are randomized to receive oral anti-coagulant (OAC) therapy or no OAC therapy for the primary prevention of stroke.

Multi-slice CT Analysis and Identification of Anatomical Types of Segmental Bronchi in Right Superior Lobe.

PURPOSE: The aims were to assess different branching patterns of segmental bronchi in the right superior lobe (RSL), as well as to investigate the anatomical diversity and sex-related variations of these branches in a large sample of the research population. METHODS: 10,000 participants (5428 males, and 4,572 females, mean age 50+/-13.5 years [SD] years; age range: 3-91 years) who underwent multi-slice CT (MSCT) scans from September 2019 to December 2021 were retrospectively included. The data were applied to generate three-dimensional (3D) and virtual bronchoscopy (VB) simulations of a bronchial tree using the syngo.via post-processing workstation. Following that, the reconstructed images were interpreted to identify and categorize various bronchial patterns in the RSL. Cross-tabulation analysis and the Pearson chi-square test (χ2) were used to calculate the component ratios of bronchial branch types and determine their relevance between male and female groups. RESULTS: Our results revealed mainly six types for the RSL bronchial tree, i.e., (B1, B2, B3, 60.70%); (B1+2, B3, 18.72%); (B2+3, B1, 6.68%); (B1+3, B2, 7.57%); (B1, B2, B3, B*, 3.19%); (B1a+B3, B1b+B2, 3.14%). There were significant sex-related differences in the proportion of bronchial branches in the RSL (P< 0.05). CONCLUSION: The current study has validated the presence of segmental bronchial variations in the RSL. These findings may have significant implications for diagnosing symptomatic patients and performing particular procedures, including bronchoscopy, endotracheal intubation, and lung resection.

Identification of anatomical types of segmental bronchi in left superior and lingular lobes using multi-slice CT.

PURPOSE: The objectives of this study were to evaluate various branching patterns of segmental bronchi in the left superior and lingular lobes and to survey the anatomical diversity and sex-related differences of these branches in a large sample of the study population. MATERIALS AND METHODS: Overall, 10,000 participants (5428 males, and 4572 females, mean age 50 ± 13.5 years [SD] years; age range: 3-91 years) who underwent multi-slice CT (MSCT) scans between September 2019 and December 2021 were retrospectively included. Using the syngo.via post-processing workstation, the data were applied to generate three-dimensional (3D) and virtual bronchoscopy (VB) simulations of a bronchial tree. The reconstructed images were then interpreted to identify and categorize distinct bronchial patterns in the left superior and lingular lobes. Cross-tabulation analysis and the Pearson Chi-square (χ2) test were used to calculate the constituent ratios of bronchial branch types and determine their significance between male and female groups. RESULTS: Our results revealed mainly four distinct types for the left superior lobe (LSL) bronchial tree, i.e., (B1 + 2, B3, 76.13%); (B1 + 2 + 3, 17.32%); (B1 + 3, B2, 5.74%); (B1a + B3, B1b + B2, 0.81%) and two types for the left lingular lobe (LLL) bronchial tree, i.e., (B4, B5, 91.05%); (B4, B5, B*, 8.95%). There were no significant sex-related differences in the proportion of bronchial branches in LLL (P > 0.05). However, sex-related differences were significant in the proportion of bronchial branches in LSL (P < 0.05). CONCLUSION: The current study has validated the presence of segmental bronchial variations in the left superior and lingular lobes. These findings may have a crucial effect on the diagnosis of symptomatic patients, as well as in carrying out procedures such as lung resections, endotracheal intubation, and bronchoscopies.

Anoctamin 4 channel currents activate glucose-inhibited neurons in the mouse ventromedial hypothalamus during hypoglycemia.

Glucose is the basic fuel essential for maintenance of viability and functionality of all cells. However, some neurons - namely, glucose-inhibited (GI) neurons - paradoxically increase their firing activity in low-glucose conditions and decrease that activity in high-glucose conditions. The ionic mechanisms mediating electric responses of GI neurons to glucose fluctuations remain unclear. Here, we showed that currents mediated by the anoctamin 4 (Ano4) channel are only detected in GI neurons in the ventromedial hypothalamic nucleus (VMH) and are functionally required for their activation in response to low glucose. Genetic disruption of the Ano4 gene in VMH neurons reduced blood glucose and impaired counterregulatory responses during hypoglycemia in mice. Activation of VMHAno4 neurons increased food intake and blood glucose, while chronic inhibition of VMHAno4 neurons ameliorated hyperglycemia in a type 1 diabetic mouse model. Finally, we showed that VMHAno4 neurons represent a unique orexigenic VMH population and transmit a positive valence, while stimulation of neurons that do not express Ano4 in the VMH (VMHnon-Ano4) suppress feeding and transmit a negative valence. Together, our results indicate that the Ano4 channel and VMHAno4 neurons are potential therapeutic targets for human diseases with abnormal feeding behavior or glucose imbalance.

Identification of anatomical types of segmental bronchi in right middle lobe using multi-slice CT.

PURPOSE: The objectives of this study were to evaluate the various branching patterns of segmental bronchi in the right middle lobe (RML) and to survey the anatomical diversity and sex-related differences of these branches in a large sample of the study population. MATERIALS AND METHODS: In this retrospective board-approved study with informed consent, 10,000 participants (5428 males and 4,572 females, mean age 50 ± 13.5 years [SD]; age range: 3-91 years) who underwent multi-slice CT (MSCT) scans from September 2019 to December 2021 were retrospectively included. The data were applied to generate three-dimensional (3D) and virtual bronchoscopy (VB) simulations of a bronchial tree using the syngo.via post-processing workstation. The reconstructed images were then interpreted to locate and classify distinct bronchial patterns in the RML. Cross-tabulation analysis and the Pearson chi-square test were used to calculate the constituent ratios of bronchial branch types and determine their significance between male and female groups. RESULTS: Our results revealed that the segmental bronchial ramifications of the RML were classified into two types mainly, i.e., bifurcation (B4, B5, 91.42%) and trifurcation (B4, B5, B*, 8.58%). There were no significant sex-related differences in the proportion of bronchial branches in the RML (P > 0.05). CONCLUSION: The current study has confirmed the presence of segmental bronchial variations in the RML lobe using 3D reconstruction and virtual bronchoscopy. These findings may have significant implications for the diagnosis of symptomatic patients and for carrying out specific procedures like bronchoscopy, endotracheal intubation, and lung resection.

Multifunctional Droplets Formed by Interfacially Self-Assembled Fluorinated Magnetic Nanoparticles for Biocompatible Single Cell Culture and Magnet-Driven Manipulation.

The ability to encapsulate and manipulate droplets with a picoliter volume of samples and reagents shows great potential for practical applications in chemistry, biology, and materials science. Magnetic control is a promising approach for droplet manipulation due to its ability for wireless control and its ease of implementation. However, it is challenged by the poor biocompatibility of magnetic materials in aqueous droplets. Moreover, current droplet technology is problematic because of the molecule leakage between droplets. In the paper, we propose multifunctional droplets with the surface coated by a layer of fluorinated magnetic nanoparticles for magnetically actuated droplet manipulation. Multifunctional droplets show excellent biocompatibility for cell culture, nonleakage of molecules, and high response to a magnetic field. We developed a strategy of coating the F-MNP@SiO2 on the outer surface of droplets instead of adding magnetic material into droplets to enable droplets with a highly magnetic response. The encapsulated bacteria and cells in droplets did not need to directly contact with the magnetic materials at the outer surface, showing high biocompatibility with living cells. These droplets can be precisely manipulated based on magnet distance, the time duration of the magnetic field, the droplet size, and the MNP composition, which well match with theoretical analysis. The precise magnetically actuated droplet manipulation shows great potential for accurate and sensitive droplet-based bioassays like single cell analysis.

Hypothalamic Grb10 enhances leptin signalling and promotes weight loss.

Leptin acts on hypothalamic neurons expressing agouti-related protein (AgRP) or pro-opiomelanocortin (POMC) to suppress appetite and increase energy expenditure, but the intracellular mechanisms that modulate central leptin signalling are not fully understood. Here we show that growth factor receptor-bound protein 10 (Grb10), an adaptor protein that binds to the insulin receptor and negatively regulates its signalling pathway, can interact with the leptin receptor and enhance leptin signalling. Ablation of Grb10 in AgRP neurons promotes weight gain, while overexpression of Grb10 in AgRP neurons reduces body weight in male and female mice. In parallel, deletion or overexpression of Grb10 in POMC neurons exacerbates or attenuates diet-induced obesity, respectively. Consistent with its role in leptin signalling, Grb10 in AgRP and POMC neurons enhances the anorexic and weight-reducing actions of leptin. Grb10 also exaggerates the inhibitory effects of leptin on AgRP neurons via ATP-sensitive potassium channel-mediated currents while facilitating the excitatory drive of leptin on POMC neurons through transient receptor potential channels. Our study identifies Grb10 as a potent leptin sensitizer that contributes to the maintenance of energy homeostasis by enhancing the response of AgRP and POMC neurons to leptin.

Human loss-of-function variants in the serotonin 2C receptor associated with obesity and maladaptive behavior.

Serotonin reuptake inhibitors and receptor agonists are used to treat obesity, anxiety and depression. Here we studied the role of the serotonin 2C receptor (5-HT2CR) in weight regulation and behavior. Using exome sequencing of 2,548 people with severe obesity and 1,117 control individuals without obesity, we identified 13 rare variants in the gene encoding 5-HT2CR (HTR2C) in 19 unrelated people (3 males and 16 females). Eleven variants caused a loss of function in HEK293 cells. All people who carried variants had hyperphagia and some degree of maladaptive behavior. Knock-in male mice harboring a human loss-of-function HTR2C variant developed obesity and reduced social exploratory behavior; female mice heterozygous for the same variant showed similar deficits with reduced severity. Using the 5-HT2CR agonist lorcaserin, we found that depolarization of appetite-suppressing proopiomelanocortin neurons was impaired in knock-in mice. In conclusion, we demonstrate that 5-HT2CR is involved in the regulation of human appetite, weight and behavior. Our findings suggest that melanocortin receptor agonists might be effective in treating severe obesity in individuals carrying HTR2C variants. We suggest that HTR2C should be included in diagnostic gene panels for severe childhood-onset obesity.

SK3 in POMC neurons plays a sexually dimorphic role in energy and glucose homeostasis.

BACKGROUND: Pro-opiomelanocortin (POMC) neurons play a sexually dimorphic role in body weight and glucose balance. However, the mechanisms for the sex differences in POMC neuron functions are not fully understood. RESULTS: We detected small conductance calcium-activated potassium (SK) current in POMC neurons. Secondary analysis of published single-cell RNA-Seq data showed that POMC neurons abundantly express SK3, one SK channel subunit. To test whether SK3 in POMC neurons regulates POMC neuron functions on energy and glucose homeostasis, we used a Cre-loxP strategy to delete SK3 specifically from mature POMC neurons. POMC-specific deletion of SK3 did not affect body weight in either male or female mice. Interestingly, male mutant mice showed not only decreased food intake but also decreased physical activity, resulting in unchanged body weight. Further, POMC-specific SK3 deficiency impaired glucose balance specifically in female mice but not in male mice. Finally, no sex differences were detected in the expression of SK3 and SK current in total POMC neurons. However, we found higher SK current but lower SK3 positive neuron population in male POMC neurons co-expressing estrogen receptor α (ERα) compared to that in females. CONCLUSION: These results revealed a sexually dimorphic role of SK3 in POMC neurons in both energy and glucose homeostasis independent of body weight control, which was associated with the sex difference of SK current in a subpopulation of POMC + ERα + neurons.

Diagnosis of fetal congenitally unguarded tricuspid valve orifice by echocardiography.

OBJECTIVE: To review the imaging characteristics and evaluate the diagnostic value of echocardiography for fetal congenitally unguarded tricuspid valve orifice (CUTVO). METHODS: Doppler echocardiography was performed and the images were compared with operative and necropsy findings in ten fetuses with CUTVO. The aim of the study was to summarize the characteristics of fetal echocardiography and analyze the causes of missed diagnoses and misdiagnoses. RESULTS: There were six cases with complete absence (60%) and four cases with partial absence of the tricuspid leaflet (40%). Among all cases, six cases were consistent with the ultrasonic diagnosis. CUTVO ultrasonographic characteristics consist of the atrioventricular connection with normal arteries and the tricuspid valve device partially or completely absent. The annulus of the tricuspid valve can be described as "empty" in the apical four-chamber view, Doppler evaluation shows to-and-fro flow across the tricuspid orifice with low velocity and two-way spectrum. CONCLUSION: Fetal echocardiography can accurately diagnose CUTVO, but missed diagnosis and misdiagnosis should be reduced.

Gabra5 plays a sexually dimorphic role in POMC neuron activity and glucose balance.

Pro-opiomelanocortin (POMC) neurons are important for the regulation of body weight and glucose balance. The inhibitory tone to POMC neurons is mediated primarily by the GABA receptors. However, the detailed mechanisms and functions of GABA receptors are not well understood. The α5 subunit of GABAA receptor, Gabra5, is reported to regulate feeding, and we found that Gabra5 is highly expressed in POMC neurons. To explore the function of Gabra5 in POMC neurons, we knocked down Gabra5 specifically from mature hypothalamic POMC neurons using the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 strategy. This POMC-specific knock-down of Gabra5 did not affect body weight or food intake in either male or female mice. Interestingly, the loss of Gabra5 caused significant increases in the firing frequency and resting membrane potential, and a decrease in the amplitude of the miniature inhibitory postsynaptic current (mIPSC) in male POMC neurons. However, the loss of Gabra5 only modestly decreased the frequency of mIPSC in female POMC neurons. Consistently, POMC-specific knock-down of Gabra5 significantly improved glucose tolerance in male mice but not in female mice. These results revealed a sexually dimorphic role of Gabra5 in POMC neuron activity and glucose balance, independent of body weight control.

Changes in and asymmetry of the proteome in the human fetal frontal lobe during early development.

Inherent hemispheric asymmetry is important for cognition, language and other functions. Describing normal brain and asymmetry development during early development will improve our understanding of how different hemispheres prioritize specific functions, which is currently unknown. Here, we analysed developmental changes in and asymmetry of the proteome in the bilateral frontal lobes of three foetal specimens in the late first trimester of pregnancy. We found that during this period, the difference in expression between gestational weeks (GWs) increased, and the difference in asymmetric expression decreased. Changes in the patterns of protein expression differed in the bilateral frontal lobes. Our results show that brain asymmetry can be observed in early development. These findings can guide researchers in further investigations of the mechanisms of brain asymmetry. We propose that both sides of the brain should be analysed separately in future multiomics and human brain mapping studies.