Programmable RNA sensing for cell monitoring and manipulation.

RNA is a central and universal mediator of genetic information underlying the diversity of cell types and cell states, which together shape tissue organization and organismal function across species and lifespans. Despite numerous advances in RNA sequencing technologies and the massive accumulation of transcriptome datasets across the life sciences1,2, the dearth of technologies that use RNAs to observe and manipulate cell types remains a bottleneck in biology and medicine. Here we describe CellREADR (Cell access through RNA sensing by Endogenous ADAR), a programmable RNA-sensing technology that leverages RNA editing mediated by ADAR to couple the detection of cell-defining RNAs with the translation of effector proteins. Viral delivery of CellREADR conferred specific cell-type access in mouse and rat brains and in ex vivo human brain tissues. Furthermore, CellREADR enabled the recording and control of specific types of neurons in behaving mice. CellREADR thus highlights the potential for RNA-based monitoring and editing of animal cells in ways that are specific, versatile, simple and generalizable across organ systems and species, with wide applications in biology, biotechnology and programmable RNA medicine.

Recent Advances in the Modification and Improvement of Bioprosthetic Heart Valves.

Valvular heart disease (VHD) has become a burden and a growing public health problem in humans, causing significant morbidity and mortality worldwide. An increasing number of patients with severe VHD need to undergo heart valve replacement surgery, and artificial heart valves are in high demand. However, allogeneic valves from donors are lacking and cannot meet clinical practice needs. A mechanical heart valve can activate the coagulation pathway after contact with blood after implantation in the cardiovascular system, leading to thrombosis. Therefore, bioprosthetic heart valves (BHVs) are still a promising way to solve this problem. However, there are still challenges in the use of BHVs. For example, their longevity is still unsatisfactory due to the defects, such as thrombosis, structural valve degeneration, calcification, insufficient re-endothelialization, and the inflammatory response. Therefore, strategies and methods are needed to effectively improve the biocompatibility and longevity of BHVs. This review describes the recent research advances in BHVs and strategies to improve their biocompatibility and longevity.

Epigallocatechin-3-Gallate Inhibits Atrial Fibrosis and Reduces the Occurrence and Maintenance of Atrial Fibrillation and its Possible Mechanisms.

BACKGROUND: Atrial fibrosis is one of the main causes of the onset and recurrence of atrial fibrillation (AF), for which there is no effective treatment. The aim of this study was to investigate the effect and mechanism of epigallocatechin-3-gallate (EGCG) on AF in rats. METHODS: The rat model of AF was established by rapid pacing induction after angiotensin-II (Ang-II) induced atrial fibrosis to verify the relationship between atrial fibrosis and the AF. The expression levels of TGF-ß/Smad3 pathway molecules and lysyl oxidase (LOX) in AF were detected. Subsequently, EGCG was used to intervene Ang-II-induced atrial fibrosis to explore the role of EGCG in the treatment of AF and its inhibitory mechanism on fibrosis. It was further verified that EGCG inhibited the production of collagen and the expression of LOX through the TGF-ß/Smad3 pathway at the cellular level. RESULTS: The results showed that the induction rate and maintenance time of AF in rats increased with the increase of the degree of atrial fibrosis. Meanwhile, the expressions of Col I, Col III, molecules related to TGF-ß/Smad3 pathway, and LOX increased significantly in the atrial tissues of rats in the Ang-II induced group. EGCG could reduce the occurrence and maintenance time of AF by inhibiting the degree of Ang-induced rat atrial fibrosis. Cell experiments confirmed that EGCG could reduce the synthesis of collagen and the expression of LOX in cardiac fibroblast induced by Ang-II. The possible mechanism is to down-regulate the expression of genes and proteins related to the TGF-ß/Smad3 pathway. CONCLUSION: EGCG could downregulate the expression levels of collagen and LOX by inhibiting the TGF-ß/Smad3 signaling pathway, alleviating Ang-II-induced atrial fibrosis, which in turn inhibited the occurrence and curtailed the duration of AF.

Tricuspid valve detachment for ventricular septal defect closure: A meta-analysis of existing evidence.

BACKGROUND: Ventricular septal defect (VSD) is one of the most common congenital cardiac defects. However, in some cases, VSD sites are difficult to expose due to obstruction from chordal attachments and leaflets of the tricuspid valve (TV). To systematically review the efficacy and safety of tricuspid valve detachment, (TVD) versus conventional surgical repair (non-TVD) in the treatment of ventricular septal defect (VSD). This article is aimed to compare the many outcomes from existing studies and provide evidence regarding the necessity of performing TVD. METHODS: We searched the following databases: PubMed via NCBI, the Cochrane Central Register of Controlled Trials (no date restriction), Medline via Ovid (from 1966 to May 2020); Embase via Ovid (no date restriction), and China National Knowledge Infrastructure for studies comparing the efficacy of TVD and other surgical techniques in VSD repair. Cardiopulmonary bypass time, Cross-clamp time; postoperative complications including residual defect, postoperative atrioventricular block, implantation of pacemakers, tricuspid regurgitation; length of stay (LOS), length of intensive care unit (ICU) stay were analyzed. RESULTS: Only nine studies were included after selection, including seven retrospective cohort studies, one respective cohort study, and one prospective observational study, a patient pool of 1404 patients with 374 underwent TVD and 1030 underwent non-TVD procedures, met the inclusion criteria. Meta analysis has drawn to the following conclusions. First, TVD prolongs CPB time (MD = 7.75, 95% confidence interval [CI] = 2.60-12.89, p = .003) and cross-clamp time (MD = 7.77, 95% CI = 4.76-10.78, p < .001) compared with non-TVD techniques in VSD repair surgeries. Second, no significant difference exists in LOS, length of ICU stay, postoperative atrioventricular block, implantation of pacemakers, incidence of ≥mild tricuspid valve regurgitation (TR) postoperatively and at discharge, as well as the incidence of ≥small residual VSD after surgery and during follow-up (all p ＞ .05). Third, application of TVD increases the risk of TR during follow-up (odds ratio [OR] = 2.42, 95% CI = 1.55-3.76, p < .001). CONCLUSION: VSD closure using TVD technique results in longer CPB and cross-clamp time, and increases risk of TR during follow-up. TVD provides equally viable and safe alternative in treating VSD.

Coarctation of aorta combined with multiple aneurysms.

We reported a case of a 53-year-old patient with coarctation of the aorta and multiple aneurysmatic changes on the aortic arch. Enhanced computed tomography and reconstruction revealed significant coarctation and multiple aneurysmatic dilatations. The patient underwent stent implantation and was discharged with symptoms relieved. Follow-up examination progression of aneurysms, however, without symptoms.

Transannular patch repair of tetralogy of Fallot with or without monocusp valve reconstruction: a meta-analysis.

BACKGROUND: Tetralogy of Fallot (TOF) is one of the most common cyanotic congenital heart diseases. Pulmonary regurgitation is the most common and severe comorbidity after transannular patch (TAP) repair of TOF patients. It has not been confirmed whether a TAP repair with monocusp valve reconstruction would benefit TOF patients in perioperative period compared to those without monocusp valve reconstruction. The purpose of the study is to review and analyze all clinical studies that have compared perioperative outcomes of TOF patients undergoing TAP repair with or without monocusp valve reconstruction and conduct a preferable surgery. METHODS: Eligible studies were identified by searching the electronic databases. The year of publication of studies was restricted from 2000 till present. The primary outcome was perioperative mortality, and secondary outcomes included cardiopulmonary bypass time, aortic cross-clamp time, ventilation duration, ICU length of stay, hospital length of stay, perioperative right ventricular outflow tract (RVOT) pressure gradient, and moderate or severe pulmonary regurgitation (PR). The meta-analysis and forest plots were drawn using Review Manager 5.3. Statistically significant was considered when p-value ≤ 0.05. RESULTS: Eight studies were included which consisted of 8 retrospective cohort study and 2 randomized controlled trial. The 10 studies formed a pool of 526 TOF patients in total, in which are 300 undergoing TAP repair with monocusp valve reconstruction (monocusp group) compared to 226 undergoing TAP repair without monocusp valve reconstruction (non-monocusp group). It demonstrated no significant differences between two groups in perioperative mortality (OR = 0.69, 95% CI 0.20-2.41, p = 0.58). It demonstrated significant differences in perioperative cardiopulmonary bypass time (minute, 95% CI 17.93-28.42, p < 0.00001), mean length of ICU stay (day, 95% CI - 2.11-0.76, p < 0.0001), and the degree of perioperative PR (OR = 0.03, 95% CI 0.010.12, p < 0.00001). Significant differences were not found in other secondary outcomes. CONCLUSION: Transannular patch repair with monocusp valve reconstruction have significant advantages on decreasing length of ICU stay and reducing degree of PR for TOF patients. Large, multicenter, randomized, prospective studies which focuse on perioperative outcomes and postoperative differences based on long-term follow-up between TAP repair with and without monocusp valve reconstruction are needed.

The Relationship between Blood Groups and Aortic Dissection.

BACKGROUND: Plenty of diseases have been found having associations with blood types, especially cardiovascular diseases. The purpose of this study was to clarify whether there is a relationship between blood groups and acute aortic dissection. We also further studied the distribution of blood groups in different types of acute aortic dissection. METHODS: A total of 291 patients diagnosed with acute aortic dissection from 2011 to 2018 were enrolled and analyzed retrospectively in this study. The control group consisted of 582 patients who received plastic surgery at West China hospital from 2011 to 2018. First, we analyzed the distribution of blood groups between the study group and the control group, including the ABO, Rh, O and non-O groups. Then, we further divided the study group into two groups by the type of acute aortic dissection to determine if there was difference in blood groups between the two types of acute aortic dissection. RESULTS: The analysis of the distribution of ABO blood groups (p = 0.302) and Rh blood groups (p = 0.502) did not reveal statistically significant differences. There were no statistically significant differences in the distributions of ABO blood groups and Rh blood groups in different types of acute aortic dissection. CONCLUSIONS: Our study did not prove the incidence of acute aortic dissection, or the type of acute aortic dissection had a relationship with common blood groups.

Anomalous aortic origin of the coronary arteries in a 12-year-old male: a case report.

BACKGROUND: Anomalous aortic origin of the coronary artery (AAOCA) is a rare congenital cardiac disease that can cause sudden cardiac death. This condition may be corrected with surgery. Among the different surgical techniques used to correct this malformation, the most common are unroofing and lateral pulmonary translocation. CASE PRESENTATION: Herein, we present a multimodal imaging approach to identifying AAOCA in a 12-year-old male. We also successfully adopted a new operative method, neo-ostium creation combined with lateral pulmonary translocation to correct AAOCA. The detailed imaging and intraoperative data has not been reported in the literature. CONCLUSIONS: Although several surgical methods exist to reverse the complications of AAOCA, we offer an innovative surgical technique that is easier, faster, and effective.

[Effects of Restrictive Transfusion on the Outcome of Mitral Valve Replacement].

OBJECTIVE: To investigate effects of restrictive transfusion on the outcome of mitral valve replacement. METHODS: We selected 120 continuous patients of mitral valve replacement from June 2011 to June 2016. Based on the different blood transfusion strategy,the patients were divided into two groups: liberal blood transfusion group and restrictive blood transfusion strategy group. The blood routine test,liver and kidney function,coagulation function,full examination before blood transfusion,blood types,echocardiography and so on were examined when the patients were admitted to hospital,also the clinical data of perioperative patients were recorded,and blood transfusion volume,major complication and mortality were compared between the two groups. RESULTS: The transfusion volume of red blood cells decreased from (3.2±1.1) to (1.8±1.5) U with restrictive transfusion,the difference was statistically significant (P=0.01),while plasma volume increased from (325.7±96.5) mL to (385.2±86.2) mL (P=0.04). There were differences in major complications between the two groups (39.2% vs. 31.7%,P=0.04),especially for respiratory-related complications such as the proportion of using ventilator >24 h (P=0.03),total time using ventilator (P=0.03),lung infection rate (P=0.04). The restrictive transfusion group had better outcome with less cost of hospitalization. The mortality was not different (P>0.05). CONCLUSION: Restrictive transfusion strategy reduces the incidence of major complications in patients of mitral valve replacement with less cost.

Unveiling genetic links between gut microbiota and asthma: a Mendelian randomization.

Background: Multiple studies suggest a potential connection between the gut microbiome and asthma. Our objective is to use advanced genetic and metagenomic techniques to elucidate the causal relationships and underlying mechanisms between gut microbiota and asthma. Methods: The study utilized comprehensive Linkage Disequilibrium Score Regression (LDSC) and Mendelian randomization (MR) analyses to examine the relationship between 119 gut microbiota genera and asthma, using publicly accessible genome-wide association studies (GWAS). The meta-analysis synthesized summary effect estimates obtained from LDSC, forward MR, and reverse MR. The MiBioGen collaboration, involving 18,340 individuals, identified genetic variations associated with gut bacteria. Asthma data were collected from the UK Biobank, FinnGen, and GERA, encompassing a total of 82,060 cases and 641,049 controls. Results: LDSC analysis revealed significant negative genetic correlations between asthma and RuminococcaceaeUCG004 (Rg = -0.55, p = 7.66 × 10-5) and Subdoligranulum (Rg = -0.35, p = 3.61 × 10-4). Forward MR analysis suggested associations between Butyricicoccus (OR = 0.92, p = 0.01), Turicibacter (OR = 0.95, p = 0.025), Butyrivibrio (OR = 0.98, p = 0.047), and reduced asthma risk. Conversely, Coprococcus2 (OR = 1.10, p = 0.035) and Roseburia (OR = 1.07, p = 0.039) were associated with increased risk. Reverse MR analysis indicated significant associations between genetically predicted asthma and Eubacteriumxylanophilumgroup (Beta = -0.08, p = 9.25 × 10-7), LachnospiraceaeNK4A136group (Beta = -0.05, p = 1.26 × 10-4), and Eisenbergiella (Beta = 0.06, p = 0.015, Rg_P = 0.043). Conclusion: The findings underscore significant genetic correlations and causal relationships between specific gut microbiota and asthma. These insights highlight the potential of gut microbiota as both markers and modulators of asthma risk, offering new avenues for targeted therapeutic strategies.

Genetic associations between gut microbiota and type 2 diabetes mediated by plasma metabolites: a Mendelian randomization study.

Background: Numerous research studies have indicated a possible association between type 2 diabetes (T2DM) and gut microbiota. To explore specific metabolic pathways connecting gut microbiota and T2DM, we employed Mendelian randomization (MR) and linkage disequilibrium score regression (LDSC) techniques. Methods: This research utilized data from genome-wide association studies (GWAS) that are publicly accessible. We evaluated the genetic correlation between gut microbiota and T2DM using LDSC. Causality was primarily determined through the inverse variance weighted (IVW) method. To verify the robustness of our results, we conducted sensitivity analyses using several approaches, including the weighted median, MR-Egger, and MR-PRESSO. We integrated summary effect estimates from LDSC, along with forward and reverse MR, into a meta-analysis for T2DM using various data sources. Additionally, mediation analysis was performed to explore the impact of plasma metabolites on the relationship between gut microbiota and T2DM. Results: Our study indicated a significant genetic correlation between genus RuminococcaceaeUCG005 (Rg = -0.26, Rg_P = 2.07×10-4) and T2DM. Moreover, the forward MR analysis identified genus RuminococcaceaeUCG010 (OR = 0.857, 95% CI 0.795, 0.924; P = 6.33×10-5) and order Clostridiales (OR = 0.936, 95% CI 0.878, 0.997; P = 0.039) as being significantly associated with a decreased risk of T2DM. The analysis also highlighted several plasma metabolites as significant mediators in these relationships, with metabolites like octadecadienedioate (C18:2-DC) and branched chain 14:0 dicarboxylic acid being notably involved. Conclusion: The findings demonstrate a significant impact of gut microbiota on T2DM via plasma metabolites, suggesting potential metabolic pathways for therapeutic targeting. This study enhances our understanding of the microbiota's role in T2DM pathogenesis and supports the development of microbiota-based interventions.

Smoking behaviors, physical activities, pulmonary diseases and COVID-19 severity: A Mendelian randomization study.

Smoking behaviors, physical activities, and pulmonary diseases have been revealed to be associated with COVID-19 severity through observational research. The possible causative effect remains undetermined. To investigate this, we thus carried out a Mendelian randomization (MR) analysis. We chose genetic variants from genome-wide association studies that are strongly linked to 5 exposures related to smoking, 1 exposure related to drinking, 3 levels of physical activity, and 3 pulmonary diseases. The COVID-19 Host Genetics Initiative provided summary-level data for severe COVID-19 (13,769 cases and 1,072,442 noncases), hospitalized COVID-19 (32,519 cases and 2,062,805 noncases), and COVID-19 susceptibility (122,616 cases and 2,475,240 noncases). Univariate and multivariate MR analyses were carried out. Significant associations were found between severe COVID-19 and cigarette smoking per day (OR = 1.357, 95% CI: 1.087-1.694), lifetime smoking index (OR = 2.277, 95% CI: 1.602-3.325), and interstitial lung disease (OR = 1.23, 95% CI: 1.112-1.362), hospitalized COVID-19 and lifetime smoking index (OR = 2.199, 95% CI: 1.738-2.781), smoking initiation (OR = 1.419, 95% CI: 1.230-1.637), and interstitial lung disease (OR = 1.146, 95% CI: 1.082-1.214), as well as COVID-19 susceptibility and lifetime smoking index (OR = 1.39, 95% CI: 1.252-1.543), smoking initiation (OR = 1.235, 95% CI: 1.163-1.311), and duration of vigorous activity per day (OR = 0.733, 95% CI: 0.574-0.935). Duration of vigorous activity per day was suggestively inversely linked to hospitalized COVID-19 (OR = 0.434, 95% CI: 0.221-0.853) and severe COVID-19 (OR = 0.323, 95% CI: 0.123-0.850). The association for lifetime smoking index remained consistent with severe COVID-19, hospitalized COVID-19, and COVID-19 susceptibility in multivariable MR analysis. Genetic liability to lifetime smoking index mediated the interstitial lung disease effects on severe COVID-19 risk (21.0%) and hospitalized COVID-19 risk (14.4%). This study identified several smoking behaviors, duration of vigorous activity per day, and interstitial lung disease that may be causally related to COVID-19 severity.

Hemostatic Interventions and All-Cause Mortality in Hemodynamically Unstable Pelvic Fractures: A Systematic Review and Meta-Analysis.

Objective: To conduct a systematic review and meta-analysis of the all-cause mortality associated with the most commonly used hemostatic treatments in patients with hemodynamically unstable pelvic fractures. Methods: Up to April 30, 2023, we searched PubMed, Embase, Web of Science, and Cochrane, including the references to qualified papers. A meta-analysis was performed on studies that reported odds ratios (ORs) or the number of events needed to calculate them. The PROSPERO registration number was CRD42023421137. Results: Of the 3452 titles identified in our original search, 29 met our criteria. Extraperitoneal packing (EPP) (OR = 0.626 and 95% CI = 0.413-0.949), external fixation (EF) (OR = 0.649 and 95% CI = 0.518-0.814), and arterial embolism (AE) (OR = 0.459 and 95% CI = 0.291-0.724) were associated with decreased mortality. Resuscitative endovascular balloon occlusion of the aorta (REBOA) (OR = 2.824 and 95% CI = 1.594-5.005) was associated with increased mortality. A random effect model meta-analysis of eight articles showed no difference in mortality between patients with AE and patients with EPP for the initial treatments for controlling blood loss (OR = 0.910 and 95% CI = 0.623-1.328). Conclusion: This meta-analysis collectively suggested EF, AE, or EPP as life-saving procedures for patients with hemodynamically unstable pelvic fractures.

Genetic associations between gut microbiota and allergic rhinitis: an LDSC and MR analysis.

Background: Several studies have suggested a potential link between allergic rhinitis (AR) and gut microbiota. In response, we conducted a meta-analysis of Linkage Disequilibrium Score Regression (LDSC) and Mendelian randomization (MR) to detect their genetic associations. Methods: Summary statistics for 211 gut microbiota taxa were gathered from the MiBioGen study, while data for AR were sourced from the Pan-UKB, the FinnGen, and the Genetic Epidemiology Research on Aging (GERA). The genetic correlation between gut microbiota and AR was assessed using LDSC. The principal estimate of causality was determined using the Inverse-Variance Weighted (IVW) method. To assess the robustness of these findings, sensitivity analyses were conducted employing methods such as the weighted median, MR-Egger, and MR-PRESSO. The summary effect estimates of LDSC, forward MR and reverse MR were combined using meta-analysis for AR from different data resources. Results: Our study indicated a significant genetic correlation between genus Sellimonas (Rg = -0.64, p = 3.64 × 10-5, Adjust_P = 3.64 × 10-5) and AR, and a suggestive genetic correlation between seven bacterial taxa and AR. Moreover, the forward MR analysis identified genus Gordonibacter, genus Coprococcus2, genus LachnospiraceaeUCG010, genus Methanobrevibacter, and family Victivallaceae as being suggestively associated with an increased risk of AR. The reverse MR analysis indicated that AR was suggestively linked to an increased risk for genus Coprococcus2 and genus RuminococcaceaeUCG011. Conclusion: Our findings indicate a causal relationship between specific gut microbiomes and AR. This enhances our understanding of the gut microbiota's contribution to the pathophysiology of AR and lays the groundwork for innovative approaches and theoretical models for future prevention and treatment strategies in this patient population.

Specific and comprehensive genetic targeting reveals brain-wide distribution and synaptic input patterns of GABAergic axo-axonic interneurons.

Axo-axonic cells (AACs), also called chandelier cells (ChCs) in the cerebral cortex, are the most distinctive type of GABAergic interneurons described in the neocortex, hippocampus, and basolateral amygdala (BLA). AACs selectively innervate glutamatergic projection neurons (PNs) at their axon initial segment (AIS), thus may exert decisive control over PN spiking and regulate PN functional ensembles. However, the brain-wide distribution, synaptic connectivity, and circuit function of AACs remains poorly understood, largely due to the lack of specific and reliable experimental tools. Here, we have established an intersectional genetic strategy that achieves specific and comprehensive targeting of AACs throughout the mouse brain based on their lineage (Nkx2.1) and molecular (Unc5b, Pthlh) markers. We discovered that AACs are deployed across essentially all the pallium-derived brain structures, including not only the dorsal pallium-derived neocortex and medial pallium-derived hippocampal formation, but also the lateral pallium-derived claustrum-insular complex, and the ventral pallium-derived extended amygdaloid complex and olfactory centers. AACs are also abundant in anterior olfactory nucleus, taenia tecta and lateral septum. AACs show characteristic variations in density across neocortical areas and layers and across subregions of the hippocampal formation. Neocortical AACs comprise multiple laminar subtypes with distinct dendritic and axonal arborization patterns. Retrograde monosynaptic tracing from AACs across neocortical, hippocampal and BLA regions reveal shared as well as distinct patterns of synaptic input. Specific and comprehensive targeting of AACs facilitates the study of their developmental genetic program and circuit function across brain structures, providing a ground truth platform for understanding the conservation and variation of a bona fide cell type across brain regions and species.

Specific and comprehensive genetic targeting reveals brain-wide distribution and synaptic input patterns of GABAergic axo-axonic interneurons.

Axo-axonic cells (AACs), also called chandelier cells (ChCs) in the cerebral cortex, are the most distinctive type of GABAergic interneurons described in the neocortex, hippocampus, and basolateral amygdala (BLA). AACs selectively innervate glutamatergic projection neurons (PNs) at their axon initial segment (AIS), thus may exert decisive control over PN spiking and regulate PN functional ensembles. However, the brain-wide distribution, synaptic connectivity, and circuit function of AACs remain poorly understood, largely due to the lack of specific and reliable experimental tools. Here, we have established an intersectional genetic strategy that achieves specific and comprehensive targeting of AACs throughout the mouse brain based on their lineage (Nkx2.1) and molecular (Unc5b, Pthlh) markers. We discovered that AACs are deployed across essentially all the pallium-derived brain structures, including not only the dorsal pallium-derived neocortex and medial pallium-derived hippocampal formation, but also the lateral pallium-derived claustrum-insular complex, and the ventral pallium-derived extended amygdaloid complex and olfactory centers. AACs are also abundant in anterior olfactory nucleus, taenia tecta, and lateral septum. AACs show characteristic variations in density across neocortical areas and layers and across subregions of the hippocampal formation. Neocortical AACs comprise multiple laminar subtypes with distinct dendritic and axonal arborization patterns. Retrograde monosynaptic tracing from AACs across neocortical, hippocampal, and BLA regions reveal shared as well as distinct patterns of synaptic input. Specific and comprehensive targeting of AACs facilitates the study of their developmental genetic program and circuit function across brain structures, providing a ground truth platform for understanding the conservation and variation of a bona fide cell type across brain regions and species.

Whether we are memorising facts or reacting to a loud noise, nerve cells in different brain areas must be able to communicate with one another through precise, meaningful signals. Specialized nerve cells known as interneurons act as "traffic lights" to precisely regulate when and where this information flows in neural circuits. Axo-axonic cells are a rare type of inhibitory interneuron that are thought to be particularly important for controlling the passage of information between different groups of excitatory neurons. This is because they only connect to one key part of their target cell ­ the axon-initial segment ­ where the electrical signals needed for brain communication (known as action potentials) are initiated. Since axo-axonic cells are inhibitory interneurons, this connection effectively allows them to 'veto' the generation of these signals at their source. Although axo-axonic cells have been identified in three brain regions using traditional anatomical methods, there were no 'tags' readily available that can reliably identify them. Therefore, much about these cells remained unknown, including how widespread they are in the mammalian brain. To solve this problem, Raudales et al. investigated which genes are switched on in axo-axonic cells but not in other cells, identifying a unique molecular signature that could be used to mark, record, and manipulate these cells. Microscopy imaging of brain tissue from mice in which axo-axonic cells had been identified revealed that they are present in many more brain areas than previously thought, including nearly all regions of the broadly defined cerebral cortex and even the hypothalamus, which controls many innate behaviors. Axo-axonic cells were also 'wired up' differently, depending on where they were located; for example, those in brain areas associated with memory and emotions had wider-ranging input connections than other areas. The finding of Raudales et al. provide, for the first time, a method to directly track and manipulate axo-axonic cells in the brain. Since dysfunction in axo-axonic cells is also associated with neurological disorders like epilepsy and schizophrenia, gaining an insight into their distribution and connectivity could help to develop better treatments for these conditions.

Precordial pain induced by the isolated cardiac hydatid cyst in interventricular septum: a case report.

BACKGROUND: Human hydatid disease occurs after infection with Echinococcus granulosus, mainly involves liver and lung, while hydatid involves heart is infrequent. A great majority of hydatid diseases could be asymptomatic, and incidentally found through examination. Here, we reported a woman who suffered an isolated cardiac hydatid cyst located at the interventricular septum. CASE PRESENTATION: A 48-year-old woman presented intermittent chest pain was admitted to the hospital. Imaging examination revealed a cyst located at the interventricular septum near the right ventricular apex. Considering medical history, radiological findings and serological results, cardiac hydatid disease was suspected. The cyst was successfully removed, while pathological biopsy confirmed the diagnosis of infection of Echinococcus granulosus. Postoperative course was uneventful, the patient was discharged from hospital without complications. CONCLUSION: For symptomatic cardiac hydatid cyst, surgical resection is necessary to avoid progression of disease. During surgical procedure, appropriate methods to reduce the potential risk of hydatid cyst metastasis are essential. Besides surgery, combined with regular drug therapy is an effective strategy to prevent reappearance.

An injectable conductive hydrogel restores electrical transmission at myocardial infarct site to preserve cardiac function and enhance repair.

Myocardial infarction (MI) leads to massive cardiomyocyte death and deposition of collagen fibers. This fibrous tissue disrupts electrical signaling in the myocardium, leading to cardiac systolic and diastolic dysfunction, as well as arrhythmias. Conductive hydrogels are a promising therapeutic strategy for MI. Here, we prepared a highly water-soluble conductive material (GP) by grafting polypyrrole (PPy) onto non-conductive gelatin. This component was added to the gel system formed by the Schiff base reaction between oxidized xanthan gum (OXG) and gelatin to construct an injectable conductive hydrogel. The prepared self-healing OGGP3 (3 wt% GP) hydrogel had good biocompatibility, elastic modulus, and electrical conductivity that matched the natural heart. The prepared biomaterials were injected into the rat myocardial scar tissue 2 days after MI. We found that the cardiac function of the rats treated with OGGP3 was improved, making it more difficult to induce arrhythmias. The electrical resistivity of myocardial fibrous tissue was reduced, and the conduction velocity of myocardial tissue was increased. Histological analysis showed reduced infarct size, increased left ventricular wall thickness, increased vessel density, and decreased inflammatory response in the infarcted area. Our findings clearly demonstrate that the OGGP3 hydrogel attenuates ventricular remodeling and inhibits infarct dilation, thus showing its potential for the treatment of MI.