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Neural circuit function is shaped both by the cell types that comprise the circuit and the connections between those cell types1. Neural cell types have previously been defined by morphology2, 3, electrophysiology4, 5, transcriptomic expression6–8, connectivity9–13, or even a combination of such modalities14–16. More recently, the Patch-seq technique has enabled the characterization of morphology (M), electrophysiology (E), and transcriptomic (T) properties from individual cells17–20. Using this technique, these properties were integrated to define 28, inhibitory multimodal, MET-types in mouse primary visual cortex21. It is unknown how these MET-types connect within the broader cortical circuitry however. Here we show that we can predict the MET-type identity of inhibitory cells within a large-scale electron microscopy (EM) dataset and these MET-types have distinct ultrastructural features and synapse connectivity patterns. We found that EM Martinotti cells, a well defined morphological cell type22, 23known to be Somatostatin positive (Sst+)24, 25, were successfully predicted to belong to Sst+ MET-types. Each identified MET-type had distinct axon myelination patterns and synapsed onto specific excitatory targets. Our results demonstrate that morphological features can be used to link cell type identities across imaging modalities, which enables further comparison of connectivity in relation to transcriptomic or electrophysiological properties. Furthermore, our results show that MET-types have distinct connectivity patterns, supporting the use of MET-types and connectivity to meaningfully define cell types.

As part of the ATLAS experiment’s Phase-II Upgrade, improved trigger hardware and algorithms will be implemented onto a single-level architecture. The global trigger (GT) subsystem is a new firmware (FW)-focused project designed to meet stringent requirements from the high-luminosity runs of the large hadron collider (LHC). The global multiplexer (MUX) is the input aggregating stage of the GT; it performs three main tasks: 1) aggregating data from several sources, connected with more than 2300 input fibers, under different protocols; 2) time-multiplexing the incoming data, to sort the packets per bunch-crossing (BC) events, by compensating the relative skews across the various serial input channels; and 3) transmitting, in a round-robin fashion, the sorted BC data to the global event processor (GEP) array, which is the following stage of the GT subsystem and is composed of 48 nodes, each one processing a single BC event. Two MUX FW prototypes for the Global Feature EXtractor (gFEX, part of the liquid argon calorimeter trigger) inputs have been designed, implemented, and validated on a gFEX production board, for up to 72 input and output channels. A four-channel version has been completed with I/O interfaces and validated in a full-chain design, accepting 8b/10b encoded inputs at 11.2 Gb/s and transmitting at 25.78125 Gb/s under Xilinx Aurora 64b/66b protocol. The total latency has been benchmarked in all of its contributing subcomponents and proven to meet the requirements from the Technical Design Report for the Phase-II Upgrade of the trigger and data acquisition system.

Our study aims to determine whether sarcopenia is a predictive factor of future hip fractures. Systematic review and meta-analysis. We searched for potentially suitable articles in PubMed, Cochrane library, Medline and EMBASE from inception to March 2020. The quality of the research was assessed by the Newcastle-Ottawa Scale (NOS). Finally, a meta-analysis was conducted with the Stata software. Older community-dwelling residents. Hip fracture due to sarcopenia. We retrieved 2129 studies through our search strategy, and five studies with 23,359 individuals were analyzed in our pooled analyses. Sarcopenia increases the risk of future hip fractures with a pooled hazard ratio (HR) of 1.42 (95% CI: 1.18–1.71, P

Purpose Radiotherapy is the main treatment method for patients with locally advanced, unresectable esophageal cancer. The aim of this study is to compare overall survival (OS) using 3D radiotherapy (3DRT) alone with concurrent chemoradiotherapy (CCRT) in 296 non-surgical esophageal carcinoma patients. Patents and methods Over 10 years, of the 480 patients with esophageal carcinoma treated with 3DRT with or without chemotherapy, 148 patients each comprised 3DRT and CCRT groups after propensity score matching. Results The 5- and 10-year OS (P = 0.337) and PFS (P = 0.715) rates for 3DRT alone were 22.0%, 14.4% and 26.1%, 23.2%, respectively, compared with 28.8%, 18.6% and 34.7%, 29.1% for CCRT, respectively. CCRT did not improve 5-year and 10-year OS or PFS in 60–70 Gy group (OS: 27.5% and 25.2%; 17.9% and 17.0%, P = 0.938; PFS: 38.3% and 31.8%; 31.9% and 27.8%, P = 0.890) nor reduce 10-year hematogenous metastasis (31.7% and 28.3%, P = 0.698). CCRT improved 5-year OS and PFS of 50.0–59.9 Gy group (OS: 33.3% and 12.0%, P = 0.029; PFS: 33.1% and 10.6%, P = 0.081). For 3DRT, the 5-year OS and PFS rates were significantly better in the 60–70 Gy group (P = 0.017) compared with 50.0–59.9 Gy group (P = 0.002). For CCRT group, 5-year OS and PFS favored the 50.0–59.9 Gy group, but the difference was insignificant. Major toxicities were greater with CCRT compared with 3DRT. Conclusion For non-surgical esophageal carcinoma patients, 3DRT combined with CCRT was effective in prolonging both OS and PFS.

Whether individuals with autism spectrum disorders (ASDs) have a higher-than-expected risk of cancer remains unknown.We carried out a population-based cohort study including 2.3 million individuals live-born to mothers from Nordic countries during 1987-2013 in Sweden with follow-up through 2016 (up to age 30 years). Individuals with ASD were ascertained through the Swedish National Patient Register. We estimated the relative risk of cancer in relation to ASD by odds ratios (ORs) and associated 95% confidence intervals (CIs) derived from logistic regression, after detailed adjustment for potential confounders. We also carried out a sibling comparison to address familial confounding and a genetic correlation analysis using the genome-wide association study summary statistics to address confounding due to potential polygenetic pleiotropy between ASD and cancer.We observed an overall increased risk of any cancer among individuals with ASD (OR 1.3, 95% CI 1.2-1.5), compared with individuals without ASD. The association for any cancer was primarily noted for narrowly defined autistic disorder (OR 1.7, 95% CI 1.3-2.1) and ASD with comorbid birth defects (OR 2.1, 95% CI 1.5-2.9) or both birth defects and intellectual disability (ID; OR 4.8, 95% CI 3.4-6.6). An association was also suggested for ASD with comorbid ID (OR 1.4; 95% CI 0.9-2.1), but was not statistically significant. ASD alone (i.e. without comorbid ID or birth defects) was not associated with an increased risk of any cancer (OR 1.0, 95% CI 0.8-1.2). Sibling comparison and genetic correlation analysis showed little evidence for familial confounding or confounding due to polygenetic pleiotropy between ASD and cancer.ASD per se is not associated with an increased risk for cancer in early life. The increased cancer risk among individuals with ASD is likely mainly attributable to co-occurring ID and/or birth defects in ASD.

Little is known about long-term sequelae of COVID-19.To describe the consequences at 4 months in patients hospitalized for COVID-19.In a prospective uncontrolled cohort study, survivors of COVID-19 who had been hospitalized in a university hospital in France between March 1 and May 29, 2020, underwent a telephone assessment 4 months after discharge, between July 15 and September 18, 2020. Patients with relevant symptoms and all patients hospitalized in an intensive care unit (ICU) were invited for further assessment at an ambulatory care visit.Survival of hospitalization for COVID-19.Respiratory, cognitive, and functional symptoms were assessed by telephone with the Q3PC cognitive screening questionnaire and a checklist of symptoms. At the ambulatory care visit, patients underwent pulmonary function tests, lung computed tomographic scan, psychometric and cognitive tests (including the 36-Item Short-Form Health Survey and 20-item Multidimensional Fatigue Inventory), and, for patients who had been hospitalized in the ICU or reported ongoing symptoms, echocardiography.Among 834 eligible patients, 478 were evaluated by telephone (mean age, 61 years [SD, 16 years]; 201 men, 277 women). During the telephone interview, 244 patients (51%) declared at least 1 symptom that did not exist before COVID-19: fatigue in 31%, cognitive symptoms in 21%, and new-onset dyspnea in 16%. There was further evaluation in 177 patients (37%), including 97 of 142 former ICU patients. The median 20-item Multidimensional Fatigue Inventory score (n = 130) was 4.5 (interquartile range, 3.0-5.0) for reduced motivation and 3.7 (interquartile range, 3.0-4.5) for mental fatigue (possible range, 1 [best] to 5 [worst]). The median 36-Item Short-Form Health Survey score (n = 145) was 25 (interquartile range, 25.0-75.0) for the subscale "role limited owing to physical problems" (possible range, 0 [best] to 100 [worst]). Computed tomographic lung-scan abnormalities were found in 108 of 171 patients (63%), mainly subtle ground-glass opacities. Fibrotic lesions were observed in 33 of 171 patients (19%), involving less than 25% of parenchyma in all but 1 patient. Fibrotic lesions were observed in 19 of 49 survivors (39%) with acute respiratory distress syndrome. Among 94 former ICU patients, anxiety, depression, and posttraumatic symptoms were observed in 23%, 18%, and 7%, respectively. The left ventricular ejection fraction was less than 50% in 8 of 83 ICU patients (10%). New-onset chronic kidney disease was observed in 2 ICU patients. Serology was positive in 172 of 177 outpatients (97%).Four months after hospitalization for COVID-19, a cohort of patients frequently reported symptoms not previously present, and lung-scan abnormalities were common among those who were tested. These findings are limited by the absence of a control group and of pre-COVID assessments in this cohort. Further research is needed to understand longer-term outcomes and whether these findings reflect associations with the disease.

The authors construct a M-shaped double superconducting dome and reveal the correlation between the CDW order and superconductivity in the Kagome metal RbV${}_{3}$Sb${}_{5}$.

The dissolved carbon concentration, which is responsible for aquatic ecosystem productivity and water quality, is tightly coupled with hydrological processes. Excess dissolved carbon may exacerbate eutrophication and hypoxia in aquatic ecosystems and lead to deterioration of water quality. Storm events dominate the dynamics of dissolved carbon concentrations, and this nonlinear behavior exhibits significant time scale dependence. Here, we identified inter- and intra-event variability in the dissolved carbon concentration-discharge (C-Q) relationship in an agriculture-intensive catchment. The driving factors of C-Q hysteresis patterns for dissolved inorganic carbon (DIC) and organic carbon (DOC) were quantified by redundancy analysis combined with hierarchical partitioning. At the inter-event scale, DIC exhibited mainly clockwise hysteresis, indicating an exhaustible, proximal source (e.g., groundwater). However, DOC hysteresis was generally counter-clockwise, indicating distal and plentiful sources (e.g., soil water) in the agricultural catchment. Hierarchical partitioning showed that total rainfall, peak discharge and flood intensity explained 28.38% of the total variation in C-Q hysteresis for DIC and 39.87% for DOC at the inter-event scale. At the intra-event scale, time series analysis of dissolved carbon concentration and discharge indicated the interconversion of supply limitation to transport limitation, which depends on the activation of the specific DIC or DOC source zones. These findings provide significant insights into understanding the dynamics of dissolved carbon during storm periods and are important for targeted watershed management practices aimed at reducing carbon loading to surface waters.

BACKGROUND Despite its high contagiousness, high recurrence rate and potential for malignant transformation, effective treatments for condyloma acuminatum (CA) have not yet been developed. Accordingly, it is necessary to clarify the mechanisms underlying CA development. AIM To investigate the expression and significance of the proteins Wnt-1 and TSLC1 in patients with CA and in normal foreskin controls. METHODS Wnt-1 and TSLC1 were assessed by immunohistochemistry in 45 patients with CA. RESULTS Positive expression rates of Wnt-1 and TSLC1 were 82.22% (37/45) and 37.78% (17/45), respectively, in CA tissues, and 29.17% (7/24) and 91.67% (22/24), respectively, in normal foreskin controls. Wnt-1 expression intensity in CA was markedly higher (positive to strongly positive) than that in normal controls (negative to weakly positive), whereas TSLC1 expression intensity ranged from weakly positive to positive in CA, and nearly strongly positive in the normal control group. The differences in the positive expression rate and expression intensity of Wnt-1 and TSLC1 between the two groups were statistically significant (P

Activated biochar has been used in various areas, i.e., wastewater treatment. However, biochar contains volatile organic compounds, some of which are toxic organic pollutants that pose health risks to human. In this study, activated biochar was prepared by pyrolysis method using rice husks as raw materials and H2O as the activator. The volatile organic compound concentration of biochar before and after activation, as well as the adsorption characteristics of activated biochar, was investigated. The structure of the biochar was characterized by FTIR, SEM, and specific surface area analyzer. The results showed that activated biochar surface was mainly composed of carboxyl groups, and no phenolic hydroxyl or lactone groups formed during the process. In total, 54 volatile organic compounds were analyzed by a gas chromatography–mass spectrometer. The detection frequency of 45 volatile organic compounds reached 100%. The concentration of sum of these compounds was 93.26 and 110.62 μg/g in the biochar before and after activation, respectively. Results of adsorption experiments showed that the adsorption and resolution of activated biochar to n-hexane were 29.33 and 5.4 mg/g, respectively. Compared to the biochar sample without activation, the activated biochar with the ratio of charcoal to water of 3:1 showed the best adsorption to n-hexane, whose surface area reached 351.23 m2/g.

OBJECTIVE: To explore the value of Glasgow Coma Scale (GCS) score and CT score combined with serum S100B protein level for evaluation of injury severity and predicting early prognosis of acute traumatic brain injury (TBI). METHODS: A total of 108 patients with TBI admitted within 24 h after injury in the Emergency Department of West China Hospital from May, 2019 to May, 2020 were enrolled in this study. The clinical data, laboratory test results, CT examination, GCS score, Full Outline of Unresponsiveness score, Fisher CT classification, Rotterdam CT score, and serum S100B protein level of the patients were collected upon admission. The patients were followed up for 28 days and divided based on their Glasgow Outcome Scale (GOS) scores into poor prognosis group (GOS 1-3) and good prognosis group (GOS 4-5). The indexes related to poor prognosis were analyzed for their efficacy for predicting the patinets' prognosis. According to the results of head CT, the patients were divided into CT(-) positive (CT(+)) group and CT(-) negative (CT(-)) group, and the efficacy of serum S100B protein level for predicting CT positivity was evaluated. RESULTS: Compared with those with favorable prognosis, the patients with poor prognosis had significantly lower GCS scores (P < 0.01) and higher Rotterdam CT score and serum S100B protein levels (P < 0.01). Among the 3 index, serum S100B protein level had the highest AUC value (0.79); among the combined indexes, GCS score combined with serum S100B protein had the highest AUC value (0.80). Serum S100B protein level was significantly higher in CT(+) group than in CT - group (P < 0.05) with a significant correlation with Rotterdam CT score (r=0.26, P < 0.01). CONCLUSION: Serum S100B protein level, GCS score, and Rotterdam CT score can be used as indicators for evaluating the severity of acute TBI, and they are all closely related with early prognosis of the patients. The combination of serum S100B protein, GCS score and Rotterdam CT score has better performance than any of the 3 indexes alone for predicting early prognosis of the patients. Serum S100B protein level is correlated with head imaging findings of patients with acute TBI, but its value in selection of appropriate imaging modalities awaits further investigation.

CsV_{3}Sb_{5} is a newly discovered Z_{2} topological kagome metal showing the coexistence of a charge-density-wave (CDW)-like order at T^{*}=94 K and superconductivity (SC) at T_{c}=2.5 K at ambient pressure. Here, we study the interplay between CDW and SC in CsV_{3}Sb_{5} via measurements of resistivity, dc and ac magnetic susceptibility under various pressures up to 6.6 GPa. We find that the CDW transition decreases with pressure and experience a subtle modification at P_{c1}≈0.6-0.9 GPa before it vanishes completely at P_{c2}≈2 GPa. Correspondingly, T_{c}(P) displays an unusual M-shaped double dome with two maxima around P_{c1} and P_{c2}, respectively, leading to a tripled enhancement of T_{c} to about 8 K at 2 GPa. The obtained temperature-pressure phase diagram resembles those of unconventional superconductors, illustrating an intimated competition between CDW-like order and SC. The competition is found to be particularly strong for the intermediate pressure range P_{c1}≤P≤P_{c2} as evidenced by the broad superconducting transition and reduced superconducting volume fraction. The modification of CDW order around P_{c1} has been discussed based on the band structure calculations. This work not only demonstrates the potential to raise T_{c} of the V-based kagome superconductors, but also offers more insights into the rich physics related to the electron correlations in this novel family of topological kagome metals.

冠状动脉微血管疾病是诸多心血管事件的高风险因素，然因其隐蔽性高、病因复杂，目前对其的病理生理机制认识十分有限，极大地限制了其的临床诊疗。在冠状动脉微血管疾病发生发展的过程中，冠状动脉微血管内皮细胞（CMEC）的损伤是核心环节，CMEC的应激、代谢、炎症等功能紊乱与冠状动脉微血管疾病具有因果关系，亦是冠状动脉微血管疾病早期的主要特征。目前，有关CMEC功能损伤的机制尚未完全阐明，该文主要综述了CMEC功能紊乱机制研究的进展，以期加深临床医师对这一复杂的病理生理过程的理解以及为后续研究提供一些参考。.

Aim To evaluate the theme trends and knowledge structure of multifetal pregnancy reduction (MPR)-related literature by using bibliometric analysis. Methods Published scientific papers regarding MPR were retrieved from the PubMed database. Data extraction and statistics were conducted using Bibliographic Item Co-Occurrence Matrix Builder (BICOMB). Furthermore, gCLUTO software was used in the study for bi-clustering analysis and strategic diagram analysis. Results According to the search strategy, 906 total papers were included. Among all the extracted MeSH terms, 41 high frequency ones were identified and hotspots were clustered into four categories. In the strategic diagram, research on intrauterine treatment of MPR was most well developed. In contrast, statistical data on the sequelae of fetal reduction surgery and applications of MPR in assisted reproductive technologies were relatively immature. Conclusion The analysis of common terms among the high-frequency network terms in multiparous pregnancy reduction can help researchers and clinicians understand the hotspots, key topics, and issues to be discovered on MPR. Research on intrauterine treatment of MPR was most well developed.

Autonomous inflow control devices (AICDs) represent a successful technology utilized in maximizing reservoir sweep and increased oil recovery. They are an evolutionary enhancement over the passive inflow control device (ICD) such as a nozzle or helix type, which have a choke that is fixed for the lifetime of the well. This paper discusses a technique which accelerated the AICD development from defining the operational parameters to delivering a fully functional product, while considering the various mechanical and hydraulic loads that are critical in providing robustness during operations. Due to limited space availability between the AICD sub-assembly, basepipe dimensions, and complex loading conditions, iterative designs were established to meet the operational parameters. Simulations using finite element analysis (FEA) facilitated the development via performance evaluation of each design under various load conditions. The FEA simulation results provided the direction to refine, optimize and finalize the design. Mechanical loads evaluated in the simulations included: tension, torque, bending, and impact shock, while hydraulic loads included: collapse, burst, and injection pressure. On finalizing the design, the simulation results were validated with prototype testing. The final design met the operational parameters through FEA, that enabled the successful development of the product, saving more than 50% of a typical development cycle time. The FEA simulations provided stress information of each feature, modelling the anticipated loading during the service life, which contributed to the improved robustness and complex features reliability. Prototype test samples were manufactured based on the final design. A full range of validation tests were conducted to validate the final design of the simulation model and to establish appropriate operational limitations of the AICD assembly when subjected to various loads. A leak test was performed before and after the applicable tests to verify that a leak path had not developed. At the conclusion of every test, each AICD element (manufactured from tungsten carbide) was inspected for damage to verify the device had not failed. The test results proved the final design could achieve or exceed the minimum requirements under various load conditions using the simulation technique that accelerated the development process. This design has been used as the basis for various other sizes, with a similar mounting system, which have been successfully deployed in field applications. The use of this technique significantly accelerated the development process. It involved several design iterations and FEA simulations to evaluate various designs throughout the development cycle. FEA has been applied as a value adding tool to guide design optimization, which has been verified by testing, to successfully anticipate the loadings as per operational parameters. In addition to the shortened development process, the validation test development cost was significantly minimized, using FEA, and a robust product was delivered. The validation test results aligned with the FEA predictions.

To explore the potential correlation between endothelin 1 (EDN1) gene polymorphisms with preeclampsia (PE).The single nucleotide polymorphisms (SNPs) of 248 PE patients and 232 healthy controls were genotyped by Polymerase Chain Reaction (PCR). The possible association between EDN1 polymorphisms and PE was revealed through the t-test and the Chi-square test.PE risk was significantly correlated with the C allele of polymorphism rs5370 in EDN1. The polymorphism rs5370 in EDN1 was remarkably associated with the onset of severe PE, rather than mild PE. The markedly increased risk of early-onset PE was related to the C allele of polymorphism rs5370 in EDN1, while no significant difference in the allele frequency of polymorphism rs1800541 was detected between the PE group and the control group. In the co-dominant model, the CC genotype of polymorphism rs5370 in EDN1 was associated with the increased PE risk. PE risk in the population carrying TC genotype was 1.59 times higher than those with TT/CC genotype, while polymorphism rs1800541 had no apparent association with PE risk. In the severe PE group, there was an evident difference in the genotype frequency between the dominant and over-dominant models of polymorphism rs5370. In the recessive model, the raised risk of early-onset PE was notably correlated with the TT/CC genotype compared with that of TT genotype. However, no evident association with the genotype frequency of polymorphism rs1800541 was observed between PE patients and controls.EDN1 gene polymorphism rs5370 is correlated with the increased risk of PE.

In December 2019, novel coronavirus pneumonia epidemic occurred in Wuhan, Hubei Province, and spread rapidly across the country. In the early stages of the epidemic, China adopted the containment strategy and implemented a series of core measures around this strategic point, including social mobilization, strengthening case isolation and close contacts tracking management, blocking epidemic areas and traffic control to reduce personnel movements and increase social distance, environmental measures and personal protection, with a view to controlling the epidemic as soon as possible in limited areas such as Wuhan. This article summarizes the background, key points and core measures in the country and provinces. It sent prospects for future prevention and control strategies.2019年12月，湖北武汉市发生新型冠状病毒肺炎疫情，并迅速向全国蔓延。在疫情发生初期，我国采用围堵策略，并围绕此策略要点实施一系列核心措施，包括社会动员、加强病例隔离和密切接触者追踪管理、封锁疫区和交通管控以减少人员流动、增加人际距离、环境卫生措施以及个人防护等，以期尽快将疫情控制在武汉等有限地区。本文对围堵策略实施的背景、主要内容、以及核心措施进行了概述，分析了我国现阶段实施的围堵策略及核心措施的公共卫生意义，并基于措施效果的全面评价与疫情发展的态势评估提出下一步考虑建议。.

In order to assess environmental exposure-associated human health risk of dioxin compounds for the population in the vicinity of a municipal solid waste incinerator (MSWI) in Shanghai, the atmospheric samples (n = 24) and soils samples (n = 96) were collected and analyzed to obtain the concentration level, pollution characteristics and seasonal changes of dioxin compounds in environmental medias. The toxicity equivalent concentration range of 2,3,7,8-substituted polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) was 30.9–409 fg WHO-TEQ·m−3 in atmosphere and 0.362–8.55 ng WHO-TEQ·kg−1 in soil. The non-carcinogenic health risk and carcinogenic health risk from PCDD/Fs environmental exposure of people living in the vicinity of the MSWI in Shanghai were all within the allowable range of the US Environmental Protection Agency, which implied that the MSWI in Shanghai did not produce additional risk for the population living in its vicinity.

Current-induced magnetization switching (CIMS) via the spin-orbit torque is technologically important for applications of spintronic devices. Existing experimental studies are focused on 5d heavy metals with large spin-orbit coupling but theoretical studies indicate that 3d or 4d light metals with weak spin-orbit coupling may also generate sizable torque through the strong orbital Hall effect. However, CIMS has seldom been experimentally demonstrated using 3d or 4d light metals. Here, we report sizable current-induced torque and a robust CIMS in weakly spin-orbit coupled Zr based perpendicular magnetized multilayers. Current-induced effective torque field changes its sign as the Zr layer thickness varies, indicating the competition of multiple effects. Possible roles of the orbital Hall effect in the competition are discussed. Our findings widen the material scope of the CIMS and imply possible applications of the orbital Hall effect.

Solid-state fermentation has been used to improve the nutritive value of feed ingredients. In the present study, we investigated the effects of solid-state fermented wheat bran (FWB) on growth performance and apparent digestibility in broiler chickens. We measured the growth performance (ADFI, ADG, feed conversion, livability, and European performance efficiency factor) over 38 d in chicks fed a corn-soybean meal control diet (CON) or CON plus wet FWB (25 g/kg [T1]; 50 g/kg [T2]); or T1 plus 3 g/kg (T3); or T2 plus 6 g/kg (T4) soybean oil). The same diets were used to determine nutrient availability in chicks aged 20 d. Regression equations for AME and AMEn were obtained using 20-day-old chicks fed either the corn-soybean meal basal diet only or basal diet partially substituted with 50, 150, or 300 g/kg DM FWB. Diets containing 25 or 50 g/kg wet FBW did not affect the growth performance of broiler chickens, nor the apparent DM, energy, and nitrogen digestibility of the feeds, compared with the control diets (all P > 0.05). Further supplementation with oil did not improve the growth performance of broiler chickens compared with controls or chickens fed FBW. However, chickens fed diets containing soybean oil (T3 or T4) had lower (P = 0.005 and P = 0.040, respectively) apparent DM and energy digestibility than the control and FWB groups. The regression equations for AME and AMEn with the substitution of FWB produced values of 1,854.3 and 1,743.9 kcal/kg DM, respectively, and the equations were Y = 1854.3X + 52.7 (R2 = 0.971, n = 24, P < 0.001), and Y = 1743.9X + 44.6 (R2 = 0.978, n = 24, P < 0.001), respectively. Supplementation with wet FWB did not affect the growth performance of broiler chickens. Therefore, FWB is a suitable feed component for broilers.

BACKGROUND Left ventricular non-compaction cardiomyopathy (LVNC) is a congenital cardiomyopathy, characterized by excessive ventricular trabeculation, with a ‘spongy’ appearance of the myocardium, deep intertrabecular recesses, and a thin compacted myocardial layer. LVNC has recently gained more attention because it has been increasingly recognized as a cause of heart failure, thromboembolism, or ventricular arrhythmia, which can all lead to sudden cardiac death. However, due to its heterogeneous anatomical and clinical features, LVNC is still a poorly understood condition. In addition, LVNC is suggested to be due to a premature arrest in the myocardial compaction process, but its genetic basis and pathologic mechanism remain largely unknown. METHODS AND RESULTS Here we introduce novel genetic factors implicated in ventricular compaction. Specifically, combinatorial loss of two Iroquois homeobox (Irx) transcription factors, Irx3, critical for development and function of the ventricular conduction system (e.g., His-bundle, bundle branches and Purkinje fibers) and Irx4, essential for establishing ventricular identity, recapitulates the clinical hallmarks of LVNC in mice. While mice lacking either Irx3 or Irx4 do not exhibit gross congenital cardiac malformations, mice lacking both Irx3 and Irx4 (Irx3;Irx4DKO) show postnatal lethality with abnormal muscular growths that resemble the polypoid pattern of LVNC, characterized by multiple muscular nodes in the left ventricle. Optical projection tomography in postnatal day 14 (P14) mutant hearts unveiled increased trabeculation, abnormal bridging below the papillary muscles, and disorganized muscle structures (Fig. 1). During embryogenesis, Irx3 and Irx4 exhibit overlapping expression in the developing ventricles. Consistent with the hypothesis that LVNC can be caused by a defect in embryonic heart growth, Irx3;Irx4DKO embryonic hearts showed abnormal trabeculation with thinner ventricular walls as early as E14.5. RNA sequencing on E14.5 Irx3;Irx4DKO ventricles revealed altered ventricular identity with atrial gene activation and enriched Bmp2/Tbx2 pathway that is critical for endocardial cushion development by suppressing cardiomyocyte differentiation. Moreover, co-immunoprecipitation discovered that Irx4 physically interacts with Irx3 and Gata4, and promoter assay further showed that Irx3, Irx4, and Gata4 synergistically suppress Tbx2 promoter activity, suggesting the repressive role of this transcriptional regulatory complex in the developing myocardium. CONCLUSION Our study demonstrates a novel mechanistic interaction of Irx3 and Irx4, in cooperation with Gata4, during the ventricular compaction process, thereby ensuring proper ventricular development. This finding can promote improvement of genetic testing for LVNC and prediction of individual outcomes with LVNC.