A novel ZRS variant causes preaxial polydactyly type I by increased sonic hedgehog expression in the developing limb bud.

PurposePreaxial polydactyly (PPD) is a common congenital hand malformation classified into four subtypes (PPD I-IV). Variants in the zone of polarizing activity regulatory sequence (ZRS) within intron 5 of the LMBR1 gene are linked to most PPD types. However, the genes responsible for PPD I and the underlying mechanisms are unknown.MethodsA rare large four-generation family with isolated PPD I was subjected to genome-wide genotyping and sequence analysis. In vitro and in vivo functional studies were performed in Caco-2 cells, 293T cells, and a knockin transgenic mouse model.ResultsA novel g.101779T>A (reference sequence: NG_009240.2; position 446 of the ZRS) variant segregates with all PPD I-affected individuals. The knockin mouse with this ZRS variant exhibited PPD I phenotype accompanying ectopic and excess expression of Shh. We confirmed that HnRNP K can bind the ZRS and SHH promoters. The ZRS mutant enhanced the binding affinity for HnRNP K and upregulated SHH expression.ConclusionOur results identify the first PPD I disease-causing variant. The variant leading to PPD I may be associated with enhancing SHH expression mediated by HnRNP K. This study adds to the ZRS-associated syndromes classification system for PPD and clarifies the underlying molecular mechanisms

Wide azimuth seismic data processing technology and application: a case study of tight gas reservoirs in western China

As the difficulty of oil and gas field exploration and development increases both domestically and internationally, onshore exploration targets have gradually shifted from the shallow to the deep and from conventional oil and gas reservoirs to unconventional ones. Particularly in the exploration and development of unconventional oil and gas horizontal wells, there is an increasing demand for higher precision and quality of seismic data to better identify formation lithology, rock fractures, and improve the characterization of reservoirs, reservoir positioning, and connectivity. Wide-azimuth seismic exploration possesses significant technical advantages in addressing exploration challenges such as lithologic exploration, small fault imaging, and detailed characterization of oil and gas reservoirs. Wide azimuth seismic data reduces blind spots in seismic acquisition and improves the imaging accuracy of small faults. Notably, there exist distinct anisotropic characteristics in fault areas and fractured reservoirs. Wide azimuth seismic data is particularly advantageous for studying amplitude variation with variations in amplitude with offset (AVO), incident angle (AVA), or azimuth (AVAZ), as well as velocity with azimuth (VVA). These variations aid in identifying faults, fractures, and changes in formation lithology. As the focus of oil and gas exploration gradually shifts to complex lithological reservoirs and unconventional oil and gas reservoirs, narrow azimuth seismic exploration has been gradually replaced by wide azimuth exploration. However, as observation azimuth increases, challenges related to velocity variations with azimuth, azimuth-related traveltime differences, and azimuth-related anisotropy arise. Based on wide-azimuth seismic data from tight gas reservoirs in western China, this study conducted wide-azimuth anisotropic velocity analysis, OVT domain data regularization processing, OVT domain prestack time/depth migration, and horizontally transverse isotropy (HTI) azimuth anisotropy correction techniques. After applying specialized processing to the wide-azimuth seismic data, significant improvements were observed in the S/N and resolution of the target layer. The delineation of fractures related to hydrocarbon sources also became more distinct. These advancements not only provided high-quality results for high-fidelity, high-resolution imaging of tight gas reservoirs but also provided azimuth volume corresponding to fast and slow wave velocities for seismic data interpretation, facilitating velocity variation with azimuth (VVAZ) fracture detection and AVO analysis research

Dielectric Screening in Perovskite Photovoltaics

The performance of perovskite photovoltaics is fundamentally impeded by the presence of undesirable defects that contribute to non-radiative losses within the devices. Although mitigating these losses has been extensively reported by numerous passivation strategies, a detailed understanding of loss origins within the devices remains elusive. Here, we demonstrate that the defect capturing probability estimated by the capture cross-section is decreased by varying the dielectric response, producing the dielectric screening effect in the perovskite. The resulting perovskites also show reduced surface recombination and a weaker electron-phonon coupling. All of these boost the power conversion efficiency to 22.3% for an inverted perovskite photovoltaic device with a high open-circuit voltage of 1.25 V and a low voltage deficit of 0.37 V (a bandgap similar to 1.62 eV). Our results provide not only an in-depth understanding of the carrier capture processes in perovskites, but also a promising pathway for realizing highly efficient devices via dielectric regulation

Human cell types important for Hepatitis C Virus replication in vivo and in vitro. Old assertions and current evidence

Hepatitis C Virus (HCV) is a single stranded RNA virus which produces negative strand RNA as a replicative intermediate. We analyzed 75 RT-PCR studies that tested for negative strand HCV RNA in liver and other human tissues. 85% of the studies that investigated extrahepatic replication of HCV found one or more samples positive for replicative RNA. Studies using in situ hybridization, immunofluorescence, immunohistochemistry, and quasispecies analysis also demonstrated the presence of replicating HCV in various extrahepatic human tissues, and provide evidence that HCV replicates in macrophages, B cells, T cells, and other extrahepatic tissues. We also analyzed both short term and long term in vitro systems used to culture HCV. These systems vary in their purposes and methods, but long term culturing of HCV in B cells, T cells, and other cell types has been used to analyze replication. It is therefore now possible to study HIV-HCV co-infections and HCV replication in vitro

Minimizing non-radiative recombination losses in perovskite solar cells

Photovoltaic solar cells based on metal halide perovskites have gained considerable attention over the past decade because of their potentially low production cost, earth-abundant raw materials, ease of fabrication and ever-increasing power conversion efficiencies of up to 25.2%. This type of solar cells offers the promise of generating electricity at a more competitive unit price than traditional fossil fuels by 2035. Nevertheless, the best research cell efficiencies are still below the theoretical limit defined by the Shockley-Queissier theory owing to the presence of non-radiative recombination losses. In this Review, we analyse the predominant pathways that contribute to non-radiative recombination losses in perovskite solar cells, and evaluate their impact on device performance. We then discuss how non-radiative recombination losses can be estimated through reliable characterization techniques, and highlight some notable advances in mitigating these losses, which hint at pathways towards defect-free perovskite solar cells. Finally, we outline directions for future work that will push the efficiency of perovskite solar cells towards the radiative limit

Energy Flow Analysis of Excavator System Based on Typical Working Condition Load

Accurate energy flow results are the premise of excavator energy-saving control research. Only through an accurate energy flow analysis based on operating data can a practical excavator energy-saving control scheme be proposed. In order to obtain the excavator’s accurate energy flow, the excavator components’ performance and operating data requirements are obtained, and the experimental schemes are designed to collect it under typical working conditions. The typical working condition load is reconstructed based on wavelet decomposition, harmonic function, and theoretical weighting methods. This paper analyzes the excavator system’s energy flow under the typical working condition load. In operation conditions, the output energy of the engine only accounts for 50.21% of the engine’s fuel energy, and the actuation and the swing system account for 9.33% and 4%, respectively. In transportation conditions, the output energy of the engine only accounts for 49.80% of the engine’s fuel energy, and the torque converter efficiency loss and excavator driving energy account for 15.09% and 17.98%, respectively. The research results show that the energy flow analysis method based on typical working condition load can accurately obtain each excavator component’s energy margin, which provides a basis for designing energy-saving schemes and control strategies

Energy Flow Analysis of Excavator System Based on Typical Working Condition Load

Accurate energy flow results are the premise of excavator energy-saving control research. Only through an accurate energy flow analysis based on operating data can a practical excavator energy-saving control scheme be proposed. In order to obtain the excavator’s accurate energy flow, the excavator components’ performance and operating data requirements are obtained, and the experimental schemes are designed to collect it under typical working conditions. The typical working condition load is reconstructed based on wavelet decomposition, harmonic function, and theoretical weighting methods. This paper analyzes the excavator system’s energy flow under the typical working condition load. In operation conditions, the output energy of the engine only accounts for 50.21% of the engine’s fuel energy, and the actuation and the swing system account for 9.33% and 4%, respectively. In transportation conditions, the output energy of the engine only accounts for 49.80% of the engine’s fuel energy, and the torque converter efficiency loss and excavator driving energy account for 15.09% and 17.98%, respectively. The research results show that the energy flow analysis method based on typical working condition load can accurately obtain each excavator component’s energy margin, which provides a basis for designing energy-saving schemes and control strategies

The preclinical pharmacological study of a novel intravenous anesthetic, ET-26 hydrochloride, in aged rats

Background ET-26 hydrochloride (ET-26HCl) is a novel analogue of etomidate approved for clinical trials. However, all results from recent studies were accomplished in young adult animals. The objective of this study was to evaluate the efficacy and safety of ET-26HCl in aged rats. Methods Aged Sprague-Dawley rats were randomly divided into three groups (three males and three females in each group) were given dose of two-fold of median effective dose (ED50) of ET-26HCl, etomidate and propofol: the measurements of loss of the righting reflex (LORR) and cardiovascular and respiratory function after injection at the two-fold dose of the median effective dose were used for evaluation of effectiveness and safety, and the modified adrenocorticotropic hormone-stimulation experiment was used to evaluate the inhibition effect of the drugs on the synthesis of adrenal cortical hormones. Results There was no significant difference in the onset time among propofol, etomidate and ET-26HCl. The duration of propofol (850.5 ± 77.4 s) was significantly longer than that caused by etomidate (489.8 ± 77.0 s, p = 0.007) and ET-26HCl (347.3 ± 49.0 s, p = 0.0004). No significant difference was observed in the time to stand and normal activity among drugs. A total of 66.7% of rats in the ET-26HCl group were evaluated to have mild hematuria. Then, etomidate and ET-26HCl had a milder blood pressure inhibition effect than propofol. Apnea was observed in all rats administered propofol and the duration for this side effect was 45.0 ± 9.0 s. For etomidate and ET-26HCl, no apnea was observed. No other clinical signs of side-effect were observed, and no rats died. No significant difference was observed in corticosterone concentrations between ET-26HCl and solvent group. However, rats administered etomidate had lower corticosterone concentrations than those administered ET-26HCl at 15, 30, and 60 min. Conclusions Our results indicate ET-26HCl in aged rats is an effective sedative-hypnotic with stable myocardial and respiratory performance and also have mild adrenocortical suppression. Thus, these findings increase the potential for the clinical use of ET-26HCl in the elderly population

Overcoming Sample Matrix Effect in Quantitative Blood Metabolomics Using Chemical Isotope Labeling Liquid Chromatography Mass Spectrometry

Blood is widely used for discovery metabolomics to search for disease biomarkers. However, blood sample matrix can have a profound effect on metabolome analysis, which can impose an undesirable restriction on the type of blood collection tubes that can be used for blood metabolomics. We investigated the effect of blood sample matrix on metabolome analysis using a high-coverage and quantitative metabolome profiling technique based on differential chemical isotope labeling (CIL) LC-MS. We used ¹²C-/¹³C-dansylation LC-MS to perform relative quantification of the amine/phenol submetabolomes of four types of samples (i.e., serum, EDTA plasma, heparin plasma, and citrate plasma) collected from healthy individuals and compare their metabolomic results. From the analysis of 80 plasma and serum samples in experimental triplicate, we detected a total of 3651 metabolites with an average of 1818 metabolites per run (<i>n</i> = 240). The number of metabolites detected and the precision and accuracy of relative quantification were found to be independent of the sample type. Within each sample type, the metabolome data set could reveal biological variation (e.g., sex separation). Although the relative concentrations of some individual metabolites might be different in the four types of samples, for sex separation, all 66 significant metabolites with larger fold-changes (FC ≥ 2 and <i>p</i> < 0.05) found in at least one sample type could be found in the other types of samples with similar or somewhat reduced, but still significant, fold-changes. Our results indicate that CIL LC-MS could overcome the sample matrix effect, thereby greatly broadening the scope of blood metabolomics; any blood samples properly collected in routine clinical settings, including those in biobanks originally used for other purposes, can potentially be used for discovery metabolomics