Bayesian-frequentist hybrid inference framework for single cell RNA-seq analyses.

BACKGROUND: Single cell RNA sequencing technology (scRNA-seq) has been proven useful in understanding cell-specific disease mechanisms. However, identifying genes of interest remains a key challenge. Pseudo-bulk methods that pool scRNA-seq counts in the same biological replicates have been commonly used to identify differentially expressed genes. However, such methods may lack power due to the limited sample size of scRNA-seq datasets, which can be prohibitively expensive. RESULTS: Motivated by this, we proposed to use the Bayesian-frequentist hybrid (BFH) framework to increase the power and we showed in simulated scenario, the proposed BFH would be an optimal method when compared with other popular single cell differential expression methods if both FDR and power were considered. As an example, the method was applied to an idiopathic pulmonary fibrosis (IPF) case study. CONCLUSION: In our IPF example, we demonstrated that with a proper informative prior, the BFH approach identified more genes of interest. Furthermore, these genes were reasonable based on the current knowledge of IPF. Thus, the BFH offers a unique and flexible framework for future scRNA-seq analyses.

Municipal solid waste gasification by hot recycling blast furnace gas coupled with in-situ decarburization to prepare blast furnace injection of hydrogen-rich gas.

Waste-to-energy is one of the most effective methods to save energy and reduce carbon emissions. This paper proposes a novel process of municipal solid waste (MSW) gasification by hot recycling blast furnace gas (BFG) coupled with in-situ decarburization to prepare blast furnace injection of hydrogen-rich gas. MSW gasification by the hot BFG is conducted by using Aspen Plus software coupled with equilibrium model or kinetic model. Compared to the equilibrium model, kinetic simulation results exhibit good agreement with the experimental results. Moreover, the technological analysis is also performed to investigate the coupled effects of gasification temperature, MSW/BFG ratio, and steam/MSW ratio on the H2-rich syngas generated from MSW gasification. The results reveal that all the investigated influencing factors have been found with a significant effect on the H2-rich syngas formation. The 25.95 vol% of H2 and 37.20 vol% of CO during MSW gasification by the hot BFG are achieved at a gasification temperature of 900 °C, steam/MSW ratio of 0.46 kg/kg, and MSW/BFG ratio of 0.34 kg/Nm3.

Bayesian-frequentist hybrid inference framework for single cell RNA-seq analyses.

Background: Single cell RNA sequencing technology (scRNA-seq) has been proven useful in understanding cell-specific disease mechanisms. However, identifying genes of interest remains a key challenge. Pseudo-bulk methods that pool scRNA-seq counts in the same biological replicates have been commonly used to identify differentially expressed genes. However, such methods may lack power due to the limited sample size of scRNA-seq datasets, which can be prohibitively expensive. Results: Motivated by this, we proposed to use the Bayesian-frequentist hybrid (BFH) framework to increase the power. Conclusion: In our idiopathic pulmonary fibrosis (IPF) case study, we demonstrated that with a proper informative prior, the BFH approach identified more genes of interest. Furthermore, these genes were reasonable based on the current knowledge of IPF. Thus, the BFH offers a unique and flexible framework for future scRNA-seq analyses.

Disorder-Enriched Magnetic Excitations in a Heisenberg-Kitaev Quantum Magnet Na_{2}Co_{2}TeO_{6}.

Using optical magnetospectroscopy, we investigate the magnetic excitations of Na_{2}Co_{2}TeO_{6} in a broad magnetic field range (0 T≤B≤17.5 T) at low temperature. Our measurements reveal rich spectra of in-plane magnetic excitations with a surprisingly large number of modes, even in the high-field spin-polarized state. Theoretical calculations find that the Na-occupation disorder in Na_{2}Co_{2}TeO_{6} plays a crucial role in generating these modes. Our Letter demonstrates the necessity to consider disorder in the spin environment in the search for Kitaev quantum spin liquid states in practicable materials.

Effects of the fundamental axes of variation in structural diversity on the forest canopy temperature in an urban area.

The spatial distribution and heterogeneity of forest canopy elements reveal the fundamental dimensions of plant structure variations. Forests characterized by greater structural complexity and diversity intercept solar radiation more effectively, directly influencing the thermal environment and energy balance of the canopy. However, the axes of variation in the distribution and heterogeneity of the canopy remain largely unknown, which limits our understanding of how structural diversity responds to canopy temperature variability. Here, we derived a set of structural diversity metrics from a dataset of canopy structure measurements obtained using unmanned aerial vehicle-light detection and ranging across major forest communities in an urban area in 2021 and 2022. We also explored the key axes of structural diversity variability and tested their predictive power for canopy temperature. The results showed that: (1) most of the variability within structural diversity (83.6 % and 81.8 %) was captured by the three key axes in 2021 and 2022. The first axis was primarily driven by structural heterogeneity, representing the heterogeneity of vegetation distribution within the canopy. The second axis was primarily influenced by the interaction between height and cover/openness, indicating the vertical structure and horizontal distribution pattern of the canopy. The third axis represented the horizontal coverage and density of the canopy. (2) In both 2021 and 2022, the second axis was identified as the most influential predictor of canopy temperature, as evidenced by R2 values of 0.46 and 0.28, respectively. The model incorporating all three axes of structural diversity achieved the highest accuracy in predicting the canopy temperature for 2021 (R2 = 0.68, AIC = 81.35, ΔAIC = 0, and RMSE = 0.89). Prior research on canopy temperature prediction has overlooked the true potential of principal component axes derived from structural diversity. The findings present a novel approach for selecting structural diversity indicators for future investigation.

Single-cell landscape analysis unravels molecular programming of the human B cell compartment in chronic GVHD.

Alloreactivity can drive autoimmune syndromes. After allogeneic hematopoietic stem cell transplantation (allo-HCT), chronic graft-versus-host disease (cGVHD), a B cell-associated autoimmune-like syndrome, commonly occurs. Because donor-derived B cells continually develop under selective pressure from host alloantigens, aberrant B cell receptor (BCR) activation and IgG production can emerge and contribute to cGVHD pathobiology. To better understand molecular programing of B cells in allo-HCT, we performed scRNA-Seq analysis on high numbers of purified B cells from patients. An unsupervised analysis revealed 10 clusters, distinguishable by signature genes for maturation, activation, and memory. Within the memory B cell compartment, we found striking transcriptional differences in allo-HCT patients compared with healthy or infected individuals, including potentially pathogenic atypical B cells (ABCs) that were expanded in active cGVHD. To identify intrinsic alterations in potentially pathological B cells, we interrogated all clusters for differentially expressed genes (DEGs) in active cGVHD versus patients who never had signs of immune tolerance loss (no cGVHD). Active cGVHD DEGs occurred in both naive and BCR-activated B cell clusters. Remarkably, some DEGs occurred across most clusters, suggesting common molecular programs that may promote B cell plasticity. Our study of human allo-HCT and cGVHD provides understanding of altered B cell memory during chronic alloantigen stimulation.

scRAA: the development of a robust and automatic annotation procedure for single-cell RNA sequencing data.

A critical task in single-cell RNA sequencing (scRNA-Seq) data analysis is to identify cell types from heterogeneous tissues. While the majority of classification methods demonstrated high performance in scRNA-Seq annotation problems, a robust and accurate solution is desired to generate reliable outcomes for downstream analyses, for instance, marker genes identification, differentially expressed genes, and pathway analysis. It is hard to establish a universally good metric. Thus, a universally good classification method for all kinds of scenarios does not exist. In addition, reference and query data in cell classification are usually from different experimental batches, and failure to consider batch effects may result in misleading conclusions. To overcome this bottleneck, we propose a robust ensemble approach to classify cells and utilize a batch correction method between reference and query data. We simulated four scenarios that comprise simple to complex batch effect and account for varying cell-type proportions. We further tested our approach on both lung and pancreas data. We found improved prediction accuracy and robust performance across simulation scenarios and real data. The incorporation of batch effect correction between reference and query, and the ensemble approach improve cell-type prediction accuracy while maintaining robustness. We demonstrated these through simulated and real scRNA-Seq data.

Vibrational spectroscopic detection and analysis of isoniazid-nicotinamide-succinic acid ternary cocrystal.

In this paper, binary and ternary cocrystals in the ternary cocrystal system of isoniazid-nicotinamide-succinic acid were prepared by solvent evaporation and grinding methods. All of them were characterized by terahertz time-domain spectroscopy (THz-TDS), confirming that the cocrystals could be obtained by the above two methods. In addition, to investigate the formation of hydrogen bonds and their influence in cocrystal, several possible forms of hydrogen bond in cocrystal were simulated by density functional theory (DFT). The simulated result was in good agreement with the experimental result, indicating that the hydrogen bonds in cocrystal were the carboxyl groups on both side of succinic acid forming a pyridine N-carboxylic acid heterosynthon with pyridine N of isoniazid or nicotinamide respectively. Meanwhile, the vibrational modes of the cocrystal were analyzed to investigate the effect of hydrogen bond to the molecules. To further understand the formation process of ternary cocrystal in this system, Raman spectroscopy was used to analyze the cocrystal samples with different time of grinding. Process information of cocrystal formation were obtained by analyzing the changes of the characteristic peaks in the corresponding Raman spectra. These results provide a wealth of information and a unique approach to the analysis of both structures and intermolecular interactions shown within ternary cocrystal.

Clustering Deviation Index (CDI): a robust and accurate internal measure for evaluating scRNA-seq data clustering.

Most single-cell RNA sequencing (scRNA-seq) analyses begin with cell clustering; thus, the clustering accuracy considerably impacts the validity of downstream analyses. In contrast with the abundance of clustering methods, the tools to assess the clustering accuracy are limited. We propose a new Clustering Deviation Index (CDI) that measures the deviation of any clustering label set from the observed single-cell data. We conduct in silico and experimental scRNA-seq studies to show that CDI can select the optimal clustering label set. As a result, CDI also informs the optimal tuning parameters for any given clustering method and the correct number of cluster components.

Experimental Study on the Mechanical Properties of Diatomite-Modified Coastal Cement Soil.

Diatomite is a non-metallic mineral resource rich in SiO2, which can be used to modify coastal cement soil. In order to explore the mechanical modification effect of diatomite on coastal cement soil at the age of 7 days, based on coastal cement soil with cement content of 5% (mass fraction), diatomite of 0%, 5%, 10%, 15% and 20% (mass fraction) was mixed for modification. Through the unconfined compressive strength test, the triaxial unconsolidated undrained test, backscattered electron imaging (BSE), and energy-dispersive spectroscopy (EDS) technology, the influence of diatomite content and confining pressure on the peak strength of modified coastal cement soil was explored. The empirical formula between the peak strength of the DE specimen and the content of diatomite and confining pressure was established by curve fitting, and the fitting effect was ideal. When diatomite was mixed with coastal cement soil, the optimal dosage of diatomite was 5% from the perspective of mechanical properties and economic benefits of the maximum growth rate of compression and shear. The unconfined compressive strength test showed that the peak strength and elastic modulus of the modified coastal cement soil with 5% diatomite content were 37% and 57% higher than those of cement soil, respectively. The triaxial unconsolidated undrained test showed that the internal friction angle of the modified coastal cement soil was stable at about 30°, and cohesion of DE-5, DE-10, DE-15, and DE-20 increased by 28%, 48%, 78%, and 97%, respectively, compared to cement soil. The microscopic test found that the pore distribution of modified coastal cement soil is closely related to the strength change. The results show that the addition of diatomite can effectively improve the mechanical properties of soil-cement.

Pharmaceutical Cocrystals of Ethenzamide: Molecular Structure Analysis Based on Vibrational Spectra and DFT Calculations.

Pharmaceutical cocrystals can offer another advanced strategy for drug preparation and development and can facilitate improvements to the physicochemical properties of active pharmaceutical ingredients (APIs) without altering their chemical structures and corresponding pharmacological activities. Therefore, cocrystals show a great deal of potential in the development and research of drugs. In this work, pharmaceutical cocrystals of ethenzamide (ETZ) with 2,6-dihydroxybenzoic acid (26DHBA), 2,4-dihydroxybenzoic acid (24DHBA) and gallic acid (GA) were synthesized by the solvent evaporation method. In order to gain a deeper understanding of the structural changes after ETZ cocrystallization, terahertz time domain spectroscopy (THz-TDS) and Raman spectroscopy were used to characterize the single starting samples, corresponding physical mixtures and the cocrystals. In addition, the possible molecular structures of ETZ-GA, ETZ-26DHBA and ETZ-24DHBA cocrystals were optimized by density functional theory (DFT). The results of THz and Raman spectra with the DFT simulations for the three cocrystals revealed that the ETZ-GA cocrystal formed an O-H∙∙∙O hydrogen bond between the -OH of GA and oxygen of the amide group of the ETZ molecule, and it was also found that ETZ formed a dimer through a supramolecular amide-amide homosynthon; meanwhile, the ETZ-26DHBA cocrystal was formed by a powerful supramolecular acid-amide heterosynthon, and the ETZ-24DHBA cocrystal formed the O-H∙∙∙O hydrogen bond between the 4-hydroxy group of 24DHBA and oxygen of the amide group of the ETZ molecule. It could be seen that in the molecular structure analysis of the three cocrystals, the position and number of hydroxyl groups in the coformers play an essential role in guiding the formation of specific supramolecular synthons.

Adsorption Properties and Mechanism of Attapulgite to Graphene Oxide in Aqueous Solution.

In order to remove toxic graphene oxide (GO) from aqueous solution, attapulgite (ATP) was used as adsorbent to recycle it by adsorption. In this paper, the effects of different pH, adsorbent mass, GO concentration, time and temperature on the adsorption of GO by attapulgite were studied, and the adsorption performance and mechanism were further explored by XRD, AFM, XPS, FTIR, TEM and SEM tests. The results show that when T = 303 K, pH = 3, and the GO concentration is 100 mg/L in 50 mL of aqueous solution, the removal rate of GO by 40 mg of attapulgite reaches 92.83%, and the partition coefficient Kd reaches 16.31. The adsorption kinetics results showed that the adsorption equilibrium was reached at 2160 min, and the adsorption process could be described by the pseudo-second-order adsorption equation, indicating that the adsorption process was accompanied by chemical adsorption and physical adsorption. The isotherm and thermodynamic parameters show that the adsorption of GO by attapulgite is more consistent with the Langmuir isotherm model, and the reaction is a spontaneous endothermic process. The analysis shows that attapulgite is a good material for removing GO, which can provide a reference for the removal of GO in an aqueous environment.

Terahertz and Raman Spectroscopic Investigation of Monohydrate Cocrystal of Antitubercular Isoniazid with Protocatechuic Acid.

Pharmaceutical cocrystal provides an alternative modification strategy for the formulation development of drugs owning to their potential ability to improve the physicochemical properties of active pharmaceutical ingredients (APIs) efficiently by changing inter-molecular interactions between raw materials. Isoniazid (INH) is an indispensable main drug for the treatment of tuberculosis, but its tablet formulation is unstable and prone to degradation. In the present study, the monohydrate cocrystal of INH and protocatechuic acid (PA) was prepared by solvent evaporation using PA as cocrystal former to optimize the properties of INH. The parent materials and corresponding 1:1 molar ratio INH-PA monohydrate cocrystal have been characterized by the terahertz time-domain (THz-TDS) and Raman spectroscopy. The THz absorption spectra displayed that there were obvious differences between the peaks of experimental cocrystal and the parent materials, and the same situation was found in Raman vibrational spectra. In addition, density functional theory (DFT) was applied to simulating and optimizing the structure of INH-PA monohydrate cocrystal and supplied corresponding vibrational modes. Our results provided a unique method to characterize the formation of INH-PA monohydrate cocrystal at the molecular-level and a lot of information about cocrystal structure and intra-molecular and/or inter-molecular hydrogen bond interactions in the emerging pharmaceutical cocrystal fields.

Vibrational spectral and structural characterization of multicomponent ternary co-crystal formation within acetazolamide, nicotinamide and 2-pyridone.

Ternary co-crystal, as a novel co-crystal design strategy developed on the basis of binary co-crystal, could be used to improve the physicochemical properties of active pharmaceutical ingredients (APIs) efficiently. However, it is difficult to obtain specific ternary co-crystals since such ternary one involves complex assembly of three different molecules. There are few reports on the micro-molecular structure respect of specific ternary co-crystal systems. In present work, 1:1:1 ternary co-crystal between acetazolamide (ACZ), nicotinamide (NAM) and 2-pyridone (2HP) has been synthesized successfully by mechanical grinding approach, and their structures are investigated by terahertz time-domain spectroscopy (THz-TDS) and Raman spectroscopy combined with theoretical calculation at the molecular level. The experimental THz spectral results showed that ACZ-NAM-2HP ternary co-crystal and the starting parent materials exhibited a few distinct spectral features in frequency-domain absorption spectra. Likewise, the Raman spectral result also shows some difference between the co-crystal and starting raw materials. Through density functional theory (DFT) calculations, the theoretical THz/Raman spectra and vibrational modes of two kind of possible ternary co-crystal theoretical forms (form I and II) between ACZ, NAM and 2HP were obtained. By comparing experimental and theoretical spectral results, the most suitable structure and vibrational modes of ACZ-NAM-2HP ternary co-crystal were determined. These results provide a wealth of information and unique method for studying molecular assembly and also inter-molecular interactions in specific ternary co-crystals at the molecular level in the emerging pharmaceutical co-crystal fields.

Effect of trust in primary care physicians on patient satisfaction: a cross-sectional study among patients with hypertension in rural China.

BACKGROUND: In rural areas of China, hypertension is on the rise and it is drawing the Chinese government's attention. The health outcomes of hypertension management can be positively impacted by patient satisfaction with primary care physicians (PCPs), and the influence of patient trust on satisfaction cannot be ignored. This study aimed to analyze the effect of trust in PCPs on patient satisfaction among patients with hypertension in rural China, and the influence of patients' socio-demographic characteristics and hypertension-management-related factors. METHODS: A multi-stage stratified random sampling method was adopted to investigate 2665 patients with hypertension in rural China. Patient trust and satisfaction were measured using the Chinese version of the Wake Forest Physician Trust Scale and the European Task Force on Patient Evaluation of General Practice. Multiple linear regression was used to analyze the factors influencing patient satisfaction, and structural equation modeling was conducted to clarify the relationships among patient trust and patient satisfaction with PCPs. RESULTS: Patients' trust in their PCPs' benevolence had a positive main effect on all three satisfaction dimensions (clinical behavior: ß = 0.940, p <  0.01; continuity and cooperation: ß = 0.910, p <  0.01; and organization of care: ß = 0.879, p <  0.01). Patients' trust in their PCPs' technical competence had a small negative effect on all three satisfaction dimensions (clinical behavior: ß = - 0.077, p <  0.01; continuity and cooperation: ß = - 0.136, p <  0.01; and organization of care: ß = - 0.064, p <  0.01). Patient satisfaction was also associated with region, gender, insurance status, distance from the nearest medical/health-service institution, and number of visits to PCPs in the past year. CONCLUSIONS: Patients focused more on physicians' benevolence than on their technical competence. Hence, medical humanities and communication skills education should be emphasized for PCPs. Regarding region-based and health-insurance-based differences, the inequities between eastern, central, and western provinces, as well as between urban and rural areas, must also be addressed.