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Abstract 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.

The challenge of precisely regulating temperature during the photo-thermal bone promotion remains unresolved. Phase change material (PCM), capable of undergoing a phase transition at a specific temperature, offers a solution by photothermal temperature regulation through the storage and release of heat. This study incorporated biocompatible polyethylene glycol (PEG) with specific phase transition points as PCM. A phase change hydrogel scaffold was then synthesized through semi-crosslinking PEG with calcium-ion-chelated sodium alginate (SA) acting as the structural framework. Additionally, the newly developed graphene oxide (GO) modified composite scaffolds (GO-PHSC), featuring 0.5 wt% GO, not only demonstrated outstanding photothermal conversion efficiency and an optimal phase change temperature (42.2 °C) but also exhibited desirable values for latent enthalpy (100 J/g) and latent heat recovered (LHR) (93.3%). Moreover, the form-stability test demonstrated the PCM scaffolds' exceptional resistance to leakage and maintenance of shape stability even at elevated temperatures (70 °C). Beyond achieving passive temperature control in photothermal therapy, experimental findings highlighted that the phase change hydrogel, incorporating calcium ions and GO, met various requirements such as physicochemical properties, microstructure, mechanics, mineralization, biocompatibility, and cell affinity. These collective attributes suggest that GO-PHSC emerges as a promising scaffold composite candidate for temperature-controlled photothermal therapy in bone regeneration.

Abstract With the expansion of the global population, the energy shortage is becoming increasingly acute. Phase change materials (PCMs) are considered green and efficient mediums for thermal energy storage, but the leakage problem caused by volume instability during phase change limits their application. Encapsulating PCMs with supporting materials can effectively avoid leakage, but most supporting materials are expensive and consume huge of natural resources. Carbon materials, which are rich and renewable resources, can be used as economical and environmentally friendly supporting skeletons to prepare form‐stable PCMs. Although many researchers have begun to use recyclable materials especially various derivatives of carbon as supporting skeletons to prepare form‐stable PCMs, the preparation methods, thermophysical properties and applications of form‐stable PCMs with recyclable skeletons have rarely been systematically summarized yet. Form‐stable PCMs with a recyclable skeleton can be used as green and efficient thermal storage materials due to their high heat storage capacity and good thermophysical stability after 2000 thermal cycles. This review investigates the effects of recyclable skeletons on the thermophysical properties including phase change temperature, latent heat, thermal conductivity, supercooling, and thermal cycling reliability. Four major kinds of recyclable skeletons are focused on: biomass, biochar, industrial by‐products as well as waste incineration ash. Additionally, the application scales of form‐stable PCMs with recyclable skeletons are explicated in depth. Moreover, the main challenges confronted by form‐stable PCMs with recyclable skeletons are discussed, and future research trends are proposed. This article provides a systematic review of the form‐stable PCMs with recyclable skeletons, giving significant guidance for further reducing carbon emissions and promoting the development of sustainable energy.

Abstract Building on previous radar‐based human activity recognition (HAR), we expand the micro‐Doppler signature to 6 domains and exploit each domain with a set of handcrafted features derived from the literature and our patents. An adaptive thresholding method to isolate the region of interest is employed, which is then applied in other domains. To reduce the computational burden and accelerate the convergence to an optimal solution for classification accuracy, a holistic approach to HAR optimisation is proposed using a surrogate model‐assisted differential evolutionary algorithm (SADEA‐I) to jointly optimise signal processing, adaptive thresholding and classification parameters for HAR. Two distinct classification models are evaluated with holistic optimisation: SADEA‐I with support vector machine classifiers (SVM) and SADEA‐I with AlexNet. They achieve an accuracy of 89.41% and 93.54%, respectively. This is an improvement of ∼11.3% for SVM and ∼2.7% for AlexNet when compared to the performance without SADEA‐I. The effectiveness of our holistic approach is validated using the University of Glasgow human radar signatures dataset. This proof of concept is significant for dimensionality reduction and computational efficiency when facing a multiplication of radar representation domains/feature spaces and transmitting/receiving channels that could be individually tuned in modern radar systems.

Abstract INTRODUCTION Individuals with Alzheimer's disease (AD) commonly experience neuropsychiatric symptoms of psychosis (AD+P) and/or affective disturbance (depression, anxiety, and/or irritability, AD+A). This study's goal was to identify the genetic architecture of AD+P and AD+A, as well as their genetically correlated phenotypes. METHODS Genome‐wide association meta‐analysis of 9988 AD participants from six source studies with participants characterized for AD+P AD+A, and a joint phenotype (AD+A+P). RESULTS AD+P and AD+A were genetically correlated. However, AD+P and AD+A diverged in their genetic correlations with psychiatric phenotypes in individuals without AD. AD+P was negatively genetically correlated with bipolar disorder and positively with depressive symptoms. AD+A was positively correlated with anxiety disorder and more strongly correlated than AD+P with depressive symptoms. AD+P and AD+A+P had significant estimated heritability, whereas AD+A did not. Examination of the loci most strongly associated with the three phenotypes revealed overlapping and unique associations. DISCUSSION AD+P, AD+A, and AD+A+P have both shared and divergent genetic associations pointing to the importance of incorporating genetic insights into future treatment development. Highlights It has long been known that psychotic and affective symptoms are often comorbid in individuals diagnosed with Alzheimer's disease. Here we examined for the first time the genetic architecture underlying this clinical observation, determining that psychotic and affective phenotypes in Alzheimer's disease are genetically correlated. Nevertheless, psychotic and affective phenotypes in Alzheimer's disease diverged in their genetic correlations with psychiatric phenotypes assessed in individuals without Alzheimer's disease. Psychosis in Alzheimer's disease was negatively genetically correlated with bipolar disorder and positively with depressive symptoms, whereas the affective phenotypes in Alzheimer's disease were positively correlated with anxiety disorder and more strongly correlated than psychosis with depressive symptoms. Psychosis in Alzheimer's disease, and the joint psychotic and affective phenotype, had significant estimated heritability, whereas the affective in AD did not. Examination of the loci most strongly associated with the psychotic, affective, or joint phenotypes revealed overlapping and unique associations.

Phase change materials (PCMs) are materials that exhibit thermal response characteristics, allowing them to be utilized in the biological field for precise and controllable temperature regulation. Due to considerations of biosafety and the spatial limitations within human tissue, the amount of PCMs used in medical applications is relatively small. Therefore, researchers often augment PCMs with various materials to enhance their performance and increase their practical value. The dispersion of nanoparticles to modify the thermophysical properties of PCMs has emerged as a mature concept. This paper aims to elucidate the role of nanomaterials in addressing deficiencies and enhancing the performance of PCMs. Specifically, it discusses the dispersion methods and stabilization mechanisms of nanoparticles within PCMs, as well as their effects on thermophysical properties such as thermal conductivity, latent heat, and specific heat capacity. Furthermore, it explores how various nano-additives contribute to improved thermal conductivity and the mechanisms underlying enhanced latent heat and specific heat. Additionally, the potential applications of PCMs in biomedical fields are proposed. Finally, this paper provides a comprehensive analysis and offers suggestions for future research to maximize the utilization of nanomaterials in enhancing the thermophysical properties of PCMs for biomedical applications.

Plain Language Summary Baricitinib is an oral agent widely approved for the treatment of moderately to severely active rheumatoid arthritis). Although baricitinib (and other agents) have demonstrated efficacy at the population level, treatment responses vary considerably between individual patients. This study assessed four baricitinib phase 3 clinical studies and categorized patient responses into response groups based on the Clinical Disease Activity Index (CDAI) using a growth mixture model. We then evaluated baseline characteristics and corresponding disease measures within the response groups. In patients with no prior treatment with biological disease-modifying anti-rheumatic drugs (bDMARDs), 65–71% of patients had rapid responses to treatment, while smaller groups had gradual (10–17%) or partial (18–22%) responses. In patients with prior bDMARD experience, rapid and partial responders each comprised 42% of patients while 15% had limited response. Gradual responders generally had higher baseline CDAI versus rapid responders, but achieved low disease activity (LDA) by 24, versus 12 weeks for rapid responders. Across response groups, patients who continued treatment generally maintained their response up to 52 weeks, and where joint erosion was assessed (in bDMARD-naïve patients), generally saw maintenance of joints during continued therapy. The identification of a gradual responder group, which demonstrated good response but required more time to achieve LDA, is relatively novel and should be considered when setting treatment expectations, particularly in patients with high baseline disease activity. In addition, in bDMARD-experienced patients, many patients did not achieve LDA but maintained a substantial partial response with continued therapy.

Fatty acid-derived products such as alkanes, fatty aldehydes, and fatty alcohols have many applications in the chemical industry. These products are predominately produced from fossil resources, but their production processes are often not environmentally friendly. While microbes like Escherichia coli have been engineered to convert fatty acids to corresponding products, the design and optimization of metabolic pathways in cells for high productivity is challenging due to low mass transfer, heavy metabolic burden, and intermediate/product toxicity. Here, we describe an E. coli-based cell-free protein synthesis (CFPS) platform for in vitro conversion of long-chain fatty acids to value-added chemicals with product selectivity, which can also avoid the above issues when using microbial production systems. We achieve the selective biotransformation by cell-free expression of different enzymes and the use of different conditions (e.g., light and heating) to drive the biocatalysis toward different final products. Specifically, in response to blue light, cell-free expressed fatty acid photodecarboxylase (CvFAP, a photoenzyme) was able to convert fatty acids to alkanes with approximately 90% conversion. When the expressed enzyme was switched to carboxylic acid reductase (CAR), fatty acids were reduced to corresponding fatty aldehydes, which, however, could be further reduced to fatty alcohols by endogenous reductases in the cell-free system. By using a thermostable CAR and a heating treatment, the endogenous reductases were deactivated and fatty aldehydes could be selectively accumulated (>97% in the product mixture) without over-reduction to alcohols. Overall, our cell-free platform provides a new strategy to convert fatty acids to valuable chemicals with notable properties of operation flexibility, reaction controllability, and product selectivity.

Abstract Correct species identification is crucial for ensuring the quality, safety, and efficacy of herbal medicine. Market research indicates that Curculigo glabrescens Rhizoma (CGR) was the major counterfeit of the medicine Curculigo orchioides Rhizoma (COR). To accurately discriminate COR and CGR remains a challenge, and it becomes even more difficult when the herbs have been heavily processed into a powder. In this work, combined with high performance liquid chromatography analysis, a novel component in CGR was discovered, and two stable isotopes (N%, C%, δ15N, δ13C) and nineteen mineral elements were determined along with multivariate statistical analysis to distinguish the authentic COR samples and counterfeit CGR samples. The results showed that there were significant differences between the mean value of N%, δ15N and δ13C according to the botanical origins. In addition, these two species can be differentiated by principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) analysis. A linear discriminant analysis (LDA) model with a good classification rate (100%) and cross-validation rate (100%) was established. Hence, stable isotope and mineral element contents combined with chemometrics analysis could be considered as an effective and reliable method for discriminating the source species of COR and CGR.

Cell-free system has emerged as a powerful platform with a wide range of in vitro applications and recently has contributed to express metabolic pathways for biosynthesis. Here we report in vitro construction of a native biosynthetic pathway for L-4-nitrotryptophan (L-4-nitro-Trp) synthesis using an Escherichia coli-based cell-free protein synthesis (CFPS) system. Naturally, a nitric oxide (NO) synthase (TxtD) and a cytochrome P450 enzyme (TxtE) are responsible for synthesizing L-4-nitro-Trp, which serves as one substrate for the biosynthesis of a nonribosomal peptide herbicide thaxtomin A. Recombinant coexpression of TxtD and TxtE in a heterologous host like E. coli for L-4-nitro-Trp production has not been achieved so far due to the poor or insoluble expression of TxtD. Using CFPS, TxtD and TxtE were successfully expressed in vitro, enabling the formation of L-4-nitro-Trp. After optimization, the cell-free system was able to synthesize approximately 360 μM L-4-nitro-Trp within 16 h. Overall, this work expands the application scope of CFPS for study and synthesis of nitro-containing compounds, which are important building blocks widely used in pharmaceuticals, agrochemicals, and industrial chemicals.

Extracellular vesicles (EVs) are nanoscale extracellular particles that have received widespread scientific attention for carrying a variety of biomolecules such as nucleic acids and proteins and participating in the process of intercellular information exchange, making them become a research hotspot due to their potential diagnostic value. Breast cancer is the leading cause of cancer-related death in women, approximately 90% of patient deaths are due to metastasis complications. Brain metastasis is an important cause of mortality in breast cancer patients, about 10–15% of breast cancer patients will develop brain metastasis. Therefore, early prevention of brain metastasis and the development of new treatments are crucial. Small EVs have been discovered to be involved in the entire process of breast cancer brain metastasis (BCBM), playing an important role in driving organ-specific metastasis, forming pre-metastatic niches, disrupting the blood-brain barrier, and promoting metastatic tumor cell proliferation. We summarize the mechanisms of small EVs in the aforementioned pathological processes at the cellular and molecular levels, and anticipate their potential applications in the treatment of breast cancer brain metastasis, with the hope of providing new ideas for the precise treatment of breast cancer brain metastasis.

Background: The regression of positive nodes in breast cancer after neoadjuvant chemotherapy (NAC) remains unknown. This study aimed to investigate this regression by injecting and tracing carbon nanoparticles (CNs) into the fusion node prior to NAC in patients with breast cancer. Methods: Guided by ultrasound, 0.3 mL of CNs suspension was injected in the fusion node prior to NAC in 110 patients with local advanced breast cancer. Then the patients underwent breast surgery and total axillary lymph node dissection following 2–6 cycles of NAC. The distribution by intercostobrachial nerves (ICBN) of positive nodes and black-stained nodes was researched, and the relationship between the distribution and lymphovascular invasion were investigated by response to NAC. Results: When patients were ranked by response to NAC (from sensitive to resistance), the number of positive nodes increased, as did the proportion of lymphovascular invasion, the number of black-stained nodes decreased. A significantly negative relationship was found between the number of positive nodes and the number of black-stained nodes (p

PurposeIt is well-known that the pathological complete response (pCR) rate in patients with luminal A cancer (LAC) is lower than those of other subtypes of breast cancer. The phenotype of cancer often alters after neoadjuvant chemotherapy (NAC) which may be related to hypoxia, and the latter might induce the drift of the estrogen receptor (ER). The phenotype drift in local advanced LAC after NAC might influence the long-term prognosis.MethodsThe oxygen concentration of cancer tissues during NAC was recorded and analyzed (n = 43). The expression of ER and claudin-6 was detected in pre- and post-NAC specimens.ResultsNAC might induce the cycling intracanceral hypoxia, and the pattern was related to NAC response. The median follow-up time was 61 months. Most of the patients (67%) with stable or increased ER and claudin-6 expression exhibited perfect prognosis (DFS = 100%, 61 months). About 20% of patients with decreased claudin-6 would undergo the poor prognosis (DFS = 22.2%, 61 months). The contrasting prognosis (100% vs. 22.2%) had nothing to do with the response of NAC in the above patients. Only 13% patients had stable claudin-6 and decreased ER, whose prognosis might relate to the response of NAC.ConclusionNAC might induce cycling intracanceral hypoxia to promote the phenotype drift in local advanced LAC, and the changes in ER and claudin-6 after NAC would determine the long-term prognosis.

The bile acid transport system is a natural physiological cycling process between the liver and the small intestine, occurring approximately 6–15 times during the day. There are various bile acid transporter proteins on hepatocytes that specifically recognize bile acids for transport. Therefore, in this paper, a novel liposome, cholic acid-modified irinotecan hydrochloride liposomes (named CA-CPT-11-Lip), was prepared based on the “Trojan horse” strategy. The liposomes preparation process was optimized, and some important quality indicators were investigated. The distribution of irinotecan hydrochloride in mice was then analyzed by high-performance liquid chromatography (HPLC), and the toxicity of liposomes to hepatocellular carcinoma cells (HepG-2) was evaluated in vitro. As a result, CA-CPT-11-Lip was successfully prepared. It was spherical with a particle size of 154.16 ± 4.92 nm, and the drug loading and encapsulation efficiency were 3.72 ± 0.04% and 82.04 ± 1.38%, respectively. Compared with the conventional liposomes (without cholic acid modification, named CPT-11-Lip), CA-CPT-11-Lip had a smaller particle size and higher encapsulation efficiency, and the drug accumulation in the liver was more efficient, enhancing the anti-hepatocellular carcinoma activity of irinotecan hydrochloride. The novel nanoliposome modified by cholic acid may help to expand the application of irinotecan hydrochloride in the treatment of hepatocellular carcinoma and construct the drug delivery system mode of drug liver targeting.

Purpose: To characterize the choroidal morphologic and vascular features in different levels of myopes and patients with myopic choroidal neovascularization (mCNV).Methods: A total of 148 subjects were enrolled in this cross-sectional study, including 78 low-to-moderate myopes (LMM), 53 high myopes (HM), and 17 high myopic patients with mCNV. Ocular biometrics were measured using an optical low-coherence reflectometry device. Retinal and choroidal imaging was performed using enhanced depth imaging (EDI) spectral domain optical coherence tomography (OCT). Retinal parameters including retinal thickness and retinal volume were obtained from a built-in software. Binarization technique was adopted to investigate choroidal parameters including choroidal thickness (CT), vascular area, stromal area, and choroidal vascularity index (CVI). Choroidal parameters were measured at five locations to cover as much area of choroid as possible, and their patterns of distribution were further analyzed.Results: Patients with mCNV had an atrophic retina of comparable thickness to HM (273.65 ± 17.28 vs. 276.49 ± 13.29 μm, p = 0.47), but the choroid was thinner than that of HM (153.94 ± 15.12 vs. 236.09 ± 38.51 μm, p < 0.001). Subfoveal CVI was greatest in the mCNV eyes (0.651 ± 0.009), followed by HM (0.645 ± 0.012) and LMM eyes (0.636 ± 0.012). Similar to CT, CVI was also found significantly different among these three groups at all five locations (p for trend < 0.001 for all locations). Axial length (AL) was negatively correlated with retinal volume (r = −0.236, p = 0.009), which is the only significant finding in associations between ocular factors and retinal parameters. Strong, negative correlations were identified between AL and subfoveal choroidal thickness (SFCT, r = −0.820, p < 0.001). However, AL was positively correlated with subfoveal CVI (r = 0.668, p < 0.001). CVI was greater in myopic eyes with thinner choroid (r = −0.578, p < 0.001). BCVA exhibited no significant association with CVI (r = 0.139, p = 0.092), but was negatively correlated with SFCT (r = −0.386, p < 0.001) and positively correlated with AL (r = 0.351, p < 0.001).Conclusion: Choroid in patients with mCNV was thinner yet more vascularized than that in HM and LMM subjects. CVI increased with a longer AL which was associated with a smaller SFCT, choroidal vascular area (VA), and total choroidal area (TCA). Better BCVA was achieved in subjects with thicker SFCT and shorter AL.

Purpose: To compare structural diameters of the ellipsoid zone (EZ) and external limiting membrane (ELM) bands on spectral domain-optical coherence tomography (SD-OCT) images between vision-improved (group A) and vision-unimproved (group B) patients, and investigate the connection between these parameters and visual prognosis.Materials and Methods: Forty-five eyes of 43 patients with idiopathic full-thickness macular hole closed after vitrectomy were retrospectively reviewed. Best-corrected visual acuity (BCVA) and SD-OCT were conducted preoperatively and at 1 week, 1 month and 6 months postoperatively. Structural and functional parameters were then measured using ImageJ software.Results: Among structural and functional parameters, the relative reflectivity of EZ and the ratio of continuous ELM and EZ in group A were significantly higher than in group B from the 1-month postoperative visit. At the 6-month follow-up, the diameter of EZ disruption in group A was significantly smaller than in group B, and the relative reflectivity of ELM/EZ was significantly higher than group B. At 6-months, BCVA was statistically significantly correlated with baseline BCVA, basal diameter (BD), macular hole index (MHI), and diameter of ELM/EZ disruption. Change in BCVA from baseline was found to be significantly correlated with axial length and diameter hole index (DHI).Conclusions: Postoperative BCVA outcome was significantly correlated with integrity, thickness and reflectivity of the EZ band. Patients with smaller diameter of EZ disruption and higher reflectivity of EZ band tended to have better visual outcomes. Given that the EZ band reflects the recovery of mitochondria in photoreceptors, it is a promising parameter for their functional evaluation.

Alkali-activated slag (AAS) is a promising cementing material for winter construction due to its continuous hydration at sub-zero temperature. In order to obtain a higher mechanical strength of AAS mortar in winter construction, the most efficient alkali activator should be selected. Potassium silicate and sodium silicate as alkaline activators of AAS mortar possess a high strength and hydration rate at ordinary temperature. Potassium silicate and sodium silicate as alkali activators showed different properties because of different alkali cations, so the effect of alkali cation on the performance of AAS mortar was studied at sub-zero temperature. The mechanical properties of potassium-silicate-activated AAS (K-AAS) mortar and sodium-silicate-activated AAS (N-AAS) mortar were thoroughly compared at the ambient temperatures of −10 °C, 0 °C, and 20 °C. The compressive and flexural strength of K-AAS mortar was increased by 130.4% and 72.3% at the age of 1 day and increased by 49% and 33.7% at the age of 28 days at the ambient temperature of −10 °C compared with N-AAS mortar. In order to reveal the mechanism behind the influence of different alkali cations on the mechanical properties of AAS mortar, the hydration heat, hydration products, and pore structures of AAS were characterized. The hydration heat exhibited that the rate of heat release and the cumulative heat release of K-AAS are higher than N-AAS, indicating the higher reaction degree of K-AAS. DTG/TG and ATR-FTIR spectra showed that K-AAS generated more gel product C(-A)-S-H compared with N-AAS at the same curing temperature. The MIP results exhibited that the porosity of K-AAS was lower than N-AAS. Finally, the mechanism explanation of the effect of alkali cation on the performance of AAS mortar was proposed. To sum up, potassium silicate should be selected as an alkali activator of AAS in winter construction.

Cell-free systems have been used to synthesize chemicals by reconstitution of in vitro expressed enzymes. However, coexpression of multiple enzymes to reconstitute long enzymatic pathways is often problematic due to resource limitation/competition (e.g., energy) in the one-pot cell-free reactions. To address this limitation, here we aim to design a modular, cell-free platform to construct long biosynthetic pathways for tunable synthesis of value-added aromatic compounds, using (S)-1-phenyl-1,2-ethanediol ((S)-PED) and 2-phenylethanol (2-PE) as models. Initially, all enzymes involved in the biosynthetic pathways were individually expressed by an E. coli-based cell-free protein synthesis (CFPS) system and their catalytic activities were confirmed. Then, three sets of enzymes were coexpressed in three cell-free modules and each with the ability to complete a partial pathway. Finally, the full biosynthetic pathways were reconstituted by mixing two related modules to synthesize (S)-PED and 2-PE, respectively. After optimization, the final conversion rates for (S)-PED and 2-PE reached 100 and 82.5%, respectively, based on the starting substrate of l-phenylalanine. We anticipate that the modular cell-free approach will make a possible efficient and high-yielding biosynthesis of value-added chemicals.

A novel electric induced curing method is introduced in this paper in order to solve the problem of cold region construction. This method applies alternating voltage (AC) to the fresh graphene/cement-based composite to generate ohmic heating, which can helps to accelerate the hydration reaction and form the structural strength of cement-based materials in deep-freeze low temperature. Graphene nanoplatelets (GNPs) were utilized to form conductive path in the fresh cement-based composite, thus reducing electrical resistivity. Numerical and experimental study was conducted to quantify the bridging behavior of GNPs and an optimum amount of GNPs of 2.0 vol% is determined as the global GNPs connection threshold. The graphene/cement-based composite by electric induced curing at −20 °C experiences an internal temperature rise and has superior mechanical properties. Further, the structural homogeneity of the hardened cement-based composite was confirmed using the nondestructive ultrasonic evaluation and microhardness measurement by one-way analysis of variance. Moreover, SEM, Raman spectra and MIP results show that the electric induced curing can accelerate the cement hydration leading to denser microstructure at low temperatures. This work provides insights into the quality control of cement-based materials for cold weather construction by means of the convenient and energy-efficient electric induced curing. Keywords: Cold region construction, Electric induced curing, Cement-based composite, Graphene nanoplatelets

In the current work, the thermal energy storage cement mortars were prepared by physical mixing between cement mortar and form-stable hydrated salt based on disodium hydrogen phosphate dodecahydrate/carbon nanofiber-expanded graphite (DSP/CNF-EG). The DSP/CNF-EG was incorporated into cement mortar through replacing standard sand of 5 wt%, 10 wt%, and 15 wt%. The pore structure results obtained from the mercury intrusion porosimeter (MIP) demonstrated that the incorporation of DSP/CNF-EG form-stable hydrated salt PCM can cause the increased porosity of the cement mortar. The mechanical strengths of the thermal energy storage cement mortars were decreased with increasing DSP/CNF-EG incorporation amount, and they still meet the strengths of the building envelope. Moreover, dynamic mechanical analysis (DMA) results suggested that the damping properties of the thermal energy storage cement mortar were enhanced by incorporating DSP/CNF-EG, which were related to the porosity and the internal friction action. In addition, the thermal conductivity and the specific heat capacity results confirmed that the introduction of DSP/CNF-EG can endow cement mortar with excellent thermal energy storage capacity. The thermal performance test further indicated that the thermal energy storage cement mortar showed good endothermic and exothermic characteristics, and it played a prominent role in weakening the indoor temperature peak.

The high-quality interaction of urban reality human settlements (RHSs), pseudo-human settlements (PHSs) and image human settlements (IHSs) can better explain the constantly updated human settlements phenomena under the human–land-relationship regional system. At present, the basic connotation, empirical exploration and optimized path of high-quality and coordinated development of “three states” of human settlements are not clear. In this paper, we take 14 prefecture-level cities in Liaoning Province as case areas and empirically explore their spatial patterns, coupling and coordination spatial relationships, driving mechanisms and development paths by using a coupling and coordination model, the entropy weight method and the geographic detector method. The results indicate that: (1) The spatial pattern of high-quality development of “three states” of human settlements varies significantly in different regions, forming a “dual-core” and “hump” spatial structure. (2) RHSs, PHSs and IHSs are not completely coordinated, forming “high–high–high” and “low–low–low” types, represented by Shenyang and Fuxin. (3) The high-quality coordinated development of “three states” of human settlements is driven by economic conditions, population conditions, entertainment systems and other factors. The population system, the social communication system and the support system, respectively, lead the high-quality coordinated development of RHSs, PHSs and IHSs.

Aiming at the problem of victim’s rational and irrational behavior during recovery stage in major natural disaster, this paper analyzed the victim’s psychological and behavioral characteristics and influencing factors during recovery stage based on lots of literatures and an interview with victims. Besides, a mechanism chart of the formation of the victim’s psychological behavior and a cusp catastrophe model are constructed. The catastrophe mechanism of the victim’s psychological behavior during recovery stage is simulated under the influence of the physical demand factors and the emotional needs factors. The two different functions of the two demand factors are analyzed. The model is partially verified by the investigation data of the disaster area. Finally, the paper put forward some strategies to cope with victim’s psychology and behavior during recovery stage based on the cusp catastrophe model analysis.

Systemic lupus erythematosus (SLE) is a chronic, remitting, and relapsing, inflammatory disease involving multiple organs, which exhibits abnormalities of both the innate and adaptive immune responses. A limited number of transcriptomic studies have characterized the gene pathways involved in SLE in an attempt to identify the key pathogenic drivers of the disease. In order to further advance our understanding of the pathogenesis of SLE, we used a novel Bayesian network algorithm to hybridize knowledge- and data-driven methods, and then applied the algorithm to build an SLE gene network using transcriptomic data from 1,760 SLE patients' RNA from the two tabalumab Phase III trials (ILLUMINATE-I & -II), the largest SLE RNA dataset to date. Further, based on the gene network, we carried out hub- and key driver-gene analyses for gene prioritization. Our analyses identified that the JAK-STAT pathway genes, including JAK2, STAT1, and STAT2, played essential roles in SLE pathogenesis, and reaffirmed the recent discovery of pathogenic relevance of JAK-STAT signaling in SLE. Additionally, we showed that other genes, such as IRF1, IRF7, PDIA4, FAM72C, TNFSF10, DHX58, SIGLEC1, and PML, may be also important in SLE and serve as potential therapeutic targets for SLE. In summary, using a hybridized network construction approach, we systematically investigated gene-gene interactions based on their transcriptomic profiles, prioritized genes based on their importance in the network structure, and revealed new insights into SLE activity.

In this study, a novel cement-lime-fly ash bound macadam (CLFBM) as pavement base material was designed by incorporating Portland cement, dihydrate gypsum (CaSO4·2H2O), and ground granulated blast furnace slag (GGBS) into the lime-fly ash bound macadam (LFBM) for the purpose of the early opening to traffic. The multifactors orthogonal test method was used to evaluate the effects of Portland cement, dihydrate gypsum, and GGBS on the early-age strength of CLFBM. Moreover, the compressive and flexural strengths at 28 days as well as the drying shrinkage development in 56 days were investigated. By conducting the comprehensive analysis for the better mechanical properties and the lowest drying shrinkage, Portland cement : dihydrate gypsum : lime : fly ash : GGBS : gravels = 2 : 1 : 6 : 5.6 : 8.4 : 80 is determined as the optimal mix proportion of CLFBM. In addition, scanning electron microscope (SEM) results confirmed the formation of a large number of ettringite and C-S-H gels, providing a powerful support for the enhanced early-age strength and suppressed drying shrinkage of CLFBM.

Valinomycin is a nonribosomal peptide that was discovered from Streptomyces in 1955. Over the past more than six decades, it has received continuous attention due to its special chemical structure and broad biological activities. Although many research papers have been published on valinomycin, there has not yet been a comprehensive review that summarizes the diverse studies ranging from structural characterization, biogenesis, and bioactivity to the identification of biosynthetic gene clusters and heterologous biosynthesis. In this review, we aim to provide an overview of valinomycin to address this gap, covering from 1955 to 2020. First, we introduce the chemical structure of valinomycin together with its chemical properties. Then, we summarize the broad spectrum of bioactivities of valinomycin. Finally, we describe the valinomycin biosynthetic gene cluster and reconstituted biosynthesis of valinomycin. With that, we discuss possible opportunities for the future research and development of valinomycin.

Fly ash (FA) has been an important ingredient for engineered cementitious composite (ECC) with excellent tensile strain capacity and multiple cracking. Unfortunately, the frost resistance of ECC with high-volume FA has always been a problem. This paper discusses the influence of silica fume (SF) and ground-granulated blast-furnace slag (GGBS) on the frost resistance of ECC with high volume of FA. Four ECC mixtures, ECC (50% FA), ECC (70% FA), ECC (30% FA + 40% SL), and ECC (65% FA + 5% SF), are evaluated by freezing-thawing cycles up to 200 cycles in tap water and sodium chloride solution. The result shows the relative dynamic elastic modulus and mass loss of ECC in sodium chloride solution by freeze-thaw cycles are larger than those in tap water by freeze-thaw cycles. Moreover, the relative dynamic elastic modulus and mass loss of ECC by freeze-thaw cycles increase with FA content increasing. However, the ECC (30% FA + 40% SL) shows a lower relative dynamic elastic modulus and mass loss, but its deflection upon four-point bending test is relatively smaller before and after freeze-thaw cycles. By contrast, the ECC (65% FA + 5% SF) exhibits a significant deflection increase with higher first cracking load, and the toughness increases sharply after freeze-thaw cycles, meaning ECC has good toughness property.

A fluid-solid-chemistry coupling model is built considering fluid flow and ion transmission induced by shale-drilling fluid system electrochemical potential osmosis, nonlinearity of flow and solute diffusion in shale-drilling fluid system, and solid deformation resulted from fluid flow and ion transmission. The model is used to compute the time-varying pore pressure, stress and damage index in formations around the wellbore of a well. The result shows that the pore pressure and stress are lower without consideration of the diffusion potential induced by ion selective character of shale membrane. The linear model overestimates the pore pressure and stress fields around the sidewall. The damage index reveals that collapse first occurs in formations near the wellbore, the caving pressure increases and changes obviously with time, the fracture pressure reduces but doesn't change significantly with time, and the drilling fluid density window narrows down with time. Key words: shale, chemical potential, electric potential, pore pressure, rock stress, wellbore damage

OBJECTIVES:Matrix metalloproteinase-8 (MMP-8) promotes lung fibrotic responses to bleomycin in mice. Although prior studies reported that MMP-8 levels are increased in plasma and bronchoalveolar lavage fluid (BALF) samples from IPF patients, neither the bioactive forms nor the cellular sources of MMP-8 in idiopathic pulmonary fibrosis (IPF) patients have been identified. It is not known whether MMP-8 expression is dys-regulated in IPF leukocytes or whether MMP-8 plasma levels correlate with IPF outcomes. Our goal was to address these knowledge gaps. METHODS:We measured MMP-8 levels and forms in blood and lung samples from IPF patients versus controls using ELISAs, western blotting, and qPCR, and assessed whether MMP-8 plasma levels in 73 IPF patients correlate with rate of lung function decline and mortality. We used immunostaining to localize MMP-8 expression in IPF lungs. We quantified MMP-8 levels and forms in blood leukocytes from IPF patients versus controls. RESULTS:IPF patients have increased BALF, whole lung, and plasma levels of soluble MMP-8 protein. Active MMP-8 is the main form elevated in IPF lungs. MMP-8 mRNA levels are increased in monocytes from IPF patients, but IPF patients and controls have similar levels of MMP-8 in PMNs. Surprisingly, macrophages and airway epithelial cells are the main cells expressing MMP-8 in IPF lungs. Plasma and BALF MMP-8 levels do not correlate with decline in lung function and/or mortality in IPF patients. CONCLUSION:Blood and lung MMP-8 levels are increased in IPF patients. Active MMP-8 is the main form elevated in IPF lungs. Surprisingly, blood monocytes, lung macrophages, and airway epithelial cells are the main cells in which MMP-8 is upregulated in IPF patients. Plasma and BALF MMP-8 levels are unlikely to serve as a prognostic biomarker for IPF patients. These results provide new information about the expression patterns of MMP-8 in IPF patients.

BackgroundWarao Amerindians, who inhabit the Orinoco Delta, are the second largest indigenous group in Venezuela. High Warao general mortality rates were mentioned in a limited study 21 years ago. However, there have been no comprehensive studies addressing child survival across the entire population.ObjectivesTo determine the Child Survival-Index (CSI) (ratio: still-living children/total-live births) in the Warao population, the principal causes of childhood death and the socio-demographic factors associated with childhood deaths.MethodsWe conducted a cross-sectional epidemiological survey of 688 women from 97 communities in 7 different subregions of the Orinoco Delta. Data collected included socio-demographic characteristics and the reproductive history of each woman surveyed. The multidimensional poverty index (MPI) was used to classify the households as deprived across the three dimensions of the Human Development Index. Multivariable linear regression and Generalized Linear Model Procedures were used to identify socioeconomic and environmental characteristics statistically associated with the CSI.FindingsThe average CSI was 73.8% ±26. The two most common causes of death were gastroenteritis/diarrhea (63%) and acute respiratory tract Infection/pneumonia (18%). Deaths in children under five years accounted for 97.3% of childhood deaths, with 54% occurring in the neonatal period or first year of life. Most of the women (95.5%) were classified as multidimensionally poor. The general MPI in the sample was 0.56. CSI was negatively correlated with MPI, maternal age, residence in a traditional dwelling and profession of the head of household other than nurse or teacher.ConclusionsThe Warao have a low CSI which is correlated with MPI and maternal age. Infectious diseases are responsible for 85% of childhood deaths. The low socioeconomic development, lack of infrastructure and geographic and cultural isolation suggest that an integrated approach is urgently needed to improve the child survival and overall health of the Warao Amerindians.

MicroRNAs (miRNAs) are endogenously expressed noncoding RNA molecules that are believed to regulate multiple neurobiological processes. Expression studies have revealed distinct temporal expression patterns in the developing rodent and porcine brain, but comprehensive profiling in the developing human brain has not been previously reported.We performed microarray and TaqMan-based expression analysis of all annotated mature miRNAs (miRBase 10.0) as well as 373 novel, predicted miRNAs. Expression levels were measured in 48 post-mortem brain tissue samples, representing gestational ages 14-24 weeks, as well as early postnatal and adult time points.Expression levels of 312 miRNAs changed significantly between at least two of the broad age categories, defined as fetal, young, and adult.We have constructed a miRNA expression atlas of the developing human brain, and we propose a classification scheme to guide future studies of neurobiological function.

Low-dose ionizing radiation (LDR) may lead to suppression of smoking-related lung cancer. We examined the effects of a known cigarette smoke carcinogen Benzo[a]pyrene (B[a]P) alone or in combination with fractionated low-dose gamma radiation (60 – 600 mGy total dose) on the induction of lung neoplasms in the A/J mouse. Our results show that 600 mGy of gamma radiation delivered in six biweekly fractions of 100 mGy starting 1 month after B[a]P injection significantly inhibits the development of lung adenomas per animal induced by B[a]P. Our data also indicated that the six biweekly doses suppressed the occurrence of spontaneous hyperplastic foci in the lung, although this suppression failed to reach statistical significance when analyzed as average foci per lung possibly related to the small sample sizes used for the control and test groups.

Person-to-person transmission of influenza viruses occurs by contact (direct and fomites) and non-contact (droplet and small particle aerosol) routes, but the quantitative dynamics and relative contributions of these routes are incompletely understood. The transmissibility of influenza strains estimated from secondary attack rates in closed human populations is confounded by large variations in population susceptibilities. An experimental method to phenotype strains for transmissibility in an animal model could provide relative efficiencies of transmission. We developed an experimental method to detect exhaled viral aerosol transmission between unanesthetized infected and susceptible ferrets, measured aerosol particle size and number, and quantified the viral genomic RNA in the exhaled aerosol. During brief 3-hour exposures to exhaled viral aerosols in airflow-controlled chambers, three strains of pandemic 2009 H1N1 strains were frequently transmitted to susceptible ferrets. In contrast one seasonal H1N1 strain was not transmitted in spite of higher levels of viral RNA in the exhaled aerosol. Among three pandemic strains, the two strains causing weight loss and illness in the intranasally infected 'donor' ferrets were transmitted less efficiently from the donor than the strain causing no detectable illness, suggesting that the mucosal inflammatory response may attenuate viable exhaled virus. Although exhaled viral RNA remained constant, transmission efficiency diminished from day 1 to day 5 after donor infection. Thus, aerosol transmission between ferrets may be dependent on at least four characteristics of virus-host relationships including the level of exhaled virus, infectious particle size, mucosal inflammation, and viral replication efficiency in susceptible mucosa.

Aberrant cytosine methylation affects regulation of hundreds of genes during cancer development. In this study, a novel aberrantly hypermethylated CpG island in cancer was discovered within the TOX2 promoter. TOX2 was unmethylated in normal cells but 28% lung (n = 190) and 23% breast (n = 80) tumors were methylated. Expression of two novel TOX2 transcripts identified was significantly reduced in primary lung tumors than distant normal lung (p

Although it is well known that epidermal growth factor receptor (EGFR) is involved in lung cancer progression, whether EGFR contributes to lung epithelial cell transformation is less clear. Mucin 1 (MUC1 in human and Muc1 in animals), a glycoprotein component of airway mucus, is overexpressed in lung tumors; however, its role and underlying mechanisms in early stage lung carcinogenesis is still elusive. This study provides strong evidence demonstrating that EGFR and MUC1 are involved in bronchial epithelial cell transformation. Knockdown of MUC1 expression significantly reduced transformation of immortalized human bronchial epithelial cells induced by benzo[a]pyrene diol epoxide (BPDE), the active form of the cigarette smoke (CS) carcinogen benzo(a)pyrene (BaP)s. BPDE exposure robustly activated a pathway consisting of EGFR, Akt and ERK, and blocking this pathway significantly increased BPDE-induced cell death and inhibited cell transformation. Suppression of MUC1 expression resulted in EGFR destabilization and inhibition of the BPDE-induced activation of Akt and ERK and increase of cytotoxicity. These results strongly suggest an important role for EGFR in BPDE-induced transformation, and substantiate that MUC1 is involved in lung cancer development, at least partly through mediating carcinogen-induced activation of the EGFR-mediated cell survival pathway that facilitates cell transformation.

Influenza virus is a major cause of morbidity and mortality worldwide, yet little quantitative understanding of transmission is available to guide evidence-based public health practice. Recent studies of influenza non-contact transmission between ferrets and guinea pigs have provided insights into the relative transmission efficiencies of pandemic and seasonal strains, but the infecting dose and subsequent contagion has not been quantified for most strains. In order to measure the aerosol infectious dose for 50% (aID(50)) of seronegative ferrets, seasonal influenza virus was nebulized into an exposure chamber with controlled airflow limiting inhalation to airborne particles less than 5 µm diameter. Airborne virus was collected by liquid impinger and Teflon filters during nebulization of varying doses of aerosolized virus. Since culturable virus was accurately captured on filters only up to 20 minutes, airborne viral RNA collected during 1-hour exposures was quantified by two assays, a high-throughput RT-PCR/mass spectrometry assay detecting 6 genome segments (Ibis T5000™ Biosensor system) and a standard real time RT-qPCR assay. Using the more sensitive T5000 assay, the aID(50) for A/New Caledonia/20/99 (H1N1) was approximately 4 infectious virus particles under the exposure conditions used. Although seroconversion and sustained levels of viral RNA in upper airway secretions suggested established mucosal infection, viral cultures were almost always negative. Thus after inhalation, this seasonal H1N1 virus may replicate less efficiently than H3N2 virus after mucosal deposition and exhibit less contagion after aerosol exposure.