Miracle-dz/UniFAR-FTUs huggingface dataset:
Seismic Tomography of the Trans-North China Orogen and Its Dynamic Implications

We present a high-resolution S wave velocity model of the Trans-North China Orogen (TNCO) and its adjacent areas derived from S wave traveltime residuals of teleseismic waveforms recorded by the dense ChinArray seismic network. Our model reveals S wave velocity anomalies beneath the study area, suggesting the strong lateral heterogeneities of the upper mantle structures. The upper mantle of the Datong volcano is dominated by the significant low velocity anomalies. In addition to the low-velocity zone rooted in the mantle transition zone beneath the Datong volcano region, two low velocity layers extend northwestward to the Hetao graben and southwestward to the southern TNCO within depths of 100–300 km, respectively. Based on these low-velocity anomalies, we provide new insights into the origin of the Datong volcano, which may be related to the asthenospheric upwelling originated from the water-rich mantle transition zone and horizontal mantle flows driven by the extrusion northeastward of the Tibetan plateau. A clear velocity contrast in the upper mantle above 300 km depth beneath the Ordos block and the TNCO implies that the Ordos block still preserves thick cratonic root while the lithosphere of the TNCO is modified. We propose that the asthenospheric upwelling and northeastward push of the Tibetan plateau account for the lithospheric deformation of the TNCO and its adjacent areas.
Cloning of Nitrate Reductase and Nitrite Reductase Genes and Their Functional Analysis in Regulating Cr(VI) Reduction in Ectomycorrhizal Fungus Pisolithus sp.1

Assimilatory-type nitrate reductase (NR) and nitrite reductase (NiR) are the key enzymes that involve in nitrate assimilation and nitrogen cycling in microorganisms. NR and NiR with NADH or NADPH and FMN or FAD domains could be coupled to the reduction process of hexavalent chromium [Cr(VI)] in microorganisms. A new assimilatory-type NR gene (named niaD) and a new assimilatory-type NiR gene (named niiA) are cloned, identified, and functionally characterized by 5′ and 3′ RACE, alignment, annotation, phylogenetic tree, and yeast mutant complementation analyses from Pisolithus sp.1, a dominant symbiotic ectomycorrhizal fungi (EMF) that can assist in phytoremediation. Assimilatory-type niaD and niiA were 2,754 bp and 3,468 bp and encode a polypeptide with 917 and 1,155 amino acid residues, respectively. The isoelectric points of NR (Pisolithus sp.1 NR) and NiR (Pisolithus sp.1 NiR) of Pisolithus sp.1 are 6.07 and 6.38, respectively. The calculated molecular mass of Pisolithus sp.1 NR and Pisolithus sp.1 NiR is 102.065 and 126.914 kDa, respectively. Yeast mutant complementation analysis, protein purification, and activities of NR and NiR under Cr treatment suggest that Pisolithus sp.1 NR is a functional NR that mediates Cr(VI) tolerance and reduction. The multiple alignment demonstrates that Pisolithus sp.1 NR is potentially a nicotinamide adenine dinucleotide phosphate-dependent flavin mononucleotide reductase and also Class II chromate reductase. Our results suggest that Pisolithus sp.1 NR plays a key role in Cr(VI) reduction in the EMF Pisolithus sp.1.
A Phenotype and Genotype Case Report of a Neonate With Congenital Bilateral Coronary Artery Fistulas and Multiple Collateral Arteries

We report a unique case of an 18-day-old girl with three coronary artery fistulas to the right atrium and right ventricle, respectively: three collateral arteries arising from the descending aorta and one from the right subclavian artery draining through a sac to the top of the right atrium, patent ductus arteriosus, and atrial septal defect. She presented symptoms of acute congestive heart failure. Cardiac catheterization and surgical interventions were performed to repair the defects. The patient recovered uneventfully and grew up well at 3 years of follow-up. Whole-genome sequencing (WES) in the patient, compared to her parents, showed 17 variants within 11 genes. Among these, only compound heterozygous mutation, c.T470G (p.L157R) and c.A1622G (p.D541G), in the DRC1 gene have been reportedly related to congenital heart disease and are the most likely causative in our patient.
Genomic Investigation of Proteus mirabilis Isolates Recovered From Pig Farms in Zhejiang Province, China

Proteus mirabilis is a common opportunistic zoonotic pathogen, and its ongoing acquisition of antimicrobial resistance genes poses challenges to clinical treatments. Human-sourced whole genomic sequencing of human P. mirabilis isolates has been reported, but pig-sourced isolates have not been thoroughly investigated even though these animals can serve as reservoirs for human infections. In the current study, we report a molecular epidemiological investigation to unravel the antimicrobial and virulence gene risk factors for P. mirabilis contamination in 9 pig farms in 3 different cities in Zhejiang Province, China. We collected 541 swab samples from healthy pigs and 30 were confirmed as P. mirabilis. All 30 isolates were resistant to tetracyclines, macrolides, sulfonamides, β-lactams and chloramphenicol, and all were multiple drug-resistant and 27 were strong biofilm formers. Phylogenetic analyses indicated these 30 isolates clustered together in 2 major groups. Whole genome sequencing demonstrated that the isolates possessed 91 different antimicrobial resistance genes belonging to 30 antimicrobial classes including rmtB, sul1, qnrS1, AAC(6′) − Ib − cr, blaCTX − M − 65 and blaOXA − 1. All isolates contained mobile genetic elements including integrative conjugative elements (ICEs) and integrative and mobilizable elements (IMEs). Minimum inhibitory concentration (MIC) testing indicated direct correlates between cognate genes and antimicrobial resistance. We also identified 95 virulence factors, almost all isolates contained 20 fimbrial and flagellar operons, and this represents the greatest number of these operon types found in a single species among all sequenced bacterial genomes. These genes regulate biofilm formation and represent a confounding variable for treating P. mirabilis infections. Our P. mirabilis isolates were present in healthy animals, and multiple drug resistance in these isolates may serve as a reservoir for other intestinal and environmental Enterobacteriaceae members. This prompts us to more strictly regulate veterinary antibiotic use.
A Barrier to Defend - Models of Pulmonary Barrier to Study Acute Inflammatory Diseases

Pulmonary diseases represent four out of ten most common causes for worldwide mortality. Thus, pulmonary infections with subsequent inflammatory responses represent a major public health concern. The pulmonary barrier is a vulnerable entry site for several stress factors, including pathogens such as viruses, and bacteria, but also environmental factors e.g. toxins, air pollutants, as well as allergens. These pathogens or pathogen-associated molecular pattern and inflammatory agents e.g. damage-associated molecular pattern cause significant disturbances in the pulmonary barrier. The physiological and biological functions, as well as the architecture and homeostatic maintenance of the pulmonary barrier are highly complex. The airway epithelium, denoting the first pulmonary barrier, encompasses cells releasing a plethora of chemokines and cytokines, and is further covered with a mucus layer containing antimicrobial peptides, which are responsible for the pathogen clearance. Submucosal antigen-presenting cells and neutrophilic granulocytes are also involved in the defense mechanisms and counterregulation of pulmonary infections, and thus may directly affect the pulmonary barrier function. The detailed understanding of the pulmonary barrier including its architecture and functions is crucial for the diagnosis, prognosis, and therapeutic treatment strategies of pulmonary diseases. Thus, considering multiple side effects and limited efficacy of current therapeutic treatment strategies in patients with inflammatory diseases make experimental in vitro and in vivo models necessary to improving clinical therapy options. This review describes existing models for studyying the pulmonary barrier function under acute inflammatory conditions, which are meant to improve the translational approaches for outcome predictions, patient monitoring, and treatment decision-making.
Bacteria Wear ICG Clothes for Rapid Detection of Intracranial Infection in Patients After Neurosurgery and Photothermal Antibacterial Therapy Against Streptococcus Mutans

Bacterial infection is one of the most serious physiological conditions threatening human health. There is an increasing demand for more effective bacterial diagnosis and treatment through non-invasive approaches. Among current antibacterial strategies of non-invasive approaches, photothermal antibacterial therapy (PTAT) has pronounced advantages with properties of minor damage to normal tissue and little chance to trigger antimicrobial resistance. Therefore, we developed a fast and simple strategy that integrated the sensitive detection and photothermal therapy of bacteria by measuring adenosine triphosphate (ATP) bioluminescence following targeted photothermal lysis. First, 3-azido-d-alanine (d-AzAla) is selectively integrated into the cell walls of bacteria, photosensitizer dibenzocyclooctyne, and double sulfonic acid-modified indocyanine green (sulfo-DBCO-ICG) are subsequently designed to react with the modified bacteria through in vivo click chemistry. Next, the sulfo-DBCO-ICG modified bacteria under irradiation of 808 nm near-infrared laser was immediately detected by ATP bioluminescence following targeted photothermal lysis and even the number of bacteria on the infected tissue can be significantly reduced through PTAT. This method has demonstrated the ability to detect the presence of the bacteria for ATP value in 32 clinical samples. As a result, the ATP value over of 100 confirmed the presence of bacteria in clinical samples for 22 patients undergoing craniotomy and ten otitis media patients. Overall, this study paves a brand new avenue to facile diagnosis and a treatment platform for clinical bacterial infections.
The Practical Utility of Imidazolium Hydrogen Sulfate Ionic Liquid in Fabrication of Lignin-Based Spheres: Structure Characteristic and Antibacterial Activity

In this study, lignin-based spherical particles (Lig-IL) with the use of 1-(propoxymethyl)-1H-imidazolium hydrogen sulfate were prepared in different biopolymer and ionic liquid (IL) weight ratios. The application of IL during the preparation of spherical particles is an innovative method, which may be beneficial for further applications. The particles were obtained with the use of the soft-templating method and their chemical, structural and morphological characterization was performed. The spherical shape of products and their size (91–615 nm) was confirmed with the use of scanning electron microscopy (SEM) images and the particle size distribution results. The attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectra were analyzed to identify functional groups of all precursors and produced material and it was confirmed, that all materials exhibit characteristic hydroxyl and carboxylic groups, but the presence of carbonyl group was detected. Moreover, the zeta potential analysis was performed to evaluate the electrokinetic behavior of obtained materials. It was confirmed, that all materials are colloidally stable in pH above 4. Produced lignin-based spherical particles were used for evaluation of their antibacterial properties. Particles were tested against Staphylococcus aureus (S. aureus), a gram-positive bacterium, and Escherichia coli (E. coli), a gram-negative one. It was observed, that only the material with the highest addition of IL showed the antibacterial properties against both strains. A reduction of 50% in the number of microorganisms was observed for particles with the addition of hydrogen sulfate ionic liquid in a 1:1 ratio after 1 h. However, all prepared materials exhibited the antibacterial activity against a gram-positive bacterium.
Fruit and Vegetable Consumption Interacts With HNF1A Variants on the C-Reactive Protein

Epidemiological studies have demonstrated the inverse association between the intake of fruits and vegetables and inflammation. However, the mechanisms by which inflammation-related genes interact with fruit and vegetable intake and the role of these combinations in inflammation remain unclear. Therefore, we assessed the effect of interactions between fruit and vegetable intake and the hepatic nuclear factor 1 alpha (HNF1A) genetic variants on the C-reactive protein (CRP) levels. Baseline data from the Ansan and Ansung Cohort Study of the Korean Genome and Epidemiology Study (KoGES) were used. A total of 7,634 participants (3,700 men and 3,934 women) were included in the analyses. Fruit and vegetable intake was assessed using semi-quantitative food frequency questionnaire data. Genotyping information for HNF1A was extracted from the Affymetrix Genome-Wide Human SNP array 5.0. Inflammation was determined after overnight fasting by measuring CRP levels using automated analyzers. Multivariable logistic regression was used to estimate the adjusted odds ratio (AOR) with a 95% confidence interval (CI). In the fully adjusted model, men and women with the GG genotype of HNF1A rs2393791 and high fruit intake had lower odds of elevated CRP levels compared to those with the AA genotype and low fruit intake (AOR 0.50, 95% CI 0.38–0.67; AOR 0.73, 95% CI 0.55–0.97, respectively). Men and women with the rs2393791 GG genotype and high vegetable intake had lower odds of having elevated CRP levels compared to those with the AA genotype and low fruit intake (AOR 0.57, 95% CI 0.43–0.75; AOR 0.65, 95% CI 0.49–0.86, respectively). Men and women with the GG genotype and high total fruit and vegetable intake had lower odds of having elevated CRP levels. These findings indicate that fruit and vegetable intake interacts with HNF1A genetic polymorphisms, consequently influencing the inflammation levels.
Effect of a Low-Carbohydrate Diet With or Without Exercise on Anxiety and Eating Behavior and Associated Changes in Cardiometabolic Health in Overweight Young Women

Background The effectiveness of low-carbohydrate diets (LCDs) on weight loss and exercise for improving cardiometabolic fitness have been well documented in the literature, but the effects of LCDs and whether adding exercise to a LCD regime could additionally benefit mental health (e. g., by lowering the level of anxiety) and associated changes in eating behavior are less clear in overweight and obese populations. Therefore, this study aimed to investigate the effects of a 4-week LCD with or without exercise on anxiety and eating behavior, and to explore the associations between changes in the psychological state and physiological parameters (i.e., body composition, aerobic fitness, blood pressure, lipid profile, and metabolic hormones). Methods Seventy-four overweight Chinese women [age: 20.8 ± 3.0 years, body mass index (BMI): 25.3 ± 3.3 kg·m−2] completed the 4-week randomized controlled trial, which included a LCD group (i.e., ~50 g daily carbohydrate intake) with exercise training 5 days/week (LC-EXE, n = 26), a LCD group without exercise training (LC-CON, n = 25) and a control group that did not modify their habitual diets and physical activity (CON, n = 23). Levels of anxiety, eating behavior scores and physiological parameters (i.e., body weight, V̇O2peak, blood pressure, fasting glucose, blood lipids, and serum metabolic hormones including insulin, C-peptide, leptin, and ghrelin) were measured before and after the intervention. Results There were significant reductions in anxiety levels in the LC-EXE compared with the LC-CON group, while no statistical changes were found in eating behaviors in any conditions after the 4-week intervention. Significant reduction in weight (~3.0 kg or 4%, p < 0.01) and decreases in insulin (~30% p < 0.01), C-peptide (~20% p < 0.01), and leptin (~40%, p < 0.01) were found in both LC-CON and LC-EXE groups, but adding exercise to a LCD regime generated no additional effects. There were significant improvements in V̇O2peak (~15% p < 0.01) and anxiety (~25% p < 0.01) in the LC-EXE compared with the LC-CON group, while no statistical differences were found between CON and LC-CON treatments. Further analysis revealed a negative association (r = −0.32, p < 0.01) between changes in levels of anxiety and changes in V̇O2peak in all participates, no other correlations were found between changes in psychological and physiological parameters. Conclusion Although the combination of a LCD and exercise may not induce additional reductions in body weight in overweight young females, exercise could be a useful add-on treatment along with a LCD to improve cardiometabolic health and lower anxiety levels.
Medial Septum Modulates Consciousness and Psychosis-Related Behaviors Through Hippocampal Gamma Activity

Abnormally high-amplitude hippocampal gamma activity (30–100 Hz) in behaving animals is seen after a hippocampal seizure, following injection of phencyclidine (PCP) or ketamine, and transiently in a delirium stage during induction of general anesthesia. High-amplitude hippocampal gamma activity in behaving rats is associated with hyperactive behavior and impairment in sensorimotor gating and sensory gating. The medial septum is necessary for the high-amplitude gamma activity and abnormal behaviors observed following a hippocampal seizure or injection of PCP/ketamine. Glutamatergic projection of the hippocampus to the nucleus accumbens (NAC) and dopaminergic transmission in NAC is necessary for abnormal behaviors. Large hippocampal gamma waves are suggested to contribute to seizure-induced automatism following temporal lobe seizures, and the schizophrenia-like symptoms induced by PCP/ketamine. Low-amplitude gamma activity is found during general anesthesia, associated with loss of consciousness in humans and loss of righting reflex in animals. Local inactivation or lesion of the medial septum, NAC, and brain areas connected to the septohippocampal-NAC system attenuates the increase in hippocampal gamma and associated behavioral disruptions induced by hippocampal seizure or PCP/ketamine. Inactivation or lesion of the septohippocampal-NAC system decreases the dose of anesthetic necessary for gamma decrease and loss of consciousness in animals. Thus, it is proposed that the septohippocampal-NAC system serves to control consciousness and the behavioral hyperactivity and neural dysfunctions during psychosis.
N-glycosylation of UNC93B1 at a Specific Asparagine Residue Is Required for TLR9 Signaling

Toll-like receptors (TLRs) play critical roles in the first line of host defense against pathogens through recognition of pathogen-associated molecular patterns and initiation of the innate immune responses. The proper localization of TLRs in specific subcellular compartments is crucial for their ligand recognition and downstream signaling to ensure appropriate responses against pathogens while avoiding erroneous or excessive activation. Several TLRs, including TLR7 and TLR9 but not TLR4, depend on UNC93B1 for their proper intracellular localization and signaling. Accumulating evidence suggest that UNC93B1 differentially regulates its various client TLRs, but the specific mechanisms by which UNC93B1 controls individual TLRs are not well understood. Protein N-glycosylation is one of the most frequent and important post-translational modification that occurs in membrane-localized or secreted proteins. UNC93B1 was previously shown to be glycosylated at Asn251 and Asn272 residues. In this study, we investigated whether N-glycosylation of UNC93B1 affects its function by comparing wild type and glycosylation-defective mutant UNC93B1 proteins. It was found that glycosylation of Asn251 and Asn272 residues can occur independently of each other and mutation of neither N251Q or N272Q in UNC93B1 altered expression and localization of UNC93B1 and TLR9. In contrast, CpG DNA-stimulated TLR9 signaling was severely inhibited in cells expressing UNC93B1(N272Q), but not in cells with UNC93B1(N251Q). Further, it was found that glycosylation at Asn272 of UNC93B1 is essential for the recruitment of MyD88 to TLR9 and the subsequent downstream signaling. On the other hand, the defective glycosylation at Asn272 did not affect TLR7 signaling. Collectively, these data demonstrate that the glycosylation at a specific asparagine residue of UNC93B1 is required for TLR9 signaling and the glycosylation status of UNC93B1 differently affects activation of TLR7 and TLR9.
Comprehensive Analysis of TRP Channel–Related Genes in Patients With Triple-Negative Breast Cancer for Guiding Prognostic Prediction

Background Triple-negative breast cancer (TNBC) is a special subtype of breast cancer. Transient Receptor Potential (TRP) channel superfamily has emerged as a novel and interesting target in a variety of tumors. However, the association of TRP channel–related genes with TNBC is still unclear. Methods The The Cancer Genome Atlas (TCGA)-TNBC and GSE58812 datasets were downloaded from the public database. The differentially expressed TRP channel–related genes (DETGs) were screened by limma package, and mutations of the above genes were analyzed. Subsequently, new molecular subtypes in TNBC-based DETGs were explored by consensus clustering analysis. In addition, Lasso–Cox regression analysis was used to divide it into two robust risk subtypes: high-risk group and low-risk group. The accuracy and distinguishing ability of above models were verified by a variety of methods, including Kaplan–Meier survival analysis, ROC analysis, calibration curve, and PCA analysis. Meanwhile, CIBERSORT algorithm was used to excavate status of immune-infiltrating cells in TNBC tissues. Last, we explored the therapeutic effect of drugs and underlying mechanisms of risk subgroups by pRRophetic package and GSEA algorithm, respectively. Results A total of 19 DETGs were identified in 115 TNBC and 113 normal samples from TCGA database. In addition, missense mutation and SNP were the most common variant classification. According to Lasso–Cox regression analysis, the risky formula performed best when nine genes were used: TRPM5, TRPV2, HTR2B, HRH1, P2RY2, MAP2K6, NTRK1, ADCY6, and PRKACB. Subsequently, Kaplan–Meier survival analysis, ROC analysis, calibration curve, and Principal Components Analysis (PCA) analysis showed an excellent accuracy for predicting OS using risky formula in each cohort (P < 0.05). Specifically, high-risk group had a shorter OS compared with low-risk group. In addition, T-cell CD4 memory activated and macrophages M1 were enriched in normal tissues, whereas Tregs were increased in tumor tissues. Note that the low-risk group was better therapeutic effect to docetaxel, doxorubicin, cisplatin, paclitaxel, and gemcitabine than the high-risk group (P < 0.05). Last, in vitro assays, Quantitative Real-time PCR (qRT-PCR) indicated that TRPM5 was significantly highly expressed in MDA-MB-231 and MDA-MB-468 cells compared with that in MCF-10A cells (P < 0.01). Conclusion We identified a risky formula based on expression of TRP channel–related genes that can predict prognosis, therapeutic effect, and status of tumor microenvironment for patients with TNBC.