Background
Lung infection is a global health problem associated with high morbidity and mortality and increasing rates of hospitalization. The correlation between pulmonary microecology and infection ...severity remains unclear. Therefore, the purpose of this study was to investigate the differences in lung microecology and potential biomarkers in patients with mild and severe pulmonary infection.
Method
Patients with pulmonary infection or suspected infection were divided into the mild group (140 cases) and the severe group (80 cases) according to pneomonia severity index (PSI) scores. Here, we used metagenomic next-generation sequencing (mNGS) to detect DNA mainly from bronchoalveolar lavage fluid (BALF) collected from patients to analyze changes in the lung microbiome of patients with different disease severity.
Result
We used the mNGS to analyze the pulmonary microecological composition in patients with pulmonary infection. The results of alpha diversity and beta diversity analysis showed that the microbial composition between mild and severe groups was similar on the whole. The dominant bacteria were
Acinetobacter
,
Bacillus
,
Mycobacterium
,
Staphylococcus
, and
Prevotella
, among others. Linear discriminant analysis effect size (LEfSe) results showed that there were significant differences in virus composition between the mild and severe patients, especially Simplexvirus and Cytomegalovirus, which were prominent in the severe group. The random forest model screened 14 kinds of pulmonary infection-related pathogens including
Corynebacterium
,
Mycobacterium
,
Streptococcus
,
Klebsiella
, and
Acinetobacter
. In addition, it was found that
Rothia
was negatively correlated with
Acinetobacter
,
Mycobacterium
,
Bacillus
,
Enterococcus
, and
Klebsiella
in the mild group through co-occurrence network, while no significant correlation was found in the severe group.
Conclusion
Here, we describe the composition and diversity of the pulmonary microbiome in patients with pulmonary infection. A significant increase in viral replication was found in the severe group, as well as a significant difference in microbial interactions between patients with mild and severe lung infections, particularly the association between the common pathogenic bacteria and
Rothia
. This suggests that both pathogen co-viral infection and microbial interactions may influence the course of disease. Of course, more research is needed to further explore the specific mechanisms by which microbial interactions influence disease severity.
The mechanism of syngas to ethanol on MoCu(211)surface has been researched by density functional theory(DFT)calculation,and the effects of Mo as a promoter on C—O bond breaking and C—C bond ...for-mation have been discussed.Calculations show that Cu-Mo atoms constitute the active sites on MoCu(211)surface after Mo atom being served as a promoter of Cu catalyst.Compared with Cu(211),MoCu(211)has two improvements.Firstly,CH3 is the most advantageous monomer on the MoCu(211)surface,which provides abundant CH3 intermediate for syngas to ethanol.Secondly,the C—C bond is formed mainly by inserting CHO into the abundant CH3,and the generated CH3CHO through multiple steps of hydrogenation to generate C2H5OH.The key of the promoter Mo on the MoCu(211)surface also has been verified by the analysis of its electronic properties.Differential charge density shows that the massive electron transfer from Mo to Cu,projected density of states(pDOS)shows that the electron trans-fer from Mo to Cu makes the d-band center of MoCu(211)nearer to the Fermi level,these indicate that the MoCu(211)catalytic capacity increased.The addition of Mo in the Cu-based catalyst not only can effectively solve the problem of C—O bond breaking,but also promote C—C bond formation.About the influence of Mo content on C—O bond breaking and C—C bond formation,compared with MoCu(211),the DFT results and the d-band center of Mo2Cu(211)show that the increase of Mo content could not promote the synergistic effect of Cu/Mo on the generation of ethanol more effectively.
This paper is concerned with the application of a machine learning approach to inverse elastic scattering problems via neural networks. In the forward problem, the displacements are approximated by ...linear combinations of the fundamental tensors of the Cauchy-Navier equations of elasticity, which are expressed in terms of sources placed inside the elastic solid. From the near-field measurement data, a two-layer neural network method consisting of a gated recurrent unit to gate recurrent unit has been used to reconstruct the shape of an unknown elastic body. Moreover, the convergence of the method is proved. Finally, the feasibility and effectiveness of the presented method are examined through numerical examples.
Shift work, with its growing prevalence globally, disrupts the body's inherent circadian rhythm. This disruption may escalate the risk of chronic diseasesxacerbate chronic disease risk by ...dysregulating physiological, behavioral, and psychosocial pathways. This study aimed to evaluate the effect of shift work on type 2 diabetes (T2DM) and Retinol binding protein 4 (RBP4) level.
The current study employed a multi-stage stratified cluster sampling technique, examining 1499 oilfield workers from the OHSPIW cohort who participated in occupational health assessments between March 2017 and June 2018.The evaluation involved shift work, sleep quality, T2DM status with questionnaires and plasma RBP4 levels in blood samples. Statistical analysis includes, Chi-square tests, t-tests, multivariate logistic regression analyses, and multivariate linear mixed models.
The prevalence rate of T2DM in shift workers (6.56%) was significantly higher than in day workers (4.21%) (OR = 1.60, 95% CI: 1.01-2.53), with no significant difference found in the family history of diabetes, hypertension, or other chronic heart diseases (P = 0.378). The shift worker (6.89 ± 3.35) also exhibited distinctly higher PSQI scores than day workers (5.99 ± 2.87) (P < 0.001). Adjusting the age, gender, BMI, family income, tobacco smoking, alcohol drinking and PSQI, hailed shift work as a risk factor for T2DM (OR = 1.91, 95% CI: 1.17-3.14). The pairwise comparison revealed significant differences in RBP4 levels across different groups: shift and non-shift workers both with and without T2DM (P < 0.001). The RBP4 level of the shift group without T2DM was higher than the non-shift group without T2DM (P < 0.05). The levels of RBP4 level in shift and non-shift groups with T2DM was higher than those without T2DM (P < 0.05). The multivariate linear mixed model showed that when age, gender, BMI, diabetes, PSQI, family income, smoking and drinking remained unchanged, the RBP4 level of the shift workers increased by an average of 9.51 μg/mL compared with the day workers.
Shift work is associated with an increased risk of T2DM and high levels of RBP4. Follow-up of RBP4 could facilitateearly detection of T2DM among shift workers.
Human hematopoietic organoids have a wide application value for modeling human bone marrow diseases, such as acute hematopoietic radiation injury. However, the manufacturing of human hematopoietic ...organoids is an unaddressed challenge because of the complexity of hematopoietic tissues.
To manufacture hematopoietic organoids, we obtained CD34
hematopoietic stem and progenitor cells (HSPCs) from human embryonic stem cells (hESCs) using stepwise induction and immunomagnetic bead-sorting. We then mixed these CD34
HSPCs with niche-related cells in Gelatin-methacryloyl (GelMA) to form a three-dimensional (3D) hematopoietic organoid. Additionally, we investigated the effects of radiation damage and response to granulocyte colony-stimulating factor (G-CSF) in hematopoietic organoids.
The GelMA hydrogel maintained the undifferentiated state of hESCs-derived HSPCs by reducing intracellular reactive oxygen species (ROS) levels. The established hematopoietic organoids in GelMA with niche-related cells were composed of HSPCs and multilineage blood cells and demonstrated the adherence of hematopoietic cells to niche cells. Notably, these hematopoietic organoids exhibited radiation-induced hematopoietic cell injury effect, including increased intracellular ROS levels, γ-H2AX positive cell percentages, and hematopoietic cell apoptosis percentages. Moreover, G-CSF supplementation in the culture medium significantly improved the survival of HSPCs and enhanced myeloid cell regeneration in these hematopoietic organoids after radiation.
These findings substantiate the successful manufacture of a preliminary 3D hematopoietic organoid from hESCs-derived HSPCs, which was utilized for modeling hematopoietic radiation injury and assessing the radiation-mitigating effects of G-CSF in vitro. Our study provides opportunities to further aid in the standard and scalable production of hematopoietic organoids for disease modeling and drug testing.
Renal fibrosis is a manifestation of kidney injury. Nephropathy 1st is a traditional Chinese herbal medicine that has been used as a therapy for kidney disease, but the underlying mechanisms remain ...elusive. The aim of this study was to investigate the role and underlying mechanisms of Nephropathy 1st on the progression of kidney disease. In the present study, unilateral ureteral obstruction was performed to establish the renal fibrosis rat model. By hematoxylin–eosin staining and immunohistochemical staining analysis, the severity of renal fibrosis was evaluated
in vivo
. Serum creatinine (CREA) and urea nitrogen (BUN) were measured by ELISA. The expression levels of Col-I, FN, PPARγ, and Klotho were measured by Western blot in rat NRK-49F cells and in fibrotic rats. GW9662 was used to inhibit PPARγ signaling. Metabonomic analysis showed metabolic differences among groups. Nephropathy 1st administration alleviated the progression of rat renal fibrosis and reduced serum creatinine (Scr) and BUN levels. Mechanistically, Nephropathy 1st promoted the expression of PPARγ and thus activated PPARγ signaling, thereby reducing the pro-fibrotic phenotypes of fibroblasts. The therapeutic effect of Nephropathy 1st was abrogated by the PPARγ inhibitor GW9662. Moreover, Nephropathy 1st normalized the dysregulated lipid metabolism in renal fibrosis rats. In conclusion, Nephropathy 1st alleviates renal fibrosis development in a PPARγ-dependent manner.
With the expansion of the aging population, age-associated sarcopenia (AAS) has become a severe clinical disease of the elderly and a key challenge for healthy aging. Regrettably, no approved ...therapies currently exist for treating AAS. In this study, clinical-grade human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) were administrated to two classic mouse models (SAMP8 mice and D-galactose-induced aging mice), and their effects on skeletal muscle mass and function were investigated by behavioral tests, immunostaining, and western blotting. Core data results showed that hUC-MSCs significantly restored skeletal muscle strength and performance in both mouse models via mechanisms including raising the expression of crucial extracellular matrix proteins, activating satellite cells, enhancing autophagy, and impeding cellular aging. For the first time, the study comprehensively evaluates and demonstrates the preclinical efficacy of clinical-grade hUC-MSCs for AAS in two mouse models, which not only provides a novel model for AAS, but also highlights a promising strategy to improve and treat AAS and other age-associated muscle diseases. This study comprehensively evaluates the preclinical efficacy of clinical-grade hUC-MSCs in treating age-associated sarcopenia (AAS), and demonstrates that hUC-MSCs restore skeletal muscle strength and performance in two AAS mouse models via raising the expression of extracellular matrix proteins, activating satellite cells, enhancing autophagy, and impeding cellular aging, which highlights a promising strategy for AAS and other age-associated muscle diseases.
A new compilation of heat flow data for the continental area of China has been constructed using both published data (up to 1999) as well as previously unpublished data. The data set is composed of ...862 observations from different sites. Within the continental area of China, heat flow values range from 23 to 319 mW/m
2, with a mean of 63±24.2 mW/m
2. If non-conductive values related to local hydrothermal systems are excluded, the representative average heat flow is 61±15.5 mW/m
2 (
n=823), with an associated range of 30–140 mW/m
2. Heat flow analysis for each specific sub-tectonic province shows discernible trends within a tectonic province. The relationships between the heat flow and geological ages based on this new dataset indicate that surface heat flow is obviously more dependent on the last tectonothermal activity than the age of the orogeny. The overall heat flow pattern exhibits high values in the east and in the southwest, and low in the center and northwest parts of the continental area of China, and appears to be dominated largely by the Meso-Cenozoic tectonothermal evolution of the lithosphere. The Cenozoic collision between the Indian and Eurasian plates, and the subsequent thickening of the lithosphere; and the lithospheric thinning and volcano-magmatic activities during the Late Mesozoic in East China; can be seen clearly in the heat flow pattern.
Generating chromosome-scale haplotype resolved assembly is important for functional studies. However, current de novo assemblers are either haploid assemblers that discard allelic information, or ...diploid assemblers that can only tackle genomes of low complexity.
Here, Using robust programs, we build a diploid genome assembly pipeline called gcaPDA (gamete cells assisted Phased Diploid Assembler), which exploits haploid gamete cells to assist in resolving haplotypes. We demonstrate the effectiveness of gcaPDA based on simulated HiFi reads of maize genome which is highly heterozygous and repetitive, and real data from rice.
With applicability of coping with complex genomes and fewer restrictions on application than most of diploid assemblers, gcaPDA is likely to find broad applications in studies of eukaryotic genomes.
Background
Achilles tendinopathy (AT) is associated with severe pain and is the cause of dysfunction and disability that are associated with significant reduction in social and economic benefits. ...Several potential risk factors have been proposed to be responsible for AT development; however, the results of observational epidemiological studies remain controversial, presumably because the designs of these studies are subject to residual confounding and reverse causality. Mendelian randomization (MR) can infer the causality between exposure and disease outcomes using genetic variants as instrumental variables, and identification of the causal risk factors for AT is beneficial for early intervention. Thus, we employed the MR strategy to evaluate the causal associations between previously reported risk factors (anthropometric parameters, lifestyle factors, blood biomarkers, and systemic diseases) and the risk of AT.
Methods
Univariable MR was performed to screen for potential causal associations between the putative risk factors and AT. Bidirectional MR was used to infer reverse causality. Multivariable MR was conducted to investigate the body mass index (BMI)-independent causal effect of other obesity-related traits, such as the waist-hip ratio, on AT.
Results
Univariable MR analyses with the inverse-variance weighted method indicated that the genetically predicted BMI was significantly associated with the risk of AT (
P
=2.0×10
-3
), and the odds ratios (95% confidence intervals) is 1.44 (1.14−1.81) per 1-SD increase in BMI. For the other tested risk factors, no causality with AT was identified using any of the MR methods. Bidirectional MR suggested that AT was not causally associated with BMI, and multivariable MR indicated that other anthropometric parameters included in this study were not likely to causally associate with the risk of AT after adjusting for BMI.
Conclusions
The causal association between BMI and AT risk suggests that weight control is a promising strategy for preventing AT and alleviating the corresponding disease burden.
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