Two new cases with the UBQLN2 gene mutation in Han Chinese.

Variations in the UBQLN2 gene are associated with a group of diseases with X-linked dominant inheritance and clinical phenotypes of amyotrophic lateral sclerosis (ALS) and/or frontal temporal lobe dementia (FTD). Cases with UBQLN2 variations have been rarely reported worldwide. The reported cases exhibit strong clinical heterogeneity. Here, we report two adult-onset cases with UBQLN2 variations in Han Chinese. Whole exome sequencing revealed the hemizygous P506S (c.1516C > T) and the heterozygous P509S variation (c.1525C > T), both of which were located within the hotspot mutation region. The patient with the P506S variation was a 24-year-old male. The clinical feature was spastic paraplegia without lower motor neuron damage. The patient's mother was an asymptomatic heterozygote carrier with skewed X-chromosome inactivation. The patient with the P509S variation was a 63-year-old female. Clinical features included ALS and parkinsonism. 18F-fluorodopa PET-CT revealed presynaptic dopaminergic deficits in bilateral posterior putamen. These cases further highlight the clinical heterogeneity of UBQLN2 cases.

Genome-wide association study reveals the candidate genes of humerus quality in laying duck.

Bone plays a crucial role in poultry's health and production. However, during the selection and cage farming, there has been a decline in bone quality. As the development of breeding theory, researchers find that it's possible to enhance bone quality through selective breeding.This study measure 8 humerus quality in 260 samples of the 350-day-old female duck. By descripting the basic characteristic traits, mechanical property traits we found that all the bone quality traits had a large variable coefficient, especially mechanical properties trait (20-70%), indicating that there was a large difference in bone health status among laying ducks. The phenotypic correlations showed a high correlation between weight and density, diameter and perimeter, breaking and toughness (r = 0.52-0.68). And then, we performed the Genome-wide association study (GWAS) to reveal the candidate genes of humerus quality in ducks. Seven candidate protein-coding genes were identified with perimeter trait, and 52 protein-coding genes were associated with toughness trait. We also analysed the candidate region and performed KEGG and GO analyse for 75 candidate genes. Furthermore, the expression analyse of the above candidate genes in different stage of humerus and different tissues were performed. Finally, AP2A2, SMAD3, SMNDC1, NFIA, EPHB2, PMEPA1, UNC5C, ESR1, VAV3, NFATC2 deserve further focus. The obtained results can contribute to new insight into bone quality and provide new genetic biomarkers for application in duck breeding programs.

Integrated Communication, Sensing, and Computation Framework for 6G Networks.

In the sixth generation (6G) era, intelligent machine network (IMN) applications, such as intelligent transportation, require collaborative machines with communication, sensing, and computation (CSC) capabilities. This article proposes an integrated communication, sensing, and computation (ICSAC) framework for 6G to achieve the reciprocity among CSC functions to enhance the reliability and latency of communication, accuracy and timeliness of sensing information acquisition, and privacy and security of computing to realize the IMN applications. Specifically, the sensing and communication functions can merge into unified platforms using the same transmit signals, and the acquired real-time sensing information can be exploited as prior information for intelligent algorithms to enhance the performance of communication networks. This is called the computing-empowered integrated sensing and communications (ISAC) reciprocity. Such reciprocity can further improve the performance of distributed computation with the assistance of networked sensing capability, which is named the sensing-empowered integrated communications and computation (ICAC) reciprocity. The above ISAC and ICAC reciprocities can enhance each other iteratively and finally lead to the ICSAC reciprocity. To achieve these reciprocities, we explore the potential enabling technologies for the ICSAC framework. Finally, we present the evaluation results of crucial enabling technologies to show the feasibility of the ICSAC framework.

Weighted gene co-expression network analysis identifies important modules and hub genes involved in the regulation of breast muscle yield in broilers.

Objective: Increasing breast meat production is one of the primary goals of the broiler industry. Over the past few decades, tremendous progress has been made in genetic selection and the identification of candidate genes for improving the breast muscle mass. However, the molecular network contributing to muscle production traits in chickens still needs to be further illuminated. Methods: A total of 150 1-day-old male 817 broilers were reared in a floor litter system. At the market age of 50 d, eighteen healthy 817 broilers were slaughtered and the left pectoralis major muscle sample from each bird was collected for RNA-seq sequencing. The birds were then plucked and eviscerated and the whole breast muscle was removed and weighed. Breast muscle yield was calculated as the ratio of the breast muscle weight to the eviscerated weight. To identify the co-expression networks and hub genes contributing to breast muscle yield in chickens, we performed weighted gene co-expression network analysis (WGCNA) based on the 18 transcriptome datasets of pectoralis major muscle from eighteen 817 broilers. Results: The WGCNA analysis classified all co-expressed genes in the pectoral muscle of 817 broilers into 44 modules. Among these modules, the turquoise and skyblue3 modules were found to be most significantly positively (r=0.78, p=1e-04) and negatively (r=-0.57, p=0.01) associated with breast meat yield, respectively. Further analysis identified several hub genes (e.g., DLX3, SH3RF2, TPM1, CAV3, MYF6, and CFL2) that involved in muscle structure and muscle development were identified as potential regulators of breast meat production. Conclusion: The present study has advanced our understanding of the molecular regulatory networks contributing to muscle growth and breast muscle production and will contribute to the molecular breeding of chickens in the future.

Protection of Qingfei Xieding prescription from idiopathic pulmonary fibrosis by regulating renin-angiotensin and ferroptosis in MLE-12 cells.

Idiopathic pulmonary fibrosis (IPF) is a lifelong lung disease, but there is no specific drug for treatment. Qingfei Xieding prescription (QF) is active in the treatment of lung diseases. More comprehensive mechanisms over how QF exhibits anti-pulmonary fibrosis need to be elucidated. TGF-ß was used to construct a pulmonary fibrosis cell model in vitro. Bleomycin was applied to induce a lung tissue fibrosis model in mice in vivo. Flow cytometry was used to detect cellular ROS and lipid oxidation levels. Cell substructure was observed by Transmission Electron Microscopy. ELISA was used to determine the levels of inflammatory factors. HE staining, Masson staining and immunohistochemistry were performed to evaluate the degree of fibrosis. Western Blot assay was used to determine the protein expressions of different molecules. In TGF-ß-exposed lung epithelial MLE-12 cell model, α-SMA and Collagen I were significantly elevated and cell viability was reduced. QF treatment restored the cell viability decreased by exogenous TGF-ß. Ferroptosis inducer Erastin administration could reverse the beneficial effects such as lipid oxidation and ROS reduction caused by QF treatment. QF was proven to inhibit ferroptosis and alleviated the process of IPF by activating ACE2 signal axis. In bleomycin induced IPF mice model, QF altered lung coefficient, body weight and the expression of inflammatory factors, which were prevented by ferroptosis activator Erastin. QF was demonstrated to affect the ACE2-ERK signaling axis in vivo. QF alleviated idiopathic pulmonary fibrosis by regulating renin-angiotensin through blocking ferroptosis. This research offers evidence for the potentiality of QF in clinical application for IPF therapy.

A unique subseafloor microbiosphere in the Mariana Trench driven by episodic sedimentation.

Hadal trenches are characterized by enhanced and infrequent high-rate episodic sedimentation events that likely introduce not only labile organic carbon and key nutrients but also new microbes that significantly alter the subseafloor microbiosphere. Currently, the role of high-rate episodic sedimentation in controlling the composition of the hadal subseafloor microbiosphere is unknown. Here, analyses of carbon isotope composition in a ~ 750 cm long sediment core from the Challenger Deep revealed noncontinuous deposition, with anomalous 14C ages likely caused by seismically driven mass transport and the funneling effect of trench geomorphology. Microbial community composition and diverse enzyme activities in the upper ~ 27 cm differed from those at lower depths, probably due to sudden sediment deposition and differences in redox condition and organic matter availability. At lower depths, microbial population numbers, and composition remained relatively constant, except at some discrete depths with altered enzyme activity and microbial phyla abundance, possibly due to additional sudden sedimentation events of different magnitude. Evidence is provided of a unique role for high-rate episodic sedimentation events in controlling the subsurface microbiosphere in Earth's deepest ocean floor and highlight the need to perform thorough analysis over a large depth range to characterize hadal benthic populations. Such depositional processes are likely crucial in shaping deep-water geochemical environments and thereby the deep subseafloor biosphere. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-023-00212-y.

Integrated 16S rRNA sequencing and metabolomic analysis reveals the potential protective mechanism of Germacrone on diabetic nephropathy in mice.

Diabetic nephropathy (DN) is a severe complication of diabetes and the leading cause of end-stage renal disease and death. Germacrone (Ger) possesses anti-inflammatory, antioxidant and anti-DN properties. However, it is unclear whether the improvement in kidney damage caused by Ger in DN mice is related to abnormal compositions and metabolites of the gut microbiota. This study generates a mouse model of DN to explore the potent therapeutic ability and mechanism of Ger in renal function by 16S rRNA sequencing and untargeted fecal metabolomics. Although there is no significant change in microbiota diversity, the structure of the gut microbiota in the DN group is quite different. Serratia_marcescens and Lactobacillus_iners are elevated in the model group but significantly decreased after Ger intervention ( P<0.05). Under the treatment of Ger, no significant differences in the diversity and richness of the gut microbiota are observed. An imbalance in the intestinal flora leads to the dysregulation of metabolites, and non-targeted metabolomics data indicate high expression of stearic acid in the DN group, and oleic acid could serve as a potential marker of the therapeutic role of Ger in the DN model. Overall, Ger improves kidney injury in diabetic mice, in part potentially by reducing the abundance of Serratia_marcescens and Lactobacillus_iners, as well as regulating the associated increase in metabolites such as oleic acid, lithocholic acid and the decrease in stearic acid. Our research expands the understanding of the relationship between the gut microbiota and metabolites in Ger-treated DN. This contributes to the usage of natural products as a therapeutic approach for the treatment of DN via microbiota regulation.

Development and validation of a major adverse limb events prediction model for peripheral arterial disease with frailty.

OBJECTIVE: To investigate the risk factors for major limb adverse events (MALE) in peripheral arterial disease (PAD) combined with frailty and to develop and validate a risk prediction model of MALE. METHODS: This prospective study was performed in the vascular surgery department of patients in six hospitals in southwest China. Prospective collection of patients with PAD combined with frailty from February 1 to December 20, 2021, with MALE as the primary outcome, and followed for 1 year. The cohort was divided into a development cohort and a validation cohort. In the development cohort, a multivariate risk prediction model was developed to predict MALE using random forests for variable selection and multivariable Cox regression analysis. The model is represented by a visualized nomogram and a web-based calculator. The model performance was tested with the validation cohort and assessed using the C-statistic and calibration plots. RESULTS: A total of 1179 patients were prospectively enrolled from February 1 to December 20, 2021. Among 816 patients with PAD who were included in the analysis, the median follow-up period for this study was 9 ± 4.07 months, the mean age was 74.64 ± 9.43 years, and 249 (30.5%) were women. Within 1 year, 222 patients (27.2%) developed MALE. Target lesion revascularizations were performed in 99 patients (12.1%), and amputations were performed in 131 patients (16.1%). The mortality rate within the whole cohort was 108 patients (13.2%). After controlling for competing risk events (death), the cumulative risk of developing MALE was not statistically different. Prealbumin (hazard ratio [HR], 0.6; 95% confidence interval [CI], 0.41-0.89; P = .010), percutaneous coronary intervention (HR, 2.31; 95% CI, 1.26-4.21; P = .006), Rutherford classification (HR, 1.77; 95% CI, 1.36-2.31; P < .001), white blood cell (HR, 1.85; 95% CI, 1.20-2.87; P = .005), high altitude area (HR, 3.1; 95% CI, 1.43-6.75; P = .004), endovascular treatment (HR, 10.2; 95% CI, 1.44-72.50; P = .020), and length of stay (HR, 1.01; 95% CI, 1.00-1.03; P = .012) were risk factors for MALE. The MALE prediction model had a C-statistic of 0.76 (95% CI, 0.70-0.79). The C-statistic was 0.68 for internal validation and 0.66 for external validation for the MALE prediction model. The MALE prediction model for PAD presented an interactive nomogram and a web-based network calculator. CONCLUSIONS: In this study, the MALE prediction model has a discriminative ability to predict MALE among patients with PAD in frailty. The MALE model can optimize clinical decision-making for patients with PAD in frailty.

Genome-wide characterization and comparison of endogenous retroviruses among 3 duck reference genomes.

Endogenous retroviruses (ERV) are viral genomes integrated into the host genome and can be stably inherited. Although ERV sequences have been reported in some avian species' genome, the duck endogenous retroviruses (DERV) genome has yet to be quantified. This study aimed to identify ERV sequences and characterize genes near ERVs in the duck genome by utilizing LTRhavest and LTRdigest tools to forecast the duck genome and analyze the distribution of ERV copies. The results revealed 1,607, 2,031, and 1,908 full-length ERV copies in the Pekin duck (ZJU1.0), Mallard (CAU_wild_1.0), and Shaoxing duck (CAU_laying_1.0) genomes, respectively, with average lengths of 7,046, 7,027, and 6,945 bp. ERVs are mainly distributed on the 1, 2, and sex chromosomes. Phylogenetic analysis demonstrated the presence of Betaretrovirus in 3 duck genomes, whereas Alpharetrovirus was exclusively identified in the Shaoxing duck genome. Through screening, 596, 315, and 343 genes adjacent to ERV were identified in 3 duck genomes, respectively, and their functions of ERV neighboring genes were predicted. Functional enrichment analysis of ERV-adjacent genes revealed enrichment for Focal adhesion, Calcium signaling pathway, and Adherens junction in 3 duck genomes. The overlapped genes were highly expressed in 8 tissues (brain, fat, heart, kidney, liver, lung, skin, and spleen) of 8-wk-old Mallard, revealing their important expression in different tissues. Our study provides a new perspective for understanding the quantity and function of DERVs, and may also provide important clues for regulating nearby genes and affecting the traits of organisms.

Genome-wide association study for bone quality of ducks during the laying period.

The cage-rearing model of the modern poultry industry makes the bones of birds, especially egg-laying birds, more vulnerable to fracture, which poses serious damage to the health of birds. Research confirms that genetic material plays an important role in regulating bone growth, development, and remodeling. However, the genetic architecture underlying bone traits is not well understood. The objectives of this study are to identify valuable genes and genetic markers through a genome-wide association study (GWAS) for breeding to improve the duck bone quality. First, we quantified the tibia and femur quality traits of 260 laying ducks. Based on GWAS, a total of 75 SNP loci significantly associated with bone quality traits were identified, and 67 potential candidate genes were annotated. According to gene function analysis, genes P4HA2, WNT3A, and BST1 et al may influence bone quality by regulating bone cell activity, calcium and phosphate metabolism, or bone collagen maturation and cross-linking. Meanwhile, combined with the transcriptome results, we found that HOXB cluster genes are also important in bone growth and development. Therefore, our findings were helpful in further understanding the genetic architecture of the duck bone quality and provided a worthy theoretical basis and technological support to improve duck bone quality by breeding.

To explore the pathogenesis of anterior resection syndrome by magnetic resonance imaging rectal defecography.

BACKGROUND: Over 90% of rectal cancer patients develop low anterior resection syndrome (LARS) after sphincter-preserving resection. The current globally recognized evaluation method has many drawbacks and its subjectivity is too strong, which hinders the research and treatment of LARS. AIM: To evaluate the anorectal function after colorectal cancer surgery by quantifying the index of magnetic resonance imaging (MRI) defecography, and pathogenesis of LARS. METHODS: We evaluated 34 patients using the standard LARS score, and a new LARS evaluation index was established using the dynamic images of MRI defecography to verify the LARS score. RESULTS: In the LARS score model, there were 10 (29.41%) mild and 24 (70.58%) severe cases of LARS. The comparison of defecation rate between the two groups was 29.36 ± 14.17% versus 46.83 ± 18.62% (P = 0.004); and MRI-rectal compliance (MRI-RC) score was 3.63 ± 1.96 versus 7.0 ± 3.21 (P = 0.001). Severe and mild LARS had significant differences using the two evaluation methods. There was a significant negative correlation between LARS and MRI-RC score (P < 0.001), and they had a negative correlation with defecation rate (P = 0.028). CONCLUSION: MRI defecography and standard LARS score can both be used as an evaluation index to study the pathogenesis of LARS.

Explorations on Key Module and Hub Genes Affecting IMP Content of Chicken Pectoralis Major Muscle Based on WGCNA.

Inosine monophosphate (IMP) is a substance that enhances flavor and plays a crucial role in the umami taste of chicken muscle. It is also an influential factor in determining chicken's economic value. However, the molecular regulatory network underlying the IMP content in muscle remains unclear. To address this issue, we performed transcriptome sequencing on 20 pectoralis major muscle samples from 120-day-old Guangde feathered-leg chicken and used weighted gene co-expression network analysis (WGCNA) to identify key regulatory factors that influence IMP content. The weighted gene co-expression network was constructed using a total of 16,344 genes, leading to the identification of 20 co-expression gene modules. Among the modules that were identified, it was observed that the purple module (R = -0.51, p = 0.02) showed a significant negative correlation with the IMP content. This suggests that the genes within the purple module had the ability to regulate the IMP content. A total of 68 hub genes were identified in the purple module through gene significance (GS) > 0.2 and module membership (MM) > 0.8. The STRING database was used for a protein-protein interaction (PPI) network of hub genes. Furthermore, troponin I type 1 (TNNI1), myozenin 2 (MYOZ2), myosin light chain 2 regulatory cardiac slow (MYL2), and myosin light chain 3 regulatory cardiac slow (MYL3) involved in the "ATP-dependent activity", "cAMP signaling pathway" and "cGMP-PKG signaling pathway" were identified as central regulators that contribute to IMP content. These results offer valuable information into the gene expression and regulation that affects IMP content in muscle.

Identification of candidate genes affecting the tibia quality in Nonghua duck.

The skeleton is a vital organ providing structural support in poultry. Weakness in bone structure can lead to deformities, osteoporosis, cage fatigue, and fractures, resulting in economic losses. Research has substantiated that genetic factors play a significant role in influencing bone quality. The discovery of genetic markers associated with bone quality holds paramount importance for enhancing genetic traits related to the skeletal system in poultry. This study analyzed nine phenotypic indicators of tibia quality in 120-day-old ducks. The phenotypic correlation revealed a high correlation among diameter, Perimeter, and weight (0.69-0.78), and a strong correlation was observed between toughness and breaking strength (0.62). Then, we conducted a genome-wide association analysis of the phenotypic indicators to elucidate the genetic basis of tibial quality in Nonghua ducks. Among the 11 candidate genes that were annotated, TAPT1, BST1, and STIM2 were related to the diameter indicator, ZNF652, IGF2BP1, CASK, and GREB1L were associated with the weight and toughness indicators. RFX8, GLP1R, and DNAAF5 were identified for ash, calcium, and phosphorus content, respectively. Finally, KEGG and GO analysis for annotated genes were performed. STIM2 and BST1 were enriched into the Calcium signalling pathway and Niacin and nicotinamide metabolic pathway, which may be key candidate genes affecting bone quality phenotypes. Gene expression analysis of the candidate genes, such as STIM2, BST1, TAPT1, and CASK showed higher expression levels in bones compared to other tissues. The obtained results can contribute to new insights into tibial quality and provide new genetic biomarkers that can be employed in duck breeding.

Transcriptome and Weighted Gene Co-Expression Network Analysis for Feather Follicle Density in a Chinese Indigenous Breed.

Feather follicle density plays an important role in appealing to consumers' first impressions when making purchasing decisions. However, the molecular network that contributes to this trait remains largely unknown. The aim of this study was to perform transcriptome and weighted gene co-expression network analyses to determine the candidate genes relating to feather follicle density in Wannan male chickens. In total, five hundred one-day-old Wannan male chickens were kept in a conventional cage system. Feather follicle density was recorded for each bird at 12 weeks of age. At 12 weeks, fifteen skin tissue samples were selected for weighted gene co-expression network analysis, of which six skin tissue samples (three birds in the H group and three birds in the L group) were selected for transcriptome analysis. The results showed that, in total, 95 DEGs were identified, and 56 genes were upregulated and 39 genes were downregulated in the high-feather-follicle-density group when compared with the low-feather-follicle-density group. Thirteen co-expression gene modules were identified. The red module was highly significantly negatively correlated with feather follicle density (p < 0.01), with a significant negative correlation coefficient of -0.72. In total, 103 hub genes from the red module were screened. Upon comparing the 103 hub genes with differentially expressed genes (DEGs), it was observed that 13 genes were common to both sets, including MELK, GTSE1, CDK1, HMMR, and CENPE. From the red module, FOXM1, GTSE1, MELK, CDK1, ECT2, and NEK2 were selected as the most important genes. These genes were enriched in the DNA binding pathway, the heterocyclic compound binding pathway, the cell cycle pathway, and the oocyte meiosis pathway. This study suggests that FOXM1, GTSE1, MELK, CDK1, ECT2, and NEK2 may be involved in regulating the development of feather follicle density in Wannan male chickens. The results of this study reveal the genetic structure and molecular regulatory network of feather follicle density in Wannan male chickens, and provide a basis for further elucidating the genetic regulatory mechanism and identifying molecular markers with breeding value.

Identification of central regulators related to abdominal fat deposition in chickens based on weighted gene co-expression network analysis.

Abdominal fat (AF) is one of the most important economic traits in chickens. Excessive AF in chickens will reduce feed utilization efficiency and negatively affect reproductive performance and disease resistance. However, the regulatory network of AF deposition needs to be further elucidated. In the present study, 300 one-day-old female Wannan chickens were reared to 17 wk of age, and 200 Wannan hens were selected to determine the abdominal fat percentage (AFP). Twenty AF tissue samples with the lowest AFP were selected as the low abdominal fat group (L-AFG), and 20 AF tissue samples with the highest AFP were selected as the high abdominal fat group (H-AFG). Eleven samples from L-AFG and 14 samples from H-AFG were selected for RNA-seq and used for weighted gene co-expression network analysis (WGCNA). Among the 25 RNA-seq samples, 5 samples with the lowest and highest AFP values were selected for differential expression gene analysis. Compared with the L-AFG, 225 and 101 genes were upregulated and downregulated in the H-AFG, respectively. A total of 20,503 genes were used to construct the WGCNA, and 44 co-expression gene modules were identified. Among these modules, 3 modules including turquoise, darkorange2, and floralwhite were identified as significantly associated with AFP traits. Furthermore, several genes including acyl-CoA oxidase 1 (ACOX1), stearoyl-CoA desaturase (SCD), aldehyde dehydrogenase 6 family member A1 (ALDH6A1), jun proto-oncogene, AP-1 transcription factor subunit (JUN), and fos proto-oncogene, AP-1 transcription factor subunit (FOS) involved in the "PPAR signaling pathway," "fatty acid metabolism," and "MAPK signaling pathway" were identified as central regulators that contribute to AF deposition. These results provide valuable information for further understanding of the gene expression and regulation of AF traits and contribute to future molecular breeding for AF in chickens.

Qingfei xieding prescription ameliorates mitochondrial DNA-initiated inflammation in bleomycin-induced pulmonary fibrosis through activating autophagy.

ETHNOPHARMACOLOGICAL RELEVANCE: Qingfei Xieding prescription was gradually refined and produced by Hangzhou Red Cross Hospital. The raw material includes Ephedra sinica Stapf, Morus alba L., Bombyx Batryticatus, Gypsum Fibrosum, Prunus armeniaca L. var. ansu Maxim., Houttuynia cordata Thunb. , Pueraria edulis Pamp. Paeonia L., Scutellaria baicalensis Georgi and Anemarrhena asphodeloides Bge. It is effective in clinical adjuvant treatment of patients with pulmonary diseases. AIM OF THE STUDY: To explore the efficacy and underlying mechanism of Qingfei Xieding (QF) in the treatment of bleomycin-induced mouse model. MATERIALS AND METHODS: TGF-ß induced fibrotic phenotype in vitro. Bleomycin injection induced lung tissue fibrosis mouse model in vivo. Flow cytometry was used to detect apoptosis, cellular ROS and lipid oxidation. Mitochondria substructure was observed by transmission electron microscopy. Autophagolysosome and nuclear entry of P65 were monitored by immunofluorescence. Quantitative real-time PCR was performed to detect the transcription of genes associated with mtDNA-cGAS-STING pathway and subsequent inflammatory signaling activation. RESULTS: TGF-ß induced the expression of α-SMA and Collagen I, inhibited cell viability in lung epithelial MLE-12 cells that was reversed by QF-containing serum. TGF-ß-mediated downregulation in autophagy, upregulation in lipid oxidation and ROS contents, and mitochondrial damage were rescued by QF-containing serum treatment, but CQ exposure, an autophagy inhibitor, prevented the protective role of QF. In addition to that, the decreased autophagolysosome in TGF-ß-exposed MLE-12 cells was reversed by QF and restored to low level in the combination treatment of QF and CQ. Mechanistically, QF-containing serum treatment significantly inhibited mtDNA-cGAS-STING pathway and subsequent inflammatory signaling in TGF-ß-challenged cells, which were abolished by CQ-mediated autophagy inhibition. In bleomycin-induced mouse model, QF ameliorated pulmonary fibrosis, reduced mortality, re-activated autophagy in lung tissues and restrained mtDNA-cGAS-STING inflammation pathway. However, the protective effects of QF in bleomycin-induced model mice were also abrogated by CQ. CONCLUSION: QF alleviated bleomycin-induced pulmonary fibrosis by activating autophagy, inhibiting mtDNA-cGAS-STING pathway-mediated inflammation. This research recognizes the protection role of QF on bleomycin-induced mouse model, and offers evidence for the potentiality of QF in clinical application for pulmonary fibrosis treatment.

Menstrual blood-derived stem cells exosomal miR-let-7 to ameliorate pulmonary fibrosis through inhibiting ferroptosis by Sp3/HDAC2/Nrf2 signaling pathway.

Idiopathic pulmonary fibrosis (IPF) is a serious, lifelong lung disease with high morbidity and high mortality. Menstrual blood-derived stem cells (MenSCs) derived exosomes (MenSCs-Exo) emerge as an attractive tool for the treatment of acute lung injury and fibrosis-related diseases. However, more comprehensive mechanism over how MenSCs derived exosomes exhibits anti-pulmonary fibrosis needs to be elucidated. In this study, TGF-ß was used to construct cell fibrosis model, and bleomycin (BLM) was applied to induce lung tissue fibrosis mice model. BLM- and TGF-ß1-induced cellular reactive oxygen species (ROS), mitochondrial DNA (mtDNA) damage, and lung epithelial cell apoptosis were alleviated by MenSCs-Exo treatment in vivo and in vitro. Besides, it was found that MenSCs-Exo delivered miR-let-7 into MLE-12 cells/lung epithelial cell and the reduction of miR-let-7 blocked the improvement produced by MenSCs-Exo. Mechanistically, miR-let-7 directly bound to Sp3 and negatively regulated its expression. Sp3 elevation promoted the expression of ferroptosis-related protein and mitochondrial DNA (mtDNA) damage markers via recruiting HDAC2, thereby inactivating keap1/Nrf2 signal cascade, which were confirmed in BLM-induced pulmonary fibrosis mice model under the combination therapy of the MenSCs-Exo and let-7 inhibitor. Collectively, MenSCs derived exosomes could transmit miR-let-7 into MLE-12 cells to inhibit the expression of Sp3, thereby weakening the recruitment effect of Sp3 on HDAC2, lifting the deacetylation restriction of HDAC2 on Nrf2, and enhancing the Nrf2 pathway. These changes further declined ferroptosis and delayed the pathological process of oxidative damage and lung epithelial cell apoptosis in PF.

Multidrug-resistant plasmid RP4 inhibits the nitrogen removal capacity of ammonia-oxidizing archaea, ammonia-oxidizing bacteria, and comammox in activated sludge.

In wastewater treatment plants (WWTPs), ammonia oxidation is primarily carried out by three types of ammonia oxidation microorganisms (AOMs): ammonia-oxidizing archaea (AOA), ammonia-oxidizing bacteria (AOB), and comammox (CMX). Antibiotic resistance genes (ARGs), which pose an important public health concern, have been identified at every stage of wastewater treatment. However, few studies have focused on the impact of ARGs on ammonia removal performance. Therefore, our study sought to investigate the effect of the representative multidrug-resistant plasmid RP4 on the functional microorganisms involved in ammonia oxidation. Using an inhibitor-based method, we first evaluated the contributions of AOA, AOB, and CMX to ammonia oxidation in activated sludge, which were determined to be 13.7%, 41.1%, and 39.1%, respectively. The inhibitory effects of C2H2, C8H14, and 3,4-dimethylpyrazole phosphate (DMPP) were then validated by qPCR. After adding donor strains to the sludge, fluorescence in situ hybridization (FISH) imaging analysis demonstrated the co-localization of RP4 plasmids and all three AOMs, thus confirming the horizontal gene transfer (HGT) of the RP4 plasmid among these microorganisms. Significant inhibitory effects of the RP4 plasmid on the ammonia nitrogen consumption of AOA, AOB, and CMX were also observed, with inhibition rates of 39.7%, 36.2%, and 49.7%, respectively. Moreover, amoA expression in AOB and CMX was variably inhibited by the RP4 plasmid, whereas AOA amoA expression was not inhibited. These results demonstrate the adverse environmental effects of the RP4 plasmid and provide indirect evidence supporting plasmid-mediated conjugation transfer from bacteria to archaea.

Accurate calibration for fringe projection profilometry based on an improved subpixel mapping with local gray distribution.

Fringe projection profilometry is an efficient and accurate technique for three-dimensional (3D) measurement to calibrate a camera and projector setup. The feature centers of circles on a calibration board are extracted on the camera image plane and mapped to the projector image plane during the calibration procedure. The accuracy of the mapping between camera pixels and projector pixels is crucial to the calibration accuracy, which directly affects the measurement precision of the system. In this paper, we investigate an improved subpixel mapping with local gray distribution from the camera to the projector. The mapped pixels and their gray values are regarded as a set of 3D grayscale space points. The subpixel coordinates of the feature centers on the projector image plane are obtained by directly processing the 3D points. The entire procedure retains the subpixel precision. Calibration experiments were designed to verify the feasibility of our calibration method, which was compared to three existing methods. The reprojection errors and object-space errors were used to evaluate the calibration accuracy of the methods. Additionally, measurement experiments of displacement and in-plane distance were employed to verify the calibration results of the methods. Compared to the three existing methods, we believe our method can improve the calibration accuracy for fringe projection profilometry.