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1.
Cell ; 183(1): 76-93.e22, 2020 10 01.
Article in English | MEDLINE | ID: mdl-32931733

ABSTRACT

Mitochondria, which play central roles in immunometabolic diseases, have their own genome. However, the functions of mitochondria-located noncoding RNAs are largely unknown due to the absence of a specific delivery system. By circular RNA (circRNA) expression profile analysis of liver fibroblasts from patients with nonalcoholic steatohepatitis (NASH), we observe that mitochondrial circRNAs account for a considerable fraction of downregulated circRNAs in NASH fibroblasts. By constructing mitochondria-targeting nanoparticles, we observe that Steatohepatitis-associated circRNA ATP5B Regulator (SCAR), which is located in mitochondria, inhibits mitochondrial ROS (mROS) output and fibroblast activation. circRNA SCAR, mediated by PGC-1α, binds to ATP5B and shuts down mPTP by blocking CypD-mPTP interaction. Lipid overload inhibits PGC-1α by endoplasmic reticulum (ER) stress-induced CHOP. In vivo, targeting circRNA SCAR alleviates high fat diet-induced cirrhosis and insulin resistance. Clinically, circRNA SCAR is associated with steatosis-to-NASH progression. Collectively, we identify a mitochondrial circRNA that drives metaflammation and serves as a therapeutic target for NASH.


Subject(s)
Mitochondria/genetics , Mitochondrial Proton-Translocating ATPases/genetics , RNA, Circular/genetics , Animals , Cell Line , Diet, High-Fat , Endoplasmic Reticulum Stress/physiology , Fibroblasts/metabolism , Fibroblasts/pathology , Gene Expression/genetics , Humans , Insulin Resistance , Liver/pathology , Liver Cirrhosis/metabolism , Male , Mice , Mice, Inbred C57BL , Mitochondria/metabolism , Mitochondrial Permeability Transition Pore/metabolism , Mitochondrial Proton-Translocating ATPases/metabolism , Non-alcoholic Fatty Liver Disease/genetics , Non-alcoholic Fatty Liver Disease/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , RNA, Circular/metabolism , Reactive Oxygen Species , Transcriptome/genetics
2.
Hum Mol Genet ; 32(22): 3181-3193, 2023 11 03.
Article in English | MEDLINE | ID: mdl-37622920

ABSTRACT

Prostate cancer (PCa) brings huge public health burden in men. A growing number of conventional observational studies report associations of multiple circulating proteins with PCa risk. However, the existing findings may be subject to incoherent biases of conventional epidemiologic studies. To better characterize their associations, herein, we evaluated associations of genetically predicted concentrations of plasma proteins with PCa risk. We developed comprehensive genetic prediction models for protein levels in plasma. After testing 1308 proteins in 79 194 cases and 61 112 controls of European ancestry included in the consortia of BPC3, CAPS, CRUK, PEGASUS, and PRACTICAL, 24 proteins showed significant associations with PCa risk, including 16 previously reported proteins and eight novel proteins. Of them, 14 proteins showed negative associations and 10 showed positive associations with PCa risk. For 18 of the identified proteins, potential functional somatic changes of encoding genes were detected in PCa patients in The Cancer Genome Atlas (TCGA). Genes encoding these proteins were significantly involved in cancer-related pathways. We further identified drugs targeting the identified proteins, which may serve as candidates for drug repurposing for treating PCa. In conclusion, this study identifies novel protein biomarker candidates for PCa risk, which may provide new perspectives on the etiology of PCa and improve its therapeutic strategies.


Subject(s)
Prostatic Neoplasms , Male , Humans , Prostatic Neoplasms/genetics , Blood Proteins/genetics , Biomarkers, Tumor/genetics
3.
Hepatology ; 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38537134

ABSTRACT

BACKGROUND AND AIMS: HBV infection is a major etiology of acute-on-chronic liver failure (ACLF). At present, the pattern and regulation of hepatocyte death during HBV-ACLF progression are still undefined. Evaluating the mode of cell death and its inducers will provide new insights for developing therapeutic strategies targeting cell death. In this study, we aimed to elucidate whether and how immune landscapes trigger hepatocyte death and lead to the progression of HBV-related ACLF. APPROACH AND RESULTS: We identified that pyroptosis represented the main cell death pattern in the liver of patients with HBV-related ACLF. Deficiency of MHC-I in HBV-reactivated hepatocytes activated cytotoxic NK cells, which in turn operated in a perforin/granzyme-dependent manner to trigger GSDMD/caspase-8-dependent pyroptosis of hepatocytes. Neutrophils selectively accumulated in the pyroptotic liver, and HMGB1 derived from the pyroptotic liver constituted an important factor triggering the generation of pathogenic extracellular traps in neutrophils (NETs). Clinically, elevated plasma levels of myeloperoxidase-DNA complexes were a promising prognostic biomarker for HBV-related ACLF. More importantly, targeting GSDMD pyroptosis-HMGB1 release in the liver abrogates NETs that intercept the development of HBV-related ACLF. CONCLUSIONS: Studying the mechanisms that selectively modulate GSDMD-dependent pyroptosis, as well as its immune landscapes, will provide a novel strategy for restoring the liver function of patients with HBV-related ACLF.

4.
Cereb Cortex ; 34(7)2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38960703

ABSTRACT

Schizophrenia, as a chronic and persistent disorder, exhibits working memory deficits across various stages of the disorder, yet the neural mechanisms underlying these deficits remain elusive with inconsistent neuroimaging findings. We aimed to compare the brain functional changes of working memory in patients at different stages: clinical high risk, first-episode psychosis, and long-term schizophrenia, using meta-analyses of functional magnetic resonance imaging studies. Following a systematic literature search, 56 whole-brain task-based functional magnetic resonance imaging studies (15 for clinical high risk, 16 for first-episode psychosis, and 25 for long-term schizophrenia) were included. The separate and pooled neurofunctional mechanisms among clinical high risk, first-episode psychosis, and long-term schizophrenia were generated by Seed-based d Mapping toolbox. The clinical high risk and first-episode psychosis groups exhibited overlapping hypoactivation in the right inferior parietal lobule, right middle frontal gyrus, and left superior parietal lobule, indicating key lesion sites in the early phase of schizophrenia. Individuals with first-episode psychosis showed lower activation in left inferior parietal lobule than those with long-term schizophrenia, reflecting a possible recovery process or more neural inefficiency. We concluded that SCZ represent as a continuum in the early stage of illness progression, while the neural bases are inversely changed with the development of illness course to long-term course.


Subject(s)
Brain , Magnetic Resonance Imaging , Memory, Short-Term , Schizophrenia , Humans , Memory, Short-Term/physiology , Schizophrenia/physiopathology , Schizophrenia/diagnostic imaging , Brain/physiopathology , Brain/diagnostic imaging , Disease Progression , Memory Disorders/physiopathology , Memory Disorders/etiology , Memory Disorders/diagnostic imaging , Schizophrenic Psychology , Brain Mapping
5.
BMC Genomics ; 25(1): 67, 2024 Jan 17.
Article in English | MEDLINE | ID: mdl-38233751

ABSTRACT

BACKGROUND: Rye (Secale cereale), one of the drought and cold-tolerant crops, is an important component of the Triticae Dumortier family of Gramineae plants. Basic helix-loop-helix (bHLH), an important family of transcription factors, has played pivotal roles in regulating numerous intriguing biological processes in plant development and abiotic stress responses. However, no systemic analysis of the bHLH transcription factor family has yet been reported in rye. RESULTS: In this study, 220 bHLH genes in S. cereale (ScbHLHs) were identified and named based on the chromosomal location. The evolutionary relationships, classifications, gene structures, motif compositions, chromosome localization, and gene replication events in these ScbHLH genes are systematically analyzed. These 220 ScbHLH members are divided into 21 subfamilies and one unclassified gene. Throughout evolution, the subfamilies 5, 9, and 18 may have experienced stronger expansion. The segmental duplications may have contributed significantly to the expansion of the bHLH family. To systematically analyze the evolutionary relationships of the bHLH family in different plants, we constructed six comparative genomic maps of homologous genes between rye and different representative monocotyledonous and dicotyledonous plants. Finally, the gene expression response characteristics of 22 ScbHLH genes in various biological processes and stress responses were analyzed. Some candidate genes, such as ScbHLH11, ScbHLH48, and ScbHLH172, related to tissue developments and environmental stresses were screened. CONCLUSIONS: The results indicate that these ScbHLH genes exhibit characteristic expression in different tissues, grain development stages, and stress treatments. These findings provided a basis for a comprehensive understanding of the bHLH family in rye.


Subject(s)
Genome, Plant , Secale , Secale/genetics , Phylogeny , Basic Helix-Loop-Helix Transcription Factors/chemistry , Transcription Factors/metabolism , Gene Expression Regulation, Plant
6.
Hum Mol Genet ; 31(7): 1067-1081, 2022 03 31.
Article in English | MEDLINE | ID: mdl-34673960

ABSTRACT

At present, there have only been a few DNA sequencing-based studies to explore the genetic determinants of bone mineral density (BMD). We carried out the largest whole genome sequencing analysis to date for femoral neck and spine BMD (n = 4981), with one of the highest average sequencing depths implemented thus far at 22×, in a multiethnic sample (58% Caucasian and 42% African American) from the Louisiana Osteoporosis Study (LOS). The LOS samples were combined with summary statistics from the GEFOS consortium and several independent samples of various ethnicities to perform GWAS meta-analysis (n = 44 506). We identified 31 and 30 genomic risk loci for femoral neck and spine BMD, respectively. The findings substantiate many previously reported susceptibility loci (e.g. WNT16 and ESR1) and reveal several others that are either novel or have not been widely replicated in GWAS for BMD, including two for femoral neck (IGF2 and ZNF423) and one for spine (SIPA1). Although we were not able to uncover ethnicity specific differences in the genetic determinants of BMD, we did identify several loci which demonstrated sex-specific associations, including two for women (PDE4D and PIGN) and three for men (TRAF3IP2, NFIB and LYSMD4). Gene-based rare variant association testing detected MAML2, a regulator of the Notch signaling pathway, which has not previously been suggested, for association with spine BMD. The findings provide novel insights into the pathophysiological mechanisms of osteoporosis.


Subject(s)
Bone Density , Genome-Wide Association Study , Bone Density/genetics , Female , Femur Neck/physiology , Humans , Male , Polymorphism, Single Nucleotide/genetics , Whole Genome Sequencing
7.
BMC Plant Biol ; 24(1): 536, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38862890

ABSTRACT

BACKGROUND: The heavy metal-associated isoprenylated plant protein (HIPP) is an important regulatory element in response to abiotic stresses, especially playing a key role in low-temperature response. RESULTS: This study investigated the potential function of PavHIPP16 up-regulated in sweet cherry under cold stress by heterologous overexpression in tobacco. The results showed that the overexpression (OE) lines' growth state was better than wild type (WT), and the germination rate, root length, and fresh weight of OE lines were significantly higher than those of WT. In addition, the relative conductivity and malondialdehyde (MDA) content of the OE of tobacco under low-temperature treatment were substantially lower than those of WT. In contrast, peroxidase (POD), superoxide dismutase (SOD), catalase (CAT) activities, hydrogen peroxide (H2O2), proline, soluble protein, and soluble sugar contents were significantly higher than those of WT. Yeast two-hybrid assay (Y2H) and luciferase complementation assay verified the interactions between PavbHLH106 and PavHIPP16, suggesting that these two proteins co-regulated the cold tolerance mechanism in plants. The research results indicated that the transgenic lines could perform better under low-temperature stress by increasing the antioxidant enzyme activity and osmoregulatory substance content of the transgenic plants. CONCLUSIONS: This study provides genetic resources for analyzing the biological functions of PavHIPPs, which is important for elucidating the mechanisms of cold resistance in sweet cherry.


Subject(s)
Nicotiana , Plant Proteins , Plants, Genetically Modified , Prunus avium , Nicotiana/genetics , Nicotiana/physiology , Plant Proteins/genetics , Plant Proteins/metabolism , Plants, Genetically Modified/genetics , Prunus avium/genetics , Prunus avium/physiology , Prunus avium/metabolism , Cold-Shock Response/genetics , Cold Temperature , Gene Expression Regulation, Plant
8.
Brief Bioinform ; 23(2)2022 03 10.
Article in English | MEDLINE | ID: mdl-35225328

ABSTRACT

N6-methyladenine (6mA) is associated with important roles in DNA replication, DNA repair, transcription, regulation of gene expression. Several experimental methods were used to identify DNA modifications. However, these experimental methods are costly and time-consuming. To detect the 6mA and complement these shortcomings of experimental methods, we proposed a novel, deep leaning approach called BERT6mA. To compare the BERT6mA with other deep learning approaches, we used the benchmark datasets including 11 species. The BERT6mA presented the highest AUCs in eight species in independent tests. Furthermore, BERT6mA showed higher and comparable performance with the state-of-the-art models while the BERT6mA showed poor performances in a few species with a small sample size. To overcome this issue, pretraining and fine-tuning between two species were applied to the BERT6mA. The pretrained and fine-tuned models on specific species presented higher performances than other models even for the species with a small sample size. In addition to the prediction, we analyzed the attention weights generated by BERT6mA to reveal how the BERT6mA model extracts critical features responsible for the 6mA prediction. To facilitate biological sciences, the BERT6mA online web server and its source codes are freely accessible at https://github.com/kuratahiroyuki/BERT6mA.git, respectively.


Subject(s)
Deep Learning , DNA/genetics , DNA Methylation , Software
9.
J Med Virol ; 96(5): e29627, 2024 May.
Article in English | MEDLINE | ID: mdl-38659381

ABSTRACT

The immune mechanism underlying hepatitis B surface antigen (HBsAg) loss, particularly type I inflammatory response, during pegylated interferon-α (PEG-IFN) therapy remains unclear. In this study, we aimed to elucidate such immune mechanisms. Overall, 82 patients with chronic hepatitis B (CHB), including 41 with HBsAg loss (cured group) and 41 uncured patients, received nucleos(t)ide analogue and PEG-IFN treatments. Blood samples from all patients, liver tissues from 14 patients with CHB, and hepatic perfusate from 8 liver donors were collected for immune analysis. Jurkat, THP-1 and HepG2.2.15 cell lines were used in cell experiments. The proportion of IFN-γ+ Th1 cells was higher in the cured group than in the uncured group, which was linearly correlated with HBsAg decline and alanine aminotransferase (ALT) levels during treatment. However, CD8+ T cells were weakly associated with HBsAg loss. Serum and intrahepatic levels of Th1 cell-associated chemokines (C-X-C motif chemokine ligand [CXCL] 9, CXCL10, CXCL11, IFN-γ) were significantly lower in the cured patients than in patients with a higher HBsAg quantification during therapy. Serum from cured patients induced more M1 (CD68+CD86+ macrophage) cells than that from uncured patients. Patients with chronic HBV infection had significantly lower proportions of CD86+ M1 and CD206+ M2 macrophages in their livers than healthy controls. M1 polarization of intrahepatic Kupffer cells promoted HBsAg loss by upregulating the effector function of tissue-resident memory T cells with increased ALT levels. IFN-γ+ Th1 activates intrahepatic resident memory T cells to promote HBsAg loss by inducing M1 macrophage polarization.


Subject(s)
Hepatitis B Surface Antigens , Hepatitis B, Chronic , Liver , Macrophages , Memory T Cells , Th1 Cells , Adult , Female , Humans , Male , Middle Aged , Antiviral Agents/therapeutic use , Antiviral Agents/pharmacology , Hepatitis B Surface Antigens/immunology , Hepatitis B virus/immunology , Hepatitis B, Chronic/immunology , Hepatitis B, Chronic/drug therapy , Interferon-alpha , Interferon-gamma , Liver/immunology , Macrophages/immunology , Memory T Cells/immunology , Th1 Cells/immunology
10.
Osteoporos Int ; 35(5): 785-794, 2024 May.
Article in English | MEDLINE | ID: mdl-38246971

ABSTRACT

Hip fracture risk assessment is an important but challenging task. Quantitative CT-based patient-specific finite element (FE) analysis (FEA) incorporates bone geometry and bone density in the proximal femur. We developed a global FEA-computed fracture risk index to increase the prediction accuracy of hip fracture incidence. PURPOSE: Quantitative CT-based patient-specific finite element (FE) analysis (FEA) incorporates bone geometry and bone density in the proximal femur to compute the force (fracture load) and energy necessary to break the proximal femur in a particular loading condition. The fracture loads and energies-to-failure are individually associated with incident hip fracture, and provide different structural information about the proximal femur. METHODS: We used principal component analysis (PCA) to develop a global FEA-computed fracture risk index that incorporates the FEA-computed yield and ultimate failure loads and energies-to-failure in four loading conditions of 110 hip fracture subjects and 235 age- and sex-matched control subjects from the AGES-Reykjavik study. Using a logistic regression model, we compared the prediction performance for hip fracture based on the stratified resampling. RESULTS: We referred the first principal component (PC1) of the FE parameters as the global FEA-computed fracture risk index, which was the significant predictor of hip fracture (p-value < 0.001). The area under the receiver operating characteristic curve (AUC) using PC1 (0.776) was higher than that using all FE parameters combined (0.737) in the males (p-value < 0.001). CONCLUSIONS: The global FEA-computed fracture risk index increased hip fracture risk prediction accuracy in males.


Subject(s)
Hip Fractures , Proximal Femoral Fractures , Male , Humans , Hip Fractures/epidemiology , Hip Fractures/etiology , Bone Density , Femur/diagnostic imaging , ROC Curve , Finite Element Analysis
11.
Chemistry ; 30(12): e202303725, 2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38032028

ABSTRACT

The design and synthesis of metal-organic frameworks (MOFs) as photocatalytic molecular reactors for varied reactions have drawn great attention. In this work, we designed a novel photoactive perylenediimides-based (PDI) carboxylate ligand N,N'-di(3',3",5',5"-tetrakis(4-carboxyphenyl))-1,2,6,7-tetrachloroperylene-3,4,9,10-tetracarboxylic acid diimide (Cl-PDI-TA) and use it to successfully synthesize a novel Zr(IV)-based MOF 1 constructed from [Zr6 O8 (H2 O)8 ]8+ clusters bridged by Cl-PDI-TA ligands. Structural analysis revealed that Zr-MOF 1 manifests a 3D framework with (4,8)-connected csq topology and possesses triangular channels of ~17 Šand mesoporous hexagonal channels of ~26 Šalong c-axis. Moreover, the synthesized Zr-MOF 1 exhibits visible-light absorption and efficient photoinduced free radical generation property, making it a promising photocatalytic molecular reactor. When Zr-MOF 1 was used as a photocatalyst for the aerobic oxidation of sulfides under irradiation of visible light, it could afford the corresponding sulfoxides with high yield and selectivity. Experimental results demonstrated that the substrate sulfides could be fixed in the pores of 1 and directly transformed to the products sulfoxides in the solid state. Furthermore, the mechanism for the photocatalytic transformation was also investigated and the results revealed that the singlet oxygen (1 O2 ) and superoxide radical (O2 ⋅- ) generated by the energy transfer and electron transfer from the photoexcited Zr-MOF to oxidants were the main active species for the catalytic reactions. This work offers a perceptive comprehension of the mechanism in PDI-based MOFs for further study on photocatalytic reactions.

12.
Neurochem Res ; 49(3): 557-567, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38063946

ABSTRACT

Stroke, the second-largest cause of death and the leading cause of disability globally, presents significant challenges in terms of prognosis and treatment. Identifying reliable prognosis biomarkers and treatment targets is crucial to address these challenges. Circular RNA (circRNA) has emerged as a promising research biomarkers and therapeutic targets because of its tissue specificity and conservation. However, the potential role of circRNA in stroke prognosis and treatment remains largely unexplored. This review briefly elucidate the mechanism underlying circRNA's involvement in stroke pathophysiology. Additionally, this review summarizes the impact of circRNA on different forms of strokes, including ischemic stroke and hemorrhagic stroke. And, this article discusses the positive effects of circRNA on promoting cerebrovascular repair and regeneration, maintaining the integrity of the blood-brain barrier (BBB), and reducing neuronal injury and immune inflammatory response. In conclusion, the significance of circRNA as a potential prognostic biomarker and a viable therapeutic target was underscored.


Subject(s)
Ischemic Stroke , Stroke , Humans , RNA, Circular/genetics , Stroke/genetics , Stroke/therapy , Biomarkers , Blood-Brain Barrier
13.
J Org Chem ; 89(12): 8804-8814, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38860924

ABSTRACT

1,4-/1,3-Regioselective bifunctionalization of 1,3-enynes with selenosulfonates in water under catalyst-free conditions for the construction of sulfonyl allene and 1,3-disulfonyl-conjugated dienes respectively have been developed. The reactions feature mild reaction conditions in aqueous solution and remarkable regioselectivity controlled by substrates.

14.
Physiol Plant ; 176(2): e14300, 2024.
Article in English | MEDLINE | ID: mdl-38629194

ABSTRACT

The flower bud differentiation plays a crucial role in cherry yield and quality. In a preliminary study, we revealed the promotion of spermidine (Spd) in bud differentiation and quality. However, the molecular mechanism underlying Spd regulating cherry bud differentiation remains unclear. To address this research gap, we cloned CpSPDS2, a gene that encodes Spd synthase and is highly expressed in whole flowers and pistils of the Chinese cherry (cv. 'Manaohong'). Furthermore, an overexpression vector with this gene was constructed to transform tobacco plants. The findings demonstrated that transgenic lines exhibited higher Spd content, an earlier flowering time by 6 d, and more lateral buds and flowers than wild-type lines. Additionally, yeast one-hybrid assays and two-luciferase experiments confirmed that the R2R3-MYB transcription factor (CpMYB44) directly binds to and activates the CpSPDS2 promoter transcription. It is indicated that CpMYB44 promotes Spd accumulation via regulating CpSPDS2 expression, thus accelerating the flower growth. This research provides a basis for resolving the molecular mechanism of CpSPDS2 involved in cherry bud differentiation.


Subject(s)
Prunus , Spermidine , Spermidine/metabolism , Nicotiana/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Gene Expression Regulation, Plant , Transcription Factors/genetics , Transcription Factors/metabolism , Prunus/genetics , Flowers/physiology
15.
Prenat Diagn ; 44(2): 167-171, 2024 02.
Article in English | MEDLINE | ID: mdl-37749763

ABSTRACT

OBJECTIVE: To elucidate an etiology in a case with persistent oligohydramnios by prenatal diagnosis and actively treat the case to achieve good prognosis. METHODS: We performed whole exome sequencing (WES) of DNA from the fetus and parents. Serial amnioinfusions were conducted until birth. Pressors were required to maintain normal blood pressure. The infant angiotensin-converting enzyme (ACE) activity, angiotensin II (Ang II, a downstream product of ACE), and compensatory enzymes (CEs) activities were measured. Compensatory enzyme activities in plasma from age-matched healthy controls were also detected. RESULTS: We identified a fetus with a severe ACE mutation prenatally. The infant was born prematurely without pulmonary dysplasia. Hypotension and anuria resolved spontaneously. He had almost no ACE activity, but his Ang II level and CE activity exceeded the upper limit of the normal range and the upper limit of the 95% confidence interval of controls, respectively. His renal function also largely recovered. CONCLUSION: Fetuses with ACE mutations can be diagnosed prenatally through WES. Serial amnioinfusion permits the continuation of pregnancy in fetal ACE deficiency. Compensatory enzymes for defective ACE appeared postnatally. Renal function may be spared by preterm delivery; furthermore, for postnatal vasopressor therapy to begin, improving renal perfusion pressure before nephrogenesis has been completed.


Subject(s)
Oligohydramnios , Peptidyl-Dipeptidase A , Pregnancy , Infant, Newborn , Male , Female , Humans , Peptidyl-Dipeptidase A/genetics , Prenatal Diagnosis , Fetus , Oligohydramnios/diagnostic imaging , Oligohydramnios/therapy , Delivery, Obstetric
16.
Genomics ; 115(3): 110603, 2023 05.
Article in English | MEDLINE | ID: mdl-36893872

ABSTRACT

The genetic code has degenerate codons that produce no change in the translated protein sequence and are generally thought to be silent. However, some synonymous variants are clearly not silent. Herein, we questioned the frequency of non-silent synonymous variants. We tested how random synonymous variants in the HIV Tat transcription factor effect transcription of an LTR-GFP reporter. Our model system has the advantage of directly measuring the function of the gene in human cells. Approximately, 67% of synonymous variants in Tat were non-silent, either having reduced activity or were full loss-of-function alleles. Eight mutant codons had higher codon usage than wild type, accompanied by reduced transcriptional activity. These were clustered on a loop in the Tat structure. We conclude that most synonymous Tat variants are not silent in human cells, and 25% are associated with changes in codon usage, likely effecting protein folding.


Subject(s)
Codon Usage , HIV Infections , Humans , Alleles , Codon , Silent Mutation , HIV Infections/genetics
17.
Int J Food Sci Nutr ; : 1-13, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38918932

ABSTRACT

Cow milk consumption (CMC) and downstream alterations of serum metabolites are commonly considered important factors regulating human health status. Foods may lead to metabolic changes directly or indirectly through remodelling gut microbiota (GM). We sought to identify the metabolic alterations in Chinese Peri-/Postmenopausal women with habitual CMC and explore if the GM mediates the CMC-metabolite associations. 346 Chinese Peri-/Postmenopausal women participants were recruited in this study. Fixed effects regression and partial least squares discriminant analysis (PLS-DA) were applied to reveal alterations of serum metabolic features in different CMC groups. Spearman correlation coefficient was computed to detect metabolome-metagenome association. 36 CMC-associated metabolites including palmitic acid (FA(16:0)), 7alpha-hydroxy-4-cholesterin-3-one (7alphaC4), citrulline were identified by both fixed effects regression (FDR < 0.05) and PLS-DA (VIP score > 2). Some significant metabolite-GM associations were observed, including FA(16:0) with gut species Bacteroides ovatus, Bacteroides sp.D2. These findings would further prompt our understanding of the effect of cow milk on human health.

18.
J Environ Manage ; 361: 121240, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38805960

ABSTRACT

Afforestation plays a crucial role in environmental management for many countries. Yet, frequently extreme high temperature (EHT) events in arid and semi-arid regions easily cause the death of artificially planted saplings. To address this, we present a new in-situ supplementary irrigation device (SID) consisting of a rainwater catching board, a storage tank, and ceramic emitters. A continuous EHT experiment combined with the HYDRUS-2D model in North China is further conducted to investigate the soil water-heat properties of the in-situ SID and the growth performance of the planted saplings (Platycladus orientalis) under EHT. The results show that in-situ SID keeps a stable and suitable soil water-heat status in the root layer of the planted saplings under EHT. Especially, the in-situ SID with one ceramic emitter maintains the soil water moisture in a narrow and suitable range from 0.149 cm3 cm-3 to 0.153 cm3 cm-3, and reduces the maximum soil temperature by 2.7 °C compared to the traditional irrigation method. Furthermore, the in-situ SID with one ceramic emitter presents the highest average leaf water content (66.9%), new shoot (35.0 mm), and tree height (62.0 mm). The economic benefit analysis finds that the in-situ SID provides a shorter time to recover high funds and saves a large amount of irrigation water resources. Overall, this study provides an effective irrigation device for forest managers to improve the ecological service effectiveness of afforestation in areas with frequent EHT events and scarce water resources.


Subject(s)
Soil , China , Agricultural Irrigation/methods , Trees/growth & development , Rain , Hot Temperature
19.
J Environ Manage ; 357: 120777, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38581893

ABSTRACT

Accurate quantification of dissolved oxygen (DO) is critically important for the protection and management of aquatic ecosystems. Successful applications have utilized mechanistic and data-driven models to simulate DO content in aquatic ecosystems. However, mechanistic models present challenges due to their complex and difficult-to-solve conditions, making them less portable. Additionally, data-driven model predictions are hindered by the challenge of numerous input variables, impacting both the running speed and prediction performance of the model. To address these challenges, water quality data and meteorological data of the Tanjiang River were obtained. The maximum information coefficient (MIC) input variable selection technique was employed to identify primary environmental factors influencing DO changes. Furthermore, coupled with support vector regression (SVR), two models (SVR and MIC-SVR) were employed to estimate the DO concentration of the Tanjiang River, and the optimal model was established. The results indicated a shift in the primary pollution factor from ammonia nitrogen to total phosphorus after recent treatment in the Tanjiang River. In comparison with the SVR model, the root mean square error (RMSE) of the MIC-SVR model was reduced by 4.46%, and the Nash-efficiency coefficient (NSE) was improved by 45.85%. In addition, study of kernel function selection revealed that considering as many kernel functions as possible is necessary for improving the performance of the SVR model. Conclusively, the proposed MIC-SVR model serves as an effective tool to analyze the relationship between DO and environmental factors, identifying the primary causes of low DO, and accurately predict the DO concentration in the Tanjiang River (especially in its middle and lower reaches), thus providing a reference for governmental decision-making on water environmental protection and water resource management.


Subject(s)
Environmental Monitoring , Oxygen , Environmental Monitoring/methods , Ecosystem , Algorithms , Machine Learning , Rivers
20.
J Environ Manage ; 351: 119997, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38160546

ABSTRACT

We report a novel modified semi-carbonized fiber (CF) prepared using cotton and acrylic clothes for derisking contaminated water to realize the resource utilization of discarded clothes in wastewater treatment. In this study, amphoteric and auxiliary modifiers were used to modify CFs for preparing amphoteric and amphoteric-auxiliary CFs. The basic physicochemical properties of different modified CFs were determined, and the microscopic morphology of modified CFs was detected. The isothermal adsorption characteristics of Cu(II) and Pb(II) on different modified CFs were investigated by the batch method, and the effect mechanisms of temperature, pH, ionic strength, and material dose were compared. Physicochemical properties and microscopic morphology results proved that amphoteric and auxiliary modifiers were modified on the CF surface and changed the surface properties of CF. The adsorption capacities of Cu(II) and Pb(II) on modified CFs increased with the increase in equilibrium concentration of Cu(II) and Pb(II), and the isotherm was more suitable for Freundlich model fitting than that of the Langmuir model. The maximum adsorption capacities (qm) of Cu(II) and Pb(II) on different modified CFs were 60.72-81.26 mg/g and 102.58-161.72 mg/g, respectively, and presented the trend of amphoteric-auxiliary CFs > amphoteric CFs > CFs. Increasing pH and temperature and decreasing ionic strength and material dose were beneficial to Cu(II) and Pb(II) adsorption. The Cu(II) and Pb(II) adsorption process was a spontaneous, endothermic, and entropy-increasing reaction, and the adsorption rate was controlled by chemisorption. The adsorption amount of amphoteric-auxiliary CFs maintained about 65% of original materials after 3 times of regeneration. Electrostatic attraction, precipitation, complexation, and ion exchange were the main adsorption mechanisms. The cation exchange capacity and total pore volume of modified CFs were key to determining qm of Cu(II) and Pb(II).


Subject(s)
Lead , Water Pollutants, Chemical , Temperature , Cations , Adsorption , Water , Clothing , Water Pollutants, Chemical/chemistry , Kinetics , Hydrogen-Ion Concentration
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