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1.
Sci Data ; 11(1): 740, 2024 Jul 07.
Article in English | MEDLINE | ID: mdl-38972916

ABSTRACT

Soil hydraulic parameters are vital for precisely characterizing soil hydrological processes, which are critical indicators for regulating climate change effects on terrestrial ecosystems and governing feedbacks between water, energy, and carbon-nitrogen cycles. Although many studies have integrated comprehensive soil datasets, data quality and cost challenges result in data completeness deficiencies, especially for deep soil information. These gaps not only impede methodological endeavours but also constrain soil parameter-based ecosystem process studies spanning from local profiles to global earth system models. We established a soil dataset across the entire Yellow River Basin (YRB) (795,000 km2) using high-density in situ field sampling. This observation-based dataset contains records of soil texture (2924), bulk density (2798), saturated hydraulic conductivity (2782), and water retention curve parameters (1035) down to a maximum depth of 5 m. This dataset, which extends the recorded data range for deep soil hydraulic parameters, is valuable as a direct data resource for environmental, agronomical and hydrological studies in the YRB and regions with similar pedological and geological backgrounds around the world.

2.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 49(3): 482-490, 2024 Mar 28.
Article in English, Chinese | MEDLINE | ID: mdl-38970523

ABSTRACT

Pelvic floor dysfunction (PFD) is a common clinical problem that can lead to bladder and bowel dysfunction such as urinary incontinence, urinary retention, fecal incontinence, pelvic organ prolapse, and sexual dysfunction. Pelvic floor rehabilitation aids are essential tools in the treatment of PFD. However, there is limited understanding of the efficacy and mechanisms of these aids, and there is a lack of standardized guidelines for selecting appropriate aids for different types of PFD. To assist patients in choosing suitable pelvic floor rehabilitation aids to their needs, it is necessary to summarize the existing types, mechanisms, and applications of these aids. Based on their mechanisms and target functions, pelvic floor rehabilitation aids can be mainly categorized into 3 main types. The first type includes aids that improve pelvic floor function, such as vaginal dumbbells, vaginal tampons, and vaginal dilators, which aim to strengthen pelvic floor muscles and enhance the contractility of the urethral, vaginal, and anal sphincters, thereby improving incontinence symptoms. The second type consists of aids that mechanically block the outlet, such as pessaries, urethral plugs, incontinence pads, incontinence pants, anal plugs, and vaginal bowel control systems, which directly or indirectly prevent incontinence leakage. The third type includes aids that assist in outlet drainage, such as catheters and anal excreta collection devices, which help patients effectively expel urine, feces, and other waste materials, preventing incontinence leakage. By summarizing the existing pelvic floor rehabilitation aids, personalized guidance can be provided to patients with PFD, helping them select the appropriate aids for their rehabilitation needs.


Subject(s)
Pelvic Floor Disorders , Pelvic Floor , Urinary Incontinence , Humans , Female , Pelvic Floor Disorders/rehabilitation , Urinary Incontinence/rehabilitation , Pelvic Floor/physiopathology , Fecal Incontinence/rehabilitation , Fecal Incontinence/etiology , Pessaries
3.
ACS Omega ; 9(27): 29478-29490, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-39005801

ABSTRACT

The quantitative structure-activity relationship (QSAR) regression model is a commonly used technique for predicting the biological activities of compounds using their molecular descriptors. Besides accurate activity estimation, obtaining a prediction uncertainty metric like a prediction interval is highly desirable. Quantifying prediction uncertainty is an active research area in statistical and machine learning (ML), but the implementation for QSAR remains challenging. However, most ML algorithms with high predictive performance require add-on companions for estimating the uncertainty of their prediction. Conformal prediction (CP) is a promising approach as its main components are agnostic to the prediction modes, and it produces valid prediction intervals under weak assumptions on the data distribution. We proposed computationally efficient CP algorithms tailored to the most widely used ML models, including random forests, deep neural networks, and gradient boosting. The algorithms use a novel approach to the derivation of nonconformity scores from the estimates of prediction uncertainty generated by the ensembles of point predictions. The validity and efficiency of proposed algorithms are demonstrated on a diverse collection of QSAR data sets as well as simulation studies. The provided software implementing our algorithms can be used as stand-alone or easily incorporated into other ML software packages for QSAR modeling.

4.
Sci Rep ; 14(1): 12740, 2024 06 03.
Article in English | MEDLINE | ID: mdl-38830945

ABSTRACT

Testicular cancer (TCa) is a rare but impactful malignancy that primarily affects young men. Understanding the mortality rate of TCa is crucial for improving prevention and treatment strategies to reduce the risk of death among patients. We obtained TCa mortality data by place (5 countries), age (20-79 years), and year (1990-2019) from the Global Burden of Disease Study 2019. Age-period-cohort model was used to estimate the net drift, local drift, age effects, period and cohort effects. In 2019, the global mortality of TCa increased to 10842 (95% UI 9961, 11902), with an increase of 50.08% compared to 1990.The all-age mortality rate for TCa in 2019 increased from 0.17/100,000 (95% UI 0.13, 0.20) in China to 0.48/100,000 (95% UI 0.38, 0.59) in Russian Federation, whereas the age-standardized mortality rate in 2019 was highest in the South Africa 0.47/100,000 (95% UI 0.42, 0.53) and lowest in the China 0.16/100,000 (95% UI 0.13, 0.19). China's aging population shifts mortality patterns towards the elderly, while in Russian Federation, young individuals are primarily affected by the distribution of deaths. To address divergent TCa mortality advancements in BRICS countries, we propose a contextually adaptive and resource-conscious approach to prioritize TCa prevention. Tailoring strategies to contextual diversity, including policy frameworks, human resources, and financial capacities, will enhance targeted interventions and effectiveness in reducing TCa mortality.


Subject(s)
Testicular Neoplasms , Humans , Male , Middle Aged , Testicular Neoplasms/mortality , Testicular Neoplasms/epidemiology , Adult , Aged , Young Adult , Russia/epidemiology , China/epidemiology , Cohort Studies , Global Burden of Disease/trends , Mortality/trends , South Africa/epidemiology , Age Factors
5.
Discov Oncol ; 15(1): 202, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38822944

ABSTRACT

BACKGROUNDS: Microfibril-associated protein 2 (MFAP2) is a protein presenting in the extracellular matrix that governs the activity of microfibrils through its interaction with fibrillin. While the involvement of MFAP2 in metabolic disorders has been documented, its expression and prognostic significance in triple-negative breast cancer (TNBC) remain unexplored. METHODS: We acquired datasets pertaining to breast cancer (BC) from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Next, a Venn diagram was used to identify the differentially expressed genes (DEGs). The DEGs were used to perform Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI), immune and survival analysis. The expressions of MFAP2, PD-1 and PD-L1 were examined by immunohistochemistry and western blot and their relationship with clinical pathological parameters were analyzed by clinical specimen samples from patients with TNBC. Tumor Immune Estimation Resource (TIMER, https://cistrome.shinyapps.io/timer/ ) was adopted to calculate the immune infiltration level of TNBC. The link between gene expression and tumor mutational burden (TMB) was described using Spearman's correlation analysis. RESULTS: We identified 66 differentially expressed genes (DEGs) that were up-regulated. Among these DEGs, MFAP2 was found to be overexpressed in TNBC and was associated with a lower probability of survival. This finding was confirmed through the use of immunohistochemistry and western blot techniques. Additionally, MFAP2 was found to be related to various pathological parameters in TNBC patients. Mechanistically, gene set enrichment analysis (GSEA) revealed that MFAP2 primarily influenced cellular biological behavior in terms of epithelial mesenchymal transition, glycolysis, and apical junction. Notably, MFAP2 expression was positively correlated with the abundance of macrophages, while a negative correlation was observed with the abundance of B cells, CD4 + T cells, CD8 + T cells, neutrophils and dendritic cells through immune analysis. Furthermore, it was observed that MFAP2 displayed a negative correlation not only with tumor mutational burden (TMB), a recognized biomarker for PD-1/PD-L1 immunotherapy, but also with PD-L1 in samples of TNBC. CONCLUSION: MFAP2 may be an important prognostic biomarker for TNBC, as well as a viable target for immunotherapy in this disease.

6.
Transl Androl Urol ; 13(5): 657-666, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38855607

ABSTRACT

Background: Stress urinary incontinence (SUI) is the most ubiquitous form of urinary incontinence in women. The therapeutic management of patients with SUI is challenging. The aim of this study is to evaluate the efficacy of whole body vibration training (WBVT) for SUI. Methods: Thirty-five female rats were randomly divided into a sham group (Sham group, n=5), SUI + WBVT group (n=15) and SUI + whole body rest group (SUI + WBR group, n=15). The SUI + WBVT group was trained as follows: frequency 30 Hz, amplitude four mm, one min/repeat, four min rest, repeated 10 times, five days/week. After the intervention, five rats were taken on the 7th, 14th and 21st day to observe the urodynamic changes, levator ani muscle and dorsal root ganglia (DRG) morphology, and to observe the expression of neurotrophic factor-3/tyrosine protein kinase C (NT-3/TrkC) by Western blot. Results: The urodynamic results showed that the difference in bladder leak point pressure/abdominal leak point pressure (BLPP/ALPP) between the Sham group and the SUI + WBR group was statistically significant (P<0.001) on 7th day, indicating successful modeling. The BLPP/ALPP of the SUI + WBVT group and the SUI + WBR group improved on 7th, 14th, and 21st day, and the BLPP/ALPP of SUI + WBVT group was higher than the SUI + WBR group. Compared with the Sham group, pathological changes appeared in the muscle shuttles in the SUI + WBVT group and SUI + WBR group. Western blot showed a gradual up-regulation of NT-3/TrkC. Conclusions: WBVT can be used to treat SUI by affecting the expression of NT-3/TrkC, improving the structural morphology of the proprioceptors, and restoring the urinary control function. This study provides evidence for the clinical practice of WBVT. Future studies could further refine the behavioral and electrophysiological aspects of the assessment.

7.
PNAS Nexus ; 3(6): pgae205, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38846777

ABSTRACT

Food safety is related to human health and sustainable development. International food trade poses food safety risks through the collateral transport of toxic chemicals that are detrimental to human health. Domestic interprovincial trade has similar effects within countries but has not been comprehensively investigated previously. Here, we assessed the effects of interprovincial trade on food safety and human dietary exposure to short-chain chlorinated paraffins (SCCPs), a group of emerging persistent toxic chemicals, in seafood across China by synthesizing data from field observation and various models. Our findings indicate that there is a higher level of SCCPs exposure risk in coastal provinces compared to inland provinces. Approximately, 70.3% of human exposure to SCCPs through seafood consumption in China was embodied in the interprovincial seafood trade in 2021. Specifically, the domestic trade led to a remarkable increase in SCCPs exposure in the coastal provinces in South China, attributable to low SCCPs pollution in these provinces and imported seafood from those provinces with high SCCPs pollution. In contrast, human exposure to SCCPs decreased in those coastal provinces in East China due to importing seafood from those provinces with low SCCPs concentrations. The interprovincial seafood trade routes were optimized by linear programming to minimize human exposure to SCCPs considering both shipping cost and health risk constraints. The optimized trade routes reduced the national per capita SCCPs exposure through seafood consumption by over 12%. This study highlights the importance of interprovincial food trade in the risk assessment of toxic chemicals.

8.
J Hepatocell Carcinoma ; 11: 1143-1156, 2024.
Article in English | MEDLINE | ID: mdl-38911291

ABSTRACT

Hepatocellular carcinoma (HCC) stands as the prevailing form of primary liver cancer, characterized by a poor prognosis and high mortality rate. A pivotal factor in HCC tumorigenesis is epigenetics, specifically the regulation of gene expression through methylation. This process relies significantly on the action of proteins that modify methylation, including methyltransferases, their associated binding proteins, and demethylases. These proteins are crucial regulators, orchestrating the methylation process by regulating enzymes and their corresponding binding proteins. This orchestration facilitates the reading, binding, detection, and catalysis of gene methylation sites. Methylation ences the development, prolisignificantly influferation, invasion, and prognosis of HCC. Furthermore, methylation modification and its regulatory mechanisms activate distinct biological characteristics in HCC cancer stem cells, such as inducing cancer-like differentiation of stem cells. They also influence the tumor microenvironment (TME) in HCC, modulate immune responses, affect chemotherapy resistance in HCC patients, and contribute to HCC progression through signaling pathway feedback. Given the essential role of methylation in genetic information, it holds promise as a potential tool for the early detection of HCC and as a target to improve drug resistance and promote apoptosis in HCC cells.

9.
Angew Chem Int Ed Engl ; : e202403671, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38887161

ABSTRACT

Electrochemical carbon dioxide (CO2) reduction reaction (CO2RR) to valuable liquid fuels, such as formic acid/formate (HCOOH/HCOO-) is a promising strategy for carbon neutrality. Enhancing CO-2RR activity while retaining high selectivity is critical for commercialization. To address this, we developed metal-doped bismuth (Bi) nanosheets via a facile hydrolysis method. These doped nanosheets efficiently generated high-purity HCOOH using a porous solid electrolyte (PSE) layer. Among the evaluated metal-doped Bi catalysts, Co-doped Bi demonstrated improved CO2RR performance compared to pristine Bi, achieving ~90% HCOO- selectivity and boosted activity with a low overpotential of ~1.0 V at a current density of 200 mA cm-2. In a solid electrolyte reactor, Co-doped Bi maintained HCOOH Faradaic efficiency of ~72% after a 100-hour operation under a current density of 100 mA cm-2, generating 0.1 M HCOOH at 3.2 V. Density functional theory (DFT) results revealed that Co-doped Bi required a lower applied potential for HCOOH generation from CO2, due to stronger binding energy to the key intermediates OCHO* compared to pure Bi. This study shows that metal doping in Bi nanosheets modifies the chemical composition, element distribution, and morphology, improving CO2RR catalytic activity performance by tuning surface adsorption affinity and reactivity.

10.
Chem Sci ; 15(19): 7160-7169, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38756794

ABSTRACT

Autonomous process optimization (APO) is a technology that has recently found utility in a multitude of process optimization challenges. In contrast to most APO examples in microflow reactor systems, we recently presented a system capable of optimization in high-throughput batch reactor systems. The drawback of APO in a high-throughput batch reactor system is the reliance on reaction sampling at a predetermined static timepoint rather than a dynamic endpoint. Static timepoint sampling can lead to the inconsistent capture of the process performance under each process parameter permutation. This is important because critical process behaviors such as rate acceleration accompanied by decomposition could be missed entirely. To address this drawback, we implemented a dynamic reaction endpoint determination strategy to capture the product purity once the process stream stabilized. We accomplished this through the incorporation of a real-time plateau detection algorithm into the APO workflow to measure and report the product purity at the dynamically determined reaction endpoint. We then applied this strategy to the autonomous optimization of a photobromination reaction towards the synthesis of a pharmaceutically relevant intermediate. In doing so, we not only uncovered process conditions to access the desired monohalogenation product in 85 UPLC area % purity with minimal decomposition risk, but also measured the effect of each parameter on the process performance. Our results highlight the advantage of incorporating dynamic sampling in APO workflows to drive optimization toward a stable and high-performing process.

11.
Mol Med Rep ; 30(1)2024 Jul.
Article in English | MEDLINE | ID: mdl-38818815

ABSTRACT

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and its morbidity is increasing worldwide due to increasing prevalence. Metabolic reprogramming has been recognized as a hallmark of cancer and serves a role in cancer progression. Glucose, lipids and amino acids are three major components whose altered metabolism can directly affect the energy production of cells, including liver cancer cells. Nutrients and energy are indispensable for the growth and proliferation of cancer cells, thus altering the metabolism of hepatoma cells can inhibit the progression of HCC. The present review summarizes recent studies on tumour regulatory molecules, including numerous noncoding RNAs, oncogenes and tumour suppressors, which regulate the metabolic activities of glucose, lipids and amino acids by targeting key enzymes, signalling pathways or interactions between the two. These regulatory molecules can regulate the rapid proliferation of cancer cells, tumour progression and treatment resistance. It is thought that these tumour regulatory factors may serve as therapeutic targets or valuable biomarkers for HCC, with the potential to mitigate HCC drug resistance. Furthermore, the advantages and disadvantages of metabolic inhibitors as a treatment approach for HCC, as well as possible solutions are discussed, providing insights for developing more effective treatment strategies for HCC.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/genetics , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Liver Neoplasms/genetics , Animals , Energy Metabolism , Signal Transduction , Gene Expression Regulation, Neoplastic , Glucose/metabolism , Lipid Metabolism , Metabolic Reprogramming
12.
J Agric Food Chem ; 72(22): 12842-12858, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38767652

ABSTRACT

Granule-associated surface lipids (GASLs) and internal lipids showed different lipid-amylose relationships, contents, and distributions, suggesting their differing biological origins and functions, among waxy, normal, and high-amylose rice starch. The GASL content mainly depended on the pore size, while internal lipids regulated starch biosynthesis, as indicated by correlations of internal lipids with the chain length distribution of amylopectin and amylose content. Of the 1346 lipids detected, 628, 562, and 408 differentially expressed lipids were observed between normal-waxy, high-amylose-waxy, and normal-high-amylose starch, respectively. After the removal of GASLs, the higher lysophospholipid content induced greater decreases in the peak and breakdown viscosity and swelling power, while the highest digestibility increase was found with the highest triacylglycerol content. Thus, different GASL compositions led to different digestibility, swelling, and pasting outcomes. This study sheds new light on the mechanism of the role of GASLs in the structure and properties of starch, as well as in potential modifications and amyloplast membrane development.


Subject(s)
Amylose , Digestion , Lipidomics , Lipids , Oryza , Starch , Oryza/chemistry , Oryza/metabolism , Amylose/metabolism , Amylose/analysis , Amylose/chemistry , Lipids/chemistry , Starch/chemistry , Starch/metabolism , Viscosity
13.
Cell Death Dis ; 15(5): 332, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38740744

ABSTRACT

Ovarian cancer (OV) poses a significant challenge in clinical settings due to its difficulty in early diagnosis and treatment resistance. FOXP4, belonging to the FOXP subfamily, plays a pivotal role in various biological processes including cancer, cell cycle regulation, and embryonic development. However, the specific role and importance of FOXP4 in OV have remained unclear. Our research showed that FOXP4 is highly expressed in OV tissues, with its elevated levels correlating with poor prognosis. We further explored FOXP4's function through RNA sequencing and functional analysis in FOXP4-deficient cells, revealing its critical role in activating the Wnt signaling pathway. This activation exacerbates the malignant phenotype in OV. Mechanistically, FOXP4 directly induces the expression of protein tyrosine kinase 7 (PTK7), a Wnt-binding receptor tyrosine pseudokinase, which causes abnormal activation of the Wnt signaling pathway. Disrupting the FOXP4-Wnt feedback loop by inactivating the Wnt signaling pathway or reducing FOXP4 expression resulted in the reduction of the malignant phenotype of OV cells, while restoring PTK7 expression reversed this effect. In conclusion, our findings underscore the significance of the FOXP4-induced Wnt pathway activation in OV, suggesting the therapeutic potential of targeting this pathway in OV treatment.


Subject(s)
Forkhead Transcription Factors , Ovarian Neoplasms , Receptor Protein-Tyrosine Kinases , Wnt Signaling Pathway , Animals , Female , Humans , Mice , beta Catenin/metabolism , Cell Adhesion Molecules/metabolism , Cell Adhesion Molecules/genetics , Cell Line, Tumor , Cell Proliferation , Forkhead Transcription Factors/metabolism , Forkhead Transcription Factors/genetics , Gene Expression Regulation, Neoplastic , Mice, Nude , Ovarian Neoplasms/pathology , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/genetics , Receptor Protein-Tyrosine Kinases/metabolism , Receptor Protein-Tyrosine Kinases/genetics
14.
Development ; 151(7)2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38603796

ABSTRACT

Embryonic diapause is a special reproductive phenomenon in mammals that helps embryos to survive various harsh stresses. However, the mechanisms of embryonic diapause induced by the maternal environment is still unclear. Here, we uncovered that nutrient deficiency in uterine fluid was essential for the induction of mouse embryonic diapause, shown by a decreased concentration of arginine, leucine, isoleucine, lysine, glucose and lactate in the uterine fluid of mice suffering from maternal starvation or ovariectomy. Moreover, mouse blastocysts cultured in a medium with reduced levels of these six components could mimic diapaused blastocysts. Our mechanistic study indicated that amino acid starvation-dependent Gator1 activation and carbohydrate starvation-dependent Tsc2 activation inhibited mTORC1, leading to induction of embryonic diapause. Our study elucidates the essential environmental factors in diapause induction.


Subject(s)
Diapause , Nutrients , Animals , Female , Mice , Blastocyst/metabolism , Diapause/physiology , Embryonic Development/physiology
15.
J Agric Food Chem ; 72(18): 10163-10178, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38653191

ABSTRACT

Oxalate decarboxylase (OXDC) is a typical Mn2+/Mn3+ dependent metal enzyme and splits oxalate to formate and CO2 without any organic cofactors. Fungi and bacteria are the main organisms expressing the OXDC gene, but with a significantly different mechanism of gene expression and regulation. Many articles reported its potential applications in the clinical treatment of hyperoxaluria, low-oxalate food processing, degradation of oxalate salt deposits, oxalate acid diagnostics, biocontrol, biodemulsifier, and electrochemical oxidation. However, some questions still remain to be clarified about the role of substrate binding and/or protein environment in modulating the redox properties of enzyme-bound Mn(II)/Mn(III), the nature of dioxygen involved in the catalytic mechanism, and how OXDC acquires Mn(II) /Mn(III). This review mainly summarizes its biochemical and structure characteristics, gene expression and regulation, and catalysis mechanism. We also deep-mined oxalate decarboxylase gene data from National Center for Biotechnology Information to give some insights to explore new OXDC with diverse biochemical properties.


Subject(s)
Bacteria , Carboxy-Lyases , Carboxy-Lyases/genetics , Carboxy-Lyases/metabolism , Carboxy-Lyases/chemistry , Bacteria/genetics , Bacteria/enzymology , Bacteria/metabolism , Fungi/genetics , Fungi/enzymology , Fungal Proteins/genetics , Fungal Proteins/metabolism , Fungal Proteins/chemistry , Biocatalysis , Oxalates/metabolism , Oxalates/chemistry , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Bacterial Proteins/chemistry , Gene Expression Regulation, Enzymologic , Humans , Catalysis , Animals
16.
J Ethnopharmacol ; 330: 118067, 2024 Aug 10.
Article in English | MEDLINE | ID: mdl-38636574

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Jingfang Baidu Powder (JFBDP) is a classic traditional Chinese medicine prescription. Although Jingfang Baidu powder obtained a general consensus on clinical efficacy in treating pneumonia, there were many Chinese herbal drugs in formula, complex components, and large oral dosage, which brings certain obstacles to clinical application. AIM OF THE STUDY: Therefore, screening of the active fraction that exerts anti-pneumonia helps improve the pharmaceutical preparation, improve the treatment compliance of patients, and further contribute to the clinical application, and the screening of the new active ingredients with anti-pneumonia. The histopathological observation, real-time quantitative PCR, western blotting, and immunofluorescence were applied to evaluate the anti-pneumonia efficacy of active fractions from JFBDP. RESULTS: Three fractions from JFBDP inhibit the gene expression of IL-1ß, IL-10, CCL3, CCL5, and CCL22 in lung tissue infected by Klebsiella at various degrees, and presented a good dose-response relationship. JF50 showed stronger anti-inflammatory effects among three fractions including JF30, JF50, and JF75. Besides, JF50 significantly reduced the protein expression of TLR4 and Myd88 in lung tissue infected with Klebsiella, and it also significantly inhibited p-ERK and p-NF-κB p65. JF50 significantly inhibits the protein expression of Caspase 3, Caspase 8, and Caspase 9 in lung tissue infected with Klebsiella at the dose of 25 mg/kg and 50 mg/kg. CONCLUSION: JF50 improves lung pathological damage in Klebsiella pneumonia mice by inhibiting the TLR4/Myd88/NF-κB-ERK signaling pathway, and inhibiting apoptosis of lung tissue cells. These findings provide a reference for further exploring the active substance basis of Jingfang Baidu Powder in treating bacterial pneumonia.


Subject(s)
Drugs, Chinese Herbal , Klebsiella Infections , Myeloid Differentiation Factor 88 , Powders , Toll-Like Receptor 4 , Animals , Toll-Like Receptor 4/metabolism , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/therapeutic use , Myeloid Differentiation Factor 88/metabolism , Mice , Male , Klebsiella Infections/drug therapy , MAP Kinase Signaling System/drug effects , Anti-Inflammatory Agents/pharmacology , Apoptosis/drug effects , Lung/drug effects , Lung/pathology , Lung/metabolism , Klebsiella pneumoniae/drug effects , Signal Transduction/drug effects , Mice, Inbred C57BL
17.
Curr Med Sci ; 44(2): 426-434, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38561594

ABSTRACT

OBJECTIVE: Glucose-6-phosphate isomerase (GPI) deficiency is a rare hereditary nonspherocytic hemolytic anemia caused by GPI gene variants. This disorder exhibits wide heterogeneity in its clinical manifestations and molecular characteristics, often posing challenges for precise diagnoses using conventional methods. To this end, this study aimed to identify the novel variants responsible for GPI deficiency in a Chinese family. METHODS: The clinical manifestations of the patient were summarized and analyzed for GPI deficiency phenotype diagnosis. Novel compound heterozygous variants of the GPI gene, c.174C>A (p.Asn58Lys) and c.1538G>T (p.Trp513Leu), were identified using whole-exome and Sanger sequencing. The AlphaFold program and Chimera software were used to analyze the effects of compound heterozygous variants on GPI structure. RESULTS: By characterizing 53 GPI missense/nonsense variants from previous literature and two novel missense variants identified in this study, we found that most variants were located in exons 3, 4, 12, and 18, with a few localized in exons 8, 9, and 14. This study identified novel compound heterozygous variants associated with GPI deficiency. These pathogenic variants disrupt hydrogen bonds formed by highly conserved GPI amino acids. CONCLUSION: Early family-based sequencing analyses, especially for patients with congenital anemia, can help increase diagnostic accuracy for GPI deficiency, improve child healthcare, and enable genetic counseling.


Subject(s)
Anemia, Hemolytic, Congenital Nonspherocytic , Anemia, Hemolytic , Child , Humans , Glucose-6-Phosphate Isomerase/genetics , Glucose-6-Phosphate Isomerase/chemistry , Anemia, Hemolytic/genetics , Anemia, Hemolytic, Congenital Nonspherocytic/diagnosis , Anemia, Hemolytic, Congenital Nonspherocytic/genetics , Mutation, Missense , Exons
18.
Front Neurosci ; 18: 1309684, 2024.
Article in English | MEDLINE | ID: mdl-38576865

ABSTRACT

The loss of dopaminergic neurons in the substantia nigra and the abnormal accumulation of synuclein proteins and neurotransmitters in Lewy bodies constitute the primary symptoms of Parkinson's disease (PD). Besides environmental factors, scholars are in the early stages of comprehending the genetic factors involved in the pathogenic mechanism of PD. Although genome-wide association studies (GWAS) have unveiled numerous genetic variants associated with PD, precisely pinpointing the causal variants remains challenging due to strong linkage disequilibrium (LD) among them. Addressing this issue, expression quantitative trait locus (eQTL) cohorts were employed in a transcriptome-wide association study (TWAS) to infer the genetic correlation between gene expression and a particular trait. Utilizing the TWAS theory alongside the enhanced Joint-Tissue Imputation (JTI) technique and Mendelian Randomization (MR) framework (MR-JTI), we identified a total of 159 PD-associated genes by amalgamating LD score, GTEx eQTL data, and GWAS summary statistic data from a substantial cohort. Subsequently, Fisher's exact test was conducted on these PD-associated genes using 5,152 differentially expressed genes sourced from 12 PD-related datasets. Ultimately, 29 highly credible PD-associated genes, including CTX1B, SCNA, and ARSA, were uncovered. Furthermore, GO and KEGG enrichment analyses indicated that these genes primarily function in tissue synthesis, regulation of neuron projection development, vesicle organization and transportation, and lysosomal impact. The potential PD-associated genes identified in this study not only offer fresh insights into the disease's pathophysiology but also suggest potential biomarkers for early disease detection.

19.
Sci Rep ; 14(1): 5582, 2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38448540

ABSTRACT

This study presents a data-driven assisted real-time optimization model which is an innovative approach to address the challenges posed by integrating Submerged Arc Furnace (SAF) systems with renewable energy sources, specifically photovoltaic (PV) and wind power, with modern intelligent energy terminals. Specifically, the proposed method is divided into two stages. The first stage is related to data-driven prediction for addressing local time-varying renewable energy and electricity market prices with predicted information, and the second stage uses an optimization model for real-time SAF dispatch. Connections between intelligent energy terminals, demand-side devices, and load management systems are established to enhance local renewable resource utilization. Additionally, mathematical formulations of the operating resistance in SAF are explored, and deep neuron networks are employed and modified for dynamic uncertainty prediction. The proposed approach is validated through a case study involving an intelligent energy terminal with a 12.5 MVA SAF system and 12 MW capacity renewable generators in an electricity market with fluctuating prices. The findings of this research underscore the efficacy of the proposed optimization model in reducing operational costs and enhancing the utilization of localized renewable energy generation. By integrating four distinct dissatisfaction coefficients into the optimization framework, we demonstrate the model's adaptability and efficiency. The application of the optimization strategy delineated herein results in the SAF system's profitability oscillating between $111 and $416 across various time intervals, contingent upon the coefficient settings. Remarkably, an aggregate daily loss recovery amounting to $1,906.84 can be realized during the optimization period. Such outcomes not only signify considerable economic advantages but also contribute to grid stability and the diminution of renewable energy curtailment, thereby underscoring the dual benefits of economic efficiency and sustainability in energy management practices.

20.
Zool Res ; 45(2): 292-298, 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38485499

ABSTRACT

Mutations in mitochondrial DNA (mtDNA) are maternally inherited and have the potential to cause severe disorders. Mitochondrial replacement therapies, including spindle, polar body, and pronuclear transfers, are promising strategies for preventing the hereditary transmission of mtDNA diseases. While pronuclear transfer has been used to generate mitochondrial replacement mouse models and human embryos, its application in non-human primates has not been previously reported. In this study, we successfully generated four healthy cynomolgus monkeys ( Macaca fascicularis) via female pronuclear transfer. These individuals all survived for more than two years and exhibited minimal mtDNA carryover (3.8%-6.7%), as well as relatively stable mtDNA heteroplasmy dynamics during development. The successful establishment of this non-human primate model highlights the considerable potential of pronuclear transfer in reducing the risk of inherited mtDNA diseases and provides a valuable preclinical research model for advancing mitochondrial replacement therapies in humans.


Subject(s)
Mitochondrial Diseases , Rodent Diseases , Mice , Humans , Female , Animals , Mitochondrial Diseases/genetics , Mitochondrial Diseases/prevention & control , Mitochondrial Diseases/veterinary , Haplorhini/genetics , Mitochondria/genetics , DNA, Mitochondrial/genetics , Primates/genetics
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