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1.
Yi Chuan ; 46(3): 256-262, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38632103

RESUMO

Hepatocyte nuclear factor 1α (HNF1α) is a transcription factor that is crucial for the regulation to maintain the function of pancreatic ß-cell, hepatic lipid metabolism, and other processes. Mature-onset diabetes of the young type 3 is a monogenic form of diabetes caused by HNF1α mutations. Although several mutation sites have been reported, the specific mechanisms remain unclear, such hot-spot mutation as the P291fsinsC mutation and the P112L mutation and so on. In preliminary studies, we discovered one MODY3 patient carrying a mutation at the c.493T>C locus of the HNF1α gene. In this study, we analyzed the pathogenic of the mutation sites by using the Mutation Surveyor software and constructed the eukaryotic expression plasmids of the wild-type and mutant type of HNF1α to detect variations in the expression levels and stability of HNF1α protein by using Western blot. The analyses of the Mutation Surveyor software showed that the c.493T>C site mutation may be pathogenic gene and the results of Western blot showed that both the amount and stability of HNF1α protein expressed by the mutation type plasmid were reduced significantly compared to those by the wild type plasmid (P<0.05). This study suggests that the c.493T>C (p.Trp165Arg) mutation dramatically impacts HNF1α expression, which might be responsible for the development of the disease and offers fresh perspectives for the following in-depth exploration of MODY3's molecular pathogenic process.


Assuntos
Diabetes Mellitus Tipo 2 , Fator 1-alfa Nuclear de Hepatócito , Células Secretoras de Insulina , Humanos , Diabetes Mellitus Tipo 2/genética , Fator 1-alfa Nuclear de Hepatócito/genética , Fator 1-alfa Nuclear de Hepatócito/metabolismo , Células Secretoras de Insulina/metabolismo , Mutação
2.
Mol Divers ; 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38609691

RESUMO

4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27; HPPD) is one of the important target enzymes in the development of herbicides. To discover novel HPPD inhibitors with unique molecular, 39 cyclohexanedione derivations containing pyrazole and pyridine groups were designed and synthesized. The preliminary herbicidal activity test results showed that some compounds had obvious inhibitory effects on monocotyledon and dicotyledonous weeds. The herbicidal spectrums of the highly active compounds were further determined, and the compound G31 exhibited the best inhibitory rate over 90% against Plantago depressa Willd and Capsella bursa-pastoris at the dosages of 75.0 and 37.5 g ai/ha, which is comparable to the control herbicide mesotrione. Moreover, compound G31 showed excellent crop safety, with less than or equal to 10% injury rates to corn, sorghum, soybean and cotton at a dosage of 225 g ai/ha. Molecular docking and molecular dynamics simulation analysis revealed that the compound G31 could stably bind to Arabidopsis thaliana HPPD (AtHPPD). This study indicated that the compound G31 could be used as a lead molecular structure for the development of novel HPPD inhibitors, which provided an idea for the design of new herbicides with unique molecular scaffold.

3.
Nat Chem ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38570729

RESUMO

Lithium metal batteries represent a promising technology for next-generation energy storage, but they still suffer from poor cycle life due to lithium dendrite formation and cathode cracking. Fluorinated solvents can improve battery longevity by improving LiF content in the solid-electrolyte interphase; however, the high cost and environmental concerns of fluorinated solvents limit battery viability. Here we designed a series of fluorine-free solvents through the methylation of 1,2-dimethoxyethane, which promotes inorganic LiF-rich interphase formation through anion reduction and achieves high oxidation stability. The anion-derived LiF interphases suppress lithium dendrite growth on the lithium anode and minimize cathode cracking under high-voltage operation. The Li+-solvent structure is investigated through in situ techniques and simulations to draw correlations between the interphase compositions and electrochemical performances. The methylation strategy provides an alternative pathway for electrolyte engineering towards high-voltage electrolytes while reducing dependence on expensive fluorinated solvents.

4.
Chem Sci ; 15(12): 4403-4415, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38516067

RESUMO

It is important to develop materials with environmental stability and long device shelf life for use in organic field-effect transistors (OFETs). The microscopic, molecular-level nature of the organic layer in OFETs is not yet well understood. The stability of geometric and electronic structures and the regulation of the external electric field (EEF) on the charge transport properties of four typical homogeneous organic semiconductors (OSCs) were investigated by density functional theory (DFT). The results showed that under the EEF, the structural changes in single-bond linked oligomers were more sensitive and complex than those of condensed molecules, and there were non-monotonic changes in their reorganization energy (λ) during charge transport under an EEF consisting of decreases and then increases (Series D). The change in λ under an EEF can be preliminarily and qualitatively determined by the change in the frontier molecular orbitals (FMOs) - the number of C-atoms with nonbonding characteristics. For single-bonded molecules, the transfer integral is basically unchanged under a low EEF, but it will greatly change at a high EEF. Because the structure and properties of the molecule will greatly change under different EEFs, the effect of an EEF should be fully considered when determining the intrinsic mobility of OSCs, which could cause a deviation 0.3-20 times in mobility. According to detailed calculations, one heterogeneous oligomer, TH-BTz, was designed. Its λ can be greatly reduced under an EEF, and the change in the energy level of FMOs can be adjusted to different degrees. This study provides a reasonable idea for verification of the experimental mobility value and also provides guidance for the directional design of stable high-mobility OSCs.

5.
Int J Clin Pract ; 2024: 1386980, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38481823

RESUMO

Background: Tenapanor is a locally acting selective sodium-hydrogen exchanger 3 inhibitor with the potential to treat sodium/phosphorus and fluid overload in various cardiac-renal diseases, which has been approved for constipation-predominant irritable bowel syndrome in the US. The pharmacokinetics (PK) of tenapanor and its metabolite tenapanor-M1 (AZ13792925), as well as the safety and tolerability of tenapanor, were investigated in healthy Chinese and Caucasian subjects. Methods: This randomized, open-label, single-center, placebo-controlled phase 1 study (https://www.chinadrugtrials.org.cn; CTR20201783) enrolled Chinese and Caucasian healthy volunteers into 4 parallel cohorts (3 cohorts for Chinese subjects, 1 cohort for Caucasian subjects). In each cohort, 15 subjects were expected to be included and received oral tenapanor (10 or 30 mg as single dose, or 50 mg as a single dose followed by a twice-daily repeated dose from Day 5 to 11, with a single dose in the morning on Day 11) or placebo in a 4 : 1 ratio. Results: 59 healthy volunteers received tenapanor 10 mg (n = 12 Chinese), 30 mg (n = 12 Chinese), or 50 mg (n = 12 (Chinese), n = 11 (Caucasian)) or placebo (n = 12, 3 per cohort). After single and twice-daily repeated doses, tenapanor plasma concentrations were all below the limit of quantitation; tenapanor-M1 appeared slowly in plasma. In single-ascending dose evaluation (10 to 50 mg) of Chinese subjects, the mean Cmax, AUC0-t, and AUC0-∞ of tenapanor-M1 increased with increasing dose level, and AUC0-t increased approximately dose proportionally. The Cmax accumulation ratio was 1.55 to 6.92 after 50 mg repeated dose in Chinese and Caucasian subjects. Exposure to tenapanor-M1 was generally similar between the Chinese and Caucasian subjects. Tenapanor was generally well-tolerated and the safety profile was similar between the Chinese and Caucasian participants receiving tenapanor 50 mg, as measured by vital signs, physical and laboratory examination, 12-lead ECG, and adverse events. No serious adverse event or adverse event leading to withdrawal occurred. Conclusion: Tenapanor was well-tolerated, with similar PK and safety profiles between Chinese and Caucasian subjects. This trial is registered with CTR20201783.


Assuntos
Síndrome do Intestino Irritável , Sulfonamidas , Humanos , Isoquinolinas/efeitos adversos , Isoquinolinas/farmacocinética , Área Sob a Curva , Método Duplo-Cego , Voluntários Saudáveis , China , Relação Dose-Resposta a Droga
6.
Huan Jing Ke Xue ; 45(3): 1561-1576, 2024 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-38471870

RESUMO

At the time when water resources are in short supply,wastewater recycling is both an important environmental protection strategy and also a resource strategy. Disinfection is essential to ensure the biological safety of reclaimed wastewater by killing pathogens and preventing the spread of waterborne diseases. However,the disinfection process could inevitably produce toxic disinfection byproducts(DBPs)due to the reaction between the disinfectants and wastewater organic matters. Regarding wastewater DBPs,this study reviewed their identification methods,formation conditions(including precursors,the effect of water quality,disinfectants,and operational parameters on DBPs),and control methods(including source control,process control,and end control). In addition,future research trends of wastewater DBPs were discussed.


Assuntos
Desinfetantes , Poluentes Químicos da Água , Purificação da Água , Desinfecção/métodos , Águas Residuárias , Purificação da Água/métodos , Poluentes Químicos da Água/análise , Halogenação
8.
Nat Commun ; 15(1): 1206, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38332019

RESUMO

Micro-sized silicon anodes can significantly increase the energy density of lithium-ion batteries with low cost. However, the large silicon volume changes during cycling cause cracks for both organic-inorganic interphases and silicon particles. The liquid electrolytes further penetrate the cracked silicon particles and reform the interphases, resulting in huge electrode swelling and quick capacity decay. Here we resolve these challenges by designing a high-voltage electrolyte that forms silicon-phobic interphases with weak bonding to lithium-silicon alloys. The designed electrolyte enables micro-sized silicon anodes (5 µm, 4.1 mAh cm-2) to achieve a Coulombic efficiency of 99.8% and capacity of 2175 mAh g-1 for >250 cycles and enable 100 mAh LiNi0.8Co0.15Al0.05O2 pouch full cells to deliver a high capacity of 172 mAh g-1 for 120 cycles with Coulombic efficiency of >99.9%. The high-voltage electrolytes that are capable of forming silicon-phobic interphases pave new ways for the commercialization of lithium-ion batteries using micro-sized silicon anodes.

9.
Langenbecks Arch Surg ; 409(1): 64, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38363369

RESUMO

BACKGROUND: The wounds failing to heal through a timely and orderly standard of care (SOC) treatment are considered as chronic wounds, which add significant burden to healthcare systems around the world. SOC treatment has been commonly applied for management of chronic wounds, but SOC alone may not be adequate to heal all ulcers effectively. Fish skin graft (FSG) is a xenogenic skin substitute which could be used for accelerating skin healing. The current study was performed with the view of evaluating the effectiveness of FSG as an adjuvant treatment of SOC for chronic ulcer treatment. METHODS: Two authors independently searched the following electronic databases: PubMed, Embase, and CENTRAL, using keywords including "diabetic foot ulcer," "fish skin graft," and "wound healing." Clinical studies that evaluated the clinical outcomes of FSG in treatment of chronic ulcers were included in this meta-analysis. Random- or fixed-effect modeled meta-analyses were performed according to the heterogeneity test result (i.e., I2), to analyze the clinical outcome of FSG. RESULTS: A total of 8 studies were included in qualitative synthesis and meta-analysis, with 145 patients treated by SOC and 245 patients treated by SOC plus FSG. There was no significant difference between two groups for time to healing (MD = 1.99, 95% CI: -3.70~7.67, p = 0.493). The complete healing rate was significantly higher in FSG group compared with SOC alone (OR = 3.44, 95% CI: 2.03~5.82, p < 0.001***). Mean percentage area reduction (PAR) was reported in six studies, with a range of 71.6~97.3%. However, many of these studies did not report the value of standard deviation (SD), so we could not pool the data. No significantly different ulcer recurrence rate (RR = 0.60, 95% CI: 0.07~5.27, p = 0.645) and severe adverse events (SAEs) risk (RR = 1.67, 95% CI: 0.42~6.61, p = 0.467) were found between two groups. CONCLUSIONS: The application of FSG treatment for patients with chronic ulcers that do not respond well to SOC management could significantly increase the complete healing rate compared with SOC alone, without increased recurrence rate and SAEs risk.


Assuntos
Pé Diabético , Transplante de Pele , Humanos , Pé Diabético/cirurgia , Pé Diabético/tratamento farmacológico , Cicatrização
10.
World J Gastrointest Oncol ; 16(1): 79-89, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38292851

RESUMO

BACKGROUND: Propofol and sevoflurane are commonly used anesthetic agents for maintenance anesthesia during radical resection of gastric cancer. However, there is a debate concerning their differential effects on cognitive function, anxiety, and depression in patients undergoing this procedure. AIM: To compare the effects of propofol and sevoflurane anesthesia on postoperative cognitive function, anxiety, depression, and organ function in patients undergoing radical resection of gastric cancer. METHODS: A total of 80 patients were involved in this research. The subjects were divided into two groups: Propofol group and sevoflurane group. The evaluation scale for cognitive function was the Loewenstein occupational therapy cognitive assessment (LOTCA), and anxiety and depression were assessed with the aid of the self-rating anxiety scale (SAS) and self-rating depression scale (SDS). Hemodynamic indicators, oxidative stress levels, and pulmonary function were also measured. RESULTS: The LOTCA score at 1 d after surgery was significantly lower in the propofol group than in the sevoflurane group. Additionally, the SAS and SDS scores of the sevoflurane group were significantly lower than those of the propofol group. The sevoflurane group showed greater stability in heart rate as well as the mean arterial pressure compared to the propofol group. Moreover, the sevoflurane group displayed better pulmonary function and less lung injury than the propofol group. CONCLUSION: Both propofol and sevoflurane could be utilized as maintenance anesthesia during radical resection of gastric cancer. Propofol anesthesia has a minimal effect on patients' pulmonary function, consequently enhancing their postoperative recovery. Sevoflurane anesthesia causes less impairment on patients' cognitive function and mitigates negative emotions, leading to an improved postoperative mental state. Therefore, the selection of anesthetic agents should be based on the individual patient's specific circumstances.

12.
Neurobiol Aging ; 135: 60-69, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38185053

RESUMO

Alzheimer's disease (AD) is more prevalent in women than men, supposing due to the decline of estrogens in menopause, accompanied by increased gonadotropins such as luteinizing hormone (LH). We and others found that the transcription factor early growth response-1 (EGR1) regulates cholinergic function including the expression of acetylcholinesterase (AChE) and plays a significant role in cognitive decline of AD. Here we investigated in APP/PS1 mice by ovariectomy (OVX) and estradiol (E2) supplementation or inhibition of LH the effect on hippocampus-related cognition and related molecular changes. We found that OVX-associated cognitive impairment was accompanied by increased dorsal hippocampal EGR1 expression, which was rescued by downregulating peripheral LH rather than by supplementing E2. We also found in postmortem AD brains a higher expression of pituitary LH-mRNA and higher EGR1 expression in the posterior hippocampus. Both, in human and mice, there was a significant positive correlation between respectively posterior/dorsal hippocampal EGR1 and peripheral LH expression. We conclude that peripheral increased LH and increased posterior hippocampal EGR1 plays a significant role in AD pathology.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Camundongos , Feminino , Animais , Humanos , Hormônio Luteinizante/metabolismo , Regulação para Baixo , Acetilcolinesterase , Disfunção Cognitiva/genética , Disfunção Cognitiva/metabolismo , Doença de Alzheimer/metabolismo , Cognição , Ovariectomia , Camundongos Transgênicos , Modelos Animais de Doenças , Hipocampo/metabolismo
13.
Plant Biotechnol J ; 22(2): 413-426, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37816143

RESUMO

Chilling injury has a negative impact on the quantity and quality of crops, especially subtropical and tropical plants. The plant cell wall is not only the main source of biomass production, but also the first barrier to various stresses. Therefore, improving the understanding of the alterations in cell wall architecture is of great significance for both biomass production and stress adaptation. Herein, we demonstrated that the cell wall principal component cellulose accumulated during chilling stress, which was caused by the activation of MaCESA proteins. The sequence-multiple comparisons show that a cold-inducible NAC transcriptional factor MaNAC1, a homologue of Secondary Wall NAC transcription factors, has high sequence similarity with Arabidopsis SND3. An increase in cell wall thickness and cellulosic glucan content was observed in MaNAC1-overexpressing Arabidopsis lines, indicating that MaNAC1 participates in cellulose biosynthesis. Over-expression of MaNAC1 in Arabidopsis mutant snd3 restored the defective secondary growth of thinner cell walls and increased cellulosic glucan content. Furthermore, the activation of MaCESA7 and MaCESA6B cellulose biosynthesis genes can be directly induced by MaNAC1 through binding to SNBE motifs within their promoters, leading to enhanced cellulose content during low-temperature stress. Ultimately, tomato fruit showed greater cold resistance in MaNAC1 overexpression lines with thickened cell walls and increased cellulosic glucan content. Our findings revealed that MaNAC1 performs a vital role as a positive modulator in modulating cell wall cellulose metabolism within banana fruit under chilling stress.


Assuntos
Arabidopsis , Musa , Celulose/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Musa/genética , Musa/metabolismo , Frutas/genética , Frutas/metabolismo , Parede Celular/metabolismo , Regulação da Expressão Gênica de Plantas/genética
14.
Food Chem ; 439: 138059, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38039608

RESUMO

Lipids are widespread in nature and play a pivotal role as a source of energy and nutrition for the human body. Vegetable oils (VOs) constitute a significant category in the food industry, containing various lipid components that have garnered attention for being natural, environmentally friendly and health-promoting. The review presented the classification of raw materials (RMs) from oil crops and quality analysis techniques of VOs, with the aim of improving comprehension and facilitating in-depth research of VOs. Brief descriptions were provided for four categories of VOs, and quality analysis techniques for both RMs and VOs were generalized. Furthermore, this study discussed the applications of lipidomics technology in component analysis, processing and utilization, quality determination, as well as nutritional function assessment of VOs. Through reviewing RMs and quality analysis techniques of VOs, this study aims to encourage further refinement and development in the processing and utilization of VOs, offering valuable references for theoretical and applied research in food chemistry and food science.


Assuntos
Lipidômica , Óleos de Plantas , Humanos , Valor Nutritivo , Alimentos
15.
Reprod Sci ; 31(3): 832-839, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37831368

RESUMO

Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology. Previous studies have suggested that metabolites may play a pivotal mediating role in the progression of phenotypic variations. Although several metabolites had been identified as potential markers for PCOS, the relationship between blood metabolites and PCOS was not comprehensively explored. Previously, Pickrell et al. designed a robust approach to infer evidence of a causal relationship between different phenotypes using independently putative causal SNPs. Our previous paper extended this approach to make it more suitable for cases where only a few independently putative causal SNPs were identified to be significantly associated with the phenotypes (i.e., metabolites). When the most significant SNPs in each independent locus (the independent lead SNPs) with p-values of < 1 × 10-5 were used, 3 metabolites (2-tetradecenoyl carnitine, threitol, 1-docosahexaenoylglycerophosphocholine) causally influencing PCOS and 2 metabolites (asparagine and phenyllactate) influenced by PCOS were identified, (relative likelihood r < 0.01). Under a less stringent threshold of r < 0.05, 7 metabolites (trans-4-hydroxyproline, glutaroyl carnitine, stachydrine, undecanoate, 7-Hoca, N-acetylalanine and 2-hydroxyisobutyrate) were identified. Taken together, this study can provide novel insights into the pathophysiological mechanisms underlying PCOS; whether these metabolites can serve as biomarkers to predict PCOS in clinical practice warrants further investigations.


Assuntos
Hiperandrogenismo , Síndrome do Ovário Policístico , Feminino , Humanos , Síndrome do Ovário Policístico/genética , Estudo de Associação Genômica Ampla , Fenótipo , Carnitina
16.
IUBMB Life ; 76(4): 182-199, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37921568

RESUMO

High prevalence and metastasis rates are characteristics of lung cancer. Glycolysis provides energy for the development and metastasis of cancer cells. The 1,25-dihydroxy vitamin D3 (1,25(OH)2 D3 ) has been linked to reducing cancer risk and regulates various physiological functions. We hypothesized that 1,25(OH)2 D3 could be associated with the expression and activity of Na+ /H+ exchanger isoform 1 (NHE1) of Lewis lung cancer cells, thus regulating glycolysis as well as migration by actin reorganization. Followed by online public data analysis, Vitamin D3 receptor, the receptor of 1,25(OH)2 D3 has been proved to be abundant in lung cancers. We demonstrated that 1,25(OH)2 D3 treatment suppressed transcript levels, protein levels, and activity of NHE1 in LLC cells. Furthermore, 1,25(OH)2 D3 treatment resets the metabolic balance between glycolysis and OXPHOS, mainly including reducing glycolytic enzymes expression and lactate production. In vivo experiments showed the inhibition effects on tumor growth as well. Therefore, we concluded that 1,25(OH)2 D3 could amend the NHE1 function, which leads to metabolic reprogramming and cytoskeleton reconstruction, finally inhibits the cell migration.


Assuntos
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Movimento Celular
17.
Br J Clin Pharmacol ; 90(4): 1115-1129, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37926561

RESUMO

AIMS: The dose-escalation phase (phase Ia study) of a novel human epidermal growth factor receptor 2 (HER2) antibody-drug conjugate (ADC) FS-1502 included a dose range from 0.1 to 3.5 mg/kg in HER2-expressing advanced malignant solid tumours. However, the defined maximum tolerated dose was not reached. This model-informed approach integrated population pharmacokinetic (PopPK) modelling and exposure-response (E-R) analysis to facilitate dose selection for phase II. METHODS: The PopPK model was constructed using PK data from 109 Chinese patients who received doses of 0.1-3.5 mg/kg FS-1502 every 3 (Q3W) or 4 weeks during a phase I dose-escalation and dose expansion trial. The structural model consisted of compartment models for FS-1502 and unconjugated monomethyl auristatin F. E-R was explored for the percentage change in tumour size, overall response rate and treatment-related adverse events. RESULTS: A semi-mechanistic 2-analyte PopPK model was developed. The FS-1502 PK data were best described by a 2-compartment PK model with parallel linear and nonlinear Michaelis-Menten eliminations. The PK of unconjugated monomethyl auristatin F was described by a 2-compartment model with first-order elimination. E-R analysis supported the clinically meaningful efficacy of FS-1502 at 2.3 mg/kg and above. However, 2.3 mg/kg Q3W was considered to have a better benefit-risk balance due to a lower incidence of safety events without a significant reduction in efficacy compared to 3.0 mg/kg Q3W. CONCLUSION: This PopPK and E-R analysis guided the recommended phase II dose selection of 2.3 mg/kg Q3W and supported body weight-based dosing for an investigational HER2 ADC FS-1502.


Assuntos
Antineoplásicos , Imunoconjugados , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/induzido quimicamente , Receptor ErbB-2 , Imunoconjugados/efeitos adversos , Imunoconjugados/farmacocinética
18.
Mol Plant ; 17(1): 112-140, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-38102833

RESUMO

Cell walls in plants, particularly forest trees, are the major carbon sink of the terrestrial ecosystem. Chemical and biosynthetic features of plant cell walls were revealed early on, focusing mostly on herbaceous model species. Recent developments in genomics, transcriptomics, epigenomics, transgenesis, and associated analytical techniques are enabling novel insights into formation of woody cell walls. Here, we review multilevel regulation of cell wall biosynthesis in forest tree species. We highlight current approaches to engineering cell walls as potential feedstock for materials and energy and survey reported field tests of such engineered transgenic trees. We outline opportunities and challenges in future research to better understand cell type biogenesis for more efficient wood cell wall modification and utilization for biomaterials or for enhanced carbon capture and storage.


Assuntos
Lignina , Madeira , Madeira/genética , Madeira/metabolismo , Lignina/metabolismo , Ecossistema , Plantas/metabolismo , Parede Celular/metabolismo , Árvores/genética
19.
Diabetol Metab Syndr ; 15(1): 260, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38115042

RESUMO

BACKGROUND AND AIMS: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is considered a new biomarker for atherosclerosis, but its ability to predict cardiovascular outcomes has been controversial. This study aimed to address the lack of data on PCSK9, coronary heart disease (CHD) severity, and major cardiovascular events (MACEs) in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 2984 T2DM patients underwent selective coronary angiography, and their serum PCSK9 levels were measured using enzyme-linked immunosorbent assay. Correlation and logistic regression analyses were performed to investigate the association between PCSK9 expression and CHD severity. This study used Cox regression analysis to assess the association between circulating PCSK9 levels and the risk of MACEs. RESULTS: Circulating PCSK9 levels were significantly higher in the CHD group than in the non-CHD group [554.62 (265.11) ng/mL vs. 496.86 (129.05) ng/mL, p < 0.001]. Circulating PCSK9 levels positively correlated with CHD severity (diseased vessels: r = 0.35, p < 0.001; Gensini score: r = 0.46, p < 0.001). Elevated PCSK9 levels are an independent risk factor for CHD risk and severity (CHD group vs. non-CHD group: OR = 2.829, 95% CI: 1.771-4.520, p < 0.001; three vessel disease group vs. one vessel disease group: OR = 4.800, 95% CI: 2.387-9.652, p < 0.001; high GS group vs. low GS group: OR = 5.534, 95% CI: 2.733-11.208, p < 0.001). Through a six-year follow-up and multivariate Cox regression analysis, elevated circulating PCSK9 levels were found to be independently associated with MACEs in all participants (HR: 3.416, 5% CI: 2.485-4.697, p < 0.001; adjusted HR: 2.780, 95% CI: 1.930-4.004, p < 0.001). CONCLUSIONS: Serum PCSK9 levels were positively correlated with multi-vessel CHD and Gensini score. Elevated circulating PCSK9 levels are an independent risk factor for CHD and increased incidence of MACEs in T2DM.

20.
Heliyon ; 9(12): e23002, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38144322

RESUMO

Background: Neurodegenerative retinal diseases such as retinitis pigmentosa are serious disorders that may cause irreversible visual impairment. Ferroptosis is a novel type of programmed cell death, and the involvement of ferroptosis in retinal degeneration is still unclear. This study aimed to investigate the related ferroptosis genes in a mice model of retinal degeneration induced by light damage. Methods: A public dataset of GSE10528 deriving from the Gene Expression Omnibus database was analyzed to identify the differentially expressed genes (DEGs). Gene set enrichment analysis between light damage and control group was conducted. The differentially expressed ferroptosis-related genes (DE-FRGs) were subsequently identified by intersecting the DEGs with a ferroptosis genes dataset retrieved from the FerrDb database. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were further performed using the DE-FRGs. A protein-protein interaction (PPI) network was constructed to identify hub ferroptosis-related genes (HFRGs). The microRNAs (miRNAs)-HFRGs, transcription factors (TFs)-HFRGs networks as well as target drugs potentially interacting with HFRGs were analyzed utilizing bioinformatics algorithms. Results: A total of 932 DEGs were identified between the light damage and control group. Among these, 25 genes were associated with ferroptosis. GO and KEGG analyses revealed that these DE-FRGs were mainly enriched in apoptotic signaling pathway, response to oxidative stress and autophagy, ferroptosis, necroptosis and cytosolic DNA-sensing pathway. Through PPI network analysis, six hub ferroptosis-related genes (Jun, Stat3, Hmox1, Atf3, Hspa5 and Ripk1) were ultimately identified. All of them were upregulated in light damage retinas, as verified by the GSE146176 dataset. Bioinformatics analyses predicated that 116 miRNAs, 23 TFs and several potential therapeutic compounds might interact with the identified HFRGs. Conclusion: Our study may provide novel potential biomarkers, therapeutic targets and new insights into the ferroptosis landscape in retinal neurodegenerative diseases.

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