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1.
Biotechnol Biofuels ; 14(1): 110, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33931115

RESUMO

BACKGROUND: The biomanufacturing of D-glucaric acid has attracted increasing interest because it is one of the top value-added chemicals produced from biomass. Saccharomyces cerevisiae is regarded as an excellent host for D-glucaric acid production. RESULTS: The opi1 gene was knocked out because of its negative regulation on myo-inositol synthesis, which is the limiting step of D-glucaric acid production by S. cerevisiae. We then constructed the biosynthesis pathway of D-glucaric acid in S. cerevisiae INVSc1 opi1Δ and obtained two engineered strains, LGA-1 and LGA-C, producing record-breaking titers of D-glucaric acid: 9.53 ± 0.46 g/L and 11.21 ± 0.63 g/L D-glucaric acid from 30 g/L glucose and 10.8 g/L myo-inositol in fed-batch fermentation mode, respectively. However, LGA-1 was preferable because of its genetic stability and its superior performance in practical applications. There have been no reports on D-glucaric acid production from lignocellulose. Therefore, the biorefinery processes, including separated hydrolysis and fermentation (SHF), simultaneous saccharification and fermentation (SSF) and consolidated bioprocessing (CBP) were investigated and compared. CBP using an artificial microbial consortium composed of Trichoderma reesei (T. reesei) Rut-C30 and S. cerevisiae LGA-1 was found to have relatively high D-glucaric acid titers and yields after 7 d of fermentation, 0.54 ± 0.12 g/L D-glucaric acid from 15 g/L Avicel and 0.45 ± 0.06 g/L D-glucaric acid from 15 g/L steam-exploded corn stover (SECS), respectively. In an attempt to design the microbial consortium for more efficient CBP, the team consisting of T. reesei Rut-C30 and S. cerevisiae LGA-1 was found to be the best, with excellent work distribution and collaboration. CONCLUSIONS: Two engineered S. cerevisiae strains, LGA-1 and LGA-C, with high titers of D-glucaric acid were obtained. This indicated that S. cerevisiae INVSc1 is an excellent host for D-glucaric acid production. Lignocellulose is a preferable substrate over myo-inositol. SHF, SSF, and CBP were studied, and CBP using an artificial microbial consortium of T. reesei Rut-C30 and S. cerevisiae LGA-1 was found to be promising because of its relatively high titer and yield. T. reesei Rut-C30 and S. cerevisiae LGA-1were proven to be the best teammates for CBP. Further work should be done to improve the efficiency of this microbial consortium for D-glucaric acid production from lignocellulose.

2.
Neuroreport ; 32(7): 577-582, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33850081

RESUMO

OBJECTIVE: This study was to detect the protective effects of Houttuynia cordata extract on the damage induced by propofol in hippocampal neuron of rats. METHODS: Propofol-induced neuron injury model and H. cordata extract administration were conducted. Immunofluorescence and immunoblot were conducted for the effect of H. cordata extract on neuronal activity and inflammation were detected in this model. RESULTS: H. cordata extracts increased neuronal activity, and reduced propofol-induced neuronal inflammation levels. H. cordata extract also reduced propofol-induced neuronal apoptosis. Mechanically, we noticed H. cordata extract activated phosphoinositide 3-kinase/AKT pathway and suppressed Toll-like receptor 4/nuclear factor kappaB pathway, therefore protected propofol-induced injury of rat hippocampal neurons. CONCLUSION: Our findings provide references for anesthetic use in infants and young children.

3.
Curr Med Chem ; 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33845719

RESUMO

Striatal-enriched protein tyrosine phosphatase (STEP) is exclusively expressed in the central nervous system and regulates various neuronal signaling factors through the dephosphorylation of different substrates. Dysregulated expression or uncontrollable enzymatic activity of STEP contributes to neurological disorders such as Alzheimer's disease, which makes it a promising pharmaceutical target. Herein, we reviewed the structure and biological functions of STEP, as well as the recent development of small- molecule STEP modulators. We hope this review will provide a reference for the further development of more potent and selective STEP inhibitors for the treatment of nervous system diseases.

4.
J Med Internet Res ; 23(4): e25094, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33847591

RESUMO

BACKGROUND: Blockchain technology has the potential to enable more secure, transparent, and equitable data management. In the health care domain, it has been applied most frequently to electronic health records. In addition to securely managing data, blockchain has significant advantages in distributing data access, control, and ownership to end users. Due to this attribute, among others, the use of blockchain to power personal health records (PHRs) is especially appealing. OBJECTIVE: This review aims to examine the current landscape, design choices, limitations, and future directions of blockchain-based PHRs. METHODS: Adopting the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines, a cross-disciplinary systematic review was performed in July 2020 on all eligible articles, including gray literature, from the following 8 databases: ACM, IEEE Xplore, MEDLINE, ScienceDirect, Scopus, SpringerLink, Web of Science, and Google Scholar. Three reviewers independently performed a full-text review and data abstraction using a standardized data collection form. RESULTS: A total of 58 articles met the inclusion criteria. In the review, we found that the blockchain PHR space has matured over the past 5 years, from purely conceptual ideas initially to an increasing trend of publications describing prototypes and even implementations. Although the eventual application of blockchain in PHRs is intended for the health care industry, the majority of the articles were found in engineering or computer science publications. Among the blockchain PHRs described, permissioned blockchains and off-chain storage were the most common design choices. Although 18 articles described a tethered blockchain PHR, all of them were at the conceptual stage. CONCLUSIONS: This review revealed that although research interest in blockchain PHRs is increasing and that the space is maturing, this technology is still largely in the conceptual stage. Being the first systematic review on blockchain PHRs, this review should serve as a basis for future reviews to track the development of the space.

5.
Gels ; 7(1)2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33672687

RESUMO

Silk sericin (SS) produced by Bombyx mori is normally discarded as waste in manufacturing processes, which causes environmental pollution. Therefore, investigating the use of silk sericin has economic and environmental benefits. As a three-dimensional structure, the sericin-derived hydrogel was explored in different applications. However, many developed gelation procedures raise concerns regarding safety, cost, and duration of gelation time. In this work, "thiol-ene" click chemistry was used to quickly and controllably prepare an SS-derived hydrogel to resolve these early concerns. Then, berberine was loaded and used as a model for investigating the drug-release profiles of the prepared hydrogel. The experimental results revealed that this hydrogel is eligible for a long-term release of berberine. Throughout the antibacterial experiments, the released berberine maintained its antibacterial activity. Our work expands the application of SS in biomedical industries in an eco-friendly way. Furthermore, the discussed strategy could provide a reference for the subsequent development of SS-derived materials.

6.
Electromagn Biol Med ; : 1-9, 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33632057

RESUMO

Extremely low-frequency electromagnetic field (ELF-EMF) exposures influence many biological systems. These effects are mainly related to the intensity, duration, frequency, and pattern of the ELF-EMF. Our intent was to characterize the effect of specific pulsed electromagnetic fields on the in vitro proliferation of MCF-7 adenocarcinoma and MDA-MB-231 breast cancer cell lines and one non-cancerous M10 breast epithelial cell line. The following four important parameters of ELF-EMF were examined: frequencies (7.83 ± 0.3, 23.49 ± 0.3, and 39.15 ± 0.3 Hz), flux density (0.5 and 1 mT), exposure duration (12, 24, and 48 h), and the exposure methodology (continuous exposure versus switching exposure). The viability of MDA-MB-231 cells exposed to the optimized ELF-EMF pattern (7.83 ± 0.3 Hz, 1 mT, and 6 h switching exposure) was 40.1%. By contrast, the optimized ELF-EMF parameters that were most cytotoxic to breast cancer MDA-MB-231 cells were not damaging to normal M10 cells. In vitro studies also showed that exposure of MDA-MB-231 cells to the optimized ELF-EMF pattern promoted Ca2+ influx and resulted in apoptosis. These data confirm that exposure to this specific ELF-EMF pattern can influence cellular processes and inhibit cancer cell growth. The specific ELF-EMF pattern determined in this study may provide a potential anti-cancer treatment in the future.

7.
Sci Total Environ ; 775: 145867, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-33621870

RESUMO

Natural conversion of metal species is an important source for nanoscale metal particles in the aquatic environment, and it could affect their fate and toxicity. Extracellular polymeric substances (EPSs) are ubiquitous and abundant in the aquatic environment, thus likely can reduce metal ions to nanoscale particles. However, the effect of natural inorganic ligand and light on this process has not been well investigated. In this work, Ag+ was readily reduced to silver nanoparticles (AgNPs, around 15 nm in size) by the EPS collected from Chlorella pyrenoidosa. AgNPs could be generated in the dark environment but at a slow rate. Visible light accelerated the photoreduction. The reaction mechanism probed by Fourier transform infrared spectroscopy and three-dimensional excitation-emission matrix spectrometry demonstrated that the reduction in Ag+ was attributed to the protein and polysaccharides in the EPS. The presence of chloride ions (Cl-) largely shortened the duration of photoreduction. Scanning electron microscopy results indicated that with the aid of EPS, the AgCl nanocrystal was converted to core-shell structure, with dot-like nano Ag acting as the shell and the AgCl nanocrystal acting as the core. Size and morphological changes were observed on transmission electron microscopy. This study adds new knowledge of the joint effect of light exposure, Cl-, and EPS on the formation of AgNPs from Ag+ and advances the understanding of the natural formation mechanism of AgNPs.


Assuntos
Chlorella , Nanopartículas Metálicas , Cloretos , Matriz Extracelular de Substâncias Poliméricas , Íons , Prata
8.
Chem Commun (Camb) ; 57(9): 1093-1096, 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33434260

RESUMO

Modulating the hypoxic microenvironment is the priority for tumor treatment. Cytometalated iridium(iii)-metformin conjugates were synthesized for treating hypoxic cancer cells for the first time, which alleviate hypoxia via mitochondria respiration inhibition, thus displaying 10-fold higher cytotoxicity, emerging anti-metastasis and anti-inflammatory activities than a metformin-free Ir(iii) complex and cisplatin against hypoxic cancer cells.

9.
Lipids Health Dis ; 20(1): 2, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407522

RESUMO

BACKGROUND: Clinical trials have demonstrated that either initiating or up-titrating a statin dose substantially reduce Low-Density Lipoprotein-Cholesterol (LDL-C) levels. However, statin adherence in actual practice tends to be suboptimal, leading to diminished effectiveness. This study aims to use real-world data to determine the effect on LDL-C levels and LDL-C goal attainment rates, when selected statins are titrated in Asian patients. METHODS: A retrospective cohort study over a 5-year period, from April 2014 to March 2019 was conducted on a cohort of multi-ethnic adult Asian patients with clinical diagnosis of Dyslipidaemia in a primary care clinic in Singapore. The statins were classified into low-intensity (LI), moderate-intensity (MI) and high-intensity (HI) groups according to the 2018 American College of Cardiology and American Heart Association (ACC/AHA) Blood Cholesterol Guidelines. Patients were grouped into "No statin", "Non-titrators" and "Titrators" cohorts based on prescribing patterns. For the "Titrators" cohort, the mean percentage change in LDL-C and absolute change in LDL-C goal attainment rates were computed for each permutation of statin intensity titration. RESULTS: Among the cohort of 11,499 patients, with a total of 266,762 visits, there were 1962 pairs of LDL-C values associated with a statin titration. Initiation of LI, MI and HI statin resulted in a lowering of LDL-C by 21.6% (95%CI = 18.9-24.3%), 28.9% (95%CI = 25.0-32.7%) and 25.2% (95%CI = 12.8-37.7%) respectively. These were comparatively lower than results from clinical trials (30 to 63%). The change of LDL-C levels due to up-titration, down-titration, and discontinuation were - 12.4% to - 28.9%, + 13.2% to + 24.6%, and + 18.1% to + 32.1% respectively. The improvement in LDL-C goal attainment ranged from 26.5% to 47.1% when statin intensity was up-titrated. CONCLUSION: In this study based on real-world data of Asian patients in primary care, it was shown that although statin titration substantially affected LDL-C levels and LDL-C goal attainment rates, the magnitude was lower than results reported from clinical trials. These results should be taken into consideration and provide further insight to clinicians when making statin adjustment recommendations in order to achieve LDL-C targets in clinical practice, particularly for Asian populations.

10.
Carbohydr Polym ; 256: 117440, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33483020

RESUMO

The present study aims to develop Chitosan-based polymeric nanoparticles of anti-HIV drug Dolutegravir, to aid appropriate dose adjustment and ease of oral administration as milk and food admixture for children. The isolated Chitosan from the crab shell species Portunus Sanguinolentus has been characterized for their physicochemical properties. Nanoparticles were developed with varying ratio of drug: Chitosan and assessed for particle size (140-548 nm), zeta potential (+26.1 mV) with a maximum of 75 % drug content. Nanoparticles exhibited improved stability and drug release in the 0.1 N HCl medium compared to pure drug. The MTT assay and the Syncytia inhibition assay in C8166 (T-lymphatic cell line) infected with HIVIIIB viral strain, which showed better therapeutic efficiency and lesser cytotoxicity compared to the pure drug. In consonance with the data obtained, the use of chitosan from a novel source for drug delivery carrier has opened exceptional prospects for delivering drugs efficiently to paediatrics.

11.
Biosens Bioelectron ; 171: 112753, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33120235

RESUMO

A polyethyleneimine (PEI)-assisted copper in-situ growth (CISG) strategy was proposed as a controlled signal amplification strategy to enhance the sensitivity of gold nanoparticle-based lateral flow sensors (AuNP-LFS). The controlled signal amplification is achieved by introducing PEI as a structure-directing agent to regulate the thermodynamics of anisotropic Cu nanoshell growth on the AuNP surface, thus controlling shape and size of the resultant AuNP@Cu core-shell nanostructures and confining free reduction and self-nucleation of Cu2+ for improved reproducibility and decreased false positives. The PEI-CISG-enhanced AuNP-LFS showed ultrahigh sensitivities with the detection limits of 50 fg mL-1 for HIV-1 capsid p24 antigen and 6 CFU mL-1 for Escherichia coli O157:H7. We further demonstrated its clinical diagnostic efficacy by configuring PEI-CISG into a commercial AuNP-LFS detection kit for SARS-CoV-2 antibody detection. Altogether, this work provides a reliable signal amplification platform to dramatically enhance the sensitivity of AuNP-LFS for rapid and accurate diagnostics of various infectious diseases.


Assuntos
Técnicas Biossensoriais/métodos , Cobre/química , Infecções por Coronavirus/diagnóstico , Infecções por Escherichia coli/diagnóstico , Ouro/química , Infecções por HIV/diagnóstico , Pneumonia Viral/diagnóstico , Betacoronavirus/isolamento & purificação , Técnicas Biossensoriais/instrumentação , Técnicas de Laboratório Clínico , Desenho de Equipamento , Escherichia coli O157/isolamento & purificação , Proteína do Núcleo p24 do HIV/análise , HIV-1/isolamento & purificação , Humanos , Limite de Detecção , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Oxirredução , Pandemias , Polietilenoimina/química , Fitas Reagentes/análise
12.
Entropy (Basel) ; 22(10)2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33286892

RESUMO

To date, testing for Granger non-causality using kernel density-based nonparametric estimates of the transfer entropy has been hindered by the intractability of the asymptotic distribution of the estimators. We overcome this by shifting from the transfer entropy to its first-order Taylor expansion near the null hypothesis, which is also non-negative and zero if and only if Granger causality is absent. The estimated Taylor expansion can be expressed in terms of a U-statistic, demonstrating asymptotic normality. After studying its size and power properties numerically, the resulting test is illustrated empirically with applications to stock indices and exchange rates.

13.
IEEE Trans Cybern ; PP2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33259311

RESUMO

In this article, we study the problem of affine formation stabilization for multiagent systems in the plane. The challenges lie in the limited access to the information of the target formation in the sense that the prescribed values of the formation parameters, that is, the scaling size and rotation angle, are known only by one agent which we call the leader. Motivated by the fact that three agents (say, leaders) can determine the shape of a planar triangular formation using the stress matrix, we propose a class of estimators to guarantee that two agents in the leader set can gain access to the formation parameters. Then, an integrated control scheme is designed such that the target formation can be uniquely stabilized among all its affine transformations. The sufficient condition ensuring the stability of the closed-loop system is also given based on the cyclic-small-gain theorem. Simulations and experiments are carried out to show the effectiveness of the proposed control strategy.

14.
Biomed Res Int ; 2020: 8851480, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33381589

RESUMO

It has been confirmed that repeated application of propofol, as an intravenous and short-fast-acting anesthetic, in neonatal animals or humans may produce long-term deficits in cognitive functions. With the aim of explaining the neurotoxic effects of repeated administration of propofol on neonatal rat pups from P7 to P9 especially from an epigenetic perspective, the present study used the Morris water maze to detect cognitive deficits in spatial learning and memory, Sequenom methylation on the CpG island located in the promoter region of epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) to assess the methylation level of this region, and Western blot to measure the expression of EFEMP1, TIMP-3, and MMP-9. As the results have shown, repeated propofol administration on neonatal rats caused significant systemic growth retardation, impairment of spatial learning and memory, and hypermethylation of the CpG sites in the promoter region of EFEMP1 accompanied by lower expression of EFEMP1 and TIMP-3 and enhanced expression of MMP-9. These data suggest that repeated propofol administration in neonatal rats may generate hypermethylation in the promoter region of EFEMP1 which results in downregulation of the expression of EFEMP1 and tissue inhibitor of metalloproteinase-3 (TIMP-3) but upregulation of the expression of matrix metalloproteinase-9 (MMP-9), which together may affect the stability of ECM to hamper the development of the central nervous system and therefore lead to deficits in cognitive functions.

15.
Bioorg Med Chem ; : 115850, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33229135

RESUMO

Development of efficient fluorescent probes for detecting the overexpressed Mcl-1 protein in living cells is imperative for the diagnosis and treatment of cancers. In this paper, a new UMI-77 based fluorescent probe (DNSH), was synthesized and characterized. DNSH bound to the hydrophobic pockets of Mcl-1 protein tightly and the binding affinity was 20-fold higher than that of previous developed Mcl-1 probe. DNSH exhibited specific fluorescence response to Mcl-1 protein rather than other proteins. In the presence of Mcl-1 protein, fluorescence emission of DNSH can be switched on. Furthermore, fluorescence colocalization experiment demonstrated that DNSH can be successfully used for imaging mitochondrial Mcl-1 protein in human prostate cancer cells without a washing process. These results showed that DNSH may find useful applications in biological research such as tracking Mcl-1 protein in living biological specimens.

16.
World J Gastroenterol ; 26(41): 6455-6474, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33244205

RESUMO

BACKGROUND: Infliximab was the first approved biologic treatment for moderate to severe Crohn's disease (MS-CD) in China. However, the cost-effectiveness of infliximab maintenance therapy (IMT) for MS-CD relative to conventional maintenance therapy remained unclarified. AIM: To assess the cost-effectiveness of IMT for MS-CD in Chinese patients from the perspective of Chinese public insurance payer. METHODS: A cohort of MS-CD patients managed in a Chinese tertiary care hospital was created to compare IMT with conventional maintenance therapy (CMT) for clinical outcomes and direct medical costs over a 1-year observation time using conventional regression analyses. A decision-analytic model with the generated evidence was constructed to assess the cost-effectiveness of IMT relative to CMT using reimbursed medical costs. RESULTS: Based on the included 389 patients, IMT was associated with significantly higher disease remission chance [odds ratio: 4.060, P = 0.003], lower risk of developing new complications (odds ratio: 0.527, P = 0.010), higher utility value for quality of life (coefficient 0.822, P = 0.008), and lower total hospital costs related to disease management (coefficient -0.378, P = 0.008) than CMT. Base-case cost-effectiveness analysis estimated that IMT could cost Chinese health insurance payers ¥55260 to gain one quality-adjusted life year (QALY). The cost-effectiveness of IMT was mainly driven by the estimate of quality of life, treatment efficacy of maintenance therapy, mortality risk associated with active disease, and unit price of infliximab. The probability that IMT was cost-effective at a willingness-to-pay threshold of three times gross domestic product [2018 Chinese gross domestic product per capita (GDPPC)] was 86.4%. CONCLUSION: IMT significantly improved real-world health outcomes and cost the Chinese public health insurance payers less than one GDPPC to gain one QALY in Chinese MS-CD patients.

17.
Curr Med Chem ; 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176627

RESUMO

As an important posttranscription modification, histone deacetylation plays significant roles in chromatin remodeling and gene expression. The aberrant modification of histone deacetylation leads to various diseases. As a critical member of histone deacetylase (HDAC), HDAC6 serves as a key modulator in many physiological processes. Abnormal expression of HDAC6 gives rise to cancer, neurodegeneration and other diseases. Here, we reviewed recent advances in physiological, protein structure and development of HDAC6 selective inhibitors.

18.
Curr Med Chem ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33208057

RESUMO

The PROTAC (PROteolysis TArgeting Chimera) technology is a target protein degradation strategy, based on the ubiquitin-proteasome system, which has been gradually developed into a potential means of targeted cancer therapy in recent years. This strategy has already shown significant advantages over traditional small-molecule inhibitors in terms of pharmacodynamics, selectivity, and drug resistance. Several small molecule PROTACs have been in a Phase I clinical trial. Herein, we introduced the mechanism, characteristics, and advantages of PROTAC strategy. And we summarize the recent advances in the development of small-molecule PROTACs for cancer treatment. We hope this review will be helpful in optimizing the design of the ideal small-molecule PROTACs and advancing targeted anticancer research.

19.
Artigo em Inglês | MEDLINE | ID: mdl-33183110

RESUMO

Introduction: Cyclin-dependent kinase 7 (CDK7) is a part of the CDK-activating kinase family (CAK) which has a key role in the cell cycle and transcriptional regulation. Several lines of evidence suggest that CDK7 is a promising therapeutic target for cancer. CDK7 selective inhibitors such as SY-5609 and CT7001 are in clinical development. Areas covered: We explore the biology of CDK7 and its role in cancer and follow this with an evaluation of the preclinical and clinical progress of CDK7 inhibitors, and their potential in the clinic. We searched PubMed and ClinicalTrials to identify relevant data from the database inception to 14 October 2020. Expert opinion: CDK7 inhibitors are next generation therapeutics for cancer. However, there are still challenges which include selectively, side effects, and drug resistance. Nevertheless, with ongoing clinical development of these inhibitors and greater analysis of their target, CDK7 inhibitors will become a promising approach for treatment of cancer in the near future.

20.
Animals (Basel) ; 10(11)2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33147724

RESUMO

Thermal stress (heat and cold) has large economic and welfare implications for the worldwide dairy industry. Therefore, it is paramount to understand the genetic background of coping mechanism related to thermal stress for the implementation of effective genetic selection schemes in dairy cattle. We performed an association study between 11 single nucleotide polymorphisms having minor allelic frequency (MAF > 0.05) in the HSP70 gene with blood biochemical parameters. The concentrations of growth hormone (GH), lactate (LA), prolactin (PRL), and superoxide dismutase (SOD) in blood were significantly higher (p < 0.05), while the concentrations of blood urea nitrogen (BUN), c-reactive protein (CRP), potassium (K+), lactate dehydrogenase (LDH), lipid peroxide (LPO), and norepinephrine (NE) were significantly lower (p < 0.05) in heat-stressed animals as compared to the control group. A significant (p < 0.05) increase in the concentrations of cortisol (COR), corticosterone (CORT), and potassium (K+) was observed (p < 0.05), while the concentrations of adrenocorticotrophic hormone (ACTH), dopamine (DA), GH, LDH, NE, PRL, and SOD were significantly lower in cold-stressed animals as compared to the control group (p < 0.05). Furthermore, SNP A-12G and C181T were significantly associated with LA (p < 0.05), while A72G was linked with LPO (p < 0.05) in heat-stressed animals. Moreover, the SNPs A-12G and SNP C131G were significantly associated (p < 0.05) with DA and SOD under cold stress condition, respectively. These SNPs markers significantly associated with fluctuations in blood biochemical parameters under thermal stress provide a better insight into the genetic mechanisms underlying climatic resilience in Holstein cattle.

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