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1.
Food Chem ; 462: 140947, 2025 Jan 01.
Article in English | MEDLINE | ID: mdl-39208736

ABSTRACT

Excess nitrites are potentially threatening to human health, so it is urgent to develop accurate and sensitive methods. The development of sensors can provide early warning of possible hazards and alert people to protect public health. This work presents an NiSx@MoS2-composite with excellent electrochemical activity, representing a key finding for highly sensitive NO2- detection and sensor development. With the assistance of NiSx@MoS2, this electrochemical sensor has excellent quantitative detection performance. It has a wide detection range (0.0001-0.0020 mg/mL) and a low detection limit (1.863*10-5 mg/mL) for NO2-. This electrochemical sensor maintains excellent specificity among numerous interferences, and it completes the accurate detection of different real food samples. Pleasingly, the electrochemical sensor has satisfactory repeatability stability, and potential for practical applications. It would demonstrate tremendous potential in scientific dietary guidance, food safety detection and other fields.


Subject(s)
Disulfides , Electrochemical Techniques , Limit of Detection , Molybdenum , Molybdenum/chemistry , Electrochemical Techniques/instrumentation , Disulfides/chemistry , Nitrites/analysis , Food Contamination/analysis
2.
Synth Syst Biotechnol ; 10(1): 58-67, 2025.
Article in English | MEDLINE | ID: mdl-39247801

ABSTRACT

Vitamin A is a micronutrient critical for versatile biological functions and has been widely used in the food, cosmetics, pharmaceutical, and nutraceutical industries. Synthetic biology and metabolic engineering enable microbes, especially the model organism Saccharomyces cerevisiae (generally recognised as safe) to possess great potential for the production of vitamin A. Herein, we first generated a vitamin A-producing strain by mining ß-carotene 15,15'-mono(di)oxygenase from different sources and identified two isoenzymes Mbblh and Ssbco with comparable catalytic properties but different catalytic mechanisms. Combinational expression of isoenzymes increased the flux from ß-carotene to vitamin A metabolism. To modulate the vitamin A components, retinol dehydrogenase 12 from Homo sapiens was introduced to achieve more than 90 % retinol purity using shake flask fermentation. Overexpressing POS5Δ17 enhanced the reduced nicotinamide adenine dinucleotide phosphate pool, and the titer of vitamin A was elevated by almost 46 %. Multi-copy integration of the key rate-limiting step gene Mbblh further improved the synthesis of vitamin A. Consequently, the titer of vitamin A in the strain harbouring the Ura3 marker was increased to 588 mg/L at the shake-flask level. Eventually, the highest reported titer of 5.21 g/L vitamin A in S. cerevisiae was achieved in a 1-L bioreactor. This study unlocked the potential of S. cerevisiae for synthesising vitamin A in a sustainable and economical way, laying the foundation for the commercial-scale production of bio-based vitamin A.

3.
Zhongguo Zhong Yao Za Zhi ; 49(15): 4044-4053, 2024 Aug.
Article in Chinese | MEDLINE | ID: mdl-39307756

ABSTRACT

Diabetic kidney disease(DKD) is a prevalent and severe microvascular complication of type 2 diabetes mellitus(T2DM). Chronic microinflammation is an important factor exacerbating renal tissue damage in DKD individuals. Macrophages play a crucial role in immune-inflammatory responses, and they can transiently and reversibly polarize into the pro-inflammatory M1 phenotype and anti-inflammatory M2 phenotype based on microenvironmental differences. The imbalance in M1/M2 macrophage polarization can exacerbate DKD progression by fostering inflammatory cytokine aggregation in the glomeruli and renal interstitium. Therefore, restoring the balance of macrophage is a pivotal avenue to ameliorate the chronic microinflammation state in DKD. Macrophage polarization is a complex and dynamic process. Various information molecules and cytokines involved in the polarization process play important roles in regulating phenotypes during the progression of DKD. They are closely related to various mechanisms such as metabolism, inflammation, fibrosis, and mitochondrial autophagy in DKD. By coordinating the inflammatory responses through polarization, they play a key role in regulating inflammation in metabolic-related diseases. The complex network of pathways involved in macrophage polarization corresponds well with the multi-pathway, multi-target treatment model of traditional Chinese medicine(TCM). Active ingredients and formulas of TCM can intervene in DKD by regulating macrophage polarization. Studies on relieving renal inflammation, repairing renal tissues, and promoting renal function recovery through macrophage polarization modulation are not uncommon. Therefore, based on exis-ting evidence, this study reviews TCM in targeting M1/M2 macrophage polarization balance to improve DKD, aiming to explore the potential of macrophage polarization in regulating DKD, which is expected to provide evidence support for the clinical diagnosis and treatment of DKD with TCM as well as the exploration of its biological mechanisms.


Subject(s)
Diabetic Nephropathies , Drugs, Chinese Herbal , Macrophages , Medicine, Chinese Traditional , Diabetic Nephropathies/drug therapy , Diabetic Nephropathies/immunology , Humans , Macrophages/immunology , Macrophages/drug effects , Animals , Diabetes Mellitus, Type 2/immunology , Diabetes Mellitus, Type 2/drug therapy
4.
Adv Healthc Mater ; : e2400016, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39285803

ABSTRACT

Topology and bioactive molecules are crucial for stimulating cellular and tissue functions. To regulate the chronic wound microenvironment, mono-assembly technology is employed to fabricate a radial egg white hydrogel loaded with lyophilized adipose tissue-extracellular vesicles (radial EWH@L-EVs). The radial architecture not only significantly modified the gene expression of functional cells, but also achieved directional and controlled release kinetics of L-EVs. Through the synergy of topographical and inherent bioactive cues, radial EWH@L-EVs effectively reduced intracellular oxidative stress and promoted the polarization of macrophages toward an anti-inflammatory phenotype during the inflammatory phase. Afterward, radial EWH@L-EVs facilitated the centripetal migration and proliferation of fibroblasts and endothelial cells as the wound transitioned to the proliferative phase. During the latter remodeling phase, radial EWH@L-EVs accelerated the regeneration of granulation tissue, angiogenesis, and collagen deposition, thereby promoting the reorganization chronic wound. Compared with the gold standard collagen scaffold, radial EWH@L-EVs actively accommodated the microenvironment via various functions throughout all stages of diabetic wound healing. This can be attributed to the orientation of topological structures and bioactive molecules, which should be considered of utmost importance in tissue engineering.

5.
Front Microbiol ; 15: 1460690, 2024.
Article in English | MEDLINE | ID: mdl-39318432

ABSTRACT

Pigment is one of the most important metabolites in red yeast rice. However, citrinin may accumulate and cause quality security issues. In the present study, the effect of ascorbic acid (EAA) on the pigment and citrinin was studied, and the metabolic mechanism was discussed using comparative transcriptomics. The introduction of EAA increased the pigment by 58.2% and decreased citrinin by 65.4%. The acid protease activity, DPPH scavenging rate, and total reducing ability also increased by 18.7, 9.0, and 26.7%, respectively. Additionally, a total of 791 differentially expressed genes were identified, and 79 metabolic pathways were annotated, among which carbon metabolism, amino acid metabolism, and fatty acid metabolism were closely related to the biosynthesis of pigment and citrinin. Ethanol dehydrogenase (M pigC), oxidoreductase (M pigE), reductase (M pigH), and monooxygenase (M pigN) may be related to the increase of pigment. ctnC and pksCT contributed to the decline of citrinin.

6.
Lipids Health Dis ; 23(1): 310, 2024 Sep 27.
Article in English | MEDLINE | ID: mdl-39334150

ABSTRACT

BACKGROUND: Lipids and thyroid hormones (TH) are closely interrelated. However, previous studies have not mentioned the linkage encompassing the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) alongside TH level, as well as sensitivity indices. METHODS: This cross-sectional study leverages expansive datasets from the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2012. Weighted multivariate linear regression, smoothed curve fitting and sensitivity analyses were used to investigate the associations of the NHHR with the thyroid. Subgroup analyses and interaction tests were conducted to determine the robustness of the findings across diverse segments of the population, ensuring the consistency and generalizability of the observed associations. RESULTS: The NHHR was significantly positively correlated with free triiodothyronine (FT3) levels, thyroid-stimulating hormone (TSH) levels, the FT3 to FT4 ratio (FT3/FT4), and the quantile-based thyroid feedback index for FT3 (TFQIFT3) and negatively correlated with free thyroxin (FT4) levels [0.17(0.07-0.27), P = 0.001; 0.60 (0.03-1.17), P = 0.040; 0.06 (0.04-0.08), P < 0.0001; 0.23 (0.16-0.30), P < 0.0001; and -0.65 (-1.05--0.24), P = 0.002]. Smoothed curve fitting revealed nonlinear correlations of the NHHR with thyroid function and thyroid hormone sensitivity indices. In subgroup analyses, interaction tests, and smoothed curve fitting analyses, different populations presented largely consistent statistical differences. CONCLUSION: Among American adults, the NHHR was significantly positively correlated with FT3 levels, TSH levels, the FT3/FT4 and the TFQIFT3. Conversely, a negative association was noted between the NHHR and FT4 levels.


Subject(s)
Cholesterol, HDL , Thyroid Hormones , Thyrotropin , Thyroxine , Triiodothyronine , Humans , Male , Female , Cross-Sectional Studies , Cholesterol, HDL/blood , Middle Aged , Triiodothyronine/blood , Adult , Thyroid Hormones/blood , Thyrotropin/blood , Thyroxine/blood , Nutrition Surveys , Cholesterol/blood , Aged
7.
Foods ; 13(17)2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39272563

ABSTRACT

To address the public health challenges posed by high-salt diets, this study utilized pepsin and flavourzyme for the continuous enzymatic hydrolysis of a soy protein isolate (SPI). The separation, purification, and identification of salt-containing peptides in SPI hydrolysate were conducted using ultrafiltration (UF), gel filtration chromatography (GFC), and Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS). Subsequently, a molecular docking model was constructed between salt receptor protein transmembrane channel 4 (TMC4) and the identified peptides. Basic bioinformatics screening was performed to obtain non-toxic, non-allergenic, and stable salt peptides. After the enzymatic hydrolysis, separation, and purification of SPI, a component with a sensory evaluation score of 7 and an electronic tongue score of 10.36 was obtained. LC-MS/MS sequencing identified a total of 1697 peptides in the above component, including 84 potential salt-containing peptides. A molecular docking analysis identified seven peptides (FPPP, GGPW, IPHF, IPKF, IPRR, LPRR, and LPHF) with a strong theoretical salty taste. Furthermore, residues Glu531, Asp491, Val495, Ala401, and Phe405 of the peptides bound to the TMC4 receptor through hydrogen bonds, hydrophobic interactions, and electrostatic interactions, thereby imparting a significant salty taste. A basic bioinformatics analysis further revealed that IPHF, LPHF, GGPW, and IPKF were non-toxic, non-allergenic, and stable salt-containing peptides. This study not only provides a new sodium reduction strategy for the food industry, but also opens up new avenues for improving the public's healthy eating habits.

8.
Bioresour Bioprocess ; 11(1): 82, 2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39177850

ABSTRACT

Bispecific antibodies (bsAbs) hold promises for enhanced therapeutic potential surpassing that of their parental monoclonal antibodies. However, bsAbs pose great challenges in their manufacturing, and one of the common reasons is their susceptibility to aggregation. Building on previous studies demonstrating the functionality and potential manufacturability of Fab-scFv format bsAb, this investigation delved into the impact of environmental factors-such as pH, buffer types, ionic strength, protein concentrations, and temperatures-on its stability and the reversal of its self-associated aggregates. Mildly acidic, low-salt conditions were found optimal, ensuring bsAb stability for 30 days even at elevated temperature of 40 °C. Furthermore, these conditions facilitated the reversal of its self-associated aggregates to monomers during the initial 7-day incubation period. Our findings underscore the robustness and resilience of Fab-scFv format bsAb, further confirming its potential manufacturability despite its current absence as commercial products.

9.
Asian J Psychiatr ; 100: 104185, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39106588

ABSTRACT

This meta-analysis aims to estimate the association between adolescent depression and adult suicidal behavior, while systematically evaluating gender differences reported in literature. A random-effects model was used to determine the pooled association, reporting odds ratios (ORs) with corresponding 95 % confidence intervals (CIs). Nine articles comprising over 6084 adolescents together showed that people with a history of depression in adolescence are more likely to gain suicidal behaviors during adulthood (OR = 3.97, 95 % Cl: 2.79, 5.63). Sex-specific analysis indicated that males who experienced depression in adolescence developed a higher incidence of suicidal behavior in adulthood compared to females with a similar history (Males: OR = 3.61, 95 % Cl: 1.02, 12.78; Females: OR = 3.56, 95 % Cl: 1.71, 7.43). Furthermore, suicide attempts emerged as the predominant outcome among various suicidal behaviors (OR = 3.43, 95 % Cl: 1.75, 6.71). This meta-analysis provides robust evidence that depression in adolescence significantly increases the risk of suicidal behavior in adulthood.


Subject(s)
Suicide, Attempted , Adolescent , Adult , Female , Humans , Male , Depression/complications , Depression/epidemiology , Depression/psychology , Depressive Disorder/complications , Depressive Disorder/epidemiology , Depressive Disorder/psychology , Sex Factors , Suicidal Ideation , Suicide, Attempted/statistics & numerical data , Young Adult
10.
Immun Inflamm Dis ; 12(8): e1367, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39119967

ABSTRACT

BACKGROUND: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a rare autosomal dominant systemic microvascular disorder attributed to TREX1 (three-prime repair exonuclease-1) gene mutations, often proned to misdiagnosed. METHODS: We reported a case of RVCL-S coexisting with systemic lupus erythematosus due to a mutation in the TREX1 gene. This study provided a summary and discussion of previously documented cases related to TREX1 mutations or RVCL-S. RESULTS: A 39-year-old female patient visited the clinic due to progressive memory loss and speech difficulties. Magnetic resonance imaging results showed corpus callosum atrophy and multiple subcortical calcifications in both brain hemispheres. Genetic testing revealed a TREX1 gene mutation (c.294dupA). Treatment with immunosuppressive therapy for 2 months led to improvements in communication and mobility. We also summarized previously reported cases providing an overview of TREX1 gene mutation or RCVL-S. CONCLUSION: Our case establishes a compelling foundation for future RVCL-S diagnosis and treatment paradigms. Notably, conducting systemic immunity screening in patients with RVCL-S emerges as a strategic approach to prevent potential diagnostic oversights.


Subject(s)
Exodeoxyribonucleases , Leukoencephalopathies , Lupus Erythematosus, Systemic , Mutation , Humans , Female , Adult , Exodeoxyribonucleases/genetics , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/genetics , Leukoencephalopathies/diagnosis , Leukoencephalopathies/genetics , Leukoencephalopathies/etiology , Phosphoproteins/genetics , Diagnostic Errors/prevention & control , Magnetic Resonance Imaging , Retinal Vasculitis/diagnosis , Retinal Vasculitis/etiology , Retinal Diseases , Vascular Diseases , Hereditary Central Nervous System Demyelinating Diseases
11.
Foods ; 13(16)2024 Aug 08.
Article in English | MEDLINE | ID: mdl-39200419

ABSTRACT

Mulberry perishes easily due to its high water content and thin skin. It is important to extend the shelf life of mulberry by proper processing methods. In the present study, the influence of three drying techniques, including hot air drying (HAD), vacuum drying (VD), and vacuum freeze-drying (VFD) on the quality maintenance of mulberry was comprehensively evaluated. Bioactive compounds, antioxidant activity, and the sensory and volatile flavor compounds of mulberry have been researched. The results showed that VFD treatment maintained the highest anthocyanins (6.99 mg/g), total flavones (3.18 mg/g), and soluble sugars (2.94 mg/g), and exhibited the best DPPH· (81.2%) and ABTS+· (79.9%) scavenging ability. Mulberry also presented the lowest hardness and the greatest brittleness after VFD. Additionally, VFD maintained the optimal color and presented the best sensory attributes. Furthermore, 30, 20, and 32 kinds of volatile flavor compounds were detected in HAD, VD, and VFD, respectively, among which aldehydes, esters, and ketones were the most abundant compounds. This study indicated the potential application value of VFD for the drying of fruit and vegetable foodstuffs.

12.
Acad Radiol ; 2024 Aug 26.
Article in English | MEDLINE | ID: mdl-39191564

ABSTRACT

OBJECTIVES: To investigate the application of the three-compartment restriction spectrum imaging (RSI) model, diffusion kurtosis imaging (DKI), and diffusion-weighted imaging (DWI) in predicting Ki-67 status in rectal carcinoma. METHODS: A total of 80 rectal carcinoma patients, including 47 high-proliferation (Ki-67 > 50%) cases and 33 low-proliferation (Ki-67 ≤ 50%) cases, underwent pelvic MRI were enrolled. Parameters derived from RSI (f1, f2, and f3), DKI (MD and MK), and DWI (ADC) were calculated and compared between the two groups. Logistic regression (LR) analysis was conducted to identify independent predictors and assess combined diagnosis. Area under the receiver operating characteristic curve (AUC), DeLong analysis, and calibration curve analyses were performed to evaluate diagnostic performance. RESULTS: The patients with high-proliferation rectal carcinoma exhibited significantly higher f1 and MK values and significantly lower ADC, MD, f2, and f3 values than those with low-proliferation rectal carcinoma (P < 0.05). LR analysis showed that MD, MK, and f2 were independent predictors for Ki-67 status in rectal carcinoma. Moreover, the combination of these three parameters achieved an optimal diagnostic efficacy (AUC = 0.877, sensitivity = 80.85%, specificity = 84.85%) that was significantly better than that obtained using ADC (AUC = 0.783, Z = 2.347, P = 0.019), f2 (AUC = 0.732, Z = 2.762, P = 0.006), and f3 (AUC = 0.700, Z = 3.071, P = 0.002). The combined diagnosis also showed good performance (AUC = 0.859) in the internal validation analysis based on 1000 bootstrap samples, while the calibration curve demonstrated that the combined diagnosis provided good stability. CONCLUSION: RSI, DKI, and DWI can effectively differentiate between patients with high- and low-proliferation rectal carcinoma. Furthermore, the MD, MK, and f2 imaging parameters may be a novel and promising combination biomarker for examining Ki-67 status in rectal carcinoma.

13.
Microbiol Resour Announc ; 13(8): e0042724, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39037310

ABSTRACT

We recovered 16 bacterial metagenome-assembled genomes from 11 flue-cured tobacco samples with different aging stage and various geographic origins. Their sizes range from 2.3 M to 5.4 M, with GC contents of 43.17%-74.45%, completeness of 78.80%-99.25%, and contamination of 0.47%-8.56%.

14.
Neuroscience ; 554: 26-33, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-38964452

ABSTRACT

In order to comprehensively understand the changes of brain networks in patients with chronic tinnitus, this study combined static and dynamic analysis methods to explore the abnormalities of brain networks. Thirty-two patients with chronic tinnitus and 30 age-, sex- and education-matched healthy controls (HC) were recruited. Independent component analysis was used to identify resting-state networks (RSNs). Static and dynamic functional network connectivity (FNC) were performed. The temporal properties of brain network including mean dwell time (MDT), fraction time (FT) and numbers of transitions (NT) were calculated. Two-sample t test and Spearman's correlation were used for group compares and correlation analysis. Four RSNs showed abnormal FNC including auditory network (AUN), default mode network (DMN), attention network (AN) and sensorimotor network (SMN). For static analysis, tinnitus patients showed significantly decreased FNC in AUN-DMN, AUN-AN, DMN-AN, and DMN-SMN than HC [p < 0.05, false discovery rate (FDR) corrected]. For dynamic analysis, tinnitus patients showed significantly decreased FNC in DMN-AN in state 3 (p < 0.05, FDR corrected). MDT in state 3 was significantly decreased in tinnitus patients (t = 2.039, P = 0.046). In the tinnitus group, the score of tinnitus functional index (TFI) was negatively correlated with MDT and FT in state 4, and the duration of tinnitus was positively correlated with FT in state 1 and NT. Chronic tinnitus causes abnormal brain network connectivity. These abnormal brain networks help to clarify the mechanism of tinnitus generation and chronicity, and provide a potential basis for the treatment of tinnitus.


Subject(s)
Brain , Magnetic Resonance Imaging , Nerve Net , Tinnitus , Humans , Tinnitus/physiopathology , Tinnitus/diagnostic imaging , Male , Female , Adult , Brain/physiopathology , Brain/diagnostic imaging , Nerve Net/physiopathology , Nerve Net/diagnostic imaging , Middle Aged , Chronic Disease , Neural Pathways/physiopathology , Neural Pathways/diagnostic imaging , Brain Mapping
15.
Harmful Algae ; 137: 102681, 2024 08.
Article in English | MEDLINE | ID: mdl-39003025

ABSTRACT

In May-June 2019, the microalga Chrysochromulina leadbeateri caused a massive fish-killing event in several fjords in Northern Norway, resulting in the largest direct impact ever on aquaculture in northern Europe due to toxic algae. Motivated by the fact that no algal toxins have previously been described from C. leadbeateri, we set out to investigate the chemical nature and toxicity of secondary metabolites in extracts of two strains (UIO 393, UIO 394) isolated from the 2019 bloom, as well as one older strain (UIO 035) isolated during a bloom in Northern Norway in 1991. Initial LC-DAD-MS/MS-based molecular networking analysis of the crude MeOH extracts of the cultivated strains showed that their profiles of small organic molecules, including a large number of known lipids, were very similar, suggesting that the same class of toxin(s) were likely the causative agents of the two harmful algal bloom (HAB) events. Next, bioassay-guided fractionation using the RTgill-W1 cell line and metabolomics analysis pointed to a major compound affording [M + H]+ ions at m/z 1399.8333 as a possible toxin, corresponding to a compound with the formula C67H127ClO27. Moreover, our study unveiled a series of minor analogues exhibiting distinct patterns of chlorination and sulfation, together defining a new family of compounds, which we propose to name leadbeaterins. Remarkably, these suspected toxins were detected in situ in samples collected during the 2019 bloom close to Tromsø, thereby consistent with a role in fish kills. The elemental compositions of the putative C. leadbeateri ichthyotoxins strongly indicate them to be long linear polyhydroxylated polyketides, structurally similar to sterolysins reported from a number of dinoflagellates.


Subject(s)
Harmful Algal Bloom , Marine Toxins , Norway , Marine Toxins/toxicity , Marine Toxins/chemistry , Marine Toxins/analysis , Estuaries , Animals , Tandem Mass Spectrometry , Haptophyta/chemistry
16.
Heliyon ; 10(12): e33005, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-39021931

ABSTRACT

In the Junggar Basin plague focus, Rhombomys opimus and Meriones meridianus live together, and their parasitic fleas have a similar community structure. However, R. opimus has significantly higher positive rates of Yersinia pestis and anti-F1 antibody compared with M. meridianus. In this study, Y. pestis- and antiF1 antibody-negative R. opimus and M. penicilliger were collected in Qitai county, Fukang city and Mulei county of the eastern part of the Junggar Basin. The genomic DNA was extracted from their spleen tissues, and RT1-Db1*exon1 was amplified through PCR procedure and then sequenced. Sequence analysis was performed and molecular diversity parameters were calculated and compared. The results showed that there were significant differences in nucleotide composition, amino acid composition, number and distribution of single nucleotide polymorphism (SNP) sites and number of haplotypes between R. opimus and M. penicilliger. The nucleotide diversity (π) for R. opimus was 0.00420 ± 0.00139, the haplotype diversity (h) was 0.833 ± 0.086, and the average number of nucleotide differences (K) was 2.02564. The π for M. penicilliger was 0.06569 ± 0.02524, and the h was 1.000 ± 0.045, and the K was 10.4444. The fixation index (FST) value between R. opimus and M. penicilliger was 0.9207. Furthermore, the FST value within R. opimus (0.0275) was significantly lower than that within M. penicilliger (0.2106), indicating a greater genetic variation of M. penicilliger compared with R. opimus. In conclusion, the genetic diversity analysis based on RT1-Db1*exon1 showed that M. penicilliger had higher gene polymorphism and greater genetic differentiation compared with R. opimus in the Junggar Basin plague focus, which might be associated with the low infection rate of Y. pestis.

17.
Nutrients ; 16(13)2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38999730

ABSTRACT

With rapid increases in incidence, diverse subtypes, and complicated etiologies, kidney disease remains a global public health problem. Iron, as an essential trace element, has pleiotropic effects on renal function and the progression of kidney diseases. A two-sample Mendelian randomization (MR) analysis was implemented to determine the potential causal effects between systemic iron status on different kidney diseases. Systemic iron status was represented by four iron-related biomarkers: serum iron, ferritin, transferrin saturation (TfSat), and total iron binding capacity (TIBC). For systemic iron status, 163,511, 246,139, 131,471, and 135,430 individuals were included in the genome-wide association study (GWAS) of serum iron, ferritin, TfSat, and TIBC, respectively. For kidney diseases, 653,143 individuals (15,658 cases and 637,485 controls), 657,076 individuals (8160 cases and 648,916 controls), and 659,320 individuals (10,404 cases and 648,916 controls) were included for immunoglobulin A nephropathy (IgAN), acute kidney disease (AKD), and chronic kidney disease (CKD), respectively. Our MR results showed that increased serum iron [odds ratio (OR): 1.10; 95% confidence interval (95% CI): 1.04, 1.16; p < 0.0042], ferritin (OR: 1.30; 95% CI: 1.14, 1.48; p < 0.0042), and TfSat (OR: 1.07; 95% CI: 1.04, 1.11; p < 0.0042)] and decreased TIBC (OR: 0.92; 95% CI: 0.88, 0.97; p < 0.0042) were associated with elevated IgAN risk. However, no significant associations were found between systemic iron status and AKD or CKD. In our MR study, the genetic evidence supports elevated systemic iron status as a causal effect on IgAN, which suggests a potential protective effect of iron chelation on IgAN patients.


Subject(s)
Ferritins , Genome-Wide Association Study , Iron , Mendelian Randomization Analysis , Humans , Iron/blood , Ferritins/blood , Biomarkers/blood , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/genetics , Transferrin/analysis , Transferrin/metabolism , Risk Factors , Kidney Diseases/blood , Kidney Diseases/genetics , Glomerulonephritis, IGA/blood , Glomerulonephritis, IGA/genetics , Male , Polymorphism, Single Nucleotide , Female
18.
J Chromatogr A ; 1731: 465206, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39053253

ABSTRACT

Appended bispecific antibody (aBsAb) with two single chain variable fragments (scFv) linked at the c-terminus of its heavy chains is one of the promising formats in bispecific therapeutics. The presence of hydrophobic and flexible scFv fragments render aBsAb molecules higher molecule hydrophobicity and structural flexibility compared to monoclonal antibody (mAb), thus making its purification more challenging. We set out to investigate how the unique molecular properties of aBsAb affect its performance on Protein A chromatography. We showed that aBsAb has a high propensity for chromatography-induced aggregation due to its high molecule hydrophobicity, and this couldn't be improved by the addition of common chaotropic salts. Moreover, the presence of chaotropic salts, such as arginine hydrochloride (Arg-HCl), retarded aBsAb elution during Protein A chromatography rather than facilitating which was widely observed in mAb Protein A elution. Nevertheless, we were able to overcome the aggregation issue by optimizing elution condition and improved aBsAb purity from 29 % to 93 % in Protein A eluate with a high molecular weight (HMW) species of less than 5 %. We also showed that the high molecular flexibility of aBsAb leads to different hydrodynamic sizes of the aBsAb molecule post Protein A elution, neutralization, and re-acidification, which are pH dependent. This is different from mAbs where their sizes do not change post neutralization even with re-exposure to acid. The above unique observations of aBsAb in Protein A chromatography were clearly explained from the perspectives of its high molecular hydrophobicity and structural flexibility.


Subject(s)
Antibodies, Bispecific , Hydrophobic and Hydrophilic Interactions , Staphylococcal Protein A , Antibodies, Bispecific/chemistry , Antibodies, Bispecific/isolation & purification , Staphylococcal Protein A/chemistry , Chromatography, Affinity/methods , Single-Chain Antibodies/chemistry , Single-Chain Antibodies/isolation & purification , Antibodies, Monoclonal/chemistry , Antibodies, Monoclonal/isolation & purification , Hydrogen-Ion Concentration , Humans
19.
Front Immunol ; 15: 1401542, 2024.
Article in English | MEDLINE | ID: mdl-39011037

ABSTRACT

Aims/hypothesis: There is increasing evidence for heterogeneity in type 1 diabetes mellitus (T1D): not only the age of onset and disease progression rate differ, but also the risk of complications varies markedly. Consequently, the presence of different disease endotypes has been suggested. Impaired T and B cell responses have been established in newly diagnosed diabetes patients. We hypothesized that deciphering the immune cell profile in peripheral blood of adults with longstanding T1D may help to understand disease heterogeneity. Methods: Adult patients with longstanding T1D and healthy controls (HC) were recruited, and their blood immune cell profile was determined using multicolour flow cytometry followed by a machine-learning based elastic-net (EN) classification model. Hierarchical clustering was performed to identify patient-specific immune cell profiles. Results were compared to those obtained in matched healthy control subjects. Results: Hierarchical clustering analysis of flow cytometry data revealed three immune cell composition-based distinct subgroups of individuals: HCs, T1D-group-A and T1D-group-B. In general, T1D patients, as compared to healthy controls, showed a more active immune profile as demonstrated by a higher percentage and absolute number of neutrophils, monocytes, total B cells and activated CD4+CD25+ T cells, while the abundance of regulatory T cells (Treg) was reduced. Patients belonging to T1D-group-A, as compared to T1D-group-B, revealed a more proinflammatory phenotype characterized by a lower percentage of FOXP3+ Treg, higher proportions of CCR4 expressing CD4 and CD8 T cell subsets, monocyte subsets, a lower Treg/conventional Tcell (Tconv) ratio, an increased proinflammatory cytokine (TNFα, IFNγ) and a decreased anti-inflammatory (IL-10) producing potential. Clinically, patients in T1D-group-A had more frequent diabetes-related macrovascular complications. Conclusions: Machine-learning based classification of multiparameter flow cytometry data revealed two distinct immunological profiles in adults with longstanding type 1 diabetes; T1D-group-A and T1D-group-B. T1D-group-A is characterized by a stronger pro-inflammatory profile and is associated with a higher rate of diabetes-related (macro)vascular complications.


Subject(s)
Diabetes Mellitus, Type 1 , Humans , Diabetes Mellitus, Type 1/immunology , Diabetes Mellitus, Type 1/blood , Male , Adult , Female , Middle Aged , Machine Learning , T-Lymphocytes, Regulatory/immunology , Flow Cytometry , Diabetic Angiopathies/immunology , Diabetic Angiopathies/blood , Case-Control Studies , Immunophenotyping
20.
Front Endocrinol (Lausanne) ; 15: 1289923, 2024.
Article in English | MEDLINE | ID: mdl-38978630

ABSTRACT

Objective: It is well known that macro-thyroid-stimulating hormone (macro-TSH) could interfere with the detection of TSH. The anti-TSH autoantibody is an essential component of macro-TSH. However, the epidemiological characteristics and the clinical interference of the anti-TSH autoantibody are unclear. Methods: In this study, the radioimmunoprecipitation technique was used to detect the anti-TSH autoantibody. Platforms with different detection mechanisms were applied to measure the TSH in patients with the anti-TSH autoantibody. Polyethylene glycol (PEG) precipitation was used to determine the immunoassay interference. Results: The prevalence of the anti-TSH autoantibody in patients with mild subclinical hypothyroidism (SCH) and autoimmune thyroiditis, but normal thyroid function, was 4.78%. All 10 patients with anti-TSH antibodies had autoimmune diseases, with five of them having significant clinical test interference. Conclusion: The appearance of the anti-TSH antibody is not associated with thyroid autoantibodies. The presence of the anti-TSH autoantibody can interfere with the detection of TSH and can affect clinical diagnosis and treatment.


Subject(s)
Autoantibodies , Hypothyroidism , Thyrotropin , Humans , Autoantibodies/blood , Autoantibodies/immunology , Thyrotropin/blood , Thyrotropin/immunology , Female , Male , Adult , Middle Aged , Hypothyroidism/diagnosis , Hypothyroidism/immunology , Hypothyroidism/blood , Thyroiditis, Autoimmune/immunology , Thyroiditis, Autoimmune/blood , Thyroiditis, Autoimmune/diagnosis , Thyroid Function Tests , Aged , Immunoassay/methods , Radioimmunoprecipitation Assay
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