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1.
Front Plant Sci ; 15: 1431097, 2024.
Article in English | MEDLINE | ID: mdl-38947949

ABSTRACT

Tender bamboo shoots undergo rapid senescence that influences their quality and commercial value after harvest. In this study, the tender sweet bamboo shoots ('Wensun') were packed by a passive modified atmosphere packaging (PMAP) to inhibit the senescence process, taking polyethylene package as control. The increase in CO2 and the decrease in O2 gas concentrations in the headspace atmosphere of the packages were remarkably modified by PMAP treatments. The modified gas atmosphere packaging inhibited the changes in firmness, as well as the content of cellulose, total pectin, and lignin in the cell walls of bamboo shoots. The enzymatic activities of cellulase, pectinase, and polygalacturonase that act on cell wall polysaccharides, and phenylalanine ammonia lyase, cinnamyl alcohol dehydrogenase, peroxidase, and laccase regulating the lignin biosynthesis were modified by PMAP treatment different from control during storage. The expression levels of the lignin biosynthesis genes PePAL3/4, PeCAD, Pe4CL5, PeC4H, PeCCOAOMT, PeCOMT, cellulose synthase PeCESA1, and related transcription factors PeSND2, PeKNAT7, PeMYB20, PeMYB63, and PeMYB85 were clearly regulated. These results suggest that PMAP efficiently retards the changes in lignin and cell wall polysaccharides, thus delaying the senescence of tender sweet bamboo shoots during storage.

2.
Theranostics ; 14(9): 3653-3673, 2024.
Article in English | MEDLINE | ID: mdl-38948066

ABSTRACT

Rationale: Recent evidence highlights the pivotal role of mitochondrial dysfunction in mood disorders, but the mechanism involved remains unclear. We studied whether the Hippo/YAP/14-3-3η signaling pathway mediates mitochondrial abnormalities that result in the onset of major depressive disorder (MDD) in a mouse model. Methods: The ROC algorithm was used to identify a subpopulation of mice that were exposed to chronic unpredictable mild stress (CUMS) and exhibited the most prominent depressive phenotype (Dep). Electron microscopy, biochemical assays, quantitative PCR, and immunoblotting were used to evaluate synaptic and mitochondrial changes in the basolateral amygdala (BLA). RNA sequencing was used to explore changes in the Hippo pathway and downstream target genes. In vitro pharmacological inhibition and immunoprecipitation was used to confirm YAP/14-3-3η interaction and its role in neuronal mitochondrial dysfunction. We used virus-mediated gene overexpression and knockout in YAP transgenic mice to verify the regulatory effect of the Hippo/YAP/14-3-3η pathway on depressive-like behavior. Results: Transcriptomic data identified a large number of genes and signaling pathways that were specifically altered from the BLA of Dep mice. Dep mice showed notable synaptic impairment in BLA neurons, as well as mitochondrial damage characterized by abnormal mitochondrial morphology, compromised function, impaired biogenesis, and alterations in mitochondrial marker proteins. The Hippo signaling pathway was activated in Dep mice during CUMS, and the transcriptional regulatory activity of YAP was suppressed by phosphorylation of its Ser127 site. 14-3-3η was identified as an important co-regulatory factor of the Hippo/YAP pathway, as it can respond to chronic stress and regulate cytoplasmic retention of YAP. Importantly, the integrated Hippo/YAP/14-3-3η pathway mediated neuronal mitochondrial dysfunction and depressive behavior in Dep mice. Conclusion: The integrated Hippo/YAP/14-3-3η pathway in the BLA neuron is critical in mediating depressive-like behaviors in mice, suggesting a causal role for this pathway in susceptibility to chronic stress-induced depression. This pathway therefore may present a therapeutic target against mitochondrial dysfunction and synaptic impairment in MDD.


Subject(s)
Basolateral Nuclear Complex , Disease Models, Animal , Hippo Signaling Pathway , Mitochondria , Protein Serine-Threonine Kinases , Signal Transduction , YAP-Signaling Proteins , Animals , Mice , Mitochondria/metabolism , YAP-Signaling Proteins/metabolism , Basolateral Nuclear Complex/metabolism , Basolateral Nuclear Complex/pathology , Protein Serine-Threonine Kinases/metabolism , Protein Serine-Threonine Kinases/genetics , Male , Stress, Psychological/complications , Stress, Psychological/metabolism , 14-3-3 Proteins/metabolism , 14-3-3 Proteins/genetics , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Signal Transducing/genetics , Depressive Disorder, Major/metabolism , Depressive Disorder, Major/pathology , Depression/metabolism , Mice, Inbred C57BL , Neurons/metabolism , Neurons/pathology , Mice, Transgenic
3.
Nat Commun ; 15(1): 5291, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38987547

ABSTRACT

Resistance to immune checkpoint therapy (ICT) presents a growing clinical challenge. The tumor microenvironment (TME) and its components, namely tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs), play a pivotal role in ICT resistance; however, the underlying mechanisms remain under investigation. In this study, we identify expression of TNF-Stimulated Factor 6 (TSG-6) in ICT-resistant pancreatic tumors, compared to ICT-sensitive melanoma tumors, both in mouse and human. TSG-6 is expressed by CAFs within the TME, where suppressive macrophages expressing Arg1, Mafb, and Mrc1, along with TSG-6 ligand Cd44, predominate. Furthermore, TSG-6 expressing CAFs co-localize with the CD44 expressing macrophages in the TME. TSG-6 inhibition in combination with ICT improves therapy response and survival in pancreatic tumor-bearing mice by reducing macrophages expressing immunosuppressive phenotypes and increasing CD8 T cells. Overall, our findings propose TSG-6 as a therapeutic target to enhance ICT response in non-responsive tumors.


Subject(s)
Cancer-Associated Fibroblasts , Cell Adhesion Molecules , Immune Checkpoint Inhibitors , Pancreatic Neoplasms , Tumor Microenvironment , Animals , Pancreatic Neoplasms/immunology , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/metabolism , Humans , Tumor Microenvironment/immunology , Cancer-Associated Fibroblasts/metabolism , Cancer-Associated Fibroblasts/drug effects , Mice , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , Cell Line, Tumor , Cell Adhesion Molecules/metabolism , Cell Adhesion Molecules/genetics , Myeloid Cells/metabolism , Myeloid Cells/immunology , Tumor-Associated Macrophages/metabolism , Tumor-Associated Macrophages/immunology , Tumor-Associated Macrophages/drug effects , Mice, Inbred C57BL , Female , Drug Resistance, Neoplasm , Macrophages/immunology , Macrophages/metabolism , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism
4.
Brain Res ; 1843: 149116, 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38977238

ABSTRACT

BACKGROUND: Diallyl trisulfide (DATS) has a direct antioxidant capacity and emerges as a promising neuroprotective agent. This study was designed to investigate the role of DATS in traumatic brain injury (TBI). METHODS: TBI mouse models were established using the controlled cortical impact, followed by DATS administration. The effects of DATS on neurological deficit, brain damage, inflammation and phosphoglycerate kinase 1 (PGK1) expression were detected using mNSS test, histological analysis, TUNEL assay, enzyme-linked immunosorbent assay and immunofluorescence. PC12 cells were subjected to H2O2-induced oxidative injury after pre-treatment with DATS, followed by cell counting kit-8 assay, flow cytometry and ROS production detection. Apoptosis-related proteins and the PGK1/nuclear factor erythroid-2 related factor 2 (Nrf2) pathway were examined using Western blot. RESULTS: DATS ameliorated the cerebral cortex damage, neurological dysfunction and apoptosis, as well as decreased PGK1 expression and expressions of pro-inflammatory cytokines (IL-6, IL-1ß, TNF-α) in mice after TBI. DATS also enhanced viability, blocked apoptosis and inhibited ROS production in H2O2-induced PC12 cells. DATS downregulated Cleaved-Caspase3, Bax and PGK1 levels, and upregulated Bcl-2 and Nrf2 levels in TBI mouse models and the injured cells. CONCLUSION: DATS regulates PGK1/Nrf2 expression and inflammation to alleviate neurological damage in mice after TBI.

6.
Medicina (Kaunas) ; 60(6)2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38929577

ABSTRACT

Background: Research on the impact of reduced time to emergent surgery in trauma patients has yielded inconsistent results. Therefore, this study investigated the relationship between waiting emergent surgery time (WEST) and outcomes in trauma patients. Methods: This retrospective, multicenter study used data from the Tzu Chi Hospital trauma database. The primary clinical outcomes were in-hospital mortality, intensive care unit (ICU) admission, and prolonged hospital length of stay (LOS) of ≥30 days. Results: A total of 15,164 patients were analyzed. The median WEST was 444 min, with an interquartile range (IQR) of 248-848 min for all patients. Patients who died in the hospital had a shorter median WEST than did those who survived (240 vs. 446 min, p < 0.001). Among the trauma patients with a WEST of <2 h, the median time was 79 min (IQR = 50-100 min). No significant difference in WEST was observed between the survival and mortality groups for patients with a WEST of <120 min (median WEST: 85 vs. 78 min, p < 0.001). Multivariable logistic regression analysis revealed that WEST was not associated with an increased risk of in-hospital mortality (adjusted odds ratio [aOR] = 1.05, 95% confidence interval [CI] = 0.17-6.35 for 30 min ≤ WEST < 60 min; aOR = 1.12, 95% CI = 0.22-5.70 for 60 min ≤ WEST < 90 min; and aOR = 0.60, 95% CI = 0.13-2.74 for WEST ≥ 90 min). Conclusions: Our findings do not support the "golden hour" concept because no association was identified between the time to definitive care and in-hospital mortality, ICU admission, and prolonged hospital stay of ≥30 days.


Subject(s)
Hospital Mortality , Length of Stay , Wounds and Injuries , Humans , Female , Male , Retrospective Studies , Middle Aged , Adult , Length of Stay/statistics & numerical data , Wounds and Injuries/mortality , Wounds and Injuries/surgery , Aged , Intensive Care Units/statistics & numerical data , Time Factors , Time-to-Treatment/statistics & numerical data , Logistic Models
7.
Langmuir ; 40(22): 11470-11480, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38768447

ABSTRACT

The inclusion of sacrificial hydrogen bonds is crucial for advancing high-performance rubber materials. However, the molecular mechanisms governing the impact of these bonds on material properties remain unclear, hindering progress in advanced rubber material research. This study employed all-atom molecular dynamics simulations to thoroughly investigate how hydrogen bonds affect the structure, dynamics, mechanics, and linear viscoelasticity of rubber materials. As the modified repeating unit ratio (ß) increased, both interchain and intrachain hydrogen bond content rose, with interchain bonds playing a predominant role. This physical cross-linking network formed through interchain hydrogen bonds restricts molecular chain movement and relaxation and raises the glass transition temperature of rubber. Within a certain content of hydrogen bonds, the mechanical strength increases with increasing ß. However, further increasing ß leads to a subsequent decrease in the mechanical performance. Optimal mechanical properties were observed at ß = 6%. On the other hand, a higher ß value yields an elevated stress relaxation modulus and an extended stress relaxation plateau, signifying a more complex hydrogen-bond cross-linking network. Additionally, higher ß increases the storage modulus, loss modulus, and complex viscosity while reducing the loss factor. In summary, this study successfully established the relationship between the structure and properties of natural rubber containing hydrogen bonds, providing a scientific foundation for the design of high-performance rubber materials.

8.
Shock ; 2024 May 27.
Article in English | MEDLINE | ID: mdl-38813929

ABSTRACT

BACKGROUND: Early prediction of sepsis onset is crucial for reducing mortality and the overall cost burden of sepsis treatment. Currently, few effective and accurate prediction tools are available for sepsis. Hence, in this study, we developed an effective sepsis clinical decision support system (S-CDSS) to assist emergency physicians to predict sepsis. METHODS: This study included patients who had visited the emergency department (ED) of Taipei Tzu Chi Hospital, Taiwan, between January 1, 2020, and June 31, 2022. The patients were divided into a derivation cohort (n = 70,758) and a validation cohort (n = 27,545). The derivation cohort was subjected to sixfold stratified cross-validation, reserving 20% of the data (n = 11,793) for model testing. The primary study outcome was a sepsis prediction (International Classification of Diseases, Tenth Revision, Clinical Modification) before discharge from the ED. The S-CDSS incorporated the LightGBM algorithm to ensure timely and accurate prediction of sepsis. The validation cohort was subjected to multivariate logistic regression to identify the associations of S-CDSS-based high- and medium-risk alerts with clinical outcomes in the overall patient cohort. For each clinical outcome in high- and medium-risk patients, we calculated the sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios, and accuracy of S-CDSS-based predictions. RESULTS: The S-CDSS was integrated into our hospital information system. The system featured three risk warning labels (red, yellow, and white, indicating high, medium, and low risks, respectively) to alert emergency physicians. The sensitivity and specificity of the S-CDSS in the derivation cohort were 86.9% and 92.5%, respectively. In the validation cohort, high- and medium-risk alerts were significantly associated with all clinical outcomes, exhibiting high prediction specificity for intubation, general ward admission, intensive care unit admission, ED mortality, and in-hospital mortality (93.29%, 97.32%, 94.03%, 93.04%, and 93.97%, respectively). CONCLUSION: Our findings suggest that the S-CDSS can effectively identify patients with suspected sepsis in the ED. Furthermore, S-CDSS-based predictions appear to be strongly associated with clinical outcomes in patients with sepsis.

9.
Medicina (Kaunas) ; 60(4)2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38674293

ABSTRACT

Background and Objectives: The Taiwan Triage and Acuity Scale (TTAS) is reliable for triaging patients in emergency departments in Taiwan; however, most triage decisions are still based on chief complaints. The reverse-shock index (SI) multiplied by the simplified motor score (rSI-sMS) is a more comprehensive approach to triage that combines the SI and a modified consciousness assessment. We investigated the combination of the TTAS and rSI-sMS for triage compared with either parameter alone as well as the SI and modified SI. Materials and Methods: We analyzed 13,144 patients with trauma from the Taipei Tzu Chi Trauma Database. We investigated the prioritization performance of the TTAS, rSI-sMS, and their combination. A subgroup analysis was performed to evaluate the trends in all clinical outcomes for different rSI-sMS values. The sensitivity and specificity of rSI-sMS were investigated at a cutoff value of 4 (based on previous study and the highest score of the Youden Index) in predicting injury severity clinical outcomes under the TTAS system were also investigated. Results: Compared with patients in triage level III, those in triage levels I and II had higher odds ratios for major injury (as indicated by revised trauma score < 7 and injury severity score [ISS] ≥ 16), intensive care unit (ICU) admission, prolonged ICU stay (≥14 days), prolonged hospital stay (≥30 days), and mortality. In all three triage levels, the rSI-sMS < 4 group had severe injury and worse outcomes than the rSI-sMS ≥ 4 group. The TTAS and rSI-sMS had higher area under the receiver operating characteristic curves (AUROCs) for mortality, ICU admission, prolonged ICU stay, and prolonged hospital stay than the SI and modified SI. The combination of the TTAS and rSI-sMS had the highest AUROC for all clinical outcomes. The prediction performance of rSI-sMS < 4 for major injury (ISS ≥ 16) exhibited 81.49% specificity in triage levels I and II and 87.6% specificity in triage level III. The specificity for mortality was 79.2% in triage levels I and II and 87.4% in triage level III. Conclusions: The combination of rSI-sMS and the TTAS yielded superior prioritization performance to TTAS alone. The integration of rSI-sMS and TTAS effectively enhances the efficiency and accuracy of identifying trauma patients at a high risk of mortality.


Subject(s)
Triage , Wounds and Injuries , Humans , Triage/methods , Triage/standards , Male , Female , Taiwan/epidemiology , Middle Aged , Adult , Wounds and Injuries/mortality , Aged , Emergency Service, Hospital/organization & administration , Emergency Service, Hospital/statistics & numerical data , Injury Severity Score , Sensitivity and Specificity , Trauma Severity Indices , Shock/mortality , Shock/diagnosis , Length of Stay/statistics & numerical data
10.
Macromol Rapid Commun ; 45(12): e2300715, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38539063

ABSTRACT

The raw materials of Poly(ethylene terephthalate) (PET) are derived from petroleum-based resources, which are no sustainable. Therefore, previous researchers introduced biomass-derived 2,5-tetrahydrofurfuryl dimethanol (THFDM) into PET. However, its heat resistance has decreased compared to PET. In this paper, a novel bio-based copolyester, poly(ethylene glycol-co-2,5-tetrahydrofuran dimethanol-co-isosorbide terephthalate) (PEIFT), is prepared by introducing biomass-derived isosorbide (ISB) and THFDM into the PET chains through melting copolymerization process. With the introduction of ISB content, copolyesters' hydrophilicity and rigidity improve. Compared to PET, glass transition temperature (Tg) increases by over 5 °C. In addition, the toughness and spinning performance of PEIFT have also been improved as a result of the addition of THFDM components. The hydrophobicity of PEIFTs electrospinning is greatly improved, with a contact angle exceeding 135°. Finally, due to the good hydrophobicity of PEIFTs nanofibers, they have potential application value in the manufacture of hydrophobic nanofiber and filter films. Given its biomass source and excellent performance, they make it easier to replace materials derived from petroleum.


Subject(s)
Hydrophobic and Hydrophilic Interactions , Nanofibers , Polyesters , Nanofibers/chemistry , Polyesters/chemistry , Polyesters/chemical synthesis , Isosorbide/chemistry , Biomass , Polyethylene Terephthalates/chemistry , Furans/chemistry
11.
Article in English | MEDLINE | ID: mdl-38363352

ABSTRACT

Glioma is one of the most common malignancies of the central nervous system. The therapeutic effect has not been satisfactory despite advances in comprehensive treatment techniques. Our previous studies have found that triptolide inhibits glioma proliferation through the ROS/JNK pathway, but in-depth mechanisms need to be explored. Recent studies have confirmed that miRNAs may function as tumor suppressor genes or oncogenes and be involved in cancer development and progression. In this study, we found that let-7b-5p expression levels closely correlated with WHO grades and overall survival in patients in tumor glioma-CGGA-mRNAseq-325, and the upregulation of let-7b-5p can inhibit the proliferation and induce apoptosis of glioma cells. Functionally, upregulation of let-7b-5p increased the inhibitory effect on cell viability and colony formation caused by triptolide and promoted the apoptosis rate of triptolide-treated U251 cells. Conversely, downregulation of let-7b-5p had the opposite effect, indicating that let-7b-5p is a tumor suppressor miRNA in glioma cells. Moreover, target prediction, luciferase reporter assays and functional experiments revealed that IGF1R was a direct target of let-7b-5p. In addition, upregulation of IGF1R reversed the triptolide-regulated inhibition of cell viability but promoted glioma cell apoptosis and activated the ROS/JNK signaling pathway induced by triptolide. The results obtained in vivo experiments substantiated those from the in vitro experiments. In summary, the current study provides evidence that triptolide inhibits the growth of glioma cells by regulating the let-7b-5p-IGF1R-ROS/JNK axis in vitro and in vivo. These findings may provide new ideas and potential targets for molecularly targeted therapies for comprehensive glioma treatment.

12.
ACS Appl Mater Interfaces ; 16(8): 10398-10406, 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38380978

ABSTRACT

The rapid evolution of the Internet of Things has engendered increased requirements for low-cost, self-powered UV photodetectors. Herein, high-performance self-driven UV photodetectors are fabricated by designing asymmetric metal-semiconductor-metal structures on the high-quality large-area CsCu2I3 microwire arrays. The asymmetrical depletion region doubles the photocurrent and response speed compared to the symmetric structure device, leading to a high responsivity of 233 mA/W to 355 nm radiation. Notably, at 0 V bias, the asymmetric device produces an open-circuit voltage of 356 mV and drives to a short-circuit current of 372 pA; meanwhile, the switch ratio (Iph/Idark) reaches up to 103, indicating its excellent potential for detecting weak light. Furthermore, the device maintains stable responses throughout 10000 UV-light switch cycles, with negligible degradation even after 90-day storage in air. Our work establishes that CsCu2I3 is a good candidate for self-powered UV detection and thoroughly demonstrates its potential as a passive device.

13.
Food Chem X ; 21: 101129, 2024 Mar 30.
Article in English | MEDLINE | ID: mdl-38298353

ABSTRACT

Fresh puffer fish (Takifugu obscurus) are susceptible to microbial contamination and have a very short shelf-life of chilled storage. Hence, this study aimed to evaluate the effects of plasma-activated lactic acid (PALA) on microbiota composition and quality attributes of puffer fish fillets during chilled storage. The results showed that PALA treatment effectively reduced the growth of bacteria and attenuated changes in physicochemical indicators (total volatile basic nitrogen, pH value, K value, and biogenic amines) of puffer fish fillets. Additionally, insignificant changes were observed in lipid oxidation during the first 8 days (p > 0.05). Illumina-MiSeq high-throughput sequencing revealed that PALA effectively inhibited the growth of Pseudomonas in puffer fish fillets and maintained the diverse characteristics of the microbial community. In combination with sensory analysis, PALA extended the shelf life of puffer fish fillets for 4 days, suggesting that PALA could be considered a potential fish fillet preservation method.

14.
Zhongguo Zhong Yao Za Zhi ; 49(2): 461-470, 2024 Jan.
Article in Chinese | MEDLINE | ID: mdl-38403322

ABSTRACT

This study aims to explore the mechanism of Liujunzi Decoction in the treatment of 4-nitroquinoline-N-oxide(4NQO)-induced esophageal cancer in mice. One hundred mice of 35-45 days were randomized into blank, model, and low-, medium-, and high-concentration(18.2, 36.4, and 54.6 g·kg~(-1), respectively) Liujunzi Decoction groups. The mice in other groups except the blank group had free access to the water containing 100 µg·mL~(-1) 4NQO for 16 weeks for the modeling of esophageal cancer. The mice in the Liujunzi Decoction groups were fed with the diets supplemented with corresponding concentrations of Liujunzi Decoction. The body weight and organ weights were weighed for the calculation of organ indexes. The pathological changes of the esophageal tissue were observed by hematoxylin-eosin(HE) staining. Ultra performance liquid chromatography-mass spectrometry(UPLC-MS/MS) was employed to collect metabolites from mouse serum samples, screen out potential biomarkers, and predict related metabolic pathways. Compared with the blank group, the model group showed decreased spleen and stomach indexes and increased lung, esophagus, and kidney indexes. Compared with the model group, Liujunzi Decoction groups had no significant changes in the organ indexes. The HE staining results showed that Liujunzi Decoction inhibited the invasive growth and cancerization of the esophageal cancer cells. A total of 9 potential biomarkers of Liujunzi Decoction in treating esophageal cancer were screened out in this study, which were urocanic acid, 1-oleoylglycerophosphoserine, 11-deoxy prostaglandin E1, Leu-Glu-Lys-Glu,(±) 4-hydroxy-5E,7Z,10Z,13Z,16Z,19Z-docosahexaenoic acid, ureidosuccinic acid,(2R)-2,4-dihydroxy-3,3-dimethylbutanoic acid, kynurenic acid, and bicyclo prostaglandin E2, which were mainly involved in histidine, pyrimidine, alanine, aspartate, glutamate, pantothenate and tryptophan metabolism and coenzyme A biosynthesis. In summary, Liujunzi Decoction may exert the therapeutic effect on the 4NQO-induced esophageal cancer in mice by regu-lating the amino acid metabolism, inflammation, and immune function.


Subject(s)
Drugs, Chinese Herbal , Esophageal Neoplasms , Tandem Mass Spectrometry , Mice , Animals , Chromatography, Liquid , Metabolomics , Biomarkers , Esophageal Neoplasms/chemically induced , Esophageal Neoplasms/drug therapy
15.
Microb Biotechnol ; 17(2): e14415, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38381074

ABSTRACT

Green manufacture of steroid precursors from diosgenin by microbial replacing multistep chemical synthesis has been elusive. It is currently limited by the lack of strain and degradation mechanisms. Here, we demonstrated the feasibility of this process using a novel strain Mycolicibacterium sp. HK-90 with efficiency in diosgenin degradation. Diosgenin degradation by strain HK-90 involves the selective removal of 5,6-spiroketal structure, followed by the oxygenolytic cleavage of steroid nuclei. Bioinformatic analyses revealed the presence of two complete steroid catabolic gene clusters, SCG-1 and SCG-2, in the genome of strain HK-90. SCG-1 cluster was found to be involved in classic phytosterols or cholesterol catabolic pathway through the deletion of key kstD1 gene, which promoted the mutant m-∆kstD1 converting phytosterols to intermediate 9α-hydroxyandrostenedione (9-OHAD). Most impressively, global transcriptomics and characterization of key genes suggested SCG-2 as a potential gene cluster encoding diosgenin degradation. The gene inactivation of kstD2 in SCG-2 resulted in the conversion of diosgenin to 9-OHAD and 9,16-dihydroxy-pregn-4-ene-3,20-dione (9,16-(OH)2 -PG) in mutant m-ΔkstD2. Moreover, the engineered strain mHust-ΔkstD1,2,3 with a triple deletion of kstDs was constructed, which can stably accumulate 9-OHAD by metabolizing phytosterols, and accumulate 9-OHAD and 9,16-(OH)2 -PG from diosgenin. Diosgenin catabolism in strain mHust-ΔkstD1,2,3 was revealed as a progression through diosgenone, 9,16-(OH)2 -PG, and 9-OHAD to 9α-hydroxytestosterone (9-OHTS). So far, this work is the first report on genetically engineered strain metabolizing diosgenin to produce 21-carbon and 19-carbon steroids. This study presents a promising biosynthetic platform for the green production of steroid precursors, and provide insights into the complex biochemical mechanism of diosgenin catabolism.


Subject(s)
Diosgenin , Phytosterols , Steroids , Carbon , Commerce
16.
Cytotherapy ; 26(3): 311-316, 2024 03.
Article in English | MEDLINE | ID: mdl-38219142

ABSTRACT

BACKGROUND: Our previous single-center, randomized, double-blinded, placebo-controlled phase 2 study evaluated the safety and effectiveness of human umbilical cord mesenchymal stromal cell (UC-MSC) transfusion for treating patients with type 2 diabetes mellitus (T2DM). Indeed, this potential treatment strategy was able to reduce insulin use by half in a considerable number of patients. However, many other patients' responses to UC-MSC transfusion were insignificant. The selection of patients who might benefit from UC-MSC treatment is crucial from a clinical standpoint. METHODS: In this post hoc analysis, 37 patients who received UC-MSC transfusions were divided into two groups based on whether their glycated hemoglobin (hemoglobin A1c, or HbA1c) level was less than 7% after receiving UC-MSC treatment. The baseline differences between the two groups were summarized, and potential factors influencing efficacy of UC-MSCs for T2DM were analyzed by univariate and multivariate logistic regression. The correlations between the relevant hormone levels and the treatment effect were further analyzed. RESULTS: At the 9-week follow-up, 59.5% of patients achieved their targeted HbA1c level. Male patients with lower baseline HbA1c and greater C-peptide area under the curve (AUCC-pep) values responded favorably to UC-MSC transfusion, according to multivariate analysis. The effectiveness of UC-MSCs transfusion was predicted by AUCC-pep (cutoff value: 14.22 ng/h/mL). Further investigation revealed that AUCC-pep was increased in male patients with greater baseline testosterone levels. CONCLUSIONS: Male patients with T2DM with greater AUCC-pep may be more likely to respond clinically to UC-MSC therapy, and further large-scale multi-ethnic clinical studies should be performed to confirm the conclusion.


Subject(s)
Diabetes Mellitus, Type 2 , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Humans , Male , Diabetes Mellitus, Type 2/therapy , Diabetes Mellitus, Type 2/metabolism , Glycated Hemoglobin , Umbilical Cord , Treatment Outcome , Mesenchymal Stem Cells/physiology
17.
J Hazard Mater ; 465: 133311, 2024 03 05.
Article in English | MEDLINE | ID: mdl-38181594

ABSTRACT

Intraparticle domains are the critical locations for storing contaminants and retarding contaminant transport in subsurface environments. While the kinetics and extent of antibiotics sorption and desorption in subsurface materials have been extensively studied, their behaviors in intraparticle domains have not been well understood. This study investigated the sorption and desorption of antibiotics (ATs) in the intraparticle domains using quartz grains and clay, and antibiotic tetracycline (TC) and levofloxacin (LEV) as examples that are commonly present in groundwater systems. Batch experiments coupled with the analyses using various microscopic and spectroscopic techniques were performed to investigate the sorption and desorption kinetics, and to provide insights into the intraparticle sorption and desorption of TC and LEV. Results indicated that both TC and LEV with different physiochemical properties can migrate into intraparticle domains that were consistent with sorptive diffusion. The rate and extent of the sorption are a function of intraparticle surface area and properties, pore volume and connectivity, and ionic properties of the ATs. The sorptive diffusion led to the slow desorption of both TC and LEV after their sorption, apparently showing an irreversible desorption behavior (with desorption percentage about 1.86-20.51%). These results implied that intraparticle domains can be important locations for storing ATs, retarding ATs transport, and may serve as a long-term secondary source for groundwater contamination.


Subject(s)
Anti-Bacterial Agents , Tetracycline , Adsorption , Clay , Levofloxacin , Kinetics
18.
Dalton Trans ; 53(2): 765-771, 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38086693

ABSTRACT

Na-ion batteries (NIBs) have attracted great interest as a possible technology for grid-scale energy storage for the past few years owing to the wide distribution, low cost and environmental friendliness of sodium resources and similar chemical mechanisms to those of established Li-ion batteries (LIBs). Nonetheless, the implementation of NIBs is seriously hindered because of their low rate capability and cycling stability. This is mainly because the large ionic size of Na+ can reduce the structural stability and cause sluggish reaction kinetics of electrode materials. Herein, three-dimensional nanoarchitectured coral-like CoSe2@N-doped carbon (CL-CoSe2@NC) was synthesized through solvothermal and selenizing techniques. As a result, CL-CoSe2@NC for NIBs at 2 A g-1 exhibits an ultrahigh specific capacity of 345.4 mA h g-1 after 2800 cycles and a superhigh initial coulombic efficiency (ICE) of 93.1%. Ex situ XRD, HRTEM, SAED and XPS were executed to study the crystal structure evolution between Na and CoSe2 during sodiation/de-sodiation processes. The aforementioned results indicate that the improved sodium storage property of CL-CoSe2@NC could be attributed to better electrode kinetics and a stable SEI film because of the 3D nanoarchitecture and the existence of the NC layer.

19.
Article in English | MEDLINE | ID: mdl-38103500

ABSTRACT

Intermuscular bones (IBs) are mineralized spicules that negatively impact the quality and value of fish products. Runx2b is a crucial modulator in promoting bone formation through regulating osteoblast differentiation. Previous studies suggested that loss of runx2b gene completely inhibited IBs formation in zebrafish. However, how the whole transcriptome, including mRNA and non-coding RNA (ncRNA), affects the IBs development in runx2b-/- zebrafish are not known. The aim of this study was to identify the regulatory networks of differentially expressed (DE) lncRNAs, miRNAs, and mRNAs in zebrafish with and without IBs (runx2b+/+ fish and runx2b-/- fish) utilizing high-throughput sequencing techniques. All together there are 1051 mRNAs, 456 lncRNAs, and 18 miRNAs differentially expressed were found between these two strains. The analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) has highlighted significant pathways linked to the development of IBs, specifically the TGF-beta and Wnt signaling pathways, and a number of genes concentrated on these two signaling pathways related to the formation of IBs. Further, 1989 competing endogenous RNA (ceRNA) networks were created according to the correlation among mRNAs, miRNAs and lncRNAs. The ceRNA networks results revealed 52 ceRNA pairs related to the IBs formation, consisting of 52 mRNAs, 37 lncRNAs, and 6 miRNAs. Of these, we found that dre-miR-2189 was the key element of ceRNA pairs, interacting with 19 mRNAs and 11 lncRNAs, and MSTRG.13175.1 could regulate sp7 expression by interacting with dre-miR-2189 to function in osteogenic differentiation. Subsequent experiments at the cellular level also revealed the interaction mechanism. The outcomes indicated a crucial role of miRNAs and lncRNAs in the development of fish IBs, which offer new views into the functions of ncRNAs involved in IBs formation.


Subject(s)
MicroRNAs , RNA, Long Noncoding , Animals , Gene Regulatory Networks , MicroRNAs/genetics , Osteogenesis/genetics , RNA, Competitive Endogenous , RNA, Long Noncoding/genetics , RNA, Messenger/genetics , Zebrafish/genetics , Zebrafish/metabolism
20.
Heliyon ; 9(12): e22957, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38076133

ABSTRACT

Phthalides are a class of unique compounds such as ligustilide, butylphthalide and butyldenephthalide, which have shown to possess multiple bioactivities in new drug research and development. Phthalides are naturally distributed in different plants that have been utilized as herbal treatments for various ailments with a long history in Asia, Europe and North America. Their extensive biological activity has led to a dramatic increase in the study of phthalide compounds in recent years. This review summarizes the latest research progress of plant-derived phthalides, and a total of 133 phthalide compounds are described based on the characteristics of chemical structures. Pharmacological properties of plant-derived phthalides are associated with hemorheological improvement, vascular function modulation and central nervous system protection. Potential treatments for a variety of diseases mainly including cardio-cerebrovascular disorders and neurological complications such as Alzheimer's disease are also concluded. In addition, key metabolic pathways have been clearly elucidated. Further investigations on the molecular mechanisms involved in biological activity are recommended for offering new insights into profound comprehension of phthalide applications.

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