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1.
BMC Anesthesiol ; 24(1): 214, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38956458

ABSTRACT

BACKGROUND: The efficacy and reliability of erector spinae plane block (ESPB) in posterior open lumbar spine surgery has been demonstrated; however, few randomized controlled trials of lumbar ESPB (L-ESPB) in lumbar unilateral bi-portal endoscopic (UBE) surgery have been reported. METHODS: A total of 120 patients, aged 18 to 65 (who underwent elective lumbar UBE surgery under general anesthesia and exhibited an American Society of Anesthesiologists physical status of I to III) were randomly assigned in a 1:1 ratio to the ESPB group and the Control group. Ultrasound(US)-guided unilateral single-shot 0.25% ropivacaine L-ESPB was performed in the ESPB group, but not in the control group. Postoperative analgesic strategy for all patients: patient controlled intravenous analgesia (PCIA, diluted and dosed with fentanyl alone) was initiated immediately after surgery combined with oral compound codeine phosphate and ibuprofen sustained release tablets (1 tablet containing ibuprofen 200 mg and codeine 13 mg, 1 tablet/q12h) commenced 6 h postoperatively. We collected and compared patient-centred correlates intraoperatively and 48 h postoperatively. The primary outcomes were intraoperative and postoperative opioid consumption and postoperative quality of recovery-15 (QoR-15) scores. RESULTS: Compared to the control group (n = 56), the ESPB group (n = 58) significantly reduced intraoperative remifentanil consumption (estimated median difference - 280 mcg, 95% confidence interval [CI] - 360 to - 200, p < 0.001, power = 100%); significantly reduced fentanyl consumption at 24 h postoperatively (estimated median difference - 80mcg, 95%[CI] - 128 to - 32, p = 0.001, power = 90%); and significantly enhanced the QoR-15 score at 24 h postoperatively (estimated median difference 11, 95%[CI] 8 to 14, p < 0.001, power = 100%). Compared to the control group, the ESPB group enhanced the resting numeric rating scale (NRS) score up to 8 h postoperatively, and the active movement NRS score up to 4 h postoperatively. The incidence of postoperative nausea and vomiting (PONV) (p = 0.015, power = 70%), abdominal distension (p = 0.024, power = 64%), and muscular calf vein thrombosis (MCVT) (p = 0.033, power = 58%) was lower in the ESPB group than in the control group. Moreover, the occurrence of L-ESPB related adverse reactions was not found herein. CONCLUSION: US-guided L-ESPB reduces intraoperative and 24 h postoperative opioid consumption and improves patients' QoR-15 scores at 24 h postoperatively. L-ESPB can be safely and effectively utilized in lumbar UBE surgery. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200061908 , date of registration: 10/07/2022. Registry URL.


Subject(s)
Analgesia, Patient-Controlled , Analgesics, Opioid , Lumbar Vertebrae , Nerve Block , Pain, Postoperative , Ropivacaine , Humans , Male , Pain, Postoperative/prevention & control , Female , Middle Aged , Nerve Block/methods , Adult , Prospective Studies , Analgesics, Opioid/administration & dosage , Lumbar Vertebrae/surgery , Analgesia, Patient-Controlled/methods , Ropivacaine/administration & dosage , Endoscopy/methods , Anesthetics, Local/administration & dosage , Ultrasonography, Interventional/methods , Aged , Young Adult , Adolescent , Ibuprofen/administration & dosage , Paraspinal Muscles
2.
Drug Des Devel Ther ; 18: 2775-2791, 2024.
Article in English | MEDLINE | ID: mdl-38984208

ABSTRACT

Background: Psoriasis is a common chronic inflammatory skin condition. The emergence of psoriasis has been linked to dysbiosis of the microbiota on the skin surface and an imbalance in the immunological microenvironment. In this study, we investigated the therapeutic impact of topical thymopentin (TP5) on imiquimod (IMQ)-induced psoriasis in mice, as well as the modulatory influence of TP5 on the skin immune milieu and the skin surface microbiota. Methods: The IMQ-induced psoriasis-like lesion mouse model was used to identify the targets and molecular mechanisms of TP5. Immunofluorescence was employed to identify differences in T-cell subset expression before and after TP5 therapy. Changes in the expression of NF-κB signaling pathway components were assessed using Western blotting (WB). 16S rRNA sequencing and network pharmacology were used to detect changes in the skin flora before and after TP5 administration. Results: In vivo, TP5 reduced IMQ-induced back inflammation in mice. H&E staining revealed decreased epidermal thickness and inflammatory cell infiltration with TP5. Masson staining revealed decreased epidermal and dermal collagen infiltration after TP5 administration. Immunohistochemistry showed that TP5 treatment dramatically reduced IL-17 expression. Results of the immunoinfiltration analyses showed psoriatic lesions with more T-cell subsets. According to the immunofluorescence results, TP5 dramatically declined the proportions of CD4+, Th17, ROR+, and CD8+ T cells. WB revealed that TP5 reduced NF-κB pathway expression in skin tissues from IMQ-induced psoriasis model mice. 16S rRNA sequencing revealed a significant increase in Burkholderia and Pseudomonadaceae_Pseudomonas and a significant decrease in Staphylococcaceae_Staphylococcus, Aquabacterium, Herbaspirillum, and Balneimonas. Firmicutes dominated the skin microbial diversity after TP5 treatment, while Bacteroidetes, Verrucomicrobia, TM7, Proteobacteria, Actinobacteria, Acidobacteria, Gemmatimonadetes, and other species dominated in the IMQ group. Conclusion: TP5 may treat psoriasis by modulating the epidermal flora, reducing NF-κB pathway expression, and influencing T-cell subsets.


Subject(s)
Imiquimod , Psoriasis , Skin , Thymopentin , Psoriasis/drug therapy , Psoriasis/chemically induced , Psoriasis/immunology , Psoriasis/pathology , Animals , Mice , Skin/drug effects , Skin/pathology , Imiquimod/pharmacology , Thymopentin/pharmacology , T-Lymphocyte Subsets/drug effects , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , Disease Models, Animal , Mice, Inbred BALB C , Female , Microbiota/drug effects , Male , Mice, Inbred C57BL
3.
Article in English | MEDLINE | ID: mdl-38985579

ABSTRACT

The effective repair of bone defects has long been a major challenge in clinical practice. Currently, research efforts mostly focus on achieving sufficiently good bone repair, with little attention paid to achieving both good and fast repair. However, achieving highly efficient (H-efficient) bone repair, which is both good and fast, can shorten the treatment cycle and facilitate rapid patient recovery. Therefore, the development of a H-efficient bone repair material is of significant importance. This study incorporated the previously developed osteoinductive photothermal agent (PTA) BPICT into printing paste to prepare a near-infrared (NIR)-responsive BPICT scaffold. Subsequently, the effects of photothermal therapy (PTT) on bone repair and drug release were assessed in vitro. To further validate the H-efficient bone repair properties of the BPICT scaffold, the scaffold was implanted into bone defects and its ability to promote bone repair in vivo was evaluated through radiology and histopathological analysis. The results indicated that compared to scaffolds containing only Icaritin (ICT), the BPICT scaffold can achieve PTT to promote bone repair through NIR irradiation, while also enabling the controlled release of ICT from the scaffold to enhance bone repair. Within the same observation period, the BPICT scaffold achieves more efficient bone repair than the ICT scaffold, significantly shortening the bone repair cycle while ensuring the effectiveness of bone repair. Therefore, the NIR-responsive scaffold based on PTT-mediated controlled release of bone growth factors represents a feasible solution for promoting H-efficient bone repair in the area of bone defects.

4.
Adv Healthc Mater ; : e2401118, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38979865

ABSTRACT

Bacteria, especially drug-resistant strains, can quickly cause wound infections, leading to delayed healing and fatal risk in clinics. With the growing need for alternative antibacterial approaches that rely less on antibiotics or eliminate their use altogether, a novel antibacterial hydrogel named Ovtgel is developed. Ovtgel is formulated by chemically crosslinking thiol-modified ovotransferrin (Ovt), a member of the transferrin family found in egg white, with olefin-modified agarose through thiol-ene click chemistry. Ovt is designed to sequester ferric ions essential for bacterial survival and protect wound tissues from damages caused by the reactive oxygen species (ROS) generated in Fenton reactions. Experimental data have shown that Ovtgel significantly enhances wound healing by inhibiting bacterial growth and shielding tissues from ROS-induced harms. Unlike traditional antibiotics, Ovtgel targets essential trace elements required for bacterial survival in the host environment, preventing the development of drug resistance in pathogenic bacteria. Ovtgel exhibits excellent biocompatibility due to the homology of Ovt to mammalian transferrin. This hydrogel has the potential to serve as an effective antibiotic-free solution for combating bacterial infections.

5.
Phys Chem Chem Phys ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38979978

ABSTRACT

Monitoring of reactive oxygen species (ROS), such as O2˙-, etc., in organisms is of great significance, not only for their essential role in biological processes, but their excessive production may also result in many diseases. Flavin (FL) is a fluorophore that naturally exists in flavoenzymes, and its fluorescent emission (FE) becomes negligible when reduced. This enables the application of FL derivatives as fluorescent sensors for ROS. We presented a theoretical investigation to address the impact of amino substitution on the photophysical properties of aminoflavins (AmFLs). Resulting from the interplay of electronic and positional effects, amination at C8 enhances the electronic coupling between the ground state and the first singlet excited state by enlarging the adiabatic energy change of the electronic transitions and the emission transition dipole moments, weakens the vibronic coupling by decreasing the contribution of isoalloxazine to the frontier molecular orbitals, redshifts the absorption band, and enhances the fluorescent emission drastically in 8AmFL. The theoretically estimated fluorescent emission intensity of 8AmFL is ∼40 times that of FL, suggesting its potential application as a fluorescent sensor.

6.
Expert Opin Ther Pat ; 34(8): 593-610, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38946486

ABSTRACT

INTRODUCTION: Focal adhesion kinase (FAK) is a cytoplasmic non-receptor tyrosine kinase over-expressed in various malignancies which is related to various cellular functions such as adhesion, metastasis and proliferation. AREAS COVERED: There is growing evidence that FAK is a promising therapeutic target for designing inhibitors by regulating the downstream pathways of FAK. Some potential FAK inhibitors have entered clinical phase research. EXPERT OPINION: FAK could be an effective target in medicinal chemistry research and there were a variety of FAKIs have been patented recently. Here, we updated an overview of design, synthesis and structure-activity relationship of chemotherapeutic FAK inhibitors (FAKIs) from 2017 until now based on our previous work. We hope our efforts can broaden the understanding of FAKIs and provide new ideas and insights for future cancer treatment from medicinal chemistry point of view.


Subject(s)
Antineoplastic Agents , Drug Design , Focal Adhesion Protein-Tyrosine Kinases , Neoplasms , Patents as Topic , Protein Kinase Inhibitors , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Neoplasms/drug therapy , Neoplasms/pathology , Neoplasms/enzymology , Animals , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/chemistry , Structure-Activity Relationship , Focal Adhesion Protein-Tyrosine Kinases/antagonists & inhibitors , Focal Adhesion Protein-Tyrosine Kinases/metabolism , Drug Development , Chemistry, Pharmaceutical , Molecular Targeted Therapy
7.
J Stroke Cerebrovasc Dis ; : 107846, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38986969

ABSTRACT

OBJECTIVE: To prospectively investigate the associations of healthy lifestyle factors on the risk of stroke and stroke subtypes, as studies exploring this relationship are limited in China. METHODS: The 22,661 participants in the prospective cohort study in Chongqing, China, aged 30-79 years and stroke-free at baseline completed follow-up from 2018 to 2022. We included seven healthy lifestyle factors, including non-smoking, non-excessive drinking, sufficient physical activity, healthy diet, sleep duration of 7-9 h/d, and standard range of body mass index and waist-to-hip ratio. The healthy lifestyle score was calculated based on the number of healthy lifestyle factors. RESULTS: Compared with participants who had scores ≤2, participants with scores ≥6 had an HRs (95% CIs) of 0.56 (0.34, 0.92) for total stroke and 0.53 (0.30, 0.93) for ischemic stroke. For every 1-point increase in healthy lifestyle scores, the HRs (95% CIs) for total stroke and ischemic stroke was 0.86 (0.78, 0.95) and 0.86 (0.77, 0.96), respectively. CONCLUSIONS: Maintaining multiple healthy lifestyle factors can significantly reduce the risk of stroke. As the number of healthy lifestyle factors increased, the stroke risk gradually decreased. Our findings emphasize the significance of comprehensive lifestyle interventions.

8.
Mil Med Res ; 11(1): 46, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38992778

ABSTRACT

BACKGROUND: Subarachnoid hemorrhage (SAH) is a subtype of hemorrhagic stroke characterized by high mortality and low rates of full recovery. This study aimed to investigate the epidemiological characteristics of SAH between 1990 and 2021. METHODS: Data on SAH incidence, mortality, and disability-adjusted life-years (DALYs) from 1990 to 2021 were obtained from the Global Burden of Disease Study (GBD) 2021. Estimated annual percentage changes (EAPCs) were calculated to evaluate changes in the age-standardized rate (ASR) of incidence and mortality, as well as trends in SAH burden. The relationship between disease burden and sociodemographic index (SDI) was also analyzed. RESULTS: In 2021, the incidence of SAH was found to be 37.09% higher than that in 1990; however, the age-standardized incidence rates (ASIRs) showed a decreased [EAPC: -1.52; 95% uncertainty interval (UI) -1.66 to -1.37]. Furthermore, both the number and rates of deaths and DALYs decreased over time. It was observed that females had lower rates compared to males. Among all regions, the high-income Asia Pacific region exhibited the highest ASIR (14.09/100,000; 95% UI 12.30/100,000 - 16.39/100,000) in 2021, with an EPAC for ASIR < 0 indicating decreasing trend over time for SAH ASIR. Oceania recorded the highest age-standardized mortality rates (ASMRs) and age-standardized DALYs rates among all regions in 2021 at values of respectively 8.61 (95% UI 6.03 - 11.95) and 285.62 (95% UI 209.42 - 379.65). The burden associated with SAH primarily affected individuals aged between 50 - 69 years old. Metabolic risks particularly elevated systolic blood pressure were identified as the main risk factors contributing towards increased disease burden associated with SAH when compared against environmental or occupational behavioral risks evaluated within the GBD framework. CONCLUSIONS: The burden of SAH varies by gender, age group, and geographical region. Although the ASRs have shown a decline over time, the burden of SAH remains significant, especially in regions with middle and low-middle SDI levels. High systolic blood pressure stands out as a key risk factor for SAH. More specific supportive measures are necessary to alleviate the global burden of SAH.


Subject(s)
Global Burden of Disease , Subarachnoid Hemorrhage , Humans , Subarachnoid Hemorrhage/epidemiology , Male , Female , Incidence , Middle Aged , Aged , Adult , Global Burden of Disease/trends , Disability-Adjusted Life Years/trends , Global Health/statistics & numerical data , Aged, 80 and over
9.
Neural Regen Res ; 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38993127

ABSTRACT

ABSTRACT: Parkinson's disease is the second most common progressive neurodegenerative disorder, and few reliable biomarkers are available to track disease progression. The proteins, DNA, mRNA, and lipids carried by exosomes reflect intracellular changes, and thus can serve as biomarkers for a variety of conditions. In this study, we investigated alterations in the protein content of plasma exosomes derived from patients with Parkinson's disease and the potential therapeutic roles of these proteins in Parkinson's disease. Using a tandem mass tag-based quantitative proteomics approach, we characterized the proteomes of plasma exosomes derived from individual patients, identified exosomal protein signatures specific to patients with Parkinson's disease, and identified N-acetyl-alpha-glucosaminidase as a differentially expressed protein. N-acetyl-alpha-glucosaminidase expression levels in exosomes from the plasma of patients and healthy controls were validated by enzyme-linked immunosorbent assay and western blot. The results demonstrated that the exosomal N-acetyl-alpha-glucosaminidase concentration was not only lower in Parkinson's disease, but also decreased with increasing Hoehn-Yahr stage, suggesting that N-acetyl- alpha-glucosaminidase could be used to rapidly evaluate Parkinson's disease severity. Furthermore, western blot and immunohistochemistry analysis showed that N-acetyl-alpha-glucosaminidase levels were markedly reduced both in cells treated with methyl-4-phenylpyridinium (MPP+) and cells overexpressing a-synuclein (α-syn) compared with control cells. Additionally, N-acetyl-alpha-glucosaminidase overexpression significantly increased cell viability and inhibited α-syn expression in MPP+-treated cells. Taken together, our findings demonstrate for the first time that exosomal N-acetyl-alpha-glucosaminidase may serve as a biomarker for Parkinson's disease diagnosis, and that N-acetyl-alpha- glucosaminidase may reduce α-syn expression and MPP+-induced neurotoxicity, thus providing a new therapeutic target for Parkinson's disease.

10.
J Gastrointest Oncol ; 15(3): 1165-1178, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38989440

ABSTRACT

Background: Pancreatic cancer is a highly aggressive malignancy with poor prognosis, and there is an urgent need to understand its molecular mechanisms for early diagnosis and treatment. Despite surgical resection being the only effective treatment, most patients are diagnosed at an advanced stage, missing the optimal window for therapy. Identifying novel biomarkers is crucial for prognostic assessment, treatment planning, and early intervention. Ephrin A4 (EFNA4), a member of the receptor tyrosine kinase family, is involved in vascular and epithelial development via regulation of cell migration and rejection. However, the role of EFNA4 in pancreatic cancer has not been reported. Therefore, our study aimed to clarify the role of EFNA4 in pancreatic cancer through bioinformatics analysis and vitro experiments. Methods: The expression of EFNA4 and its potential value as a diagnostic and prognostic biomarker in pancreatic cancer was analyzed using data from The Cancer Genome Atlas (TCGA) and the Gene Expression Profiling Interactive Analysis (GEPIA) database. According to the expression level of EFNA4, patients were divided into high expression group and low expression group, and the correlation between overall survival (OS) and disease-free survival (DFS) with different expression levels of EFNA4 and clinical parameters were analyzed. Subsequently, reverse-transcription quantitative polymerase chain reaction (RT-qPCR) was performed to detect EFNA4 expression. The proliferation, invasion, and cloning ability of the cells were detected via Cell Counting Kit 8 (CCK8), Transwell, and plate cloning assays, respectively. Results: EFNA4 is highly expressed in pancreatic cancer, and upregulation of EFNA4 is associated with poor prognosis. In this study, EFNA4 expression was correlated with T stage and TNM (tumor-node-metastasis) stage of pancreatic cancer, and the median survival time and progression-free survival (PFS) were worse in those with high EFNA4 expression (394 days) than in those with low expression (525 days) [hazard ratio (HR): 1.47, 95% confidence interval (CI): 1.00-2.16, P=0.047]. In addition, EFNA4 was also found to be involved in the regulation of signal pathways such as cell adhesion, cyclic AMP, insulin secretion, pancreatic secretion, and protein digestion and absorption. In vitro experiments demonstrated that EFNA4 knockdown significantly inhibited the proliferation, cloning ability, and invasiveness of the PANC-1 and SW1990 pancreatic cancer cell lines. Conclusions: The abnormal expression of EFNA4 in pancreatic cancer is associated with poor prognosis. Knockout of EFNA4 gene could significantly inhibit the proliferation and invasion of pancreatic cancer cells. Therefore, EFNA4 may be one of the molecular targets for poor prognosis of patients with pancreatic cancer.

11.
Front Oncol ; 14: 1364608, 2024.
Article in English | MEDLINE | ID: mdl-38978734

ABSTRACT

Background: Breast cancer (BC) in adolescents and young adults (AYAs, aged 15-39 years), remains inadequately understood. The incidence of BC in AYAs has been steadily increasing, making it the second leading cause of cancer-related mortality among females aged 0-39 globally. This study aimed to elucidate the clinical characteristics and long-term outcomes of AYAs and older adults (OAs, aged > 39 years) with BC who underwent surgery. Methods: From January 2011 to June 2017, BC patients who underwent surgery were enrolled in this study and divided into AYA group and OA group. Clinical characteristics, recurrence-free survival (RFS), and overall survival (OS) were compared between these two groups, both before and after propensity score matching (PSM). Univariate and multivariate Cox proportional hazard regression analyses were performed to assess the influence of age on OS and RFS. Results: Compared to the OA group, the AYA group exhibited a younger age at menarche (p < 0.001), a lower prevalence of menopausal status (p < 0.001), a reduced occurrence of comorbid conditions (p < 0.001), fewer instances of undergoing mastectomy (p = 0.031), a higher incidence of Triple-Negative Breast Cancer (TNBC) (p = 0.046), and elevated Ki-67 levels (p = 0.036). In terms of prognostic outcomes, within the study cohort, AYAs had a higher mortality rate and poorer long-term survival compared to OAs, both before and after PSM. In the PSM cohort, AYAs experienced a significantly shorter median OS (p < 0.001) and RFS (p < 0.001). Young age (15-39 years) emerged as an independent risk factor for OS (HR 2.659, 95% CI 1.385-5.106, p = 0.003) and RFS (HR 3.235, 95% CI 2.085-5.022, p < 0.001) in BC patients following surgery. Conclusion: Significant differences were identified in the clinicopathological characteristics between AYA and OA patients with BC. In comparison to OA patients, AYA patients exhibited a less favorable long-term prognosis, with young age emerging as an independent prognostic risk factor for both OS and RFS in BC patients following surgery. Further investigations are warranted to develop age-specific therapeutic approaches for AYA BC patients.

12.
Nat Cell Biol ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38977847

ABSTRACT

Currently, the dynamic accessible elements that determine regulatory programs responsible for the unique identity and function of each cell type during zebrafish embryogenesis lack detailed study. Here we present SPATAC-seq: a split-pool ligation-based assay for transposase-accessible chromatin using sequencing. Using SPATAC-seq, we profiled chromatin accessibility in more than 800,000 individual nuclei across 20 developmental stages spanning the sphere stage to the early larval protruding mouth stage. Using this chromatin accessibility map, we identified 604 cell states and inferred their developmental relationships. We also identified 959,040 candidate cis-regulatory elements (cCREs) and delineated development-specific cCREs, as well as transcription factors defining diverse cell identities. Importantly, enhancer reporter assays confirmed that the majority of tested cCREs exhibited robust enhanced green fluorescent protein expression in restricted cell types or tissues. Finally, we explored gene regulatory programs that drive pigment and notochord cell differentiation. Our work provides a valuable open resource for exploring driver regulators of cell fate decisions in zebrafish embryogenesis.

13.
Nat Cell Biol ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38977846

ABSTRACT

Organogenesis is a highly complex and precisely regulated process. Here we profiled the chromatin accessibility in >350,000 cells derived from 13 mouse embryos at four developmental stages from embryonic day (E) 10.5 to E13.5 by SPATAC-seq in a single experiment. The resulting atlas revealed the status of 830,873 candidate cis-regulatory elements in 43 major cell types. By integrating the chromatin accessibility atlas with the previous transcriptomic dataset, we characterized cis-regulatory sequences and transcription factors associated with cell fate commitment, such as Nr5a2 in the development of gastrointestinal tract, which was preliminarily supported by the in vivo experiment in zebrafish. Finally, we integrated this atlas with the previous single-cell chromatin accessibility dataset from 13 adult mouse tissues to delineate the developmental stage-specific gene regulatory programmes within and across different cell types and identify potential molecular switches throughout lineage development. This comprehensive dataset provides a foundation for exploring transcriptional regulation in organogenesis.

14.
Int J Surg ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38954664

ABSTRACT

BACKGROUND: Liver failure remains a critical clinical challenge with limited treatment options. Cross-circulation, the establishment of vascular connections between individuals, has historically been explored as a potential supportive therapy but with limited success. This study investigated the feasibility of combining cross-circulation with a rapidly deployable veno-venous bypass (VVB) graft for multi-organ support in a rat model of total hepatectomy, representing the most severe form of liver failure. MATERIALS AND METHODS: A Y-shaped VVB graft was fabricated using coaxial electrospinning of PLCL/heparin nanofibers and magnetic rings for rapid anastomosis. After total hepatectomy in rats, the VVB graft was implanted to divert blood flow. Cross-circulation was then established between anhepatic and normal host rats. Hemodynamics, biochemical parameters, blood gases, and survival were analyzed across three groups: hepatectomy with blocked vessels (block group), hepatectomy with VVB only (VVB group), and hepatectomy with VVB and cross-circulation (VVB/cross-circulation group). RESULTS: The VVB graft exhibited suitable mechanical properties and hemocompatibility. VVB rapidly restored hemodynamic stability and mitigated abdominal congestion post-hepatectomy. Cross-circulation further ameliorated liver dysfunction, metabolic derangements, and coagulation disorders in anhepatic rats, significantly prolonging survival compared to the VVB group (mean 6.56±0.58 vs 4.05±0.51 h, P<0.05) and the block group (mean 1.01±0.05 h, P<0.05). CONCLUSION: Combining cross-circulation with a rapidly deployed VVB graft provided effective multi-organ biosystemic support in a rat model of total hepatectomy, substantially improving the biochemical status and survival time. This approach holds promise for novel liver failure therapies and could facilitate liver transplantation procedures.

15.
Bioconjug Chem ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38954775

ABSTRACT

The chemical synthesis of homogeneously ubiquitylated histones is a powerful approach to decipher histone ubiquitylation-dependent epigenetic regulation. Among the various methods, α-halogen ketone-mediated conjugation chemistry has recently been an attractive strategy to generate single-monoubiquitylated histones for biochemical and structural studies. Herein, we report the use of this strategy to prepare not only dual- and even triple-monoubiquitylated histones but also diubiquitin-modified histones. We were surprised to find that the synthetic efficiencies of multi-monoubiquitylated histones were comparable to those of single-monoubiquitylated ones, suggesting that this strategy is highly tolerant to the number of ubiquitin monomers installed onto histones. The facile generation of a series of single-, dual-, and triple-monoubiquitylated H3 proteins enabled us to evaluate the influence of ubiquitylation patterns on the binding of DNA methyltransferase 1 (DNMT1) to nucleosomes. Our study highlights the potential of site-specific conjugation chemistry to generate chemically defined histones for epigenetic studies.

16.
Inorg Chem ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38954791

ABSTRACT

We report the structural defects in Zr-metal-organic framework (MOFs) for achieving highly efficient CO2 reduction under visible light irradiation. A series of defective Zr-MOF-X (X = 160, 240, 320, or 400) are synthesized by acid-regulated defect engineering. Compared to pristine defect-free Zr-MOF (NNU-28), N2 uptake increases for Zr-MOF-X synthesized with the HAc modulator, producing a larger pore space and Brunauer-Emmett-Teller surface area. The pore size distribution demonstrates that defective Zr-MOF-X exhibits mesoporous structures. Electrochemistry tests show that defective Zr-MOF-X possesses a more negative reduction potential and a higher photocurrent responsive signal than that of pristine NNU-28. Consequently, the defective samples exhibit a significantly higher efficiency in the photoreduction of CO2 to formate. Transient absorption spectroscopies manifest that structural defects modulate the excited-state behivior of Zr-MOF-X and improve the photogenerated charge separation of Zr-MOF-X. Furthermore, electron paramagnetic resonance and in-suit X-ray photoelectron spectroscopy provide additional evidence of the high photocatalytic performance exhibited by defective Zr-MOF-X. Results demonstrate that structural defects in Zr-MOF-X also improve the charge transfer, producing abundant Zr(III) catalytically active sites, exhibiting a slower decay process than defect-free Zr-MOF. The long-lifetime Zr(III) species in defective Zr-MOF-X are fully exposed to a high-concentration CO2 atmosphere, thereby enhancing the photocatalytic efficiency of CO2 reduction.

17.
Se Pu ; 42(7): 669-680, 2024 Jul.
Article in Chinese | MEDLINE | ID: mdl-38966975

ABSTRACT

Mass spectrometry imaging (MSI) is a promising method for characterizing the spatial distribution of compounds. Given the diversified development of acquisition methods and continuous improvements in the sensitivity of this technology, both the total amount of generated data and complexity of analysis have exponentially increased, rendering increasing challenges of data postprocessing, such as large amounts of noise, background signal interferences, as well as image registration deviations caused by sample position changes and scan deviations, and etc. Deep learning (DL) is a powerful tool widely used in data analysis and image reconstruction. This tool enables the automatic feature extraction of data by building and training a neural network model, and achieves comprehensive and in-depth analysis of target data through transfer learning, which has great potential for MSI data analysis. This paper reviews the current research status, application progress and challenges of DL in MSI data analysis, focusing on four core stages: data preprocessing, image reconstruction, cluster analysis, and multimodal fusion. The application of a combination of DL and mass spectrometry imaging in the study of tumor diagnosis and subtype classification is also illustrated. This review also discusses trends of development in the future, aiming to promote a better combination of artificial intelligence and mass spectrometry technology.


Subject(s)
Deep Learning , Image Processing, Computer-Assisted , Mass Spectrometry , Mass Spectrometry/methods , Image Processing, Computer-Assisted/methods , Humans , Data Analysis
18.
Environ Sci Technol ; 58(26): 11675-11684, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38952298

ABSTRACT

Excessive anthropogenic phosphorus (P) emissions put constant pressure on aquatic ecosystems. This pressure can be quantified as the freshwater eutrophication potential (FEP) by linking P emissions, P fate in environmental compartments, and the potentially disappeared fraction of species due to increase of P concentrations in freshwater. However, previous fate modeling on global and regional scales is mainly based on the eight-direction algorithm without distinguishing pollution sources. The algorithm fails to characterize the fate paths of point-source emissions via subsurface pipelines and wastewater treatment infrastructure, and exhibits suboptimal performance in accounting for multidirectional paths caused by river bifurcations, especially in flat terrains. Here we aim to improve the fate modeling by incorporating various fate paths and addressing multidirectional scenarios. We also update the P estimates by complementing potential untreated point-source emissions (PSu). The improved method is examined in a rapidly urbanizing area in Taihu Lake Basin, China in 2017 at a spatial resolution of 100 m × 100 m. Results show that the contribution of PSu on FEP (62.6%) is greater than that on P emissions (58.5%). The FEP is more spatially widely distributed with the improved fate modeling, facilitating targeted regulatory strategies tailored to local conditions.


Subject(s)
Eutrophication , Fresh Water , Phosphorus , Fresh Water/chemistry , Models, Theoretical , Environmental Monitoring , China , Water Pollutants, Chemical/analysis , Ecosystem
19.
Front Microbiol ; 15: 1394332, 2024.
Article in English | MEDLINE | ID: mdl-38946904

ABSTRACT

Introduction: As a symbiotic probiotic for the host, Clostridium butyricum (CB) has the potential to strengthen the body's immune system and improve intestinal health. However, the probiotic mechanism of CB is not completely understood. The Clostridium butyricum CBX 2021 strain isolated by our team from a health pig independently exhibits strong butyric acid production ability and stress resistance. Therefore, this study comprehensively investigated the efficacy of CBX 2021 in pigs and its mechanism of improving pig health. Methods: In this study, we systematically revealed the probiotic effect and potential mechanism of the strain by using various methods such as microbiome, metabolites and transcriptome through animal experiments in vivo and cell experiments in vitro. Results: Our in vivo study showed that CBX 2021 improved growth indicators such as daily weight gain in weaned piglets and also reduced diarrhea rates. Meanwhile, CBX 2021 significantly increased immunoglobulin levels in piglets, reduced contents of inflammatory factors and improved the intestinal barrier. Subsequently, 16S rRNA sequencing showed that CBX 2021 treatment implanted more butyric acid-producing bacteria (such as Faecalibacterium) in piglets and reduced the number of potentially pathogenic bacteria (like Rikenellaceae RC9_gut_group). With significant changes in the microbial community, CBX 2021 improved tryptophan metabolism and several alkaloids synthesis in piglets. Further in vitro experiments showed that CBX 2021 adhesion directly promoted the proliferation of a porcine intestinal epithelial cell line (IPEC-J2). Moreover, transcriptome analysis revealed that bacterial adhesion increased the expression of intracellular G protein-coupled receptors, inhibited the Notch signaling pathway, and led to a decrease in intracellular pro-inflammatory molecules. Discussion: These results suggest that CBX 2021 may accelerate piglet growth by optimizing the intestinal microbiota, improving metabolic function and enhancing intestinal health.

20.
Talanta ; 278: 126524, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38986308

ABSTRACT

The high efficient surface-enhanced Raman scatterring (SERS) methods to detect thiacloprid and imidacloprid were established using ZIF-8-wrapped Ag nanoparticles (AgNPs) modified with ß-cyclodextrin (ß-CD). The substrate of ZIF-8/ß-CD@AgNPs was characterized by ultraviolet visible spectra (UV-vis), thermogravimetric analysis (TGA), X-ray diffraction (XRD), transmission electron microscopy (TEM) and scanning transmission electron microscopy (STEM). The interaction between the substrate and thiacloprid/imidacloprid was also explored. The optimum measurement conditions were obtained by response surface model based on single-factor experiments. Enhancement factors (EFs) of thiacloprid and imidacloprid were respectively 2.29 × 106 and 2.60 × 106. A good linearity between the scattering intensity and the concentration of thiacloprid/imidacloprid within 3-1000 nmol L-1/6-400 nmol L-1 was established. The interference experiments indicated that the methods had good selectivity. The SERS methods were successfully applied to detect thiacloprid and imidacloprid in several vegetables samples. The recoveries ranged from 95.5 % to 105 % (n = 5). The detection limits (LODs) (S/N = 3) for thiacloprid and imidacloprid were 1.50 and 0.83 nmol L-1, respectively.

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