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1.
Hum Exp Toxicol ; 43: 9603271241282584, 2024.
Article in English | MEDLINE | ID: mdl-39240701

ABSTRACT

OBJECTIVE: Environmental factors such as noise and music can significantly impact physiological responses, including inflammation. This study explored how environmental factors like noise and music affect lipopolysaccharide (LPS)-induced inflammation, with a focus on systemic and organ-specific responses. MATERIALS AND METHODS: 24 Wistar rats were divided into four groups (n = 6 per group): Control group, LPS group, noise-exposed group, and music-exposed group. All rats, except for the Control group, received 10 mg/kg LPS intraperitoneally. The rats in the noise-exposed group were exposed to 95 dB noise, and the music-exposed group listened to Mozart's K. 448 music (65-75 dB) for 1 h daily over 7 days. An enzyme-linked immunosorbent assay was utilized to detect the levels of inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß), in serum and tissues (lung, liver, and kidney). Western blot examined the phosphorylation levels of nuclear factor-κB (NF-κB) p65 in organ tissues. RESULTS: Compared with the Control group, LPS-induced sepsis rats displayed a significant increase in the levels of TNF-α and IL-1ß in serum, lung, liver, and kidney tissues, as well as a remarkable elevation in the p-NF-κB p65 protein expression in lung, liver, and kidney tissues. Noise exposure further amplified these inflammatory markers, while music exposure reduced them in LPS-induced sepsis rats. CONCLUSION: Noise exposure exacerbates inflammation by activating the NF-κB pathway, leading to the up-regulation of inflammatory markers during sepsis. On the contrary, music exposure inhibits NF-κB signaling, indicating a potential therapeutic effect in reducing inflammation.


Subject(s)
Lipopolysaccharides , Music , Noise , Rats, Wistar , Sepsis , Animals , Lipopolysaccharides/toxicity , Sepsis/immunology , Sepsis/complications , Noise/adverse effects , Male , Interleukin-1beta/blood , Tumor Necrosis Factor-alpha/blood , Tumor Necrosis Factor-alpha/metabolism , Lung/immunology , Lung/metabolism , Inflammation , Liver/metabolism , Rats , Kidney/metabolism , NF-kappa B/metabolism , Cytokines/blood , Cytokines/metabolism
2.
J Org Chem ; 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39252666

ABSTRACT

A palladium-catalyzed [4 + 1] annulation of N-arylimidoyl chlorides with ß-keto esters has been developed. In the presence of Pd(OAc)2, PCy3, and K3PO4, a variety of fluoalkyl-containing N-arylimidoyl chlorides smoothly underwent the cascade C-H imidoylation/deacylative Heck-type reactions to afford biologically important 2-fluoroalkyl indoles in moderate to good yields.

3.
Sci Rep ; 14(1): 20879, 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39242594

ABSTRACT

Underground cavities have complex spatial structures and geological settings, their arrangement is dense and crisscrossed. The construction system involves multiple work surfaces, levels, and processes. The close integration of construction simulation with actual production conditions is crucial for enhancing the guidance that simulation results provide for practical engineering. Therefore, from the perspective of optimizing construction organization and management, this article comprehensively considers various factors in the construction process, innovatively introduces the principle of production line balance and the concept of rule cycle, and combines technology and management, an underground cavities construction simulation system (UCCSS) is developed. In UCCSS, a hierarchical model is built and calculation are performed on models with different construction methods by modifying the parameters as per the actual engineering characteristics. The simulation results are comprehensively analysed to determine the optimal construction programme. An application case is proposed based on the construction organisation design of the long and parallel diversion tunnels at the CB Hydropower Station. The results show that the system has good practicality and credibility and can provide guidance for the construction organisation design of underground cavities with various features.

4.
Cell Commun Signal ; 22(1): 416, 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39192337

ABSTRACT

Bone cancer pain (BCP) represents a prevalent symptom among cancer patients with bone metastases, yet its underlying mechanisms remain elusive. This study investigated the transcriptional regulation mechanism of Kv7(KCNQ)/M potassium channels in DRG neurons and its involvement in the development of BCP in rats. We show that HDAC2-mediated transcriptional repression of kcnq2/kcnq3 genes, which encode Kv7(KCNQ)/M potassium channels in dorsal root ganglion (DRG), contributes to the sensitization of DRG neurons and the pathogenesis of BCP in rats. Also, HDAC2 requires the formation of a corepressor complex with MeCP2 and Sin3A to execute transcriptional regulation of kcnq2/kcnq3 genes. Moreover, EREG is identified as an upstream signal molecule for HDAC2-mediated kcnq2/kcnq3 genes transcription repression. Activation of EREG/EGFR-ERK-Runx1 signaling, followed by the induction of HDAC2-mediated transcriptional repression of kcnq2/kcnq3 genes in DRG neurons, leads to neuronal hyperexcitability and pain hypersensitivity in tumor-bearing rats. Consequently, the activation of EREG/EGFR-ERK-Runx1 signaling, along with the subsequent transcriptional repression of kcnq2/kcnq3 genes by HDAC2 in DRG neurons, underlies the sensitization of DRG neurons and the pathogenesis of BCP in rats. These findings uncover a potentially targetable mechanism contributing to bone metastasis-associated pain in cancer patients.


Subject(s)
Bone Neoplasms , Cancer Pain , ErbB Receptors , Ganglia, Spinal , Histone Deacetylase 2 , KCNQ2 Potassium Channel , Animals , Histone Deacetylase 2/metabolism , Histone Deacetylase 2/genetics , KCNQ2 Potassium Channel/genetics , KCNQ2 Potassium Channel/metabolism , Ganglia, Spinal/metabolism , Ganglia, Spinal/pathology , Bone Neoplasms/genetics , Bone Neoplasms/metabolism , Bone Neoplasms/secondary , Bone Neoplasms/pathology , Rats , Cancer Pain/genetics , Cancer Pain/metabolism , Cancer Pain/pathology , ErbB Receptors/metabolism , ErbB Receptors/genetics , KCNQ3 Potassium Channel/genetics , KCNQ3 Potassium Channel/metabolism , Transcription, Genetic , Methyl-CpG-Binding Protein 2/genetics , Methyl-CpG-Binding Protein 2/metabolism , Sin3 Histone Deacetylase and Corepressor Complex/genetics , Signal Transduction/genetics , Core Binding Factor Alpha 2 Subunit/genetics , Core Binding Factor Alpha 2 Subunit/metabolism , Humans , Female , Extracellular Signal-Regulated MAP Kinases/metabolism , Repressor Proteins/genetics , Repressor Proteins/metabolism , Rats, Sprague-Dawley , MAP Kinase Signaling System/genetics
5.
Int J Colorectal Dis ; 39(1): 99, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38926205

ABSTRACT

PURPOSE: Achieving a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (NCRT) remains a challenge for most patients with rectal cancer. Exploring the potential of combining NCRT with immunotherapy or targeted therapy for those achieving a partial response (PR) offers a promising avenue to enhance treatment efficacy. This study investigated the impact of NCRT on the tumor microenvironment in locally advanced rectal cancer (LARC) patients who exhibited a PR. METHODS: This was a retrospective, observational study. Five patients demonstrating a PR after neoadjuvant treatment for LARC were enrolled in the study. Biopsy samples before treatment and resected specimens after treatment were stained with a panel of 26 antibodies targeting various immune and tumor-related markers, each labeled with distinct metal tags. The labeled samples were then analyzed using the Hyperion imaging system. RESULTS: Heterogeneity within the tumor microenvironment was observed both before and after NCRT. Notably, tumor-associated macrophages, CD4 + T cells, CD8 + T cells, CD56 + natural killer cells, tumor-associated neutrophils, cytokeratin, and E-cadherin exhibited slight increase in abundance within the tumor microenvironment following treatment (change ratios = 0.78, 0.2, 0.27, 0.32, 0.17, 0.46, 0.32, respectively). Conversely, the number of CD14 + monocytes, CD19 + B cells, CD45 + CD4 + T cells, collagen I, α-smooth muscle actin, vimentin, and ß-catenin proteins displayed significant decreases post-treatment (change ratios = 1.73, 1.92, 1.52, 1.25, 1.52, 1.12, 2.66, respectively). Meanwhile, Foxp3 + regulatory cells demonstrated no significant change (change ratio = 0.001). CONCLUSIONS: NCRT has diverse effects on various components of the tumor microenvironment in LARC patients who achieve a PR after treatment. Leveraging combination therapies may optimize treatment outcomes in this patient population.


Subject(s)
Neoadjuvant Therapy , Rectal Neoplasms , Tumor Microenvironment , Humans , Rectal Neoplasms/therapy , Rectal Neoplasms/pathology , Rectal Neoplasms/drug therapy , Male , Female , Middle Aged , Aged , Chemoradiotherapy , Treatment Outcome , Retrospective Studies
6.
CNS Neurosci Ther ; 30(4): e14703, 2024 04.
Article in English | MEDLINE | ID: mdl-38572816

ABSTRACT

INTRODUCTION: Painful diabetic neuropathy (PDN) is a common complication of diabetes. Previous studies have implicated that mitochondrial dysfunction plays a role in the development of PDN, but its pathogenesis and mechanism have not been fully investigated. METHODS: In this study, we used high-fat diet/low-dose streptozotocin-induced rats as a model of type 2 diabetes mellitus. Behavioral testing, whole-cell patch-clamp recordings of dorsal root ganglion (DRG) neurons, and complex sensory nerve conduction velocity studies were used to assess peripheral neuropathy. Mitochondrial membrane potential (MMP), ATP, tissue reactive oxygen species, and transmission electron microscopy were used to evaluate the function and morphology of mitochondria in DRG. Real-time PCR, western blot, and immunofluorescence were performed to investigate the mechanism. RESULTS: We found that damaged mitochondria were accumulated and mitophagy was inhibited in PDN rats. The expression of sirtuin 3 (SIRT3), which is an NAD+-dependent deacetylase in mitochondria, was inhibited. Overexpression of SIRT3 in DRG neurons by intrathecally administered LV-SIRT3 lentivirus ameliorated neurological and mitochondrial dysfunctions. This was evidenced by the reversal of allodynia and nociceptor hyperexcitability, as well as the restoration of MMP and ATP levels. Overexpression of SIRT3 restored the inhibited mitophagy by activating the FoxO3a-PINK1-Parkin signaling pathway. The effects of SIRT3 overexpression, including the reversal of allodynia and nociceptor hyperexcitability, the improvement of impaired mitochondria and mitophagy, and the restoration of PINK1 and Parkin expression, were counteracted when FoxO3a siRNA was intrathecally injected. CONCLUSION: These results showed that SIRT3 overexpression ameliorates PDN via activation of FoxO3a-PINK1-Parkin-mediated mitophagy, suggesting that SIRT3 may become an encouraging therapeutic strategy for PDN.


Subject(s)
Diabetes Mellitus, Type 2 , Diabetic Neuropathies , Sirtuin 3 , Animals , Rats , Adenosine Triphosphate/pharmacology , Hyperalgesia , Mitophagy , Protein Kinases/metabolism , Signal Transduction , Sirtuin 3/genetics , Sirtuin 3/metabolism , Ubiquitin-Protein Ligases/genetics
7.
Brief Bioinform ; 25(2)2024 Jan 22.
Article in English | MEDLINE | ID: mdl-38517696

ABSTRACT

With the rapid development of single-molecule sequencing (SMS) technologies, the output read length is continuously increasing. Mapping such reads onto a reference genome is one of the most fundamental tasks in sequence analysis. Mapping sensitivity is becoming a major concern since high sensitivity can detect more aligned regions on the reference and obtain more aligned bases, which are useful for downstream analysis. In this study, we present pathMap, a novel k-mer graph-based mapper that is specifically designed for mapping SMS reads with high sensitivity. By viewing the alignment chain as a path containing as many anchors as possible in the matched k-mer graph, pathMap treats chaining as a path selection problem in the directed graph. pathMap iteratively searches the longest path in the remaining nodes; more candidate chains with high quality can be effectively detected and aligned. Compared to other state-of-the-art mapping methods such as minimap2 and Winnowmap2, experiment results on simulated and real-life datasets demonstrate that pathMap obtains the number of mapped chains at least 11.50% more than its closest competitor and increases the mapping sensitivity by 17.28% and 13.84% of bases over the next-best mapper for Pacific Biosciences and Oxford Nanopore sequencing data, respectively. In addition, pathMap is more robust to sequence errors and more sensitive to species- and strain-specific identification of pathogens using MinION reads.


Subject(s)
High-Throughput Nucleotide Sequencing , Nanopore Sequencing , Sequence Analysis, DNA/methods , High-Throughput Nucleotide Sequencing/methods , Genome , Software , Algorithms
8.
Zhongguo Gu Shang ; 37(3): 278-80, 2024 Mar 25.
Article in Chinese | MEDLINE | ID: mdl-38515415

ABSTRACT

OBJECTIVE: To explore feasibility of 3D metal printing technology combined with virtual design proximal clavicle anatomical plate. METHODS: A 52-year-old male healthy volunteer was retrospectively selected to design proximal clavicle anatomical plate system by using Mimics15.01,NX12.0 and other software. STL data were input into 3D printer to print 1:1 clavicle model and proximal clavicle anatomical plate. The fit of the plate was tested in vitro and the accuracy of screw position was evaluated by imaging. Printing time of model,nail path design and fabrication time of the anatomical plate at proximal clavicle were recorded. RESULTS: The 3D metal printing proximal clavicle anatomical plate fitted well to clavicle model,orientation of proximal clavicle locking screw was accurate,and X-ray and CT scan showed the screw position was good. Printing time of model,the time of nail path design,and the time of making anatomical plate of proximal clavicle were 120,15 and 300 min respectively. CONCLUSION: The proximal clavicular anatomical plate system based on 3D metal printing technology could achieve good lamination of proximal clavicular fracture plate and precise screw placement,providing a new and accurate surgical method for the treatment of the proximal clavicular fracture.


Subject(s)
Fracture Fixation, Internal , Fractures, Bone , Male , Humans , Middle Aged , Fracture Fixation, Internal/methods , Retrospective Studies , Clavicle/diagnostic imaging , Clavicle/surgery , Fractures, Bone/diagnostic imaging , Fractures, Bone/surgery , Printing, Three-Dimensional , Bone Plates
9.
Huan Jing Ke Xue ; 45(2): 862-872, 2024 Feb 08.
Article in Chinese | MEDLINE | ID: mdl-38471925

ABSTRACT

Calcium-containing biochar (ES-BC) was prepared by pyrolyzing eggshell and kitchen wastes, and the ES-BC composite was used to remove phosphate (marked as ES-BC/P). Based on the high affinity of phosphate and carbonate to lead, the ES-BC/P was then used to remove lead from the water. The results showed that, in the appropriate dosage, ES-BC/P could remove lead efficiently at different initial concentrations (1-100 mg·L-1), and the removal efficiency could reach to 99%. Meanwhile, the release of phosphorus could be ignored after the reaction. As ES-BC/P was alkaline, and the lead-containing solution was weakly acidic, the addition of ES-BC/P could adjust the pH of the system automatically. The reaction kinetics and isotherm experiments showed that the lead removal by ES-BC/P was mainly monolayer chemisorption with a maximum adsorption capacity of 493.12 mg·g-1 (318 K). The characterization results showed that lead was mainly removed through the ion exchanges of Pb2+ in the solution with Ca2+ in ES-BC/P. Then, the Pb2+ combined with CO32- and PO42- to form many precipitates, including Pb5(PO4)3OH, Pb10(PO4)6(OH)2, PbCO3, and Pb3(CO3)2(OH)2. In summary, the ES-BC/P material could achieve the efficient removal of lead from the water, thereby realizing the resource utilization of the wastes.

10.
J Pain ; 25(8): 104495, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38354968

ABSTRACT

Exacerbation of pain by chronic stress and comorbidity of pain with stress-related disorders such as depression and post-traumatic stress disorder, represent significant clinical challenges. Previously we have documented that chronic forced swim (FS) stress exacerbates neuropathic pain in spared nerve injury (SNI) rats, associated with an up-regulation of GluN2B-containing N-methyl-D-aspartate receptors (GluN2B-NMDARs) in the central nucleus of the amygdala (CeA). However, the molecular mechanisms underlying chronic FS stress (CFSS)-mediated exacerbation of pain sensitivity in SNI rats still remain unclear. In this study, we demonstrated that exposure of CFSS to rats activated the corticotropin-releasing factor (CRF)/CRF receptor type 1 (CRFR1) signaling in the CeA, which was shown to be necessary for CFSS-induced depressive-like symptoms in stressed rats, and as well, for CFSS-induced exacerbation of pain hypersensitivity in SNI rats exposed to chronic FS stress. Furthermore, we discovered that activation of CRF/CRFR1 signaling in the CeA upregulated the phosphorylation of GluN2B-NMDARs at tyrosine 1472 (pGluN2BY1472) in the synaptosomal fraction of CeA, which is highly correlated to the enhancement of synaptic GluN2B-NMDARs expression that has been observed in the CeA in CFSS-treated SNI rats. In addition, we revealed that activation of CRF/CRFR1 signaling in the CeA facilitated the CFSS-induced reinforcement of long-term potentiation as well as the enhancement of NMDAR-mediated excitatory postsynaptic currents in the basolateral amygdala (BLA)-CeA pathway in SNI rats. These findings suggest that activation of CRF/CRFR1 signaling in the CeA contributes to chronic stress-induced exacerbation of neuropathic pain by enhancing GluN2B-NMDAR-mediated synaptic plasticity in rats subjected to nerve injury. PERSPECTIVE: Our present study provides a novel mechanism for elucidating stress-induced hyperalgesia and highlights that the CRF/CRFR1 signaling and the GluN2B-NMDAR-mediated synaptic plasticity in the CeA may be important as potential therapeutic targets for chronic stress-induced pain exacerbation in human neuropathic pain. DATA AVAILABILITY: The data that support the findings of this study are available from the corresponding author upon reasonable request.


Subject(s)
Central Amygdaloid Nucleus , Corticotropin-Releasing Hormone , Neuralgia , Neuronal Plasticity , Rats, Sprague-Dawley , Receptors, Corticotropin-Releasing Hormone , Receptors, N-Methyl-D-Aspartate , Signal Transduction , Stress, Psychological , Animals , Receptors, N-Methyl-D-Aspartate/metabolism , Male , Neuralgia/metabolism , Neuralgia/physiopathology , Central Amygdaloid Nucleus/metabolism , Receptors, Corticotropin-Releasing Hormone/metabolism , Stress, Psychological/metabolism , Stress, Psychological/physiopathology , Stress, Psychological/complications , Corticotropin-Releasing Hormone/metabolism , Neuronal Plasticity/physiology , Rats , Signal Transduction/physiology , Disease Models, Animal
11.
J Org Chem ; 89(4): 2351-2363, 2024 Feb 16.
Article in English | MEDLINE | ID: mdl-38301039

ABSTRACT

An effective and stereoselective synthesis of halogenated (E)-4-methylenechromanes with a sulfonyl group was developed via the copper-catalyzed sulfonylative annulation/halogenation of 1,7-enynes, in which sodium sulfinates were used as the sulfonyl reagents and tetrabutylammonium halide provided the halogen sources. The formed alkenyl C-X bonds were valuable and can efficiently undergo the subsequent hydrolysis, alkenylation, alkynylation, arylation, alkylthiolation, and alkoxylation to furnish a series of highly functionalized 4-methylenechromanes.

12.
J Org Chem ; 89(5): 3403-3412, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38331393

ABSTRACT

A practical and efficient copper-catalyzed carbocyclization of 2-functionalized anilines with ethyl bromodifluoroacetate has been developed. Ethyl bromodifluoroacetate is employed as the C1 source via quadruple cleavage in this transformation. This reaction can afford a variety of N-containing heterocyclics with satisfactory yields and excellent functional group compatibility.

13.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(1): 6-13, 2024 Feb.
Article in Chinese | MEDLINE | ID: mdl-38387892

ABSTRACT

OBJECTIVE: To evaluate the efficacy of acute T-cell lymphoblastic leukemia (T-ALL) in children and explore the prognostic risk factors. METHODS: The clinical data of 127 newly diagnosed children with T-ALL admitted to five hospitals in Fujian province from April 2011 to December 2020 were retrospectively analyzed, and compared with children with newly diagnosed acute precursor B-cell lymphoblastic leukemia (B-ALL) in the same period. Kaplan-Meier analysis was used to evaluate the overall survival (OS) and event-free survival (EFS), and COX proportional hazard regression model was used to evaluate the prognostic factors. Among 116 children with T-ALL who received standard treatment, 78 cases received the Chinese Childhood Leukemia Collaborative Group (CCLG)-ALL 2008 protocol (CCLG-ALL 2008 group), and 38 cases received the China Childhood Cancer Collaborative Group (CCCG)-ALL 2015 protocol (CCCG-ALL 2015 group). The efficacy and serious adverse event (SAE) incidence of the two groups were compared. RESULTS: Proportion of male, age≥10 years old, white blood cell count (WBC)≥50×109/L, central nervous system leukemia, minimal residual disease (MRD)≥1% during induction therapy, and MRD≥0.01% at the end of induction in T-ALL children were significantly higher than those in B-ALL children (P <0.05). The expected 10-year EFS and OS of T-ALL were 59.7% and 66.0%, respectively, which were significantly lower than those of B-ALL (P <0.001). COX analysis showed that WBC≥100×109/L at initial diagnosis and failure to achieve complete remission (CR) after induction were independent risk factors for poor prognosis. Compared with CCLG-ALL 2008 group, CCCG-ALL 2015 group had lower incidence of infection-related SAE (15.8% vs 34.6%, P =0.042), but higher EFS and OS (73.9% vs 57.2%, P EFS=0.090; 86.5% vs 62.3%, P OS=0.023). CONCLUSIONS: The prognosis of children with T-ALL is worse than children with B-ALL. WBC≥100×109 /L at initial diagnosis and non-CR after induction (especially mediastinal mass has not disappeared) are the risk factors for poor prognosis. CCCG-ALL 2015 regimen may reduce infection-related SAE and improve efficacy.


Subject(s)
Burkitt Lymphoma , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , Child , Humans , Male , Retrospective Studies , Disease-Free Survival , Prognosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , T-Lymphocytes , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Pathologic Complete Response , Neoplasm, Residual/diagnosis , Neoplasm, Residual/drug therapy , Burkitt Lymphoma/drug therapy
14.
World J Diabetes ; 15(1): 53-71, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38313852

ABSTRACT

BACKGROUND: The lack of specific predictors for type-2 diabetes mellitus (T2DM) severely impacts early intervention/prevention efforts. Elevated branched-chain amino acids (BCAAs: Isoleucine, leucine, valine) and aromatic amino acids (AAAs: Tyrosine, tryptophan, phenylalanine)) show high sensitivity and specificity in predicting diabetes in animals and predict T2DM 10-19 years before T2DM onset in clinical studies. However, improvement is needed to support its clinical utility. AIM: To evaluate the effects of body mass index (BMI) and sex on BCAAs/AAAs in new-onset T2DM individuals with varying body weight. METHODS: Ninety-seven new-onset T2DM patients (< 12 mo) differing in BMI [normal weight (NW), n = 33, BMI = 22.23 ± 1.60; overweight, n = 42, BMI = 25.9 ± 1.07; obesity (OB), n = 22, BMI = 31.23 ± 2.31] from the First People's Hospital of Yunnan Province, Kunming, China, were studied. One-way and 2-way ANOVAs were conducted to determine the effects of BMI and sex on BCAAs/AAAs. RESULTS: Fasting serum AAAs, BCAAs, glutamate, and alanine were greater and high-density lipoprotein (HDL) was lower (P < 0.05, each) in OB-T2DM patients than in NW-T2DM patients, especially in male OB-T2DM patients. Arginine, histidine, leucine, methionine, and lysine were greater in male patients than in female patients. Moreover, histidine, alanine, glutamate, lysine, valine, methionine, leucine, isoleucine, tyrosine, phenylalanine, and tryptophan were significantly correlated with abdominal adiposity, body weight and BMI, whereas isoleucine, leucine and phenylalanine were negatively correlated with HDL. CONCLUSION: Heterogeneously elevated amino acids, especially BCAAs/AAAs, across new-onset T2DM patients in differing BMI categories revealed a potentially skewed prediction of T2DM development. The higher BCAA/AAA levels in obese T2DM patients would support T2DM prediction in obese individuals, whereas the lower levels of BCAAs/AAAs in NW-T2DM individuals may underestimate T2DM risk in NW individuals. This potentially skewed T2DM prediction should be considered when BCAAs/AAAs are to be used as the T2DM predictor.

15.
Acta Pharmacol Sin ; 45(2): 436-448, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37749238

ABSTRACT

Extracellular matrix metalloproteinase inducer CD147 is a glycoprotein on the cell surface. There is minimal expression of CD147 in normal epithelial and fetal tissues, but it is highly expressed in a number of aggressive tumors. CD147 has been implicated in pan-cancer immunity and progression. With the development of CD147-targeting therapeutic strategy, accurate detection of CD147 expression in tumors and its changes during the therapy is necessary. In this study we constructed a novel radiotracer by labeling the anti-CD147 mAb with radionuclide 124/125I (124/125I-anti-CD147) for noninvasive detection of CD147 expression in pan-cancers, and characterized its physicochemical properties, affinity, metabolic characteristics, biodistribution and immunoPET imaging with 124I-IgG and 18F-FDG as controls. By examining the expression of CD147 in cancer cell lines, we found high CD147 expression in colon cancer cells LS174T, FADU human pharyngeal squamous cancer cells and 22RV1 human prostate cancer cells, and low expression of CD147 in human pancreatic cancer cells ASPC1 and human gastric cancer cells BGC823. 124/125I-anti-CD147 was prepared using N-bromine succinimide (NBS) as oxidant and purified by PD-10 column. Its radiochemical purity (RCP) was over 99% and maintained over 85% in saline or 5% human serum albumin (HSA) for more than 7 d; the RCP of 125I-anti-CD147 in blood was over 90% at 3 h post injection (p.i.) in healthy mice. The Kd value of 125I-anti-CD147 to CD147 protein was 6.344 nM, while that of 125I-IgG was over 100 nM. 125I-anti-CD147 showed much greater uptake in CD147 high-expression cancer cells compared to CD147 low-expression cancer cells. After intravenous injection in healthy mice, 125I-anti-CD147 showed high initial uptake in blood pool and liver, the uptake was decreased with time. The biological half-life of distribution and clearance phases in healthy mice were 0.63 h and 19.60 h, respectively. The effective dose of 124I-anti-CD147 was estimated as 0.104 mSv/MBq. We conducted immunoPET imaging in tumor-bearing mice, and demonstrated a significantly higher tumor-to-muscle ratio of 124I-anti-CD147 compared to that of 124I-IgG and 18F-FDG in CD147 (+) tumors. The expression levels of CD147 in cells and tumors were positively correlated with the maximum standardized uptake value (SUVmax) (P < 0.01). In conclusion, 124/125I-anti-CD147 displays high affinity to CD147, and represents potential for the imaging of CD147-positive tumors. The development of 124I-anti-CD147 may provide new insights into the regulation of tumor microenvironment and formulation of precision diagnosis and treatment programs for tumors.


Subject(s)
Fluorodeoxyglucose F18 , Prostatic Neoplasms , Male , Humans , Mice , Animals , Tissue Distribution , Radiopharmaceuticals , Iodine Radioisotopes , Immunoglobulin G , Cell Line, Tumor , Tumor Microenvironment
16.
Phys Rev Lett ; 131(18): 186302, 2023 Nov 03.
Article in English | MEDLINE | ID: mdl-37977647

ABSTRACT

We reveal the gate-tunable Berry curvature dipole polarizability in Dirac semimetal Cd_{3}As_{2} nanoplates through measurements of the third-order nonlinear Hall effect. Under an applied electric field, the Berry curvature exhibits an asymmetric distribution, forming a field-induced Berry curvature dipole, resulting in a measurable third-order Hall voltage with a cubic relationship to the longitudinal electric field. Notably, the magnitude and polarity of this third-order nonlinear Hall effect can be effectively modulated by gate voltages. Furthermore, our scaling relation analysis demonstrates that the sign of the Berry curvature dipole polarizability changes when tuning the Fermi level across the Dirac point, in agreement with theoretical calculations. The results highlight the gate control of nonlinear quantum transport in Dirac semimetals, paving the way for promising advancements in topological electronics.

17.
Infect Dis Ther ; 12(11): 2611-2620, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37870693

ABSTRACT

INTRODUCTION: Bloodstream infection (BSI) is a significant factor contributing to hospitalization and high mortality rates among human immunodeficiency virus(HIV)-positive patients. Therefore, the timely detection of this condition is of utmost importance. Blood culture is considered the gold standard for diagnosing BSIs. Currently, BD BACTEC™ Plus Aerobic/F culture bottles and the BD BACTEC™ Myco/F Lytic culture bottles can be used for blood culture. This study aimed to evaluate the efficacy of two different types of culture bottles in diagnosing BSIs in patients with HIV. METHODS: A retrospective analysis was conducted on HIV-positive patients hospitalized in the Infection Department of Wenzhou Central Hospital between July 2019 and October 2021. A total of 246 pairs of blood samples were included, consisting of an aerobic culture vial and a Myco/F culture vial. Blood culture results and clinical diagnosis were utilized to identify the presence of BSI. RESULTS: Out of 246 cases, 84 cases had positive blood cultures. Fungal BSIs, particularly Talaromyces marneffei BSIs, were the most prevalent among patients with HIV. The positive rate of Myco/F culture bottles (89.29%) was significantly higher compared with aerobic culture bottles (69.05%; P = 0.001). In the diagnosis of fungal BSIs, the positive rate of Myco/F culture bottles was 88.57%, which was significantly higher than that of aerobic culture bottles (72.86%; P = 0.018). The Myco/F culture bottle has more advantages in diagnosing Talaromyces marneffei BSIs (P=0.028). In addition, mycobacteria were exclusively detected in Myco/F culture bottles. CONCLUSIONS: Fungal BSIs are the predominant type of infections in HIV-positive patients. Myco/F culture bottles exhibit noteworthy attributes of high positive rate in diagnosing HIV combined with BSI. These advantages are conducive to obtaining accurate culture results and minimizing missed diagnoses.

18.
J Fungi (Basel) ; 9(10)2023 Sep 25.
Article in English | MEDLINE | ID: mdl-37888219

ABSTRACT

During the investigation of lignicolous freshwater fungi in plateau lakes in Yunnan Province, China, eight Lentitheciaceae species were collected from five lakes viz. Luguhu, Qiluhu, Xingyunhu, Cibihu, and Xihu lake. Based on morphological characters and phylogenetic analysis of combined ITS, LSU, SSU, and tef 1-α sequence data, a new genus Paralentithecium, two new species (Paralentithecium suae, and Setoseptoria suae), three new records (Halobyssothecium phragmitis, H. unicellulare, and Lentithecium yunnanensis) and three known species viz. Halobyssothecium aquifusiforme, Lentithecium pseudoclioninum, and Setoseptoria bambusae are reported.

19.
Sci Bull (Beijing) ; 68(22): 2743-2749, 2023 Nov 30.
Article in English | MEDLINE | ID: mdl-37872061

ABSTRACT

The non-volatile magnetoresistive random access memory (MRAM) is believed to facilitate emerging applications, such as in-memory computing, neuromorphic computing and stochastic computing. Two-dimensional (2D) materials and their van der Waals heterostructures promote the development of MRAM technology, due to their atomically smooth interfaces and tunable physical properties. Here we report the all-2D magnetoresistive memories featuring all-electrical data reading and writing at room temperature based on WTe2/Fe3GaTe2/BN/Fe3GaTe2 heterostructures. The data reading process relies on the tunnel magnetoresistance of Fe3GaTe2/BN/Fe3GaTe2. The data writing is achieved through current induced polarization of orbital magnetic moments in WTe2, which exert torques on Fe3GaTe2, known as the orbit-transfer torque (OTT) effect. In contrast to the conventional reliance on spin moments in spin-transfer torque and spin-orbit torque, the OTT effect leverages the natural out-of-plane orbital moments, facilitating field-free perpendicular magnetization switching through interface currents. Our results indicate that the emerging OTT-MRAM is promising for low-power, high-performance memory applications.

20.
Se Pu ; 41(10): 835-842, 2023 Oct.
Article in Chinese | MEDLINE | ID: mdl-37875406

ABSTRACT

Capillary electrochromatography (CEC) has received increased attention from the academic community because it combines the excellent selectivity of high performance liquid chromatography (HPLC) and the high efficiency of capillary electrophoresis (CE). Selecting the most appropriate stationary phase material is crucial to achieve better separation effects in CEC. In recent years, a considerable number of materials, such as graphene oxide, proteins, metal organic frameworks, and covalent organic frameworks (COFs), have been widely used as stationary phases in CEC to further improve its separation performance and extend its scope of potential applications. Among these materials, COFs have shown great application prospects in CEC owing to their unique properties, which include high porosity, large surface area, excellent stability, tunable pore size, and high designability of the framework structure. This review systematically summarizes published papers on the development and application of COFs in CEC from 2016 to 2023. First, two COF-based capillary columns (i. e., open-tube CEC columns and monolithic CEC columns) and their preparation methods are introduced. Second, the applications of CEC based on COF stationary phases in the separation of environmental endocrine disruptors, pesticides, aromatic compounds, amino acids, and drugs, particularly chiral drugs, are systematically summarized. The separation mechanism of CEC based on COF stationary phases is also introduced. At present, the good separation ability of COF-based CEC is mainly attributed to two factors: 1) The size exclusion effect of the pores of the COF stationary phase. Because of differences in the sizes of their organic molecular building units and side chains, COFs have varying pore sizes and topological structures. Thus, target analytes smaller than the pores of the COFs can enter the frameworks and interact with them during separation. On the other hand, target analytes larger than the pores of the COFs cannot enter the frameworks and interact with them during separation; thus, they can be separated. 2) The interactions between the target analytes and side chains (e. g., hydrophobic interactions, hydrogen bonding, π-π interactions, etc.) of the COFs. Since COFs usually contain alkyl side chains, aromatic structures, and oxygen and/or nitrogen atoms with high electronegativity, various interactions could occur between the COFs and target analytes. Finally, directions for the future development and strategic application of CEC based on COF stationary phases are proposed. We believe that future research in CEC based on COF stationary phases should focus on the following aspects: 1) The use of cheminformatics to design and construct COFs to improve the efficiency of COF capillary column preparation; 2) the development of milder methods to synthesize COFs that can meet the requirements of high performance COF capillary columns; and 3) in-depth research to explore the separation mechanism of CEC based on COF stationary phases to provide theoretical guidance for developing CEC methods suitable for the separation and analysis of complex samples.

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