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1.
J Environ Sci (China) ; 147: 83-92, 2025 Jan.
Article in English | MEDLINE | ID: mdl-39003086

ABSTRACT

The environmental threat posed by stibnite is an important geoenvironmental issue of current concern. To better understand stibnite oxidation pathways, aerobic abiotic batch experiments were conducted in aqueous solution with varying δ18OH2O value at initial neutral pH for different lengths of time (15-300 days). The sulfate oxygen and sulfur isotope compositions as well as concentrations of sulfur and antimony species were determined. The sulfur isotope fractionation factor (Δ34SSO4-stibnite) values decreased from 0.8‰ to -2.1‰ during the first 90 days, and increased to 2.6‰ at the 180 days, indicating the dominated intermediate sulfur species such as S2O32-, S0, and H2S (g) involved in Sb2S3 oxidation processes. The incorporation of O into sulfate derived from O2 (∼100%) indicated that the dissociated O2 was only directly adsorbed on the stibnite-S sites in the initial stage (0-90 days). The proportion of O incorporation into sulfate from water (27%-52%) increased in the late stage (90-300 days), which suggested the oxidation mechanism changed to hydroxyl attack on stibnite-S sites promoted by nearby adsorbed O2 on stibnite-Sb sites. The exchange of oxygen between sulfite and water may also contributed to the increase of water derived O into SO42-. The new insight of stibnite oxidation pathway contributes to the understanding of sulfide oxidation mechanism and helps to interpret field data.


Subject(s)
Oxidation-Reduction , Oxygen Isotopes , Sulfates , Sulfur Isotopes , Sulfur Isotopes/analysis , Sulfates/chemistry , Oxygen Isotopes/analysis , Antimony/chemistry , Models, Chemical , Aerobiosis , Oxygen/chemistry , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/chemistry , Oxides
2.
World J Gastrointest Surg ; 16(9): 3020-3031, 2024 Sep 27.
Article in English | MEDLINE | ID: mdl-39351552

ABSTRACT

BACKGROUND: Postoperative ileus (POI) is a common complication after abdominal surgery with high morbidity, which hinders patient recovery, prolongs hospitalization, and increases healthcare costs. Therefore, POI has become a global public health challenge. POI triggering is multifactorial. Autonomic and hormonal mechanisms are generally involved in POI pathogenesis. Recent studies have shown that beta adrenergic signaling of enteric glia is a POI trigger. Currently, the status quo, trends, and frontiers of global research on POI remain unclear. AIM: To explore the current status, trends, and frontiers of POI research from 2011 to the present based on bibliometric analysis. METHODS: Publications published on POI research from 2011 to 2023 were retrieved on June 1, 2023, from the Web of Science Core Collection. CiteSpace 6.2.R2 and VOSviewer were used to conduct bibliometric visualization. RESULTS: In total, 778 POI records published from 2011 to 2023 were retrieved. Over the past few decades, the annual cumulative number of related articles has linearly increased, with China and the United States of America contributing prominently. All publications were from 59 countries and territories. China and the University of Bonn were the top contributing country and institution, respectively. Neurogastroenterology & Motility was the most prolific journal. The Journal of Gastrointestinal Surgery had the highest number of citations. Wehner Sven was the most productive author. Burst keywords (e.g., colon, prolonged ileus, acupuncture, paralytic ileus, pathophysiology, rectal cancer, gastrointestinal function, risk) and a series of reference citation bursts provided evidence for the research frontiers in recent years. CONCLUSION: This study demonstrates trends in the published literature on POI and provides new insights for researchers. It emphasizes the importance of multidisciplinary cooperation in the development of this field.

3.
J Craniofac Surg ; 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39352398

ABSTRACT

BACKGROUND: Ear keloids are pathologic scar hyperplasia in the ear region. The most therapeutic approach was surgical shave excision with radiation therapy. However, radiation therapy is easily delivered to healthy surrounding tissues. In the last years, injections with botulinum toxin type A (BTX-A) have been proven to improve surgical scars effectively in clinical trials. This study aimed to evaluate the effect of immediate injections of BTX-A after surgical excision for ear keloids. METHODS: From January 2020 to January 2023, 33 consecutive patients with ear keloids were enrolled. All patients underwent scar excision and revision at the same time when they needed BTX-A. It was injected into surgical wound closure immediately after surgery. The results of this study were evaluated at follow-up from 7 to 18 months using the Vancouver Scar Scale (VSS) and the Visual Analogue Scale (VAS). RESULTS: From January 2020 to January 2023, 33 patients received concomitant therapy of immediate injections of BTX-A after surgery for ear keloids. The patients were evaluated at follow-ups lasting 7 to 18 months. Only one case recurred within the follow-up period, and no adverse effects were reported. CONCLUSION: This study demonstrates that significant cosmetic outcomes in ear keloid treatment were achieved after early postsurgical BTX-A injections. The patients reported high satisfaction and few complications.

4.
Zhongguo Zhong Yao Za Zhi ; 49(16): 4407-4419, 2024 Aug.
Article in Chinese | MEDLINE | ID: mdl-39307777

ABSTRACT

The MYB(v-myb avian myeloblastosis viral oncogene homolog) family of transcription factors is the largest class of genes among higher plant transcription factors, which can be divided into four subfamilies, with the R2R3-MYB being the most common subfamily type. R2R3-MYB transcription factors are widely involved in the regulation of organ development and secondary metabolite biosynthesis in plants. To investigate the role of R2R3-MYB family transcription factors in the synthesis of flavonoids and glandular trichome development in Artemisia argyi, this study screened and identified 92 R2R3-MYB transcription factors based on the whole genome data of A. argyi, and predicted their potential functions based on bioinformatics. The results showed that the amino acid lengths of the 92 transcription factors ranged from 168 to 547 aa, with relative molecular weights ranging from 19. 6 to 60. 5 kDa, all of which were hydrophilic proteins. Subcellular localization analysis showed that 89 AaMYB proteins were located in the nucleus, while three proteins were simultaneously located in the nucleus and cytoplasm. According to the classification of Arabidopsis R2R3-MYB family, the 92 A. argyi R2R3-MYB proteins were divided into 26 subfamilies, with similar gene structures within the same subfamily.Cis-acting element prediction results showed that light-responsive elements, methyl jasmonate elements, and abscisic acid elements were widely distributed in the promoter regions of R2R3-MYB genes. Transcriptome expression analysis results showed that the expression of AaMYB60, AaMYB63, and AaMYB86 in leaves was higher than that in stems and roots, indicating that these three transcription factors mainly function in leaves. Additionally, five candidate R2R3-MYB transcription factors involved in A. argyi flavonoid biosynthesis or glandular trichome development were selected through phylogenetic analysis. This study provides important genetic resources for the breeding of superior varieties and germplasm innovation of A. argyi in the future.


Subject(s)
Artemisia , Gene Expression Regulation, Plant , Phylogeny , Plant Proteins , Transcription Factors , Artemisia/genetics , Artemisia/metabolism , Artemisia/growth & development , Transcription Factors/genetics , Transcription Factors/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Gene Expression Profiling , Amino Acid Sequence
5.
Zhongguo Zhong Yao Za Zhi ; 49(17): 4650-4657, 2024 Sep.
Article in Chinese | MEDLINE | ID: mdl-39307803

ABSTRACT

Central nervous system(CNS) disorders can significantly impact patients' daily lives, impairing their ability to work and imposing a substantial financial burden on their families. In recent years, the incidence of CNS diseases has shown a significant increase with the continuous improvement of the quality of life and the aging problem. Therefore, the search for new preventive and curative drugs has been a research hotspot for this group of diseases. Osthole(OST), isolated from Umbelliferae such as Cnidium monnieri, Angelica sinensis, and Heracleum hemsleyanum, possesses a variety of pharmacological effects such as neuroprotective, antioxidant, anti-inflammatory, and antithrombotic effects. There is increasing evidence that OST has demonstrated significant preventive and curative effects in various CNS disease models. This paper systematically reviewed the research progress of OST in preventing and treating CNS diseases by reviewing domestic and international literature to provide more in-depth theoretical support for the future clinical application of OST in the prevention and treatment of CNS diseases.


Subject(s)
Central Nervous System Diseases , Coumarins , Coumarins/therapeutic use , Humans , Central Nervous System Diseases/drug therapy , Central Nervous System Diseases/prevention & control , Animals , Drugs, Chinese Herbal/therapeutic use , Neuroprotective Agents/therapeutic use
6.
J Immunol ; 2024 Sep 23.
Article in English | MEDLINE | ID: mdl-39311660

ABSTRACT

IL-7 is a cytokine produced by stromal cells, which binds to IL-7Rα and plays an important role for homeostasis of T lymphocytes. Excessive activities of IL-7-triggered signaling pathways causes autoimmune diseases. How IL-7-triggered signaling and immune effects are regulated is not fully understood. In this study, we show that the membrane-associated RING-CH (MARCH) E3 ligase family member MARCH8 mediates K27-linked polyubiquitination of IL-7Rα, leading to its lysosomal degradation. Site-directed mutagenesis suggests that MARCH8 meditates polyubiquitination of IL-7Rα at K265/K266, and mutation of these residues renders IL-7Rα resistance to MARCH8-mediated polyubiquitination and degradation. MARCH8 deficiency increases IL-7-triggered activation of the downstream transcription factor STAT5 and transcriptional induction of the effector genes in human T lymphoma cells. MARCH8 deficiency also promotes IL-7-triggered T cell proliferation and splenic memory CD8+ T cell differentiation in mice. Our findings suggest that MARCH8 negatively regulates IL-7-triggered signaling by mediating K27-linked polyubiquitination and lysosomal degradation of IL-7Rα, which reveals a negative regulatory mechanism of IL-7-triggered T cell homeostasis.

7.
Chem Commun (Camb) ; 2024 Sep 23.
Article in English | MEDLINE | ID: mdl-39311923

ABSTRACT

Previous studies demonstrated the requirement of four enzymes including a cupin-domain containing protein for the formation of alkyl salicylaldehydes and derivatives. Heterologous expression of three biosynthetic genes from Aspergillus ustus resulted in the formation of such compounds in high-yields without involvement of a cupin analogue.

8.
Curr Med Res Opin ; : 1-7, 2024 Sep 18.
Article in English | MEDLINE | ID: mdl-39235266

ABSTRACT

OBJECTIVE: To compare the efficacy and safety of insulin degludec biosimilar B01411 (HS-IDeg) with originator insulin degludec-Tresiba (NN-IDeg) in Chinese patients with type 2 diabetes mellitus (T2DM) who were inadequately controlled on oral antidiabetic drugs (OADs) for at least 3 months. METHODS: This multicenter, randomized, open-label, parallel-group, active-controlled, phase 3 study enrolled 362 participants with T2DM. Participants were stratified according to whether the insulin secretagogue (sulfonylurea or glinide) had been used before the screening and then randomized 1:1 to receive once-daily subcutaneous injections of HS-IDeg (n = 180) or NN-IDeg (n = 182) for 18 weeks. The primary endpoint was the change from baseline in glycated hemoglobin (HbA1c) to week 18. RESULTS: At week 18, the least squares (LS) mean change in HbA1c from baseline was -1.34% (95% CI -1.47 to -1.21) and -1.25% (95% CI -1.38 to -1.12) with HS-IDeg and NN-IDeg, respectively. The LS mean difference (HS-IDeg minus NN-IDeg) in HbA1c at week 18 was -0.09% (95% CI -0.28 to 0.10), demonstrating non-inferiority of HS-IDeg to NN-IDeg. Participants achieving HbA1c <7.0% at week 18 were 34.5% and 29.5% with HS-IDeg and NN-IDeg, respectively. Mean decreases in fasting plasma glucose and standard deviation of blood glucose were similar between both groups. Safety and tolerability, including hypoglycemia, adverse events, and weight change were similar between both groups. No severe hypoglycemia and no death occurred in the study. CONCLUSIONS: HS-IDeg and NN-IDeg demonstrated similar efficacy and safety over 18 weeks of treatment in Chinese patients with T2DM who had inadequate responses to OADs for at least 3 months.

9.
J Orthop Translat ; 48: 217-231, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39290849

ABSTRACT

Background: Increasing attention to liver-bone crosstalk has spurred interest in targeted interventions for various forms of osteoporosis. Liver injury induced by different liver diseases can cause an imbalance in bone metabolism, indicating a novel regulatory paradigm between the liver and bone. However, the role of the liver-bone axis in both primary and secondary osteoporosis remains inadequately elucidated. Therefore, exploring the exact regulatory mechanisms of the liver-bone axis may offer innovative clinical approaches for treating diseases associated with the liver and bone. Methods: Here, we summarize the latest research on the liver-bone axis by searching the PubMed and Web of Science databases and discuss the possible mechanism of the liver-bone axis in different types of osteoporosis. The literature directly reporting the regulatory role of the liver-bone axis in different types of osteoporosis from the PubMed and Web of Science databases has been included in the discussion of this review (including but not limited to the definition of the liver-bone axis, clinical studies, and basic research). In addition, articles discussing changes in bone metabolism caused by different etiologies of liver injury have also been included in the discussion of this review (including but not limited to clinical studies and basic research). Results: Several endocrine factors (IGF-1, FGF21, hepcidin, vitamin D, osteocalcin, OPN, LCAT, Fetuin-A, PGs, BMP2/9, IL-1/6/17, and TNF-α) and key genes (SIRT2, ABCB4, ALDH2, TFR2, SPTBN1, ZNF687 and SREBP2) might be involved in the regulation of the liver-bone axis. In addition to the classic metabolic pathways involved in inflammation and oxidative stress, iron metabolism, cholesterol metabolism, lipid metabolism and immunometabolism mediated by the liver-bone axis require more research to elucidate the regulatory mechanisms involved in osteoporosis. Conclusion: During primary and secondary osteoporosis, the liver-bone axis is responsible for liver and bone homeostasis via several hepatokines and osteokines as well as biochemical signaling. Combining multiomics technology and data mining technology could further advance our understanding of the liver-bone axis, providing new clinical strategies for managing liver and bone-related diseases.The translational potential of this article is as follows: Abnormal metabolism in the liver could seriously affect the metabolic imbalance of bone. This review summarizes the indispensable role of several endocrine factors and biochemical signaling pathways involved in the liver-bone axis and emphasizes the important role of liver metabolic homeostasis in the pathogenesis of osteoporosis, which provides novel potential directions for the prevention, diagnosis, and treatment of liver and bone-related diseases.

10.
J Immunol ; 2024 Sep 20.
Article in English | MEDLINE | ID: mdl-39302088

ABSTRACT

Alemtuzumab induction with belatacept/rapamycin-based maintenance immunotherapy (ABR) prevents kidney allograft rejection and specifically limits early costimulation blockade-resistant rejection (CoBRR). To evaluate the mechanisms by which this regimen alters CoBRR, we characterized the phenotype and functional response of preexisting memory cells to allogeneic endothelial cells using intracellular cytokine staining and flow cytometry. IL-7-induced lymphocyte proliferation in the presence or absence of rapamycin was assessed to characterize the phenotype of proliferating cells. Lymphocytes from 40 recipients who underwent transplant using the ABR regimen were studied longitudinally. The rapid immunoresponses of preexisting alloreactive cells to allogeneic endothelial cells were predominantly CD8+TNF-α+/IFN-γ+ cells. These cells were effector memory (TEM) and terminally differentiated effector memory cells lacking CD28 expression, and most were CD57+PD1-. Neither rapamycin nor belatacept directly inhibited these cells. IL-7, a cytokine induced during lymphopenia postdepletion, provoked dramatic CD8+ TEM cell proliferation and a low level of CD8+CD57+PD1- cell expansion in vitro. The IL-7 stimulation induced CD8+ cell mTOR phosphorylation, and rapamycin treatment markedly inhibited IL-7-induced TEM and CD57+PD1- cell expansion. This effect was evident in patients receiving the ABR in that the repopulation of CD8+CD57+PD1- TEM cells was substantially suppressed for at least 36 mo after transplant. These findings help define one mechanism by which a costimulation blockade/rapamycin-based therapy following alemtuzumab induction minimizes CoBRR, namely that in the presence of rapamycin, costimulation-resistant alloreactive cells are disproportionately ineffective at repopulating following post-transplant T cell depletion.

11.
Sensors (Basel) ; 24(17)2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39275373

ABSTRACT

For nonlinear systems with uncertain state time delays, an adaptive neural optimal tracking control method based on finite time is designed. With the help of the appropriate LKFs, the time-delay problem is handled. A novel nonquadratic Hamilton-Jacobi-Bellman (HJB) function is defined, where finite time is selected as the upper limit of integration. This function contains information on the state time delay, while also maintaining the basic information. To meet specific requirements, the integral reinforcement learning method is employed to solve the ideal HJB function. Then, a tracking controller is designed to ensure finite-time convergence and optimization of the controlled system. This involves the evaluation and execution of gradient descent updates of neural network weights based on a reinforcement learning architecture. The semi-global practical finite-time stability of the controlled system and the finite-time convergence of the tracking error are guaranteed.

12.
Food Chem ; 463(Pt 2): 141179, 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39276556

ABSTRACT

In this study, an antimicrobial component, silk protease inhibitors (SPIs), was extracted from discarded silkworm cocoons, and a suitable degumming method for obtaining regenerated silk fibroin (SF) was screened. An edible antimicrobial coating was prepared by mixing SPIs with SF for evaluation of potential in strawberries preservation. Results demonstrated that SPI could effectively inhibit mycelial growth and spore germination. The alkaline protease method exhibited the highest degumming rate of 24.4 %. The SPI-SF coating exhibited excellent mechanical properties, high water vapor permeability, and easy washability. Within 10 days, seedlings treatment with SPI-SF coating solution showed a germination rate of 94.3 %, and exhibited good biocompatibility with HepG2 cells. Coating with SPI-SF led to increase in the storage period of strawberries to 10-14 days, concurrent with considerable reduction in decay rate at room temperature. Conclusively, this study demonstrates the potential of SPI-SF edible coating in strawberries preservation.

13.
Pestic Biochem Physiol ; 204: 106091, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39277418

ABSTRACT

The vegetable leafminer (Liriomyza sativae) is a devastating invasive pest of many vegetable crops and horticultural plants worldwide, causing serious economic loss. Conventional control strategy against this pest mainly relies on the synthetic chemical pesticides, but widespread use of insecticides easily causes insecticide resistance development and is harmful to beneficial organisms and environment. In this context, a more environmentally friendly pest management strategy based on RNA interference (RNAi) has emerged as a powerful tool to control of insect pests. Here we report a successful oral RNAi in L. sativae after feeding on pak choi (Brassica rapa ssp. chinensis) that transiently express hairpin RNAs targeting vital genes in this pest. First, potentially lethal genes are identified by searching an L. sativae transcriptome for orthologs of the widely used V-ATPase A and actin genes, then expression levels are assessed during different life stages and in different adult tissues. Interestingly, the highest expression levels for V-ATPase A are observed in the adult heads (males and females) and for actin in the abdomens of adult females. We also assessed expression patterns of the target hairpin RNAs in pak choi leaves and found that they reach peak levels 72 h post agroinfiltration. RNAi-mediated knockdown of each target was then assessed by letting adult L. sativae feed on agroinfiltrated pak choi leaves. Relative transcript levels of each target gene exhibit significant reductions over the feeding time, and adversely affect survival of adult L. sativae at 24 h post infestation in genetically unmodified pak choi plants. These results demonstrate that the agroinfiltration-mediated RNAi system has potential for advancing innovative environmentally safe pest management strategies for the control of leaf-mining species.


Subject(s)
Brassica rapa , Plant Leaves , RNA Interference , Plant Leaves/parasitology , Brassica rapa/genetics , Brassica rapa/parasitology , Animals , RNA, Small Interfering/genetics , Female , Male
14.
BMC Endocr Disord ; 24(1): 187, 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39261907

ABSTRACT

BACKGROUD: The relationship between serum uric acid (SUA) and 25-hydroxyvitamin D (25(OH)D) has been variably characterized in existing literature, with inconsistent results regarding its nature and implications in the Chinese population. This study aims to clarify this association, considering the potential impact of vitamin D levels on SUA. METHODS: This cross-sectional study involved 7,086 individuals from the Second Affiliated Hospital of Zhejiang University School of Medicine, screened throughout 2020. We collected data on 25(OH)D, SUA, and other metabolic markers. Logistic regression models adjusted for confounding factors were utilized to analyze the relationships. RESULTS: Our findings illustrate a statistically significant inverted U-shaped relationship between 25(OH)D and SUA. The identified threshold effect at 28.82 ng/ml is pivotal; with 25(OH)D levels below this point associated with an increased risk of hyperuricemia (odds ratio: 1.0146, p = 0.0148), and levels above it offering protective benefits (odds ratio: 0.9616, p = 0.0164). CONCLUSIONS: Our findings confirm a nonlinear, inverted U-shaped correlation between 25(OH)D and SUA, emphasizing the importance of maintaining vitamin D levels within a specific range to effectively manage hyperuricemia. These results support the implementation of personalized vitamin D supplementation strategies to optimize metabolic health outcomes, highlighting the complex interplay between vitamin D status and uric acid levels.


Subject(s)
Hyperuricemia , Uric Acid , Vitamin D , Humans , Cross-Sectional Studies , Uric Acid/blood , Vitamin D/blood , Vitamin D/analogs & derivatives , Male , Female , Middle Aged , China/epidemiology , Adult , Hyperuricemia/blood , Hyperuricemia/epidemiology , Biomarkers/blood , Aged , Vitamin D Deficiency/blood , Vitamin D Deficiency/epidemiology , Asian People , East Asian People
16.
Inorg Chem ; 63(38): 17856-17863, 2024 Sep 23.
Article in English | MEDLINE | ID: mdl-39250883

ABSTRACT

Regulation of the two-photon excited fluorescence (TPEF) emission intensity and wavelength of metal-organic framework (MOF) crystals with similar constitutions presents a significant challenge. In this study, two MOFs, Zn-BTPPA and Cd3-BTPPA, were constructed using tetrakis(1,1'-biphenyl-4-carboxylic acid)-1,4-benzenediamine (H4BTPPA) as the organic ligand and mononuclear Zn and trinuclear Cd3 inorganic nodes, respectively. The incorporation of H4BTPPA within the MOF structures enables effective TPEF emission in both Zn-BTPPA and Cd3-BTPPA. The TPEF results show that Zn-BTPPA and Cd3-BTPPA exhibited strong emissions at 523 and 463 nm, respectively, when excited with a 780 nm laser. Moreover, Zn-BTPPA and Cd3-BTPPA exhibited much higher two-photon absorption cross sections, approximately 4.9 and 5.2 times higher than that of the reported dinuclear MOF, Cd2-BTPPA, with a similar composition, respectively. With different inorganic nodes, the stacking of chromophores, π···π interactions, and ligand geometry were found to correlate with the enhanced TPEF in Cd3-BTPPA and the blue-shifted TPEF in Zn-BTPPA. This work serves as an inspiration for designing efficient TPEF MOF materials based on the structure-property relationship.

17.
Article in English | MEDLINE | ID: mdl-39286403

ABSTRACT

Objective: In this study, we aimed to establish the role of regenerating islet-derived family member 4 (Reg IV) as an independent risk factor and prognostic predictor in patients with T2-3 stage breast cancer who exhibit a non-pathological complete response (non-pCR) following neoadjuvant chemotherapy (NACT). Additionally, we examined the potential correlation and interaction between Reg IV and epidermal growth factor receptor (EGFR). Methods: A total of 67 patients with T2-3 stage breast cancer exhibiting non-pCR after NACT between September 2019 and December 2021 were included in this study. The analysis involved Kaplan-Meier survival comparisons, pooled hazard ratios for risk quantification, Cox regression analysis to isolate the impact of Reg IV on prognosis, Riskplots for visualizing risk profiles, and SHAP analysis to assess the importance of variables in predicting outcomes. Results: The findings indicate that patients positive for Reg IV had a significantly poorer prognosis (HR: 2.62, 95% CI: 1.06-6.47). Co-expression of Reg IV and EGFR was associated with the worst outcomes compared to patients negative for both markers. Cox regression analysis confirmed the independent prognostic impact of Reg IV (HR: 2.63, 95% CI: 1.66-3.59). Riskplot analysis showed that patients positive for both Reg IV and EGFR predominantly experienced disease progression. SHAP analysis further reinforced the significant effect of Reg IV on the disease course, without substantial interaction with EGFR. Conclusion: Reg IV may serve as an independent risk factor and predictive marker for adverse outcomes in patients with T2-3 stage breast cancer who do not achieve non-pCR following NACT.

18.
Adv Sci (Weinh) ; : e2407493, 2024 Sep 17.
Article in English | MEDLINE | ID: mdl-39287113

ABSTRACT

Triple negative breast cancer (TNBC) is the most aggressive subtype in breast tumors. When re-analyzing TCGA breast cancer dataset, we found cell adhesion molecules are highly enriched in differentially expressed genes in TNBC samples, among which Focal Adhesion Kinase (FAK) is most significantly associated with poor survival of TNBC patients. FAK is precisely modulated in the focal adhesion dynamics. To investigate whether lncRNAs regulate FAK signaling, we performed RNA immunoprecipitation sequencing and found FAISL (FAK Interacting and Stabilizing LncRNA) abundantly enriched in FAK-interacting lncRNAs and frequently overexpressed in TCGA TNBC tissues. FAISL promotes TNBC cell adhesion, cytoskeleton spreading, proliferation, and anchor-independent survival. FAISL doesn't affect FAK mRNA but positively regulates FAK protein level by blocking Calpain 2-mediated proteolysis. FAISL interacts with the C-terminus domain of FAK, whereby masks the binding site of Calpain 2 and prevents FAK cleavage. High level of FAISL correlates with FAK expression in tumor tissues and poor prognosis of TNBC patients. A siRNA delivery system targeting FAISL using reduction-responsive nanoparticles effectively inhibits tumor growth and metastasis in TNBC mouse models. Together, these findings uncover a lncRNA-mediated mechanism of regulating FAK proteolysis in the TNBC progression, and highlight the potential of targeting lncRNA FAISL for TNBC treatment.

19.
Anesthesiology ; 2024 Sep 23.
Article in English | MEDLINE | ID: mdl-39312634

ABSTRACT

BACKGROUND: The efficacy of superficial cervical plexus blocks for reducing persistent pain after craniotomies remains unclear. We therefore tested the primary hypothesis that preoperative ultrasound-guided superficial cervical plexus blocks reduce persistent pain 3 months after suboccipital craniotomies. METHODS: We conducted a single-center randomized and blinded parallel-group trial. Eligible patients having suboccipital craniotomies were randomly allocated to superficial cervical plexus blocks with 10 ml of 0.5% ropivacaine or a comparable amount of normal saline. Injections were into the superficial layer of prevertebral fascia. The primary outcome was the incidence of persistent pain three months after surgery. RESULTS: From Nov 2021 to August 2023, 292 qualifying patients were randomly allocated to blocks with ropivacaine (n=146) or saline (n=146). The average ± SD age of participating patients was 45±12 years and the duration of surgery was 4.2±1.3 hours. Persistent pain 3 months after surgery was reported by 48 (34%) of patients randomized to ropivacaine versus 73 (51%) in those assigned to saline (relative risk 0.66; 95% CI, 0.50 to 0.88; P = 0.003) in the per-protocol population, and by 53 (36%) of patients randomized to ropivacaine versus 77 (53%) in those assigned to saline (relative risk 0.69, 95% CI, 0.53 to 0.90; P = 0.005) in the intention-to-treat population. CONCLUSION: Superficial cervical plexus blocks reduce the incidence of persistent incisional pain by about a third in patients recovering from suboccipital craniotomies.

20.
Chem Sci ; 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39296993

ABSTRACT

A C-H functionalizing annulation reaction of boron-doped polycyclic aromatic hydrocarbons (PAHs) with alkynes is described. This metal-free π-extension provides a new synthetic route to fusion atom B-doped polycyclic aromatic hydrocarbons (PAHs) that is demonstrated with the synthesis of a family of new, functionalized, structurally constrained 6a,15a-diborabenzo[tuv]naphtho[2,1-b]picenes. These annulation products exhibit deep LUMO energy levels, strong visible-range absorptions, and sterically accessible π-systems that can adopt herringbone or π-stacked solid-state structures based on choice of substituents. From regioselectivity and DFT calculations, we propose an annulation mechanism involving intramolecular electrophilic aromatic substitution of a zwitterionic intermediate.

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