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1.
Nat Commun ; 15(1): 3901, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38724505

ABSTRACT

Activation of the NF-κB pathway is strictly regulated to prevent excessive inflammatory and immune responses. In a well-known negative feedback model, IκBα-dependent NF-κB termination is a delayed response pattern in the later stage of activation, and the mechanisms mediating the rapid termination of active NF-κB remain unclear. Here, we showed IκBα-independent rapid termination of nuclear NF-κB mediated by CLK2, which negatively regulated active NF-κB by phosphorylating the RelA/p65 subunit of NF-κB at Ser180 in the nucleus to limit its transcriptional activation through degradation and nuclear export. Depletion of CLK2 increased the production of inflammatory cytokines, reduced viral replication and increased the survival of the mice. Mechanistically, CLK2 phosphorylated RelA/p65 at Ser180 in the nucleus, leading to ubiquitin‒proteasome-mediated degradation and cytoplasmic redistribution. Importantly, a CLK2 inhibitor promoted cytokine production, reduced viral replication, and accelerated murine psoriasis. This study revealed an IκBα-independent mechanism of early-stage termination of NF-κB in which phosphorylated Ser180 RelA/p65 turned off posttranslational modifications associated with transcriptional activation, ultimately resulting in the degradation and nuclear export of RelA/p65 to inhibit excessive inflammatory activation. Our findings showed that the phosphorylation of RelA/p65 at Ser180 in the nucleus inhibits early-stage NF-κB activation, thereby mediating the negative regulation of NF-κB.


Subject(s)
Cytoplasm , NF-KappaB Inhibitor alpha , NF-kappa B , Protein-Tyrosine Kinases , Transcription Factor RelA , Animals , Phosphorylation , NF-KappaB Inhibitor alpha/metabolism , NF-KappaB Inhibitor alpha/genetics , Mice , Transcription Factor RelA/metabolism , Humans , Protein-Tyrosine Kinases/metabolism , Protein-Tyrosine Kinases/genetics , NF-kappa B/metabolism , Cytoplasm/metabolism , Proteolysis , Cell Nucleus/metabolism , Virus Replication , HEK293 Cells , Signal Transduction , Mice, Inbred C57BL , Cytokines/metabolism , Active Transport, Cell Nucleus , Protein Serine-Threonine Kinases
2.
Dig Liver Dis ; 2024 May 13.
Article in English | MEDLINE | ID: mdl-38744556

ABSTRACT

OBJECTIVE: The primary purpose of the study was to explore the clinical efficacy of the novel snare assisted endoscopic resection of extraluminal growing gastric gastrointestinal stromal tumors (gastric GISTs) using external traction, and the secondary purpose was to compare the novel snare assisted endoscopic resection of extraluminal GISTs with the standard laparoscopic procedure. METHODS: We retrospectively analyzed the patients who underwent novel external traction assisted endoscopic resection or laparoscopic resection for their extraluminal gastric GIST ≤5 cm in diameter. RESULTS: A total of 111 patients (27 in the endoscopic group and 84 in the laparoscopic group) were included in this study. There was no significant difference in tumor diameter and complication rate between the two groups. The overall procedure time was slightly higher in the endoscopic group compared to the laparoscopic group (P = 0.034). However, postoperative hospitalization time (P < 0.001) and postoperative fasting time (P = 0.005) were shorter in the endoscopic group compared to the laparoscopic group. CONCLUSION: Snare external traction-assisted endoscopic resection of extraluminal growing gastric GISTs is safe and effective, and it provides a new adjunctive method for endoscopic resection of GIST.

3.
Nanoscale ; 2024 May 07.
Article in English | MEDLINE | ID: mdl-38712853

ABSTRACT

The widespread applicability of perovskite nanocrystals (PeNCs) is impeded by their intrinsic instability. A promising solution is utilizing robust chalcogenides as a protective shell to shield the sensitive luminescent cores from the external environment. However, the inferior structural stability and surface lability of PeNCs usually lead to perovskite phase transition during shell growth. Herein, we introduced smaller Zn ions to partially replace Pb ions in perovskites, which reduces the Pb-X bond length and enhances the Pb-X bond energy for inner lattice stabilization. Simultaneously, extra oleylammonium bromide (OAmBr) was added to protect the labile surface of PeNCs by compensating for the detachment of ligands and the loss of surface Br ions. As a result, the dual strategies enable the epitaxial growth of a ZnS shell and significantly enhance the chemical stability of CsZnPbBr3/ZnS core/shell PeNCs. After three thermal cycles ranging from 300 to 450 K, the core/shell PeNCs retained 70% of their initial photoluminescence (PL) intensity. In stark contrast, the pristine CsPbBr3 PeNCs exhibit complete PL quenching after just the first temperature cycle. For practical applications, the green core/shell PeNCs were integrated with commercially available red-emitting phosphors on a blue-emitting InGaN chip to fabricate a white light-emitting diode (WLED), which demonstrates a high luminous efficacy (LE) of 61.3 lm W-1 and nearly constant Commission Internationale de l'Eclairage (CIE) coordinates under varying operating currents.

4.
Eur J Radiol ; 175: 111479, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38663124

ABSTRACT

PURPOSE: To construct and validate CT radiomics model based on the peritumoral adipose region of gastric adenocarcinoma to preoperatively predict lymph node metastasis (LNM). METHODS AND METHODS: 293 consecutive gastric adenocarcinoma patients receiving radical gastrectomy with lymph node dissection in two medical institutions were stratified into a development set (from Institution A, n = 237), and an external validation set (from Institution B, n = 56). Volume of interest of peritumoral adipose region was segmented on preoperative portal-phase CT images. The least absolute shrinkage and selection operator method and stepwise logistic regression were used to select features and build radiomics models. Manual classification was performed according to routine CT characteristics. A classifier incorporating the radiomics score and CT characteristics was developed for predicting LNM. Area under the receiver operating characteristic curve (AUC) was used to show discrimination between tumors with and without LNM, and the calibration curves and Brier score were used to evaluate the predictive accuracy. Violin plots were used to show the distribution of radiomics score. RESULTS: AUC values of radiomics model to predict LNM were 0.938, 0.905, and 0.872 in the training, internal test, and external validation sets, respectively, higher than that of manual classification (0.674, all P values < 0.01). The radiomics score of the positive LNM group were higher than that of the negative group in all sets (both P-values < 0.001). The classifier showed no improved predictive power compared with the radiomics signature alone with AUC values of 0.916 and 0.872 in the development and external validation sets, respectively. Multivariate analysis showed that radiomics score was an independent predictor. CONCLUSIONS: Radiomics model based on peritumoral adipose region could be a useful approach for preoperative LNM prediction in gastric adenocarcinoma.

5.
Heliyon ; 10(7): e28119, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38601615

ABSTRACT

Background: The association between dietary vitamin B1 intake and cognitive performance in the noninstitutionalized older adult population of the United States remains unclear. Purpose: This study aimed to investigate the association between vitamin B1 intake and cognitive performance in older adults in the United States. Methods: Vitamin B1 intake was assessed through two 24-h dietary recalls. Weighted logistic regression was used to evaluate the association between vitamin B1 intake and three cognitive scores (immediate recall test [IRT], animal fluency test [AFT], and digit symbol substitution test [DSST]). Cognitive performance was measured by these three tests, and individuals scoring below the lowest quartile were categorized as cognitive impairment. Sensitivity analysis, including dose-response curves, subgroup analyses, interaction effects, per 1 SD, and quartiles, were performed to ensure the accuracy of the conclusion. Results: A total of 2896 participants over the age of 60 were included in this study. In the adjusted final model, the association between vitamin B1 intake and low cognitive performance in old age was statistically significant, with the following odds ratios (ORs) and 95% confidence intervals (CIs): IRT, 0.75 (0.57, 0.97), P = 0.018; AFT, 0.68 (0.50, 0.92), P = 0.007; DSST, 0.71 (0.54, 0.92), P = 0.005. Subgroup analyses showed that this association was statistically significant among males, white, low-education, and no memory impairment. The results of the sensitivity analyses confirmed the association between VB1 and cognitive function in old age and the absence of interactions in the final calibrated model. Conclusion: Dietary vitamin B1 intake is negatively associated with cognitive performance in older adults.

6.
Zhongguo Zhong Yao Za Zhi ; 49(6): 1517-1525, 2024 Mar.
Article in Chinese | MEDLINE | ID: mdl-38621935

ABSTRACT

Cervi Cornu is the ossified antler, or the base antler that falls off in the spring of the following year after the pilose antler is sawn off from Cervus elaphus or C. nippon, as a precious traditional Chinese medicine, has been recognized for its medicinal value and widely used in clinical practice. However, the origins of Cervi Cornu are miscellaneous, and Cervi Cornu is even mixed with adulterants in the market. Currently, there is a shortage of ways to identify Cervi Cornu and no standard to control the quality of Cervi Cornu. So it is valuable to develop a way to effectively identify Cervi Cornu from the adulterants. In this study, the differences in the mitochondrial barcode cytochrome b(Cytb) gene sequences of C. elaphus, C. nippon and their related species were compared and the specific single nucleotide polymorphism(SNP) sites on the Cytb sequences of Cervi Cornu were screened out. According to the screened SNPs, Cervi Cornu-specific primers dishmy-F and dishmy-R were designed. The PCR system was established and optimized, and the tolerance and feasibility of Taq polymerases and PCR systems affecting the repeatability of the PCR method were investigated. The amplification products of C. elaphus and C. nippon were digested using the restriction enzyme MseⅠ. The results showed that after electrophoresis of the product from PCR with the annealing temperature of 56 ℃ and 35 cycles, a single specific band at about 100 bp was observed for C. elaphus samples, and the product of C. elaphus samples was 60 bp shorter than that of C. nippon samples. There was no band for adulterants from other similar species such as Alces alces, Rangifer tarandus, Odocoileus virginianus, O. hemionus, Cap-reolus pygargus, Przewalskium albirostis and negative controls. The polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) method established in this study can quickly and accurately identify Cervi Cornu originated from C. elaphus in crude drugs, standard decoctions, and formula granules, and distinguish the origins of Cervi Cornu products, i.e., C. nippon and similar species. This study can be a reference for other studies on the quality standard of other formula granules of traditional Chinese medicines.


Subject(s)
Cornus , Deer , Animals , Polymorphism, Restriction Fragment Length , Cornus/genetics , Polymerase Chain Reaction/methods , Deer/genetics , DNA Primers
7.
Abdom Radiol (NY) ; 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38600228

ABSTRACT

PURPOSE: To explore the feasibility of predicting the pathological activity of Crohn's disease (CD) based on dual-energy CT enterography (DECTE). METHODS: The clinical, endoscopic, imaging and pathological data of 55 patients with CD scanned by DECTE were retrospectively analyzed; the pathological results were used as a reference standard to classify the diseased bowel segments into active and inactive phases. The normalized iodine concentration (NIC), energy-spectrum curve slope K, dual energy index (DEI), fat fraction (FF) of the arterial phases and venous phases were compared. To assess the parameters' predictive ability, receiver-operating characteristic curves were used. The Delong test was used to compare the differences between the diagnostic efficiency of each parameter. RESULTS: A total of 84 intestinal segments were included in the study, including 54 active intestinal segments and 30 inactive intestinal segments. The NIC, energy-spectrum curve slope K and DEI were significantly different between active and inactive bowel segments in the arterial and venous phases (P < 0.05), while FF were not significantly different (P > 0.05). The largest area under the curve (AUC) of NIC, energy-spectrum curve slope K and DEI were higher in arterial phase than in venous phase. For identifying the intestinal activity of CD, the maximum AUC of NIC in arterial phase was 0.908, with a sensitivity of 0.833 and a specificity of 0.800, and the DEI in arterial phase had the highest sensitivity (0.944). CONCLUSION: The NIC, energy-spectrum curve slope K and DEI can effectively distinguish the active and inactive phases of the intestinal segments of CD patients and provide good assistance for determining further treatment.

8.
Drug Des Devel Ther ; 18: 1189-1198, 2024.
Article in English | MEDLINE | ID: mdl-38645990

ABSTRACT

Purpose: Postoperative nausea and vomiting (PONV) frequently occur in patients after surgery. In this study, the authors investigated whether perioperative S-ketamine infusion could decrease the incidence of PONV in patients undergoing video-assisted thoracoscopic surgery (VATS) lobectomy. Patients and Methods: This prospective, randomized, double-blinded, controlled study was conducted a total of 420 patients from September 2021 to May 2023 at Xuzhou Central Hospital in China, who underwent elective VATS lobectomy under general anesthesia with tracheal intubation. The patients were randomly assigned to either the S-ketamine group or the control group. The S-ketamine group received a bolus injection of 0.5 mg/kg S-ketamine and an intraoperative continuous infusion of S-ketamine at a rate of 0.25 mg/kg/h. The control group received an equivalent volume of saline. All patients were equipped with patient-controlled intravenous analgesia (PCIA), with a continuous infusion rate of 0.03 mg/kg/h S-ketamine in the S-ketamine group or 0.03 µg/kg/h sufentanil in the control group. The primary outcome was the incidence of PONV. Secondary outcomes included perioperative opioid consumption, hemodynamics, postoperative pain, and adverse events. Results: The incidence of PONV in the S-ketamine group (9.7%) was significantly lower than in the control group (30.5%). Analysis of perioperative opioid usage revealed that remifentanil usage was 40.0% lower in the S-ketamine group compared to the control group (1414.8 µg vs 2358.2 µg), while sufentanil consumption was 75.2% lower (33.1 µg vs 133.6 µg). The S-ketamine group demonstrated better maintenance of hemodynamic stability. Additionally, the visual analogue scale (VAS) scores on postoperative day 1 (POD-1) and postoperative day 3 (POD-3) were significantly lower in the S-ketamine group. Finally, no statistically significant difference in other postoperative adverse reactions was observed between the two groups. Conclusion: The results of this trial indicate that perioperative S-ketamine infusion can effectively reduce the incidence of PONV in patients undergoing VATS lobectomy.


Subject(s)
Ketamine , Postoperative Nausea and Vomiting , Thoracic Surgery, Video-Assisted , Adult , Aged , Female , Humans , Male , Middle Aged , Double-Blind Method , Ketamine/administration & dosage , Postoperative Nausea and Vomiting/prevention & control , Prospective Studies , Thoracic Surgery, Video-Assisted/adverse effects
9.
Heliyon ; 10(5): e26862, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38486739

ABSTRACT

Flavonoids are natural phytochemicals that have therapeutic effects and act in the prevention of several pathologies. These phytochemicals can be found in lemon, sweet orange, bitter orange, clementine. Hesperidin and hesperetin are citrus flavonoids from the flavanones subclass that have anti-inflammatory, antioxidant, antitumor and antibacterial potential. Preclinical studies and clinical trials demonstrated therapeutical effects of hesperidin and its aglycone hesperetin in various diseases, such as bone diseases, cardiovascular diseases, neurological diseases, respiratory diseases, digestive diseases, urinary tract diseases. This review provides a comprehensive overview of the biological activities of hesperidin and hesperetin, their therapeutic potential in various diseases and their associated molecular mechanisms. This article also discusses future considerations for the clinical applications of hesperidin and hesperetin.

10.
Plant Biotechnol J ; 2024 Mar 25.
Article in English | MEDLINE | ID: mdl-38526838

ABSTRACT

Inter-subspecific indica-japonica hybrid rice (Oryza sativa) has the potential for increased yields over traditional indica intra-subspecies hybrid rice, but limited yield of F1 hybrid seed production (FHSP) hinders the development of indica-japonica hybrid rice breeding. Diurnal flower-opening time (DFOT) divergence between indica and japonica rice has been a major contributing factor to this issue, but few DFOT genes have been cloned. Here, we found that manipulating the expression of jasmonate (JA) pathway genes can effectively modulate DFOT to improve the yield of FHSP in rice. Treating japonica cultivar Zhonghua 11 (ZH11) with methyl jasmonate (MeJA) substantially advanced DFOT. Furthermore, overexpressing the JA biosynthesis gene OPDA REDUCTASE 7 (OsOPR7) and knocking out the JA inactivation gene CHILLING TOLERANCE 1 (OsHAN1) in ZH11 advanced DFOT by 1- and 2-h respectively; and knockout of the JA signal suppressor genes JASMONATE ZIM-DOMAIN PROTEIN 7 (OsJAZ7) and OsJAZ9 resulted in 50-min and 1.5-h earlier DFOT respectively. The yields of FHSP using japonica male-sterile lines GAZS with manipulated JA pathway genes were significantly higher than that of GAZS wildtype. Transcriptome analysis, cytological observations, measurements of elastic modulus and determination of cell wall components indicated that the JA pathway could affect the loosening of the lodicule cell walls by regulating their composition through controlling sugar metabolism, which in turn influences DFOT. This research has vital implications for breeding japonica rice cultivars with early DFOT to facilitate indica-japonica hybrid rice breeding.

11.
J Cardiothorac Surg ; 19(1): 141, 2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38504347

ABSTRACT

BACKGROUND: Non-small cell lung cancer (NSCLC) is the leading cause of morality among all malignant tumors. Smoking is one of the most important causes of NSCLC, which contributes not only to the initiation of NSCLC but also to its progression. The identification of specific biomarkers associated with smoking will promote diagnosis and treatment. METHODS: Data mining was used to identify the smoking associated gene SERPINB12. CCK8 assays, colony formation assays, a mouse xenograft model and transwell assays were performed to measure the biological functions of SERPINB12 in NSCLC. GSEA, luciferase reporter assays and immunofluorescence were conducted to explore the potential molecular mechanisms of SERPINB12 in NSCLC. RESULTS: In this study, by data mining the TCGA database, we found that SERPINB12 was greatly upregulated in NSCLC patients with cigarette consumption behavior, while the expression level was positively correlated with disease grade and poor prognosis. SERPINB12 is a kind of serpin peptidase inhibitor, but its function in malignant tumors remains largely unknown. Functionally, knockdown of SERPINB12 observably inhibited the proliferation and metastasis of NSCLC cells in vitro and in vivo. Moreover, downregulation of SERPINB12 attenuated Wnt signaling by inhibiting the nuclear translocation of ß-catenin, which explained the molecular mechanism underlying tumor progression. CONCLUSIONS: In conclusion, SERPINB12 functions as a tumorigenesis factor, which could be a promising biomarker for NSCLC patients with smoking behavior, as well as a therapeutic target.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Serpins , Humans , Animals , Mice , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , Wnt Signaling Pathway/genetics , Up-Regulation , Cell Line, Tumor , Smoking/adverse effects , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Cell Movement , Serpins/genetics
12.
Zhongguo Gu Shang ; 37(2): 196-206, 2024 Feb 25.
Article in Chinese | MEDLINE | ID: mdl-38425073

ABSTRACT

OBJECTIVE: To investigate whether Bushen Huoxue recipe can protect articular cartilage by regulating Akt/mTOR signaling pathway to promote the autophagy of chondrocytes in ovariectomized rats. METHODS: Among 30 SPF 12-week-old female SD rats weighing (247.0±7.0) g, 6 were randomly selected as the blank control group, and the remaining rats were randomly divided into model group, BSHXR-L group, BSHXR-M group and BSHXR-H group, with 6 rats in each group. The protective effect of Bushen Huoxue recipe on articular cartilage injury in rats was determined by visual observation score, muscovine O-solid green staining and immunohistochemistry. The expression of autophagy related proteins was detected by Western-blot, and the relative expression of Akt, mTOR and downstream autophagy genes was detected by qPCR. RESULTS: After modeling, BSHXR (L, M, H) groups could alleviate the histological damage of cartilage. Immunohistochemistry showed that the expression of Collagen-Ⅱand Aggrecan gradually increased, and the expression of MMP-13 gradually decreased, and the differences between BSHXR-M and BSHXR-H groups and model group were statistically significant (P<0.05). The results of Western-blot showed that the autophagy pathway proteins p-Akt/Akt and p-mTOR/mTOR were inhibited in the BSHXR(L, M, H) groups, and the expressions of downstream proteins Beclin-1 and LC3Ⅱwere gradually increased, while p62 was gradually decreased, showing a dose effect. QPCR results showed that BSHXR(L, M, H) groups could promote the relative expression of Beclin-1 and LC3ⅡmRNA, and inhibit the relative expression of p62, Akt, mTOR mRNA, and the differences were statistically significant compared with model group (P<0.05). CONCLUSION: Bushen Huoxue recipe can enhance the cartilage autophagy response by inhibiting the Akt/mTOR signaling pathway, and then protect the cartilage.


Subject(s)
Cartilage, Articular , Chondrocytes , Drugs, Chinese Herbal , Rats , Female , Animals , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-akt/pharmacology , Beclin-1/genetics , Beclin-1/metabolism , Beclin-1/pharmacology , Rats, Sprague-Dawley , Signal Transduction , TOR Serine-Threonine Kinases/genetics , TOR Serine-Threonine Kinases/metabolism , Autophagy/genetics
13.
Adv Mater ; : e2313889, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38536181

ABSTRACT

Two-dimensional (2D) Dion-Jacobson (DJ) perovskites typically outperform Ruddlesden-Popper (RP) analogs in terms of photodetection (PD). However, the mechanism behind this enhanced performance remains elusive. Theoretical calculations for elucidating interlayer spacer conformation-induced multiple hydrogen bonds in 2D perovskite are presented, along with the synthesis of DPAPbBr4 (DPB) single crystals (SCs) and their PD properties under X-ray/ultraviolet (UV) excitation. The high-quality DPB SC enhances PD with exceptional photoresponse attributes, including a high on/off ratio (4.89 × 104), high responsivity (2.44 A W⁻1), along with large dynamic linear range (154 dB) and low detection limit (7.1 nW cm⁻2), which are currently the best results among 2D perovskite SC detectors, respectively. Importantly, high-resolution images are obtained under UV illumination with weak light levels. The SC X-ray detector exhibits a high sensitivity of 663 µC Gyair⁻1 cm-2 at 10 V and a detection limit of 1.44 µGyair s⁻1. This study explores 2D DJ perovskites for efficient and innovative optoelectronic applications.

14.
Int Orthop ; 48(6): 1401-1409, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38478021

ABSTRACT

PURPOSE: To assess the efficacy of arthroscopic debridement and reduction through two medial portals for the treatment of developmental dislocation of the hip (DDH) with failure of initial closed reduction and to explore key pathological structures obstructing reduction. METHODS: Forty-eight children with 58 irreducible dislocated hips treated by arthroscopic reduction between January 2017 and December 2020 were retrospectively evaluated. Arthroscopic reduction was performed via two medial portals located in the superior and inferior adductor longus. All intra-articular obstacles were eliminated via arthroscopy, followed by manual reduction and spica cast immobilization. The surgical duration, extent of improvement in the safe zone, and extent of secondary surgical treatment were noted. All the children were followed up for > 24 months. Hip function and radiographic outcomes were evaluated. RESULTS: All 58 hips showed safe zone improvement and concentric reduction after arthroscopic debridement. Hypertrophic ligamentum teres and thickened pulvinars were detected and resected in all hips. Constrictive capsules preventing reduction were observed in 15 hips, which needed to be further released. No inverted labrum was observed. Secondary surgery was performed in four hips with redislocation and seven hips with subluxation during follow-up. The remaining 47 hips (81.03%) maintained their reduction at the last follow-up. Excellent and good clinical outcomes were achieved in 95.74% of patients according to McKay's criteria. Two hips, three hips, and one hip were diagnosed with grade I, II, and III osteonecrosis of the femoral head, respectively. CONCLUSION: This study demonstrated that arthroscopic debridement and reduction is a safe and feasible choice for treating irreducible DDH.


Subject(s)
Arthroscopy , Debridement , Humans , Arthroscopy/methods , Male , Debridement/methods , Female , Retrospective Studies , Child, Preschool , Treatment Outcome , Hip Dislocation, Congenital/surgery , Infant , Treatment Failure , Developmental Dysplasia of the Hip/surgery , Child
15.
Eur J Med Chem ; 268: 116236, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38367494

ABSTRACT

Estrogen receptor (ER) ß and histone deacetylases (HDACs), when overexpressed, are associated closely with the occurrence and development of prostate cancer and are, therefore, considered important targets and biomarkers used in the clinical treatment of prostate cancer. The present study involved the design and synthesis of the first ERß and HDAC dual-target near-infrared fluorescent probe with both imaging capacity and antitumor activity for prostate cancer. Both P1 and P2 probes exhibited excellent ERß selectivity, with P1 being almost exclusively selective for ERß compared to ERα. In addition, P1 exhibited good optical properties, such as strong near-infrared emission, large Stokes shift, and better anti-interference ability, along with excellent imaging ability for living cells. P1 also exhibited potent inhibitory activity against HDAC6 and DU-145 cells, with IC50 values of 52 nM and 0.96 µM, respectively. Further, P1 was applied successfully for the in vivo imaging of prostate cancer in a mouse model, and significant in vivo antitumor efficacy was achieved. The developed dual-target NIR fluorescent probe is expected to serve as an effective tool in the research on prostate cancer, leading to novel insights for the theranostic study of diseases related to ERß and HDACs.


Subject(s)
Histone Deacetylases , Prostatic Neoplasms , Humans , Male , Mice , Animals , Estrogen Receptor beta , Fluorescent Dyes/pharmacology , Precision Medicine , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/drug therapy
16.
Curr Med Imaging ; 20: 1-10, 2024.
Article in English | MEDLINE | ID: mdl-38389354

ABSTRACT

BACKGROUND: Chest wall tuberculosis may develop if tuberculous (TB) lesions spread through the chest wall and invade the thoracic cavity. The presence of a mass on the patient's chest wall may be the first indication of TB, and a chest CT scan can help diagnose external penetrating chest wall TB, the incursion of tuberculosis from the lungs into the chest wall. OBJECTIVE: This study examines the safety and efficacy of thoracoscopic-assisted surgery for the treatment of penetrating chest wall tuberculosis as a means of exploring novel concepts of minimally invasive surgery. METHODS: Our hospital conducted a retrospective study of 25 patients with penetrating chest wall TB who underwent thoracoscopic surgery between January 2020 and June 2021. General demographics, CT scan data linked to surgery, and postoperative patient outcomes were compared between the two groups. The data was also evaluated to determine the range of operation time and the volume of bleeding from different foci in the thoracic cavity. RESULTS: All procedures went well after patients took conventional antituberculosis medication for at least two weeks prior to surgery. CT scans showed that thoracoscopic surgery needed a smaller incision than traditional chest wall TB surgery, with no discernible increase in surgical time. Postoperative tube use, length of hospital stay, and blood loss were all significantly lower than they would have been with conventional surgery. In addition, thoracoscopy was associated with a significantly reduced rate of subsequent treatment. Fibrous plate development and calcification caused the longest operation times in the thoracoscopic surgery group, whereas multiple pleural tuberculomas generated the most hemorrhage. Thoracoscopic surgery usually reveals tuberculous foci hiding in the thoracic cavity. CONCLUSION: Thethoracic surgery can eliminate the TB focus in the chest wall and intrathoracic while treating penetrating chest wall tuberculosis. The CT scan is a crucial part of the diagnostic process for these patients. Minor surgical trauma, low complication and recurrence rates, and good results. There is a greater distinction between the two surgical approaches for patients with penetrating chest wall TB as opposed to those with basic chest wall tuberculosis.


Subject(s)
Thoracic Wall , Tuberculosis , Humans , Thoracic Wall/diagnostic imaging , Thoracic Wall/surgery , Thoracic Surgery, Video-Assisted/methods , Retrospective Studies , Feasibility Studies , Tomography , Tomography, X-Ray Computed , Computers
17.
Curr Med Imaging ; 20: 1-11, 2024.
Article in English | MEDLINE | ID: mdl-38389371

ABSTRACT

BACKGROUND: The prediction power of MRI radiomics for microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC) remains uncertain. OBJECTIVE: To investigate the prediction performance of MRI radiomics for MVI in HCC. METHODS: Original studies focusing on preoperative prediction performance of MRI radiomics for MVI in HCC, were systematically searched from databases of PubMed, Embase, Web of Science and Cochrane Library. Radiomics quality score (RQS) and risk of bias of involved studies were evaluated. Meta-analysis was carried out to demonstrate the value of MRI radiomics for MVI prediction in HCC. Influencing factors of the prediction performance of MRI radiomics were identified by subgroup analyses. RESULTS: 13 studies classified as type 2a or above according to the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis statement were eligible for this systematic review and meta-analysis. The studies achieved an average RQS of 14 (ranging from 11 to 17), accounting for 38.9% of the total points. MRI radiomics achieved a pooled sensitivity of 0.82 (95%CI: 0.78 - 0.86), specificity of 0.79 (95%CI: 0.76 - 0.83) and area under the summary receiver operator characteristic curve (AUC) of 0.88 (95%CI: 0.84 - 0.91) to predict MVI in HCC. Radiomics models combined with clinical features achieved superior performances compared to models without the combination (AUC: 0.90 vs 0.85, P < 0.05). CONCLUSION: MRI radiomics has the potential for preoperative prediction of MVI in HCC. Further studies with high methodological quality should be designed to improve the reliability and reproducibility of the radiomics models for clinical application. The systematic review and meta-analysis was registered prospectively in the International Prospective Register of Systematic Reviews (No. CRD42022333822).


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/diagnostic imaging , Liver Neoplasms/diagnostic imaging , Radiomics , Reproducibility of Results , Magnetic Resonance Imaging
18.
Eur J Med Chem ; 267: 116184, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38320426

ABSTRACT

Proteolysis targeting chimera (PROTAC) technology, a groundbreaking strategy for degradation of pathogenic proteins by hijacking of the ubiquitin-proteasome-system has become a promising strategy in drug design. However, the real-time monitoring and visualization of protein degradation processes have been long-standing challenges in the realm of drug development. In this research, we sought to amalgamate the highly efficient protein-degrading capabilities of PROTAC technology with the visualization attributes of fluorescent probes, with the potential to pave the path for the design and development of a novel class of visual PROTACs. These novel PROTACs uniquely possess both fluorescence imaging and therapeutic characteristics, all with the goal of enabling real-time observations of protein degradation processes. Our approach involved the utilization of a high ER-targeting fluorescent probe, previously reported in our laboratory, which served as a warhead that specifically binds to the protein of interest (POI). Additionally, a VHL ligand for recruiting E3 ligase and linkers of various lengths were incorporated to synthesize a series of novel ER-inherent fluorescence PROTACs. Among them, compound A3 demonstrated remarkable efficiency in degrading ERα proteins (DC50 = 0.12 µM) and displaying exceptional anti-proliferative activity against MCF-7 cells (IC50 = 0.051 µM). Furthermore, it exhibited impressive fluorescence imaging performance, boasting an emission wavelength of up to 582 nm, a Stokes shift of 116 nm, and consistent optical properties. These attributes make it especially suitable for the real-time, in situ tracking of ERα protein degradation processes, thus may serve as a privileged visual theranostic PROTAC for ERα+ breast cancer. This study not only broadens the application spectrum of PROTAC technology but also introduces a novel approach for real-time visualization of protein degradation processes, ultimately enhancing the diagnostic and treatment efficacy of PROTACs.


Subject(s)
Estrogen Receptor alpha , Proteolysis Targeting Chimera , Humans , Proteolysis , Estrogen Receptor alpha/metabolism , Precision Medicine , Ubiquitin-Protein Ligases/metabolism , Proteins/metabolism
19.
Sci Total Environ ; 920: 170558, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38325459

ABSTRACT

The trees of the Dongzhai Harbor mangrove forest suffer from antibiotic contamination from surrounding aquaculture areas. Despite this being one of the largest mangrove forests in China, few studies have focused on the antibiotic pollution status in these aquaculture areas. In the present study, the occurrence, distribution, and risk assessment of 37 antibiotics in surface water and sediment samples from aquaculture areas around Dongzhai Harbor mangrove forests were analyzed. The concentration of total antibiotics (∑antibiotics) ranged from 78.4 ng/L to 225.6 ng/L in surface water (except S14-A2) and from 19.5 ng/g dry weight (dw) to 229 ng/g dw in sediment. In the sediment, the concentrations of ∑antibiotics were relatively low (19.5-52.3 ng/g dw) at 75 % of the sampling sites, while they were high (95.7-229.0 ng/g dw) at a few sampling sites (S13-A1, S13D, S8D). The correlation analysis results showed that the Kd values of the 9 antibiotics were significantly positively correlated with molecular weight (MW), Kow, and LogKow. Risk assessment revealed that sulfamethoxazole (SMX) in surface water and SMX, enoxacin (ENX), ciprofloxacin (CFX), enrofloxacin (EFX), ofloxacin (OFX), and norfloxacin (NFX) in sediment had medium/high risk quotients (RQs) at 62.5 % and 25-100 %, respectively, of the sampling sites. The antibiotic mixture in surface water (0.06-3.36) and sediment (0.43-309) posed a high risk at 37.5 % and 66.7 %, respectively, of the sampling sites. SMX was selected as an indicator of antibiotic pollution in surface water to assist regulatory authorities in monitoring and managing antibiotic pollution in the aquaculture zone of Dongzhai Harbor. Overall, the results of the present study provide a comprehensive and detailed analysis of the characteristics of antibiotics in the aquaculture environment around the Dongzhai Harbor mangrove system and provide a theoretical basis for the source control of antibiotics in mangrove systems.


Subject(s)
Anti-Bacterial Agents , Water Pollutants, Chemical , Anti-Bacterial Agents/analysis , Wetlands , Aquaculture , Sulfamethoxazole/analysis , Water/analysis , Risk Assessment , China , Water Pollutants, Chemical/analysis , Environmental Monitoring
20.
Nat Commun ; 15(1): 1609, 2024 Feb 21.
Article in English | MEDLINE | ID: mdl-38383585

ABSTRACT

The scalable and low-cost room temperature (RT) synthesis for pure-iodine all-inorganic perovskite colloidal quantum dots (QDs) is a challenge due to the phase transition induced by thermal unequilibrium. Here, we introduce a direct RT strongly confined spontaneous crystallization strategy in a Cs-deficient reaction system without polar solvents for synthesizing stable pure-iodine all-inorganic tin-lead (Sn-Pb) alloyed perovskite colloidal QDs, which exhibit bright yellow luminescence. By tuning the ratio of Cs/Pb precursors, the size confinement effect and optical band gap of the resultant CsSnxPb1-xI3 perovskite QDs can be well controlled. This strongly confined RT approach is universal for wider bandgap bromine- and chlorine-based all-inorganic and iodine-based hybrid perovskite QDs. The alloyed CsSn0.09Pb0.91I3 QDs show superior yellow emission properties with prolonged carrier lifetime and significantly increased colloidal stability compared to the pristine CsPbI3 QDs, which is enabled by strong size confinement, Sn2+ passivation and enhanced formation energy. These findings provide a RT size-stabilized synthesis pathway to achieve high-performance pure-iodine all-inorganic Sn-Pb mixed perovskite colloidal QDs for optoelectronic applications.

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