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2.
J Am Chem Soc ; 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38943601

RESUMO

Carbonyl nitrenes are versatile intermediates that have been extensively characterized; however, their phosphorus analogues remain largely unknown. Herein, we report the observation of a rare example of carbonyl phosphinidene NH2C(O)P, which was generated through the photolytic (193 nm) dehydrogenation of phosphinecarboxamide (NH2C(O)PH2) in a solid N2-matrix at 12 K. The characterization of NH2C(O)P in the triplet ground state with matrix-isolation IR and ultraviolet-visible (UV-vis) spectroscopy is supported by comprehensive isotope labeling experiments (D and 15N) and quantum chemical calculations. Upon visible-light irradiation at 680 nm, NH2C(O)P inserts into dihydrogen by the reformation of NH2C(O)PH2 with concomitant isomerization to the more stable aminophosphaketene (NH2PCO). Additionally, the photoisomerization of NH2C(O)PH2 to NH2C(OH) = PH along with decomposition by yielding hydrogen-bonded complexes HNCO···PH3 and HPCO···NH3 has been observed in the matrix.

3.
Med Phys ; 2024 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-38922975

RESUMO

BACKGROUND: Intensity Modulated Proton Therapy (IMPT) is a sophisticated radiation treatment allowing for precise dose distributions. However, conventional spot selection strategies in IMPT face challenges, particularly with minimum monitor unit (MU) constraints, affecting planning quality and efficiency. PURPOSE: This study introduces an innovative Two-Stage Mixed Integer Linear Programming (MILP) method to optimize spot intensity in IMPT with Lower Bound (LB) constraints. This method seeks to improve treatment planning efficiency and precision, overcoming limitations of existing strategies. METHODS: Our approach evaluates prevalent IMPT spot selection strategies, identifying their limitations, especially concerning MU constraints. We integrated LB constraints into a MILP framework, using a novel three-phase strategy for spot pool selection, to enhance performance over traditional heuristic methods and L1 + L∞ strategies. The method's efficacy was tested in eight study cases, using Dose-Volume Histograms (DVHs), spot selection efficiency, and computation time analysis for benchmarking against established methods. RESULTS: The proposed method showed superior performance in DVH quality, adhering to LB constraints while maintaining high-quality treatment plans. It outperformed existing techniques in spot selection, reducing unnecessary spots and balancing precision with efficiency. Cases studies confirmed the method's effectiveness in producing clinically feasible plans with enhanced dose distributions and reduced hotspots, especially in cases with elevated LB constraints. CONCLUSIONS: Our Two-Stage MILP strategy signifies a significant advancement in IMPT treatment planning. By incorporating LB constraints directly into the optimization process, it achieves superior plan quality and deliverability compared to current methods. This approach is particularly advantageous in clinical settings requiring minimum spot number and high MU LB constraints, offering the potential for improved patient outcomes through more precise and efficient radiation therapy plans.

4.
Orthop Surg ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38923347

RESUMO

Osteoporosis (OP) is a systemic metabolic bone disease that is characterized by decreased bone mineral density and microstructural damage to bone tissue. Recent studies have demonstrated significant advances in the research of programmed cell death (PCD) in OP. However, there is no bibliometric analysis in this research field. This study searched the Web of Science Core Collection (WoSCC) database for literature related to OP and PCD from 2000 to 2023. This study used VOSviewers 1.6.20, the "bibliometrix" R package, and CiteSpace (6.2.R3) for bibliometric and visualization analysis. A total of 2905 articles from 80 countries were included, with China and the United States leading the way. The number of publications related to PCD in OP is increasing year by year. The main research institutions are Shanghai Jiao Tong University, Chinese Medical University, Southern Medical University, Zhejiang University, and Soochow University. Bone is the most popular journal in the field of PCD in OP, and the Journal of Bone and Mineral Research is the most co-cited journal. These publications come from 14,801 authors, with Liu Zong-Ping, Yang Lei, Manolagas Stavros C, Zhang Wei, and Zhao Hong-Yan having published the most papers. Ronald S. Weinstein was co-cited most often. Oxidative stress and autophagy are the current research hot spots for PCD in OP. This bibliometric study provides the first comprehensive summary of trends and developments in PCD research in OP. This information identifies the most recent research frontiers and hot directions, which will provide a definitive reference for scholars studying PCD in OP.

5.
Curr Issues Mol Biol ; 46(6): 5682-5700, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38921011

RESUMO

It is known that sialyllactose (SL) in mammalians is a major source of sialic acid (Sia), which can further form cytidine monophosphate sialic acid (CMP-Sia), and the final product is polysialic acid (polySia) using polysialyltransferases (polySTs) on the neural cell adhesion molecule (NCAM). This process is called NCAM polysialylation. The overexpression of polysialylation is strongly related to cancer cell migration, invasion, and metastasis. In order to inhibit the overexpression of polysialylation, in this study, SL was selected as an inhibitor to test whether polysialylation could be inhibited. Our results suggest that the interactions between the polysialyltransferase domain (PSTD) in polyST and CMP-Siaand the PSTD and polySia could be inhibited when the 3'-sialyllactose (3'-SL) or 6'-sialyllactose (6'-SL) concentration is about 0.5 mM or 6'-SL and 3 mM, respectively. The results also show that SLs (particularly for 3'-SL) are the ideal inhibitors compared with another two inhibitors, low-molecular-weight heparin (LMWH) and cytidine monophosphate (CMP), because 3'-SL can not only be used to inhibit NCAM polysialylation, but is also one of the best supplements for infant formula and the gut health system.

6.
Biomimetics (Basel) ; 9(6)2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38921223

RESUMO

The beetle, of the order Coleoptera, possesses outstanding flight capabilities. After completing flight, they can fold their hindwings under the elytra and swiftly unfold them again when they take off. This sophisticated hindwing structure is a result of biological evolution, showcasing the strong environmental adaptability of this species. The beetle's hindwings can provide biomimetic inspiration for the design of flapping-wing micro air vehicles (FWMAVs). In this study, the Asian ladybird (Harmonia axyridis Pallas) was chosen as the bionic research object. Various kinematic parameters of its flapping flight were analyzed, including the flight characteristics of the hindwings, wing tip motion trajectories, and aerodynamic characteristics. Based on these results, a flapping kinematic model of the Asian ladybird was established. Then, three bionic deployable wing models were designed and their structural mechanical properties were analyzed. The results show that the structure of wing vein bars determined the mechanical properties of the bionic wing. This study can provide a theoretical basis and technical reference for further bionic wing design.

7.
Sci Total Environ ; 945: 173914, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38885715

RESUMO

As anthropogenic disturbance on deep-sea seamount ecosystems grows, there is an urgent need for a better understanding of the biodiversity and community structure in benthic ecosystems, which can vary at local and regional scales. A survey of the benthic megafauna on two adjacent deep-water seamounts in the northwestern Pacific Ocean was conducted, which are covered by cobalt-rich crusts, to assess the biodiversity patterns and dissimilarity of assemblage composition. Based on a multidisciplinary dataset generated from video recordings, multibeam bathymetry data, and near-bottom currents, environmental and spatial factors impacting the megabenthic communities were explored. Results showed that these two deep-water seamounts were dominated by hexactinellids, crinoids, and octocorals. The seamounts were able to support diverse and moderately abundant megafauna, with a total of 6436 individuals classified into 94 morphospecies. The survey covered a distance of 52.2 km across a depth range of 1421-3335 m, revealing multiple distinct megabenthic assemblages. The megabenthic communities of the two deep-water seamounts, with comparable environmental conditions, exhibited similarities in overall density, richness, and faunal lists, while dissimilarities in the relative abundance of taxa and assemblage composition. No gradual depth-related change in terms of abundance, richness, or species turnover was observed across the two seamounts, despite the statistical significance of depth in structuring the overall communities. The spatial distribution of megabenthic communities displayed a discontinuous and patchy pattern throughout the two deep-water seamounts. This patchiness was driven by the interactive effects of multiple environmental factors. Near-bottom currents and microhabitat features were the primary drivers influencing their dissimilarities in megabenthic community structure. This case study on the megabenthic community structure of two adjacent seamounts with cobalt-rich crusts can serve as an environmental baseline, providing a reference status for the conservation and management of seamount ecosystems, particularly valuable for areas being considered for deep-sea mining.

8.
Am Surg ; : 31348241260274, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38848748

RESUMO

PURPOSE: The Boston naming test (BNT), as a simple, fast, and easily administered neuropsychological test, was demonstrated to be useful in detecting language function. In this study, BNT was investigated whether it could be a screening tool for early postoperative cognitive dysfunction (POCD). METHODS: This prospective observational cohort study included 132 major noncardiac surgery patients and 81 nonsurgical controls. All participants underwent a mini-mental state examination (MMSE) and BNT 1 day before and 7 days after surgery. Early POCD was assessed by reliable change index and control group results. RESULTS: Seven days after surgery, among 132 patients, POCD was detected in 30 (22.7%) patients (95% CI, 15.5%-30.0%) based on MMSE, and 45 (34.1%) patients (95% CI, 26.3%-41.9%) were found with postoperative language function decline based on BNT and MMSE. Agreement between the BNT spontaneous naming and MMSE total scoring was moderate (Kappa .523), and the sensitivity of BNT spontaneous naming for detecting early POCD was .767. Further analysis showed that areas under receiver operating characteristics curves (AUC) did not show statistically significant differences when BNT spontaneous naming (AUC .862) was compared with MMSE language functional subtests (AUC .889), or non-language functional subtests (AUC .933). CONCLUSION: This study indicates the feasibility of implementing the BNT spontaneous naming test to screen early POCD in elderly patients after major noncardiac surgery.

9.
Sci Rep ; 14(1): 13489, 2024 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-38866931

RESUMO

Chieh-qua (Benincasa hispida Cogn. var. Chieh-qua How.) fruit development starts post pollination. With the continuous expansion of the fruit, the soluble solid content of the fruit decreases. Because there are no reports on the early development of Chieh-qua fruit, this study compared fruit transcriptomes at 0-, 3-, and 7 day post pollination (dpp). 104,747 unigenes were assembled from clean reads and compared using six public databases for similarity searching. Compared with those of 0 dpp (C), there were differences in the expression of 12,982 and 6541 genes in the fruit tissue at 3 dpp and 7 dpp, respectively. Compared with 3 dpp (B), there were 14,314 differentially expressed genes in the fruit at 7 dpp (A). Based on the analysis of transcription factors, 213 nucleotides in the MYB superfamily were identified; among them, 94 unigenes of the MYB superfamily were differentially expressed at the three stages. In the pairwise comparison of differential expression, eight unigenes (Gene_id: TRINITY_DN32880_c1_g2, TRINITY_DN35142_c2_g2, TRINITY_DN32454_c11_g6, TRINITY_DN34105_c2_g7, TRINITY_DN32758_c3_g3, TRINITY_DN33604_c4_g10, TRINITY_DN34466_c3_g1, TRINITY_DN35924_c3_g2) were homologous to those of MYB59, MYB-GT3b, MYB18, MYB4, MYB108, MYB306, MYB340, and MYB-bHLH13. These unigenes differed significantly among the three stages. Furthermore, MYB59 and MYB18 exhibited higher expression at 7 dpp. MYB4, MYB-GT3b, MYB108, and MYB306 showed the highest expression levels in fruits at 3 dpp. In addition, MYB340 and MYB-bHLH13 showed higher expression levels during the unpollinated stage. MYB59, MYB-GT3b, MYB18, MYB4, MYB108, MYB306, MYB340, and MYB-bHLH13 may play crucial roles in Chieh-qua fruit development, defense, and blossoming. This study provides a basis for further investigation of MYB superfamily genes involved in early fruit expansion in chieh-qua.


Assuntos
Frutas , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Fatores de Transcrição , Frutas/genética , Frutas/crescimento & desenvolvimento , Frutas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Perfilação da Expressão Gênica/métodos , Transcriptoma , RNA-Seq/métodos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Anotação de Sequência Molecular
10.
Phys Rev Lett ; 132(16): 160801, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38701444

RESUMO

A solid-state approach for quantum networks is advantageous, as it allows the integration of nanophotonics to enhance the photon emission and the utilization of weakly coupled nuclear spins for long-lived storage. Silicon carbide, specifically point defects within it, shows great promise in this regard due to the easy of availability and well-established nanofabrication techniques. Despite of remarkable progresses made, achieving spin-photon entanglement remains a crucial aspect to be realized. In this Letter, we experimentally generate entanglement between a silicon vacancy defect in silicon carbide and a scattered single photon in the zero-phonon line. The spin state is measured by detecting photons scattered in the phonon sideband. The photonic qubit is encoded in the time-bin degree of freedom and measured using an unbalanced Mach-Zehnder interferometer. Photonic correlations not only reveal the quality of the entanglement but also verify the deterministic nature of the entanglement creation process. By harnessing two pairs of such spin-photon entanglement, it becomes straightforward to entangle remote quantum nodes at long distance.

11.
Zhongguo Zhong Yao Za Zhi ; 49(7): 1882-1887, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-38812200

RESUMO

Chemical constituents from the ethanol extract of Picrorhiza scrophulariiflora were isolated and purified by column chromatography. Their structures were identified by HR-MS, 1D and 2D-NMR, and their cytotoxicity was assessed by CCK-8 assay. Four compounds were isolated and identified as follows: 2ß-D-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosterol-5,25-diene-22-one(1), 2ß-D-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5,24-diene-22-one(2), 25-acetoxy-2ß-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5-ene-22-one(3) and 25-acetoxy-2ß-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5,23-(E)-diene-22-one(4). Compound 1 represents a new cucurbitane glycoside. The half inhibitory concentrations of the 4 compounds exceeded 100 µmol·L~(-1) against four tumor cell lines, indicating no significant cytotoxicity.


Assuntos
Glicosídeos , Picrorhiza , Glicosídeos/química , Glicosídeos/isolamento & purificação , Humanos , Linhagem Celular Tumoral , Picrorhiza/química , Estrutura Molecular , Espectroscopia de Ressonância Magnética , Medicamentos de Ervas Chinesas/química , Triterpenos
12.
J Integr Med ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38789290

RESUMO

BACKGROUND: Hypertension, a prevalent disease, is a significant risk factor for coronary heart disease. Huoxue Qianyang Qutan Recipe (HQQR), a traditional Chinese herbal remedy, has been used for treating hypertension over several years. OBJECTIVE: This study assesses HQQR's efficacy for controlling blood pressure among patients with hypertension related to blood stasis, yang hyperactivity and phlegm. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A randomized controlled trial was conducted at the Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, China, from July 2020 to June 2022. Major components of HQQR were identified using thin-layer chromatography and high-performance liquid chromatography. Participants aged 18-80 years, exhibiting traditional Chinese medicine syndromes of blood stasis, yang hyperactivity or phlegm, along with grades 1 or 2 hypertension, were randomly categorized into two groups. The intervention group was given HQQR granules alongside conventional hypertension treatment, while the control group was given placebo granules in addition to conventional treatment for 12 weeks. MAIN OUTCOME MEASURES: The primary outcome was clinic blood pressure, whereas secondary outcomes included metabolic indices (e.g., homeostasis model assessment of insulin resistance [HOMA-IR], total cholesterol [TC], low-density lipoprotein cholesterol and triglyceride), target organ damage indices (left ventricular mass index and urinary albumin creatinine ratio [UACR]) and inflammation indices (interleukin-6 [IL-6] and high-sensitivity C-reactive protein [hs-CRP]). RESULTS: HQQR's primary components were identified as salvianolic acid B, emodin and ferulic acid. Of the 216 participants (108 in each group), compared to the control, the intervention group exhibited significant improvements (P < 0.001) in clinic systolic blood pressure ([136.24 ± 7.63] vs [130.06 ± 8.50] mmHg), clinic diastolic blood pressure ([84.34 ± 8.72] vs [80.46 ± 6.05] mmHg), home systolic blood pressure ([131.64 ± 8.74] vs [122.36 ± 8.45] mmHg) and home diastolic blood pressure ([78.47 ± 9.53] vs [71.79 ± 6.82] mmHg). HQQR demonstrated a reduction in ambulatory blood pressure (24-hour systolic blood pressure: [133.75 ± 10.49] vs [132.46 ± 8.84] mmHg and 24-hour diastolic blood pressure: [84.12 ± 8.01] vs [82.11 ± 7.45] mmHg) and an improvement in HOMA-IR ([4.09 ± 1.72] vs [3.98 ± 1.44]), TC ([4.66 ± 1.47] vs [3.75 ± 1.81] mmol/L) and UACR (75.94 [5.12, 401.12] vs 45.61 [4.26, 234.26]). Moreover, HQQR demonstrated a decrease in hs-CRP (1.46 [0.10, 10.53] vs 0.57 [0.12, 3.99] mg/L) and IL-6 (6.69 [2.00, 29.74] vs 5.27 [2.00, 9.73] pg/mL), with no reported side effects (P < 0.001). CONCLUSION: This study highlights the therapeutic potential of HQQR use in ameliorating blood pressure, glycolipid metabolism, and inflammation in patients with hypertension. TRIAL REGISTRATION: ChiCTR2000035092 (https://www.chictr.org.cn/). Please cite this article as: Xie J, Ma YL, Gui MT, Yao L, Li JH, Wang MZ, Zhou XJ, Wang YF, Zhao MY, Cao H, Lu B, Fu DY. Efficacy of Huoxue Qianyang Qutan Recipe on essential hypertension: A randomized, double-blind, placebo-controlled trial. J Integr Med. 2024; Epub ahead of print.

13.
Int J Mol Sci ; 25(9)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38731861

RESUMO

The expression of polysialic acid (polySia) on the neuronal cell adhesion molecule (NCAM) is called NCAM-polysialylation, which is strongly related to the migration and invasion of tumor cells and aggressive clinical status. Thus, it is important to select a proper drug to block tumor cell migration during clinical treatment. In this study, we proposed that lactoferrin (LFcinB11) may be a better candidate for inhibiting NCAM polysialylation when compared with CMP and low-molecular-weight heparin (LMWH), which were determined based on our NMR studies. Furthermore, neutrophil extracellular traps (NETs) represent the most dramatic stage in the cell death process, and the release of NETs is related to the pathogenesis of autoimmune and inflammatory disorders, with proposed involvement in glomerulonephritis, chronic lung disease, sepsis, and vascular disorders. In this study, the molecular mechanisms involved in the inhibition of NET release using LFcinB11 as an inhibitor were also determined. Based on these results, LFcinB11 is proposed as being a bifunctional inhibitor for inhibiting both NCAM polysialylation and the release of NETs.


Assuntos
Armadilhas Extracelulares , Lactoferrina , Moléculas de Adesão de Célula Nervosa , Ácidos Siálicos , Lactoferrina/farmacologia , Lactoferrina/metabolismo , Humanos , Armadilhas Extracelulares/metabolismo , Armadilhas Extracelulares/efeitos dos fármacos , Moléculas de Adesão de Célula Nervosa/metabolismo , Ácidos Siálicos/metabolismo , Neutrófilos/metabolismo , Neutrófilos/efeitos dos fármacos , Heparina de Baixo Peso Molecular/farmacologia
14.
J Agric Food Chem ; 72(23): 13138-13153, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38814319

RESUMO

The fruit of Alpinia oxyphylla Miq is an important food spice in southern China and has been used in the treatment of kidney disorders for centuries. In order to discover the natural products with potent renoprotective activities in A. oxyphylla and provide some references for its usage, systematic phytochemical studies were carried out and 24 new diverse sesquiterpenoids, including seven guaiane sesquiterpenoids (1-7), 10 eudesmane sesquiterpenoids (9-13, 18, 19, and 21-23), six cadinane sesquiterpenoids (31-35 and 38), and an eremophilane sesquiterpenoid (40), along with 24 known analogues were isolated and elucidated by analysis of spectroscopic data and quantum-chemical calculations. Biological evaluation showed that 6 sesquiterpenoids could significantly inhibit the expression of extracellular matrix components, α-SMA in TGF-ß1 induced kidney proximal tubular cells (NRK-52e) at low concentrations, and 9 sesquiterpenoids could also downregulate fibronectin and collagen I in a concentration-dependent manner, showing their potential in renal fibrosis. Further action mechanism study displayed that TGF-ß1/Smads pathway might be involved in the antifibrotic effects of active sesquiterpenoids 15 and 43. These studies suggest that A. oxyphylla may have a potential to serve as a functional food in preventing renal fibrosis-associated diseases.


Assuntos
Alpinia , Frutas , Extratos Vegetais , Sesquiterpenos , Proteínas Smad , Fator de Crescimento Transformador beta1 , Alpinia/química , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Frutas/química , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/genética , Animais , Fosforilação/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Proteínas Smad/metabolismo , Proteínas Smad/genética , Humanos , Ratos , Linhagem Celular , Substâncias Protetoras/farmacologia , Substâncias Protetoras/química , Estrutura Molecular
15.
Drug Alcohol Depend ; 259: 111316, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38704886

RESUMO

BACKGROUND: Emerging data indicate that many adolescents and young adults ("youth") engage in infrequent, or occasional, e-cigarette use. However, little is known about this population as they are often subsumed into the broader "any past-30-day use" category used to define youth "current use." This study aimed to focus on infrequent e-cigarette use by youth, examining its correlates and transitional outcomes. METHODS: Participants were from a prospective cohort study of youth (aged 15-24 at baseline). Among youth who had used e-cigarettes, we classified "infrequent use" as using e-cigarettes ≤5 days in the last 30 days (n=273) and "frequent use" as using e-cigarettes ≥6 days in the last 30 days (n=278). Descriptive statistics, Markov modeling, and logistic regression were utilized. RESULTS: By the 12-month follow-up, 76.8% of those using infrequently at baseline remained in the "infrequent use" category, 6.3% reported no recent use, and 16.8% had escalated to the "frequent use" category. Among the youth using infrequently at baseline, those who did (vs. did not) escalate to frequent use by follow-up had higher baseline nicotine dependence and were more likely to have family members who used tobacco. CONCLUSIONS: Infrequent e-cigarette use is extremely common, and often fairly stable, among young people. Prevention efforts must certainly attempt to reduce escalation and attend to both individual and interpersonal factors (e.g., nicotine dependence, family use). Yet prevention efforts must additionally attend to the case of continued infrequent use, given the high prevalence of people in this category and their regular exposure to e-cigarette harms.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Vaping , Humanos , Adolescente , Masculino , Feminino , Adulto Jovem , Estudos Prospectivos , Vaping/epidemiologia , Estudos de Coortes
16.
J Appl Clin Med Phys ; : e14342, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38590112

RESUMO

BACKGROUND: Rescanning is a common technique used in proton pencil beam scanning to mitigate the interplay effect. Advances in machine operating parameters across different generations of particle therapy systems have led to improvements in beam delivery time (BDT). However, the potential impact of these improvements on the effectiveness of rescanning remains an underexplored area in the existing research. METHODS: We systematically investigated the impact of proton machine operating parameters on the effectiveness of layer rescanning in mitigating interplay effect during lung SBRT treatment, using the CIRS phantom. Focused on the Hitachi synchrotron particle therapy system, we explored machine operating parameters from our institution's current (2015) and upcoming systems (2025A and 2025B). Accumulated dynamic 4D dose were reconstructed to assess the interplay effect and layer rescanning effectiveness. RESULTS: Achieving target coverage and dose homogeneity within 2% deviation required 6, 6, and 20 times layer rescanning for the 2015, 2025A, and 2025B machine parameters, respectively. Beyond this point, further increasing the number of layer rescanning did not further improve the dose distribution. BDTs without rescanning were 50.4, 24.4, and 11.4 s for 2015, 2025A, and 2025B, respectively. However, after incorporating proper number of layer rescanning (six for 2015 and 2025A, 20 for 2025B), BDTs increased to 67.0, 39.6, and 42.3 s for 2015, 2025A, and 2025B machine parameters. Our data also demonstrated the potential problem of false negative and false positive if the randomness of the respiratory phase at which the beam is initiated is not considered in the evaluation of interplay effect. CONCLUSION: The effectiveness of layer rescanning for mitigating interplay effect is affected by machine operating parameters. Therefore, past clinical experiences may not be applicable to modern machines.

17.
Cell Stem Cell ; 31(4): 554-569.e17, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38579685

RESUMO

The YAP/Hippo pathway is an organ growth and size regulation rheostat safeguarding multiple tissue stem cell compartments. LATS kinases phosphorylate and thereby inactivate YAP, thus representing a potential direct drug target for promoting tissue regeneration. Here, we report the identification and characterization of the selective small-molecule LATS kinase inhibitor NIBR-LTSi. NIBR-LTSi activates YAP signaling, shows good oral bioavailability, and expands organoids derived from several mouse and human tissues. In tissue stem cells, NIBR-LTSi promotes proliferation, maintains stemness, and blocks differentiation in vitro and in vivo. NIBR-LTSi accelerates liver regeneration following extended hepatectomy in mice. However, increased proliferation and cell dedifferentiation in multiple organs prevent prolonged systemic LATS inhibition, thus limiting potential therapeutic benefit. Together, we report a selective LATS kinase inhibitor agonizing YAP signaling and promoting tissue regeneration in vitro and in vivo, enabling future research on the regenerative potential of the YAP/Hippo pathway.


Assuntos
Inibidores de Proteínas Quinases , Proteínas Serina-Treonina Quinases , Proteínas de Sinalização YAP , Animais , Humanos , Camundongos , Proliferação de Células , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/metabolismo , Células-Tronco/metabolismo , Fatores de Transcrição/metabolismo , Proteínas de Sinalização YAP/agonistas , Proteínas de Sinalização YAP/efeitos dos fármacos , Proteínas de Sinalização YAP/metabolismo , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia
18.
Artigo em Inglês | MEDLINE | ID: mdl-38666216

RESUMO

INTRODUCTION: E-cigarette use is most prevalent among adolescents and young adults - and there are often misperceptions about product risk. The purpose of this study was to determine what nicotine information is provided on e-cigarette brand websites. METHODS: Based on national and local surveys, we identified 44 e-cigarette brands commonly used in the US by adolescents and young adults. For each of these brands, their associated websites were analyzed for disclosed nicotine information. Specifically, for each brand's website, we coded whether there was information on nicotine concentration (recorded if a numerical value was provided such as '5% nicotine'), nicotine form (free-base, nicotine salts, or not stated), and nicotine type (tobacco-derived, synthetically derived, or not stated). Coding allowed for both lay (e.g. 'nic salts') as well as scientific (e.g. 'isomers') terms. RESULTS: Of the 44 brands examined, all provided basic information on nicotine concentration (e.g. '5% nicotine'). However, 23% of brands did not disclose information on nicotine form (i.e. nicotine salt vs free-base), and 66% of brands did not disclose information on nicotine type (i.e. synthetic vs tobacco-derived). CONCLUSIONS: Overall, these results suggest that the e-cigarette industry is not fully informing its consumers about the nicotine in their products. Given that nicotine form and type have implications for e-cigarette addiction potential, these findings highlight a public health concern. There is a need for more comprehensive national regulations for mandating product constituents and emissions disclosures.

19.
J Integr Med ; 22(3): 279-285, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38688809

RESUMO

BACKGROUND: Yiqi Peiyuan (YQPY) prescription, a composite prescription of traditional Chinese medicine, has been used to prevent or delay the continued deterioration of renal function after acute kidney injury (AKI) in some institutions and has shown considerable efficacy. OBJECTIVE: This is the first randomized controlled trial to assess efficacy and safety of YQPY for improving short-term prognosis in adult patients with AKI. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This is a prospective, double-blind, multicenter, randomized, and placebo-controlled clinical trial. A total of 144 enrolled participants were randomly allocated to two groups according to a randomization schedule. Participants, caregivers and investigators assessing the outcomes were blinded to group assignment. Patients in the YQPY group received 36 g YQPY granules twice a day for 28 days. Patients in the placebo group received a placebo in the same dose as the YQPY granules. MAIN OUTCOME MEASURES: The primary outcome was the change in the estimated glomerular filtration rate (eGFR) between baseline and after 4 and 24 weeks of treatment. The secondary outcomes were the change of serum creatinine (Scr) level between baseline and after treatment, and the incidence of endpoint events, defined as eGFR increasing by more than 25% above baseline, eGFR >75 mL/min per 1.73 m2 or the composite endpoint, which was defined as the sum of patients meeting either of the above criteria. RESULTS: Data from a total of 114 patients (59 in the YQPY group and 55 in the control group) were analyzed. The mean changes in eGFR and Scr in weeks 4 and 24 had no difference between the two groups. In further subgroup analysis (22 in the YQPY group and 31 in the control group), the mean change in eGFR after treatment for 4 weeks was 27.39 mL/min per 1.73 m2 in the YQPY group and 5.78 mL/min per 1.73 m2 in the placebo group, and the mean difference between groups was 21.61 mL/min per 1.73 m2 (P < 0.001). Thirteen (59.1%) patients in the YQPY group and 5 (16.1%) in the placebo group reached the composite endpoints (P = 0.002). During the intervention, 2 and 4 severe adverse events were reported in the YQPY and placebo groups, respectively. CONCLUSION: The YQPY granules can effectively improve the renal function of patients 4 weeks after the onset of AKI, indicating that it has good efficacy for improving short-term renal outcomes in patients with AKI. The YQPY granules may be a promising therapy for adults with AKI. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100051723. Please cite this article as: Wu JJ, Zhang TY, Qi YH, Zhu MY, Fang Y, Qi CJ, Cao LO, Lu JF, Lu BH, Tang LM, Shen JX, Mou S. Efficacy and safety of Yiqi Peiyuan granules for improving the short-term prognosis of patients with acute kidney injury: a multicenter, double-blind, placebo-controlled, randomized trial. J Integr Med. 2024; 22(3): 279-285.


Assuntos
Injúria Renal Aguda , Medicamentos de Ervas Chinesas , Taxa de Filtração Glomerular , Humanos , Masculino , Injúria Renal Aguda/tratamento farmacológico , Feminino , Método Duplo-Cego , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/administração & dosagem , Pessoa de Meia-Idade , Taxa de Filtração Glomerular/efeitos dos fármacos , Idoso , Prognóstico , Estudos Prospectivos , Resultado do Tratamento , Adulto , Creatinina/sangue
20.
PLoS One ; 19(3): e0301066, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38547302

RESUMO

BACKGROUND: Subacromial spurs are considered the one of the pathology underlying shoulder impingement syndrome. Furthermore, few studies have focused on the morphology of the subacromial spurs in normal Chinese people. This study aimed to study the spur distribution and to illustrate the morphology of spurs, which may help guide the extent of acromioplasty. METHODS: A total of 93 normal individuals were enrolled, and both shoulders of all enrolled individuals were analyzed. The subjects were divided and classified into three different groups by ages: group I = 18-40 years, group II = 41-60 years, and group III ≥ 61 years. The osteophyte distribution, osteophyte area, subacromial surface area and osteophyte area/subacromial surface area ratio were measured and illustrated using Mimics and 3-matic software. The shape of the acromion was classified according to the Bigliani and Morrison classification system. The acromial angle was also classified. Then, the relationship between osteophytes, acromial classification and acromial angle was analyzed. RESULTS: Type II (curved shape) was the most common type of acromion, and the hooked shape was a rare form. A significant increase in the left subacromial surface area in males was observed in group III compared with group I (P < 0.001) and group II (P = 0.004). The total spur/subacromial area ratio was significantly higher in group II than I. An obvious increase in the right subacromial area was observed in group III compared with group I (P = 0.004). Furthermore, there was a significant increase in the right spur area (P = 0.021) and total spur/subacromial area ratio (P = 0.006) in females in group II compared with group I. Fewer spurs were observed on the left than on the right side (p = 0.0482). One spur was most common among type II acromions (29/36) (80.56%) on the left side and the right side (34/52, 65.38%). CONCLUSIONS: Spurs osteophytes are mainly distributed with an irregular shape and mostly run through the medial and lateral sides of the subacromial surface in normal subjects. The characteristics of subacromial spurs are so diverse that a surgeon must conduct subacromial decompression completely based on the morphology of individual spurs.


Assuntos
Acrômio , População do Leste Asiático , Osteófito , Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto Jovem , Acrômio/diagnóstico por imagem , Acrômio/anatomia & histologia , Artroplastia , Osteófito/diagnóstico por imagem , Osteófito/patologia , Síndrome de Colisão do Ombro/diagnóstico por imagem , Pessoa de Meia-Idade
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