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RATIONALE AND OBJECTIVES: To validate the image quality of low-dose ultra-high-resolution (UHR) scanning mode of photon-counting detector CT (PCD-CT) for visceral artery computed tomography angiography (CTA). MATERIAL AND METHODS: We prospectively enrolled 57 patients each in the full dose (FD) and low-dose (LD) protocols, respectively, to undergo abdominal CT scans using the UHR mode on a PCD-CT system (NAEOTOM Alpha), between April 2023 and September 2023. Both the FD data and LD data were then reconstructed into two series of images: (a) 0.2 mm slice thickness, reconstruction kernel Bv48, quantum iterative reconstruction (QIR) 4; (b)1 mm slice thickness, Bv40, QIR 3. The signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) of seven arteries were objectively measured. The image noise, vessel sharpness, overall quality, and visibility of nine arteries were subjectively assessed by three radiologists. RESULTS: The SNRs and CNRs of 0.2 mm reconstruction set was inferior to that of 1 mm reconstruction set (p < 0.001 for all the arteries and noise), however, the image quality of 0.2 mm reconstruction set was higher than that of 1 mm reconstruction set in qualitative evaluation especially for tiny arteries in Volume-rendered (VR) image (p < 0.001). The SNRs and CNRs were not significantly higher for FD group than LD group on the same slice thickness except for SNRs of common hepatic artery, splenic artery and bilateral renal arteries in 0.2 mm reconstruction set. In the comparison on image quality between normal weight and overweight patients within the same reconstruction set, the results showed that low-dose scan did not significantly impact the image quality in overweight patients. The ratings of visibility of nine visceral arteries were not significantly different among FD and LD at the same thickness reconstruction set except for superior mesenteric artery (p = 0.002 and 0.007 for 0.2 mm and 1 mm reconstruction set in axial image; p = 0.002 and 0.007 for 0.2 mm and 1 mm reconstruction set in coronal image, respectively) and left gastric artery (p = 0.002 and p < 0.001 for 0.2 mm and 1 mm reconstruction set in VR image, respectively). CONCLUSION: The low-dose UHR scanning mode of PCD-CT has proven to be adequate for the clinical evaluation of visceral arteries. Utilizing a reconstruction with a slice thickness of 0.2 mm could enhance arterial depiction, particularly for small vessels.
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The mechanisms underlying subclinical hypothyroidism (SCH) remain unclear, making timely and accurate differentiation between hypothyroidism and SCH, as well as severity assessment, challenging. This study aimed to investigate the role of NFE2 like bZIP transcription factor 2 (Nrf2), gp91phox, and interleukin-17 (IL-17) in the pathogenesis of SCH. In this prospective comparative study, 105 SCH patients, 105 hypothyroidism patients, and 105 healthy individuals were enrolled from January 2022 to August 2023. SCH patients were categorized into mild-moderate and severe groups based on thyroid-stimulating hormone (TSH) levels. Levels of TSH, free T4 (FT4), free T3 (FT3), thyroglobulin antibodies (TG-Ab), thyroid peroxidase antibodies (TPO-Ab), cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-ch), and low-density lipoprotein-cholesterol (LDL-ch) were measured. Nrf2, IL-1ß, IL-6, IL-17, and gp91phox levels were tested using ELISA. Nrf2, IL-17 and gp91phox were significantly higher in SCH and hypothyroidism patients compared to the healthy controls, with hypothyroidism patients showing the highest levels. Nrf2 levels were negatively correlated with TSH, TG-Ab and IL-17, but not gp91phox. Nrf2, IL-17 and gp91phox could be used for diagnosis of SCH and severe SCH. Only TG-Ab, IL-17 and gp91phox were independent risk factors for severe SCH. This study demonstrates a negative correlation between serum Nrf2 levels and SCH severity. TG-Ab, IL-17, and gp91phox are independent risk factors, and their associations with SCH pathology suggest their potential roles in the disease mechanism. These findings provide insights into SCH pathogenesis and highlight the need for further research to elucidate their diagnostic or prognostic significance.
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Purple phototrophic bacteria possess light-harvesting 1 and reaction center (LH1-RC) core complexes that play a key role in converting solar energy to chemical energy. High-resolution structures of LH1-RC and RC complexes have been intensively studied and have yielded critical insight into the architecture and interactions of their proteins, pigments, and cofactors. Nevertheless, a detailed picture of the structure and assembly of LH1-only complexes is lacking due to the intimate association between LH1 and the RC. To study the intrinsic properties and structure of an LH1-only complex, a genetic system was constructed to express the Thermochromatium (Tch.) tepidum LH1 complex heterologously in a modified Rhodospirillum rubrum mutant strain. The heterologously expressed Tch. tepidum LH1 complex was isolated in a pure form free of the RC and exhibited the characteristic absorption properties of Tch. tepidum. Cryo-EM structures of the LH1-only complexes revealed a closed circular ring consisting of either 14 or 15 αß-subunits, making it the smallest completely closed LH1 complex discovered thus far. Surprisingly, the Tch. tepidum LH1-only complex displayed even higher thermostability than that of the native LH1-RC complex. These results reveal previously unsuspected plasticity of the LH1 complex, provide new insights into the structure and assembly of the LH1-RC complex, and show how molecular genetics can be exploited to study membrane proteins from phototrophic organisms whose genetic manipulation is not yet possible.
Subject(s)
Chromatiaceae , Light-Harvesting Protein Complexes , Light-Harvesting Protein Complexes/metabolism , Light-Harvesting Protein Complexes/chemistry , Light-Harvesting Protein Complexes/genetics , Chromatiaceae/metabolism , Chromatiaceae/genetics , Bacterial Proteins/chemistry , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Rhodospirillum rubrum/genetics , Rhodospirillum rubrum/metabolismABSTRACT
Enhancing the thermoelectric performance of n-type polycrystalline SnSe is essential, addressing challenges posed by elevated thermal conductivity and compromised power factor inherent in its intrinsic p-type characteristics. This investigation utilized solid-state reactions and spark plasma sintering techniques for the synthesis of n-type SnSe. A significant improvement in the figure of merit (ZT) is achieved through strategic reduction in Se concentration and optimization of crystal orientation. The co-doping with Br and Ge further improves the material; Br amplifies carrier concentration, enhancing electrical conductivity, while Ge introduces effective phonon scattering centers. In the Br/Ge co-doped SnSe sample, thermal conductivity dropped to 0.38 Wm⻹K⻹, yielding a remarkable power factor of 662 µW mK- 2 at 773 K, culminating in a ZT of 1.34. This signifies a noteworthy 605% improvement over the pristine sample, underscoring the pivotal role of Ge doping in enhancing n-type material thermoelectric properties. The enhancement is attributed to Br doping introducing additional electronic states near the valence band, and Ge doping modifying the band structure, fostering resonant states near the conduction band. The Br/Ge co-doping further transforms the band structure, influencing electrical conductivity, Seebeck coefficient, and thermal conductivity, advancing the understanding and application of n-type SnSe materials for superior thermoelectric performance.
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P2X7 receptor (P2X7R) plays an important role in modulating inflammation and fibrosis, but information is limited whether Zusanli (ST36) can inhibit inflammation and fibrosis by regulating P2X7R. Isoprenaline at 5 mg/kg was subcutaneously injected to wild-type and P2X7R knockout mice for 7 days, while treatment groups received electroacupuncture (EA) stimulation at ST36 for 7 sessions. Following 7-session treatment, Masson's trichrome staining was performed to assess the fibrosis. Morphology, electrocardiogram, and echocardiography were carried out to evaluate the cardiac function and structure. Western blotting, hematoxylin and eosin staining, immunohistochemistry, and biochemical analysis of inflammatory cytokine and transmission electron microscopy were carried out to characterize the effect of ST36 on inflammation. P2X7R was overexpressed in ISO-treated mice. EA at ST36, but not at non-points, reduced ISO-induced cardiac fibrosis, increases in HW/BW, R+S wave relative to mice in ISO groups. In addition, EA at ST36 downregulated ISO-upregulated P2X7R and NLRP3 in ventricle. Moreover, EA reduced cytokines of IL-1ß, IL-6, and IL-18 in serum, and inhibited foam cell gathering, inflammatory cell infiltration, and autophagy. However, EA at ST36 failed to attenuate the cardiac fibrosis and hypertrophy in P2X7R knockout mice. In conclusion, EA at ST36 attenuated ISO-induced fibrosis possibly via P2X7R.
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ETHNOPHARMACOLOGICAL RELEVANCE: The adverse effects of Fructus Psoraleae (FP), especially liver injury, have attracted wide attention in recent years. AIM OF THE STUDY: To establish a system to explore potential hepatotoxic targets and the chief culprit of liver injury based on clinical experience, network pharmacological method, molecular docking, and in vitro and in vivo experiments. MATERIALS AND METHODS: Clinical applications and adverse reactions to FP were obtained from public literatures. Components absorbed in the blood were selected as candidates to search for potential active targets (PATs) of FP. Subsequently, potential pharmacological core targets (PPCTs) were screened through the "drug targets-disease targets" network. Non-drug active targets (NPATs) were obtained by subtracting the PPCTs from the PATs. The potential hepatotoxic targets (PHTs) of FP were the intersection targets obtained from Venn analysis using NPATs, hepatotoxic targets, and adverse drug reaction (ADR) targets provided by the databases. Then, potential hepatotoxic components and targets were obtained using the "NPATS-component" network relationship. Molecular docking and in vitro and in vivo hepatotoxicity experiments were performed to verify the targets and related components. RESULTS: Overall, 234 NPATs were acquired from our analysis, and 6 targets were identified as PHTs. Results from molecular docking and in vitro and in vivo experiments showed that angelicin is the leading cause of liver injury in FP, and VKORC1 plays an important role. CONCLUSION: The results indicate that six targets, especially VKORC1, are associated with the PHTs of FP, and angelicin is the leading culprit involved in FP liver injury via inhibition of VKORC1.
Subject(s)
Drugs, Chinese Herbal , Furocoumarins , Psoralea , Molecular Docking Simulation , Liver , Furocoumarins/adverse effects , Plant Extracts/pharmacology , Drugs, Chinese Herbal/pharmacologyABSTRACT
OBJECTIVE: The study was performed to explore the association between blood lipids and cognitive impairment in patients with type 2 diabetes mellitus (T2DM). METHODS: This study included 336 patients with T2DM. Relevant clinical data including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), apolipoprotein A1, apolipoprotein B were collected, and the Mini-Mental State Examination (MMSE) score and Montreal Cognitive Assessment (MoCA) score were used to assess the cognitive function in patients with T2DM. RESULTS: Serum apolipoprotein A1 levels were significantly increased in T2DM patients with cognitive impairment compared with T2DM patients without cognitive impairment (p = 0.017). Serum apolipoprotein A1 levels were significantly negatively correlated with MoCA score (r = - 0.143, p = 0.009) and MMSE score (r = - 0.132, p = 0.016) in patients with T2DM. In multivariable-adjusted regression model, serum apolipoprotein A1 was independently associated with cognitive impairment in patients with T2DM (OR = 5.201, p = 0.024). CONCLUSION: Serum apolipoprotein A1 is associated with cognitive impairment in patients with T2DM, but not TC, TG, HDL-C, LDL-C, and apolipoprotein B, indicating that increased serum apolipoprotein A1 may be a risk factor of cognitive impairment in patients with T2DM.
Subject(s)
Cognitive Dysfunction , Diabetes Mellitus, Type 2 , Humans , Diabetes Mellitus, Type 2/complications , Apolipoprotein A-I , Cholesterol, LDL , Lipids , Triglycerides , Cholesterol, HDL , Cognitive Dysfunction/complicationsABSTRACT
Monogenic diabetes caused by GATA6 mutations were almost described as neonatal diabetes, and the phenotypic spectrum has expanded since then. Our study underscores the broad phenotypic spectrum by reporting a de novo GATA6 mutation in a family. Furthermore, we reviewed related literature to summarize the clinical and genetic characteristics of monogenic diabetes with GATA6 mutations (n = 39) in order to improve clinicians' understanding of the disease. We conclude that the GATA6 missense mutation (c. 749G > T, p. Gly250Val) is not reported presently, characterized by adult-onset diabetes with pancreatic dysplasia and located in transcriptional activation region. Carries with GATA6 mutations (n = 55) have a variable spectrum of diabetes, ranging from neonatal (72.7%), childhood-onset (20%) to adults-onset (7.5%). 83.5% of patients with abnormal pancreatic development. Heart and hepatobillary defects are the most common abnormalities of extrapancreatic features. Most mutations with GATA6 are loss of function (LOF, 71.8%) and located in functional region. Functional studies mostly support loss-of-function as the pathophysiological mechanism. In conclusion, there are various types of diabetes with GATA6 mutations, which can also occur in adult diabetes. Phenotypic defects with GATA6 mutations are most frequently malformations of pancreas and heart. This highlights the importance of comprehensive clinical evaluation of identified carriers to evaluate their full phenotypic spectrum.
Subject(s)
Diabetes Mellitus, Type 2 , Heart Defects, Congenital , Infant, Newborn , Adult , Humans , Child , Heart Defects, Congenital/genetics , Pancreas/abnormalities , Mutation , Phenotype , GATA6 Transcription Factor/geneticsABSTRACT
OBJECTIVE To evaluate the cost-effectiveness of trastuzumab biosimilars (Hanquyou) versus original drug (Hesaiting) in the treatment of recurrent/metastatic human epidermal growth factor receptor-2 (HER-2) positive breast cancer. METHODS A partitional survival model was constructed based on the NCT03084237 trial data. The simulation period was 3 weeks, and the simulation time was 10 years. Using costs and quality-adjusted life year (QALY) as the output indicator, the cost- utility analysis method was used to evaluate the cost-effectiveness of the two schemes mentioned above. Univariate and probabilistic sensitivity analyses were performed to verify the robustness of the basic analysis. RESULTS The costs of the trastuzumab biosimilars group and original drug group were 111 516.72 yuan and 111 122.30 yuan respectively, with health utility values of 1.52 QALYs and 1.36 QALYs, and ICER of 2 465.12 yuan/QALY, which were less than 3 times China’s per capita gross domestic product (GDP) in 2023 as the threshold for willingness-to-pay (WTP) (268 200 yuan/QALY). Univariate sensitivity analysis showed that the cost of the trastuzumab biosimilars and original drug had a great impact on the ICER. The probabilistic sensitivity analysis showed that the probability of trastuzumab biosimilars being cost-effective was 100% at WTP threshold of 14 902 yuan/QALY. CONCLUSIONS When WTP threshold is 3 times China’s GDP in 2023 (268 200 yuan/QALY), compared with original drug, trastuzumab biosimilars have good cost-effectiveness in the treatment of recurrent/metastatic HER-2 positive breast cancer.
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Objective To investigate the therapeutic effect of Huatan Jieyu Anshen Decoction(mainly with the actions of resolving phlegm,relieving depression and calming mind)combined with abdominal vibration tuina manipulations on chronic insomnia in the elderly.Methods Ninety-four cases of elderly patients with chronic insomnia of phlegm-heat harassing the interior type were randomly divided into the observation group and the control group,with 47 cases in each group.The control group was given Huatan Jieyu Anshen Decoction orally,while the observation group was given oral use of Huatan Jieyu Anshen Decoction combined with abdominal vibration tuina manipulations.The course of treatment for the two groups lasted for 4 weeks.Before and after the treatment,the two groups were observed in the changes of traditional Chinese medicine(TCM)syndrome scores,Pittsburgh Sleep Quality Index(PSQI)score,Athens Insomnia Scale(AIS)score,Fatigue Scale-14(FS-14)score,World Health Organization Quality-of-Life Brief Scale(WHOQOL-BREF)score,and the serum levels of melatonin(MT),dopamine(DA),and cortisol(CORT).After treatment,the clinical efficacy of the two groups was evaluated.Results(1)After 4 weeks of treatment,the total effective rate of the observation group was 97.88%(46/47),while that of the control group was 87.23%(41/47),and the intergroup comparison(tested by chi-square test)showed that the therapeutic efficacy of the observation group was superior to that of the control group(P<0.01).(2)After treatment,the scores of primary and secondary TCM symptoms in the two groups were significantly decreased compared with those before treatment(P<0.05),and the decrease of the scores of primary and secondary TCM symptoms in the observation group was significantly superior to that in the control group(P<0.01).(3)After treatment,the PSQI scores,AIS scores,and FS-14 scores in the two groups were significantly decreased compared with those before treatment(P<0.05),and the WHOQOL-BREF scores were significantly increased compared with those before treatment(P<0.05).The decrease of the PSQI scores,AIS scores and FS-14 scores as well as the increase of the WHOQOL-BREF scores in the observation group was significantly superior to that in the control group(P<0.01).(4)After treatment,the serum MT level of both groups was significantly higher than that before treatment(P<0.05),and the serum DA and CORT levels were significantly lower than those before treatment(P<0.05).The increase in serum MT level and the decrease in serum DA and CORT levels of the observation group were significantly superior to those of the control group(P<0.01).Conclusion The combined therapy of Huatan Jieyu Anshen Decoction combined with vibration tuina manipulations can achieve satisfactory efficacy in the elderly patients with chronic insomnia of phlegm-heat harassing the interior syndrome.The therapy is effective on regulating the central nervous system of the patients,improving the quality of the sleep,and promoting the relief of fatigue and the enhancement of the quality of life,which has great significance to the enhancement of the overall therapeutic efficacy of insomnia.
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Moringa oleifera leaves are known for their "Virechana"(purgative) effect in Ayurvedic medicine in India. This study compared the purgative effects and mechanisms of M. oleifera leaves with the reference Rhei Radix et Rhizoma to establish a foundation for the further application of M. oleifera leaves in traditional Chinese medicine(TCM). Using network pharmacology and molecular docking methods, this study identified the material basis, common targets, and signaling pathways through which Rhei Radix et Rhizoma and M. oleifera leaves exerted their purgative pharmacological effects. A low-fiber diet-induced constipation mouse model was established to measure fecal parameters and small intestinal propulsion rate, and histological changes in the colon were observed using HE staining. Relative expression levels of relevant genes and target proteins were assessed using RT-qPCR and immunohistochemistry, respectively. The results showed that mapping the targets of Rhei Radix et Rhizoma and M. oleifera leaves onto the biological process network of constipation revealed close proximity, indicating that they may exert their therapeutic effects on constipation through similar biological processes. Molecular docking results indicated that compounds such as sennoside C and isoquercitrin could target serine/threonine protein kinases(AKT1) and mitogen-activated protein kinase 3(MAPK3), thereby affecting MAPK and calcium signaling pathways to promote defecation. Animal experiments demonstrated that both M. oleifera leaves and Rhei Radix et Rhizoma increased the number of fecal pellets and water content in constipated mice, improved small intestine motility, colon mucosal thickness, and muscle layer thickness, upregulated the gene expression levels of AKT1 and MAPK3 in the colon, and downregulated the expression of AQP3 protein. These findings suggest that M. oleifera leaves and Rhei Radix et Rhizoma share similarities in their therapeutic efficacy and mechanisms for treating constipation. Using Rhei Radix et Rhizoma as a reference can provide a better understanding of the characteristics of the "Virechana"(purgative) effect of M. oleifera leaves in TCM.
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Drugs, Chinese Herbal , Moringa oleifera , Mice , Animals , Cathartics , Molecular Docking Simulation , Drugs, Chinese Herbal/chemistry , ConstipationABSTRACT
Herein, an n-type Ag2Se thermoelectric flexible thin film has been fabricated on a polyimide (PI) substrate via a novel thermal diffusion method, and the thermoelectric performance is well-optimized by adjusting the pressure and temperature of thermal diffusion. All of the Ag2Se films are beneficial to grow (013) preferred orientations, which is conducive to performing a high Seebeck coefficient. By increasing the thermal diffusion temperature, the electrical conductivity can be rationally regulated while maintaining the independence of the Seebeck coefficient, which is mainly attributed to the increased electric mobility. As a result, the fabricated Ag2Se thin film achieves a high power factor of 18.25 µW cm-1 K-2 at room temperature and a maximum value of 21.7 µW cm-1 K-2 at 393 K. Additionally, the thermal diffusion method has resulted in a wave-shaped buckling, which is further verified as a promising structure to realize a larger temperature difference by the simulation results of finite element analysis (FEA). Additionally, this unique surface morphology of the Ag2Se thin film also exhibits outstanding mechanical properties, for which the elasticity modulus is only 0.42 GPa. Finally, a flexible round-shaped module assembled with Sb2Te3 has demonstrated an output power of 166 nW at a temperature difference of 50 K. This work not only introduces a new method of preparing Ag2Se thin films but also offers a convincing strategy of optimizing the microstructure to enhance low-grade heat utilization efficiency.
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A new pathway via a cyclic intermediate for the synthesis of ketones from aldehydes and sulfonylhydrazone derivatives under basic conditions is proposed. Several control experiments were performed along with analysis of the mass spectra and in-situ IR spectra of the reaction mixture. Inspired by the new mechanism, an efficient and scalable method for homologation of aldehydes to ketones was developed. A wide variety of target ketones were obtained in yields of 42-95 % by simply heating the 3-(trifluoromethyl)benzene sulfonylhydrazones (3-(Tfsyl)hydrazone) for 2â h at 110 °C with aldehydes and with K2 CO3 and DMSO as base and solvent, respectively.
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OBJECTIVE: Secondary constipation refers to constipation that occurs after certain diseases or medications, such as acute stroke or opioids, and the efficacy of electroacupuncture for secondary constipation is controversial. So, this study aimed to explore the efficacy and safety of electroacupuncture for secondary constipation through a meta-analysis and systematic review. METHOD: We retrieved articles from PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, and VIP databases up to 28 February 2023. The study was screened strictly according to inclusion and exclusion criteria. Revman5.4 was used for quality evaluation; grade rating was used for index evaluation, and stata15.0 was used for data consolidation analysis. RESULT: Thirteen randomized controlled studies, involving a total of 1437 people (722 electroacupuncture and 715 control groups), were included in this review. Meta-analysis results indicated that electroacupuncture significantly improved constipation overall response (RR = 1.31, 95%CI: 1.11, 1.55, P < 0.001), reduced defecation straining score (MD = - 0.46, 95%CI: - 0.67, - 0.251, P < 0.001), increased weekly complete spontaneous bowel movements (MD = 0.41, 95%CI: 0.20, 0.63, P = 0.002), and increased in the weekly spontaneous bowel movements (MD = 0.80, 95%CI (0.49, 01.11), P < 0.001), and electroacupuncture had no effect on change stool consistency score compared (MD = - 0.03, 95%CI (- 0.38, 0.33), P = 0.88) and did not increase adverse events (RR = 0.50, 95%CI: 0.18, 1.44, P = 0.20). CONCLUSION: According to the current studies, the overall relief rate of patients with secondary constipation after electroacupuncture treatment was improved, the defecation pressure score was reduced, the weekly natural defecation was more complete, and adverse reactions were not increased. Electroacupuncture therefore shows potential for treating constipation, but more high-quality studies are needed to confirm these findings.
Subject(s)
Electroacupuncture , Humans , Electroacupuncture/adverse effects , Defecation , Constipation/therapy , Research Design , Control GroupsABSTRACT
Diatomic-site catalysts (DACs) garner tremendous attention for selective CO2 photoreduction, especially in the thermodynamical and kinetical mechanism of CO2 to C2+ products. Herein, we first engineer a novel Zn-porphyrin/RuCu-pincer complex DAC (ZnPor-RuCuDAC). The heteronuclear ZnPor-RuCuDAC exhibits the best acetate selectivity (95.1%), while the homoatomic counterparts (ZnPor-Ru2DAC and ZnPor-Cu2DAC) present the best CO selectivity. In-situ spectroscopic measurements reveal that the heteronuclear Ru-Cu sites easily appear C1 intermediate coupling. The in-depth analyses confirm that due to the strong gradient orbital coupling of Ru4d-Cu3d resonance, two formed *CO intermediates of Ru-Cu heteroatom show a significantly weaker electrostatic repulsion for an asymmetric charge distribution, which result from a side-to-side absorption and narrow dihedral angle distortion. Moreover, the strongly overlapped Ru/Cu-d and CO molecular orbitals split into bonding and antibonding orbitals easily, resulting in decreasing energy splitting levels of C1 intermediates. These results collectively augment the collision probability of the two *CO intermediates on heteronuclear DACs. This work first provides a crucial perspective on the symmetry-forbidden coupling mechanism of C1 intermediates on diatomic sites.
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Background: The treatment of bone defects remains a clinical challenge. The effect of negative pressure wound therapy (NPWT) on osteogenesis in bone defects has been recognized; however, bone marrow fluid dynamics under negative pressure (NP) remain unknown. In this study, we aimed to examine the marrow fluid mechanics within trabeculae by computational fluid dynamics (CFD), and to verify osteogenic gene expression, osteogenic differentiation to investigate the osteogenic depth under NP. Methods: The human femoral head is scanned using micro-CT to segment the volume of interest (VOI) trabeculae. The VOI trabeculae CFD model simulating the bone marrow cavity is developed by combining the Hypermesh and ANSYS software. The effect of trabecular anisotropy is investigated, and bone regeneration effects are simulated under NP scales of -80, -120, -160, and -200 mmHg. The working distance (WD) is proposed to describe the suction depth of the NP. Finally, gene sequence analysis, cytological experiments including bone mesenchymal stem cells (BMSCs) proliferation and osteogenic differentiation are conducted after the BMSCs are cultured under the same NP scale. Results: The pressure, shear stress on trabeculae, and marrow fluid velocity decrease exponentially with an increase in WD. The hydromechanics of fluid at any WD inside the marrow cavity can be theoretically quantified. The NP scale significantly affects the fluid properties, especially those fluid close to the NP source; however, the effect of the NP scale become marginal as WD deepens. Anisotropy of trabecular structure coupled with the anisotropic hydrodynamic behavior of bone marrow; An NP of -120 mmHg demonstrates the majority of bone formation-related genes, as well as the most effective proliferation and osteogenic differentiation of BMSCs compared to the other NP scales. Conclusion: An NP of -120 mmHg may have the optimal activated ability to promote osteogenesis, but the effective WD may be limited to a certain depth. These findings help improve the understanding of fluid mechanisms behind NPWT in treating bone defects.
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BACKGROUND: A large percentage of patients with ectopic pancreas are asymptomatic. When present, the symptoms are typically non-specific. These lesions are predominantly located in the stomach and benign in nature. Synchronous multiple early gastric cancer (SMEGC) (two or more simultaneous malignant lesions with early gastric cancer) is relatively rare and particularly easy to overlook during endoscopic examination. The prognosis of SMEGC is generally poor. We report a rare case of ectopic pancreas with concomitant SMEGC. CASE SUMMARY: A 74-year-old woman presented with paroxysmal upper abdominal pain. On initial investigations, she tested positive for Helicobacter pylori (H. pylori). She underwent esophagogastroduodenoscopy which revealed a 1.5 cm × 2 cm major lesion at the greater curvature and a 1 cm minor lesion at the lesser curvature of the stomach. On endoscopic ultrasound, the major lesion showed hypoechoic changes, uneven internal echoes and unclear boundaries between some areas and the muscularis propria. Endoscopic submucosal dissection was performed to excise the minor lesion. A laparoscopic resection was chosen for the major lesion. On histopathological examination, the major lesion contained high grade intraepithelial neoplasia with a small focus of cancer. A separate underlying ectopic pancreas was found under this lesion. The minor lesion contained high grade intraepithelial neoplasia. In this case, the patient was diagnosed with SMEGC with concomitant ectopic pancreas in the stomach. CONCLUSION: Patients with atrophy, H. pylori, and other risk factors should be carefully investigated to avoid missing other lesions including SMEGC and ectopic pancreas.
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Objective: The objective of this study was to screen lymphoma radiotherapy-resistant genes using CRISPR activation (CRISPRa). Methods: The Human CRISPRa library virus was packaged and then transfected into lymphoma cells to construct an activation library cell line, which was irradiated at the minimum lethal radiation dose to screen radiotherapy-resistant cells. Radiotherapy-resistant cell single-guide RNA (sgRNA) was first amplified by quantitative polymerase chain reaction (qPCR) in the coding region and then subject to next-generation sequencing (NGS) and bioinformatics analysis to screen radiotherapy-resistant genes. Certain radiotherapy-resistant genes were then selected to construct activated cell lines transfected with a single gene so as to further verify the relationship between gene expression and radiotherapy resistance. Results: A total of 16 radiotherapy-resistant genes, namely, C20orf203, MTFR1, TAF1L, MYADM, NIPSNAP1, ZUP1, RASL11A, PSMB2, PSMA6, OR8H3, TMSB4Y, CD300LF, EEF1A1, ATP6AP1L, TRAF3IP2, and SNRNP35, were screened based on the NGS results and bioinformatics analysis of the radiotherapy-resistant cells. Activated cell lines transfected with a single gene were constructed using 10 radiotherapy-resistant genes. The qPCR findings showed that, when compared with the control group, the experimental group had significantly up-regulated mRNA expression of MTFR1, NIPSNAP1, ZUP1, PSMB2, PSMA6, EEF1A1, TMSB4Y and TAF1L (p < 0.05). No significant difference in the mRNA expression of AKT3 or TRAF3IP2 (p > 0.05) was found between the two groups (p > 0.05). Conclusion: The 16 genes screened are potential lymphoma radiotherapy-resistant genes. It was initially determined that the high expression of 8 genes was associated with lymphoma radiotherapy resistance, and these genes could serve as the potential biomarkers for predicting lymphoma radiotherapy resistance or as new targets for therapy.
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Background: Sepsis is a common complication of severe trauma, burns, infection, or major surgery. This disease-related end-organ dysfunction results from systemic inflammatory response syndrome (SIRS). Acute kidney damage (AKI), also known as acute renal failure, is one of the most frequent and serious sequelae of sepsis. Nuclear transcription factor-κB (NF-κB) regulates the transcription of inflammation-related genes and operates as a mediator in the immune system. While parthenolide (PTL) has been reported to prevent harmful inflammatory reactions, its effects on sepsis-associated AKI are unknown. The current study investigates the effects of PTL in sepsis-associated AKI using cell and cecal ligation and puncture (CLP) models. Methods: Lipopolysaccharide (LPS)-stimulated rat glomerular mesangial cells were treated with 10 µM PTL. Inflammatory mediators, including TNF-α, IL-6, and IL-1ß, in the culture supernatants were measured by ELISA, and NF-κB levels were assessed by qPCR. After the generation of the septic CLP model, rats were intraperitoneally injected with 500 g/kg PTL and were euthanized after 72 h. Serum and kidney samples were analyzed. Results: TNF-α, IL-1ß, and IL-6 levels were elevated after LPS treatment of rat glomerular mesangial cells (p=0.004, p=0.002, and p=0.004, respectively) but were significantly reduced in the PTL treatment group (p ≤ 0.001, p=0.01, and p ≤ 0.001). NF-κB p65 levels were also increased after LPS treatment in this group and were reduced in the PTL treatment group. PTL treatment also reduced kidney damage after CLP induction, as shown by histological analysis and reductions in the levels of BUN, Cre, KIM-1, and NAGL. CLP-induced kidney inflammation together with increased levels of proinflammatory cytokines and inflammatory-related proteins. The elevated levels of renal TNF-α, IL-6, and IL-1ß were downregulated after PTL treatment. The PTL treatment also reduced the CLP-induced activation of NF-κB p65 in the damaged kidneys. Conclusion: PTL reduced inflammation induced by CLP-induced AKI in rat models and LPS-induced damage to glomerular mesangial cells by suppressing NF-κB signaling.
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For thermoelectric thin film, the substrate plays an important role during the growing process and produces effects on its thermoelectric properties. Some special kinds of substrates provide an optimal combination of influences on both the structure and thermoelectric properties. In this work, Bi-Sb-Te films are deposited on Si substrates with different initial orientations by magnetron sputtering in two ways: with and without a pre-coating process. The preferred orientations of the Bi-Sb-Te films are greatly affected by the substrates, in which the thin film tends to deposit on Si substrate with (100) initial orientation and high (015)-texture, while the (00l)-textured Bi-Sb-Te film easily deposits on Si substrate with (110) initial orientation. The experimental and theoretical calculation results indicate that Bi-Sb-Te film with (00l)-texture presents good electrical conductivity and a higher power factor than that of film with (015)-texture.