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Introduction: Numerous studies have explored the treatment outcomes of Nirmatrelvir-Ritonavir and Azvudine in older patients with COVID-19. However, direct comparisons between these two drugs are still relatively limited. This study aims to compare the safety and effectiveness of these two drugs in Chinese older patients with early infection to provide strategies for clinical treatment. Methods: Older COVID-19 patients (age ≥65) hospitalized during the winter 2022 epidemic in China were included and divided into Nirmatrelvir-Ritonavir and Azvudine. Demographics, medication information, laboratory parameters, and treatment outcomes were collected. All-cause 28-day mortality, delta cycle threshold (ΔCt), nucleic acid negative conversion time, and incidence of adverse events were defined as outcomes. Propensity score matching (PSM), Kaplan-Meier, Cox proportional hazards model, subgroup analysis, and nomograms were selected to evaluate the outcomes. Results: A total of 1,508 older COVID-19 patients were screened. Based on the inclusion and exclusion criteria, 1,075 patients were eligible for the study. After PSM, the final number of older COVID-19 patients included in the study was 375, and there were no significant differences in demographic characteristics between the two groups (p > 0.05). Compared to the Azvudine group, the Nirmatrelvir-Ritonavir group showed a higher incidence of multiple adverse events (12.8% vs 5.2%, p = 0.009). The incidence of adverse events related to abnormal renal function was higher in the Nirmatrelvir-Ritonavir group compared to the Azvudine group (13.6% vs 7.2%, p = 0.045). There were no significant differences between the two groups in terms of all-cause 28-day mortality (HR = 1.020, 95% CI: 0.542 - 1.921, p = 0.951), whereas there were significant differences in nucleic acid negative conversion time (HR = 1.659, 95% CI: 1.166 - 2.360, p = 0.005) and ΔCt values (HR = 1.442, 95% CI: 1.084 - 1.918, p = 0.012). Conclusion: Azvudine and Nirmatrelvir-Ritonavir have comparable effectiveness in reducing mortality risk. Azvudine may perform better in nucleic acid negative conversion time and virus clearance and shows slightly better safety in older patients. Further studies with a larger sample size were needed to validate the result.
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Photoelectrochemical (PEC) cell is an ideal platform for organic transformation because of its green benefits and minimal energy consumption. As an emerging methodology, the reaction types of photoelectrocatalytic organic synthesis (PECOS) are limited to simple oxidation and C-H activation at current stage. Metal catalysis for the construction of C(sp2)-N bonds has not been touched yet in PECOS. We introduce here a PEC method that successfully engages Ni catalysis for the mild production of aniline derivatives. Experimental and computational investigations elucidate that the addition of photoanode-generated amine radical to Ni catalyst avoids the sluggish nucleophilic attack, enabling the reaction to proceed at an ultra-low potential (-0.4 V vs. Ag/AgNO3) and preventing the overoxidation of products in conventional electrochemical synthesis. This synergistic catalysis strategy exhibits good functional group tolerance and wide substrate scope on both aryl halides and amines, by which some important natural products and pharmaceutical chemicals have been successfully modified.
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Photoelectrochemistry (PEC) is burgeoning as an innovative solution to organic synthesis. However, the current PEC system suffers limited reaction types and unsatisfactory performances. Herein, we employ efficient BiVO4 photoanode with tailored deposition layers for customizing two PEC approaches toward C-N and C-P formation. Notably, our process proceeds under mild reaction conditions, easily available substrates, and ultra-low potentials. Beyond photocatalysis and electrocatalysis, customized PEC offers high efficiency, good functional group tolerance, and substantial applicability for decorating drug molecules, highlighting its promising potential to enrich the synthetic toolbox for broader organic chemistry of practical applications.
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Increased expression of immune check point genes, such as PD-L1, is one of the main reasons for immunosuppression, especially for colon cancer. Development of novel therapeutic strategies is of great importance to improve the prognosis. In this study, outer membrane vesicles (OMV) derived from Gram-negative bacteria are engineered to immune checkpoint blockade nanosystem for efficient elicitation of anti-tumor immunity. Briefly, the OMVs are engineered with Lyp1-Traptavidin (S52G, R53D mutant of streptavidin) fusion protein displayed on the surface. The Lyp-1 endows the OMV with the capacity to target tumor tissues, while the Traptavidin ensures easy decoration of biotinylated anti-PD-L1 and biotinylated M6P (mannose 6-phosphate). The simultaneously anchored anti-PD-L1 and M6P (ligand for cation-independent mannose 6-phosphate receptor) on the engineered OMVs coordinately direct the membrane PD-L1 to lysosome for degradation, and thus unleash the anti-tumor immunity. With syngeneic tumor model, the engineered OMVs are confirmed to boost immunity, inhibit cancer growth, and thus prolong survival. Together, A proposed OMV-based modular nanosystem that enables assembly of biotinylated anti-PD-L1 and M6P on the surface for tumor-targeted immune checkpoint blockade.
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Taurine is used to bolster immunity, but its effects on antitumor immunity are unclear. Here, we report that cancer-related taurine consumption causes T cell exhaustion and tumor progression. The taurine transporter SLC6A6 is correlated with aggressiveness and poor outcomes in multiple cancers. SLC6A6-mediated taurine uptake promotes the malignant behaviors of tumor cells but also increases the survival and effector function of CD8+ T cells. Tumor cells outcompete CD8+ T cells for taurine by overexpressing SLC6A6, which induces T cell death and malfunction, thereby fueling tumor progression. Mechanistically, taurine deficiency in CD8+ T cells increases ER stress, promoting ATF4 transcription in a PERK-JAK1-STAT3 signaling-dependent manner. Increased ATF4 transactivates multiple immune checkpoint genes and induces T cell exhaustion. In gastric cancer, we identify a chemotherapy-induced SP1-SLC6A6 regulatory axis. Our findings suggest that tumoral-SLC6A6-mediated taurine deficiency promotes immune evasion and that taurine supplementation reinvigorates exhausted CD8+ T cells and increases the efficacy of cancer therapies.
Subject(s)
CD8-Positive T-Lymphocytes , Membrane Glycoproteins , Taurine , Taurine/metabolism , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Animals , Humans , Mice , Cell Line, Tumor , Mice, Inbred C57BL , Endoplasmic Reticulum Stress , Activating Transcription Factor 4/metabolism , Signal Transduction , Female , Membrane Transport Proteins/metabolism , Membrane Transport Proteins/genetics , STAT3 Transcription Factor/metabolismABSTRACT
Photoelectrochemistry is becoming an innovative approach to organic synthesis. Generally, the current photoelectrocatalytic organic transformations suffer from limited reaction type, low conversion efficiency and poor stability. Herein, we develop efficient and stable photoelectrode materials using metal oxide protective layer, with a focus on achieving regioselective activation of amine compounds. Notably, our photoelectrochemistry process is implemented under mild reaction conditions and does not involve any directing groups, transition metals or oxidants. The results demonstrate that beyond photocatalysis and electrocatalysis, photoelectrocatalysis exhibits high efficiency, remarkable repeatability and good functional group tolerance, highlighting its great potential for applications.
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Background: Neoadjuvant chemotherapy (NACT) is increasingly becoming the recommended treatment for locally advanced gastric cancer (LAGC) with promising results. According to previous reports, few studies have evaluated the benefits of laparoscopic gastrectomy (LG) after NACT. Methods: 135 patients from our center who underwent gastrectomy with NACT were available, including 41 patients of LG and 94 OG between July 2018 and July 2022. To reduce selection bias, we used the nearest neighbor method and set caliper = 0.2 for 3:1 matching between LG and OG groups for propensity score matching method (PSM). After PSM, the matched 41 patients with LG and 80 patients with OG formed the cohort, respectively. Univariate and multivariate Cox analyses were performed on all variables to determine independent risk factors associated with survival. Results: LG had a longer operating time compared to OG [260.00 min (220.00 min, 300.00 min) vs. 200.00 min (160.00 min, 260 min), P < 0.001]. The estimated blood loss, metastatic lymph nodes (LN), total LN examined, postoperative hospital stays, blood transfusion (P>0.05) and the incidence of postoperative complications did not show statistical differences from the OG group (P = 0.084). The type of surgery (LG vs. OG) did not show a significant risk propensity in the univariate and multivariate Cox analysis (HR = 0.69, P = 0.36, 95 % CI: 0.31-1.53). Through the Kaplan-Meier curves, a certain trend showed that the LG group had a better long-term survival outcomes than the OG group, although there was no statistical difference between two groups (P>0.05). Conclusion: LG is a promising treatment option for LAGC patients receiving NACT and had an acceptable safety and efficacy compared to OG.
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Cytochrome P450 (CYP74) family members participate in the generation of oxylipins and play essential roles in plant adaptation. However, the metabolic reprogramming mediated by CYP74s under cold stress remains largely unexplored. Herein, we report how cold-triggered OsHPL1, a member of the CYP74 family, modulates rice metabolism. Cold stress significantly induced the expression of OsHPL1 and the accumulation of OPDA (12-oxo-phytodienoic acid) and jasmonates in the wild-type (WT) plants. The absence of OsHPL1 attenuates OPDA accumulation to a low temperature. Then, we performed a widely targeted metabolomics study covering 597 structurally annotated compounds. In the WT and hpl1 plants, cold stress remodeled the metabolism of lipids and amino acids. Although the WT and hpl1 mutants shared over one hundred cold-affected differentially accumulated metabolites (DAMs), some displayed distinct cold-responding patterns. Furthermore, we identified 114 and 56 cold-responding DAMs, specifically in the WT and hpl1 mutants. In conclusion, our work characterized cold-triggered metabolic rewiring and the metabolic role of OsHPL1 in rice.
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BACKGROUND: Our previous study has revealed that EphA7 was upregulated in patient-derived esophageal squamous cell carcinoma (ESCC) xenografts with hyper-activated STAT3, but its mechanism was still unclear. MATERIALS AND METHODS: To assess the association between EphA7 and STAT3, western blotting, immunofluorescence, ChIP assay, and qRT-PCR were conducted. Truncated mutation and luciferase assay were performed to examine the promoter activity of EphA7. CCK-8 assay and colony formation were performed to assess the proliferation of ESCC. Cell-derived xenograft models were established to evaluate the effects of EphA7 on ESCC tumor growth. RNA-seq analyses were used to assess the effects of EphA7 on related signals. RESULTS: In this study, EphA7 was found upregulated in ESCC cell lines with high STAT3 activation, and immunofluorescence also showed that EphA7 was co-localized with phospho-STAT3 in ESCC cells. Interestingly, suppressing STAT3 activation by the STAT3 inhibitor Stattic markedly inhibited the protein expression of EphA7 in ESCC cells, in contrast, activation of STAT3 by IL-6 obviously upregulated the protein expression of EphA7. Moreover, the transcription of EphA7 was also mediated by the activation of STAT3 in ESCC cells, and the -2000â¼-1500 region was identified as the key promoter of EphA7. Our results also indicated that EphA7 enhanced the cell proliferation of ESCC, and silence of EphA7 significantly suppressed ESCC tumor growth. Moreover, EphA7 silence markedly abolished STAT3 activation-derived cell proliferation of ESCC. Additionally, RNA-seq analyses indicated that several tumor-related signaling pathways were significantly changed after EphA7 downregulation in ESCC cells. CONCLUSION: Our results showed that the transcriptional expression of EphA7 was increased by activated STAT3, and the STAT3 signaling may act through EphA7 to promote the development of ESCC.
Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Receptor, EphA7 , STAT3 Transcription Factor , Humans , Cell Line, Tumor , Cell Movement , Cell Proliferation/genetics , Esophageal Neoplasms/genetics , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma/genetics , Esophageal Squamous Cell Carcinoma/pathology , Gene Expression Regulation, Neoplastic , Signal Transduction , STAT3 Transcription Factor/genetics , STAT3 Transcription Factor/metabolism , Receptor, EphA7/metabolismABSTRACT
Aims: We sought to objectively assess left ventricular myocardial work (MW) parameters after right ventricular septal pacing (VSP) and His-Purkinje system area pacing (HPSAP) procedures. Materials and methods: Patients undergoing double-chamber pacemaker implantation for III-degree atrioventricular block (III° AVB) were assessed 1 year after implantation. VSP and HPSAP groups (20 and 23 patients, respectively) were compared against 40 healthy age-matched volunteers. Two-dimensional ultrasound speckle tracking imaging was used to obtain the global myocardial work index (GWI), global myocardial work efficiency (GWE), global myocardial constructive work (GCW), global myocardial wasted work (GWW), left ventricular stratified strain, and peak strain dispersion (PSD). Results: GWI, GWE, and GCW parameters were improved in HPSAP compared to VSP, while GWW was significantly larger in the VSP group compared to the HPSAP group (all p < 0.05). HPSAP outperformed the VSP group in comparisons of global left ventricular longitudinal strain and stratified strain. Compared to controls, the GCW of all segmental myocardium (17/17 segments) in the VSP group was significantly reduced, while 70.59% (12/17 segments) in the HPSAP group was lower than the control group. GCW in the left ventricular segment of the HPSAP group was bigger than the VSP group (29.41%; 5/17 segments) and mainly concentrated in the ventricular septum and inferior wall. Conclusion: Our findings suggest that HPSAP performance outcomes are improved over VSP after 1 year, especially in left ventricular contractile synchrony, and HPSAP is beneficial to the effective myocardial work of the left ventricle.
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BACKGROUND: Clinical guidelines indicate that chronic highland exposure could induce pulmonary hypertension; chronic hepatic disease may affect cardiac structure and functions. However, the simultaneous impact of hepatic echinococcosis (HE) and chronic highland exposure on cardiac structure and function in Tibetan residents are under-investigated. METHODS: One hundred and twenty patients with HE, 23 healthy high-altitude migrants with a mean residence time of 7.15 ± 1.12 years, and 46 healthy Tibetan permanent residents were enrolled in this study. All participants received comprehensive transthoracic echocardiography. RESULTS: High-altitude migrants have a relatively lower pulmonary artery flow velocity (PV) and a slightly higher pulmonary artery mean pressure (PAMP) than the Tibetan permanent residents. Patients with HE presented relatively smaller dimensions of the main pulmonary artery and branches and a bigger right atrium and right ventricular cavity size than the two control groups. PV, PAMP and numbers of detectable tricuspid regurgitation jet velocity (TRJV), right ventricular fractional area change (RV_FAC), tricuspid annular plane systolic excursion (TAPSE), the ratio of tricuspid inflow velocities at early diastole to tricuspid annular early diastolic excursion velocity (RV_E/e') and right ventricular myocardial performance index (RV_MPI) were increased in patients with HE compared to the two control groups. Similarly, decreased LVEF and Impaired left ventricular diastolic function were identified in patients with HE compared to the two control groups. CONCLUSIONS: Patients with HE presented with impaired biventricular contractile performance and diastolic dysfunction.
Subject(s)
Echinococcosis, Hepatic , Ventricular Dysfunction, Right , Humans , Case-Control Studies , Echocardiography , Tibet , Ventricular Function, RightABSTRACT
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a common malignant tumor of the digestive tract, which is very harmful to human health. The JAK-STAT signaling pathway is a recognized carcinogenic pathway that plays a role in the proliferation, apoptosis, migration, and invasion of a variety of cancer cells. Some studies have shown that the activation status of STAT3 affects the expression of KIRREL3. However, the expression of KIRREL3 in ESCC and its relationship with KIRREL3 or the JAK-STAT signaling pathway is still unclear. METHODS: In this study, we used immunohistochemistry and western blotting to analyze the protein expression levels of KIRREL3 in tumor tissues and ESCC cell lines. We applied proliferation assays, plate clone formation assays, Transwell assays, flow cytometry analysis, and CDX animal models to examine the role of KIRREL3 in ESCC. RESULTS: The results indicate that KIRREL3 is highly expressed to varying degrees in ESCC tissues and cell lines. Knocking down KIRREL3 expression in ESCC cells could correspondingly inhibit cell proliferation, colony formation, invasion, and migration, and had some effects on cell cycle progression and apoptosis. In addition, overexpressing KIRREL3 in these cells had opposite effects. Tumor formation in nude mice experiments also confirmed that KIRREL3 is involved in the growth of ESCC cells in vivo. CONCLUSIONS: These data suggest that KIRREL3 plays a key role in the development of ESCC, and KIRREL3 is a potential new target for the early diagnosis and clinical treatment of this disease.
Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Membrane Proteins , Animals , Humans , Mice , Cell Line, Tumor , Cell Movement/physiology , Cell Proliferation/physiology , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma/pathology , Gene Expression Regulation, Neoplastic , Membrane Proteins/metabolism , Mice, NudeABSTRACT
We investigated the ellipsometer-based characterization method being used to quickly evaluate the depth of the damage layer in ion-implanted 4H-SiC. This method had the advantages of low cost, convenience, and non-destructiveness. Optical absorption of n-type 4H-SiC substrate, P+ ion-implanted, laser-annealed, and conventional high-temperature annealed wafers were investigated at room temperature. Three peaks were observed in the absorption spectra collected for various samples. The degree of electrical activation after laser annealing or high-temperature annealing was evaluated qualitatively from the absorption peak intensity at 2.67 eV. The circular transmission line method (CTLM) results were consistent with the optical absorption results. However, it was found that the effective carrier concentration after laser annealing was significantly lower than that after high-temperature annealing.
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PURPOSE: Left ventricular (LV) contractile reserve is commonly used for LV systolic function assessment, while data on normal LV contractile reserve to exercise and the effect of gender on it are contradictory and limited, especially in Chinese adults. The aims of the present study are to clarify echocardiographic normal reference of LV contractile reserve during treadmill exercise stress echocardiography in healthy Chinese adults and to evaluate the sex-specific impact on it. PATIENTS AND METHODS: The study population consisted of 157 healthy Chinese adults. All subjects underwent comprehensive echocardiographic assessment at rest and immediately after a symptom-limited treadmill stress test. The impact of gender on LV contractile reserve was analyzed. RESULTS: The study population consisted of 157 healthy Chinese adults. All subjects underwent comprehensive echocardiographic assessment at rest and immediately after a symptom-limited treadmill stress test. The impact of gender on LV contractile reserve was analyzed. CONCLUSION: Traditional LV contractile reserve of men was much higher than that of women in a healthy Chinese population. The difference might be because of higher BSA in men. ΔGLS was less influenced by METs and CI at rest compared to ΔEF. ΔGLS, and especially the ΔGLS index, might be considered as a more preferable contractile reserve parameter for clinical cardiac function evaluation.
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The polarization extinction ratio (PER) of the multifunction integrated optic circuit (MIOC) is significant in maintaining polarization reciprocity in the fiber-optic gyroscope (FOG), and a high PER value is required, particularly in high-precision FOGs. Practically, the value of the PER decreases owing to the recoupling of the TM mode to the output port, thereby degrading the performance of the FOG. To improve the PER, the propagation of the leaking TM mode in the substrate is analyzed first. The variation of the PER with the chip structure is simulated based on the overlap integral algorithm of the optical mode. According to the analysis results, a structure of double absorption trenches at the bottom of the MIOC is proposed to block the TM mode from reflecting to the output port. In comparison with the traditional design, the optimized MIOC exhibits a higher PER that increases by approximately 25 dB and the average value of the PER reaches 75 dB. The MIOC design proposed in this study has good potential for application in high-precision FOGs.
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With the development of the designing and manufacturing level for micro-electromechanical system (MEMS) gyroscopes, the control circuit system has become a key point to determine their internal performance. Nevertheless, the phase delay of electronic components may result in some serious hazards. This study described a real-time circuit phase delay correction system for MEMS vibratory gyroscopes. A detailed theoretical analysis was provided to clarify the influence of circuit phase delay on the in-phase and quadrature (IQ) coupling characteristics and the zero-rate output (ZRO) utilizing a force-to-rebalance (FTR) closed-loop detection and quadrature correction system. By deducing the relationship between the amplitude-frequency, the phase-frequency of the MEMS gyroscope, and the phase relationship of the whole control loop, a real-time correction system was proposed to automatically adjust the phase reference value of the phase-locked loop (PLL) and thus compensate for the real-time circuit phase delay. The experimental results showed that the correction system can accurately measure and compensate the circuit phase delay in real time. Furthermore, the unwanted IQ coupling can be eliminated and the ZRO was decreased by 755% to 0.095°/s. This correction system realized a small angle random walk of 0.978°/âh and a low bias instability of 9.458°/h together with a scale factor nonlinearity of 255 ppm at room temperature. The thermal drift of the ZRO was reduced to 0.0034°/s/°C at a temperature range from -20 to 70 °C.
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In this study, two types of cooling methods (vacuum cooling and air cooling) were used to cool cooked macro-porous sausage. Alterations in the microbiological conditions, pH, instrumental color (L*, a*, and b*), total volatile nitrogenous bases (TVB-N), lipid oxidation (TBARS), water activity (aW), moisture content, and texture indicators were evaluated to determine sausages' quality changes during storage under refrigeration for up to 10 days. In general, the shelf life of sausages chilled by vacuum cooling (8 days) was similar to that of sausages cooled by air cooling (9 days). For pH, no significant difference (p > .05) was obtained between two cooling methods. However, vacuum-cooled sausages have lower L* value (p < .05), lower moisture content, and water activity compared with the air-cooled sausages. However, sausages cooled by vacuum cooling showed a sharp increase in TBARS and TVB-N values but maintained texture characteristics for a longer time compared with air-cooled sausages. Although the results indicated that the quality of sausages treated by those two methods remarkably decreased after 7 days, characteristics of sausages cooled by vacuum cooling are better within accepted standards compared with air-cooled sausages. In conclusion, vacuum cooling can be a feasible cooling method with great potential to be used in cooked macro-porous sausages to maintain the quality and may provide reference experiences for the food with similar structure.
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In modern ion implanters, a plasma flood gun (PFG) is used to neutralize wafer charge during the doping process, preventing the breakdown of floating wafers caused by the space charge accumulation. Typically, there are two kinds of PFGs, namely, dc arc discharge with filament and RF discharge. As a PFG, the filament one has limited lifetime and cannot avoid metallic contamination because of the thermal emitting filament. RF discharge PFG has been developed to solve these problems, including prolonging the source lifetime and avoiding metal pollution. Recently, a 2.45 GHz electron cyclotron resonance (ECR) ion source is also regarded as a potential choice for PFG. However, the dimension of the 2.45 GHz ECR source system including the size of the source itself and its meter's length RF subsidiary limits its application within an ion implanter. At Peking University, a miniaturized 2.45 GHz permanent magnet electron cyclotron resonance plasma flood gun with a coaxial RF transmission line has been built and tested. The dimensions of the ECR source body are Φ60 mm × Φ88 mm with a Φ30 mm × Φ40 mm plasma chamber. Its RF transmission line consists of a 200 W microwave generator, a 30 cm coaxial line, a 7 cm coaxial-to-waveguide transducer, and a microwave window that also serves as a vacuum seal. In continuous wave experiments, the electron extraction currents can be as high as 8.8 mA at an input RF power of 22 W with argon gas. The gas flow is less than 1.0 SCCM for this test.
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A 2.45 GHz microwave-driven ion source for the generation of multicharged ions has been designed and built at Peking University recently. The magnetic field configuration of this ion source is a minimum-B type with a combination of a hexapole field and an axial mirror field. Argon was selected as the first tested beam generated by this ion source. A 63 µA Ar4+ ion beam at 35 kV extraction voltage was obtained in the pulsed mode (50 Hz/500 µs). Without the hexapole magnetic field, the highest charge state was only Ar2+, and no Ar4+ ion beam was detected. The comparison between the two sets of experimental results with different magnetic configurations has proven the rationality of the production of multicharged ions with this ion source. Both experimental results and discussion will be presented in this paper.
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Breast cancer has become a worldwide threat, and chemotherapy remains a routine treatment. Patients are forced to receive continuous chemotherapy and suffer from severe side effects and poor prognosis. Natural alkaloids, such as piperine (PP) and piperlongumine (PL), are expected to become a new strategy against breast cancer due to their reliable anticancer potential. In the present study, cell viability, flow cytometry, and Western blot assays were performed to evaluate the suppression effect of PP and PL, alone or in combination. Data showed that PP and PL synergistically inhibited breast cancer cells proliferation at lower doses, while only weak killing effect was observed in normal breast cells, indicating a good selectivity. Furthermore, apoptosis and STAT3 signaling pathway-associated protein levels were analyzed. We demonstrated that PP and PL in combination inhibit STAT3 phosphorylation and regulate downstream molecules to induce apoptosis in breast cancer cells. Taken together, these results revealed that inactivation of STAT3 was a novel mechanism with treatment of PP and PL, suggesting that combination application of natural alkaloids may be a potential strategy for prevention and therapy of breast cancer.