[The effect of strengthening nutrition education in the second trimester on the basis of the first trimester on blood glucose].

Objective: To explore the effect of strengthening individualized nutrition education in the second trimester based on first trimester on blood glucose. Methods: A retrospective study was conducted on 398 pregnant women aged (31.79±3.48) (23-41) years old who underwent an oral glucose tolerance test (OGTT) from October 2021 to December 2022 at Beijing Tsinghua Changgung Hospital. They were divided into two groups according to whether the women were re-visited in second trimester or not. The routine group consisted of 205 pregnant women aged between 24 and 41 (31.49±3.36) years old who only received the first trimester nutrition education and the strengthening group consisted of 193 pregnant women aged (31.92±3.97) (23-41) years old who received both the first and second trimester nutrition education. Then according to pre pregnancy body mass index (BMI), they were divided into normal (18.5 kg/m2≤BMI<24 kg/m2) and overweight (24 kg/m2≤BMI<28 kg/m2). The OGTT blood glucose level, the positive rate of gestational diabetes (GDM) and the weight gain during pregnancy were compared between the two groups with different BMI, in order to analyze the effect of strengthening nutrition education in the second trimester of pregnancy on blood glucose. Results: The differences between the two groups were not statistically significant in terms of the pregnant women's age, proportion of pregnant women aged≥35, proportion of pre-pregnancy BMI and overweight, parity and early pregnancy blood glucose (all P>0.05). The blood glucose levels of OGTT at 0, 1, and 2 hour were (4.57±0.37), (8.41±1.70), and (7.28±1.51) mmol/L, respectively, lower than those in the routine group [(4.74±0.48), (9.44±1.55), and (8.27±1.58) mmol/L, respectively, all P<0.001]. The positive rate of GDM in the strengthening group was 35.23% (68/193), which was lower than that in the routine group (91.71%, 188/205) (P<0.001). After the BMI stratification, the OGTT blood glucose levels and the positive rate of GDM in the strengthening group were still lower than those in the routine group (all P<0.05). The weight gain with normal BMI in the early pregnancy in routine group was higher than that in the strengthening group (P=0.003), but there was no significant statistical difference in weight gain of overweight pregnant women at different gestational weeks (all P>0.05). Conclusion: Strengthening a nutrition education about second trimester for pregnant women in the early stages of pregnancy can effectively improve blood glucose levels and reduce the positive rate of GDM.

[Diagnostic values of urinary citrate for kidney stones in patients with primary gout].

OBJECTIVE: To evaluate the relationship between 24 h urinary ion content and kidney stones, and to explore the diagnostic values of kidney stone in primary gout patients. METHODS: Patients diagnosed with primary gout had ultrasound scanning of both feet and kidneys in Peking University First Hospital from Jan. 2020 to May 2021. Their clinical characteristics were compared between the positive and negative kidney stone groups, and the relationship between kidney stone and urinary ion composition were analyzed. Risk factors of kidney stone were analyzed. The explored diagnostic values were evaluated for urinary oxalate and citrate according with uric acid kidney stones by dual-energy computed tomography (DECT). RESULTS: Among the 100 gouty patients, 80 patients had uric acid crystal deposition in lower joints of extremity by ultrasonography, 61 patients had kidney stone, and 34 had kidney uric acid stones by DECT. All the multiple kidney stones were proved as uric acid kidney stones by DECT. Compared with patients without kidney stone group proved by ultrasonography, patients with kidney stone had longer gouty duration [(48.7±26.6) months vs. (84.0±30.6) months, P=0.01], higher 24 h urinary oxalate [(20.1±9.6) mg vs. (28.6±20.7) mg, P=0.001] and lower 24 h urinary citrate [(506.3±315.4) mg vs. (355.7±219.6) mg, P=0.001]. Compared with the patients without kidney stone by DECT, the patients with uric acid kidney stone also had longer disease duration [(49.1±28.4) months vs. (108.3±72.2) months, P=0.001], higher 24 h urinary oxalate [(23.6±16.9) mg vs. (28.5±18.8) mg, P < 0.05], lower 24 h urinary citrate [(556.0±316.3) mg vs. (391.7±261.2) mg, P < 0.05], higher serum uric acid [(466.2±134.5) µmol/L vs. (517.2±18.1) µmol/L, P < 0.05] and higher 24 h urinary uric acid [(1 518.1±893.4) mg vs. (1 684.2±812.1) mg, P < 0.05]. Logistic regression analysis showed long gout disease duration (OR=1.229, 95%CI: 1.062-1.522, P < 0.05), high serum uric acid level (OR=1.137, 95%CI: 1.001-1.213, P=0.01), low 24 h urinary citrate (OR=0.821, 95%CI: 0.659-0.952, P=0.01) were all risk factors of kidney stones by ultrasonography. Also, long gout disease duration (OR=1.201, 95%CI: 1.101-1.437, P=0.005), high serum creatine uric level (OR=1.145, 95%CI: 1.001-1.182, P=0.04), low 24 h urinary citrate (OR=0.837, 95%CI: 0.739-0.931, P=0.02) were all risk factors of kidney uric acid stones by DECT. CONCLUSION: Long disease duration and low 24 h urinary citrate were risk factors for kidney stones.

MiR-30c-5p inhibits high glucose-induced EMT and renal fibrogenesis by down-regulation of JAK1 in diabetic nephropathy.

OBJECTIVE: Diabetic nephropathy (DN) is one of the most serious complications of diabetes mellitus (DM) and has become the major cause of end-stage renal failure. MicroRNAs (miRs) play key roles in many pathologic processes for initiating and progressing, including DN. Epithelial-mesenchymal transition (EMT) and renal fibrogenesis are important features of DN. However, the role of miR-30c-5p in high glucose (HG)-induced EMT and renal fibrogenesis is not clear. This study was aimed at determining the regulatory network of miR-30c-5p and JAK1 in DN. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot assays were performed to detect expressions of miR-30c-5p, JAK1, vimentin, α-SMA, and E-cadherin. The possible binding sites between miR-30c-5p and JAK1 were predicted by TargetScan online database and verified by Luciferase report assay. The secretion of fibronectin (FN) and Collagen IV (Col IV) in the supernatant was detected by Enzyme-linked immunosorbent (ELISA) assay. RESULTS: MiR-30c-5p was downregulated and JAK1 was upregulated in renal fibrosis tissue and HG stimulated HK2 cells. Transfection of miR-30c-5p inhibited HG-induced EMT and renal fibrogenesis in HK2 cells, which was reversed by miR-30c-5p inhibitor. Moreover, JAK1 was confirmed as a direct target of miR-30c-5 and knockdown of JAK1 markedly inhibited HG-induced renal fibrogenesis and EMT in HK2 cells. Furthermore, overexpression of JAK1 attenuated the inhibitory effect of miR-30c-5p on HG-induced EMT and renal fibrogenesis in HK2 cells. CONCLUSIONS: MiR-30c-5p evidently inhibited HG-induced EMT and renal fibrogenesis by down-regulation JAK1 in DN, providing a promising therapeutic strategy for the treatment of DN.

[Analysis of risk factors influencing the detection rate of urate crystal by dual energy computed tomography].

OBJECTIVE: To explore the risk factors of detection of uric acid crystals by dual energy CT (DECT) in patients with gout diagnosed by gold standard. METHODS: From June 2011 to December 2018, clinical data of 29 patients were collected who were diagnosed with acute or chronic gout by positive polarized light analysis of joint synovial fluid in First Hospital of Peking University. Chi-square test, Logistic regression and t-test were used. The relationship between DECT and the clinical data, laboratory examination and drug treatment were analyzed. RESULTS: In this study, 29 patients were included, of whom, 22 patients were detected with uric acid crystals by DECT, and 7 patients were not. According to whether the uric acid crystals were detected or not by DECT, the patients were divided into two groups. Compared with the negative group, the patients were older in positive group [(47±12) vs. (39±11) years, P=0.15], had higher body bass index (BMI) [(27.9±3.7) vs. (22.8±2.1) kg/m2, P=0.002], longer gout disease duration [(135±102) vs.(45±53) months, P=0.035], higher in the highest serum uric acid in history [(643±121) vs. (543±103) µmol/L, P=0.043]. Although uric acid near DECT in positive group was higher than in negative group, there was no statistical difference [(558±150) vs. (513±89) µmol/L, P=0.497]. Comparing positive group with negative group, the percentage of the patients in acute phase was higher than in chronic phase [18(81.8%) vs. 4(57%), P=0.311];the percentage of the patients taking uric-acid-lowering drugs was higher than the other group [22(100%) vs. 5 (71%), P=0.052];the percentage of the patients with recurrent typical attacks was higher than that of those without typical attacks [22 (100%) vs.6 (85%), P=0.241]. The consistency of symptoms and the finding of uric acid crystals by DECT had been compared between the joints. The right knee joint had the highest consistency (Kappa=0.627), followed by the left MTP1 (Kappa=0.58), the right metatarsophalangeal 1(MTP1, Kappa=0.551) and the left knee (Kappa=0.494), all of which had statistical significance. The consistency of the ankle joint was lower (the right ankle joint: Kappa=0.19, the left ankle joint: Kappa=0.256), showing no statistical significance. BMI (kg/m2) [2.307 (1.139-4.670), P=0.02], gout duration (years) [0.306 (0.906-4.881), P=0.186], and the highest uric acid level in history (mg/dL) [0.023 (0.981-2.764), P=0.137] had relationship to the positive result of urate crystals in DECT. CONCLUSION: Gout patients with larger BMI, higher previous highest uric acid value and longer gout duration had higher sensitivity of the positive result in DECT.

[Risk factors and diagnostic value for ultrasound-detected tendon monosodium urate crystal deposition in patients with gout].

OBJECTIVE: To evaluate frequency and patterns, risk factors of MSU (monosodium urate) crystal deposition at lower extremity tendon by ultrasonography in gout patients, and to explore diagnostic value by ultrasonography. METHODS: Patients diagnosed with gout and age matched healthy controls had ultrasound scanning of both feet and knees including joints and tendons (achilles, quadriceps, and patellar tendon). Readers who scored the ultrasound scans for MSU crystal deposition were blinded to the patients' clinical diagnoses. Clinical characteristics were compared between positive and negative crystal deposition groups by US, and risk factors of MSU deposition in tendons were analyzed. Diagnostic values of MSU deposition were evaluated by ultrasonography according with positive MSU crystal in synovial fluid or tophi by polarized microscopy. RESULTS: Eighty patients and eighty healthy controls were included. Thity-three patients (47.5%) had tophi by physical examination. The achilles tendon was the most commonly involved tendon site 41(51.2%), followed by the quadriceps tendons 22(27.5%), and patella tendon 10(12.5%). There were no MSU deposition in healthy control group at tendon by ultrasonography. Compared with negative MSU deposition at tendon site by ultrasonography, tendon MSU positive patients had longer mean gout duration [(87.3±40.9) months vs. (7.7±2.6) months, P=0.001];higher frequency of gout flare [2(1, 2) /year vs. 1(1, 1) /year, P=0.001]; higher BMI [(26.3±2.5) kg/m2vs. (23.3±2.1) kg/m2, P=0.05]. Also, the mean serum uric acid and creatinine levels were higher in tendon MSU positive group [(584.6±87.6) µmol/L vs. (460.4±96.7) µmol/L, P=0.001] and [(90.9±33.3) µmol/L vs. (70.6±40.2) µmol/L, P=0.02] separately. Logistic regression analysis showed gout duration and flare frequency were independent risk factors for MSU deposition at tendon by ultrasonography (P < 0.01). Joint or tophi aspirations were performed in all the eighty gout patients, and positive MSU crystals in synovial fluid analysis by polarized microscopy were defined as the golden standard of gout diagnosis. When compared with the golden standard, the sensitivity and specificity were 94.0% and 78.0% separately for MSU deposition at tendon by ultrasonography. CONCLUSION: Tendon involvement at the lower extremity tendons in gout is very common. Long gout disease duration and high frequency of gout flare are both independent risk factors of tendon MSU deposition by ultrasonography. Ultrasonography had good sensitivity and specificity for detecting tendinous tophi and aggregates.

The emission of γ-Ray beams with orbital angular momentum in laser-driven micro-channel plasma target.

We investigated the emission of multi-MeV γ-Ray beams with orbital angular momentum (OAM) from the interaction of an intense circularly polarized (CP) laser with a micro-channel plasma target. The driving laser can generate high energy electrons via direct laser acceleration within the channel. By attaching a plasma foil as the reflecting mirror, the CP laser is reflected and automatically colliding with the electrons. High energy gamma-photons are emitted through inverse Compton scattering (ICS) during collision. Three-dimensional particle-in-cell simulations reveal that the spin angular momentum (SAM) of the CP laser can be transferred to the OAM of accelerated electrons and further to the emitted gamma-ray beam. These results may guide future experiments in laser-driven gamma-ray sources using micro-structures.

[A case of gout secondary to primary myelofibrosis].

A 52-year-old man was referred to our department with a 2-year history of polyarthritis. He was diagnosed as gout due to acute arthritis of bilateral feet dorsum 2 years ago,but he didn't receive any standard treatment. 1 year ago,there were more and more joints evolved during the gout attack, and many subcutaneous nodules occurred. When he presented to our clinic 1 month ago,the urate acid level was as high as 715 µmol/L. Moreover, we could find bone erosion in the X rays of his hand and foot,as well as synovitis,double contour sign and tophus on the ultrasound examination. The diagnosis of gout was clearly and definitely. However, he had leukocytosis and thrombocytosis for 4 years in the past history, and the urate acid level was only 400 µmol/L at that time. He also had well-controlled hypertension. The family history was unremarkable. Furthermore, we found megalosplenia on his physical examination. The bone marrow examination showed myelofibrosis and JAK2 V617F gene was positive. He was diagnosed as primary myelofibrosis and treated with interferon-α, together with urate acid-lowing therapy (febuxostat 60 mg once daily). Following-up for 1 year,the dosage of febuxostat decreased to 40 mg once daily, and the patient didn't have gout attack again, some of the tophus diminished, and the urate acid level ranged from 400 to 500 µmol/L. Gout is a common disease in clinical practice,usually combined with metabolic syndrome,chronic renal failure and specific drugs using (diuretic and calcineurin inhibitors). However,it is relatively rare to see gout associated with myeloproliferative diseases, including polycythemia vera, primary thrombocythemia, primary myelofibrosis and chronic myelocytic leukemia. In these diseases, the turnover of nucleic acids is greatly augmented, and an excess of purine metabolites, including uric acid, is released. In the natural course of gout, the appearance of tophus from the first onset of arthritis usually takes several years. This patient only had one traditional risk factor, but his urate acid level was remarkably high and he developed tophus in a short term. After treatment of primary myelofibrosis, the symptom of gout partially alleviated. Careful physical examination and medical history taking lead to the diagnosis of secondary gout, which should be reminded in the daily practice.

[Correlation between nailfold capillaroscopic findings and presence of interstitial lung disease in systemic sclerosis patients].

OBJECTIVE: To evaluate the correlation between nailfold capillaroscopic (NC) findings and the presence of interstitial lung disease (ILD) in systemic sclerosis (SSc) patients. METHODS: We retrospectively involved 71 SSc patients, 45 patients with ILD. NC was performed in all the patients according to the standard method. The NC findings were semi-quantitatively scored, including enlarged and giant capillaries, hemorrhages, loss of capillaries, avascular areas, ramified/bushy capillaries and disorganization of the vascular array. The demographic and clinical data collected were gender, age, presence/absence of Raynaud phenomenon (RP), duration of RP, serological acute phase reactants and antibodies, presence of ILD (also evaluated the CT score for ILD) and pulmonary function parameters. RESULTS: Among the 71 patients, the frequency of the women was 91.5%, the mean age was (52.59±12.77) years, and disease duration was (3.00±6.00) years. NC changes of the scleroderma pattern were observed in 90.1% patients. There were 45 patients with ILD and 26 patients without ILD. The patients with ILD had significantly higher loss of capillaries score [0.50 (1.03) vs. 0.00 (0.43), P=0.003], avascular area score [0.75 (1.24) vs. 0.25 (0.83), P=0.006] and ramified/bushy capillaries score [0.33 (0.88) vs. 0.13 (0.25), P=0.006] compared with those without ILD. Moreover, ramified/bushy capillaries score together with diffused SSc were independent risk factors for the presence of ILD. And the score of giant capillaries were significantly lower in the patients with more severe ILD group [0.25 (0.94) vs. 0.00 (0.28), for the mild and severe ILD groups respectively, P=0.019]. There was no statistically significant difference between the two groups with respect to the scores of enlarged capillaries, hemorrhages, or disorganization of the vascular array. CONCLUSION: Capillary deletion and severe deformity in NC were associated with the presence of ILD in SSc patients. And patients with less giant capillaries had more severe ILD involvement. These indicated that NC maybe a useful tool to evaluate ILD in SSc.

Effects of tumor necrosis factor and E-selectin on coronary artery flow.

OBJECTIVE: The aim of the study is to investigate the correlation between tumor necrosis factor (TNF-α), E-selectin and coronary artery flow following myocardial ischemia-reperfusion model (IR) in Yorkshire pigs. MATERIALS AND METHODS: Establishment of IR model in pigs. Following the injury model, Experiment group was administrated intravenously Shenfu injection solution (SFI, 1 mL/kg). The control group received the same amount of saline. After 30 min of blood reflux, thrombolysis in myocardial infarction frame count (TFC) was recorded following surgery. TNF-α, E-selectin expression was determined by ELISA in the venous sheath, coronary sinus, artery sinus, and proximal segment of the coronary artery. RESULTS: After the blood reflowing, TFC in both groups were upregulated, and TFC increased more than the control group. The difference is statistically significant (p<0.05) at the time of 30 min. TNF-α, E-selectin expression increased after IR. After reperfusion, TNF-α, E-selectin levels further increased and the myocardial injury was aggravated. SFI inhibited inflammation in the experimental group. TNF-α, E-selectin levels at coronary sinus, artery sinus, and distal segment of coronary artery after surgery was positively correlated with TIMI in the experimental group (p<0.05). TNF-α, E-selectin levels significantly increased after reperfusion (p<0.05). CONCLUSIONS: The result demonstrated that TNF-α, E-selectin levels were positively correlated with coronary artery reflow only in the experimental group but not in the control group.

Correlation study between interleukin-6 levels and coronary reflow.

OBJECTIVE: To analyze the correlation between local interleukin-6 (IL-6) levels in different parts of blood vessel and the record of Thrombolysis in Myocardial Infarction (TIMI) frame count (TFC) after myocardial ischemia-reperfusion (IR) model. MATERIALS AND METHODS: Establishment of IR model in Yorkshire pigs, the pigs were divided into two groups (n=6). Experiment group pigs were administrated with Shenfu injection (SF) intravenously (1 mL/kg), control group was given saline injection. The blood reflowed after 30 min. TIMI was recorded to evaluate the coronary blood flow and myocardial perfusion. IL-6 levels in venous sheath, coronary sinus, artery sinus, and proximal coronary artery were determined by ELISA. RESULTS: The records of TIMI in experimental group were higher than that in control group. The difference was statistically significant (p < 0.05). The level of IL-6 increased obviously compared with control group after reperfusion (p < 0.05). Shenfu injection reduced the level of IL-6. IL-6 level at the coronary sinus was positively correlated with TIMI in experimental group (p = 0.03, R2 = 0.97) but not in control group. CONCLUSIONS: IL-6 levels were significantly increased after reperfusion, which aggravated myocardial injury. IL-6 may be associated with coronary reflow, but further study is needed.

[Detection of peripheral follicular helper T cells in rheumatoid arthritis].

OBJECTIVE: To detect cell frequency and surface markers of peripheral CD4+CXCR5+ follicular helper T (Tfh) cells and analyze the correlation between CD4+CXCR5+Tfh cells and rheumatoid arthritis (RA) disease activity. METHODS: Forty RA patients meeting the American College of Rheumatology classification criteria for RA and twenty healthy controls (HC) were included. The peripheral blood mononuclear cells and sera were collected. The expressions of CD4+CXCR5+Tfh cells (CXCR5, C-X-C chemokine receptor type 5) and inducible T cell costimulator (ICOS), programmed death 1 positive (PD-1), interleukin-21 receptor (IL-21R) and CD40 ligand (CD40L) positive on CD4+CXCR5+Tfh cells were analyzed by flow cytometry. The transcript levels of B-cell lymphoma 6 (Bcl-6), as well as IL-21 and IL-21R, were measured by real-time polymerase chain reaction. Besides, serum IL-21 and CXCL13 concentrations were determined by enzyme-linked immunosorbent assay. The potential association between Tfh cells and RA disease activity was detected. RESULTS: The cell surface marker of CXCR5+ on CD4+ cells was significantly increasingly higher across the following groups versus HC: total RA patients (16.75±3.92 vs.7.49±1.84, P<0.001); RA patients with low disease activity or remission (16.62±3.43 vs. 7.49±1.84, P<0.001); RA patients with moderate disease activity (16.82±3.07 vs. 7.49±1.84, P<0.001) and RA patients with high disease activity (16.87±5.50 vs. 7.49±1.84, P<0.001). Besides, the percentages of ICOS+, PD-1+, IL-21R+ on CD4+CXCR5+Tfh cells in the RA patients were significantly higher than that of HC (ICOS+CD4+CXCR5+cells, 8.37±4.28 vs. 3.72±1.81, P<0.001; PD-1+CD4+CXCR5+cells, 1.57±1.10 vs. 0.24±0.30, P=0.035; IL-21R+CD4+CXCR5+ cells, 4.60 ±4.05 vs. 0.20±0.19, P=0.006). But the percentage of CD40L+ on CXCR5+CD4+Tfh cells in the RA patients was not significantly higher than that of HC (3.38±3.71 vs. 0.54±0.34, P=0.135). The IL-21R mRNA expression was elevated significantly (5.00±4.94 vs. 0.74±0.55, P<0.001) in the RA patients but not in Bcl-6 mRNA[4.54(3.33, 7.23) vs. 5.31(2.81, 7.44), P=0.329]or IL-21 mRAN[0.72(0.26, 3.45) vs. 0.56(0.27, 3.71), P=0.195]. Additionally, the serum interleukin-21 (IL-21) and CXCL13 levels in the RA patients were higher than in the healthy controls [IL-21, (200.49±154.56) ng/L vs. (8.21±5.95) ng/L, P<0.001; CXCL13, (93.72±49.72) ng/L vs. (43.09±1.28) ng/L, P<0.001] and were both positively correlated with RA disease activity indexes, including erythrocyte sedimentation rate, the disease activity score in 28 joints (ESR-based or CRP-based), clinical disease activity index, and simplified disease activity index. However, none of the Tfh cells, anti-citrullinated protein antibody or rheumatoid factor had any relationship with RA disease activity. CONCLUSION: Peripheral Tfh cells and their relevant cytokines are higher in RA patients than healthy controls, indicating Tfh cells may participate in the pathogenesis of RA, therefore, blocking the pathway of Tfh cells may be reasonable cellular targets for therapeutic intervention.

Muscle immobilization activates mitophagy and disrupts mitochondrial dynamics in mice.

AIM: Skeletal muscle atrophy following prolonged immobilization (IM) is a catabolic state characterized by increased proteolysis and functional deterioration. Previous research indicates that discord of mitochondrial homoeostasis plays a critical role in muscle atrophy. We hypothesized that muscle IM would activate the ubiquitin-proteolysis, autophagy-lysosome (mitophagy) pathway, mitochondrial dynamics remodelling and apoptosis partially controlled by the FoxO signalling pathway. METHODS: Female FVB/N mice were randomly divided into five groups (n = 8 each): control (CON), IM with banding of one of the hindlimbs for 1, 2 and 3 weeks (1w-, 2w- and 3w-IM) and 2w-IM followed by 1 week of remobilization (RM). RESULTS: Mitochondrial density and DNA copies in tibialis anterior (TA) muscle were reduced by approx. 80% (P < 0.05 for 2w-IM; P < 0.01 for 3w-IM), along with activation of FoxO3a, atrogin-1 and MuRF1 following 2w- and 3w-IM (P < 0.01). Protein markers of autophagy/mitophagy, such as beclin 1 (approx. 2.7-fold; P < 0.01), LC3, ubiquitin-binding adaptor (approx. 1.47-fold; P < 0.01), Rheb (approx. 1.9-fold; P < 0.05) and parkin (approx. 70%; P < 0.05), were all increased by IM and remained activated after RM, whereas BNIP3 and PINK1 levels were decreased by IM (P < 0.05), but elevated upon RM (P < 0.01). IM decreased Mfn2 expression (approx. 50%; P < 0.01) and increased Fis-1 expression (approx. 2.4-fold; P < 0.05). Muscle apoptosis indicator Bax/Bcl2 ratio was elevated at 2w- to 3w-IM (approx. 3.7-fold; P < 0.01), whereas caspase-3 activity was five- to sixfold higher (P < 0.01) and remained threefold higher above CON (P < 0.05). CONCLUSION: Our data indicate that IM-induced mitochondrial deterioration is associated with altered protein expressions in the autophagic/mitophagic pathway, more fragmented mitochondrial network and activation of apoptosis partly under the influence of FoxO3 activation.

Microengineering Laser Plasma Interactions at Relativistic Intensities.

We report on the first successful proof-of-principle experiment to manipulate laser-matter interactions on microscales using highly ordered Si microwire arrays. The interaction of a high-contrast short-pulse laser with a flat target via periodic Si microwires yields a substantial enhancement in both the total and cutoff energies of the produced electron beam. The self-generated electric and magnetic fields behave as an electromagnetic lens that confines and guides electrons between the microwires as they acquire relativistic energies via direct laser acceleration.

Towards manipulating relativistic laser pulses with micro-tube plasma lenses.

Efficient coupling of intense laser pulses to solid-density matter is critical to many applications including ion acceleration for cancer therapy. At relativistic intensities, the focus has been mainly on investigating various laser beams irradiating initially overdense flat interfaces with little or no control over the interaction. Here, we propose a novel approach that leverages recent advancements in 3D direct laser writing (DLW) of materials and high contrast lasers to manipulate the laser-matter interactions on the micro-scales. We demonstrate, via simulations, that usable intensities ≥10(23) Wcm(-2) could be achieved with current tabletop lasers coupled to micro-engineered plasma lenses. We show that these plasma optical elements act as a lens to focus laser light. These results open new paths to engineering light-matter interactions at ultra-relativistic intensities.

Radiation-reaction trapping of electrons in extreme laser fields.

A radiation-reaction trapping (RRT) of electrons is revealed in the near-QED regime of laser-plasma interaction. Electrons quivering in laser pulse experience radiation reaction (RR) recoil force by radiating photons. When the laser field reaches the threshold, the RR force becomes significant enough to compensate for the expelling laser ponderomotive force. Then electrons are trapped inside the laser pulse instead of being scattered off transversely and form a dense plasma bunch. The mechanism is demonstrated both by full three-dimensional particle-in-cell simulations using the QED photonic approach and numerical test-particle modeling based on the classical Landau-Lifshitz formula of RR force. Furthermore, the proposed analysis shows that the threshold of laser field amplitude for RRT is approximately the cubic root of laser wavelength over classical electron radius. Because of the pinching effect of the trapped electron bunch, the required laser intensity for RRT can be further reduced.

Antioxidant and anti-inflammatory effects of exercise: role of redox signaling.

Contraction-induced production of reactive oxygen species (ROS) has been implicated in oxidative stress to skeletal muscle for the past few decades. As research advances more evidence has revealed a more complete role of ROS under both physiological and pathological conditions. The current review postulated that moderate intensity of physical exercise has antioxidant and anti-inflammatory effects due to the operation and cross-talks of several redox-sensitive signal transduction pathways. The functional roles and mechanisms of action of the nuclear factor κB, mitogen-activated protein kinase, and peroxisome proliferator-activated receptor γ co-activator 1α are highlighted.

Influence of glutathione levels and activity of glutathione-related enzymes in the brains of tumor-bearing mice.

Oxidative stress takes place due to an imbalance between the production of reactive oxygen species (ROS) and the protection provided by cellular antioxidants. High levels of ROS are caused by tumor cells during tumor progression and may affect the functions of other important organs. The present study sought to investigate whether non-primary brain tumors affect reduced glutathione (GSH) levels and the activity of related enzymes in the brain. GSH contents, the activity of glutathione peroxidase (GPx), glutathione-s-transferase (GST), glutathione reductase (GR) as well as glutamate cysteine ligase (GCL) were determined in the brains of normal and tumor-bearing mice treated with the chemotherapy drug 5-Fluorouracil (5-Fu) or not. The results in S180 and H22 tumor-bearing mice showed that GSH levels and the activity of GPx, GST, and GCL all decreased while GR activity markedly increased in the brains of tumor-bearing mice compared to those of normal mice. Further investigation found that 5-Fu, a typical chemotherapy drug, significantly inhibited tumor growth but did not improve the loss of redox homeostasis in the brain caused by non-primary brain tumors. Overall, these results suggest that non-primary brain tumors can induce an ROS burden in the brain that cannot be reversed by the chemotherapy drug 5-Fu.

Relativistic single-cycled short-wavelength laser pulse compressed from a chirped pulse induced by laser-foil interaction.

By particle-in-cell simulation and analysis, we propose a plasma approach to generate a relativistic chirped pulse based on a laser-foil interaction. When two counterpropagating circularly polarized pulses interact with an overdense foil, the driving pulse (with a larger laser field amplitude) will accelerate the whole foil to form a double-layer structure, and the scattered pulse (with a smaller laser field amplitude) is reflected by this flying layer. Because of the Doppler effect and the varying velocity of the layer, the reflected pulse is up-shifted for frequency and chirped; thus, it could be compressed to a nearly single-cycled relativistic laser pulse with a short wavelength. Simulations show that a nearly single-cycled subfemtosecond relativistic pulse can be generated with a wavelength of 0.2 µm after dispersion compensation.

Synergistic antitumor effect of TRAIL and adriamycin on the human breast cancer cell line MCF-7.

The aim of the present study was to determine the effect of the combination of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and adriamycin (ADM) on the human breast cancer cell line MCF-7 and to identify potential mechanisms of apoptosis. Cell viability was analyzed by the MTT assay and the synergistic effect was assessed by the Webb coefficient. Apoptosis was quantified using the annexin V-FITC and propidium iodide staining flow cytometry. The mRNA expression of TRAIL receptors was measured by RT-PCR. Changes in the quantities of Bax and caspase-9 proteins were determined by Western blot. MCF-7 cells were relatively resistant to TRAIL (IC50 >10 microg/mL), while MCF-7 cells were sensitive to ADM (IC50 <10 microg/mL). A subtoxic concentration of ADM (0.5 microg/mL) combined with 0.1, 1, or 10 microg/mL TRAIL had a synergistic cytotoxic effect on MCF-7 cells, which was more marked with the combination of TRAIL (0.1 microg/mL) and ADM (0.5 microg/mL). In addition, the combined treatment with TRAIL and ADM significantly increased cell apoptosis from 9.8% (TRAIL) or 17% (ADM) to 38.7%, resulting in a synergistic apoptotic effect, which is proposed to be mediated by up-regulation of DR4 and DR5 mRNA expression and increased expression of Bax and caspase-9 proteins. These results suggest that the combination of TRAIL and ADM might be a promising therapy for breast cancer.