Observation of anti-damping spin-orbit torques generated by in-plane and out-of-plane spin polarizations in MnPd3.

Large spin-orbit torques (SOTs) generated by topological materials and heavy metals interfaced with ferromagnets are promising for next-generation magnetic memory and logic devices. SOTs generated from y spin originating from spin Hall and Edelstein effects can realize field-free magnetization switching only when the magnetization and spin are collinear. Here we circumvent the above limitation by utilizing unconventional spins generated in a MnPd3 thin film grown on an oxidized silicon substrate. We observe conventional SOT due to y spin, and out-of-plane and in-plane anti-damping-like torques originated from z spin and x spin, respectively, in MnPd3/CoFeB heterostructures. Notably, we have demonstrated complete field-free switching of perpendicular cobalt via out-of-plane anti-damping-like SOT. Density functional theory calculations show that the observed unconventional torques are due to the low symmetry of the (114)-oriented MnPd3 films. Altogether our results provide a path toward realization of a practical spin channel in ultrafast magnetic memory and logic devices.

Perpendicular magnetic anisotropy, tunneling magnetoresistance and spin-transfer torque effect in magnetic tunnel junctions with Nb layers.

Nb and its compounds are widely used in quantum computing due to their high superconducting transition temperatures and high critical fields. Devices that combine superconducting performance and spintronic non-volatility could deliver unique functionality. Here we report the study of magnetic tunnel junctions with Nb as the heavy metal layers. An interfacial perpendicular magnetic anisotropy energy density of 1.85 mJ/m2 was obtained in Nb/CoFeB/MgO heterostructures. The tunneling magnetoresistance was evaluated in junctions with different thickness combinations and different annealing conditions. An optimized magnetoresistance of 120% was obtained at room temperature, with a damping parameter of 0.011 determined by ferromagnetic resonance. In addition, spin-transfer torque switching has also been successfully observed in these junctions with a quasistatic switching current density of 7.3 [Formula: see text] A/cm2.

Prevalence and molecular characterization of Clostridioides difficile infection in China over the past 5 years: a systematic review and meta-analysis.

OBJECTIVES: The aim of this study was to provide an overview of the prevalence and molecular characteristics of Clostridioides difficile infection (CDI) in China in the past 5 years. METHODS: A systematic literature review was conducted according to the preferred reporting items for systematic reviews and meta-analyses guidelines. Nine databases were searched for relevant studies published between January 2017 and February 2022. The Joanna Briggs Institute critical appraisal tool was used to assess the quality of included studies, and R software version 4.1.3 was used for data analysis. Funnel plots and Egger regression tests were also performed to assess publication bias. RESULTS: A total of 50 studies were included in the analysis. The pooled prevalence of CDI in China was 11.4% (2696/26,852). The main circulating C. difficile strains in southern China were ST54, ST3, and ST37, consistent with the overall situation in China. However, the most prevalent genotype in northern China was ST2, which was previously underappreciated. CONCLUSION: Based on our findings, increased awareness and management of CDI is necessary to reduce the prevalence of CDI in China.

[Comparison of distribution of verbascoside in normoxic and hypoxic rats].

This study established a high performance liquid chromatography(HPLC) method for the simultaneous determination of verbascoside(VB) and its main metabolite caffeic acid(CA) in rat tissue samples. A low-pressure low-oxygen animal experimental chamber was used to simulate the plateau environment for establishing the hypoxic rat model. After intragastric administration of 300 mg·kg~(-1) VB, the normoxic and hypoxic rats were sacrificed for the collection of heart, liver, spleen, lung, kidney, brain, muscle, large intestine, small intestine, and stomach tissue samples at the time points of 30, 60, and 90 min. VB and CA concentrations in each tissue sample were measured by HPLC, and the distribution of VB and CA in normoxic and hypoxic rats was compared. The results showed that after intragastric administration, VB can be rapidly absorbed and distributed into various tissues including brain in both normoxic and hypoxic rats, indicating that VB can pass through the blood-brain barrier. In the gastrointestinal tract, VB was mainly distributed in small intestine, which suggested that the main absorption site of VB was small intestine. A large amount of VB was detected in muscle and lung, and only a small amount in other tissues. CA was detected in other tissues except brain, heart, and muscle. Small intestine had the most abundant CA, followed by stomach, large intestine, and kidney, and only a small amount of CA was detected in the liver, spleen, and lung(<50 ng·mL~(-1)). The results indicated that VB may be mainly absorbed and metabolized in the gastrointestinal tract to produce CA and was possibly excreted through kidney. Compared with normoxic rats, hypoxic rats had reduced and slow distribution of VB and increased ratio of VB concentration in tissue to plasma, which implied that the relative proportion of VB from systemic circulation to tissues was increased in hypoxic rats. This study provides a basis for the application of VB in anti-hypoxia therapy and for the formulation of anti-hypoxia dosing regimens.

Effects of Altitude and Duration of Differing Levels of Hypoxic Exposure on Hypoxia-Inducible Factor-1α in Rat Tissues.

Li, Xiao-lin, Wei-gang Wang, Mao-xing Li, Tian-long Liu, Xiu-yu Tian, and Lan Wu. Effects of altitude and duration of differing levels of hypoxic exposure on hypoxia-inducible factor-1α in rat tissues. High Alt Med Biol. 23:173-184, 2022. Objective: This research aimed to evaluate the effects of hypoxia at different altitudes and durations on the expression of hypoxia-inducible factor-1α (HIF-1α) in rat tissues. Methods: A total of 72 Wistar rats were used to investigate the effect of hypoxia at different durations on rat tissues and 72 Wistar rats were used to investigate the effect of hypoxia at different altitudes. Hematoxylin and Eosin (HE) staining was performed to observe the pathological changes of hippocampus tissues, and the expression of HIF-1α of rats under conditions of hypoxia was detected by quantitative real-time polymerase chain reaction and western blotting. Results: According to the pathological results, we found that the degree of the brain, lung, and heart damage and HIF-1α expression, showed an increasing trend as the altitude (1,500, 3,000, 4,500, 6,000, 7,500, and 8,000 m for 12 hours) and duration (0, 6, 12, 24, 36, and 72 hours at 7,500 m) of hypoxia increased. Although there is a significant difference at 8,000 m, considering model stability, animal ethics and cost, we chose 7,500 m as a fixed altitude during hypoxia at different durations. Compared with the normoxic group, the expression of HIF-1α mRNA in the 7,500 m significantly increased by 30.48%, 21.00%, and 12.62%, in brain, lung, and heart tissue (p < 0.01), and HIF-1α mRNA in the 72-hour hypoxic exposure group significantly increased by 52.58%, 20.39%, 27.88% in tissues (p < 0.05). Compared with the normoxic group, HIF-1α protein expressions in the 7,500 m significantly increased by 10.26%, 31.71%, and 13.33% in brain, lung, and heart tissue (p < 0.01, p < 0.01, p < 0.05), and HIF-1α protein expressions in the 72-hour hypoxic exposure group significantly increased by 18.89%, 22.89%, and 29.75% in tissues (p < 0.05). Conclusion: HIF-1α expression in the rat was correlated with altitude and duration of hypoxic exposure.

The role of short-chain fatty acids in Clostridioides difficile infection: A review.

Clostridioides difficile is a Gram-positive, obligate anaerobic, spore-producing intestinal opportunistic pathogen. CDI outbreaks in Europe and the Americas in recent years are a major health concern. Intestinal short-chain fatty acids (SCFAs) are an important energy source for colonic epithelial cells, and the roles of SCFAs in reducing intestinal inflammation, inhibiting intestinal tumors, and regulating gut microbial homeostasis are being actively researched. Furthermore, SCFAs attenuate CDI or directly inhibit C. difficile growth through different pathways in vivo and in vitro. This review assesses the role of SCFAs in CDI and discusses the potential use of these molecules as therapeutic targets for CDI.

[Effects of Combination of Organic and Inorganic Nitrogen on Nitrification and Denitrification in Two Salinized Soils].

Focusing on typical mildly saline soil, S1 (EC, 0.62 dS·m-1), and moderately saline soil, S2 (EC, 1.17 dS·m-1), in Hetao Irrigation District of Inner Mongolia, the response of nitrification and denitrification process to salinization degree and the proportion of organic and inorganic nitrogen application were studied. The experimental treatments consisted of(1) no nitrogen(CK), (2) only inorganic nitrogen(U1), and(3) organic nitrogen(U3O1, U1O1, U1O3, and O1) compared to 25%, 50%, 75%, and 100% inorganic nitrogen. The results showed that increasing salinity reduced the soil nitrification potential and increased the soil denitrification capacity. The soil nitrification potential of the S1 soil was 28.81%-69.67% higher than that of the S2 soil, while the denitrification capacity was reduced by 17.16%-88.91%. With an increase in salinity, the AOB abundance and nitrification contribution rate were reduced, but the AOA abundance and nitrification contribution rate were increased. Furthermore, an increase in salinity increased the abundance of nirK and nirS bacteria, and increased N2O/(N2O+N2) production, but reduced the abundance of nosZ. In the S1 soil, the nitrification potential and denitrification capacity of U1O1 were highest, increasing by as much as 18.59% and 15.87%, respectively, compared to the U1 treatment. In the S2 soil, the difference in the soil nitrification potential between the various fertilization treatments was not significant, and the denitrification capacity of the O1 treatment was highest. The S1 and S2 saline soils treated with U1O1 and O1, respectively, had higher AOB gene abundance and nitrification contribution rates, increased nirS and nosZ gene abundances, and significantly reduced N2O/(N2O+N2) product ratios. Our findings suggested that mildly saline soils(120 kg·hm-2 urea+120 kg·hm-2 organic fertilizer) and moderately saline soils(240 kg·hm-2 organic fertilizer) are more conducive to soil nitrification and denitrification processes compared to soils to which inorganic nitrogen is applied alone.

Crocetin: A Systematic Review.

Crocetin is an aglycone of crocin naturally occurring in saffron and produced in biological systems by hydrolysis of crocin as a bioactive metabolite. It is known to exist in several medicinal plants, the desiccative ripe fruit of the cape jasmine belonging to the Rubiaceae family, and stigmas of the saffron plant of the Iridaceae family. According to modern pharmacological investigations, crocetin possesses cardioprotective, hepatoprotective, neuroprotective, antidepressant, antiviral, anticancer, atherosclerotic, antidiabetic, and memory-enhancing properties. Although poor bioavailability hinders therapeutic applications, derivatization and formulation preparation technologies have broadened the application prospects for crocetin. To promote the research and development of crocetin, we summarized the distribution, preparation and production, total synthesis and derivatization technology, pharmacological activity, pharmacokinetics, drug safety, drug formulations, and preparation of crocetin.

Carriage of Clostridioides difficile in healthy infants in the community of Handan, China: A 1-year follow-up study.

OBJECTIVE: Clostridioides difficile may colonize healthy infants and young children asymptomatically and for the long-term. C. difficile genotypes and the rate and determinants of colonization differ substantially and vary among countries and regions. A 1-year follow-up study was performed to determine the incidence, kinetics and influencing factors of C. difficile intestinal colonization. METHODS: Twenty-nine healthy infants (14 girls and 15 boys) living at home with their parents in Handan City were followed by survey from birth to 1 year of age, specifically from October 2014 through December 2015. C. difficile isolates were typed by PCR ribotyping and analyzed for the presence of toxin genes. RESULTS: During the follow-up study period in the first year of life, 20 of the 29 total enrolled infants acquired C. difficile. A total of 437 fecal samples were obtained, and 111 (25.4%) samples contained C. difficile, including 79 (71.2%) toxigenic strains. The toxigenic isolates comprised six PCR ribotypes, and two PCR ribotypes were identified as nontoxigenic strains. CONCLUSION: Our study showed that C. difficile colonization increase with age during the 12-month period, and the dominant toxigenic types of C. difficile isolates in infants were those involved in long-term colonization. Feeding patterns may affect the dynamic progress of C. difficile colonization.

LINC00452 promotes ovarian carcinogenesis through increasing ROCK1 by sponging miR-501-3p and suppressing ubiquitin-mediated degradation.

Ovarian cancer refers to all sorts of cancerous growth that starts from the ovary. Dysregulation of long non-coding RNAs (lncRNAs) is associated with ovarian cancer development and progression. Cellular expression and localization of LINC00452 in ovarian cancer cells were detected by qPCR and FISH. The roles of LINC00452 in ovarian carcinogenesis were characterized by MTT, transwell and colony-formation assays in vitro as well as xenograft mouse model. The underlying mechanism was explored by microarray, RIP, Co-IP and luciferase reporter assays. This study identified a novel lncRNA LINC00452 being elevated in both ovarian cancer cells and tumor tissues in patients. Such aberrant expression of LINC00452 was negatively correlated with relapse-free survival of ovarian cancer patients. Overexpression of LINC00452 potentiated CaOV3 cell viability, migration and invasion in vitro as well as xenograft tumor growth in vivo. Evidence from the current study suggests that the carcinogenicity of LINC00452 is partially due to competitive sponging of miR-501-3p followed with release of repression on the ROCK1, a key effector in Rho signaling pathway. Irrespective of its miRNA sponge function, LINC00452 is capable of preventing ROCK1 protein from ubiquitin/proteasome-mediated degradation via their mutual physical interaction. Our study makes LINC00452 a potential therapeutic target for ovarian cancer.

[Effects of the Combined Application of Organic and Inorganic fertilizers on N2 O Emissions from Saline Soil].

Combining organic fertilizer with chemical fertilizer may affect the microbial processes related to nitrous oxide (N2O) emissions under different degrees of soil salinization. A mild saline soil (S1; electrical conductivity (EC) 0.46 dS·m-1) and moderate saline soil (S2; EC 1.07 dS·m-1) in the Hetao irrigation district of Inner Mongolia were selected. Under equal N rates, the study involved five treatments:U1 (240 kg·hm-2 of chemical fertilizer), U3O1 (180 kg·hm-2 of chemical fertilizer+60 kg·hm-2 of organic fertilizer), U1O1 (120 kg·hm-2 of chemical fertilizer+120 kg·hm-2 of organic fertilizer), U1O3 (60 kg·hm-2 of chemical fertilizer+180 kg·hm-2 of organic fertilizer), and O1 (240 kg·hm-2 of organic fertilizer). In addition, a blank control treatment (CK) was employed to investigate the effects of different fertilization treatments on the N2O emissions from the two saline soils. The results showed that the total N2O emissions from the S2 soil in the same treatment were between 11.86% and 47.23% higher than those from the S1 soil (P<0.05). the dynamic trend of the soil N2O fluxes among the different treatments were similar. The peak N2O emissions occurred after fertilization, and the N2O cumulative emission fluxes accounted for nearly 60% of the emissions during the entire growth period. The proper application of organic fertilizer could significantly reduce the soil N2O emission; the S1 and S2 saline soils treated with U1O1 and O1, respectively, had the lowest N2O emissions, whereby there were significant reductions of 33.62% and 28.51% in comparison to the U1 treatment (P<0.05). Moreover, higher maize yields could be obtained and the N2O flux was significantly positively correlated with the NH4+-N content (P<0.01) but negatively correlated with the NO3--N content. The results demonstrated that nitrification was the main way to produce N2O in the studied salinized maize farmland, and that the addition of organic fertilizer could reduce the N2O production by decreasing the soil NH4+-N content. Based on the changes in the corn yield and a reduction in the greenhouse effect, suitable organic and inorganic fertilizer management models for the Hetao irrigation area were the mild saline soil:120 kg·hm-2 of urea +120 kg·hm-2 of organic fertilizer), and the moderate saline soil:240 kg·hm-2 of organic fertilizer.

A Fluorescent and Colorimetric Chemosensor for Hg2+ Based on Rhodamine 6G With a Two-Step Reaction Mechanism.

A fluorescent and colorimetric chemosensor L based on rhodamine 6G was designed, synthesized, and characterized. Based on a two-step reaction, the chemosensor L effectively recognized Hg2+. The interaction between the chemosensor and Hg2+ was confirmed by ultraviolet-visible spectrophotometry, fluorescence spectroscopy, electrospray ionization-mass spectrometry, Fourier-transform infrared spectroscopy, and frontier molecular orbital calculations. The chemosensor L was also incorporated into test strips and silica gel plates, which demonstrated good selectivity and high sensitivity for Hg2+.

Stereotactic Radiosurgery for Cavernous Sinus Versus Noncavernous Sinus Dural Arteriovenous Fistulas: Outcomes and Outcome Predictors.

BACKGROUND: Dural arteriovenous fistulas (DAVFs) can be categorized based on location. OBJECTIVE: To compare stereotactic radiosurgery (SRS) outcomes between cavernous sinus (CS) and non-CS DAVFs and to identify respective outcome predictors. METHODS: This is a retrospective study of DAVFs treated with SRS between 1988 and 2016 at 10 institutions. Patients' variables, DAVF characters, and SRS parameters were included for analyses. Favorable clinical outcome was defined as angiography-confirmed obliteration without radiological radiation-induced changes (RIC) or post-SRS hemorrhage. Other outcomes were DAVFs obliteration and adverse events (including RIC, symptomatic RIC, and post-SRS hemorrhage). RESULTS: The overall study cohort comprised 131 patients, including 20 patients with CS DAVFs (15%) and 111 patients with non-CS DAVFs (85%). Rates of favorable clinical outcome were comparable between the 2 groups (45% vs 37%, P = .824). Obliteration rate after SRS was higher in the CS DAVFs group, even adjusted for baseline difference (OR = 4.189, P = .044). Predictors of favorable clinical outcome included higher maximum dose (P = .014) for CS DAVFs. Symptomatic improvement was associated with obliteration in non-CS DAVFs (P = .005), but symptoms improved regardless of whether obliteration was confirmed in CS DAVFs. Non-CS DAVFs patients with adverse events after SRS were more likely to be male (P = .020), multiple arterial feeding fistulas (P = .018), and lower maximum dose (P = .041). CONCLUSION: After SRS, CS DAVFs are more likely to obliterate than non-CS ones. Because these 2 groups have different total predictors for clinical and radiologic outcomes after SRS, they should be considered as different entities.

Hemorrhage risk of cerebral dural arteriovenous fistulas following Gamma Knife radiosurgery in a multicenter international consortium.

OBJECTIVE: The authors performed a study to evaluate the hemorrhagic rates of cerebral dural arteriovenous fistulas (dAVFs) and the risk factors of hemorrhage following Gamma Knife radiosurgery (GKRS). METHODS: Data from a cohort of patients undergoing GKRS for cerebral dAVFs were compiled from the International Radiosurgery Research Foundation. The annual posttreatment hemorrhage rate was calculated as the number of hemorrhages divided by the patient-years at risk. Risk factors for dAVF hemorrhage prior to GKRS and during the latency period after radiosurgery were evaluated in a multivariate analysis. RESULTS: A total of 147 patients with dAVFs were treated with GKRS. Thirty-six patients (24.5%) presented with hemorrhage. dAVFs that had any cortical venous drainage (CVD) (OR = 3.8, p = 0.003) or convexity or torcula location (OR = 3.3, p = 0.017) were more likely to present with hemorrhage in multivariate analysis. Half of the patients had prior treatment (49.7%). Post-GRKS hemorrhage occurred in 4 patients, with an overall annual risk of 0.84% during the latency period. The annual risks of post-GKRS hemorrhage for Borden type 2-3 dAVFs and Borden type 2-3 hemorrhagic dAVFs were 1.45% and 0.93%, respectively. No hemorrhage occurred after radiological confirmation of obliteration. Independent predictors of hemorrhage following GKRS included nonhemorrhagic neural deficit presentation (HR = 21.6, p = 0.027) and increasing number of past endovascular treatments (HR = 1.81, p = 0.036). CONCLUSIONS: Patients have similar rates of hemorrhage before and after radiosurgery until obliteration is achieved. dAVFs that have any CVD or are located in the convexity or torcula were more likely to present with hemorrhage. Patients presenting with nonhemorrhagic neural deficits and a history of endovascular treatments had higher risks of post-GKRS hemorrhage.

Evaluation of stereotactic radiosurgery for cerebral dural arteriovenous fistulas in a multicenter international consortium.

OBJECTIVE: In this multicenter study, the authors reviewed the results obtained in patients who underwent Gamma Knife radiosurgery (GKRS) for dural arteriovenous fistulas (dAVFs) and determined predictors of outcome. METHODS: Data from a cohort of 114 patients who underwent GKRS for cerebral dAVFs were compiled from the International Gamma Knife Research Foundation. Favorable outcome was defined as dAVF obliteration and no posttreatment hemorrhage or permanent symptomatic radiation-induced complications. Patient and dAVF characteristics were assessed to determine predictors of outcome in a multivariate logistic regression analysis; dAVF-free obliteration was calculated in a competing-risk survival analysis; and Youden indices were used to determine optimal radiosurgical dose. RESULTS: A mean margin dose of 21.8 Gy was delivered. The mean follow-up duration was 4 years (range 0.5-18 years). The overall obliteration rate was 68.4%. The postradiosurgery actuarial rates of obliteration at 3, 5, 7, and 10 years were 41.3%, 61.1%, 70.1%, and 82.0%, respectively. Post-GRKS hemorrhage occurred in 4 patients (annual risk of 0.9%). Radiation-induced imaging changes occurred in 10.4% of patients; 5.2% were symptomatic, and 3.5% had permanent deficits. Favorable outcome was achieved in 63.2% of patients. Patients with middle fossa and tentorial dAVFs (OR 2.4, p = 0.048) and those receiving a margin dose greater than 23 Gy (OR 2.6, p = 0.030) were less likely to achieve a favorable outcome. Commonly used grading scales (e.g., Borden and Cognard) were not predictive of outcome. Female sex (OR 1.7, p = 0.03), absent venous ectasia (OR 3.4, p < 0.001), and cavernous carotid location (OR 2.1, p = 0.019) were predictors of GKRS-induced dAVF obliteration. CONCLUSIONS: GKRS for cerebral dAVFs achieved obliteration and avoided permanent complications in the majority of patients. Those with cavernous carotid location and no venous ectasia were more likely to have fistula obliteration following radiosurgery. Commonly used grading scales were not reliable predictors of outcome following radiosurgery.

[Electroacupuncture Intervention Reduces Mammary Gland Hyperplasia by Regulating Serum Estradiol and Progesterone Levels and Their Mammary Receptor Expression in Female Rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) intervention on hyperplastic mammary glands, serum estradiol (E2) and progesterone (P) contents, estrogen receptor alpha (ERα) and progesterone receptor (PR) expression of breast tissues in mammary gland hyperplasia (MGH) rats, so as to reveal its mechanisms underlying improvement of MGH. METHODS: Sixty female SD rats were randomly divided into control, model, EA, EA＋ovariectomy(OVX) and EA＋sham-OVX groups (n＝12 in each). The MGH model was established by injection of Estradiol Benzoate injection (0.5 mg/kg, once daily for 25 d) and P injection (0.5 mg/kg, once daily for 5 d after estradiol injection) into the medial hind-leg muscle. After model establishment, bilateral OVX was performed for rats of the EA＋OVX group, and sham OVX (only exposure of ovaries) was performed for rats of the EA＋sham OVX group. EA (2 Hz, 2 mA) was applied to bilateral "Tianzong"(SI 11), "Ganshu"(BL 18), "Zusanli" (ST 36) for point group A, and "Wuyi"(ST 15), "Hegu"(LI 4), "Danzhong" (CV 17) for point group B for 20 min, once daily, 5 days a week for 4 weeks. The two acupoint groups were used alternately. The height of the rats' nipples (the 2nd pairs) were measured. Serum E2 and P levels were assayed by ELISA. The expression of ERα and PR in mammary tissues was detected by immunofluorescence staining and Western blot, separately. RESULTS: The height of nipples, serum E2content, and mammary ERα protein expression level were significantly higher in the model group than in the control group (P<0.01), while serum P content and PR expression were remarkably lower in the model group than in the control group (P<0.01). Following EA intervention, the height of nipples, serum E2content and mammary ERα protein expression level in both EA and EA＋sham OVX groups, and ERα expression in the EA＋OVX group were considerably lower in comparison with those of the model group(P<0.01), and serum P content and PR expression in the 3 EA groups were significantly higher than those in the model group (P<0.01，P<0.05). But there were no significant changes in the nipple height and serum E2 levels in the EA＋OVX group relevant to the model group (P>0.05), suggesting an important role of the ovary in producing EA's effect. CONCLUSION: EA intervention can improve hyperplastic mammary glands by down-regulating serum E2content and mammary ERα protein expression, and up-regulating serum P content and PR expression in MGH rats, which has a close relation with the intact ovaries.

Outcomes and toxicity from a prospective study of moderately hypofractionated radiation therapy for prostate cancer.

PURPOSE: The purpose of this study is to report the long-term outcomes and toxicity results of a prospective trial of moderately hypofractionated, image guided radiation therapy (RT) for localized prostate cancer. METHODS AND MATERIALS: Patients were enrolled between December 2006 and February 2012. Patients in group 1 were stage T1-T2b, had a Gleason score (GS) of 2 to 6 or 7 (3 + 4) with only 1 lobe involved, and had prostate-specific antigen levels ≤10 ng/mL. Group 2 patients were stage ≥T2c, had a GS ≥7 (4 + 3), a GS 7 (3 + 4) involving both lobes, or a PSA >10 ng/mL and ≤30 ng/mL. All patients underwent transrectal ultrasound guided fiducial (Visicoil) placement prior to computed tomography/magnetic resonance imaging simulation. Daily cone beam computed tomography with online correction was used. The prescribed dose was 64 Gy in 20 fractions. The primary endpoint was acute and late toxicity. The secondary endpoint was biochemical control. RESULTS: A total of 40 patients with a median age of 70 years were recruited for the study. Twenty-two patients (55%) were in group 1, and 18 patients (45%) were in group 2. Thirteen patients (32.5%) were classified as low, 26 patients (65%) as intermediate, and 1 patient (2.5%) as high risk per the National Comprehensive Cancer Network criteria. The median follow-up time was 59 months. Five-year biochemical control was 100% and 94.4% for groups 1 and 2, respectively. Thirteen patients (32.5%) developed acute gastrointestinal (GI) toxicities grade ≥2 and 3 (7.5%) developed acute grade 3 GI toxicity. A total of 17 patients (42.5%) developed grade ≥2 acute genitourinary toxicities and 1 (2.5%) developed acute grade 3 dysuria. Two patients (5%) developed late GI toxicities grade ≥2. There was 1 case (2.5%) of grade 4 fistula requiring sigmoid resection. Seven patients (17.5%) developed grade ≥2 late genitourinary toxicities; 2 patients (5%) late grade 3 urinary frequency/urgency. CONCLUSIONS: Moderately hypofractionated RT is effective with favorable toxicity and biochemical control, providing further evidence that increasing daily fractional dose can be safely and effectively delivered with contemporary RT techniques.

Practice patterns and survival outcomes of intracranial germinoma: an analysis of the National Cancer Database.

The goal of the study is to examine the practice pattern and survival outcome of adult and pediatric patients with intracranial germinoma. Patients from the National Cancer Database (NCDB) brain tumor registry between the years 2004-2014 with intracranial germinoma were extracted for analysis. Patients who had distant metastasis, received no treatments, or only surgery/chemotherapy alone were excluded. An age cutoff of > 21 years old was used to define the pediatric population. Patients were stratified by the treatments radiation therapy alone (RT) and chemotherapy followed by radiation therapy (C + RT). 445 patients with intracranial germinoma meeting our inclusion criteria were identified. Of the adult patients, 65.7% received RT and 34.3% received C + RT, compared to the pediatric patients, where 31.8% received RT and 68.2% received C + RT. Those patients who received C + RT had a lower radiation dose compared to the RT group (p < 0.001). The 5 and 10 year overall survival (OS) for the entire cohort was 92.6 and 87.9%, respectively. Univariate analysis demonstrated improved OS with younger age, private insurance, C + RT treatment, and pediatric patients. Only age and insurance type remained significant on multivariate analysis. The 5 year OS was 92.6% (RT) versus 97.2% (C + RT) (p = 0.307) and 83.4% (RT) versus 95.4% (C + RT) (p = 0.122) in the pediatric and adult patients, respectively. There is a higher use of C + RT with an accompanied reduction in RT dose in the treatment of intracranial germinoma. There is no difference in survival between the treatment approaches of RT or C + RT in the NCDB patient cohort.

SPARCL1 suppresses cell migration and invasion in renal cell carcinoma.

Previous studies have shown that the human SPARC­like 1 (SPARCL1) is crucial for human cancer migration and invasion. In the present study, the expression, biological function and possible molecular regulatory mechanisms of SPARCL1 were investigated in human renal cell carcinoma (RCC). The protein expression of SPARCL1 in cells was evaluated using western blot analysis and immunohistochemical staining in the tissue microarray. The effects of SPARCL1 on the biological behaviors of RCC cells were assessed using in vitro assays. The present study also provisionally investigated the role of SPARCL1 on the mitogen­activated protein kinase (MAPK) signaling pathway. The results revealed that the expression of SPARCL1 was decreased in the RCC cell lines examined and in the tissue microarray. The overexpression of SPARCL1 significantly inhibited cell migration and invasion, and this may have been due to the inactivation of p38/c­Jun N­terminal kinase (JNK)/extracellular signal­regulated kinase (ERK) MAPKs. The results showed that high expression levels of SPARCL1 offered potential as a useful prognostic factor in RCC. Taken together, the present study demonstrated that the expression of SPARCL1 was downregulated in RCC cells and tissues, however, the overexpression of SPARCL1 inhibited RCC cell migration and invasion. SPARCL1 also reduced the expression of phosphorylated p38/JNK/ERK MAPKs. These data suggested that increasing the protein expression level of SPARCL1 may be novel strategy for treating RCC.

Cell Cycle Arrest as a Therapeutic Target of Acute Kidney Injury.

The current lack of complete understanding of the pathogenesis of acute kidney injury (AKI) is a significant barrier to its early diagnosis and treatment. Cell cycle arrest plays an important role in the protection of renal tubular epithelial cells and maladaptive repair following AKI. G1 phase cell arrest serves as a protective mechanism following AKI, avoiding replication of damaged DNA. Insulinlike growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinase-2 (TIMP-2) are closely associated with G1 cell cycle arrest during the very early phase of cellular damage and can serve as an ideal biomarker to predict AKI. However, sustained cell cycle arrest after severe AKI may result in cell senescence and maladaptive repair, with typical characteristics of the development of cell cycle arrest in the gap 2 (G2) or mitotic (M) phase. Markers of cell cycle arrest signal and spread the "alarm" from the site of injury to adjacent cells in an autocrine or paracrine manner, giving rise to abnormal amplification and release of profibrogenic factors, activation of pericytes/perivascular fibroblasts, and eventually fibrosis. Therefore, cell cycle regulation has become a potentially new target for the prevention and treatment of AKI. In this review, we summarize the characteristics of the cell cycle following AKI and the markers of cell cycle arrest that enable the early detection of AKI. We also discuss how to prevent the progression of chronic kidney disease (CKD) by regulating cell cycle arrest.