Using terahertz time domain spectroscopy we demonstrate tunable polarization rotation and circular dichroism in intrinsically non-chiral planar terahertz metamaterials without twofold rotational ...symmetry. The observed effect is due to extrinsic chirality arising from the mutual orientation of the metamaterial plane and the propagation direction of the incident terahertz wave.
Essential hypertension has been recognized as a disease resulting from a combination of environmental and genetic factors. Recent studies demonstrated that microRNAs (miRNAs) are involved in cardiac ...hypertrophy and heart failure. However, little is known about the roles of miRNAs in essential hypertension.
Using microarray-based miRNA expression profiling, we compared the miRNA expressions in plasma samples from 13 hypertensive patients and 5 healthy control subjects. Twenty-seven miRNAs were found to be differentially expressed. The expressions of selected miRNAs (miR-296-5p, let-7e, and a human cytomegalovirus HCMV-encoded miRNA, hcmv-miR-UL112) were validated independently in plasma samples from 24 hypertensive patients and 22 control subjects. The absolute expression levels of hcmv-miR-UL112, miR-296-5p, and let-7e were further determined in 127 patients and 67 control subjects (fold changes are 2.5, 0.5, and 1.7 respectively; all P<0.0001). Additionally, we demonstrated that interferon regulatory factor 1 is a direct target of hcmv-miR-UL112. Increased HCMV seropositivity and quantitative titers were found in the hypertension group compared with the control group (52.7% versus 30.9%, P=0.0005; 1870 versus 54 copies per 1 mL plasma, P<0.0001). Seropositivity, log-transformed copies of HCMV, and hcmv-miR-UL112 were independently associated with an increased risk of hypertension (odds ratio, 2.48; 95% confidence interval, 1.48 to 4.15; P=0.0005; odds ratio, 1.97; 95% confidence interval, 1.58 to 2.46; P<0.0001; and odds ratio, 2.55; 95% confidence interval, 1.98 to 3.27; P<0.0001, respectively).
We report for the first time a circulating miRNA profile for hypertensive patients and demonstrate a novel link between HCMV infection and essential hypertension. These findings may reveal important insights into the pathogenesis of essential hypertension.
URL: http://www.clinicaltrials.gov. UNIQUE IDENTIFIER: NCT00420784.
Oxaliplatin is a widely used chemotherapy drug for patients with advanced colorectal cancer (CRC); however, frequent drug resistance limits its therapeutic efficacy in patients. Here, this work ...identifies cyclin‐dependent kinase 1 (CDK1) as a critical contributor to oxaliplatin resistance via in vitro and in vivo CRISPR/Cas9 screening. CDK1 is highly expressed in oxaliplatin‐resistant cells and tissues due to the loss of N6‐methyladenosine modification. Genetic and pharmacological blockade of CDK1 restore the susceptibility of CRC cells to oxaliplatin in vitro and in cell/patient‐derived xenograft models. Mechanistically, CDK1 directly binds to and phosphorylates Acyl‐CoA synthetase long‐chain family 4 (ACSL4) at S447, followed by recruitment of E3 ubiquitin ligase UBR5 and polyubiquitination of ACSL4 at K388, K498, and K690, which leads to ACSL4 protein degradation. Reduced ACSL4 subsequently blocks the biosynthesis of polyunsaturated fatty acid containing lipids, thereby inhibiting lipid peroxidation and ferroptosis, a unique iron‐dependent form of oxidative cell death. Moreover, treatment with a ferroptosis inhibitor nullifies the enhancement of CRC cell sensitivity to oxaliplatin by CDK1 blockade in vitro and in vivo. Collectively, the findings indicate that CDK1 confers oxaliplatin resistance to cells by suppressing ferroptosis. Therefore, administration of a CDK1 inhibitor may be an attractive strategy to treat patients with oxaliplatin‐resistant CRC.
Oxaliplatin resistance is a thorny issue in the clinical treatment of colorectal cancer (CRC). The current study demonstrates that CDK1 facilitates oxaliplatin resistance in a cell cycle‐independent manner. CDK1 directly phosphorylates and ubiquitinates ACSL4 protein, resulting in ACSL4 degradation, thereby inhibiting ferroptosis and promoting oxaliplatin resistance. CDK1 blockade may be an attractive strategy to treat CRC patients with oxaliplatin resistance.
BackgroundThe log odds of positive lymph nodes (LODDS) was considered a superior staging system to N stage in colon cancer, yet its value in determining the optimal duration of adjuvant chemotherapy ...for stage III colon cancer patients has not been evaluated. This study aims to assess the prognostic value of a model that combines LODDS with clinicopathological information for stage III colon cancer patients and aims to stratify these patients using the model, identifying individuals who could benefit from varying durations of adjuvant chemotherapy.MethodA total of 663 consecutive patients diagnosed with stage III colon cancer, who underwent colon tumor resection between November 2007 and June 2020 at Sun Yat-sen University Cancer Center and Longyan First Affiliated Hospital of Fujian Medical University, were enrolled in this study. Survival outcomes were analyzed using Kaplan–Meier, Cox regression. Nomograms were developed to forecast patient DFS, with the Area Under the Curve (AUC) values of time-dependent Receiver Operating Characteristic (timeROC) and calibration plots utilized to assess the accuracy and reliability of the nomograms.ResultsMultivariate analysis revealed that perineural invasion (HR = 1.776, 95% CI: 1.052–3.003, P = 0.032), poor tumor differentiation (HR = 1.638, 95% CI: 1.084–2.475, P = 0.019), and LODDS groupings of 2 and 1 (HR = 1.920, 95% CI: 1.297–2.842, P = 0.001) were independent predictors of disease-free survival (DFS) in the training cohort. Nomograms constructed from LODDS, perineural invasion, and poor tumor differentiation demonstrated robust predictive performance for 3-year and 5-year DFS in both training (3-year AUC = 0.706, 5-year AUC = 0.678) and validation cohorts (3-year AUC = 0.744, 5-year AUC = 0.762). Stratification according to this model showed that patients in the high-risk group derived significant benefit from completing 8 cycles of chemotherapy (training cohort, 82.97% vs 67.17%, P = 0.013; validation cohort, 89.49% vs 63.97%, P = 0.030).ConclusionThe prognostic model, integrating LODDS, pathological differentiation, and neural invasion, demonstrates strong predictive accuracy for stage III colon cancer prognosis. Moreover, stratification via this model offers valuable insights into optimal durations of postoperative adjuvant chemotherapy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We present a double-ring-chain metamaterial that enables efficient polarization conversion of terahertz waves. The experimental results and numerical simulations reveal that the linear-to-linear ...polarization rotation and linear-to-elliptic polarization transformation are simply accomplished by altering the dimensional parameters of the metamaterial unit cells. The polarization state conversion is found to be critically related to the resonant properties of the long bars and the rings in the unit geometries and is well described by the Jones matrix. This approach promises both passive and active polarization conversion of terahertz radiation using planar metamaterials.
We experimentally demonstrate a highly efficient, broadband linear polarization converter functioning at terahertz frequencies. The linear polarization converter is composed of three metasurfaces and ...two dielectric layers interlaced with each other. The neighboring unit cells of the central metasurface layer of the linear polarization converter exhibit strong electromagnetic coupling, which increases the number of resonances and results in significant bandwidth broadening. The simulation and experimental results show that in the frequency range of 0.2 to 0.4 THz, the proposed polarization converter has a flat transmission curve and exhibits a transmission efficiency that is higher than 80%. High performance terahertz polarization conversion is desirable in many fields, such as terahertz spectroscopy, imaging, and communications.
In this paper, we thoroughly analyze the role of the point reflector's reflectivity in the performance of forward-pumped random fiber laser, in both the long- and short-cavity cases. The results show ...that the power performance is sensitive to the small reflection added on the pump side of the fiber end, whereas both the power distribution and threshold tend to be stable when the reflectivity reaches a relatively high level (>0.4). Moreover, for the short cavity case (e.g. 500m), the maximum achievable 1st-oder random lasing output can even increase when the reflectivity decreases from 0.9 to 0.01, due to the different lasing power distributions with different reflectivity values. This work reveals a new and unique property of random fiber lasers and provides insights into their design for the applications such as distributed amplification and high power sources.
Changes in kidney function and the progression of chronic kidney disease (CKD) are associated with the risk of cardiovascular disease (CVD) and influenced by genetic factors. However, the association ...between genetic variants and kidney function in patients treated with antihypertensive drugs remains uncertain. This study aimed to examine the association between 30 variants locating at the 22 genes and the risk of kidney function evaluated by the estimated glomerular filtration rate (eGFR) in 1911 patients with hypertension from a Chinese community-based longitudinal cohort (including 1220 participants with CKD and 691 without CKD at baseline). By using multivariate linear regression analysis after adjustment for age, sex, traditional cardiovascular risk factors, and the use of antihypertensive drugs, as well as after correction for multiple comparison, patients with rs10767873T allele of the metallophosphoesterase domain containing 2 (MPPED2) gene were associated with higher level of eGFR (β = 0.041, p = 0.01) and lower levels of serum creatinine (β = -0.068, p = 0.001) and serum uric acid (β = -0.047, p = 0.02). But variant rs10767873 was not found to be associated with the risk of CKD, regardless of the types of antihypertensive drugs used. During a median 2.25-year follow-up, 152 CVD events were documented. Interestingly, patients with the rs10767873TT genotype had an increased risk of CVD events (hazard ratio, 1.74, 95% confidence interval, 1.11 to 2.73; p = 0.02) compared with patients carrying the wild-type genotype of rs10767873CC. In conclusion, our findings suggest variant rs10767873 of the MPPED2 gene is associated with kidney function and risk of CVD in Chinese hypertensive patients.
With a rapidly aging population, adequate blood pressure (BP) control is critical for hypertension management and prevention of cardiovascular events. Impressive cardiovascular benefits have been ...observed with intensive BP control (SBP target, <120 mmHg) in the SPRINT (Systolic Blood Pressure Intervention Trial) study, even in patients 75 years of age or older. A most recent meta-analysis including 51 randomized trials with over 350,000 participants from the BPLTTC (The Blood Pressure Lowering Treatment Trialists’ Collaboration) showed that BP lowering is effective in older people for reducing major cardiovascular events. The STEP (Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients) study-a multicenter, randomized, controlled trial conducted in China, provided important evidence that intensive BP treatment (SBP target, 110 mmHg to < 130 mmHg) benefits older hypertensive patients (aged 60–80 years) and reduced the incidence of cardiovascular events than standard treatment (target 130 mmHg to < 150 mmHg). Because Asian people have a higher burden of hypertension and stroke than Caucasian people, intensive BP treatment has more advantages in reducing the risk of cardiovascular events including stroke in Asian hypertensive patients than in Caucasian people. Home BP monitoring is helpful to facilitate hypertension management for older patients. It should also be noted that clinical decision-making should be on a patient basis, such as fragility, diabetes, stroke, and other comorbidities, with tailored BP targets.
PDF
