Integrating fecal pollution markers and fluorescence analysis for water quality assessment of urban river.

Human fecal contamination in urban rivers poses significant health risks, but their potential connections with other substances like dissolved organic matter (DOM) remain underexplored. In this study, five fecal pollution markers related to fecal Bacteroides or human fecal contamination (AllBac, HF183, BacH, Hum2, and Hum163) and DOM along an urban river were analyzed using quantitative polymerase chain reaction (qPCR) and three-dimensional excitation-emission (3D EEM) fluorescence spectrometry. All five markers were detected with average absolute abundance ranging from 2.51 to 6.28 lg gene copies/100 mL, showing a progressive increase along the river (R2 = 0.29-0.92, p < 0.05). Parallel factor analysis identified three dominant DOM components (humic acid-like, fulvic acid-like, and protein-like), with strong positive correlations between protein-like components and all fecal markers (R2 = 0.59-0.66, p < 0.001). Both fecal and DOM distributions consistently showed significant differences between upstream and downstream areas (p < 0.001), suggesting their complementary assessment. While DOM was more sensitive to environmental variables such as rainfall, rubber dam, and tidal dynamic, the combination of fecal pollution markers and 3D EEM analysis allowed a more comprehensive assessment of contamination levels, mitigating potential biases caused by the influence of multiple factors on a single method. Furthermore, due to the strong correlation between protein-like and fecal markers in the DOM, 3D EEM can be used as a pre-detection means for qPCR detection, reducing testing time and costs.

Chitosan inhibits vascular intimal hyperplasia via LINC01615/MIR-185-5p/PIK3R2 signaling pathway.

The abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are the main pathological processes which are involved in the formation of new intima. In our previous study, we found that chitosan can inhibit the formation of new intima in the arteriovenous fistulas of uremic patients, and the expression of LINC01615 was significantly increased in patients after treatment with chitosan. Therefore, this study aims to further explore the effect of chitosan on the intimal hyperplasia and elucidate the potential molecular mechanism. In vitro, we found that in chitosan-treated VSMC, the levels of Il-1ß, IL-6 and TNF-α decreased, and the intimal hyperplasia was inhibited along with significantly downregulated PIK3R2 and upregualted PI3K, AKT and p-AKT. Meanwhile, we observed the phenotypic transformation of hVSMCs after LINC01615 was upregulated. In addition, inflammatory factors showed the same changes in the process of up-regulating LINC01615. Moreover, only in the LINC01615 overexpression and miR-185-5p mimic experimental group, the inhibition of intimal hyperplasia was the most obvious. The interaction between LINC01615 and miR-185-5p, miR-185-5p and PIK3R2 was further confirmed by the dual luciferase assay. These results suggest that chitosan has a potential preventive effect on neointimal hyperplasia and related vascular remodeling.

Association between Baijiu chemistry and taste change: Constituents, sensory properties, and analytical approaches.

Typical flavors, such as sourness, sweetness, and bitterness, possess numerous functions and physiological significance, and are closely related to Baijiu production management, quality control, and product development. However, current research on Baijiu flavor primarily focuses on the volatile constituents and distinctive aroma compounds. Furthermore, studies on taste substance recognition, identification, and formation are remain in the preliminary phase. Herein, we take an integrated account of the signal transduction, recognition, composition, and sensory properties of the three main basic tastes of Baijiu, including sourness, sweetness, and bitterness. Moreover, to elucidate the factors that might influence the taste perception of Baijiu, we also discussed the biotic and abiotic factors within the fermentation system. Finally, further elucidating the contribution underlying the three main tastes in Baijiu using a combination of the "Sensomics" and "Flavoromics", will allow for Baijiu taste characteristics to be manipulated.

Histologic characterization of primary ciliary dyskinesia chronic rhinosinusitis.

KEY POINTS: We present the largest cohort of structured histopathology reports on primary ciliary dyskinesia-related chronic rhinosinusitis (PCD-CRS). Despite endoscopic differences, PCD-CRS and cystic fibrosis-related chronic rhinosinusitis (CF-CRS) had similar structured histopathology reports. Compared to healthy patients and those with idiopathic chronic rhinosinusitis without nasal polyps, patients with PCD-CRS had an increased neutrophil count.

Paraneoplastic anti-GAD65 extralimbic encephalitis presented with epilepsy: A case report.

RATIONALE: Autoimmunity targeting glutamic acid decarboxylase 65 (GAD65) is associated with type 1 diabetes mellitus as well as various neurological diseases. In the central nervous system, GAD65 autoimmunity usually presents with limbic encephalitis, whereas extralimbic encephalitis (ELE) has only been reported in a few cases. Moreover, anti-GAD65 ELE in the paraneoplastic context has not yet been reported. PATIENT CONCERNS: A 60-year-old man presented with intermittent cough and sputum for 10 years, with no other diseases. The patient presented with recurrent seizures that were resistant to antiepileptic drugs (AEDs). Chest computed tomography and pathological results confirmed the diagnosis of small cell lung cancer. Paraneoplastic testing found a high level of GAD65 antibodies in his serum, and cerebrospinal fluid analysis revealed lymphocytic pleocytosis, indicating autoimmune encephalitis. Brain magnetic resonance imaging showed multifocal T2 fluid-attenuated inversion recovery hyperintensities in the extralimbic areas including the subcortex and deep white matter of the bilateral frontal lobe, parietal lobe, and insula lobes. DIAGNOSES: Finally, a diagnosis of anti-GAD65 autoimmune ELE with a paraneoplastic etiology from the small cell lung cancer was suspected. INTERVENTIONS: The patient refused any tumor-suppressive treatment or immunotherapy for potential side effects and only received AEDs levetiracetam, sodium valproate, and diazepam. OUTCOMES: The epilepsy of the patient was resistant to AEDs, and the patient died a week after discharge due to disease progression. LESSONS: Anti-GAD65 autoimmune encephalitis can be extralimbic, can present with isolated epilepsy, and extralimbic anti-GAD65 encephalitis can occur with an underlying malignancy.

Causal associations between modifiable risk factors and intervertebral disc degeneration.

BACKGROUND: Intervertebral disc degeneration (IVDD) is a common degenerative condition, which is thought to be a major cause of lower back pain (LBP). However, the etiology and pathophysiology of IVDD are not yet completely clear. PURPOSE: To examine potential causal effects of modifiable risk factors on IVDD. STUDY DESIGN: Bidirectional Mendelian randomization (MR) study. PATIENT SAMPLE: Genome-wide association studies (GWAS) with sample sizes between 54,358 and 766,345 participants. OUTCOME MEASURES: Outcomes included (1) Modifiable risk factors associated with IVDD use in the forward MR; and (2) modifiable risk factors that were determined to have a causal association with IVDD in the reverse MR, including smoking, alcohol intake, standing height, education level, household income, sleeplessness, hypertension, hip osteoarthritis, HDL, triglycerides, apolipoprotein A-I, type 2 diabetes, fasting glucose, HbA1c, BMI and obesity trait. METHODS: We obtained genetic variants associated with 33 exposure factors from genome-wide association studies. Summary statistics for IVDD were obtained from the FinnGen consortium. The risk factors of IVDD were analyzed by inverse variance weighting method, MR-Egger method, weighted median method, MR-PRESSO method and multivariate MR Method. Reverse Mendelian randomization analysis was performed on risk factors found to be caustically associated with IVDD in the forward Mendelian randomization analysis. The heterogeneity of instrumental variables was quantified using Cochran's Q statistic. RESULTS: Genetic predisposition to smoking (OR=1.221, 95% CI: 1.068-1.396), alcohol intake (OR=1.208, 95% CI: 1.056-1.328) and standing height (OR=1.149, 95% CI: 1.072-1.231) were associated with increased risk of IVDD. In addition, education level (OR=0.573, 95%CI: 0.502-0.654)and household income (OR=0.614, 95%CI: 0.445-0.847) had a protective effect on IVDD. Sleeplessness (OR=1.799, 95%CI: 1.162-2.783), hypertension (OR=2.113, 95%CI: 1.132-3.944) and type 2 diabetes (OR=1.069, 95%CI: 1.024-1.115) are three important risk factors causally associated with the IVDD. In addition, we demonstrated that increased levels of triglycerides (OR=1.080, 95%CI:1.013-1.151), fasting glucose (OR=1.189, 95%CI:1.007-1.405), and HbA1c (OR=1.308, 95%CI:1.017-1.683) could significantly increase the odds of IVDD. Hip osteoarthritis, HDL, apolipoprotein A-I, BMI and obesity trait factors showed bidirectional causal associations with IVDD, therefore we considered the causal associations between these risk factors and IVDD to be uncertain. CONCLUSIONS: This MR study provides evidence of complex causal associations between modifiable risk factors and IVDD. It is noteworthy that metabolic disturbances appear to have a more significant effect on IVDD than biomechanical alterations, as individuals with type 2 diabetes, elevated triglycerides, fasting glucose, and elevated HbA1c are at higher risk for IVDD, and the causal association of obesity-related characteristics with IVDD incidence is unclear. These findings provide new insights into potential therapeutic and prevention strategies. Further research is needed to clarify the mechanisms of these risk factors on IVDD.

Association between Dietary Acid Load and Hypertension in Chinese Adults: Analysis of the China Health and Nutrition Survey (2009).

(1) Background: Current studies show conflicting results regarding the relationship between dietary acid load (DAL) and blood pressure. (2) Methods: The study used data from the Chinese Health and Nutrition Survey (CHNS) 2009. DAL was assessed on the basis of potential renal acid load (PRAL) and net endogenous acid production (NEAP). To examine the link between DAL and the risk of hypertension, a multivariate logistic regression model was utilized. (3) Results: A total of 7912 subjects were enrolled in the study, of whom 2133 participants had hypertension, a prevalence of 27.0%. After accounting for potential covariates, higher PRAL and NEAP scores were associated with a greater likelihood of developing hypertension, with ORs of 1.34 (95% CI, 1.10-1.62) and 1.29 (95% CI, 1.09-1.53) for PRAL and NEAP scores in Q4, respectively, compared with Q1. In the male group, PRAL and NEAP scores were positively linked to hypertension risk, with ORs of 1.33 (95% CI, 1.06-1.67) and 1.46 (95% CI, 1.14-1.85) for PRAL and NEAP scores in Q4, respectively, compared with Q1, while no significant associations were observed in the female group. Correlations between PRAL scores and hypertension risk lacked significance in the subgroup analyses for participants aged <60 years. There was a significant nonlinear connection observed in the dose-response relationship between DAL (based on PRAL) and hypertension; (4) Conclusions: In Chinese adults, higher PRAL and NEAP scores were positively linked to hypertension risk. This implies that a diet with a low DAL may be a favorable dietary pattern for lowering blood pressure.

Functional to structural plasticity in unilateral sudden sensorineural hearing loss: neuroimaging evidence.

A cortical plasticity after long-duration single side deafness (SSD) is advocated with neuroimaging evidence while little is known about the short-duration SSDs. In this case-cohort study, we recruited unilateral sudden sensorineural hearing loss (SSNHL) patients and age-, gender-matched health controls (HC), followed by comprehensive neuroimaging analyses. The primary outcome measures were temporal alterations of varied dynamic functional network connectivity (dFNC) states, neurovascular coupling (NVC) and brain region volume at different stages of SSNHL. The secondary outcome measures were pure-tone audiograms of SSNHL patients before and after treatment. A total of 38 SSNHL patients (21 [55%] male; mean [standard deviation] age, 45.05 [15.83] years) and 44 HC (28 [64%] male; mean [standard deviation] age, 43.55 [12.80] years) were enrolled. SSNHL patients were categorized into subgroups based on the time from disease onset to the initial magnetic resonance imaging scan: early- (n = 16; 1-6 days), intermediate- (n = 9; 7-13 days), and late- stage (n = 13; 14-30 days) groups. We first identified slow state transitions between varied dFNC states at early-stage SSNHL, then revealed the decreased NVC restricted to the auditory cortex at the intermediate- and late-stage SSNHL. Finally, a significantly decreased volume of the left medial superior frontal gyrus (SFGmed) was observed only in the late-stage SSNHL cohort. Furthermore, the volume of the left SFGmed is robustly correlated with both disease duration and patient prognosis. Our study offered neuroimaging evidence for the evolvement from functional to structural brain alterations of SSNHL patients with disease duration less than 1 month, which may explain, from a neuroimaging perspective, why early-stage SSNHL patients have better therapeutic responses and hearing recovery.

Comparison of surgical and endovascular left subclavian artery revascularization during thoracic aortic endovascular repair: a systematic review and meta-analysis.

Objective: The purpose of this systematic review and meta-analysis was to incorporate data from the latest clinical studies and compare the safety and efficacy of surgical left subclavian artery (LSA) revascularization and endovascular LSA revascularization during thoracic endovascular aortic repair (TEVAR). Methods: This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered with the PROSPERO database on 16 April 2023 (CRD42023414579). The Embase, MEDLINE (PubMed), and the Cochrane Library databases were searched from January 2000 to May 2023. Results: A total of 14 retrospective cohort studies with a total of 1,695 patients, were included for review. The peri-operative stroke rates of the surgical and endovascular LSA revascularization groups were 3.8% and 2.6%, respectively (P = 0.97). The peri-operative technical success rates for the surgical and endovascular LSA revascularization groups were 95.6% and 93.0%, respectively (P = 0.24). The peri-operative spinal cord ischemia rates were 1.6% (n = 18) and 1.9% (n = 7) in the surgical and endovascular LSA revascularization groups, respectively (P = 0.90). The peri-operative type Ⅰ endoleak rates for the surgical and endovascular LSA revascularization groups were 6.6% and 23.2%, respectively (P = 0.25). The subgroup analysis showed that the incidence of peri-operative type I endoleak in the parallel stent group was significantly higher than that in the surgical LSA revascularization group (P < 0.0001). The peri-operative left upper limb ischemia rates for the surgical and endovascular LSA revascularization groups were 1.2% and 0.6%, respectively (P = 0.96). The peri-operative mortality rates of the surgical and endovascular LSA revascularization groups were 2.0% and 2.0%, respectively (P = 0.88). Conclusion: There was no significant difference in the terms of short-term outcomes when comparing the two revascularization techniques. The quality of evidence assessed by GRADE scale was low to very-low. Surgical and endovascular LSA revascularization during TEVAR were both safe and effective. Compared with surgical LSA revascularization techniques, parallel stent revascularization of LSA significantly increased the rate of type I endoleak.

Controllable self-assembled DNA nanomachine enable homogeneous rapid electrochemical one-pot assay of lung cancer circulating tumor cells.

A homogeneous rapid (45 min) one-pot electrochemical (EC) aptasensor was established to quantitatively detect circulating tumor cells (CTCs) in lung cancer patients using mucin 1 as a marker. The core of this study is that the three single-stranded DNA (Y1, Y2, and Y3) could be hybridized to form Y-shaped DNA (Y-DNA) and further self-assemble to form DNA nanosphere. The aptamer of mucin 1 could be complementary and paired with Y1, thus disrupting the conformation of the DNA nanosphere. When mucin 1 was present, the aptamer combined specifically with mucin 1, thus preserving the DNA nanosphere structure. Methylene blue (MB) acted as a signal reporter, which could be embedded between two base pairs in the DNA nanosphere to form a DNA nanosphere-MB complex, reducing free MB and resulting in a lower electrochemical signal. The results demonstrated that the linear ranges for mucin 1 and A549 cells were 1 ag/mL-1 fg/mL and 1-100 cells/mL, respectively, with minimum detectable concentrations were 1 ag/mL and 1 cell/mL, respectively. The quantitative analysis of CTCs in 44 clinical blood samples was performed, and the results were consistent with the computerized tomography (CT) images, pathological findings and folate receptor-polymerase chain reaction (FR-PCR) kits. The receiver operating characteristic (ROC) curve exhibited an area under the curve (AUC) value of 0.970. The assay revealed 100% specificity and 94.1% sensitivity. It is believed that this electrochemical aptasensor could provide a new approach to detect CTCs.

Development of a C3 humanized rat as a new model for evaluating novel C3 inhibitors.

INTRODUCTION: C3 is central for all complement activation pathways, thus an attractive therapeutic target. Many C3-targeted agents are under extensive development with one already approved for clinical use. However, most, if not all, C3 inhibitors are human or non-human primate C3-specific, making evaluating their efficacies in vivo before a clinical trial extremely difficult and costly. METHODS: We first studied the compatibility of human C3 in the rat complement system, then developed a C3 humanized rat using the CRISPR/Cas9 technology. We thoroughly characterized the resultant human C3 humanized rats and tested the treatment efficacy of an established primate-specific C3 inhibitor in a model of complement-mediated hemolysis in the C3 humanized rats. RESULTS: We found that supplementing human C3 protein into the C3-deficient rat blood restored its complement activity, which was inhibited by rat Factor H or compstatin, , suggesting that human C3 is compatible to the rat complement system. The newly developed C3 humanized rats appeared healthy and expressed human but not rat C3 without detectable spontaneous C3 activation. More importantly, complement-mediated hemolysis in the C3 humanized rats was also inhibited by compstatin both in vitro and in vivo. CONCLUSION: The successfully developed C3 humanized rats provided a much-desired rodent model to evaluate novel C3 inhibitors in vivo as potential drugs.

Amorphous-crystalline phase transition and intrinsic magnetic property of nickel organic framework for easy immobilization and recycling of ß-Galactosidase.

This work describes the synthesis of fibrous nickel-based metal organic framework (Ni-ZIF) via simple solvothermal method. The material formed was calcinated at 400, 600, 800 °C to improve its surface area, porosity and enzyme binding capacity. Changes in X-ray diffraction pattern after calcination revealed the Ni-ZIF transitioned from amorphous to crystalline structure. The surface area, pore volume and pore size for Ni-ZIF@600 were found to be 312.15 m2/g, 0.88 cm3/g and 10.28 nm, with an enzyme loading capacity of 593.85 mg/g after 30 h The free (ß-Gal-LEH) and immobilized ß-Galactosidase were stable at pH 7.5, temperature 50 °C, and yielded 70.70 and 63.95 mM glucose after milk lactose hydrolysis, respectively. The Ni-ZIF@600@ß-Gal-LEH exhibited high enzyme retention capacity, maintaining 59.44 % of its original activity after 6-cycles. The enhanced magnetic property, enzyme binding capacity and easy recoverability of the calcinated Ni-ZIF could guarantee its industrial significance as immobilization module for enzyme-mediated catalysis.

Obacunone alleviates chronic pelvic pain and pro-inflammatory depolarization of macrophage induced by experimental autoimmune prostatitis in mice.

Chronic pelvic pain syndrome (CPPS) is a common complication of prostatitis, which was associated with the pathological depolarization of macrophage and the neuroinflammation. However, its underlying reason is far from clear and few effective treatments is applicable. In this study, we tested the effect of obacunone (Oba), a highly oxygenated triterpenoid, on CPPS. The experimental autoimmune prostatitis (EAP) was induced by subcutaneous injection of heterologous prostate homogenate in mice. We found that EAP led to prostatodynia, neuronal activation of spinal dorsal horn, and the pro-inflammatory depolarization of macrophage within prostate, which was significantly alleviated by oral administration of Oba in a dose-dependent manner. Mechanistically, EAP-induced production of IL-6 on prostatic macrophage was suppressed by Oba. Moreover, co-administration of Oba and MIF inhibitor ISO-1 did not lead to additive effect when compared with either alone. In summary, we conclude that Oba prevents the production of macrophage-derived pro-inflammatory factors by inhibiting MIF, which eventually alleviates CPPS after prostatitis.

Heart rate variability and risk of agitation in Alzheimer's disease: the Atherosclerosis Risk in Communities Study.

Agitation in Alzheimer's disease is common and may be related to impaired emotion regulation capacity. Heart rate variability, a proposed index of autonomic and emotion regulation neural network integrity, could be associated with agitation propensity in Alzheimer's disease. We used the Atherosclerosis Risk in Communities Study cohort data, collected over seven visits spanning over two decades, to investigate whether heart rate variability (change) was associated with agitation risk in individuals clinically diagnosed with dementia due to Alzheimer's disease. Agitation (absence/presence) at Visit 5, the primary outcome, was based on the Neuropsychiatric Inventory agitation/aggression subscale, or a composite score comprising the total number of agitation/aggression, irritability, disinhibition and aberrant motor behaviour subscales present. Visit 1-5 heart rate variability measures were the log-transformed root mean square of successive differences in R-R intervals and standard deviation of normal-to-normal R-R intervals obtained from resting, supine, standard 12-lead ECGs. To aid interpretability, heart rate variability data were scaled such that model outputs were expressed for each 0.05 log-unit change in heart rate variability (which approximated to the observed difference in heart rate variability with every 5 years of age). Among 456 participants who had dementia, 120 were clinically classified to have dementia solely attributable to Alzheimer's disease. This group showed a positive relationship between heart rate variability and agitation risk in regression models, which was strongest for measures of (potentially vagally mediated) heart rate variability change over the preceding two decades. Here, a 0.05 log-unit of heart rate variability change was associated with an up to 10-fold increase in the odds of agitation and around a half-unit increase in the composite agitation score. Associations persisted after controlling for participants' cognitive status, heart rate (change), sociodemographic factors, co-morbidities and medications with autonomic effects. Further confirmatory studies, incorporating measures of emotion regulation, are needed to support heart rate variability indices as potential agitation propensity markers in Alzheimer's disease and to explore underlying mechanisms as targets for treatment development.

On the Asymmetric Relationship Between Physician Mental Health Disorders on Quality of Healthcare Under the COVID-19 Pandemic in Taiwan: Quantile on Quantile Regression Analyses.

Purpose: When examining the nexus of physician mental health disorders and healthcare quality from the empirical perspective, mental health disorders are frequently associated with cyclical patterns corresponding to cyclic seasonality, mood swings, emission of air pollution and business cycles, the potential asymmetric effects of physician mental health disorders on healthcare quality have not received adequate attention from researchers. Therefore, the purpose of this study is to explore the asymmetric relationship between physician mental health disorders and healthcare quality during the pandemic outbreak in Taiwan. Methods: Daily data for care quality indicators and physician mental health disorders were collected from the National Insurance Research Database in Taiwan, and the quantile-on-quantile regression model was applied to proceed with our analyses. Results: Our results indicated that the overall aggregate effects of each quantile of physician mental health disorders on the cumulative quantiles of healthcare quality are negative (positive) for the 14-day readmission rate (preventable hospitalization rate and non-urgent ED-visit rate). Positively (negatively) cumulative effects of each quantile of physician mental health disorders were detected in the middle (low and high) quantiles of the preventable hospitalization rate. The cumulative effects of each quantile of physician mental health disorders on the high (low and middle) quantiles of the 14-day readmission rate are negative (positive), but the cumulative effects on various quantiles of the non-urgent ED-visit rate exhibit the opposite pattern. Conclusion: The observed variation in the relationship between physician mental health disorders and different quantiles of healthcare quality suggests the need for tailored strategic interventions based on distinct levels of healthcare quality when addressing the higher risk of physician mental health disorders during the pandemic outbreak conditions.

A nomogram-based model to predict postoperative transient neurological dysfunctions in patients receiving acute type A aortic dissection surgery.

The purposes of this study were to develop and validate a nomogram for predicting postoperative transient neurological dysfunctions (TND) in patients with acute type A aortic dissection (AAAD) who underwent modified triple-branched stent graft implantation. This retrospective study developed a nomogram-based model in a consecutive cohort of 146 patients. Patient characteristics, preoperative clinical indices, and operative data were analyzed. Univariate and multivariable analyses were applied to identify the most useful predictive variables for constructing the nomogram. Discrimination and the calibration of the model was evaluated through the receiver operating characteristic curve (ROC), the Hosmer-Lemeshow goodness-of-fit test and the decision curve analysis (DCA). At the same time, to identify and compare long-term cumulative survival rate, Kaplan-Meier survival curve was plotted. The incidence rate of postoperative TND observed in our cohort were 40.9%. Supra-aortic dissection with or without thrombosis, creatinine >115 µmol and albumin <39.7 g/L, selective antegrade cerebral perfusion (SACP) time >7 min and total operation time >303 min, were confirmed as independent predictors that enhanced the likelihood of TND. Internal validation showed good discrimination of the model with under the ROC curve (AUC) of 0.818 and good calibration (Hosmer-Lemeshow test, p > .05). DCA revealed that the nomogram was clinically useful. In the long-term survival there was no significant difference between patients with or without TND history. The results showed the predict model based on readily available predictors has sufficient validity to identify TND risk in this population, that maybe useful for clinical decision-making.

Full-space and multi-polarization holograms realized by a non-Hermitian bilayer metasurface.

Multilayer metasurfaces break the mirror symmetry along the path of light propagation, thereby increasing the potential for light manipulation. Herein, a paradigm is proposed that building a non-Hermitian bilayer metasurface, which is composed of two identical, orthogonally oriented, chiral J-shaped Au structures in each layer, allows exceptional points (EPs) to exist in full-space. Specifically, in the reflected half-space that adheres to mirror symmetry, the circularly polarized eigenstates coalesce at the EP, while in the transmission half-space, where mirror symmetry is broken, the linearly polarized eigenstates converge at the EP. By considering the intrinsic property of topologically protected 2π-phase accumulation encircling both EPs, we investigated full-space holography through using circularly polarized light (in reflection half-space) and linearly polarized light (in transmission half-space).

The relationship between endplate defect scores and lumbar sagittal translation stability in lumbar spondylolisthesis patients.

BACKGROUND: Lumbar instability and endplate defects are commonly seen in patients with spondylolisthesis. However, little is known about associations between segmental stability and endplate defects. The present study explored associations between stability-related radiographic parameters and endplate defect scores and assessed whether endplate defect scores can predict lumbar stability in lumbar spondylolisthesis. METHODS: Neutral, flexion and extension radiographs of 159 patients with monosegmental lumbar spondylolisthesis were analyzed. Radiographic parameters included average intervertebral disc height (IDH), slip distance, sagittal translation (ST) and sagittal angulation (SA). Correlation analysis and linear regression analysis were used to explore associations between endplate defect scores and radiographic parameters. Logistic regression analysis was used to assess associations between endplate defect scores and ST stability. Receiver-operating characteristic curve (ROC) analysis was used to evaluate the value of the endplate defect score in predicting ST stability. RESULTS: A total of 11.9% of patients had ST≥4 mm, and 30% of patients had SA≥10 degrees. Endplate defect scores were negatively correlated with ST and IDH and positively correlated with slip distance in isthmic spondylolisthesis but not in degenerative spondylolisthesis. In multiple regression analysis, endplate defect scores were significantly associated with ST, slip distance, IDH, and disc degeneration. ST instability was associated with endplate defect scores in isthmic spondylolisthesis (OR=0.460, P=0.010). The AUCs for using the endplate defect score to evaluate ST stability in overall patients and isthmic spondylolisthesis patients were 0.672 and 0.774, respectively. The optimal threshold of the endplate defect score constructed by the Youden index was 7.5 for predicting ST stability. CONCLUSIONS: Endplate defect scores increase with a reduction in IDH, progression of slippage and a decrease in ST in isthmic spondylolisthesis but not in degenerative spondylolisthesis. ST instability was associated with endplate defect scores in isthmic spondylolisthesis, and endplate defect scores could be used to reflect lumbar stability at the slippage segment.

A Dual-Mechanism Targeted Bioorthogonal Prodrug Therapy.

Bioorthogonal prodrug therapies offer an intriguing two-component system that features enhanced circulating stability and controlled activation on demand. Current strategies often deliver either the prodrug or its complementary activator to the tumor with a monomechanism targeted mechanism, which cannot achieve the desired antitumor efficacy and safety profile. The orchestration of two distinct and orthogonal mechanisms should overcome the hierarchical heterogeneity of solid tumors to improve the delivery efficiency of both components simultaneously for bio-orthogonal prodrug therapies. We herein developed a dual-mechanism targeted bioorthogonal prodrug therapy by integrating two orthogonal, receptor-independent tumor-targeting strategies. We first employed the endogenous albumin transport system to generate the in situ albumin-bound, bioorthogonal-caged doxorubicin prodrug with extended plasma circulation and selective accumulation at the tumor site. We then employed enzyme-instructed self-assembly (EISA) to specifically enrich the bioorthogonal activators within tumor cells. As each targeted delivery mode induced an intrinsic pharmacokinetic profile, further optimization of the administration sequence according to their pharmacokinetics allowed the spatiotemporally controlled prodrug activation on-target and on-demand. Taken together, by orchestrating two discrete and receptor-independent targeting strategies, we developed an all-small-molecule based bioorthogonal prodrug system for dual-mechanism targeted anticancer therapies to maximize therapeutic efficacy and minimize adverse drug reactions for chemotherapeutic agents.

Design of a dual randomized trial in a type 2 hybrid effectiveness-implementation study.

BACKGROUND: Dual randomized controlled trials (DRCT) are type 2 hybrid studies that include two randomized trials: one testing implementation strategies and one testing an intervention. We argue that this study design offers efficiency by providing rigorous investigation of both implementation and intervention in one study and has potential to accelerate generation of the evidence needed to translate interventions that work into real-world practice. Nevertheless, studies using this design are rare in the literature. MAIN TEXT: We construct a paradigm that breaks down the components of the DRCT and provide a step-by-step explanation of features of the design and recommendations for use. A clear distinction is made between the dual strands that test the implementation versus the intervention, and a minimum of three randomized arms is advocated. We suggest an active treatment arm that includes both the implementation strategy and intervention that are hypothesized to be superior. We suggest two comparison/control arms: one to test the implementation strategy and the second to test the intervention. Further, we recommend selection criteria for the two control arms that place emphasis on maximizing the utility of the study design to advance public health practice. CONCLUSIONS: On the surface, the design of a DRCT can appear simple, but actual application is complex. We believe it is that complexity that has limited its use in the literature. We hope that this paper will give both implementation scientists and trialists who are not familiar with implementation science a better understanding of the DRCT design and encouragement to use it.