Toward 95.5% Efficient Red Emissive Carbon Dots: Oxidation State Enhancing Radiative Electron-Transition of Indole Fluorophore.

Red fluorescence carbon dots (CDs) are promising for diverse applications and have attracted tremendous research interest. However, it is still challenging to achieve red fluorescence CDs with high fluorescence quantum yields (QYs > 50%). Herein, three kinds of red fluorescence CDs with QYs of 53.48, 85.21, and 59.18% are prepared. Benefiting from the oxidation induced by atmospheric-pressure O2 plasma processing, 95.5% efficient red fluorescence emission is achieved. It is revealed that the indole based fluorophores act as the red-emitting photoluminescence center. The synergistic effect between the C-O-C structure and indole based fluorophores plays a key role in promoting the efficiency of radiative electron transition and controlling the red fluorescence QYs. Additionally, the CDs show promising prospects for in vivo bioimaging and low in vivo toxicity. This work shows a new way for achieving high-efficiency red fluorescence CDs, and it may guide the development of high-performance CDs for diverse applications.

GhMAC3e is involved in plant growth and defense response to Verticillium dahliae.

KEY MESSAGE: GhMAC3e expression was induced by various stresses and hormones. GhMAC3e may regulate plant growth by influencing auxin distribution, and play important roles in Verticillium wilt resistance via mediating SA signaling. The MOS4-Associated Complex (MAC) is a highly conserved protein complex involved in pre-mRNA splicing and spliceosome assembly, which plays a vital role in plant immunity. It comprises key components such as MOS4, CDC5, and PRL1. MAC3A/B, as U-box E3 ubiquitin ligases, are crucial for various plant processes including development, stress responses, and disease resistance. However, their roles in cotton remain largely unknown. In this study, we first cloned the GhMAC3e gene from cotton and explored its biological functions by using virus-induced gene silencing (VIGS) in cotton and transgenic overexpression in Arabidopsis. The results showed that GhMAC3e is ubiquitously expressed in cotton tissues and could be induced by salt stress, Verticillium dahliae (VD) infection, PEG, ABA, ETH, GA3, MeJA, and SA. Silencing GhMAC3e retarded primary stem growth and reduced biomass of cotton coupled with the reduced auxin content in the petioles and veins. Silencing GhMAC3e up-regulated expression of cell growth-related genes GhXTH16 and Gh3.6, while down-regulated GhSAUR12 expression. Ectopic expression of GhMAC3e in Arabidopsis significantly enhanced its resistance to Verticillium wilt (VW) in terms of decreased pathogen biomass and lowered plant mortality. Overexpression of GhMAC3e dramatically upregulated AtPR1 by around 15 fold and more than 262 fold under basal and VD inoculation condition, respectively. This change was not associated with the expression of GhNPR1. In conclusion, GhMAC3e may not only regulate plant growth by influencing auxin distribution and growth-related gene expression, but also play important roles in VW resistance via mediating SA signaling independent of NPR1 transcription level.

Self-stacked small molecules for ultrasensitive, substrate-free Raman imaging in vivo.

Raman spectroscopy using surface-enhanced Raman scattering (SERS) nanoprobes represents an ultrasensitive and high-precision technique for in vivo imaging. Clinical translation of SERS nanoprobes has been hampered by biosafety concerns about the metal substrates used to enhance Raman signals. We report a set of small molecules with bis-thienyl-substituted benzobisthiadiazole structures that enhance Raman signal through self-stacking rather than external substrates. In our technique, called stacking-induced charge transfer-enhanced Raman scattering (SICTERS), the self-stacked small molecules form an ordered spatial arrangement that enables three-dimensional charge transfer between neighboring molecules. The Raman scattering cross-section of SICTERS nanoprobes is 1350 times higher than that of conventional SERS gold nanoprobes of similar particle size. SICTERS outperforms SERS in terms of in vivo imaging sensitivity, resolution and depth. SICTERS is capable of noninvasive Raman imaging of blood and lymphatic vasculatures, which has not been achieved by SERS. SICTERS represents an alternative technique to enhance Raman scattering for guiding the design of ultrasensitive substrate-free Raman imaging probes.

Covalent Organic Framework-Structured Raman Probes for Ultrasensitive In Vivo Bioimaging.

Organic Raman probes, including polymers and small molecules, have attracted great attention in biomedical imaging owing to their excellent biocompatibility. However, the development of organic Raman probes is usually hindered by a mismatch between their absorption spectra and wavelength-fixed excitation, which makes it difficult to achieve resonance excitation necessary to obtain strong Raman signals. Herein, we introduce a covalent organic framework (COF) into the fine absorption spectrum regulation of organic Raman probes, resulting in their significant Raman signal enhancement. In representative examples, a polymer poly(diketopyrrolopyrrole-p-phenylenediamine) (DPP-PD) and a small molecule azobenzene are transformed into the corresponding COF-structured Raman probes. Their absorption peaks show an accurate match of less than 5 nm with the NIR excitation. As such, the COF-structured Raman probes acquire highly sensitive bioimaging capabilities compared to their precursors with negligible signals. By further mechanism studies, we discover that the crystallinity and size of COFs directly affect the π-conjugation degree of Raman probes, thus changing their bandgaps and absorption spectra. Our study offers a universal and flexible method for improving the signal performance of organic Raman probes without changing their structural units, making it more convenient to obtain the highly sensitive organic Raman probes for in vivo bioimaging.

A Visual Raman Nano-Delivery System Based on Thiophene Polymer for Microtumor Detection.

A visual Raman nano-delivery system (NS) is a widely used technique for the visualization and diagnosis of tumors and various biological processes. Thiophene-based organic polymers exhibit excellent biocompatibility, making them promising candidates for development as a visual Raman NS. However, materials based on thiophene face limitations due to their absorption spectra not matching with NIR (near-infrared) excitation light, which makes it difficult to achieve enhanced Raman properties and also introduces potential fluorescence interference. In this study, we introduce a donor-acceptor (D-A)-structured thiophene-based polymer, PBDB-T. Due to the D-A molecular modulation, PBDB-T exhibits a narrow bandgap of Eg = 2.63 eV and a red-shifted absorption spectrum, with the absorption edge extending into the NIR region. Upon optimal excitation with 785 nm light, it achieves ultra-strong pre-resonant Raman enhancement while avoiding fluorescence interference. As an intrinsically sensitive visual Raman NS for in vivo imaging, the PBDB-T NS enables the diagnosis of microtumor regions with dimensions of 0.5 mm × 0.9 mm, and also successfully diagnoses deeper tumor tissues, with an in vivo circulation half-life of 14.5 h. This research unveils the potential application of PBDB-T as a NIR excited visual Raman NS for microtumor diagnosis, introducing a new platform for the advancement of "Visualized Drug Delivery Systems". Moreover, the aforementioned platform enables the development of a more diverse range of targeted visual drug delivery methods, which can be tailored to specific regions.

One-Dimensional MoS2 Nanoscrolls as Miniaturized Memories.

Dimensionality of materials is closely related to their physical properties. For two-dimensional (2D) semiconductors such as monolayer molybdenum disulfide (MoS2), converting them from 2D nanosheets to one-dimensional (1D) nanoscrolls could contribute to remarkable electronic and optoelectronic properties, yet the rolling-up process still lacks sufficient controllability, which limits the development of their device applications. Herein we report a modified solvent evaporation-induced rolling process that halts at intermediate states and achieve MoS2 nanoscrolls with high yield and decent axial uniformity. The accordingly fabricated nanoscroll memories exhibit an on/off ratio of ∼104 and a retention time exceeding 103 s and can realize multilevel storage with pulsed gate voltages. Such open-end, high-curvature, and hollow 1D nanostructures provide new possibilities to manipulate the hysteresis windows and, consequently, the charge storage characteristics of nanoscale field-effect transistors, thereby holding great promise for the development of miniaturized memories.

Microwave ablation combined with percutaneous vertebroplasty for treating painful non-small cell lung cancer with spinal metastases under real-time temperature monitoring.

PURPOSE: To retrospectively study the therapeutic effect and safety performance of the combination strategies of the computed tomography (CT)-guided microwave ablation (MWA) and percutaneous vertebroplasty (PVP) as a treatment for painful non-small cell lung cancer (NSCLC) with spinal metastases. MATERIALS AND METHODS: A retrospective review included 71 patients with 109 vertebral metastases who underwent microwave ablation combined with percutaneous vertebroplasty by the image-guided and real-time temperature monitoring. Treatment efficacy was determined by comparing visual analog scale (VAS) scores, daily morphine equivalent opioid consumption, and Oswestry Disability Index (ODI) scores before treatment and during the follow-up period. RESULTS: Technical success was achieved in all patients. The mean pre-procedure VAS score and morphine doses were 6.6 ± 1.8 (4-10) and 137.2 ± 38.7 (40-200) mg, respectively. The mean VAS scores and daily morphine doses at 24 h and 1, 4, 12, and 24 weeks postoperatively were 3.3 ± 1.9 and 73.5 ± 39.4 mg; 2.2 ± 1.5 and 40.2 ± 29.8 mg; 1.7 ± 1.2 and 31.3 ± 23.6 mg; 1.4 ± 1.1 and 27.3 ± 21.4 mg; and 1.3 ± 1.1 and 24.8 ± 21.0 mg, respectively (all P < 0.001). ODI scores significantly decreased (P < 0.05). Minor cement leakage occurred in 51 cases (46.8%), with one patient having a grade 3 neural injury. No local tumor progression was observed by follow-up imaging. CONCLUSIONS: MWA combined with PVP can significantly relieve pain and improve patients' quality of life, which implied this is an effective treatment option for painful NSCLC with spinal metastases. Additionally, its efficacy should be further verified through the mid- and long-term studies.

USP40 promotes hepatocellular carcinoma cell proliferation, migration and stemness by deubiquitinating and stabilizing Claudin1.

BACKGROUND: Hepatocellular carcinoma (HCC) is a prevalent malignant tumor that poses a major threat to people's lives and health. Previous studies have found that multiple deubiquitinating enzymes are involved in the pathogenesis of HCC. The purpose of this work was to elucidate the function and mechanism of the deubiquitinating enzyme USP40 in HCC progression. METHODS: The expression of USP40 in human HCC tissues and HCC cell lines was investigated using RT-qPCR, western blotting and immunohistochemistry (IHC). Both in vitro and in vivo experiments were conducted to determine the crucial role of USP40 in HCC progression. The interaction between USP40 and Claudin1 was identified by immunofluorescence, co-immunoprecipitation and ubiquitination assays. RESULTS: We discovered that USP40 is elevated in HCC tissues and predicts poor prognosis in HCC patients. USP40 knockdown inhibits HCC cell proliferation, migration and stemness, whereas USP40 overexpression shows the opposite impact. Furthermore, we confirmed that Claudin1 is a downstream gene of USP40. Mechanistically, USP40 interacts with Claudin1 and inhibits its polyubiquitination to stabilize Claudin1 protein. CONCLUSIONS: Our study reveals that USP40 enhances HCC malignant development by deubiquitinating and stabilizing Claudin1, suggesting that targeting USP40 may be a novel approach for HCC therapy.

Analysis of facial redness by comparing VISIA and YLGTD.

BACKGROUND: Erythema, characterized by redness of the skin, is a common symptom in various facial skin conditions. Recent advancements in image processing and analysis techniques have led to the development of methods for analyzing and assessing skin texture. This study aimed to investigate the correlation between the parameters of "You Look Good Today" (YLGTD) and VISIA in the detection and assessment of facial redness. MATERIALS AND METHODS: Thirty female subjects participated in this experiment, undergoing assessments using both YLGTD and VISIA. The subjects were evaluated for facial redness, and the feature count results within the red zone were measured by VISIA. YLGTD analyzed the number and percentage of red zone pixels. The assessments were conducted between [specific dates] in [location]. RESULTS: The results demonstrated a significant positive correlation between the feature count results within the red zone measured by VISIA and the number of red zone pixels. Similarly, YLGTD exhibited a significant positive correlation with the number and percentage of red zone pixels. CONCLUSION: In conclusion, our findings suggest a correlation between YLGTD and VISIA in the measurement of facial erythema. YLGTD can serve as a portable device for primary screening assessments, offering a convenient and reliable method to evaluate facial redness. This research contributes to the development of non-invasive techniques for assessing and monitoring facial skin conditions, providing valuable insights for dermatological diagnosis and cosmetic testing.

Wastewater surveillance monitoring of SARS-CoV-2 variants of concern and dynamics of transmission and community burden of COVID-19.

Wastewater-based surveillance is a valuable approach for monitoring COVID-19 at community level. Monitoring SARS-CoV-2 variants of concern (VOC) in wastewater has become increasingly relevant when clinical testing capacity and case-based surveillance are limited. In this study, we ascertained the turnover of six VOC in Alberta wastewater from May 2020 to May 2022. Wastewater samples from nine wastewater treatment plants across Alberta were analysed using VOC-specific RT-qPCR assays. The performance of the RT-qPCR assays in identifying VOC in wastewater was evaluated against next generation sequencing. The relative abundance of each VOC in wastewater was compared to positivity rate in COVID-19 testing. VOC-specific RT-qPCR assays performed comparatively well against next generation sequencing; concordance rates ranged from 89% to 98% for detection of Alpha, Beta, Gamma, Omicron BA.1 and Omicron BA.2, with a slightly lower rate of 85% for Delta (p < 0.01). Elevated relative abundance of Alpha, Delta, Omicron BA.1 and BA.2 were each associated with increased COVID-19 positivity rate. Alpha, Delta and Omicron BA.2 reached 90% relative abundance in wastewater within 80, 111 and 62 days after their initial detection, respectively. Omicron BA.1 increased more rapidly, reaching a 90% relative abundance in wastewater after 35 days. Our results from VOC surveillance in wastewater correspond with clinical observations that Omicron is the VOC with highest disease burden over the shortest period in Alberta to date. The findings suggest that changes in relative abundance of a VOC in wastewater can be used as a supplementary indicator to track and perhaps predict COVID-19 burden in a population.

Significantly Longer Shedding of Norovirus Compared to Rotavirus and Adenovirus in Children with Acute Gastroenteritis.

Worldwide, acute gastroenteritis (AGE) is a major cause of morbidity and mortality in children under 5 years of age. Viruses, including norovirus, rotavirus, and enteric adenovirus, are the leading causes of pediatric AGE. In this prospective cohort study, we investigated the viral load and duration of shedding of norovirus, rotavirus, and adenovirus in stool samples collected from 173 children (median age: 15 months) with AGE who presented to emergency departments (EDs) across Canada on Day 0 (day of enrollment), and 5 and 28 days after enrollment. Quantitative RT-qPCR was performed to assess the viral load. On Day 0, norovirus viral load was significantly lower compared to that of rotavirus and adenovirus (p < 0.001). However, on Days 5 and 28, the viral load of norovirus was higher than that of adenovirus and rotavirus (p < 0.05). On Day 28, norovirus was detected in 70% (35/50) of children who submitted stool specimens, while rotavirus and adenovirus were detected in 52.4% (11/24) and 13.6% (3/22) of children (p < 0.001), respectively. Overall, in stool samples of children with AGE who presented to EDs, rotavirus and adenovirus had higher viral loads at presentation compared to norovirus; however, norovirus was shed in stool for the longest duration.

Effect of repeated intravitreal anti-vascular endothelial growth factor drugs on corneal nerves.

To investigate the potential effect of repeated intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) drugs on corneal nerves. A total of 64 patients were treated with intravitreal injection of anti-VEGF drugs. There were 19 cases of neovascular age-related macular degeneration (AMD), 20 cases of diabetic macular edema (DME) and 25 cases of retinal vein occlusion (RVO). Twenty-nine cases were treated with aflibercept (2 mg/0.05 mL) whereas 35 cases were managed with ranibizumab (0.5 mg/0.05 mL). A corneal confocal microscope was used to collect images of corneal subbasal nerve plexus, and Image J was used for image analysis. The changes in corneal nerve were compared between 1 month after each injection and before injection. There were no significant differences in the density and length of corneal nerve at specific time after the surgery in comparison with baseline in patients who were given 3 intravitreal injections. There was no significant correlation between the numbers of injections and the changes of the corneal nerves. After 3rd injection, the nerve length of the DME group was markedly lower than that of AMD and RVO groups, the difference was statistically significant (P < .05). The nerve density of the DME group was not significantly different from that of AMD and RVO groups, whereas the nerve length and nerve density of the AMD and RVO groups were not statistically significant between each other also. The corneal nerve length after the 2nd and 3rd injections of Aflibercept were lower than that before surgery, the difference was statistically significant. There were no significant differences in nerve density and nerve length at each time point after Ranibizumab injection. The length and density of the corneal nerve after multiple injections in contralateral eye displayed no significant changes compared with the baseline. Repeated intravitreal anti-VEGF drug can reduce the length of corneal nerves. For patients who need repeated intravitreal injections of anti-VEGF drugs, especially in DM, attention should be paid on the changes affecting the corneal nerves. It is also needed to strengthen the local anti-inflammatory therapy to avoid infection and to use artificial tears to protect the microenvironment of the ocular surface after the surgery.

Microwave ablation combined with vertebral augmentation under real-time temperature monitoring for the treatment of painful spinal osteogenic metastases.

OBJECTIVE: To evaluate the safety and efficacy of computed tomography (CT)-guided microwave ablation combined with vertebral augmentation under real-time temperature monitoring in the treatment of painful osteogenic spinal metastases. METHODS: This retrospective study included 38 patients with 63 osteogenic metastatic spinal lesions treated using CT-guided microwave ablation and vertebral augmentation under real-time temperature monitoring. Visual analog scale scores, daily morphine consumption, and Oswestry Disability Index scores were used to evaluate efficacy of the treatment. RESULTS: Microwave ablation combined with vertebral augmentation reduced the mean visual analog scale scores from 6.40 ± 1.90 preoperatively to 3.32 ± 0.96 at 24 h, 2.24 ± 0.91 at 1 week, 1.92 ± 1.32 at 4 weeks, 1.79 ± 1.45 at 12 weeks, and 1.39 ± 1.12 at 24 weeks postoperatively (all p < 0.001). The mean preoperative daily morphine consumption was 108.95 ± 56.41 mg, which decreased to 50.13 ± 25.46 mg at 24 h, 31.18 ± 18.58 mg at 1 week, 22.50 ± 16.63 mg at 4 weeks, 21.71 ± 17.68 mg at 12 weeks, and 17.27 ± 16.82 mg at 24 weeks postoperatively (all p < 0.001). During the follow-up period, the Oswestry Disability Index scores significantly reduced (p < 0.001). Bone cement leakage occurred in 25 vertebral bodies, with an incidence of 39.7% (25/63). CONCLUSIONS: The results indicate that microwave ablation combined with vertebral augmentation under real-time temperature monitoring is a feasible, effective, and safe treatment for painful osteoblast spinal metastases.

Development and validation of a nomogram to predict protein-energy wasting in patients with peritoneal dialysis: a multicenter cohort study.

Background: Protein-energy wasting (PEW) is a common complication in patients with peritoneal dialysis (PD). Few investigations involved risk factors identification and predictive model construction related to PEW. We aimed to develop a nomogram to predict PEW risk in patients with peritoneal dialysis. Methods: We collected data from end-stage renal disease (ESRD) patients who regularly underwent peritoneal dialysis between January 2011 and November 2022 at two hospitals retrospectively. The outcome of the nomogram was PEW. Multivariate logistic regression screened predictors and established a nomogram. We measured the predictive performance based on discrimination ability, calibration, and clinical utility. Evaluation indicators were receiver operating characteristic (ROC), calibrate curve, and decision curve analysis (DCA). The performance calculation of the internal validation cohort validated the nomogram. Results: In this study, 369 enrolled patients were divided into development (n = 210) and validation (n = 159) cohorts according to the proportion of 6:4. The incidence of PEW was 49.86%. Predictors were age, dialysis duration, glucose, C-reactive protein (CRP), creatinine clearance rate (Ccr), serum creatinine (Scr), serum calcium, and triglyceride (TG). These variables showed a good discriminate performance in development and validation cohorts (ROC = 0.769, 95% CI [0.705-0.832], ROC = 0.669, 95% CI [0.585-0.753]). This nomogram was adequately calibrated. The predicted probability was consistent with the observed outcome. Conclusion: This nomogram can predict the risk of PEW in patients with PD and provide valuable evidence for PEW prevention and decision-making.

Hydrogen Promotes the Effectiveness of Bone Mesenchymal Stem Cell Transplantation in Rats with Spinal Cord Injury.

Although bone mesenchymal stem cell (BMSC) transplantation has been applied to the treatment of spinal cord injury (SCI), the effect is unsatisfactory due to the specific microenvironment (inflammation and oxidative stress) in the SCI area, which leads to the low survival rate of transplanted cells. Thus, additional strategies are required to improve the efficacy of transplanted cells in the treatment of SCI. Hydrogen possesses antioxidant and anti-inflammatory properties. However, whether hydrogen can enhance the effect of BMSC transplantation in the treatment of SCI has not yet been reported. This study was aimed at investigating whether hydrogen promotes the therapeutic effect of BMSC transplantation in the treatment of SCI in rats. In vitro, BMSCs were cultured in a normal medium and a hydrogen-rich medium to study the effect of hydrogen on the proliferation and migration of BMSCs. BMSCs were treated with a serum-deprived medium (SDM), and the effects of hydrogen on the apoptosis of BMSCs were studied. In vivo, BMSCs were injected into the rat model of SCI. Hydrogen-rich saline (5 ml/kg) and saline (5 ml/kg) were given once a day via intraperitoneal injection. Neurological function was evaluated using the Basso, Beattie, and Bresnahan (BBB) and CatWalk gait analyses. Histopathological analysis, oxidative stress, inflammatory factors (TNF-α, IL-1ß, and IL-6), and transplanted cell viability were detected at 3 and 28 days after SCI. Hydrogen can significantly enhance BMSC proliferation and migration and tolerance to SDM. Hydrogen and BMSC codelivery can significantly enhance neurological function recovery by improving the transplant cell survival rate and migration. Hydrogen can enhance the migration and proliferation capacity of BMSCs to repair SCI by reducing the inflammatory response and oxidative stress in the injured area. Hydrogen and BMSC codelivery is an effective method to improve BMSC transplantation in the treatment of SCI.

An efficient method to enhance recovery and detection of SARS-CoV-2 RNA in wastewater.

Wastewater surveillance (WS) of SARS-CoV-2 currently requires multiple steps and suffers low recoveries and poor sensitivity. Here, we report an improved analytical method with high sensitivity and recovery to quantify SARS-CoV-2 RNA in wastewater. To improve the recovery, we concentrated SARS-CoV-2 viral particles and RNA from both the solid and aqueous phases of wastewater using an electronegative membrane (EM). The captured viral particles and RNA on the EM were incubated in our newly developed viral inactivation and RNA preservation (VIP) buffer. Subsequently, the RNA was concentrated on magnetic beads and inhibitors removed by washing. Without eluting, the RNA on the magnetic beads was directly detected using reverse transcription quantitative polymerase chain reaction (RT-qPCR). Analysis of SARS-CoV-2 pseudovirus (SARS-CoV-2 RNA in a noninfectious viral coat) spiked to wastewater samples showed an improved recovery of 80%. Analysis of 120 wastewater samples collected twice weekly between May 2021 and February 2022 from two wastewater treatment plants showed 100% positive detection, which agreed with the results independently obtained by a provincial public health laboratory. The concentrations of SARS-CoV-2 RNA in these wastewater samples ranged from 2.4×102 to 2.9×106 copies per 100 mL of wastewater. Our method's capability of detecting trace and diverse concentrations of SARS-CoV-2 in complex wastewater samples is attributed to the enhanced recovery of SARS-CoV-2 RNA and efficient removal of PCR inhibitors. The improved method for the recovery and detection of viral RNA in wastewater is important for wastewater surveillance, complementing clinical diagnostic tests for public health protection.

Efficacy and safety of bimekizumab for the treatment of psoriasis: a systematic review and meta-analysis of randomized clinical trials.

AIM: This study aimed to evaluate the efficacy and safety of bimekizumab for psoriasis. METHODS: The PubMed, Web of Science, Cochrane Library, and Embase databases were systematically searched until November 20, 2022, to identify randomized controlled trials (RCTs) reporting the efficacy and safety of bimekizumab. The identified studies were screened according to inclusion and exclusion criteria, and a meta-analysis was performed on the selected studies using the Stata (version 17.0) software to investigate the efficacy and safety of bimekizumab. RESULTS: Six studies involving 1252 participants were considered. Compared with the control group which received placebo, the bimekizumab group had a larger number of patients with improvement in Psoriasis Area and Severity Index (PASI) of at least 75% (PASI75) (RR: 20.54, 95%CI: 12.41-33.99; p = .000), at least 90% (PASI90) (RR:16.99, 95%CI: 7.09-40.68; p = .000) and 100%(PASI100) (RR:14.57; 95%CI: 5.26-40.35; p = .000) and a larger number with improvement in Investigator Global Assessment (IGA) response (RR:22.57; 95%CI: 12.74-39.98; p = .000). There was no obvious difference between the bimekizumab and placebo groups in treatment of emergent adverse events (TEAEs) (RR:1.17; 95%CI: 0.93-1.47; p > .05) and serious TEAEs (RR: 0.67; 95%CI: 0.28-1.61; p > .05). CONCLUSIONS: Bimekizumab shows promising efficacy for the treatment of psoriasis with favorable safety records.

Realizing the value in "non-standard" parts of the qPCR standard curve by integrating fundamentals of quantitative microbiology.

The real-time polymerase chain reaction (PCR), commonly known as quantitative PCR (qPCR), is increasingly common in environmental microbiology applications. During the COVID-19 pandemic, qPCR combined with reverse transcription (RT-qPCR) has been used to detect and quantify SARS-CoV-2 in clinical diagnoses and wastewater monitoring of local trends. Estimation of concentrations using qPCR often features a log-linear standard curve model calibrating quantification cycle (Cq) values obtained from underlying fluorescence measurements to standard concentrations. This process works well at high concentrations within a linear dynamic range but has diminishing reliability at low concentrations because it cannot explain "non-standard" data such as Cq values reflecting increasing variability at low concentrations or non-detects that do not yield Cq values at all. Here, fundamental probabilistic modeling concepts from classical quantitative microbiology were integrated into standard curve modeling approaches by reflecting well-understood mechanisms for random error in microbial data. This work showed that data diverging from the log-linear regression model at low concentrations as well as non-detects can be seamlessly integrated into enhanced standard curve analysis. The newly developed model provides improved representation of standard curve data at low concentrations while converging asymptotically upon conventional log-linear regression at high concentrations and adding no fitting parameters. Such modeling facilitates exploration of the effects of various random error mechanisms in experiments generating standard curve data, enables quantification of uncertainty in standard curve parameters, and is an important step toward quantifying uncertainty in qPCR-based concentration estimates. Improving understanding of the random error in qPCR data and standard curve modeling is especially important when low concentrations are of particular interest and inappropriate analysis can unduly affect interpretation, conclusions regarding lab performance, reported concentration estimates, and associated decision-making.

Association between triglyceride to high-density lipoprotein cholesterol ratio and type 2 diabetes risk in Japanese.

Abnormal lipid metabolism is known to increases the risk for metabolic diseases, such as type 2 diabetes mellitus(T2DM). The relationship between baseline ratio of triglyceride to HDL cholesterol (TG/HDL-C) and T2DM in Japanese adults was investigated in this study. Our secondary analysis included 8419 male and 7034 female Japanese subjects who were free of diabetes at baseline. The correlation between baseline TG/HDL-C and T2DM was analyzed by a proportional risk regression model, the nonlinear correlation between baseline TG/HDL-C and T2DM was analyzed by a generalized additive model (GAM), and the threshold effect analysis was performed by a segmented regression model. We conducted subgroup analyses in different populations. During the median 5.39 years follow-up, 373 participants, 286 males and 87 females, developed diabetes mellitus. After full adjustment for confounders, the baseline TG/HDL-C ratio positively correlated with the risk of diabetes (hazard ratio 1.19, 95% confidence interval 1.09-1.3), and smoothed curve fitting and two-stage linear regression analysis revealed a J-shaped relationship between baseline TG/HDL-C and T2DM. The inflection point for baseline TG/HDL-C was 0.35. baseline TG/HDL-C > 0.35 was positively associated with the development of T2DM (hazard ratio 1.2, 95% confidence interval 1.10-1.31). Subgroup analysis showed no significant differences in the effect between TG/HDL-C and T2DM in different populations. A J-shaped relationship was observed between baseline TG/HDL-C and T2DM risk in the Japanese population. When TG/HDL-C was higher than 0.35, there was a positive relationship between baseline TG/HDL-C and the incidence of diabetes mellitus.

Performance and mechanism of sacrificed iron anode coupled with constructed wetlands (E-Fe) for simultaneous nitrogen and phosphorus removal.

Three anodic biofilm electrode coupled CWs (BECWs) with graphite (E-C), aluminum (E-Al), and iron (E-Fe), respectively, and a control system (CK) were constructed to evaluate the removal performance of N and P in the secondary effluent of wastewater treatment plants (WWTPs) under different hydraulic retention time (HRT), electrified time (ET), and current density (CD). Microbial communities, and different P speciation, were analyzed to reveal the potential removal pathways and mechanism of N and P in BECWs. Results showed that the optimal average TN and TP removal rates of CK (34.10% and 55.66%), E-C (66.77% and 71.33%), E-Al (63.46% and 84.93%), and E-Fe (74.93% and 91.22%) were obtained under the optimum conditions (HRT 10 h, ET 4 h, CD 0.13 mA/cm2), which demonstrated that the biofilm electrode could significantly improve N and P removal. Microbial community analysis showed that E-Fe owned the highest abundance of chemotrophic Fe(II) (Dechloromonas) and hydrogen autotrophic denitrifying bacteria (Hydrogenophaga). N was mainly removed by hydrogen and iron autotrophic denitrification in E-Fe. Moreover, the highest TP removal rate of E-Fe was attributed to the iron ion formed on the anode, causing co-precipitation of Fe(II) or Fe(III) with PO43--P. The Fe released from the anode acted as carriers for electron transport and accelerated the efficiency of biological and chemical reactions to enhance the simultaneous removal of N and P. Thus, BECWs provide a new perspective for the treatment of the secondary effluent from WWTPs.