Dependency-aware deep generative models for multitasking analysis of spatial omics data.

Spatially resolved transcriptomics (SRT) technologies have significantly advanced biomedical research, but their data analysis remains challenging due to the discrete nature of the data and the high levels of noise, compounded by complex spatial dependencies. Here, we propose spaVAE, a dependency-aware, deep generative spatial variational autoencoder model that probabilistically characterizes count data while capturing spatial correlations. spaVAE introduces a hybrid embedding combining a Gaussian process prior with a Gaussian prior to explicitly capture spatial correlations among spots. It then optimizes the parameters of deep neural networks to approximate the distributions underlying the SRT data. With the approximated distributions, spaVAE can contribute to several analytical tasks that are essential for SRT data analysis, including dimensionality reduction, visualization, clustering, batch integration, denoising, differential expression, spatial interpolation, resolution enhancement and identification of spatially variable genes. Moreover, we have extended spaVAE to spaPeakVAE and spaMultiVAE to characterize spatial ATAC-seq (assay for transposase-accessible chromatin using sequencing) data and spatial multi-omics data, respectively.

Zbtb16 increases susceptibility of atrial fibrillation in type 2 diabetic mice via Txnip-Trx2 signaling.

Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia, and recent epidemiological studies suggested type 2 diabetes mellitus (T2DM) is an independent risk factor for the development of AF. Zinc finger and BTB (broad-complex, tram-track and bric-a-brac) domain containing 16 (Zbtb16) serve as transcriptional factors to regulate many biological processes. However, the potential effects of Zbtb16 in AF under T2DM condition remain unclear. Here, we reported that db/db mice displayed higher AF vulnerability and Zbtb16 was identified as the most significantly enriched gene by RNA sequencing (RNA-seq) analysis in atrium. In addition, thioredoxin interacting protein (Txnip) was distinguished as the key downstream gene of Zbtb16 by Cleavage Under Targets and Tagmentation (CUT&Tag) assay. Mechanistically, increased Txnip combined with thioredoxin 2 (Trx2) in mitochondrion induced excess reactive oxygen species (ROS) release, calcium/calmodulin-dependent protein kinase II (CaMKII) overactivation, and spontaneous Ca2+ waves (SCWs) occurrence, which could be inhibited through atrial-specific knockdown (KD) of Zbtb16 or Txnip by adeno-associated virus 9 (AAV9) or Mito-TEMPO treatment. High glucose (HG)-treated HL-1 cells were used to mimic the setting of diabetic in vitro. Zbtb16-Txnip-Trx2 signaling-induced excess ROS release and CaMKII activation were also verified in HL-1 cells under HG condition. Furthermore, atrial-specific Zbtb16 or Txnip-KD reduced incidence and duration of AF in db/db mice. Altogether, we demonstrated that interrupting Zbtb16-Txnip-Trx2 signaling in atrium could decrease AF susceptibility via reducing ROS release and CaMKII activation in the setting of T2DM.

A safety and efficacy study of allogeneic haematopoietic stem cell transplantation for refractory and relapsed T-cell acute lymphoblastic leukaemia/lymphoblastic lymphoma patients who achieved complete remission after autologous CD7 chimeric antigen receptor T-cell therapy.

CD7-targeted chimeric antigen receptor T-cell (CAR-T) therapy has shown promising initial complete remission (CR) rates in patients with refractory or relapsed (r/r) T-cell acute lymphoblastic leukaemia and lymphoblastic lymphoma (T-ALL/LBL). To enhance the remission duration, consolidation with allogeneic haematopoietic stem cell transplantation (allo-HSCT) is considered. Our study delved into the outcomes of 34 patients with r/r T-ALL/LBL who underwent allo-HSCT after achieving CR with autologous CD7 CAR-T therapy. These were compared with 124 consecutive T-ALL/LBL patients who received allo-HSCT in CR following chemotherapy. The study revealed that both the CAR-T and chemotherapy cohorts exhibited comparable 2-year overall survival (OS) (61.9% [95% CI, 44.1-78.1] vs. 67.6% [95% CI, 57.5-76.9], p = 0.210), leukaemia-free survival (LFS) (62.3% [95% CI, 44.6-78.4] vs. 62.0% [95% CI, 51.8-71.7], p = 0.548), non-relapse mortality (NRM) rates (32.0% [95% CI, 19.0-54.0] vs. 25.3% [95% CI, 17.9-35.8], p = 0.288) and relapse incidence rates (8.8% [95% CI, 3.0-26.0] vs. 15.8% [95% CI, 9.8-25.2], p = 0.557). Patients aged ≤14 in the CD7 CAR-T group achieved high 2-year OS and LFS rates of 87.5%. Our study indicates that CD7 CAR-T therapy followed by allo-HSCT is not only effective and safe for r/r T-ALL/LBL patients but also on par with the outcomes of those achieving CR through chemotherapy, without increasing NRM.

ADAR-mediated RNA editing regulates PVR immune checkpoint in colorectal cancer.

Recent studies have revealed that tumor immunotherapy resistance is influenced by ADAR-mediated RNA editing, but its targets remain unelucidated. Our current study identified the poliovirus receptor (PVR) oncogene, which encodes an immune checkpoint in colorectal cancer (CRC), as a potential target for RNA editing. We performed transcriptome sequencing analysis and experimental validation in two Chinese CRC cohorts. PVR and ADAR expressions significantly increased in CRC tumors and showed positive correlations in both cohorts, coupled with upregulated PVR RNA editing in CRC tumors. Manipulation of ADAR expression by over-expression or knockdown substantially changed PVR expression and RNA editing in HTC116 CRC cells. Luciferase reporter and actinomycin D assays further revealed that RNA editing in PVR 3'-UTR could upregulate PVR RNA expression, probably by increasing the RNA stability. By increasing PVR expression, ADAR-mediate RNA editing might contribute to tumor- and immune-related gene functions and pathways in CRC. Moreover, a signature combining PVR RNA editing and expression showed promising predictive performance in CRC diagnosis in both Chinese CRC cohorts. Our findings thus highlight the importance of ADAR-mediated RNA editing in PVR up-regulation in CRC tumors and provide new insight into the application of PVR RNA editing as a novel diagnostic biomarker for CRC.

F11R RNA trinucleotide over-edited by ADAR in gastric and colorectal cancers: Cross-cohort validation, gene expression regulation, and diagnostic significance.

The F11 receptor (F11R) gene encoding junctional adhesion molecule A has been associated with gastric cancer (GC) and colorectal cancer (CRC), in which its role and regulation remain to be further elucidated. Recently F11R was also identified as a potential target of adenosine-to-inosine (A-to-I) mediated by the adenosine deaminases acting on RNA (ADARs). Herein, using RNA-Seq and experimental validation, our current study revealed an F11R RNA trinucleotide over-edited by ADAR, with its regulation of gene expression and clinical significance in four GC and three CRC cohorts. Our results found an over-edited AAA trinucleotide in an AluSg located in the F11R 3'-untranslated region (3'-UTR), which showed editing levels correlated with elevated ADAR expression across all GC and CRC cohorts in our study. Overexpression and knockdown of ADAR in GC and CRC cells, followed by RNA-Seq and Sanger sequencing, confirmed the ADAR-mediated F11R 3'-UTR trinucleotide editing, which potentially disrupted an RBM45 binding site identified by crosslinking immunoprecipitation sequencing (CLIP-seq) and regulated F11R expression in luciferase reporter assays. Moreover, the F11R trinucleotide editing showed promising predictive performance for diagnosing GC and CRC across GC and CRC cohorts. Our findings thus highlight both the potential biological and clinical significance of an ADAR-edited F11R trinucleotide in GC and CRC, providing new insights into its application as a novel diagnostic biomarker for both cancers.

UV-A radiation increases biomass yield by enhancing energy flow and carbon assimilation in the edible cyanobacterium Nostoc sphaeroides.

Ultraviolet (UV) A radiation (315-400 nm) is the predominant component of solar UV radiation that reaches the Earth's surface. However, the underlying mechanisms of the positive effects of UV-A on photosynthetic organisms have not yet been elucidated. In this study, we investigated the effects of UV-A radiation on the growth, photosynthetic ability, and metabolome of the edible cyanobacterium Nostoc sphaeroides. Exposures to 5-15 W m-2 (15-46 µmol photons m-2 s-1) UV-A and 4.35 W m-2 (20 µmol photons m-2 s-1) visible light for 16 days significantly increased the growth rate and biomass production of N. sphaeroides cells by 18%-30% and 15%-56%, respectively, compared to the non-UV-A-acclimated cells. Additionally, the UV-A-acclimated cells exhibited a 1.8-fold increase in the cellular nicotinamide adenine dinucleotide phosphate (NADP) pool with an increase in photosynthetic capacity (58%), photosynthetic efficiency (24%), QA re-oxidation, photosystem I abundance, and cyclic electron flow (87%), which further led to an increase in light-induced NADPH generation (31%) and ATP content (83%). Moreover, the UV-A-acclimated cells showed a 2.3-fold increase in ribulose-1,5-bisphosphate carboxylase/oxygenase activity, indicating an increase in their carbon-fixing capacity. Gas chromatography-mass spectrometry-based metabolomics further revealed that UV-A radiation upregulated the energy-storing carbon metabolism, as evidenced by the enhanced accumulation of sugars, fatty acids, and citrate in the UV-A-acclimated cells. Therefore, our results demonstrate that UV-A radiation enhances energy flow and carbon assimilation in the cyanobacterium N. sphaeroides.IMPORTANCEUltraviolet (UV) radiation exerts harmful effects on photo-autotrophs; however, several studies demonstrated the positive effects of UV radiation, especially UV-A radiation (315-400 nm), on primary productivity. Therefore, understanding the underlying mechanisms associated with the promotive effects of UV-A radiation on primary productivity can facilitate the application of UV-A for CO2 sequestration and lead to the advancement of photobiological sciences. In this study, we used the cyanobacterium Nostoc sphaeroides, which has an over 1,700-year history of human use as food and medicine, to explore its photosynthetic acclimation response to UV-A radiation. As per our knowledge, this is the first study to demonstrate that UV-A radiation increases the biomass yield of N. sphaeroides by enhancing energy flow and carbon assimilation. Our findings provide novel insights into UV-A-mediated photosynthetic acclimation and provide a scientific basis for the application of UV-A radiation for optimizing light absorption capacity and enhancing CO2 sequestration in the frame of a future CO2 neutral, circular, and sustainable bioeconomy.

Preparation of Matrix Product States with Log-Depth Quantum Circuits.

We consider the preparation of matrix product states (MPS) on quantum devices via quantum circuits of local gates. We first prove that faithfully preparing translation-invariant normal MPS of N sites requires a circuit depth T=Ω(logN). We then introduce an algorithm based on the renormalization-group transformation to prepare normal MPS with an error ε in depth T=O[log(N/ε)], which is optimal. We also show that measurement and feedback leads to an exponential speedup of the algorithm to T=O[loglog(N/ε)]. Measurements also allow one to prepare arbitrary translation-invariant MPS, including long-range non-normal ones, in the same depth. Finally, the algorithm naturally extends to inhomogeneous MPS.

Efficient photoanode with a MoS2/TiO2/Au nanoparticle heterostructure for ultraviolet-visible photoelectrocatalysis.

Green energy technology is generally becoming one of hot issues that need to be solved due to the adverse effects on the environment of fossil fuels. One of the strategies being studied and developed by theorists and experimentalists is the use of photoelectrochemical (PEC) cells, which are emerging as a candidate to produce hydrogen from water splitting. However, creating photoelectrodes that meet the requirements for PEC water splitting has emerged as the primary obstacle in bringing this technology to commercial fruition. Here, we construct a heterostructure, which consists of MoS2/TiO2/Au nanoparticles (NPs) to overcome the drawbacks of the photoanode. Owing to the dependence on charge transfer, the bandgap of MoS2/TiO2and the utilization the Au NPs as a stimulant for charges separation of TiO2by localized surface plasmon resonances effect as well as the increase of hot electron injection to cathode, leading to photocatalytic activities are improved. The results have recorded a significant increase in the photocurrent density from 2.3µAcm-2of TiO2to approximately 16.3µAcm-2of MoS2/TiO2/Au NPs. This work unveils a promising route to enhance the visible light adsorption and charge transfer in photo-electrode of the PEC cells by combining two-dimensional materials with metal NPs.

Stability and chemical bonding in a series of inverse sandwich actinide boride clusters (An2B8) with δ bonding.

An inverse sandwich structure has been computationally predicted for uranium boride and extended to the series of actinide elements (An) from Th to Cm. The electronic structure and chemical bonding of these novel compounds have been analyzed using density functional theory and multireference wave-function based methods. We report the trends in electronic structure and bonding for An2B8, and found that (d-π)π and (d-p)δ are the most important factors in the stability of An2B8. The (f-p)δ bond provides extra stabilization for Pa2B8 and U2B8, owing to the extensive interactions of An-B8-An, resulting in a short distance for the Pa-Pa and U-U bonds.

A novel small-molecule PCSK9 inhibitor E28362 ameliorates hyperlipidemia and atherosclerosis.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the epidermal growth factor precursor homologous domain A (EGF-A) of low-density lipoprotein receptor (LDLR) in the liver and triggers the degradation of LDLR via the lysosomal pathway, consequently leading to an elevation in plasma LDL-C levels. Inhibiting PCSK9 prolongs the lifespan of LDLR and maintains cholesterol homeostasis in the body. Thus, PCSK9 is an innovative pharmacological target for treating hypercholesterolemia and atherosclerosis. In this study, we discovered that E28362 was a novel small-molecule PCSK9 inhibitor by conducting a virtual screening of a library containing 40,000 compounds. E28362 (5, 10, 20 µM) dose-dependently increased the protein levels of LDLR in both total protein and the membrane fraction in both HepG2 and AML12 cells, and enhanced the uptake of DiI-LDL in AML12 cells. MTT assay showed that E28362 up to 80 µM had no obvious toxicity in HepG2, AML12, and HEK293a cells. The effects of E28362 on hyperlipidemia and atherosclerosis were evaluated in three different animal models. In high-fat diet-fed golden hamsters, administration of E28362 (6.7, 20, 60 mg·kg-1·d-1, i.g.) for 4 weeks significantly reduced plasma total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C) and PCSK9 levels, and reduced liver TC and TG contents. In Western diet-fed ApoE-/- mice (20, 60 mg·kg-1·d-1, i.g.) and human PCSK9 D374Y overexpression mice (60 mg·kg-1·d-1, i.g.), administration of E28362 for 12 weeks significantly decreased plasma LDL-C levels and the area of atherosclerotic lesions in en face aortas and aortic roots. Moreover, E28362 significantly increased the protein expression level of LDLR in the liver. We revealed that E28362 selectively bound to PCSK9 in HepG2 and AML12 cells, blocked the interaction between LDLR and PCSK9, and induced the degradation of PCSK9 through the ubiquitin-proteasome pathway, which finally resulted in increased LDLR protein levels. In conclusion, E28362 can block the interaction between PCSK9 and LDLR, induce the degradation of PCSK9, increase LDLR protein levels, and alleviate hyperlipidemia and atherosclerosis in three distinct animal models, suggesting that E28362 is a promising lead compound for the treatment of hyperlipidemia and atherosclerosis.

Initial arch wires used in orthodontic treatment with fixed appliances.

BACKGROUND: Initial arch wires are the first arch wires inserted into fixed appliance at the beginning of orthodontic treatment. With a number of different types of orthodontic arch wires available for initial tooth alignment, it is important to understand which are most efficient and which cause the least amount of root resorption and pain during the initial aligning stage of treatment. This is the third update of a Cochrane review first published in 2010. OBJECTIVES: To assess the effects of initial arch wires for the alignment of teeth with fixed orthodontic braces, in terms of the rate of tooth alignment, amount of root resorption accompanying tooth movement, and intensity of pain experienced by patients during the initial alignment stage of treatment. SEARCH METHODS: We searched Cochrane Oral Health's Trials Register, CENTRAL, MEDLINE, Embase, and two ongoing trials registries on 4 July 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of different initial arch wires used to align teeth with fixed orthodontic braces. We included people with full-arch fixed orthodontic appliances on the upper arch, lower arch, or both arches. DATA COLLECTION AND ANALYSIS: Two independent review authors were responsible for study selection, data extraction, and assessment of risk of bias in included studies. We contacted corresponding authors of included studies to obtain missing information. We resolved disagreements by discussion between the review authors. Our main outcomes were alignment rate (movement of teeth in mm), root resorption, time to alignment, and intensity of pain measured on a 100-mm visual analogue scale (VAS). We pooled data from studies with similar interventions and outcomes using random-effects models. We reported mean differences (MDs) with 95% confidence intervals (CIs) for continuous data, risk ratios (RRs) with 95% CIs for dichotomous data, and alignment rate ratios with 95% CIs for time-to-event data. Two independent review authors assessed the certainty of evidence. We resolved disagreements by discussion between the review authors. MAIN RESULTS: We included 29 RCTs with 1915 participants (2581 arches) in this review. Studies were generally small (sample sizes ranged from 14 to 200 participants). Duration of follow-up varied between three days and six months. Eleven studies received funding, six received no funding, and 12 provided no information about funding sources. We judged eight studies at high risk of bias, nine at low risk, and 12 at unclear risk. We grouped the studies into six main comparisons. Multistrand stainless steel wires versus wires composed of other materials Six studies with 409 participants (545 arches) evaluated multistrand stainless steel (StSt) wires versus wires composed of other materials. We are very uncertain about the effect of multistrand StSt wires versus other wires on alignment rate (4 studies, 281 participants, 417 arches; very low-certainty evidence). There may be little to no difference between multistrand StSt wires and other wires in terms of intensity of pain (MD -2.68 mm, 95% CI -6.75 to 1.38; 2 studies, 127 participants, 127 arches; low-certainty evidence). Conventional nickel-titanium wires versus superelastic nickel-titanium wires Four studies with 266 participants (274 arches) evaluated conventional nickel-titanium (NiTi) wires versus superelastic NiTi wires. There may be little to no difference between the different wire types in terms of alignment rate (124 participants, 124 arches, 2 studies; low-certainty evidence) and intensity of pain (MD -0.29 mm, 95% CI -1.10 to 0.52; 2 studies, 142 participants, 150 arches; low-certainty evidence). Conventional nickel-titanium wires versus thermoelastic copper-nickel-titanium wires Three studies with 210 participants (210 arches) evaluated conventional Ni-Ti versus thermoelastic copper-nickel-titanium (CuNiTi) wires. We are very uncertain about the effects of the different arch wires on alignment rate (1 study, 66 participants, 66 arches; very low-certainty evidence). There may be little to no difference between conventional NiTi wires and thermoelastic CuNiTi wires in terms of time to alignment (alignment rate ratio 1.30, 95% CI 0.68 to 2.50; 1 study, 60 participants, 60 arches; low-certainty evidence). Superelastic nickel-titanium wires versus thermoelastic nickel-titanium wires Twelve studies with 703 participants (936 arches) evaluated superelastic NiTi versus thermoelastic NiTi wires. There may be little to no difference between superelastic NiTi wires and thermoelastic NiTi wires in alignment rate at four weeks (MD -0.28 mm, 95% CI 0.62 to 0.06; 5 studies, 183 participants, 183 arches; low-certainty evidence). We are very uncertain about the effects of the different wires on root resorption (2 studies, 52 participants, 312 teeth; very low-certainty evidence). Superelastic NiTi wires compared with thermoelastic NiTi wires may result in a slight increase in time to alignment (MD 0.5 months, 95% CI 0.21 to 0.79; 1 study, 32 participants, 32 arches; low-certainty evidence) but are probably associated with a slight increase in intensity of pain (MD 6.96 mm, 95% CI 1.82 to 12.10; 3 studies, 94 participants, 138 arches, moderate-certainty evidence). Single-strand superelastic nickel-titanium wires versus coaxial superelastic nickel-titanium wires Three studies with 104 participants (104 arches) evaluated single-strand superelastic NiTi versus coaxial superelastic NiTi wires. Use of single-strand superelastic NiTi wires compared with coaxial superelastic NiTi wires probably results in a slight reduction in alignment rate at four weeks (MD -2.64 mm, 95% CI -4.61 to -0.67; 2 studies, 64 participants, 64 arches, moderate-certainty evidence). Different sizes of nickel-titanium wires Two studies with 149 participants (232 arches) compared different types of NiTi wires. There may be little to no difference between different sizes of NiTi wires in terms of pain (low-certainty evidence). AUTHORS' CONCLUSIONS: Superelastic NiTi wires probably produce slightly more pain after one day than thermoelastic NiTi wires, and single-strand superelastic NiTi wires probably have a lower alignment rate over four weeks compared with coaxial superelastic NiTi wires. All other evidence on alignment rate, root resorption, time to alignment, and pain is of low or very low certainty in all comparisons. Therefore, there is insufficient evidence to determine whether any particular arch wire material or size is superior to any other. The findings of this review are imprecise and unreliable; well-designed larger studies are needed to give better estimates of the benefits and harms of different arch wires. Orthodontists should exercise caution when interpreting the findings of this review and be prepared to adapt their treatment plans based on individual patient needs.

Diagnosis of colorectal cancer based on folate receptor-positive circulating tumor cell analysis: a retrospective cohort study.

BACKGROUND: Early diagnosis and treatment are crucial to improve the prognosis of colorectal cancer (CRC). At present, there is a lack of an accurate CRC screening factor. We conducted folate receptor-positive circulating tumor cell analysis (FR + CTC analysis) in distinguishing CRC from benign colorectal diseases to evaluate the diagnostic efficiency. METHODS: Clinical data of patients admitted to The First Affiliated Hospital of Anhui Medical University from January 2021 to July 2022 were retrospectively collected. Levels of FR + CTC and other indicators were analyzed. Receiver operating characteristic (ROC) analysis was performed to assess the diagnostic performance of these molecular biomarkers. RESULTS: Data of 103 patients with CRC and 54 patients with benign colorectal diseases were collected. FR + CTC levels were observed significantly higher in CRC patients than in patients with benign colorectal diseases (P < 0.001). FR + CTC level was correlated with tumor diameter, differentiation, T-stage, pathological stage, clinical stage, and intravascular tumor thrombus in patients with CRC (P < 0.05). The optimal cutoff value of FR + CTC level for diagnosing CRC patients was 7.66 FU/3 ml, with a sensitivity of 85.4%, a specificity of 74.1%, and an Area Under Curve (AUC) of 0.855 (95% CI 0.77-0.923). In < 50-years old patients with CRC, the diagnostic efficiency of FR + CTC was excellent, with an AUC of 0.936 (95% CI 0.877-0.995). CONCLUSION: FR + CTC counting has excellent diagnostic efficiency in screening of CRC. FR + CTC count can also predict the tumor stage of CRC patients before surgery, and guide the choice of treatment.

Blocking Gremlin1 inhibits M1 macrophage polarization through Notch1/Hes1 signaling pathway in apical periodontitis.

BACKGROUND: Gremlin1 is a multifunctional protein whose expression is demonstrated to be involved in a series of physiology and pathological processes. The association between Gremlin1 and apcial periodontitis (AP) has been established. M1-polarized macrophages are crucial immune cells that exacerbate the progression of apical periodontal inflammatory response, but the function of Gremlin1 during macrophages activation in periapical lesions is still unclear. This study attempts to explore the regulatory effects of Gremlin1 on macrophage polarization on apical periodontitis microenviroment. METHODS: Clinical specimens were used to determine the expression of Gremlin1 in periapical tissues by immunohistochemical (IHC) staining. Then, the disease models of periapical inflammation in rats were established, and adenovirus- associated virus (AAVs) was used to blockade Gremlin1 expression. Lentivirus carrying sh-Gremlin1 particles were used to transfect THP-1 induced M1-subtype macrophages. To assess the expression of associated molecules, Western-blot, immunofluorescence staining were performed. RESULTS: Gremlin1 was significantly up-regulated in the periapical tissues of subjects with AP as identified by IHC staining, and positively correlated with levels of M1 macrophage-associated genes. Rats AP model with inhibition of Gremlin1 in periapical lesions exhibited limited infiltration of macrophages and decreased expression of M1 macrophage-related genes in periapical lesions. Furthermore, Gremlin1 blockade substantially decreased the Notch1/Hes1 signaling pathway activation level. The in vitro experiments confirmed the above results. CONCLUSION: Taken together, current study illustrated that the Gremlin1 suppression in periapical lesions inhibited M1 macrophage polarization through Notch1/Hes1 axis. Moreover, Gremlin1 may act as a potential candidate in the treatment of AP.

Predicting 1 Repetition Maximum Squat With Peak Force Obtained From Isometric Squat at Multiple Positions.

ABSTRACT: Tan, WZN and Lum, D. Predicting 1 repetition maximum squat with peak force obtained from isometric squat at multiple positions. J Strength Cond Res XX(X): 000-000, 2024-This study investigated whether the use of peak force (PF) obtained from multiple joint positions during isometric squat (IsoSqt) can predict of 1-repetition maximum (1RM) squat with high precision. Twenty-nine male and female resistance-trained athletes (age = 23.0 ± 3.7 years, height = 1.57 ± 0.06 m, body mass = 56.6 ± 9.1 kg, 1RM squat = 104.6 ± 24.2) performed the 1RM squat, and IsoSqt at 60°, 90°, and 120° knee angles on 3 separate occasions. Peak force obtained from IsoSqt at all positions significantly correlated with 1RM squat (r = 0.684-0.940, p < 0.05). Linear regression analysis based on group data showed r2 = 0.903, based on male data only, r2 = 0.826, and based on female data only, r2 = 0.855. Predicted 1RM squat using linear regression equations based on group, male-only, and female-only data showed nonsignificant differences of 0.02-0.6% from actual 1RM squat (p = 0.812-0.947, 95% CI = -8.00 to 10.08), with error of estimate of 1.5-2.3%. In addition, Bland-Altman analysis showed a mean bias of -1.04 to 0.35 kg, 95% CI = -10.08 to 8.00 kg. The results showed that using PF obtained from IsoSqt at multiple positions was able to predict 1RM squat with low difference from actual 1RM squat. Furthermore, using linear regression equation derived from gender-specific data was able to predict 1RM squat with higher precision than that based on group data.

Flexible Substrate-Compatible and Efficiency-Improved Quantum-Dot Light-Emitting Diodes with Reduced Annealing Temperature of NiOx Hole-Injecting Layer.

The growing demand for wearable and attachable displays has sparked significant interest in flexible quantum-dot light-emitting diodes (QLEDs). However, the challenges of fabricating and operating QLEDs on flexible substrates persist due to the lack of stable and low-temperature processable charge-injection/-transporting layers with aligned energy levels. In this study, we utilized NiOx nanoparticles that are compatible with flexible substrates as a hole-injection layer (HIL). To enhance the work function of the NiOx HIL, we introduced a self-assembled dipole modifier called 4-(trifluoromethyl)benzoic acid (4-CF3-BA) onto the surface of the NiOx nanoparticles. The incorporation of the dipole molecules through adsorption treatment has significantly changed the wettability and electronic characteristics of NiOx nanoparticles, resulting in the formation of NiO(OH) at the interface and a shift in vacuum level. The alteration of surface electronic states of the NiOx nanoparticles not only improves the carrier balance by reducing the hole injection barrier but also prevents exciton quenching by passivating defects in the film. Consequently, the NiOx-based red QLEDs with interfacial modification demonstrate a maximum current efficiency of 16.1 cd/A and a peak external quantum efficiency of 10.3%. This represents a nearly twofold efficiency enhancement compared to control devices. The mild fabrication requirements and low annealing temperatures suggest potential applications of dipole molecule-modified NiOx nanoparticles in flexible optoelectronic devices.

Rapid Screening of 34 Emerging Contaminants in Surface Water by UHPLC-Q-TOF-MS.

OBJECTIVES: To establish a rapid screening method for 34 emerging contaminants in surface water by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry (UHPLC-Q-TOF-MS). METHODS: The pretreatment conditions of solid phase extraction (SPE) were optimized by orthogonal experimental design and the surface water samples were concentrated and extracted by Oasis® HLB and Oasis® MCX SPE columns in series. The extracts were separated by Kinetex® EVO C18 column, with gradient elution of 0.1% formic acid aqueous solution and 0.1% formic acid methanol solution. Q-TOF-MS 'fullscan' and 'targeted MS/MS' modes were used to detect 34 emerging contaminants and to establish a database with 34 emerging contaminants precursor ion, product ion and retention times. RESULTS: The 34 emerging contaminants exhibited good linearity in the concentration range respectively and the correlation coefficients (r) were higher than 0.97. The limit of detection was 0.2-10 ng/L and the recoveries were 81.2%-119.2%. The intra-day precision was 0.78%-18.70%. The method was applied to analyze multiple surface water samples and 6 emerging contaminants were detected, with a concentration range of 1.93-157.71 ng/L. CONCLUSIONS: The method is simple and rapid for screening various emerging contaminants at the trace level in surface water.

Toxicokinetics of MDMA and Its Metabolite MDA in Rats.

OBJECTIVES: To investigate the toxicokinetic differences of 3,4-methylenedioxy-N-methylamphetamine (MDMA) and its metabolite 4,5-methylene dioxy amphetamine (MDA) in rats after single and continuous administration of MDMA, providing reference data for the forensic identification of MDMA. METHODS: A total of 24 rats in the single administration group were randomly divided into 5, 10 and 20 mg/kg experimental groups and the control group, with 6 rats in each group. The experimental group was given intraperitoneal injection of MDMA, and the control group was given intraperitoneal injection of the same volume of normal saline as the experimental group. The amount of 0.5 mL blood was collected from the medial canthus 5 min, 30 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h after administration. In the continuous administration group, 24 rats were randomly divided into the experimental group (18 rats) and the control group (6 rats). The experimental group was given MDMA 7 d by continuous intraperitoneal injection in increments of 5, 7, 9, 11, 13, 15, 17 mg/kg per day, respectively, while the control group was given the same volume of normal saline as the experimental group by intraperitoneal injection. On the eighth day, the experimental rats were randomly divided into 5, 10 and 20 mg/kg dose groups, with 6 rats in each group. MDMA was injected intraperitoneally, and the control group was injected intraperitoneally with the same volume of normal saline as the experimental group. On the eighth day, 0.5 mL of blood was taken from the medial canthus 5 min, 30 min, 1 h, 1.5 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h after administration. Liquid chromatography-triple quadrupole tandem mass spectrometry was used to detect MDMA and MDA levels, and statistical software was employed for data analysis. RESULTS: In the single-administration group, peak concentrations of MDMA and MDA were reached at 5 min and 1 h after administration, respectively, with the largest detection time limit of 12 h. In the continuous administration group, peak concentrations were reached at 30 min and 1.5 h after administration, respectively, with the largest detection time limit of 10 h. Nonlinear fitting equations for the concentration ratio of MDMA and MDA in plasma and administration time in the single-administration group and continuous administration group were as follows: T=10.362C-1.183, R2=0.974 6; T=7.397 3C-0.694, R2=0.961 5 (T: injection time; C: concentration ratio of MDMA to MDA in plasma). CONCLUSIONS: The toxicokinetic data of MDMA and its metabolite MDA in rats, obtained through single and continuous administration, including peak concentration, peak time, detection time limit, and the relationship between concentration ratio and administration time, provide a theoretical and data foundation for relevant forensic identification.

Ligand-solvent coordination enables comprehensive trap passivation for efficient quantum dot near-infrared light-emitting diodes.

Near-infrared light-emitting diodes (NIR LEDs) based on perovskite quantum dots (QDs) have produced external quantum efficiency (EQE) of ~15%. However, these high-performance NIR-QLEDs suffer from immediate carrier quenching because of the accumulation of migratable ions at the surface of the QDs. These uncoordinated ions and carriers - if not bound to the nanocrystal surface - serve as centers for exciton quenching and device degradation. In this work, we overcome this issue and fabricate high-performance NIR QLEDs by devising a ligand anchoring strategy, which entails dissolving the strong-binding ligand (Guanidine Hydroiodide, GAI) in the mediate-polar solvent. By employing the dye-sensitized device structure (phosphorescent indicator), we demonstrate the elimination of the interface defects. The treated QDs films exhibit an exciton binding energy of 117 meV: this represents a 1.5-fold increase compared to that of the control (74 meV). We report, as a result, the NIR QLEDs with an EQE of 21% which is a record among NIR perovskite QLEDs. These QLEDs also exhibit a 7-fold higher operational stability than that of the best previously reported NIR QLEDs. Furthermore, we demonstrate that the QDs are compatible with large-area QLEDs: we showcase 900 mm2 QLEDs with EQE approaching 20%.

[Identification of lncrnas associated with aniline toxicity in male bladder cancer and construction of tumor risk prediction models].

OBJECTIVE: Aniline poisoning is considered to be an important factor mediating the development and progression of male bladder cancer,and long non-coding RNA(lncRNA)has also been shown to affect the prognosis of male bladder cancer.Therefore,this study intended to screen and identify lncrnas associated with highly sensitive aniline poisoning of male bladder cancer,and to construct a tumor risk prediction model accordingly. METHODS: Gene expression and clinical data from 410 tissues were downloaded from the Cancer Genome Atlas(TCGA),and all samples were randomly divided into training and testing groups.Lncrnas associated with aniline poisoning were distinguished.We then performed univariate COX and multivariate COX regressions,in parallel with LASSO regression,to establish a lncRNA risk model associated with aniline poisoning.Kaplan-Meier curve,scatterplot,C-index,ROCcurve,nomogram,PCAanalysis,and univariate and multivariate Cox regression were used to test the accuracy of the risk model and predict patient survival. RESULTS: Seven lncrnas associated with aniline poisoning(LINC01184, LINC00513,LINC02443,SMARCA5-AS1,BDNF-AS,SOD2-OT1,HYI-AS1)were screened and identified,and based on this,a risk prediction model with high sensitivity to the malignant progression of bladder cancer was constructed.It is also verified that the model can effectively predict the overall survival(OS)of the test group and the whole cohort at different stages. CONCLUSIONS: We identified 7 lncrnas associated with aniline poisoning and established a novel risk model of lncrnas associated with aniline poisoning,which provides new insights for prognosis assessment and may guide the comprehensive treatment of male bladder cancer.

Anti-aging effects of icariin and the underlying mechanisms: A mini-review.

Aging is an extremely intricate and progressive phenomenon that is implicated in many physiological and pathological conditions. Icariin (ICA) is the main active ingredient of Epimedium and has exhibited multiple bioactivities, such as anti-tumor, neuroprotective, antioxidant, anti-inflammatory, and anti-aging properties. ICA could extend healthspan in both invertebrate and vertebrate models. In this review, the roles of ICA in protection from declined reproductive function, neurodegeneration, osteoporosis, aging intestinal microecology, and senescence of cardiovascular system will be summarized. Furthermore, the underlying mechanisms of ICA-mediated anti-aging effects will be introduced. Finally, we will discuss some key aspects that constrain the usage of ICA in clinical practice and the corresponding strategies to solve these issues.