Tailorable Fluorescent Perovskite Quantum Dots for Multiform Manufacturing via Two-Step Thiol-Ene Click Chemistry.

In practical applications, fluorescent perovskite quantum dots (PQDs) must exhibit high efficiency, stability, and processibility. So far, it remains a challenge to synthesize PQDs with stable dispersibility in tailorable monomers both before and after photocuring. In this work, a novel strategy of UV-induced two-step thiol-ene "click chemistry" is proposed to prepare PQDs with these attributes. The first step aims to epitaxially grow a shell around the PQD core to ensure stable dispersibility in a thiol-ene monomer solution. The second step is to achieve stable dispersibility in the photocured thiol-ene matrixes for multiform manufacturing processes. The tailorable PQDs (T-PQDs) not only have the highest photoluminescence quantum yield (PLQY) to ≈100% for green emission and over 96% for red emission, but also exhibit remarkable stability under severe conditions, including "double 85" aging, water exposure, and mechanical stress. Moreover, their exceptional processability allows for various processing techniques, including slot-die coating, inkjet printing, direct-laser writing, UV-light 3D printing, nanoimprinting, and spin coating. The high efficiency and stability of T-PQDs facilitate their multiform manufacturing for a wide range of applications.

A causal relationship between bone mineral density and breast cancer risk: a mendelian randomization study based on east Asian population.

BACKGROUND: Breast cancer (BC) poses significant burdens on women globally. While past research suggests a potential link between bone mineral density (BMD) and BC risk, findings remain inconsistent. Our study aims to elucidate the causal relationship between BMD and BC in East Asians using bidirectional Mendelian randomization (MR). METHODS: Genetic association data for bone mineral density T-scores (BMD-T) and Z-scores (BMD-Z) (Sample size = 92,615) and BC from two different sources (Sample size1 = 98,283; Sample size2 = 79,550) were collected from publicly available genome-wide association studies (GWAS). Single-nucleotide polymorphisms (SNPs) associated with BMD-T and BMD-Z as phenotype-related instrumental variables (IVs) were used, with BC as the outcome. As the primary means of causal inference, the inverse variance weighted (IVW) approach was employed. Heterogeneity analysis was conducted using Cochran's Q test, while MR-Egger regression analysis was implemented to assess the pleiotropic effects of the IVs. Sensitivity analyses were performed using methods such as MR-Egger, weighted median, and weighted mode to analyze the robustness and reliability of the results. The MR-PRESSO method and the RadialMR were used to detect and remove outliers. The PhenoScanner V2 website was utilized to exclude confounding factors shared between BMD and BC. Besides, the Bonferroni correction was also used to adjust the significance threshold. Then, the meta-analysis method was applied to combine the MR analysis results from the two BC sources. Finally, a reverse MR analysis was conducted. RESULTS: The results of the IVW method were consolidated through meta-analysis, revealing a positive correlation between genetically predicted BMD-T ([Formula: see text], [Formula: see text], [Formula: see text]) and BMD-Z ([Formula: see text],[Formula: see text], [Formula: see text]) with increased BC risk. The Cochran's [Formula: see text] test and MR-Egger regression suggested that neither of these causal relationships was affected by heterogeneity or horizontal pleiotropy. The sensitivity analyses supported the IVW results, indicating the robustness of the findings. Reverse MR analysis showed no causal relationship between BC and BMD. CONCLUSION: Our MR study results provide evidence for the causal relationship between BMD and BC risk in East Asian populations, suggesting that BMD screening is of great significance in detecting and preventing BC.

Urban meteorological drought comprehensive index based on a composite fuzzy matter element-moment estimation weighting model.

Due to rapid urbanization and climate change, cities face hidden drought risks. A single drought index may inadequately reflect urban meteorological drought. The indicator weight combination method does not fully consider index correlation and weight. This study constructed an urban meteorological drought evaluation index system and developed the Composite Fuzzy Matter Element Meteorological drought Comprehensive Index (CFEMCI) by combining the moment estimation weighting model. Analyzing Zhengzhou City from 2000 to 2019, CFEMCI effectively captured meteorological drought events, with a probability of detection (POD) > 0.78, critical success index (CSI) > 0.70, false alarm rate (FAR) < 0.13 and failure ratio (FR) < 0.22. Most meteorological droughts were classified as Grade I (no drought), with 26% being light and moderate (Grades II-III). Droughts mainly occurred in spring, and the summer drought showed a more significantly aggravating trend. This index provides reliable urban drought monitoring and supports disaster prevention and mitigation efforts.

Real-time mapping of photo-sono therapy induced cavitation using Doppler optical coherence tomography.

Photo-sono therapy (PST) is an innovative anti-vascular approach based on cavitation-induced spallation. Currently, passive cavitation detection (PCD) is the prevalent technique for cavitation monitoring during treatment. However, the limitations of PCD are the lack of spatial information of bubbles and the difficulty of integration with the PST system. To address this, we proposed a new, to the best of our knowledge, cavitation mapping method that integrates Doppler optical coherence tomography (OCT) with PST to visualize bubble dynamics in real time. The feasibility of the proposed system has been confirmed through experiments on vascular-mimicking phantoms and in vivo rabbit ear vessels, and the results are compared to high-speed camera observations and PCD data. The findings demonstrate that Doppler OCT effectively maps cavitation in real time and holds promise for guiding PST treatments and other cavitation-related clinical applications.

Concrete Defect Localization Based on Multilevel Convolutional Neural Networks.

Concrete structures frequently manifest diverse defects throughout their manufacturing and usage processes due to factors such as design, construction, environmental conditions and distress mechanisms. In this paper, a multilevel convolutional neural network (CNN) combined with array ultrasonic testing (AUT) is proposed for identifying the locations of hole defects in concrete structures. By refining the detection area layer by layer, AUT is used to collect ultrasonic signals containing hole defect information, and the original echo signal is input to CNN for the classification of hole locations. The advantage of the proposed method is that the corresponding defect location information can be obtained directly from the input ultrasonic signal without manual discrimination. It effectively addresses the issue of traditional methods being insufficiently accurate when dealing with complex structures or hidden defects. The analysis process is as follows. First, COMSOL-Multiphysics finite element software is utilized to simulate the AUT detection process and generate a large amount of ultrasonic echo data. Next, the extracted signal data are trained and learned using the proposed multilevel CNN approach to achieve progressive localization of internal structural defects. Afterwards, a comparative analysis is conducted between the proposed multilevel CNN method and traditional CNN approaches. The results show that the defect localization accuracy of the proposed multilevel CNN approach improved from 85.38% to 95.27% compared to traditional CNN methods. Furthermore, the computation time required for this process is reduced, indicating that the method not only achieves higher recognition precision but also operates with greater efficiency. Finally, a simple experimental verification is conducted; the results show that this method has strong robustness in recognizing noisy ultrasonic signals, provides effective solutions, and can be used as a reference for future defect detection.

Hirudin delays the progression of diabetic kidney disease by inhibiting glomerular endothelial cell migration and abnormal angiogenesis.

BACKGROUND: In the early stages of diabetic kidney disease (DKD), the pathogenesis involves abnormal angiogenesis in the glomerulus. Hirudin, as a natural specific inhibitor of thrombin, has been shown in previous studies to inhibit the migration of various tumor endothelial cells and abnormal angiogenesis. However, its role in DKD remains unclear. METHODS: The effects of hirudin in DKD were studied using spontaneous type 2 diabetic db/db mice (which develop kidney damage at 8 weeks). Network pharmacology was utilized to identify relevant targets. An in vitro high glucose model was established using mouse glomerular endothelial cells (MGECs) to investigate the effects of hirudin on the migration and angiogenic capacity of MGECs. RESULTS: Hirudin can ameliorate kidney damage in db/db mice. Network pharmacology suggests its potential association with the VEGFA/VEGFR2 pathway. Western blot and immunohistochemistry demonstrated elevated protein expression levels of VEGFA, VEGFR2, AQP1, and CD31 in db/db mice, while hirudin treatment reduced their expression. In the MGECs high glucose model, hirudin may reverse the enhanced migration and angiogenic capacity of MGECs in a high glucose environment by altering the expression of VEGFA, VEGFR2, AQP1, and CD31. Moreover, the drug effect gradually increases with higher concentrations of hirudin. CONCLUSIONS: This study suggests that hirudin can improve early-stage diabetic kidney disease kidney damage by inhibiting the migration and angiogenesis of glomerular endothelial cells, thereby further expanding the application scope of hirudin. Additionally, the study found increased expression of AQP1 in DKD, providing a new perspective for further research on the potential pathogenesis of DKD.

Model informed drug development: HSK21542 PBPK model supporting dose decisions in specific populations.

HKS21542, a highly selective activator of peripheral kappa opioid receptor agonists, plays a critical role in antinociception and itch inhibition during clinical development. Due to its indication population and elimination characteristics, it is imperative to evaluate the potential HSK21542 systemic exposure in individuals with renal impairment, hepatic impairment, the elderly, and the geriatric population. Here, a physiologically-based pharmacokinetic (PBPK) model for HSK21542 was developed based on in vitro metabolism and transport characteristics and in vivo elimination mechanism. Meanwhile, the potential systemic exposure of HSK21542 in specific populations was evaluated. The predicted results indicated increased systemic exposure in patients with renal impairment, hepatic impairment and in the elderly. Compared to the healthy volunteers aged 20-60 years, the AUC0-24h increased by 52 %-71 % in population with moderate to severe renal impairment, by 46 %-77 % in those with mild to severe hepatic impairment, and by 45 %-85 % in the elderly population aged 65-95-years. Conversely, the pediatric population demonstrated a potential decrease in systemic exposure, ranging from 20 % to 37 % in patients aged 0-17 years due to the physiological characteristics. Combined with the predicted results and the exposure-response relationship observed for HSK21542 and its analog (CR845), dosage regimens were designed for the target population with renal and hepatic impairment, supporting the successfully conducted trials (CTR20201702 and CTR20211940). Moreover, the observed exposure of HSK21542 in the elderly closely matched the predicted results within the same age group. Additionally, based on the predicted results, potential reductions in systemic exposure in pediatric patients should be carefully considered to avoid potential treatment failure in future clinical trials.

Biotransformation and disposition characteristics of HSK7653, a novel long-acting dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes.

AIM: To investigate the metabolism and disposition characteristics of HSK7653 in healthy male Chinese participants. METHODS: A single oral dose of 80 µCi (25 mg) [14C]HSK7653 capsules was administered to six healthy participants, and blood, plasma, urine and faeces were collected. Quantitative and qualitative analysis was conducted to investigate the pharmacokinetics, blood-to-plasma ratio, mass balance and metabolism of HSK7653. RESULTS: The drug was well absorbed and reached a maximum concentration at 1.25 h. The drug-related components (HSK7653 and its metabolites) were eliminated slowly, with a half-life (t1/2) of 111 h. Unchanged HSK7653 contributed to more than 97% of the total radioactivity in all plasma samples. The blood-to-plasma ratio (0.573-0.845) indicated that HSK7653 did not tend to distribute into blood cells. At 504 h postdose, up to 95.9% of the dose was excreted, including 79.8% in urine and 16.1% in faeces. Most of the radioactivity (75.5% dose) in excreta was unchanged HSK7653. In addition, nine metabolites were detected in urine and faeces. The most abundant metabolite was M6-2, a dioxidation product of HSK7653, which accounted for 4.73% and 2.63% of the dose in urine and faeces, respectively. The main metabolic pathways of HSK7653 in vivo included oxidation, pyrrole ring opening and sulphonamide hydrolysation. CONCLUSION: HSK7653 was well absorbed, slightly metabolized and slowly excreted in humans. The high plasma exposure and long t1/2 of HSK7653 may contribute to its long-lasting efficacy as a long-acting dipeptidyl peptidase-4 inhibitor.

Evaluating the effect of pulse energy on femtosecond laser trabeculotomy (FLT) outflow channels for glaucoma treatment in human cadaver eyes.

BACKGROUND AND OBJECTIVES: Femtosecond laser trabeculotomy (FLT) creates aqueous humor outflow channels through the trabecular meshwork (TM) and is an emerging noninvasive treatment for open-angle glaucoma. The purpose of this study is to investigate the effect of pulse energy on outflow channel creation during FLT. MATERIALS AND METHODS: An FLT laser (ViaLase Inc.) was used to create outflow channels through the TM (500 µm wide by 200 µm high) in human cadaver eyes using pulse energies of 10, 15, and 20 µJ. Following treatment, tissues were fixed in 4% paraformaldehyde. The channels were imaged using optical coherence tomography (OCT) and assessed as full thickness, partial thickness, or not observable. RESULTS: Pulse energies of 15 and 20 µJ had a 100% success rate in creating full-thickness FLT channels as imaged by OCT. A pulse energy of 10 µJ resulted in no channels (n = 6), a partial-thickness channel (n = 2), and a full-thickness FLT channel (n = 2). There was a statistically significant difference in cutting widths between the 10 and 15 µJ groups (p < 0.0001), as well as between the 10 and 20 µJ groups (p < 0.0001). However, there was no statistically significant difference between the 15 and 20 µJ groups (p = 0.416). CONCLUSIONS: Fifteen microjoules is an adequate pulse energy to reliably create aqueous humor outflow channels during FLT in human cadaver eyes. OCT is a valuable tool when evaluating FLT.

Associations of pyrethroid exposure with bone mineral density and osteopenia in adults.

INTRODUCTION: This study was to investigate the correlations between pyrethroid exposure and bone mineral density (BMD) and osteopenia. MATERIALS AND METHODS: This cross-sectional study included 1389 participants over 50 years of age drawn from the 2007-2010 and 2013-2014 National Health and Nutrition Examination Survey (NHANES). Three pyrethroid metabolites, 3-phenoxybenzoic acid (3-PBA), trans-3-(2,2-dichlorovinyl)-2,2-dimethyl-cyclopropane-1-carboxylic acid (trans-DCCA), and 4-fluoro-3-phenoxybenzoic acid (4-F-3PBA) were used as indicators of pyrethroid exposure. Low BMD was defined as T-score < - 1.0, including osteopenia. Weighted multivariable linear regression analysis or logistic regression analysis was utilized to evaluate the correlation between pyrethroid exposure and BMD and low BMD. Bayesian kernel machine regression (BKMR) model was utilized to analyze the correlation between pyrethroids mixed exposure and low BMD. RESULTS: There were 648 (48.41%) patients with low BMD. In individual pyrethroid metabolite analysis, both tertile 2 and tertile 3 of trans-DCCA were negatively related to total femur, femur neck, and total spine BMD [coefficient (ß) = - 0.041 to - 0.028; all P < 0.05]. Both tertile 2 and tertile 3 of 4-F-3PBA were negatively related to total femur BMD (P < 0.05). Only tertile 2 [odds ratio (OR) = 1.63; 95% CI = 1.07, 2.48] and tertile 3 (OR = 1.65; 95% CI = 1.10, 2.50) of trans-DCCA was correlated with an increased risk of low BMD. The BKMR analysis indicated that there was a positive tendency between mixed pyrethroids exposure and low BMD. CONCLUSION: In conclusion, pyrethroids exposure was negatively correlated with BMD levels, and the associations of pyrethroids with BMD and low BMD varied by specific pyrethroids, pyrethroid concentrations, and bone sites.

Small dense low density lipoprotein predominance in patients with type 2 diabetes mellitus using Mendelian randomization.

BACKGROUND: Patients with T2DM often suffer from CVD-related complications, significantly impacting morbidity and mortality rates. The upsurge in CVD prevalence among them is partly linked to sd LDL particles. Understanding the mechanisms behind elevated sd LDL levels is critical for preventing and managing cardiovascular complications in diabetes. METHODS: MR was employed to identify instrumental variables and establish causality, exploring underlying mechanisms. RESULTS: Notably, T2DM itself, insulin resistance, and fasting glucose seemingly do not directly impact sd LDL levels. Instead, the presence of T2DM or insulin resistance, leading to reduced HDL cholesterol or elevated TG levels, directly contributes to subsequent sd LDL increases, indicating a comprehensive mediating effect. While LDL cholesterol levels correlate positively with sd LDL, they appear unaffected by T2DM or insulin resistance. Importantly, hypertension induced by T2DM or insulin resistance exhibits a positive effect on sd LDL reversal. Unlike T2DM or insulin resistance, blood glucose levels show no significant impact on all processes. CONCLUSIONS: It is hoped that these insights might influence the treatment of patients with diabetes and the management of blood parameters in clinical practice. Examining the effect of T2DM or insulin resistance on sd LDL within HDL cholesterol and triglycerides pathways might provide valuable insights for targeted cardiovascular treatments. Additionally, the study's exploration of the potential positive effects of elevated blood pressure on sd LDL reversal may introduce novel considerations for blood pressure management in patients with diabetes.

Genetic analysis and QTL mapping of seed hardness trait in a soybean (Glycine max) recombinant inbred line (RIL) population.

Seed hardness is a critical quality trait impacting both the suitability of soybeans for consumption and their processing. The primary objective of this study was to explore the genetic foundations underlying seed hardness in soybeans. A 234 recombinant inbred line (RIL) population was evaluated for seed hardness across three years (2015 in Gansu, 2016, and 2017 in Hainan). Notably, the parent varieties, Zhonghuang35 and Jindou21, displayed significant differences in seed hardness. Also, the RIL population exhibited a wide range of genetic variation in seed hardness, with coefficients of variation between 70.53 % and 94.94 %. The frequency distribution of this trait conformed to a relatively normal distribution, making it suitable for QTL analysis. Six QTLs associated with seed hardness were identified with three located on chromosome 2 and three on chromosome 16. The major QTL, qHS-2-1, consistently exhibited the highest percentage of PVE and LOD in Gansu 2015, Hainan 2016, and Hainan 2017, suggesting its central role in determining seed hardness. Further investigation revealed four genes within the qHS-2-1 interval potentially related to seed hardness. GO enrichment analysis provided insights into their functions, including factors such as Glyma.02G307000, a pectin lyase-like superfamily protein, which could influence seed hardness through its role in pectin lyase enzyme activity. Expression analysis of these candidate genes demonstrated significant differences between the two parent varieties, further highlighting their potential role in seed coat hardness. This study offers valuable insights into the genetic mechanisms governing soybean seed coat hardness, providing a foundation for future research and crop improvement efforts.

Pharmacokinetics, Pharmacodynamics, and Safety of Single Dose HSK7653 Tablets in Chinese Subjects with Normal or Impaired Renal Function.

OBJECTIVE: HSK7653 is a novel, ultralong-acting dipeptidyl peptidase-4 (DPP-4) inhibitor, promising for type 2 diabetes mellitus with a dosing regimen of once every 2 weeks. This trial investigates the pharmacokinetics (PKs), pharmacodynamics (PDs),and safety of HSK7653 in outpatients with normal or impaired renal function. METHODS: This is a multicenter, open-label, nonrandomized, parallel-controlled phase I clinical study that investigates the pharmacokinetic profiles of HSK7653 after a single oral administration in 42 subjects with mild (n = 8), moderate (n = 10), severe renal impairment (n = 10), and end-stage renal disease (without dialysis, n = 5) compared with matched control subjects with normal renal function (n = 9). Safety was evaluated throughout the study, and the pharmacodynamic effects were assessed on the basis of a DPP-4 inhibition rate. RESULTS: HSK7653 exposure levels including the maximum plasma concentration (Cmax), area under the plasma concentration-time curve from zero to last time of quantifiable concentration (AUC0-t), and area under the plasma concentration-time curve from zero to infinity (AUC0-inf) showed no significant differences related to the severity of renal impairment. Renal clearance (CLR) showed a certain downtrend along with the severity of renal impairment. The CLR of the group with severe renal impairment and the group with end-stage renal disease were basically similar. The DPP-4 inhibition rate-time curve graph was similar among the renal function groups. All groups had favorable safety, and no serious adverse events occurred. CONCLUSIONS: HSK7653 is a potent oral DPP-4 inhibitor with a long plasma half-life, supporting a dosing regimen of once every 2 weeks. Impaired renal function does not appear to impact the pharmacokinetic and pharmacodynamic properties of HSK7653 after a single administration in Chinese subjects. HSK7653 is also well tolerated without an increase in adverse events with increasing renal impairment. These results indicate that dose adjustment of HSK7653 may not be required in patients with renal impairment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05497297.

Quantitative Optical Coherence Elastography of the Optic Nerve Head In Vivo.

OBJECTIVE: Optical coherence elastography (OCE) was used to demonstrate the relationship between the elasticity of the optic nerve head (ONH) and different intraocular pressure (IOP) levels in an in-vivo rabbit model for the first time. METHOD: Both ex-vivo and in-vivo rabbit ONH were imaged using OCE system. A mechanical shaker initiated the propagation of elastic waves, and the elasticity of the ONH was determined by tracking the wave propagation speed. The elasticity of the ONH under varying IOP levels was reconstructed based on the wave speed. Notably, the ONH exhibited increased stiffness with elevated IOP. RESULTS: In the in-vivo rabbit models, the Young's modulus of ONH increased from 14 kPa to 81 kPa with the IOP increased from 15 mmHg to 35 mmHg. This revealed a positive correlation between the Young's modulus of the ONH and intraocular pressure. CONCLUSION: The OCE system proved effective in measuring the mechanical properties of ONH at different IOP levels, with validation in an in-vivo rabbit model. SIGNIFICANCE: Considering ONH plays a critical role in vision and eye diseases, the capability to image and quantify in vivo ONH biomechanical properties has great potential to advance vision science research and improve the clinical management of glaucoma patients.

Adaptive bias-variance trade-off in advantage estimator for actor-critic algorithms.

Actor-critic methods are leading in many challenging continuous control tasks. Advantage estimators, the most common critics in the actor-critic framework, combine state values from bootstrapping value functions and sample returns. Different combinations balance the bias introduced by state values and the variance returned by samples to reduce estimation errors. The bias and variance constantly fluctuate throughout training, leading to different optimal combinations. However, existing advantage estimators usually use fixed combinations that fail to account for the trade-off between minimizing bias and variance to find the optimal estimate. Our previous work on adaptive advantage estimation (AAE) analyzed the sources of bias and variance and offered two indicators. This paper further explores the relationship between the indicators and their optimal combination through typical numerical experiments. These analyses develop a general form of adaptive combinations of state values and sample returns to achieve low estimation errors. Empirical results on simulated robotic locomotion tasks show that our proposed estimators achieve similar or superior performance compared to previous generalized advantage estimators (GAE).

Causal association of physical activity with low back pain, intervertebral disc degeneration and sciatica: a two-sample mendelian randomization analysis study.

Objective: Previous studies are insufficient to confirm a causal association between physical activity (PA) and low back pain (LBP), intervertebral disc degeneration (IDD), and sciatica. The present study used a two-sample Mendelian randomization (MR) analysis method to demonstrate whether or not there was a causal connection. Methods: First, four PA phenotypes were selected [accelerometer-based PA (average acceleration), accelerometer-based PA (acceleration fraction >425 mg), self-reported moderate-to-vigorous PA, and self-reported vigorous PA], setting thresholds for single nucleotide polymorphisms (SNPs) significantly concerned with PA p < 5 × 10-8, linkage disequilibrium (LD) r 2 < 0.01, genetic distance >5,000 kb, and F-value >10. SNPs associated with the outcome and confounding factors were then excluded using the PhenoScanncer database. Finally, after coordinating the genetic instruments from genome-wide association studies (GWAS) effect alleles for exposure and outcomes, multiplicative random effects inverse variance weighting (IVW), MR-Egger, weighted median method (WMM), and weighted mode method were used to assess exposure-outcome causality and perform sensitivity analysis on the estimated results. Results: The current study's IVW findings revealed proof of a causal connection between PA and LBP. While there was a positive causal tie between accelerometer-based PA (acceleration fraction >425 mg) and LBP [OR: 1.818, 95% CI:1.129-2.926, p = 0.012], there was a negative causal link between accelerometer-based PA (average acceleration) and LBP [OR: 0.945, 95% CI: 0.909-0.984, p = 0.005]. However causal relationship between PA and IDD or sciatica was not found. Conclusion: Increasing average PA but needing to avoid high-intensity PA may be an effective means of preventing low back pain. Although PA is not directly causally related to disc degeneration and sciatica, it can act through indirect pathways.

The Chinese version of the brief pain inventory-Facial (BPI-F) among different populations: Factor structure and measurement invariance.

OBJECTIVE: This study aimed to translate and adapt the Brief Pain Inventory-Facial (BPI-F) into Chinese, proposing a validated Chinese version for clinical application. METHODS: To evaluate the applicability of Chinese BPI-F, this study included two groups: clinical sample (406 patients with OFP) and non-clinical sample (514 college students without OFP medical history). Content validity was improved through patient interviews. Cronbach's α was used to evaluate the reliability of BPI-F in both groups. The best-fit factor structure was tested on clinical sample via exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). Convergent and discriminant validity of BPI-F was evaluated by Spearman's coefficient. Serial CFA was used to assess measurement invariance between the two groups. RESULTS: Content validity and reliability of BPI-F were verified. EFA results support a two-factor structure, interference with general activities (1-7 items) and face-specific pain interference (8-14 items). CFA results demonstrated this two-factor structure is appropriate for different populations. Spearman results showed that BPI-F had good convergent and discriminant validity. Full measurement invariance is observed across the two groups. CONCLUSION: The Chinese BPI-F, with two-factor structure (interference with general / orofacial functions), enables accurate assessment of functional interference caused by OFP. BPI-F has the same significance in different clinical populations, which expands its application. CLINICAL SIGNIFICANCE: This manuscript proposed the Chinese version of the BPI-F and examined its psychometric characteristics for the first time. This validated scale provides a favorable instrument for aiding individual diagnosis and treatment for OFP patients in China.

Pharmacokinetics, Mass Balance and Metabolism of [14C]HSK21542, a Novel Kappa Opioid Receptor Agonist, in Humans.

BACKGROUND AND OBJECTIVE: HSK21542, a synthetic short-chain polypeptide, is a selective peripheral kappa opioid receptor (KOR) agonist. In this single-centre, non-randomized, open-label study, the pharmacokinetics, mass balance, metabolism and excretion of HSK21542 were investigated. METHODS: A single intravenous dose of 2 µg/0.212 µCi/kg [14C]HSK21542 was administered to six healthy male subjects. Samples of blood, urine and faeces were collected for quantitative determination of total radioactivity and unchanged HSK21542, and identification of metabolites. RESULTS: The mean total recovery was 81.89% of the radiolabelled dose over 240 h post-dose, with 35.60% and 46.30% excreted in faeces and urine, respectively. The mean maximum concentration (Cmax), the half-life (t1/2) and the area under the concentration-time curve (AUC0-t) of total radioactivity (TRA) in plasma were 20.4 ±4.16 ng Eq./g, 1.93 ± 0.322 h and 21.8 ± 2.93 h·ng Eq./g, respectively, while the Cmax, t1/2 and the AUC0-t of unchanged HSK21542 were 18.3 ± 3.36 ng/mL, 1.66 ± 0.185 h and 18.4 ± 2.24 h·ng/mL, respectively. The blood-to-plasma ratios of TRA at several times ranged from 0.46 to 0.54. [14C]HSK21542 was detected as the main circulating substance in plasma, accounting for 92.17% of the AUC of TRA. The unchanged parent compound was the only major radioactive chemical in urine (100.00% of TRA) and faeces (93.53% of TRA). Metabolites were very minor components. CONCLUSIONS: HSK21542 was barely metabolized in vivo and mainly excreted with unchanged HSK21542 as its main circulating component in plasma. It was speculated that renal excretion was the principal excretion pathway, and faecal excretion was the secondary pathway. CLINICAL TRIAL REGISTRATION NUMBER: NCT05835934.

Effect of vascular endothelial growth factor 165 on dopamine level in the retinas of guinea pigs with form-deprivation myopia.

Background: Myopia is the most common refractive error because excessive increase in the axial length of a myopic eye leads to the thinning of the posterior scleral pole and can cause serious complications resulting in blindness. Thus, myopia has become a great concern worldwide. Dopamine (DA) plays a role in the development of myopia. Moreover, in Parkinson's disease, it has been proved that vascular endothelial growth factor 165 (VEGF165) can promote the survival and recovery of DA neurons, resulting in increased DA secretion in the striatum, thereby treating neuropathy. Therefore, we speculate that VEGF165 can also promote the release of DA in the retina to inhibit the occurrence and development of myopia. We aimed to investigate the effect of VEGF165 on DA levels in the retinas of guinea pigs with form-deprivation myopia (FDM) and the effects of DA on myopia prevention and control. Methods: Healthy 3-week-old pigmented guinea pigs were randomly divided into blank, FDM, phosphate buffer saline (PBS), 1, 5, and 10 ng groups. The FDM model was established by covering the right eye continuously with a translucent latex balloon pullover for 14 days. The pigs in the PBS, 1, 5, and 10 ng groups were injected with PBS buffer and 1, 5, and 10 ng of VEGF165 recombinant human protein, respectively, in the vitreous of the right eye before masking. The refractive error and axial length were measured before and after modeling. All retinas were used for biomolecular analyses after 14 days. Results: We found that the intravitreal injection of VEGF165 elevated DA levels in the retina and was effective in slowing the progression of myopia, and 1 ng of VEGF165 was the most effective. Moreover, the number of vascular endothelial cell nuclei in the 1 ng group was lower than that in the other VEGF165 groups. Conclusions: Our data suggest that VEGF165 has a promoting effect on DA in the retinas of guinea pigs with FDM, potentially controlling the development of myopia.

Manipulating rhizosphere microorganisms to improve crop yield in saline-alkali soil: a study on soybean growth and development.

Introduction: Rhizosphere microorganisms can effectively promote the stress resistance of plants, and some beneficial rhizosphere microorganisms can significantly promote the growth of crops under salt stress, which has the potential to develop special microbial fertilizers for increasing the yield of saline-alkali land and provides a low-cost and environmentally friendly new strategy for improving the crop yield of saline-alkali cultivated land by using agricultural microbial technology. Methods: In May 2022, a field study in a completely randomized block design was conducted at the Heilongjiang Academy of Agricultural Sciences to explore the correlation between plant rhizosphere microorganisms and soybean growth in saline-alkali soil. Two soybean cultivars (Hening 531, a salt-tolerant variety, and 20_1846, a salt-sensitive variety) were planted at two experimental sites [Daqing (normal condition) and Harbin (saline-alkali conditions)], aiming to investigate the performance of soybean in saline-alkali environments. Results: Soybeans grown in saline-alkali soil showed substantial reductions in key traits: plant height (25%), pod number (26.6%), seed yield (33%), and 100 seed weight (13%). This underscores the unsuitability of this soil type for soybean cultivation. Additionally, microbial analysis revealed 43 depleted and 56 enriched operational taxonomic units (OTUs) in the saline-alkali soil compared to normal soil. Furthermore, an analysis of ion-associated microbes identified 85 mOTUs with significant correlations with various ions. A co-occurrence network analysis revealed strong relationships between specific mOTUs and ions, such as Proteobacteria with multiple ions. In addition, the study investigated the differences in rhizosphere species between salt-tolerant and salt-sensitive soybean varieties under saline-alkali soil conditions. Redundancy analysis (RDA) indicated that mOTUs in saline-alkali soil were associated with pH and ions, while mOTUs in normal soil were correlated with Ca2+ and K+. Comparative analyses identified significant differences in mOTUs between salt-tolerant and salt-sensitive varieties under both saline-alkali and normal soil conditions. Planctomycetes, Proteobacteria, and Actinobacteria were dominant in the bacterial community of saline-alkali soil, with significant enrichment compared to normal soil. The study explored the functioning of the soybean rhizosphere key microbiome by comparing metagenomic data to four databases related to the carbon, nitrogen, phosphorus, and sulfur cycles. A total of 141 KOs (KEGG orthologues) were identified, with 66 KOs related to the carbon cycle, 16 KOs related to the nitrogen cycle, 48 KOs associated with the phosphorus cycle, and 11 KOs linked to the sulfur cycle. Significant correlations were found between specific mOTUs, functional genes, and phenotypic traits, including per mu yield (PMY), grain weight, and effective pod number per plant. Conclusion: Overall, this study provides comprehensive insights into the structure, function, and salt-related species of soil microorganisms in saline-alkali soil and their associations with salt tolerance and soybean phenotype. The identification of key microbial species and functional categories offers valuable information for understanding the mechanisms underlying plant-microbe interactions in challenging soil conditions.