Pharmacokinetics and safety profiles of beinaglutide injection, a recombinant human GLP-1, in adults with overweight/obesity: results from a phase I clinical trial.

Background: Beinaglutide, whose active ingredient is rhGLP-1, has been widely used as a pharmacological therapy for T2DM. We explored the safety and pharmacokinetics of beinaglutide in Chinese overweight/obese volunteers to lay a foundation for clinical applications of beinaglutide as an anti-obesity drug. Methods: An open-label, single center, multiple ascending dose phase I clinical trial was conducted in 16 overweight/obese Chinese volunteers. The plasma concentrations of beinaglutide were determined by a validated ELISA method and the pharmacokinetic parameters were estimated via non-compartmental analysis methods. Adverse events were also recorded. Results: Beinaglutide sequentially multiple dosing (three times daily) at different doses were generally well tolerated, without serious AEs leading to discontinuation of the trial. After multiple subcutaneous injections of different doses (0.1, 0.14 and 0.2 mg), the average blood concentration of beinaglutide with or without baseline correction showed a similar trend among different dose groups on different study days. After reaching the peak concentration around 15 min, it began to decrease, and the median of Tmax and Tmax,adj was 10-15 min. The exposure in vivo increased in proportion to the dosage increment, demonstrating linear pharmacokinetic characteristics. There were no statistically significant differences in the main PK parameters and no accumulation of beinaglutide after multiple dosing. After multiple subcutaneous injections, a gender difference was observed, while no differences in BMI were found under the grouping conditions. Conclusion: The safety profile and pharmacokinetic properties support further development and clinical applications of beinaglutide as an anti-obesity drug. Systematic Review Registration: [https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000BPEI&selectaction=Edit&uid=U00050YQ&ts=2&cx=wy0ioj].

Giant Optical Anisotropy Induced by Magnetic Order in FePS3/WSe2 Heterostructures.

Magnetic 2D materials offer a promising platform for manipulating quantum states at the nanoscale. Recent studies have underscored the significant influence of 2D magnetic materials on the optical behaviors of transition-metal dichalcogenides (TMDs), revealing phenomena such as interlayer exciton-magnon interactions, magnetization-dependent valley polarization, and an enhanced Zeeman effect. However, the controlled manipulation of anisotropic optical properties in TMDs via magnetism remains challenging. Here, the magnetic ordering in FePS3 profoundly impacts the optical characteristics of WSe2, achieving a giant linear polarization degree of 5.1 in exciton emission is demonstrated. This is supported by a detailed analysis of low-temperature photoluminescence (PL) and Raman spectra from nL-FePS3/WSe2 heterostructures. These findings indicate that a phase transition in FePS3 from paramagnetic to antiferromagnetic enhances interlayer Coulomb interactions, inducing a transition from non-polar to polar behavior in the heterostructures. Additionally, valley-polarized PL spectra under magnetic fields from -9 to 9 T reveal the influence of FePS3 on valley polarization and Zeeman splitting of excitons in monolayer WSe2. These results present a novel strategy for tailoring the optoelectronic properties of 2D magnetic van der Waals heterostructures, paving the way for advancements in nanoscale device design.

Relationship of vegetarianism with body weight loss and ASCVD.

Introduction: The association between a plant-based diet and weight loss and atherosclerotic cardiovascular disease (ASCVD) has not been fully elucidated. We performed a pooled analysis and Mendelian randomization (MR) analysis to investigate this question. Methods: We searched for randomized controlled trials on the effects of a plant-based diet on weight loss compared with a non-plant-based diet. In addition, a two-sample MR study was conducted. IVs were obtained from the genome-wide association studies (GWAS) on the exposures, and we obtained summary statistics on the outcomes. The inverse-variance weighted (IVW) method was used as the main analysis and other MR methods were performed as supplementary analyses. Results: Individuals on the plant-based diet lost more weight than the non-plant-based diet group (WMD -0.96 kg; 95% CI: -1.32 to -0.60). Population conditions and energy restriction were identified as the study-level factors that influenced the pooling results in the subgroup analyses. Increased consumption of raw vegetables was significantly associated with lower BMI (IVW, ß -0.35, 95% CI: -0.62 to -0.08, p = 0.012) and lower risk of obesity (IVW, OR 0.11, 95% CI: 0.01 to 0.99, p = 0.048), coronary heart disease (IVW, OR 0.44, 95% CI: 0.21 to 0.92, p = 0.029) and myocardial infarction (IVW, OR 0.39,95% CI: 0.15 to 0.98, p = 0.045) and a higher HDL-C (IVW, ß 0.47, 95% CI: 0.24 to 0.70, p = 4×10-5). Discussion: The present findings suggest that raw vegetable intake is beneficial for weight loss and prevention of ASCVD.

Upcycling of nutrients from kitchen waste: Integration of anaerobic digestion system and microbial protein production system.

To upcycle the nutrients from kitchen waste (KW), an integrated system consisting of anaerobic digestion (AD) reactor and microbial protein (MP) production reactor was established in this study. The subsystem I (AD system) demonstrated an efficient bio-energy production (282.37 mL CH4/g VS), with 553.54 mg/L of NH4+-N remained in the digestate. The subsystem II (MP production system) utilized the nitrogenous constituents of the digestate, with 2.04 g/L MP production. In order to further enhance the recovery efficiency, C/N ratio in the subsystem II was studied. NH4+-N recovery efficiency was 23.08% higher after C/N ratio optimization along with 0.24 g/L increment on MP production. Over 0.7 g/L of essential amino acids was obtained, according with the qualitative necessary for the feeds. Also, the key enzyme abundance of CO2 releasing and amino acid biosynthesis was obviously increased with max. 55.21%. Meanwhile, the integrated system was profitable via a simplified economic assessment.

The value of SDC2 and Septin9 combined with serum tumor markers in early diagnosis of colorectal cancer.

OBJECTIVE: The aim of this study is to evaluate the significance of combined detection of Septin9 and syndecan-2 (SDC2) methylation markers and serum tumor markers for the early diagnosis of colorectal cancer. METHODS: A total of 116 patients diagnosed with colorectal cancer between December 2022 and February 2024 were designated as the colorectal cancer group. Additionally, 31 patients with colorectal adenoma were assigned to the adenoma group, while 44 individuals undergoing routine physical examinations were included in the control group. Concentrations of Septin9, SDC2, fecal occult blood (FOB), and four tumor markers-carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), carbohydrate antigen 125 (CA125), and carbohydrate antigen 724 (CA724)-were measured. Diagnostic performance was assessed using receiver operating characteristic (ROC) curves for Septin9, SDC2, the four tumor markers, FOB, the combination of Septin9 and SDC2, and the combined use of all seven indicators (CEA, CA19-9, CA125, CA72-4, FOB, Septin9, and SDC2). RESULTS: The colorectal cancer group exhibited the highest positive rates for Septin9, SDC2, the four tumor markers, the combined detection of Septin9 and SDC2, and the combined detection of all seven indicators, compared to both the adenoma and control groups (P < 0.05). The adenoma group also showed higher positive rates than the control group (P < 0.05). For patients with stage I-III colorectal cancer, the positive rates for the combined detection of Septin9 and SDC2 were 81.3%, 78.9%, and 90.2%, respectively, surpassing those for the combined detection of the four tumor markers (43.8%, 55.3%, and 61.0%). Additionally, the positive rates for the two-gene combination in stage III colorectal cancer were higher than those for FOB (P < 0.05). The sensitivity and area under the curve (AUC) for SDC2 were 73.3% and 0.855, respectively, exceeding the sensitivity and AUC for the combined four tumor markers, which were 60.3% and 0.734 (P < 0.05). The combined detection of the two methylated genes demonstrated a sensitivity of 86.2% and an AUC of 0.908, outperforming both FOB and the combined detection of the four tumor markers (P < 0.05). CONCLUSION: The detection of SDC2 exhibits high sensitivity for colorectal cancer, and when combined with Septin9, it significantly enhances the diagnostic accuracy for early-stage colorectal cancer, offering substantial clinical value.

2-Arylbenzofurans from the stems and leaves of Artocarpus tonkinensis and their potential antiproliferative activities.

Phytochemical study on the stems and leaves of Artocarpus tonkinensis led to the isolation of a new 2-arylbenzofuran, artocartone (1), as well as seven known 2-arylbenzofurans (2-8). The chemical structure of 1 was established by means of comprehensive spectroscopic analyses and the known compounds were determined by comparing their MS and NMR data with those reported data in literature. The antiproliferative activities of all isolates 1-8 against five human cancer cell lines: HL-60, SMMC-7721, A-375, MCF-7 and SW480 in vitro were evaluated. As a result, compounds 1- 8 displayed notable antiproliferative activities against various human cancer cell lines with IC50 values in the range of 0.28 ± 0.05-26.89 ± 0.18 µM.

Development and validation of a clinical nomogram for predicting in-hospital mortality in patients with traumatic brain injury prehospital: A retrospective study.

Objective: Traumatic brain injury (TBI) is among the leading causes of death and disability globally. Identifying and assessing the risk of in-hospital mortality in traumatic brain injury patients at an early stage is challenging. This study aimed to develop a model for predicting in-hospital mortality in TBI patients using prehospital data from China. Methods: We retrospectively included traumatic brain injury patients who sustained injuries due to external forces and were treated by pre-hospital emergency medical services (EMS) at a tertiary hospital. Data from the pre-hospital emergency database were analyzed, including demographics, trauma mechanisms, comorbidities, vital signs, clinical symptoms, and trauma scores. Eligible patients were randomly divided into a training set (241 cases) and a validation set (104 cases) at a 7:3 ratio. Least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression were employed to identify independent risk factors. Analyzed the discrimination, calibration, and net benefit of the nomogram across both groups. Results: 17.40 % (42/241) of TBI patients died in the hospital in the training set, while 18.30 % (19/104) in the validation set. After analysis, chest trauma (odds ratio [OR] = 4.556, 95 % confidence interval [CI] = 1.861-11.152, P = 0.001), vomiting (OR = 2.944, 95%CI = 1.194-7.258, P = 0.019), systolic blood pressure (OR = 0.939, 95%CI = 0.913-0.966, P < 0.001), SpO2 (OR = 0.778, 95%CI = 0.688-0.881, P < 0.001), and heart rate (OR = 1.046, 95%CI = 1.015-1.078, P = 0.003) were identified as independent risk factors for in-hospital mortality in TBI patients. The nomogram based on the five factors demonstrated well-predictive power, with an area under the curve (AUC) of 0.881 in the training set and 0.866 in the validation set. The calibration curve and decision curve analysis showed that the predictive model exhibited good consistency and covered a wide range of threshold probabilities in both sets. Conclusion: The nomogram based on prehospital data demonstrated well-predictive performance for in-hospital mortality in TBI patients, helping prehospital emergency physicians identify and assess severe TBI patients earlier, thereby improving the efficiency of prehospital emergency care.

Tunable Valley Pseudospin and Electron-Phonon Coupling in WSe2/1T-VSe2 Heterostructures.

Heterostructure engineering provides versatile platforms for exploring exotic physics and enhancing the device performance through interface coupling. Despite the rich array of physical phenomena presented by heterostructures composed of semiconductor and metal van der Waals materials, significant gaps remain in understanding their optical, thermal, and electronic properties. Here, we demonstrate that the valley pseudospin and electron-phonon coupling in monolayer WSe2 are significantly influenced by interface coupling with 1T-VSe2. The heterointerface alters the relaxation process of valley excitons, leading to a transition in magnetic-field-dependent valley polarization from a linear to a "V" shape. Furthermore, we uncover that enhanced electron-phonon coupling exacerbates variations in exciton and valley exciton behavior with temperature, involving higher phonon energies and a shift from acoustic to optical phonons. These findings highlight a promising pathway to manipulate valley excitons and investigate electron-phonon coupling through van der Waals interface interactions.

Direct lexical control of eye movements in Chinese reading: Evidence from the co-registration of EEG and eye tracking.

The direct-lexical-control hypothesis stipulates that some aspect of a word's processing determines the duration of the fixation on that word and/or the next. Although the direct lexical control is incorporated into most current models of eye-movement control in reading, the precise implementation varies and the assumptions of the hypothesis may not be feasible given that lexical processing must occur rapidly enough to influence fixation durations. Conclusive empirical evidence supporting this hypothesis is therefore lacking. In this article, we report the results of an eye-tracking experiment using the boundary paradigm in which native speakers of Chinese read sentences in which target words were either high- or low-frequency and preceded by a valid or invalid preview. Eye movements were co-registered with electroencephalography, allowing standard analyses of eye-movement measures, divergence point analyses of fixation-duration distributions, and fixated-related potentials on the target words. These analyses collectively provide strong behavioral and neural evidence of early lexical processing and thus strong support for the direct-lexical-control hypothesis. We discuss the implications of the findings for our understanding of how the hypothesis might be implemented, the neural systems that support skilled reading, and the nature of eye-movement control in the reading of Chinese versus alphabetic scripts.

Towards a model of eye-movement control in Chinese reading.

The Chinese writing system has several features that make it markedly different from the alphabetic systems that have most often been examined in reading research, including the fact that individual words consist of various uniformly sized, box-shaped characters whose boundaries are not clearly demarcated (e.g., by blank spaces). These features raise the question: How do readers of Chinese "know" where to move their eyes for the purpose of efficiently segmenting and/or identifying words? To answer this question, we used the E-Z Reader model of eye-movement control in reading to run an 'experiment' involving a series of simulations in which two saccade-targeting assumptions (i.e., directing the eyes towards default targets vs. adjusting saccade length as a function of parafoveal processing difficulty) were factorially manipulated with three word-segmentation heuristics (i.e., ideal-observer knowledge of word boundaries vs. probabilistic guessing vs. familiarity-based segmentation) to examine which combination of assumptions provide the best quantitative account of eye-movement control during the reading of Chinese. Based on these simulations, we conclude the best account is one in which readers use relative differences in the familiarity of groups of parafoveal characters to dynamically adjust the lengths of saccades in a manner that affords efficient word identification. We discuss the broader theoretical implications of these conclusions for models of Chinese reading and for models of reading more generally.

Polyprenylated xanthones with potential anti-inflammatory and anti-HIV effects from the stems and leaves of Cratoxylum cochinchinense (Lour.) Blume.

A phytochemical study on the stems and leaves of Cratoxylum cochinchinense (Lour.) Blume resulted in the isolation and characterisation of a new polyprenylated xanthone, cratocochinone (1), as well as seven known analogues, fuscaxanthone K (2), pruniflorone Q (3), 1,3,5,8-tetrahy-droxy- 2-(3-methybut-2-enyl)-4-(3,7-dimethylocta-2,6-dienyl) xanthone (4), cochinensoxanthone (5), cratoxylum-xanthone B (6), cochinchinone I (7) and cochinchinone K (8). The chemical structure of 1 was determined by comprehensive spectral analyses. The known compounds 2 - 8 were identified by comparing their experimental spectroscopic data with those reported data in the literature. The anti-inflammatory and anti-HIV effects of all isolates 1-8 were evaluated. As a result, compounds 1-8 showed remarkable inhibitory effects against nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells showing IC50 values ranging from 0.68 ± 0.06 to 10.27 ± 0.18 µM. Meanwhile, compounds 1-8 displayed notable anti-HIV-1 reverse transcriptase (RT) effects with EC50 values ranging from 0.19 to 10.72 µM.

Serum copper assessment in patients with polycystic ovary syndrome and tubal infertility: A retrospective 5-year study.

The association between serum copper and polycystic ovary syndrome (PCOS) lacks definitive conclusions, and the intricate interactions with in vitro fertilization (IVF) cycle characteristics in infertility remain insufficiently explored. This retrospective study included 560 patients with tubal infertility (no-PCOS) and 266 patients with PCOS undergoing IVF at the Affiliated Suzhou Hospital of Nanjing Medical University from January 2018 to December 2022. Patients' basic characteristics, hormonal and metabolic parameters, essential trace elements, and IVF cycle characteristics were measured and analyzed. The results revealed a significantly elevated serum copper level in the PCOS group compared to the control group [17.27 (15.54, 19.67) vs 15.4 (13.87, 17.35), µmol/L; p < .001]. Spearman correlation analyses revealed a significant positive correlation between serum copper concentration and body mass index (BMI), fasting glucose (FG), triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL) in the no-PCOS group. Additionally, a notable negative correlation with high-density lipoprotein (HDL) was observed (r = -.184, p < .001). Within the PCOS group, serum copper concentration correlated significantly with BMI (r = .198, p = .004) and TG (r = .214, p = .002). The linear trend analysis indicated no significant relationship between serum copper concentration and ovarian response as well as preimplantation outcomes in both groups after adjusting for confounding factors. Our study provided evidence of elevated serum copper concentration in PCOS patients, closely associated with lipid metabolism but showing no correlation with IVF outcomes. These findings provide valuable real-world data, enriching our nuanced understanding of the role of copper in female fertility.

Vascular plants and biocrusts ameliorate soil properties serving to increase the stability of the Great Wall of China.

The Great Wall, as a World Heritage Site, is constructed with rammed earth and is currently facing the threat of erosion from wind and rain. Vascular plants and biocrusts are the main coverings of the Great Wall, and their role in mitigating soil erosion has attracted increased amounts of attention; however, the understanding of their underlying mechanisms is limited. Here, we conducted an extensive survey of vascular plants, biocrusts, soil properties (soil organic and inorganic binding materials, aggregates, and texture), soil aggregate stability, and soil erodibility at the top of the Great Wall in four different defensive zones in Northwest China. Vascular plants covered 13.6 % to 63.9 % of the tops of the Great Wall, and their rich diversity was mainly derived from perennial herbs. Moss, lichen, and cyanobacterial crusts collectively covered 36.3 % to 67.8 % of the top of the Great Wall. Redundancy analysis and structural equation modeling revealed that the synergistic effects of vascular plants and biocrusts enhanced soil aggregation stability (including geometric mean diameter, GMD; water-stable macroaggregate content, R) by increasing the accumulation of soil organic carbon (SOC), amorphous iron oxide (Feo), and amorphous alumina (Alo) and promoting the formation of macroaggregates (ASD>0.25 mm) and microaggregates (ASD0.053-0.25 mm). Furthermore, soil erodibility was primarily influenced negatively by the synergistic promotion of SOC accumulation by vascular plants and biocrusts and positively by the reduction in soil sand (PSD>0.05 mm) content by biocrusts. Our work highlights the mechanisms and importance of vascular plants and biocrusts as natural covers for altering the intrinsic properties of soil for the protection of the Great Wall. These findings provide reliable theoretical support for the protection of the Great Wall from erosion by vascular plants and biocrusts and offer new insights for the conservation of global earthen sites and similar wall habitats.

Role of the circRNA_34414/miR-6960a-5p/SIRT3 axis in postoperative delirium via CA1 Vglut1+ neurons in older mice.

AIMS: Postoperative delirium (POD) is a common neurological complication in elderly patients after anesthesia/surgery. The main purpose of this study is to explore the effect of circRNA-targeted miRNA regulating SIRT3 on mitochondrial function through ceRNA mechanism under the surgical model of tibial fracture and to further explore the potential mechanism of postoperative delirium mediated by circRNA, so as to provide new ideas for clinical diagnosis and prevention of POD. METHODS: The surgical model of tibial fracture under sevoflurane anesthesia caused acute delirium-like behavior in elderly mice. We observed that the decrease of SIRT3 and mitochondrial dysfunction was related to POD, and miRNA and circRNA (circRNA_34414) related to SIRT3 were further studied. Through luciferase and RAP, we observed that circRNA_34414, as a miRNA sponge, was involved in the regulation of SIRT3 expression. RESULTS: Postoperative delirium in elderly mice showed decreased expression of hippocampal circRNA_34414, increased expression of miR-6960-5p, decreased expression of SIRT3, and impaired mitochondrial membrane potential. Overexpression of circRNA_34414, or knockdown of miR-6960-5p, or overexpression of SIRT3 in hippocampal CA1 glutamatergic neurons significantly upregulated hippocampal SIRT3 expression, increased mitochondrial membrane potential levels, and significantly ameliorated postoperative delirium in aged mice; CircRNA_34414 ameliorates postoperative delirium in mice, possibly by targeting miR-6960-5p to upregulate SIRT3. CONCLUSIONS: CircRNA_34414 is involved in the improvement of postoperative delirium induced by anesthesia/surgery by upregulating SIRT3 via sponging miR-6960-5p.

Exploring the mechanisms of Huangqin Qingfei Decoction on acute lung injury by LC-MS combined network pharmacology analysis.

BACKGROUND: Acute lung injury (ALI) is a respiratory disease characterized by pulmonary inflammation and increased microvascular permeability, resulting in significant mortality and a lack of effective pharmacological treatment. Huangqin Qingfei Decoction (HQQFD), a Traditional Chinese Medicine (TCM) prescription known for its heat-clearing and detoxifying properties, has shown efficacy in treating ALI. However, the underlying mechanisms of HQQFD to against ALI remain to be elucidated. PURPOSE: This study aims to discover the mechanisms and the principal bioactive compounds contributing to HQQFD's protective effects in the treatment of ALI. METHODS: An ultra-high performance liquid chromatography-Orbitrap high-resolution mass spectrometry (UHPLC-Orbitrap HRMS) method was employed to characterize the chemical profile in HQQFD and xenobiotics (prototypes and metabolites) in rat lung tissue. Based on prototypes identified, a symptom-guided pharmacological networks of ALI were performed. Molecular docking and extensive literature reviews were conducted to validate our findings. RESULTS: A total of 105 compounds were identified in HQQFD, and a total of 194 HQQFD-related xenobiotics (30 prototypes and 163 metabolites) were detected in rat lung tissue. Based on prototypes identified in rat lung, a symptom-guided pharmacological networks of ALI were constructed, AKT1, TNF, EGFR, MMP2, GSK3B, STAT3, MAPK8, IL-6, CDK2 and TP53 were finally identified as key targets. Subsequently, 11 compounds with protective and therapeutic activity were selected by molecular docking analysis, including genipin 1-gentiobioside, chrysin-6-C-α-L-arabinoside-8-C-ß-d-glucoside, scutellarin, chrysin-6-C-ß-d-glucoside-8-C-α-L-arabinoside, 6''-O-[(E)-p-coumaroyl] genipin-gentiobioside, apigenin 7-O-glucoside, baicalin, dihydrobaicalin, wogonoside, crocin I, crocetin. Bioinformatics and literature analysis suggested that, baicalin, wogonoside, genipin 1-gentiobioside and crocetin may be the primary active compounds of HQQFD, potentially targeting GSK3B, MAPK8, IL-6, AKT1 and TNF for HQQFD in addressing ALI. The therapeutic effects of HQQFD may be mediated through the IL-17 and PI3K-AKT signaling pathways. CONCLUSION: The predominant components of HQQFD against ALI are baicalein, wogonoside, genipin 1-gentiobiosid and crocetin, with the IL-17 and PI3K-AKT pathways playing crucial roles. This study provides a foundational guide for future research and introduces innovative methods for exploring the mechanisms of other drug combinations or TCM formulas.

Blockage of the NLRP3 inflammasome by MCC950 inhibits migration and invasion in adenomyosis.

RESEARCH QUESTION: Does the NOD-like receptor protein 3 (NLRP3) inflammasome have an effect in adenomyosis? DESIGN: Fresh-frozen endometrial tissues and paraffin specimens were obtained from endometrial tissues from patients with adenomyosis and controls. Western blot, quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) were applied to assess expression of the NLRP3 inflammasome components. Primary eutopic endometrial stromal cells were isolated from the uteri of patients with adenomyosis. After NLRP3 was knocked down using small interfering RNA, proliferation, invasion and epithelial-mesenchymal transition (EMT) were evaluated using EdU, CCK8, transwell assays and western blot. Importantly, a mouse model of adenomyosis was established to evaluate the effects of the NLRP3 inhibitor MCC950 on the formation of adenomyosis. RESULTS: Expression of the NLRP3 inflammasome components was elevated in the ectopic or eutopic endometrium of patients with adenomyosis. NLRP3 knockdown inhibited migration, invasion and EMT in endometrial cells and primary endometrial cells (P < 0.0001). MCC950, which blocks the NLRP3 inflammasome, reduced migration and invasion of endometrial cells (P < 0.01) and primary endometrial cells (P < 0.0001) considerably. Importantly, in the mouse model of adenomyosis, MCC950 had a mitigating effect on the severity of adenomyosis (P < 0.01). CONCLUSIONS: NLRP3 was found to enhance migration, invasion and EMT of human endometrial cells in adenomyosis. Notably, the NLRP3 inhibitor MCC950 reduced migration and invasion of endometrial cells effectively. Furthermore, in the mouse model of adenomyosis, MCC950 exhibited a therapeutic effect by alleviating the severity of adenomyosis.

Associations Between Serum Vitamin A Levels in Early Pregnancy and the Risk of Gestational Diabetes Mellitus.

Background: The relationship between vitamin A levels and gestational diabetes mellitus (GDM) is not well understood, and prospective studies are lacking. Methods: This was a prospective, longitudinal study. A total of 391 women in early pregnancy were recruited between October and December 2018 at Shunyi District Maternal and Child Health Hospital (Beijing, China). Serum vitamin A concentration was measured at enrollment. GDM was diagnosed on the basis of a 75 g oral glucose-tolerance test at 24-28 weeks of follow-up. Logistic regression was used for the analysis. Results: None of the subjects in the cohort had vitamin A deficiency or excess. At the follow-up, 76 participants had developed GDM. Participants who developed GDM were older and had higher body mass index, fasting insulin, HbA1c, fasting glucose, homeostasis model assessment for insulin resistance, triglyceride, low-density lipoprotein cholesterol, and high-sensitivity CRP levels, as well as higher serum vitamin A levels at baseline. On logistic multivariate analysis, higher vitamin A was positively associated with higher risk of GDM. The adjusted OR was 2.85 (95% CI 1.04-7.80, P=0.042) for Q4 versus Q1 and 1.59 (95% CI 1.11-2.28, P=0.011) for every 1 SD increase in serum vitamin A levels. In participants within the vitamin A reference range (0.33-0.78 mg/L), the positive association also maintained significance. Conclusion: Higher serum vitamin A levels were associated with higher GDM risks, even within the reference range. The results and possible mechanisms need to be further verified and clarified.

Bioequivalence study of two formulations of afatinib dimaleate tablets in healthy subjects under fasting conditions: A randomized, open-label, single-dose, crossover trial.

OBJECTIVE: To evaluate the bioequivalence of two different afatinib dimaleate formulations in healthy Chinese subjects under fasting conditions and to assess their pharmacokinetic and safety profiles. MATERIALS AND METHODS: This randomized, open-label, 2-period, crossover, bioequivalence study included 32 healthy Chinese subjects. The subjects were assigned to receive a single 40-mg dose of generic or brand-named afatinib dimaleate tablet. Blood samples were collected pre-dose and up to 120 hours after dosing. Healthy subjects orally took the trial preparation (T) (afatinib maleate tablets developed by Jiangxi Shanxiang Pharmaceutical Co., Ltd., Gan Zhou, China) and the reference preparation (R) (afatinib maleate tablets developed by Boehringer Ingelheim Pharma GmbH & Co., Ingelheim, Germany) under fasting conditions in the appropriate period according to the randomization. We measured the blood concentrations, calculated the pharmacokinetic parameters of the two preparations in the human body, and evaluated whether formulations were bioequivalent. Safety of the preparations in healthy subjects was monitored during the whole trial. Safety assessment was conducted by vital signs, physical examination, laboratory examination, and 12-lead electrocardiogram during the study, i.e., from the time the subject received the test drug to the end of the last visit. RESULTS: Under fasting conditions, the 90% confidence intervals (CIs) of the geometric mean ratios of the test/reference for afatinib dimaleate were 93.34 - 103.92% for AUC0-t, 90.26 - 105.52% for Cmax, and 93.49 - 104.05% for AUC0-∞. CONCLUSION: The 90% CI for the geometric mean ratios (test/reference) of Cmax, AUC0-t, and AUC0-∞ were within the range of 80.00 - 125.00%, indicating that the test formulation was equivalent to the reference formulation in healthy Chinese subjects under fasting conditions. Both products were similar in terms of safety.

Analysis on the minimum structure of harmonic spectra from MgO crystals.

Recent theoretical and experimental findings have demonstrated the minimum characteristic in the harmonic spectrum of bulk MgO crystals subjected to intense laser pulses. However, the dominant mechanism behind this minimum structure is still under debate. This study simulates the harmonic spectrum from a MgO crystal in a linearly polarized laser pulse by solving multi-band semiconductor Bloch equations. The results show that the minimum feature at 20 eV in the MgO harmonic spectra from 1700 and 800 nm laser pulses is due to band dispersion and interference between interband harmonics. Notably, the disappearance of the minimum structure at 14 eV in the harmonic spectrum from the 800 nm laser is attributed to the intensity suppression of higher energy harmonics, caused by decreased electron population at the boundary of the first Brillouin zone in the multi-band case. These findings offer insights into the spectral structure of solid-state harmonics, contributing to the all-optical reconstruction of the crystal band based on its harmonic spectrum.

Neural correlates for word-frequency effect in Chinese natural reading.

Word frequency effect has always been of interest for reading research because of its critical role in exploring mental processing underlying reading behaviors. Access to word frequency information has long been considered an indicator of the beginning of lexical processing and the most sensitive marker for studying when the brain begins to extract semantic information Sereno & Rayner, Brain and Cognition, 42, 78-81, (2000), Trends in Cognitive Sciences, 7, 489-493, (2003). While the word frequency effect has been extensively studied in numerous eye-tracking and traditional EEG research using the RSVP paradigm, there is a lack of corresponding evidence in studies of natural reading. To find the neural correlates of the word frequency effect, we conducted a study of Chinese natural reading using EEG and eye-tracking coregistration to examine the time course of lexical processing. Our results reliably showed that the word frequency effect first appeared in the N200 time window and the bilateral occipitotemporal regions. Additionally, the word frequency effect was reflected in the N400 time window, spreading from the occipital region to the central parietal and frontal regions. Our current study provides the first neural correlates for word-frequency effect in natural Chinese reading so far, shedding new light on understanding lexical processing in natural reading and could serve as an important basis for further reading study when considering neural correlates in a realistic manner.