Search

Pharmaceuticals and personal care products (PPCPs) have received global attention owing to their potential risks to human health and the ecological environment. However, limited research has explored the occurrence and ecological risks of PPCPs in the Qiantang River (QTR). QTR, the largest water system in Zhejiang Province, China, is significantly influenced by human activities. This study investigated the occurrence, distribution, and ecological risks of 10 types of PPCPs in both surface water and sediment within QTR. The findings revealed that the concentrations of PPCPs detected in surface water ranged from 81.26 to 149.45 ng L−1 during the wet season (April) and from 98.66 to 198.55 ng L−1 during the dry season (September). Moreover, in the sediments, PPCP concentration ranged from 63.24 to 80.66 and 72.54 to 75.06 ng per g dw during both wet and dry seasons, respectively. Among the selected PPCPs, triclosan (TCS) exhibited the highest concentration across, different phases and seasons, followed by benzotriazole in surface water. The analysis of sediment–water equilibrium distribution indicated that the diffusion tendency of PPCPs was closely correlated with their molecular weights. Particularly, TCS exhibited dynamic equilibrium between water and sediment. Principal component analysis and positive matrix factorization model results indicated similar pollution sources for the detected PPCPs. The dominant sources of the detected PPCPs were identified as wastewater of electroplating enterprises, discharge from wastewater treatment plants, and domestic sewage. The ecological risk assessment based on the risk quotient method revealed that TCS with the highest detected concentration posed a high risk in surface water and a low risk in sediment across all sampling sites. However, other detected PPCPs showed either no or low risks. Additionally, PPCPs showed a higher ecological risk during the dry season than during the wet season. [ABSTRACT FROM AUTHOR]

Intestinal lymphatic transport offers an alternative and effective way to deliver drugs, such as avoiding first-pass metabolism, enhancing oral bioavailability, and facilitating the treatment of targeted lymphoid-related diseases. However, the clinical use of luteolin (LUT) is limited by its poor water solubility and low bioavailability, and enhancing lymphatic transport by nanoemulsion may be an efficient way to enhance its oral bioavailability. The objective of this work is to prepare the luteolin nanoemulsions (LUT NEs), optimized its preparation parameters by using Box-Behnken design optimization (BBD) and evaluated it in vitro and in vivo. An Caco-2 / Raji B cell co-incubation monolayer model was established to simulate the M-cell pathway, and the differences in the transmembrane transport of LUT and NEs were compared. Cycloheximide (CHX) was utilized to establish rat chylomicron (CM) blocking model, and for investigating the influence of pharmacokinetic parameters in rats thereafter. The results showed that LUT NEs have good stability, the particle sizes were about 23.87 ± 0.57 nm. Compared with LUT suspension, The Papp of LUT NEs was enhanced for 3.5-folds, the oral bioavailability was increased by about 2.97-folds. In addition, after binding with chylomicron, the oral bioavailability of LUT NEs was decreased for about 30% (AUC 0–∞ (μg/L*h): 5.356 ± 1.144 vs 3.753 ± 0.188). These results demonstrated that NEs could enhance the oral absorption of luteolin via lymphatic transport routes. [ABSTRACT FROM AUTHOR]

Sustained compressive injury (SCI) in the brain is observed in numerous injury and pathological scenarios, including tumors, ischemic stroke, and traumatic brain injury-related tissue swelling. Sustained compressive injury is characterized by tissue loading over time, and currently, there are few in vitro models suitable to study neural cell responses to strain-dependent sustained compressive injury. Here, we present an in vitro model of sustained compressive neural injury via centrifugation. Spheroids were made from neonatal rat cortical cells seeded at 4000 cells/spheroid and cultured for 14 days in vitro. A subset of spheroids was centrifuged at 104, 209, 313 or 419 rads/s for 2 minutes. Modeling the physical deformation of the spheroids via finite element analyses, we found that spheroids centrifuged at the aforementioned angular velocities experienced pressures of 10, 38, 84 and 149 kPa, respectively, and compressive (resp. tensile) strains of 10% (5%), 18% (9%), 27% (14%) and 35% (18%), respectively. Quantification of LIVE-DEAD assay and Hoechst 33342 nuclear staining showed that centrifuged spheroids subjected to pressures above 10 kPa exhibited significantly higher DNA damage than control spheroids at 2, 8, and 24 hours post-injury. Immunohistochemistry of β3-tubulin networks at 2, 8, and 24 hours post-centrifugation injury showed increasing degradation of microtubules over time with increasing strain. Our findings show that cellular injuries occur as a result of specific levels and timings of sustained tissue strains. This experimental SCI model provides a high throughput in vitro platform to examine cellular injury, to gain insights into brain injury that could be targeted with therapeutic strategies. [ABSTRACT FROM AUTHOR]

With the increasing requirements of agricultural machinery, the study of the contact relationship between the tire–soil interface and the improvement of traction efficiency has gradually become a main concern. In this study, the pattern on the agricultural tire was simplified into single-pitch pattern blocks. The pattern blocks were made of rubber material that was highly resistant to abrasion and bending. The experiment was carried out by pressing the three types of patterned block construction into the soil and the pure sliding under the soil. The simulation used the Coupled Eulerian–Lagrangian Method (CEL) to verify the experimental results. We found that the herringbone pattern block was subjected to the highest stress for the same depth of downward pressure. The horizontal force generated by the pure sliding was also the highest. The results showed that the numerically simulated and experimentally measured data exhibited similar trends and average values. In addition, the increase in the contact area between the tire and the soil reduced the compaction and sinking of the soil. The herringbone pattern structure not only had a large contact area but also produced the most significant shear force on the soil. Thus, it may generate greater traction in actual operations. [ABSTRACT FROM AUTHOR]

Brain injuries resulting from mechanical trauma represent an ongoing global public health issue. Several in vitro and in vivo models for traumatic brain injury (TBI) continue to be developed for delineating the various complex pathophysiological processes involved in its onset and progression. Developing an in vitro TBI model that is based on cortical spheroids is especially of great interest currently because they can replicate key aspects of in vivo brain tissue, including its electrophysiology, physicochemical microenvironment, and extracellular matrix composition. Being able to mechanically deform the spheroids are a key requirement in any effective in vitro TBI model. The spheroids' shape and size, however, make mechanically loading them, especially in a high-throughput, sterile, and reproducible manner, quite challenging. To address this challenge, we present an idea for a spheroid-based, in vitro TBI model in which the spheroids are mechanically loaded by being spun by a centrifuge. (An experimental demonstration of this new idea will be published shortly elsewhere.) An issue that can limit its utility and scope is that imaging techniques used in 2D and 3D in vitro TBI models cannot be readily applied in it to determine spheroid strains. In order to address this issue, we developed a continuum mechanics-based theory to estimate the spheroids' strains when they are being spun at a constant angular velocity. The mechanics theory, while applicable here to a special case of the centrifuge-based TBI model, is also of general value since it can help with the further exploration and development of TBI models. [ABSTRACT FROM AUTHOR]

Background and aims: H-type hypertension is essential hypertension combined with high homocysteine, and both synergistically increase the risk of cardiovascular and cerebrovascular events. The aim of this study was to investigate the risk factors of H-type hypertension in Tibetan plateau population and correlation with MTHFR C677T gene. Methods and results: A multi-stage cluster random sampling method was used to select the research subjects in Tibet Autonomous Region from June 2020 to November 2021. Among Tibetans, the incidence of H-type hypertension accounted for 84.31% of hypertensive patients. The logistic regression analysis demonstrated that age, uric acid (UA), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) were risk factors for the prevalence of H-type hypertension, the OR (95% CI) was 1.083(1.073–1.094), 1.002(1.001–1.004), 1.240(1.050–1.464) and 2.274(1.432–3.611), respectively. MTHFR C677T TT genotype patients with H-type hypertension OR (95% CI) was 1.629(1.004–2.643). Based on this, a nomogram model was established, and the reliability of the model was proved by area under ROC curve, Brier score and average absolute error. The model's results indicate that for every five years of age, the score increases by 6 points; for a 2mmol/L increase in TG, the score increases by 5.5 points; for a 1mmol/L increase in LDL-C, the score increases by 10 points; and individuals with the TT genotype receive 8 points. The higher the score, the greater the risk of disease. Conclusion: The MTHFR C677T TT genotype is a risk locus for Tibetan patients with H-type hypertension, with age, TG, and LDL-C were identified as risk factors for the disease. [ABSTRACT FROM AUTHOR]

Sex ratio is crucial in the reproductive dynamics of bisexual insects. In the Aphelinidae family, heteronomous hyperparasitoids like Encarsia sophia show distinct behaviors where females (from fertilized eggs) target primary hosts, and males (from unfertilized eggs) parasitize secondary hosts. This sex determination pattern means that host resource abundance significantly impacts sex ratio, affecting population dynamics. However, the sex distribution of these parasitoids remains a topic of debate. This study examined E. sophia targeting Bemisia tabaci, adjusting host densities (30, 50, 70 hosts/9.6 cm²) and secondary host ratios (0.2, 0.5, 0.8). Females were observed for recognition of varying host conditions and adjustments in offspring sex ratio and behavior. When ratio of secondary hosts surpassed that of primary hosts or in cases of low host density (host limitation), E. sophia's offspring sex ratio adapted according to the relative abundance of primary and secondary hosts. Conversely, with low secondary host ratios (< 0.5) and higher host density, the sex ratio approached 1:1. Observations showed that females quickly perceived host density, increasing oviposition on secondary hosts with higher density, resulting in more males, and increasing feeding on primary hosts, reducing female offspring. Importantly, by examining oviposition and feeding under different host resource conditions, we identified the optimal rearing strategy: a secondary host ratio of 0.2 and a host density of 30 hosts/9.6 cm². This study not only introduces the sex ratio theory for heteronomous hyperparasitoids but also provides a framework for more accurately assessing their environmental adaptability and for large-scale production. [ABSTRACT FROM AUTHOR]

Background: The association between serum lipids and migraine is controversial. However, randomized controlled trials have suggested that statins may be efficacious for the prevention of migraine. In this study, we aim to investigate the relationship between lipids metabolism and migraine risk. Methods: Single‐nucleotide polymorphisms (SNPs), relating to the serum lipid traits and the effect of lipid‐lowering drugs that target APOB, CETP, HMGCR, NPC1L1, and PCSK9, were extracted from genome‐wide association studies (GWAS) summary data. The GWAS summary data were obtained from the Global Lipids Genetic Consortium (GLGC), the UK Biobank, and the FinnGen study, respectively. Mendelian randomization (MR) analysis was performed to evaluate the association between serum lipid traits and lipid‐lowering drugs with migraine risk. Results: Regarding serum lipids, it was found that SNPs related to high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C), non‐high‐density lipoprotein cholesterol (non‐HDL‐C), total cholesterol (TC), or triglycerides (TG) levels were not associated with migraine, migraine with aura (MA) or migraine without aura (MO). In addition, genotypes of HMGCR related to higher LDL‐C levels were associated with increased risk of migraine (OR = 1.46, p = 0.035) and MA (OR = 2.03, p = 0.008); However, genotypes of PCSK9 related to higher LDL‐C levels were associated with decreased risk of migraine (OR = 0.75, p = 0.001) and MA (OR = 0.69, p = 0.004); And genotypes of APOB related to higher LDL‐C levels were associated with decreased risk of MO (OR = 0.62, p = 0.000). Conclusions: There is a relationship between lipid metabolism characteristics and migraine risk. Significance: Based on the genome‐wide association summary data, single‐nucleotide polymorphisms (SNPs) related to high‐density lipoprotein cholesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C), non‐high‐density lipoprotein cholesterol (non‐HDL‐C), total cholesterol (TC), or triglycerides (TG) level were not associated with risk of migraine, migraine with aura (MA) or migraine without aura (MO). However, genotypes of HMGCR related to higher LDL‐C levels have shown an increased risk on migraine and MA. And genotypes of APOB or PCSK9 related to higher LDL‐C levels have shown a decreased risk on MO, or migraine and MA, respectively. These results suggested that there may be a relationship between lipid metabolism characteristics and the risk for migraine development. [ABSTRACT FROM AUTHOR]

It is important to identify the discriminative features for high dimensional clustering. However, due to the lack of cluster labels, the regularization methods developed for supervised feature selection can not be directly applied. To learn the pseudo labels and select the discriminative features simultaneously, we propose a new unsupervised feature selection method, named GlObal and Local information combined Feature Selection (GOLFS), for high dimensional clustering problems. The GOLFS algorithm combines both local geometric structure via manifold learning and global correlation structure of samples via regularized self-representation to select the discriminative features. The combination improves the accuracy of both feature selection and clustering by exploiting more comprehensive information. In addition, an iterative algorithm is proposed to solve the optimization problem and the convergency is proved. Simulations and two real data applications demonstrate the excellent finite-sample performance of GOLFS on both feature selection and clustering. [ABSTRACT FROM AUTHOR]

The Early Cretaceous Yamama Formation of X oilfield, deposited in a semi-restricted setting, holds considerable oil reserves. However, the reservoir is extremely heterogeneous and is poorly studied. Integrating outcrops, cores, cast thin sections, regular or special core analysis, wireline logging data from six wells, and seismic data, this study provides an improved understanding of reservoir petrophysical characteristics and geological controlling factors including sedimentation, diagenesis, and sequence. The results showed that eight lithologies are developed in the Yamama Formation, of which packstone and wackstone are dominant. The physical properties span a wide range, with porosity mainly distributed between 10% and 25%, and the permeability mainly distributed between 0.1 mD and 1 mD. Nine types of pores are developed, with moldic pores, micropores, and skeletal pores being the most developed. The reservoir has six types of microstructures, of which the poorly sorted with mega-throat represent the best reservoir. The Yamama Formation was mainly deposited in a lagoon, along with five other facies, such as supratidal flat, patchy reef, back shoal, shoal, and open shelf. Six types of diageneses are developed, with dissolution during the penecontemporaneous stage being the most beneficial to the reservoir and cementation being the most destructive. Three sequences were recognized in the Yamama Formation. It concluded that the hydrodynamics in semi-restricted depositional setting is weak overall and does not have the potential to develop large-scale high-quality reservoirs. A wide range of bioclasts were selectively dissolved to form a large number of secondary pores. Sediments rich in Algae, Bacinella, and peloids tend to form moldic pores, skeletal pores, and intergranular pores, respectively, which are prone to be favorable reservoirs. Controlled by the coupling of sedimentation and diagenesis driven by sequence, the reservoir is extremely heterogenous. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndrome (MDS) is a rare clonal hematopoietic disorder in children. The risk stratification system and treatment strategy for adults are unfit for children. The role of hypomethylating agents (HMAs) in higher-risk childhood MDS has not been identified. This study aimed to investigate the outcomes of hematopoietic stem cell transplantation (HSCT) in children with higher-risk MDS at one single center. A retrospective study was conducted in children with higher-risk MDS undergoing HSCT between September 2019 and March 2023 at Blood Diseases Hospital CAMS. The clinical characteristics and transplantation information were reviewed and analyzed. A total of 27 patients were analyzed, including 11 with MDS with excess blasts (MDS-EB), 14 with MDS-EB in transformation (MDS-EBt) or acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), and 2 with therapy-related MDS/AML (t-MDS/AML). Eight patients harbored monosomy 7. Before transplantation, induction therapy was administered to 25 patients, and 19 of them achieved bone marrow blasts <5% before HSCT. The stem cell source was unmanipulated-related bone marrow or peripheral blood stem cells for nineteen patients and unrelated cord blood for eight. All patients received decitabine-containing and Bu/Cy-based myeloablative conditioning; 26 patients achieved initial engraftment. The cumulative incidences of grade II–IV and grade III–IV acute graft-versus-host disease (GvHD) at 100 days were 65.4% and 42.3%, respectively. The incidence of cGvHD was 38.5%. The median follow-up was 26 (range 4–49) months after transplantation. By the end of follow-up, two patients died of complications and two died of disease progression. The probability of 3-year overall survival (OS) was 84.8% (95%CI, 71.1 to 98.5%). In summary, decitabine-containing myeloablative conditioning resulted in excellent outcomes for children with higher-risk MDS undergoing allogeneic HSCT. [ABSTRACT FROM AUTHOR]

This paper presents a novel nonlinear local bond-slip model for fiber-reinforced polymer (FRP) laminates externally bonded to thermally damaged concrete substrates. The proposed model is an extension of an existing two-parameter bond-slip model and incorporates two key parameters including interfacial fracture energy ( G f ) and interfacial brittleness index (B). To study the variations of G f and B with different thermal damage levels of the concrete substrate, an extensive experimental database of shear tests on FRP-to-thermally damaged concrete bonded joints was collected from the existing literature. The G f values were calculated from the peak pull loads with proper consideration of the bond length and width effects, while the B values were obtained by least-squares regression analysis using experimental load-displacement curves or measured strain distributions in the FRP laminates. The results have indicated that the G f values initially exhibit a slight increase accompanied by mild thermal damage of the concrete substrate after exposure to moderately high temperatures; however, these values significantly decrease when the exposure temperature exceeds 300°C. The B values initially decrease with high-temperature exposure and stabilize at around 50% of the initial values when the temperatures reach around 400°C. Despite the inherent variability in the test database, the proposed temperature-dependent bond-slip model has demonstrated its accuracy, as demonstrated by the comparisons between the theoretical predictions generated by the model and the corresponding shear test results. This interfacial bond-slip model is expected to serve as a constitutive law to characterize the bond behavior between externally bonded FRP laminates and thermally damaged concrete substrate, thus facilitating the practical application of high-performance FRP composites in the repair and strengthening of thermally or fire-damaged RC members. [ABSTRACT FROM AUTHOR]

Growth differentiation factor 15 (GDF15), a member of the transforming growth factor-beta superfamily, is expressed in several human organs. In particular, it is highly expressed in the placenta, prostate, and liver. The expression of GDF15 increases under cellular stress and pathological conditions. Although numerous transcription factors directly up-regulate the expression of GDF15, the receptors and downstream mediators of GDF15 signal transduction in most tissues have not yet been determined. Glial cell-derived neurotrophic factor family receptor α-like protein was recently identified as a specific receptor that plays a mediating role in anorexia. However, the specific receptors of GDF15 in other tissues and organs remain unclear. As a marker of cell stress, GDF15 appears to exert different effects under different pathological conditions. Cell senescence may be an important pathogenetic process and could be used to assess the progression of various lung diseases, including COVID-19. As a key member of the senescence-associated secretory phenotype protein repertoire, GDF15 seems to be associated with mitochondrial dysfunction, although the specific molecular mechanism linking GDF15 expression with ageing remains to be elucidated. Here, we focus on research progress linking GDF15 expression with the pathogenesis of various chronic lung diseases, including neonatal bronchopulmonary dysplasia, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, and pulmonary hypertension, suggesting that GDF15 may be a key biomarker for diagnosis and prognosis. Thus, in this review, we aimed to provide new insights into the molecular biological mechanism and emerging clinical data associated with GDF15 in lung-related diseases, while highlighting promising research and clinical prospects. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical value of positive copy number variations (CNVs) results by non‐invasive prenatal testing (NIPT) without fetal ultrasonography‐identified structural anomalies, especially with several known CNVs results. Methods: A total of 135,981 results of NIPT performed between April 1, 2017, and March 31, 2020, enrolled in the free NIPT service program implemented by the local government were retrospectively analyzed. Of these, 87 cases with positive NIPT screens for CNVs and no fetal ultrasonography‐identified anomalies were recalled and provided genetic counseling. After obtaining full informed consent, these cases were provided invasive prenatal diagnosis by karyotyping and chromosomal microarray analysis (CMA)/copy number variation sequencing (CNV‐seq) with follow‐up. One case was lost, while 86 cases were successfully followed up. Results: A total of 44 (50.6%) cases underwent invasive prenatal diagnosis, of which six cases were detected with abnormal karyotype. CMA/CNV‐Seq revealed 11 fetuses with positive results for CNVs, among whom eight were consistent with NIPT results, two were partially consistent, one was inconsistent, and positive predictive value (PPV) was 22.7% (10/44). For known CNVs, PPVs were 20% (15q11.2‐q13 microdeletion) and 33.3% (5p end deletions). Among 11 pregnant women with positive prenatal diagnosis, seven were confirmed to have pathogenic CNVs in their fetuses; four had CNVs of unknown clinical significance. Conclusions: Even in pregnancies without ultrasonography‐identified anomalies, a positive NIPT screen for CNVs must be interpreted with caution and validated by additional diagnostic study. [ABSTRACT FROM AUTHOR]

Background: Utilizing the traditional Cox regression model to identify the factors affecting the risk of mortality due to microinvasive cutaneous squamous cell carcinoma (micSCC) may produce skewed results. Since cause-specific mortality can guide clinical decision-making, this study employed the Fine-Gray model based on the Surveillance, Epidemiology, and End Results (SEER) database to identify significant predictive variables for the risk of micSCC-related mortality. Methods: This study used the information of patients with micSCC who were listed in the SEER database during 2000–2015. Cox regression and Fine-Gray models were utilized for the multivariable analysis, and Gray's test and the cumulative incidence function were used for the univariable analyses. Results: There were 100 patients who died from other reasons and 38 who died from micSCC among the 1259 qualified patients with micSCC. Most were female, white, married, had localized metastasis, etc. According to the univariable Gray's test (P < 0.05), the cumulative incidence rate for events of interest was strongly associated with age, sex, marital status, American Joint Committee on Cancer staging, radiation status, summary stage, chemotherapy status, surgery status, and tumor size. Multivariable Cox regression analysis and multivariable competing-risks analysis indicated that age, tumor size, and income were independent risk variables for the prognosis of patients with micSCC. In both age and tumor size variables, the competing-risks model showed a slight decrease in the hazard ratio and a slight narrowing of the 95% confidence interval compared with the Cox regression model. However, this pattern is not evident in the income variable. Conclusions: This study established a Fine-Gray model for identifying the independent risk factors that influence the risk of mortality among patients with micSCC. This study uncovers that, in the context of competing risks, age, tumor size, and income serve as independent risk factors influencing the risk of mortality due to micSCC among patients. Our findings have the potential to provide more accurate risk assessments for patient outcomes and contribute to the development of individualized treatment plans. [ABSTRACT FROM AUTHOR]

Background: Individuals diagnosed with Fanconi anemia (FA), an uncommon disorder characterized by chromosomal instability affecting the FA signaling pathway, exhibit heightened vulnerability to the onset of myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML). Methods: Herein, we employed diverse bioinformatics and statistical analyses to investigate the potential associations between the expression/mutation patterns of FA pathway genes and MDS/AML. Results: The study included 4295 samples, comprising 3235 AML and 1024 MDS from our and nine other online cohorts. We investigated the distinct proportion of race, age, French-American-British, and gender factors. Compared to the FA wild-type group, we observed a decrease in the expression of FNACD2, FANCI, and RAD51C in the FA mutation group. The FA mutation group exhibited a more favorable clinical overall survival prognosis. We developed a random forest classifier and a decision tree based on FA gene expression for cytogenetic risk assessment. Furthermore, we created an FA-related Nomogram to predict survival rates in AML patients. Conclusions: This investigation facilitates a deeper understanding of the functional links between FA and MDS/AML. [ABSTRACT FROM AUTHOR]

Electroacupuncture (EA) can effectively reduce surgical stress reactions and promote postoperative recovery, but the mechanisms remain unclear. The present study aims to examine the effects of EA on the hyperactivity of the hypothalamic‒pituitary‒adrenal (HPA) axis and investigate its potential mechanisms. Male C57BL/6 mice were subjected to partial hepatectomy (HT). The results showed that HT increased the concentrations of corticotrophin-releasing hormone (CRH), corticosterone (CORT), and adrenocorticotropic hormone (ACTH) in the peripheral blood and upregulated the expression of CRH and glucocorticoid receptors (GR) proteins in the hypothalamus. EA treatment significantly inhibited the hyperactivity of the HPA axis by decreasing the concentration of CRH, CORT, and ACTH in peripheral blood and downregulating the expression of CRH and GR in the hypothalamus. Moreover, EA treatment reversed the HT-induced downregulation of oxytocin (OXT) and oxytocin receptor (OXTR) in the hypothalamus. Furthermore, intracerebroventricular injection of the OXTR antagonist atosiban blocked the effects of EA. Thus, our findings implied that EA mitigated surgical stress-induced HPA axis dysfunction by activating the OXT/OXTR signaling pathway. [ABSTRACT FROM AUTHOR]

GNASis a complex locus characterized by multiple transcripts and an imprinting effect. It orchestrates a variety of physiological processes via numerous signaling pathways. Human diseases associated with the GNAS gene encompass fibrous dysplasia (FD), Albright's Hereditary Osteodystrophy (AHO), parathyroid hormone (PTH) resistance, and Progressive Osseous Heteroplasia (POH), among others. To facilitate the study of the GNAS locus and its associated diseases, researchers have developed a range of mouse models. In this review, we will systematically explore the GNAS locus, its related signaling pathways, the bone diseases associated with it, and the mouse models pertinent to these bone diseases. [ABSTRACT FROM AUTHOR]

Background: This study aimed to provide a reference for the prevention and treatment of abnormal bone mass in postmenopausal women by analysing the current situation and influencing factors of bone mass abnormalities in Tibet. Methods: A total of 229 postmenopausal Tibetan women were randomly selected from six counties by a multistage cluster random sampling method. Multiple logistic regression was utilized to analyse the status and influencing factors of bone mass abnormalities in postmenopausal Tibetan women. Results: Among 229 postmenopausal Tibetan women, the prevalence of osteopenia and osteoporosis was 54.6% and 9.6%, respectively. Age {odds ratio (OR) = 0.022 [95% confidence interval (CI) = 0.003 ~ 0.163]}, BMI [OR = 441.902 (20.899,9343.717)], altitude [OR = 18.818 (1.391,254.585)], and creatinine (CREA) levels [OR = 0.895 (0.825 ~ 0.971)] were significantly associated with the risk of osteoporosis. Conclusion: Postmenopausal Tibetan women had high rates of abnormal bone mass. Age, BMI, altitude and CREA levels were associated with osteoporosis. It is suggested that relevant departments should take targeted measures to promote health education on the prevention of osteoporosis in the general population and increase the screening of high-risk groups for osteoporosis to improve the bone health of postmenopausal Tibetan women. [ABSTRACT FROM AUTHOR]

Objective To understand the epidemiological status of hypertension and related influencing factors in the areas of very high altitude in Tibet, and provide a basis for the prevention and control of hypertension in high altitude areas. Methods Using the whole-group random sampling method, questionnaires and physical examinations were conducted to collect basic personal information, height, weight, and blood pressure from adult Tibetan residents living in Jiaqiong Township, Bange County, Naked City, Tibet Autonomous Region. SPSS 26. 0 software was used for descriptive analysis, univariate analysis and Logistic regression analysis. Results The prevalence of hypertension among native adult Tibetan residents in Jiaqiong Town, Bange County, Naked City was 25. 4%, with 30. 5% in males and 21. 3% in females. The results of the multifactorial logistic regression analysis showed that the age group was middle-aged group (45 -59 years old) (OR = 3. 570, 95% CI = 2. 036-6.260, P <0. 001), elderly group (≤60 years old) (OR =6.213, 95% CI = 2. 744-14.067, P < 0. 001), obesity (OR = 3. 292,95% CI = 1. 721-6. 298, P < 0. 001), waist-to-height-ratio 0. 5 (OR =2. 733, 95% CI = 1. 278-5. 844, P < 0. 05 ) were the independent risk factors for hypertension. Female gender (OR = 0. 402,95 % CI =0. 237-0. 682, P = 0. 001) were protective factors for hypertension. Conclusion The prevalence of hypertension in native Tibetans living in the very high altitude areas of Tibet is at an average level, and people with advanced age, obesity, and waist-to-height ratio ≤0. 5 are at high risk of hypertension. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a neurodegenerative disorder associated with α‐synuclein aggregation and dopaminergic neuron loss in the midbrain. There is evidence that psychological stress promotes PD progression by enhancing glucocorticoids‐related oxidative damage, however, the mechanisms involved are unknown. The present study demonstrated that plasma membrane phospholipid peroxides, as determined by phospholipidomics, triggered ferroptosis in dopaminergic neurons, which in turn contributed to stress exacerbated PD‐like motor disorder in mice overexpressing mutant human α‐synuclein. Using hormonomics, we identified that stress stimulated corticosteroid release and promoted 15‐lipoxygenase‐1 (ALOX15)‐mediated phospholipid peroxidation. ALOX15 was upregulated by α‐synuclein overexpression and acted as a fundamental risk factor in the development of chronic stress‐induced parkinsonism and neurodegeneration. Further, we demonstrated the mechanism by which corticosteroids activated the PKC pathway and induced phosphatidylethanolamine‐binding protein‐1 (PEBP1) to form a complex with ALOX15, thereby facilitating ALOX15 to locate on the plasma membrane phospholipids. A natural product isolated from herbs, leonurine, was screened with activities of inhibiting the ALOX15/PEBP1 interaction and thereby attenuating membrane phospholipid peroxidation. Collectively, our findings demonstrate that stress increases the susceptibility of PD by driving membrane lipid peroxidation of dopaminergic neurons and suggest the ALOX15/PEBP1 complex as a potential intervention target. [ABSTRACT FROM AUTHOR]

Photocatalytic mineralization of organic pollutions and simultaneously converting CO2 to CO (tetracycline → CO2 → CO) represents a fascinating way to solve the environmental and energy crisis. This work demonstrates the excellent mineralization and CO2 reduction performance of S-vacancy CdS and reveals the high efficiency of the carbon self-recycling two-in-one photocatalytic system. [ABSTRACT FROM AUTHOR]

The high intensities reached today by powerful lasers enable us to explore the interaction with matter in the relativistic regime, unveiling a fertile domain of modern science that is pushing far away the frontiers of plasma physics. In this context, refractive-plasma optics are being utilized in well established wave guiding schemes in laser plasma accelerators. However, their use for spatial phase control of the laser beam has never been successfully implemented, partly due to the complication in manufacturing such optics. We here demonstrate this concept which enables phase manipulation near the focus position, where the intensity is already relativistic. Offering such flexible control, high-intensity high-density interaction is becoming accessible, allowing for example, to produce multiple energetic electron beams with high pointing stability and reproducibility. Cancelling the refractive effect with adaptive mirrors at the far field confirms this concept and furthermore improves the coupling of the laser to the plasma in comparison to the null test case, with potential benefits in dense-target applications. Intense laser interaction with matter creates plasma which can act as a nonlinear optical medium. Here the authors demonstrate plasma as a refractive optics for relativistic intensity radiation, evident by the acceleration of multiple electron beams from a single laser pulse passing through the plasma. [ABSTRACT FROM AUTHOR]

Background: Contemporary risk‐directed treatment has improved the outcome of patients with acute lymphoblastic leukemia (ALL) and TCF3::PBX1 fusion. In this study, the authors seek to identify prognostic factors that can be used to further improve outcome. Methods: The authors studied 384 patients with this genotype treated on Chinese Children's Cancer Group ALL‐2015 protocol between January 1, 2015 and December 31, 2019. All patients provisionally received intensified chemotherapy in the intermediate‐risk arm without prophylactic cranial irradiation; those with high minimal residual disease (MRD) ≥1% at day 46 (end) of remission induction were candidates for hematopoietic cell transplantation. Results: The overall 5‐year event‐free survival was 84.4% (95% confidence interval [CI], 80.6–88.3) and 5‐year overall survival 88.9% (95% CI, 85.5–92.4). Independent factors associated with lower 5‐year event‐free survival were male sex (80.4%, [95% CI, 74.8–86.4] vs. 88.9%, [95% CI, 84.1–93.9] in female, p =.03) and positive day 46 MRD (≥0.01%) (62.1%, [95% CI, 44.2–87.4] vs. 87.1%, [95% CI, 83.4–90.9] in patients with negative MRD, p <.001). The presence of testicular leukemia at diagnosis (n = 10) was associated with particularly dismal 5‐year event‐free survival (33.3% [95% CI, 11.6–96.1] vs. 83.0% [95% CI, 77.5–88.9] in the other 192 male patients, p <.001) and was an independent risk factor (hazard ratio [HR], 5.7; [95% CI, 2.2–14.5], p <.001). Conclusions: These data suggest that the presence of positive MRD after intensive remission induction and testicular leukemia at diagnosis are indicators for new molecular therapeutics or immunotherapy in patients with TCF3::PBX1 ALL. Minimal residual disease ≥0.01% at the end of remission induction was associated with an inferior event‐free survival in patients with TCF3::PBX1 acute lymphoblastic leukemia despite intensified chemotherapy. The presence of overt testicular leukemia conferred a particularly poor outcome. [ABSTRACT FROM AUTHOR]

Most variations in the human genome refer to single-nucleotide variation (SNV), small fragment insertions and deletions, and genomic copy number variation (CNV). Many human diseases including genetic disorders are associated with variations in the genome. These disorders are often difficult to be diagnosed because of their complex clinical conditions, therefore, an effective detection method is needed to facilitate clinical diagnosis and prevent birth defects. With the development of high-throughput sequencing technology, the method of targeted sequence capture chip has been extensively used owing to its high throughput, high accuracy, fast speed, and low cost. In this study, we designed a chip that potentially captured the coding region of 3043 genes associated with 4013 monogenic diseases, with an addition of 148 chromosomal abnormalities that can be identified by targeting specific regions. To assess the efficiency, a strategy of combining the BGISEQ500 sequencing platform with the designed chip was utilized to screen variants in 63 patients. Eventually, 67 disease-associated variants were found, 31 of which were novel. The results of the evaluation test also show that this combined strategy complies with the requirements of clinical testing and has proper clinical application value. Genetic testing: One-step targeted sequencing helps diagnose genetic disorders A new DNA screening method potentially offers a one-step solution to the challenge of diagnosing genetic diseases. A team from China led by Xiaoming Wei from BGI Genomics in Shenzhen and Yang Wan from the Fuyang People's Hospital has designed a DNA chip that captures the coding regions of 4,013 disease-causing genes plus another 148 common chromosomal abnormalities. The targeted next-generation sequencing strategy can detect a variety of genomic alterations including single-letter mutations as well as chromosomal abnormalities including insertions, deletions and duplications of larger pieces of DNA. The researchers ran the test on blood samples from 63 patients with genetic disorders. In 52 of these individuals, they found a total of 67 different disease-related variants, including 31 novel variants, demonstrating the clinical utility of the approach. [ABSTRACT FROM AUTHOR]

Organic pollutants in wastewater are the biggest problem facing the world today due to population growth, rapid increase in industrialization, urbanization, and technological advancement. There have been numerous attempts to use conventional wastewater treatment techniques to address the issue of worldwide water contamination. However, conventional wastewater treatment has a number of shortcomings, including high operating costs, low efficiency, difficult preparation, fast recombination of charge carriers, generation of secondary waste, and limited light absorption. Therefore, plasmonic-based heterojunction photocatalysts have attracted much attention as a promising method to reduce organic pollutant problems in water due to their excellent efficiency, low operating cost, ease of fabrication, and environmental friendliness. In addition, plasmonic-based heterojunction photocatalysts contain a local surface plasmon resonance that enhances the performance of photocatalysts by improving light absorption and separation of photoexcited charge carriers. This review summarizes the major plasmonic effects in photocatalysts, including hot electron, local field effect, and photothermal effect, and explains the plasmonic-based heterojunction photocatalysts with five junction systems for the degradation of pollutants. Recent work on the development of plasmonic-based heterojunction photocatalysts for the degradation of various organic pollutants in wastewater is also discussed. Lastly, the conclusions and challenges are briefly described and the direction of future development of heterojunction photocatalysts with plasmonic materials is explored. This review could serve as a guide for the understanding, investigation, and construction of plasmonic-based heterojunction photocatalysts for various organic pollutants degradation. Herein, the plasmonic effects in photocatalysts, such as hot electrons, local field effect, and photothermal effect, as well as the plasmonic-based heterojunction photocatalysts with five junction systems for the degradation of pollutants are explained. Recent work on plasmonic-based heterojunction photocatalysts for the degradation of various organic pollutants in wastewater such as dyes, pesticides, phenols, and antibiotics is discussed. Challenges and future developments are also described. [ABSTRACT FROM AUTHOR]

A gas chromatography-mass spectrometry (GC-MS) method for the determination of four key aroma compounds, 3 -methylbutanal, 3 -methylbutanol, 3 -methylthio -propionic aldehyde and phenylethanol in quick - brewed fish sauce was established. Headspace solid phase microextraction (HS-SPME) and mass spectrometry (GC-MS) were used to identify four key aroma compounds in fish sauce. The influence of extraction temperature, extraction time and selection of internal standard on the analysis results were examined. The results showed that the optimized SPME conditions were as follows: the internal standard substance was 2-methyl-3-heptanone, extraction temperature 45 extraction time 40 minutes. The four key aroma compounds had a good linear relationship, and the correlation coefficient R2 was higher than 0.98. In addition, the standard recovery experiment showed that the recovery rate of the samples was 75.47%-134.41%, and the relative standard deviation was less than 10%, which met the requirements of trace quantification. The gas chromatography-mass spectrometry method used for the quantitative detection of the key aroma compounds in fish sauce was simple, fast with high precision, meeting the needs of detection of the four key aroma compounds in fish sauce, and contributing to the establishment of aroma quality evaluation system. [ABSTRACT FROM AUTHOR]

Density downramp injection has been demonstrated to be an elegant and efficient approach for generating high-quality electron beams in laser wakefield accelerators. Recent studies have demonstrated the possibilities of generating electron beams with charges ranging from tens to hundreds of picocoulombs while maintaining good beam quality. However, the plasma and laser parameters in these studies have been limited to specific ranges or attention has been focused on separate physical processes such as beam loading, which affects the uniformity of the accelerating field and thus the energy spread of the trapped electrons, the repulsive force from the rear spike of the bubble, which reduces the transverse momentum p⊥ of the trapped electrons and results in small beam emittance, and the laser evolution when traveling in the plasma. In this work, we present a comprehensive numerical study of downramp injection in the laser wakefield, and we demonstrate that the current profile of the injected electron beam is directly correlated with the density transition parameters, which further affects the beam charge and energy evolution. By fine-tuning the plasma density parameters, electron beams with high charge (up to several hundreds of picocoulombs) and low energy spread (around 1% FWHM) can be obtained. All these results are supported by large-scale quasi-three-dimensional particle-in-cell simulations. We anticipate that the electron beams with tunable beam properties generated using this approach will be suitable for a wide range of applications. [ABSTRACT FROM AUTHOR]

Background: Conducting routine mild cognitive impairment (MCI) and dementia screening for older adults in the community is important, which not only can improve our understanding of these diseases but also can increase early detection and treatment. Methods: To analyze the reliability and validity of the informant AD8 and explore the cut‐off values for screening MCI and dementia in the community‐dwelling older adults, this study adopted a multi‐stage cluster sampling method to recruit 327 participants aged 60 and over in communities. The informant AD8 and Clinical Dementia Rating (CDR) scales were used to evaluate cognitive function of the subjects, and the receiver operating characteristic curves (ROC) was conducted to test the screening efficacy. Results: Among the 327 participants, 33.0% of them met the criteria of MCI, and 3.4% of them met the criteria of dementia. The area under the receiver operating characteristic curve (AUC) of the informant AD8 for screening dementia was 0.974, with a screening cut‐off of three, sensitivity of 90.9% and specificity of 89.0%. But it has a poor discriminability in MCI screening [AUC = 0.645, 95% confidence interval (CI): 0.578–0.711]. Conclusions: This study suggests that the informant AD8 is an ideal and useful tool for dementia screening in community‐dwelling older adults. However, it is less capable to distinguish older adults with MCI from those with normal cognitive function. [ABSTRACT FROM AUTHOR]

Juvenile myelomonocytic leukemia (JMML) is an aggressive pediatric myeloproliferative disease, and newly diagnosed patients frequently cannot tolerate hematopoietic stem cell transplantation (HSCT) at diagnosis due to their poor condition. This retrospective analysis aimed to explore the short-term effect of decitabine-dominant therapy on improving the condition of JMML patients before HSCT. The subjects were 10 JMML patients. All patients were treated with decitabine after low-dose chemotherapy with an interval of 4 weeks before bridging to HSCT. The median treatment course was 3 cycles, and the overall response rate (ORR) was 70.0% after one cycle and 71.4% after three cycles. White blood cell (WBC) and monocyte counts were significantly lower after treatment, and spleen volume was also lower, though not significantly lower. The 12 month progression-free survival rate (PFS) was 80.0 ± 12.6%. Decitabine-dominant therapy was beneficial for reducing tumor burden and improving clinical condition. [ABSTRACT FROM AUTHOR]

As China's economy and the U.S. economy have shown a definite interaction, there is considerable interest in studying the correlation between the Chinese stock market and the US financial markets. This paper uses an Asymmetric Dynamic Conditional Correlation (ADCC)-GARCH to investigate the correlation between the Shanghai Composite Index (SHCI) and the U.S. financial markets, including SP500, NASDAQ, and US dollar indexes. The empirical results show that the time-varying daily and the lag-one correlation between China and the US stock markets have different performances during global events and national events. Compared with the complicated effect of negative events on the correlation of the stock market, SHCI and USD are negatively correlated with higher negative correlation during the global negative events. In addition, we found Chinese investors are more contagious to the news than American investors, indicating that the Chinese government's policy are more indicated to Chinese investors. Finally, some policy suggestions are provided, and are beneficial to risk prevention and control, and investment. [ABSTRACT FROM AUTHOR]

Hypertension is characterized by sympathetic hyperactivity, which is related to the overexcitation of the presympathetic neurons in the rostral ventrolateral medulla (RVLM). Nitric oxide (NO) has been reported to be a vital neuromodulator involved in central cardiovascular regulation. However, the mechanism of interleukin-enhanced binding factor 3 (ILF3) participating in blood pressure (BP) regulation is still unclear. Therefore, this study aims to clarify the role of ILF3 within the rostral ventrolateral medulla (RVLM) in regulating NO in hypertension. It was found that the expression level of ILF3 was significantly increased in the RVLM of spontaneously hypertensive rats (SHR) compared with Wistar-Kyoto (WKY) rats through microarray gene expression analysis, Western blot, and immunofluorescence. Overexpression of ILF3 by injecting constructed adenovirus into the RVLM increased the BP and renal sympathetic nerve activity (RSNA) of the WKY rats, significantly decreasing NO production and neuronal nitric oxide synthase (nNOS) expression. Knockdown of ILF3 in the RVLM of SHR significantly reduced BP but increased NO production and the neuronal nitric oxide synthase (nNOS) expression. Furthermore, it was found that the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway was activated via Western blotting in the RVLM after overexpression of ILF3, whereas it was attenuated after knockdown of ILF3 in SHR. In addition, inhibition of PI3K by intracisternal infusion of the PI-103 attenuated the increase in Akt phosphorylation and decrease in nNOS expression and NO production caused by overexpressing ILF3, which ultimately blunted high BP induced by overexpressing ILF3. Taken together, this current study suggests that ILF3 participates in high BP via reducing NO production in the RVLM through PI3K/Akt pathway. [ABSTRACT FROM AUTHOR]

Summary: The effect of prolonged pulse therapy with vincristine and dexamethasone (VD) during maintenance therapy on the outcome of paediatric patients with TCF3‐PBX1 positive acute lymphoblastic leukaemia (ALL) remains uncertain. We conducted non‐inferiority analysis of 263 newly diagnosed TCF3‐PBX1 positive ALL children who were stratified and randomly assigned (1:1) to receive seven additional VD pulses (the control group) or not (the experimental group) in the CCCG‐ALL‐2015 clinical trial from January 2015 to December 2019 (ChiCTR‐IPR‐14005706). There was no significant difference in baseline characteristics between the two groups. With a median follow‐up of 4.2 years, the 5‐year event‐free survival (EFS) and 5‐year overall survival (OS) in the control group were 90.1% (95% confidence interval [CI] 85.1–95.4) and 94.7% (95% CI, 90.9–98.6) comparable to those in the experimental group 89.2% (95% CI 84.1–94.7) and 95.6% (95% CI 91.8–99.6), respectively. Non‐inferiority was established as a one‐sided 95% upper confidence bound for the difference in probability of 5‐year EFS was 0.003, and that for 5‐year OS was 0.01 by as‐treated analysis. Thus, omission of pulse therapy with VD beyond one year of treatment did not affect the outcome of children with TCF3‐PBX1 positive ALL. [ABSTRACT FROM AUTHOR]

Background: At present, the empty nest phenomenon is becoming more and more serious in the world, especially in China, and its health problems deserve attention. Therefore, the purpose of this study is to explore the impact of community social capital on the health-related quality of life of empty-nest elderly. Methods: The study used data collected from a survey study conducted between 2018 and 2019 in Sichuan province, China, with 638 empty-nest elderly meeting our criteria. SF-12 scale and self-made social capital scale were used to evaluate the health-related quality of life and community social capital of empty-nest elderly. Through descriptive statistical analysis, bivariate analysis and hierarchical multiple regression model, this study analyzes the relationship between community social capital and health-related quality of life of empty-nest elderly. Considering the role of living arrangements, this study further uses the simple effect analysis method to explore the moderating role of living arrangements. Results: After controlling the relevant variables, the cognitive social capital (CSC) of empty-nest elderly had a positive relationship with the physical health summary (PCS) (β = 0.188, p＜0.001) and mental health summary (MCS) (β = 0.205, p＜0.001). No effect of structural social capital on quality of life was found as a result. Living arrangements played a moderation effect on the relationship between CSC and MCS (β=-2.018, p＜0.05). The MCS score of high CSC group (55.516 ± 0.757) was significantly higher than that of low CSC group (49.383 ± 0.722). Conclusion: The results suggest empty-nest elderly has poorer physical health and weaker structural social capital, while the cognitive social capital has a greater positive impact on their quality of life. Targeted interventions to enhance community social capital may be beneficial to improve health status of this vulnerable population. [ABSTRACT FROM AUTHOR]

Due to obvious differences in the properties of the filling body and surrounding rock, deformation always develops near the contact zone. Thus, determining the damage and failure characteristics of the contact zone between the backfill and surrounding rock is a precondition for safe production in mines. Taking Jinchuan mine as study area, the backfill-surrounding rock contact zones are divided into three models according to their different geometric shapes, namely, a linear model, embedded model, and multiple broken line model. A combined numerical simulation and physical model test method was adopted in this study. The research results show that the damage in the linear model begins at the seam, the failure is mainly concentrated in the filling body, and shear failure is dominant. The damage in the embedded model initially occurs around the inflection points, while the damage in the multiple broken line model initially occurs at the seams, and cracks always appear on the vertical contact surface first. Among the three contact models, the stability increases as follows: embedded > multiple broken line > linear. Moreover, the filling body enclosed by surrounding rock is the most stable, and the surrounding rock located in the footwall is more stable than the filling body located in the footwall. The conclusions of this study provide a theoretical basis for designing a mining scheme for Jinchuan mine and other mines with similar geological conditions and mining methods, and they provide a reference for studying the mechanical properties and stability of composite materials. [ABSTRACT FROM AUTHOR]

Background: Fanconi anemia (FA) is a rare disease of bone marrow failure. FA patients are prone to develop myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). However, the molecular clonal evolution of the progression from FA to MDS/AML remains elusive. Methods: Herein, we performed a comprehensive genomic analysis using an FA patient (P1001) sample that transformed to MDS and subsequently AML, together with other three FA patient samples at the MDS stage. Results: Our finding showed the existence of polyclonal pattern in these cases at MDS stage. The clonal evolution analysis of FA case (P1001) showed the mutations of UBASH3A, SF3B1, RUNX1 and ASXL1 gradually appeared at the later stage of MDS, while the IDH2 alteration become the dominant clone at the leukemia stage. Moreover, single-cell sequencing analyses further demonstrated a polyclonal pattern was present at either MDS or AML stages, whereas IDH2 mutated cell clones appeared only at the leukemia stage. Conclusions: We thus propose a clonal evolution model from FA to MDS and AML for this patient. The results of our study on the clonal evolution and mutated genes of the progression of FA to AML are conducive to understanding the progression of the disease that still perplexes us. [ABSTRACT FROM AUTHOR]

Background: The clinical dementia rating (CDR) scale is commonly used to diagnose dementia due to Alzheimer's disease (AD). The sum of boxes of the CDR (CDR-SB) has recently been emphasized and applied to interventional trials for tracing the progression of cognitive impairment (CI) in the early stages of AD. We aimed to study the influence of baseline CDR-SB on disease progression to dementia or reversion to normal cognition (NC). Materials and methods: The baseline CDR < 1 cohort registered from September 2015 to August 2020 with longitudinal follow-up in the Historybased Artificial Intelligence Clinical Dementia Diagnostic System (HAICDDS) database was retrospectively analyzed for the rates of conversion to CDR ≥ 1. A Cox regression model was applied to study the influence of CDR-SB levels on progression, adjusting for age, education, sex, neuropsychological tests, neuropsychiatric symptoms, parkinsonism, and multiple vascular risk factors. Results: A total of 1,827 participants were analyzed, including 1,258 (68.9%) non-converters, and 569 (31.1%) converters with mean follow-up of 2.1 (range 0.4-5.5) and 1.8 (range 0.3-5.0) years, respectively. Conversion rates increased with increasing CDR-SB scores. Compared to a CDR-SB score of 0, the hazard ratios (HR) for conversion to dementia were 1.51, 1.91, 2.58, 2.13, 3.46, 3.85, 3.19, 5.12, and 5.22 for CDR-SB scores of 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, and ≥4.5, respectively (all p < 0.05 except for CDR-SB score = 0.5). In addition, older age, lower education, lower cognitive performance, and a history of diabetes also increased conversion rates. Furthermore, reversions to NC were 12.5, 5.6, 0.9, and 0% for CDR-SB scores of 0.5, 1.0-2.0, 2.5-3.5 and ≥4.0, respectively (p < 0.001). Conclusion: CDR-SB in predementia or very mild dementia (VMD) stages highly predicts progression to dementia or reversion to NC. Therefore, CDRSB could be a good candidate for tracing the effectiveness of pharmacological and non-pharmacological interventions in populations without dementia. [ABSTRACT FROM AUTHOR]

The quartz-crystal resonator is the core device for frequency control in modern communication systems and network technology. At present, in modern resonator blanks manufacturing, BOE solution is usually used as the etching solution, but its etching rate is relatively volatile, and the surface morphology of the blanks is prone to defects after etching, which brings certain difficulties to the deep-etching process of the wafer. To solve the above challenges, this paper systematically compares a BOE solution and anhydrous etching solution in terms of etching rate, surface morphology, and electrical properties of the blanks after etching. Seven groups of blanks were etched using different etching solutions with different etching conditions to verify their effect on the surface morphology and electrical properties of quartz blanks. The experimental results suggest that the application of anhydrous etching solution has achieved better surface morphology and electrical properties and can be more suitable for application in batch manufacturing. In general, when using anhydrous etching solution, it is possible to reduce surface roughness by up to 70% and equivalent resistance by 32%, and the etch rate is almost 10 times lower than BOE solution under the same temperature, which is more conducive to the rate control of wafers in the etching process. [ABSTRACT FROM AUTHOR]

Summary: To create a personal prognostic model and modify the risk stratification of paediatric acute myeloid leukaemia, we downloaded the clinical data of 597 patients from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database as a training set and included 189 patients from our centre as a validation set. In the training set, age at diagnosis, ‐7/del(7q) or ‐5/del(5q), core binding factor fusion genes, FMS‐like tyrosine kinase 3‐internal tandem duplication (FLT3‐ITD)/nucleophosmin 1 (NPM1) status, Wilms tumour 1 (WT1) mutation, biallelic CCAAT enhancer binding protein alpha (CEBPA) mutation were strongly correlated with overall survival and included to construct the model. The prognostic model demonstrated excellent discriminative ability with the Harrell's concordance index of 0.68, 3‐ and 5‐year area under the receiver operating characteristic curve of 0.71 and 0.72 respectively. The model was validated in the validation set and outperformed existing prognostic systems. Additionally, patients were stratified into three risk groups (low, intermediate and high risk) with significantly distinct prognosis, and the model successfully identified candidates for haematopoietic stem cell transplantation. The newly developed prognostic model showed robust ability and utility in survival prediction and risk stratification, which could be helpful in modifying treatment selection in clinical routine. [ABSTRACT FROM AUTHOR]

The backfill mining method transports treated tailings to the mined-out area, which not only improves the surrounding environment of the mine but also enables the mined-out area to continue mining and production under the support of the filling body. However, with the growth in the depth and scale of mining, ground subsidence, and backfill deformation are becoming increasingly serious problems. As an example, in the Jinchuan mine, a typical multi-stage filling mining mine in China, the deformation law of surface rock mass and backfill are studied through a method combining field monitoring and numerical simulation. The major findings are as follows: (a) A settlement funnel is formed on the ground, and its radius gradually expands with continuous mining and filling. The location of the settlement center moves toward the surface above the footwall of the ore body, and the maximum subsidence reaches 739 mm in 14.5 years. (b) Three-section mining significantly affects the surface deformation, and the single subsidence center on the upper wall develops into the double subsidence center with the mining and filling. When the three-section mining is finished, the maximum value of the surface subsidence reaches about 1.35 m and the mining area is still in a relatively stable state. (c) The whole filling body presents obvious subsidence, with the development of the multi-stage mining and filling. Bed separation phenomena are found between the filling layers, and the closer to the interior, the more obvious it becomes. The backfill's subsidence characteristics are similar to the surface's; that is, both the subsidence amount and speed are higher on the hanging wall than on the footwall. (d) The backfill mainly shrinks inward in the horizontal direction, and the deformation is mainly manifested as an internal uplift and an external subsidence in the vertical direction. The mass instability of the backfill is difficult because of the insufficient deformation space, and the influence of large-scale deformation on the mining and overlying strata needs to be considered, as well as the local deformation near the rock contact zone surrounding the backfill. The results provide technical support for filling mining in the Jinchuan mine and provide a reference for other projects with similar engineering conditions. [ABSTRACT FROM AUTHOR]