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Ischemic stroke (IS) is a leading cause of adult disability that can severely compromise the quality of life for patients. Accurately predicting the IS functional outcome is crucial for precise risk stratification and effective therapeutic interventions. We developed a predictive model integrating genetic, environmental, and clinical factors using data from 7819 IS patients in the Third China National Stroke Registry. Employing an 80:20 split, we randomly divided the dataset into development and internal validation cohorts. The discrimination and calibration performance of models were evaluated using the area under the receiver operating characteristic curves (AUC) for discrimination and Brier score with calibration curve in the internal validation cohort. We conducted genome-wide association studies (GWAS) in the development cohort, identifying rs11109607 (ANKS1B) as the most significant variant associated with IS functional outcome. We employed principal component analysis to reduce dimensionality on the top 100 significant variants identified by the GWAS, incorporating them as genetic factors in the predictive model. We employed a machine learning algorithm capable of identifying nonlinear relationships to establish predictive models for IS patient functional outcome. The optimal model was the XGBoost model, which outperformed the logistic regression model (AUC 0.818 versus 0.756, P  < .05) and significantly improved reclassification efficiency. Our study innovatively incorporated genetic, environmental, and clinical factors for predicting the IS functional outcome in East Asian populations, thereby offering novel insights into IS functional outcome. [ABSTRACT FROM AUTHOR]

Selenium, as an essential trace element, is intricately linked to the onset and progression of numerous diseases due to deficiencies in selenium intake. Selenium compounds exhibit tumor specificity and can efficiently inhibit the growth of tumor cells, making them potential candidates for cancer treatment. Nevertheless, given its status as one of the most widely consumed crops globally, increasing the selenium content in rice could prove advantageous in alleviating the prevailing issue of selenium intake deficiency, particularly in China. This review explored the regulatory role of selenium in rice growth, the regional distribution characteristics of soil selenium content in various rice-growing regions in China, and the impact of cultivation practices on selenium fortification in rice, aiming to suggest improved rice cultivation management strategies to enhance the capacity for rice selenium biofortification. The findings revealed that: (1) In Northeast and North China, characterized by alkaline soils and severe selenium deficiency, it is advisable to moderately decrease the duration of flooding, elevate the soil redox potential, and apply organic and nitrogen fertilizers in a judicious manner. (2) In Southwest China, which is characterized by acidic soils, alternating wet and dry irrigation should be employed, and the biofortification of selenium can be facilitated by applying lime and foliar spraying of selenium fertilizer. (3) In the south-central region of China, distinguished by acidic soils and double-cropped rice, it is recommended that intermittent or alternating wet and dry irrigation be employed, and the reasonable application of organic, silica, and selenium fertilizers is advocated. (4) In the northwest region, characterized by slightly alkaline soil and mild selenium deficiency, it is recommended to implement various water management practices, including shallow water during the seedling stage, deep water during the booting stage, and wet grain filling. Additionally, a rational application of nitrogen, phosphorus, and potassium fertilizers, along with foliar application of selenium fertilizer, should be employed. (5) Cultivating selenium-enriched, high-yielding, and high-quality rice varieties proves to be an effective strategy in addressing selenium deficiency. In conclusion, the unique characteristics of diverse rice-growing regions in China indicate that suitable water management, fertilization techniques, and varietal selection practices can effectively enhance the selenium content in rice, thereby maximizing the nutritional requirements for selenium. [ABSTRACT FROM AUTHOR]

The lack of effective treatments for alleviating irreversible skeletal muscle atrophy caused by peripheral nerve dysfunction is a clinical problem. To identify therapeutic targets, signaling pathways in muscle cells activated by denervation have been explored, including the important roles of Cx43, a kind of protein that forms gap junctions, in other types of pathological process. The present study investigated the negative role of Cx43 in aggravated muscle cell degeneration following denervation. The blueberry extract was applied orally on mice models, and its protective effect against denervated skeletal muscle atrophy was found by wet weight measurement and tissue staining observation. Cx43/Akt pathway in denervated muscle cells was modulated by blueberry extract. In conclusion, the negative effects of Cx43 on denervated skeletal muscle atrophy were attenuated by blueberry extract by regulating the Akt pathway. [ABSTRACT FROM AUTHOR]

Introduction: We utilized data from the Third China National Stroke Registry to investigate the prevalence of atrial cardiopathy markers in patients with embolic stroke of undetermined source (ESUS) and to assess their association with death and stroke recurrence. Methods: In China, patients experiencing transient ischemic attack or ischemic stroke were recruited consecutively by the Third China National Stroke Registry. We compared atrial cardiopathy markers, such as left atrial (LA) enlargement, increased P-wave terminal force in lead V1 (PTFV1), premature atrial contractions, paroxysmal supraventricular tachycardia, advanced interatrial block, prolonged PR interval, prolonged P-wave dispersion, and prolonged P-wave duration between ESUS patients and those with small vessel disease and large artery atherosclerosis strokes. The association between these markers and the recurrence of stroke as well as mortality risk in ESUS patients was evaluated using Cox regression analysis. Results: Of 8,528 ischemic stroke patients who underwent a standard diagnostic workup, 2,415 were identified as having ESUS. Multivariable analysis revealed a significant association between elevated PTFV1 and an increased risk of stroke recurrence (HR: 2.50; 95% CI: 1.53–4.09; p < 0.01) as well as mortality (HR: 3.76; 95% CI: 1.58–8.91; p < 0.01) at 1 year in patients with ESUS. Furthermore, we observed that moderate-severe LA enlargement slightly increased the risk of stroke recurrence in patients with ESUS (HR: 1.95; 95% CI: 0.90–4.26; p = 0.09). Both LA diameter (HR: 1.03; 95% CI: 1.00–1.06; p = 0.03) and the top quartile of the LA diameter index (HR: 1.56; 95% CI: 1.03–2.40; p = 0.04) were associated with stroke recurrence in patients with ESUS. Conclusions: PTFV1 was independently associated with an elevated risk of stroke recurrence and mortality in ESUS patients. Additionally, a trend toward a correlation between LA enlargement and high stroke recurrence risk after ESUS was observed. [ABSTRACT FROM AUTHOR]

The ecological compensation system also implements the concept of intergenerational equity. By actively exploring and perfecting the ecological compensation system, resource-based cities can carry out ecological restoration and restoration in time while developing oil and gas resources, so that the carrying capacity of ecological environment can support the benign development of social economy and environment in resource-based cities, which is of great significance not only to resource-based cities, but also to the sustainable development of the entire oil and gas resources industry. Taking ecological compensation as the breakthrough point, this paper points out the necessity of oil and gas resources tax system from the perspective of ecological compensation, and puts forward some ideas and suggestions, such as levying environmental protection tax, establishing the legal system of ecological compensation for oil and gas resources development, improving the integrity and rationality of oil and gas resources tax system and other guarantee mechanisms.

This study utilizes polyethylene terephthalate (PET) aggregate of different particle sizes (21 μm, 107 μm, and 244 μm) to replace natural aggregate in the preparation of PET-modified engineered cementitious composite (P-ECC). The impact of PET aggregate particle size on the performance of P-ECC is examined herein from micro to macro levels. The focus is on the influence patterns and mechanisms of P-ECC's workability, its basic mechanical properties, and its microstructure. Crack parameters are processed to quantitatively analyze crack development patterns. Using microscopic techniques, the interfacial transition zone (ITZ) between different aggregates and the cement matrix is compared, and the failure mechanism of P-ECC is analyzed. The results show that the incorporation of PET aggregate can improve P-ECC's workability and reduce its self-weight, but incorporation has a negative effect on compressive strength. Additionally, the particle size of PET aggregate significantly affects the uniaxial tensile performance of P-ECC. Compared to conventional ECC, the tensile strength of P-S (21 μm PET) increased the most markedly (18.1%), and the ultimate tensile strain of P-M (107 μm PET) increased the most markedly (66.0%), with both demonstrating good crack control and deformation energy dissipation capabilities. The uniaxial tensile performance of P-L (244 μm PET) was lower than that of the conventional ECC. Microscopic tests revealed that the increase in PET aggregate particle size enlarges the ITZ width and its surrounding pores. Appropriate pore enlargement is beneficial for enhancing tensile ductility, while excessive pores have a negative effect. The study results reveal the impact of PET aggregate particle size on the performance of P-ECC, providing new insights for the performance optimization of ECC. [ABSTRACT FROM AUTHOR]

Background: Comorbidities reduce quality of life for people with dementia and caregivers. Some comorbidities share a genetic basis with dementia. Objective: The objective of this study is to assess comorbidity in patients with different dementia subtypes in order to better understand the pathogenesis of dementias. Methods: A total of 298 patients with dementia were included. We collected some common comorbidities. We analyzed the differences in comorbidities among patients with dementia according to clinical diagnosis, age of onset (early-onset: < 65 and late-onset: ≥65 years old) and apolipoprotein (APOE) genotypes by using the univariate and multivariate approaches. Results: Among 298 participants, there were 183 Alzheimer's disease (AD), 40 vascular dementia (VaD), 37 frontotemporal dementia (FTLD), 20 Lewy body dementia (LBD), and 18 other types of dementia. Based on age of onset, 156 cases had early-onset dementia and 142 cases had late-onset dementia. The most common comorbidities observed in all dementia patients were hyperlipidemia (68.1%), hypertension (39.9%), insomnia (21.1%), diabetes mellitus (19.5%), and hearing impairment (18.1%). The prevalence of hypertension and cerebrovascular disease was found to be higher in patients with VaD compared to those with AD (p = 0.002, p < 0.001, respectively) and FTLD (p = 0.028, p = 0.004, respectively). Additionally, patients with late-onset dementia had a higher burden of comorbidities compared to those with early-onset dementia. It was observed that APOE ɛ4/ɛ4 carriers were less likely to have insomnia (p = 0.031). Conclusions: Comorbidities are prevalent in patients with dementia, with hyperlipidemia, hypertension, insomnia, diabetes, and hearing impairment being the most commonly observed. Comorbidity differences existed among different dementia subtypes. [ABSTRACT FROM AUTHOR]

Background: Previous studies on APOE have mostly focused on APOE ε4, while less attention has been paid to APOE ε2. The aim of this study was to clarify the effect of APOE ε2 on different cognitive domains in dementia patients. Method: All subjects were from the Peking Union Medical College Hospital (PUMCH) dementia cohort and included clinical diagnoses of AD, VaD, FTLD, and LBD. All included individuals had completed the neuropsychological assessment. Genotypes were used to bin participants into five groups based on carrier status: ε2 carriers (ε2/ε2 or ε2/ε3), ε2/ε4 carriers, ε3/ε3 carriers, ε3/ε4 carriers, and ε4/ε4 carriers. The effect of APOE ε2 on different cognitive domains of the patients with dementia was assessed by using multivariate regression models. Result: A total of 348 dementia patients were included in this study, with a mean age of 68.4± 9.8 years, 69.3% with AD, 14.4% with VaD, 10.1% with FTLD, and 6.3% with DLB. 19.5% were ε2 carriers, 3.4% were ε2/ε4 carriers, 30.7% were ε3/ε3 carriers, 32.3% were ε3/ε4 carriers, and 14.1% were ε4/ε4 carriers. Compared to ε3/ε3 carriers, ε2 carriers were more successful in MOCA (β = 1.93, P = 0.016), trail making test part A (β = 1.18, P = 0.025), nonverbal memory (β = 1.08, P = 0.003), AVLT 5 (β = 0.27, P = 0.039), episodic memory (β = 0.41, P = 0.005), calculation (β = 1.05, P = 0.045) and word fluency (β = 1.82, P = 0.03). Compared to ε4/ε4 carriers, ε2 carriers performed better in nonverbal memory (β = 1.59, P<0.001), AVLT 4 (β = 0.68, P<0.001), AVLT 5 (β = 0.62, P<0.001), associative learning test (β = 0.57, P<0.001), episodic memory (β = 0.46, P = 0.007) performed better. When adjusted for clinical diagnosis, the above significant differences remained statistically significant. While ε2/ε4 carriers performed better in associative learning (β = 1.38, P<0.001) compared to ε3/ε3, visuospatial (β = ‐1.94, P = 0.020) function was worse than ε3/ε3 carriers. Compared to ε4/ε4, ε2/ε4 carriers performed worse in similarity test and visuospatial function, while in verbal memory performed better Conclusion: The present study found complex effects of APOE ε2 and APOE ε2/ε4 on cognitive domains that varied according to the selected control group, whereas different clinical diagnoses did not seem to influence their effects. [ABSTRACT FROM AUTHOR]

Background: Arterial spin labeling (ASL) is helpful in early diagnosis and differential diagnosis of Alzheimer's disease (AD), with advantages including no exposure to radioactivity, no injection of a contrast agent, more accessible, and relatively less expensive. Objective: To establish the perfusion pattern of different dementia in Chinese population and evaluate the effectiveness of ASL in differentiating AD from cognitive unimpaired (CU), mild cognitive impairment (MCI), and frontotemporal dementia (FTD). Methods: Four groups of participants were enrolled, including AD, FTD, MCI, and CU based on clinical diagnosis from PUMCH dementia cohort. ASL image was collected using 3D spiral fast spin echo–based pseudo-continuous ASL pulse sequence with background suppression and a high resolution T1-weighted scan covering the whole brain. Data processing was performed using Dr. Brain Platform to get cerebral blood flow (ml/100g/min) in every region of interest cortices. Results: Participants included 66 AD, 26 FTD, 21 MCI, and 21 CU. Statistically, widespread hypoperfusion neocortices, most significantly in temporal-parietal-occipital cortices, but not hippocampus and subcortical nucleus were found in AD. Hypoperfusion in parietal lobe was most significantly associated with cognitive decline in AD. Hypoperfusion in parietal lobe was found in MCI and extended to adjacent temporal, occipital and posterior cingulate cortices in AD. Significant reduced perfusion in frontal and temporal cortices, including subcortical nucleus and anterior cingulate cortex were found in FTD. Hypoperfusion regions were relatively symmetrical in AD and left predominant especially in FTD. Conclusion: Specific patterns of ASL hypoperfusion were helpful in differentiating AD from CU, MCI, and FTD. [ABSTRACT FROM AUTHOR]

Little is known about the role of high-sensitivity C-reactive protein (hsCRP) in the relationship between P-wave terminal force in lead V1 (PTFV1) and stroke prognosis. We aimed to investigate how hsCRP influences the effect of PTFV1 on ischemic stroke recurrence and mortality. In this study, patients enrolled in the Third China National Stroke Registry, which enrolled consecutive patients who had suffered an ischemic stroke or transient ischemic attack in China, were analyzed. After excluding patients with atrial fibrillation, 8271 patients with PTFV1 and hsCRP measurements were included in this analysis. Cox regression analyses were used to assess the association between PTFV1 and stroke prognosis according to different inflammation statuses stratified by an hsCRP level of 3 mg/L. A total of 216 (2.6%) patients died, and 715 (8.6%) patients experienced ischemic stroke recurrence within 1 year. In patients with hsCRP levels ≥ 3 mg/L, elevated PTFV1 was significantly associated with mortality (HR, 1.75; 95% CI, 1.05–2.92; p = 0.03), while in those with hsCRP levels < 3 mg/L, such an association did not exist. In contrast, in patients with hsCRP levels < 3 mg/L and those with hsCRP levels ≥ 3 mg/L, elevated PTFV1 remained significantly associated with ischemic stroke recurrence. The predictive role of PTFV1 towards mortality but not ischemic stroke recurrence differed in terms of hsCRP levels. [ABSTRACT FROM AUTHOR]

We showed that the chemokine receptor C‐X‐C Motif Chemokine Receptor 2 (CXCR2) is essential for cartilage homeostasis. Here, we reveal that the CXCR2 ligand granulocyte chemotactic protein 2 (GCP‐2) was expressed, during embryonic development, within the prospective permanent articular cartilage, but not in the epiphyseal cartilage destined to be replaced by bone. GCP‐2 expression was retained in adult articular cartilage. GCP‐2 loss‐of‐function inhibited extracellular matrix production. GCP‐2 treatment promoted chondrogenesis in vitro and in human cartilage organoids implanted in nude mice in vivo. To exploit the chondrogenic activity of GCP‐2, we disrupted its chemotactic activity, by mutagenizing a glycosaminoglycan binding sequence, which we hypothesized to be required for the formation of a GCP‐2 haptotactic gradient on endothelia. This mutated version (GCP‐2‐T) had reduced capacity to induce transendothelial migration in vitro and in vivo, without affecting downstream receptor signaling through AKT, and chondrogenic activity. Intra‐articular adenoviral overexpression of GCP‐2‐T, but not wild‐type GCP‐2, reduced pain and cartilage loss in instability‐induced osteoarthritis in mice. We suggest that GCP‐2‐T may be used for disease modification in osteoarthritis. Synopsis: Osteoarthritis, which is the most common cause of disability, leads to breakdown of the articular cartilage and causes joint pain and loss of mobility; however, we do not have a pharmacological treatment for arresting or reverting its course. The chemokine GCP‐2 is expressed within the articular cartilage where it supports extracellular matrix production and inhibits chondrocyte hypertrophy and cartilage mineralization.Mutagenesis of three lysines in GCP‐2 (GCP‐2‐T) disrupted its binding to glycosaminoglycans (e.g. on endothelium), reducing its induction of transendothelial migration of pro‐inflammatory leukocytes in vitro and in vivo.GCP‐2‐T retained the capacity of wild‐type GPC‐2 to activate receptor signaling on chondrocytes, thereby mediating a pro‐anabolic, chondrogenic, activity.Overexpression of GCP‐2‐T improved cartilage integrity and reduced pain in experimental osteoarthritis in mice without inducing local accumulation of neutrophils. [ABSTRACT FROM AUTHOR]

Background: There are relatively few data on the genetic spectrum of Chinese frontotemporal dementia (FTD) population.Objective: With the dementia cohort of Peking Union Medical College Hospital, we aim to illustrate the genetic spectrum of FTD patients, as well as the phenotypic heterogeneity of FTD-gene variant carriers.Methods: 204 unrelated, clinically diagnosed FTD patients of Chinese ancestry were enrolled. All the participants received demographic survey, history inquiry, physical examination, cognitive assessment, blood biochemical test, brain CT/MRI, and gene sequencing.Results: 56.4% (115/204) participants were clinically diagnosed with behavioral variant of FTD, 20.6% (42/204) with nonfluent/agrammatic variant primary progressive aphasia (PPA), 20.1% (41/204) with semantic variant PPA, and 2.9% (6/204) with mixed variant PPA. 11.8% (24/204) subjects harbored the potential causative variants in FTD-related genes, including the MAPT (n = 7), TBK1 (n = 7), GRN (n = 2), TBK1+GRN (n = 1), VCP (n = 1), TARDBP (n = 1), UBQLN2 (n = 1), SQSTM1 (n = 1), DCTN1 (n = 1), HNRNPA1 (n = 1), and C9orf72 GGGGCC repeats (n = 1). The TBK1 T31fs, T457fs, K622fs, c.359-1G>A, the VCP P188T, and the GRN P50fs, P439fs were novel pathogenic/likely pathogenic variants. The TBK1 carriers showed a later disease onset and a higher incidence of parietal atrophy relative to the MAPTcarriers.Conclusion: There is genetic and clinical heterogeneity among Chinese FTD population. The TBK1 has a high mutation frequency in Chinese FTD patients. [ABSTRACT FROM AUTHOR]

Homeostasis in skeletal muscle is sustained by the balance of functional and physical interactions between muscle and myofibre microenvironment. Various factors, such as ageing, disuse and denervation, tip the balance and induce skeletal muscle atrophy. Skeletal muscle atrophy, which involves complex physiological and biochemical changes, is accompanied by adverse outcomes and even increased mortality. Multiple studies have investigated the role of neutrophils in atrophied skeletal muscles; however, neutrophil intrusion in muscle is still a polemical knot. As technical obstacles have been overcome, people have gradually discovered new functions of neutrophils. The classical view of neutrophils is no longer applicable to their biological characteristics. To date, no clear association between the hidden injurious effect of neutrophil intrusion and muscle atrophy has been convincingly proven. Throughout this review, we have discussed the neutrophil activities that mediate muscle atrophy for distinct disease occurrences. Hopefully, this review will help both clinicians and researchers of skeletal muscle atrophy with relevant targets to further explore efficient medical interventions and treatments. [ABSTRACT FROM AUTHOR]

Tetrocarcin A (TCA), produced by Micromonospora chalcea NRRL 11289, is a spirotetronate antibiotic with potent antitumor activity and versatile modes of action. In this study, the biosynthetic gene cluster of TCA was cloned and localized to a 108-kb contiguous DNA region. In silico sequence analysis revealed 36 putative genes that constitute this cluster (including 11 for unusual sugar biosynthesis, 13 for aglycone formation, and 4 for glycosylations) and allowed us to propose the biosynthetic pathway of TCA. The formation of D-tetronitrose, L-amicetose, and L-digitoxose may begin with D-glucose-1-phosphate, share early enzymatic steps, and branch into different pathways by competitive actions of specific enzymes. Tetronolide biosynthesis involves the incorporation of a 3-C unit with a polyketide intermediate to form the characteristic spirotetronate moiety and trans-decalin system. Further substitution of tetronolide with five deoxysugars (one being a deoxynitrosugar) was likely due to the activities of four glycosyltransferases. In vitro characterization of the first enzymatic step by utilization of 1,3-biphosphoglycerate as the substrate and in vivo cross-complementation of the bifunctional fused gene tcaD3 (with the functions of chlD3 and chlD4) to [DELTA]chlD3 and [DELTA]chlD4 in chlorothricin biosynthesis supported the highly conserved tetronate biosynthetic strategy in the spirotetronate family. Deletion of a large DNA fragment encoding polyketide synthases resulted in a non-TCA-producing strain, providing a clear background for the identification of novel analogs. These findings provide insights into spirotetronate biosynthesis and demonstrate that combinatorial-biosynthesis methods can be applied to the TCA biosynthetic machinery to generate structural diversity.