The FAITHS2 Model Predicts Functional Disability in Patients With Acute Ischemic Stroke.

The present study aimed to develop a model to predict functional disability at 3 months in patients with acute ischemic stroke (AIS) (n = 5,406). The primary outcome was functional disability (modified Rankin Scale [mRS] >2) at 3 months. A prediction model including blood biomarkers was developed based on a multivariable logistic regression model, which was internally validated by the 100-time bootstrap method. A nomogram and a web-based calculator were developed for usage in clinical practice. At 3 months, 11% (638/5,406) of the patients had functional disability. Seven independent predictors of functional disability at 3 months were incorporated into the FAITHS2 model (fasting plasma glucose, age, interleukin-6, stroke history, National Institute of Health Stroke Scale [NIHSS] at admission, sex, and systolic blood pressure). The Area Under Curves (AUCs) were 0.814 (95% confidence interval [CI] 0.796-0.832) and 0.808 (95% CI 0.806-0.810), and the Brier scores were 0.088 ± 0.214 and 0.089 ± 0.003 for the derivation cohort and internal validation, respectively, showing optimal performance of the model. The FAITHS2 model has excellent potential to be a dependable application for individualized clinical decision making.

Synergetic conditioning via oxalic acid enhanced Fe2+/CaO2 and skeleton construct to achieve deep dewatering of sewage sludge.

Extracellular polymeric substance (EPS) with highly hydrophilic groups and sludge with high compressibility are determined sludge dewaterability. Herein, Fe2+ catalyzed calcium peroxide (CaO2) assisted by oxalic acid (OA) Fenton-like process combined with coal slime was applied to improve sludge dewaterability. Results demonstrated that the sludge treated by 0.45/1/1.1-OA/Fe2+/CaO2 mM/g DS, the water content (WC), specific resistance to filtration and capillary suction time dropped to 53.01%, 24.3 s and 1.2 × 1012 m/kg, respectively. Under coal slime ratio as 0.6, WC and compressibility were further reduced to 42.72% and 0.66, respectively. The hydroxyl radicals generated by OA/Fe2+/CaO2 under near-neutral pH layer by layer collapsed EPS, resulting in the degradation and migration of inner releasing components and the exposure of inner sludge flocs skeleton. The hydrophilic tryptophan-like protein of TB-EPS were degraded into aromatic protein of S-EPS and exposed inner hydrophobic sites. The protein secondary structures were transformed by destroying hydrophilic functional groups, which were attributed to the reducing α-helix ratio and reconstructing ß-sheet. Moreover, coal slime as the skeleton builder lowered compressibility and formed more macropores to increase the filterability of pre-oxidized sludge for the higher intensity of rigid substances. This study deepened the understanding of OA enhanced Fenton-like system effects on sludge dewaterability and proposed a cost-effective and synergistic waste treatment strategy in sludge dewatering.

Characterization and Flame-Retardant Properties of Cobalt-Coordinated Cyclic Phosphonitrile in Thermoplastic Polyurethane Composites.

Halogen-free organophosphorus flame retardants have promising application prospects due to their excellent safety and environmental protection properties. A cobalt-coordinated cyclic phosphonitrile flame retardant (Co@CPA) was synthesized via a hydrothermal method using hexachlorocyclotriphosphonitrile (HCCP), 5-amino-tetrazolium (5-AT), and cobalt nitrate hexahydrate (Co(NO3)2∙6H2O) as starting materials. The structure was characterized using Fourier transform infrared (FTIR), nuclear magnetic resonance spectroscopy (1H-NMR), scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). Thermoplastic polyurethane (TPU) composites were prepared by incorporating 10-(2,5-dihydroxyphenyl)-9,10-dihydro-9-oxa-10-phosphame-10-oxide (ODOPB), Co@CPA, and silicon dioxide (SiO2) via melt blending. The flame-retardant performance and thermal stability of the TPU composites were evaluated through limiting oxygen index (LOI), vertical combustion (UL-94), TG, and cone calorimetric (CCT) tests. SEM and Raman spectroscopy were used to analyze the surface morphology and structure of the residual carbon. A synergistic flame-retardant effect of ODOPB and Co@CPA was observed, with the most effective flame retardancy achieved at a TPU:ODOPB:Co@CPA:SiO2 ratio of 75:16:8:1. This composition exhibited an LOI value of 26.5% and achieved a V-0 rating in the UL-94 test. Furthermore, compared to pure TPU, the composite showed reductions in total heat release, CO production, and CO2 production by 6.6%, 39.4%, and 48.9%, respectively. Our research findings suggest that Co@CPA demonstrates outstanding performance, with potential for further expansion in application areas. Different metal-based cyclic phosphonitrile compounds are significant in enriching phosphorus-based fine chemicals.

A Combined Manual Annotation and Deep-Learning Natural Language Processing Study on Accurate Entity Extraction in Hereditary Disease Related Biomedical Literature.

We report a combined manual annotation and deep-learning natural language processing study to make accurate entity extraction in hereditary disease related biomedical literature. A total of 400 full articles were manually annotated based on published guidelines by experienced genetic interpreters at Beijing Genomics Institute (BGI). The performance of our manual annotations was assessed by comparing our re-annotated results with those publicly available. The overall Jaccard index was calculated to be 0.866 for the four entity types-gene, variant, disease and species. Both a BERT-based large name entity recognition (NER) model and a DistilBERT-based simplified NER model were trained, validated and tested, respectively. Due to the limited manually annotated corpus, Such NER models were fine-tuned with two phases. The F1-scores of BERT-based NER for gene, variant, disease and species are 97.28%, 93.52%, 92.54% and 95.76%, respectively, while those of DistilBERT-based NER are 95.14%, 86.26%, 91.37% and 89.92%, respectively. Most importantly, the entity type of variant has been extracted by a large language model for the first time and a comparable F1-score with the state-of-the-art variant extraction model tmVar has been achieved.

Pharmacokinetic and Bioequivalence Study of Lisinopril/Hydrochlorothiazide Tablet Under Fasting and Postprandial Conditions in Healthy Chinese Subjects.

The objective of this research was to evaluate and compare the pharmacokinetic profiles and safety of lisinopril/hydrochlorothiazide (10 mg/12.5 mg) tablets in the test and reference formulations administered to participants in both fasting and postprandial states and to evaluate the bioequivalence of the 2 products in healthy Chinese volunteers. This study employed a single-center, randomized, open-label, single-dose dosing trial involving a cumulative 96 healthy adult participants (60 in the fasting group and 36 in the postprandial group). Each group comprised 2 sequence sets, and a 2-week washout period was implemented. There were no statistically significant differences in time to maximum concentration and terminal elimination half-life between the test and control groups under fasting and postprandial conditions (P > .05), and the 90% CIs for area under the plasma concentration-time curve and maximum plasma concentration were within the bioequivalence range of 80%-125%. Pharmacokinetic results indicate a large food effect for lisinopril, meaning that there is a loss of approximately 20%-25% of systemic exposure from fasting to postprandial administration for both preparations. The study demonstrated that a single oral dose of generic lisinopril/hydrochlorothiazide is bioequivalent to the reference product and well tolerated, with no significant adverse events observed, and that both products are similarly safe in a cohort of healthy Chinese male and female participants, following administration under fasting and postprandial conditions.

RAD54L2-mediated DNA damage avoidance pathway specifically preserves genome integrity in response to topoisomerase 2 poisons.

Type II topoisomerases (TOP2) form transient TOP2 cleavage complexes (TOP2ccs) during their catalytic cycle to relieve topological stress. TOP2ccs are covalently linked TOP2-DNA intermediates that are reversible but can be trapped by TOP2 poisons. Trapped TOP2ccs block transactions on DNA and generate genotoxic stress, which are the mechanisms of action of TOP2 poisons. How cells avoid TOP2cc accumulation remains largely unknown. In this study, we uncovered RAD54 like 2 (RAD54L2) as a key factor that mediates a TOP2-specific DNA damage avoidance pathway. RAD54L2 deficiency conferred unique sensitivity to treatment with TOP2 poisons. RAD54L2 interacted with TOP2A/TOP2B and ZATT/ZNF451 and promoted the turnover of TOP2 from DNA with or without TOP2 poisons. Additionally, inhibition of proteasome activity enhanced the chromatin binding of RAD54L2, which in turn led to the removal of TOP2 from chromatin. In conclusion, we propose that RAD54L2-mediated TOP2 turnover is critically important for the avoidance of potential TOP2-linked DNA damage under physiological conditions and in response to TOP2 poisons.

Blockade of adenosine A2A receptors reverses early spatial memory defects in the APP/PS1 mouse model of Alzheimer's disease by promoting synaptic plasticity of adult-born granule cells.

BACKGROUND: The over-activation of adenosine A2A receptors (A2AR) is closely implicated in cognitive impairments of Alzheimer's disease (AD). Growing evidence shows that A2AR blockade possesses neuroprotective effects on AD. Spatial navigation impairment is an early manifestation of cognitive deficits in AD. However, whether A2AR blockade can prevent early impairments in spatial cognitive function and the underlying mechanism is still unclear. METHODS: A transgenic APP/PS1 mouse model of AD amyloidosis was used in this study. Behavioral tests were conducted to observe the protective effects of A2AR blockade on early spatial memory deficits in 4-month old APP/PS1 mice. To investigate the underlying synaptic mechanism of the protective effects of A2AR blockade, we further examined long-term potentiation (LTP) and network excitation/inhibition balance of dentate gyrus (DG) region, which is relevant to unique synaptic functions of immature adult-born granule cells (abGCs). Subsequently, the protective effects of A2AR blockade on dendritic morphology and synaptic plasticity of 6-week-old abGCs was investigated using retrovirus infection and electrophysiological recordings. The molecular mechanisms underlying neuroprotective properties of A2AR blockade on the synaptic plasticity of abGCs were further explored using molecular biology methods. RESULTS: APP/PS1 mice displayed DG-dependent spatial memory deficits at an early stage. Additionally, impaired LTP and an imbalance in network excitation/inhibition were observed in the DG region of APP/PS1 mice, indicating synaptic structural and functional abnormalities of abGCs. A2AR was found to be upregulated in the hippocampus of the APP/PS1 mouse model of AD. Treatment with the selective A2AR antagonist SCH58261 for three weeks significantly ameliorated spatial memory deficits in APP/PS1 mice and markedly restored LTP and network excitation/inhibition balance in the DG region. Moreover, SCH58261 treatment restored dendritic morphology complexity and enhanced synaptic plasticity of abGCs in APP/PS1 mice. Furthermore, SCH58261 treatment alleviated the impairment of synaptic plasticity in abGCs. It achieved this by remodeling the subunit composition of NMDA receptors and increasing the proportion of NR2B receptors in abGCs of APP/PS1 mice. CONCLUSIONS: Blockade of A2AR improves early spatial memory deficits in APP/PS1 mice, possibly by reversing synaptic defects of abGCs. This finding suggests that A2AR blockade could be a potential therapy for AD.

Mediation effect of stroke recurrence in the association between post-stroke interleukin-6 and functional disability.

AIM: Post-stroke inflammation increases the risk of functional disability through enlarged cerebral infarct size directly and follow-up stroke event indirectly. We aimed to use post-stroke proinflammatory cytokine interleukin-6 (IL-6) as a marker of inflammatory burden and quantify post-stroke inflammation's direct and indirect effect on functional disability. METHODS: We analyzed patients with acute ischemic stroke admitted to 169 hospitals in the Third China National Stroke Registry. Blood samples were collected within 24 h of admission. Stroke recurrence and functional outcome measured by the modified Rankin scale (mRS) were assessed via face-to-face interviews at 3 months. Functional disability was defined as an mRS score ≥2. Mediation analyses under the counterfactual framework were performed to examine the potential causal chain in which stroke recurrence may mediate the relationship between IL-6 and functional outcome. RESULTS: Among the 7053 analyzed patients, the median (interquartile range [IQR]) NIHSS score was 3 (1-5), and the median (IQR) level of IL-6 was 2.61 (1.60-4.73) pg/mL. Stroke recurrence was observed in 458 (6.5%) patients, and functional disability was seen in 1708 (24.2%) patients at the 90-day follow-up. Per stand deviation (4.26 pg/mL) increase in the concentration of IL-6 was associated with an increased risk of stroke recurrence (adjusted odds ratio [aOR], 1.19; 95% CI, 1.09-1.29) and disability (aOR, 1.22; 95% CI, 1.15-1.30) within 90 days. Mediation analyses revealed that 18.72% (95% CI, 9.26%-28.18%) of the relationship between IL-6 and functional disability was mediated by stroke recurrence. CONCLUSIONS: Stroke recurrence mediates less than 20% of the association between IL-6 and functional outcome at 90 days among patients with acute ischemic stroke. In addition to typical secondary prevention strategies for preventing stroke recurrence, more attention should be paid to novel anti-inflammatory therapy to improve functional outcomes directly.

Efficacy of 3D-printed assisted percutaneous transhepatic one-step biliary fistulation combined with rigid choledochoscopy for intrahepatic bile duct stones.

This study evaluated the efficacy and safety of three-dimensional printing model-assisted percutaneous transhepatic one-step biliary fistulation (PTOBF) combined with rigid choledochoscopy for intrahepatic bile duct stones in patients with type I bile duct classification. The clinical data of 63 patients with a type I intrahepatic bile duct were reviewed from January 2019 to January 2023; 30 patients who underwent 3D printed model-assisted PTOBF combined with rigid choledochoscopy composed the experimental group and 33 patients who underwent simple PTOBF combined with rigid choledochoscopy composed the control group. Six indicators, including one-stage operation time and clearance rate, final removal rate, bleeding volume, channel size and complications, were observed and analyzed in the two groups. The one-stage and final removal rate in the experimental group was higher than that in the control group (P = 0.034, P = 0.014 versus control group). The time of one-stage operation, bleeding volume, and incidence of complications in the experimental group were significantly lower than those in the control group (P < 0.001, P = 0.039, P = 0.026 versus control group). Compared with simple PTOBF combined with rigid choledochoscopy, 3D printed model-assisted PTOBF combined with rigid choledochoscopy is a safer and more effective method for treating intrahepatic bile duct stones.

Optimization of optical and structural properties of Al2O3/TiO2 nano-laminates deposited by atomic layer deposition for optical coating.

Optimizing the atomic layer deposition (ALD) process of films is particularly important in preparing multilayer interference films. In this work, a series of Al2O3/TiO2 nano-laminates with a fixed growth cycle ratio of 1:10 were deposited on Si and fused quartz substrates at 300 °C by ALD. The optical properties, crystallization behavior, surface appearance and microstructures of those laminated layers were systematically investigated by spectroscopic ellipsometry, spectrophotometry, X-ray diffraction, atomic force microscope and transmission electron microscopy. By inserting Al2O3 interlayers into TiO2 layers, the crystallization of the TiO2 is reduced and the surface roughness becomes smaller. The TEM images show that excessively dense distribution of Al2O3 intercalation leads to the appearance of TiO2 nodules, which in turn leads to increased roughness. The Al2O3/TiO2 nano-laminate with a cycle ratio 40:400 has relatively small surface roughness. Additionally, oxygen-deficient defects exist at the interface of Al2O3 and TiO2, leading to evident absorption. Using O3 as an oxidant instead of H2O for depositing Al2O3 interlayers was verified to be effective in reducing absorption during broadband antireflective coating experiments.

Genetic and neural mechanisms of sleep disorders in children with autism spectrum disorder: a review.

Background: The incidence of sleep disorders in children with autism spectrum disorder (ASD) is very high. Sleep disorders can exacerbate the development of ASD and impose a heavy burden on families and society. The pathological mechanism of sleep disorders in autism is complex, but gene mutations and neural abnormalities may be involved. Methods: In this review, we examined literature addressing the genetic and neural mechanisms of sleep disorders in children with ASD. The databases PubMed and Scopus were searched for eligible studies published between 2013 and 2023. Results: Prolonged awakenings of children with ASD may be caused by the following processes. Mutations in the MECP2, VGAT and SLC6A1 genes can decrease GABA inhibition on neurons in the locus coeruleus, leading to hyperactivity of noradrenergic neurons and prolonged awakenings in children with ASD. Mutations in the HRH1, HRH2, and HRH3 genes heighten the expression of histamine receptors in the posterior hypothalamus, potentially intensifying histamine's ability to promote arousal. Mutations in the KCNQ3 and PCDH10 genes cause atypical modulation of amygdala impact on orexinergic neurons, potentially causing hyperexcitability of the hypothalamic orexin system. Mutations in the AHI1, ARHGEF10, UBE3A, and SLC6A3 genes affect dopamine synthesis, catabolism, and reuptake processes, which can elevate dopamine concentrations in the midbrain. Secondly, non-rapid eye movement sleep disorder is closely related to the lack of butyric acid, iron deficiency and dysfunction of the thalamic reticular nucleus induced by PTCHD1 gene alterations. Thirdly, mutations in the HTR2A, SLC6A4, MAOA, MAOB, TPH2, VMATs, SHANK3, and CADPS2 genes induce structural and functional abnormalities of the dorsal raphe nucleus (DRN) and amygdala, which may disturb REM sleep. In addition, the decrease in melatonin levels caused by ASMT, MTNR1A, and MTNR1B gene mutations, along with functional abnormalities of basal forebrain cholinergic neurons, may lead to abnormal sleep-wake rhythm transitions. Conclusion: Our review revealed that the functional and structural abnormalities of sleep-wake related neural circuits induced by gene mutations are strongly correlated with sleep disorders in children with ASD. Exploring the neural mechanisms of sleep disorders and the underlying genetic pathology in children with ASD is significant for further studies of therapy.

Genome-Wide CRISPR Screens Reveal ZATT as a Synthetic Lethal Target of TOP2-Poison Etoposide That Can Act in a TDP2-Independent Pathway.

Etoposide (ETO) is an anticancer drug that targets topoisomerase II (TOP2). It stabilizes a normally transient TOP2-DNA covalent complex (TOP2cc), thus leading to DNA double-strand breaks (DSBs). Tyrosyl-DNA phosphodiesterases two (TDP2) is directly involved in the repair of TOP2cc by removing phosphotyrosyl peptides from 5'-termini of DSBs. Recent studies suggest that additional factors are required for TOP2cc repair, which include the proteasome and the zinc finger protein associated with TDP2 and TOP2, named ZATT. ZATT may alter the conformation of TOP2cc in a way that renders the accessibility of TDP2 for TOP2cc removal. In this study, our genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screens revealed that ZATT also has a TDP2-independent role in promoting cell survival following ETO treatment. ZATT KO cells showed relatively higher ETO sensitivity than TDP2-KO cells, and ZATT/TDP2 DKO cells displayed additive hypersensitivity to ETO treatment. The study using a series of deletion mutants of ZATT determined that the N-terminal 1-168 residues of ZATT are required for interaction with TOP2 and this interaction is critical to ETO sensitivity. Moreover, depletion of ZATT resulted in accelerated TOP2 degradation after ETO or cycloheximide (CHX) treatment, suggesting that ZATT may increase TOP2 stability and likely participate in TOP2 turnover. Taken together, this study suggests that ZATT is a critical determinant that dictates responses to ETO treatment and targeting. ZATT is a promising strategy to increase ETO efficacy for cancer therapy.

Widely targeted metabolomics analysis reveals the differences in nonvolatile compounds of citronella before and after drying.

Citronella is used as a spice and a traditional herbal medicine. Dried citronella is easy to store and transport, and it is unclear whether dried citronella has more or fewer medicinal components compared to fresh citronella. In the present study, various metabolites in fresh and dry citronella were detected using a widely targeted metabolomics strategy. We identified 712 metabolites and classified them into 31 categories, and we identified 132 flavonoids. After citronella was dried, the quantities of most kinds of flavonoids increased, but the quantities of amino acids, organic acids, and vitamins decreased, and the quantity of quercetin increased significantly. Therefore, the medicinal value of dry citronella may have increased, and the nutritional value of amino acids and vitamins may have decreased. The results of this study can serve as a new theoretical reference to study citronella and promote its nutrition and medicinal chemical composition.

Integrative Analysis of Metabolome and Transcriptome Reveals the Mechanism of Color Formation in Yellow-Fleshed Kiwifruit.

During the development of yellow-fleshed kiwifruit (Actinidia chinensis), the flesh appeared light pink at the initial stage, the pink faded at the fastest growth stage, and gradually changed into green. At the maturity stage, it showed bright yellow. In order to analyze the mechanism of flesh color change at the metabolic and gene transcription level, the relationship between color and changes of metabolites and key enzyme genes was studied. In this study, five time points (20 d, 58 d, 97 d, 136 d, and 175 d) of yellow-fleshed kiwifruit were used for flavonoid metabolites detection and transcriptome, and four time points (20 d, 97 d, 136 d, and 175 d) were used for targeted detection of carotenoids. Through the analysis of the content changes of flavonoid metabolites, it was found that the accumulation of pelargonidin and cyanidin and their respective anthocyanin derivatives was related to the pink flesh of young fruit, but not to delphinidin and its derivative anthocyanins. A total of 140 flavonoid compounds were detected in the flesh, among which anthocyanin and 76% of the flavonoid compounds had the highest content at 20 d, and began to decrease significantly at 58 d until 175 d, resulting in the pale-pink fading of the flesh. At the mature stage of fruit development (175 d), the degradation of chlorophyll and the increase of carotenoids jointly led to the change of flesh color from green to yellow, in addition to chlorophyll degradation. In kiwifruit flesh, 10 carotenoids were detected, with none of them being linear carotenoids. During the whole development process of kiwifruit, the content of ß-carotene was always higher than that of α-carotene. In addition, ß-cryptoxanthin was the most-accumulated pigment in the kiwifruit at 175 d. Through transcriptome analysis of kiwifruit flesh, seven key transcription factors for flavonoid biosynthesis and ten key transcription factors for carotenoid synthesis were screened. This study was the first to analyze the effect of flavonoid accumulation on the pink color of yellow-fleshed kiwifruit. The high proportion of ß-cryptoxanthin in yellow-fleshed kiwifruit was preliminarily found. This provides information on metabolite accumulation for further revealing the pink color of yellow-fleshed kiwifruit, and also provides a new direction for the study of carotenoid biosynthesis and regulation in yellow-fleshed kiwifruit.

Chelating Bis-silylenes As Powerful Ligands To Enable Unusual Low-Valent Main-Group Element Functions.

ConspectusSilylenes are divalent silicon species with an unoccupied 3p orbital and one lone pair of electrons at the SiII center. Owing to the excellent σ-donating ability of amidinato-based silylenes, which stems from the intramolecular imino-N donor interaction with the vacant 3p orbital of the silicon atom, N-heterocyclic amidinato bis(silylenes) [bis(NHSi)s] can serve as versatile strong donating ligands for cooperative stabilization of central atoms in unusually low oxidation states. Herein, we present our recent achievement on the application of bis(NHSi) ligands with electronically and spatially different spacers to main-group chemistry, which has allowed the isolation of a variety of low-valent compounds consisting of monatomic zero-valent group 14 E0 complexes (named "metallylones", E = Si, Ge, Sn, Pb); monovalent group 15 EI complexes (E = N, P, isoelectronic with metallylones); and diatomic low-valent E2 complexes (E = Si, Ge, P) with intriguing electronic structures and chemical reactivities.The role of the SiII···SiII distance was revealed to be crucial in this chemistry. Utilizing the pyridine-based bis(NHSi) (Si···Si distance: 7.8 Å) ligand, germanium(0) complexes with additional Fe(CO)4 protection at the Ge0 site have been isolated. Featuring a shorter Si···Si distance of 4.3 Å, the xanthene-based bis(NHSi) has allowed the realization of the full series of heavy zero-valent group 14 element E0 complexes (E = Si, Ge, Sn, Pb), while the o-carborane-based bis(NHSi) (Si···Si distance: 3.3 Å) has enabled the isolation of Si0 and Ge0 complexes. Remarkably, reduction of the o-carborane-based bis(NHSi)-supported Si0 and Ge0 complexes induces the movement of two electrons into the o-carborane core and provides access to SiI-SiI and GeI-GeI species as oxidation products. Additionally, the o-carborane-based bis(NHSi) reacts with adamantyl azide, leading to a series of nitrogen(I) complexes as isoelectronic species of a carbone (C0 complex). Moreover, cooperative activation of white phosphorus gives bis(NHSi)-supported phosphorus complexes with varying and unexpected electronic structures when employing the xanthene-, o-carborane-, and aniline-based bis(NHSi)s. With the better kinetic protection provided by the xanthene-based bis(NHSi), small-molecule activation and functionalization of the bis(NHSi)-supported central E or E2 atoms (E = Si, Ge, P) are possible and furnish several novel functionalized silicon, germanium, and phosphorus compounds.With knowledge of the ability of chelating bis(NHSi)s in coordinating and functionalizing low-valent group 14 and 15 elements, the application of these ligand systems to other main-group elements such as group 2 and 13 is quite promising. To fully understand the role of the NHSi in a bis(NHSi) ligand, introducing a mixed ligand, i.e., the combination of an NHSi with other functional groups, such as Lewis acidic borane or Lewis basic borylene, in one chelating ligand could lead to new types of low-valent main-group species. Furthermore, the development of a genuine acyclic silylene, without an imino-N interaction with the vacant 3p orbital at the silicon(II) atom, as part of a chelating bis(acyclic silylene) has the potential to form very electronically different main-group element complexes that could achieve even more challenging bond activations such as N2 or unactivated C-H bonds.

Short-term effect of PM2.5 on stroke in susceptible populations: A case-crossover study.

BACKGROUND: Fine particulate matter (PM2.5) is a risk factor for stroke, and patients with pre-existing diseases appear to be particularly susceptible. We conducted a case-crossover study to examine the association between short-term exposure to fine particulate matter (PM2.5) and hospital admission for stroke in individuals with atrial fibrillation (AF), hypertension, diabetes, or hyperlipidemia. METHODS: Patients diagnosed with acute ischemic stroke (AIS) were recruited from 2015 to 2017 in Chinese Stroke Center Alliances. We estimated daily PM2.5 average exposures with a spatial resolution of 0.1° using a data assimilation approach combining satellite measurements, air model simulations, and monitoring values. Conditional logistic regression was used to assess PM2.5-related stroke risk in patients with pre-existing medical co-morbidities. RESULTS: A total of 155,616 patients diagnosed with AIS were admitted. Patients with a history of AF (n = 15,430), hypertension (n = 138,220), diabetes (n = 43,737), or hyperlipidemia (n = 16,855) were assessed separately. A 10 µg/m3 increase in daily PM2.5 was associated with a significant increase in AIS for individuals with AF at lag 4 (odds ratio (OR), 1.008; 95% confidence interval (CI), 1.002-1.014), and with hypertension (OR, 1.008; 95% CI, 1.006-1.010), diabetes (OR, 1.006; 95% CI, 1.003-1.010), and hyperlipidemia (OR, 1.007; 95% CI, 1.001-1.012) at lags 0-7. Elderly (⩾ 65 years old) and female patients with AF had significantly higher associations at lag 5 (OR, 1.009; 95% CI, 1.002-1.015) and lag 5 (OR, 1.010; 95% CI, 1.002-1.018), respectively. CONCLUSION: Short-term exposure to PM2.5 is significantly associated with hospital admission for stroke in individuals with pre-existing medical histories, especially in older or female patients with AF. Preventive measures to reduce PM2.5 concentrations are particularly important in individuals with other medical co-morbidities.

Learning from undercoded clinical records for automated International Classification of Diseases (ICD) coding.

OBJECTIVES: To develop an unbiased objective for learning automatic coding algorithms from clinical records annotated with only partial relevant International Classification of Diseases codes, as annotation noise in undercoded clinical records used as training data can mislead the learning process of deep neural networks. MATERIALS AND METHODS: We use Medical Information Mart for Intensive Care III as our dataset. We employ positive-unlabeled learning to achieve unbiased loss estimation, which is free of misleading training signal. We then utilize reweighting mechanism to compensate for the imbalance between positive and negative samples. To further close the performance gap caused by poor quality annotation, we integrate the supervision provided by the automatic annotation tool Medical Concept Annotation Toolkit which can ease the heavy burden of manual validation. RESULTS: Our benchmarking results show that positive-unlabeled learning with reweighting outperforms competitive baseline methods over a range of missing label ratios. Integrating supervision provided by annotation tool further boosted the performance. DISCUSSION: Considering the annotation noise and severe imbalance, unbiased loss estimation and reweighting mechanism are both important for learning from undercoded clinical records. Unbiased loss requires the estimation of false negative ratios and estimation through trained models is practical and competitive. CONCLUSIONS: The combination of positive-unlabeled learning with reweighting and supervision provided by the annotation tool is a promising solution to learn from undercoded clinical records.

Phenolic and carotenoid characterization of the ethanol extract of an Australian native plant Haemodorum spicatum.

Bloodroot (Haemodorum spicatum) is an Australian native bulb plant yielding red pigment. This study aimed to characterize the phenolic and carotenoid profiles of the 80% ethanol extract of the H. spicatum bulb by HPLC-DAD-ESI-QTOF-MS/MS and HPLC-DAD. Results revealed the relatively low total phenolic content and antioxidant activity of the bulb extract with the maximum absorbance at 477 nm. Only 2 carotenoids (lutein and capsanthin) were detected at relatively low levels in the extract. A total of 40 phenolic compounds were tentatively identified, including 5 phenolic acids, 13 flavonoids and 22 other phenolic compounds, where 35 were reported for the first time in H. spicatum, together with 3 previously reported phenylphenalenones, haemodorol, haemoxiphidone and 2,5,6-trimethoxy-9-phenyl-1H-phenalen-1-one, and 2 oxabenzochrysenones, 5-hydroxy-2-methoxy-1H-naphtho[2,1,8-mna]xanthen-1-one and 5-hydroxy-1H-naphtho[2,1,8-mna]xanthen-1-one. This study provided the most comprehensive phenolic and carotenoid profiles of H. spicatum up to date.

Widely targeted metabolomics analysis of different parts of kudzu.

Pueraria lobata is a traditional medicinal and edible plant. Its root is often used as a nutritional supplement, but its stems and leaves are often discarded. In this study, the types and contents of compounds in roots, stems and leaves of kudzu were studied by ultra-high-performance liquid chromatography electrospray ionization tandem mass spectrometry. A total of 446 metabolites were identified, which were mainly divided into eight categories; 40 unique compounds were detected in roots. Multivariate statistical analysis showed that there were significant differences in the contents of metabolites in the roots, stems and leaves of kudzu, and the most significant differences were found in the roots and stems. Most flavonoids and terpenoids accumulated in roots, while alkaloids, flavonoid glycosides, lignans and coumarins accumulated in stems and leaves. In addition, isoflavones accumulated least in stems and most in roots. These results improved our understanding of the accumulation of metabolites in kudzu and provided a reference for the full study of the medicinal value of different parts of kudzu.

Pharmacokinetic and Bioequivalent Study of Potassium Chloride Sustained-Release Tablet Under Different Dietary Conditions in Healthy Chinese Subjects.

Potassium (K+ ) is an endogenous substance that is an essential dietary component. However, the interaction between dietary arrangements and specific effects of dietary K+ intake in bioequivalence studies remains unclear. To investigate the influence of dietary arrangement on the bioequivalence of potassium chloride (KCl) sustained-release tablets in healthy Chinese volunteers, the pharmacokinetics of KCl were compared in two open-label, single-center, randomized, two-period crossover studies with different dietary conditions. All volunteers received an oral dose of 6 g of KCl sustained-release tablets under fasting conditions, with different dietary arrangements. Urine samples were collected on baseline days and 48 hours after tablet consumption. Inductively coupled plasma-optical emission spectrometry was used to measure the concentration of K+ in the urine samples. Pharmacokinetic parameters were analyzed using Phoenix WinNonlin software in a noncompartmental model. In either clinical trial, no significant differences were observed in the maximal rate of urinary excretion and cumulative urinary excretion from 0 to 24 hours of K+ between the reference and test drugs. The bioequivalence studies of both KCl sustained-release tablet formulations were successfully conducted under different dietary conditions.