Early identification of macrophage activation syndrome secondary to systemic lupus erythematosus with machine learning.

OBJECTIVE: The macrophage activation syndrome (MAS) secondary to systemic lupus erythematosus (SLE) is a severe and life-threatening complication. Early diagnosis of MAS is particularly challenging. In this study, machine learning models and diagnostic scoring card were developed to aid in clinical decision-making using clinical characteristics. METHODS: We retrospectively collected clinical data from 188 patients with either SLE or the MAS secondary to SLE. 13 significant clinical predictor variables were filtered out using the Least Absolute Shrinkage and Selection Operator (LASSO). These variables were subsequently utilized as inputs in five machine learning models. The performance of the models was evaluated using the area under the receiver operating characteristic curve (ROC-AUC), F1 score, and F2 score. To enhance clinical usability, we developed a diagnostic scoring card based on logistic regression (LR) analysis and Chi-Square binning, establishing probability thresholds and stratification for the card. Additionally, this study collected data from four other domestic hospitals for external validation. RESULTS: Among all the machine learning models, the LR model demonstrates the highest level of performance in internal validation, achieving a ROC-AUC of 0.998, an F1 score of 0.96, and an F2 score of 0.952. The score card we constructed identifies the probability threshold at a score of 49, achieving a ROC-AUC of 0.994 and an F2 score of 0.936. The score results were categorized into five groups based on diagnostic probability: extremely low (below 5%), low (5-25%), normal (25-75%), high (75-95%), and extremely high (above 95%). During external validation, the performance evaluation revealed that the Support Vector Machine (SVM) model outperformed other models with an AUC value of 0.947, and the scorecard model has an AUC of 0.915. Additionally, we have established an online assessment system for early identification of MAS secondary to SLE. CONCLUSION: Machine learning models can significantly improve the diagnostic accuracy of MAS secondary to SLE, and the diagnostic scorecard model can facilitate personalized probabilistic predictions of disease occurrence in clinical environments.

Membrane-Active All-Hydrocarbon-Stapled α-Helical Amphiphilic Tat Peptides: Broad-Spectrum Antibacterial Activity and Low Incidence of Drug Resistance.

Multidrug resistance against conventional antibiotics has dramatically increased the difficulty of treatment and accelerated the need for novel antibacterial agents. The peptide Tat (47-57) is derived from the transactivating transcriptional activator of human immunodeficiency virus 1, which is well-known as a cell-penetrating peptide in mammalian cells. However, it is also reported that the Tat peptide (47-57) has antifungal activity. In this study, a series of membrane-active hydrocarbon-stapled α-helical amphiphilic peptides were synthesized and evaluated as antibacterial agents against Gram-positive and Gram-negative bacteria, including multidrug-resistant strains. The impact of hydrocarbon staple, the position of aromatic amino acid residue in the hydrophobic face, the various types of aromatic amino acids, and the hydrophobicity on bioactivity were also investigated and discussed in this study. Among those synthesized peptides, analogues P3 and P10 bearing a l-2-naphthylalanine (Φ) residue at the first position and a Tyr residue at the eighth position demonstrated the highest antimicrobial activity and negligible hemolytic toxicity. Notably, P3 and P10 showed obviously enhanced antimicrobial activity against multidrug-resistant bacteria, low drug resistance, high cell selectivity, extended half-life in plasma, and excellent performance against biofilm. The antibacterial mechanisms of P3 and P10 were also preliminarily investigated in this effort. In conclusion, P3 and P10 are promising antimicrobial alternatives for the treatment of the antimicrobial-resistance crisis.

Data-dependent and -independent acquisition lipidomics analysis reveals the tissue-dependent effect of metformin on lipid metabolism.

INTRODUCTION: Despite the well-recognized health benefits, the mechanisms and site of action of metformin remains elusive. Metformin-induced global lipidomic changes in plasma of animal models and human subjects have been reported. However, there is a lack of systemic evaluation of metformin-induced lipidomic changes in different tissues. Metformin uptake requires active transporters such as organic cation transporters (OCTs), and hence, it is anticipated that metformin actions are tissue-dependent. In this study, we aim to characterize metformin effects in non-diabetic male mice with a special focus on lipidomics analysis. The findings from this study will help us to better understand the cell-autonomous (direct actions in target cells) or non-cell-autonomous (indirect actions in target cells) mechanisms of metformin and provide insights into the development of more potent yet safe drugs targeting a particular organ instead of systemic metabolism for metabolic regulations without major side effects. OBJECTIVES: To characterize metformin-induced lipidomic alterations in different tissues of non-diabetic male mice and further identify lipids affected by metformin through cell-autonomous or systemic mechanisms based on the correlation between lipid alterations in tissues and the corresponding in-tissue metformin concentrations. METHODS: A dual extraction method involving 80% methanol followed by MTBE (methyl tert-butyl ether) extraction enables the analysis of free fatty acids, polar metabolites, and lipids. Extracts from tissues and plasma of male mice treated with or without metformin in drinking water for 12 days were analyzed using HILIC chromatography coupled to Q Exactive Plus mass spectrometer or reversed-phase liquid chromatography coupled to MS/MS scan workflow (hybrid mode) on LC-Orbitrap Exploris 480 mass spectrometer using biologically relevant lipids-containing inclusion list for data-independent acquisition (DIA), named as BRI-DIA workflow followed by data-dependent acquisition (DDA), to maximum the coverage of lipids and minimize the negative effect of stochasticity of precursor selection on experimental consistency and reproducibility. RESULTS: Lipidomics analysis of 6 mouse tissues and plasma allowed a systemic evaluation of lipidomic changes induced by metformin in different tissues. We observed that (1) the degrees of lipidomic changes induced by metformin treatment overly correlated with tissue concentrations of metformin; (2) the impact on lysophosphatidylcholine (lysoPC) and cardiolipins was positively correlated with tissue concentrations of metformin, while neutral lipids such as triglycerides did not correlate with the corresponding tissue metformin concentrations; (3) increase of intestinal tricarboxylic acid (TCA) cycle intermediates after metformin treatment. CONCLUSION: The data collected in this study from non-diabetic mice with 12-day metformin treatment suggest that the overall metabolic effect of metformin is positively correlated with tissue concentrations and the effect on individual lipid subclass is via both cell-autonomous mechanisms (cardiolipins and lysoPC) and non-cell-autonomous mechanisms (triglycerides).

Transient simulation of the electrical hysteresis in a metal/polymer/metal nanostructure.

The time-dependent quantum transportation through a metal/polymer/metal system is theoretically investigated on the basis of a Su-Schrieffer-Heeger model combined with the hierarchical equations of motion formalism. Using a non-adiabatic dynamical method, the evolution of the electron subspace and lattice atoms with time can be obtained. It is found that the calculated transient currents vary with time and reach stable values after a response time under the bias voltages. However, the stable current as the system reaches its dynamical steady state exhibits a discrepancy between two sweep directions of the bias voltage, which results in pronounced electrical hysteresis loops in the current-voltage curve. By analyzing the evolution of instantaneous energy eigenstates, the occupation number of the instantaneous eigenstates, and the lattice of the polymer, we show that the formation of excitons and the delay of their annihilation are responsible for the hysteretic current-voltage characteristics, where electron-phonon interactions play the key factor. Furthermore, the hysteresis width and amplitude can also be modulated by the strength of the electron-phonon coupling, level-width broadening function, and temperature. We hope these results about past condition-dependent switching performance at a sweep voltage can provide further insight into some of the basic issues of interest in hysteresis processes in conducting polymers.

Nanodiamond Coating in Energy and Engineering Fields: Synthesis Methods, Characteristics, and Applications.

Nanodiamonds are metastable allotropes of carbon. Based on their high hardness, chemical inertness, high thermal conductivity, and wide bandgap, nanodiamonds are widely used in energy and engineering applications in the form of coatings, such as mechanical processing, nuclear engineering, semiconductors, etc., particularly focusing on the reinforcement in mechanical performance, corrosion resistance, heat transfer, and electrical behavior. In mechanical performance, nanodiamond coatings can elevate hardness and wear resistance, improve the efficiency of mechanical components, and concomitantly reduce friction, diminish maintenance costs, particularly under high-load conditions. Concerning chemical inertness and corrosion resistance, nanodiamond coatings are gradually becoming the preferred manufacturing material or surface modification material for equipment in harsh environments. As for heat transfer, the extremely high coefficient of thermal conductivity of nanodiamond coatings makes them one of the main surface modification materials for heat exchange equipment. The increase of nucleation sites results in excellent performance of nanodiamond coatings during the boiling heat transfer stage. Additionally, concerning electrical properties, nanodiamond coatings elevate the efficiency of solar cells and fuel cells, and great performance in electrochemical and electrocatalytic is found. This article will briefly describe the application and mechanism analysis of nanodiamonds in the above-mentioned fields.

IDO-1 inhibition improves outcome after fluid percussion injury in adult male rats.

The enzyme indoleamine 2,3 dioxygenase 1 (IDO1) catalyzes the rate-limiting step in the kynurenine pathway (KP) which produces both neuroprotective and neurotoxic metabolites. Neuroinflammatory signals produced as a result of pathological conditions can increase production of IDO1 and boost its enzymatic capacity. IDO1 and the KP have been implicated in behavioral recovery after human traumatic brain injury (TBI), but their roles in experimental models of TBI are for the most part unknown. We hypothesized there is an increase in KP activity in the fluid percussion injury (FPI) model of TBI, and that administration of an IDO1 inhibitor will improve neurological recovery. In this study, adult male Sprague Dawley rats were subjected to FPI or sham injury and received twice-daily oral administration of the IDO1 inhibitor PF-06840003 (100 mg/kg) or vehicle control. FPI resulted in a significant increase in KP activity, as demonstrated by an increased ratio of kynurenine: tryptophan, in the perilesional neocortex and ipsilateral hippocampus 3 days postinjury (DPI), which normalized by 7 DPI. The increase in KP activity was prevented by PF-06840003. IDO1 inhibition also improved memory performance as assessed in the Barnes maze and anxiety behaviors as assessed in open field testing in the first 28 DPI. These results suggest increased KP activity after FPI may mediate neurological dysfunction, and IDO1 inhibition should be further investigated as a potential therapeutic target to improve recovery.

Effect of Bystander Hydrogen Atoms on Hydrogen Desorption on Single-Atom Alloy Surfaces: Insights from Simulated Temperature-Programmed Desorption Spectra.

Single-atom alloy (SAA) catalysts exhibit unique and excellent catalytic properties in heterogeneous hydrogenation/dehydrogenation reactions. A thorough understanding of the microscopic surface processes is essential to improve the catalytic performance. Here, from a new perspective of the temperature-programmed desorption (TPD) spectra of hydrogen (H) on two common SAA surfaces, Pt@Cu(111) and Pd@Cu(111), we reveal and confirm the key influence of H atoms attached to Pt/Pd dopants, i.e., the H atom bystander, on the desorption process of surface H atoms. It is found that only after considering the effect of the H atom bystander can the simulated TPD spectra well reproduce the experimentally observed higher desorption temperature on Pt@Cu(111) than on Pd@Cu(111) and the leftward shift of the TPD peak with increasing H atom coverage; otherwise, the features are inconsistent with experiments. Our work provides direct evidence for the effect of bystander H atoms from a simulation perspective.

Impact of Type 2 Diabetes Mellitus on Left Atrioventricular Coupling and Left Atrial Deformation in Patients with Essential Hypertension: An MRI Feature Tracking Study.

BACKGROUND: Hypertension (HTN) and type 2 diabetes mellitus (T2DM) are both associated with left ventricular (LV) and left atrial (LA) structural and functional abnormalities; however, the relationship between the left atrium and ventricle in this population is unclear. PURPOSE: To identify differences between hypertensive patients with and without T2DM as the basis for further investigation the atrioventricular coupling relationship. STUDY TYPE: Cross-sectional, retrospective study. POPULATION: 89 hypertensive patients without T2DM [HTN (T2DM-)] (age: 58.4 +/- 11.9 years, 48 male), 62 hypertensive patients with T2DM [HTN (T2DM+)] (age: 58.5 +/- 9.1 years, 32 male) and 70 matched controls (age: 55.0 +/- 9.6 years, 37 male). FIELD STRENGTH/SEQUENCE: 2D balanced steady-state free precession cine sequence at 3.0 T. ASSESSMENT: LA reservoir, conduit, and booster strain (εs, εe, and εa) and strain rate (SRs, SRe, and SRa), LV radial, circumferential and longitudinal peak strain (PS) and peak systolic strain rate and peak diastolic strain rate (PSSR and PDSR) were derived from LA and LV cine images and compared between groups. STATISTICAL TESTS: Chi-square or Fisher's exact test, one-way analysis of variance, analysis of covariance, Pearson's correlation, multivariable linear regression analysis, and intraclass correlation coefficient. A P value <0.05 was considered significant. RESULTS: Compared with controls, εs, εe, SRe and PS-longitudinal, PDSR-radial, and PDSR-longitudinal were significantly lower in HTN (T2DM-) group, and they were even lower in HTN (T2DM+) group than in both controls and HTN (T2DM-) group. SRs, εa, SRa, as well as PS-radial, PS-circumferential, PSSR-radial, and PSSR-circumferential were significantly lower in HTN (T2DM+) compared with controls. Multivariable regression analyses demonstrated that: T2DM and PS-circumferential and PS-longitudinal (ß = -4.026, -0.486, and -0.670, respectively) were significantly associated with εs; T2DM and PDSR-radial and PDSR-circumferential were significantly associated with εe (ß = -3.406, -3.352, and -6.290, respectively); T2DM and PDSR-radial were significantly associated with SRe (ß = 0.371 and 0.270, respectively); T2DM and PDSR-longitudinal were significantly associated with εa (ß = -1.831 and 5.215, respectively); and PDSR-longitudinal was significantly associated with SRa (ß = 1.07). DATA CONCLUSION: In hypertensive patients, there was severer LA dysfunction in those with coexisting T2DM, which may be associated with more severe LV dysfunction and suggests adverse atrioventricular coupling. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 3.

Comparative study of the multiple wavelength lasing of nitrogen ions: the role of vibrational level-dependent photoionization.

We report on an optical amplification and energy threshold of the two most prominent emission lines, 391.4 and 427.8 nm, of the cavity-less lasing of nitrogen ions pumped by femtosecond laser pulses. It was found that the two transitions both show optical amplification under a low gas pressure condition, while the 391.4 nm emission is barely amplified under high gas pressure. Moreover, the 427.8 nm emission presents a significant lower pump laser energy threshold and a larger gain factor than the 391.4 nm emission. Numerical simulations based on a three-state coupling model suggest that the smaller ionization Franck-Condon factor from the ground state of N2 to the vibrational level ν = 1 in X 2 Σ g+ state of N2 + favors the formation of population inversion corresponding to the 427.8 nm emission. Meanwhile, the competition between the strong field ionization and excitation induced by the pumping laser requires higher laser intensity to acquire the population inversion for the 391.4 nm radiation, leading to a corresponding larger energy threshold.

Central precocious puberty secondary to postoperative craniopharyngioma: two case reports and a literature review.

BACKGROUND: Craniopharyngioma is a common intracranial tumour in children. Clinical manifestations are related to hypothalamic/pituitary deficiencies, visual impairment, and increased intracranial pressure. Defects in pituitary function cause shortages of growth hormone, gonadotropin, corticotropin, thyrotropin, and vasopressin, resulting in short stature, delayed puberty, feebleness, lethargy, polyuria, etc. However, manifestations involving precocious puberty (PP) are rare. CASE REPORT: In both patients, surgical resection was performed after the diagnosis of craniopharyngioma, and breast development occurred postoperatively at one month in one patient and at one year and three months in the other patient. Central precocious puberty (CPP) was diagnosed via relevant examinations. Leuprorelin was injected subcutaneously every 28 days, and changes in height, weight, bone age, gonadal ultrasound and sex hormones were recorded. During the follow-up of the two children, the sex hormone levels were significantly reduced, and significant acceleration in bone age was not observed. CONCLUSIONS: CPP was induced by craniopharyngioma surgery, and treatment with gonadotropin-releasing hormone analogues (GnRHa) inhibited sexual development and bone age progression. More attention should be given to monitoring for CPP during long-term follow-up of craniopharyngiomas in the clinic.

Development of a Decafluorobiphenyl Cyclized Peptide Targeting the NEMO-IKKα/ß Interaction that Enhances Cell Penetration and Attenuates Lipopolysaccharide-Induced Acute Lung Injury.

Aberrant canonical NF-κB signaling has been implicated in diseases, such as autoimmune disorders and cancer. Direct disruption of the interaction of NEMO and IKKα/ß has been developed as a novel way to inhibit the overactivation of NF-κB. Peptides are a potential solution for disrupting protein-protein interactions (PPIs); however, they typically suffer from poor stability in vivo and limited tissue penetration permeability, hampering their widespread use as new chemical biology tools and potential therapeutics. In this work, decafluorobiphenyl-cysteine SNAr chemistry, molecular modeling, and biological validation allowed the development of peptide PPI inhibitors. The resulting cyclic peptide specifically inhibited canonical NF-κB signaling in vitro and in vivo, and presented positive metabolic stability, anti-inflammatory effects, and low cytotoxicity. Importantly, our results also revealed that cyclic peptides had huge potential in acute lung injury (ALI) treatment, and confirmed the role of the decafluorobiphenyl-based cyclization strategy in enhancing the biological activity of peptide NEMO-IKKα/ß inhibitors. Moreover, it provided a promising method for the development of peptide-PPI inhibitors.

Corrosive effect on saturated pool boiling heat transfer characteristics of metallic surfaces with hierarchical micro/nano structures.

Surface modification is of critical interest to enhance boiling heat transfer in terms of heat transfer coefficient or critical heat flux (CHF), which is significantly affected by distinct surface morphology and wettability and it can improve the efficiency and safety of equipment. Furthermore, actual service environment may cause severe corrosion to the processed structured surfaces while its consequence on boiling heat transfer is still obscure. In this article, comprehensive researches are conducted to unravel corrosive effect on metallic samples made of stainless steel (SS) and Inconel materials with microstructures. Different constructions (i.e., microgroove, microcavity and micropillar array) and characteristic dimensions (∼20, 50 µm) of microstructure, various duration time (up to 300 days) and pH values (∼7.0-8.5) of corrosive environment are compared thoroughly. Conclusions can be drawn that not all microstructures can enhance pool boiling heat transfer characteristics, especially in terms of CHF values. More importantly, CHF value of SS microgroove sample firstly increases from 60.94 to 94.09 W·cm-2 in 50 days, then decreases to 47.77 W·cm-2 in 300 days, which can be attributed to competition result between formation of hierarchical micro/nano structure with enhancing wicking capability and chemistry condition with increasing contact angle. In addition, distinct bubble dynamics during pool boiling is also analyzed. The insights obtained from this article can be used to guide surface modification method and to reveal evolvement rule of engineered metallic surface in highly corrosive and harsh boiling heating transfer environment.

Custom-designed, mass silk production in genetically engineered silkworms.

Genetically engineered silkworms have been widely used to obtain silk with modified characteristics especially by introducing spider silk genes. However, these attempts are still challenging due to limitations in transformation strategies and difficulties in integration of the large DNA fragments. Here, we describe three different transformation strategies in genetically engineered silkworms, including transcription-activator-like effector nuclease (TALEN)-mediated fibroin light chain (FibL) fusion (BmFibL-F), TALEN-mediated FibH replacement (BmFibH-R), and transposon-mediated genetic transformation with the silk gland-specific fibroin heavy chain (FibH) promoter (BmFibH-T). As the result, the yields of exogenous silk proteins, a 160 kDa major ampullate spidroin 2 (MaSp2) from the orb-weaving spider Nephila clavipes and a 226 kDa fibroin heavy chain protein (EvFibH) from the bagworm Eumeta variegate, reach 51.02 and 64.13% in BmFibH-R transformed cocoon shells, respectively. Moreover, the presence of MaSp2 or EvFibH significantly enhances the toughness of genetically engineered silk fibers by ∼86% in BmFibH-T and ∼80% in BmFibH-R silkworms, respectively. Structural analysis reveals a substantial ∼40% increase in fiber crystallinity, primarily attributed to the presence of unique polyalanines in the repetitive sequences of MaSp2 or EvFibH. In addition, RNA-seq analysis reveals that BmFibH-R system only causes minor impact on the expression of endogenous genes. Our study thus provides insights into developing custom-designed silk production using the genetically engineered silkworm as the bioreactor.

Joint association and interaction of birth weight and lifestyle with hypertension: A cohort study in UK Biobank.

Low birth weight and unhealthy lifestyle are both associated with an increased risk of hypertension. The authors aimed to assess the joint association and interaction of birth weight and lifestyle with incident hypertension. The authors included 205 522 participants free of hypertension at baseline from UK Biobank. A healthy lifestyle score was constructed using information on body mass index, physical activity, diet, smoking status and alcohol intake. Cox proportional hazard models were used to investigate the impact of birth weight, healthy lifestyle score and their joint effect on hypertension. The authors documented 13 548 (6.59%) incident hypertension cases during a median of 8.6 years of follow-up. The multivariate adjusted hazard ratios and 95% confidence intervals were 1.12 (1.09, 1.15) per kg lower birth weight and 0.76 (0.75, 0.77) per score increment in healthy lifestyle score. Healthy lifestyle reduced the risk of hypertension in any category of different birth weight groups. The preventive effect of healthy lifestyle on hypertension was the most pronounced at lower birth weight with <2500 g and 2500-2999 g, respectively. Addictive interaction between birth weight and healthy lifestyle score was observed with the relative excess risk due to interaction of 0.04 (0.03, 0.05). Our findings emphasized the importance of healthy lifestyle for hypertension prevention, especially among the high-risk population with lower birth weight.

Regulation of urea cycle by reversible high-stoichiometry lysine succinylation.

The post-translational modification lysine succinylation is implicated in the regulation of various metabolic pathways. However, its biological relevance remains uncertain due to methodological difficulties in determining high-impact succinylation sites. Here, using stable isotope labelling and data-independent acquisition mass spectrometry, we quantified lysine succinylation stoichiometries in mouse livers. Despite the low overall stoichiometry of lysine succinylation, several high-stoichiometry sites were identified, especially upon deletion of the desuccinylase SIRT5. In particular, multiple high-stoichiometry lysine sites identified in argininosuccinate synthase (ASS1), a key enzyme in the urea cycle, are regulated by SIRT5. Mutation of the high-stoichiometry lysine in ASS1 to succinyl-mimetic glutamic acid significantly decreased its enzymatic activity. Metabolomics profiling confirms that SIRT5 deficiency decreases urea cycle activity in liver. Importantly, SIRT5 deficiency compromises ammonia tolerance, which can be reversed by the overexpression of wild-type, but not succinyl-mimetic, ASS1. Therefore, lysine succinylation is functionally important in ammonia metabolism.

Phosphate-mediated degradation of organic pollutants in water with peroxymonosulfate revisited: Radical or non-radical oxidation?

Whilst it is generally recognized that phosphate enables to promote the removal of some organic pollutants with peroxymonosulfate (PMS) oxidation, however, there is an ongoing debate as to whether free radicals are involved. By integrating different methodologies, here we provide new insights into the reaction mechanism of the binary mixture of phosphates (i.e., NaH2PO4, Na2HPO3, and NaH2PO2) with peroxymonosulfate (PMS) or hydrogen peroxide (H2O2). Enhanced degradation of organic pollutants and observation of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) adducts (i.e. DMPOOH and 5,5-dimethyl-2-oxopyrroline-1-oxyl (DMPOX)) with electron paramagnetic resonance (EPR) in most phosphates/PMS system seemly support a radical-dominant mechanism. However, fluorescence probe experiments confirm that no significant amount of hydroxyl radicals (•OH) are produced in such reaction systems. PMS in the phosphate solutions (without any organics) remains relatively stable, but is only consumed while organic substrates are present, which is distinct from a typical radical-dominant Co2+/PMS system where PMS is continuously decomposed. Through density functional theory (DFT) calculation, the energy barriers of the phosphates/PMS reaction processes are greatly decreased when non-radical mechanism dominates. Complementary evidence suggests that the reactive intermediates of PMS-phosphate complex, rather than the free radicals, are capable of oxidizing electron-rich substrates such as DMPO and organic pollutants. Taking the case of phosphate/PMS system as an example, this study demonstrates the necessity of acquisition of lines of evidence for resolving paradoxes in identifying EPR adducts.

Advantages of Edaravone Dextrosanol in Elderly Patients with Acute Cerebral Infarction versus Edaravone: A preliminary study.

OBJECTIVE: To analyze and compare the application advantages of Edaravone and Edaravone Dextrosanol in elderly patients with acute cerebral infarction (ACI). METHODS: A retrospective analysis of clinical data from 113 elderly AIS patients admitted to our hospital between January 2022 and January 2023 was conducted. Based on the treatment interventions received, patients were divided into a control group (n = 56) and an observation group (n = 57). The control group received Edaravone in addition to routine treatment, while the observation group received Edaravone Dextrosanol in addition to routine treatment. compared clinical outcomes, motor and neurological function, self-care ability, neural damage indicators, inflammatory markers, and adverse reactions between the two groups. RESULTS: ① Total effective rate in the observation group (91.23%) was significantly higher than that in the control group (75.00%) (P < 0.05). ② After treatment, higher FMA and Barthel scores, lower NDS score in observation group vs control group (P < 0.05). ③ After treatment, lower NSE and MMP-9 levels in observation group vs control group (P < 0.05). ④ After treatment, lower IL-1ß, IL-6, and hs-CRP levels in observation group vs control group (P < 0.05). ⑤ No significant difference in adverse reaction incidence between groups (P > 0.05). CONCLUSION: Edaravone Dextrosanol proves effective in treating elderly AIS patients. Compared to Edaravone, it boosts effectiveness, neurological recovery, motor & self-care abilities, and reduces neural damage & inflammation markers. Its safety profile is comparable to Edaravone, without significantly increasing adverse reactions. These findings suggest that Edaravone Dextrosanol is worthy of clinical promotion.

Quantification of metabolic activity from isotope tracing data using automated methodology.

Isotope tracing is a widely used technique to study metabolic activities by introducing heavy labeled nutrients into living cells and organisms. However, interpreting isotope tracing data is often heuristic, and application of automated methods using artificial intelligence is limited due to the paucity of evaluative knowledge. Our study developed a new pipeline that efficiently predicts metabolic activity in expansive metabolic networks and systematically quantifies flux uncertainty of traditional computational methods. We further developed an algorithm adept at significantly reducing this uncertainty, enabling robust evaluations of metabolic activity with limited data. Using this technology, we discovered highly reprogrammed mitochondria-cytosol exchange cycles in tumor tissue of patients, and observed similar metabolic patterns influenced by nutritional conditions in cancer cells. Thus, our refined methodology provides robust automated quantification of metabolism allowing for new insight into metabolic network activity.

Fiber Flexibility Reconciles Matrix Recruitment and the Fiber Modulus to Promote Cell Mechanosensing.

The mechanical interaction between cells and the extracellular matrix is pervasive in biological systems. On fibrous substrates, cells possess the ability to recruit neighboring fibers, thereby augmenting their own adhesion and facilitating the generation of mechanical cues. However, the matrices with high moduli impede fiber recruitment, restricting the cell mechanoresponse. Herein, by harnessing the inherent swelling properties of gelatin, the flexible gelatin methacryloyl network empowers cells to recruit fibers spanning a broad spectrum of physiological moduli during adhesion. The high flexibility concurrently facilitates the optimization of fiber distribution, deformability, and modulus, contributing to the promotion of cell mechanosensing. Consequently, the randomly distributed flexible fibers with high moduli maximize the cell adhesive forces. This study uncovers the impact of fiber recruitment on cell mechanosensing and introduces fiber flexibility as a previously unexplored property, offering an innovative perspective for the design and development of novel biomaterials.

Co-exposure to phthalates and polycyclic aromatic hydrocarbons and the risk of gestational hypertension in Chinese women.

Phthalates (PAEs) and polycyclic aromatic hydrocarbons (PAHs) are frequently detected in females of reproductive age. Many studies have found that environmental PAE and PAH levels are independent risk factors for gestational hypertension. However, exposure to both components is a more realistic scenario. To better assess the health effects of PAEs and PAHs in pregnant women, we explored the associations of exposure to both individual and combined PAEs and PAHs with gestational hypertension. This nested case-control study was a component of a prospective cohort study conducted in Beijing, China. We included 206 women with gestational hypertension and 214 pregnant controls. We used gas chromatography/tandem mass spectrometry (GC-MS/MS) to detect 8 PAEs and 13 PAHs in > 80 % of all collected hair samples. Multiple linear regression models were employed to test the individual associations between each component and gestational hypertension. A quantile-based g-computation (qgcomp) model and a weighted quantile sum (WQS) regression model were used to estimate whether exposure to both PAEs and PAHs increased the risk of gestational hypertension. The individual exposure analyses revealed that diethyl phthalate (DEP), diisobutyl phthalate (DIBP) (both PAEs), benzo(k)fluoranthene (BKF), anthracene, (ANT), and benzo(a)pyrene (BAP) (all PAHs) were positively associated with increased risk of gestational hypertension. In mixed-effect analyses, the qgcomp model indicated that co-exposure to PAEs and PAHs increased the risk of gestational hypertension (odds ratio = 2.01; 95 % confidence interval: 1.02, 3.94); this finding was verified by the WQS regression model. Our findings support earlier evidence that both PAEs and PAHs increase the risk of gestational hypertension, both individually and in combination. This suggests that reductions in exposure to endocrine system-disrupting chemicals such as PAEs and PAHs might reduce the risk of gestational hypertension.