Atypical dynamic neural configuration in autism spectrum disorder and its relationship to gene expression profiles.

Although it is well recognized that autism spectrum disorder (ASD) is associated with atypical dynamic functional connectivity patterns, the dynamic changes in brain intrinsic activity over each time point and the potential molecular mechanisms associated with atypical dynamic temporal characteristics in ASD remain unclear. Here, we employed the Hidden Markov Model (HMM) to explore the atypical neural configuration at every scanning time point in ASD, based on resting-state functional magnetic resonance imaging (rs-fMRI) data from the Autism Brain Imaging Data Exchange. Subsequently, partial least squares regression and pathway enrichment analysis were employed to explore the potential molecular mechanism associated with atypical neural dynamics in ASD. 8 HMM states were inferred from rs-fMRI data. Compared to typically developing, individuals on the autism spectrum showed atypical state-specific temporal characteristics, including number of states and occurrences, mean life time and transition probability between states. Moreover, these atypical temporal characteristics could predict communication difficulties of ASD, and states assoicated with negative activation in default mode network and frontoparietal network, and positive activation in somatomotor network, ventral attention network, and limbic network, had higher predictive contribution. Furthermore, a total of 321 genes was revealed to be significantly associated with atypical dynamic brain states of ASD, and these genes are mainly enriched in neurodevelopmental pathways. Our study provides new insights into characterizing the atypical neural dynamics from a moment-to-moment perspective, and indicates a linkage between atypical neural configuration and gene expression in ASD.

Performance Analysis and Optimization of a Series Heat Exchangers Organic Rankine Cycle Utilizing Multi-Heat Sources from a Marine Diesel Engine.

Organic Rankine Cycle (ORC) is an effective way to recycle waste heat sources of a marine diesel engine. The aim of the present paper is to analyze and optimize the thermoeconomic performance of a Series Heat Exchangers ORC (SHEORC) for recovering energy from jacket water, scavenge air, and exhaust gas. The three sources are combined into three groups of jacket water (JW)→exhaust gas (EG), scavenge air (SA)→exhaust gas, and jacket water→scavenge air→exhaust gas. The influence of fluid mass flow rate, evaporation pressure, and heat source recovery proportion on the thermal performance and economic performance of SHEORC was studied. A single-objective optimization with power output as the objective and multi-objective optimization with exergy efficiency and levelized cost of energy (LCOE) as the objectives are carried out. The analysis results show that in jacket water→exhaust gas and jacket water→scavenge air→exhaust gas source combination, there is an optimal heat recovery proportion through which the SHEORC could obtain the best performance. The optimization results showed that R245ca has the best performance in thermoeconomic performance in all three source combinations. With scavenge air→exhaust, the power output, exergy efficiency, and LCOE are 354.19 kW, 59.02%, and 0.1150 $/kWh, respectively. Integrating the jacket water into the SA→EG group would not increase the power output, but would decrease the LCOE.

Configuration Selection of the Multi-Loop Organic Rankine Cycle for Recovering Energy from a Single Source.

The Organic Rankine Cycle (ORC) is a well-established way to recover energy from a single waste heat source. This paper aims to select the suitable configuration, number of loops, and working fluids for the Multi-Loop ORC (MLORC) by using multi-objective optimization. The thermodynamic and economic performance of MLORC in three various configurations was analyzed. Multi-objective optimizations of the series and parallel MLORC using different working fluid groups were conducted to find the optimal configuration, number of loops, and working fluid combination. The analysis results show that the series-parallel MLORC performed the worst among the three configurations. The optimization results reveal that series MLORC has a higher exergy efficiency than the parallel MLORC. The exergy efficiency of the optimal solution in series dual-loop, triple-loop, and quadruple-loop ORC is 9.3%, 7.98%, and 6.23% higher than that of parallel ORC, respectively. Furthermore, dual-loop is the optimal number of cycles for recovering energy from a single heat source, according to the grey relational grade. Finally, the series dual-loop ORC using cyclohexane\cyclohexane was the suitable configuration for utilizing a single waste heat source. The exergy efficiency and levelized cost of electricity of the series dual-loop ORC with the optimal parameters are 62.18% and 0.1509 $/kWh, respectively.

Specific convulsions and brain damage in children hospitalized for Omicron BA.5 infection: an observational study using two cohorts.

BACKGROUND: SARS-CoV-2 continues to mutate over time, and reports on children infected with Omicron BA.5 are limited. We aimed to analyze the specific symptoms of Omicron-infected children and to improve patient care. METHODS: We selected 315 consecutively hospitalized children with Omicron BA.5 and 16,744 non-Omicron-infected febrile children visiting the fever clinic at our hospital between December 8 and 30, 2022. Specific convulsions and body temperatures were compared between the two cohorts. We analyzed potential associations between convulsions and vaccination, and additionally evaluated the brain damage among severe Omicron-infected children. RESULTS: Convulsion rates (97.5% vs. 4.3%, P < 0.001) and frequencies (median: 2.0 vs. 1.6, P < 0.001) significantly differed between Omicron-infected and non-Omicron-infected febrile children. The body temperatures of Omicron-infected children were significantly higher during convulsions than when they were not convulsing and those of non-Omicron-infected febrile children during convulsions (median: 39.5 vs. 38.2 and 38.6 °C, both P < 0.001). In the three Omicron-subgroups, the temperature during convulsions was proportional to the percentage of patients and significantly differed ( P < 0.001), while not in the three non-Omicron-subgroups ( P = 0.244). The convulsion frequency was lower in the 55 vaccinated children compared to the 260 non-vaccinated children (average: 1.8 vs. 2.1, P < 0.001). The vaccination dose and convulsion frequency in Omicron-infected children were significantly correlated ( P < 0.001). Fifteen of the 112 severe Omicron cases had brain damage. CONCLUSIONS: Omicron-infected children experience higher body temperatures and frequencies during convulsions than those of non-Omicron-infected febrile children. We additionally found evidence of brain damage caused by infection with omicron BA.5. Vaccination and prompt fever reduction may relieve symptoms.

High-Throughput Optical Controlling and Recording Calcium Signal in iPSC-Derived Cardiomyocytes for Toxicity Testing and Phenotypic Drug Screening.

Understanding how excitable cells work in health and disease and how that behavior can be altered by small molecules or genetic manipulation is important. Genetically encoded calcium indicators (GECIs) with multiple emission windows can be combined (e.g., for simultaneous observation of distinct subcellular events) or used in extended applications with other light-dependent actuators in excitable cells (e.g., combining genetically encoded optogenetic control with spectrally compatible calcium indicators). Such approaches have been used in primary or stem cell-derived neurons, cardiomyocytes, and pancreatic beta-cells. However, it has been challenging to increase the throughput, or duration of observation, of such approaches due to limitations of the instruments, analysis software, indicator performance, and gene delivery efficiency. Here, a high-performance green GECI, mNeonGreen-GECO (mNG-GECO), and red-shifted GECI, K-GECO, is combined with optogenetic control to achieve all-optical control and visualization of cellular activity in a high-throughput imaging format using a High-Content Imaging System. Applications demonstrating cardiotoxicity testing and phenotypic drug screening with healthy and patient-derived iPSC-CMs are shown. In addition, multi-parametric assessments using combinations of spectral and calcium affinity indicator variants (NIR-GECO, LAR-GECO, and mtGCEPIA or Orai1-G-GECO) are restricted to different cellular compartments are also demonstrated in the iPSC-CM model.

Evaluation of traumatic retinopathy with ultra-wide field imaging under corneal scar or fixed small pupil.

AIM: To evaluate the value of ultra-wide field (UWF) imaging in the management of traumatic retinopathy under the condition of corneal scar or fixed small pupil after complicated ocular trauma. METHODS: Twenty-eight patients (28 eyes) with complicated ocular trauma were enrolled in the study from June 2016 to May 2017, including 19 males and 9 females with age ranged from 11 to 64 (43.42±12.62)y. All patients were treated with secondary vitrectomy after emergency operation for wound repair of open ocular trauma. Direct ophthalmoscopy and 45-degree fundus photography were taken at each time point of follow up for comparison of findings with UWF images. Routine eye examination including visual acuity, intraocular pressure, slit lamp examination were performed and analyzed as well. RESULTS: Among the 28 traumatized eyes, the positive rate for identification of traumatic retinopathed was 32.1% (9 cases), 14.9% (5 cases), and 85.7% (24 cases) with direct ophthalmoscopy, 45-degree fundus photography, and UWF imaging, respectively. The detective rate of UWF imaging under the condition of corneal scar or fixed small pupil was statistically greater than that of 45-degree fundus photography and direct ophthalmoscopy (Bonferroni correction, P<0.001). UWF image was obtained in 19 eyes with opaque corneal scar, otherwise their fundus could not be seen by conventional methods. The additional findings of traumatic retinopathies by UWF imaging included periretinal membranes or pre-retinal proliferating strip, retinal holes, hemorrhage in the vitreous or sub-retinal space. CONCLUSION: UWF imaging is superior to traditional fundus photography in the evaluation of traumatic retinopathies under the condition of corneal scar or fixed small pupil after complicated ocular trauma.

Identification of key genes in Gram­positive and Gram­negative sepsis using stochastic perturbation.

Sepsis is an inflammatory response to pathogens (such as Gram­positive and Gram­negative bacteria), which has high morbidity and mortality in critically ill patients. The present study aimed to identify the key genes in Gram­positive and Gram­negative sepsis. GSE6535 was downloaded from Gene Expression Omnibus, containing 17 control samples, 18 Gram­positive samples and 25 Gram­negative samples. Subsequently, the limma package in R was used to screen the differentially expressed genes (DEGs). Hierarchical clustering was conducted for the specific DEGs in Gram­negative and Gram­negative samples using cluster software and the TreeView software. To analyze the correlation of samples at the gene level, a similarity network was constructed using Cytoscape software. Functional and pathway enrichment analyses were conducted for the DEGs using DAVID. Finally, stochastic perturbation was used to determine the significantly differential functions between Gram­positive and Gram­negative samples. A total of 340 and 485 DEGs were obtained in Gram­positive and Gram­negative samples, respectively. Hierarchical clustering revealed that there were significant differences between control and sepsis samples. In Gram­positive and Gram­negative samples, myeloid cell leukemia sequence 1 was associated with apoptosis and programmed cell death. Additionally, NADH:ubiquinone oxidoreductase subunit S4 was associated with mitochondrial respiratory chain complex I assembly. Stochastic perturbation analysis revealed that NADH:ubiquinone oxidoreductase subunit B2 (NDUFB2), NDUFB8 and ubiquinol­cytochrome c reductase hinge protein (UQCRH) were associated with cellular respiration in Gram­negative samples, whereas large tumor suppressor kinase 2 (LATS2) was associated with G1/S transition of the mitotic cell cycle in Gram­positive samples. NDUFB2, NDUFB8 and UQCRH may be biomarkers for Gram­negative sepsis, whereas LATS2 may be a biomarker for Gram­positive sepsis. These findings may promote the therapies of sepsis caused by Gram­positive and Gram­negative bacteria.

Inhibitory effects of wild bitter melon leaf extract on Propionibacterium acnes-induced skin inflammation in mice and cytokine production in vitro.

Propionibacterium acnes is a key pathogen involved in acne inflammation. Wild bitter melon (WBM, Momordica charantia L. var. abbreviate Seringe) is consumed as both a vegetable and as folk medicine in Taiwan. We examined the inhibitory activity of the total phenolic extract (TPE) of WBM leaf on P. acnes-induced inflammatory responses in vivo and in vitro. Our data showed that TPE significantly attenuated P. acnes-induced ear swelling in mice along with microabscess. Flow cytometry analysis revealed that TPE treatment significantly decreased the migration of neutrophils and interleukin (IL)-1ß(+) populations in vivo. In P. acnes-stimulated human monocytic THP-1 cells, TPE suppressed the mRNA levels and production of IL-8, IL-1ß, and tumor necrosis factor (TNF)-αin vitro. In addition, TPE suppressed P. acnes-induced matrix metalloproteinase-9 levels. TPE blocked nuclear factor-κB (NF-κB) activation and inactivated mitogen-activated protein kinases (MAPK); these actions may partially account for its inhibitory effect on cytokine production. The quantitative HPLC analysis revealed gallic, chlorogenic, caffeic, ferulic, and cinnamic acids, myricetin, quercetin, luteolin, apigenin, and thymol in TPE. All these phenolics significantly suppressed P. acnes-induced IL-8 production in vitro. Our results suggest that WBM leaf extract effectively inhibits P. acnes-induced inflammatory responses and may be useful to relieve the inflammation of acne.

Anti-bacterial and anti-inflammatory properties of capric acid against Propionibacterium acnes: a comparative study with lauric acid.

BACKGROUND: Propionibacterium acnes (P. acnes) is a commensal bacterium which is possibly involved in acne inflammation. The saturated fatty acid, lauric acid (C12:0) has been shown to possess antibacterial and anti-inflammatory properties against P. acnes. Little is known concerning the potential effects of its decanoic counterpart, capric acid (C10:0). OBJECTIVE: To examine the antibacterial and anti-inflammatory activities of capric acid against P. acnes and to investigate the mechanism of the anti-inflammatory action. METHODS: The antimicrobial activity of fatty acids was detected using the broth dilution method. An evaluation of P. acnes-induced ear edema in mice was conducted to evaluate the in vivo anti-inflammatory effect. To elucidate the in vitro anti-inflammatory effect, human SZ95 sebocytes and monocytic THP-1 cells were treated with P. acnes alone or in the presence of a fatty acid. The mRNA levels and secretion of pro-inflammatory cytokines were measured by qRT-PCR and enzyme immunoassay, respectively. NF-κB activation and MAPK expression were analyzed by ELISA and Western blot, respectively. RESULTS: Lauric acid had stronger antimicrobial activity against P. acnes than capric acid in vitro and in vivo. However, both fatty acids attenuated P. acnes-induced ear swelling in mice along with microabscess and significantly reduced interleukin (IL)-6 and CXCL8 (also known as IL-8) production in P. acnes-stimulated SZ95 sebocytes. P. acnes-induced mRNA levels and secretion of IL-8 and TNF-α in THP-1 cells were suppressed by both fatty acids, which inhibited NF-κB activation and the phosphorylation of MAP kinases. CONCLUSION: Our data demonstrate that both capric acid and lauric acid exert bactericidal and anti-inflammatory activities against P. acnes. The anti-inflammatory effect may partially occur through the inhibition of NF-κB activation and the phosphorylation of MAP kinases.

Wild bitter melon (Momordica charantia Linn. var. abbreviata Ser.) extract and its bioactive components suppress Propionibacterium acnes-induced inflammation.

In this study, we aimed to evaluate the inhibitory effect of wild bitter melons (WBM; Momordica charantia Linn. var. abbreviata Ser.) on Propionibacterium acnes-induced inflammation and to identify the bioactive components. Our results showed that ethyl acetate (EA) extract of WBM fruit in vitro potently suppressed pro-inflammatory cytokine and matrix metalloproteinase (MMP)-9 levels in P. acnes-stimulated THP-1 cells. Furthermore, concomitant intradermal injection of WBM EA extract in mice effectively attenuated P. acnes-induced ear swelling and granulomatous inflammation. To further investigate the bioactive components, we found that both saponifiable (S) and nonsaponifiable (NS) fractions of WBM EA extract significantly suppressed pro-inflammatory cytokine and MMP-9 levels. Phytol and lutein, identified in the NS fraction, also inhibited cytokine production. Moreover, S and NS fractions of EA extract, phytol and lutein, activated peroxisome proliferator-activated receptor (PPAR) α and ß in the transactivation assay. Our results suggested that PPARα or PPARγ signalling may contribute, at least in part, to the anti-inflammatory activity of WBM.

Response of stable carbon isotope in epilithic mosses to atmospheric nitrogen deposition.

Epilithic mosses are characterized by insulation from substratum N and hence meet their N demand only by deposited N. This study investigated tissue C, total Chl and delta13C of epilithic mosses along 2 transects across Guiyang urban (SW China), aiming at testing their responses to N deposition. Tissue C and total Chl decreased from the urban to rural, but delta13C(moss) became less negative. With measurements of atmospheric CO2 and delta13CO2, elevated N deposition was inferred as a primary factor for changes in moss C and isotopic signatures. Correlations between total Chl, tissue C and N signals indicated a nutritional effect on C fixation of epilithic mosses, but the response of delta13C(moss) to N deposition could not be clearly differentiated from effects of other factors. Collective evidences suggest that C signals of epilithic mosses are useful proxies for N deposition but further works on physiological mechanisms are still needed.

[Responses of tissue carbon and delta 13C in epilithic mosses to the variations of anthropogenic CO2 and atmospheric nitrogen deposition in city area].

We investigated the carbon (C) and nitrogen (N) concentrations and isotopic signatures (delta 13C and delta15 N) in epilithic mosses collected from urban sites to rural sites along four directions at Guiyang area. Mosses C (34.47%-52.76%) decreased significantly with distance from urban to rural area and strongly correlated with tissue N (0.85%-2.97%), showing atmospheric N deposition has positive effect on C assimilation of epilithic mosses, higher atmospheric N/NHx deposition at urban area has improved the photosynthesis and C fixation of mosses near urban, which also caused greater 13C discrimination for urban mosses. Mosses delta 13C signatures (-30.69% per hundred - -26.96% per hundred) got less negative with distance from urban to rural area, which was also related to the anthropogenic CO2 emissions in the city, and these 12C-enriched CO2 sources would lead to more negative mosses delta 13C through enhancing the atmospheric CO2 concentration in urban area. Moreover, according to the characteristics of mosses C and delta 13C variations with distance, it is estimated that the influences of urban anthropogenic CO2 sources on plants was mainly within 20 km from city center. This study mainly focused on the factors regulating tissue C and delta 13C of mosses in city area and the interaction between C and N in mosses, the responses of mosses C and delta 13C to urban CO2 emission and atmospheric N deposition have been revealed, which could provide new geochemical evidences for the control of city atmospheric pollution and the protection of ecosystems around city.

[Nitrogen concentration and nitrogen isotope in epilithic mosses for indicating the spatial variation and sources of atmospheric nitrogen deposition at Guiyang area].

Tissue N concentration and delta15 N signature in epilithic mosses were investigated along 4 directions from urban area to rural area at Guiyang city. Mosses N concentration ranged from 0.85% to 2.97% and showed significant decrease from urban area (2.24% +/- 0.32%) to suburb (1.27% +/- 0.13%), reflecting the level of atmospheric N deposition decreased away from urban. While slightly higher tissue N re-emerged at rural area beyond 25km (mean = 1.33%-1.75%), suggesting increased N deposition occurred in the rural area. Mosses delta15 N values varied from - 12.50 per thousand to - 1.39 per thousand characterized with getting less negative from urban to rural area. More negative delta15 N signatures of urban mosses (mean= - 8.87 per thousand(-) - 8.59 per thousand) mainly indicated the extensive NH3 sources released from excretory wastes and sewage, while mosses growing at farther suburb or rural area had less depleted delta15 N values (mean = - 3.83 per thousand(-) - 2.48 per thousand), indicating the large sources of agricultural NH3 emission connected with fertilizer application. Moreover, the pattern of mosses delta15 N variation in this study was opposite to areas where N deposition was dominated by oxidized form N (NO(x)) with generally positive mosses delta15 N. Accordingly, we concluded that reduced NH, was the dominant N form in atmospheric deposition at Guiyang area, which would be of great value for understanding the spatial variation and sources of atmospheric N deposition.

Atmospheric transport of urban-derived NH(x): Evidence from nitrogen concentration and delta(15)N in epilithic mosses at Guiyang, SW China.

Nitrogen concentration and delta15N in 175 epilithic moss samples were investigated along four directions from urban to rural sites in Guiyang, SW China. The spatial variations of moss N concentration and delta15N revealed that atmospheric N deposition is dominated by NHx-N from two major sources (urban sewage NH3 and agricultural NH3), the deposition of urban-derived NHx followed a point source pattern characterized by an exponential decline with distance from the urban center, while the agricultural-derived NHx was shown to be a non-point source. The relationship between moss N concentration and distance (y=1.5e(-0.13x)+1.26) indicated that the maximum transporting distance of urban-derived NHx averaged 41 km from the urban center, and it could be determined from the relationship between moss delta(15)N and distance [y=2.54ln(x)-12.227] that urban-derived NHx was proportionally lower than agricultural-derived NHx in N deposition at sites beyond 17.2 km from the urban center. Consequently, the variation of urban-derived NHx with distance from the urban center could be modeled as y=56.272e(-0.116x)-0.481 in the Guiyang area.