cGAS-STING, an important signaling pathway in diseases and their therapy.

Since cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway was discovered in 2013, great progress has been made to elucidate the origin, function, and regulating mechanism of cGAS-STING signaling pathway in the past decade. Meanwhile, the triggering and transduction mechanisms have been continuously illuminated. cGAS-STING plays a key role in human diseases, particularly DNA-triggered inflammatory diseases, making it a potentially effective therapeutic target for inflammation-related diseases. Here, we aim to summarize the ancient origin of the cGAS-STING defense mechanism, as well as the triggers, transduction, and regulating mechanisms of the cGAS-STING. We will also focus on the important roles of cGAS-STING signal under pathological conditions, such as infections, cancers, autoimmune diseases, neurological diseases, and visceral inflammations, and review the progress in drug development targeting cGAS-STING signaling pathway. The main directions and potential obstacles in the regulating mechanism research and therapeutic drug development of the cGAS-STING signaling pathway for inflammatory diseases and cancers will be discussed. These research advancements expand our understanding of cGAS-STING, provide a theoretical basis for further exploration of the roles of cGAS-STING in diseases, and open up new strategies for targeting cGAS-STING as a promising therapeutic intervention in multiple diseases.

Emerging trends and focus of research on the relationship between traumatic brain injury and gut microbiota: a visualized study.

Background: Traumatic brain injury (TBI) is one of the most serious types of trauma and imposes a heavy social and economic burden on healthcare systems worldwide. The development of emerging biotechnologies is uncovering the relationship between TBI and gut flora, and gut flora as a potential intervention target is of increasing interest to researchers. Nevertheless, there is a paucity of research employing bibliometric methodologies to scrutinize the interrelation between these two. Therefore, this study visualized the relationship between TBI and gut flora based on bibliometric methods to reveal research trends and hotspots in the field. The ultimate objective is to catalyze progress in the preclinical and clinical evolution of strategies for treating and managing TBI. Methods: Terms related to TBI and gut microbiota were combined to search the Scopus database for relevant documents from inception to February 2023. Visual analysis was performed using CiteSpace and VOSviewer. Results: From September 1972 to February 2023, 2,957 documents published from 98 countries or regions were analyzed. The number of published studies on the relationship between TBI and gut flora has risen exponentially, with the United States, China, and the United Kingdom being representative of countries publishing in related fields. Research has formed strong collaborations around highly productive authors, but there is a relative lack of international cooperation. Research in this area is mainly published in high-impact journals in the field of neurology. The "intestinal microbiota and its metabolites," "interventions," "mechanism of action" and "other diseases associated with traumatic brain injury" are the most promising and valuable research sites. Targeting the gut flora to elucidate the mechanisms for the development of the course of TBI and to develop precisely targeted interventions and clinical management of TBI comorbidities are of great significant research direction and of interest to researchers. Conclusion: The findings suggest that close attention should be paid to the relationship between gut microbiota and TBI, especially the interaction, potential mechanisms, development of emerging interventions, and treatment of TBI comorbidities. Further investigation is needed to understand the causal relationship between gut flora and TBI and its specific mechanisms, especially the "brain-gut microbial axis."

Non-invasive monitoring of cardiac function through Ballistocardiogram: an algorithm integrating short-time Fourier transform and ensemble empirical mode decomposition.

The Ballistocardiogram (BCG) is a vibration signal that is generated by the displacement of the entire body due to the injection of blood during each heartbeat. It has been extensively utilized to monitor heart rate. The morphological features of the BCG signal serve as effective indicators for the identification of atrial fibrillation and heart failure, holding great significance for BCG signal analysis. The IJK-complex identification allows for the estimation of inter-beat intervals (IBI) and enables a more detailed analysis of BCG amplitude and interval waves. This study presents a novel algorithm for identifying the IJK-complex in BCG signals, which is an improvement over most existing algorithms that only perform IBI estimation. The proposed algorithm employs a short-time Fourier transform and summation across frequencies to initially estimate the occurrence of the J wave using peak finding, followed by Ensemble Empirical Mode Decomposition and a regional search to precisely identify the J wave. The algorithm's ability to detect the morphological features of BCG signals and estimate heart rates was validated through experiments conducted on 10 healthy subjects and 2 patients with coronary heart disease. In comparison to commonly used methods, the presented scheme ensures accurate heart rate estimation and exhibits superior capability in detecting BCG morphological features. This advancement holds significant value for future applications involving BCG signals.

[Status Quo and Prospects of Research on Precision Nursing of Life-Cycle Health and Disease].

With the changing lifestyle and spectrum of diseases among Chinese people, the life-cycle approach to health has been given national strategic importance. Over the past decade, global nursing researchers have gradually started to pay more attention to the research related to precision nursing at different stages of the life cycle. Researchers have applied multi-omics to explore the pathogenesis and novel biomarkers of relevant symptoms in tumor patients or patients with chronic diseases in order to manage symptoms with better precision. However, systematic theories of precision nursing of life-cycle health and disease have not yet been developed, and the research field and its implications still need to be continuously expanded and innovated. In the nursing discipline, the advantages of interdisciplinary integration should be given full play and the precise and effective resolution of life-cycle health problems should be taken as its goal. Through accurately defining key quantitative objective indicators of nursing care, the nursing discipline will be able to achieve early identification of life-cycle health problems, clarify the occurrence and patterns of change in life-cycle health problems, and gain a better understanding of the regulatory mechanisms. Precise and effective nursing-related technologies and products of non-medication and non-surgery nature should be developed to achieve better precision in nursing interventions, thereby effectively promoting recovery from diseases and improving the overall health of the people.

Enhanced secondary organic aerosol formation during dust episodes by photochemical reactions in the winter in Wuhan.

To investigate the effect of frequently occurring mineral dust on the formation of secondary organic aerosol (SOA), 106 volatile organic compounds (VOCs), trace gas pollutants and chemical components of PM2.5 were measured continuously in January 2021 in Wuhan, Central China. The observation period was divided into two stages that included a haze period and a following dust period, based on the ratio of PM2.5 and PM10 concentrations. The average ratio of secondary organic carbon (SOC) to elemental carbon (EC) was 1.98 during the dust period, which was higher than that during the haze period (0.69). The contribution of SOA to PM2.5 also increased from 2.75% to 8.64%. The analysis of the relationships between the SOA and relative humidity (RH) and the odd oxygen (e.g., OX = O3 + NO2) levels suggested that photochemical reactions played a more important role in the enhancement of SOA production during the dust period than the aqueous-phase reactions. The heterogeneous photochemical production of OH radicals in the presence of metal oxides during the dust period was believed to be enhanced. Meanwhile, the ratios of trans-2-butene to cis-2-butene and m-/p-xylene to ethylbenzene (X/E) dropped significantly, confirming that stronger photochemical reactions occurred and SOA precursors formed efficiently. These results verified the laboratory findings that metal oxides in mineral dust could catalyse the oxidation of VOCs and induce higher SOA production.

A retrospect of ozone formation mechanisms during the COVID-19 lockdown: The potential role of isoprene.

Wuhan took strict measures to prevent the spread of COVID-19 from January 26 to April 7 in 2020. The lockdown reduced the concentrations of atmospheric pollutants, except ozone (O3). To investigate the increase in O3 during the lockdown, trace gas pollutants were collected. The initial concentrations of volatile organic compounds (VOCs) were calculated based on a photochemical ratio method, and the ozone formation potential (OFP) was obtained using the initial and measured VOC concentrations. The O3 formation regime was NOX-limited based on the VOCs/NOX diurnal ratios during the lockdown period. The reduced nitric oxide (NO) concentrations and lower wind speed (WS) could explain the night-time O3 accumulation. The initial total VOCs (TVOCs) during the lockdown were 47.6 ± 2.9 ppbv, and alkenes contributed 48.1%. The photochemical loss amounts of alkenes were an order of magnitude higher than those of alkenes in the same period in 2019 and increased from 16.6 to 28.0 ppbv in the daytime. The higher initial alkene concentrations sustained higher OFP during the lockdown, reaching between 252.4 and 504.4 ppbv. The initial isoprene contributed approximately 35.0-55.0% to the total OFP and had a positive correlation with the increasing O3 concentrations. Approximately 75.5% of the temperatures were concentrated in the range of 5 and 20 °C, which were higher than those in 2019. In addition to stronger solar radiation, the higher temperatures induced higher isoprene emission rates, partially accounting for the higher isoprene concentrations. Lower isoprene-emitting trees should be considered for future urban vegetation to control O3 episodes.

Fractal Geometry Illustrated Left Atrial Appendage Morphology That Predicted Thrombosis and Stroke in Patients With Atrial Fibrillation.

Background: This study aims to correlate the morphological complexity of left atrial appendage (LAA) with thrombosis and stroke in patients with atrial fibrillation (AF). Methods: The training cohort consisted of 46 patients with AF (age 55.8 ± 7.2 years, 73.9% men) who were referred for radiofrequency catheter ablation. An independent validation cohort consisting of 443 patients with AF was enrolled for further verification. All patients in the training cohort underwent both transesophageal echocardiography (TEE) and enhanced computed tomography (CT). Fractal dimension (FD) analysis was performed to evaluate the morphological complexity of LAAs quantitatively. Clinical and imaging manifestations, FD of LAAs, and diagnostic accuracy were investigated and compared between patients with AF in both training and validation cohorts. Results: In the training cohort, LAAs (n = 22) with thrombi had significantly higher FD than those without thrombi (n = 24) h 0.44 ± 0.07 vs. 2.35 ± 0.11, p = 0.003). Receiver-operating characteristic (ROC) analysis suggested that the diagnostic accuracy of FD combined with a CHA2DS2-VaSc score was significantly higher than that of the CHA2DS2-VaSc score alone in low- to moderate-risk patients with AF (area under the curve 0.8479 vs. 0.6958, p = 0.009). The results were also validated in an independent external validation cohort and demonstrated that increased FD was associated with stroke. Hemodynamic analysis revealed that LAAs with thrombi and high FD were prone to blood stasis and lower blood flow rate. Conclusion: LAA morphological complexity is closely associated with thrombosis and stroke in patients with paroxysmal AF. A new risk assessment system combining CHA2DS2-VaSc score and FD has a higher diagnostic accuracy in predicting LAA thrombosis.

Physical modelling of energy losses at surcharged three-way junction manholes in drainage system.

Motivated by the observation that vortex flow structure was evident in the energy loss at the surcharged junction manhole due to changes of hydraulic and geometrical parameters, a physical model was used to calculate energy loss coefficients and investigate the relationship between flow structure and energy loss at the surcharged three-way junction manhole. The effects of the flow discharge ratio, the connected angle between two inflow pipes, the manhole geometry, and the downstream water depth on the energy loss were analyzed based on the quantified energy loss coefficients and the identified flow structure. Moreover, two empirical formulae for head loss coefficients were validated by the experimental data. Results indicate that the effect of flow discharge ratio and connected angle are significant, while the effect of downstream water depth is not obvious. With the increase of the lateral inflow discharge, the flow velocity distribution and vortex structure are both enhanced. It is also found that a circular manhole can reduce local energy loss when compared to a square manhole. In addition, the tested empirical formulae can reproduce the trend of total head loss coefficient.

Optimized electroencephalogram and functional near-infrared spectroscopy-based mental workload detection method for practical applications.

BACKGROUND: Mental workload is a critical consideration in complex man-machine systems design. Among various mental workload detection techniques, multimodal detection techniques integrating electroencephalogram (EEG) and functional near-infrared spectroscopy (fNIRS) signals have attracted considerable attention. However, existing EEG-fNIRS-based mental workload detection methods have certain defects, such as complex signal acquisition channels and low detection accuracy, which restrict their practical application. METHODS: The signal acquisition configuration was optimized by analyzing the feature importance in mental workload recognition model and a more accurate and convenient EEG-fNIRS-based mental workload detection method was constructed. A classical Multi-Task Attribute Battery (MATB) task was conducted with 20 participating volunteers. Subjective scale data, 64-channel EEG data, and two-channel fNIRS data were collected. RESULTS: A higher number of EEG channels correspond to higher detection accuracy. However, there is no obvious improvement in accuracy once the number of EEG channels reaches 26, with a four-level mental workload detection accuracy of 76.25 ± 5.21%. Partial results of physiological analysis verify the results of previous studies, such as that the θ power of EEG and concentration of O2Hb in the prefrontal region increase while the concentration of HHb decreases with task difficulty. It was further observed, for the first time, that the energy of each band of EEG signals was significantly different in the occipital lobe region, and the power of [Formula: see text] and [Formula: see text] bands in the occipital region increased significantly with task difficulty. The changing range and the mean amplitude of O2Hb in high-difficulty tasks were significantly higher compared with those in low-difficulty tasks. CONCLUSIONS: The channel configuration of EEG-fNIRS-based mental workload detection was optimized to 26 EEG channels and two frontal fNIRS channels. A four-level mental workload detection accuracy of 76.25 ± 5.21% was obtained, which is higher than previously reported results. The proposed configuration can promote the application of mental workload detection technology in military, driving, and other complex human-computer interaction systems.

Integrated modeling of 2D urban surface and 1D sewer hydrodynamic processes and flood risk assessment of people and vehicles.

In order to accurately simulate the whole urban flooding processes and assess the flood risks to people and vehicles in floodwaters, a 2D-surface and a 1D-sewer integrated hydrodynamic model was proposed in this study, with the module of flood risk assessment of people and vehicles being included. The proposed model was firstly validated by a dual-drainage laboratory experiment on the flood inundation process over a typical urban street, and the relative importance of model parameters and model uncertainties were evaluated using the GSA-GLUE method. Then the model was applied to simulate an actual urban flooding process that occurred in Glasgow, UK, with the influence of the sewer drainage system on flood inundation processes and hazard degree distributions of people and vehicles being comprehensively discussed. The following conclusions are drawn from this study: (i) The proposed model has a high degree of accuracy with the NSE values of key hydraulic variables greater than 0.8 and the GSA indicates that Manning roughness coefficients for surface and sewer flows, inlet weir and orifice discharge coefficients, are the most relevant parameters to influence the simulated results; (ii) vehicles are vulnerable to larger water depths while human stability is significantly influenced by higher flow velocities, with the overall flood risk of people being less than that of vehicles; and (iii) about 88.7% of the total inflow volume was drained to the sewer network, and the sewer drainage system greatly reduced the flood risks to people and vehicles except the local areas with large inundation water depths, where the sewer drainage increased the local flow velocity leading to higher flood risks especially for people.

On Iterative Proportional Updating: Limitations and Improvements for General Population Synthesis.

Population synthesis is the foundation of the agent-based social simulation. Current approaches mostly consider basic population and households, rather than other social organizations. This article starts with a theoretical analysis of the iterative proportional updating (IPU) algorithm, a representative method in this field, and then gives an extension to consider more social organization types. The IPU method, for the first time, proves to be unable to converge to an optimal population distribution that simultaneously satisfies the constraints from individual and household levels. It is further improved to a bilevel optimization, which can solve such a problem and include more than one type of social organization. Numerical simulations, as well as population synthesis using actual Chinese nationwide census data, support our theoretical conclusions and indicate that our proposed bilevel optimization can both synthesize more social organization types and get more accurate results.

Dual-target one-step nested PCR for sensitive detection of SARS-CoV-2 nucleic acids.

The Corona Virus Disease reported in 2019 (COVID-19) poses a significant threat to human and public health. Its early and accurate detection can reduce the spread and recurrence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Real-time reverse transcription fluorescent quantitative polymerase chain reaction (RT-qPCR) is the "gold standard" for detecting the nucleic acid of SARS-CoV-2. This study developed and tested a dual-target (ORF1ab and N gene) one-step nested RT-qPCR (DTO-N-PCR) to detect SARS-CoV-2. Ten-fold serial dilutions of mixed synthetic DNA from SARS-CoV-2 ORF1ab and N gene were used as templates to test the sensitivity of DTO-N-PCR. Its specificity was subsequently tested using throat swab specimens from 10 COVID-19 patients and 35 healthy participants. DTO-N-PCR was more sensitive and specific than conventional RT-qPCR. It has unique features, including a dual-target (ORF1ab and N gene), rapid one-step operation of reverse transcription and PCR, four pairs of inner and outer primers, and specific probes. These features aid in its rapid, accurate, and efficient detection of SARS-CoV-2 RNA.

[Research on enhancement of mental rotation ability based on transcranial direct current stimulation].

Transcranial direct current stimulation (tDCS) is a non-invasive low-current brain stimulation technique, which is mainly based on the different polarity of electrode stimulation to make the activation threshold of neurons different, thereby regulating the excitability of the cerebral cortex. In this paper, healthy subjects were randomly divided into three groups: anodal stimulation group, cathodal stimulation group and sham stimulation group, with 5 subjects in each group. Then, the performance data of the three groups of subjects were recorded before and after stimulation to test their mental rotation ability, and resting state and task state electroencephalogram (EEG) data were collected. Finally, through comparative analysis of the behavioral data and EEG data of the three groups of subjects, the effect of electrical stimulation of different polarities on the three-dimensional mental rotation ability was explored. The results of the study found that the correct response time/accuracy rate and the accuracy rate performance of the anodal stimulation group were higher than those of the cathodal stimulation and sham stimulation groups, and there was a significant difference ( P < 0.05). The alpha wave power analysis found that the mental rotation mainly activates the frontal lobe, central area, parietal lobe and occipital lobe. In the anodal stimulation group, the alpha wave power changed significantly in the frontal lobe and occipital lobe ( P < 0.05). The results of this paper show that anodal stimulation group can improve the mental rotation ability of the subjects to a certain extent. The results of this paper can provide important theoretical support for further research on the mechanism of tDCS on mental rotation ability.

Exosomal MicroRNA-21 Promotes Keloid Fibroblast Proliferation and Collagen Production by Inhibiting Smad7.

In keloid fibroblasts, microRNA-21 (miR-21) enhances activation of the TGF-ß-Smad signaling pathway by down-regulating Smad7 expression, thereby promoting keloid fibroblast proliferation and collagen production. However, it is unclear whether miR-21 performs the above-mentioned functions through exosomal transport. Here, we extracted exosomes from the culture supernatants of keloid and normal skin fibroblasts and observed that both types of cells above secrete exosomes; however, keloid fibroblasts secreted significantly more exosomal miR-21 than normal skin fibroblasts (P < .001). Interestingly, we also observed that exosomal miR-21 could enter target keloid fibroblasts. In addition, inhibiting exosomal miR-21 up-regulated Smad7 protein expression and reduced Smad2 and Smad3 protein levels in target keloid fibroblasts. Furthermore, inhibiting exosomal miR-21 down-regulated collagen I and collagen III expression in target keloid fibroblasts, increased the proportion of apoptotic cells, and reduced cell proliferation. Taken together, these results show that exosomal miR-21 promoted proliferation and collagen production in keloid fibroblasts by inhibiting Smad7. Thus, we identified regulatory roles for miR-21 in promoting keloid fibroblast proliferation and participating in keloid formation and development. These findings imply that miR-21 may serve as a novel target for controlling the development of keloids.

Increased sensitivity to TNF-α promotes keloid fibroblast hyperproliferation by activating the NF-κB, JNK and p38 MAPK pathways.

Hyperproliferation of fibroblasts is the main cause of keloid formation. However, the pathogenesis of keloids has yet to be fully elucidated. Tumor necrosis factor (TNF)-α may play an important role in the formation and proliferation of keloids, as it is implicated in the pathogenesis of various fibrous disorders. In the present study, the expression level of TNF-α and its receptors, soluble TNF receptor (sTNFR)1 and sTNFR2, in the peripheral blood and skin tissues was detected by ELISA, reverse transcription-quantitative PCR or immunohistochemistry. There was no statistically significant difference in the expression of TNF-α and sTNFR2 in the peripheral blood and skin tissues between patients with keloids and healthy participants (P>0.05), while the sTNFR1 mRNA level in fibroblasts cultured in vitro and its protein level in keloid skin samples were significantly higher compared with those in normal skin (P<0.05). Subsequently, TNF-α recombinant protein was used to treat keloid-derived and normal skin fibroblasts, and it was observed that TNF-α promoted the proliferation of keloid fibroblasts (KFs), but had little effect on normal skin fibroblasts. Furthermore, it was observed that TNF-α stimulation led to the activation of the nuclear factor (NF)-κB, c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) pathways in KFs. In conclusion, KFs exhibited increased expression of sTNFR1, which may contribute to the increased sensitivity to TNF-α, resulting in low concentrations of TNF-α activating the NF-κB, JNK and p38 MAPK pathways, thereby promoting the sustained and excessive proliferation of KFs.

Recent Advances in Collaborative Scheduling of Computing Tasks in an Edge Computing Paradigm.

In edge computing, edge devices can offload their overloaded computing tasks to an edge server. This can give full play to an edge server's advantages in computing and storage, and efficiently execute computing tasks. However, if they together offload all the overloaded computing tasks to an edge server, it can be overloaded, thereby resulting in the high processing delay of many computing tasks and unexpectedly high energy consumption. On the other hand, the resources in idle edge devices may be wasted and resource-rich cloud centers may be underutilized. Therefore, it is essential to explore a computing task collaborative scheduling mechanism with an edge server, a cloud center and edge devices according to task characteristics, optimization objectives and system status. It can help one realize efficient collaborative scheduling and precise execution of all computing tasks. This work analyzes and summarizes the edge computing scenarios in an edge computing paradigm. It then classifies the computing tasks in edge computing scenarios. Next, it formulates the optimization problem of computation offloading for an edge computing system. According to the problem formulation, the collaborative scheduling methods of computing tasks are then reviewed. Finally, future research issues for advanced collaborative scheduling in the context of edge computing are indicated.

[Review of cognitive enhancement techniques based on the combination of cognitive training and transcranial direct current stimulation].

Cognitive enhancement refers to the technology of enhancing or expanding the cognitive and emotional abilities of people without psychosis based on relevant knowledge of neurobiology. The common methods of cognitive enhancement include transcranial direct current stimulation (tDCS) and cognitive training (CT). tDCS takes effect quickly, with a short effective time, while CT takes longer to work, requiring several weeks of training, with a longer effective time. In recent years, some researchers have begun to use the method of tDCS combined with CT to regulate the cognitive function. This paper will sort out and summarize this topic from five aspects: perception, attention, working memory, decision-making and other cognitive abilities. Finally, the application prospect and challenges of technology are prospected.

On-going nitrification in chloraminated drinking water distribution system (DWDS) is conditioned by hydraulics and disinfection strategies.

Within the drinking water distribution system (DWDS) using chloramine as disinfectant, nitrification caused by nitrifying bacteria is increasingly becoming a concern as it poses a great challenge for maintaining water quality. To investigate efficient control strategies, operational conditions including hydraulic regimes and disinfectant scenarios were controlled within a flow cell experimental facility. Two test phases were conducted to investigate the effects on the extent of nitrification of three flow rates (Q = 2, 6, and 10 L/min) and four disinfection scenarios (total Cl2=1 mg/L, Cl2/NH3-N=3:1; total Cl2=1 mg/L, Cl2/NH3-N=5:1; total Cl2=5 mg/L, Cl2/NH3-N=3:1; and total Cl2=5 mg/L, Cl2/NH3-N=5:1). Physico-chemical parameters and nitrification indicators were monitored during the tests. The characteristics of biofilm extracellular polymetric substance (EPS) were evaluated after the experiment. The main results from the study indicate that nitrification is affected by hydraulic conditions and the process tends to be severe when the fluid flow transforms from laminar to turbulent (2300