Interleukin-18 in chronic pain: Focus on pathogenic mechanisms and potential therapeutic targets.

Chronic pain has been proven to be an independent disease, other than an accompanying symptom of certain diseases. Interleukin-18 (IL-18), a pro-inflammatory cytokine with pleiotropic biological effects, participates in immune modulation, inflammatory response, tumor growth, as well as the process of chronic pain. Compelling evidence suggests that IL-18 is upregulated in the occurrence of chronic pain. Antagonism or inhibition of IL-18 expression can alleviate the occurrence and development of chronic pain. And IL-18 is located in microglia, while IL-18R is mostly located in astrocytes in the spinal cord. This indicates that the interaction between microglia and astrocytes mediated by the IL-18/IL-18R axis is involved in the occurrence of chronic pain. In this review, we described the role and mechanism of IL-18 in different types of chronic pain. This review provides strong evidence that IL-18 is a potential therapeutic target in pain management.

A Single Amino Acid Residue Defines the Difference in NLRP3 Inflammasome Activation between NEK7 and NEK6.

The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is a critical component of the innate immune system that is activated by microbial infections and cellular stress signals. The molecular mechanism of NLRP3 inflammasome activation remains not fully understood. As an NLRP3-interacting partner, NEK7 has emerged as a critical mediator for NLRP3 inflammasome activation. In contrast to NEK7, NEK6, the closely related member of the NEK family, does not support NLRP3 inflammasome activation. In this study, we show that the mouse NEK7 catalytic domain, which shares high sequence identity with the counterpart of NEK6, mediates its interaction with NLRP3 and inflammasome activation in mouse macrophages. Within their catalytic domains, a single amino acid residue at a corresponding position (R121NEK7, Q132NEK6) differentiates their function in NLRP3 inflammasome activation. Surprisingly, substitution of the glutamine residue to an arginine residue at position 132 confers NEK6 the ability of NLRP3 binding and inflammasome activation in mouse macrophages. Furthermore, our results suggest a structural pocket surrounding the residue R121 of NEK7 that is essential for NLRP3 binding and inflammasome activation.

Enhanced chromium and nitrogen removal by constructing a biofilm reaction system based on denitrifying bacteria preferential colonization theory.

Understanding the developmental characteristics of microbial communities in biofilms is crucial for designing targeted functional microbial enhancements for the remediation of complex contamination scenarios. The strong prioritization effect of microorganisms confers the ability to colonize strains that arrive first dominantly. In this study, the auto-aggregating denitrifying bacterial Pseudomonas stutzeri strain YC-34, which has both nitrogen and chromium removal characteristics, was used as a biological material to form a stable biofilm system based on the principle of dominant colonization and biofortification. The effect of the biofilm system on nitrogen and chromium removal was characterized by measuring the changes in the quality of influent and effluent water. The pattern of biofilm changes was analyzed by measuring biofilm content and thickness and characterizing extracellular polymer substances (EPS). Further analysis of the biofilm microbiota characteristics and potential functions revealed the mechanism of strain YC-34 biofortified biofilm. The results revealed that the biofilm system formed could achieve 90.56% nitrate-nitrogen removal with an average initial nitrate-nitrogen concentration of 51.9 mg/L and 40% chromium removal with an average initial hexavalent chromium Cr(VI) concentration of 7.12 mg/L. The biofilm properties of the system were comparatively analyzed during the biofilm formation period, the fluctuation period of Cr(VI)-stressed water quality, and the stabilization period of Cr(VI)-stressed water quality. The biofilm system may be able to increase the structure of hydrogen bonds, the type of protein secondary structure, and the abundance of amino acid-like components in the EPS, which may confer biofilm tolerance to Cr(VI) stress and allow the system to maintain a stable biofilm structure. Furthermore, microbial characterization indicated an increase in microbial diversity in the face of chromium stress, with an increase in the abundance of nitrogen removal-associated functional microbiota and an increasing trend in the abundance of nitrogen transfer pathways. These results demonstrate that the biofilm system is stable in nitrogen and chromium removal. This bioaugmentation method may provide a new way for the remediation of heavy metal-polluted water bodies and also provides theoretical and application parameters for the popularization and application of biofilm systems.

Light-Boosting Highly Sensitive and Ultrafast Piezoelectric Sensor Based on Composite Membrane of Copper Phthalocyanine and Graphene Oxide.

Self-powered wearable pressure sensors based on flexible electronics have emerged as a new trend due to the increasing demand for intelligent and portable devices. Improvements in pressure-sensing performance, including in the output voltage, sensitivity and response time, can greatly expand their related applications; however, this remains challenging. Here, we report on a highly sensitive piezoelectric sensor with novel light-boosting pressure-sensing performance, based on a composite membrane of copper phthalocyanine (CuPC) and graphene oxide (GO) (CuPC@GO). Under light illumination, the CuPC@GO piezoelectric sensor demonstrates a remarkable increase in output voltage (381.17 mV, 50 kPa) and sensitivity (116.80 mV/kPa, <5 kPa), which are approximately twice and three times of that the sensor without light illumination, respectively. Furthermore, light exposure significantly improves the response speed of the sensor with a response time of 38.04 µs and recovery time of 58.48 µs, while maintaining excellent mechanical stability even after 2000 cycles. Density functional theory calculations reveal that increased electron transfer from graphene to CuPC can occur when the CuPC is in the excited state, which indicates that the light illumination promotes the electron excitation of CuPC, and thus brings about the high polarization of the sensor. Importantly, these sensors exhibit universal spatial non-contact adjustability, highlighting their versatility and applicability in various settings.

Regulating Microstructure and Macroscopic Properties in Saturated Salt Solutions Containing Disordered Anions and Cations by Magnetic Field.

Saturated aqueous salt solutions have diverse applications in food production, mineral processing, pharmaceuticals, and environmental monitoring. However, the random and disordered arrangement of ions in these solutions poses limitations across different fields. In this study, we employ magnetic fields to regulate the disordered arrangement by a comprehensive methodology combining contact angle measurement, Raman spectroscopy, X-ray diffraction, and molecular dynamics simulations on saturated KCl solutions. Our findings reveal that weak magnetic fields impede the formation of K-Cl contact pairs and disrupt hydrogen bond networks, particularly DDAA and free OH types. However, they facilitate the interaction between water molecules and ions, leading to an increase in the number of K-O and Cl-H contact pairs, along with an expansion in ion hydration radius. These changes affect macroscopic properties, including the interaction with solid substrates and potential solubility increases. Our experimental and simulation results mutually validate each other, contributing to a theoretical framework for studying magnetic field-material interactions.

The leucine-rich repeat (LRR) domain of NLRP3 is required for NLRP3 inflammasome activation in macrophages.

The NLRP3 inflammasome is a critical component of innate immunity that defends the host from microbial infections. However, its aberrant activation contributes to the pathogenesis of several inflammatory diseases. Activation of the NLRP3 inflammasome induces the secretion of proinflammatory cytokines IL-1ß and IL-18 and pyroptotic cell death. NLRP3 contains a leucine-rich repeat (LRR) domain at its C terminus. Although posttranslational modifications in this LRR domain have been shown to regulate NLRP3 inflammasome activation, the role of the entire LRR domain in NLRP3 inflammasome activation remains controversial. Here, we generated mouse macrophages that express an endogenous NLRP3 mutant lacking the LRR domain. Deletion of the LRR domain diminished NLRP3 inflammasome activation in macrophages. Furthermore, using NLRP3-deficient macrophages that are reconstituted with NLRP3 mutants lacking the LRR domain, we found that deletion of the LRR domain inhibited NLRP3 inflammasome activation. Mechanistically, deletion of the LRR domain inhibited NLRP3 self-association, oligomerization, and interaction with the essential regulator NEK7. Our results demonstrate a critical role for the LRR domain in NLRP3 inflammasome activation.

Transcriptomic Analysis of Yunwu Tribute Tea Leaves under Cold Stress.

Background: Cold stress usually occurs in winter and is one of the most significant environmental factors restricting the growth of the tea plant as well as its geographical distribution. Objective: It is necessary to identify the physiological and molecular mechanisms of plants under cold stress so that cold-tolerant crop varieties can be cultivated to limit production losses. At the same time, this would allow the crop planting area to be expanded, hence improving the economic benefits. Methods: In this study, the transcriptome data of Yunwu Tribute Tea under cold conditions were obtained using the Illumina HiSeq platform. By analyzing changes in transcriptome data associated with the antioxidant enzyme system, plant hormone signal transduction, proline and tyrosine metabolism pathways, and transcription factors, the molecular mechanisms involved in Yunwu Tribute Tea under cold stress were investigated. Results: In this study, Illumina HiSeq technology was applied to investigate the cold-tolerance mechanism. For this purpose, cDNA libraries were obtained from two groups of samples, namely the cold-treated group (DW) and the control group (CK). A total of 185,973 unigenes were produced from 511,987 assembled transcripts; among these, 16,020 differentially expressed genes (DEGs) (corrected p-value < 0.01, |log2(fold change)| >3), including 9606 up-regulated and 6414 down-regulated genes, were obtained. Moreover, the antioxidant enzyme system, plant hormone signal transduction, proline and tyrosine metabolism pathways, and transcription factors were analyzed; based on these results, a series of candidate genes related to cold stress were screened out and discussed. The physiological indexes related to the low-temperature response were tested, along with five DEGs which were validated by quantitative real-time PCR. Conclusions: Differential gene expression analysis has confirmed that substantial cold-responsive genes are related to the antioxidant enzyme system, plant hormone signal transduction, proline metabolism pathway, tyrosine metabolism pathway, and transcription factors.

Flexible SERS Biosensor Based on Core-Shell Nanotags for Sensitive and Multiple Detection of T1DM Biomarkers.

Sensitive and multiple detection of the biomarkers of type 1 diabetes mellitus (T1DM) is vital to the early diagnosis and clinical treatment of T1DM. Herein, we developed a SERS-based biosensor using polyvinylidene fluoride (PVDF) membranes as a flexible support for the detection of glutamic acid decarboxylase antibodies (GADA) and insulin autoantibodies (IAA). Two kinds of silver-gold core-shell nanotags embedded with Raman probes and attached with GADA or IAA antibodies were synthesized to capture the targets, enabling highly sensitive and highly selective detection of GADA and IAA. The embedded Raman probes sandwiched between silver and gold layers guaranteed spectral stability and reliability. Moreover, the utilization of two Raman probes enables simultaneous and multiplexing detection of both GADA and IAA, improving the detection accuracy for T1DM. The proposed SERS-based method has been proven feasible for clinical sample detection, demonstrating its great potential in sensitive, reliable, and rapid diagnosis of T1DM.

Toll-like Receptor 2-Melatonin Feedback Loop Regulates the Activation of Spinal NLRP3 Inflammasome in Morphine-Tolerant Rats.

BACKGROUND AND PURPOSE: Morphine is amongst the most effective analgesics available for the management of severe pain. However, prolonged morphine treatment leads to analgesic tolerance which limits its clinical usage. Previous studies have demonstrated that melatonin ameliorates morphine tolerance by reducing neuroinflammation. However, little is known about the relationship between Toll like receptor 2 (TLR2) and neuroinflammation in morphine tolerance. The aim of this study was to explore the role of TLR2 in morphine tolerance and its connections with melatonin and Nod-like receptor protein 3 (NLRP3) inflammasome. METHODS: Sprague-Dawley rats were treated with morphine for 7 days and tail-flick latency test was performed to identify the induction of analgesic tolerance. The roles of TLR2 in microglia activation and morphine tolerance were assessed pharmacologically, and the possible interactions between melatonin, TLR2 and NLRP3 inflammasome were investigated. KEY RESULTS: Morphine tolerance was accompanied by increased TLR2 expression and NLRP3 inflammasome activation in spinal cord. whereas melatonin level was down-regulated. Chronic melatonin administration resulted in a reduced TLR2 expression and NLRP3 inflammasome activation. Moreover, the analgesic effect of morphine was partially restored. Inhibition of TLR2 suppressed the microglia and NLRP3 inflammasome activation, as well as restored the spinal melatonin level while attenuated the development of morphine tolerance. Furthermore, the inhibition of microglia activation ameliorated morphine tolerance via inhibiting TLR2-NLRP3 inflammasome signaling in spinal cord. CONCLUSION: In this study, we directly demonstrate a TLR2-melatonin negative feedback loop regulating microglia and NLRP3 inflammasome activation during the development of morphine tolerance.

Electrocatalytic activity of MoSi2N4monolayers decorated with single transition metal atoms: a computational study.

Two-dimensional (2D) MoSi2N4is a newly created material that has superstability and ultrahigh carrier mobility. Besides, the hydrogen evolution reaction activity was proved excellent by doping transition metal (TM) atoms and introducing N vacancies. But, the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) of 2D MoSi2N4is unclear even. We have explored the electrocatalytic properties (OER/ORR) of MoSi2N4by introducing Si vacancies and attaching various TM atoms. The structure and optoelectronic characteristics of MoSi2N4have been researched in detail using density functional theory calculations. By analyzing the density of states, the free energy change diagram and contour maps of TM@VSi-MoSiN, the results show that Co@VSi-MoSiN has the lowest OER overpotential (0.53 V) among all samples. Additionally, the d-band center is used to explain the electrocatalytic origin of the OER and ORR of TM@VSi-MoSiN. Our discoveries expand the 2D TM@VSi-MoSiN applicability in the realm of catalysis.

Topological alterations in white matter structural networks in fibromyalgia.

PURPOSE: Neuroimaging studies employing analyses dependent on regional assumptions and specific neuronal circuits could miss characteristics of whole-brain structural connectivity critical to the pathophysiology of fibromyalgia (FM). This study applied the whole-brain graph-theoretical approach to identify whole-brain structural connectivity disturbances in FM. METHODS: This cross-sectional study used probabilistic diffusion tractography and graph theory analysis to evaluate the topological organization of brain white matter networks in 20 patients with FM and 20 healthy controls (HCs). The relationship between brain network metrics and clinical variables was evaluated. RESULTS: Compared with HCs, FM patients had lower clustering coefficient, local efficiency, hierarchy, synchronization, and higher normalized characteristic path length. Regionally, patients demonstrated a significant reduction in nodal efficiency and centrality; these regions were mainly located in the prefrontal, temporal cortex, and basal ganglia. The network-based statistical analysis (NBS) identified decreased structural connectivity in a subnetwork of prefrontal cortex, basal ganglia, and thalamus in FM. There was no correlation between network metrics and clinical variables (false discovery rate corrected). CONCLUSIONS: The current research demonstrated disrupted topological architecture of white matter networks in FM. Our results suggested compromised neural integration and segregation and reduced structural connectivity in FM.

Prevalence estimates of the insulin resistance and associated prevalence of heart failure among United Status adults.

BACKGROUND: The triglyceride glucose (TyG) index, a metric for estimating insulin resistance (IR), is linked with cardiovascular disease (CVD) morbidity and mortality among the population regardless of diabetic status. However, IR prevalence and the association between the TyG index and heart failure (HF) in Americans is unclear. METHODS: The Nation Health and Nutrition Examination Survey (NHANES) (2009-2018) dataset was used. IR was defined by homeostatic model assessment of insulin resistance (HOMA-IR) > 2.0 and 1.5. The TyG index was calculated as Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. A weighted logistic regression was applied to evaluate the association between the TyG index and the prevalence of HF. RESULTS: This study comprised 12,388 people, including 322 (2.6%) individuals with HF. The average prevalence of IR was found to be 13.9% and 22.7% for cutoff values greater than 2.0 and 1.5, respectively. HOMA-IR and the TyG index showed a moderate correlation (r = 0.30). There is a significant positive association between the TyG index and HF prevalence (per 1-unit increment; adjusted OR [aOR]: 1.34; 95% confidence interval [CI]: 1.02-1.76). Patients with higher TyG values were associated with a prevalence of HF (OR:1.41; 95% CI: 1.01,1.95) (quartiles 4 vs 1-3). The TyG index is associated with a higher prevalence of dyslipidemia, coronary heart disease, and hypertension but not a stroke (cerebrovascular disease). CONCLUSIONS: Our results show that IR does not considerably increase from 2008 to 2018 in American adults. A moderate correlation is noted between HOMA-IR and the TyG index. TyG index is associated with the prevalence of HF, as were other cardiovascular diseases.

Mitochondrial Sirtuins in Parkinson's Disease.

Parkinson's disease (PD), the main risk factor for which is age, is one of the most common neurodegenerative diseases and imposes a substantial burden on affected individuals and the economy. While the aetiology of PD is still largely unclear, substantial evidence indicates that mitochondrial dysfunction, aggregation of α-synuclein (α-syn), oxidative stress, inflammation, and autophagy play major roles in the pathogenesis of PD. Sirtuins are NAD+-dependent protein deacetylases, includeing seven members, i.e., SIRT1-SIRT7. Among these sirtuins, SIRT3, SIRT4 and SIRT5 are located in mitochondria and are called mitochondrial sirtuins. Mitochondrial sirtuins regulate the activity and biological function of mitochondrial proteins through posttranslational modification of substrate proteins. Increasing evidence shows that mitochondrial sirtuins play an important role in degenerative diseases, including PD. Mitochondrial sirtuins exert a beneficial neuroprotective effect in various models of PD. This paper summarizes a large number of studies and discusses the latest research progress on the role of mitochondrial sirtuins in PD, focusing especially on the regulation of the mitochondrial respiratory chain (MRC), oxidative stress, the inflammatory response and autophagy, to provide new insight into the pathogenesis of PD and new targets for the diagnosis and treatment of the disease.

The advanced treatment of textile printing and dyeing wastewater by hydrodynamic cavitation and ozone: Degradation, mechanism, and transformation of dissolved organic matter.

The emission standards for textile printing and dyeing wastewater are stricter due to serious environmental issues. A novel technology, hydrodynamic cavitation combined with ozone (HC + O3), has attracted wide attention in wastewater advanced treatment, whereas the contaminants removal mechanism and transformation of dissolved organic matter (DOM) were rarely reported. This study investigated the removal efficiency and mechanism of HC + O3. The maximum removal rates of UV254, chrominance, CODCr, and TOC were 64.99%, 91.90%, 32.30%, and 36.67% in 60 min, respectively, at the inlet pressure of 0.15 MPa and O3 dosage of 6.25 mmol/L. The synergetic coefficient of HC + O3 was 2.77. The removal of contaminants was the synergy of 1O2, ·OH and ·O2-, and high molecular weight and strong aromaticity organic matters were degraded effectively. The main components in DOM were tryptophan-like and tyrosine-like, which were effectively removed after HC + O3. Meanwhile, most DOM had decreased to low apparent relative molecular weight (LARMW) compounds. Additionally, the HC + O3 effluent can reach the emission standard in 60 min for 8.07 USD/m3. It can be concluded that HC + O3 is an effective technology for the advanced treatment of industrial wastewater. This study will provide suggestions for the engineering application of HC + O3.

Degradation of acid red 73 wastewater by hydrodynamic cavitation combined with ozone and its mechanism.

Many azo dyes are consumed in the textile and dyeing industry, which makes the wastewater recalcitrant and toxic to the aquatic environment. Dye degradation by the combination of hydrodynamic cavitation and ozone (HC + O3) has caused extensive interest. The degradation mechanism of the hybrid system needs further investigation. This study investigated the degradation of acid red 73 (AR73) by HC + O3. Meanwhile, the degradation pathways and mechanisms were present. The optimal operation parameters were: inlet pressure of 0.15 MPa, O3 dosage of 45 mg/min, initial dye concentration of 10 mg/L, and initial pH at 7.5. As a result, the decolorization rate, removal of UV254 and NH3-N were 100%, 71.28%, and 87.36% in 30 min, respectively. Humic acid and most of the co-existing anions (HCO3-, SO42-, Cl-, PO43-, NO3-) played a positive role in the degradation of AR73, while NO2- restrained. The reactive species of singlet oxygen (1O2), hydroxyl radicals (·OH) and super oxygen radicals (·O2-) showed synergism in the hybrid system, and the decolorization was attributed to the fracture of azo bonds by 1O2. Meanwhile, aromatic amines were generated and further degraded into small molecule compounds. The research certificated that the HC + O3 can be an effective technology for azo dye degradation.

Cortical Abnormalities in Patients with Fibromyalgia: A Pilot Study of Surface-Based Morphometry Analysis.

BACKGROUND: Although neuroanatomical studies correlated to fibromyalgia (FM) are gaining increasing interest, the cortical morphology of patients are largely unknown, and data on cortical gyrification are scarce. The objective of the present study is to assess the cortical morphology in female patients with FM compared with healthy controls (HC) using surface-based morphometry (SBM) analysis of magnetic resonance imaging (MRI). METHODS: T1-MRIs and clinical data of 20 FM patients and 20 HC subjects were obtained from a public data set via OpenNeuro. For each subject, surface parameters including cortical thickness, local gyrification index (LGI), sulcal depth, and fractal dimensionality were estimated using SBM analysis. These data were compared between two groups controlled by age. The correlations between regional SBM parameters showing group differences and clinical profiles were analyzed. RESULTS: Compared with HC subjects, FM patients showed reduced cortical thickness in right primary motor cortex, lower LGI in right rostral anterior cingulate and higher sulcal depth in right precuneus (P < 0.05 cluster level family- wise error corrected). In FM patients, correlation analysis showed that the cortical thickness in right primary motor cortex were inversely correlated with scores of pain catastrophizing scale (r = -0.498, P = 0.030) and pain self-perception scale (r = -0.527, P = 0.020), and disease duration (r = -0.488, P = 0.034), respectively. CONCLUSIONS: Our findings provide evidence of neuroanatomical aberrations in FM patients, which may provide insight into the neuropathology of FM.

Prevalence of and factors associated with astigmatism in preschool children in Wuxi City, China.

PURPOSE: To investigate the status of astigmatism in preschool children in Wuxi City, and explore the risk factors related to astigmatism. The risk factors related to astigmatism development as predictors can help us identify preschool children who need vision screening at an early stage to ensure good visual quality. METHODS: The cross-sectional study was conducted in 10 kindergartens randomly selected in five districts of Wuxi City in November 2018. All preschool children were measured by objective refractometry under non-cycloplegic refraction. The basic information of preschool children was collected. The relevant factors of astigmatism in the questionnaire were completed by parents. Spss 26. 0 software was used for univariate and multivariate correlation analysis. RESULTS: A total of 889 preschool children participated in the study, 864 were finally included in the study. The prevalence of astigmatism was 36.0%. The risk of astigmatism in premature children was higher than that in non-premature children (adjusted odds ratio = 1.841). The prevalence of astigmatism with parents' astigmatism history was higher, compared with preschool children without parents' astigmatism history (adjusted odds ratio = 2.037). When maternal age at childbirth was older (≥ 35 years old), the risk of astigmatism increased in preschool children (adjusted odds ratio = 2.181). Compared with bottle feeding, the risk of astigmatism for mixed feeding and breastfeeding reduced in preschool children. Compared with preschool children exposed to electronic screen for less than 2 h every day, preschool children exposed to electronic screen for more than 2 h had an increased risk of astigmatism (P = 0.004). CONCLUSION: The prevalence of astigmatism among preschool children in Wuxi City was high. Some risk factors such as premature birth, parents' astigmatism history, maternal age at childbirth, feeding pattern, and electronic screen exposure time were closely related to the occurrence of astigmatism among preschool children. For preschool children with significant risk factors, their eyesight should be checked regularly to ensure their visual quality.

Netizens' risk perception in new coronary pneumonia public health events: an analysis of spatiotemporal distribution and influencing factors.

BACKGROUND: Internet search volume reflects the level of Internet users' risk perception during public health events. The Internet search volume index model, an algorithm of concentration of Internet users, and statistical analysis of popular topics on Weibo are used to analyze the effects of time, space, and space-time interaction. We conducted in-depth research on the characteristics of the spatial and temporal distribution of Internet users' risk perceptions of public health events and the associated influential factors. METHODS: We analyzed the spatiotemporal distribution characteristics of Internet users' risk perception after the Wuhan "city closing" order during the coronavirus disease 2019 (COVID-19) pandemic. We established five linear regression models according to different time periods and analyzed factors influencing Internet users' risk perception by employing a Poisson and spatial distribution and topic modeling analysis. RESULTS: Economy, education, health, and the degree of information disclosure affect Internet users' risk perception significantly. Internet users' risk perception conforms to the exponential distribution law in time and has periodic characteristics and stability trends. Additionally, Internet users' average arrival rate dropped from week 1 to week 8 after the "city closing." Internet users' risk perception has a uniform distribution in space, economic and social development level distribution consistency, spatial agglomeration, and other characteristics. The results of the time-space interaction show that after 8 weeks of COVID-19, Internet search hot topics have become more stable, and Internet users' information demand structure has become more rational. CONCLUSIONS: The Internet search cycle of the COVID-19 event is synchronized with the evolution cycle of the epidemic. The physical risk of Internet users is at the top of the risk structure, focusing on the strong concern about the government's ability to control COVID-19 and its future trend. The government should strengthen network management; seize the risk control focus of key time nodes, regional locations, and information content of online communication; actively adjust the information content supply; effectively control the rebound of Internet users' risk perception; establish a data-driven, risk-aware intelligence system for internet users; and guide people to actively face and overcome the potential risks and threats of COVID-19.

Impact of geometric distortion on dose deviation for photon and proton treatment plans.

We investigated the dose deviation related to geometric distortion and dose gradient on magnetic resonance-only treatment planning for intensity-modulated radiation therapy and proton therapy. The residual geometric distortion of two different magnetic resonance imaging (MRI) sequences (A) and (B) was applied in the computed tomography image and the structure set of each patient through a polynomial MRI geometric distortion model to simulate MRI-based treatment planning. A 3D histogram was generated to specify the relationship of dose deviation to geometric distortion and dose gradient. When the dose gradient (Gd ) approached zero, the maximum dose deviation reached 1.64% and 2.71% for photon plans of sequences A and B, respectively. For proton plans, the maximum dose deviation reached 3.15% and 4.89% for sequences A and B, respectively. When the geometric distortion (d) was close to zero, the maximum dose deviation was less than 0.8% for photon and proton plans of both sequences. Under extreme conditions (d = 2 mm and Gd  = 4.5%/mm), the median value of dose deviation reached 3% and 3.49% for photon and proton plans, respectively for sequence A, and 2.93% and 4.55% for photon and proton plans, respectively, for sequence B. We demonstrate that the dose deviation is specific to MRI hardware parameters. Compared to the photon plan, the proton plan is more sensitive to the changes in geometric distortion. For typical clinical MRI geometric distortion (d ≤2 mm), the median dose deviation is expected to be within 3% and 5% for photon and proton plans, respectively.

rAj-Tspin, a novel recombinant peptide from Apostichopus japonicus, suppresses the proliferation, migration, and invasion of BEL-7402 cells via a mechanism associated with the ITGB1-FAK-AKT pathway.

Purpose Our study aimed to investigate the antitumor effects of rAj-Tspin on BEL-7402 hepatocellular carcinoma cells and to explore the underlying mechanism. Method For the in vivo experiment, BEL-7402 cells were inoculated subcutaneously into the axilla of nude mice to generate a BEL-7402 cell-bearing model, and model mice were then treated with different doses of rAj-Tspin. A CCK-8 assay was used to evaluate the in vitro viability of BEL-7402 and LO2 cells after treatment with different concentrations of rAj-Tspin. The effects of rAj-Tspin on BEL-7402 cell apoptosis, migration and invasion were evaluated by AO/EB and Hoechst fluorescent staining and by scratch and Transwell assays, and the tumor-suppressive mechanism of rAj-Tspin was explored by Western blotting. Results rAj-Tspin suppressed the proliferation of BEL-7402 cells with an IC50 of 0.89 µM. The results of both microscopic analysis and Western blotting suggested that rAj-Tspin induced the apoptosis of BEL-7402 cells through a mitochondria-dependent pathway. Furthermore, rAj-Tspin disrupted EMT; this disruption ultimately caused BEL-7402 cells to lose their shape and decreased their migration and invasion. Moreover, rAj-Tspin might inhibit the proliferation and metastasis of BEL-7402 cells through the ITGB1-FAK-AKT pathway. Conclusion rAj-Tspin exerts an antitumor effect through the ITGB1-FAK-Akt signaling pathway and exhibits low toxicity at an effective dose.