Corrigendum: Material basis and molecular mechanisms of Chaihuang Qingyi Huoxue Granule in the treatment of acute pancreatitis based on network pharmacology and molecular docking-based strategy.

[This corrects the article DOI: 10.3389/fimmu.2024.1353695.].

Material basis and molecular mechanisms of Chaihuang Qingyi Huoxue Granule in the treatment of acute pancreatitis based on network pharmacology and molecular docking-based strategy.

Objectives: This study aimed to analyze active compounds and signaling pathways of CH applying network pharmacology methods, and to additionally verify the molecular mechanism of CH in treating AP. Materials and methods: Network pharmacology and molecular docking were firstly used to identify the active components of CH and its potential targets in the treatment of AP. The pancreaticobiliary duct was retrogradely injected with sodium taurocholate (3.5%) to create an acute pancreatitis (AP) model in rats. Histological examination, enzyme-linked immunosorbent assay, Western blot and TUNEL staining were used to determine the pathway and mechanism of action of CH in AP. Results: Network pharmacological analysis identified 168 active compounds and 276 target proteins. In addition, there were 2060 targets associated with AP, and CH had 177 targets in common with AP. These shared targets, including STAT3, IL6, MYC, CDKN1A, AKT1, MAPK1, MAPK3, MAPK14, HSP90AA1, HIF1A, ESR1, TP53, FOS, and RELA, were recognized as core targets. Furthermore, we filtered out 5252 entries from the Gene Ontology(GO) and 186 signaling pathways from the Kyoto Encyclopedia of Genes and Genomes(KEGG). Enrichment and network analyses of protein-protein interactions predicted that CH significantly affected the PI3K/AKT signaling pathway, which played a critical role in programmed cell death. The core components and key targets showed strong binding activity based on molecular docking results. Subsequently, experimental validation demonstrated that CH inhibited the phosphorylation of PI3K and AKT in pancreatic tissues, promoted the apoptosis of pancreatic acinar cells, and further alleviated inflammation and histopathological damage to the pancreas in AP rats. Conclusion: Apoptosis of pancreatic acinar cells can be enhanced and the inflammatory response can be reduced through the modulation of the PI3K/AKT signaling pathway, resulting in the amelioration of pancreatic disease.

Risk Assessment of Heavy Metals in Soils from Four Different Industrial Plants in a Medium-Sized City in North China.

Laboratory experiments were carried out to analyze 39 soil samples collected from four industrial areas in Xuzhou City using inductively coupled plasma mass spectrometry and atomic fluorescence spectrometry. The descriptive statistics of heavy metals (HMs) in the soil profiles showed that the HM content at three depths was highly variable, and most coefficients of variation (CVs) showed moderate variability. The enrichment of Cd at all depths exceeded the risk screening value, and Cd pollution occurred in four plants. The enrichment of the other HMs at three depths was mainly concentrated in the pharmaceutical plant A and chemical plant C. It was found that the different HMs had different vertical distribution characteristics. For the different industrial plants, the raw materials and products not only made the spatial distribution characteristics of the HMs different, but also caused the HM types and contents to differ. The average single pollution indices of Cd in plant A, iron-steel plant B, and plant C indicated a slight pollution level. The other seven HMs in A, B, and C and all HMs in chemical plant D belonged to the safe category. The mean values of the Nemerow pollution index in the four industrial plants belonged to the warning category. The analysis showed that none of the HMs posed potential noncarcinogenic health risks, and only the carcinogenic health risks of Cr in plants A and C were unacceptable. The carcinogenic effect of Cr through the inhalation intake of resuspended soil particulates and that of Cd, Ni, and As via direct oral ingestion were the main exposure pathways.

Market survey on the traditional medicine of the Lijiang area in Yunnan Province, China.

BACKGROUND: Traditional markets are important trading places for medicinal plants, and researchers performing market surveys often engage in ethnobotanical research to record the herbal plants used locally and any related traditional knowledge. However, information on market-traded medicinal plants from traditional markets in the Lijiang area of Yunnan is not well documented. This research is an ethnobotanical survey focusing on medicinal plants traded in the traditional markets of the Lijiang area and contributes to the understanding of medicinal plants and related information used by the Naxi people. METHODS: Ethnobotanical surveys were performed for two years (2019-2020). Three traditional markets in the Lijiang area were investigated. The methods we used included literature research, participatory surveys and group discussions. The collected voucher specimens were identified using the botanical taxonomy method and were deposited in the herbarium. The data were analysed through the informant consensus factor and use frequency (UF). These medicinal plants were compared with the Information System of Chinese Rare and Endangered Plants from the Chinese Academy of Sciences. Those results were in turn compared with the Dongba Sutras and Yulong Ben Cao. RESULTS: A total of 277 species from 97 families were recorded, with Asteraceae providing the maximum numbers of medicinal plants. Among them, 248 species (89%) were wild plants and 266 species (92.39%) were from the local area. Root (40.43%) was the most common medicinal part. A total of 267 species (96.04%) had a UF value above 0.5. Eighty-three investigated human ailments were grouped into 16 categories. Diseases of the digestive system (166 mentions) were most frequently mentioned in this study. There were 19 species of nationally protected plants in China, including 2 species of first-level nationally protected plants and 17 species of second-level nationally protected plants. A total of 31 species of these medicinal plants can be found in the Dongba Sutra or Yulong Ben Cao. CONCLUSION: We surveyed the herbal medicine in the markets covering the Lijiang area, analysing and revealing the resource composition and current market situations. The medicinal plants used by the Naxi people are diverse and are used to treat a wide spectrum of body disorders. There are many wild medicinal plants, and to ensure sustainable development, their natural protection should be strengthened. Knowledge of the medicinal plants recorded in Naxi medical classics has ethnobotanical value and should be further developed.

Tetrandrine ameliorated Alzheimer's disease through suppressing microglial inflammatory activation and neurotoxicity in the 5XFAD mouse.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder prevalent in the aged population. Tetrandrine is a natural metabolite isolated from herbal medicine Stephania tetrandra with various activities. PURPOSE: In this study, we investigated the therapeutic role of tetrandrine in 5XFAD mouse, a transgenic model of AD. METHODS: 5XFAD mice were intraperitoneally injected with saline or different doses of tetrandrine (10, 20, and 40 mg/kg per 2 days) from the age of 5 months to 7 months followed by the determination of cognitive ability, amyloid plaque load, cell apoptosis, and inflammation in the brain. In vitro, the protective roles of tetrandrine against inflammatory activation of microglia and the resulting neurotoxicity were studied in BV2 cells and differentiated PC12 cells, respectively. RESULTS: Morris water maze test showed that two months of tetrandrine treatment dose-dependently improved the cognitive ability of 5XFAD mice. Immunostaining against Aß 1-42 demonstrated reduced amyloid plaque deposition in the brain of tetrandrine-treated 5XFAD mice. TUNEL assay revealed decreased cell apoptosis in the hippocampus after tetrandrine treatment. Further, RT-PCR showed that the ectopic transcription of inflammation-associated genes including TNFα, IL-1ß, IL-6, COX-2, iNOS, and p65 was reversed in 5XFAD mice treated with tetrandrine. In vitro, Aß 1-42 stimulated the secretion of inflammatory cytokines TNFα and IL-1ß in microglial BV2 cells as determined by ELISA, which was suppressed by tetrandrine pre-treatment. Tetrandrine pre-treatment also inhibited the expression of TLR4, p65, iNOS, and COX-2 in BV2 cells induced by Aß 1-42. Most importantly, treatment of PC12-derived neuron-like cells with conditional medium from Aß 1-42-stimulated BV2 cells remarkably impaired cell viability and promoted cell apoptosis, which was attenuated by the conditional medium from BV2 cells with tetrandrine pre-treatment. CONCLUSION: Collectively, findings in this study demonstrated that tetrandrine ameliorates AD by suppressing microglia-mediated inflammation and neurotoxicity.

Ethnobiological study on traditional medicinal plants and fungi recorded in the Naxi Dongba sutras.

BACKGROUND: The Naxi people, living in Southwest China, have a long history and rich characteristic culture. Their ancestors recorded their life practices by ancient hieroglyphs and gradually formed the Dongba Sutras, which, among other knowledge, included the traditional knowledge of Naxi medicine. In the past, most studies on the Dongba Sutras focused on the humanistic culture of Naxi people, whereas studies have rarely focused on Naxi herbal medicinal plants and fungi described in the Dongba Sutras. Studying this aspect is helpful for exploring the traditional culture of Naxi people from the perspective of traditional medicine. METHODS: From February to September 2019, we screened the medicinal plants and fungi from the Dongba Sutras with the help of Dongba. Then, we carried out field investigations and collected voucher specimens of traditional medicinal plants and fungi with the help of 104 Naxi folk healers. The specimens were identified and stored in the Herbarium of Yunnan Branch, Institute of Medicinal Plants, Chinese Academy of Medical Sciences (IMDY). Through semi-structured interviews, we obtained ethnobotanical information of medicinal plants and fungi. The obtained quantitative data were analyzed using the informant consensus factor (ICF) method and the number of citations. RESULTS: A total of 85 species of medicinal plants and fungi belonging to 51 families and 71 genera were recorded in the Dongba Sutras. Among them, 25 species were endemic to China, and eight species were only distributed in Naxi distribution areas. These medicinal plants and fungi were mainly obtained from the wild, and 22 species could be used as food. The most frequent method of taking medicinal materials was oral-taking after decoction, followed by topical and sometimes buccal. The methods of processing these medicinal materials included water decoction, warm water flushing, and drinking after soaking. The medicinal plants and fungi in the Dongba Sutras are used to treat 96 conditions classified into 13 disease groups according to the International Classification of Primary Care second edition. Further analysis indicated that most of these species were utilized for treating diseases from the digestive (D) group, followed by those from the respiratory (R) group, musculoskeletal (L) group, general, and unspecified (A) group. Moreover, the Naxi people have a high consensus on the treatments of diseases from these four pathological groups. CONCLUSIONS: The Naxi traditional medicine is characterized by simple materials, easy operation, and distinctive national characteristics. The ancient Naxi people recorded their highly developed medical culture in the Dongba Sutras. Natural plant resources found around them were their primary choices for both medicine and diet therapy. The ecological ethics of Naxi people have positive significance for the conservation of wild resources in their area.

[Usage of ethnomedicine on COVID-19 in China].

In December 2019, an outbreak of viral pneumonia began in Wuhan, Hubei Province, which caused the spread of infectious pneumonia to a certain extent in China and neighboring countries and regions, and triggered the epidemic crisis. The coronavirus disease 2019(COVID-19) is an acute respiratory infectious disease listed as a B infectious disease, which is managed according to standards for A infectious disease. Traditional Chinese medicine and integrated traditional Chinese and Western medicine have played an active role in the prevention and control of this epidemic. China's ethnomedicine has recognized infectious diseases since ancient times, and formed a medical system including theory, therapies, formula and herbal medicines for such diseases. Since the outbreak of the COVID-19 epidemic, Tibet Autonomous Region, Qinghai Province, Inner Mongolia Autonomous Region, Xinjiang Uygur Autonomous Region and Chuxiong Autonomous Prefecture of Yunnan, Qiandongnan Autonomous Prefecture of Guizhou have issued the prevention and control programs for COVID-19 using Tibetan, Mongolian, Uygur, Yi and Miao medicines. These programs reflect the wisdom of ethnomedicine in preventing and treating diseases, which have successfully extracted prescriptions and preventive measures for the outbreak of the epidemic from their own medical theories and traditional experiences. In this paper, we summarized and explained the prescriptions and medicinal materials of ethnomedicine in these programs, and the origin of Tibetan medicine prescriptions and Mongolian medicine prescriptions in ancient books were studied. These become the common characteristics of medical prevention and treatment programs for ethnomedicine to formulate therapeutic programs under the guidance of traditional medicine theories, recommend prescriptions and prevention and treatment methods with characteristics of ethnomedicine, and focus on the conve-nience and standardization. However, strengthening the support of science and technology and the popularization to the public, and improving the participation of ethnomedicine in national public health services and the capacity-building to deal with sudden and critical diseases are key contents in the development of ethnomedicine in the future.

Analysis of Chaotic Resonance in Izhikevich Neuron Model.

In stochastic resonance (SR), the presence of noise helps a nonlinear system amplify a weak (sub-threshold) signal. Chaotic resonance (CR) is a phenomenon similar to SR but without stochastic noise, which has been observed in neural systems. However, no study to date has investigated and compared the characteristics and performance of the signal responses of a spiking neural system in some chaotic states in CR. In this paper, we focus on the Izhikevich neuron model, which can reproduce major spike patterns that have been experimentally observed. We examine and classify the chaotic characteristics of this model by using Lyapunov exponents with a saltation matrix and Poincaré section methods in order to address the measurement challenge posed by the state-dependent jump in the resetting process. We found the existence of two distinctive states, a chaotic state involving primarily turbulent movement and an intermittent chaotic state. In order to assess the signal responses of CR in these classified states, we introduced an extended Izhikevich neuron model by considering weak periodic signals, and defined the cycle histogram of neuron spikes as well as the corresponding mutual correlation and information. Through computer simulations, we confirmed that both chaotic states in CR can sensitively respond to weak signals. Moreover, we found that the intermittent chaotic state exhibited a prompter response than the chaotic state with primarily turbulent movement.

Modeling fluctuations in default-mode brain network using a spiking neural network.

Recently, numerous attempts have been made to understand the dynamic behavior of complex brain systems using neural network models. The fluctuations in blood-oxygen-level-dependent (BOLD) brain signals at less than 0.1 Hz have been observed by functional magnetic resonance imaging (fMRI) for subjects in a resting state. This phenomenon is referred to as a "default-mode brain network." In this study, we model the default-mode brain network by functionally connecting neural communities composed of spiking neurons in a complex network. Through computational simulations of the model, including transmission delays and complex connectivity, the network dynamics of the neural system and its behavior are discussed. The results show that the power spectrum of the modeled fluctuations in the neuron firing patterns is consistent with the default-mode brain network's BOLD signals when transmission delays, a characteristic property of the brain, have finite values in a given range.

[Association of a high ankle brachial index with microvascular diseases of diabetes].

OBJECTIVE: To evaluate the association of a high ankle brachial index (ABI) with microvascular diseases of diabetes and to compare its strength with that of a low ABI. METHODS: ABI was obtained in 3293 patients undergoing the screening of chronic complications at the Diabetic Center, No. 306 Hospital of PLA during the period of September 2003 to June 2010. The patient profiles and laboratory data were reviewed. The associations of ABI with microvascular diseases of diabetes were determined by univariate and stepwise Logistic regression analysis. RESULTS: ABI was normal in 3060 patients. 44 had ABI measurements < 0.7, 139 had ABI measurements between 0.7 - 0.9, and 50 had ABI measurements > 1.3. Multivariate analysis indicated that the factors significantly associated with a high ABI were smoking (OR: 2.605; 95%CI: 1.458 - 4.656, P = 0.001) and systolic blood pressure (OR: 1.019; 95%CI: 1.005 - 1.033, P = 0.006). The conditions of nephropathy, neuropathy and retinopathy were not associated with a high ABI. CONCLUSION: Diabetics with a high ABI carry not more adverse atherosclerotic risk factors and suffer no more severe microvascular diabetic complications than those with a normal ABI.

Prevalence and risk factors of prolonged QTc interval among Chinese patients with type 2 diabetes.

OBJECTIVES: The aim of this study was to evaluate the prevalence and the risk factors of prolonged QTc interval among Chinese patients with type 2 diabetes. METHODS: The retrospective study included 3156 outpatients from the Diabetes Centre, the 306th Hospital of PLA, during the period from September 2003 to June 2010. QT interval was measured manually in the 12-lead conventional electrocardiogram. The QT interval corrected for heart rate (QTc) was calculated using Bazett's formula. Additional demographic and laboratory data were also collected. Potential risk factors of prolonged QTc interval were assessed using multivariable regression. RESULTS: The prevalence of prolonged QTc interval among Chinese patients with type 2 diabetes was 30.1%. Height (OR 0.156, 95% CI 0.032~0.748), waist circumference (OR 1.025, 95% CI 1.010~1.040), diastolic blood pressure (OR 1.016, 95% CI 1.007~1.026), postprandial glucose (OR 1.040, 95% CI 1.022~1.059), fasting insulin (OR 1.014, 95% CI 1.003~1.025), and presence of microalbuminuria (OR 1.266, 95% CI 1.033~1.551) were significant risk factors. CONCLUSIONS: The prevalence of prolonged QTc interval among Chinese patients with type 2 diabetes is high. Risk factors for prolongation of QTc interval were low height, high waist circumference, increasing diastolic blood pressure levels, high postprandial glucose levels, high fasting insulin levels, and presence of microalbuminuria.

Design and analysis of molecular relay channels: an information theoretic approach.

In this paper, we consider a molecular relay channel in which signal molecules are transmitted by a sender of communication, propagated, amplified, removed in the channel, and sensed by the receiver of communication that decodes the signal molecules. To understand and characterize the communication capacity of the molecular relay channel, we develop an information communication model that consists of the transmitter, channel, and receiver. Mutual information is used to quantify the amount of information that is transfered from the transmitter through the channel to the receiver. The method employed and results presented in this paper may help elucidate design principles of biological systems as well as help in the design and engineering of synthetic biological systems from the perspective of information theory.

Fullerol-fluorescein isothiocyanate phosphorescent labeling reagent for the determination of glucose and alkaline phosphatase.

The active -OH group in fullerol (F-ol) could react with the dissociated -COOH group in fluorescein isothiocyanate (FITC) to form F-ol-(FITC)(n), which could emit room temperature phosphorescence (RTP) signal of F-ol and FITC on acetate cellulose membrane (ACM), respectively. Their RTP signals were enhanced by N,N-dimethylaniline (DMA). The labeling reaction between the -NCS group of FITC in DMA-F-ol-(FITC)(n) and the -NH2 group in wheat germ agglutinin (WGA) produced DMA-F-ol-(FITC)(n)-WGA, which could further take affinity adsorption (AA) reaction with bioactive substances (BS), such as glucose and alkaline phosphatase (AP), to produce DMA-F-ol-(FITC)(n)-WGA-BS. Both of these two products could maintain the good RTP characteristics of F-ol and FITC. Based on the facts above, a new phosphorescent labeling reagent, DMA-F-ol-FITC, was developed, and a new affinity adsorption solid substrate room temperature phosphorimetry (AASSRTP) for the determination of BS was established. This method was applied to the determination of BS in human serum and the diagnosis of diseases, with the results agreeing very well with those of enzyme-linked immunosorbent assay (ELISA). The mechanism of DMA-F-ol-(FITC)(n) labeling of WGA and AASSRTP for the determination of BS is discussed.

Solid substrate-room temperature phosphorimetry for the determination of trace lead using p-nitro-phenyl-fluorone-multi-wall carbon nanotubes-Tween-80 micellae compound and diagnosis about human diseases.

The structures of multi-wall carbon nanotubes (MWNTs) were modified by H(2)SO(4)-HNO(3) and H(2)SO(4)-H(2)O(2), respectively. The corresponding products were water-soluble MWNTs-A and MWNTs-B. According to the experiment, it was found that MWNTs-B could emit stable solid substrate-room temperature phosphorescence (RTP) on the surface of paper with Ag(+) as perturber. Under the conditions of 70 degrees C and 15 min, MWNTs-B can react with Tween-80 and p-nitro-phenyl-fluorone (R) to form R-MWNTs-B-Tween-80 micellae compound, which could emit RTP of R and MWNTs-B on the surface of paper, respectively. Pb(2+) could cause the RTP of R and MWNTs-B enhanced sharply, respectively. DeltaI(p) is directly proportional to the content of Pb(2+). A new solid substrate-room temperature phosphorimetry (SS-RTP) for the determination of trace Pb(2+) has been established based on R-MWNTs-B-Tween-80 micellae compound containing double luminescent molecule. The detection limit of this method were 0.035 ag Pb(2+) spot(-1) (8.8 x 10(-17) g Pb(2+) ml(-1), MWNTs-B) and 0.028 ag Pb(2+) spot(-1) (7.1 x 10(-17) g Pb(2+) ml(-1), R). This method is of high sensitivity, good selectivity, high precision and accuracy. It could be applied to determine trace Pb(2+) in serum samples at wavelength of 453.7/623.0 nm (R) or 475.9/645.0 nm (MWNTs-B) with satisfactory results, showing that SS-RTP has flexibility and utility value. Simultaneously, this method can be used to diagnose human diseases. The reaction mechanism for the determination of trace Pb(2+) by SS-RTP based on R-MWNTs-B-Tween-80 micellae compound containing double luminescent molecule was also discussed.

Dynamics and energetics of single-step hole transport in DNA hairpins.

The dynamics of single-step hole transport processes have been investigated in a number of DNA conjugates possessing a stilbenedicarboxamide electron acceptor, a guanine primary donor, and several secondary donors. Rate constants for both forward and return hole transport between the primary and secondary donor are obtained from kinetic modeling of the nanosecond transient absorption decay profiles of the stilbene anion radical. The kinetic model requires that the hole be localized on either the primary or the secondary donor and not delocalized over both the primary and the secondary donor. Rate constants for hole transport are found to be dependent upon the identity of the secondary donor, the intervening bases, and the location of the secondary donor in the same strand as the primary donor or in the complementary strand. Rate constants for hole transport are much slower than those for the superexchange process used to inject the hole on the primary donor. This difference is attributed to the larger solvent reorganization energy for charge transport versus charge separation. The hole transport rate constants obtained in these experiments are consistent with experimental data for single-step hole transport from other transient absorption studies. Their relevance to long-distance hole migration over tens of base pairs remains to be determined. The forward and return hole transport rate constants provide equilibrium constants and free energies for hole transport equilibria. Secondary GG and GGG donors are found to form very shallow hole traps, whereas the nucleobase deazaguanine forms a relatively deep hole trap. This conclusion is in accord with selected strand cleavage data and thus appears to be representative of the behavior of holes in duplex DNA. Our results are discussed in the context of current theoretical models of hole transport in DNA.

A biomolecular computing method based on Rho family GTPases.

In this paper, we propose a new biomolecular computing method based on Rho family GTPases, and discuss the schemes of representation and operations of molecular computing by Rho family GTPases applied to solve large-scale 3-SAT problems. We also present the optimal condition for the regulation schemes dependent on the temperature, kinase activity, and types of cells. This work is important for potential implementation of biomolecular computers using Rho family GTPases in which an optimized controlling scheme can make the best use of the interactions of signaling pathways in a computing system made by the large-scale abundance of kinases and phosphatases in cells.

Donor-bridge-acceptor energetics determine the distance dependence of electron tunneling in DNA.

Electron transfer (ET) processes in DNA are of current interest because of their involvement in oxidative strand cleavage reactions and their relevance to the development of molecular electronics. Two mechanisms have been identified for ET in DNA, a single-step tunneling process and a multistep charge-hopping process. The dynamics of tunneling reactions depend on both the distance between the electron donor and acceptor and the nature of the molecular bridge separating the donor and acceptor. In the case of protein and alkane bridges, the distance dependence is not strongly dependent on the properties of the donor and acceptor. In contrast, we show here that the distance decay of DNA ET rates varies markedly with the energetics of the donor and acceptor relative to the bridge. Specifically, we find that an increase in the energy of the bridge states by 0.25 eV (1 eV = 1.602 x 10(-19) J) relative to the donor and acceptor energies for photochemical oxidation of nucleotides, without changing the reaction free energy, results in an increase in the characteristic exponential distance decay constant for the ET rates from 0.71 to 1.1 A(-1). These results show that, in the small tunneling energy gap regime of DNA ET, the distance dependence is not universal; it varies strongly with the tunneling energy gap. These DNA ET reactions fill a "missing link" or transition regime between the large barrier (rapidly decaying) tunneling regime and the (slowly decaying) hopping regime in the general theory of bridge-mediated ET processes.

Dynamics of inter- and intrastrand hole transport in DNA hairpins.

The dynamics of photoinduced electron transfer has been investigated in DNA hairpins possessing a stilbenedicarboxamide (Sa) electron acceptor, a guanine (G) primary donor, and two adjacent guanines (GG) as secondary donors. Hole transport from G to GG across a single A is more rapid than across AA or T by factors of 20 +/- 7 and 40 +/- 15, respectively. Intrastrand hole transport across a single A is more rapid than interstrand transport by a factor of 7 +/- 3.