Biosynthesis of Indigo Dyes and Their Application in Green Chemical and Visual Biosensing for Heavy Metals.

Fermentative production of natural colorants using microbial strains has emerged as a cost-effective and sustainable alternative to chemical synthesis. Visual pigments are used as signal outputs in colorimetric bacterial biosensors, a promising method for monitoring environmental pollutants. In this study, we engineered four self-sufficient indigo-forming enzymes, including HbpAv, bFMO, cFMO, and rFPMO, in a model bacterium E. coli. TrxA-bFMO was chosen for its strong ability to produce indigo under T7 lac and mer promoters' regulation. The choice of bacterial hosts, the supplementation of substrate l-tryptophan, and ventilation were crucial factors affecting indigo production. The indigo reporter validated the biosensors for Hg(II), Pb(II), As(III), and Cd(II). The biosensors reported Hg(II) as low as 14.1 nM, Pb(II) as low as 1.5 nM, and As(III) as low as 4.5 nM but increased to 25 µM for Cd(II). The detection ranges for Hg(II), Pb(II), As(III), and Cd(II) were quantified from 14.1 to 225 nM, 1.5 to 24.4 nM, 4.5 to 73.2 nM, and 25 to 200 µM, respectively. The sensitivity, responsive concentration range, and selectivity are comparable to ß-galactosidase and luciferase reporter enzymes. This study suggests that engineered enzymes for indigo production have great potential for green chemical synthesis. Additionally, heterologous biosynthesis of indigo production can lead to the development of novel, low-cost, and mini-equipment bacterial biosensors with zero background noise for visual monitoring of pollutant heavy metals.

Visual arsenic detection in environmental waters: Innovating with a naked-eye biosensor for universal application.

Arsenic contamination in environmental water sources poses a significant threat to human health, necessitating the development of sensitive and accessible detection methods. This study presents a multidimensional optimization of a bacterial biosensor for the susceptible and deoxyviolacein (DV)-based visual detection of arsenic. The research involved screening six different arsenic resistance (ars) operons and optimizing the genetic circuit to minimize background noise. Introducing an arsenic-specific transport channel enhanced the sensor's sensitivity to 1 nM with a quantitative range from 0.036 to 1.171 µM. The pigment-based biosensor offers a simple colorimetric approach for arsenic detection without complex instrumentation. The preferred biosensor demonstrated characteristics of anti-chelating agent interference, consistently quantified As(III) concentrations ranging from 0.036 to 1.171 µM covering the World Health Organization (WHO) drinking water limit. Innovatively, it effectively detects arsenic in seawater within a linear regression range of 0.071 to 1.125 µM. The biosensor's selectivity for arsenic was confirmed, with minimal cross-response to group 15 metals. Our naked-eye biosensor offers a novel approach for the rapid, on-site detection of arsenic in various water sources. Its simplicity, cost-effectiveness, and versatility make it a valuable tool for environmental monitoring and public health initiatives.

Activation of pregnane X receptor protects against cholestatic liver injury by inhibiting hepatocyte pyroptosis.

Our previous study shows that activation of pregnane X receptor (PXR) exerts hepatoprotection against lithocholic acid (LCA)-induced cholestatic liver injury. In this study we investigated whether PXR activation could inhibit hepatocyte pyroptosis, as well as the underlying mechanisms. Male mice were treated with mouse PXR agonist pregnenolone 16α-carbonitrile (PCN, 50 mg·kg-1·d-1, i.p.) for 7 days, and received LCA (125 mg/kg, i.p., bid) from D4, then sacrificed 12 h after the last LCA injection. We showed that LCA injection resulted in severe cholestatic liver injury characterized by significant increases in gallbladder size, hepatocellular necrosis, and neutrophil infiltration with a mortality rate of 68%; PCN treatment significantly inhibited hepatocyte pyroptosis during LCA-induced cholestatic liver injury, as evidenced by reduced serum lactic dehydrogenase (LDH) levels, TUNEL-positive cells and hepatocyte membrane damage. Furthermore, PXR activation suppressed both the NOD-like receptor protein 3 (NLRP3) inflammasome-induced canonical pyroptosis and the apoptosis protease activating factor-1 (APAF-1) pyroptosome-induced non-canonical pyroptosis. Inhibition of the nuclear factor kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways was also observed following PXR activation. Notably, dual luciferase reporter assay showed that PXR activation inhibited the transcriptional effects of NF-κB on NLRP3, as well as FOXO1 on APAF-1. Our results demonstrate that PXR activation protects against cholestatic liver injury by inhibiting the canonical pyroptosis through the NF-κB-NLRP3 axis and the non-canonical pyroptosis through the FOXO1-APAF-1 axis, providing new evidence for PXR as a prospective anti-cholestatic target.

Risk stratification and survival time of patients with gram-negative bacillary pneumonia in the intensive care unit.

Introduction: Pneumonia is a common infection in the intensive care unit (ICU), and gram-negative bacilli are the most common bacterial cause. The purpose of the study was to investigate the risk factors for 30-day mortality in patients with gram-negative bacillary pneumonia in the ICU, construct a predictive model, and stratify patients based on risk to assess their short-term survival. Methods: Patients admitted to the ICU with gram-negative bacillary pneumonia at Fujian Medical University Affiliated First Hospital between January 2018 and September 2020 were selected. Patients were divided into deceased and survivor groups based on whether death occurred within 30 days. Multifactorial logistic regression analysis was used to identify independent risk factors for 30-day mortality in these patients, and a predictive nomogram model was constructed based on these factors. Patients were categorized into low-, medium-, and high-risk groups according to the model's predicted probability, and Kaplan-Meier survival curves were plotted to assess short-term survival. Results: The study included 305 patients. Lactic acid (odds ratio [OR], 1.524, 95% CI: 1.057-2.197), tracheal intubation (OR: 4.202, 95% CI: 1.092-16.169), and acute kidney injury (OR:4.776, 95% CI: 1.632-13.978) were identified as independent risk factors for 30-day mortality. A nomogram prediction model was established based on these three factors. Internal validation of the model showed a Hosmer-Lemeshow test result of X2=5.770, P=0.834, and an area under the ROC curve of 0.791 (95% CI: 0.688-0.893). Bootstrap resampling of the original data 1000 times yielded a C-index of 0.791, and a decision curve analysis indicated a high net benefit when the threshold probability was between 15%-90%. The survival time for low-, medium-, and high-risk patients was 30 (30, 30), 30 (16.5, 30), and 17 (11, 27) days, respectively, which were significantly different. Conclusion: Lactic acid, tracheal intubation, and acute kidney injury were independent risk factors for 30-day mortality in patients in the ICU with gram-negative bacillary pneumonia. The predictive model constructed based on these factors showed good predictive performance and helped assess short-term survival, facilitating early intervention and treatment.

Synthetic bacteria designed using ars operons: a promising solution for arsenic biosensing and bioremediation.

The global concern over arsenic contamination in water due to its natural occurrence and human activities has led to the development of innovative solutions for its detection and remediation. Microbial metabolism and mobilization play crucial roles in the global cycle of arsenic. Many microbial arsenic-resistance systems, especially the ars operons, prevalent in bacterial plasmids and genomes, play vital roles in arsenic resistance and are utilized as templates for designing synthetic bacteria. This review novelty focuses on the use of these tailored bacteria, engineered with ars operons, for arsenic biosensing and bioremediation. We discuss the advantages and disadvantages of using synthetic bacteria in arsenic pollution treatment. We highlight the importance of genetic circuit design, reporter development, and chassis cell optimization to improve biosensors' performance. Bacterial arsenic resistances involving several processes, such as uptake, transformation, and methylation, engineered in customized bacteria have been summarized for arsenic bioaccumulation, detoxification, and biosorption. In this review, we present recent insights on the use of synthetic bacteria designed with ars operons for developing tailored bacteria for controlling arsenic pollution, offering a promising avenue for future research and application in environmental protection.

Detection of Cadmium in Human Biospecimens by a Cadmium-Selective Whole-Cell Biosensor Based on Deoxyviolacein.

Cadmium poses a severe health risk, impacting various bodily systems. Monitoring human exposure is vital. Urine and blood cadmium serve as critical biomarkers. However, current urine and blood cadmium detection methods are expensive and complex. Being cost-effective, user-friendly, and efficient, visual biosensing offers a promising complement to existing techniques. Therefore, we constructed a cadmium whole-cell biosensor using CadR10 and deoxyviolacein pigment in this study. We assessed the sensor for time-dose response, specific response to cadmium, sensitivity response to cadmium, and stability response to cadmium. The results showed that (1) the sensor had a preferred signal-to-noise ratio when the incubation time was 4 h; (2) the sensor showed excellent specificity for cadmium compared to the group 12 metals and lead; (3) the sensor was responsive to cadmium down to 1.53 nM under experimental conditions and had good linearity over a wide range from 1.53 nM to 100 µM with good linearity (R2 = 0.979); and (4) the sensor had good stability. Based on the excellent results of the performance tests, we developed a cost-effective, high-throughput method for detecting urinary and blood cadmium. Specifically, this was realized by adding the blood or urine samples into the culture system in a particular proportion. Then, the whole-cell biosensor was subjected to culture, n-butanol extraction, and microplate reading. The results showed that (1) at 20% urine addition ratio, the sensor had an excellent curvilinear relationship (R2 = 0.986) in the range of 3.05 nM to 100 µM, and the detection limit could reach 3.05 nM. (2) At a 10% blood addition ratio, the sensor had an excellent nonlinear relationship (R2 = 0.978) in the range of 0.097-50 µM, and the detection limit reached 0.195 µM. Overall, we developed a sensitive and wide-range method based on a whole-cell biosensor for the detection of cadmium in blood and urine, which has the advantages of being cost-effective, ease of operation, fast response, and low dependence on instrumentation and has the potential to be applied in the monitoring of cadmium exposure in humans as a complementary to the mainstream detection techniques.

Tailored bacteria tackling with environmental mercury: Inspired by natural mercuric detoxification operons.

Mercury (Hg) and its inorganic and organic compounds significantly threaten the ecosystem and human health. However, the natural and anthropogenic Hg environmental inputs exceed 5000 metric tons annually. Hg is usually discharged in elemental or ionic forms, accumulating in surface water and sediments where Hg-methylating microbes-mediated biotransformation occurs. Microbial genetic factors such as the mer operon play a significant role in the complex Hg biogeochemical cycle. Previous reviews summarize the fate of environmental Hg, its biogeochemistry, and the mechanism of bacterial Hg resistance. This review mainly focuses on the mer operon and its components in detecting, absorbing, bioaccumulating, and detoxifying environmental Hg. Four components of the mer operon, including the MerR regulator, divergent mer promoter, and detoxification factors MerA and MerB, are rare bio-parts for assembling synthetic bacteria, which tackle pollutant Hg. Bacteria are designed to integrate synthetic biology, protein engineering, and metabolic engineering. In summary, this review highlights that designed bacteria based on the mer operon can potentially sense and bioremediate pollutant Hg in a green and low-cost manner.

An updated review of the genus Rhododendron since 2010: Traditional uses, phytochemistry, and pharmacology.

Rhododendron, the largest genus of Ericaceae, consists of approximately 1000 species that are widely distributed in Europe, Asia, and North America but mainly exist in Asia. Rhododendron plants have not only good ornamental and economic value but also significant medicinal potential. In China, many Rhododendron plants are used as traditional Chinese medicine or ethnic medicine for the treatment of respiratory diseases, pain, bleeding and inflammation. Rhododendron is known for its abundant metabolites, especially diterpenoids. In the past 13 years, a total of 610 chemical constituents were reported from Rhododendron plants, including 222 diterpenoids, 122 triterpenoids, 103 meroterpenoids, 71 flavonoids and 92 other constituents (lignans, phenylpropanoids, phenolic acids, monoterpenoids, sesquiterpenoids, coumarins, steroids, fatty acids). Moreover, the bioactivities of various extracts and isolates, both in vitro and in vivo, were also investigated. Our review summarized the research progress of Rhododendron regarding traditional uses, phytochemistry and pharmacology in the past 13 years (2010 to December 2022), which will provide new insight for prompting further research on Rhododendron application and drug development.

High-throughput screening of human mercury exposure based on a low-cost naked eye-recognized biosensing platform.

Whole-cell biosensors could be helpful for in situ disease diagnosis. However, their use in analyzing biological samples has been hindered by unstable responses, low signal enhancement, and growth inhibition in complex media. Here, we offered a solution by building a visual whole-cell biosensor for urinary mercury determination. With deoxyviolacein as the preferred signal for the mercury biosensor for the first time, it enabled the quantitative detection of urinary mercury with a favorable linear range from 1.57 to 100 nM. The biosensor can accurately diagnose urine mercury levels exceeding the biological exposure index with 95.8% accuracy. Thus, our study provided a biosensing platform with great potential to serve as a stable, user-friendly, and high-throughput alternative for the daily monitoring or estimating of urinary mercury.

Designed bacteria based on natural pbr operons for detecting and detoxifying environmental lead: A mini-review.

Lead (Pb), a naturally occurring element, is redistributed in the environment mainly due to anthropogenic activities. Pb pollution is a crucial public health problem worldwide due to its adverse effects. Environmental bacteria have evolved various protective mechanisms against high levels of Pb. The pbr operon, first identified in Cupriavidus metallidurans CH34, encodes a unique Pb(II) resistance mechanism involving transport, efflux, sequestration, biomineralization, and precipitation. Similar pbr operons are gradually found in diverse bacterial strains. This review focuses on the pbr-encoded Pb(II) resistance system. It summarizes various whole-cell biosensors harboring artificially designed pbr operons for Pb(II) biomonitoring with fluorescent, luminescent, and colorimetric signal output. Optimization of genetic circuits, employment of pigment-based reporters, and screening of host cells are promising in improving the sensitivity, selectivity, and response range of whole-cell biosensors. Engineered bacteria displaying Pb(II) binding and sequestration proteins, including PbrR and its derivatives, PbrR2 and PbrD, for adsorption are involved. Although synthetic bacteria show great potential in determining and removing Pb at the nanomolar level for environmental protection and food safety, some challenges must be addressed to meet demanding application requirements.

Pb(II)-inducible proviolacein biosynthesis enables a dual-color biosensor toward environmental lead.

With the rapid development of synthetic biology, various whole-cell biosensors have been designed as valuable biological devices for the selective and sensitive detection of toxic heavy metals in environmental water. However, most proposed biosensors are based on fluorescent and bioluminescent signals invisible to the naked eye. The development of visible pigment-based biosensors can address this issue. The pbr operon from Klebsiella pneumoniae is selectively induced by bioavailable Pb(II). In the present study, the proviolacein biosynthetic gene cluster was transcriptionally fused to the pbr Pb(II) responsive element and introduced into Escherichia coli. The resultant biosensor responded to Pb(II) in a time- and dose-dependent manner. After a 5-h incubation with Pb(II), the brown pigment was produced, which could be extracted into n-butanol. Extra hydrogen peroxide treatment during n-butanol extract resulted in the generation of a stable green pigment. An increased brown signal was observed upon exposure to lead concentrations above 2.93 nM, and a linear regression was fitted from 2.93 to 3,000 nM. Extra oxidation significantly decreased the difference between parallel groups. The green signal responded to as low as 0.183 nM Pb(II), and a non-linear regression was fitted in a wide concentration range from 0.183 to 3,000 nM. The specific response toward Pb(II) was not interfered with by various metals except for Cd(II) and Hg(II). The PV-based biosensor was validated in monitoring bioaccessible Pb(II) spiked into environmental water. The complex matrices did not influence the regression relationship between spiked Pb(II) and the dual-color signals. Direct reading with the naked eye and colorimetric quantification enable the PV-based biosensor to be a dual-color and low-cost bioindicator for pollutant heavy metal.

A panel of visual bacterial biosensors for the rapid detection of genotoxic and oxidative damage: A proof of concept study.

The emergence of new compounds during the past decade requires a high-throughput screening method for toxicity assay. The stress-responsive whole-cell biosensor is a powerful tool to evaluate direct or indirect damages of biological macromolecules induced by toxic chemicals. In this proof-of-concept study, nine well-characterized stress-responsive promoters were first selected to assemble a set of blue indigoidine-based biosensors. The PuspA-based, PfabA-based, and PgrpE-based biosensors were eliminated due to their high background. A dose-dependent increase of visible blue signal was observed in PrecA-, PkatG-, and PuvrA-based biosensors, responsive to potent mutagens, including mitomycin and nalidixic acid, but not to genotoxic lead and cadmium. The PrecA, PkatG, and Ppgi gene promoters were further fused to a purple deoxyviolacein synthetic enzyme cluster. Although high basal production of deoxyviolacein is unavoidable, an enhanced visible purple signal in response to mitomycin and nalidixic acid was observed as dose-dependent, especially in PkatG-based biosensors. The study shows that a set of stress-responsive biosensors employing visible pigment as a reporter is pre-validating in detecting extensive DNA damage and intense oxidative stress. Unlike widely-used fluorescent and bioluminescent biosensors, the visual pigment-based biosensor can become a novel, low-cost, mini-equipment, and high-throughput colorimetric device for the toxicity assessment of chemicals. However, combining multiple improvements can further improve the biosensing performance in future studies.

Peroxisome proliferator-activated receptor α agonist induces mouse hepatomegaly through the spatial hepatocyte enlargement and proliferation.

Peroxisome proliferator-activated receptor alpha (PPARα) activation-induced hepatomegaly is accompanied by hepatocyte hypertrophy around the central vein (CV) area and hepatocyte proliferation around the portal vein (PV) area. However, the molecular mechanisms underlying this spatial change of hepatocytes remains unclear. In this study, we examined the characteristics and possible reasons for the zonation distinction of hypertrophy and proliferation during PPARα activation-induced mouse liver enlargement. Mice were injected with corn oil or a typical mouse PPARα agonist WY-14643 (100 mg·kg-1·d-1, i.p.) for 1, 2, 3, 5 or 10 days. At each time point, the mice were sacrificed after the final dose, and liver tissues and serum were harvested for analysis. We showed that PPARα activation induced zonal changes in hepatocyte hypertrophy and proliferation in the mice. In order to determine the zonal expression of proteins related to hepatocyte hypertrophy and proliferation in PPARα-induced liver enlargement, we performed digitonin liver perfusion to separately destroy the hepatocytes around the CV or PV areas, and found that PPARα activation-induced increase magnitude of its downstream targets such as cytochrome P450 (CYP) 4 A and acyl-coenzyme A oxidase 1 (ACOX1) levels around the CV area were higher compared with those around the PV area. Upregulation of proliferation-related proteins such as cell nuclear antigen (PCNA) and cyclin A1 (CCNA1) after WY-14643-induced PPARα activation mainly occurred around the PV area. This study reveals that the zonal expression of PPARα targets and proliferation-related proteins is responsible for the spatial change of hepatocyte hypertrophy and proliferation after PPARα activation. These findings provide a new insight into the understanding of PPARα activation-induced liver enlargement and regeneration.

Survey-Based Analysis of the Clinical Treatment Status of Irritable Bowel Syndrome in Korea.

BACKGROUND: The quality-of-life of patients with irritable bowel syndrome is low; incorrect diagnosis/treatment causes economic burden and inappropriate consumption of medical resources. This survey-based study aimed to analyze the current status of irritable bowel syndrome treatment to examine differences in doctors' perceptions of the disease, and treatment patterns. METHODS: From October 2019 to February 2020, the irritable bowel syndrome and Intestinal Function Research Study Group of the Korean Society of Neurogastroenterology and Motility conducted a survey on doctors working in primary, secondary, and tertiary healthcare institutions. The questionnaire included 37 items and was completed anonymously using the NAVER platform (a web-based platform), e-mails, and written forms. RESULTS: A total of 272 doctors responded; respondents reported using the Rome IV diagnostic criteria (amended in 2016) for diagnosing and treating irritable bowel syndrome. Several differences were noted between the primary, secondary, and tertiary physicians' groups. The rate of colonoscopy was high in tertiary healthcare institutions. During a colonoscopy, the necessity of random biopsy was higher among physicians who worked at tertiary institutions. 'The patient did not adhere to the diet' as a reason for ineffectiveness using low-fermentable oligo-, di-, and mono-saccharides, and polyols diet treatment was higher among physicians in primary/secondary institutions, and 'There are individual differences in terms of effectiveness' was higher among physicians in tertiary institutions. In irritable bowel syndrome constipation predominant subtype, the use of serotonin type 3 receptor antagonist (ramosetron) and probiotics was higher in primary/secondary institutions, while serotonin type 4 receptor agonist was used more in tertiary institutions. In irritable bowel syndrome diarrhea predominant subtype, the use of antispasmodics was higher in primary/secondary institutions, while the use of serotonin type 3 receptor antagonist (ramosetron) was higher in tertiary institutions. CONCLUSION: Notable differences were observed between physicians in primary/secondary and tertiary institiutions regarding the rate of colonoscopy, necessity of random biopsy, the reason for the ineffectiveness of low-fermentable oligo-, di-, and mono-saccharides, and polyols diet, and use of drug therapy in irritable bowel syndrome. In South Korea, irritable bowel syndrome is diagnosed and treated according to the Rome IV diagnostic criteria, revised in 2016.

Platelet-Rich Plasma Gel-Loaded Collagen/Chitosan Composite Film Accelerated Rat Sciatic Nerve Injury Repair.

Peripheral nerve injury (PNI) is a common clinical disease caused by severe limb trauma, congenital malformations, and tumor resection, which may lead to significant functional impairment and permanent disability. Nerve conduit as a method for treating peripheral nerve injury shows good application prospects. In this work, the COL/CS composite films with different mass ratios of 1:0, 1:1, and 1:3 were fabricated by combining physical doping. Physicochemical characterization results showed that the COL/CS composite films possessed good swelling properties, ideal mechanical properties, degradability and suitable hydrophilicity, which could meet the requirements of nerve tissue engineering. In vitro cell experiments showed that the loading of platelet-rich plasma (PRP) gel on the surface of COL/CS composite films could significantly improve the biocompatibility of films and promote the proliferation of Schwann cells. In addition, a rat model of sciatic nerve defect was constructed to evaluate the effect of COL/CS composite films on peripheral nerve repair and the results showed that COL/CS composite films loaded with PRP gel could promote nerve regeneration and functional recovery in rats with sciatic nerve injury, indicating that the combination of PRP gel with the COL/CS composite film would be a potential approach for the treatment of peripheral nerve injury.

New metal-free one-pot synthesis of α-2-deoxy-Ulosides by microwave-assisted double Michael Addition of ß-enamino ketones.

New metal-free one-pot synthesis of α-2-deoxy-ulosides in moderate to good yields by microwave-assisted double Michael addition of various O-nucleophiles to ß-enamino ketones in the presence of 12 N HCl. These glycosyl additions occurred with high α-stereoselectivity and were complete in 10-25 min in 51-93% yield. In addition, high α-stereoselectivity was also observed when S-nucleophiles were examined.

Long-term treatment with the mPXR agonist PCN promotes hepatomegaly and lipid accumulation without hepatocyte proliferation in mice.

Pregnane X receptor (PXR) is highly expressed in the liver and plays a pivotal role in xenobiotic and endobiotic metabolism. We previously reported that PXR activation by its specific mouse agonist pregnenolone 16α-carbonitrile (PCN) significantly induces liver enlargement and lipid accumulation. However, the effect of long-term PCN treatment on PXR and mouse liver is still unknown. This study aimed to explore the influence of long-term administration of PCN on mouse liver and hepatic lipid homeostasis. Male C57BL/6 mice were injected intraperitoneally with PCN (100 mg/kg once a week) for 42 weeks. Serum and liver samples were collected for biochemical and histological analysis. PXR activation was investigated by Western blot. Ultra-high-performance liquid chromatography coupled with electrospray ionization high-resolution mass spectrometry (UHPLC-ESI-HRMS)-based lipidomics analysis was performed to explore the change in different lipid categories. The results showed that long-term treatment with PCN significantly promoted hepatomegaly without hepatocyte proliferation and enlargement. Long-term treatment with PCN did not upregulate PXR target proteins in mice, and there was no significant upregulation of CYP3A11, CYP2B10, UGT1A1, MRP2, or MRP4. Lipidomics analysis showed obvious hepatic lipid accumulation in the PCN-treated mice, and the most significant change was found in triglycerides (TGs). Additionally, long-term treatment with PCN had no risk for carcinogenesis. These findings demonstrated that long-term PCN treatment induces hepatomegaly and lipid accumulation without hepatocyte proliferation or enlargement.

Herbal Textual Research on Rhapontici Radix in Famous Classical Formulas / 中国实验方剂学杂志

This article systematically sorted out and researched the name， origin， harvesting and other aspects of Rhapontici Radix by referring to ancient materia medica， medical books and prescription books， combined with modern literature， in order to provide a reference basis for the development of the famous classical formulas containing this herb. According to the results of the herbal textual research， it can be seen that all the generations of the materia medica have taken Loulu as the proper name， and there are also aliases such as Luligen， Laowenghua and Jiahao. The mainstream base of Rhapontici Radix recorded in the past dynasties was the present Compositae plant Rhaponticum uniflorum， which is mostly used as medicine with roots. Since the Tang dynasty， the stems and leaves of Siphonostegia chinensis have been used as Rhapontici Radix in the northern region. Until modern times， Qizhou Pharmacognosy began to differentiate it into two categories， Qizhou Loulu and Yuzhou Loulu， according to the commodity circulation at that time， producing area and origin， of which Yuzhou Loulu is the roots of Echinops latifolius， a plant of Compositae family. In ancient times， the quality of Loulu was based on "the one that comes out of Shanzhou is the best". However， in modern times， the quality of Qizhou Loulu is better if the surface is black， neat， sturdy， firm， not broken， and without a withered heart， while the quality of Yuzhou Loulu is better if the branches are thick and long with an earthy-brown surface， solid texture and neat in length. In ancient times， most of the harvesting and processing of Loulu was "harvesting the roots in lunar August and drying them in the shade"， while in modern times， the roots are mostly excavated in the spring and autumn， and dried in the sun. Its ancient method of processing is to mix and steam with licorice， nowadays， it is prepared by removing impurities， washing， moistening thoroughly， cutting into thick slices and drying in the sun， and then taking the raw products as medicine. Based on the research conclusion， it is suggested that when developing and utilizing the famous classical formulas containing Loulu， the background of the formula should be verified， and if the original formula indicated the requirement of processing， it should be processed according to the requirement， but if not， it is recommended to use raw products as medicine.

Simulation design and experimental study of magnetic stimulation coil for robot pigeon / 生物医学工程学杂志

To explore the feasibility of applying magnetic stimulation technology to the movement control of animal robots, the influence of coil radius, number of turns and other factors on the intensity, depth and focus of magnetic stimulation was simulated and analyzed for robot pigeons. The coil design scheme was proposed. The coil was placed on the head and one of the legs of the pigeon, and the leg electromyography (EMG) was recorded when magnetic stimulation was performed. Results showed that the EMG was significantly strengthened during magnetic stimulation. With the reduction of the output frequency of the magnetic stimulation system, the output current was increased and the EMG was enhanced accordingly. Compared with the brain magnetic stimulation, sciatic nerve stimulation produced a more significant EMG enhancement response. This indicated that the magnetic stimulation system could effectively modulate the functions of brain and peripheral nerves by driving the coil. This study provides theoretical and experimental guidance for the subsequent optimization and improvement of practical coils, and lays a preliminary theoretical and experimental foundation for the implementation of magnetic stimulation motion control of animal robots.

Analysis of incidence and influencing factors of congenital heart disease in perinatal infants in Henan province / 新乡医学院学报

Objective To analyze the incidence, trend and influencing factors of congenital heart disease(CHD) in perinatal infants in Henan province. Methods From 2011 to 2020,1 356 838 perinatal infants born from 28 weeks of pregnancy to 7 days after delivery were selected from 37 national birth defect monitoring points in Henan province as the research subjects, and the incidence of CHD in perinatal infants from different regions, fetal sex and maternal age were compared. The Joinpiont regression model was established to analyze the temporal change trend of the incidence rate of CHD in perinatal infants in Henan province from 2011 to 2020; the annual percentage change (APC) represented the internal trend of each segment, and the average annual percentage change (AAPC) represented the overall change trend. The trend of gap in incidence rate of CHD in different regions, mother's age and perinatal sex was compared by the Joinpiont parallel test. Results From 2011 to 2020,19 004 cases of perinatal infants with CHD were detected in Henan province, with a total incidence of 140.06/10 000; the incidence of CHD in perinatal infants showed an increasing trend year by year (AAPC=43.3% ,P<0.05) From 2011 to 2020, the incidence of CHD in urban perinatal infants in Henan province was significantly higher than that in rural areas, the incidence of CHD in male perinatal infants was significantly higher than that in female perinatal infants，and the incidence of CHD in perinatal infants in older mothers was significantly higher than that in younger mothers (X2=7 259.160,5 415.473,499.520; P<0.05). From 2011 to 2020,the incidence of CHD in perinatal infants in urban and rural areas of Henan province showed an increasing trend year by year (AAPC=42.5% ,44.5% ;P<0.05); the difference between urban and rural areas in the incidence of CHD in perinatal infants was increasing year by year(P<0.05). From 2011 to 2020,the incidence of CHD in male perinatal and famale perinatal infants in Henan province showed an increasing trend year by year(AAPC=44.3%，42.7% ;P<0.05). From 2011 to 2020, the incidence of CHD in perinatal infants of non-elderly and elderly pregnant women in Henan province showed an increasing trend year by year (AAPC=42.9% ,42.7% ;P<0.05).the difference between the elderly arid non-elderly pregnant women in the incidence of CHD In perinatal infants was increasing year by year (P<0.05). Conclusion From 2011 to 2020 ,the incidence of CHD in perinatal infants in Henan province showed an upward trend, and the regional distribution, fetal sex and maternal age were related to the incidence of perinatal CHD.