Efficacy and safety of transcutaneous electrical acupoint stimulation for the management of primary dysmenorrhoea: protocol for a randomised controlled trial in China.

INTRODUCTION: Primary dysmenorrhoea (PD) is a common menstrual concern with significant physical and psychosocial impacts. The effectiveness and safety of transcutaneous electrical acupoint stimulation (TEAS) in alleviating PD symptoms remain uncertain due to insufficient evidence. This single-centre, parallel, randomised controlled study intends to evaluate the efficacy and safety of TEAS for PD management. METHODS AND ANALYSIS: 60 participants aged 18-40 years diagnosed with moderate to severe PD will be recruited from Tai'an Hospital of Traditional Chinese Medicine (TCM) and randomly assigned to either a TEAS group or a TEAS-sham group (1:1). The TEAS group will undergo 12 sessions of TEAS treatment over two menstrual cycles, with 30 min per session, three sessions weekly. Participants in the TEAS-sham group will receive TEAS stimulation using identical devices and protocols but without current output. The primary outcome is the Visual Analogue Scale (VAS) for pain assessment. Secondary outcomes are Short-Form McGill Pain Questionnaire, total effective rate, uterine artery haemodynamics, prostaglandin and ß-endorphin level, mental well-being and quality of life. Adverse events and their potential reasons and the use of analgesics will also be recorded. ETHICS AND DISSEMINATION: This study was approved by the Medical Ethics Committee of Tai'an Hospital of TCM. Written informed consent will be obtained from each participant. The results will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ChiCTR2300071686.

Firing feature-driven neural circuits with scalable memristive neurons for robotic obstacle avoidance.

Neural circuits with specific structures and diverse neuronal firing features are the foundation for supporting intelligent tasks in biology and are regarded as the driver for catalyzing next-generation artificial intelligence. Emulating neural circuits in hardware underpins engineering highly efficient neuromorphic chips, however, implementing a firing features-driven functional neural circuit is still an open question. In this work, inspired by avoidance neural circuits of crickets, we construct a spiking feature-driven sensorimotor control neural circuit consisting of three memristive Hodgkin-Huxley neurons. The ascending neurons exhibit mixed tonic spiking and bursting features, which are used for encoding sensing input. Additionally, we innovatively introduce a selective communication scheme in biology to decode mixed firing features using two descending neurons. We proceed to integrate such a neural circuit with a robot for avoidance control and achieve lower latency than conventional platforms. These results provide a foundation for implementing real brain-like systems driven by firing features with memristive neurons and put constructing high-order intelligent machines on the agenda.

Curcuminoids Modulated the IL-6/JAK/STAT3 Signaling Pathway in LoVo and HT-29 Colorectal Cancer Cells.

BACKGROUND: Curcuminoids, including curcumin, desmethoxycurcumin, and bisdesmethoxycurcumin, are natural polyphenolic compounds that exhibit various biological properties, such as antioxidant, anti-inflammatory, and anticancer activities. Dysregulation of the interleukin (IL)-6-mediated Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) signaling pathway is closely associated with the development of colorectal cancer (CRC). METHODS: Here, we have evaluated the modulation of the IL-6/JAK/STAT3 pathway of curcumin, desmethoxycurcumin, and bisdesmethoxycurcumin in LoVo and HT-29 colorectal cancer cells with a single molecular array (Simoa), western blot analysis, real-time polymerase chain reaction (PCR), and pathway analysis system. RESULTS: The study showed that curcuminoids suppressed the amount of IL-6 in LoVo and HT-29 colorectal cancer cells. Meanwhile, curcuminoids inhibited the expression of inflammation regulator-related microRNA (miRNA). We also found that the expression of total STAT3 was downregulated by curcuminoids. Moreover, the pathway analysis system showed that curcuminoids inactivated the JAK/STAT3 signaling pathway. Taken together, we demonstrated that the anti-cancer activities of curcuminoids against colorectal cancer are due to the modulation of the IL-6/JAK/STAT3 cascade. CONCLUSION: Curcuminoids could be a promising anti-cancer agent for the treatment of human colorectal cancer.

Study on the Interaction between Silibinin and Neuraminidase.

BACKGROUND: Neuraminidase is a pathogenic protein of the avian influenza virus. Previous studies have shown that silibinin has the potential to inhibit neuraminidase activity. OBJECTIVE: This study aims to explore the interaction between silibinin and neuraminidase and the effect of silibinin on the structure and activity of neuraminidase. METHODS: In this study, two-dimensional fluorescence spectrum, three-dimensional fluorescence spectrometry, Uv-vis spectroscopy, and circular dichroism analysis were used. RESULTS: Silibinin alters the secondary structure of neuraminidase and inhibits the activity of neuraminidase. CONCLUSION: Silibinin can interact with neuraminidase and inhibit its activity.

Genetic labeling reveals spatial and cellular expression pattern of neuregulin 1 in mouse brain.

BACKGROUND: Where the gene is expressed determines the function of the gene. Neuregulin 1 (Nrg1) encodes a tropic factor and is genetically linked with several neuropsychiatry diseases such as schizophrenia, bipolar disorder and depression. Nrg1 has broad functions ranging from regulating neurodevelopment to neurotransmission in the nervous system. However, the expression pattern of Nrg1 at the cellular and circuit levels in rodent brain is not full addressed. METHODS: Here we used CRISPR/Cas9 techniques to generate a knockin mouse line (Nrg1Cre/+) that expresses a P2A-Cre cassette right before the stop codon of Nrg1 gene. Since Cre recombinase and Nrg1 are expressed in the same types of cells in Nrg1Cre/+ mice, the Nrg1 expression pattern can be revealed through the Cre-reporting mice or adeno-associated virus (AAV) that express fluorescent proteins in a Cre-dependent way. Using unbiased stereology and fluorescence imaging, the cellular expression pattern of Nrg1 and axon projections of Nrg1-positive neurons were investigated. RESULTS: In the olfactory bulb (OB), Nrg1 is expressed in GABAergic interneurons including periglomerular (PG) and granule cells. In the cerebral cortex, Nrg1 is mainly expressed in the pyramidal neurons of superficial layers that mediate intercortical communications. In the striatum, Nrg1 is highly expressed in the Drd1-positive medium spiny neurons (MSNs) in the shell of nucleus accumbens (NAc) that project to substantia nigra pars reticulata (SNr). In the hippocampus, Nrg1 is mainly expressed in granule neurons in the dentate gyrus and pyramidal neurons in the subiculum. The Nrg1-expressing neurons in the subiculum project to retrosplenial granular cortex (RSG) and mammillary nucleus (MM). Nrg1 is highly expressed in the median eminence (ME) of hypothalamus and Purkinje cells in the cerebellum. CONCLUSIONS: Nrg1 is broadly expressed in mouse brain, mainly in neurons, but has unique expression patterns in different brain regions.

Emergency decompression for patients with ureteral stones and SIRS: a prospective randomized clinical study.

OBJECTIVE: Patients with ureteral calculi and systemic inflammatory response syndrome (SIRS) often require emergency drainage, and percutaneous nephrostomy (PCN) and retrograde ureteral stent insertion (RUSI) are the most commonly used methods. Our study aimed to identify the best choice (PCN or RUSI) for these patients and to examine the risk factors for progression to urosepsis after decompression. METHODS: A prospective, randomized clinical study was performed at our hospital from March 2017 to March 2022. Patients with ureteral stones and SIRS were enrolled and randomized to the PCN or RUSI group. Demographic information, clinical features and examination results were collected. RESULTS: Patients (n = 150) with ureteral stones and SIRS were enrolled into our study, with 78 (52%) patients in the PCN group and 72 (48%) patients in the RUSI group. Demographic information was not significantly different between the groups. The final treatment of calculi was significantly different between the two groups (p < .001). After emergency decompression, urosepsis developed in 28 patients. Patients with urosepsis had a higher procalcitonin (p = .012) and blood culture positivity rate (p < .001) and more pyogenic fluids during primary drainage (p < .001) than patients without urosepsis. CONCLUSION: PCN and RUSI were effective methods of emergency decompression in patients with ureteral stone and SIRS. Patients with pyonephrosis and a higher PCT should be carefully treated to prevent the progression to urosepsis after decompression.Key messageIn this study, we evaluate the best choice (PCN or RUSI) for patients who have ureteral stones and SIRS and to examine the risk factors for progression to urosepsis after decompression. This study found that PCN and RUSI were effective methods of emergency decompression. Pyonephrosis and higher PCT were risk factors for patients to develop to urosepsis after decompression.

Loureirin B promotes insulin secretion through GLP-1R and AKT/PDX1 pathways.

Loureirin B (LB), a natural product derived from Sanguis draconis, has hypoglycemic effects in diabetic mice. However, there are no studies on how LB lowers blood glucose. In this study, we first treated a diabetic model in mice with LB, and the results showed that LB lowered blood glucose and alleviated islet damage in mice. Next, Ins-1 cells were treated with LB. The results showed that LB could promote cell proliferation and reduce apoptosis of Ins-1 cells. Loureirin B (LB), a natural product derived from Sanguis draconis, has hypoglycemic effects in diabetic mice. However, there are no studies on how LB lowers blood glucose. In this study, we first treated mice with LB in a diabetic model and showed that LB lowered blood glucose and reduced islet damage in mice. Next, Ins-1 cells were treated with LB. The results showed that LB could promote cell proliferation and reduce apoptosis of Ins-1 cells. Further, after inhibiting GLP-1R activity, the results showed that LB promoted insulin secretion, Ins-1 cell proliferation and reduced Ins-1 cell apoptosis with reduced effect, indicating that LB achieved the above effects by activating GLP-1Ra. Meanwhile, cellular cAMP levels increased when GLP-1R was overexpressed, which also demonstrated the interaction between LB and GLP-1R. Subsequently, the effect of LB on cellular potassium channels was examined by membrane clamp, and the results showed that LB increased intracellular Ca2+ concentration and stimulated insulin secretion by activating GLP-1R and thus closing the ATP-sensitive potassium channels. On the other hand, the activation effect of LB on AKT/PDX1 signaling pathway was verified.

A bioinspired configurable cochlea based on memristors.

Cochleas are the basis for biology to process and recognize speech information, emulating which with electronic devices helps us construct high-efficient intelligent voice systems. Memristor provides novel physics for performing neuromorphic engineering beyond complementary metal-oxide-semiconductor technology. This work presents an artificial cochlea based on the shallen-key filter model configured with memristors, in which one filter emulates one channel. We first fabricate a memristor with the TiN/HfOx/TaOx/TiN structure to implement such a cochlea and demonstrate the non-volatile multilevel states through electrical operations. Then, we build the shallen-key filter circuit and experimentally demonstrate the frequency-selection function of cochlea's five channels, whose central frequency is determined by the memristor's resistance. To further demonstrate the feasibility of the cochlea for system applications, we use it to extract the speech signal features and then combine it with a convolutional neural network to recognize the Free Spoken Digit Dataset. The recognition accuracy reaches 92% with 64 channels, compatible with the traditional 64 Fourier transform transformation points of mel-frequency cepstral coefficients method with 95% recognition accuracy. This work provides a novel strategy for building cochleas, which has a great potential to conduct configurable, high-parallel, and high-efficient auditory systems for neuromorphic robots.

Loureirin B attenuates insulin resistance in HepG2 cells by regulating gluconeogenesis signaling pathway.

Insulin resistance (IR) is the main cause of type 2 diabetes. The liver is the organ where insulin is secreted from the pancreas, and it regulates the storage and release of glucose according to the body's demand. Althouth Loureirin B (LB) has been reported to promote insulin secretion and decrease blood glucose, the effects of LB on glucose metabolism in the liver and the mechanism is still unclear. Different concentrations of LB were applied to treat on insulin resistance model (IR-HepG2) cells. The research results showed that LB inhibited the production of ROS (Reactive oxygen species) in IR-HepG2 cells, promoted the phosphorylation of AKT, down-regulated the expression of FoxO1, and up-regulated the expression of IRS1 and GLUT4. In addition, LB also down regulated the glucose metabolism related genes PEPCK and GSK3ß. The glucose uptake, consumption and glycogen content were increased. Moreover, LB-treated diabetic mice also showed hypoglycaemic effects. In summary, LB may ameliorate type 2 diabetes by preventing the inactivation of IRS1/AKT pathway in IR-HepG2 cells, increasing insulin sensitivity, and regulating glucose uptake and production.

Risk assessment and integrated surveillance of foot-and-mouth disease outbreaks in Russia based on Monte Carlo simulation.

BACKGROUND: Foot-and-mouth disease (FMD) is a highly contagious disease of livestock worldwide. Russia is a big agricultural country with a wide geographical area where FMD outbreaks have become an obstacle for the development of the animal and animal products trade. In this study, we aimed to assess the export risk of FMD from Russia. RESULTS: After simulation by Monte Carlo, the results showed that the probability of cattle infected with FMD in the surveillance zone (Surrounding the areas where no epidemic disease has occurred within the prescribed time limit, the construction of buffer areas is called surveillance zone.) of Russia was 1.29 × 10- 6. The probability that at least one FMD positive case was exported from Russia per year in the surveillance zone was 6 %. The predicted number of positive cattle of the 39,530 - 50,576 exported from Russia per year was 0.06. A key node in the impact model was the probability of occurrence of FMD outbreaks in the Russian surveillance zone. By semi-quantitative model calculation, the risk probability of FMD defense system defects was 1.84 × 10- 5, indicating that there was a potential risk in the prevention and control measures of FMD in Russia. The spatial time scan model found that the most likely FMD cluster (P < 0.01) was in the Eastern and Siberian Central regions. CONCLUSIONS: There was a risk of FMDV among cattle exported from Russia, and the infection rate of cattle in the monitored area was the key factor. Understanding the export risk of FMD in Russia and relevant epidemic prevention measures will help policymakers to develop targeted surveillance plans.

Engineering Spiking Neurons Using Threshold Switching Devices for High-Efficient Neuromorphic Computing.

Inspired by the human brain, the spike-based neuromorphic system has attracted strong research enthusiasm because of the high energy efficiency and powerful computational capability, in which the spiking neurons and plastic synapses are two fundamental building blocks. Recently, two-terminal threshold switching (TS) devices have been regarded as promising candidates for building spiking neurons in hardware. However, how circuit parameters affect the spiking behavior of TS-based neurons is still an open question. Here, based on a leaky integrate-and-fire (LIF) neuron circuit, we systematically study the effect of both the extrinsic and intrinsic factors of NbO x -based TS neurons on their spiking behaviors. The extrinsic influence factors contain input intensities, connected synaptic weights, and parallel capacitances. To illustrate the effect of intrinsic factors, including the threshold voltage, holding voltage, and high/low resistance states of NbO x devices, we propose an empirical model of the fabricated NbO x devices, fitting well with the experimental results. The results indicate that with enhancing the input intensity, the spiking frequency increases first then decreases after reaching a peak value. Except for the connected synaptic weights, all other parameters can modulate the spiking peak frequency under high enough input intensity. Also, the relationship between energy consumption per spike and frequency of the neuron cell is further studied, leading guidance to design neuron circuits in a system to obtain the lowest energy consumption. At last, to demonstrate the practical applications of TS-based neurons, we construct a spiking neural network (SNN) to control the cart-pole using reinforcement learning, obtaining a reward score up to 450. This work provides valuable guidance on building compact LIF neurons based on TS devices and further bolsters the construction of high-efficiency neuromorphic systems.

Loureirin B activates GLP-1R and promotes insulin secretion in Ins-1 cells.

Loureirin B (LB) is a natural product derived from Sanguis draconis, which has hypoglycaemic effects. In order to research the possible target of LB in the treatment of diabetes, molecular docking was used to simulate the interaction between LB and potential targets, and among them, glucagon-like peptide-1 receptor (GLP-1R) had the optimal results. Further, spectroscopy and surface plasmon resonance (SPR) experiments were applied to detect the interaction between LB and GLP-1R. Ultimately, after GLP-1R siRNA interfering the expression of GLP-1R in Ins-1 cell, the promoting insulin secretion of LB was weaken, which directly proved that GLP-1R plays an important role. These results show that LB promotes insulin secretion of Ins-1 cells through GLP-1R. Hence, the strategy of LB as a prodrug will provide a potential approach for non-peptide GLP-1R agonist.

Effects of Maillard reaction on structural modification and potential allergenicity of peanut 7S globulin (Ara h 1).

BACKGROUND: Ara h 1 is a major food allergen in peanuts. Recently, many studies have revealed that the Maillard reaction (MR) affects the allergenicity of food proteins. RESULTS: To investigate the influence of the MR on the allergenicity of Ara h 1, R-Ara h 1 was processed with glucose in dry heating conditions for different periods. The extent of the MR was assessed by four methods. The changes in secondary and tertiary structures were characterized through spectroscopy assays. Advanced glycation end products (AGE) structures were identified by protein sample dry heating for 60 min, indicating the formation of AGE-Ara h 1. Simulated gastric fluid (SGF) digestion analysis showed that AGE-Ara h 1 has higher resistance to peptic digestion than R-Ara h 1. The BALB/c mouse model was also utilized to explore the effect of the MR on the allergenicity of Ara h 1, and the results showed that the Th2-type cytokines, antibodies, and histamine content increased, and there was a greater degree of degranulation of rat basophilic leukemia (RBL) cells in the AGE-Ara h 1 group compared with the R-Ara h 1 group. CONCLUSION: During the process of dry heating, proteins participated in the MR with changes in secondary and tertiary structures. The condition applying a temperature of 100 °C for 60 min caused the formation of AGE-Ara h 1. Simulated gastric fluid digestion analysis showed that AGE-Ara h 1 had a greater resistance to peptic digestion than R-Ara h 1. The BALB/c mouse model showed that AGE-Ara h 1 had more allergenicity, indicating that the MR could enhance the allergenicity of Ara h 1. © 2020 Society of Chemical Industry.

Dairy Safety Prediction Based on Machine Learning Combined with Chemicals.

BACKGROUND: Dairy safety has caused widespread concern in society. Unsafe dairy products have threatened people's health and lives. In order to improve the safety of dairy products and effectively prevent the occurrence of dairy insecurity, countries have established different prevention and control measures and safety warnings. OBJECTIVE: The purpose of this study is to establish a dairy safety prediction model based on machine learning to determine whether the dairy products are qualified. METHODS: The 34 common items in the dairy sampling inspection were used as features in this study. Feature selection was performed on the data to obtain a better subset of features, and different algorithms were applied to construct the classification model. RESULTS: The results show that the prediction model constructed by using a subset of features including "total plate", "water" and "nitrate" is superior. The SN, SP and ACC of the model were 62.50%, 91.67% and 72.22%, respectively. It was found that the accuracy of the model established by the integrated algorithm is higher than that by the non-integrated algorithm. CONCLUSION: This study provides a new method for assessing dairy safety. It helps to improve the quality of dairy products, ensure the safety of dairy products, and reduce the risk of dairy safety.

The First 2D Homochiral Lead Iodide Perovskite Ferroelectrics: [R- and S-1-(4-Chlorophenyl)ethylammonium]2 PbI4.

2D organic-inorganic lead iodide perovskites have recently received tremendous attention as promising light absorbers for solar cells, due to their excellent optoelectronic properties, structural tunability, and environmental stability. However, although great efforts have been made, no 2D lead iodide perovskites have been discovered as ferroelectrics, in which the ferroelectricity may improve the photovoltaic performance. Here, by incorporating homochiral cations, 2D lead iodide perovskite ferroelectrics [R-1-(4-chlorophenyl)ethylammonium]2 PbI4 and [S-1-(4-chlorophenyl)ethylammonium]2 PbI4 are successfully obtained. The vibrational circular dichroism spectra and crystal structural analysis reveal their homochirality. They both crystalize in a polar space group P1 at room temperature, and undergo a 422F1 type ferroelectric phase transition with transition temperature as high as 483 and 473.2 K, respectively, showing a multiaxial ferroelectric nature. They also possess semiconductor characteristics with a direct bandgap of 2.34 eV. Nevertheless, their racemic analogue adopts a centrosymmetric space group P21 /c at room temperature, exhibiting no high-temperature phase transition. The homochirality in 2D lead iodide perovskites facilitates crystallization in polar space groups. This finding indicates an effective way to design high-performance 2D lead iodide perovskite ferroelectrics with great application prospects.

Directional Intermolecular Interactions for Precise Molecular Design of a High- Tc Multiaxial Molecular Ferroelectric.

Quasi-spherical molecules have recently been developed as promising building blocks for constructing high-performance molecular ferroelectrics. However, although the modification of spherical molecules into quasi-spherical ones can efficiently lower the crystal symmetry, it is still a challenge to precisely arouse a low-symmetric polar crystal structure. Here, by introducing directional hydrogen-bonding interactions in the molecular modification, we successfully reduced the cubic centrosymmetric Pm3̅ m space group of [quinuclidinium]ClO4 at room temperature to the orthorhombic polar Pna21 space group of [3-oxoquinuclidinium]ClO4. Different from the substituent groups of -OH, -CH3, and ═CH2, the addition of a ═O group with H-acceptor to [quinuclidinium]+ forms directionally N-H···O═C hydrogen-bonded chains, which plays a critical role in the generation of polar structure in [3-oxoquinuclidinium]ClO4. Systematic characterization indicates that [3-oxoquinuclidinium]ClO4 is an excellent molecular ferroelectric with a high Curie temperature of 457 K, a large saturate polarization of 6.7 µC/cm2, and a multiaxial feature of 6 equiv ferroelectric axes. This work demonstrates that the strategy of combining quasi-spherical molecule building blocks with directional intermolecular interactions provides an efficient route to precisely design new eminent molecular ferroelectrics.

Advances in Antidiabetic Drugs Targeting Insulin Secretion.

BACKGROUND: Diabetes mellitus (DM) is a disease of systemic metabolic disorders caused by the decrease of secretion or sensitivity of insulin. In recent years, the study of insulin-related drug targets and the development of new drugs have become the popular topic of current medical research, and studies have shown that multiple signaling pathways are associated with diabetes treatment. At present, some new drugs based on the new target design have been listed on the market and have achieved good hypoglycemic effect. However, most of the drugs are still in the clinical or pre-clinical stage. The efficacy and safety of the drugs need further clinical validation. OBJECTIVE: This article will introduce the advancements of targets and drugs to promote insulin secretion.

Phytotoxicity of ionic liquids with different structures on wheat seedlings and evaluation of their toxicity attenuation at the presence of modified biochar by adsorption effect.

The toxic effects of eight common ionic liquids (ILs) on wheat seedlings was evaluated with specific emphasis on the influence of concentration range, anion species and cation chain length of ILs. The growth of wheat seeds was significantly inhibited by ILs, especially under higher concentration, presence of the fluoride anion and the longer alkyl chain length of the cation. The modified biochar (PB-K-N) efficiently removed the ILs from aqueous solutions, the order of the adsorption capacities was as follows: [Bmim]OAc [Bmim]C7H5O2 [Bmim]BF4 [Bmim]Br, [Domim]Br [BPy]Br [Omim]Br [Bmim]Br [Emim]Br. Furthermore, the wheat growth of all ILs groups except [Bmim]BF4 group in the presence of PB-K-N was also similar to that of the control groups, which clearly demonstrated that PB-K-N could decrease or alleviate toxicity of ILs toward wheat by adsorption effect. Therefore, the biochar application was effective in improving plant resistance to ILs stress by adsorption, to reduce the phytotoxicity of ILs and provide an alternative approach for the utilization of PB-K-N in ILs contaminated water and soils.