The role of purinergic signaling in acupuncture-mediated relief of neuropathic and inflammatory pain.

Acupuncture is a traditional medicinal practice in China that has been increasingly recognized in other countries in recent decades. Notably, several reports have demonstrated that acupuncture can effectively aid in pain management. However, the analgesic mechanisms through which acupuncture provides such benefits remain poorly understood. Purinergic signaling, which is mediated by purine nucleotides and purinergic receptors, has been proposed to play a central role in acupuncture analgesia. On the one hand, acupuncture affects the transmission of nociception by increasing adenosine triphosphate dephosphorylation and thereby decreasing downstream P2X3, P2X4, and P2X7 receptors signaling activity, regulating the levels of inflammatory factors, neurotrophic factors, and synapsin I. On the other hand, acupuncture exerts analgesic effects by promoting the production of adenosine, enhancing the expression of downstream adenosine A1 and A2A receptors, and regulating downstream inflammatory factors or synaptic plasticity. Together, this systematic overview of the field provides a sound, evidence-based foundation for future research focused on the application of acupuncture as a means of relieving pain.

Mechanisms of acupuncture-electroacupuncture on inflammatory pain.

Acupuncture, as a traditional treatment, has been extensively used in China for thousands of years. According to the World Health Organization (WHO), acupuncture is recommended for the treatment of 77 diseases. And 16 of these diseases are related to inflammatory pain. As a combination of traditional acupuncture and modern electrotherapy, electroacupuncture (EA) has satisfactory analgesic effects on various acute and chronic pain. Because of its good analgesic effects and no side effects, acupuncture has been widely accepted all over the world. Despite the increase in the number of studies, the mechanisms via which acupuncture exerts its analgesic effects have not been conclusively established. A literature review of related research is of great significance to elaborate on its mechanisms and to inform on further research directions. We elucidated on its mechanisms of action on inflammatory pain from two levels: peripheral and central. It includes the mechanisms of acupuncture in the periphery (immune cells and neurons, purinergic pathway, nociceptive ion channel, cannabinoid receptor and endogenous opioid peptide system) and central nervous system (TPRV1, glutamate and its receptors, glial cells, GABAergic interneurons and signaling molecules). In this review, we collected relevant recent studies to systematically explain the mechanisms of acupuncture in treating inflammatory pain, with a view to providing direction for future applications of acupuncture in inflammatory pain and promoting clinical development.

Enhanced identification of Tau acetylation and phosphorylation with an engineered aerolysin nanopore.

Posttranslational modifications (PTMs) affect protein function/dysfunction, playing important roles in the occurrence and development of tauopathies including Alzheimer's disease. PTM detection is significant and still challenging due to the requirements of high sensitivity to identify the subtle structural differences between modifications. Herein, in terms of the unique geometry of the aerolysin (AeL) nanopore, we elaborately engineered a T232K AeL nanopore to detect the acetylation and phosphorylation of Tau segment (Pep). By replacing neutral threonine (T) with positively charged lysine (K) at the 232 sites, the T232K and K238 rings of this engineered T232K AeL nanopore corporately work together to enhance electrostatic trapping of the acetylated and phosphorylated Tau peptides. Translocation speed of the monophosphorylated Pep-P was decelerated by up to 46 folds compared to the wild-type (WT) AeL nanopore. The prolonged residences within the T232K AeL nanopore enabled to simultaneously identify the monoacetylated Pep-Ac, monophosphorylated Pep-P, di-modified Pep-P-Ac and non-modified Pep. The tremendous potential is demonstrated for PTM sensing by manipulating non-covalent interactions between nanopores and single analytes.

Is the Volume Exclusion Model Practicable for Nanopore Protein Sequencing?

The nanopore approach holds the possibility for achieving single-molecule protein sequencing. However, ongoing challenges still remain in the biological nanopore technology, which aims to identify 20 natural amino acids by reading the ionic current difference with the traditional current-sensing model. In this paper, taking aerolysin nanopores as an example, we calculate and compare the current blockage of each of 20 natural amino acids, which are all far from producing a detectable current blockage difference. Then, we propose a modified solution conductivity of σ' in the traditional volume exclusion model for nanopore sensing of a peptide. The σ' value describes the comprehensive result of ion mobility inside a nanopore, which is related to but not limited to nanopore-peptide interactions, and the positions, orientations, and conformations of peptides inside the nanopore. The nanopore experiments of a short peptide (VQIVYK) in wild type and mutant nanopores further demonstrate that the traditional volume exclusion model is not enough to fully explain the current blockage contribution and that many other factors such as enhanced nanopore-peptide interactions could contribute to a dominant part of the current change. This modified sensing model provides insights into the further development of nanopore protein sequencing methods.

Effect of endometrial thickness changes on clinical pregnancy rates after progesterone administration in a single frozen-thawed euploid blastocyst transfer cycle using natural cycles with luteal support for PGT-SR- and PGT-M-assisted reproduction: a retrospective cohort study.

BACKGROUND: To investigate whether the endometrial thickness change ratio from the progesterone administration day to the blastocyst transfer day is associated with pregnancy outcomes in a single frozen-thawed euploid blastocyst transfer cycle. METHODS: All patients used natural cycles with luteal support for endometrial preparation and selected a single euploid blastocyst for transfer after a biopsy for preimplantation genetic testing. The endometrial thickness was measured by transvaginal ultrasound on the progesterone administration day and the transfer day, the change in endometrial thickness was measured, and the endometrial thickness change ratio was calculated. According to the change rate of endometrial thickness, the patients were divided into three groups: the endometrial thickness compaction group, endometrial thickness non-change group and endometrial thickness expansion group. Among them, the endometrial thickness non-change and expansion groups were combined into the endometrial thickness noncompaction group. RESULTS: Ultrasound images of the endometrium in 219 frozen-thawed euploid blastocyst transfer cycles were evaluated. The clinical pregnancy rate increased with the increase in endometrial thickness change ratio, while the miscarriage rate and live birth rate were comparable among the groups. The multiple logistic regression results showed that in the fully adjusted model a higher endometrial thickness change ratio (per 10%) was associated with a higher clinical pregnancy rate (adjusted odds ratio [aOR] 1.29; 95% confidence interval [CI], 1.01-1.64; P = .040). Similarly, when the patients were divided into three groups according to the change rate of endometrial thickness, the endometrial thickness noncompaction group had a significant positive effect on the clinical pregnancy rate compared with the endometrial thickness compaction group after adjusting for all covariates. CONCLUSIONS: In frozen-thawed euploid blastocyst transfer cycles in which the endometrium was prepared by natural cycles with luteal support, the clinical pregnancy rate was higher in cycles without endometrial compaction after progesterone administration.

Live birth rates after natural cycle versus hormone replacement therapy for single euploid blastocyst transfers: a retrospective cohort study.

RESEARCH QUESTION: Is there any difference in live birth rate between the natural cycle and hormone replacement therapy (HRT) endometrial preparation protocols for women with regular menstrual cycles undergoing their first single vitrified-warmed euploid blastocyst transfer? DESIGN: This was a retrospective cohort study that enrolled 722 women who underwent vitrified-warmed euploid blastocyst transfer at assisted reproductive technology (ART) centre of The First Affiliated Hospital of Zhengzhou University, from January 2013 to December 2019. Univariate and multivariate logistic regression models were used to analyse the relationship between the endometrial preparation protocols and live birth rates. Stratified analyses and sensitivity analyses were performed to ensure the reliability and stability of the results. RESULTS: A total of 722 single vitrified-warmed euploid blastocyst transfer cycles were included. Overall, the live birth rates were 50.00% (110/220) in the natural cycle group and 47.61% (239/502) in the HRT group. Multiple logistic regression analyses showed that there was no significant association (adjusted odds ratio 0.82; 95% confidence interval 0.56-1.20; P = 0.313) between natural cycle and HRT protocols and the live birth rate. Interaction analysis showed that there was no significant difference in live birth rates between the two groups for any subgroup after adjusting for confounding factors. CONCLUSIONS: For single vitrified-warmed euploid blastocyst transfer, natural cycle and HRT endometrial preparation protocols result in similar live birth rates among women with regular menstrual cycles. Further studies are needed into the effects of endometrial preparation protocols on pregnancy outcomes.

[Preimplantation genetic testing for a couple where the husband is affected by osteogenesis imperfecta combined with balanced translocation using karyomapping technique].

OBJECTIVE: To carry out preimplantation genetic testing (PGT) for a couple where the husband was affected by osteogenesis imperfecta combined with balanced translocation using the karyomapping technique. METHODS: Blastocysts were detected using karyomapping, the carrier status of COL1A1 c.760G>A (p.Gly254Arg) variant and the carrier status of the translocated chromosome were analyzed simultaneously. RESULTS: For a total of 10 blastocysts, two euploid blastocysts were found to not carry the COL1A1 c.760G>A (p.Gly254Arg) variant but a balanced translocation. After transplanting one of the blastocysts, clinical pregnancy was achieved. Amniocentesis at 18th gestational week and prenatal genetic testing was in keeping with the result of PGT.A healthy female was born at 40+4 weeks gestation. CONCLUSION: For patients simultaneously carrying genetic variant and balanced chromosomal translocation, PGT can be performed with efficiency by the use of karyomapping method.

[Up-regulated SUMO1 expression by inhibition of miRNA-548m as a potential cause of congenital orofacial cleft in a fetus].

OBJECTIVE: To explore the genetic etiology for a fetus with congenital orofacial cleft. METHODS: Single nucleotide polymorphism microarray (SNP array) was carried out on skin tissues sampled from the fetus following induced abortion for the detection of copy number variation (CNVs). Pathogenicity of the candidate gene was validated through experiment. RESULTS: SNP array revealed that the fetus has carried a hemizygous 9.23Mb deletion at Xq21.31-q22.1(91 063 807-100 293 555), which was inherited from its mother. The region contained 13 OMIM genes and 1 ncRNA coding gene(MIR548M). Inhibiting of the expression of the MIR548M gene in oral epithelial celllines has resulted in up-regulation of the expression of SUMO1 gene which was known to involve in the pathogenesis of orofacial cleft. CONCLUSION: Dosage insufficiency of the MIR548M gene may underlie the etiology of orofacial cleft in this fetus.

Biological Nanopore Approach for Single-Molecule Protein Sequencing.

Proteins are responsible for the occurrence and treatment of many diseases, and therefore protein sequencing will revolutionize proteomics and clinical diagnostics. Biological nanopore approach has proved successful for single-molecule DNA sequencing, which resolves the identities of 4 natural deoxyribonucleotides based on the current blockages and duration times of their translocations across the nanopore confinement. However, open challenges still remain for biological nanopores to sequentially identify each amino acid (AA) of single proteins due to the inherent complexity of 20 proteinogenic AAs in charges, volumes, hydrophobicity and structures. Herein, we focus on recent exciting advances in biological nanopores for single-molecule protein sequencing (SMPS) from native protein unfolding, control of peptide translocation, AA identification to applications in disease detection.

Myopia: Its Status and Environmental Correlations Among School Students in Fushun, China.

Our objective was to investigate the status and influence of myopia among primary school students in Fushun, Liaoning Province, China. We aimed to provide a theoretical and epistemological basis for implementing myopia prevention initiatives. We employed cluster sampling and surveyed 5216 primary school students from grades 1-6 across eight primary schools in Fushun City. Our participants included 2606 males and 2610 females whose average age was 9.25 (SD = 1.76) years. The rate of myopia among these primary school students was 29.54%, with statistically significant differences among students of different genders and grades. Logistic regression analysis further identified several possible protective factors, including appropriate reading distance, adequate home lighting, regular breaks between classes, conscientious eye exercises, and daily outdoor physical activity. Conversely, the associated risk factors were being female, being in a higher grade level, spending more than 4 hours on homework, occasionally reading while lying down, and having one or both parents with myopia. Overall, our results indicated a high incidence of myopia, highlighting the need for scientifically controlled interventions to manage and mitigate the occurrence and progression of myopia in this population.

[Research progress in biosensors for adiponectin].

Adiponectin, a cytokine associated with adipose tissue, is a recently defined adipocytokine involved in insulin, glucose, and adipocyte metabolism. Reduced adiponectin levels can increase the risk of developing metabolic syndrome (MS). Adiponectin is considered an important target for the treatment of type 2 diabetes mellitus (T2DM) and MS due to its anti-atherosclerotic and insulin-sensitizing effects. Therefore, the accurate determination of adiponectin concentrations in human plasma is necessary for the management of both T2DM and MS. A variety of biosensors have been developed for the detection of biomarkers such as adiponectin. This paper reviews the applications of electrochemical sensors, surface-enhanced Raman scattering sensors, and microfluidic chip-based chemiluminescence sensors in the detection of adiponectin and the recent research progress in the sensors for the detection of adiponectin, aiming to provide a reference for the research and application of sensors for adiponectin in the medical field.

The mechanistic basis for the effects of electroacupuncture on neuropathic pain within the central nervous system.

Nociceptive signaling responses to painful stimuli are transmitted to the central nervous system (CNS) from the afferent nerves of the periphery through a series of neurotransmitters and associated signaling mechanisms. Electroacupuncture (EA) is a pain management strategy that is widely used, with clinical evidence suggesting that a frequency of 2-10 Hz is better able to suppress neuropathic pain in comparison to higher frequencies such as 100 Hz. While EA is widely recognized as a viable approach to alleviating neuralgia, the mechanistic basis underlying such analgesic activity remains poorly understood. The present review offers an overview of current research pertaining to the mechanisms whereby EA can alleviate neuropathic pain in the CNS, with a particular focus on the serotonin/norepinephrine, endogenous opioid, endogenous cannabinoid, amino acid neurotransmitter, and purinergic pathways. Moreover, the corresponding neurotransmitters, neuromodulatory compounds, neuropeptides, and associated receptors that shape these responses are discussed. Together, this review seeks to provide a robust foundation for further studies of the EA-mediated alleviation of neuropathic pain.

Flexible needle-type Microbiosensor for real-time monitoring traditional acupuncture-mediated adenosine release In vivo.

Rapid adenosine (ADO) signaling, on the time frame of seconds, regulates physiological and pathological processes, including the therapeutic efficacy of acupuncture. Nevertheless, standard monitoring strategies are limited by poor temporal resolution. Herein, an implantable needle-type microsensor capable of monitoring ADO release in vivo in response to acupuncture in real time has been developed. Electrocatalytic Prussian Blue nanoparticles, an immobilized multienzyme system, and a permselective poly-o-phenylenediamine-based membrane were used for the sequential modification of the sensing region of the electrode. The resultant sensor can perform amperometric measurements of ADO levels in response to a very low level of applied potential (-0.05 V vs Ag/AgCl). This microsensor also functioned across a broad linear range (0-50 µM) and exhibited good sensitivity (1.1 nA/µM) with a rapid response time of under 5 s. Importantly, the sensor also exhibited good reproducibility and high selectivity. For in vivo animal studies, the microsensor was employed for the continuous assessment of instantaneous ADO release at the ST36 (Zusanli) acupoint when this acupoint was subjected to twirling-rotating acupuncture manipulation. Benefiting from superior sensor in vivo performance and stability, the positive correlation between the variability in acupuncture-induced ADO release and the stimulus intensity levels that affect the clinical benefit can be demonstrated for the first time. Overall, these results highlight a powerful approach to analyzing the in vivo physiological effects of acupuncture, expanding application realm of micro-nano sensor technology on a fast time scale.

Gene Spectrum and Clinical Traits of Nine Patients With Oocyte Maturation Arrest.

Background: Oocyte maturation arrest is a disease that produces immature oocytes and cannot be mature after culturing in vitro, which leads to female primary infertility. We aimed to summarize nine representative patients in our center to retrospectively analyze the genetic variants and clinical characteristics of oocyte maturation arrest. Methods: This study examined and analyzed nine families with oocyte maturation arrest. Whole-exome sequencing (WES) of the probands was performed to detect the pathogenic variants. Sanger sequencing verified the WES findings in patients and available parents. ExAC database was used to search the variant frequency. The variants were assessed by pathogenicity and conservational property prediction analysis and according to the American College of Medical Genetics and Genomics (ACMG). Phenotypes of oocytes were evaluated by a light microscopy, and the phenotype-genotype correlation was also evaluated. Results: Nine pathogenic variants in five genes were detected in nine patients, of which three were novel variants, including PATL2 [c.1374A > G (p. Ile458Met)] and [1289-1291del TCC (p. Leu430del)] and ZP2 [c.1543C > T (p. Pro515Ser)]. Nine variants were predicted to be pathogenic, resulting in different types of oocyte maturation arrest and clinical phenotypes. Conclusion: Three novel pathogenic variants were identified, enabling the expansion of the gene variant spectrum. The related pathogenic mutations of the PATL2, TUBB8, and ZP1∼3 genes were highly suggestive of being causative of oocyte maturation arrest.

Carbon Nanomaterials-Based Electrochemical Sensors for Heavy Metal Detection.

Heavy metals are commonly found in a wide range of environmental settings metals, but the potential toxicity associated with heavy metal exposure represents a major threat to global public health. It is thus vital that approaches to efficiently, reliably, and effectively detecting heavy metals in a range of sample types be established. Carbon nanomaterials offer many advantageous properties that make them well-suited to the design of sensitive, selective, easy-to-operate electrochemical biosensors ideal for detecting heavy metal ions. The present review offers an overview of recent progress in the development of carbon nanomaterial-based electrochemical sensors used to detect heavy metals. In addition to providing a detailed discussion of certain carbon nanomaterials such as carbon nanotubes, graphene, carbon fibers, carbon quantum dots, carbon nanospheres, mesoporous carbon, and Graphdiyne, we survey the challenges and future directions for this field. Overall, the studies discussed herein suggest that the further development of carbon nanomaterial-modified electrochemical sensors will support the integration of increasingly advanced sensor platforms to aid in detecting heavy metals in foods, environmental samples, and other settings, thereby benefitting human health and society as a whole.

Endometrial thickness changes after progesterone administration do not affect the pregnancy outcomes of frozen-thawed euploid blastocyst transfer: a retrospective cohort study.

OBJECTIVE: To evaluate whether the change in endometrial thickness from progesterone administration day to transfer day is related to pregnancy outcomes in single frozen-thawed euploid blastocyst transfer cycles. DESIGN: Observational cohort study. SETTING: Single reproductive medical center. PATIENT(S): All patients were transferred with a single biopsied euploid blastocyst, and their endometrium was prepared with hormone replacement therapy (HRT). INTERVENTION(S): The endometrial thickness on the day of blastocyst transfer and progesterone administration was measured by transvaginal ultrasound, and the difference between them and the change ratio were calculated. MAIN OUTCOME MEASURE(S): Clinical pregnancy rates and live birth rates. RESULT(S): Endometrial ultrasound images of 508 euploid blastocyst transfer cycles using HRT were evaluated by transvaginal ultrasound. Overall, pregnancy outcomes were comparable in different groups of endometrial thickness changes. The results of multiple logistic regression showed that the clinical pregnancy rate and live birth rate did not significantly increase with the increase in endometrial thickness change ratios (per 10%) in the fully adjusted model as a continuous variable. In the adjustment model as a categorical variable, there was no statistical difference in pregnancy outcomes among the groups with changes in endometrial thickness. Interaction analysis showed that after adjusting for confounders, there was no statistically significant interaction between the endometrial thickness change ratio and pregnancy outcomes in all subgroups. CONCLUSION(S): In the euploid blastocyst transfer cycle of preparing the endometrium with HRT, the endometrial thickness change ratio after progesterone administration was not related to pregnancy outcomes.

Corrigendum: Effects of Gender of Reciprocal Chromosomal Translocation on Blastocyst Formation and Pregnancy Outcome in Preimplantation Genetic Testing.

[This corrects the article DOI: 10.3389/fendo.2021.704299.].

Effects of Gender of Reciprocal Chromosomal Translocation on Blastocyst Formation and Pregnancy Outcome in Preimplantation Genetic Testing.

Objective: To determine the effect of gender of reciprocal chromosomal translocation on blastocyst formation and pregnancy outcome in preimplantation genetic testing, including different parental ages. Methods: This was a retrospective cohort study that enrolled 1034 couples undergoing preimplantation genetic testing-structural rearrangement on account of a carrier of reciprocal chromosomal translocation from the Reproductive Medicine Center of the First Affiliated Hospital of Zhengzhou University from January 2015 to December 2019. Group A represented 528 couples in which the man was the carrier of reciprocal translocation and group B represented 506 couples in which the woman was the carrier of reciprocal translocation. All patients were divided into two groups according to their age: female age<35 and female age≥35. Furthermore, the differences in blastocyst condition and pregnancy outcome between male and female carriers in each group were further explored according to their father's age. Results: The blastocyst formation rate of group A (55.3%) is higher than that of group B (50%) and the results were statistically significant (P<0.05). The blastocyst formation rate of group A is higher than that of group B, no matter in young maternal age or in advanced maternal age (P<0.05). The blastocyst formation rate in maternal age<35y and paternal age<30y in group A(57.1%) is higher than that of Group B(50%); Similarly, the blastocyst formation rate in maternal age≥35 and paternal age≥38y(66.7%) is higher than that of Group B(33.3%)(all P<0.05). There was no difference in fertilization rate, aeuploidy rate, clinical pregnancy rate, miscarriage rate and live birth rate between Group A and Group B. Conclusion: When the carrier of reciprocal translocation is male, the blastocyst formation rate is higher than that of female carrier. While there is no significant difference between the two in terms of fertilization rate, aeuploidy rate, clinical pregnancy rate, miscarriage rate and live birth rate.

Transport of nano zerovalent iron (nZVI) coupling with Alcaligenes sp. strain in porous media.

Coupling nano zerovalent iron (nZVI) particles with anaerobic bacteria is a potentially powerful approach for remediating polluted groundwater. However, little is known about the transport of these mixed systems in porous media, which could potentially affect the system's activity and half-life in aqueous environments. This study assessed the transport and stability of nZVI coupled with Alcaligenes sp. TB by column experiments and sedimentation tests. The results showed that combined bio-nZVI systems experienced significantly higher transport and lower sedimentation rates than stand-alone nZVI. The transmission electron microscopy (TEM) and scanning electron microscopy (SEM) images showed that Alcaligenes sp. TB reduced aggregation of nZVI to some extent, though slight toxicity to bacteria was observed. The results of ζ-potential measurements demonstrated that the presence of bacteria increased the electrostatic force between the particles. Voltammetry, X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) analysis confirmed that the bio-nZVI system undergoes different redox processes. The presence of bacteria favored the formation of FeOOH not Fe2O3 or Fe3O4, resulting in weaker surface magnetic properties.

Effects of music training on response inhibition among children with developmental dyslexia / 中国学校卫生

Objective@#To explore the influence of music training on the response inhibition ability of children with developmental dysplasia, and to provide a theoretical basis for improving the response inhibition ability of children with developmental dyslexia.@*Methods@#From September to October 2020, students from grades 3-6 in a primary school in Shenyang, Liaoning Province were selected. A total of 27 children with dyslexia were selected through literacy test and intelligence test, and 23 children with matched reading level were selected. The Go/No-go experimental paradigm was used to investigate the changes of response inhibition in children with developmental dyslexia before and after ALF music training, induding solfeggio, physical rhythm, music scene performance and chorus.@*Results@#The results before and after music training showed that the main effect in the test stage was significant among two groups[ F(1,48)=6.13, P<0.05, η-p 2=0.11], and The accuracy of post-test [(91.80±0.80)%] was significantly higher than that of pre-test [(89.10±0.90)%]; the accuracy of the children with developmental dyslexia in response to the symbolic stimulus No-go was significantly higher in the post-test [(81.81±10.97)%] than in the pre-test [(73.78±15.26)%]( t =-2.33, P = 0.03 ); the accuracy of reading matched children s response to Chinese characters stimulation No-go was significantly better in the post-test [(85.59±12.11)%] than in the pre-test [(78.33±12.98)%]( t = -2.20, P <0.05). In terms of response time, the post-test scores of developmental dyslexia children [(444.06±77.49)ms] were significantly better than those of pre-test children [(519.01±70.75)ms], and there was no significant difference between symbol stimulus and Chinese stimulus in developmental dyslexia children ( P>0.05). @*Conclusion@#Response inhibition is deficient in children with developmental dyslexia. Compared with symbols, the response inhibition ability of Chinese characters is impaired; Music training significantly improved the inhibitory ability of signs in children with developmental dyslexia.