Puerarin Alleviates Experimental Autoimmune Thyroiditis by Regulating Macrophages.

Hashimoto's thyroiditis (HT) is the most common organ-specific autoimmune disease, predominantly affecting women. Although the pathogenesis of HT is incompletely understood, some studies have found that macrophage polarization plays a role. Puerarin is a soy isoflavone compound that has anti-inflammatory and immunomodulatory effects and regulates macrophage immune activity. This study aimed to verify the therapeutic effect of puerarin on HT and explored its regulatory effect on macrophage polarization imbalance in HT. Through bioinformatics analysis and molecular biology methods, it was found that macrophages increased significantly in HT patients and model mice. Immunological staining showed that puerarin intervention could reduce tissue inflammatory cell infiltration. Molecular biological examination displayed that puerarin could inhibit local and systemic inflammation levels, and the expression of marker thyroglobulin and thyroid peroxidase Abs. In vivo experimental results indicated that puerarin regulated macrophage polarity and reduced inflammatory damage, possibly by inhibiting the pyroptosis signaling pathway. In vivo macrophage clearance experiments demonstrated that puerarin relied on macrophages to exert its mechanism of action in treating HT. The results of this study indicate that macrophages are important mediators in the development of HT, and puerarin can regulate macrophage polarity and inflammatory status to provide thyroid tissue protection, which provides a new idea for the treatment of HT.

Exome risk score for predicting susceptibility to and severity of isolated thoracic aortic aneurysm.

Isolated thoracic aortic aneurysms (TAAs) are asymptomatic before dissection or rupture and heterogeneous in clinical phenotype. It is urgent need but difficult to identify individuals at high risk to enable enhanced screening or preventive therapies. Because TAAs have a genetic component, one possible approach is to stratify individuals based on inherited DNA variations. Here, we constructed an integrated exome risk score (ERS) based on both common and rare variants found in whole-exome sequencing through a machine-learning framework in discovery population consisting of 551 cases and 1071 controls. We evaluated the performance of the ERS in an independent population including 151 cases and 779 controls with a raw odds ratio (OR) per 1 standard deviation (SD) = 1.95 and area under the receiver operating characteristic curve (AUC) = 0.680. When adjusted by gender and the first four principal components, OR per SD = 1.68 and AUC reached 0.783. Individuals in the top 20% of ERS distribution had an OR of 3.20 compared with others. Finally, we found that individuals with top 20% ERS developed TAA at a younger age (P = 0.002) and with a larger diameter (P = 0.016) compared with lower ERS, and were more likely to suffer from aortic root aneurysms (P = 0.009). Our analysis provides a global view of the genetic components of isolated TAA. The exome score developed and evaluated here is the first polygenic risk score for TAA and is a promising predictor of disease risk and severity, which will facilitate the implementation of the risk-reduction strategies.

A novel technique of penetrating keratoplasty to prevent intraocular contents extrusion for infectious keratitis.

PURPOSE: To evaluate the safety and the effectiveness of our novel penetrating keratoplasty for infectious keratitis. METHODS: Retrospective, noncomparative, interventional case series of patients with infectious keratitis who received the novel penetrating keratoplasty technique were analyzed. A prepared plastic sheet was located between the diseased cornea and iris-lens diaphragm. After the diseased lesions were removed, the graft was positioned on the plastic sheet and sutured to the recipient bed. The plastic sheet was pulled out from the anterior chamber before the all interrupted sutures were placed. The intra- and post-operative complications, the outcome of the graft and the number of corneal endothelial cells were analyzed. RESULTS: A total of 82 eyes of 82 patients was included. The mean follow-up period was 29 ± 16 months (range from 13 to 45 months). No intraocular content extrusion, simultaneous cataract extraction and suprachoroidal hemorrhage occurred. Direct contact between the infectious cornea and the graft was successfully avoided. Greater than expected endothelial cell reduction or complications were not found. CONCLUSIONS: This modified technique effectively prevents the extrusion of intraocular contents while avoiding the direct contact with donor endothelium during the procedure. The occurrence rate of complications such as endothelial cell loss is not higher than the conventional methods.

A novel pupilloplasty in crescent-shaped suturing pattern for coloboma and traumatic iris defects.

OBJECTIVE: PURPOSE: To observe the safety and effect of the C-pupilloplasty for the treatment of iris coloboma and traumatic iris defects. METHODS: A total of 21 cases (21 eyes) with iris coloboma or traumatic iris defects who underwent C-pupilloplasty (a single-pass three-throw technique) from Feb. 2016 to Mar. 2020 were analyzed retrospectively. Uncorrected visual acuity, refraction, corneal topographic keratometry and endothelial cell density were examined. RESULTS: All the patients were successfully treated, and a central and round pupil was restored. The mean follow-up duration was 8.76 ± 3.58 months (ranging from 2 to 14 months). All patients had round or round-like pupils with a diameter less than or equal to 3 mm after the C-pupilloplasty. Very slightly endothelial loss, negligible symptoms such as glare, distortion, dizziness and photophobia were observed. CONCLUSION: We introduced a new technique of pupilloplasty (C-pupilloplasty) which could be a more straight forward and more effective treatment for iris coloboma and traumatic iris defect.

Integrated Network Pharmacology and Molecular Docking to Elucidate the Efficacy and Potential Mechanisms of Tea Ingredients in Sepsis Treatment.

Sepsis, a critical health condition induced by an overactive innate immune response and reactive oxygen species (ROS)-driven host damage through apoptosis and ferroptosis, continues to pose a significant mortality risk. Despite accumulating evidence of the potential therapeutic properties of tea ingredients, their specific anti-sepsis potential remains inadequately explored. This study comprehensively investigates the targeted genes of tea ingredients, notably epigallocatechin 3-gallate (EGCG), and their correlation with sepsis signature genes. Our findings elucidate that tea ingredients, especially EGCG, exhibit substantial potential in mitigating inflammation and sepsis-induced damage. Through the inhibition of the MAPK cascade and macrophage activation and by impeding the transcriptional activity of RELA (transcription factor p65) in sepsis, EGCG demonstrates significant anti-sepsis efficacy. Molecular docking analysis further underpins this by revealing the close proximity of EGCG and (-)-catechin gallate binding sites to that of RELA on DNA. Subsequent in vitro assays illuminated EGCG's instrumental role in modulating macrophage M2 polarization, balancing M1 and M2 differentiation of bone marrow-derived macrophages (BMDMs), curtailing inflammatory factor secretion, and inhibiting ROS production. Moreover, EGCG effectively suppresses the expression of ferroptosis/apoptosis markers in LPS-induced macrophages during their early stages. Our study advances our understanding of sepsis prevention and treatment strategies, suggesting that tea ingredients such as EGCG could play a pivotal role in developing future sepsis therapies due to their protective effects.

How to Measure a Two-Sided Market.

Applying the theories of complex network and entropy measurement to the market, the two-sided market structure is analyzed in constructing the O2O platform transaction on the entropy measurement of the nodes and links. Market structure entropy (MSE) is initially introduced to measure the consistency degree of the individuals and the groups in the O2O market, according to the interaction in the profits, the time/space, and the information relationship. Considering that the market structure entropies are changing upward or downward, MSE is used to judge the consistency degree between the individuals and the groups. Respectively, considering the scale, the cost and the value dimensions, MSE is expanded to explain the market quality entropy, the market time-effect entropy, and the market capacity entropy.MSE provides a methodology in studying the O2O platform transaction and gives the quantitative index in the evaluation of the O2O market state.

Investigation on Atypical Pathogens related with Community Acquired Pneumonia and the Factors Associated with Mycoplasma Pneumoniae Infection in Jiangsu, China.

BACKGROUND: Community acquired pneumonia remains a leading infectious cause of hospitalization with substantial morbidity and mortality in China. At present, the role of atypical pathogens in CAP arouses peoples' concern. Previous studies indicated that MP was the dominant pathogen of CAP, but the associated factors of MP infection were rarely reported. METHODS: We retrospectively investigated the distribution of atypical pathogens related with CAP and compared their differences among various populations. Furthermore, we accessed the associated factors of MP infection in various population. RESULTS: A total of 3,675 patients were enrolled and divided into three groups. One thousand and eighty-nine subjects (29.6%) were infected with at least one atypical pathogen. MP was the most predominant pathogen in these CAP patients. Our study found that infection rates of the atypical pathogens were significantly different among three groups. Our results also revealed, in a pediatric group, as the temperature increased, so did the infection rate of MP, while it was the opposite in adult and elderly groups. Furthermore, in preschool and school-age children, high temperature, female, PIVs, ADV, and INFB infection were independent risk factors for MP infection, INFA infection was a protection factor for MP infection. However, in adult and elderly groups, the associated factors might be different. CONCLUSIONS: The infection of atypical pathogens related with CAP is quite serious, and MP infection plays a key role in CAP. Besides, the infection rates of the atypical pathogens are different in various populations, as are the associated factors for MP infection.

Cyclocarya paliurus extract attenuates hepatic lipid deposition in HepG2 cells by the lipophagy pathway.

CONTEXT: Cyclocarya paliurus (CP) (Batal.) Iljinsk (Cyclocaryaceae), a plant native to China, is the sole species in the genus Cyclocarya. Its leaves have been widely used as a remedy for hyperlipidaemia in traditional folk medicine. However, the mechanism underlying CP-induced lipolysis, especially in the liver, has not been entirely elucidated. OBJECTIVE: This study investigates the effect of CP ethanol extract (CPE) on hepatic steatosis and the underlying molecular mechanisms involved. MATERIALS AND METHODS: The effect of CPE at concentrations of 0, 6.25, 12.5, 25, 50, and 100 µg/mL on the viability of HepG2 cells was examined using the cell counting kit-8 (CCK-8) assay after incubation for 24 h. CPE-induced changes in intracellular lipid content were assessed by measuring the absorbance of oil red O staining at 520 nm, and the possible underlying mechanisms were further studied using quantitative reverse transcription polymerase chain reaction (RT-qPCR) analysis, western blotting, immunofluorescence studies and transmission electron microscopy. RESULTS: The half-maximal inhibitory concentration (IC50) of CPE in HepG2 cells was 97.27 µg/mL. Treatment with 50 µg/mL CPE increased lipid clearance, which was associated with increased autophagy in HepG2 cells. CPE-induced autophagy involved downregulation of phosphorylation level of mammalian target of rapamycin (0.87 ± 0.08 vs. 1.31 ± 0.10). Fluorescent double staining and electron microscopy images showed lipid deposits within autolysosomes, thereby confirming the abovementioned findings. DISCUSSION AND CONCLUSIONS: CPE can induce hepatic fat clearance through the autophagy-lysosome pathway known as lipophagy. CPE has potential as a functional food.

Comparison of a Newly Developed HPV Genotyping Assay (Mojin HPV Kit) with Cobas 4800 HPV Test for Detection of High-Risk HPV in Specimens Collected in SurePath Solution.

BACKGROUND: Human papillomavirus (HPV) detection based on cervical cytology specimens is useful for cervical cancer screening. The aim of this study was to compare Mojin HPV kit (a newly developed HPV genotyping assay) with the Cobas 4800 HPV test in detecting high-risk (HR) HPV. METHODS: A total of 347 cervical exfoliated cell specimens were tested using the Mojin HPV kit and Cobas 4800 HPV test. When the results from the two tests were inconsistent, gene sequencing was performed for correction. RESULTS: For HR-HPV, the results of the two assays agreed by 96.3% [Kappa = 0.911; 95% confidence interval (CI): 0.863 - 0.958)]. The positive and negative coincidence rates between the two tests were 96.0% (95% CI: 92.7% - 98.0%) and 97.0% (95% CI: 91.5% - 99.4%), respectively. Of the 13 samples with discordant results, 3 samples were false positive and 10 samples were true negative for Mojin HPV test, according to the identification by sequencing. For HPV16 genotyping, the total coincidence rate between the 2 tests was 100% (Kappa = 1.000), and 99.7% (Kappa = 0.973; 95% CI: 0.905 - 1.000) for HPV18. CONCLUSIONS: Mojin HPV kit may be as effective as Cobas 4800 HPV assay in detecting the total HR-HPV, especially HPV16 or HPV18.

The draft genome of Tibetan hulless barley reveals adaptive patterns to the high stressful Tibetan Plateau.

The Tibetan hulless barley (Hordeum vulgare L. var. nudum), also called "Qingke" in Chinese and "Ne" in Tibetan, is the staple food for Tibetans and an important livestock feed in the Tibetan Plateau. The diploid nature and adaptation to diverse environments of the highland give it unique resources for genetic research and crop improvement. Here we produced a 3.89-Gb draft assembly of Tibetan hulless barley with 36,151 predicted protein-coding genes. Comparative analyses revealed the divergence times and synteny between barley and other representative Poaceae genomes. The expansion of the gene family related to stress responses was found in Tibetan hulless barley. Resequencing of 10 barley accessions uncovered high levels of genetic variation in Tibetan wild barley and genetic divergence between Tibetan and non-Tibetan barley genomes. Selective sweep analyses demonstrate adaptive correlations of genes under selection with extensive environmental variables. Our results not only construct a genomic framework for crop improvement but also provide evolutionary insights of highland adaptation of Tibetan hulless barley.

Bystander mechanism for complement-initiated early oligodendrocyte injury in neuromyelitis optica.

Neuromyelitis optica spectrum disorder (herein called NMO) is an autoimmune inflammatory disease of the central nervous system in which immunoglobulin G antibodies against astrocyte water channel aquaporin-4 (AQP4-IgG) cause demyelination and neurological deficit. Injury to oligodendrocytes, which do not express AQP4, links the initiating pathogenic event of AQP4-IgG binding to astrocyte AQP4 to demyelination. Here, we report evidence for a complement 'bystander mechanism' to account for early oligodendrocyte injury in NMO in which activated, soluble complement proteins following AQP4-IgG binding to astrocyte AQP4 result in deposition of the complement membrane attack complex (MAC) on nearby oligodendrocytes. Primary cocultures of rat astrocytes and mature oligodendrocytes exposed to AQP4-IgG and complement showed early death of oligodendrocytes in close contact with astrocytes, which was not seen in pure oligodendrocyte cultures, in cocultures exposed to AQP4-IgG and C6-depleted serum, or when astrocytes were damaged by a complement-independent mechanism. Astrocyte-oligodendrocyte cocultures exposed to AQP4-IgG and complement showed prominent MAC deposition on oligodendrocytes in contact with astrocytes, whereas C1q, the initiating protein in the classical complement pathway, and C3d, a component of the alternative complement pathway, were deposited only on astrocytes. Early oligodendrocyte injury with MAC deposition was also found in rat brain following intracerebral injection of AQP4-IgG, complement and a fixable dead-cell stain. These results support a novel complement bystander mechanism for early oligodendrocyte injury and demyelination in NMO.

Aquaporin-Targeted Therapeutics: State-of-the-Field.

Drugs targeting aquaporins have broad potential clinical applications, including cancer, obesity, edema, glaucoma, skin diseases and others. The astrocyte water channel aquaporin-4 is a particularly compelling target because of its role of brain water movement, neuroexcitation and glia scarring, and because it is the target of pathogenic autoantibodies in the neuroinflammatory demyelinating disease neuromyelitis optica . There has been considerable interest in the identification of small molecule inhibitors of aquaporins, with various candidates emerging from testing of known ion transport inhibitors, as well as compound screening and computational chemistry. However, in general, the activity of reported aquaporin inhibitors has not been confirmed on retesting, which may be due to technical problems in water transport assays used in the original identification studies, and the challenges in modulating the activity of small, compact, pore-containing membrane proteins. We review here the state of the field of aquaporin-modulating small molecules and biologics, and the challenges and opportunities in moving forward.

Whole-genome sequencing of cultivated and wild peppers provides insights into Capsicum domestication and specialization.

As an economic crop, pepper satisfies people's spicy taste and has medicinal uses worldwide. To gain a better understanding of Capsicum evolution, domestication, and specialization, we present here the genome sequence of the cultivated pepper Zunla-1 (C. annuum L.) and its wild progenitor Chiltepin (C. annuum var. glabriusculum). We estimate that the pepper genome expanded ∼0.3 Mya (with respect to the genome of other Solanaceae) by a rapid amplification of retrotransposons elements, resulting in a genome comprised of ∼81% repetitive sequences. Approximately 79% of 3.48-Gb scaffolds containing 34,476 protein-coding genes were anchored to chromosomes by a high-density genetic map. Comparison of cultivated and wild pepper genomes with 20 resequencing accessions revealed molecular footprints of artificial selection, providing us with a list of candidate domestication genes. We also found that dosage compensation effect of tandem duplication genes probably contributed to the pungent diversification in pepper. The Capsicum reference genome provides crucial information for the study of not only the evolution of the pepper genome but also, the Solanaceae family, and it will facilitate the establishment of more effective pepper breeding programs.

Aquaporin Water Channels and Hydrocephalus.

The aquaporins (AQPs) are a family of water-transporting proteins that are broadly expressed in mammalian cells. Two AQPs in the central nervous system, AQP1 and AQP4, might play a role in hydrocephalus and are thus potential drug targets. AQP1 is expressed in the ventricular-facing membrane of choroid plexus epithelial cells, where it facilitates the secretion of cerebrospinal fluid (CSF). AQP4 is expressed in astrocyte foot processes and ependymal cells lining ventricles, where it appears to facilitate the transport of excess water out of the brain. Altered expression of these AQPs in experimental animal models of hydrocephalus and limited human specimens suggests their involvement in the pathophysiology of hydrocephalus, as do data in knockout mice demonstrating a protective effect of AQP1 deletion and a deleterious effect of AQP4 deletion in hydrocephalus. Though significant questions remain, including the precise contribution of AQP1 to CSF secretion in humans and the mechanisms by which AQP4 facilitates clearance of excess brain water, AQP1 and AQP4 have been proposed as potential drug targets to reduce ventricular enlargement in hydrocephalus.

[The design of weight-loss walking rehabilitation training system of differential-pressure style].

This research is to develop a weight-loss walking rehabilitation training system based on differential air pressure. The system adopted Proportion-Integral-Derivative (PID) algorithm to improve the precision of weight loss, taking MSP430F149 microprocessor of Texas Instruments as the core of pressure control system. The training software is designed based on Microsoft Visual C++ 6.0 of Microsoft. The system can provide comfortable training environment for patients with lower limb motor function impediment, and can collect electromyographic signals from patients, so as to further the scientific and normative management of the patient's information. Based on this training system, the initial bearing weight, bearing weight after maximum weight loss, and maximum weight loss percentage of 10 normal adults' lower limbs were collected. It was found that the intraclass correlation coefficient (ICC) values were all greater than 0.6. The training system has a good reliability, which can provide scientific data for clinical weight-loss lower limb rehabilitation training.

Aquaporin-4 regulates the velocity and frequency of cortical spreading depression in mice.

The astrocyte water channel aquaporin-4 (AQP4) regulates extracellular space (ECS) K(+) concentration ([K(+)]e) and volume dynamics following neuronal activation. Here, we investigated how AQP4-mediated changes in [K(+)]e and ECS volume affect the velocity, frequency, and amplitude of cortical spreading depression (CSD) depolarizations produced by surface KCl application in wild-type (AQP4(+/+)) and AQP4-deficient (AQP4(-/-)) mice. In contrast to initial expectations, both the velocity and the frequency of CSD were significantly reduced in AQP4(-/-) mice when compared with AQP4(+/+) mice, by 22% and 32%, respectively. Measurement of [K(+)]e with K(+)-selective microelectrodes demonstrated an increase to ∼35 mM during spreading depolarizations in both AQP4(+/+) and AQP4(-/-) mice, but the rates of [K(+)]e increase (3.5 vs. 1.5 mM/s) and reuptake (t1/2 33 vs. 61 s) were significantly reduced in AQP4(-/-) mice. ECS volume fraction measured by tetramethylammonium iontophoresis was greatly reduced during depolarizations from 0.18 to 0.053 in AQP4(+/+) mice, and 0.23 to 0.063 in AQP4(-/-) mice. Analysis of the experimental data using a mathematical model of CSD propagation suggested that the reduced velocity of CSD depolarizations in AQP4(-/-) mice was primarily a consequence of the slowed increase in [K(+)]e during neuronal depolarization. These results demonstrate that AQP4 effects on [K(+)]e and ECS volume dynamics accelerate CSD propagation.

Cyclocarya paliurus prevents high fat diet induced hyperlipidemia and obesity in Sprague-Dawley rats.

Cyclocarya paliurus (CP; qing qian liu), which is used as an herbal tea in China, has been confirmed to have therapeutic effects on hyperlipidemia and obesity, and therefore it is widely consumed to prevent metabolic diseases such as hyperlipidemia and diabetes. In this study, we investigated the preventive effects of CP on obesity and hyperlipidemia, as well as the underlying mechanisms involved in intestinal secretion of apolipoprotein (apo) B48. Sprague-Dawley rats were fed a high-fat diet (HFD) and with or without various concentrations of an ethanol extract of CP (CPE; 2, 4, or 8 g·(kg body mass)(-1)) administered by gavage for 8 weeks. From the results we see that CPE dose-dependently blocked increases in body mass, and decreased food utilization as well as visceral fat mass. Decreased serum levels of total cholesterol, triglycerides, and low density lipoprotein cholesterol, and elevated levels of high density lipoprotein cholesterol, as well as lowered levels of total cholesterol and triglycerides in the liver were also noticed in CPE-treated rats. Magnetic resonance images indicated that the abnormal fat storage induced by the HFD was obviously suppressed by CPE. In addition, ELISA analysis showed reduced fasting serum apoB48 in the CPE treatment groups. Based on the above results, CPE shows a promising preventive effect on obesity and hyperlipidemia, partially through suppressing intestinal apoB48 overproduction.

[Development of Muscle Strength Evaluating System Based on Mobile Platform].

The development of muscle strength evaluating system based on Android system was developed in this research. The system consists of a lower unit and an intelligent mobile terminal. The pressure sensor of the lower unit was used to collect muscle strength parameters. And the parameters were sent to the Android device through the wireless Bluetooth serial port. Then the Android device would send the parameters to the doctor monitored platform through the Internet. The system realized analyzing the muscle strength parameters and real-time displaying them. After it ran on the Android mobile phones, it showed an effective result which proved that the system combined with mobile platform could make more convenient for the patients to assess their own muscle strength. It also provided reliable data references for doctors to know the patients' rehabilitation condition and to make the next rehabilitation plan.

Serum microRNA-205 as a novel biomarker for cervical cancer patients.

OBJECTIVE: Serum microRNAs (miRNAs) are a novel class of diagnostic and prognostic biomarkers for numerous cancers. However, the level and clinical relevance of circulating miR-205 transcripts in human serum of cervical cancer patients are unclear. The purpose of this study was to determine serum miR-205 levels in cervical cancer patients and explore its association with clinicopathological factors and prognosis. METHODS: Serum miR-205 expression was investigated in 60 cervical cancer patients and 60 healthy normal controls by using real-time PCR. Correlations between miR-205 expression and the clinicopathological features and prognosis of cervical cancer patients were then evaluated. Receiver operating characteristic curves were used to evaluate the sensitivity and specificity of serum miR-205. RESULTS: Serum miR-205 was significantly upregulated in cervical cancer patients compared with healthy donors (p < 0.01), and a high level of miR-205 expression was correlated with poor tumor differentiation (p = 0.009), lymph node metastasis (p = 0.015) and increased tumor stage (p = 0.001). The serum miR-205 level was capable of separating advanced stage from early stage metastatic cervical cancer from non-metastatic samples and poorly differentiated tumors from differentiated tumors with an area under the curve values of 0.74, 0.694 and 0.717, respectively. The expression of miR-205 was also higher in the cervical cancer tissues compared with the para-carcinoma tissues. In addition, Kaplan-Meier survival analysis showed that cervical cancer patients with high miR-205 expression tended to have shorter overall survival. In multivariate Cox regression analysis, miR-205 was identified as an independent prognostic marker. CONCLUSIONS: Serum miR-205, which is upregulated in cervical cancer, represents a predictive biomarker for the prognosis of cervical cancer patients.