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Cystic kidney disease is the progressive development of multiple fluid-filled cysts that may severely compromise kidney functions and lead to renal failure. TNS1 (tensin-1) knockout mice develop cystic kidneys and die from renal failure. Here, we have established TNS1-knockout MDCK cells and applied 3D culture system to investigate the mechanism leading to cyst formation. Unlike wild-type MDCK cells, which form cysts with a single lumen, TNS1-knockout cysts contain multiple lumens and upregulated Mek/Erk activities. The multiple lumen phenotype and Mek/Erk hyperactivities are rescued by re-expression of wild-type TNS1 but not the TNS1 mutant lacking a fragment essential for its cell-cell junction localization. Furthermore, Mek inhibitor treatments restore the multiple lumens back to single lumen cysts. Mek/Erk hyperactivities are also detected in TNS1-knockout mouse kidneys. Treatment with the Mek inhibitor trametinib significantly reduces the levels of interstitial infiltrates, fibrosis and dilated tubules in TNS1-knockout kidneys. These studies establish a critical role of subcellular localization of TNS1 in suppressing Mek/Erk signaling and maintaining lumenogenesis, and provide potential therapeutic strategies by targeting the Mek/Erk pathway for cystic kidney diseases.

Ulcerative colitis (UC), a chronic and nonspecific inflammatory disease of the intestine, has become a prevalent global health concern. This guideline aims to equip clinicians and caregivers with effective strategies for the treatment and management of adult UC patients using traditional Chinese medicine (TCM). The guideline systematically evaluated contemporary evidence through the Grading of Recommendations Assessment, Development, and Evaluation framework. Additionally, it incorporated insights from ancient Chinese medical sources, employing the evidence grading method found in traditional TCM literature. The development process involved collaboration with multidisciplinary experts and included input from patients with UC. The guideline, based on a comprehensive review of available evidence, present 40 recommendations. They offer a condensed overview of TCM's role in understanding the pathogenesis, diagnosis, and treatment of UC, along with an assessment of the efficacy of various TCM‐based treatments. TCM exhibits promising outcomes in the treatment of UC. However, to establish its efficacy conclusively, further high‐quality clinical studies on TCM for UC are essential. [ABSTRACT FROM AUTHOR]

Esophageal tuberculosis (ET) is a rare infectious disease of the gastrointestinal tract. Awareness of ET is deficient due to its low incidence. Unexplained dysphagia and upper gastrointestinal bleeding are the most common symptoms of ET. The prognosis is generally good if patients are diagnosed properly and receive anti-tubercular treatment promptly. However, ET is difficult to differentiate from other diseases. Endoscopic techniques such as esophagogastroduodenoscopy (EGD), endoscopic ultrasonography (EUS), contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS), elastography, and endoscopic ultrasound--guided fine-needle aspiration (EUS-FNA) improve the diagnosis of ET. Thus, the characteristics of ET and other difficult-to-detect diseases according to EGD and EUS were summarized. Intriguingly, there is no literature relevant to the application of CH-EUS and elastography in ET. The authors' research center was first in introducing CH-EUS and elastography into the field of ET. The specific manifestation of ET based on CH-EUS was discovered for the first time. Correlative experience and representative cases were shared. The role of endoscopy in acquiring esophageal specimens and treatment for ET was also established. In this review, we aim to introduce a promising technology for the diagnosis and treatment of ET. [ABSTRACT FROM AUTHOR]

To investigate the relationship between cardiac diastolic dysfunction and outcomes in patients with pulmonary arterial hypertension (PAH) and to clarify the potential effect of two-dimensional echocardiography (2D-echo) on prognostic value in patients with PAH.Patients diagnosed with PAH (as WSPH (World Symposia on Pulmonary Hypertension) classification I) confirmed by right heart catheterization (RHC), received targeted monotherapy or combination therapy. 2D-echo parameters, World Health Organization (WHO) functional classification and 6-minute walking distance (6MWD) were recorded. The clinical prognosis of patients was assessed by the correlation between echo parameters and clinical 6MWD using receiver operating characteristic (ROC) curve analysis.Fifty-eight patients were included. Left and right ventricular diastolic dysfunction (LVDD and RVDD) scores measured by 2D-echo had good correlation with 6MWD at baseline (rLVDD = -0.699; rRVDD = -0.818, both P < 0.001) and at last follow-up (rLVDD = -0.701; rRVDD = -0.666, both P

Adaptation of enzymes in a metabolic pathway can occur not only through changes in amino acid sequences but also through variations in transcriptional activation, mRNA splicing and mRNA translation. The heme biosynthesis pathway, a linear pathway comprised of eight consecutive enzymes in animals, provides researchers with ample information for multiple types of evolutionary analyses performed with respect to the position of each enzyme in the pathway. Through bioinformatics analysis, we found that the protein-coding sequences of all enzymes in this pathway are under strong purifying selection, from cnidarians to mammals. However, loose evolutionary constraints are observed for enzymes in which self-catalysis occurs. Through comparative genomics, we found that in animals, the first intron of the enzyme-encoding genes has been co-opted for transcriptional activation of the genes in this pathway. Organisms sense the cellular content of iron, and through iron-responsive elements in the 5' untranslated regions of mRNAs and the intron-exon boundary regions of pathway genes, translational inhibition and exon choice in enzymes may be enabled, respectively. Pathway product (heme)-mediated negative feedback control can affect the transport of pathway enzymes into the mitochondria as well as the ubiquitin-mediated stability of enzymes. Remarkably, the positions of these controls on pathway activity are not ubiquitous but are biased towards the enzymes in the upstream portion of the pathway. We revealed that multiple-level controls on the activity of the heme biosynthesis pathway depend on the linear depth of the enzymes in the pathway, indicating a new strategy for discovering the molecular constraints that shape the evolution of a metabolic pathway.

Disposable gastroscopes have recently been developed to eliminate the risk of infection transmission from contaminated reusable gastroscopes. We compared the performance of disposable and reusable gastroscopes in patients undergoing gastroscopy. Patients requiring gastroscopy were randomized to either the disposable or reusable digital gastroscope group. The primary endpoint was the success rate of photographing customary anatomic sites, with a noninferiority margin of –8%. Secondary endpoints were technical performance factors such as gastroscope imaging quality, maneuverability, gastroscopy completion rate, device failure/defect rate, operating time, and safety. Data were analyzed using the Newcombe-Wilson score method and Fisher exact 2-tailed t test. Of 110 patients, 55 were treated using disposable gastroscopes and 55 using reusable gastroscopes. The success rate for capturing images of customary anatomic sites was 100% in both groups. The average imaging quality score was significantly lower (37.02 ± 3.09 vs 39.47 ± 1.92, P <.001) and the operating time significantly longer (P <.001) in the disposable gastroscope group. No significant differences in maneuverability, gastroscopy completion rate, device failure/defect rate, operating time, or safety were found between the 2 groups. Given the overall safety profile and similar technical performance, disposable gastroscopes represent an alternative to reusable gastroscopes for routine examination, bedside first aid, and some certain circumstances. [ABSTRACT FROM AUTHOR]

Background: Chronic stress is associated with activation of the HPA axis, elevation in pro‐inflammatory cytokines, decrease in intestinal epithelial cell tight junction (TJ) proteins, and enhanced visceral pain. It is unknown whether epigenetic regulatory pathways play a role in chronic stress–induced intestinal barrier dysfunction and visceral hyperalgesia. Methods: Young adult male rats were subjected to water avoidance stress ± H3K9 methylation inhibitors or siRNAs. Visceral pain response was assessed. Differentiated Caco‐2/BBE cells and human colonoids were treated with cortisol or IL‐6 ± antagonists. Expression of TJ, IL‐6, and H3K9 methylation status at gene promoters was measured. Transepithelial electrical resistance and FITC‐dextran permeability were evaluated. Key Results: Chronic stress induced IL‐6 up‐regulation prior to a decrease in TJ proteins in the rat colon. The IL‐6 level inversely correlated with occludin expression. Treatment with IL‐6 decreased occludin and induced visceral hyperalgesia. Chronic stress and IL‐6 increased H3K9 methylation and decreased transcriptional GR binding to the occludin gene promoter, leading to down‐regulation of protein expression and increase in paracellular permeability. Intrarectal administration of a H3K9 methylation antagonist prevented chronic stress–induced visceral hyperalgesia in the rat. In a human colonoid model, cortisol decreased occludin expression, which was prevented by the GR antagonist RU486, and IL‐6 increased H3K9 methylation and decreased TJ protein levels, which were prevented by inhibitors of H3K9 methylation. Conclusions & Inferences: Our findings support a novel role for methylation of the repressive histone H3K9 to regulate chronic stress, pro‐inflammatory cytokine–mediated reduction in colon TJ protein levels, and increase in paracellular permeability and visceral hyperalgesia. [ABSTRACT FROM AUTHOR]

The article deals with certain approaches and methods using the latest technology to improve the results of piano teaching. The aim of the study is to analyze and compare the most popular and latest technologies of learning to play the piano in terms of their availability, effectiveness and the need for a teacher. In the work, methods of synthesis and analysis, comparisons were used, with the help of which various technologies of learning to play the piano were studied. As a result, two approaches for introducing modern technologies have become apparent in piano teaching: making group lessons more interactive and increase the scope of individual learning along with the gradual withdrawal of the teacher. However, some new technical solutions are far from being ready for use by educational institutions and individuals; therefore, it currently seems relevant to combine modern technology with conventional music teaching practices. [ABSTRACT FROM AUTHOR]

Intrahepatic cholangiocarcinoma is a relatively uncommon malignant neoplasm. We recently encountered an unusual case of intrahepatic cholangiocarcinoma that histologically resembled a thyroid carcinoma. A thorough review of the English literature revealed only 2 similar cases that have been previously reported. Immunohistochemical studies are imperative to confirm the diagnosis of cholangiocarcinoma and to exclude the possibility of metastatic thyroid carcinoma and other malignancies with thyroid-like features. [ABSTRACT FROM AUTHOR]

The synthesis and membrane activity of eight oligoester bolaamphiphiles based on a terephthalate diester core with variable terminal groups is reported. The conductance activity observed in a majority of cases is predominantly erratic at the single-channel level. All active compounds show both Ohmic and non-linear current-voltage responses with some examples of rectified conductance. Non-linear responses arise from inherent asymmetry in the experimental system coupled with structures that must form dissymmetric hairpin insertions in the bilayer membrane. [ABSTRACT FROM PUBLISHER]

Fluid and ion secretion from the submandibular gland ( SMG) is mainly regulated by parasympathetic nerves. This study evaluated the effect of parasympathectomy on salivary secretion from normal and irradiated rat SMGs from 1 to 24 wk after denervation. Although stimulated salivary secretion was significantly lower in denervated SMGs compared with contralateral self-controls, the resting salivary flow rates were markedly higher in the denervated SMGs at 1, 12, and 24 wk after denervation. The levels of muscarinic acetylcholine M1 and M3 receptors, as well as of aquaporin 5, were up-regulated. Notably, although irradiated SMGs showed significantly lower resting and stimulated salivary secretion rates than non-irradiated SMGs, the resting salivary secretion rates of the irradiated and denervated SMGs were markedly higher than seen in the irradiated self-control SMGs at 1, 12, and 24 wk after parasympathectomy, and were even higher than seen in the non-irradiated sham-operated rats. The expression of M1 and M3 receptors was similarly elevated. Taken together, our results suggest that parasympathetic denervation increases resting salivary secretion of both normal and irradiated SMGs. This approach might provide a potential modality for relieving radiation-induced xerostomia, which is a common complication following treatment of head and neck cancer. [ABSTRACT FROM AUTHOR]

Four series of rodlike racemic Schiff base mesogens possessing different alkyl chains and two types of linkages, ester and alkynyl linkages, were synthesized and applied to induce cubic blue phases (BPs) in simple binary mixture systems. The mesophases of these Schiff base mesogens were confirmed by variable-temperature X-ray diffraction and the characteristic texture from polarized optical microscopy (POM). In general, when chiral additive S-(+)-2-octyl 4-(4-hexyloxybenzoyloxy)benzoate (S811; 20-40 wt %) is added into the rodlike racemic salicylaldimine-based mesogens, the cubic BPs could be observed and its temperature range is larger than 20 K. The widest temperature range of the cubic BP (35 K) can be observed in the blending mixture composed of rodlike racemic salicylaldimine-based mesogen OH-TIn possessing alkynyl linkage and 35-40 wt % S811. However, Schiff base mesogens possessing alkynyl linkage show a direct isotropic to chiral nematic transition when equal amount of chiral dopant is added. Notably, the termination temperature of BPs is very close to room temperature (ca. 35 °C) after 40.0 wt % S811 is added into the salicylaldimine-based mesogens possessing terminal alkyl chains and ester linkage. Interestingly, wide BPs (>30 K) can also be induced by adding chiral additive 1,4:3,6-dianhydro-2,5-bis[4-(n-hexyl-1-oxy)benzoic acid]sorbitol (ISO(6OBA)2) with a high helical twisting power into the racemic Schiff base mesogen possessing ester linkage. Cubic BPI and BPII can be confirmed by reflectance spectra and POM. The results of reflectance spectra indicate that the binary mixture composed of salicylaldimine-based mesogens and S811 easily exhibits a supercooling effect and induces BPI. However, only BPII can be observed in all binary mixtures containing Schiff base mesogens. On the basis of our experimental results and molecular modeling, we suppose that the values of biaxiality, polarizability, and the dipole moment of molecular geometry are the main factors that affect BP stabilization. [ABSTRACT FROM AUTHOR]

Although deep brain stimulation (DBS) has been a promising alternative for treating several neural disorders, the mechanisms underlying the DBS remain not fully understood. As rat models provide the advantage of recording and stimulating different disease-related regions simultaneously, this paper proposes a battery-less, implantable neuro-electronic interface suitable for studying DBS mechanisms with a freely-moving rat. The neuro-electronic interface mainly consists of a microsystem able to interact with eight different brain regions bi-directionally and simultaneously. To minimize the size of the implant, the microsystem receives power and transmits data through a single coil. In addition, particular attention is paid to the capability of recording neural activities right after each stimulation, so as to acquire information on how stimulations modulate neural activities. The microsystem has been fabricated with the standard 0.18 \mum CMOS technology. The chip area is 7.74 mm^2, and the microsystem is able to operate with a single supply voltage of 1 V. The wireless interface allows a maximum power of 10 mW to be transmitted together with either uplink or downlink data at a rate of 2 Mbps or 100 kbps, respectively. The input referred noise of recording amplifiers is 1.16 \muVrms, and the stimulation voltage is tunable from 1.5 V to 4.5 V with 5-bit resolution. After the electrical functionality of the microsystem is tested, the capability of the microsystem to interface with rat brain is further examined and compared with conventional instruments. All experimental results are presented and discussed in this paper. [ABSTRACT FROM PUBLISHER]

Background & Aims: Cyclooxygenase-2 (COX-2) is known to promote the carcinogenesis of esophageal squamous cell carcinoma (ESCC). There are no reports on whether microRNAs (miRNAs) regulate COX-2 expression in ESCC. This study investigated the effect of miR-101 on ESCC through modulating COX-2 expression in ESCC. Methods: Real-time quantitative reverse transcription–polymerase chain reaction (RT-PCR) was used to quantify miR-101 expression in ESCC clinical tissues and cell lines. The effects of miR-101 on ESCC progression were evaluated by cell counting kit-8 (CCK8), transwell migration and invasion assays, as well as by flow cytometry. The COX-2 and PEG2 levels were determined by western blot and enzyme-linked immunosorbent assays (ELISA). The luciferase reporter assay was used to verify COX-2 as a direct target of miR-101. The anti-tumor activity of miR-101 in vivo was investigated in a xenograft nude mouse model of ESCC. Results: Downregulation of miR-101 was confirmed through comparison of 30 pairs of ESCC tumor and adjacent normal tissues (P < 0.001), as well as in 11 ESCC cell lines and a human immortalized esophageal cell line (P < 0.001). Transfection of miR-101 in ESCC cell lines significantly suppressed cell proliferation, migration, and invasion (all P < 0.001). The antitumor effect of miR-101 was verified in a xenograft model. Furthermore, COX-2 was shown to be a target of miR-101. Conclusions: Overexpression of miR-101 in ESCC inhibits proliferation and metastasis. Therefore, the miR-101/COX-2 pathway might be a therapeutic target in ESCC. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between cardiac diastolic dysfunction and outcomes in patients with pulmonary arterial hypertension (PAH) and to clarify the potential effect of two-dimensional echocardiography (2D-echo) on prognostic value in patients with PAH. Methods: Patients diagnosed with PAH (as WSPH (World Symposia on Pulmonary Hypertension) classification I) confirmed by right heart catheterization (RHC), received targeted monotherapy or combination therapy. 2D-echo parameters, World Health Organization (WHO) functional classification and 6-minute walking distance (6MWD) were recorded. The clinical prognosis of patients was assessed by the correlation between echo parameters and clinical 6MWD using receiver operating characteristic (ROC) curve analysis. Results: Fifty-eight patients were included. Left and right ventricular diastolic dysfunction (LVDD and RVDD) scores measured by 2D-echo had good correlation with 6MWD at baseline (rLVDD  = −0.699; rRVDD  = −0.818, both P<0.001) and at last follow-up (rLVDD  = −0.701; rRVDD  = −0.666, both P<0.001). Furthermore, bi-ventricular (LVDD+RVDD) scores measured by 2D-echo had a better correlation with 6MWD at baseline and last follow-up (r = −0.831; r = −0.771, both P<0.001). ROC curve analysis showed that the area under curves (AUCs) for LVDD score, RVDD score and (LVDD+RVDD) scores were 0.823 (P<0.0001), 0.737 (P = 0.0002), and 0.825 (P<0.0001), respectively. Compared with ROC analysis of other single parameters, cardiac diastolic function score was more accurate in predicting survival in patients with PAH. Conclusion: LVDD score, RVDD score and (LVDD+RVDD) scores yielded a comprehensive quantitative assessment of LV and RV diastolic function that correlated moderately with clinical functional parameters and might be useful in the assessment of PAH. [ABSTRACT FROM AUTHOR]

In order to solve the problem that theoretical teaching and practice of knowledge are simple in the course of Measurement and Control, a teaching experiment platform was developed based on real industrial production process. This platform combines the advantages of televisions with the structure of general machines. Meanwhile, the platform uses the operating system of uC/OS--II, the controlling frame of STM32 and the sensor module of camera, encoder and optical grating ruler. It effectively broadens the horizon of students and lecture content, improves their ability of programming and designing. Therefore, the objectives of the lecture are naturally achieved. [ABSTRACT FROM AUTHOR]