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Objective: The objective of this study was to develop a combined model based on radiomics features of Sonazoid contrast-enhanced ultrasound (CEUS) during the Kupffer phase and to evaluate its value in differentiating well-differentiated hepatocellular carcinoma (w-HCC) from atypical benign focal liver lesions (FLLs). Methods: A total of 116 patients with preoperatively Sonazoid-CEUS confirmed w-HCC or benign FLL were selected from a prospective multiple study on the clinical application of Sonazoid in FLLs conducted from August 2020 to March 2021. According to the randomization principle, the patients were divided into a training cohort and a test cohort in a 7:3 ratio. Seventy-nine patients were used for establishing and training the radiomics model and combined model. In comparison, 37 patients were used for validating and comparing the performance of the models. The diagnostic efficacy of the models for w-HCC and atypical benign FLLs was evaluated using ROCs curves and decision curves. A combined model nomogram was created to assess its value in reducing unnecessary biopsies. Results: Among the patients, there were 55 cases of w-HCC and 61 cases of atypical benign FLLs, including 28 cases of early liver abscess, 16 cases of atypical hepatic hemangioma, 8 cases of hepatocellular dysplastic nodules (DN), and 9 cases of focal nodular hyperplasia (FNH). The radiomics model and combined model we established had AUCs of 0.905 and 0.951, respectively, in the training cohort, and the AUCs of the two models in the test cohort were 0.826 and 0.912, respectively. The combined model outperformed the radiomics feature model significantly. Decision curve analysis demonstrated that the combined model achieved a higher net benefit within a specific threshold probability range (0.25 to 1.00). A nomogram of the combined model was developed. Conclusion: The combined model based on the radiomics features of Sonazoid-CEUS in the Kupffer phase showed satisfactory performance in diagnosing w-HCC and atypical benign FLLs. It can assist clinicians in timely detecting malignant FLLs and reducing unnecessary biopsies for benign diseases. [ABSTRACT FROM AUTHOR]

Norepinephrine transporter (NET; encoded by SLC6A2) reuptakes the majority of the released noradrenaline back to the presynaptic terminals, thereby affecting the synaptic noradrenaline level1. Genetic mutations and dysregulation of NET are associated with a spectrum of neurological conditions in humans, making NET an important therapeutic target1. However, the structure and mechanism of NET remain unclear. Here we provide cryogenic electron microscopy structures of the human NET (hNET) in three functional states—the apo state, and in states bound to the substrate meta-iodobenzylguanidine (MIBG) or the orthosteric inhibitor radafaxine. These structures were captured in an inward-facing conformation, with a tightly sealed extracellular gate and an open intracellular gate. The substrate MIBG binds at the centre of hNET. Radafaxine also occupies the substrate-binding site and might block the structural transition of hNET for inhibition. These structures provide insights into the mechanism of substrate recognition and orthosteric inhibition of hNET.Structures of human NET in the apo state and bound to meta-iodobenzylguanidine and radafaxine provide insights into the mechanism of substrate recognition and orthosteric inhibition of hNET. [ABSTRACT FROM AUTHOR]

Cotesia ruficrus (Hymenoptera: Braconidae) is an endoparasitic natural enemy of various Lepidopteran pests, and it plays a significant role in integrated pest management. In the field survey of maize fields, we found for the first time that the indigenous parasitoid C. ruficrus parasitized the major invasive pest Spodoptera frugiperda (Lepidoptera: Noctuidae) in China. We identified 18 odorant-binding proteins (CrufOBPs) of C. ruficrus through the RNA-Seq method, and PCR analysis showed that 13 out of the CrufOBPs were highly expressed in antennae. Two CrufOBPs, CrufOBP3 with the highest antennal expression and CrufOBP17 with antenna-specific expression, were selected for protein biosynthesis in the prokaryotic protein expression system and subjected to protein purification. Through fluorescence binding assay, seven maize volatile compounds were selected for the antennal electroantennography (EAG) study, and the results indicated that female C. ruficrus exhibited distinct responses to these volatiles at different concentrations. Octanal and 2-heptanone of 10 mg mL−1 were chosen for olfactory behavioral experiments because of their high EAG responses, and the results showed that C. ruficrus adults were significantly attracted at certain concentrations. Furthermore, in the cage experiments, 10 mg mL−1 of 2-heptanone significantly increased the parasitism rate of C. ruficrus on S. frugiperda. These findings not only provide a theoretical basis for studying the odorant-binding protein family of C. ruficrus but also contribute to the development of novel pest control strategies for this invasive pest management. [ABSTRACT FROM AUTHOR]

This study conducted and evaluated 44 experiments using the non-hydrostatic version of the regional climate model RegCM4 (RegCM4-NH) and an additional three experiments with RegCM version 5 (RegCM5) over Southeast Asia for the period 2010–2015. The initiative was part of the coordinated regional climate downscaling experiment—Southeast Asia (CORDEX-SEA) project, in preparation for downscaling the latest coupled model intercomparison project Phase 6 (CMIP6) global climate models (GCMs). The RegCM4-NH experiments, forced by the ERA5 reanalysis, were configured using combinations of four cumulus, three planetary boundary layer (PBL), and three explicit moisture schemes. The spatiotemporal variability of simulated 2 m-temperature and rainfall for 2010–2015 was evaluated against observational datasets. The best experiments demonstrated reasonable reproduction of observed annual cycles and spatial distribution, while many exhibited unrealistic biases. A score ranking system was implemented to objectively compare the performance of experiments, enabling the identification of top-ranked experiments for Southeast Asia. The ensemble mean of the 44 RegCM4-NH experiments exhibited commendable performance, ranking 11th overall. Furthermore, the three additional RegCM5 experiments did not yield improved results compared to RegCM4-NH under the same physical configuration, suggesting that opting for RegCM4-NH would be a prudent choice for the CORDEX-SEA community in the forthcoming CMIP6 downscaling cycle for Southeast Asia. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the diagnostic performance of attenuation coefficient (AC), hepato-renal index (HRI) and controlled attenuation parameter (CAP) in quantitative assessment of hepatic steatosis by employing histopathology as reference standard. Methods: Participants with suspected metabolic-associated fatty liver disease (MAFLD) who underwent US-based parameter examinations and liver biopsy were prospectively recruited. The distributions of US parameters across different grades of steatosis were calculated, and diagnostic performance was determined based on the areas under the receiver operating characteristic curve (AUC). Results: A total of 73 participants were included, with hepatic steatosis grades S0, S1, S2, and S3 distributed as follows: 13, 20, 27, and 13 respectively. The correlation coefficients for CAP, AC, and HRI ranged from 0.67 to 0.74. AC and HRI showed a strong correlation with steatosis grade. The AUC for CAP and AC in diagnosing steatosis ≥ S1 were significantly higher at 0.99 and 0.98 compared to HRI's value. For diagnosing steatosis ≥ S2, the AUC of CAP (AUC: 0.85) was lower than that of AC (AUC: 0.94), and HRI (AUC: 0.94). Similarly for diagnosing steatosis S3, the AUC of CAP (AUC: 0.68) was lower than that of AC (AUC: 0.88), and HRI (AUC: 0.88). Conclusion: The AC and HRI values increased with the progression of hepatic steatosis grade, while CAP increased from S0 to S2 but not from S2 to S3. For mild steatosis diagnosis, CAP and AC showed superior diagnostic performance compared to HRI, while AC and HRI were more advantageous in differentiating moderate and severe steatosis. [ABSTRACT FROM AUTHOR]

Copyright of Rare Metals is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: To assess the use of evidence-based research (EBR) approach in randomized controlled trials (RCTs) of acupuncture-related therapies for primary dysmenorrhea (PD). Methods: PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, Chinese Biomedical Database, and China Science and Technology Journal Database were searched from January 2013 to December 2022 for RCTs of acupuncture on PD. The full text and references of each RCT were read to assess whether systematic reviews (SRs) or other types of studies with similar research questions and end-users' perspectives were cited to justify and design the trial. In addition, the discussion section were analyzed to evaluate whether trials placed the new result in the existing SRs to draw a conclusion. Multivariable logistic regression was used to find variables that associated with 3 aspects of EBR approach: (1) citing clinical studies for justification, (2) citing relevant studies that obtain the perspectives of end users, and (3) citing clinical studies for results discussion. Results: Of 473 RCTs included, 45.67% (216) of the trials cited relevant similar studies, 21.56% (102) referenced to the studies that collected end-users' perspectives, and 10.99% (52) placed result in the context of the previous research. Few RCTs appropriately applied EBR approach. Among all the included studies, 3.17% (15) of the trials used SRs to inform study questions but none of them used updated SRs with acceptable quality; 1.05% (5) of the trials cited SRs of end-user's perspectives in the justification and design of the study, and only 1 trial added results in existing SR to draw a conclusion. Year of publication, language, funding, registration, ethical approval and number of sites were significantly associated with 1 of the 3 aspects of EBR approach. Conclusions: Few RCTs in acupuncture-related therapies for PD used the EBR approach to minimize research redundancy. Researchers, research institutes, funding agencies, ethics committees, journals and peer reviewers in acupuncture should make efforts to use and promote the EBR approach to ensure the value of new trials. [ABSTRACT FROM AUTHOR]

Since OpenAI opened access to ChatGPT, large language models (LLMs) become an increasingly popular topic attracting researchers' attention from abundant domains. However, public researchers meet some problems when developing LLMs given that most of the LLMs are produced by industries and the training details are typically unrevealed. Since datasets are an important setup of LLMs, this paper does a holistic survey on the training datasets used in both the pre-train and fine-tune processes. The paper first summarizes 16 pre-train datasets and 16 fine-tune datasets used in the state-of-the-art LLMs. Secondly, based on the properties of the pre-train and fine-tune processes, it comments on pre-train datasets from quality, quantity, and relation with models, and comments on fine-tune datasets from quality, quantity, and concerns. This study then critically figures out the problems and research trends that exist in current LLM datasets. The study helps public researchers train and investigate LLMs by visual cases and provides useful comments to the research community regarding data development. To the best of our knowledge, this paper is the first to summarize and discuss datasets used in both autoregressive and chat LLMs. The survey offers insights and suggestions to researchers and LLM developers as they build their models, and contributes to the LLM study by pointing out the existing problems of LLM studies from the perspective of data. [ABSTRACT FROM AUTHOR]

Background: The effects of acupuncture have varied in different randomized controlled trials (RCTs), and there are many factors that influence treatment effect of acupuncture in different outcomes, with conflicting results. Objective: To identify factors and their impact on the treatment effect of acupuncture in different outcomes. Methods: Acupuncture RCTs were searched from 7 databases including Medline (PubMed), Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and China Biology Medicine disc between January 1st, 2015 and December 31st, 2019. Eligible studies must compare acupuncture to no acupuncture, sham acupuncture, or waiting lists, and report at least 1 patient-important outcome. A multi-level meta-regression was conducted using a 3-level robust mixed model and univariate analyses were performed for all independent variables, even those excluded from the multivariable model due to collinearities. We used thresholds of 0.2 and 0.4 for the difference of standardized mean differences (SMDs), categorising them as small (<0.2), moderate (0.2–0.4), or large (>0.4) effects. Results: The pain construct analysis involved 211 effect estimates from 153 studies and 14 independent variables. High-frequency acupuncture treatment sessions produced larger effects compared to low-frequency sessions [large magnitude, the difference of adjusted SMDs 0.46, 95% confidence interval (CI) 0.07 to 0.84; P=0.02]. The non-pain symptoms construct analysis comprised 323 effect estimates from 231 studies and 15 independent variables. Penetrating acupuncture showed moderately larger effects when compared to non-penetrating acupuncture (0.30, 95% CI 0.06 to 0.53; P=0.01). The function construct analysis included 495 effect estimates from 274 studies and 14 independent variables. Penetrating acupuncture and the flexible acupuncture regimen showed moderately larger effects, compared to non-penetrating acupuncture and fixed regimen, respectively (0.40, 95% CI 0 to 0.80; P=0.05; 0.29, 95% CI 0.06 to 0.53; P=0.01). Conclusions: High-frequency acupuncture sessions appear to be a more effective approach to managing painful symptoms. Penetrating acupuncture demonstrated greater effect in relieving non-painful symptoms. Both penetrating acupuncture type and flexible acupuncture regimen were linked to significant treatment effects in function outcomes. Future studies should consider the factors that are significantly associated with the effects of acupuncture in patient-important outcomes. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to develop a predictive model based on Sonazoid contrast-enhanced ultrasound (SCEUS) and clinical features to discriminate poorly differentiated hepatocellular carcinoma (P-HCC) from intrahepatic cholangiocarcinoma (ICC). Patients and method: Forty-one ICC and forty-nine P-HCC patients were enrolled in this study. The CEUS LI-RADS category was assigned according to CEUS LI-RADS version 2017. Based on SCEUS and clinical features, a predicated model was established. Multivariate logistic regression analysis and LASSO logistic regression were used to identify the most valuable features, 400 times repeated 3-fold cross-validation was performed on the nomogram model and the model performance was determined by its discrimination, calibration, and clinical usefulness. Results: Multivariate logistic regression and LASSO logistic regression indicated that age (> 51 y), viral hepatitis (No), AFP level (≤ 20 µg/L), washout time (≤ 45 s), and enhancement level in the Kupffer phase (Defect) were valuable predictors related to ICC. The area under the receiver operating characteristic (AUC) of the nomogram was 0.930 (95% CI: 0.856–0.973), much higher than the subjective assessment by the sonographers and CEUS LI-RADS categories. The calibration curve showed that the predicted incidence was more consistent with the actual incidence of ICC, and 400 times repeated 3-fold cross-validation revealed good discrimination with a mean AUC of 0.851. Decision curve analysis showed that the nomogram could increase the net benefit for patients. Conclusions: The nomogram based on SCEUS and clinical features can effectively differentiate P-HCC from ICC [ABSTRACT FROM AUTHOR]

Copyright of Rare Metals is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives: The aim of this study was to evaluate the potential of Sonazoid contrast-enhanced ultrasound (SNZ-CEUS) as an imaging biomarker for preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC). Methods: From August 2020 to March 2021, we conducted a prospective multicenter study on the clinical application of Sonazoid in liver tumor; a MVI prediction model was developed and validated by integrating clinical and imaging variables. Multivariate logistic regression analysis was used to establish the MVI prediction model; three models were developed: a clinical model, a SNZ-CEUS model, and a combined model and conduct external validation. We conducted subgroup analysis to investigate the performance of the SNZ-CEUS model in non-invasive prediction of MVI. Results: Overall, 211 patients were evaluated. All patients were split into derivation (n = 170) and external validation (n = 41) cohorts. Patients who had MVI accounted for 89 of 211 (42.2%) patients. Multivariate analysis revealed that tumor size (> 49.2 mm), pathology differentiation, arterial phase heterogeneous enhancement pattern, non-single nodular gross morphology, washout time (< 90 s), and gray value ratio (≤ 0.50) were significantly associated with MVI. Combining these factors, the area under the receiver operating characteristic (AUROC) of the combined model in the derivation and external validation cohorts was 0.859 (95% confidence interval (CI): 0.803–0.914) and 0.812 (95% CI: 0.691–0.915), respectively. In subgroup analysis, the AUROC of the SNZ-CEUS model in diameter ≤ 30 mm and ˃ 30 mm cohorts were 0.819 (95% CI: 0.698–0.941) and 0.747 (95% CI: 0.670–0.824). Conclusions: Our model predicted the risk of MVI in HCC patients with high accuracy preoperatively. Clinical relevance statement: Sonazoid, a novel second-generation ultrasound contrast agent, can accumulate in the endothelial network and form a unique Kupffer phase in liver imaging. The preoperative non-invasive prediction model based on Sonazoid for MVI is helpful for clinicians to make individualized treatment decisions. Key Points: • This is the first prospective multicenter study to analyze the possibility of SNZ-CEUS preoperatively predicting MVI. • The model established by combining SNZ-CEUS image features and clinical features has high predictive performance in both derivation cohort and external validation cohort. • The findings can help clinicians predict MVI in HCC patients before surgery and provide a basis for optimizing surgical management and monitoring strategies for HCC patients. [ABSTRACT FROM AUTHOR]

The latest guideline about ulcerative colitis (UC) clinical practice stresses that mucosal healing, rather than anti-inflammation, is the main target in UC clinical management. Current mucosal dysfunction mainly closely relates to the endoscopic intestinal wall (mechanical barrier) injury with the imbalance between intestinal epithelial cells (IECs) regeneration and death, as well as tight junction (TJ) dysfunction. It is suggested that biological barrier (gut microbiota), chemical barrier (mucus protein layer, MUC) and immune barrier (immune cells) all take part in the imbalance, leading to mechanical barrier injury. Lots of experimental studies reported that acupuncture and moxibustion on UC recovery by adjusting the gut microbiota, MUC and immune cells on multiple targets and pathways, which contributes to the balance of IEC regeneration and death, as well as TJ structure recovery in animals. Moreover, the validity and superiority of acupuncture and moxibustion were also demonstrated in clinic. This study aims to review the achievements of acupuncture and moxibustion on mucosal healing and analyse the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Objective: To summarize and identify the available instruments/methods assessing the adequacy of acupuncture in randomized controlled trials (RCTs) for proposing a new improved instrument. Methods: A systematic literature search was carried out in 7 electronic databases from inception until 21st November 2022. Any study evaluating the adequacy or quality of acupuncture, specifying specific acupuncture treatment-related factors as criteria of subgroup analysis, or developing an instrument/tool to assess the adequacy or quality of acupuncture in an RCT was included. Basic information, characteristics and contents of acupuncture adequacy assessment were presented as frequencies and percentages. Results: Forty studies were included in this systematic review. Thirty-five studies (87.50%) were systematic reviews, none of which used formal methods to develop the assessment instruments/methods of acupuncture adequacy; of 5 methodological studies, only 1 study used a relatively formal method. Thirty-two studies (82.05%) assessed the components of acupuncture, while 7 (17.95%) assessed the overall quality of acupuncture. An independent assessment instrument/method was used to assess acupuncture adequacy in 29 studies (74.35%), whereas as one part of a methodological quality assessment scale in 10 (25.65%). Only 9 (23.00%) studies used the assessment results for subgroup analysis, sensitivity analysis or the criteria for inclusion in the meta-analysis. Conclusion: Assessment contents for adequacy or quality of acupuncture in RCTs hadn't still reached consensus and no widely used assessment tools appeared. The methodology of available assessment instruments/scales is far from formal and rigorous. A new instrument/tool assessing adequacy of acupuncture should be developed using a formal method. [ABSTRACT FROM AUTHOR]

KATP channels are metabolic sensors for intracellular ATP/ADP ratios, play essential roles in many physiological processes, and are implicated in a spectrum of pathological conditions. SUR2A-containing KATP channels differ from other subtypes in their sensitivity to Mg-ADP activation. However, the underlying structural mechanism remains poorly understood. Here we present a series of cryo-EM structures of SUR2A in the presence of different combinations of Mg-nucleotides and the allosteric inhibitor repaglinide. These structures uncover regulatory helix (R helix) on the NBD1-TMD2 linker, which wedges between NBD1 and NBD2. R helix stabilizes SUR2A in the NBD-separated conformation to inhibit channel activation. The competitive binding of Mg-ADP with Mg-ATP to NBD2 mobilizes the R helix to relieve such inhibition, allowing channel activation. The structures of SUR2B in similar conditions suggest that the C-terminal 42 residues of SUR2B enhance the structural dynamics of NBD2 and facilitate the dissociation of the R helix and the binding of Mg-ADP to NBD2, promoting NBD dimerization and subsequent channel activation. Cardiac KATP channels consisting of SUR2A are poorly activated by Mg-ADP compared to other subtypes. Here, the authors present structures of SUR2A and SUR2B, uncovering a regulatory helix that inhibits SUR2A activation. [ABSTRACT FROM AUTHOR]

The Dandy–Walker malformation (DWM) is characterized by neuron dysregulation in embryonic development; however, the regulatory mechanisms associated with it are unclear. This study aimed to investigate the role of NADH dehydrogenase 1 alpha subcomplex 4 (NDUFA4) in regulating downstream signaling cascades and neuronal proliferation and apoptosis. Ndufa4 overexpression promoted the proliferation of neurons and inhibited their apoptosis in vitro, which underwent reverse regulation by the Ndufa4 short hairpin RNAs. Ndufa4-knockout (KO) mice showed abnormal histological alterations in the brain tissue, in addition to impaired spatial learning capacity and exploratory activity. Ndufa4 depletion altered the microRNA expressional profiles of the cerebellum: Ndufa4 inhibited miR-145a-5p expression both in the cerebellum and neurons. miR-145a-5p inhibited the proliferation of neurons and promoted their apoptosis. Ndufa4 promoted and miR-145a-5p inhibited the expression of human homer protein homolog 1 and cyclin D2 in neurons. Thus, Ndufa4 promotes the proliferation of neurons and inhibits their apoptosis by inhibiting miR-145a-5p, which directly targets and inhibits the untranslated regions of Homer1 and Ccnd2 expression. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to evaluate the safety of the ultrasound contrast agent sulfur hexafluoride microbubbles in a large group of patients referred for routine contrast-enhanced ultrasound (CEUS). Methods: A retrospective assessment was made of all patients that received sulfur hexafluoride microbubbles intravenously for CEUS at 24 centers between January 2006 and April 2019. Patient demographic details, examination type, and the dose of sulfur hexafluoride microbubbles administered were recorded with specific adverse events (AEs) documentation tools at each center. All AEs were recorded as serious or non-serious. Non-serious AEs were classified by intensity as mild, moderate, or severe according to ACR criteria. The frequencies of AEs across patient subgroups were compared using the chi-square test. Results: A total of 463,434 examinations were evaluated. Overall, 157 AEs (153 [0.033%] non-serious; 4 [0.001%] serious) were reported after sulfur hexafluoride microbubbles administration, giving an AE frequency of 0.034% (157/463,434). Among the non-serious AEs, 66 (0.014%) were mild, 70 (0.015%) moderate, and 17 (0.004%) severe in intensity. The liver was the most common examination site, presenting an AE frequency of 0.026%. The highest AE frequency (0.092%) was for patients undergoing CEUS for vascular disease. There were no significant gender differences in either the total number or the severity of non-serious AEs (chi-square = 2.497, p = 0.287). The onset of AEs occurred within 30 min of sulfur hexafluoride microbubbles administration in 91% of cases. Conclusion: The frequency of AEs to sulfur hexafluoride microbubbles is very low and severe reactions are rare, confirming that sulfur hexafluoride microbubbles are appropriate for routine CEUS applications. Key Point: • The frequency of AEs to sulfur hexafluoride microbubbles is very low and severe reactions are rare. [ABSTRACT FROM AUTHOR]

Objective: To observe the pressure pain threshold (PPT), skin conductance (SC) and blood perfusion (BP) of the sensitized acupoints in patients with knee osteoarthritis (KOA), and explore the mechanism of acupuncture at the sensitized acupoints for treating diseases. Methods: Eleven healthy subjects and 11 unilateral KOA patients were recruited from July 2020 to March 2021 in this study. The PPT, SC and BP of control acupoints in healthy controls, and non-sensitized and sensitized acupoints in KOA patients were measured and compared between baseline and after manual acupuncture (MA) treatment. Results: Before MA treatment, lower PPT was observed at the sensitized acupoints compared with non-sensitized and control acupoints (P<0.05). After MA treatment, PPT at the sensitized acupoints increased significantly in KOA patients (P<0.05). Before MA treatment, there was no statistical difference in SC and BP among control, non-sensitized and sensitized acupoints (P>0.05). Compared with the control and non-sensitized acupoints, there were significant increases of SC and BP in sensitized acupoints of KOA patients after MA treatment (P<0.05 or P<0.01). Conclusion: MA at sensitized acupoints could elevate PPT of KOA patients, which may be associated with the increment of SC and BP. [ABSTRACT FROM AUTHOR]

ATP-sensitive potassium channels (KATP) are metabolic sensors that convert the intracellular ATP/ADP ratio to the excitability of cells. They are involved in many physiological processes and implicated in several human diseases. Here we present the cryo-EM structures of the pancreatic KATP channel in both the closed state and the pre-open state, resolved in the same sample. We observe the binding of nucleotides at the inhibitory sites of the Kir6.2 channel in the closed but not in the pre-open state. Structural comparisons reveal the mechanism for ATP inhibition and Mg-ADP activation, two fundamental properties of KATP channels. Moreover, the structures also uncover the activation mechanism of diazoxide-type KATP openers. KATP channels are energy sensors. Here, authors report the Cryo-EM structures of pancreatic KATP in both the closed state and the pre-open state. These structures illuminate the mechanism of KATP channel regulation by the intracellular nucleotides. [ABSTRACT FROM AUTHOR]

ATP-sensitive potassium channels (KATP), composed of Kir6 and SUR subunits, convert the metabolic status of the cell into electrical signals. Pharmacological activation of SUR2- containing KATP channels by class of small molecule drugs known as KATP openers leads to hyperpolarization of excitable cells and to vasodilation. Thus, KATP openers could be used to treat cardiovascular diseases. However, where these vasodilators bind to KATP and how they activate the channel remains elusive. Here, we present cryo-EM structures of SUR2A and SUR2B subunits in complex with Mg-nucleotides and P1075 or levcromakalim, two chemically distinct KATP openers that are specific to SUR2. Both P1075 and levcromakalim bind to a common site in the transmembrane domain (TMD) of the SUR2 subunit, which is between TMD1 and TMD2 and is embraced by TM10, TM11, TM12, TM14, and TM17. These KATP openers synergize with Mg-nucleotides to stabilize SUR2 in the NBD-dimerized occluded state to activate the channel. SUR2-containing KATP channels are drug targets for certain vasodilators. Here, the authors determine high-resolution cryo-EM structures of SUR2 in complex with two vasodilators, P1075 and levcromakalim, uncovering the mechanisms of these drugs. [ABSTRACT FROM AUTHOR]

Objectives: To identify, examine and summarize the available evidence on the effectiveness and safety of acupuncture for in vitro fertilisation (IVF) outcomes. Methods: Eight electronic databases, including PubMed, EMBASE, Cochrane Database of Systematic Review, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang Database, Chinese Biomedical Database and VIP Database, were searched, supplemented by manual searches. Two researchers independently conducted the literature screening, data extraction, and methodological quality assessments. A narrative description was provided to show the general information and specific characteristics of the included studies. A bubble plot was used to visually display the overall effects of acupuncture on IVF outcomes. Results: Eighty-two studies were identified, including 64 primary studies and 18 systematic reviews. Transcutaneous electrical acupoint stimulation, electric acupuncture and manual acupuncture were applied in most studies and compared with no acupuncture, sham acupuncture and placebo acupuncture control groups. Sixty-three (98.4%) primary studies reported clinical pregnancy rate, and positive effects of acupuncture were found in 34 studies (54.0%). Live birth rate was reported in only 18 (28.1%) primary studies, of which 10 (55.6%) showed positive results. In addition, only 8 and 2 systematic reviews showed that acupuncture could increase clinical pregnancy events and live birth events, respectively. However, none of these reviews was of high methodological quality. Conclusions: Available evidence suggests that acupuncture therapy could improve clinical pregnancy rates. However, whether acupuncture could increase live birth events was difficult to determine based on the few studies that have reported this outcome indicator. Furthermore, the methodological quality of most systematic reviews was assessed as critically low or low. Studies with a rigorous design and standardized implementation should be performed to refine the available evidence. [ABSTRACT FROM AUTHOR]

Background and aims: Hepato-renal index (HRI) has been investigated extensively in various clinical studies. New linear scale HRI (LS-HRI) is proposed as an alternative to conventional grayscale HRI (GS-HRI) that suffers from lack of a widely accepted cut-off value for differentiation of fatty from normal livers. To investigate the diagnostic performance of conventional GS-HRI and new LS-HRI for a relatively large Chinese population with NAFLD using a well-established ultrasonographic fatty liver indicator (US-FLI) as the reference standard for steatosis grades. Materials and methods: A total of 106 patients with various stages of NAFLD were prospectively enrolled. All ultrasound images for these patients were first acquired by a highly experienced ultrasound doctor and their US-FLI scores then obtained by the same doctor. Both GS-HRI and LS-HRI values were measured off-line by two additional ultrasound doctors. Four steatosis grades were determined from US-FLI scores for steatosis detection and staging. Results: Inter-observer agreements for both GS-HRI and LS-HRI were excellent with the respective concordance correlation coefficient (CCC) of 0.900 for GS-HRI and 0.822 for LS-HRI. A linear correlation to US-FLI for LS-HRI (R = 0.74) was substantially superior to that for GS-HRI (R = 0.46). LS-HRI had a sensitivity of 85.9% and a specificity of 96.3% to differentiate steatosis from the normal liver (AUROC: 95.5%) while GS-HRI had a sensitivity of 85.9% and a specificity of 92.6% to distinguish steatosis from the normal liver (AUROC: 94.7%). Conclusions: Both GS-HRI and LS-HRI measurements are reproducible between two ultrasonographic clinicians and are evidently effective for steatosis detection. [ABSTRACT FROM AUTHOR]

Plants use nitrate and ammonium as major nitrogen (N) sources, each affecting root development through different mechanisms. However, the exact signaling pathways involved in root development are poorly understood. Here, we show that, in Arabidopsis thaliana, either disruption of the cell wall-localized ferroxidase LPR2 or a decrease in iron supplementation efficiently alleviates the growth inhibition of primary roots in response to NH4+ as the N source. Further study revealed that, compared with nitrate, ammonium led to excess iron accumulation in the apoplast of phloem in an LPR2-dependent manner. Such an aberrant iron accumulation subsequently causes massive callose deposition in the phloem from a resulting burst of reactive oxygen species, which impairs the function of the phloem. Therefore, ammonium attenuates primary root development by insufficiently allocating sucrose to the growth zone. Our results link phloem iron to root morphology in response to environmental cues. Ammonium affects plant root development through different mechanisms than nitrate. Here, the authors show that the Arabidopsis cell wall-localized ferroxidase LPR2 is required to attenuate root growth in response to ammonium. [ABSTRACT FROM AUTHOR]

Background: Previously, we published that 4′-azid-2′-deoxy-2′-fluorarabinoside (FNC), a novel cytosine nucleoside analog, has good anti-viral and anti-tumor activity. Objective: This study aimed to further explore the role and molecular mechanism of FNC in non-small cell lung cancer (NSCLC). Methods: FNC was tested in the NSCLC H460 cell line, the Lewis mouse model, and the H460 cell xenograft model. The effects of FNC were assessed by cell viability, transwell migration, and wound scratch analyses of cell migration and invasion. Apoptosis was assessed by flow cytometry. Proteins expression was assessed by western blot and immunohistochemistry staining (IHC). Results: FNC inhibits the proliferation and metastasis of H460 cells in a time- and dose-dependent manner. FNC treatment showed efficacy and low toxicity in the Lewis mouse lung cancer model as well as in the H460 cell xenograft model. Further, FNC induced H460 cell apoptosis through the activation of the mitochondrial pathway. Notably, FNC inhibited invasion by increasing E-cadherin protein and reducing the protein expression of VEGF, MMP-2, MMP-9, and CD31. Conclusion: FNC inhibits NSCLC by activating the mitochondrial apoptosis pathway and regulating the expressions of multiple proteins related to cell adhesion and invasion, highlighting its potential as an NSCLC therapeutic. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this article is to introduce the recent advance on the studies of fungal keratitis published over past 5 years. Methods: We performed literature review of articles published on PubMed, Google Scholar, CNKI and Web of Science relevant to the diagnosis, pathogenesis and novel treatment of fungal keratitis. Results: Excessive inflammation can lead to stromal damage and corneal opacification, hence the research on immune mechanism provides many potential therapeutic targets for fungal keratitis. Many researchers discussed the importance of earlier definitive diagnosis and were trying to find rapid and accurate diagnostic methods of pathogens. Develop new drug delivery systems and new routes of administration with better corneal penetration, prolonged ocular residence time, and better mucoadhesive properties is also one of the research hotspots. Additionally, many novel therapeutic agents and methods have been gradually applied in clinical ophthalmology. Conclusion: The diagnosis and treatment of fungal keratitis are still a challenge for ophthalmologist, and many researches provide new methods to conquer these problems. [ABSTRACT FROM AUTHOR]

To explore mutations in the additional sex combs-like 3 (ASXL3) gene in two Chinese families with congenital heart disease (CHD). Whole-exome sequencing (WES) was used to reveal a novel compound heterozygous mutation in the ASXL3 gene that was associated with CHD. Sanger sequencing of a further 122 CHD patients was used to determine an additional compound heterozygous mutation in the ASXL3 gene. Cell apoptosis was examined by MTS assay and flow cytometry. The cardiac structure was identified via hematoxylin–eosin (HE), Masson's trichrome, and ultrasound scanning. RNA sequencing was performed to identify a series of differentially expressed mRNAs. The mRNA and protein expressions were identified by quantitative real-time PCR and western blotting, respectively. A compound heterozygous mutation c.2168C > G (p.Pro723Arg) and c.5449C > G (p.Pro1817Ala) in the ASXL3 gene associated with CHD was identified. Overexpression of this compound heterozygous mutation in HL-1 cells resulted in increased apoptosis and reduced cell viability. Moreover, it affected cardiac structure and fibrosis in mice. There were 126 downregulated mRNAs and 117 upregulated mRNAs between the ASXL3 compound heterozygous mutation c.2168C > G (p.Pro723Arg) and c.5449C > G (p.Pro1817Ala) mice and wild-type mice. Ezh2, Slc6a4, and Socs3, which could interact with ASXL3 through proteins, were all upregulated. Another compound heterozygous mutation c.3526C > T (p.Arg1176Trp) and c.4643A > G (p.Asp1548Gly) in the ASXL3 gene was identified by screening a further 122 patients with CHD. The ASXL3 gene is important in cardiac development and may exert this influence by affecting the expression of mRNAs associated with cell apoptosis and cell proliferation. [ABSTRACT FROM AUTHOR]

Objective: To compare the classification based on contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) with that of contrast-enhanced CT and MRI (CECT/MRI) LI-RADS for liver nodules in patients at high risk of hepatocellular carcinoma.Methods: Two hundred thirty-nine patients with 273 nodules were enrolled in this retrospective study. Each nodule was categorized according to the CEUS LI-RADS version 2017 and CECT/MRI LI-RADS version 2017. The diagnostic performance of CEUS and CECT/MRI was compared. The reference standard was histopathology diagnosis. Inter-modality agreement was assessed with Cohen's kappa.Results: The inter-modality agreement for CEUS LI-RADS and CECT/MRI LI-RADS was fair with a kappa value of 0.319 (p < 0.001). The positive predictive values (PPVs) of hepatocellular carcinoma (HCC) in LR-5, LR-4, and LR-3 were 98.3%, 60.0%, and 25.0% in CEUS, and 95.9%, 65.7%, and 48.1% in CECT/MRI, respectively. The sensitivities and specificities of LR-5 for diagnosing HCC were 75.6% and 93.8% in CEUS, and 83.6% and 83.3% in CECT/MRI, respectively. The positive predictive values of non-HCC malignancy in CEUS LR-M and CECT/MRI LR-M were 33.9% and 93.3%, respectively. The sensitivity, specificity, and accuracy for diagnosing non-HCC malignancy were 90.9%, 84.5%, and 85.0% in CEUS LR-M and 63.6%, 99.6%, and 96.7% in CECT/MRI LR-M, respectively.Conclusions: The inter-modality agreement of the LI-RADS category between CEUS and CECT/MRI is fair. The positive predictive values of HCCs in LR-5 of the CEUS and CECT/MRI LI-RADS are comparable. CECT/MRI LR-M has better diagnostic performance for non-HCC malignancy than CEUS LR-M.Key Points: • The inter-modality agreement for the final LI-RADS category between CEUS and CECT/MRI is fair. • The LR-5 of CEUS and CECT/MRI LI-RADS corresponds to comparable positive predictive values (PPVs) of HCC. For LR-3 and LR-4 nodules categorized by CECT/MRI, CEUS examination should be performed, at least if they can be detected on plain ultrasound. • CECT/MRI LR-M has better diagnostic performance for non-HCC malignancy than CEUS LR-M. For LR-M nodules categorized by CEUS, re-evaluation by CECT/MRI is necessary. [ABSTRACT FROM AUTHOR]

Dual oxidases (DUOXs) produce hydrogen peroxide by transferring electrons from intracellular NADPH to extracellular oxygen. They are involved in many crucial biological processes and human diseases, especially in thyroid diseases. DUOXs are protein complexes co-assembled from the catalytic DUOX subunits and the auxiliary DUOXA subunits and their activities are regulated by intracellular calcium concentrations. Here, we report the cryo-EM structures of human DUOX1-DUOXA1 complex in both high-calcium and low-calcium states. These structures reveal the DUOX1 complex is a symmetric 2:2 hetero-tetramer stabilized by extensive inter-subunit interactions. Substrate NADPH and cofactor FAD are sandwiched between transmembrane domain and the cytosolic dehydrogenase domain of DUOX. In the presence of calcium ions, intracellular EF-hand modules might enhance the catalytic activity of DUOX by stabilizing the dehydrogenase domain in a conformation that allows electron transfer. Dual oxidases (DUOXs), assembled from the catalytic DUOX and the auxiliary DUOXA subunits, produce hydrogen peroxide by transferring electrons from intracellular NADPH to extracellular oxygen in a calcium-activated manner. Here authors report the cryo-EM structures of human DUOX1-DUOXA1 complex in both high-calcium and low-calcium states. [ABSTRACT FROM AUTHOR]

Contrast-enhanced ultrasound (CEUS) has become an established modality in various clinical indications for liver diseases. SonoVue®, a pure blood pure agent, and Sonazoid®, which exhibits an additional Kupffer phase, are contrast agents approved for liver imaging. This review discusses and compares the current clinical evidence for these two ultrasound contrast agents in the characterization and detection of focal liver lesions in the non-cirrhotic and cirrhotic liver, as well as for the use in interventional procedures such as liver biopsy guidance, and local ablation treatment monitoring. Reference is made to clinical studies which evaluated the accuracy of CEUS using a standard of reference, its safety, or to comparative studies of these two agents. [ABSTRACT FROM AUTHOR]

This paper examines the projected changes in rainfall in Southeast Asia (SEA) in the twenty-first century based on the multi-model simulations of the Southeast Asia Regional Climate Downscaling/Coordinated Regional Climate Downscaling Experiment–Southeast Asia (SEACLID/CORDEX–SEA). A total of 11 General Circulation Models (GCMs) have been downscaled using 7 Regional Climate Models (RCMs) to a resolution of 25 km × 25 km over the SEA domain (89.5° E–146.5° E, 14.8° S–27.0° N) for two different representative concentration pathways (RCP) scenarios, RCP4.5 and RCP8.5. The 1976–2005 period is considered as the historical period for evaluating the changes in seasonal precipitation of December–January–February (DJF) and June–July–August (JJA) over future periods of the early (2011–2040), mid (2041–2070) and late twenty-first century (2071–2099). The ensemble mean shows a good reproduction of the SEA climatological mean spatial precipitation pattern with systematic wet biases, which originated largely from simulations using the RegCM4 model. Increases in mean rainfall (10–20%) are projected throughout the twenty-first century over Indochina and eastern Philippines during DJF while a drying tendency prevails over the Maritime Continent. For JJA, projections of both RCPs indicate reductions in mean rainfall (10–30%) over the Maritime Continent, particularly over the Indonesian region by mid and late twenty-first century. However, examination of individual member responses shows prominent inter-model variations, reflecting uncertainty in the projections. [ABSTRACT FROM AUTHOR]

Sterol O-acyltransferase 1 (SOAT1) is an endoplasmic reticulum (ER) resident, multi-transmembrane enzyme that belongs to the membrane-bound O-acyltransferase (MBOAT) family. It catalyzes the esterification of cholesterol to generate cholesteryl esters for cholesterol storage. SOAT1 is a target to treat several human diseases. However, its structure and mechanism remain elusive since its discovery. Here, we report the structure of human SOAT1 (hSOAT1) determined by cryo-EM. hSOAT1 is a tetramer consisted of a dimer of dimer. The structure of hSOAT1 dimer at 3.5 Å resolution reveals that a small molecule inhibitor CI-976 binds inside the catalytic chamber and blocks the accessibility of the active site residues H460, N421 and W420. Our results pave the way for future mechanistic study and rational drug design targeting hSOAT1 and other mammalian MBOAT family members. [ABSTRACT FROM AUTHOR]

With the vigorous development of the national economy, the pace and scale of urban construction have been unfolded at an unprecedented speed. A large number of construction projects have made the urban engineering geological exploration activities reach a considerable scale in depth and breadth. The survey results of these projects are very valuable information resources, which not only played an important role in urban planning and construction at that time, but also had high reuse value. Based on BP neural network theory, this paper uses engineering geological database as the research and development platform. Based on the theory of BP neural network and the engineering geological database as the research and development platform, this paper establishes the prediction of geotechnical parameters based on the analysis of the characteristics of geotechnical materials and the distribution of geotechnical sediments and geotechnical parameters. Based on the survey data and specific engineering information, the prediction model of the project was established, and the distribution of the stratum and the relevant geotechnical parameters were predicted. Based on the study of geotechnical properties and BP neural network, a new parameter prediction model is established. Taking the engineering geological database as the platform, using the programming language such as MATLAB, the preliminary research and construction of this prediction system were carried out. The results show that the generalization ability of the prediction model meets the requirements. [ABSTRACT FROM AUTHOR]

Soluble guanylate cyclase (sGC) is the primary sensor of nitric oxide. It has a central role in nitric oxide signalling and has been implicated in many essential physiological processes and disease conditions. The binding of nitric oxide boosts the enzymatic activity of sGC. However, the mechanism by which nitric oxide activates the enzyme is unclear. Here we report the cryo-electron microscopy structures of the human sGCα1β1 heterodimer in different functional states. These structures revealed that the transducer module bridges the nitric oxide sensor module and the catalytic module. Binding of nitric oxide to the β1 haem-nitric oxide and oxygen binding (H-NOX) domain triggers the structural rearrangement of the sensor module and a conformational switch of the transducer module from bending to straightening. The resulting movement of the N termini of the catalytic domains drives structural changes within the catalytic module, which in turn boost the enzymatic activity of sGC. Cryo-electron microscopy structures of human soluble guanylate cyclase in inactive and activated states shed light on the activation mechanism of this enzyme by nitric oxide. [ABSTRACT FROM AUTHOR]

Many variants of join operations of graphs have been introduced, and their spectral properties have been studied extensively by many researchers. This paper mainly focuses on the Laplacian spectra of some double join operations of graphs. We first introduce the conception of double join matrix and provide a complete information about its eigenvalues and the corresponding eigenvectors. Further, we define four variants of double join operations based on subdivision graph, Q-graph, R-graph and total graph. Applying the result obtained about double join matrices, we give an explicit complete characterization of the Laplacian eigenvalues and the corresponding eigenvectors of four variants in terms of the Laplacian eigenvalues and the eigenvectors of factor graphs. These results generalize some well-known results on the Laplacian spectra of some join operations of graphs. [ABSTRACT FROM AUTHOR]

Fat deposition in muscle includes intramuscular fat (IMF) and intermuscular fat. IMF content is an index of pork quality; however, because IMF content is difficult to measure in vivo in young animals, conventional breeding for IMF content is difficult to carry out. The mechanism and progression of animal fat deposition is not well understood, and there are currently no effective control methods. In this study, using Laiwu and large white pigs as the research subjects and RNA sequencing technology, we analyzed the genetic mechanism of animal fat deposition in pigs. Specifically, we analyzed the features of lncRNAs and their potential target genes. We obtained 464 million clean reads, from which 907 lncRNAs were identified. The cis and trans analysis identified target genes, including genes that were upregulated (286) and downregulated (621) in the fatty and lean pigs. ENSSSCG00000008692_ADD1, ENSSSCG00000023124_ADD1 and ENSSSCG00000005918_DGAT1 were validated as target genes of the lncRNAs and were shown to be closely related to fat deposition. These results provide a basis for studying the different metabolic lncRNA expression of IMF deposition. In addition, as the valuable model animal to study the mechanisms of obesity, pigs may represent a new avenue for studying human obesity. [ABSTRACT FROM AUTHOR]

Glossogyne tenuifolia is a high economic value crop cultivated on Penghu Island, Taiwan. However, there is no extraction optimization of G. tenuifolia reported in the literature. Simplex lattice and central composite design of response surface methodology (RSM) were used in this study to investigate the extraction variables (solvent proportion, extraction temperature, the ratio of liquid to solid and pH) in the extraction of solvent from G. tenuifolia. The total phenolic content (TPC), total flavonoid content (TFC), total triterpenoid content (TTC) and antioxidant capacity of G. tenuifolia were considered as the response variables, while the solvent proportion, extraction temperature, the ratio of liquid to solid (L/S) and the pH effect were considered for determining the optimal conditions. Quadratic models were used by the RSM optimization approach to obtain the optimal conditions and to predict the relative response variables. ANOVA analysis results exhibited a high coefficient of determination (R2) and adjusted-R2, which indicated that the quadratic models were adequate for the response variables. The results demonstrated that the extract of G. tenuifolia is a good source of antioxidant and has the potential to be applied in various industries. [ABSTRACT FROM AUTHOR]

An experimental investigation of R22 and R410A condensation outside a horizontal smooth tube, a herringbone tube and a newly developed 3D enhanced heat transfer (1EHT) dimple tube has been conducted. The herringbone tube has a fin root diameter of 11.43 mm, a helical angle of 21.3 °, 48 fins with a fin height of 0.262 mm and an apex angle of 36 °; the 1EHT tube has an inner diameter of 11.5 mm with a dimple enhancement; while the smooth tube has an inner diameter of 11.43 mm; and all the tubes have an outer diameter of 12.7 mm. Experiments were performed for a constant saturation temperature of 45°C; with a constant inlet vapor quality of 0.8 and a constant outlet vapor quality of 0.1; for a mass flux ranging from 5 kg/(m2 s) to 250 kg/(m2 s). In addition, annular side condensation experiments were performed using an outer shell tube with outer diameters of 17 mm and 25.4 mm. Heat transfer performance varied with mass flux. At a low mass flux the enhanced dimple tube had the smallest heat transfer coefficient; while at higher values of mass flux, the smooth tube had the smallest heat transfer coefficient. Finally, the effect of average vapor quality on the heat transfer coefficient was also investigated. Characteristic analysis was performed in order to account for the various phenomena found in this series of experiments. Annular side heat transfer performance combined with pressure drop measurements reveal that the herringbone tube generally had a better heat transfer performance than the other tubes, and can be a good choice for use in annular side condensation applications. [ABSTRACT FROM AUTHOR]

This study aims to provide a basis for understanding the mechanisms of diurnal rainfall variability over Peninsular Malaysia by utilising the Non-Hydrostatic Regional Climate Model (NHRCM). The present day climate simulations at 5 km resolution over a period of 20 years, from 1st December 1989 to 31st January 2010 were conducted using the six-hourly Japanese re-analysis 55 years (JRA-55) data and monthly Centennial in situ Observation Based Estimates (COBE) of sea surface temperature as lateral and lower boundary conditions. Despite some biases, the NHRCM performed reasonably well in simulating diurnal rainfall cycles over Peninsular Malaysia. During inter-monsoon periods, the availability of atmospheric moisture played a major role in modulating afternoon rainfall maxima over the foothills of the Titiwangsa mountain range (FT sub-region). During the southwest monsoon, a lack of atmospheric moisture inhibits the occurrence of convective rainfall over the FT sub-region. The NHRCM was also able to simulate the suppression of the diurnal rainfall cycle over the east coast of Peninsular Malaysia (EC sub-region) and afternoon rainfall maximum over the Peninsular Malaysia inland-valley (IN sub-region) area during the northeast monsoon. Over the EC sub-region, daytime radiational warming of the top of clouds enhanced atmospheric stability, thus reducing afternoon rainfall. On the other hand, night-time radiational cooling from cloud tops decreases atmospheric stability and increases nocturnal rainfall. In the early morning, the rainfall maximum was confined to the EC sub-region due to the retardation of the north-easterly monsoonal wind by the land breeze and orographic blocking. However, in the afternoon, superimposition of the sea breeze on the north-easterly monsoonal wind strengthened the north-easterly wind, thus causing the zone of convection to expand further inland. [ABSTRACT FROM AUTHOR]

In recent years, acupuncture has been applied to treat more and more patients suffering from polycystic ovary syndrome (PCOS). On June 27, 2017 a paper titled 'Effect of acupuncture and clomiphene in Chinese women with polycystic ovary syndrome: a randomized clinical trial' was published in Journal of the American Medical Association (JAMA). The results did not support acupuncture as an effective therapy for improving the live births in PCOS. The aim of this article was to analyze the therapeutic regimen and design of the clinical trial. The primary outcome and the conclusion of the paper were discussed as well. There are 5 doubts in the paper. (1) The therapeutic regimen decided by trigger points in the paper was different from that of the traditional Chinese acupuncture. (2) The live birth as the primary outcome was limited during the PCOS recovery. (3) In addition the period of the treatment was too short to reflect the therapeutic effect. (4) Although there was no significant difference between active acupuncture and control acupuncture, the conclusion that acupuncture was not effective for PCOS was not confirmed because the control acupuncture plus clomiphene was also more effective than that of clomiphene alone. (5) The proposal and the statistics were not in accordance with the one planned before. Therefore the result was worth to be discussed so as to provide some suggestions and references for improving the clinical research of acupuncture. [ABSTRACT FROM AUTHOR]

Purpose: The present study aims to evaluate the utility of high-resolution single-nucleotide polymorphism (SNP) arrays in fetuses with ventricular septal defects (VSDs) with or without other structural anomalies but with normal karyotypes and to investigate the outcomes of cases of prenatal VSDs via clinical follow-up.Methods: We analyzed 144 fetuses with VSDs and normal karyotypes using Affymetrix CytoScan HD arrays and the analyses were carried out a year after birth.Results: Clinically significant CNVs were detected in 12 fetuses (8.3%). The most common pathogenic CNV was a 22q11.2 deletion with a detection rate of 2.8% (4/144). Well-known microdeletion or microduplication syndromes, including Smith-Magenis, Miller-Dieker, 9q subtelomeric deletion, 1p36 microdeletion, 1q21.1 microduplication, and terminal 4q deletion syndrome, were identified in six cases. Three regions of chromosomal imbalance were also identified: microduplication at 12q24.32q24.33, microdeletion at 16p13.13p13.12 and microdeletion at Xp21.1. The genes TBX1, SKI, GJA5, EHMT1, NOTCH1 were identified as established genes and LZTR1, PRDM26, YWHAE, FAT1, AKAP10, ERCC4, and ULK1 were identified as potential candidate genes of fetal VSDs. There was no significant difference in pathogenic CNVs between isolated VSDs and VSDs with additional structural abnormalities. Ninety-five (74.8%) pregnant women with fetuses with benign CNVs chose to continue the pregnancy and had a favorable prognosis, while nine (75%) pregnant women with fetuses with pathogenic CNVs chose to terminate the pregnancy.Conclusions: High-resolution SNP arrays are valuable tools for identifying submicroscopic chromosomal abnormalities in the prenatal diagnosis of VSDs. An excellent outcome can be expected for VSD fetuses that are negative for chromosomal anomalies and other severe anatomic abnormalities. [ABSTRACT FROM AUTHOR]

Objective: To investigate the biochemical characteristic of the neurons associated Zusanli (ST 36) in the rat by using Alexa Fluor 594 conjugated cholera toxin subunit B (AF594-CTB) neural tracing and calcitonin gene-related peptide (CGRP) fluorescent immunohistochemical techniques. Methods: Four male Sprague Dawley rats were injected with AF594-CTB into the corresponding area of the Zusanli in the human body. After 3 surviving days, the rat's spinal cord and dorsal root ganglia (DRGs) at lumbar segments were dissected following perfusion with 4% paraformaldehyde, cut into sections, and then stained with CGRPfluorescent immunohistochemical method. Results: AF594-CTB labeled sensory neurons were detected in the L3-L6 DRGs with high concentration in L4 DRG, and the labeled motor neurons located in the dorsolateral and intermediate regions of lamina IX from L3-L5 segments with high concentration at L4. Meanwhile, CGRPpositive neural labeling distributed symmetrically on both sides of DRGs, anterior and dorsal horns of spinal cord. In the AF594-CTB labeled neurons, 37% sensory neurons and 100% motor neurons expressed CGRPpositive. Conclusion: These findings present the morphological evidence to demonstrate that the sensory and motor neurons associated Zusanli in the rat distributed with segmental and regional patterns, and contained CGRP-expression. [ABSTRACT FROM AUTHOR]

Background: Recent advances in migraine research have shown that the cerebral cortex serves a primary role in the pathogenesis of migraine. Since aberrant brain activity in migraine can be noninvasively detected with magnetoencephalography (MEG), The object of this study was to investigate the resting state cortical activity differences between migraineurs and controls and its related clinical characteristics. Methods: Twenty-two subjects with an acute migraine and twenty-two age- and gender-matched controls were studied using MEG. MEG recordings were recorded 120 seconds during the headache attack. Analyze MEG signals from low (1-4 Hz) to high (200-1000 Hz)-frequency ranges. Results: In comparison with the controls, brain activity in migraine subjects was significantly different from that of the controls both in two frequency ranges (55-90 Hz, p < 0.001) and (90-200 Hz, p < 0.004). But the power value showed no significantly differences between control and migraines in all frequency ranges (p > 0.05). All the clinical characteristics had no significant correlation with aberrant brain activity. Conclusions: The results demonstrated that migraine subjects in resting state had significantly aberrant ictal brain activity that can be measured with neuromagnetic imaging techniques. The findings may facilitate the development of new therapeutic strategies in migraine treatment via alterations in cortical excitability with TMS and other medications in the future. [ABSTRACT FROM AUTHOR]

Background: Ischemia-reperfusion injury (IRI) after lung transplantation remains a significant cause of morbidity and mortality. Lung IRI induces nitric oxide synthesis (iNOS) and reactive nitrogen species, decreasing nitric oxide bioavailability. We hypothesized that ischemia-induced iNOS intensifies with reperfusion and contributes to IRI-induced pulmonary arterial regulatory dysfunction, which may lead to early graft failure and cause pulmonary edema. The aim of this study was to determine whether ischemia-reperfusion alters inducible and endothelial nitric oxide synthase expression, potentially affecting pulmonary perfusion. We further evaluated the role of iNOS in post-transplantation pulmonary arterial disorder. Methods: We randomized 32 Sprague-Dawley rats into two groups. The control group was given a sham operation whilst the experimental group received orthotropic lung transplants with a modified three-cuff technique. Changes in lung iNOS, and endothelial nitric oxide synthase expression were measured after lung transplantation by enzyme-linked immunosorbent assay (ELISA). Vasoconstriction in response to exogenous phenylephrine and vasodilation in response to exogenous acetylcholine of pulmonary arterial rings were measured in vitro as a measure of vascular dysfunction. To elucidate the roles of iNOS in regulating vascular function, an iNOS activity inhibitor (N6-(1-iminoethyl)-L-lysine, L-NIL) was used to treat isolated arterial rings. In order to test whether iNOS inhibition has a therapeutic effect, we further used L-NIL to pre-treat transplanted lungs and then measured post-transplantation arterial responses. Results: Lung transplantation caused upregulation of iNOS expression. This was also accompanied by suppression of both vasoconstriction and vasodilation of arterial rings from transplanted lungs. Removal of endothelium did not interfere with the contraction of pulmonary arterial rings from transplanted lungs. In contrast, iNOS inhibition rescued the vasoconstriction response to exogenous phenylephrine of pulmonary arterial rings from transplanted lungs. In addition, lung transplantation led to suppression of PaO/FiO ratio, increased intrapulmonary shunt ( Q/ Q), and increase of lung wet to dry ratio (W/D), malondialdehyde and myeloperoxidase levels, all of which were reversed upon iNOS inhibition. Furthermore, inhibition of iNOS significantly rescued vascular function and alleviated edema and inflammatory cell infiltration in the transplanted lung. Conclusions: Our data suggest that lung transplantation causes upregulation of iNOS expression, and pulmonary vascular dysfunction. iNOS inhibition reverses the post-transplantational pulmonary vascular dysfunction. [ABSTRACT FROM AUTHOR]

Healing defects in hexagonal boron nitride ( h-BN sheet) or doping it with oxygen can modify or restore its physical properties, which would increase its range of potential applications. Thus, it is very important to find an efficient method of healing or a BN sheet or doping it with oxygen. In this work, using density functional theory (DFT) calculations, we identified a mechanism for healing h-BN sheets with nitrogen vacancies (V) or doping BN sheets with oxygen using NO molecules. The results indicate that such reactions involve three steps: (1) the chemisorption of NO, (2) the incorporation of the N or O atom of NO into the defective h-BN sheet, and (3) the removal of the adsorbed O atom or NO molecule. We found that the proposed mechanism is theoretically possible and has the following advantages. First, the barrier is about 0.60 eV for the formation of the O-doped h-BN sheet. For the healing process, because the energy released during NO chemisorption (−4.94 eV) completely offsets the subsequent barrier (1.17 eV), a perfect h-BN sheet can easily be achieved by using NO and an h-BN sheet with V defects as reactants. Second, no catalyst is needed, and thus there is no need for a purification step to remove the catalyst. Third, NO, a toxic gas, can be used as a reactant and will then be reduced to O or NO. Fourth, NO shows high selectivity for vacancy defect sites. Our findings show that this is an effective theoretical method of synthesizing O-doped h-BN sheets or of healing defective h-BN sheets, which should prove useful in the design of h-BN sheet-based devices. [ABSTRACT FROM AUTHOR]

Treatment determination based on syndrome differentiation is the key of Chinese medicine. A feasible way of improving the clinical therapy effectiveness is needed to correctly differentiate the syndrome classifications based on the clinical manifestations. In this paper, a novel data mining method based on manifold ranking (MR) is proposed to explore the relation between syndromes and symptoms for viral hepatitis. Since MR could take the symptom data with expert differentiation and the symptom data without expert differentiation into the task of syndrome classification, the clinical information used for modeling the syndrome features is greatly enlarged so as to improve the precise of syndrome classification. In addition, the proposed method of syndrome classification could also avoid two disadvantages in previous methods: linear relation of the clinical data and mutually exclusive symptoms among different syndromes. And it could help exploit the latent relation between syndromes and symptoms more effectively. Better performance of syndrome classification is able to be achieved according to the experimental results and the clinical experts. [ABSTRACT FROM AUTHOR]

By performing density functional theory (DFT) calculations, we study the oxidation of monovacancies in hexagonal boron nitride ( h-BN) sheet by oxygen molecules. In particular, the changes in structural, electronic, and magnetic properties of defective h-BN sheet are mainly addressed. The results indicate that the local magnetic moments of h-BN sheet would remain intact if its dangling bonds around monovacancy are not fully saturated. In contrast, because the dangling bonds of defective h-BN sheet in the lowest energy configurations are completely saturated, the magnetism of the system is mainly contributed by the adsorbed O. Moreover, these oxidized h-BN sheets are converted to semiconductor with various band gaps, which depends on the adsorption site and chemical bonding of O on substrates. Our results may be useful to provide guidance to experimentally study the behavior of h-BN sheet under exposure to the oxygen plasma, which is necessary to estimate its stability in air. [ABSTRACT FROM AUTHOR]