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Abstract Objective To explore the impact of preoperative HbA1c levels on postoperative complications in coronary heart disease patients undergoing coronary artery bypass grafting (CABG). Methods From September 2020 to November 2022, 98 patients with coronary heart disease who were preparing to receive CABG treatment in a cardiac surgery department of a certain hospital were included in the study using the retrospective analysis. According to the preoperative serum hemoglobin A1C (HbA1c) test results, patients were divided into a low-level group (HbA1c 7%, 19 cases). The surgical outcomes and postoperative complications among the three groups were compared. Results There was no statistically significant difference in the number of bypass grafts, mechanical ventilation time, and hospitalization time among the three groups of patients (P > 0.05). The high-level group stayed in the ICU longer than the other two groups, while the middle level group had a longer stay than the low-level group (P 0.05). Among them, the incidence of acute kidney injury in the high-level group was higher than that in the other groups (P 0.05. The incidence of infection in the middle level group was higher than that in the low level group (P 0.05 compared to the medium level group. Conclusion For patients with coronary heart disease undergoing CABG, the higher the preoperative HbA1c level, the longer their postoperative stay in the ICU, and the higher the risk of acute renal function damage.

Abstract Rigid solenoid coils have long been indispensable in modern intelligent devices. However, their sparse structure and challenging preparation of flexible coils for soft robots impose limitations. Here, a transformable 3D curved high-density liquid metal coil (HD-LMC) is introduced that surpasses the structural density level of enameled wire. The fabrication technique employed for high-density channels in elastomers is universally applicable. Such HD-LMCs demonstrated excellent performance in pressure, temperature, non-contact distance sensors, and near-field communication. Soft electromagnetic actuators thus achieved significantly improved the electromagnetic force and power density. Moreover, precise control of swinging tail motion enables a bionic pufferfish to swim. Finally, HD-LMC is further utilized to successfully implement a soft rotary robot with integrated sensing and actuation capabilities. This groundbreaking research provides a theoretical and experimental basis for expanding the applications of liquid metal-based multi-dimensional complex flexible electronics and is expected to be widely used in liquid metal-integrated robotic systems.

Abstract This article explores the criteria used to ascertain whether or not, and how, ancient Chinese bronze bells might form sets of musical instruments, thus clarifying their original intended use by ancient musicians. The focus is on ten bells unearthed from Changsha city in Hunan province in China, which date to the twelfth century BCE. A range of diverse relationships between these bells provide valuable insights that can be explored. Debate is ongoing among music historians regarding the nature of the bells. Some argue that the ten bells do not constitute a set of musical instruments because their designs and acoustic properties lack sufficient similarity and correlation. Conversely, another group of historians suggests that nine of the ten bells could indeed be seen as a set, but with the tenth bell being an outlier due to its distinct design. The third group of historians contends that the ten bells should be considered a musical set because of their organized sequence of consecutive semi-tones, while the design differences of the bells are less significant and can be overlooked if we focus on their musical functions. In this study, we scrutinize the assumptions made by these music historians, including their definitions of design similarity and the sequence of progressive pitches. Further previously overlooked criteria, such as the geographical proximity of these ten bells and others found in neighboring areas, and the incremental changes in the bell sizes, are also considered. Through the use of these criteria we aim to explore a wide range of relationships between ancient Chinese bells and to reassess what other new evidence the bells may offer to the study of ancient Chinese musical concepts. The concept of the chromatic scale discovered by ancient Chinese musicians was embodied on the casting of bronze bells.

Abstract CO2 electroreduction has garnered significant attention from both the academic and industrial communities. Extracting crucial information related to catalysts from domain literature can help scientists find new and effective electrocatalysts. Herein, we used various advanced machine learning, natural language processing techniques and large language models (LLMs) approaches to extract relevant information about the CO2 electrocatalytic reduction process from scientific literature. By applying the extraction pipeline, we present an open-source corpus for electrocatalytic CO2 reduction. The database contains two types of corpus: (1) the benchmark corpus, which is a collection of 6,985 records extracted from 1,081 publications by catalysis postgraduates; and (2) the extended corpus, which consists of content extracted from 5,941 documents using traditional NLP techniques and LLMs techniques. The Extended Corpus I and II contain 77,016 and 30,283 records, respectively. Furthermore, several domain literature fine-tuned LLMs were developed. Overall, this work will contribute to the exploration of new and effective electrocatalysts by leveraging information from domain literature using cutting-edge computer techniques.

GaN, a third-generation semiconductor, has gained widespread attention owing to its high temperature resistance, wide bandgap, and high critical breakdown electric fields. Magnetron sputtering has a broad potential in the field of low-cost growth of GaN on account of high efficiency, superior quality, and convenient operation. However, challenges caused from the pure Ga targets with a huge refrigeration system need to be resolved for wide practices. Here, a new and cost-effective Ga target for magnetron sputtering was fabricated by utilizing the wetting properties of CuGa2 and Ga. Mixed microcrystalline and amorphous GaN films were obtained via reactive magnetron sputtering employing the Ga target. The average deposition rate is about 1.68 nm/min, and the average roughness is ∼7.45 ± 0.26 nm under 100 W of sputtering power. In addition, the sputtered GaN films were found to be wide-bandgap and p-type semiconductors with high transmittance, as revealed by x-ray photoelectron spectroscopy and absorption spectra. The GaN films display a bandgap of ∼3.60 eV and a transmittance exceeding 88.5% in the visible range. Furthermore, field-effect transistors and metal–semiconductor–metal photodetectors have been fabricated using the obtained GaN films, demonstrating favorable response characteristics. The prospects of microcrystalline/amorphous GaN films in sensing, power devices, and flexible electronics were forecasted. Overall, a low-cost and pervasive route of target fabrication process expands the possibilities of using low melting point metals in magnetron sputtering.

The notion of a transposed Poisson $ n $-Lie algebra has been developed as a natural generalization of a transposed Poisson algebra. It was conjectured that a transposed Poisson $ n $-Lie algebra with a derivation gives rise to a transposed Poisson $ (n+1) $-Lie algebra. In this paper, we focus on transposed Poisson $ n $-Lie algebras. We have obtained a rich family of identities for these algebras. As an application of these formulas, we provide a construction of $ (n+1) $-Lie algebras from transposed Poisson $ n $-Lie algebras with derivations under a certain strong condition, and we prove the conjecture in these cases.

The notion of generalized quantum cluster algebras was introduced as a natural generalization of Berenstein and Zelevinsky's quantum cluster algebras as well as Chekhov and Shapiro's generalized cluster algebras. In this paper, we focus on a generalized quantum cluster algebra of Kronecker type which possesses infinitely many cluster variables. We obtain the cluster multiplication formulas for this algebra. As an application of these formulas, a positive bar-invariant basis is explicitly constructed. Both results generalize those known for the Kronecker cluster algebra and quantum cluster algebra.

Abstract Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases, whose severe form is associated with oxidative stress. Vitamin E as an antioxidant has a protective potential in NAFLD. Whether dietary intake of vitamin E, supplementary vitamin E use, and total vitamin E have a preventive effect on NAFLD requires investigation. A cross-sectional study used data from the National Health and Nutrition Examination Survey (2017–2020) was conducted. Vitamin E intake, including dietary vitamin E, supplementary vitamin E use, and total vitamin E, was obtained from the average of two 24-h dietary recall interviews. The extent of hepatic steatosis was measured by liver ultrasound transient elastography and presented as controlled attenuated parameter (CAP) scores. Participants were diagnosed with NAFLD based on CAP threshold values of 288 dB/m and 263 dB/m. The statistical software R and survey-weighted statistical models were used to examine the association between vitamin E intake and hepatic steatosis and NAFLD. Overall, 6122 participants were included for NAFLD analysis. After adjusting for age, gender, race, poverty level index, alcohol consumption, smoking status, vigorous recreational activity, body mass index, abdominal circumference, hyperlipidemia, hypertension, diabetes, and supplementary vitamin E use, dietary vitamin E was inversely associated with NAFLD. The corresponding odds ratios (OR) and 95% confidence intervals (CI) of NAFLD for dietary vitamin E intake as continuous and the highest quartile were 0.9592 (0.9340–0.9851, P = 0.0039) and 0.5983 (0.4136–0.8654, P = 0.0091) (P trend = 0.0056). Supplementary vitamin E was significantly inversely associated with NAFLD (fully adjusted model: OR = 0.6565 95% CI 0.4569–0.9432, P = 0.0249). A marginal improvement in total vitamin E for NAFLD was identified. The ORs (95% CIs, P) for the total vitamin E intake as continuous and the highest quartile in the fully adjusted model were 0.9669 (0.9471–0.9871, P = 0.0029) and 0.6743 (0.4515–1.0071, P = 0.0538). Sensitivity analysis indicated these findings were robust. The protective effects of vitamin E significantly differed in the stratum of hyperlipidemia (P interaction

Abstract Background Invasive candidiasis is the most common hospital-acquired fungal infection in intensive care units (ICU). The Geriatric Nutritional Risk Index (GNRI) score was developed to evaluate the nutritional status of elderly adults. We aimed to assess the association between the GNRI score and the risk of invasive candidiasis in elderly patients admitted to ICU. Methods Hospitalization information of elderly patients with invasive candidiasis was collected retrospectively from Medical Information Mart for Intensive Care (MIMIC) IV and MIMIC-III Clinical Database CareVue subset from 2001 to 2019. The main outcome of this study was the diagnosis of invasive candidiasis in patients. We employed a multivariable Cox regression and propensity score matching to balance the influence of confounding factors on the outcome. Furthermore, we conducted sensitivity analyses by categorizing the GNRI into classes based on thresholds of 98, 92, and 81. Results A total of 6739 patients were included in the study, among whom 134 individuals (2%) were diagnosed with invasive candidiasis. The GNRI scores of patients with invasive candidiasis upon admission to the ICU were significantly lower, measuring 88.67 [79.26–98.27], compared to the control group with a score of 99.36 [87.98-110.45] (P

Abstract Background Insulin has been reported to exhibit anti-inflammatory activities in the context of bowel inflammation. However, the role of the interaction between insulin and the microbiota in gut health is unclear. Our goal was to investigate the mechanism of action of insulin in bowel inflammation and the relationship between insulin and the gut microbiota. Methods We used acute and chronic murine models of inflammatory bowel disease (IBD) to evaluate whether insulin influences the progression of colitis. Colonic tissues, the host metabolome and the gut microbiome were analyzed to investigate the relationship among insulin treatment, the microbiome, and disease. Experiments involving antibiotic (Abx) treatment and fecal microbiota transplantation (FMT) confirmed the association among the gut microbiota, insulin and IBD. In a series of experiments, we further defined the mechanisms underlying the anti-inflammatory effects of insulin. Results We found that low-dose insulin treatment alleviated intestinal inflammation but did not cause death. These effects were dependent on the gut microbiota, as confirmed by experiments involving Abx treatment and FMT. Using untargeted metabolomic profiling and 16S rRNA sequencing, we discovered that the level of the secondary bile acid lithocholic acid (LCA) was notably increased and the LCA levels were significantly associated with the abundance of Blautia, Enterorhadus and Rumi-NK4A214_group. Furthermore, LCA exerted anti-inflammatory effects by activating a G-protein-coupled bile acid receptor (TGR5), which inhibited the polarization of classically activated (M1) macrophages. Conclusion Together, these data suggest that insulin alters the gut microbiota and affects LCA production, ultimately delaying the progression of IBD. Graphical Abstract

ACE2 has been confirmed to be a functional receptor for SARS-CoV and SARS-CoV-2, but research on animal coronaviruses, especially PEDV, are still unknown. The present study investigated whether ACE2 plays a role in receptor recognition and subsequent infection during PEDV invasion of host cells. IPEC-J2 cells stably expressing porcine ACE2 did not increase the production of PEDV-N but inhibited its expression. Porcine ACE2 knockout cells was generated by CRISPR/Cas9 genome editing in IPEC-J2 cells. The expression of PEDV-N did not decrease but slightly increased. The Co-IP results showed that there was no significant association between ACE2 and PEDV-S. There were no obvious interaction between PEDV-S, PEDV-E, PEDV-M and porcine ACE2 promoters, but PEDV-N could inhibit the activity of ACE2 promoters. PEDV-N degraded STAT1 and prevented its phosphorylation, thereby inhibiting the expression of interferon-stimulated genes. Repeated infection of PEDV further confirmed the above results. PEDV activated ACE-Ang II-AT1R axis, while ACE2-Ang (1–7)-MasR axis activity was decreased and inflammatory response was intensified. However, excess ACE2 can reverse this reaction. These results reveal that ACE2 does not facilitate PEDV entry into cells, but relieves PEDV-induced inflammation by promoting STAT1 phosphorylation.

Growing studies have shown the preventive effects of isomalt against metabolic diseases, nevertheless, its efficacy and action mechanisms on nonalcoholic fatty liver disease (NAFLD) remain unknown. Herein, isomalt supplementation significantly attenuated the high-sucrose diet-induced hepatic steatosis. Mechanically, dietary isomalt restored hepatic de novo lipogenesis dysfunction and intestinal epithelial integrity. Moreover, isomalt consumption regulated gut microbiota composition, including improving abundance of probiotic Akkermansia, but suppressing pathogens Acinetobacter and Corynebacterium_1. Quantification analyses of short-chain fatty acids showed that isomalt reduced faecal acetate concentrations, whereas elevated propionate and butyrate in hepatic steatosis. Additionally, targeted metabolomics profiling of tryptophan metabolism showed that isomalt increased faecal levels of 5-hydroxytryptophan, indole-3-carboxaldehyde and kynurenic acid, but reduced concentrations of 5-hydroxyindoleacetic acid and xanthurenic acid in rats. Thereby, our data demonstrate that dietary isomalt attenuates hepatic steatosis possibly via modulation of gut microbiota and its metabolic function, which provides new insights into preventing and treating NAFLD in future.

Abstract The electrocatalytic CO2 reduction process has gained enormous attention for both environmental protection and chemicals production. Thereinto, the design of new electrocatalysts with high activity and selectivity can draw inspiration from the abundant scientific literature. An annotated and verified corpus made from massive literature can assist the development of natural language processing (NLP) models, which can offer insight to help guide the understanding of these underlying mechanisms. To facilitate data mining in this direction, we present a benchmark corpus of 6,086 records manually extracted from 835 electrocatalytic publications, along with an extended corpus with 145,179 records in this article. In this corpus, nine types of knowledge such as material, regulation method, product, faradaic efficiency, cell setup, electrolyte, synthesis method, current density, and voltage are provided by either annotating or extracting. Machine learning algorithms can be applied to the corpus to help scientists find new and effective electrocatalysts. Furthermore, researchers familiar with NLP can use this corpus to design domain-specific named entity recognition (NER) models.

Wnt signaling pathways are transmitted via 10 homologous frizzled receptors (FZD1-10) in humans. Reagents broadly inhibiting Wnt signaling pathways reduce growth and metastasis of many tumors, but their therapeutic development has been hampered by the side effect. Inhibitors targeting specific Wnt-FZD pair(s) enriched in cancer cells may reduce side effect, but the therapeutic effect of narrow-spectrum Wnt-FZD inhibitors remains to be established in vivo. Here, we developed a fragment of C. difficile toxin B (TcdBFBD), which recognizes and inhibits a subclass of FZDs, FZD1/2/7, and examined whether targeting this FZD subgroup may offer therapeutic benefits for treating breast cancer models in mice. Utilizing 2 basal-like and 1 luminal-like breast cancer models, we found that TcdBFBD reduces tumor-initiating cells and attenuates growth of basal-like mammary tumor organoids and xenografted tumors, without damaging Wnt-sensitive tissues such as bones in vivo. Furthermore, FZD1/2/7-positive cells are enriched in chemotherapy-resistant cells in both basal-like and luminal mammary tumors treated with cisplatin, and TcdBFBD synergizes strongly with cisplatin in inhibiting both tumor types. These data demonstrate the therapeutic value of narrow-spectrum Wnt signaling inhibitor in treating breast cancers.

China’s agricultural and rural greenhouse gas emissions account for about 15% of its total emissions. Studying how to reduce China’s agricultural carbon emissions (ACEs) is of great strategic significance. Based on the panel data of 31 provinces (cities) in China from 2007 to 2020, this paper empirically tests the impact of fiscal environmental protection expenditure (FEPE) on ACEs. The results reveal that: FEPE has significant negative impacts on ACEs; FEPE has a heterogeneous impact on ACEs in different regions, which shows that it has a significant impact on the eastern and central regions and provinces with relatively “high” carbon emissions, while it has no significant impact on the western regions and provinces with relatively “low” carbon emissions; Further the results of mechanism analysis show that the impact of FEPE on ACEs is mainly manifested in its inhibiting effect on agricultural diesel, fertilizer and film use of carbon emissions. In light of these findings, it is imperative for the government to ensure steady and substantial investments in environmental protection. Moreover, implementing region-specific measures is essential to effectively curbing ACEs. The findings of this study offer invaluable insights that can guide the formulation of policies aimed at effectively reducing ACEs.

BackgroundIn recent years, there has been considerable growth in abnormal inflammatory reactions and immune system dysfunction, which are implicated in chronic inflammatory illnesses and a variety of other conditions. Dietary fibers have emerged as potential regulators of the human immune and inflammatory response. Therefore, this study aims to investigate the associations between dietary fibers intake and systemic immune and inflammatory biomarkers.MethodsThis cross-sectional study used data from the National Health and Nutrition Examination Survey (2015–2020). Dietary fibers intake was defined as the mean of two 24-h dietary recall interviews. The systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), neutrophil-to-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), red blood cell distribution width-to-albumin ratio (RA), ferritin, high-sensitivity C-reactive protein (hs-CRP), and white blood cell (WBC) count were measured to evaluate systemic immune and inflammatory states of the body. The statistical software packages R and EmpowerStats were used to examine the associations between dietary fibers intake and systemic immune and inflammatory biomarkers.ResultsOverall, 14,392 participants were included in this study. After adjusting for age, gender, race, family monthly poverty level index, alcohol consumption, smoking status, vigorous recreational activity, body mass index, hyperlipidemia, hypertension, diabetes, and dietary inflammatory index, dietary fibers intake was inversely associated with SII (β = −2.19885, 95% CI: −3.21476 to −1.18294, p = 0.000248), SIRI (β = −0.00642, 95% CI: −0.01021 to −0.00263, p = 0.001738), NLR (β = −0.00803, 95% CI: −0.01179 to −0.00427, p = 0.000284), RA (β = −0.00266, 95% CI: −0.00401 to −0.00131, p = 0.000644), ferritin (β = −0.73086, 95% CI: −1.31385 to −0.14787, p = 0.020716), hs-CRP (β = −0.04629, 95% CI: −0.0743 to −0.01829, p = 0.002119), WBC (β = −0.01624, 95% CI: −0.02685 to −0.00563, p = 0.004066), neutrophils (β = −0.01346, 95% CI: −0.01929 to −0.00764, p = 0.000064). An inverse association between dietary fibers and PLR was observed in the middle (β = −3.11979, 95% CI: −5.74119 to −0.4984, p = 0.028014) and the highest tertile (β = −4.48801, 95% CI: −7.92369 to −1.05234, p = 0.016881) and the trend test (βtrend = −2.2626, 95% CI: −3.9648 to −0.5604, Ptrend = 0.0150). The observed associations between dietary fibers intake and SII, SIRI, NLR, RA, ferritin, hs-CRP, WBC, and neutrophils remained robust and consistent in the sensitivity analysis. No significant interaction by race was found.ConclusionDietary fibers intake is associated with the improvement of the parameters of the immune response and inflammatory biomarkers, supporting recommendations to increase dietary fibers intake for enhanced immune health.

BackgroundTo assess the causal role of lipid traits and lipid-lowering agents in inflammatory bowel disease (IBD).MethodsUnivariable mendelian randomization (MR) and multivariable MR (MVMR) analyses were conducted to evaluate the causal association between low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and IBD. Drug-targeted MR analyzed the effects of lipid-lowering drugs on IBD, and network MR was used to analyze potential mediation effects.ResultsThe levels of HDL-C had an inverse relationship with the risk of Crohn’s disease (CD, OR: 0.85, 95% CI: 0.73-0.98, P = 0.024). In MVMR, the inverse relationships were found in all three outcomes. Drug-targeted MR analyses showed that with one-SD LDL-C decrease predicted by variants at or near proprotein convertase subtilisin/kexin type 9 (PCSK9), the OR values of people diagnosed with IBD, ulcerative colitis (UC) and CD were 1.75 (95%CI: 1.13-2.69, P = 0.011), 2.1 (95%CI: 1.28-3.42, P = 0.003) and 2.24 (95%CI: 1.11-4.5, P = 0.024), respectively. With one-SD LDL-C decrease predicted by variants at or near cholesteryl ester transfer protein (CETP), the OR value of people diagnosed with CD was 0.12 (95%CI: 0.03-0.51, P = 0.004). Network-MR showed that HDL-C mediated the causal pathway from variants at or near CETP to CD.ConclusionOur study suggested a causal association between HDL-C and IBD, UC and CD. Genetically proxied inhibition of PCSK9 increased the risk of IBD, UC and CD, while inhibition of CETP decreased the risk of CD. Further studies are needed to clarify the long-term effect of lipid-lowering drugs on the gastrointestinal disorders.

Butylphthalide, a prescription medicine recognized for its efficacy in treating ischemic strokes approved by the State Food and Drug Administration of China in 2005, is sourced from the traditional botanical remedy Ligusticum chuanxiong. While chemical synthesis offers a viable route, limitations in the production of isomeric variants with compromised bioactivity necessitate alternative strategies. Addressing this issue, biosynthesis offers a promising solution. However, the intricate in vivo pathway for butylphthalide biosynthesis remains elusive. In this study, we examined the distribution of butylphthalide across various tissues of L. chuanxiong and found a significant accumulation in the rhizome. By searching transcriptome data from different tissues of L. chuanxiong, we identified four rhizome-specific genes annotated as 2-oxoglutarate-dependent dioxygenase (2-OGDs) that emerged as promising candidates involved in butylphthalide biosynthesis. Among them, LcSAO1 demonstrates the ability to catalyze the desaturation of senkyunolide A at the C-4 and C-5 positions, yielding the production of butylphthalide. Experimental validation through transient expression assays in Nicotiana benthamiana corroborates this transformative enzymatic activity. Notably, phylogenetic analysis of LcSAO1 revealed that it belongs to the DOXB clade, which typically encompasses genes with hydroxylation activity, rather than desaturation. Further structure modelling and site-directed mutagenesis highlighted the critical roles of three amino acid residues, T98, S176, and T178, in substrate binding and enzyme activity. By unraveling the intricacies of the senkyunolide A desaturase, the penultimate step in the butylphthalide biosynthesis cascade, our findings illuminate novel avenues for advancing synthetic biology research in the realm of medicinal natural products.

Summary: Epithelial ovarian cancer (EOC) can originate from either fallopian tube epithelial (FTE) or ovarian surface epithelial (OSE) cells, but with different latencies and disease outcomes. To address the basis of these differences, we performed single cell RNA-sequencing of mouse cells isolated from the distal half of fallopian tube (FT) and surface layer of ovary. We find at the molecular level, FTE secretory stem/progenitor cells and OSE cells resemble mammary luminal progenitors and basal cells, respectively. An FT stromal subpopulation, enriched with Pdgfra+ and Esr1+ cells, expresses multiple secreted factor (e.g., IGF1) and Hedgehog pathway genes and may serve as a niche for FTE cells. In contrast, Lgr5+ OSE cells express similar genes largely by themselves, raising a possibility that they serve as their own niche. The differences in intrinsic expression programs and niche organizations of FTE and OSE cells may contribute to their different courses toward the development of EOCs.

Abstract Notch signaling is required to repress the formation of vertebrate cone photoreceptors and to maintain the proliferative potential of multipotent retinal progenitor cells. However, the mechanism by which Notch signaling controls these processes is unknown. Recently, restricted retinal progenitor cells with limited proliferation capacity and that preferentially generate cone photoreceptors have been identified. Thus, there are several potential steps during cone genesis that Notch signaling could act. Here we use cell type specific cis-regulatory elements to localize the primary role of Notch signaling in cone genesis to the formation of restricted retinal progenitor cells from multipotent retinal progenitor cells. Localized inhibition of Notch signaling in restricted progenitor cells does not alter the number of cones derived from these cells. Cell cycle promotion is not a primary effect of Notch signaling but an indirect effect on progenitor cell state transitions that leads to depletion of the multipotent progenitor cell population. Taken together, this suggests that the role of Notch signaling in cone photoreceptor formation and proliferation are both mediated by a localized function of Notch in multipotent retinal progenitor cells to repress the formation of restricted progenitor cells.

Cochlear nerve deficiency (CND) is often associated with variable outcomes of cochlear implantation (CI). We assessed previous investigations aiming to identify the main factors that determine CI outcomes, which would enable us to develop predictive models. Seventy patients with CND and normal cochlea who underwent CI surgery were retrospectively examined. First, using a data-driven approach, we collected demographic information, radiographic measurements, audiological findings, and audition and speech assessments. Next, CI outcomes were evaluated based on the scores obtained after 2 years of CI from the Categories of Auditory Performance index, Speech Intelligibility Rating, Infant/Toddler Meaningful Auditory Integration Scale or Meaningful Auditory Integration Scale, and Meaningful Use of Speech Scale. Then, we measured and averaged the audiological and radiographic characteristics of the patients to form feature vectors, adopting a multivariate feature selection method, called stability selection, to select the features that were consistent within a certain range of model parameters. Stability selection analysis identified two out of six characteristics, namely the vestibulocochlear nerve (VCN) area and the number of nerve bundles, which played an important role in predicting the hearing and speech rehabilitation results of CND patients. Finally, we used a parameter-optimized support vector machine (SVM) as a classifier to study the postoperative hearing and speech rehabilitation of the patients. For hearing rehabilitation, the accuracy rate was 71% for both the SVM classification and the area under the curve (AUC), whereas for speech rehabilitation, the accuracy rate for SVM classification and AUC was 93% and 94%, respectively. Our results identified that a greater number of nerve bundles and a larger VCN area were associated with better CI outcomes. The number of nerve bundles and VCN area can predict CI outcomes in patients with CND. These findings can help surgeons in selecting the side for CI and provide reasonable expectations for the outcomes of CI surgery.

Background and AimsHepatic ischemia–reperfusion injury (IRI) is a common phenomenon that occurs after liver transplantation and liver tumor surgery. It can cause liver dysfunction and recovery failure after liver surgery, even leading to acute liver failure. Our aim is to investigate the protective effect and related potential mechanism of [D-Ala2, D-Leu5] enkephalin (DADLE) treatment on hepatic IRI in cirrhotic livers of rats.MethodsThe models of liver cirrhosis and hepatic IRI were established with male Sprague–Dawley rats. DADLE at a dose series of 0.5, 1, or 5 mg·kg−1 was injected intravenously to rats 10 min prior hepatic ischemia, followed by a 6- h reperfusion. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), histological changes, and liver cell apoptosis were used to assess liver IRI. The optimal dose of DADLE was assessed by using the Suzuki score and ALT and AST levels. We repeated the hepatic IRI procedure on the optimal dose of the DADLE group and the delta opioid receptor (DOR) antagonist natrindole hydrochloride (NTD) injection group. Serum ALT and AST levels, histological staining, hepatic apoptosis, and serum levels of tumor necrosis factor alpha (TNF-α) and interleukin 1 β (IL-1β) were measured. The expression of protein kinase B (Akt) and its downstream proteins were evaluated by using quantitative real-time polymerase chain action (qRT-PCR) and Western blotting.ResultsCompared with the control group, DADLE treatment at a dose of 5 mg·kg−1 reduced the Suzuki score (mean: 5.8, range: 5.0–6.6 vs. mean: 8.0, range: 7.0–8.9), the ALT level (134.3 ± 44.7 vs. 247.8 ± 104.6), and the AST (297.1 ± 112.7 vs. 660.8 ± 104.3) level. DOR antagonist NTD aggravated hepatic IRI. Compared with the control group, DADLE treatment decreased the number of apoptosis cells and microphages and neutrophils, increased the expression of Akt and its mRNA to much higher levels, and upregulated the mRNA and protein expression of Bcl-2 and Bcl-2-associated death promoter (BAD).ConclusionDADLE treatment at a dose of 5 mg·kg−1 injected intravenously 10 min prior hepatic ischemia could contain rats’ hepatic IRI by activating DOR in cirrhotic livers. The effects of DADLE could be offset by NTD. The potential molecular mechanism seems to be involved in the phosphatidylinositol-3-kinase (PI3K)/Akt pathway.

ABSTRACT Interleukin-17 (IL-17) is associated with nonalcoholic fatty liver disease (NAFLD) and gut microbiota, and how IL-17 mediates the NAFLD/nonalcoholic steatohepatitis (NASH) process depending on the gut microbiota is unclear. We found that T helper 17 (TH17) cells were decreased in the small intestine in a methionine choline-deficient (MCD) diet-induced NASH model. IL-17-deficient (Il17−/−) mice showed alterations in intestinal microbiota, including the inhibition of probiotic growth and the overgrowth of certain pathogenic bacteria, and were prone to higher endotoxemia levels and more severe gastrointestinal barrier defects than wild-type (WT) mice. Furthermore, TH17 cells were responsible for restoring the intestinal barrier after administration of recombinant IL-17 to Il17−/− mice or injection of CD4+ T cells into a Rag1−/− mouse model. Additionally, transplantation of the microbiota from WT mice to Il17−/− mice restored the intestinal barrier. Notably, microbiota-depleted Il17−/− mice were resistant to MCD diet-induced intestinal barrier impairment. Fecal microbiota transplantation from Il17−/− mice to microbiota-depleted mice aggravated intestinal barrier impairment and then promoted the development of NASH. Collectively, this study showed that host IL-17 could strengthen intestinal mucosal barrier integrity and reduce dysbiosis-induced intestinal injury and secondary extraintestinal organ injury induced by a special diet. IMPORTANCE The morbidity of NASH has increased, with limited effective treatment options. IL-17 plays a protective role in the gut mucosa in high-fat-diet (HFD)-related metabolic disorders, and HFD-related microbiota dysbiosis is responsible for a decreased number of T helper 17 (TH17) cells in the lamina propria. The mechanism by which IL-17 mediates the NAFLD/NASH process depending on the gut microbiota is unclear. In our study, IL-17 originating from TH17 cells maintained intestinal barrier integrity and determined the outcomes of diet-related disease, which may be a target strategy for NAFLD/NASH.

Fuel conversion and clean energy reaction systems involve a variety of catalytic and non-catalytic gas-solid thermochemical reactions. A good understanding of the correct reaction mechanism and kinetics, as well as the profiles of reaction products, is of great significance to the development, design, and operation of such reaction systems. The micro fluidized bed reaction analysis provides an efficient and reliable method to acquire this essential information with low capital and operating costs, low energy consumption and enhanced safety. This paper provides an overview of the system and its characteristics for the micro fluidized bed reaction analyzer that has been well proven to be a reliable new approach as well as an instrument for characterizing various gas-solid thermochemical reactions.

The emerging and spreading of multi-drug resistant (MDR) bacteria have been becoming one of the most severe threats to human health. Enhancing oxidative stress as mimicking immune system was considered as a potential strategy to fight against infection of MDR bacteria. In this study, we investigated the antibacterial efficiency of such a strategy which combines silver nanoparticles (AgNPs) with ebselen. The results showed that AgNPs and ebselen combination had significant synergistic killing effects both on Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) in vitro, including model strains of China Veterinary Culture Collection and MDR clinical isolates, which is similar as the combination of silver ion and ebselen. AgNPs exhibited to be a strong inhibitor of bacterial thioredoxin reductase, same as a free silver ion. Ebselen mitigated the cytotoxicity of AgNPs to HeLa cells. However, in a bacteria-cell coexistence condition, the synergistic bactericidal effect was only observed on S. aureus (p

Castration-resistant prostate cancer (CRPC) continues to be a major clinical problem and its underlying mechanisms are still not fully understood. The epidermal growth factor receptor (EGFR) activation is an important event that regulates mitogenic signaling. EGFR signaling plays an important role in the transition from androgen dependence to castration-resistant state in prostate cancer (PCa). Kinesin family member 15 (KIF15) has been suggested to be overexpressed in multiple malignancies. Here, we demonstrate that KIF15 expression is elevated in CRPC. We show that KIF15 contributes to CRPC progression by enhancing the EGFR signaling pathway, which includes complex network intermediates such as mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/AKT pathways. In CRPC tumors, increased expression of KIF15 is positively correlated with EGFR protein level. KIF15 binds to EGFR, and prevents EGFR proteins from degradation in a Cdc42-dependent manner. These findings highlight the key role of KIF15 in the development of CRPC and rationalize KIF15 as a potential therapeutic target.

ObjectiveThis study was aimed at examining the effects of an adaptive non-linear frequency compression algorithm implemented in hearing aids (i.e., SoundRecover2, or SR2) at different parameter settings and auditory acclimatization on speech and sound-quality perception in native Mandarin-speaking adult listeners with sensorineural hearing loss.DesignData consisted of participants’ unaided and aided hearing thresholds, Mandarin consonant and vowel recognition in quiet, and sentence recognition in noise, as well as sound-quality ratings through five sessions in a 12-week period with three SR2 settings (i.e., SR2 off, SR2 default, and SR2 strong).Study SampleTwenty-nine native Mandarin-speaking adults aged 37–76 years old with symmetric sloping moderate-to-profound sensorineural hearing loss were recruited. They were all fitted bilaterally with Phonak Naida V90-SP BTE hearing aids with hard ear-molds.ResultsThe participants demonstrated a significant improvement of aided hearing in detecting high frequency sounds at 8 kHz. For consonant recognition and overall sound-quality rating, the participants performed significantly better with the SR2 default setting than the other two settings. No significant differences were found in vowel and sentence recognition among the three SR2 settings. Test session was a significant factor that contributed to the participants’ performance in all speech and sound-quality perception tests. Specifically, the participants benefited from a longer duration of hearing aid use.ConclusionFindings from this study suggested possible perceptual benefit from the adaptive non-linear frequency compression algorithm for native Mandarin-speaking adults with moderate-to-profound hearing loss. Periods of acclimatization should be taken for better performance in novel technologies in hearing aids.

BackgroundPatients with severe profound hearing loss could benefit from cochlear implantation (CI). However, the neural mechanism of such benefit is still unclear. Therefore, we analyzed the electroencephalogram (EEG) and behavioral indicators of auditory function remodeling in patients with CI. Both indicators were sampled at multiple time points after implantation (1, 90, and 180 days).MethodsFirst, the speech perception ability was evaluated with the recording of a list of Chinese words and sentences in 15 healthy controls (HC group) and 10 patients with CI (CI group). EEG data were collected using an oddball paradigm. Then, the characteristics of event-related potentials (ERPs) and mismatch negative (MMN) were compared between the CI group and the HC group. In addition, we analyzed the phase lag indices (PLI) in the CI group and the HC group and calculated the difference in functional connectivity between the two groups at different stages after implantation.ResultsThe behavioral indicator, speech recognition ability, in CI patients improved as the implantation time increased. The MMN analysis showed that CI patients could recognize the difference between standard and deviation stimuli just like the HCs 90 days after cochlear implantation. Comparing the latencies of N1/P2/MMN between the CI group and the HC group, we found that the latency of N1/P2 in CI patients was longer, while the latency of MMN in CI users was shorter. In addition, PLI-based whole-brain functional connectivity (PLI-FC) showed that the difference between the CI group and the HC group mainly exists in electrode pairs between the bilateral auditory area and the frontal area. Furthermore, all those differences gradually decreased with the increase in implantation time.ConclusionThe N1 amplitude, N1/P2/MMN latency, and PLI-FC in the alpha band may reflect the process of auditory function remodeling and could be an objective index for the assessment of speech perception ability and the effect of cochlear implantation.

Clonorchiasis, caused by chronic infection with Clonorchis sinensis (C. sinensis), is an important food-borne parasitic disease that seriously afflicts more than 35 million people globally, resulting in a socioeconomic burden in endemic regions. C. sinensis adults long-term inhabit the microaerobic and limited-glucose environment of the bile ducts. Energy metabolism plays a key role in facilitating the adaptation of adult flukes to crowded habitat and hostile environment. To understand energy source for adult flukes, we compared the component and content of free amino acids between C. sinensis-infected and uninfected bile. The results showed that the concentrations of free amino acids, including aspartic acid, serine, glycine, alanine, histidine, asparagine, threonine, lysine, hydroxylysine, and urea, were significantly higher in C. sinensis-infected bile than those in uninfected bile. Furthermore, exogenous amino acids could be utilized by adult flukes via the gluconeogenesis pathway regardless of the absence or presence of exogenous glucose, and the rate-limiting enzymes, such as C. sinensis glucose-6-phosphatase, fructose-1,6-bisphosphatase, phosphoenolpyruvate carboxykinase, and pyruvate carboxylase, exhibited high expression levels by quantitative real-time PCR analysis. Interestingly, no matter whether exogenous glucose was present, inhibition of gluconeogenesis reduced the glucose and glycogen levels as well as the viability and survival time of adult flukes. These results suggest that gluconeogenesis might play a vital role in energy metabolism of C. sinensis and exogenous amino acids probably serve as an important energy source that benefits the continued survival of adult flukes in the host. Our study will be a cornerstone for illuminating the biological characteristics of C. sinensis and the host-parasite interactions.

Abstract Background Clonorchis sinensis (C. sinensis) inhabits in bile duct of the host. However, the mechanisms involved in why C. sinensis can survive in the bile environment containing lipids have not yet been explored. In this study, C. sinensis acetoacetyl-CoA thiolase (CsACAT), a member of the thiolase family which has a key role in the beta oxidation pathway of fatty acid production, was identified and characterized to understand its potential role in adapting to the bile environment. Methods The encoding sequence, conserved domains and spatial structure of CsACAT were identified and analyzed by bioinformatic tools. Recombinant CsACAT (rCsACAT) was obtained using a procaryotic expression system. The expression pattern of CsACAT was confirmed by quantitative real-time PCR, western blotting, and immunofluorescence. Gradients of lecithin were then set to culture C. sinensis adults in vitro and the survival rate of C. sinensis was analyzed, as well as the expression level and enzymatic activity of CsACAT in different lipid environments. Hypercholesteremia rabbit models were established by feeding with a hyperlipidemic diet and then infected intragastrically with C. sinensis. One and a half months later, the worm burdens and the expression level of CsACAT was detected. Results CsACAT was confirmed to be a member of the thiolase family and present in the excretory/secretory proteins of C. sinensis. CsACAT was specifically localized at the vitellarium and sub-tegumental muscle layer in adult worms. The mRNA level of CsACAT in eggs was higher than those in adult worms and metacercariae. When adult worms were cultured with higher concentration of lecithin, the expression level and enzyme activity of CsACAT were up-regulated. The survival rate of adult worms was higher than control group. More adult worms were recovered from hypercholesteremia rabbit models. The expression level of CsACAT in these worms was higher than control group. Conclusions Our results implied that C. sinensis might sense lipid levels and survive better in the bile environment with higher lipid levels. C. sinensis might modulate the expression and enzymatic activity of CsACAT, an enzyme involved in fatty acid metabolism, for energy or physical requirements to adapt to the host.

Abstract Background Clonorchiasis is a globally important, neglected food-borne disease caused by Clonorchis sinensis (C. sinensis), and it is highly related to cholangiocarcinoma and hepatocellular carcinoma. Increased molecular evidence has strongly suggested that the adult worm of C. sinensis continuously releases excretory-secretory proteins (ESPs), which play important roles in the parasite-host interactions, to establish successful infection and ensure its own survival. Myoglobin, a hemoprotein, is present in high concentrations in trematodes and ESPs. To further understand the biological function of Cs Mb and its putative roles in the interactions of C. sinensis with its host, we explored the molecular characterization of Cs Mb in this paper. Methods We expressed Cs Mb and its mutants in E. coli BL21 and identified its molecular characteristics using bioinformatics analysis and experimental approaches. Reverse transcription PCR analysis was used to measure myoglobin transcripts of C. sinensis with different culture conditions. The peroxidase activity of Cs Mb was confirmed by spectrophotometry. We co-cultured RAW264.7 cells with recombinant Cs Mb (rCs Mb), and we then measured the production of hydrogen peroxide (H2O2) and nitric oxide (NO) in addition to the mRNA levels of inducible nitric oxide synthase (iNOS), Cu-Zn superoxide dismutase (SOD1) and Mn superoxide dismutase (SOD2) in activated RAW264.7 cells. Results In the in vitro culture of adult worms, the transcripts of Cs Mb increased with the increase of oxygen content. Oxidative stress conditions induced by H2O2 increased the levels of Cs Mb transcripts in a dose-dependent manner. Furthermore, Cs Mb catalyzed oxidation reactions in the presence of H2O2, and amino acid 34 of Cs Mb played an essential role in its reaction with H2O2. In addition, Cs Mb significantly reduced H2O2 and NO levels in LPS-activated macrophages, and Cs Mb downregulated iNOS and SOD expression in activated macrophages. Conclusion The present study is the first to investigate the peroxidase activity of Cs Mb. This investigation suggested that C. sinensis may decrease the redox activation of macrophages by Cs Mb expression to evade host immune responses. These studies contribute to a better understanding of the role of Cs Mb in the molecular mechanisms involved in ROS detoxification by C. sinensis.

The aim of this study is to survey and compare the development of auditory skills in young children with Mondini dysplasia and profoundly-deaf young children with radiologically normal inner ears over a period of 3 years after cochlear implantation. A total of 545 young children (age 7 to 36 months) with prelingual, severe to profound hearing loss participated in this study. All children received cochlear implantation. Based on whether or not there was a Mondini dysplasia as diagnosed with CT scanning, the subjects were divided into 2 groups: (A) 514 young children with radiologically normal inner ears and (B) 31 young children with Mondini dysplasia. The Infant-Toddler Meaningful Auditory Integration Scale (IT-MAIS) was used to assess the children's auditory skills that include vocalization changes, spontaneous alerting to sounds in everyday living environments, and the ability to derive meaning from sounds. The assessment was performed prior to surgery and at 1, 3, 6, 9, 12, 24, and 36 months after implant device switch-on. The mean scores for overall auditory skills were not significantly different between groups A and B at pre-surgery, 1, 12, 24, and 36 months post-surgery, but were significantly different at 3, 6, and 9 months post-surgery. The mean scores for all auditory skills in children with Mondini dysplasia showed significant improvement over time. The mean scores for the three subcategories of auditory skills in children with Mondini dysplasia also showed significant differences at pre-surgery, 1, 3, 6, and 9 months, however, there were no significant differences at 12, 24, and 36 months. Overall, the auditory skills of young children with Mondini dysplasia developed rapidly after cochlear implantation, in a similar manner to that of young children with radiologically normal inner ears. Cochlear implantation is an effective intervention for young children with Mondini dysplasia.

BACKGROUND: Clonorchiasis, caused by the infection of Clonorchis sinensis (C. sinensis), is a kind of neglected tropical disease, but it is highly related to cholangiocarcinoma and hepatocellular carcinoma (HCC). It has been well known that the excretory/secretory products of C. sinensis (CsESPs) play key roles in clonorchiasis associated carcinoma. From genome and transcriptome of C. sinensis, we identified one component of CsESPs, severin (Csseverin), which had three putative gelsolin domains. Its homologues are supposed to play a vital role in apoptosis resistance of tumour cell. METHODOLOGY/PRINCIPAL FINDINGS: There was significant similarity in tertiary structures between human gelsolin and Csseverin by bioinformatics analysis. We identified that Csseverin expressed at life stage of adult worm, metacercaria and egg by the method of quantitative real-time PCR and western blotting. Csseverin distributed in vitellarium and intrauterine eggs of adult worm and tegument of metacercaria by immunofluorence assay. We obtained recombinant Csseverin (rCsseverin) and confirmed that rCsseverin could bind with calciumion in circular dichroism spectrum analysis. It was demonstrated that rCsseverin was of the capability of actin binding by gel overlay assay and immunocytochemistry. Both Annexin V/PI assay and mitochondrial membrane potential assay of human hepatocarcinoma cell line PLC showed apoptosis resistance after incubation with different concentrations of rCsseverin. Morphological analysis, apoptosis-associated changes of mitochondrial membrane potential and Annexin V/PI apoptosis assay showed that co-incubation of PLC cells with rCsseverin in vitro led to an inhibition of apoptosis induced by serum-starved for 24 h. CONCLUSIONS/SIGNIFICANCE: Collectively, the molecular properties of Csseverin, a molecule of CsESPs, were characterized in our study. rCsseverin could cause obvious apoptotic inhibition in human HCC cell line. Csseverin might exacerbate the process of HCC patients combined with C. sinensis infection.

Possible risks in reservoir flood control and regulation cannot be objectively assessed by deterministic flood forecasts, resulting in the probability of reservoir failure. We demonstrated a risk analysis of reservoir flood routing calculation accounting for inflow forecast uncertainty in a sub-basin of Huaihe River, China. The Xinanjiang model was used to provide deterministic flood forecasts, and was combined with the Hydrologic Uncertainty Processor (HUP) to quantify reservoir inflow uncertainty in the probability density function (PDF) form. Furthermore, the PDFs of reservoir water level (RWL) and the risk rate of RWL exceeding a defined safety control level could be obtained. Results suggested that the median forecast (50th percentiles) of HUP showed better agreement with observed inflows than the Xinanjiang model did in terms of the performance measures of flood process, peak, and volume. In addition, most observations (77.2%) were bracketed by the uncertainty band of 90% confidence interval, with some small exceptions of high flows. Results proved that this framework of risk analysis could provide not only the deterministic forecasts of inflow and RWL, but also the fundamental uncertainty information (e.g., 90% confidence band) for the reservoir flood routing calculation.

ABSTRACT Aims/Introduction To assess the effect of empagliflozin treatment on left ventricular (LV), right ventricular (RV) and left atrial (LA) functions in diabetes patients with normal ejection fraction. Materials and Methods The study included a total of 128 diabetes patients with multiple cardiovascular risk factors who were subjected to a 6‐month follow up from the initiation of empagliflozin treatment. Before and after treatment with empagliflozin, LV, RV and LA strain, and noninvasive myocardial work parameters were evaluated by speckle tracking echocardiography. Results In 128 diabetes patients (mean age 56 ± 8 years, 85 men) with multiple cardiovascular risk factors, myocardial strain and work parameters were impaired, despite the absence of significant clinical symptoms of heart failure. After 6‐month treatment with empagliflozin, the absolute value of LV strain in all directions increased, represented by LV global longitudinal strain (−18.0 ± 1.7% to −19.2 ± 1.7% [mean ± SD]). The same trend in LV global work efficiency (93 [91–94] % to 94 [93–95] % [median (IQR)]), RV free‐wall longitudinal strain (−24.0 ± 2.7% to −25.0 ± 2.8%), LA reservoir (31 ± 5% to 34 ± 5%) and conduit strain (−14 ± 4% to −16 ± 4%) was also observed. LV mass index (106.9 ± 16.8–103.6 ± 16.4 g/m2) and LV global wasted work (143 [111–185] mmHg% to 108 [88–141] mmHg%) decreased after treatment (P

Background The benchmark dose (BMD) method calculates the dose associated with a specific change in response based on a specific dose-response relationship. Compared with the traditional no observed adverse effect level (NOAEL) method, the BMD method has many advantages, and the 95% lower confidence limit of benchmark dose lower limit (BMDL) is recommended to replace NOAEL in deriving biological exposure limits. No authority has yet published any health-based guideline for rare earth elements. Objective To evaluate genotoxicity threshold induced by acute exposure to neodymium nitrate in mice using BMD modeling through micronucleus test and comet assay. Methods SPF grade mice (n=90) were randomly divided into nine groups, including seven neodymium nitrate exposure groups, one control group (distilled water), and one positive control group (200 mg·kg−1 ethyl methanesulfonate), 10 mice in each group, half male and half female. The seven dose groups were fed by gavage with different concentrations of neodymium nitrate solution (male: 14, 27, 39, 55, 77, 109, and 219 mg·kg−1; female: 24, 49, 69, 97, 138, 195, and 389 mg·kg−1) twice at an interval of 21 h. Three hours after the last exposure, the animals were neutralized by cervical dislocation. The bone marrow of mice femur was taken to calculate the micronucleus rate of bone marrow cells, and the liver and stomach were taken for comet test. Results The best fitting models for the increase of polychromatophil micronucleus rate in bone marrow of female and male mice induced by neodymium nitrate were the exponential 4 model and the hill model, respectively. The BMD and the BMDL of female mice were calculated to be 31.37 mg·kg−1 and 21.90 mg·kg−1, and those of male mice were calculated to be 58.62 mg·kg−1 and 54.31 mg·kg−1, respectively. The best fitting models for DNA damage induced by neodymium nitrate in female and male mouse hepatocytes were the exponential 5 model and the exponential 4 model, respectively, and the calculated BMD and BMDL were 27.15 mg·kg−1 and 11.99 mg·kg−1 for female mice, and 16.28 mg·kg−1 and 10.47 mg·kg−1 for male mice, respectively. The hill model was the best fitting model for DNA damage of gastric adenocytes in both female and male mice, and the calculated BMD and BMDL were 36.73 mg·kg−1 and 19.92 mg·kg−1 for female mice, and 24.74 mg·kg−1 and 14.08 mg·kg−1 for male mice, respectively. Conclusion Taken the micronucleus rate of bone marrow cells, DNA damage of liver cells and gastric gland cells as the end points of genotoxicity, the BMDL of neodymium nitrate is 10.47 mg·kg−1, which can be used as the threshold of genotoxic effects induced by acute exposure to neodymium nitrate in mice.

Abstract Objectives To develop and validate a predictive model based on clinical features and multiparametric magnetic resonance imaging (mpMRI) to reduce unnecessary systematic biopsies (SBs) in biopsy-naïve patients with suspected prostate cancer (PCa). Methods A total of 274 patients who underwent combined cognitive MRI-targeted biopsy (MRTB) with SB were retrospectively enrolled and temporally split into development (n = 201) and validation (n = 73) cohorts. Multivariable logistic regression analyses were used to determine independent predictors of clinically significant PCa (csPCa) on cognitive MRTB, and the clinical, MRI, and combined models were established respectively. Area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analyses were assessed. Results Prostate imaging data and reporting system (PI-RADS) score, index lesion (IL) on the peripheral zone, age, and prostate-specific antigen density (PSAD) were independent predictors and included in the combined model. The combined model achieved the best discrimination (AUC 0.88) as compared to both the MRI model incorporated by PI-RADS score, IL level, and zone (AUC 0.86) and the clinical model incorporated by age and PSAD (AUC 0.70). The combined model also showed good calibration and enabled great net benefit. Applying the combined model as a reference for performing MRTB alone with a cutoff of 60% would reduce 43.8% of additional SB, while missing 2.9% csPCa. Conclusions The combined model based on clinical and mpMRI findings improved csPCa prediction and might be useful in making a decision about which patient could safely avoid unnecessary SB in addition to MRTB in biopsy-naïve patients. Critical relevance statement The combined model based on clinical and mpMRI findings improved csPCa prediction and might be useful in making a decision about which patient could safely avoid unnecessary SB in addition to MRTB in biopsy-naïve patients. Key points • Age, PSAD, PI-RADS score, and peripheral index lesion were independent predictors of csPCa. • Risk models were used to predict the probability of detecting csPCa on cognitive MRTB. • The combined model might reduce 43.8% of unnecessary SBs, while missing 2.9% csPCa. Graphical Abstract

Abstract Background Ultrasound (US) guided transoral biopsy is a novel and safe procedure for obtaining tissue in patients with oral masses. However, this procedure is less commonly used in comparison to US guided transcutaneous biopsy. The aim of this study is to compare the efficacy and safety of US-guided transoral and transcutaneous core needle biopsy (CNB) in patients with oral masses. Methods From November 2019 to March 2021, consecutive patients with oral masses were randomly assigned to undergo US-guided transoral CNB (transoral group) and US-guided transcutaneous CNB from a submental approach (transcutaneous group). During the operation, procedure time, intra‑operative blood loss volume, diagnostic performance, rate of complications and pain level were recorded and compared. Results There were 112 patients (62 in the transoral group and 50 in the transcutaneous group) evaluated in this study. The postprocedural complication rate of the transcutaneous group was significantly higher than the transoral group (24% vs. 0%, P = 0.000). There was no significant difference in accuracy (95.2% vs. 88%, P = 0.30), biopsy time (76 ± 12 s vs. 80 ± 13 s, p = 0.09), blood losses (2.6 ± 0.5 mL vs. 2.7 ± 0.4 mL, p = 0.17) and visual analogue score (p = 0.327 and p = 0.444 before and after the sampling procedure) between the two groups. Conclusion US-guided transoral CNB results in high rates of technical success and lower rates of postprocedural complications.

PurposeTo determine whether additional systematic biopsy is necessary in all biopsy naïve patients with MRI visible lesions by taking PI-RADS score and prostate volume into consideration.Materials and MethodsPatients who underwent combined systematic biopsy (SB) and cognitive MRI-targeted biopsy (TB) in our hospital between May 2018 and June 2020 were retrospectively reviewed. The detection rate of clinical significant prostate cancer (csPCa), biopsy grade group (GG) concordance, and disease upgrading rate on radical prostatectomy were compared between SB and TB and further stratified by PI-RADS v2.0 category and prostate volume.ResultsA total of 234 patients were analyzed in this study. TB alone detected more csPCa and less clinically insignificant prostate cancer (cisPCa) than SB alone in the whole cohort (57.3 vs 53%, P = 0.041; 3.8 vs 7.7%, P = 0.049 respectively). The additional SB indicated only a marginal increase of csPCa detection but a remarkable increase of cisPCa detection compared with targeted biopsy (59.4 vs 57.3%, P = 0.064; 3.8 vs 7.7%, P = 0.012). As stratified by PI-RADS category, the difference of csPCa detection rate between TB and SB was not significant either in PI-RADS 5 subgroup (83.8 vs 76.3%, P = 0.07) or in PI-RADS 3–4 subgroup (43.5 vs 40.9%, P = 1.0). Additional SB decreased the rate of disease upgrading on radical prostatectomy (RP) than TB alone in PI-RADS 3–4 subgroup (14.5 vs 25.5%, P = 0.031) other than PI-RADS 5 subgroup (6 vs 6%, P = 1.0). When stratified by prostate volume (PV), TB alone detected more csPCa than SB in small prostate (PV < 30 ml) group (81.0 vs 71.0%, P = 0.021) but not in large prostate (PV ≥ 30 ml) group (44.0 vs 42.7%, P = 0.754). The additional SB did not significantly decrease the rate of disease upgrading on RP than TB alone in either small or large prostate (6.4 vs 8.5%, P = 1.0; 13.8 vs 22.4%, P = 0.063).ConclusionThe combination biopsy method was no superior than targeted biopsy alone in PI-RADS 5 or in small volume prostate subgroup.

Abstract Adhesive capsulitis (AC) is a painful and disabling disorder, which caused restricted motion and chronic pain of shoulder. Intracavitary contrast-enhanced ultrasound has been recently applied to assess obstructive bile duct diseases, tubal patency, vesicoureteric reflux and so on. The aim of this study was to detect the value of US-arthrography by injecting the contrast agent SonoVue into glenohumeral joint compared with US in diagnosing AC. Utrasound (US) and US-arthrography images of 45 patients with AC were compared with that of 45 control subjects without AC with MRI as a gold standard. Patients with AC had a significantly thickened coracohumeral ligment (CHL, 3.1 mm) and inferior capsule (3.5 mm) on US, and a decreased volume of axillary recess (1.14 ml) on US-arthrography compared with the control subjects (1.59 ml). Filling defect (91.1%) and synovitis-like abnormality (75.6%) in the joint on US-arthrography were more sensitive than that of rotator interval abnormality (71.1%), thickened CHL more than 3 mm (64.4%), thickened inferior capsule more than 3.5 mm (66.7%) on US respectively for diagnosis of AC. Consequently, US-arthrography was more effective method than US for assessment of AC. Filling defects of joint cavity and synovitis-like abnormality in the joint are characteristic US-arthrography findings for diagnosing AC.

Reliable cell tracking is essential to understand the fate of stem cells following implantation, and thus promote the clinical application of stem cell therapy. Dual or multiple modal imaging modalities mediated by different types of multifunctional contrast agent are generally needed for efficient cell tracking. Here, we created a new contrast agent-PLGA/iron oxide microparticles (PLGA/IO MPs) and characterized the morphology, structure and function of enhancing both photoacoustic (PA) and magnetic resonance imaging (MRI). Both PA and MRI signal increased with increased Fe concentration of PLGA/IO MPs. Fluorescent staining, Prussian blue staining and transmission electron microscope (TEM) certified that PLGA/IO MPs were successfully encapsulated in the labeled TSCs. The established PLGA/IO MPs demonstrated superior ability of dual-modal PA/MRI tracking of TSCs without cytotoxicity at relatively lower Fe concentrations (50, 100 and 200 μg/mL). The optimal Fe concentration of PLGA/IO MPs was determined to be 100 μg/mL, thus laying a foundation for the further study of dual-modal PA/MRI tracking of TSCs in vivo and promoting the repair of injured tendon.

The purpose of this retrospective study is to evaluate the diagnostic value of contrast enhanced sonography plus gastric distention sonography, the Double Contrast-enhanced Ultrasound (DCUS) in gastric lesions.107 cases with pathology confirmed gastric lesions were retrospectively reviewed, DCUS and oral contrast agent ultrasound (US) were performed in all cases prior to operation. Perfusion parameters including arrival time (AT), peak intensity (PI), time to peak (TTP), and area under the curve (AUC) of the lesion and surrounding normal tissue were analyzed. A reader blinded to pathology results were asked to rate and compare each case with surgical or resection biopsy pathology results.From the 107 gastric lesions, 75 were malignant gastric lesions (33 gastric cancers,42 gastrointestinal stromal tumors (GISTs)) and 32 were benign gastric lesions (11 inflammatory masses and 21 polypoid adenomas). Compared with US, DCUS achieved higher value in sensitivity (90.6% vs. 70.6%), specificity (75% vs. 62.5%), positive predictive value (89.5% vs. 81.5%), negative predictive value (77.4% vs. 47.6%), and overall accuracy (85.9% vs. 68.2%). When US was tested against DCUS, the increase in correct diagnoses value was significant (P = .01). Furthermore, gastric cancer had faster AT, higher PI and AUC than normal tissue (P