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Purpose: To evaluate nnU-net's performance in automatically segmenting and volumetrically measuring ocular adnexal lymphoma (OAL) on multi-sequence MRI., Methods: We collected T1-weighted (T1), T2-weighted and T1-weighted contrast-enhanced images with/without fat saturation (T2_FS/T2_nFS, T1c_FS/T1c_nFS) of OAL from four institutions. Two radiologists manually annotated lesions as the ground truth using ITK-SNAP. A deep learning framework, nnU-net, was developed and trained using two models. Model 1 was trained on T1, T2, and T1c, while Model 2 was trained exclusively on T1 and T2. A 5-fold cross-validation was utilized in the training process. Segmentation performance was evaluated using the Dice similarity coefficient (DSC), sensitivity, and positive prediction value (PPV). Volumetric assessment was performed using Bland-Altman plots and Lin's concordance correlation coefficient (CCC)., Results: A total of 147 patients from one center were selected as training set and 33 patients from three centers were regarded as test set. For both Model 1 and 2, nnU-net demonstrated outstanding segmentation performance on T2_FS with DSC of 0.80-0.82, PPV of 84.5-86.1%, and sensitivity of 77.6-81.2%, respectively. Model 2 failed to detect 19 cases of T1c, whereas the DSC, PPV, and sensitivity for T1_nFS were 0.59, 91.2%, and 51.4%, respectively. Bland-Altman plots revealed minor tumor volume differences with 0.22-1.24 cm 3 between nnU-net prediction and ground truth on T2_FS. The CCC were 0.96 and 0.93 in Model 1 and 2 for T2_FS images, respectively., Conclusion: The nnU-net offered excellent performance in automated segmentation and volumetric assessment in MRI of OAL, particularly on T2_FS images., (© 2024. The Author(s).)

Background and Purpose: Reliable preoperative visualization of facial nerve morphology and understanding the spatial relationship between the facial nerve and tumors in the parotid gland can help clinicians perform safe and effective surgeries. Hence, this study aimed to compare the image quality of extracranial facial nerves obtained by using double-echo steady state with water excitation (DESS-WE) and CISS sequences and evaluate their diagnostic efficacy in the localization of parotid tumors., Materials and Methods: In total, 32 facial nerves of 16 healthy volunteers and 25 facial nerves of 25 patients with parotid tumors were included in this retrospective study. All participants underwent noncontrast-enhanced extracranial facial nerve MR imaging with DESS-WE and CISS with a 3T MR scanner equipped with a 64-channel head and neck coil. Image quality was subjectively evaluated by using a 5-point Likert scale by 2 radiologists. Inter- and intrarater agreements were assessed by using the Cohen κ coefficient. Receiver operating characteristic analysis was performed, and the diagnostic efficacies of DESS-WE and CISS images in localizing parotid tumors were calculated., Results: For healthy volunteers (11 men and 5 women; median age, 26 years), image quality scores for CISS were significantly higher than those for DESS-WE for the discrimination of the temporofacial and cervicofacial trunks (both, P < .001). In patients with parotid tumors (12 men and 13 women; median age, 58 years), CISS performed better than DESS-WE in terms of visualizing the spatial relationship of the facial nerve to the tumor and diagnostic confidence (both, P  < .001). Regarding the localization of parotid tumors, CISS showed excellent performance, comparable to that of DESS-WE (area under the curve, 0.981 versus 0.942, P  = .1489)., Conclusions: CISS achieved diagnostic performance comparable to DESS-WE in parotid tumor localization, with favorable image quality and more reliable morphologic visualization of the facial nerve., (© 2024 by American Journal of Neuroradiology.)

Robotics for scientific research are evolving from grasping macro-scale solid materials to directly actuating micro-scale liquid samples. However, current liquid actuation mechanisms often restrict operable liquid types or compromise the activity of biochemical samples by introducing interfering mediums. Here, we propose a robotic liquid handling system enabled by a novel droplet actuation mechanism, termed electret-induced polarization on droplet (EPD). EPD enables all-liquid actuation in principle and experimentally exhibits generality for actuating various inorganic/organic liquids with relative permittivity ranging from 2.25 to 84.2 and volume from 500 nL to 1 mL. Moreover, EPD is capable of actuating various biochemical samples without compromising their activities, including various body fluids, living cells, and proteins. A robotic system is also coupled with the EPD mechanism to enable full automation. EPD's high adaptability with liquid types and biochemical samples thus promotes the automation of liquid-based scientific experiments across multiple disciplines., (© 2024. The Author(s).)

Background and Objective: Current automatic electrocardiogram (ECG) diagnostic systems could provide classification outcomes but often lack explanations for these results. This limitation hampers their application in clinical diagnoses. Previous supervised learning could not highlight abnormal segmentation output accurately enough for clinical application without manual labeling of large ECG datasets., Method: In this study, we present a multi-instance learning framework called MA-MIL, which has designed a multi-layer and multi-instance structure that is aggregated step by step at different scales. We evaluated our method using the public MIT-BIH dataset and our private dataset., Results: The results show that our model performed well in both ECG classification output and heartbeat level, sub-heartbeat level abnormal segment detection, with accuracy and F1 scores of 0.987 and 0.986 for ECG classification and 0.968 and 0.949 for heartbeat level abnormal detection, respectively. Compared to visualization methods, the IoU values of MA-MIL improved by at least 17 % and at most 31 % across all categories., Conclusions: MA-MIL could accurately locate the abnormal ECG segment, offering more trustworthy results for clinical application., Competing Interests: Declaration of competing interest The authors have no competing interests to declare that are relevant to the content of this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Honeybees are an indispensable pollinator in nature with pivotal ecological, economic, and scientific value. However, a full-length transcriptome for Apis mellifera , assembled with the advanced third-generation nanopore sequencing technology, has yet to be reported. Here, nanopore sequencing of the midgut tissues of uninoculated and Nosema ceranae -inoculated A. mellifera workers was conducted, and the full-length transcriptome was then constructed and annotated based on high-quality long reads. Next followed improvement of sequences and annotations of the current reference genome of A. mellifera. A total of 5,942,745 and 6,664,923 raw reads were produced from midguts of workers at 7 days post-inoculation (dpi) with N. ceranae and 10 dpi, while 7,100,161 and 6,506,665 raw reads were generated from the midguts of corresponding uninoculated workers. After strict quality control, 6,928,170, 6,353,066, 5,745,048, and 6,416,987 clean reads were obtained, with a length distribution ranging from 1 kb to 10 kb. Additionally, 16,824, 17,708, 15,744, and 18,246 full-length transcripts were respectively detected, including 28,019 nonredundant ones. Among these, 43,666, 30,945, 41,771, 26,442, and 24,532 full-length transcripts could be annotated to the Nr, KOG, eggNOG, GO, and KEGG databases, respectively. Additionally, 501 novel genes (20,326 novel transcripts) were identified for the first time, among which 401 (20,255), 193 (13,365), 414 (19,186), 228 (12,093), and 202 (11,703) were respectively annotated to each of the aforementioned five databases. The expression and sequences of three randomly selected novel transcripts were confirmed by RT-PCR and Sanger sequencing. The 5' UTR of 2082 genes, the 3' UTR of 2029 genes, and both the 5' and 3' UTRs of 730 genes were extended. Moreover, 17,345 SSRs, 14,789 complete ORFs, 1224 long non-coding RNAs (lncRNAs), and 650 transcription factors (TFs) from 37 families were detected. Findings from this work not only refine the annotation of the A. mellifera reference genome, but also provide a valuable resource and basis for relevant molecular and -omics studies.

This study investigates the sedimentation behaviors of microplastics (MPs) within a typical meso-scale river estuary, the Yalu River Estuary (YRE) and its riverine reservoir. It analyzes sediment cores in two habitats of Yalu River, revealing changing MPs abundance over time. Results highlight significant differences in riverine and estuarine MPs deposition. Reservoir sample contains more MPs in fragments. Color variations are notable in estuarine samples but minimal in reservoir sample. After 1980, estuarine cores show an increase in coarser MPs, likely due to growth of aquaculture activities. Although sediment accumulates at 1/10 of the rate in reservoir compared to estuary, MPs in reservoir sediments exceeds estuarine level by over threefold. A possible mechanistic framework is then proposed to discuss the varying MPs behaviors in the two habitats, indicating reservoirs accumulate MPs at a higher rate due to the barrier effect of an upper-stream reservoir, stable hydrodynamics, and weak salinity-induced buoyancy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In the present study, small RNA (sRNA) data from Ascosphaera apis were filtered from sRNA-seq datasets from the gut tissues of A. apis -infected Apis mellifera ligustica worker larvae, which were combined with the previously gained sRNA-seq data from A. apis spores to screen differentially expressed milRNAs (DEmilRNAs), followed by trend analysis and investigation of the DEmilRNAs in relation to significant trends. Additionally, the interactions between the DEmilRNAs and their target mRNAs were verified using a dual-luciferase reporter assay. In total, 974 A. apis milRNAs were identified. The first base of these milRNAs was biased toward U. The expression of six milRNAs was confirmed by stem-loop RT-PCR, and the sequences of milR-3245-y and milR-10285-y were validated using Sanger sequencing. These miRNAs grouped into four significant trends, with the target mRNAs of DEmilRNAs involving 42 GO terms and 120 KEGG pathways, such as the fungal-type cell wall and biosynthesis of secondary metabolites. Further investigation demonstrated that 299 DEmilRNAs (novel-m0011-3p, milR-10048-y, bantam-y, etc.) potentially targeted nine genes encoding secondary metabolite-associated enzymes, while 258 (milR-25-y, milR-14-y, milR-932-x, etc.) and 419 (milR-4561-y, milR-10125-y, let-7-x, etc.) DEmilRNAs putatively targeted virulence factor-encoded genes and nine genes involved in the MAPK signaling pathway, respectively. Additionally, the interaction between ADM-B and milR-6882-x, as well as between PKIA and milR-7009-x were verified. Together, these results not only offer a basis for clarifying the mechanisms underlying DEmilRNA-regulated pathogenesis of A. apis and a novel insight into the interaction between A. apis and honey bee larvae, but also provide candidate DEmilRNA-gene axis for further investigation., Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of the study, the collection, analyses, the interpretation of data, the writing of the manuscript and the decision to publish the results., (Copyright © 2024 Fan, Gao, Zang, Liu, Jing, Liu, Guo, Jiang, Wu, Huang, Chen and Guo.)

Platinum supramolecular complexes based on photosensitizers have garnered great interest in photodynamic therapy (PDT) due to Pt (II) centers as chemotherapeutic agents to eliminate tumor cells completely, which greatly improve the antitumor efficacy of PDT. However, in comparison to precursor photosensitizer ligand, the formed platinum supramolecular complexes typically exhibit inferior outcomes in terms of reactive oxygen species (ROS) generation. How to boost ROS generation in the formed platinum supramolecular complexes for enhanced PDT is an enticing yet highly challenging task. Here we report a Pt-coordination-based dimeric photosensitizer complex (Cz-BTZ-Py) 2 Pt(OTf) 2 . It is found that comparing with photosensitizer ligand Cz-BTZ-Py, the formed supramolecular complex exhibit redshifts of absorption wavelength as well as enhanced ROS generation efficiency. Moreover, type-I ROS generation (O 2 ⋅ - ) is produced in the formed platinum supramolecular complexes mainly due to a reduced energy gap ΔE ST resulting from exciton coupling between two photosensitizer ligands. And type-I ROS (O 2 ⋅ - ) generation significantly amplifies the photodynamic therapy (PDT) outcomes. In vitro evaluation shows excellent photochemotherapy performance of (Cz-BTZ-Py) 2 Pt(OTf) 2 nanoparticles. We anticipate this work would provide a novel approach to design type-I photosensitizers for efficient PDT., (© 2024 Wiley‐VCH GmbH.)

Background: Coronary artery segmentation is a prerequisite in computer-aided diagnosis of Coronary Artery Disease (CAD). However, segmentation of coronary arteries in Coronary Computed Tomography Angiography (CCTA) images faces several challenges. The current segmentation approaches are unable to effectively address these challenges and existing problems such as the need for manual interaction or low segmentation accuracy., Objective: A Multi-scale Feature Learning and Rectification (MFLR) network is proposed to tackle the challenges and achieve automatic and accurate segmentation of coronary arteries., Methods: The MFLR network introduces a multi-scale feature extraction module in the encoder to effectively capture contextual information under different receptive fields. In the decoder, a feature correction and fusion module is proposed, which employs high-level features containing multi-scale information to correct and guide low-level features, achieving fusion between the two-level features to further improve segmentation performance., Results: The MFLR network achieved the best performance on the dice similarity coefficient, Jaccard index, Recall, F1-score, and 95% Hausdorff distance, for both in-house and public datasets., Conclusion: Experimental results demonstrate the superiority and good generalization ability of the MFLR approach. This study contributes to the accurate diagnosis and treatment of CAD, and it also informs other segmentation applications in medicine.

Circular RNAs (circRNAs) are a class of novel non-coding RNAs (ncRNAs) that play essential roles in the development and growth of vertebrates through multiple manners. However, the mechanism by which circRNAs modulate the honey bee gut development is currently poorly understood. Utilizing the transcriptome data we obtained earlier, the highly expressed circRNAs in the Apis mellifera worker 4-, 5-, and 6-day-old larval guts were analyzed, which was followed by an in-depth investigation of the expression pattern of circRNAs during the process of larval guts development and the potential regulatory roles of differentially expressed circRNAs (DEcircRNAs). In total, 1728 expressed circRNAs were detected in the A. mellifera larval guts. Among the most highly expressed 10 circRNAs, seven (novel&#95;circ&#95;000069, novel&#95;circ&#95;000027, novel&#95;circ&#95;000438, etc.) were shared by the 4-, 5-, and 6-day-old larval guts. In addition, 21 (46) up-regulated and 22 (27) down-regulated circRNAs were, respectively, screened in the Am4 vs. Am5 (Am5 vs. Am6) comparison groups. Additionally, nine DEcircRNAs, such as novel&#95;circ&#95;000340, novel&#95;circ&#95;000758 and novel&#95;circ&#95;001116, were shared by these two comparison groups. These DEcircRNAs were predicted to be transcribed from 14 and 29 parental genes; these were respectively annotated to 15 and 22 GO terms such as biological regulation and catalytic activity as well as 16 and 21 KEGG pathways such as dorsoventral axis formation and apoptosis. Moreover, a complicated competing endogenous RNA (ceRNA) network was observed; novel&#95;circ&#95;000838 in the Am4 vs. Am5 comparison group potentially targeted ame-miR-6000a-3p, further targeting 518 mRNAs engaged in several developmental signaling pathways (e.g., TGF-beta, hedgehog, and wnt signaling pathway) and immune pathways (e.g., phagosome, lysosome, and MAPK signaling pathway). The results demonstrated that the novel&#95;circ&#95;000838-ame-miR-6000a-3p axis may plays a critical regulatory part in the larval gut development and immunity. Furthermore, back-splicing sites of six randomly selected DEcircRNAs were amplified and verified by PCR; an RT-qPCR assay of these six DEcircRNAs confirmed the reliability of the used high-throughput sequencing data. Our findings provide a novel insight into the honey bee gut development and pave a way for illustration of the circRNA-modulated developmental mechanisms underlying the A. mellifera worker larval guts.

piRNAs are a class of small non-coding RNAs that play essential roles in modulating gene expression and abundant biological processes. To decode the piRNA-regulated larval response of western honeybees ( Apis mellifera ) to Ascosphaera apis infection, the expression pattern of piRNAs in Apis mellifera ligustica larval guts after A. apis inoculation was analyzed based on previously obtained high-quality small RNA-seq datasets, followed by structural characterization, target prediction, regulatory network investigation, and functional dissection. Here, 504, 657, and 587 piRNAs were respectively identified in the 4-, 5-, and 6-day-old larval guts after inoculation with A. apis , with 411 ones shared. These piRNAs shared a similar length distribution and first base bias with mammal piRNAs. Additionally, 96, 103, and 143 DEpiRNAs were detected in the 4-, 5-, and 6-day-old comparison groups. Targets of the DEpiRNAs were engaged in diverse pathways such as the phosphatidylinositol signaling system, inositol phosphate metabolism, and Wnt signaling pathway. These targets were involved in three energy metabolism-related pathways, eight development-associated signaling pathways, and seven immune-relevant pathways such as the Jak-STAT signaling pathway. The expression trends of five randomly selected DEpiRNAs were verified using a combination of RT-PCR and RT-qPCR. The effective overexpression and knockdown of piR-ame-945760 in A. apis -infected larval guts were achieved by feeding a specific mimic and inhibitor. Furthermore, piR-ame-945760 negatively regulated the expression of two target immune mRNAs, SOCS 5 and ARF 1, in the larval gut during the A. apis infection. These findings indicated that the overall expression level of piRNAs was increased and the expression pattern of piRNAs in larval guts was altered due to the A. apis infection, DEpiRNAs were putative regulators in the A. apis -response of A. m. ligustica worker larvae. Our data provide not only a platform for the functional investigation of piRNAs in honeybees, especially in bee larvae, but also a foundation for illuminating the piRNA-involved mechanisms underlying the host response to the A. apis infection.

In proteomics research, with advantages including short digestion times and reusable applications, immobilized enzyme reactors (IMERs) have been paid increasing attention. However, traditional IMERs ignore the reasonable spatial arrangement of trypsin on the supporting matrixes, resulting in the partial overlapping of the active domain on trypsin and reducing digesting efficiency. In this work, a DNA tetrahedron (DNA TET)-based IMER Fe 3 O 4 -GO-AuNPs-DNA TET-Trypsin was designed and prepared. The distance between vertices of DNA TETs effectively controls the distribution of trypsin on the nanomaterials; thus, highly efficient protein digestion and accurate quantitative results can be achieved. Compared to the in-solution digestion (12-16 h), the sequence coverage of bovine serum albumin was up to 91% after a 2-min digestion by the new IMER. In addition, 3328 proteins and 18,488 peptides can be identified from HeLa cell protein extract after a 20-min digestion. For the first time, human growth hormone reference material was rapidly and accurately quantified after a 4-h digestion by IMER. Therefore, this new IMER has great application potential in proteomics research and SI traceable quantification.

Long non-coding RNAs (lncRNAs) are crucial modulators in a variety of biological processes, such as gene expression, development, and immune defense. However, little is known about the function of lncRNAs in the development of Asian honey bee ( Apis cerana ) larval guts. Here, on the basis of our previously obtained deep-sequencing data from the 4-, 5-, and 6-day-old larval guts of A. cerana workers (Ac4, Ac5, and Ac6 groups), an in-depth transcriptome-wide investigation was conducted to decipher the expression pattern, regulatory manners, and potential roles of lncRNAs during the developmental process of A. cerana worker larval guts, followed by the verification of the relative expression of differentially expressed lncRNAs (DElncRNAs) and the targeting relationships within a competing endogenous RNA (ceRNA) axis. In the Ac4 vs. Ac5 and Ac5 vs. Ac6 comparison groups, 527 and 498 DElncRNAs were identified, respectively, which is suggestive of the dynamic expression of lncRNAs during the developmental process of larval guts. A cis -acting analysis showed that 330 and 393 neighboring genes of the aforementioned DElncRNAs were respectively involved in 29 and 32 functional terms, such as cellular processes and metabolic processes; these neighboring genes were also respectively engaged in 246 and 246 pathways such as the Hedgehog signaling pathway and the Wnt signaling pathway. Additionally, it was found that 79 and 76 DElncRNAs as potential antisense lncRNAs may, respectively, interact with 72 and 60 sense-strand mRNAs. An investigation of competing endogenous RNA (ceRNA) networks suggested that 75 (155) DElncRNAs in the Ac4 vs. Ac5 (Ac5 vs. Ac6) comparison group could target 7 (5) DEmiRNAs and further bind to 334 (248) DEmRNAs, which can be annotated to 33 (29) functional terms and 186 (210) pathways, including 12 (16) cellular- and humoral-immune pathways (lysosome pathway, necroptosis, MAPK signaling pathway, etc.) and 11 (10) development-associated signaling pathways (Wnt, Hippo, AMPK, etc.). The RT-qPCR detection of five randomly selected DElncRNAs confirmed the reliability of the used sequencing data. Moreover, the results of a dual-luciferase reporter assay were indicative of the binding relationship between MSTRG.11294.1 and miR-6001-y and between miR-6001-y and ncbi&#95;107992440. These results demonstrate that DElncRNAs are likely to modulate the developmental process of larval guts via the regulation of the source genes' transcription, interaction with mRNAs, and ceRNA networks. Our findings not only yield new insights into the developmental mechanism underlying A. cerana larval guts, but also provide a candidate ceRNA axis for further functional dissection.

Light plays a dominant role in the biosynthesis and accumulation of photosynthetic products. However, the metabolism and translocation of photosynthetic products in plants under different light spectra remain elusive. In this study, tomato ( Solanum lycopersicum L.) seedlings were treated with different light spectra delivered by light-emitting diodes (LEDs) with the same photosynthetic photon flux density at 300 μmol m -2 s -1 , including monochromatic red (660 nm, R), blue (450 nm, B), sun-like white (W, 380-780 nm), or a combination of R and B lights (R:B = 1:1, RB). Compared with W, the biomass distribution ratio for leaves under R, B, and RB decreased by 5.01-9.53%, while the ratio for stems and roots increased by 3.71-6.92% and 0.14-2.81%, respectively. The photosynthetic carbon distribution expressed as 13 C enrichment was higher in stems and roots under RB and R, while B led to more 13 C transported from leaves and enriched in stems when compared with W. Meanwhile, RB led to significant increases in the activities of phosphate synthase (SPS), sucrose synthase (SS), vacuolar acid invertase (VI), and neutral invertase (NI). The R was more efficient in increasing the activity of SPS and SS, while B was more effective in promoting the activity of VI and NI. The transcript levels of SPS , SS3 , NI6 , and VI were upregulated under R, B, and RB. However, the transcript patterns of SPS , SS3 , NI6 , and VI were not consistent with the changes in their encoded enzymes, especially the transcript patterns of SPS and SS3 . Our study suggests that the red- and blue-light-induced long-distance and short-distance transport of photosynthetic products in plants, respectively, might result from different regulation of sucrose-metabolizing enzymes from transcriptional and post-transcriptional levels.

Long non-coding RNAs (lncRNAs) play an essential part in controlling gene expression and a variety of biological processes such as immune defense and stress-response. However, whether and how lncRNAs regulate responses of Apis cerana larvae to Ascosphaera apis invasion has remained unclear until now. Here, the identification and structural analysis of lncRNAs in the guts of A. cerana worker larvae were conducted, and the expression profile of larval lncRNAs during the A. apis infection process was then analyzed, followed by an investigation of the regulatory roles of differentially expressed lncRNAs (DElncRNAs) in the host response. In total, 76 sense lncRNAs, 836 antisense lncRNAs, 184 intron lncRNAs, 362 bidirectional lncRNAs, and 2181 intron lncRNAs were discovered in the larval guts. Additionally, 30 known and 9 novel lncRNAs were potential precursors for 36 and 11 miRNAs, respectively. In the three comparison groups, 386, 351, and 272 DElncRNAs were respectively identified, indicating the change in the overall expression pattern of host lncRNAs following the A. apis invasion. Analysis of cis -acting effect showed that DElncRNAs in the 4-, 5-, and 6-day-old comparison groups putatively regulated 55, 30, and 20 up- and down-stream genes, respectively, which were involved in a series of crucial functional terms and pathways, such as MAPK signaling pathway, and cell process. Analysis showed that 31, 8, and 11 DElncRNAs as potential antisense lncRNAs may interact with 26, 8, and 9 sense-strand mRNAs. Moreover, investigation of the competing endogenous RNA (ceRNA) network indicated that 148, 283, and 257 DElncRNAs were putatively regulated. The expression of target genes by targeting corresponding DEmiRNAs included those associated with antioxidant enzymes and immune responses. These results suggested that DElncRNAs played a potential part in the larval guts responding to the A. apis infection through a cis -acting manner and ceRNA mechanisms. Our findings deepen our understanding of interactions between A. cerana larvae and A. apis and offer a basis for clarifying the DElncRNA-mediated mechanisms underlying the host response to fungal invasion.

Light-emitting diodes (LEDs) have been widely used as light sources for plant production in plant factories with artificial lighting (PFALs), and light spectrum and light amount have great impacts on plant growth and development. With the expansion of the product list of PFALs, tomato production in PFALs has received attention, but studies on fruit quality influenced by artificial light are lacking. In this study, precisely modulated LED light sources based on white light combined with additional red, blue, and green lights were used to investigate the effects of light spectrum and daily light integral (DLI) on the main quality indicators and flavor substances of "Micro-Tom" tomato fruits. The highest sugar-acid ratio was obtained under the white light with addition of red light with high DLI and blue light with low DLI. The contents of β-carotene, lycopene, and lutein were significantly increased by higher DLI conditions except for under the blue light treatment, and the cross-interactions between the light spectrum and DLI were observed. The accumulation of the main flavor substances in tomato fruits was decreased by addition of green light with a high DLI and red light with a low DLI; notably, the percentage of 2-isobutylthiazole, which is associated with fresh tomato aroma, was decreased by green light. This study provides insights for improving tomato fruit quality and flavor by regulating light conditions in PFALs.

MiRNAs, as a kind of key regulators in gene expression, play vital roles in numerous life activities from cellular proliferation and differentiation to development and immunity. However, little is known about the regulatory manner of miRNAs in the development of Asian honey bee ( Apis cerana ) guts. Here, on basis of our previously gained high-quality transcriptome data, transcriptome-wide identification of miRNAs in the larval guts of Apis cerana cerana was conducted, followed by investigation of the miRNAs' differential expression profile during the gut development. In addition to the regulatory network, the potential function of differentially expressed miRNAs (DEmiRNAs) was further analyzed. In total, 330, 351, and 321 miRNAs were identified in the 4-, 5-, and 6-day-old larval guts, respectively; among these, 257 miRNAs were shared, while 38, 51, and 36 ones were specifically expressed. Sequences of six miRNAs were confirmed by stem-loop RT-PCR and Sanger sequencing. Additionally, in the "Ac4 vs. Ac5" comparison group, there were seven up-regulated and eight down-regulated miRNAs; these DEmiRNAs could target 5041 mRNAs, involving a series of GO terms and KEGG pathways associated with growth and development, such as cellular process, cell part, Wnt, and Hippo. Comparatively, four up-regulated and six down-regulated miRNAs detected in the "Ac5 vs. Ac6" comparison group and the targets were associated with diverse development-related terms and pathways, including cell, organelle, Notch and Wnt. Intriguingly, it was noticed that miR-6001-y presented a continuous up-regulation trend across the developmental process of larval guts, implying that miR-6001-y may be a potential essential modulator in the development process of larval guts. Further investigation indicated that 43 targets in the "Ac4 vs. Ac5" comparison group and 31 targets in the "Ac5 vs. Ac6" comparison group were engaged in several crucial development-associated signaling pathways such as Wnt, Hippo, and Notch. Ultimately, the expression trends of five randomly selected DEmiRNAs were verified using RT-qPCR. These results demonstrated that dynamic expression and structural alteration of miRNAs were accompanied by the development of A. c. cerana larval guts, and DEmiRNAs were likely to participate in the modulation of growth as well as development of larval guts by affecting several critical pathways via regulation of the expression of target genes. Our data offer a basis for elucidating the developmental mechanism underlying Asian honey bee larval guts.

Background: Branched-chain fatty acid (BCFA) is effective in preventing and helping to treat neonatal necrotizing enterocolitis. It is essential to supplement goat-milk powder for formula-fed preterm infants with BCFA. In this study, the quality and microstructures of milk powders supplemented with different concentrations of BCFA were evaluated, using goat milk powder without BCFA as the control group (CG)., Results: In comparison with the CG, goat milk powder supplemented with BCFA exhibited smaller fat globules and a significant drop in overall particle size. During 16 weeks of storage, BCFA-supplemented groups showed suitable moisture content and viscosity and good solubility. The BCFA also helped reduce the number of folds on the surface of the milk powder particles., Conclusion: The findings of this study indicate that goat milk powders with BCFA exhibit differences in quality and microstructure in comparison with ordinary goat milk powder, which is relevant for the future development and application of BCFA in foods. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)

Long noncoding RNAs (lncRNAs) are pivotal regulators in gene expression and diverse biological processes, such as immune defense and host-pathogen interactions. However, little is known about the roles of lncRNAs in the response of the Asian honey bee ( Apis cerana ) to microsporidian infestation. Based on our previously obtained high-quality transcriptome datasets from the midgut tissues of Apis cerana cerana workers at 7 days post inoculation (dpi) and 10 dpi with Nosema ceranae (AcT7 and AcT10 groups) and the corresponding un-inoculated midgut tissues (AcCK7 and AcCK10 groups), the transcriptome-wide identification and structural characterization of lncRNAs were conducted, and the differential expression pattern of lncRNAs was then analyzed, followed by investigation of the regulatory roles of differentially expressed lncRNAs (DElncRNAs) in host response. Here, 2365, 2322, 2487, and 1986 lncRNAs were, respectively, identified in the AcCK7, AcT7, AcCK7, and AcT10 groups. After removing redundant ones, a total of 3496 A. c. cerana lncRNAs were identified, which shared similar structural characteristics with those discovered in other animals and plants, such as shorter exons and introns than mRNAs. Additionally, 79 and 73 DElncRNAs were screened from the workers' midguts at 7 dpi and 10 dpi, respectively, indicating the alteration of the overall expression pattern of lncRNAs in host midguts after N. ceranae infestation. These DElncRNAs could, respectively, regulate 87 and 73 upstream and downstream genes, involving a suite of functional terms and pathways, such as metabolic process and Hippo signaling pathway. Additionally, 235 and 209 genes co-expressed with DElncRNAs were found to enrich in 29 and 27 terms, as well as 112 and 123 pathways, such as ABC transporters and the cAMP signaling pathway. Further, it was detected that 79 (73) DElncRNAs in the host midguts at 7 (10) dpi could target 321 (313) DEmiRNAs and further target 3631 (3130) DEmRNAs. TCONS&#95;00024312 and XR&#95;001765805.1 were potential precursors for ame-miR-315 and ame-miR-927, while TCONS&#95;00006120 was the putative precursor for both ame-miR-87-1 and ame-miR-87-2. These results together suggested that DElncRNAs are likely to play regulatory roles in the host response to N. ceranae infestation through the regulation of neighboring genes via a cis -acting effect, modulation of co-expressed mRNAs via trans -acting effect, and control of downstream target genes' expression via competing endogenous RNA networks. Our findings provide a basis for disclosing the mechanism underlying DElncRNA-mediated host N. ceranae response and a new perspective into the interaction between A. c. cerana and N. ceranae .

Ascosphaera apis infects exclusively bee larvae and causes chalkbrood, a lethal fungal disease that results in a sharp reduction in adult bees and colony productivity. However, little is known about the effect of A. apis infestation on the activities of antioxidant enzymes in bee larvae. Here, A. apis spores were purified and used to inoculate Asian honey bee (Apis cerana) larvae, followed by the detection of the host survival rate and an evaluation of the activities of four major antioxidant enzymes. At 6 days after inoculation (dpi) with A. apis spores, obvious symptoms of chalkbrood disease similar to what occurs in Apis mellifera larvae were observed. PCR identification verified the A. apis infection of A. cerana larvae. Additionally, the survival rate of larvae inoculated with A. apis was high at 1−2 dpi, which sharply decreased to 4.16% at 4 dpi and which reached 0% at 5 dpi, whereas that of uninoculated larvae was always high at 1~8 dpi, with an average survival rate of 95.37%, indicating the negative impact of A. apis infection on larval survival. As compared with those in the corresponding uninoculated groups, the superoxide dismutase (SOD) and catalase (CAT) activities in the 5- and 6-day-old larval guts in the A. apis−inoculated groups were significantly decreased (p < 0.05) and the glutathione S-transferase (GST) activity in the 4- and 5-day-old larval guts was significantly increased (p < 0.05), which suggests that the inhibition of SOD and CAT activities and the activation of GST activity in the larval guts was caused by A. apis infestation. In comparison with that in the corresponding uninoculated groups, the polyphenol oxidase (PPO) activity was significantly increased (p < 0.05) in the 5-day-old larval gut but significantly reduced (p < 0.01) in the 6-day-old larval gut, indicating that the PPO activity in the larval guts was first enhanced and then suppressed. Our findings not only unravel the response of A. cerana larvae to A. apis infestation from a biochemical perspective but also offer a valuable insight into the interaction between Asian honey bee larvae and A. apis.

MiRNAs are critical regulators of numerous physiological and pathological processes. Ascosphaera apis exclusively infects bee larvae and causes chalkbrood disease. However, the function and mechanism of miRNAs in the bee larval response to A. apis infection is poorly understood. Here, ame-miR-34, a previously predicted miRNA involved in the response of Apis mellifera larvae to A. apis invasion, was subjected to molecular validation, and overexpression and knockdown were then conducted to explore the regulatory functions of ame-miR-34 in larval body weight and immune response. Stem-loop RT-PCR and Sanger sequencing confirmed the authenticity of ame-miR-34 in the larval gut of A. mellifera. RT-qPCR results demonstrated that compared with that in the uninfected larval guts, the expression level of ame-miR-34 was significantly downregulated (p < 0.001) in the guts of A. apis-infected 4-, 5-, and 6-day-old larvae, indicative of the remarkable suppression of host ame-miR-34 due to A. apis infection. In comparison with the corresponding negative control (NC) groups, the expression level of ame-miR-34 in the larval guts in the mimic-miR-34 group was significantly upregulated (p < 0.001), while that in the inhibitor-miR-34 group was significantly downregulated (p < 0.01). Similarly, effective overexpression and knockdown of ame-miR-34 were achieved. In addition, the body weights of 5- and 6-day-old larvae were significantly increased compared with those in the mimic-NC group; the weights of 5-day-old larvae in the inhibitor-miR-34 group were significantly decreased in comparison with those in the inhibitor-NC group, while the weights of 4- and 6-day-old larvae in the inhibitor-miR-34 group were significantly increased, indicating the involvement of ame-miR-34 in modulating larval body weight. Furthermore, the expression levels of both hsp and abct in the guts of A. apis-infected 4-, 5-, and 6-day-old larvae were significantly upregulated after ame-miR-34 overexpression. In contrast, after ame-miR-34 knockdown, the expression levels of the aforementioned two key genes in the A. apis-infected 4-, 5-, and 6-day-old larval guts were significantly downregulated. Together, the results demonstrated that effective overexpression and knockdown of ame-miR-34 in both noninfected and A. apis-infected A. mellifera larval guts could be achieved by the feeding method, and ame-miR-34 exerted a regulatory function in the host immune response to A. apis invasion through positive regulation of the expression of hsp and abct. Our findings not only provide a valuable reference for the functional investigation of bee larval miRNAs but also reveal the regulatory role of ame-miR-34 in A. mellifera larval weight and immune response. Additionally, the results of this study may provide a promising molecular target for the treatment of chalkbrood disease.

Objective: The aim of the study is to evaluate the application of high-resolution computed tomography (HRCT) and turbo spin-echo diffusion-weighted imaging (TSE-DWI) fusion imaging for localization of middle ear cholesteatomas., Methods: Eighty-six patients with clinically suspected middle ear cholesteatomas were enrolled prospectively. Ear TSE-DWI and HRCT scans were performed using a postprocessing workstation to generate a TSE-DWI-CT fusion image. Subsequently, all the enrolled patients received surgical treatment. According to the STAM system (difficult access sites [S], the tympanic cavity [T], the attic [A], and the mastoid [M]), the agreement between the localization of lesions evaluated by HRCT, TSE-DWI, and TSE-DWI-CT fusion images and the intraoperatively recorded localization were computed using Cohen κ statistic., Results: Based on the pathological results, the enrolled patients were divided into a cholesteatoma (n = 50) and a noncholesteatoma group (n = 36). The area under the receiver operator characteristic curve for diagnosis of cholesteatoma with TSE-DWI-CT fusion imaging was identical to that using the TSE-DWI images (0.924 vs 0.924, P > 0.05), but was significantly higher than that with HRCT imaging (0.924 vs 0.767, P = 0.0005). Furthermore, the diagnostic sensitivity and specificity of TSE-DWI-CT fusion imaging for cholesteatomas were 96.0% and 88.9%, respectively. Depending on whether the cholesteatoma extended to the mastoid, TSE-DWI-CT fusion imaging demonstrated good agreement with the intraoperative record for localization of lesions (κ = 0.808) and had a high accuracy of localization by the STAM system., Conclusions: Turbo spin-echo-DWI-CT fusion images have a very high diagnostic value for the preoperative localization of cholesteatomas., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Western honey bee ( Apis mellifera ), a eusocial insect with a superior economic and ecological value, is widely used in the beekeeping industry throughout the world. As a new class of non-coding RNAs (ncRNAs), circular RNAs (circRNAs) participate in the modulation of considerable biological processes, such as the immune response via diverse manners. Here, the identification, characteristic investigation, and molecular verification of circRNAs in the Apis mellifera ligustica larval guts were conducted, and the expression pattern of larval circRNAs during the Ascosphaera apis infection was analyzed, followed by the exploration of the potential regulatory part of differentially expressed circRNAs (DEcircRNAs) in host immune responses. A total of 2083 circRNAs in the larval guts of A. m. ligustcia were identified, with a length distribution ranging from 106 nt to 92,798 nt. Among these, exonic circRNAs were the most abundant type and LG1 was the most distributed chromosome. Additionally, 25, 14, and 30 up-regulated circRNAs as well as 26, 25, and 62 down-regulated ones were identified in the A. apis -inoculated 4-, 5-, and 6-day-old larval guts in comparison with the corresponding un-inoculated larval guts. These DEcircRNAs were predicted to target 35, 70, and 129 source genes, which were relative to 12, 23, and 20 GO terms as well as 11, 10, and 27 KEGG pathways, including 5 cellular and humoral immune pathways containing apoptosis, autophagy, endocytosis, MAPK, Toll, and Imd signaling pathways. Furthermore, complex competing endogenous RNA (ceRNA) regulatory networks were detected to be formed among DEcircRNAs, DEmiRNAs, and DEmRNAs. The Target DEmRNAs were engaged in 24, 20, and 25 functional terms as well as 62, 80, and 159 pathways, including several vital immune defense-associated pathways, namely the lysosome, endocytosis, phagosome, autophagy, apoptosis, MAPK, Jak-STAT, Toll, and Imd signaling pathways. Finally, back-splicing sites within 15 circRNAs and the difference in the 9 DEcircRNAs' expression between un-inoculated and A. apis -inoculated larval guts were confirmed utilizing molecular methods. These findings not only enrich our understanding of bee host-fungal pathogen interactions, but also lay a foundation for illuminating the mechanism underlying the DEcircRNA-mediated immune defense of A. m. ligustica larvae against A. apis invasion.

Ascosphaera apis is a fungal pathogen that exclusively infects bee larvae, causing chalkbrood disease, which results in severe damage for beekeeping industry. Long non-coding RNAs (lncRNAs) are versatile regulators in various biological processes such as immune defense and host-pathogen interaction. However, expression pattern and regulatory role of lncRNAs involved in immune response of bee host to A. apis invasion is still very limited. Here, the gut tissues of Apis mellifera ligustica 4-, 5-, and 6-day-old larvae inoculated by A. apis spores (AmT1, AmT2, and AmT3 groups) and corresponding un-inoculated larval guts (AmCK1, AmCK2, and AmCK3 groups) were prepared and subjected to deep sequencing, followed by identification of lncRNAs, analysis of differentially expressed lncRNAs (DElncRNAs), and investigation of competing endogenous RNA (ceRNA) network. In total, 3,746 A. m. ligustica lncRNAs were identified, including 78 sense lncRNAs, 891 antisense lncRNAs, 1,893 intergenic lncRNAs, 346 bidirectional lncRNAs, and 210 intronic lncRNAs. In the 4-, 5-, and 6- comparison groups, 357, 236, and 505 DElncRNAs were discovered. Additionally, 217, 129, and 272 DElncRNAs were respectively predicted to regulate neighboring genes via cis -acting manner, and these targets were associated with a series of GO terms and KEGG pathways of great importance, such as response to stimulus and Jak-STAT signaling pathway. Moreover, 197, 95, and 356 DElncRNAs were observed to target 10, eight, and 21 DEmiRNAs and further target 147, 79, and 315 DEmRNAs, forming complex regulatory networks. Further investigation suggested that these targets were engaged in several key cellular and humoral immune pathways, such as phagosome and MAPK signaling pathway. Ultimately, the expression trends of nine randomly selected DElncRNAs were verified by RT-qPCR, confirming the authenticity and reliability of our transcriptome data. Findings in this current work not only provide candidate DElncRNAs for functional study, but also lay a foundation for unclosing the mechanism underlying DElncRNA-regulated larval immune responses to A. apis invasion., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ye, Fan, Long, Wang, Zhang, Cai, Sun, Gu, Zou, Chen and Guo.)

Nosema ceranae is a widespread fungal parasite for honey bees, causing bee nosemosis. Based on deep sequencing and bioinformatics, identification of circular RNAs (circRNAs) in Apis cerana workers' midguts and circRNA-regulated immune response of host to N. ceranae invasion were conducted in this current work, followed by molecular verification of back-splicing sites and expression trends of circRNAs. Here, 10185 and 7405 circRNAs were identified in the midguts of workers at 7 days (AcT1) and 10 days (AcT2) post inoculation days post-inoculation with N. ceranae . PCR amplification result verified the back-splicing sites within three specific circRNAs (novel&#95;circ&#95;005123, novel&#95;circ&#95;007177, and novel&#95;circ&#95;015140) expressed in N. ceranae -inoculated midgut. In combination with transcriptome data from corresponding un-inoculated midguts (AcCK1 and AcCK2), 2266 circRNAs were found to be shared by the aforementioned four groups, whereas the numbers of specific ones were 2618, 1917, 5691, and 3723 respectively. Further, 83 52) differentially expressed circRNAs (DEcircRNAs) were identified in AcCK1 vs. AcT1 (AcCK2 vs. AcT2) comparison group. Source genes of DEcircRNAs in workers' midgut at seven dpi were involved in two cellular immune-related pathways such as endocytosis and ubiquitin mediated proteolysis. Additionally, competing endogenous RNA (ceRNA) network analysis showed that 23 13) DEcircRNAs in AcCK1 vs. AcT1 (AcCK2 vs. AcT2) comparison group could target 18 14) miRNAs and further link to 1111 (1093) mRNAs. These target mRNAs were annotated to six cellular immunity pathways including endocytosis, lysosome, phagosome, ubiquitin mediated proteolysis, metabolism of xenobiotics by cytochrome P450, and insect hormone biosynthesis. Moreover, 284 164) internal ribosome entry site and 54 26) ORFs were identified from DEcircRNAs in AcCK1 vs. AcT1 (AcCK2 vs. AcT2) comparison group; additionally, ORFs in DEcircRNAs in midgut at seven dpi with N. ceranae were associated with several cellular immune pathways including endocytosis and ubiquitin-mediated proteolysis. Ultimately, RT-qPCR results showed that the expression trends of six DEcircRNAs were consistent with those in transcriptome data. These results demonstrated that N. ceranae altered the expression pattern of circRNAs in A. c. cerana workers' midguts, and DEcircRNAs were likely to regulate host cellular and humoral immune response to microsporidian infection. Our findings lay a foundation for clarifying the mechanism underlying host immune response to N. ceranae infection and provide a new insight into interaction between Asian honey bee and microsporidian., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhu, Wang, Fan, Long, Chen, Ye, Zhang, Ren, Zhang, Niu, Chen and Guo.)

Asian honey bee Apis cerana is the original host for Nosema ceranae , a unicellular fungal parasite that causes bee nosemosis throughout the world. Currently, interaction between A. cerana and N. ceranae is largely unknown. Our group previously prepared A. c. cerana workers' midguts at 7 days post inoculation (dpi) and 10 dpi with N. ceranae spores as well as corresponding un-inoculated workers' midguts, followed by cDNA library construction and a combination of RNAs-seq and small RNA-seq. Meanwhile, we previously prepared clean spores of N. ceranae , which were then subjected to cDNA library construction and deep sequencing. Here, based on the gained high-quality transcriptome datasets, N. ceranae differentially expressed mRNAs (DEmiRNAs) targeted by host DEmiRNAs, and A. c. cerana DEmRNAs targeted by microsporidian DEmiRNAs were deeply investigated, with a focus on targets involved in N. ceranae glycolysis/glyconeogenesis as well as virulence factors, and A. c. cerana energy metabolism and immune response. In A. c. cerana worker's midguts at 7 (10) dpi (days post inoculation), eight (seven) up-regulated and six (two) down-regulated miRNAs were observed to target 97 (44) down-regulated and 60 (15) up-regulated N. ceranae mRNAs, respectively. Additionally, two up-regulated miRNAs (miR-60-y and miR-676-y) in host midgut at 7 dpi could target genes engaged in N. ceranae spore wall protein and glycolysis/gluconeogenesis, indicating potential host miRNA-mediated regulation of microsporidian virulence factor and energy metabolism. Meanwhile, in N. ceranae at 7 (10) dpi, 121 (110) up-regulated and 112 (104) down-regulated miRNAs were found to, respectively, target 343 (247) down-regulated and 138 (110) down-regulated mRNAs in A. c. cerana workers' midguts. These targets in host were relevant to several crucial cellular and humoral immune pathways, such as phagasome, endocytosis, lysosomes, regulation of autophagy, and Jak-STAT signaling pathway, indicative of the involvement of N. ceranae DEmiRNAs in regulating these cellular and humoral immune pathways. In addition, N. ceranae miR-21-x was up-regulated at 7 dpi and had a target relative to oxidative phosphorylation, suggesting that miR-21-x may be used as a weapon to modulate this pivotal energy metabolism pathway. Furthermore, potential targeting relationships between two pairs of host DEmiRNAs-microsporidian DEmRNAs and two pairs of microsporidian DEmiRNAs-host DEmRNAs were validated using RT-qPCR. Our findings not only lay a foundation for exploring the molecular mechanism underlying cross-kingdom regulation between A. c. cerana workers and N. ceranae , but also offer valuable insights into Asian honey bee-microsporidian interaction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fan, Zhang, Zhang, Zhang, Long, Wu, Zhang, Zhu, Chen and Guo.)

Photothermal therapy (PTT) has attracted great attention due to its noninvasive and low side effects. Photothermal agents (PTAs) which could convert absorbing light into heat play a critical role in PTT. For conventional small organic PTAs, the photothermal conversion ability is mainly achieved by intermolecular noncovalent interactions such as π-π interactions. However, in terms of organic fluorophores with rotator or vibrator segments, the balance between fluorescence emission and heat generation is mainly regulated by intramolecular motions which could be mediated by molecular engineering. Following this designing principle, various fluorophores with intramolecular motions for effective PTT have been reported. In this review, we highlight the recent progress of PTAs based on small organic fluorophores with intramolecular motions for enhanced PTT. Designing tactics of these fluorophores to afford long-wavelength absorption, high photothermal conversion ability, and effective accumulation capability are emphasized. Finally, one-for-all phototheranostics achieved by mediating intramolecular motions of these fluorophores are highlighted. We hope this review could pave a new avenue to developing fluorophores with intramolecular motion as PTAs to advance their clinical transition. STATEMENT OF SIGNIFICANCE: Recent progress of photothermal agents (PTAs) based on small organic fluorophores with intramolecular motion is summarized in this review. Molecular engineering of these small organic fluorophores to afford long-wavelength absorption, high photothermal conversion ability, and effective accumulation at tumor sites for enhanced photothermal therapy (PTT) is highlighted. Strategies to tune the intramolecular motions of these fluorophores to achieve multimodal phototherapy are emphasized as well., Competing Interests: Declaration of Competing Interest There is no conflict of interest., (Copyright © 2022. Published by Elsevier Ltd.)

This study aimed to obtain high Fischer's ratio oligopeptides from goat whey (HFO) and investigate antioxidant property of it. Hydrolysis of goat whey was done with the approach of sequential digestion of pepsin and flavourzyme. With the adsorption of aromatic amino acids by activated carbon, HFO with a Fischer's ratio of 27.070 and a molecular weight of 200-1,000 Da were obtained, and the branched-chain amino acids accounted for 22.87%. Then the antioxidant activity of HFO was evaluated. At the concentrations of 2.0 mg/mL and 0.50 mg/mL, HFO scavenged 77.27% and 99.63% of 1,1-diphenyl-2-picrylhydrazyl and 3-ethylbenzthiazoline-6-sulphonate free radicals respectively. The scavenging rate of HFO against hydroxyl radicals reached 92.31% at the concentration of 0.25 mg/mL. Animal experiments demonstrated that HFO could moderate the changes of malondialdehyde, superoxide dismutase and glutathione peroxidase caused by CCl 4 -induced oxidative stress in vivo . This study indicated that HFO from goat whey was capable of oxidation resistance both in vivo and in vitro , which provided a scientific basis for the high-value processing and application of goat milk whey., Competing Interests: The authors declare no potential conflicts of interest., (© Korean Society for Food Science of Animal Resources.)

Vairimorpha ceranae is a widespread fungal parasite of adult honey bees that leads to a serious disease called nosemosis. Circular RNAs (circRNAs) are newly discovered non-coding RNAs (ncRNAs) that regulate biological processes such as immune defense and development. Here, 8199 and 8711 circRNAs were predicted from the midguts of Apis mellifera ligustica workers at 7 d (Am7T) and 10 d (Am10T) after inoculation (dpi) with V. ceranae spores. In combination with transcriptome data from corresponding uninoculated midguts (Am7CK and Am10CK), 4464 circRNAs were found to be shared by these four groups. Additionally, 16 circRNAs were highly conserved among A. m. ligustica , Apis cerana cerana , and Homo sapiens . In the Am7CK vs. Am7T (Am10CK vs. Am10T) comparison group, 168 (306) differentially expressed circRNAs (DEcircRNAs) were identified. RT-qPCR results showed that the expression trend of eight DEcircRNAs was consistent with that in the transcriptome datasets. The source genes of DEcircRNAs in Am7CK vs. Am7T (Am10CK vs. Am10T) were engaged in 27 (35) GO functional terms, including 1 (1) immunity-associated terms. Moreover, the aforementioned source genes were involved in three cellular immune-related pathways. Moreover, 86 (178) DEcircRNAs in workers' midguts at 7 (10) dpi could interact with 75 (103) miRNAs, further targeting 215 (305) mRNAs. These targets were associated with cellular renewal, cellular structure, carbohydrate and energy metabolism, and cellular and humoral immunity. Findings in the present study unraveled the mechanism underlying circRNA-mediated immune responses of western honey bee workers to V. ceranae invasion, but also provided new insights into host-microsporidian interaction during nosemosis., Competing Interests: The authors declare no conflict of interest.

Developing a small molecular photosensitizer to achieve multimodal phototherapy has recently garnered attention as a promising strategy for efficient cancer treatment. However, synthesis of a multifunctional small molecular photosensitizer has remained challenging. Here we report an aggregation-induced-emission (AIE)-featured luminogen (AIEgen) TPA-BTZ decorated with long and branched alkyl chains. TPA-BTZ shows long-wavelength emission at ca . 800 nm in the NIR-I region. Moreover, upon laser irradiation, TPA-BTZ could produce O 2 ˙ - and 1 O 2 via both type I and type II mechanisms for enhanced photodynamic therapy (PDT). The propeller-like structure triphenylamine (TPA) rotators not only endow TPA-BTZ with AIE characteristics but also facilitate heat generation by intramolecular rotation for photothermal therapy (PTT). More importantly, long and branched alkyl chains can create intermolecular spatial isolation in the fabricated TPA-BTZ@PEG2000 nanoparticles (NPs) to allow sufficient intramolecular motion for photothermal conversion. Due to these unique features, in vitro and in vivo evaluations demonstrate that the TPA-BTZ@PEG2000 NPs exhibited long-term NIR-imaging ability, superior tumoricidal activity, and suppressed tumor growth. This research provides new insights for developing new AIEgens for NIR imaging-guided multimodal phototherapy.

This study investigated the effects of different treatment of alkaline pH-shifting on milk protein concentrate (MPC), micellar casein concentrate (MCC) and whey protein isolate (WPI) assisted by the same ultrasound conditions, including changes in the physicochemical properties, solubility and foaming capacity. The solubility of milk proteins had a significant increase with gradual enhancement of ultrasound-assisted alkaline pH-shifting (p < 0.05), especially for MCC up to 99.50 %. Also, treatment made a significant decline in the particle size of MPC and MCC, as well as the turbidity of the proteins (p < 0.05). The foaming capacity of MPC, MCC, and WPI was all improved, especially at pH 11, and at this pH, the milk protein also showed the highest surface hydrophobicity. The best foaming capacity at pH 11 was the result of the combined effect of particle size, potential, protein conformation, solubility, and surface hydrophobicity. In conclusion, ultrasound-assisted pH-shifting treatment was found to be effective in improving the physicochemical properties and solubility and foaming capacity of milk proteins, especially MCC, with promising application prospect in food industry., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Silicon Photomultiplier (SiPM) is a sensor that can detect low-light signals lower than the single-photon level. In order to study the properties of neutrinos at a low detection threshold and low radioactivity experimental background, a low-temperature CsI neutrino coherent scattering detector is designed to be read by the SiPM sensor. Less thermal noise of SiPM and more light yield of CsI crystals can be obtained at the working temperature of liquid nitrogen. The breakdown voltage (V bd ) and dark count rate (DCR) of SiPM at liquid nitrogen temperature are two key parameters for coherent scattering detection. In this paper, a low-temperature test is conducted on the mass-produced ON Semiconductor J-Series SiPM. We design a cryogenic system for cooling SiPM at liquid nitrogen temperature and the changes of operating voltage and dark noise from room to liquid nitrogen temperature are measured in detail. The results show that SiPM works at the liquid nitrogen temperature, and the dark count rate drops by six orders of magnitude from room temperature (120 kHz/mm 2 ) to liquid nitrogen temperature (0.1 Hz/mm 2 ).

Background: The latest guidelines recommend the use of proton pump inhibitors (PPIs) to minimize gastrointestinal bleeding (GIB) in patients receiving dual antiplatelet therapy (DAPT), even though this co-administration may increase the risk of ischemia due to drug interactions. We have noticed that there are few studies conducted on patients with a lower risk of GIB. Therefore, we investigated the clinical effect of co-administration of PPI on DAPT patients with low GIB risk. Methods and Results: From January 2013 to September 2014, a total of 17,274 consecutive patients on DAPT from 108 hospitals with low risk for GIB in the China Acute Myocardial Infarction (CAMI) registry were analyzed. The primary endpoints were GIB and major adverse cardiovascular and cerebrovascular events (MACCE). Multivariate logistic regression analysis and Cox proportional hazard models were used to assess the effect of PPIs use. Of the analyzed patients, 66.6% ( n = 11,487) were treated with PPIs. PPI use did not show an extra gastrointestinal protective effect in patients with low risk for GIB who were hospitalized and on follow-up after 2 years. Moreover, it was associated with an increased risk of stroke during the 2-year follow-up [hazard ratio (HR) 2.072, 95% confidence interval (CI) 1.388-3.091, p = 0.0003] and an increased risk of MI after 6 months (HR 1.580, 95% CI 1.102-2.265, p = 0.0119). We found the same results after propensity score matching. Conclusion: PPI use is prevalent in DAPT patients with low GIB risk. PPIs did not show an extra gastrointestinal protective effect, while an increased risk of stroke was observed during the 2-year follow-up. Clinical Trial Registration: www.clinicaltrials.gov, identifier NCT01874691., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Shi, Ni, Yang, Fan, Yu, Yang, Yu, Yang and China Acute Myocardial Infarction (CAMI) Registry study group.)

Objective: To investigate the incidence of gastrointestinal bleeding (GIB) in patients with acute myocardial infarction (AMI), clarify the association between adverse clinical outcomes and GIB and identify risk factors for in-hospital GIB after AMI., Design: Retrospective cohort study., Setting: 108 hospitals across three levels in China., Participants: From 1 January 2013 to 31 August 2014, after excluding 2659 patients because of incorrect age and missing GIB data, 23 794 patients with AMI from 108 hospitals enrolled in the China Acute Myocardial Infarction Registry were divided into GIB-positive (n=282) and GIB-negative (n=23 512) groups and were compared., Primary and Secondary Outcome Measures: Major adverse cardiovascular and cerebrovascular events (MACCEs) are a composite of all-cause death, reinfarction and stroke. The association between GIB and endpoints was examined using multivariate logistic regression and Cox proportional hazards models. Independent risk factors associated with GIB were identified using multivariate logistic regression analysis., Results: The incidence of in-hospital GIB in patients with AMI was 1.19%. GIB was significantly associated with an increased risk of MACCEs both in-hospital (OR 2.314; p<0.001) and at 2-year follow-up (HR 1.407; p=0.0008). Glycoprotein IIb/IIIa (GPIIb/IIIa) receptor inhibitor, percutaneous coronary intervention (PCI) and thrombolysis were novel independent risk factors for GIB identified in the Chinese AMI population (p<0.05)., Conclusions: GIB is associated with both in-hospital and follow-up MACCEs. Gastrointestinal prophylactic treatment should be administered to patients with AMI who receive primary PCI, thrombolytic therapy or GPIIb/IIIa receptor inhibitor., Trial Registration Number: NCT01874691., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

We investigated H 2 O molecule adsorption that had an effect on the luminescence properties of the CsI(Na) crystal using experiments and first-principle calculations. We measured the emission spectra of the CsI(Na) crystal at different exposure times under gamma ray excitation. The experimental results showed that the energy resolution of the CsI(Na) crystal was worse when the crystal surface adsorbed more H 2 O molecules, and the crystal surface deliquescence decreased the luminescence efficiency of the CsI(Na) crystal. We studied the band structure, density of states, and optical properties changes caused by H 2 O molecule adsorption on the CsI(Na) (010) surface. The generalized gradient approximation (GGA) was used to describe the exchange and correlation potential between the electrons. Our calculation results showed that the band gap width of the CsI(Na) (010) surface decreased after adsorbing H 2 O molecules, while three new peaks appeared in the valence band, and the absorption coefficient decreased from 90,000 cm -1 to 65,000 cm -1 , and the reflection coefficient decreased from 0.195 to 0.105. Further, the absorption coefficient was reduced by at least 25% because of H 2 O molecule adsorption, which led to the luminescence degradation of the CsI(Na) crystal.

Background: The current status of gastrointestinal prophylaxis (GIP) usage and its effects on hospitalized acute myocardial infarction (AMI) patients is not clear. We investigate the appropriateness of GIP usage and its relationship with clinical events in China., Hypothesis: Appropriate use of GIP is not associated with increased adverse outcomes., Methods: From January 2013 to September 2014, a total of 24 001 consecutive patients from 108 hospitals with AMI in China Acute Myocardial Infarction (CAMI) registry were analyzed. The appropriateness of GIP was evaluated using the current American College of Cardiology Foundation/American Heart Association (ACCF/AHA) and European Society of Cardiology (ESC) guidelines. The primary endpoint was in-hospital gastrointestinal bleeding (GIB), while the secondary endpoints were in-hospital and 2-year follow-up net adverse cardiovascular and cerebrovascular events (NACCE). Multivariate logistic regression analysis and Cox proportional hazard models were used to assess the effect of appropriate GIP., Results: There were 16 413 (68.38%) AMI patients co-medicated with GIP. Among 108 involved hospitals, only 35 (32.4%) hospitals prescribed more than 50% appropriate GIP. Totally, 59.7% (14 340) AMI patients received inappropriate GIP. Inappropriate GIP use was independently associated with use of GPIIb/IIIa receptor inhibitor and primary percutaneous coronary intervention (PCI). Moreover, appropriate GIP use was associated with decreased GIB risk (OR: 0.692, 95% CI: 0.507-0.944, P = .0202) during hospitalization, while not with increased in-hospital and 2-year follow-up NACCE., Conclusion: The use of GIP is prevalent in patients with AMI in China but only 40% of hospitalized patients received appropriate GIP. Appropriate prophylactic therapy was associated with decreased GIB risk during hospitalization., (© 2020 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Background: Risk stratification of patients with non-ST-segment elevation myocardial infarction (NSTEMI) is important in terms of treatment strategy selection. Current efforts have focused on short-term risk prediction after discharge, but we aimed to establish a risk score to predict the 24-month mortality risk in survivors of NSTEMI., Methods and results: A total of 5,509 patients diagnosed with NSTEMI between January 2013 and September 2014 were included. Primary endpoint was all-cause death at 24 months. A multivariable Cox regression model was used to establish a practical risk score based on independent risk factors of death. The risk score included 9 variables: age, body mass index, left ventricular ejection fraction, reperfusion therapy during hospitalization, Killip classification, prescription of diuretics at discharge, heart rate, and hemoglobin and creatinine levels. The C-statistics for the risk model were 0.83 (95% confidence interval [CI]: 0.81-0.85) and 0.83 (95% CI: 0.79-0.86) in the development and validation cohorts, respectively. Mortality risk increased significantly across groups: 1.34% in the low-risk group (score: 0-58), 5.40% in intermediate group (score: 59-93), and 23.87% in high-risk group (score: ≥94)., Conclusions: The current study established and validated a practical risk score based on 9 variables to predict 24-month mortality risk in patients who survive NSTEMI. This score could help identify patients who are at high risk for future adverse events who may benefit from good adherence to guideline-recommended secondary prevention treatment.

Purple pakchoi ( Brassica rapa ssp. Chinensis ) is particularly appreciated due to its high edible quality and ornamental value, but there are few studies on the underlying mechanisms of leaf color formation. To comprehensively assess the differences in purple formation in pakchoi, four lines of pakchoi with different purple leaves were used in this experiment to determine the pigment content and to investigate the distribution and components of anthocyanin using LCMS (Liquid Chromatography Mass Spectrometry) and leaf cross-sections. Moreover, the expression levels of anthocyanin synthesis-related genes in four lines were calculated by qRT-PCR. The results showed that three new purple lines rich in anthocyanin and of high-quality were bred, and the anthocyanin were mainly distributed in both the upper epidermis and lower epidermis of leaves. Thirteen anthocyanin components were separated and identified, all the anthocyanins were acylated and glycosylated cyanidins; the main anthocyanins in purple pakchoi were a diacylated form of cyanidin 3- trans -(feruloyl)diglucoside-5-(malonyl)glucoside. Both the ratio of non-aromatic acylated cyanidin to aromatic acylated cyanidin and the ratio of anthocyanin content to chlorophyll content were responsible for the color formation in different purple pakchoi lines. When the ratio was high, the leaf appeared reddish purple, and when the ratio was low, the leaf appeared deep purple, even blackish purple. The expression level of BrF3H was significantly correlated with the content of anthocyanin through the correlation coefficient, which was speculated to be the main anthocyanin synthesis-related gene resulting in color differences among the four purple pakchoi lines. These results will enhance our understanding for the cultivation of new purple pakchoi varieties.

Ascosphaera apis is a widespread fungal pathogen of honeybee larvae that results in chalkbrood disease, leading to heavy losses for the beekeeping industry in China and many other countries. This work was aimed at generating a full-length transcriptome of A. apis using PacBio single-molecule real-time (SMRT) sequencing. Here, more than 23.97 Gb of clean reads was generated from long-read sequencing of A. apis mycelia, including 464,043 circular consensus sequences (CCS) and 394,142 full-length non-chimeric (FLNC) reads. In total, we identified 174,095 high-confidence transcripts covering 5141 known genes with an average length of 2728 bp. We also discovered 2405 genic loci and 11,623 isoforms that have not been annotated yet within the current reference genome. Additionally, 16,049, 10,682, 4520 and 7253 of the discovered transcripts have annotations in the Non-redundant protein (Nr), Clusters of Eukaryotic Orthologous Groups (KOG), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Moreover, 1205 long non-coding RNAs (lncRNAs) were identified, which have less exons, shorter exon and intron lengths, shorter transcript lengths, lower GC percent, lower expression levels, and fewer alternative splicing (AS) evens, compared with protein-coding transcripts. A total of 253 members from 17 transcription factor (TF) families were identified from our transcript datasets. Finally, the expression of A. apis isoforms was validated using a molecular approach. Overall, this is the first report of a full-length transcriptome of entomogenous fungi including A. apis. Our data offer a comprehensive set of reference transcripts and hence contributes to improving the genome annotation and transcriptomic study of A. apis., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Expansins are plant cell-wall loosening proteins involved in cell enlargement, adaptive responses to environmental stimuli, and various developmental processes. Although expansins have been characterized in many plant species, little is reported on this family in watermelon. In this study, 30 expansin genes in the watermelon genome (ClEXPs) were identified. These genes which were divided into four subfamilies (7 ClEXLAs, 2 ClEXLBs, 18 ClEXPAs, and 3 ClEXPBs) are unevenly distribute on 10 of 11 watermelon chromosomes. Chromosome mapping suggested that tandem duplication events may have played important roles in the expanding of watermelon expansins. Gene structure and motif identification revealed that same subfamily and subgroup have conserved gene structure and motif. Detection of cis -acting elements revealed that ClEXPs gene promoter regions were enriched with light-responsive elements, hormone-responsive, environmental stress-related, and development-related elements. Expression patterns of ClEXPs were investigated by qRT-PCR. The results showed that expression patterns of 15 ClEXP genes differed in three tissues. Through our own and public RNA-seq analysis, we found that ClEXPs had different expression patterns in fruit flesh, fruit rind, and seed at various developmental stages, and most of ClEXPs were highly responsive to abiotic and biotic stresses. Remarkably, 7 ClEXPs ( ClEXLA1 , ClEXLA6 , ClEXLB1 , ClEXLB2 , ClEXPA5 , ClEXPA10, and ClEXPA16 ) exhibited positive response to at least three kinds of stresses, suggesting that they might play important roles in the crosstalk of stress signal pathways. The results of this study provide useful insights for the functional identification of expansin gene family in watermelon., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest in the publication., (© King Abdulaziz City for Science and Technology 2020.)

Objective: The aim of this study is to evaluate the diagnostic value of turbo spin-echo（TSE） diffusion weighted imaging（DWI） in temporal bone cholesteatoma. Method: A prospective evaluated of 76 patients with suspected sacral cholesteatoma was performed using a Philips Ingenia 3.0T superconducting magnetic resonance scanner and a 32-channel head coil with turbo spin-echo diffusion weighted imaging（TSE-DWI） sequence and conventional magnetic resonance scan, and underwent surgery within the next two weeks. The pathological result is the gold standard, and the imaging diagnosis and surgery are performed. The intraoperative observation and pathological results were compared. The diagnostic accuracy, sensitivity, specificity, positive predictive value and negative predictive value of TSE-DWI sequence in the diagnosis of temporal bone cholesteatoma were calculated. Result: Of the 76 patients with suspected temporal bone cholesteatoma, TSE-DWI scan was performed, 44 cases were diagnosed as cholesteatoma and 32 cases were non-cholesteatoma. Based on the pathology results, 46 cases were diagnosed as cholesteatoma, 30 cases were non-cholesteatoma. The accuracy of TSW-DWI sequence in the diagnosis of cholesteatoma was 89.47%, 3 cases were false negative and 5 cases was false positive. The sensitivity, specificity, positive predictive value and negative predictive value of TSE-DWI in the diagnosis of temporal bone cholesteatoma were 89.13%, 90.00%, 93.18%, and 84.38%, respectively. Conclusion: The TSE-DWI sequence has high signal-to-noise ratio and can improve the diagnostic accuracy and specificity. TSE-DWI sequence is of great value in clinical diagnosis and treatment., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Background: Few studies have investigated the use of invasive strategy for patients with non-ST-segment elevation myocardial infarction (NSTEMI) in China. We aimed to describe the contemporary pattern of management, medically and invasively, in patients with NSTEMI across China., Methods: Using data of China Acute Myocardial Infarction Registry, we analyzed the baseline characteristics, in-hospital medication, index coronary angiography (CAG) and revascularization by stratification of gender, age, and risk assessment. Primary outcomes included in-hospital major adverse cardio-cerebral events (MACCE, a composite of all-cause death, myocardial (re)infarction, and stroke) and length of stay (LOS)., Results: A total of 10,266 NSTEMI patients were enrolled between January 2013 and November 2016. Dual antiplatelet therapy and statins were prescribed in 92.9% and 92.1% of overall patients respectively. CAG was performed in 45.6% of these patients, and 40.9% had an index revascularization. Female, older or higher risk patients were less likely to receive CAG or revascularization. The rates of CAG were 67.9% in the provincial-level, 46.2% in the prefectural, and 12.1% in the county-level hospitals. Of those patients undergoing revascularization, 77.0% (1,156/1,501) very-high-risk patients received urgent revascularization and 16.2% (440/2,699) high-risk patients underwent early revascularization as recommended. The overall in-hospital MACCE was 6.7%, and the median LOS was 10 (6) days. Revascularization was associated with reduction for in-hospital MACCE regardless of risk and age., Conclusion: Invasive management was underused and profoundly deferred among patients with NSTEMI in China. The risk-treatment paradox, procedure deferral and medical resources distribution imbalance may represent opportunities for improvement., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Smoking is a well-established risk factor for cardiovascular disease. However, the effect of smoking on in-hospital mortality in patients with acute myocardial infarction (AMI) who are managed by contemporary treatment is still unclear., Methods: A cohort study was conducted using data from the China AMI registry between 2013 and 2016. Eligible patients were diagnosed with AMI in accordance with the third universal definition of MI. Propensity score (PS) matching and multivariable logistic regression were used to control for confounders. Subgroup analysis was performed to examine whether the association between smoking and in-hospital mortality varies according to baseline characteristics., Results: A total of 37 614 patients were included. Smokers were younger and more frequently men with fewer comorbidities than non-smokers. After PS matching and multivariable log regression analysis were performed, the difference in in-hospital mortality between current smokers versus non-smokers was reduced, but it was still significant (5.1% vs 6.1%, p=0.0045; adjusted OR 0.78, 95% CI 0.69 to 0.88, p<0.001). Among all subgroups, there was a trend towards lower in-hospital mortality in current or ex-smokers compared with non-smokers., Conclusions: Smoking is associated with lower in-hospital mortality in patients with AMI, even after multiple analyses to control for potential confounders. This 'smoker's paradox' cannot be fully explained by confounding alone., Trial Registration Number: NCT01874691., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Here, the expression profiles and differentially expressed miRNAs (DEmiRNAs) in the midguts of Apis cerana cerana workers at 7 d and 10 d post-inoculation (dpi) with N. ceranae were investigated via small RNA sequencing and bioinformatics. Five hundred and twenty nine (529) known miRNAs and 25 novel miRNAs were identified in this study, and the expression of 16 predicted miRNAs was confirmed by Stem-loop RT-PCR. A total of 14 DEmiRNAs were detected in the midgut at 7 dpi, including eight up-regulated and six down-regulated miRNAs, while 12 DEmiRNAs were observed in the midgut at 10 dpi, including nine up-regulated and three down-regulated ones. Additionally, five DEmiRNAs were shared, while nine and seven DEmiRNAs were specifically expressed in midguts at 7 dpi and 10 dpi. Gene ontology analysis suggested some DEmiRNAs and corresponding target mRNAs were involved in various functions including immune system processes and response to stimulus. KEGG pathway analysis shed light on the potential functions of some DEmiRNAs in regulating target mRNAs engaged in material and energy metabolisms, cellular immunity and the humoral immune system. Further investigation demonstrated a complex regulation network between DEmiRNAs and their target mRNAs, with miR-598-y, miR-252-y, miR-92-x and miR-3654-y at the center. Our results can facilitate future exploration of the regulatory roles of miRNAs in host responses to N. ceranae , and provide potential candidates for further investigation of the molecular mechanisms underlying eastern honeybee-microsporidian interactions., Competing Interests: The authors declare that they have no conflict of interest.

Background: The relationship between body mass index (BMI) and in-hospital mortality risk among patients with acute myocardial infarction (AMI) remains controversial., Methods and Results: We included 35,964 patients diagnosed with AMI in China Acute Myocardial Infarction registry between January 2013 and December 2016. Patients were categorized into 4 groups according to BMI level: BMI <18.5, 18.5-24.9, 25-30, and ≥30 kg/m 2 for underweight, normal, overweight, and obese groups, respectively. Clinical data were extracted for each patient, and multivariable logistic regression analysis was used to examine the association between BMI level and in-hospital mortality. Compared with normal-weight patients, obese patients were younger, more often current smokers, and more likely to have hypertension, hyperlipidemia, and diabetes. Multivariable regression analysis results demonstrated that compared with normal group, underweight group had significantly higher in-hospital mortality (odds ratio [OR]: 1.34; 95% confidence interval [CI]: 1.06-1.69; p = 0.016), while overweight group (OR: 0.86; 95% CI: 0.77-0.97; p = 0.011) and obese group (OR: 0.65; 95% CI: 0.46-0.91; p = 0.013) had lower mortality. All subgroups showed a trend toward lower in-hospital mortality risk as BMI increased., Conclusions: Our study provided robust evidence supporting "obesity paradox" in a contemporary large-scale cohort of patients with AMI and demonstrated that increased BMI was independently associated with lower in-hospital mortality., (Copyright © 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Captopril (Cap) as angiotensin-converting enzyme inhibitor (ACEi) is commonly used to treat hypertension and some types of congestive heart failure. However, few studies reported on whether Cap exerts a protective effect on myocardial apoptosis induced by transverse aortic constriction (TAC). This study aimed at investigating the possible mechanism of Cap on myocardial apoptosis induced by pressure overload. Results showed that Cap significantly decreased heart-to-body weight ratios (HBWR). Cap markedly improved cardiac function, and reduced inner diameter of ascending aorta (Asc Ao) in TAC mice as shown by echocardiography. Enzyme-linked immunosorbent assay (ELISA) results demonstrated that Cap treatment also markedly decreased the level of N-terminal pro-B-type natriuretic peptide (NT-proBNP), atrial natriuretic peptide (ANP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Cardiac pathological changes and fibrosis have been improved after Cap treatment as shown by hematoxylin-eosin (H&E) staining and Masson's trichrome staining. Moreover, Terminal deoxynucleotidyl transferase-mediated dexoxyuridine triphosphate nick-end labeling (TUNEL) staining result indicated Cap treatment also significantly inhibited cardiac apoptosis. Western Blot results showed that Cap obviously decreased the expression of cleaved capase-3, Bax, phosphorylated Jak2 (p-Jak2), phosphorylated Stat3 (p-Stat3), Wnt3a and β-catenin proteins, as well as increased Bcl-2 expression. In conclusion, Cap showed a protective effect on TAC-induced cardiac apoptosis, which could be attributed to the inhibition of Wnt3a/β-catenin signaling pathway. Cap also attenuated myocardial hypertrophy induced by TAC via suppression of Jak2/Stat3 pathway., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The YiQiFuMai powder injection (YQFM), a traditional Chinese medicine (TCM) prescription re-developed based on Sheng-Mai-San, is widely applied for the treatment of cardiovascular diseases. However, its potential molecular mechanism remains obscure. The present study was designed to observe the effects of YQFM and underlying mechanisms on coronary artery ligation (CAL)-induced heart failure (HF) and cell hypoxia of 24 h oxygen-glucose deprivation (OGD) in neonatal rat ventricular myocytes (NRVMs). HF was induced by permanent CAL for 2 weeks in ICR mice. The results demonstrated that YQFM significantly attenuated CAL-induced HF via improving the cardiac function, cardiac systolic function, cardiac structure impairment, cardiac histological features and fibrosis. YQFM markedly attenuated mitochondrial dysfunction through improving mitochondrial morphology, increasing mitochondria membrane potential (Δψm), mitochondrial ROS generation and expression of Mitofusin-2 (Mfn2), meanwhile, decreasing phosphorylation of dynamin-related protein 1 (p-Drp1). Mechanistically, YQFM could significantly decrease the expression of isoforms of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit NADPH oxidase 2 (NOX2), p67 phox and NADPH oxidase 4 (NOX4), ultimately reducing reactive oxygen species (ROS) generation. In addition, YQFM could down-regulate expression of calcium voltage-gated channel subunit α1C (CACNA1C) and phosphorylation of calmodulin dependent protein kinase II (p-CaMKII). These results suggest that YQFM ameliorates mitochondrial function in HF mice, partially through inhibiting ROS generation and CaMKII signaling pathways. Therefore, the present study provided scientific evidence for the underlying mechanism of YQFM.

Background: Mitochondrial fission is the essential mechanisms of myocardial ischemia/reperfusion (MI/R)-induced cardiomyocytes apoptosis. Myosin II plays a key role in fission due to the recruitment and actomyosin constriction at the fission site in U2OS cells. However, the role of myosin IIA-actin interaction in regulating MI/R-induced cardiomyocytes mitochondrial fission and apoptosis remains to be fully elucidated., Methods and Results: When cardiomyocytes are exposed to simulated I/R injury, the myosin IIA protein translocated from the juxtamembrane to the cytoplasm, interacted with actin filaments, formed stress fibers and generated contractile forces. Treatment with the myosin II inhibitor blebbistatin attenuated the myosin IIA-actin complex induced actomyosin contractility and prevented cardiomyocytes apoptosis as reflected by inhibition of cleaved caspase-3 expression, normalization of Bcl-2/Bax levels and decreased apoptotic cells. Meanwhile, blebbistatin inhibited the activation of PINK1/Parkin pathway and ameliorated mitochondrial fission as evidenced by improvement of mitochondrial morphology, inhibition of Drp1 phosphorylation at Ser616 and translocation. Furthermore, CRISPR/Cas9 knockout of myosin IIA blocked I/R-induced apoptosis, suppressed PINK1/Parkin pathway and reduced mitochondrial fission. Importantly, blebbistatin attenuated myocardial apoptosis, inhibited myosin IIA-actin interaction and PINK1/Parkin pathway, suppressed myocardial ultrastructure abnormalities and mitochondrial fission in a mouse MI/R injury model., Conclusions: Inhibition of actomyosin contractility induced by myosin IIA-actin interaction could impede myocardial apoptosis and MI/R injury via PINK1/Parkin pathway and mitochondrial fission modulation both in vitro and in vivo, which may be applicable for the development of therapies for cardiovascular diseases., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In the present study, we examined the effects of rhein on pituitary gland implantation-induced adenomyosis, an animal model which mimics human adenomyosis. Oral administration of rhein dose-dependently attenuated hyperplastic and hypertrophic myometrium and improved adenomyosis. The activation of NF-κB and β-catenin signaling pathway was observed in the ectopic endometria. While, rhein dose dependently inhibited the expressions of p-p65, p-AKT and actived Rac1. As Rac1 activation controlled nuclear localization of β-catenin during canonical Wnt signaling, we found that the degradation complex of β-catenin was improved by rhein. In addition, β-catenin nuclear translocation and its downstream genes were markedly suppressed by different doses of rhein. At the same time, decreased activation of epithelial-mesenchymal transition (EMT)-associated proteins including Snail and ZEB1 was detected in rhein-treated mice, indicating that the activation of Wnt signaling pathway was suppressed by rhein. The in vitro study verified a negative regulation of rhein on β-catenin in stromal cells. Stimulation of IL-1β significantly increased the nuclear translocation of β-catenin and improved its target genes expressions. While, rhein remarkably abolished the enhancement in a dose dependent manner. Taken together, our results demonstrated the ability of rhein to inhibit Wnt/β-catenin activation and its potential use in the treatment of adenomyosis and other abnormal activation of β-catenin -associated diseases., (Copyright © 2017. Published by Elsevier Masson SAS.)