High-Resolution Network with Dynamic Convolution and Coordinate Attention for Classification of Chest X-ray Images.

The development of automatic chest X-ray (CXR) disease classification algorithms is significant for diagnosing thoracic diseases. Owing to the characteristics of lesions in CXR images, including high similarity in appearance of the disease, varied sizes, and different occurrence locations, most existing convolutional neural network-based methods have insufficient feature extraction for thoracic lesions and struggle to adapt to changes in lesion size and location. To address these issues, this study proposes a high-resolution classification network with dynamic convolution and coordinate attention (HRCC-Net). In the method, this study suggests a parallel multi-resolution network in which a high-resolution branch acquires essential detailed features of the lesion and multi-resolution feature swapping and fusion to obtain multiple receptive fields to extract complicated disease features adequately. Furthermore, this study proposes dynamic convolution to enhance the network's ability to represent multi-scale information to accommodate lesions of diverse scales. In addition, this study introduces a coordinate attention mechanism, which enables automatic focus on pathologically relevant regions and capturing the variations in lesion location. The proposed method is evaluated on ChestX-ray14 and CheXpert datasets. The average AUC (area under ROC curve) values reach 0.845 and 0.913, respectively, indicating this method's advantages compared with the currently available methods. Meanwhile, with its specificity and sensitivity to measure the performance of medical diagnostic systems, the network can improve diagnostic efficiency while reducing the rate of misdiagnosis. The proposed algorithm has great potential for thoracic disease diagnosis and treatment.

Ni-Catalyzed Asymmetric Reductive Alkenylation of α-Chlorosulfones with Vinyl Bromides.

A nickel-catalyzed enantioconvergent reductive cross-coupling of α-chlorosulfones with vinyl bromides is described here. This strategy enables the enantioselective construction of chiral allylic sulfones from simple α-chlorosulfones and vinyl bromides. The mild reaction conditions lead to excellent functional group compatibility, as evidenced by the broad substrate scope and tolerance of complex bioactive molecules. Our preliminary mechanistic study suggests that this enantioselective vinylation process operates through a radical intermediate.

Intestinal Tuft-2 cells exert antimicrobial immunity via sensing bacterial metabolite N-undecanoylglycine.

Tuft cells are a type of intestinal epithelial cells that exist in epithelial barriers and play a critical role in immunity against parasite infection. It remains insufficiently clear whether Tuft cells participate in bacterial eradication. Here, we identified Sh2d6 as a signature marker for CD45+ Tuft-2 cells. Depletion of Tuft-2 cells resulted in susceptibility to bacterial infection. Tuft-2 cells quickly expanded in response to bacterial infection and sensed the bacterial metabolite N-undecanoylglycine through vomeronasal receptor Vmn2r26. Mechanistically, Vmn2r26 engaged with N-undecanoylglycine activated G-protein-coupled receptor-phospholipase C gamma2 (GPCR-PLCγ2)-Ca2+ signaling axis, which initiated prostaglandin D2 (PGD2) production. PGD2 enhanced the mucus secretion of goblet cells and induced antibacterial immunity. Moreover, Vmn2r26 signaling also promoted SpiB transcription factor expression, which is responsible for Tuft-2 cell development and expansion in response to bacterial challenge. Our findings reveal an additional function of Tuft-2 cells in immunity against bacterial infection through Vmn2r26-mediated recognition of bacterial metabolites.

Multiple-responsive supramolecular vesicle based on azobenzene-cyclodextrin host-guest interaction.

Multiple-responsive supramolecular vesicles have been successfully fabricated by the complexation between ß-cyclodextrin (ß-CD) and a pH/photo dual-responsive amphiphile 4-(4-(hexyloxy)phenylazo)benzoate sodium (HPB) with azobenzene and carboxylate groups. When mixing ß-CD with HPB to reach a host/guest molar ratio of 1 : 1, the azobenzene group of HPB could be spontaneously included by ß-CD molecules. Then, the formed inclusion complexes (HPB@ß-CD) could self-assemble into vesicles, which was driven by the hydrophobic interaction of the alkyl chain of HPB and the hydrogen bonds between neighboring ß-CDs. The reversible assembly/disassembly of the vesicles could be simply regulated under UV or visible light irradiation. The reversible phase transformation between vesicles and microbelts could also be realized by adjusting the pH values of the sample. Adding both competitive guest molecules (1-adamantane carboxylic acid sodium (ADA)) and α-amylase would result in the phase transformation from vesicles to micelles. Moreover, the vesicles would be destroyed when ß-CD was continuously added until the ratio of host/guest reached 2 : 1. Such an interesting quintuple-responsive vesicle system reported here not only has potential applications in various fields such as controlled release or drug delivery, but also provides a reference for the design and construction of multiple responsive systems.

Glutamylation of deubiquitinase BAP1 controls self-renewal of hematopoietic stem cells and hematopoiesis.

All hematopoietic lineages are derived from a limited pool of hematopoietic stem cells (HSCs). Although the mechanisms underlying HSC self-renewal have been extensively studied, little is known about the role of protein glutamylation and deglutamylation in hematopoiesis. Here, we show that carboxypeptidase CCP3 is most highly expressed in BM cells among CCP members. CCP3 deficiency impairs HSC self-renewal and hematopoiesis. Deubiquitinase BAP1 is a substrate for CCP3 in HSCs. BAP1 is glutamylated at Glu651 by TTLL5 and TTLL7, and BAP1-E651A mutation abrogates BAP1 glutamylation. BAP1 glutamylation accelerates its ubiquitination to trigger its degradation. CCP3 can remove glutamylation of BAP1 to promote its stability, which enhances Hoxa1 expression, leading to HSC self-renewal. Bap1E651A mice produce higher numbers of LT-HSCs and peripheral blood cells. Moreover, TTLL5 and TTLL7 deficiencies sustain BAP1 stability to promote HSC self-renewal and hematopoiesis. Therefore, glutamylation and deglutamylation of BAP1 modulate HSC self-renewal and hematopoiesis.

Function Prediction for G Protein-Coupled Receptors through Text Mining and Induction Matrix Completion.

G protein-coupled receptors (GPCRs) constitute the key component of cellular signal transduction. Accurately annotating the biological functions of GPCR proteins is vital to the understanding of the physiological processes they involve in. With the rapid development of text mining technologies and the exponential growth of biomedical literature, it becomes urgent to explore biological functional information from various literature for systematically and reliably annotating these known GPCRs. We design a novel three-stage approach, TM-IMC, using text mining and inductive matrix completion, for automated prediction of the gene ontology (GO) terms of the GPCR proteins. Large-scale benchmark tests show that inductive matrix completion models contribute to GPCR-GO association prediction for both molecular function and biological process aspects. Moreover, our detailed data analysis shows that information extracted from GPCR-associated literature indeed contributes to the prediction of GPCR-GO associations. The study demonstrated a new avenue to enhance the accuracy of GPCR function annotation through the combination of text mining and induction matrix completion over baseline methods in critical assessment of protein function annotation algorithms and literature-based GO annotation methods. Source codes of TM-IMC and the involved datasets can be freely downloaded from https://zhanglab.ccmb.med.umich.edu/TM-IMC for academic purposes.

Overexpression of PtrbHLH, a basic helix-loop-helix transcription factor from Poncirus trifoliata, confers enhanced cold tolerance in pummelo (Citrus grandis) by modulation of H2O2 level via regulating a CAT gene.

The basic helix-loop-helix (bHLH) family of transcription factors (TFs) plays a crucial role in regulating plant response to abiotic stress by targeting a large spectrum of stress-responsive genes. However, the physiological mechanisms underlying the TF-mediated stress response are still poorly understood for most of the bHLH genes. In this study, transgenic pummelo (Citrus grandis) plants overexpressing PtrbHLH, a TF previously identified from Poncirus trifoliata, were generated via Agrobacterium-mediated transformation. In comparison with the wild-type plants, the transgenic lines exhibited significantly lower electrolyte leakage and malondialdehyde content after cold treatment, thereby resulting in a more tolerant phenotype. Meanwhile, the transgenic lines accumulated dramatically lower reactive oxygen species (ROS) levels, consistent with elevated activity and expression levels of antioxidant enzymes (genes), including catalase (CAT), peroxidase and superoxide dismutase. In addition, PtrbHLH was shown to specifically bind to and activate the promoter of PtrCAT gene. Taken together, these results demonstrated that overexpression of PtrbHLH leads to enhanced cold tolerance in transgenic pummelo, which may be due, at least partly, to modulation of ROS levels by regulating the CAT gene.

Long-Term Effects of Tai Chi Intervention on Sleep and Mental Health of Female Individuals With Dependence on Amphetamine-Type Stimulants.

Previous studies provide evidence that Tai Chi (TC) can reduce the symptoms of sleep problems and be of benefit for the rehabilitation of substance abusers. In this study, we investigated if TC practice can improve sleep quality and mood of females who are dependent on amphetamine-type stimulant (ATS). Eighty subjects were randomly assigned to TC intervention and standard care (SC) for 6 months. We applied analysis of variance on repeated-measure with the year of drug dependence as the covariate to test the changes of the self-rated Pittsburg Sleep Quality Index (PSQI), Self-Rating Depression Scale (SDS), as well as fitness after 3 and 6 months. Relapse investigation was conducted by checking the database of China's National Surveillance System on Drug Abuse and that of the Shanghai Drug Control Committee's illicit drug dependents. Our investigation focused on the relapse of participants who had undergone and completed treatment in the Shanghai Mandatory Detoxification and Rehabilitation Center in 2015. The result showed that the PSQI scores of sleep duration [F(2, 92) = 9.86], need for sleep medications [F(2, 92) = 36.44] and daytime dysfunction [F(2, 92) = 5.15] were found to have a significant difference by time × group interaction after 6 months. SDS showed no significant difference between the two groups; however, the score of SDS in TC decreased after 6-month intervention, and no changes were observed in SC. Pulse rate had significantly decreased in the TC group compared with the SC group after 6 months. 9.5% (4) ATS dependents in TC and 26.3% (10) ATS dependents in SC were found to have relapsed. Our result suggested that TC had positive effects on sleep quality, depression and fitness. Long-term study demonstrated that TC may be a cheap and potential supplementary treatment for ATS-dependent individuals. TC may also be considered as an alternative exercise to escalate abstinence for ATS-dependent females. CLINICAL TRIAL REGISTRATION: ChiCTR-IPR-14005343 chictr. org.cn.

Molecular Identification of Rickettsia Species in Haemaphysalis Ticks Collected from Southwest China.

Rickettsia species are obligate intracellular Gram-negative bacteria that can infect a wide range of vertebrate hosts, including humans, through arthropod vectors such as Ixodid ticks. These ticks are a threat to humans and animals because they are the primary vectors or reservoirs for rickettsiae, which is of public health importance. In this study, we report the identification and percent of positive of Rickettsia spp. in ticks collected from Cangxi County, Southwest China. Haemaphysalis longicornis comprised 48.4% of the 188 ticks collected followed by Haemaphysalis flava (29.3%), H. doenitzi (12.2%), and Haemaphysalis hystricis (10.1%). A total of 63 (33.5%) ticks were positive with Rickettsia spp., with 48 (57%) of those being H. longicornis and 15 (27.3%) being H. flava. The other two tick species, however, did not have any ticks positive for rickettsial DNA. In addition, two different Rickettsia spp. were identified using gltA and ompA as molecular markers. The sequence of Rickettsia sp. infecting H. longicornis ticks was found to be identical to the Rickettsia sequences from Northeastern China and Japan (KF728367, AB516964). Phylogenetic analyses using these molecular markers support the notion that Rickettsia species from H. flava is the most close to a member of the Candidatus Rickettsia gannanii subgroup. The high percentage of Rickettsia positive in this Southwest China region suggests potential public health threat in the future and warrants to be monitored.

The transcription factor CsbHLH18 of sweet orange functions in modulation of cold tolerance and homeostasis of reactive oxygen species by regulating the antioxidant gene.

The basic helix-loop-helix (bHLH) transcription factors (TFs) comprise one of the largest gene families in plants, and participate in various physiological processes, but the physiological role and regulatory function of the majority of bHLHs remain poorly understood. Here, a total of 56 putative CsbHLH genes were identified in sweet orange (Citrus sinensis) based on a genome-wide analysis. The CsbHLH genes, except four members, were distributed throughout nine chromosomes and divided into 19 subgroups. Most of the CsbHLH genes were responsive to cold stress, with the greatest up-regulation being observed in CsbHLH18. CsbHLH18 is localized in the nuclei and has transcriptional activation activity. Overexpression of CsbHLH18 conferred enhanced cold tolerance in transgenic tobacco. The transgenic plants accumulated significantly less reactive oxygen species (ROS), concurrent with increased activities and transcript levels of antioxidant enzymes. In contrast, knockdown of bHLH18 by RNAi in trifoliate orange promoted cold susceptibility, accompanied by down-regulation of antioxidant genes and accumulation of more ROS. Protein-DNA interaction assays demonstrate that CsbHLH18 directly and specifically binds to and activates the promoter of CsPOD. Taken together, these findings indicate that CsbHLH18 plays a positive role in cold tolerance through, at least partly, modulation of ROS homeostasis by directly regulating the antioxidant gene.

The complete mitochondrial genome and phylogenetic analysis of Haemaphysalis longicornis Neumann (Acari: Ixodidae).

Haemaphysalis longicornis ticks are vectors or reservoirs of numerous infectious pathogens and cause a variety of human and animal diseases worldwide. However, there is limited knowledge on available genetic sequence. Herein, we extracted the complete mitochondrial genome (mitogenome) from enriched mitochondria of H. longicornis first time in ticks and gained its sequence with 14,718bp in length. The mitogenome consisted of 13 PCGs, 22 tRNA, 2 rRNA, and 2 noncoding regions. Also, the monophyletic phylogenetic position of H. longicornis is inferred based on 28 complete mitogenomes in total comprised of various species from Ixodida ticks in addition to the mitogenome of H. longicornis.

PCBs and OCPs in fish along coastal fisheries in China: Distribution and health risk assessment.

PCBs and OCPs were analyzed in fish (bass) taken along Chinese coastal fisheries. In the bass muscle, PCB, DDT and HCH concentrations were in the range of 1.02-2.2ng/g, 0.44-1.74 and 2.84-106.11ng/gww, respectively. Spatial distribution showed that the concentrations of target contaminants in bass from south fisheries were in general much lower than those from north fisheries in China. The ratios of OCP congeners suggested that technical DDT was not the main input and a recent usage of lindane or old technical HCH residuals could be the source of HCHs. The OCC concentrations in liver (127-442.43ng/gww) from selected samples were 8-12 and 10-14 times higher than those in gills and muscles, respectively. Based on the maximum allowable fish assumption rate (CRlim and CRmm), it could cause human health risk, by consuming bass samples taken from highly contaminated fisheries including QD and ST.

Nutrients and contaminants in tissues of five fish species obtained from Shanghai markets: Risk-benefit evaluation from human health perspectives.

Shanghai is a Chinese megacity in the Yangtze River Delta area, one of the most polluted coastal areas in China. The inhabitants of Shanghai have very high aquatic product consumption rates. A risk-benefit assessment of the co-ingestion of fish nutrients and contaminants has not previously been performed for Shanghai residents. Samples of five farmed fish species (marine and freshwater) with different feeding habits were collected from Shanghai markets in winter and summer. Fatty acids, protein, mercury, cadmium, lead, copper, polychlorinated biphenyls, hexachlorocyclohexanes, and dichlorodiphenyltrichloroethanes were measured in liver, abdominal fat, and dorsal, abdominal, and tail muscles from fish. Tolerable daily intakes and benefit-risk quotients were calculated to allow the benefits and risks of co-ingesting n-3 long-chain polyunsaturated fatty acids and contaminants to be assessed according to the cancer slope factors and reference doses of selected pollutants. All of the contaminant concentrations in the muscle tissues were much lower than the national maximum limits, but the livers generally contained high Hg concentrations, exceeding the regulatory limit. The organic pollutant and n-3 long-chain polyunsaturated fatty acid concentrations correlated with the lipid contents of the fish tissues, and were higher in carnivorous marine fish than in omnivorous and herbivorous freshwater fish. The tolerable daily intakes, risk-benefit quotients, and current daily aquatic product intakes for residents of large Chinese cities indicated that the muscle tissues of most of the fish analyzed can be consumed regularly without significant contaminant-related risks to health. However, attention should be paid to the potential risks posed by dichlorodiphenyltrichloroethane in large yellow croaker and Hg in tilapia. Based on the results of this study, we encourage people to consume equal portions of marine and freshwater fish.

[Concentration and distribution characteristics of estrogen in aquatic organism from Chongming Island].

Five typical estrogens, including estrone (E1), 17ß-estradiol (E2), estriol (E3), 17α-ethynyl estradiol (EE2) and bisphenol A (BPA), were simultaneously determined in typical aquatic organisms from Chongming Island by ultrahigh-performance liquid chromatography equipped with tandem mass spectrometry (UHPLC-MS2). The distribution pattern of estrogens was studied and preliminary heath risk assessment was discussed. The results showed that the total dry weight concentrations of estrogens were from 1.1 ng x g(-1) to 7.38 ng x g(-1) with a mean of 4.25 ng x g(-1). The lipid content-standardized estrogens concentrations were in the range of 5.01- 83.41 ng x g(-1) with a mean of 40.75 ng x g(-1), showing a descending order of fish > shrimp > crab. Fish and crab, fish and shrimp showed a significant difference in lipid content-standardized estrogen concentrations, whereas no significant difference was found between crab and shrimp. Compared to BPA, the dry weight concentrations of steroids (E1, E2, E3 and EE2) were found at lower levels (0.17-0.69 ng x g(-1)) with lower detection frequency (< 66.67%) in aquatic organisms from Chongming Island. In contrast, the detection rate of BPA reached 100%, and the average dry weight concentration detected was 2.60 ng x g(-1). The results of health risk assessment showed the concentration of estrogens in aquatic products from Chongming Island could not cause any adverse population-level effects.