Integrating Metabolic Oligosaccharide Engineering and SPAAC Click Chemistry for Constructing Fibrinolytic Cell Surfaces.

To effectively solve the problem of significant loss of transplanted cells caused by thrombosis during cell transplantation, this study simulates the human fibrinolytic system and combines metabolic oligosaccharide engineering with strain-promoted azide-alkyne cycloaddition (SPAAC) click chemistry to construct a cell surface with fibrinolytic activity. First, a copolymer (POL) of oligoethylene glycol methacrylate (OEGMA) and 6-amino-2-(2-methylamido)hexanoic acid (Lys) was synthesized by reversible addition-fragmentation chain transfer (RAFT) copolymerization, and the dibenzocyclooctyne (DBCO) functional group was introduced into the side chain of the copolymer through an active ester reaction, resulting in a functionalized copolymer DBCO-PEG4-POL with ε-lysine ligands. Then, azide functional groups were introduced onto the surface of HeLa model cells through metabolic oligosaccharide engineering, and DBCO-PEG4-POL was further specifically modified onto the surface of HeLa cells via the SPAAC "click" reaction. In vitro investigations revealed that compared with unmodified HeLa cells, modified cells not only resist the adsorption of nonspecific proteins such as fibrinogen and human serum albumin but also selectively bind to plasminogen in plasma while maintaining good cell viability and proliferative activity. More importantly, upon the activation of adsorbed plasminogen into plasmin, the modified cells exhibited remarkable fibrinolytic activity and were capable of promptly dissolving the primary thrombus formed on their surfaces. This research not only provides a novel approach for constructing transplantable cells with fibrinolytic activity but also offers a new perspective for effectively addressing the significant loss of transplanted cells caused by thrombosis.

High-density mapping of durable and broad-spectrum stripe rust resistance gene Yr30 in wheat.

KEY MESSAGE: The durable stripe rust resistance gene Yr30 was fine-mapped to a 610-kb region in which five candidate genes were identified by expression analysis and sequence polymorphisms. The emergence of genetically diverse and more aggressive races of Puccinia striiformis f. sp. tritici (Pst) in the past twenty years has resulted in global stripe rust outbreaks and the rapid breakdown of resistance genes. Yr30 is an adult plant resistance (APR) gene with broad-spectrum effectiveness and its durability. Here, we fine-mapped the YR30 locus to a 0.52-cM interval using 1629 individuals derived from residual heterozygous F5:6 plants in a Yaco"S"/Mingxian169 recombinant inbred line population. This interval corresponded to a 610-kb region in the International Wheat Genome Sequencing Consortium (IWGSC) RefSeq version 2.1 on chromosome arm 3BS harboring 30 high-confidence genes. Five genes were identified as candidate genes based on functional annotation, expression analysis by RNA-seq and sequence polymorphisms between cultivars with and without Yr30 based on resequencing. Haplotype analysis of the target region identified six haplotypes (YR30_h1-YR30_h6) in a panel of 1215 wheat accessions based on the 660K feature genotyping array. Lines with YR30_h6 displayed more resistance to stripe rust than the other five haplotypes. Near-isogenic lines (NILs) with Yr30 showed a 32.94% higher grain yield than susceptible counterparts when grown in a stripe rust nursery, whereas there was no difference in grain yield under rust-free conditions. These results lay a foundation for map-based cloning Yr30.

Classification and Treatment Strategies of Tibial Tubercle Fractures in Adults.

OBJECTIVES: Tibial tubercle is a crucial player in maintaining the structural integrity and functional stability of the knee joint. Currently, there is no standardized protocol for the classification and treatment of tibial tubercle fractures in adults. This study analyzed the incidence and treatment strategies of tibial tubercle fractures in adults according to the four-column and nine-segment classification system. METHODS: Data of patients with proximal tibial fractures involving tibial tubercle fractures who were treated at our hospital from August 2007 to March 2023 were retrospectively reviewed. The fractures were classified using the AO/OTA classification and four-column and nine-segment classification systems, and the treatment protocol (surgically treated or conservatively treated) was recorded. The number and distribution proportion of patients were counted. A two-sided t-test was conducted to determine the significance of differences between the gender and sides. RESULTS: In total, 169 tibial tubercle fractures were found in 1484 proximal tibial fractures. According to the AO/OTA classification, seven of the 169 patients, (4.1%) were type A, 36 patients (21.3%) were type B, and 126 patients (74.6%) were type C. According to the four-column and nine-segment classification, type 1 cleavage without free fragments was the most common type of fracture (93/169, 55.0%), followed by type 2 dissociative segmental fragments (48/169, 28.4%) and type 3 comminuted fractures (28/169, 16.6%). Overall, 139 of the 169 proximal tibial fractures with tuberosity involvement were treated surgically. Among them, additional fixation of the tubercle fragment was performed in 52 fractures. CONCLUSION: The incidence of tibial tubercle fractures involved in proximal tibial fractures was approximately 11.4% (169/1484) in adults, and approximately one-third of the tubercle bone fragment required additional fixation (30.8%, 52/169). The injury types in the four-column and nine-segment classifications are helpful for accurately judging and making treatment-related decisions for tibial tubercle fractures.

Racial and ethnic minorities disproportionately exposed to extreme daily temperature variation in the United States.

In the history of Homo sapiens, well-populated habitats have featured relatively stable temperatures with generally small daily variations. As the global population is increasingly residing in highly disparate climates, a burgeoning literature has documented the adverse health effects of single-day and day-to-day variation in temperature, raising questions of inequality in exposure to this environmental health risk. Yet, we continue to lack understanding of inequality in exposure to daily temperature variation (DTV) in the highly unequal United States. Using nighttime and daytime land surface temperature data between 2000 and 2017, this study analyzes population exposure to long-term DTV by race and ethnicity, income, and age for the 50 states and the District of Columbia. The analysis is based on population-weighted exposure at the census-tract level. We find that, on average, non-White (especially Black and Hispanic) and low-income Americans are exposed disproportionately to larger DTV. Race-based inequalities in exposure to DTV are larger than income-based disparities, with inequalities heightened in the summer months. In May, for example, the DTV difference by race and ethnicity of 51 states is between 0.20 and 3.01 °C (up to 21.0%). We find that younger populations are, on average, exposed to larger DTV, though the difference is marginal.

Pyrroloquinoline quinone promotes human mesenchymal stem cell-derived mitochondria to improve premature ovarian insufficiency in mice through the SIRT1/ATM/p53 pathway.

BACKGROUND: DNA damage and oxidative stress induced by chemotherapy are important factors in the onset of premature ovarian insufficiency (POI). Studies have shown that mitochondria derived from mesenchymal stem cells (MSC-Mito) are beneficial for age-related diseases, but their efficacy alone is limited. Pyrroloquinoline quinone (PQQ) is a potent antioxidant with significant antiaging and fertility enhancement effects. This study aimed to investigate the therapeutic effect of MSC-Mito in combination with PQQ on POI and the underlying mechanisms involved. METHODS: A POI animal model was established in C57BL/6J mice by cyclophosphamide and busulfan. The effects of MSC-Mito and PQQ administration on the estrous cycle, ovarian pathological damage, sex hormone secretion, and oxidative stress in mice were evaluated using methods such as vaginal smears and ELISAs. Western blotting and immunohistochemistry were used to assess the expression of SIRT1, PGC-1α, and ATM/p53 pathway proteins in ovarian tissues. A cell model was constructed using KGN cells treated with phosphoramide mustard to investigate DNA damage and apoptosis through comet assays and flow cytometry. SIRT1 siRNA was transfected into KGN cells to further explore the role of the SIRT1/ATM/p53 pathway in combination therapy with MSC-Mito and PQQ for POI. RESULTS: The combined treatment of MSC-Mito and PQQ significantly restored ovarian function and antioxidant capacity in mice with POI. This treatment also reduced the loss of follicles at various stages, improving the disrupted estrous cycle. In vitro experiments demonstrated that PQQ facilitated the proliferation of MitoTracker-labelled MSC-Mito, synergistically restoring mitochondrial function and inhibiting oxidative stress in combination with MSC-Mito. Both in vivo and in vitro, the combination of MSC-Mito and PQQ increased mitochondrial biogenesis mediated by SIRT1 and PGC-1α while inhibiting the activation of ATM and p53, consequently reducing DNA damage-mediated cell apoptosis. Furthermore, pretreatment of KGN cells with SIRT1 siRNA reversed nearly all the aforementioned changes induced by the combined treatment. CONCLUSIONS: Our research findings indicate that PQQ facilitates MSC-Mito proliferation and, in combination with MSC-Mito, ameliorates chemotherapy-induced POI through the SIRT1/ATM/p53 signaling pathway.

Identification of two novel QTL for Fusarium head blight resistance in German wheat cultivar Centrum.

Fusarium head blight (FHB) is a devastating disease that occurs in warm and humid environments. The German wheat Centrum has displayed moderate to high levels of FHB resistance in the field for many years. In this study, an F6:8 recombinant inbred line (RIL) population derived from cross Centrum × Xinong 979 was evaluated for FHB response following point inoculation in five environments. The population and parents were genotyped using the GenoBaits Wheat 16 K Panel. Stable quantitative trait loci (QTL) associated with FHB resistance in Centrum were mapped on chromosome arms 2DS and 5BS. The most effective QTL, located in 2DS, was identified as a new chromosome region represented by a 1.4 Mb interval containing 17 candidate genes. Another novel QTL was mapped in chromosome arm 5BS of a 5BS-7BS translocation chromosome. In addition, two environmentally-sensitive QTL were mapped on chromosome arms 2BL from Centrum and 5AS from Xinong 979. Polymorphisms of flanking allele-specifc quantitative PCR (AQP) markers AQP-6 for QFhb.nwafu-2DS and 16K-13073 for QFhb.nwafu-5BS were validated in a panel of 217 cultivars and breeding lines. These markers could be useful for marker-assisted selection of FHB resistance and also provide a starting point for fine mapping and marker-based cloning of the resistance genes.

Genetic dissection and identification of stripe rust resistance genes in the wheat cultivar Lanhangxuan 121, a cultivar selected from a space mutation population.

Stripe rust is a devastating disease of wheat worldwide. Chinese wheat cultivar Lanhangxuan 121 (LHX121), selected from an advanced line L92-47 population that had been subjected to space mutation breeding displayed a consistently higher level of resistance to stipe rust than its parent in multiple field environments. The aim of this research was to establish the number and types of resistance genes in parental lines L92-47 and LHX121 using separate segregating populations. The first population developed from a cross between LHX121 and susceptible cultivar Xinong 822 comprised 278 F2:3 lines. The second validation population comprised 301 F2:3 lines from a cross between L92-47 and susceptible cultivar Xinong 979. Lines of two population were evaluated for stripe rust response at three sites during the 2018-2020 cropping season. Affymetrix 660 K SNP arrays were used to genotype the lines and parents. Inclusive composite interval mapping detected QTL QYrLHX.nwafu-2BS, QYrLHX.nwafu-3BS, and QYrLHX.nwafu-5BS for resistance in all three environments. Based on previous studies and pedigree information, QYrLHX.nwafu-2BS and QYrLHX.nwafu-3BS were likely to be Yr27 and Yr30 that are present in the L92-47 parent. QYrLHX.nwafu-5BS (YrL121) detected only in LHX121 was mapped to a 7.60 cM interval and explained 10.67-22.57% of the phenotypic variation. Compared to stripe rust resistance genes previously mapped to chromosome 5B, YrL121 might be a new adult plant resistance QTL. Furthermore, there were a number of variations signals using 35 K SNP array and differentially expressed genes using RNA-seq between L92-47 and LHX121 in the YrL121 region, indicating that they probably impair the presence and/or function of YrL121. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01461-0.

The effectiveness of interventions to reduce cancer-related stigma: An integrative review.

AIMS: The clinical significance of cancer-related stigma on patients' well-being has been widely established. Stigma can be perceived and internalised by cancer patients or implemented by the general population and healthcare workers. Various interventions have been carried out to reduce cancer-related stigma, but their effectiveness is not well-understood. This review aims to synthesise evidence on the effectiveness of interventions to reduce cancer-related stigma. DESIGN: An integrative review. METHODS: This integrative review combined both qualitative and quantitative studies and followed five steps to identify problems, search for the literature, appraise the literature quality, analyse data, and present data. Mixed Methods Appraisal Tool (version 2018) was applied to evaluate the quality of the included studies. DATA SOURCES: Databases included Web of Science, MEDLINE, SpringerLink, Wiley Online Journals, Cochrane Library, ScienceDirect, OVID, and China National Knowledge Infrastructure (from the inception of each database to 30 April 2021). RESULTS: Eighteen quantitative, six qualitative, and five mixed-methods studies were included in this review. Cultural factors should be considered when conducting interventions to reduce cancer-related stigma. For cancer patients, multi-component interventions have demonstrated a positive effect on their perceived stigma. For general population, interactive interventions show promise to reduce their implemented stigma towards cancer patients. For healthcare workers, there is a paucity of studies to reduce their implemented stigma. Existing studies reported inconclusive evidence, partially due to the lack of a robust study design with an adequate sample size. CONCLUSIONS: Multi-component and interactive interventions show promise to relieve cancer-related stigma. More methodologically robust studies should be conducted in different cultures to elucidate the most appropriate interventions for different populations to reduce cancer-related stigma. IMPLICATION FOR THE PROFESSION AND PATIENT CARE: These findings will facilitate healthcare workers to design and implement interventions to reduce cancer-related stigma, thus improving the quality of life for cancer patients. PATIENT AND PUBLIC CONTRIBUTION: No patient and public contribution.

Temperature Field Characterization of Iron Tailings Based on Microwave Maintenance Technology.

Microwave maintenance technology, as a new development trend, can realize the environmentally noninvasive and rapid repair of asphalt pavement and gradually replace traditional maintenance methods. Iron tailings were used as a self-healing material in this study to investigate the temperature response matching of microwave maintenance technology. Firstly, the physical properties and the mechanism of iron tailings were elaborated through macroscopic physical index testing and microscopic X-ray diffraction (XRD) analysis. Secondly, the applicability of aggregates to microwave heating was demonstrated by analyzing the temperature rise characteristics of the granules using infrared imaging. Then, the temperature field variation rules of the iron tailing asphalt mixture were summarized by microwave heating Marshall specimens. Finally, the road performance was assessed by conducting high-temperature dynamic stability, low-temperature tensile, water immersion Marshall, and freeze-thaw splitting tests. The experimental results showed that the iron tailings can be used as an aggregate for high-grade asphalt pavement and as the preferred aggregate for microwave maintenance technology. The iron tailings temperature field was radial from the inside out to provide different temperature response states for different pavement diseases, so the asphalt was dissolved and precipitated in a short time. The particle size of iron tailings was inversely proportional to the wave-absorbing heating rate, and the heating efficiency of the small particle size (0-4.75 mm) was the highest. The specimens doped with 4.75-13.2 mm iron tailings showed the best heating performance and road performance, with the average surface temperature of the specimens reaching 126.0 °C within 2 min. In summary, according to different disease types and construction needs, iron tailings can be used as an aggregate for asphalt pavement, providing an appropriate temperature field and improving the efficiency of the microwave maintenance of asphalt pavements.

Effects of socioeconomic status and greenspace on respiratory emergency department visits under short-term temperature variations: An age-stratified case time-series study.

INTRODUCTION: Neighborhood socioeconomic status (SES) and greenspace can affect respiratory health. However, it is unclear whether effects of neighborhood SES and greenspace on respiratory health still exist regardless of temperature variations. METHODS: This paper conducted a two-stage, age-stratified case time-series study. The first goal is to examine the associations between two temperature metrics (daily mean temperature [DMT] and diurnal temperature range [DTR]) and respiratory emergency department (ED) visits among four age groups in New York City. The second goal is to evaluate whether neighborhood SES and greenspace would be determinants of respiratory ED visits independent from temperature varying factors. A distributed lag nonlinear model was applied on ED data from 135 zip codes (October 2016 - February 2020). RESULTS: Our first-stage analysis indicated that older adults aged 65+ had higher risk of ED visits (RR=2.78, 95% eCI: 2.41, 3.22; with 7 days of lag) on days with low DMT (-10°C), followed by adults aged 18-64 (RR=2.48, 95% eCI: 2.32, 2.65), children and youth aged 5-17 (RR=1.38, 95% eCI: 1.24, 1.53), and young children aged 0-4 (RR=1.04, 95% eCI: 0.96, 1.13). However, no excess respiratory ED visits were observed on days with high DMT (30°C). Higher DTR was associated with higher risk, with children and youth more susceptible when DTR was high (DTR 20°C; RR=5.70, 95% eCI: 3.42, 9.49; with 7 days of lag). The second-stage analysis indicated neighborhood SES and greenspace had significant associations with respiratory ED visits regardless of temperature variations. Specifically, Higher income and greenspace exposure were negatively associated with ED visits among all age groups. CONCLUSIONS: Neighborhood SES and greenspace could affect respiratory morbidity regardless of weather conditions. Daily temperature variations accelerated the short-term risk among population subgroups under different weather conditions (e.g., higher risk of days with low DMT among older adults, higher risk of days with high DTR among children and youth aged 5-17), which could create co-effects with neighborhood SES and greenspace on respiratory health.

Regulation of RAS palmitoyltransferases by accessory proteins and palmitoylation.

Palmitoylation of cysteine residues at the C-terminal hypervariable regions in human HRAS and NRAS, which is necessary for RAS signaling, is catalyzed by the acyltransferase DHHC9 in complex with its accessory protein GCP16. The molecular basis for the acyltransferase activity and the regulation of DHHC9 by GCP16 is not clear. Here we report the cryo-electron microscopy structures of the human DHHC9-GCP16 complex and its yeast counterpart-the Erf2-Erf4 complex, demonstrating that GCP16 and Erf4 are not directly involved in the catalytic process but stabilize the architecture of DHHC9 and Erf2, respectively. We found that a phospholipid binding to an arginine-rich region of DHHC9 and palmitoylation on three residues (C24, C25 and C288) were essential for the catalytic activity of the DHHC9-GCP16 complex. Moreover, we showed that GCP16 also formed complexes with DHHC14 and DHHC18 to catalyze RAS palmitoylation. These findings provide insights into the regulatory mechanism of RAS palmitoyltransferases.

Janus-type ionic conductive gels based on poly(N,N-dimethyl)acrylamide for strain/pressure sensors.

Strain/pressure sensors with high sensitivity and a wide operation range have broad application prospects in wearable medical equipment, human-computer interactions, electronic skin, and so on. In this work, based on the different solubilities of Zr4+ in the aqueous phase and the hydrophobic ionic liquid [BMIM][Tf2N], we used N,N-dimethylacrylamide (DMA) as a vinyl monomer to prepare a Janus-type ionic conductive gel with one-sided adhesion through "one-step" UV irradiation polymerization. The Janus-type gel has satisfactory mechanical properties (tensile strength: 217.06 kPa, elongation at break: 1121.01%), electrical conductivity (conductivity: 0.10 S m-1), one-sided adhesion (adhesion strength to glass: 72.35 kPa) and antibacterial properties. The sensor based on the Janus gel can be used not only for real-time monitoring of strain changes caused by various movements of the human body (such as finger bending, muscle contraction, smiling, and swallowing) but also for real-time monitoring of pressure changes (such as pressing, water droplets, and writing movements). Therefore, based on the simplicity of this method for constructing Janus-type ionic conductive gels and the excellent electromechanical properties of the prepared gel, we believe that the method provided in this study has broad application prospects in the field of multifunctional wearable sensors.

Modulus difference-induced embedding strategy to construct iontronic pressure sensor with high sensitivity and wide linear response range.

Sensitivity and linearity are two crucial indices to assess the sensing capability of pressure sensors; unfortunately, the two mutually exclusive parameters usually result in limited applications. Although a series of microengineering strategies including micropatterned, multilayered, and porous approach have been provided in detail, the conflict between the two parameters still continues. Here, we present an efficient strategy to resolve this contradiction via modulus difference-induced embedding deformation. Both the microscopic observation and finite element simulation results confirm the embedding deformation behavior ascribed to the elastic modulus difference between soft electrode and rigid microstructures. The iontronic pressure sensor with high sensitivity (35 kPa-1) and wide linear response range (0-250 kPa) is further fabricated and demonstrates the potential applications in monitoring of high-fidelity pulse waveforms and human motion. This work provides an alternative strategy to guide targeted design of all-around and comprehensive pressure sensor.

Slow stripe rusting in Chinese wheat Jimai 44 conferred by Yr29 in combination with a major QTL on chromosome arm 6AL.

KEY MESSAGE: YrJ44, a more effective slow rusting gene than Yr29, was localized to a 3.5-cM interval between AQP markers AX-109373479 and AX-109563479 on chromosome 6AL. "Slow rusting" (SR) is a type of adult plant resistance (APR) that can provide non-specific durable resistance to stripe rust in wheat. Chinese elite wheat cultivar Jimai 44 (JM44) has maintained SR to stripe rust in China since its release despite exposure to a changing and variable pathogen population. An F2:6 population comprising 295 recombinant inbred lines (RILs) derived from a cross between JM44 and susceptible cultivar Jimai 229 (JM229) was used in genetic analysis of the SR. The RILs and parental lines were evaluated for stripe rust response in five field environments and genotyped using the Affymetrix Wheat55K SNP array and 13 allele-specific quantitative PCR-based (AQP) markers. Two stable QTL on chromosome arms 1BL and 6AL were identified by inclusive composite interval mapping. The 1BL QTL was probably the pleiotropic gene Lr46/Yr29/Sr58. QYr.nwafu-6AL (hereafter named YrJ44), mapped in a 3.5-cM interval between AQP markers AX-109373479 and AX-109563479, was more effective than Yr29 in reducing disease severity and relative area under the disease progress curve (rAUDPC). RILs harboring both YrJ44 and Yr29 displayed levels of SR equal to the resistant parent JM44. The AQP markers linked with YrJ44 were polymorphic and significantly correlated with stripe rust resistance in a panel of 1,019 wheat cultivars and breeding lines. These results suggested that adequate SR resistance can be obtained by combining YrJ44 and Yr29 and the AQP markers can be used in breeding for durable stripe rust resistance.

Development of breeder chip for gene detection and molecular-assisted selection by target sequencing in wheat.

Wheat is an essential food crop and its high and stable yield is suffering from great challenges due to the limitations of current breeding technology and various stresses. Accelerating molecularly assisted stress-resistance breeding is critical. Through a meta-analysis of published loci in wheat over the last two decades, we selected 60 loci with main breeding objectives, high heritability, and reliable genotyping, such as stress resistance, yield, plant height, and resistance to spike germination. Then, using genotyping by target sequencing (GBTS) technology, we developed a liquid phase chip based on 101 functional or closely linked markers. The genotyping of 42 loci was confirmed in an extensive collection of Chinese wheat cultivars, indicating that the chip can be used in molecular-assisted selection (MAS) for target breeding goals. Besides, we can perform the preliminary parentage analysis with the genotype data. The most significant contribution of this work lies in translating a large number of molecular markers into a viable chip and providing reliable genotypes. Breeders can quickly screen germplasm resources, parental breeding materials, and intermediate materials for the presence of excellent allelic variants using the genotyping data by this chip, which is high throughput, convenient, reliable, and cost-efficient. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01359-3.

Deep Learning With Convolutional Neural Networks for Motor Brain-Computer Interfaces Based on Stereo-Electroencephalography (SEEG).

OBJECTIVE: Deep learning based on convolutional neural networks (CNN) has achieved success in brain-computer interfaces (BCIs) using scalp electroencephalography (EEG). However, the interpretation of the so-called 'black box' method and its application in stereo-electroencephalography (SEEG)-based BCIs remain largely unknown. Therefore, in this paper, an evaluation is performed on the decoding performance of deep learning methods on SEEG signals. METHODS: Thirty epilepsy patients were recruited, and a paradigm including five hand and forearm motion types was designed. Six methods, including filter bank common spatial pattern (FBCSP) and five deep learning methods (EEGNet, shallow and deep CNN, ResNet, and a deep CNN variant named STSCNN), were used to classify the SEEG data. Various experiments were conducted to investigate the effect of windowing, model structure, and the decoding process of ResNet and STSCNN. RESULTS: The average classification accuracy for EEGNet, FBCSP, shallow CNN, deep CNN, STSCNN, and ResNet were 35 ± 6.1%, 38 ± 4.9%, 60 ± 3.9%, 60 ± 3.3%, 61 ± 3.2%, and 63 ± 3.1% respectively. Further analysis of the proposed method demonstrated clear separability between different classes in the spectral domain. CONCLUSION: ResNet and STSCNN achieved the first- and second-highest decoding accuracy, respectively. The STSCNN demonstrated that an extra spatial convolution layer was beneficial, and the decoding process can be partially interpreted from spatial and spectral perspectives. SIGNIFICANCE: This study is the first to investigate the performance of deep learning on SEEG signals. In addition, this paper demonstrated that the so-called 'black-box' method can be partially interpreted.

High density mapping of wheat stripe rust resistance gene QYrXN3517-1BL using QTL mapping, BSE-Seq and candidate gene analysis.

KEY MESSAGE: Fine mapping of a major stripe rust resistance locus QYrXN3517-1BL to a 336 kb region that includes 12 candidate genes. Utilization of genetic resistance is an effective strategy to control stripe rust disease in wheat. Cultivar XINONG-3517 (XN3517) has remained highly resistant to stripe rust since its release in 2008. To understand the genetic architecture of stripe rust resistance, Avocet S (AvS) × XN3517 F6 RIL population was assessed for stripe rust severity in five field environments. The parents and RILs were genotyped by using the GenoBaits Wheat 16 K Panel. Four stable QTL from XINONG-3517 were detected on chromosome arms 1BL, 2AL, 2BL, and 6BS, named as QYrXN3517-1BL, QYrXN3517-2AL, QYrXN3517-2BL, and QYrXN3517-6BS, respectively. Based on the Wheat 660 K array and bulked segregant exome sequencing (BSE-Seq), the most effective QTL on chromosome 1BL is most likely different from the known adult plant resistance gene Yr29 and was mapped to a 1.7 cM region [336 kb, including twelve candidate genes in International Wheat Genome Sequencing Consortium (IWGSC) RefSeq version 1.0]. The 6BS QTL was identified as Yr78, and the 2AL QTL was probably same as QYr.caas-2AL or QYrqin.nwafu-2AL. The novel QTL on 2BL was effective in seedling stage against the races used in phenotyping. In addition, allele-specifc quantitative PCR (AQP) marker nwafu.a5 was developed for QYrXN3517-1BL to assist marker-assisted breeding.

Discovery of Orally Bioavailable N-Benzylpiperidinol Derivatives as Potent and Selective USP7 Inhibitors with In Vivo Antitumor Immunity Activity against Colon Cancer.

USP7 emerges as a potential therapeutic target for cancers, as it plays an important role in the development of tumorigenesis by stabilizing multiple cancer-relevant proteins. Nevertheless, the discovery of drug-like USP7 inhibitors remains challenging. Herein, we report a series of N-benzylpiperidinol derivatives as potent and selective USP7 inhibitors (e.g., X20 and X26: IC50 = 7.6 and 8.2 nM), whose binding modes were revealed by crystallographic studies to be distinct from the known N-acylpiperidinol USP7 inhibitors. Among them, X36 with good oral PK profiles (rat: F = 40.8% and T1/2 = 3.5 h) exhibited significant antitumor efficacy in the MC38 colon cancer syngeneic mouse model, at least partly through upregulating the tumor infiltration of CD8+ T, NK, and NKT cells and downregulating that of Tregs and MDSCs. These findings may further pave the way for the development of USP7 inhibitors as novel cancer immunotherapy drugs.

Effects of aerobics training on anxiety, depression and sleep quality in perimenopausal women.

Objective: To investigate the effect of aerobics training on anxiety, depression and sleep disturbance in perimenopausal women. Materials and methods: A total of 289 perimenopausal women with anxiety, depression or sleep disorder in Lishi district of Luliang city were treated with aerobics training. Self-rating anxiety scale, self-rating depression scale and Pittsburgh sleep scale were used to investigate the anxiety, depression and sleep status of perimenopausal women before and after intervention. Results: After aerobics training, the scores of self-rating anxiety scale, self-rating depression scale and Pittsburgh sleep questionnaire were 48.26 ± 6.47, 50.27 ± 6.54 and 10.64 ± 4.38, respectively. The levels of anxiety, depression and sleep disorder in 289 subjects were significantly lower than those before intervention (t = 3.865, 4.541, 5.596, P < 0.01). The remission rate of symptoms was significantly different in subjects with different frequency of spontaneous practice (P < 0.01), and the higher the number of spontaneous practice, the higher the remission rate of anxiety, depression and sleep disorders in subjects (P < 0.01). Conclusion: aerobics training can effectively improve the anxiety and depression of perimenopausal women, improve sleep quality, the more frequency of practice, the more obvious the effect. It can be used as an intervention to improve the mental health level of perimenopausal women in terms of anxiety, depression and sleep quality in clinical promotion.