Understanding genome structure facilitates the use of wild lentil germplasm for breeding: A case study with shattering loci.

Plant breeders are generally reluctant to cross elite crop cultivars with their wild relatives to introgress novel desirable traits due to associated negative traits such as pod shattering. This results in a genetic bottleneck that could be reduced through better understanding of the genomic locations of the gene(s) controlling this trait. We integrated information on parental genomes, pod shattering data from multiple environments, and high-density genetic linkage maps to identify pod shattering quantitative trait loci (QTLs) in three lentil interspecific recombinant inbred line populations. The broad-sense heritability on a multi-environment basis varied from 0.46 (in LR-70, Lens culinaris × Lens odemensis) to 0.77 (in LR-68, Lens orientalis × L. culinaris). Genetic linkage maps of the interspecific populations revealed reciprocal translocations of chromosomal segments that differed among the populations, and which were associated with reduced recombination. LR-68 had a 2-5 translocation, LR-70 had 1-5, 2-6, and 2-7 translocations, and LR-86 had a 2-7 translocation in one parent relative to the other. Segregation distortion was also observed for clusters of single nucleotide polymorphisms on multiple chromosomes per population, further affecting introgression. Two major QTL, on chromosomes 4 and 7, were repeatedly detected in the three populations and contain several candidate genes. These findings will be of significant value for lentil breeders to strategically access novel superior alleles while minimizing the genetic impact of pod shattering from wild parents.

Application and subgroup analysis of competing risks model based on different lymph node staging systems in differentiated thyroid cancer.

Differentiated thyroid cancer (DTC) is the most common endocrine malignancy, with a rising incidence worldwide. Accurate prognostic models are essential for effective patient management. This study evaluates the prognostic value of various lymph node staging systems in DTC using a competing risks model. We used SEER database records (1998-2016) of 16,527 DTC patients, analyzing N stage, positive lymph node numbers (PLNNs), metastatic lymph node ratio (MLNR), log odds of positive lymph nodes (LODDS), and log odds of the negative lymph node (NLN)/T stage ratio (LONT). Univariate and multivariate analyses in a competing risks model were performed, along with subgroup analyses based on demographic and clinical characteristics. In this study of 16,527 patients with DTC, different lymph node staging systems showed different prognostic correlations in univariate and multivariate analyses. In particular, PLNNs showed significant prognostic correlations in several subgroups. Additionally, PLNNs were more suitable as a lymph node staging system for DTC than LODDS and MLNR in N1 stage subgroups, with an optimal cut-off of 13. Receiver operating characteristic curves, calibration curves and nomograms improved the clinical utility of the prognostic model based on PLNNs. Using competing risks model and subgroup analyses, we found that PLNNs had the best prognostic discriminatory efficacy for patients with DTC, especially those with N1 stage disease, and had an optimal cut-off value of 13.

Measurements of All-Particle Energy Spectrum and Mean Logarithmic Mass of Cosmic Rays from 0.3 to 30 PeV with LHAASO-KM2A.

We present the measurements of all-particle energy spectrum and mean logarithmic mass of cosmic rays in the energy range of 0.3-30 PeV using data collected from LHAASO-KM2A between September 2021 and December 2022, which is based on a nearly composition-independent energy reconstruction method, achieving unprecedented accuracy. Our analysis reveals the position of the knee at 3.67±0.05±0.15 PeV. Below the knee, the spectral index is found to be -2.7413±0.0004±0.0050, while above the knee, it is -3.128±0.005±0.027, with the sharpness of the transition measured with a statistical error of 2%. The mean logarithmic mass of cosmic rays is almost heavier than helium in the whole measured energy range. It decreases from 1.7 at 0.3 PeV to 1.3 at 3 PeV, representing a 24% decline following a power law with an index of -0.1200±0.0003±0.0341. This is equivalent to an increase in abundance of light components. Above the knee, the mean logarithmic mass exhibits a power law trend towards heavier components, which is reversal to the behavior observed in the all-particle energy spectrum. Additionally, the knee position and the change in power-law index are approximately the same. These findings suggest that the knee observed in the all-particle spectrum corresponds to the knee of the light component, rather than the medium-heavy components.

The NF-κB/NUAK2 signaling axis regulates pancreatic cancer progression by targeting SMAD2/3.

Nuclear factor kappa B (NF-κB) plays a pivotal role in the development of pancreatic cancer, and its phosphorylation has previously been linked to the regulation of NUAK2. However, the regulatory connection between NF-κB and NUAK2, as well as NUAK2's role in pancreatic cancer, remains unclear. In this study, we observed that inhibiting NUAK2 impeded the proliferation, migration, and invasion of pancreatic cancer cells while triggering apoptosis. NUAK2 overexpression partially resisted apoptosis and reversed the inhibitory effects of the NF-κB inhibitor. NF-κB transcriptionally regulated NUAK2 transcription by binding to the promoter region of NUAK2. Mechanistically, NUAK2 knockdown remarkably reduced the expression levels of p-SMAD2/3 and SMAD2/3, resulting in decreased nuclear translocation of SMAD4. In SMAD4-negative cells, NUAK2 knockdown impacted FAK signaling by downregulating SMAD2/3. Moreover, NUAK2 knockdown heightened the sensitivity of pancreatic cancer cells to gemcitabine, suggesting that NUAK2 inhibitors could be a promising strategy for pancreatic cancer treatment.

A Novel Bifunctional Alginate Lyase and Antioxidant Activity of the Enzymatic Hydrolysates.

Alginate lyase Aly448, a potential new member of the polysaccharide lyase (PL) 7 family, which was cloned and identified from the macroalgae-associated bacterial metagenomic library, showed bifunctionality. The molecular docking results revealed that Aly448 has two completely different binding sites for alginate (polyMG), poly-α-l-guluronic acid (polyG), and poly-ß-d-mannuronic acid (polyM) substrates, respectively, which might be the molecular basis for the enzyme's bifunctionality. Truncational results confirmed that predicted key residues affected the bifunctionality of Aly448, but did not wholly explain. Besides, Aly448 presented excellent biochemical characteristics, such as higher thermal stability and pH tolerance. Degradation of polyMG, polyM, and polyG substrates by Aly448 produced tetrasaccharide (DP4), disaccharide (DP2), and galactose (DP1), which exhibited excellent antioxidant activity. These findings provide novel insights into the substrate recognition mechanism of bifunctional alginate lyases and pave a new path for the exploitation of natural antioxidant agents.

Cognition-Driven Structural Prior for Instance-Dependent Label Transition Matrix Estimation.

The label transition matrix has emerged as a widely accepted method for mitigating label noise in machine learning. In recent years, numerous studies have centered on leveraging deep neural networks to estimate the label transition matrix for individual instances within the context of instance-dependent noise. However, these methods suffer from low search efficiency due to the large space of feasible solutions. Behind this drawback, we have explored that the real murderer lies in the invalid class transitions, that is, the actual transition probability between certain classes is zero but is estimated to have a certain value. To mask the invalid class transitions, we introduced a human-cognition-assisted method with structural information from human cognition. Specifically, we introduce a structured transition matrix network (STMN) designed with an adversarial learning process to balance instance features and prior information from human cognition. The proposed method offers two advantages: 1) better estimation effectiveness is obtained by sparing the transition matrix and 2) better estimation accuracy is obtained with the assistance of human cognition. By exploiting these two advantages, our method parametrically estimates a sparse label transition matrix, effectively converting noisy labels into true labels. The efficiency and superiority of our proposed method are substantiated through comprehensive comparisons with state-of-the-art methods on three synthetic datasets and a real-world dataset. Our code will be available at https://github.com/WheatCao/STMN-Pytorch.

High-precision time measurement electronics using the bandpass sampling method.

Waveform digitization at sampling rates up to several giga-samples per second is one of the approaches to achieve high-precision time measurements. In recent years, achieving high precision at lower sampling rates has emerged as a significant research topic. In this article, we focus on time measurement electronics, in which the bandpass sampling method is applied to obtain high precision at a sampling rate of roughly 100 MSps. An analog front-end circuit is designed, in which the input pulse signal is bandpass-filtered and amplified before sampling. A pipelined real-time time extraction algorithm is designed using the techniques of interpolation and cross correlation. A 1024-point fast Fourier transform algorithm is adopted to implement the cross correlation operation. Four time measurement channels are implemented in a mid-range field-programmable gate array, and the measurement rate of 116 kHz is achieved. Tests are conducted to evaluate the performance of the timing system. The typical RMS precision is better than 0.4 ps.

Serum Aldo-Keto Reductase Family 1 Member B10 (AKR1B10) as a Potential Biomarker for Diagnosis of Hepatocellular Carcinoma.

Objective: To evaluate the diagnostic performance of aldo-keto reductase family 1 member B10 (AKR1B10) in a Beijing cohort with hepatocellular carcinoma (HCC). Methods: This study included 521 subjects who visited Peking Union Medical College Hospital from June 2017 to May 2023, including 109 cases of HCC, 165 cases of healthy controls, 106 cases of benign liver diseases, and 141 cases of other cancers. Serum AKR1B10 levels were measured and compared across various groups. Diagnostic performances of serum AKR1B10 and other tumor markers were assessed using receiver operator characteristic (ROC) curves. In addition, a subset of HCC patients who underwent surgical resection were recruited for clinical follow-up study. Results: We found that serum AKR1B10 expression was higher in patients with HCC relative to other control groups. The association between serum AKR1B10 and clinical features of HCC was not observed. Serum AKR1B10 showed a high diagnostic performance for HCC, and when combined with AFP, the diagnostic effectiveness was significantly improved. Specifically, serum AKR1B10 showed superior diagnostic effectiveness for AFP-negative HCC. The clinical follow-up study indicated a gradual decrease in serum AKR1B10 after surgery. Conclusion: Our study demonstrated that serum AKR1B10 is a promising biomarker for HCC, and when used in combination with AFP can significantly improve the detection rate of HCC.

Comparing the antibacterial activity of chitin nanocrystals with chitin: exploring the feasibility of chitin nanocrystals as novel pesticide nanocarriers in agriculture.

BACKGROUND: In recent years, nanomaterials-based pesticide carriers have garnered significant attention and sparked extensive research. However, most studies have primarily focused on investigating the impact of physical properties of nanomaterials, such as size and modifiable sites, on drug delivery efficiency of nano-pesticides. The limited exploration of biologically active nanomaterials poses a significant obstacle to the advancement and widespread adoption of nano-pesticides. In this study, we prepared chitin nanocrystals (ChNC) based on acid hydrolysis and systematically investigated the differences between nano- and normal chitin against plant bacteria (Pseudomonas syringae pv. tabaci). The primary objective was to seek out nanocarriers with heightened biological activity for the synthesis of nano-pesticides. RESULTS: Zeta potential analysis, Fourier Transform infrared spectrometry (FTIR), X-Ray diffraction (XRD), Atomic force microscopy (AFM) and Transmission electron microscopy (TEM) identified the successful synthesis of ChNC. ChNC showcased remarkable bactericidal activity at comparable concentrations, surpassing that of chitin, particularly in its ability to inhibit bacterial biofilm formation. Furthermore, ChNC displayed heightened effectiveness in disrupting bacterial cell membranes, resulting in the leakage of bacterial cell contents, structural DNA damage, and impairment of DNA replication. Lastly, potting experiments revealed that ChNC is notably more effective in inhibiting the spread and propagation of bacteria on plant leaves. CONCLUSION: ChNC exhibited higher antibacterial activity compared to chitin, enabling efficient control of plant bacterial diseases through enhanced interaction with bacteria. These findings offer compelling evidence of ChNC's superior bacterial inhibition capabilities, underscoring its potential as a promising nanocarrier for nano-pesticide research. © 2023 Society of Chemical Industry.

Measurement of Ultra-High-Energy Diffuse Gamma-Ray Emission of the Galactic Plane from 10 TeV to 1 PeV with LHAASO-KM2A.

The diffuse Galactic γ-ray emission, mainly produced via interactions between cosmic rays and the interstellar medium and/or radiation field, is a very important probe of the distribution, propagation, and interaction of cosmic rays in the Milky Way. In this Letter, we report the measurements of diffuse γ rays from the Galactic plane between 10 TeV and 1 PeV energies, with the square kilometer array of the Large High Altitude Air Shower Observatory (LHAASO). Diffuse emissions from the inner (15°10 TeV). The energy spectrum in the inner Galaxy regions can be described by a power-law function with an index of -2.99±0.04, which is different from the curved spectrum as expected from hadronic interactions between locally measured cosmic rays and the line-of-sight integrated gas content. Furthermore, the measured flux is higher by a factor of ∼3 than the prediction. A similar spectrum with an index of -2.99±0.07 is found in the outer Galaxy region, and the absolute flux for 10≲E≲60 TeV is again higher than the prediction for hadronic cosmic ray interactions. The latitude distributions of the diffuse emission are consistent with the gas distribution, while the longitude distributions show clear deviation from the gas distribution. The LHAASO measurements imply that either additional emission sources exist or cosmic ray intensities have spatial variations.

Study on pore structure and the mechanical properties of sandstone-concrete binary under freeze-thaw environment.

In China's cold region water conservancy and hydropower projects, the contact interface between the dam and the reservoir bank rock is prone to cracking under external loading and freeze-thaw action, which may lead to dam-bank failure and damage and cause engineering disasters. The NMR (Nuclear Magnetic Resonance) tests and uniaxial compression tests of concrete, sandstone, and sandstone-concrete composite after different numbers of freeze-thaw cycles were carried out to analyze the pore structure development and uniaxial compression mechanical properties of the three types of specimens under different numbers of freeze-thaw cycles. The results show that freeze-thaw cycling promotes the development of pores in sandstone and concrete, and sandstone is more sensitive to low-temperature freeze-thaw than concrete. The UCS (uniaxial compressive strength) of the sandstone-concrete binary changed in a V-shaped with the increase of the dip angle of the cemented interface, and the angle had no obvious effect on the microscopic pores. The freeze-thaw effect on the deterioration of the microscopic pore structure and mechanical properties of the sandstone-concrete binary has a similar effect pattern, in which the deterioration rate of porosity and compressive strength is faster in the early freeze-thaw period, slower in the middle period, and increases in the later period compared with the middle period, but the increase is smaller than that in the early period of freeze-thaw. In addition, the relationship between the porosity and UCS of the sandstone-concrete binary under the freeze-thaw cycle environment is a quadratic parabola.

Gut microbiota-driven regulation of queen bee ovarian metabolism.

With the global prevalence of Varroa mites, more and more beekeepers resort to confining the queen bee in a queen cage to control mite infestation or to breed superior and robust queen bees. However, the impact of such practices on the queen bee remains largely unknown. Therefore, we subjected the queen bees to a 21-day egg-laying restriction treatment (from the egg stage to the emergence of adult worker bees) and analyzed the queen bees' ovarian metabolites and gut microbiota after 21 days, aiming to assess the queen bees' quality and assist beekeepers in better hive management. Our findings revealed a significant reduction in the relative expression levels of Vg and Hex110 genes in the ovaries of egg laying-restricted queen bees compared to unrestricted egg-laying queens. The diversity of gut microbiota in the queen bee exhibited a notable decrease, accompanied by corresponding changes in the core bacteria of the microbial community, the relative abundance of Lactobacillus and Bifidobacterium increased from 22.34% to 53.14% (P = 0.01) and from 0.053% to 0.580% (P = 0.04), respectively. The relative abundance of Bombella decreased from 25.85% to 1.720% (P = 0.002). Following egg-laying restriction, the activity of the queen bee's ovaries decreased, while the metabolism of glycerophospholipids remained or stored more lipid molecules, awaiting environmental changes for the queen bee to resume egg laying promptly. Furthermore, we observed that Bombella in the queen bee's gut may regulate the queen's ovarian metabolism through tryptophan metabolism. These findings provide novel insights into the interplay among queen egg laying, gut microbiota, and ovarian metabolism. IMPORTANCE With Varroa mite infestation, beekeepers often confine the queen bee in cages for control or breeding. However, the impact on the queen bee is largely unknown. We evaluated queen bee quality by restricting egg laying and analyzing ovarian metabolites and gut microbiota. In this study, we provided a comprehensive explanation of the expression of ovarian genes, the diversity of gut microbiota, and changes in ovarian metabolism in the queen bee. Through integrated analysis of the queen bee's gut microbiota and ovarian metabolism, we discovered that the gut microbiota can regulate the queen bee's ovarian metabolism. These findings provide valuable insights into the interplay among egg laying, gut microbiota, and the reproductive health of the queen bee. Understanding these relationships can contribute to the development of better strategies for Varroa mite control and queen bee breeding.

Use of Ceftazidime-Avibactam for Suspected or Confirmed Carbapenem-Resistant Organisms in Children: A Retrospective Study.

Background: The incidence of carbapenem-resistant organism (CRO) infections is increasing in children. However, pediatric-specific treatment strategies present unique challenges. Ceftazidime/avibactam is a ß-lactam/ß-lactamase inhibitor combination, showing adequate efficiency against CRO isolates. However, clinical data on the efficacy of ceftazidime/avibactam in children are still lacking. Methods: This was a retrospective study of children (aged <18 years) infected with confirmed or suspected carbapenem-resistant pathogens and treated with ceftazidime-avibactam at the First Affiliated Hospital of Zhengzhou University between 2020 and 2022. Results: We identified 38 children aged 14 (5.0-16.3) years; 20 (52.6%) had hematologic malignancies. 25 children with confirmed CRO infections were administered ceftazidime-avibactam as targeted therapy. The median treatment was 10 (6.0-16.5) days. Among them, 24 had infections caused by carbapenem-resistant Enterobacterales (CRE) (18 carbapenem-resistant Klebsiella pneumoniae and six carbapenem-resistant Escherichia coli species) and one with carbapenem-resistant Pseudomonas aeruginosa strains. The source of infection was the bloodstream in 60.0% of the cases (15/25). The clinical response rate was 84.0% (21/25), and 30-day mortality rate was 20% (5/25). 13 children were administered ceftazidime-avibactam as empiric therapy for suspected infections. The median treatment was 8 (6.0-13.0) days. No deaths occurred and clinical response was achieved in 12 of the 13 patients (92.3%) who empirically treated with ceftazidime-avibactam. Conclusion: Ceftazidime-avibactam is important for improving survival, and clinical response in children with infections caused by CRO.

From basic research to clinical application: targeting fibroblast activation protein for cancer diagnosis and treatment.

PURPOSE: This study aims to review the multifaceted roles of a membrane protein named Fibroblast Activation Protein (FAP) expressed in tumor tissue, including its molecular functionalities, regulatory mechanisms governing its expression, prognostic significance, and its crucial role in cancer diagnosis and treatment. METHODS: Articles that have uncovered the regulatory role of FAP in tumor, as well as its potential utility within clinical realms, spanning diagnosis to therapeutic intervention has been screened for a comprehensive review. RESULTS: Our review reveals that FAP plays a pivotal role in solid tumor progression by undertaking a multitude of enzymatic and nonenzymatic roles within the tumor stroma. The exclusive presence of FAP within tumor tissues highlights its potential as a diagnostic marker and therapeutic target. The review also emphasizes the prognostic significance of FAP in predicting tumor progression and patient outcomes. Furthermore, the emerging strategies involving FAPI inhibitor (FAPI) in cancer research and clinical trials for PET/CT diagnosis are discussed. And targeted therapy utilizing FAP including FAPI, chimeric antigen receptor (CAR) T cell therapy, tumor vaccine, antibody-drug conjugates, bispecific T-cell engagers, FAP cleavable prodrugs, and drug delivery system are also introduced. CONCLUSION: FAP's intricate interactions with tumor cells and the tumor microenvironment make it a promising target for diagnosis and treatment. Promising strategies such as FAPI offer potential avenues for accurate tumor diagnosis, while multiple therapeutic strategies highlight the prospects of FAP targeting treatments which needs further clinical evaluation.

Characterization of bifunctional alginate lyase Aly644 and antimicrobial activity of enzymatic hydrolysates.

An alginate lyase gene aly644 encoding a member of polysaccharide lyase family 6 was obtained from a metagenome of Antarctic macroalgae-associated microbes. The gene was expressed heterologously in Escherichia coli, and the recombinant protein was purified using a Ni-NTA His Tag Kit. With sodium alginate as the substrate, recombinant Aly644 exhibited an optimum reaction temperature of 50°C and an optimum reaction pH of 7.0. The Vmax and Km values of Aly644 toward sodium alginate were 112.36 mg/mL·min and 16.75 mg/mL, respectively. Substrate specificity analysis showed that Aly644 was a bifunctional alginate lyase that hydrolyzed both polyguluronic acid and polymannuronic acid. The hydrolysis products of Aly644 with sodium alginate as the substrate were detected by thin-layer chromatography, and were mainly di- and trisaccharides. The oligosaccharides produced by degradation of sodium alginate by Aly644 inhibited the mycelial growth of the plant pathogens Phytophthora capsici and Fulvia fulva; the 50% maximal effective concentration (EC50) values were 297.45 and 452.89 mg/L, and the 90% maximal effective concentration (EC90) values were 1341.45 and 2693.83 mg/L, respectively. This highlights that Aly644 is a potential candidate enzyme for the industrial production of alginate oligosaccharides with low degree of polymerization. Enzyme-hydrolyzed alginate oligosaccharides could support the development of green agriculture as natural antimicrobial agents. KEY POINTS: • An alginate lyase was obtained from a metagenome of Antarctic macroalgae-associated microbes. • Aly644 is a bifunctional alginate lyase with excellent thermostability and pH stability. • The enzymatic hydrolysates of Aly644 directly inhibited Phytophthora capsici and Fulvia fulva.

Synthesis of chitin nanocrystals supported Zn2+ with high activity against tobacco mosaic virus.

Chitin is a kind of natural nitrogenous organic polysaccharide. It contains antibacterial and antiviral properties, and it can induce plant disease resistance and promote plant growth. However, its application is constrained due to its insolubility and intricate molecular structure. Tobacco mosaic disease is caused by tobacco mosaic virus (TMV) infection, which seriously harms tobacco production. Zinc-containing chemical agents are commonly used to control tobacco mosaic disease, but overuse of chemical agents will cause serious environmental pollution. In this study, a novel nanomaterial (ChNC@Zn) was prepared by using chitin nanocrystals loaded with Zn2+, which has the function of inducing disease resistance to plants and reducing virus activity. When the Zn2+ concentration of ChNC@Zn is 105.6 µg/mL, it shows higher resistance to TMV than Lentinan (LNT). ChNC@Zn can improve the enzymes activities of peroxidase (POD) and catalase (CAT) in tobacco, and reduce the damage of reactive oxygen species (ROS) caused by TMV infection, thereby inducing resistance to TMV in tobacco. Besides, it can promote the growth of tobacco. As a result, ChNC@Zn can exhibit strong antiviral activity at low Zn2+ concentration and minimize the pollution of Zn2+ to the environment, which has high potential application value in the control of virus disease.

Metagenomic Insights Reveal the Microbial Diversity and Associated Algal-Polysaccharide-Degrading Enzymes on the Surface of Red Algae among Remote Regions.

Macroalgae and macroalgae-associated bacteria together constitute the most efficient metabolic cycling system in the ocean. Their interactions, especially the responses of macroalgae-associated bacteria communities to algae in different geographical locations, are mostly unknown. In this study, metagenomics was used to analyze the microbial diversity and associated algal-polysaccharide-degrading enzymes on the surface of red algae among three remote regions. There were significant differences in the macroalgae-associated bacteria community composition and diversity among the different regions. At the phylum level, Proteobacteria, Bacteroidetes, and Actinobacteria had a significantly high relative abundance among the regions. From the perspective of species diversity, samples from China had the highest macroalgae-associated bacteria diversity, followed by those from Antarctica and Indonesia. In addition, in the functional prediction of the bacterial community, genes associated with amino acid metabolism, carbohydrate metabolism, energy metabolism, metabolism of cofactors and vitamins, and membrane transport had a high relative abundance. Canonical correspondence analysis and redundancy analysis of environmental factors showed that, without considering algae species and composition, pH and temperature were the main environmental factors affecting bacterial community structure. Furthermore, there were significant differences in algal-polysaccharide-degrading enzymes among the regions. Samples from China and Antarctica had high abundances of algal-polysaccharide-degrading enzymes, while those from Indonesia had extremely low abundances. The environmental differences between these three regions may impose a strong geographic differentiation regarding the biodiversity of algal microbiomes and their expressed enzyme genes. This work expands our knowledge of algal microbial ecology, and contributes to an in-depth study of their metabolic characteristics, ecological functions, and applications.

Gut microbiome helps honeybee (Apis mellifera) resist the stress of toxic nectar plant (Bidens pilosa) exposure: Evidence for survival and immunity.

Honeybee (Apis mellifera) ingestion of toxic nectar plants can threaten their health and survival. However, little is known about how to help honeybees mitigate the effects of toxic nectar plant poisoning. We exposed honeybees to different concentrations of Bidens pilosa flower extracts and found that B. pilosa exposure significantly reduced honeybee survival in a dose-dependent manner. By measuring changes in detoxification and antioxidant enzymes and the gut microbiome, we found that superoxide dismutase, glutathione-S-transferase and carboxylesterase activities were significantly activated with increasing concentrations of B. pilosa and that different concentrations of B. pilosa exposure changed the structure of the honeybee gut microbiome, causing a significant reduction in the abundance of Bartonella (p < 0.001) and an increase in Lactobacillus. Importantly, by using Germ-Free bees, we found that colonization by the gut microbes Bartonella apis and Apilactobacillus kunkeei (original classification as Lactobacillus kunkeei) significantly increased the resistance of honeybees to B. pilosa and significantly upregulated bee-associated immune genes. These results suggest that honeybee detoxification systems possess a level of resistance to the toxic nectar plant B. pilosa and that the gut microbes B. apis and A. kunkeei may augment resistance to B. pilosa stress by improving host immunity.

A tera-electron volt afterglow from a narrow jet in an extremely bright gamma-ray burst.

Some gamma-ray bursts (GRBs) have a tera-electron volt (TeV) afterglow, but the early onset of this has not been observed. We report observations with the Large High Altitude Air Shower Observatory (LHAASO) of the bright GRB 221009A, which serendipitously occurred within the instrument's field of view. More than 64,000 photons >0.2 TeV were detected within the first 3000 seconds. The TeV flux began several minutes after the GRB trigger and then rose to a peak ~10 seconds later. This was followed by a decay phase, which became more rapid ~650 seconds after the peak. We interpret the emission using a model of a relativistic jet with half-opening angle of ~0.8°. This is consistent with the core of a structured jet and could explain the high isotropic energy of this GRB.

Impact of cytotoxic chemotherapy on aldo-keto reductase family 1 member B10 expression.

OBJECTIVE: Aldo-keto reductase family 1 member B10 (AKR1B10) is a protein that is produced and secreted by a significant number of breast cancers. However, a potential confounder to the use of AKR1B10 as a tumor marker is its elevation in patients given cytotoxic chemotherapy. We therefore conducted a prospective study to analyze AKR1B10 levels in patients with breast cancer receiving neoadjuvant cytotoxic chemotherapy. METHODS: The study enrolled 10 patients from November 2015 to July 2017. All patients had locally advanced, but non-metastatic, breast cancer, and they received neoadjuvant chemotherapy followed by surgery. Serum AKR1B10 levels and tumor imaging were assessed before, during, and after chemotherapy. RESULTS: No increase in serum AKR1B10 levels was noted in patients receiving chemotherapy whose levels were elevated at diagnosis. CONCLUSION: The findings are complex, but the overall data suggest that AKR1B10 is suitable as a tumor marker in patients with elevated levels at the time of diagnosis.