Macrolones target bacterial ribosomes and DNA gyrase and can evade resistance mechanisms.

Growing resistance toward ribosome-targeting macrolide antibiotics has limited their clinical utility and urged the search for superior compounds. Macrolones are synthetic macrolide derivatives with a quinolone side chain, structurally similar to DNA topoisomerase-targeting fluoroquinolones. While macrolones show enhanced activity, their modes of action have remained unknown. Here, we present the first structures of ribosome-bound macrolones, showing that the macrolide part occupies the macrolide-binding site in the ribosomal exit tunnel, whereas the quinolone moiety establishes new interactions with the tunnel. Macrolones efficiently inhibit both the ribosome and DNA topoisomerase in vitro. However, in the cell, they target either the ribosome or DNA gyrase or concurrently both of them. In contrast to macrolide or fluoroquinolone antibiotics alone, dual-targeting macrolones are less prone to select resistant bacteria carrying target-site mutations or to activate inducible macrolide resistance genes. Furthermore, because some macrolones engage Erm-modified ribosomes, they retain activity even against strains with constitutive erm resistance genes.

Transcriptomic and proteomic strategies to reveal the mechanism of Gymnocypris przewalskii scale development.

BACKGROUND: Fish scales are typical products of biomineralization and play an important role in the adaptation of fish to their environment. The Gymnocypris przewalskii scales are highly specialized, with scales embedded in only specific parts of the dermis, such as the areas around the anal fin and branchiostegite, making G. przewalskii an ideal material for biomineralization research. In this study, we aimed to unveil genes and pathways controlling scale formation through an integrated analysis of both transcriptome and proteome, of which G. przewalskii tissues of the dorsal skin (no scales) and the rump side skin (with scales) were sequenced. The sequencing results were further combined with cellular experiments to clarify the relationship between genes and signaling pathways. RESULTS: The results indicated the following: (1) a total of 4,904 differentially expressed genes were screened out, including 3,294 upregulated genes and 1,610 downregulated genes (with a filtering threshold of |log2Fold-Change|> 1 and p-adjust < 0.05). The identified differentially expressed genes contained family members such as FGF, EDAR, Wnt10, and bmp. (2) A total of 535 differentially expressed proteins (DEPs) were filtered out from the proteome, with 204 DEPs downregulated and 331 DEPs upregulated (with a filtering threshold of |Fold-Change|> 1.5 and p < 0.05). (3) Integrated analyses of transcriptome and proteome revealed that emefp1, col1a1, col6a2, col16a1, krt8, and krt18 were important genes contributing to scale development and that PI3K-AKT was the most important signaling pathway involved. (4) With the use of the constructed G. przewalskii fibroblast cell line, emefp1, col1a1, col6a2, col16a1, krt8, and krt18 were confirmed to be positively regulated by the PI3K-AKT signaling pathway. CONCLUSION: This study provides experimental evidence for PI3K-AKT controlled scale development in G. przewalskii and would benefit further study on stress adaptation, scale biomineralization, and the development of skin appendages.

Activation of STING by the novel liposomal TLC388 enhances the therapeutic response to anti-PD-1 antibodies in combination with radiotherapy.

Current immune checkpoint inhibiters (ICIs) have contrasting clinical results in poorly immunogenic cancers such as microsatellite-stable colorectal cancer (MSS-CRC). Therefore, understanding and developing the combinational therapeutics for ICI-unresponsive cancers is critical. Here, we demonstrated that the novel topoisomerase I inhibitor TLC388 can reshape the tumor immune landscape, corroborating their antitumor effects combined with radiotherapy as well as immunotherapy. We found that TLC388 significantly triggered cytosolic single-stranded DNA (ssDNA) accumulation for STING activation, leading to type I interferons (IFN-Is) production for increased cancer immunogenicity to enhance antitumor immunity. TLC388-treated tumors were infiltrated by a vast number of dendritic cells, immune cells, and costimulatory molecules, contributing to the favorable antitumor immune response within the tumor microenvironment. The infiltration of cytotoxic T and NK cells were more profoundly existed within tumors in combination with radiotherapy and ICIs, leading to superior therapeutic efficacy in poorly immunogenic MSS-CRC. Taken together, these results showed that the novel topoisomerase I inhibitor TLC388 increased cancer immunogenicity by ssDNA/STING-mediated IFN-I production, enhancing antitumor immunity for better therapeutic efficacy in combination with radiotherapy and ICIs for poorly immunogenic cancer.

Electronic structures and quantum capacitance of twisted bilayer graphene with defects based on three-band tight-binding model.

Twisted bilayer graphene (tBLG) with C vacancies would greatly improve the density of states (DOS) around the Fermi level (EF) and quantum capacitance; however, the single-band tight-binding model only considering pz orbitals cannot accurately capture the low-energy physics of tBLG with C vacancies. In this work, a three-band tight-binding model containing three p orbitals of C atoms is proposed to explore the modulation mechanism of C vacancies on the DOS and quantum capacitance of tBLG. We first obtain the hopping integral parameters of the three-band tight-binding model, and then explore the electronic structures and the quantum capacitance of tBLG at a twisting angle of θ = 1.47° under different C vacancy concentrations. The impurity states contributed by C atoms with dangling bonds located around the EF and the interlayer hopping interaction could induce band splitting of the impurity states. Therefore, compared with the quantum capacitance of pristine tBLG (∼18.82 µF cm-2) at zero bias, the quantum capacitance is improved to ∼172.76 µF cm-2 at zero bias, and the working window with relatively large quantum capacitance in the low-voltage range is broadened in tBLG with C vacancies due to the enhanced DOS around the EF. Moreover, the quantum capacitance of tBLG is further increased at zero bias with an increase of the C vacancy concentration induced by more impurity states. These findings not only provide a suitable multi-band tight-binding model to describe tBLG with C vacancies but also offer theoretical insight for designing electrode candidates for low-power consumption devices with improved quantum capacitance.

The usefulness of contrast echocardiography in the evaluation of cardiac masses: a multicenter study.

BACKGROUND: Cardiac masses can encompass a variety of conditions, such as tumors, thrombi, vegetations, calcific lesions, and other rare diseases. Treatment and management of these types of cardiac masses differ considerably. Thus, accurately distinguishing among thrombi, benign tumors, and malignant tumors in the heart is of great importance. Contrast echocardiography (CE) has emerged as a promising technology. Although published guidelines suggest that CE can enhance image quality and assist in differentiating between benign and malignant lesions, most studies on CE diagnosis of cardiac masses are limited to case reports or retrospective/small-sample-sized prospective cohorts. This study aims to evaluate the diagnostic accuracy of CE in patients with suspected cardiac masses and address the insufficient evidence for differential diagnosis using CE. METHODS: Between April 2018 and July 2022, a prospective multicenter study was conducted, which included 145 consecutive patients suspected to have cardiac masses based on transthoracic echocardiography. All patients underwent CE examinations. The echocardiographic diagnosis relied on qualitative factors such as echogenicity, boundary, morphology of the base, mass perfusion, pericardial effusion, and motility as well as quantitative factors such as the area of the masses and the peak intensity ratio of the masses to adjacent myocardium (A1/A2). RESULTS: The final confirmed diagnoses were as follows: 2 patients had no cardiac mass, 4 patients had pseudomass, 43 patients had thrombus, 66 patients had benign tumors, and 30 patients had malignant tumors. The receiver operating characteristic (ROC) analysis indicated that an optimal A1/A2 cutoff value of 0.499 distinguished a cardiac tumor from a thrombus, with AUC, sensitivity, specificity, PPV, and NPV of 0.977, 97.9%, 90.7%, 95.9%, and 95.1%, respectively. The optimal A1/A2 cutoff value of 1.583 distinguished a cardiac tumor from a thrombus, with AUC, sensitivity, specificity, PPV, and NPV of 0.950, 93.3%, 93.9%, 87.5%, and 96.9%, respectively. CONCLUSIONS: Combined with qualitative and quantitative analyses, CE has the potential to accurately differentiate among different types of cardiac masses.

Design and structure-activity relationships of ether-linked alkylides: Hybrids of 3-O-descladinosyl macrolides and quinolone motifs.

Ketolides (3-keto) such as TE-802 and acylides (3-O-acyl) like TEA0929 are ineffective against constitutively resistant pathogens harboring erythromycin ribosomal methylation (erm) genes. Following our previous work on alkylides (3-O-alkyl), we explored the structure-activity relationships of hybrids combining (R/S) 3-descladinosyl erythromycin with 6/7-quinolone motifs, featuring extended ether-linked spacers, with a focus on their efficacy against pathogens bearing constitutive erm gene resistance. Optimized compounds 17a and 31f not only reinstated efficacy against inducibly resistant pathogens but also demonstrated significantly augmented activities against constitutively resistant strains of Streptococcus pneumoniae and Streptococcus pyogenes, which are typically refractory to existing C-3 modified macrolides. Notably, hybrid 31f (coded ZN-51) represented a pioneering class of agents distinguished by its dual modes of action, with ribosomes as the primary target and topoisomerases as the secondary target. As a novel chemotype of macrolide-quinolone hybrids, alkylide 31f is a valuable addition to our armamentarium against macrolide-resistant bacteria.

Recent advance of ATP citrate lyase inhibitors for the treatment of cancer and related diseases.

ATP citrate lyase (ACLY), a strategic metabolic enzyme that catalyzes the glycolytic to lipidic metabolism, has gained increasing attention as an attractive therapeutic target for hyperlipidemia, cancers and other human diseases. Despite of continual research efforts, targeting ACLY has been very challenging. In this field, most reported ACLY inhibitors are "substrate-like" analogues, which occupied with the same active pockets. Besides, some ACLY inhibitors have been disclosed through biochemical screening or high throughput virtual screening. In this review, we briefly summarized the cancer-related functions and the recent advance of ACLY inhibitors with a particular focus on the SAR studies and their modes of action. We hope to provide a timely and updated overview of ACLY and the discovery of new ACLY inhibitors.

Immunocyte membrane-derived biomimetic nano-drug delivery system: a pioneering platform for tumour immunotherapy.

Tumor immunotherapy characterized by its high specificity and minimal side effects has achieved revolutionary progress in the field of cancer treatment. However, the complex mechanisms of tumor immune microenvironment (TIME) and the individual variability of patients' immune system still present significant challenges to its clinical application. Immunocyte membrane-coated nanocarrier systems, as an innovative biomimetic drug delivery platform, exhibit remarkable advantages in tumor immunotherapy due to their high targeting capability, good biocompatibility and low immunogenicity. In this review we summarize the latest research advances in biomimetic delivery systems based on immune cells for tumor immunotherapy. We outline the existing methods of tumor immunotherapy including immune checkpoint therapy, adoptive cell transfer therapy and cancer vaccines etc. with a focus on the application of various immunocyte membranes in tumor immunotherapy and their prospects and challenges in drug delivery and immune modulation. We look forward to further exploring the application of biomimetic delivery systems based on immunocyte membrane-coated nanoparticles, aiming to provide a new framework for the clinical treatment of tumor immunity.

Preoperative chemoradiotherapy in older patients with rectal cancer guided by comprehensive geriatric assessment within a multidisciplinary team-a multicenter phase II trial.

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of preoperative concurrent chemoradiotherapy (preCRT) for locally advanced rectal cancer in older people who were classified as "fit" by comprehensive geriatric assessment (CGA). METHODS: A single-arm, multicenter, phase II trial was designed. Patients were eligible for this study if they were aged 70 years or above and met the standards of "fit" (SIOG1) as evaluated by CGA and of the locally advanced risk category. The primary endpoint was 2-year disease-free survival (DFS). Patients were scheduled to receive preCRT (50 Gy) with raltitrexed (3 mg/m2 on days 1 and 22). RESULTS: One hundred and nine patients were evaluated by CGA, of whom eighty-six, eleven and twelve were classified into the fit, intermediate and frail category. Sixty-eight fit patients with a median age of 74 years were enrolled. Sixty-four patients (94.1%) finished radiotherapy without dose reduction. Fifty-four (79.3%) patients finished the prescribed raltitrexed therapy as planned. Serious toxicity (grade 3 or above) was observed in twenty-four patients (35.3%), and fourteen patients (20.6%) experienced non-hematological side effects. Within a median follow-up time of 36.0 months (range: 5.9-63.1 months), the 2-year overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS) rates were 89.6% (95% CI: 82.3-96.9), 92.4% (95% CI: 85.9-98.9) and 75.6% (95% CI: 65.2-86.0), respectively. Forty-eight patients (70.6%) underwent surgery (R0 resection 95.8%, R1 resection 4.2%), the corresponding R0 resection rate among the patients with positive mesorectal fascia status was 76.6% (36/47). CONCLUSION: This phase II trial suggests that preCRT is efficient with tolerable toxicities in older rectal cancer patients who were evaluated as fit based on CGA. TRIAL REGISTRATION: The registration number on ClinicalTrials.gov was NCT02992886 (14/12/2016).

A memory-based spatial evolutionary game with the dynamic interaction between learners and profiteers.

Spatial evolutionary games provide a valuable framework for elucidating the emergence and maintenance of cooperative behaviors. However, most previous studies assume that individuals are profiteers and neglect to consider the effects of memory. To bridge this gap, in this paper, we propose a memory-based spatial evolutionary game with dynamic interaction between learners and profiteers. Specifically, there are two different categories of individuals in the network, including profiteers and learners with different strategy updating rules. Notably, there is a dynamic interaction between profiteers and learners, i.e., each individual has the transition probability between profiteers and learners, which is portrayed by a Markov process. Besides, the payoff of each individual is not only determined by a single round of the game but also depends on the memory mechanism of the individual. Extensive numerical simulations validate the theoretical analysis and uncover that dynamic interactions between profiteers and learners foster cooperation, memory mechanisms facilitate the emergence of cooperative behaviors among profiteers, and increasing the learning rate of learners promotes a rise in the number of cooperators. In addition, the robustness of the model is verified through simulations across various network sizes. Overall, this work contributes to a deeper understanding of the mechanisms driving the formation and evolution of cooperation.

Spacecraft Homography Pose Estimation with Single-Stage Deep Convolutional Neural Network.

Spacecraft pose estimation using computer vision has garnered increasing attention in research areas such as automation system theory, control theory, sensors and instruments, robot technology, and automation software. Confronted with the extreme environment of space, existing spacecraft pose estimation methods are predominantly multi-stage networks with complex operations. In this study, we propose an approach for spacecraft homography pose estimation with a single-stage deep convolutional neural network for the first time. We formulated a homomorphic geometric constraint equation for spacecraft with planar features. Additionally, we employed a single-stage 2D keypoint regression network to obtain homography 2D keypoint coordinates for spacecraft. After decomposition to obtain the rough spacecraft pose based on the homography matrix constructed according to the geometric constraint equation, a loss function based on pixel errors was employed to refine the spacecraft pose. We conducted extensive experiments using widely used spacecraft pose estimation datasets and compared our method with state-of-the-art techniques in the field to demonstrate its effectiveness.

Full-Automatic High-Efficiency Mueller Matrix Microscopy Imaging for Tissue Microarray Inspection.

This paper proposes a full-automatic high-efficiency Mueller matrix microscopic imaging (MMMI) system based on the tissue microarray (TMA) for cancer inspection for the first time. By performing a polar decomposition on the sample's Mueller matrix (MM) obtained by a transmissive MMMI system we established, the linear phase retardance equivalent waveplate fast-axis azimuth and the linear phase retardance are obtained for distinguishing the cancerous tissues from the normal ones based on the differences in their polarization characteristics, where three analyses methods including statistical analysis, the gray-level co-occurrence matrix analysis (GLCM) and the Tamura image processing method (TIPM) are used. Previous MMMI medical diagnostics typically utilized discrete slices for inspection under a high-magnification objective (20×-50×) with a small field of view, while we use the TMA under a low-magnification objective (5×) with a large field of view. Experimental results indicate that MMMI based on TMA can effectively analyze the pathological variations in biological tissues, inspect cancerous cervical tissues, and thus contribute to the diagnosis of postoperative cancer biopsies. Such an inspection method, using a large number of samples within a TMA, is beneficial for obtaining consistent findings and good reproducibility.

Rationally Designed Novel Antimicrobial Peptides Targeting Chitin Synthase for Combating Soybean Phytophthora Blight.

Soybean phytophthora blight is a severe menace to global agriculture, causing annual losses surpassing USD 1 billion. Present crop loss mitigation strategies primarily rely on chemical pesticides and disease-resistant breeding, frequently surpassed by the pathogens' quick adaptive evolution. In this urgent scenario, our research delves into innovative antimicrobial peptides characterized by low drug resistance and environmental friendliness. Inhibiting chitin synthase gene activity in Phytophthora sojae impairs vital functions such as growth and sporulation, presenting an effective method to reduce its pathogenic impact. In our study, we screened 16 previously tested peptides to evaluate their antimicrobial effects against Phytophthora using structure-guided drug design, which involves molecular docking, saturation mutagenesis, molecular dynamics, and toxicity prediction. The in silico analysis identified AMP_04 with potential inhibitory activity against Phytophthora sojae's chitin synthase. Through three rounds of saturation mutagenesis, we pin-pointed the most effective triple mutant, TP (D10K, G11I, S14L). Molecular dynamic simulations revealed TP's stability in the chitin synthase-TP complex and its transmembrane mechanism, employing an all-atom force field. Our findings demonstrate the efficacy of TP in occupying the substrate-binding pocket and translocation catalytic channel. Effective inhibition of the chitin synthase enzyme can be achieved. Specifically, the triple mutant demonstrates enhanced antimicrobial potency and decreased toxicity relative to the wild-type AMP_04, utilizing a mechanism akin to the barrel-stave model during membrane translocation. Collectively, our study provides a new strategy that could be used as a potent antimicrobial agent in combatting soybean blight, contributing to sustainable agricultural practices.

Discovery of Novel Diphenyl Acrylonitrile Derivatives That Promote Adult Rats' Hippocampal Neurogenesis.

We previously discovered WS-6 as a new antidepressant in correlation to its function of stimulating neurogenesis. Herein, several different scaffolds (stilbene, 1,3-diphenyl 1-propene, 1,3-diphenyl 2-propene, 1,2-diphenyl acrylo-1-nitrile, 1,2-diphenyl acrylo-2-nitrile, 1,3-diphenyl trimethylamine), further varied through substitutions of twelve amide substituents plus the addition of a methylene unit and an inverted amide, were examined to elucidate the SARs for promoting adult rat neurogenesis. Most of the compounds could stimulate proliferation of progenitors, but just a few chemicals possessing a specific structural profile, exemplified by diphenyl acrylonitrile 29b, 32a, and 32b, showed better activity than the clinical drug NSI-189 in promoting newborn cells differentiation into mature neurons. The most potent diphenyl acrylonitrile 32b had an excellent brain AUC to plasma AUC ratio (B/P = 1.6), suggesting its potential for further development as a new lead.

Development of a Non-Target Screening and Quantitative Analysis Strategy Based on UPLC-Q-TOF/MS and UPLC-QQQ/MS to Improve the Quality Control of Wuling Capsule.

Herbal medicine has been widely valued because of its remarkable efficacy and minimal side effects. The quantitative analysis of herbal medicines is essential to ensure their safety and efficacy. The simultaneous detection of multiple quality markers (Q-markers) has emerged as an important approach and trend in herbal medicine quality control. In recent years, non-targeted screening has become an effective strategy for the discovery and identification of unknown compounds. This study developed a non-targeted screening and quantitative analysis strategy to discover, identify and quantify the multiple components that truly represent the efficacy of Wuling capsule. Within this strategy, 18 types of flavonoids were tentatively discovered and identified from Wuling capsule by analyzing mass cleavage pathways, the precise molecular weights of compounds, and comparing the data with a database. Ten types of flavonoids were determined after the comparison of the standards. Additionally, following the evaluation of the regression equation, linear range, limit of detection (LOD), limit of quantitation (LOQ), precision, repeatability, and recovery of the proposed quantitative method, six flavonoids were quantified. This method successfully screened, identified, and quantified the potential active components in Wuling capsule, providing insights for improving the quality control standards in other herbal medicines.

First report of Epicoccum nigrum causing brown leaf spot of sweet cherry (Prunus avium) in China.

Sweet cherry (Prunus avium L.) has become an important economic fruit in China, mainly produced in Shandong Province. In recent years, the planting area of Aba Prefecture in Sichuan Province has increased. In June 2022, sweet cherry brown leaf spot was found in a cherry plantation (100ha) in Wenchuan County (30°54'50.21″N, 103°24'49.10″E), with an incidence of 50 - 70%. The symptoms appeared as brown circular spots on the leaf, gradually expanding until multiple lesions coalesced to form large irregular brown spots; eventually entire leaves were killed. To isolate the causal pathogens, 10 diseased trees were randomly selected from an orchard, one diseased leaf was taken from each tree, and samples (4×4 mm2) were cut from the border between diseased and healthy tissues of 10 diseased leaves, surface sterilized with 75% ethanol for 30 sec, washed three times with sterilized water, dried on sterilized filter paper and placed on potato dextrose agar (PDA). After 5d at 25℃, five morphologically similar colonies were obtained, colony appears yellow fluffy and released a large amount of red-orangepigment. Microscopy revealed circular to ovoid, verrucose, and multicellular conidia measuring 20×25 µm diameter (n = 30) were produced on the mycelia. The morphological characteristics were consistent with the description of Epicoccum nigrum (Lima et al 2011). To further identify the strains, the internal transcribed spacer (ITS), ß-tubulin, and RNA polymerase second largest subunit (RPB2) gene regions were amplified with ITS1/ITS4 , Bt2a/Bt2b, and 5f2/7cr (White et al. 1990; Glass and Donaldson 1995; Sung et al. 2007), respectively. BLAST analysis revealed that the ITS, ß-tubulin, and RPB2 sequences were 99.2%, 100% and 99.6% homologous, with those of E. nigrum (KU204750.1, OL782123.1, and MW602294.1), respectively. The sequences of the five isolates were identical; and those of representative strain TY3 were deposited in GenBank (ITS, OP410968; ß-tubulin, OR502448; RPB2, OP484927). Maximum likelihood phylogenetic analyses were performed for the combined data set with ITS , ß-tubulin and RPB2 using MEGA6 under the Tamura-Nei model (Tamura et al. 1993). Isolate TY3 clustered with E. nigrum type strain CBS 505.85. The pathogenicity of TY3 was tested on 10 sweet cherry trees aged 3 years (there were about 50 leaves per plant). Five plants were sprayed with 50 mL of spore suspension (1×105 spores/mL), while the controls (Five plants) were sprayed with 50 mL of sterile water. All plants were in closed plastic bags to maintain high humidity, placed in a greenhouse, and incubated at 25℃with a 12-h photoperiod. Twelve days after inoculation, 35% of the inoculated leaves showed lesions; that were consistent with those observed in the field, and the control group was asymptomatic. To confirm Koch´s postulates, two isolates were taken from the margins of leaf lesions and both were confirmed to be E. nigrum based on morphological observations and molecular identification using ITS ß-tubulin, and RPB2 sequences. This is the first report of brown leaf spot caused by E. nigrum on P. avium in China. This discovery needs to be considered in developing and implementing disease management programs in sweet cherry production.

Signal and Information Processing in Networks.

Networks are omnipresent in the realm of science, serving as a central focus in our modern world [...].

[Guiqi Yiyuan Ointment protects rat left lung from bystander effect of right lung injury induced by ~(12)C~(6+) beam].

This study observed the effects of Guiqi Yiyuan Ointment(GQYY) on the left lung subjecting to bystander effect of right lung injury induced by ~(12)C~(6+) beam in rats and decipher the underlying mechanism from NOD-like receptor protein 3(NLRP3)/apoptosis-associated speck-like protein containing a CARD(ASC)/cysteinyl aspartate specific proteinase-1(caspase-1) pathway. Wistar rats were randomized into 7 groups: blank, model, inhibitor [200 mg·kg~(-1), N-acetylcysteine(NAC)], western drug [140 mg·kg~(-1) amifostine(AMI)], and high-, medium-, and low-dose(4.8, 2.4, and 1.2 g·kg~(-1), respectively) GQYY groups. The model of bystander effect damage was established by 4 Gy ~(12)C~(6+) beam irradiation of the right lung(with the other part shielded by a lead plate). The pathological changes in the lung tissue, the level of reactive oxygen species(ROS) in the lung tissue, and the levels of superoxide dismutase(SOD) and malondialdehyde(MDA) in the serum were observed and measured in each group. Furthermore, the mRNA and protein levels of NLRP3, ASC, caspase-1, and phosphorylated nuclear factor-κB p65(p-NF-κB p65)/nuclear factor-κB p65(NF-κB p65) were determined. Compared with the blank group, the model group showed thickened alveolar wall, narrowed alveolar cavity, and presence of massive red blood cells and inflammatory infiltration in the alveolar wall and alveolar cavity. In addition, the model group showed elevated ROS levels in both left and right lungs, elevated MDA level, lowered SOD level, and up-regulated mRNA and protein levels of NLRP3, ASC, caspase-1, and p-NF-κB p65/NF-κB p65. Compared with the model group, the drug administration in all the groups reduced inflammatory cell infiltration in the lung tissue. The inhibitor group and the western drug group showed enlarged alveolar cavity, thinned interstitium, and reduced inflammation. There was a small amount of alveolar wall rupture in the high-and medium-dose GQYY groups and reduced inflammatory cell infiltration in the low dose GQYY group. Compared with the model group, drug administration lowered level of ROS in the left and right lungs, lowered the MDA level, elevated the SOD level, and down-regulated the mRNA and protein levels of NLRP3, ASC, caspase-1, and p-NF-κB p65/NF-κB p65. GQYY can effectively reduce the damage caused by radiation and bystander effect, which may be associated with the ROS-mediated NLRP3 inflammasome activation.

Compact snapshot dual-mode interferometric system for on-machine measurement.

To meet the need of on-machine metrology in optical manufacturing, a compact and snapshot dual-mode interferometric system is proposed for surface shape and roughness measurement. To simplify the measurement process between surface shape and roughness, a novel concept of using optical filters to separate the beam paths in the reference arm is introduced. A pixelated camera with a micro-polarizer array acquires four pi/2 phase-shifted interferograms simultaneously to minimize the environmental disturbance. Besides, the configuration-optimization-based subaperture stitching technique is introduced to extend the measurable aperture range. Both numerical analysis and experiments have been carried out to demonstrate the feasibility of the proposed compact snapshot dual-mode interferometer. The proposed system provides a powerful and portable tool to achieve on-machine surface characterization of various optical elements over a wide range of spatial frequencies and aperture sizes.

A Curriculum-style Self-training Approach for Source-Free Semantic Segmentation.

Source-free domain adaptation has developed rapidly in recent years, where the well-trained source model is adapted to the target domain instead of the source data, offering the potential for privacy concerns and intellectual property protection. However, a number of feature alignment techniques in prior domain adaptation methods are not feasible in this challenging problem setting. Thereby, we resort to probing inherent domain-invariant feature learning and propose a curriculum-style self-training approach for source-free domain adaptive semantic segmentation. In particular, we introduce a curriculum-style entropy minimization method to explore the implicit knowledge from the source model, which fits the trained source model to the target data using certain information from easy-to-hard predictions. We then train the segmentation network by the proposed complementary curriculum-style self-training, which utilizes the negative and positive pseudo labels following the curriculum-learning manner. Although negative pseudo-labels with high uncertainty cannot be identified with the correct labels, they can definitely indicate absent classes. Moreover, we employ an information propagation scheme to further reduce the intra-domain discrepancy within the target domain, which could act as a standard post-processing method for the domain adaptation field. Furthermore, we extend the proposed method to a more challenging black-box source model scenario where only the source model's predictions are available. Extensive experiments validate that our method yields state-of-the-art performance on source-free semantic segmentation tasks for both synthetic-to-real and adverse conditions datasets. The code and corresponding trained models are released at https://github.com/yxiwang/ATP.