Outcomes of the EMDataResource cryo-EM Ligand Modeling Challenge.

The EMDataResource Ligand Model Challenge aimed to assess the reliability and reproducibility of modeling ligands bound to protein and protein-nucleic acid complexes in cryogenic electron microscopy (cryo-EM) maps determined at near-atomic (1.9-2.5 Å) resolution. Three published maps were selected as targets: Escherichia coli beta-galactosidase with inhibitor, SARS-CoV-2 virus RNA-dependent RNA polymerase with covalently bound nucleotide analog and SARS-CoV-2 virus ion channel ORF3a with bound lipid. Sixty-one models were submitted from 17 independent research groups, each with supporting workflow details. The quality of submitted ligand models and surrounding atoms were analyzed by visual inspection and quantification of local map quality, model-to-map fit, geometry, energetics and contact scores. A composite rather than a single score was needed to assess macromolecule+ligand model quality. These observations lead us to recommend best practices for assessing cryo-EM structures of liganded macromolecules reported at near-atomic resolution.

Enhancing cryo-EM structure prediction with DeepTracer and AlphaFold2 integration.

Understanding the protein structures is invaluable in various biomedical applications, such as vaccine development. Protein structure model building from experimental electron density maps is a time-consuming and labor-intensive task. To address the challenge, machine learning approaches have been proposed to automate this process. Currently, the majority of the experimental maps in the database lack atomic resolution features, making it challenging for machine learning-based methods to precisely determine protein structures from cryogenic electron microscopy density maps. On the other hand, protein structure prediction methods, such as AlphaFold2, leverage evolutionary information from protein sequences and have recently achieved groundbreaking accuracy. However, these methods often require manual refinement, which is labor intensive and time consuming. In this study, we present DeepTracer-Refine, an automated method that refines AlphaFold predicted structures by aligning them to DeepTracers modeled structure. Our method was evaluated on 39 multi-domain proteins and we improved the average residue coverage from 78.2 to 90.0% and average local Distance Difference Test score from 0.67 to 0.71. We also compared DeepTracer-Refine with Phenixs AlphaFold refinement and demonstrated that our method not only performs better when the initial AlphaFold model is less precise but also surpasses Phenix in run-time performance.

Dual vector millimeter-wave signal generation based on optical carrier suppression modulation and direct detection with one photodetector.

We propose a novel, to the best of our knowledge, scheme for dual vector millimeter-wave (mm-wave) signal generation and transmission, based on optical carrier suppression (OCS) modulation, precoding, and direct detection by a single-ended photodiode (PD). At the transmitter side, two independent vector radio frequency (RF) signals with precoding, generated via digital signal processing (DSP), are used to drive an in-phase/quadrature (I/Q) modulator operating at the optical OCS modulation mode to simultaneously generate two independent frequency-doubling optical vector mm-wave signals, which can reduce the bandwidth requirement of transmitter's components and enhance spectral efficiency. With the aid of the single-ended PD and subsequent DSP at the receiver side, two independent frequency-doubling vector mm-wave signals can be separated and demodulated without data error. Based on our proposed scheme, we experimentally demonstrate the generation, transmission, and detection of 2-Gbaud 30-GHz quadrature-phase-shift-keying (QPSK) and 2-Gbaud 46-GHz QPSK signals over 10-km single-mode fiber-28 (SMF-28) and 1-m wireless transmission. The results indicate that the bit-error ratio (BER) of the dual vector mm-wave signals can each reach the hard-decision forward-error-correction (HD-FEC) threshold of 3.8 × 10-3.

Electron Donor-Acceptor Complex Driven Photocatalyst-Free Trifluoromethylation of Heterocycles.

Heterocyclic trifluoromethylation is efficiently initiated through a photochemical reaction utilizing an electron donor-acceptor (EDA) complex, proceeding smoothly without the use of photocatalysts, transition-metal catalysts, or additional oxidants. This method has been optimized through extensive experimentation, demonstrating its versatility and efficacy across various substrates, including quinoxalinones, coumarins, and indolones. Notably, this approach enables the practical synthesis of trifluoromethylated quinoxalinones on a gram scale. Mechanistic investigations that incorporate radical trapping and ultraviolet/visible spectroscopy, confirmed the formation of the an EDA complex and elucidated the reaction pathways. This study highlights the crucial role of EDA photoactivation in trifluoromethylation, significantly expanding the application scope of EDA complexes in chemical synthesis.

Phosphine-Catalyzed Stereospecific and Enantioselective Desymmetrizative [3+2] Cycloaddition of MBH Carbonates and N-(2-tert-Butylphenyl)maleimides.

Herein, we report an l-valine-derived amide phosphine-catalyzed [3+2] cyclization of MBH carbonates and N-(2-tert-butylphenyl)maleimides via asymmetric desymmetrization. Bicyclic N-aryl succinimide derivatives bearing three continuous chiral centers with a remote C-N atropisomeric chirality were constructed stereospecifically and enantioselectively. A wide variety of MBH carbonates could be employed in this process to deliver highly optically pure succinimide derivatives in moderate to excellent yields.

Modulatory effects of necroptosis: A potential preventive approach to control diseases in fish.

Necroptosis is a caspase-independent programmed cell death process characterized by morphological similarities to necrosis and the potential to cause significant inflammatory reactions. The initiation, execution, and inhibition of necroptosis involve a complex interplay of various signaling proteins. When death receptors bind to ligands, necroptosis is triggered through the receptor-interacting serine/threonine-protein kinase 1 (RIPK1)/RIPK3/Mixed Lineage Kinase Domain-Like (MLKL) axis, leading to inflammatory reactions in the surrounding tissues. This process encompasses numerous physiological regulatory mechanisms and contributes to the development and progression of certain diseases. The mechanisms of necroptosis were not well conserved across terrestrial and aquatic organisms, with differences in some components and functions. Given the significant challenges that aquatic animal diseases pose to aquaculture, research interest in necroptosis has surged recently, particularly in studies focusing on fish. Understanding necroptosis in fish can lead to interventions that offer potential breakthroughs in disease inhibition and fish health improvement.

Design, Synthesis, and Biological Evaluation of Chroman Derivatives as PD-1/PD-L1 Antagonists.

Programmed death-ligand 1 (PD-L1) has emerged as a promising therapeutic target for various cancers due to its crucial role in promoting tumor immune evasion. Here, we report a novel class of chroman-like small-molecule PD-L1 inhibitors exhibiting significant activity in inhibiting the PD-1/PD-L1 interaction. Employing a "ring-close" strategy for conformational restriction, we have achieved compound C27, which demonstrates superior PD-1/PD-L1 inhibitory activity compared to the positive control. Molecular dynamics simulation and binding free energy calculation predict that (R)-C27 with inhibitory activity surpassed (S)-C27. The experimental results from bioassay and X-ray structural analysis corroborate these findings. All these results collectively indicate that (R)-C27 is a promising lead compound deserving further exploration.

Ferric Oxide Nanomaterials and Plant-Rhizobacteria Symbionts Cogenerate Iron Plaque for Removing Highly Chlorinated Contaminants in Dryland Soils.

Rhizosphere iron plaques derived from Fe-based nanomaterials (NMs) are a promising tool for sustainable agriculture. However, the requirement for flooded conditions to generate iron plaque limits the scope of the NM application. In this study, we achieved in situ Fenton oxidation of a highly chlorinated persistent organic pollutant (2,2',4,5,5'-pentachlorobiphenyl, PCB101) through iron plaque mediated by the interaction between α-Fe2O3 NMs and plant-rhizobacteria symbionts under dryland conditions. Mechanistically, the coexistence of α-Fe2O3 NMs and Pseudomonas chlororaphis JD37 stimulated alfalfa roots to secrete acidic and reductive agents as well as H2O2, which together mediated the rhizosphere Fenton reaction and converted α-Fe2O3 NMs into iron plaque rich in Fe(II)-silicate. Further verifications reproduced the Fenton reaction in vitro using α-Fe2O3 NMs and rhizosphere compounds, confirming the critical role of •OH in the oxidative degradation of PCB101. Significant reductions in PCB101 content by 18.6%, 42.9%, and 23.2% were respectively found in stem, leaf, and soil after a 120-d treatment, proving the effectiveness of this NMs-plant-rhizobacteria technique for simultaneously safe crop production and soil remediation. These findings can help expand the potential applications of nanobio interaction and its mediated iron plaque generation for both agricultural practice and soil remediation.

Prediction of neoadjuvant chemotherapy pathological complete response for breast cancer based on radiomics nomogram of intratumoral and derived tissue.

BACKGROUND: Non-invasive identification of breast cancer (BCa) patients with pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) is critical to determine appropriate surgical strategies and guide the resection range of tumor. This study aimed to examine the effectiveness of a nomogram created by combining radiomics signatures from both intratumoral and derived tissues with clinical characteristics for predicting pCR after NACT. METHODS: The clinical data of 133 BCa patients were analyzed retrospectively and divided into training and validation sets. The radiomics features for Intratumoral, peritumoral, and background parenchymal enhancement (BPE) in the training set were dimensionalized. Logistic regression analysis was used to select the optimal feature set, and a radiomics signature was constructed using a decision tree. The signature was combined with clinical features to build joint models and generate nomograms. The area under curve (AUC) value of receiver operating characteristic (ROC) curve was then used to assess the performance of the nomogram and independent predictors. RESULTS: Among single region, intratumoral had the best predictive value. The diagnostic performance of the intratumoral improved after adding the BPE features. The AUC values of the radiomics signature were 0.822 and 0.82 in the training and validation sets. Multivariate logistic regression analysis revealed that age, ER, PR, Ki-67, and radiomics signature were independent predictors of pCR in constructing a nomogram. The AUC of the nomogram in the training and validation sets were 0.947 and 0.933. The DeLong test showed that the nomogram had statistically significant differences compared to other independent predictors in both the training and validation sets (P < 0.05). CONCLUSION: BPE has value in predicting the efficacy of neoadjuvant chemotherapy, thereby revealing the potential impact of tumor growth environment on the efficacy of neoadjuvant chemotherapy.

Predicting major adverse cardiovascular events within 3 years by optimization of radiomics model derived from pericoronary adipose tissue on coronary computed tomography angiography: a case-control study.

BACKGROUND: Coronary inflammation induces changes in pericoronary adipose tissue (PCAT) can be detected by coronary computed tomography angiography (CCTA). Our aim was to investigate whether different PCAT radiomics model based on CCTA could improve the prediction of major adverse cardiovascular events (MACE) within 3 years. METHODS: This retrospective study included 141 consecutive patients with MACE and matched to patients with non-MACE (n = 141). Patients were randomly assigned into training and test datasets at a ratio of 8:2. After the robust radiomics features were selected by using the Spearman correlation analysis and the least absolute shrinkage and selection operator, radiomics models were built based on different machine learning algorithms. The clinical model was then calculated according to independent clinical risk factors. Finally, an overall model was established using the radiomics features and the clinical factors. Performance of the models was evaluated for discrimination degree, calibration degree, and clinical usefulness. RESULTS: The diagnostic performance of the PCAT model was superior to that of the RCA-model, LAD-model, and LCX-model alone, with AUCs of 0.723, 0.675, 0.664, and 0.623, respectively. The overall model showed superior diagnostic performance than that of the PCAT-model and Cli-model, with AUCs of 0.797, 0.723, and 0.706, respectively. Calibration curve showed good fitness of the overall model, and decision curve analyze demonstrated that the model provides greater clinical benefit. CONCLUSION: The CCTA-based PCAT radiomics features of three major coronary arteries have the potential to be used as a predictor for MACE. The overall model incorporating the radiomics features and clinical factors offered significantly higher discrimination ability for MACE than using radiomics or clinical factors alone.

Epithelial thickness remodeling after small incision lenticule intrastromal keratoplasty in correcting hyperopia measured by RTVue OCT.

PURPOSE: To characterize the in vivo corneal epithelial thickness (CET) remodeling profile in a population of eyes after small incision lenticule intrastromal keratoplasty (SMI-LIKE) for hyperopia. METHODS: The CET profile was measured by RTVue-100 Fourier-domain OCT system across the central 6-mm diameter of the cornea of 17 eyes from 12 subjects (five males and seven females) who accepted corneal stromal lens implantation surgery for correcting hyperopia. The CET were measured at positions with a radius of 0-1.0 mm, 1.0-2.5 mm (divided into eight quadrants) and 2.5-3.0 mm (divided into eight quadrants) from the corneal center. Corneal maximum simulated keratometry (Km) was measured by Pentacam HR anterior segment analyzer to analyze CET changes. The examination data of subjects were collected in four time periods, which were preoperative, short-term postoperative (one week after surgery), mid-term postoperative (the last review within 3-6 months after surgery), and long-term postoperative (the last review over 1-2.5 years after surgery). The changes of CET were compared and analyzed in the four time periods. RESULTS: Mean CET in 0-1.0 mm, 1.0-2.5 mm and 2.5-3.0 mm of the cornea decreased in one week after surgery, respectively, as compared to CET in the preoperative period, which turned from 55.06 ± 0.82 µm、54.42 ± 0.75 µm、53.46 ± 0.60 µm to 51.18 ± 1.05 µm (P = 0.005), 49.38 ± 0.70 µm (P = 0.000), 51.29 ± 0.59 µm (P = 0.025). In the mid-term postoperative period, mean CET in 0-1.0 mm and 1.0-2.5 mm areas kept thinner than mean CET in the preoperative period, CET in 0-1.0 mm is 50.59 ± 0.76 µm (P = 0.000),CET in 1.0-2.5 mm is 50.23 ± 0.57 µm (P = 0.000), while mean CET in 2.5-3.0 mm area recovered to the same thickness as the preoperative level, which is 54.36 ± 0.66 µm (P = 1.000), until the long-term period, CET stabilized in the above doughnut pattern. CONCLUSIONS: After stromal lenticule implantation for hyperopia, CET showed a remodeled form of thinning in the 0-2.5 mm area and thickening in the 2.5-3.0 mm area, and remained stable within one year after surgery.

Sodium aescinate ameliorates chronic neuropathic pain in male mice via suppressing JNK/p38-mediated microglia activation.

OBJECTIVE: A study confirmed that sodium aescinate (SA) can effectively relieve bone cancer pain, but its role in neuropathic pain (NP) remains confused. METHODS: Eighty male mice were randomly divided into four groups: sham+vehicle, sham+SA (40 µg/L, intrathecal injection), chronic contraction injury (CCI)+vehicle, CCI+SA. Behavioral assessments were used to evaluate the locomotor activity and paw withdrawal threshold (PWT) of mice. At the end of the study, spinal cord tissues were collected for histopathological analysis. The JNK/p38 signaling activation, Iba-1 expression, pro-inflammatory cytokines levels, and microglia subtype were assessed by western blotting, immunohistochemical staining, enzyme-linked immunosorbent assay, and flow cytometry with CD86/CD206, respectively. RESULTS: Early treatment with SA delayed the development of mechanical allodynia in CCI mice. Repeated SA treatment could prominently increase the reduction of PWT induced by CCI, and improve the locomotor activity of CCI mice. Mechanically, CCI surgery induced significant up-regulation of p-JNK and p-p38 protein levels, increased number and M1/M2 ratio of microglia, as well as pro-inflammatory factors in the spinal cords of mice, which could be blocked after SA administration. CONCLUSIONS: SA might suppress the activation of microglia and neuroinflammation by selectively inhibiting the JNK/p38 signaling pathway, thereby alleviating CCI-induced NP in male mice.

FPIRST: Fatigue Driving Recognition Method Based on Feature Parameter Images and a Residual Swin Transformer.

Fatigue driving is a serious threat to road safety, which is why accurately identifying fatigue driving behavior and warning drivers in time are of great significance in improving traffic safety. However, accurately recognizing fatigue driving is still challenging due to large intra-class variations in facial expression, continuity of behaviors, and illumination conditions. A fatigue driving recognition method based on feature parameter images and a residual Swin Transformer is proposed in this paper. First, the face region is detected through spatial pyramid pooling and a multi-scale feature output module. Then, a multi-scale facial landmark detector is used to locate 23 key points on the face. The aspect ratios of the eyes and mouth are calculated based on the coordinates of these key points, and a feature parameter matrix for fatigue driving recognition is obtained. Finally, the feature parameter matrix is converted into an image, and the residual Swin Transformer network is presented to recognize fatigue driving. Experimental results on the HNUFD dataset show that the proposed method achieves an accuracy of 96.512%, thus outperforming state-of-the-art methods.

Cold shock treatment alleviates pitting in sweet cherry fruit by enhancing antioxidant enzymes activity and regulating membrane lipid metabolism.

BACKGROUND: In order to comprehend the regulatory mechanisms that result in the alleviation of sweet cherry pitting disorder through cold shock (0 °C ice-water mixture for 10 min), an investigation was conducted into the impacts of cold shock treatment (CST) on membrane lipid metabolism, antioxidant enzyme activity, as well as pitting of cold-stored sweet cherry fruit. RESULTS: CST significantly inhibited the increase in pitting incidence, pitting index, and decay incidence. The CST treatment provided greater titratable acidity, firmness as well as total content of soluble solids. The use of CST prevented the build-up of superoxide anions, hydrogen peroxide, malondialdehyde, and reduced permeability of cell membranes. When in contrast to control group, the CST also raised the expression levels along with activity of the antioxidant enzymes ascorbate peroxidase (APX), glutathione reductase (GR), superoxide dismutase (SOD), and catalase (CAT). Furthermore, CST reduced the amount of fruit cell membrane peroxidation, suppressed the activity of phospholipase and lipoxygenase, postponed the rise in saturated fatty acids (SFAs) and decrease in unsaturated fatty acids (USFAs), ultimately keeping a high ratio of USFAs to SFAs. CONCLUSION: CST can alleviating pitting disorder in sweet cherry fruit via preventing peroxidation of membrane lipid and elevating the antioxidant enzymes activity. © 2024 Society of Chemical Industry.

[Anisotropy and viscoelasticity of different corneal regions in rabbit corneal ectasia model].

The mechanical properties of the cornea in corneal ectasia disease undergo a significant reduction, yet the alterations in mechanical properties within distinct corneal regions remain unclear. In this study, we established a rabbit corneal ectasia model by employing collagenase II to degrade the corneal matrix within a central diameter of 6 mm. Optical coherence tomography was employed for the in vivo assessment of corneal morphology (corneal thickness and corneal curvature) one month after operation. Anisotropy and viscoelastic characteristics of corneal tissue were evaluated through biaxial and uniaxial testing, respectively. The results demonstrated a marked decrease in central corneal thickness, with no significant changes observed in corneal curvature. Under different strains, the elastic modulus of the cornea exhibited no significant differences in the up-down and naso-temporal directions between the control and model groups. However, the cornea in the model group displayed a significantly lower elastic modulus compared to the control group. Specifically, the elastic modulus of the central region cornea in the model group was significantly lower than that of the entire cornea within the same group. Moreover, in comparison to the control group, the cornea in the model group exhibited a significant increase in both creep rate and overall deformation rate. The instantaneous modulus and equilibrium modulus were significantly reduced in the model cornea. No significant differences were observed between the entire cornea and the central cornea concerning these parameters. The results indicate that corneal anisotropy remains unchanged in collagenase-induced ectatic cornea. However, a significant reduction in viscoelastic properties is noticed. This study provides valuable insights for investigating changes in corneal mechanical properties within different regions of ectatic corneal disease.

Guest-guided anchoring patterns of cyclodextrin supramolecular microcrystals on droplet surfaces.

The growth of cyclodextrin inclusion complexes (ICs) on oil/water interfaces represents a beautiful example of spontaneous pattern formation in nature. How the supramolecules evolve remains a challenge because surface confinement can frustrate microcrystal growth and give rise to unusual phase transitions. Here we investigate the self-assembly of ICs on droplet surfaces using microfluidics, which allows directly visualizing packing, wetting and ordering of the microcrystals anchored on the surface. The oil guests of distinct molecular structures can direct the assembly of the ICs and largely affect anchoring dynamics of the ICs microcrystals, leading to a range of behaviors including orientating, slipping, buckling, jamming, or merging. We discuss the behaviors observed in terms of the flexibility of the building blocks, which offers a new degree of freedom through which to tailor their properties and gives rise to a striking feature of anchoring patterns that have no counterpart in normal colloidal crystals.

Faceted crystal growth of cyclodextrin-oil inclusion complexes.

The spontaneous formation of cyclodextrin (CD)-oil inclusion complexes (ICs) and their further growth into patterned crystals present a bottom-up route to the fabrication of periodic macroscopic structure. Although the inclusion processes are well established for the molecules, understanding intermediate structures during the crystal growth and emerging of persistent crystalline order has been lacking. Here we build a hierarchy of oriented micro/nanostructures of CD-oil ICs in solution by choosing different oil guests including several straight-chain alkanes of C12, C14 and C16, oleic acid (OA), glycerol trioleate (TG) and soybean oil (SO), in an attempt to reveal the roles of oil guests in the formation of their crystallites. Remarkably, the ICs tend to grow into clusters and terminate at a certain finite size as long columns or lamella plates with well-defined facets, dependent on the type of oil used. For the first time, we report a non-equilibrium growth of crystallites with surface faceting directed by the guests by means of Arching and Bundling.

Contamination and Control of Mycotoxins in Grain and Oil Crops.

Mycotoxins are carcinogenic, teratogenic and mutagenic toxic compounds produced by some filamentous fungi, which are extremely harmful to corn, rice, wheat, peanut, soybean, rapeseed and other grain and oil crops, and seriously threaten environmental safety, food safety and human health. With the rapid increase in the global population and the expansion of the main crop planting area, mycotoxin contamination has increased year by year in agricultural products. The current review aimed to summarize the contamination status and harmful effects of major mycotoxins of grain and oil crops and the environmental factors that impact mycotoxin contamination. Further, control measures of mycotoxin contamination, especially the biological control strategies, were discussed.

Relevant mycotoxins in oil crops, vegetable oils, de-oiled cake and meals: Occurrence, control, and recent advances in elimination.

Mycotoxins in agricultural commodities have always been a concern due to their negative impacts on human and livestock health. Issues associated with quality control, hot and humid climate, improper storage, and inappropriate production can support the development of fungus, causing oil crops to suffer from mycotoxin contamination, which in turn migrates to the resulting oil, de-oiled cake and meals during the oil processing. Related research which supports the development of multi-mycotoxin prevention programs has resulted in satisfactory mitigation effects, mainly in the pre-harvest stage. Nevertheless, preventive actions are unlikely to avoid the occurrence of mycotoxins completely, so removal strategies may still be necessary to protect consumers. Elimination of mycotoxin has been achieved broadly through the physical, biological, or chemical course. In view of the steadily increasing volume of scientific literature regarding mycotoxins, there is a need for ongoing integrated knowledge systems. This work revisited the knowledge of mycotoxins affecting oilseeds, food oils, cake, and meals, focusing more on their varieties, toxicity, and preventive strategies, including the methods adopted in the decontamination, which supplement the available information.

Fostering employees' innovative behavior: The importance of proactive personality and work-related flow.

Employees' innovative behaviors (EIB) play a crucial role in driving enterprises' innovation and enabling them to adapt to the complex business environment. The purpose of this study is to examine the role of proactive personality in EIB, whereby a mediating effect of work-related flow is proposed in this relationship. The moderating effect of organizational innovation climate is also examined on the indirect of proactive personality on EIB through work-related flow. With purposive sampling, a questionnaire survey was conducted on front-line employees of two digital cultural and creative industrial parks in Southwest China. A total of 279 valid questionnaires were used for hypothesis verification. The findings indicate that employees' proactive personality has a significant positive effect on EIB. Employees with a proactive personality are more likely to experience work-related flow, which in turn promotes their EIB. However, we did not find evidence of the organizational innovation climate moderating the relationship between proactive personality and EIB.