A Selective FGFR1/2 PROTAC Degrader with Antitumor Activity.

The aberrant activation of FGFR acts as a potent driver of multiple types of human cancers. Despite the development of several conventional small-molecular FGFR inhibitors, their clinical efficacy is largely compromised because of low selectivity and side effects. In this study, we report the selective FGFR1/2-targeting proteolysis-targeting chimera BR-cpd7 that displays significant isoform specificity to FGFR1/2 with half maximal degradation concentration values around 10 nmol/L while sparing FGFR3. The following mechanistic investigation reveals the reduced FGFR signaling, through which BR-cpd7 induces cell-cycle arrest and consequently blocks the proliferation of multiple FGFR1/2-dependent tumor cells. Importantly, BR-cpd7 has almost no antiproliferative activity against cancer cells without FGFR aberrations, furtherly supporting its selectivity. In vivo, BR-cpd7 exhibits robust antitumor effects in FGFR1-dependent lung cancer at well-tolerated dose schedules, accompanied by complete FGFR1 depletion. Overall, we identify BR-cpd7 as a promising candidate for developing a selective FGFR1/2-targeted agent, thereby offering a new therapeutic strategy for human cancers in which FGFR1/2 plays a critical role.

Association between serum cotinine and hepatic steatosis and liver fibrosis in adolescent: a population-based study in the United States.

Tobacco exposure is known to be associated with a higher prevalence and incidence of liver diseases. Cotinine, a metabolite of nicotine, is a typical indicator of tobacco exposure. However, the relationship of serum cotinine levels with hepatic steatosis and liver fibrosis remains controversial and these relationships need more research to explored in American teenagers. Cross-sectional data included 1433 participants aged 12-19 from the National Health and Nutrition Examination Survey (NHANES) from 2017 to 2020 were thoroughly used for this study. The linear relationships between serum cotinine levels and the Liver Stiffness Measurement (LSM) and Controlled Attenuation Parameter (CAP) were examined using multiple linear regression models. Subgroup analysis, interaction tests, and nonlinear interactions were also carried out. Serum cotinine levels > 2.99 ng/ml [ß = 0.41 (0.07, 0.76), p = 0.018] and 0.05-2.99 ng/ml [ß = 0.24 (0.00, 0.49), p = 0.048] showed a significant positive connection with LSM in multivariate linear regression analysis when compared to serum cotinine levels ≤ 0.05 ng/ml (p for trend = 0.006). Moreover, we discovered an inverted U-shaped association of log2-transformed cotinine with LSM with an inflection point of 4.53 using a two-stage linear regression model. However, according to multiple regression analysis, serum cotinine and CAP did not significantly correlate (p = 0.512). In conclusion, this study demonstrated that smoking cessation and keep away from secondhand smoking may beneficial for liver health in American teenagers.

Mechanisms for the Enhancement of Caproic Acid and H2 Production in Ruminococcaceae Bacterium CPB6 by Fe(II) and Mg(II): Growth and Gene Transcription Analyses.

The production of caproic acid (CA) and hydrogen gas (H2) from organic wastewater is economically attractive. The Ruminococcaceae bacterium CPB6 has demonstrated potential for CA production from lactate-containing wastewater. However, our understanding of the effects of Fe2+ and Mg2+ on the growth and metabolism of strain CPB6 remains limited. Therefore, this study aims to investigate the impact of Fe2+ and Mg2+ on CA and H2 production, as well as on the expression of key genes involved in CA and H2 biosynthesis pathway. The results indicate that Fe2+ positively affects cell proliferation and H2 production while minimally impacting CA production. The highest levels of H2 production were achieved with the addition of 200 mg/L Fe2+. Conversely, Mg2+ significantly enhances CA and H2 production, with the optimal yield observed in a medium enriched with 300 mg/L Mg2+. Reverse transcription quantitative PCR (RT-qPCR) analysis reveals that Fe2+ promotes the expression of the hydrogenase gene, whereas Mg2+ has a negligible effect on hydrogenase expression. Notably, Fe2+ and Mg2+ inhibit the expression of key genes involved in CA synthesis. These findings suggest that Fe2+ enhances H2 production by boosting cell biomass and the expression of the hydrogenase gene, whereas Mg2+ improves CA and H2 production primarily by increasing cell biomass rather than influencing the expression of functional genes involved in CA biosynthesis.

A selective Fibroblast Growth Factor Receptor 1/2 PROTAC degrader with antitumor activity.

The aberrant activation of fibroblast growth factor receptor (FGFR) acts as a potent driver of multiple types of human cancers. Despite the development of several conventional small-molecular FGFR inhibitors, their clinical efficacy is largely compromised due to low selectivity and side effects. Here, we report the selective FGFR1/2-targeting proteolysis targeting chimeric (PROTAC), BR-cpd7 that displays significant isoform specificity to FGFR1/2 with DC50 values around 10 nM, while sparing FGFR3. The following mechanistic investigation reveals the reduced FGFR signaling, through which BR-cpd7 induces cell cycle arrest and consequently blocks the proliferation of multiple FGFR1/2-dependent tumor cells. Importantly, BR-cpd7 has almost no anti-proliferative activity against cancer cells without FGFR aberrations, furtherly supporting its selectivity. In vivo, BR-cpd7 exhibits robust antitumor effects in FGFR1-dependent lung cancer at well-tolerated dose schedules, accompanied by complete FGFR1 depletion. Overall, we identify BR-cpd7 as a promising candidate for developing a selective FGFR1/2-targeted agent, thereby offering a new therapeutic strategy for human cancers in which FGFR1/2 plays a critical role.

Morphological Innovation Drives Sperm Release in Bryophytes.

Plant movements for survival are nontrivial. Antheridia in the moss Physcomitrium patens (P. patens) use motion to eject sperm in the presence of water. However, the biological and mechanical mechanisms that actuate the process are unknown. Here, the burst of the antheridium of P. patens, triggered by water, results from elastic instability and is determined by an asymmetric change in cell geometry. The tension generated in jacket cell walls of antheridium arises from turgor pressure, and is further promoted when the inner walls of apex burst in hydration, causing water and cellular contents of apex quickly influx into sperm chamber. The outer walls of the jacket cells are strengthened by NAC transcription factor VNS4 and serve as key morphomechanical innovations to store hydrostatic energy in a confined space in P. patens. However, the antheridium in liverwort Marchantia polymorpha (M. polymorpha) adopts a different strategy for sperm release; like jacket cell outer walls of P. patens, the cells surrounding the antheridium of M. polymorpha appear to play a similar role in the storage of energy. Collectively, the work shows that plants have evolved different ingenious devices for sperm discharge and that morphological innovations can differ.

Endoplasmic reticulum stress and therapeutic strategies in metabolic, neurodegenerative diseases and cancer.

The accumulation of unfolded or misfolded proteins within the endoplasmic reticulum (ER), due to genetic determinants and extrinsic environmental factors, leads to endoplasmic reticulum stress (ER stress). As ER stress ensues, the unfolded protein response (UPR), comprising three signaling pathways-inositol-requiring enzyme 1, protein kinase R-like endoplasmic reticulum kinase, and activating transcription factor 6 promptly activates to enhance the ER's protein-folding capacity and restore ER homeostasis. However, prolonged ER stress levels propels the UPR towards cellular demise and the subsequent inflammatory cascade, contributing to the development of human diseases, including cancer, neurodegenerative disorders, and diabetes. Notably, increased expression of all three UPR signaling pathways has been observed in these pathologies, and reduction in signaling molecule expression correlates with decreased proliferation of disease-associated target cells. Consequently, therapeutic strategies targeting ER stress-related interventions have attracted significant research interest. In this review, we elucidate the critical role of ER stress in cancer, metabolic, and neurodegenerative diseases, offering novel therapeutic approaches for these conditions.

Mechanochemical Synthesis of Cuprous Complexes for X-ray Scintillation and Imaging.

Cuprous complex scintillators show promise for X-ray detection with abundant raw materials, diverse luminescent mechanisms, and adjustable structures. However, their synthesis typically requires a significant amount of organic solvents, which conflict with green chemistry principles. Herein, we present the synthesis of two high-performance cuprous complex scintillators using a simple mechanochemical method for the first time, namely [CuI(PPh3)2R] (R = 4-phenylpyridine hydroiodide (PH, Cu-1) and 4-(4-bromophenyl)pyridine hydroiodide (PH-Br, Cu-2). Both materials demonstrated remarkable scintillation performances, exhibiting radioluminescence (RL) intensities 1.52 times (Cu-1) and 2.52 times (Cu-2) greater than those of Bi4Ge3O12 (BGO), respectively. Compared to Cu-1, the enhanced RL performance of Cu-2 can be ascribed to its elevated quantum yield of 51.54%, significantly surpassing that of Cu-1 at 37.75%. This excellent luminescent performance is derived from the introduction of PH-Br, providing a more diverse array of intermolecular interactions that effectively constrain molecular vibration and rotation, further suppressing the nonradiative transition process. Furthermore, Cu-2 powder can be prepared into scintillator film with excellent X-ray imaging capabilities. This work establishes a pathway for the rapid, eco-friendly, and cost-effective synthesis of high-performance cuprous complex scintillators.

A novel loss function to reproduce texture features for deep learning-based MRI-to-CT synthesis.

BACKGROUND: Studies on computed tomography (CT) synthesis based on magnetic resonance imaging (MRI) have mainly focused on pixel-wise consistency, but the texture features of regions of interest (ROIs) have not received appropriate attention. PURPOSE: This study aimed to propose a novel loss function to reproduce texture features of ROIs and pixel-wise consistency for deep learning-based MRI-to-CT synthesis. The method was expected to assist the multi-modality studies for radiomics. METHODS: The study retrospectively enrolled 127 patients with nasopharyngeal carcinoma. CT and MRI images were collected for each patient, and then rigidly registered as pre-procession. We proposed a gray-level co-occurrence matrix (GLCM)-based loss function to improve the reproducibility of texture features. This novel loss function could be embedded into the present deep learning-based framework for image synthesis. In this study, a typical image synthesis model was selected as the baseline, which contained a Unet trained mean square error (MSE) loss function. We embedded the proposed loss function and designed experiments to supervise different ROIs to prove its effectiveness. The concordance correlation coefficient (CCC) of the GLCM feature was employed to evaluate the reproducibility of GLCM features, which are typical texture features. Besides, we used a publicly available dataset of brain tumors to verify our loss function. RESULTS: Compared with the baseline, the proposed method improved the pixel-wise image quality metrics (MAE: 107.5 to 106.8 HU; SSIM: 0.9728 to 0.9730). CCC values of the GLCM features in GTVnx were significantly improved from 0.78 ± 0.12 to 0.82 ± 0.11 (p < 0.05 for paired t-test). Generally, > 90% (22/24) of the GLCM-based features were improved compared with the baseline, where the Informational Measure of Correlation feature was improved the most (CCC: 0.74 to 0.83). For the public dataset, the loss function also shows its effectiveness. With our proposed loss function added, the ability to reproduce texture features was improved in the ROIs. CONCLUSIONS: The proposed method reproduced texture features for MRI-to-CT synthesis, which would benefit radiomics studies based on image multi-modality synthesis.

Halogen-bonding boosting the high performance X-ray imaging of organic scintillators.

Organic scintillators with efficient X-ray excited luminescence are essential for medical diagnostics and security screening. However, achieving excellent organic scintillation materials is challenging due to low X-ray absorption coefficients and inferior radioluminescence (RL) intensity. Herein, supramolecular interactions are incorporated, particularly halogen bonding, into organic scintillators to enhance their radioluminescence properties. By introducing heavy atoms (X = Cl, Br, I) into 9,10-bis(4-pyridyl)anthracene (BPA), the formation of halogen bonding (BPA-X) enhances their X-ray absorption coefficient and restricts the molecular vibration and rotation, which boosts their RL intensity. The RL intensity of BPA-Cl and BPA-Br fluorochromes increased by over 2 and 6.3 times compared to BPA, respectively. Especially, BPA-Br exhibits an ultrafast decay time of 8.25 ns and low detection limits of 25.95 ± 2.49 nGy s-1. The flexible film constructed with BPA-Br exhibited excellent X-ray imaging capabilities. Furthermore, this approach is also applicable to organic phosphors. The formation of halogen bonding in bromophenyl-methylpyridinium iodide (PYI) led to a fourfold increase in RL intensity compared to bromophenyl-methyl-pyridinium (PY). It suggests that halogen bonding serves as a promising and effective molecular design strategy for the development of high-performance organic scintillator materials, presenting new opportunities for their applications in radiology and security screening.

Comprehensive evaluation of similarity between synthetic and real CT images for nasopharyngeal carcinoma.

BACKGROUND: Although magnetic resonance imaging (MRI)-to-computed tomography (CT) synthesis studies based on deep learning have significantly progressed, the similarity between synthetic CT (sCT) and real CT (rCT) has only been evaluated in image quality metrics (IQMs). To evaluate the similarity between synthetic CT (sCT) and real CT (rCT) comprehensively, we comprehensively evaluated IQMs and radiomic features for the first time. METHODS: This study enrolled 127 patients with nasopharyngeal carcinoma who underwent CT and MRI scans. Supervised-learning (Unet) and unsupervised-learning (CycleGAN) methods were applied to build MRI-to-CT synthesis models. The regions of interest (ROIs) included nasopharynx gross tumor volume (GTVnx), brainstem, parotid glands, and temporal lobes. The peak signal-to-noise ratio (PSNR), mean absolute error (MAE), root mean square error (RMSE), and structural similarity (SSIM) were used to evaluate image quality. Additionally, 837 radiomic features were extracted for each ROI, and the correlation was evaluated using the concordance correlation coefficient (CCC). RESULTS: The MAE, RMSE, SSIM, and PSNR of the body were 91.99, 187.12, 0.97, and 51.15 for Unet and 108.30, 211.63, 0.96, and 49.84 for CycleGAN. For the metrics, Unet was superior to CycleGAN (P < 0.05). For the radiomic features, the percentage of four levels (i.e., excellent, good, moderate, and poor, respectively) were as follows: GTVnx, 8.5%, 14.6%, 26.5%, and 50.4% for Unet and 12.3%, 25%, 38.4%, and 24.4% for CycleGAN; other ROIs, 5.44% ± 3.27%, 5.56% ± 2.92%, 21.38% ± 6.91%, and 67.58% ± 8.96% for Unet and 5.16% ± 1.69%, 3.5% ± 1.52%, 12.68% ± 7.51%, and 78.62% ± 8.57% for CycleGAN. CONCLUSIONS: Unet-sCT was superior to CycleGAN-sCT for the IQMs. However, neither exhibited absolute superiority in radiomic features, and both were far less similar to rCT. Therefore, further work is required to improve the radiomic similarity for MRI-to-CT synthesis. TRIAL REGISTRATION: This study was a retrospective study, so it was free from registration.

Stable Operation Induced by Plastic Crystal Electrolyte Used in Ni-Rich NMC811 Cathodes for Li-Ion Batteries.

The LiNi0.8Mn0.1Co0.1O2 (NMC811) cathode material has been of significant consideration owing to its high energy density for Li-ion batteries. However, the poor cycling stability in a carbonate electrolyte limits its further development. In this work, we report the excellent electrochemical performance of the NMC811 cathode using a rational electrolyte based on organic ionic plastic crystal N-ethyl-N-methyl pyrrolidinium bis(fluorosulfonyl)imide C2mpyr[FSI], with the addition of (1:1 mol) LiFSI salt. This plastic crystal electrolyte (PC) is a thick viscous liquid with an ionic conductivity of 2.3 × 10-3 S cm-1 and a high Li+ transference number of 0.4 at ambient temperature. The NMC811@PC cathode delivers a discharge capacity of 188 mA h g-1 at a rate of 0.2 C with a capacity retention of 94.5% after 200 cycles, much higher than that of using a carbonate electrolyte (54.3%). Moreover, the NMC811@PC cathode also exhibits a superior high-rate capability with a discharge capacity of 111.0 mA h g-1 at the 10 C rate. The significantly improved cycle performance of the NMC811@PC cathode can be attributed to the high Li+ conductivity of the PC electrolyte, the stable Li+ conductive CEI film, and the maintaining of particle integrity during long-term cycling. The admirable electrochemical performance of the NMC811|C2mpyr[FSI]:[LiFSI] system exhibits a promising application of the plastic crystal electrolyte for high voltage layered oxide cathode materials in advanced lithium-ion batteries.

Comparative Analysis of Volatile Flavor Compounds in Strongly Flavored Baijiu under Two Different Pit Cap Sealing Processes.

The solid-state fermentation process of strongly flavored Baijiu is complicated by the co-fermentation of many different microorganisms in the fermentation pools. The traditional fermentation pools of strong flavor Baijiu are sealed with mud, and this sealed-pit mud is not easy to maintain; therefore, the pit cap is prone to cracks and to caving in. The destruction of the sealed-pit mud may lead to instability in the composition and an abundance of microorganisms in the fermentation process that results in fluctuations of product quality. Thus, the production method of replacing the mud cap with a new steel cap is gradually attracting the attention of scientific and technical workers in the industry. However, so far, there have been relatively few reports on the use of steel lids for sealing pits for fermentation and brewing. In this study, the volatile flavor components of 270 Baijiu samples from mud-sealing and steel-sealing pits of a Chinese Baijiu distillery were studied qualitatively and quantitatively using Gas Chromatography-Mass Spectrometry (Abbreviated as GC-MS). Our statistical methods included Hierarchical Cluster Analysis (Abbreviated as HCA), Principal Component Analysis (Abbreviated as PCA), and Discriminant Analysis (Abbreviated as DA). A statistical analysis was carried out on the yield of strongly flavored Baijiu, and we made a comprehensive evaluation of the Baijiu produced under the two pit-sealing modes with regard to flavor and economic efficiency. The yield of strong flavored Baijiu was 6.7% higher with steel-sealing pits compared with mud-sealing pits. Cluster analysis categorized the strongly flavored Baijiu samples into two categories initially: (1) samples produced using mud-sealing pits and (2) samples using steel-sealing pits. Our analysis also indicated that the 28 compounds used for quantification were selected correctly. Surprising to the experimental staff, the overall score for the steel-sealing pits was greater than that of the mud-sealing pits based on PCA. Using DA, the prediction results were 100% accurate. In summary, through a comparative analysis of the flavor and yield, which are the two main factors that affect the quality of Baijiu in a distillery, and systematic combination at both experimental and theoretical levels, the differences between the Baijiu production by steel-sealing and the traditional mud-sealing were clear. Regardless of the impact of age, the detectable flavor components of Baijiu from the mud-steeling pits were very consistent with those of the steel-sealing pits in terms of richness or concentration. However, steel-sealing pits were significantly superior to mud-sealing pits with respect to output, consistency in quality, and cost (human and economic) savings.

Ultrafast Charge-Discharge Capable and Long-Life Na3.9 Mn0.95 Zr0.05 V(PO4 )3 /C Cathode Material for Advanced Sodium-Ion Batteries.

Na4 MnV(PO4 )3 /C (NMVP) has been considered an attractive cathode for sodium-ion batteries with higher working voltage and lower cost than Na3 V2 (PO4 )3 /C. However, the poor intrinsic electronic conductivity and Jahn-Teller distortion caused by Mn3+ inhibit its practical application. In this work, the remarkable effects of Zr-substitution on prompting electronic and Na-ion conductivity and also structural stabilization are reported. The optimized Na3.9 Mn0.95 Zr0.05 V(PO4 )3 /C sample shows ultrafast charge-discharge capability with discharge capacities of 108.8, 103.1, 99.1, and 88.0 mAh g-1 at 0.2, 1, 20, and 50 C, respectively, which is the best result for cation substituted NMVP samples reported so far. This sample also shows excellent cycling stability with a capacity retention of 81.2% at 1 C after 500 cycles. XRD analyses confirm the introduction of Zr into the lattice structure which expands the lattice volume and facilitates the Na+ diffusion. First-principle calculation indicates that Zr modification reduces the band gap energy and leads to increased electronic conductivity. In situ XRD analyses confirm the same structure evolution mechanism of the Zr-modified sample as pristine NMVP, however the strong ZrO bond obviously stabilizes the structure framework that ensures long-term cycling stability.

P2-Type Moisture-Stable and High-Voltage-Tolerable Cathodes for High-Energy and Long-Life Sodium-Ion Batteries.

P2-Na0.67Ni0.33Mn0.67O2 represents a promising cathode for Na-ion batteries, but it suffers from severe structural degradation upon storing in a humid atmosphere and cycling at a high cutoff voltage. Here we propose an in situ construction to achieve simultaneous material synthesis and Mg/Sn cosubstitution of Na0.67Ni0.33Mn0.67O2 via one-pot solid-state sintering. The materials exhibit superior structural reversibility and moisture insensitivity. In-operando XRD reveals an essential correlation between cycling stability and phase reversibility, whereas Mg substitution suppressed the P2-O2 phase transition by forming a new Z phase, and Mg/Sn cosubstitution enhanced the P2-Z transition reversibility benefiting from strong Sn-O bonds. DFT calculations disclosed high chemical tolerance to moisture, as the adsorption energy to H2O was lower than that of the pure Na0.67Ni0.33Mn0.67O2. A representative Na0.67Ni0.23Mg0.1Mn0.65Sn0.02O2 cathode exhibits high reversible capacities of 123 mAh g-1 (10 mA g-1), 110 mAh g-1 (200 mA g-1), and 100 mAh g-1 (500 mA g-1) and a high capacity retention of 80% (500 mA g-1, 500 cycles).

In Situ Constructing Ultrathin, Robust-Flexible Polymeric Electrolytes with Rapid Interfacial Ion Transport in Lithium Metal Batteries.

Safety of lithium metal batteries (LMBs) has been improved by using the solid-state polymer electrolytes, but the performance of LMBs is still troubled by the poor interface of solid electrolytes/electrodes, leading to insufficient interfacial Li+ transport. Here, a novel ultrathin, robust-flexible polymeric electrolyte is achieved by in situ polymerization of 1,3-dioxolane in soft nanofibrous skeleton at room temperature without any extra initiator or plasticizer, leading to the electrolyte with rapid interfacial ion transport. This facilitated Li+ transportation is demonstrated by molecular dynamics simulation. Consequently, the as-prepared electrolyte exhibits excellent cycling performance. The results indicate that the electrolyte works well in the LiFePO4 //Li cell at elevated temperature up to 90 °C, and further matches with the high-voltage LiNi0.8 Mn0.1 Co0.1 O2 cathode. This study provides an effective approach to constructing a practical polymeric electrolyte for fabrication of safe, high performance LMBs.

A more effective CT synthesizer using transformers for cone-beam CT-guided adaptive radiotherapy.

Purpose: The challenge of cone-beam computed tomography (CBCT) is its low image quality, which limits its application for adaptive radiotherapy (ART). Despite recent substantial improvement in CBCT imaging using the deep learning method, the image quality still needs to be improved for effective ART application. Spurred by the advantages of transformers, which employs multi-head attention mechanisms to capture long-range contextual relations between image pixels, we proposed a novel transformer-based network (called TransCBCT) to generate synthetic CT (sCT) from CBCT. This study aimed to further improve the accuracy and efficiency of ART. Materials and methods: In this study, 91 patients diagnosed with prostate cancer were enrolled. We constructed a transformer-based hierarchical encoder-decoder structure with skip connection, called TransCBCT. The network also employed several convolutional layers to capture local context. The proposed TransCBCT was trained and validated on 6,144 paired CBCT/deformed CT images from 76 patients and tested on 1,026 paired images from 15 patients. The performance of the proposed TransCBCT was compared with a widely recognized style transferring deep learning method, the cycle-consistent adversarial network (CycleGAN). We evaluated the image quality and clinical value (application in auto-segmentation and dose calculation) for ART need. Results: TransCBCT had superior performance in generating sCT from CBCT. The mean absolute error of TransCBCT was 28.8 ± 16.7 HU, compared to 66.5 ± 13.2 for raw CBCT, and 34.3 ± 17.3 for CycleGAN. It can preserve the structure of raw CBCT and reduce artifacts. When applied in auto-segmentation, the Dice similarity coefficients of bladder and rectum between auto-segmentation and oncologist manual contours were 0.92 and 0.84 for TransCBCT, respectively, compared to 0.90 and 0.83 for CycleGAN. When applied in dose calculation, the gamma passing rate (1%/1 mm criterion) was 97.5% ± 1.1% for TransCBCT, compared to 96.9% ± 1.8% for CycleGAN. Conclusions: The proposed TransCBCT can effectively generate sCT for CBCT. It has the potential to improve radiotherapy accuracy.

Porous Polymer Cubosomes with Ordered Single Primitive Bicontinuous Architecture and Their Sodium-Iodine Batteries.

Bicontinuous porous materials, which possess 3D interconnected pore channels facilitating a smooth mass transport, have attracted much interest in the fields of energy and catalysis. However, their synthesis remains very challenging. We report a general approach, using polymer cubosomes as the template, for the controllable synthesis of bicontinuous porous polymers with an ordered single primitive (SP) cubic structure, including polypyrrole (SP-PPy), poly-m-phenylenediamine (SP-PmPD), and polydopamine (SP-PDA). Specifically, the resultant SP-PPy had a unit cell parameter of 99 nm, pore diameter of 45 nm, and specific surface area of approximately 60 m2·g-1. As a proof of concept, the I2-adsorbed SP-PPy was employed as the cathode materials of newly emerged Na-I2 batteries, which delivered a record-high specific capacity (235 mA·h·g-1 at 0.5 C), excellent rate capability, and cycling stability (with a low capacity decay of 0.12% per cycle within 400 cycles at 1 C). The advantageous contributions of the bicontinuous structure and I3- adsorption mechanism of SP-PPy were revealed by a combination of ion diffusion experiments and theoretical calculations. This study opens a new avenue for the synthesis of porous polymers with new topologies, broadens the spectrum of bicontinuous-structured materials, and also develops a novel potential application for porous polymers.

Caproic Acid-Producing Bacteria in Chinese Baijiu Brewing.

Caproic acid can be used as spices, preservatives, animal feed additives, and biofuels. At the same time, caproic acid plays an important role in Chinese Baijiu. It is the precursor substance for the synthesis of ethyl caproate, which directly affects the quality of Chinese Baijiu. Caproic acid-producing bacteria are the main microorganisms that synthesize caproic acid in Chinese Baijiu, and the most common strain is Clostridium kluyveri. Caproic acid-producing bacteria synthesize n-caproic acid through reverse ß-oxidation to extend the carboxylic acid chain. This method mainly uses ethanol and lactic acid as substrates. Ethanol and lactic acid are converted into acetyl-CoA, and acetyl-CoA undergoes a series of condensation, dehydrogenation, dehydration, and reduction to extend the carboxylic acid chain. This review addresses the important issues of caproic acid-producing bacteria in the brewing process of Baijiu: the common caproic acid-producing bacteria that have been reported metabolic pathways, factors affecting acid production, biological competition pathways, and the effect of mixed bacteria fermentation on acid production. It is hoped that this will provide new ideas for the study of caproic acid-producing bacteria in Chinese Baijiu.

Deep learning improves image quality and radiomics reproducibility for high-speed four-dimensional computed tomography reconstruction.

BACKGROUND AND PURPOSE: Hybrid iterative reconstruction (HIR) is the most commonly used algorithm for four-dimensional computed tomography (4DCT) reconstruction due to its high speed. However, the image quality is worse than that of model-based iterative reconstruction (MIR). Different reconstruction methods affect the stability of radiomics features. Herein, we developed a deep learning method to improve the quality and radiomics reproducibility of the high-speed reconstruction. MATERIALS AND METHODS: The 4DCT images of 70 patients were reconstructed using both the HIR and MIR algorithms. A cycle-consistent adversarial network was adopted to learn the mapping from HIR to MIR, and then generate synthetic MIR (sMIR) images from HIR. The performance was evaluated using the testing set (10 patients). RESULTS: The total reconstruction times for the HIR, MIR, and proposed sMIR images were approximately 2.5, 15, and 3.1 mins, respectively. The quality of sMIR images was close to that of MIR and was superior to that of HIR images, with noise reduced by 45-77% and contrast-to-noise ratio improved by 91-296%. The concordance correlation coefficients (CCC) of radiomic features improved from 0.89 ± 0.15 for HIR to 0.97 ± 0.07 for the proposed sMIR. The percentage of reproducible features (CCC ≥ 0.85) increased from 76.08% for HIR to 95.86% for sMIR, with an improvement of 19.78%. CONCLUSION: Compared to existing HIR algorithm, the proposed method improves the image quality and radiomics reproducibility of 4DCT images under high-speed reconstruction. It is computationally efficient and has potential to be integrated into any CT system.

Inhibitory Effect of Bovine Adipose-Derived Mesenchymal Stem Cells on Lipopolysaccharide Induced Inflammation of Endometrial Epithelial Cells in Dairy Cows.

Endometritis is a disease that affects reproductive health in dairy cows and causes serious economic damage to the dairy industry world-wide. Although in recent years, the application of mesenchymal stem cell (MSC) therapy for the treatment of inflammatory diseases has attracted much attention, there are few reports of the use of MSCs in dairy cows. In the present study, our objective was to explore the inhibitory effects of bovine adipose-derived mesenchymal stem cells (bAD-MSCs) on lipopolysaccharide (LPS) induced inflammation in bovine endometrial epithelial cells (bEECs) along with the potential underlying molecular mechanisms. We characterized isolated bAD-MSCs using cell surface marker staining and adipogenic/osteogenic differentiation, and analyzed them using immunofluorescence, flow cytometry (surface marker staining), and adipogenic and osteogenic differentiation. Furthermore, to understand the anti-inflammatory effects of bAD-MSCs on LPS induced bEEC inflammation, we used a bAD-MSC/bEEC co-culture system. The results showed that bAD-MSC treatments could significantly decrease LPS induced bEEC apoptosis and pro-inflammatory cytokine expression levels, such as interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). Furthermore, our results showed that bAD-MSC treatments could also significantly downregulate LPS induced p38, IkB-a, and JAK1 phosphorylation and Bax protein expression levels, which are closely related to inflammatory progress and cellular apoptosis in bEECs. Our findings demonstrate that bAD-MSCs play an inhibitory role in LPS induced bEEC inflammation and provide new insights for the clinical therapy of endometritis in dairy cows.