Excessive nucleic acid R-loops induce mitochondria-dependent epithelial cell necroptosis and drive spontaneous intestinal inflammation.

Oxidative stress, which can be activated by a variety of environmental risk factors, has been implicated as an important pathogenic factor for inflammatory bowel disease (IBD). However, how oxidative stress drives IBD onset remains elusive. Here, we found that oxidative stress was strongly activated in inflamed tissues from both ulcerative colitis patients and Crohn's disease patients, and it caused nuclear-to-cytosolic TDP-43 transport and a reduction in the TDP-43 protein level. To investigate the function of TDP-43 in IBD, we inducibly deleted exons 2 to 3 of Tardbp (encoding Tdp-43) in mouse intestinal epithelium, which disrupted its nuclear localization and RNA-processing function. The deletion gave rise to spontaneous intestinal inflammation by inducing epithelial cell necroptosis. Suppression of the necroptotic pathway with deletion of Mlkl or the RIP1 inhibitor Nec-1 rescued colitis phenotypes. Mechanistically, disruption of nuclear TDP-43 caused excessive R-loop accumulation, which triggered DNA damage and genome instability and thereby induced PARP1 hyperactivation, leading to subsequent NAD+ depletion and ATP loss, consequently activating mitochondrion-dependent necroptosis in intestinal epithelial cells. Importantly, restoration of cellular NAD+ levels with NAD+ or NMN supplementation, as well as suppression of ALKBH7, an α-ketoglutarate dioxygenase in mitochondria, rescued TDP-43 deficiency-induced cell death and intestinal inflammation. Furthermore, TDP-43 protein levels were significantly inversely correlated with γ-H2A.X and p-MLKL levels in clinical IBD samples, suggesting the clinical relevance of TDP-43 deficiency-induced mitochondrion-dependent necroptosis. Taken together, these findings identify a unique pathogenic mechanism that links oxidative stress to intestinal inflammation and provide a potent and valid strategy for IBD intervention.

Blood- and Urine-Based Liquid Biopsy for Early-Stage Cancer Investigation: Taken Clear Renal Cell Carcinoma as a Model.

Liquid biopsy is a noninvasive technique that can provide valuable information for disease characterization by using biofluids as a source of biomarkers. Proteins found in biofluids can offer a wealth of information for understanding pathological processes. In this study, we used early-stage clear cell renal cell carcinoma (ccRCC) as a model to explore the proteomic relationships among tissue, plasma, and urine. We analyzed samples of tumor tissue, plasma, and urine from a cohort of 27 ccRCC patients with T1-2 stage and 27 matched healthy controls, using liquid chromatography-mass spectrometry (LC-MS) for proteomic analysis. We integrated the differential proteins found in the three types of samples to explore ccRCC-associated molecular changes. Our results showed that both plasma and urine proteomes could reflect functional changes in tumor tissue. In plasma, cytoskeletal proteins and metabolic enzymes were differentially expressed, while in urine, adhesion molecules and defense proteins showed differential levels. The differential proteins found in plasma and urine both reflect the binding and catalytic activity of tumor tissue. Additionally, proteins only changed in biofluids could reflect body immune response changes, with plasma proteins involved in actin cytoskeleton and oxidative stress, and urine proteins involved in granulocyte adhesion and leukocyte extravasation signaling. Plasma and urine proteins could effectively distinguish RCC from control, with good performances (plasma/urine: 92.6%/92.6% specificity, 96.3%/92.6% sensitivity, and an area under the curve of 0.981/0.97). In conclusion, biofluids could not only reflect functional changes in tumor tissue but also reflect changes in the body's immune response. These findings will benefit the understanding of body biomarkers in tumors and the discovery of potential disease biomarkers.

Crystal Plane Engineering to Boost Water Cluster Evaporation for Enhanced Solar Steam Generation.

Polymer based low evaporation enthalpy materials have become a universal selection for improving the efficiency of solar steam generation. Although water cluster and intermediate water mechanisms have been proposed to explain the low evaporation enthalpy, the production process and microstructure of activated water are still unclear. Here, crystal plane engineering is used to investigate the intermediate water state and the water cluster activation mechanism. The unique open-closed coordination structure on the optimized crystal surface promotes the generation of firm water clusters by optimizing the intermediate water state. Under the similar solar energy absorption of all materials, crystal plane engineering increased the solar steam generation rate of the evaporator by 31.2% and increased the energy efficiency to 94.8%. Exploring the micro-evaporation process and activated water structure is expected to stimulate the development of the next generation low evaporation enthalpy materials.

Self-Assembly of Ultrathin, Ultrastrong Layered Membranes by Protic Solvent Penetration.

Flexible membranes with ultrathin thickness and excellent mechanical properties have shown great potential for broad uses in solid polymer electrolytes (SPEs), on-skin electronics, etc. However, an ultrathin membrane (<5 µm) is rarely reported in the above applications due to the inherent trade-off between thickness and antifailure ability. We discover a protic solvent penetration strategy to prepare ultrathin, ultrastrong layered films through a continuous interweaving of aramid nanofibers (ANFs) with the assistance of simultaneous protonation and penetration of a protic solvent. The thickness of a pure ANF film can be controlled below 5 µm, with a tensile strength of 556.6 MPa, allowing us to produce the thinnest SPE (3.4 µm). The resultant SPEs enable Li-S batteries to cycle over a thousand times at a high rate of 1C due to the small ionic impedance conferred by the ultrathin characteristic and regulated ionic transportation. Besides, a high loading of the sulfur cathode (4 mg cm-2) with good sulfur utilization was achieved at a mild temperature (35 °C), which is difficult to realize in previously reported solid-state Li-S batteries. Through a simple laminating process at the wet state, the thicker film (tens of micrometers) obtained exhibits mechanical properties comparable to those of thin films and possesses the capability to withstand high-velocity projectile impacts, indicating that our technique features a high degree of thickness controllability. We believe that it can serve as a valuable tool to assemble nanomaterials into ultrathin, ultrastrong membranes for various applications.

Dielectric Design of High Dielectric Constant Poly(Urea-Urethane) Elastomer for Low-Voltage High-Mobility Intrinsically Stretchable All-Solution-Processed Organic Transistors.

Stretchable organic transistors for skin-like biomedical applications require low-voltage operation to accommodate limited power supply and safe concerns. However, most of the currently reported stretchable organic transistors operate at relatively high voltages. Decreasing their operational voltage while keeping the high mobility still remains a key challenge. Here, the study presents a new dielectric design to achieve high-dielectric constant poly(urea-urethane) (PUU) elastomer, by incorporating a flexible small-molecular diamine crosslinking agent 4-aminophenyl disulfide (APDS) into the main chain of (poly (propylene glycol), tolylene 2,4-diiso-cyanate terminated) (PPG-TDI). Compared with commercial elastomers, the PUU elastomer as dielectric of the stretchable organic transistors shows the outstanding advantages including lower surface roughness (0.33 nm), higher adhesion (45.18 nN), higher dielectric constant (13.5), as well as higher stretchability (896%). The PUU dielectric enables the intrinsically stretchable, all-solution-processed organic transistor to operate at a low operational voltage down to -10 V, while preserving a substantial mobility of 1.39 cm2  V-1  s-1 . Impressively, the transistor also demonstrates excellent electrical stability under repeated switching of 10 000 cycles, and remarkable mechanical robustness when stretched up to 100%. The work opens up a new molecular engineering strategy to successfully realize low-voltage high-mobility stretchable all-solution-processed organic transistors.

Gemini: memory-efficient integration of hundreds of gene networks with high-order pooling.

MOTIVATION: The exponential growth of genomic sequencing data has created ever-expanding repositories of gene networks. Unsupervised network integration methods are critical to learn informative representations for each gene, which are later used as features for downstream applications. However, these network integration methods must be scalable to account for the increasing number of networks and robust to an uneven distribution of network types within hundreds of gene networks. RESULTS: To address these needs, we present Gemini, a novel network integration method that uses memory-efficient high-order pooling to represent and weight each network according to its uniqueness. Gemini then mitigates the uneven network distribution through mixing up existing networks to create many new networks. We find that Gemini leads to more than a 10% improvement in F1 score, 15% improvement in micro-AUPRC, and 63% improvement in macro-AUPRC for human protein function prediction by integrating hundreds of networks from BioGRID, and that Gemini's performance significantly improves when more networks are added to the input network collection, while Mashup and BIONIC embeddings' performance deteriorates. Gemini thereby enables memory-efficient and informative network integration for large gene networks and can be used to massively integrate and analyze networks in other domains. AVAILABILITY AND IMPLEMENTATION: Gemini can be accessed at: https://github.com/MinxZ/Gemini.

Survival benefits of human papillomavirus 16 infection in patients with esophageal squamous cell carcinoma undergoing chemoradiotherapy: A retrospective cohort study.

The role of human papillomavirus 16 (HPV 16) in esophageal squamous cell carcinoma (ESCC) remains uncertain. Therefore, this study aimed to investigate the prevalence of HPV 16 in patients with ESCC and its impact on theirprognosis. HPV 16 was detected using FISH, and TP53 status was evaluated via immunohistochemistry. The factors influencing prognosis were ananalyzed using the Log-rank test and Cox regression analyses. Among 178 patients with ESCC, 105 and 73 patients were categorized into concurrent chemoradiotherapy (CCRT) and postoperative chemoradiotherapy (POCRT) cohorts, respectively. Among 178 patients, 87 (48.87%) tested positive for HPV 16. Log-rank tests revealed that the overall survival (OS) of patients with ESCC who were HPV 16-positive was longer than that of those who were HPV 16-negative (median OS: 57 months vs. 27 months, p < 0.01**). HPV 16 infection and TP53 mutation status were identified as independent events. The OS of patients with mutant TP53 who were HPV 16-positive was longer than that of those who were HPV 16-negative in both CCRT and POCRT cohorts (p = 0.002** for CCRT cohorts and p = 0.0023** for POCRT cohorts). Conversely, HPV 16 infection had no effect on OS in the wild-type TP53 subgroup (p = 0.13 and 0.052 for CCRT and POCRT cohorts, respectively). As a conclusion, the positive rate of HPV 16 in ESCC in this study was 48.87% (87/178). Among the patients with ESCC who had TP53 mutation, those who were HPV 16-positive exhibited a better prognosis than those who were HPV 16-negative.

Therapeutic Effect of Tympanoplasty on Patients with Chronic Otitis Media with Tinnitus and Influencing Factors.

Objective: This research was conducted to investigate the therapeutic effects of tympanoplasty on patients with chronic otitis media with tinnitus and analyze the possible influencing factors for patient prognosis. Methods: This is a pre-post control group study, 86 patients with chronic otitis media were included as the subjects and enrolled into tinnitus group (n = 46) and the non-tinnitus group (n = 40). All patients underwent tympanoplasty under microscope or ear endoscopy. A tinnitus severity and efficacy assessment scale was employed for the evaluation of the severity of tinnitus among the subjects. In addition, tinnitus handicap inventory (THI) was utilized to evaluate disease alleviation. Results: Before treatment, the proportions of the patients with tinnitus at grades I, II, III, IV, and V amounted to 15.22%, 32.61%, 21.74%, 17.39%, and 13.04%, respectively, while they were 30.43%, 45.65%, 13.04%, 8.71%, and 2.17%, respectively 3 months after treatment (P < .05). THI scores for the patients in the tinnitus group before and 3 months after treatment amounted to 17.96 ± 3.66 and 16.21 ± 3.29, respectively (P < .05). After treatment, the air conduction (AC) and bone conduction (BC) thresholds and air-bone gap (ABG) of the two groups apparently declined (P < .05). No statistical significance was detected in the differences in disease classification, disease courses, and whether an electric drill was used among the patients between effective and invalid groups (P > .05). Conclusion: To some extent, tympanoplasty alleviated tinnitus among patients with chronic otitis media and promoted the restoration of hearing. Hence, it is worthy of application in clinical treatment.

Multimodal-Synergistic-Modulation Neuromorphic Imaging Systems for Simulating Dry Eye Imaging.

Inspired by human eyes, the neuromorphic visual system employs a highly efficient imaging and recognition process, which offers tremendous advantages in image acquisition, data pre-processing, and dynamic storage. However, it is still an enormous challenge to simultaneously simulate the structure, function, and environmental adaptive behavior of the human eye based on one device. Here, a multimodal-synergistic-modulation neuromorphic imaging system based on ultraflexible synaptic transistors is successfully presented and firstly simulates the dry eye imaging behavior at the device level. Moreover, important functions of the human visual system in relation to optoelectronic synaptic plasticity, image erasure and enhancement, real-time preprocessing, and dynamic storage are simulated by versatile devices. This work not only simplifies the complexity of traditional neuromorphic visual systems, but also plays a positive role in the publicity of biomedical eye care.

The Antimalaria Drug Artesunate Inhibits Porcine Reproductive and Respiratory Syndrome Virus Replication by Activating AMPK and Nrf2/HO-1 Signaling Pathways.

Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant economic losses to the pork industry worldwide. Currently, vaccine strategies provide limited protection against PRRSV transmission, and no effective drug is commercially available. Therefore, there is an urgent need to develop novel antiviral strategies to prevent PRRSV pandemics. This study showed that artesunate (AS), one of the antimalarial drugs, potently suppressed PRRSV replication in Marc-145 cells and ex vivo primary porcine alveolar macrophages (PAMs) at micromolar concentrations. Furthermore, we demonstrated that this suppression was closely associated with AS-activated AMPK (energy homeostasis) and Nrf2/HO-1 (inflammation) signaling pathways. AS treatment promoted p-AMPK, Nrf2, and HO-1 expression and, thus, inhibited PRRSV replication in Marc-145 and PAM cells in a time- and dose-dependent manner. These effects of AS were reversed when the AMPK or HO-1 gene was silenced by short interfering RNA. In addition, we demonstrated that AMPK works upstream of Nrf2/HO-1, as its activation by AS is AMPK dependent. Adenosine phosphate analysis showed that AS activates AMPK via improving the AMP/ADP-to-ATP ratio rather than direct interaction with AMPK. Altogether, our findings indicate that AS is a promising novel therapeutic for controlling PRRSV and that its anti-PRRSV mechanism, which involves the functional link between energy homeostasis and inflammation suppression pathways, may provide opportunities for developing novel antiviral agents. IMPORTANCE Porcine reproductive and respiratory syndrome virus (PRRSV) infections have continuously threatened the pork industry worldwide. Vaccination strategies provide very limited protection against PRRSV infection, and no effective drug is commercially available. We show that artesunate (AS), one of the antimalarial drugs, is a potent inhibitor against PRRSV replication in Marc-145 cells and ex vivo primary porcine alveolar macrophages (PAMs). Furthermore, we demonstrate that AS inhibits PRRSV replication via activation of AMPK-dependent Nrf2/HO-1 signaling pathways, revealing a novel link between energy homeostasis (AMPK) and inflammation suppression (Nrf2/HO-1) during viral infection. Therefore, we believe that AS may be a promising novel therapeutics for controlling PRRSV, and its anti-PRRSV mechanism may provide a strategy to develop novel antiviral agents.

Probing Hidden Mott Gap and Incommensurate Charge Modulation on the Polar Surfaces of PdCrO_{2}.

Here we report a combined study of low-temperature scanning tunneling microscopy and dynamical mean-field theory on PdCrO_{2}, a delafossite metal with an antiferromagnetic order below ∼37.5 K. First, on the CrO_{2}-terminated polar surface we detect a gaplike feature both below and above the Néel temperature. The dynamical mean-field theory calculations indicate that this gap is opened due to the strong correlations of Cr-3d electrons, suggesting the hidden Mott nature of the gap. Then, we observe two kinds of Pd-terminated polar surfaces. One is a well-ordered Pd surface with the Fermi-surface-nesting-induced incommensurate charge modulation, while the other one is a reconstructed Pd surface with the individual nanoscale nonperiodic domain structures. On the well-ordered Pd surface, the interference between the incommensurate charge modulation and the atomic lattice forms the periodic moiré pattern. Our results provide important microscopic information for fully understanding the correlated electronic properties of this class of materials.

Development and validation of a machine learning-based model for varices screening in compensated cirrhosis (CHESS2001): an international multicenter study.

BACKGROUND AND AIMS: The prevalence of high-risk varices (HRV) is low among compensated cirrhotic patients undergoing EGD. Our study aimed to identify a novel machine learning (ML)-based model, named ML EGD, for ruling out HRV and avoiding unnecessary EGDs in patients with compensated cirrhosis. METHODS: An international cohort from 17 institutions from China, Singapore, and India were enrolled (CHESS2001). The variables with the top 3 importance scores (liver stiffness, platelet count, and total bilirubin) were selected by the Shapley additive explanation and input into a light gradient-boosting machine algorithm to develop ML EGD for identification of HRV. Furthermore, we built a web-based calculator for ML EGD, which is free with open access (http://www.pan-chess.cn/calculator/MLEGD_score). Unnecessary EGDs that were not performed and the rates of missed HRV were used to assess the efficacy and safety for varices screening. RESULTS: Of 2794 enrolled patients, 1283 patients formed a real-world cohort from 1 university hospital in China used to develop and internally validate the performance of ML EGD for varices screening. They were randomly assigned into the training (n = 1154) and validation (n = 129) cohorts with a ratio of 9:1. In the training cohort, ML EGD spared 607 (52.6%) unnecessary EGDs with a missed HRV rate of 3.6%. In the validation cohort, ML EGD spared 75 (58.1%) EGDs with a missed HRV rate of 1.4%. To externally test the performance of ML EGD, 966 patients from 14 university hospitals in China (test cohort 1) and 545 from 2 hospitals in Singapore and India (test cohort 2) comprised the 2 test cohorts. In test cohort 1, ML EGD spared 506 (52.4%) EGDs with a missed HRV rate of 2.8%. In test cohort 2, ML EGD spared 224 (41.1%) EGDs with a missed HRV rate of 3.1%. When compared with the Baveno VI criteria, ML EGD spared more screening EGDs in all cohorts (training cohort, 52.6% vs 29.4%; validation cohort, 58.1% vs 44.2%; test cohort 1, 52.4% vs 26.5%; test cohort 2, 41.1% vs 21.1%, respectively; P < .001). CONCLUSIONS: We identified a novel model based on liver stiffness, platelet count, and total bilirubin, named ML EGD, as a free web-based calculator. ML EGD could efficiently help rule out HRV and avoid unnecessary EGDs in patients with compensated cirrhosis. (Clinical trial registration number: NCT04307264.).

A CT-based deep learning radiomics nomogram outperforms the existing prognostic models for outcome prediction in clear cell renal cell carcinoma: a multicenter study.

OBJECTIVES: To develop and validate a CT-based deep learning radiomics nomogram (DLRN) for outcome prediction in clear cell renal cell carcinoma (ccRCC), and its performance was compared with the Stage, Size, Grade, and Necrosis (SSIGN) score, the University of California, Los Angeles, Integrated Staging System (UISS), the Memorial Sloan-Kettering Cancer Center (MSKCC), and the International Metastatic Renal Cell Database Consortium (IMDC). METHODS: A multicenter of 799 localized (training/ test cohort, 558/241) and 45 metastatic ccRCC patients were studied. A DLRN was developed for predicting recurrence-free survival (RFS) in localized ccRCC patients, and another DLRN was developed for predicting overall survival (OS) in metastatic ccRCC patients. The performance of the two DLRNs was compared with that of the SSIGN, UISS, MSKCC, and IMDC. Model performance was assessed with Kaplan-Meier curves, time-dependent area under the curve (time-AUC), Harrell's concordance index (C-index), and decision curve analysis (DCA). RESULTS: In the test cohort, the DLRN achieved higher time-AUCs (0.921, 0.911, and 0.900 for 1, 3, and 5 years, respectively), C-index (0.883), and net benefit than SSIGN and UISS in predicting RFS for localized ccRCC patients. The DLRN provided higher time-AUCs (0.594, 0.649, and 0.754 for 1, 3, and 5 years, respectively) than MSKCC and IMDC in predicting OS for metastatic ccRCC patients. CONCLUSIONS: The DLRN can accurately predict outcomes and outperformed the existing prognostic models in ccRCC patients. CLINICAL RELEVANCE STATEMENT: This deep learning radiomics nomogram may facilitate individualized treatment, surveillance, and adjuvant trial design for patients with clear cell renal cell carcinoma. KEY POINTS: • SSIGN, UISS, MSKCC, and IMDC may be insufficient for outcome prediction in ccRCC patients. • Radiomics and deep learning allow for the characterization of tumor heterogeneity. • The CT-based deep learning radiomics nomogram outperforms the existing prognostic models in ccRCC outcome prediction.

Prediction model of gleason score upgrading after radical prostatectomy based on a bayesian network.

OBJECTIVE: To explore the clinical value of the Gleason score upgrading (GSU) prediction model after radical prostatectomy (RP) based on a Bayesian network. METHODS: The data of 356 patients who underwent prostate biopsy and RP in our hospital from January 2018 to May 2021 were retrospectively analysed. Fourteen risk factors, including age, body mass index (BMI), total prostate-specific antigen (tPSA), prostate volume, total prostate-specific antigen density (PSAD), the number and proportion of positive biopsy cores, PI-RADS score, clinical stage and postoperative pathological characteristics, were included in the analysis. Data were used to establish a prediction model for Gleason score elevation based on the tree augmented naive (TAN) Bayesian algorithm. Moreover, the Bayesia Lab validation function was used to calculate the importance of polymorphic Birnbaum according to the results of the posterior analysis and to obtain the importance of each risk factor. RESULTS: In the overall cohort, 110 patients (30.89%) had GSU. Based on all of the risk factors that were included in this study, the AUC of the model was 81.06%, and the accuracy was 76.64%. The importance ranking results showed that lymphatic metastasis, the number of positive biopsy cores, ISUP stage and PI-RADS score were the top four influencing factors for GSU after RP. CONCLUSIONS: The prediction model of GSU after RP based on a Bayesian network has high accuracy and can more accurately evaluate the Gleason score of prostate biopsy specimens and guide treatment decisions.

A multimodal imaging-based classification for pediatric diffuse intrinsic pontine gliomas.

OBJECT: Pediatric diffuse intrinsic pontine glioma (DIPG) is a radiologically heterogeneous disease entity, here we aim to establish a multimodal imaging-based radiological classification and evaluate the outcome of different treatment strategies under this classification frame. METHODS: This retrospective study included 103 children diagnosed with DIPGs between January 2015 and August 2018 in Beijing Tiantan Hospital (Beijing, China). Multimodal radiological characteristics, including conventional magnetic resonance imaging (MRI), diffuse tensor imaging/diffuse tensor tractography (DTI/DTT), and positron emission tomography (PET) were reviewed to construct the classification. The outcome of different treatment strategies was compared in each DIPG subgroup using Kaplan-Meier method (log-rank test) to determine the optimal treatment for specific DIPGs. RESULTS: Four radiological DIPG types were identified: Type A ("homocentric", n=13), Type B ("ventral", n=41), Type C ("eccentric", n=37), and Type D ("dorsal", n=12). Their treatment modalities were grouped as observation (43.7%), cytoreductive surgery (CRS) plus radiotherapy (RT) (24.3%), RT alone (11.7%), and CRS alone (20.4%). CRS+RT mainly fell into type C (29.7%), followed by type B1 (21.9%) and type D (50%). Overall, CRS+RT exhibited a potential survival advantage compared to RT alone, which was more pronounced in specific type, but this did not reach statistical significance, due to limited sample size and unbalanced distribution. CONCLUSION: We proposed a multimodality imaging-based radiological classification for pediatric DIPG, which was useful for selecting optimal treatment strategies, especially for identifying candidates who may benefit from CRS plus RT. This classification opened a window into image-guided integrated treatment for pediatric DIPG.

Ultrasound Sonosensitizers for Tumor Sonodynamic Therapy and Imaging: A New Direction with Clinical Translation.

With the rapid development of sonodynamic therapy (SDT), sonosensitizers have evolved from traditional treatments to comprehensive diagnostics and therapies. Sonosensitizers play a crucial role in the integration of ultrasound imaging (USI), X-ray computed tomography (CT), and magnetic resonance imaging (MRI) diagnostics while also playing a therapeutic role. This review was based on recent articles on multifunctional sonosensitizers that were used in SDT for the treatment of cancer and have the potential for clinical USI, CT, and MRI applications. Next, some of the shortcomings of the clinical examination and the results of sonosensitizers in animal imaging were described. Finally, this paper attempted to inform the future development of sonosensitizers in the field of integrative diagnostics and therapeutics and to point out current problems and prospects for their application.

A Photocurable Polysaccharide-Based Hydrogel Delivery of Polydeoxyribonucleotide-Loaded Vectors for Wound Treatment.

The wounds caused by war, accidents, and diseases require timely and effective treatment. Polysaccharides, as natural macromolecules, have good biocompatibility and unique functions, and are excellent substrates for constructing new wound dressings. Short-chain chitosan (SCS) has good water solubility and, importantly, retains a large number of active amino groups. We first introduce double bonds to SCS. This chitosan derivative can be entangled with sodium alginate (SA) through electrostatic interaction. The flowing sol can be applied to a wound with an irregular shape. Under the initiation of a photoinitiator, the internal double bonds are broken and cross-linked to form a gel. The prepared hydrogel wound dressing exhibited good antibacterial properties and can provide a microenvironment conducive to wound repair. A polydeoxyribonucleotide (PDRN) has been proven to have encouraging therapeutic effects for wound healing. PDRN can be condensed by branched polyethylenimine (PEI) to form a nucleic acid delivery system, which can be efficiently uptaken by cells. The cooperation of hydrogel and nucleic-acid-based therapy presented good results in a mouse full-thickness skin wound model.

Protective effect of Limosilactobacillus reuteri-fermented yogurt on mouse intestinal barrier injury induced by enterotoxigenic Escherichia coli.

BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) is a pathogen that causes traveler's diarrhea, for which an effective vaccine is lacking. Previous studies showed that Limosilactobacillus reuteri could inhibit E. coli, effectively increase the expression of its tight junction protein, and reduce the adhesion of ETEC to the intestinal epithelial Caco-2 cell line. In this study, three kinds of yogurt with different starter cultures were first prepared: Lm. reuteri yogurt (fermented by Lm. reuteri alone), traditional yogurt (fermented by Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus at a ratio of 1:1) and mixed yogurt (fermented by Lm. reuteri, S. thermophilus and L. delbrueckii subsp. bulgaricus at a ratio of 1:1:1). The physiological properties, oxidative stress, intestinal barrier function, tight junction protein, pathological conditions and intestinal microbiota composition were investigated. RESULTS: The data showed that Lm. reuteri-fermented yogurt pregavage could effectively alleviate the intestinal barrier impairment caused by ETEC in mice. It alleviated intestinal villus shortening and inflammatory cell infiltration, decreased plasma diamine oxidase concentration and increased claudin-1 and occludin expression in the jejunum of ETEC-infected mice. In addition, Lm. reuteri-fermented yogurt significantly reduced the ETEC load in fecal samples, reversed the increase in Pseudomonadota abundance and decreased Bacteroidota abundance caused by ETEC infection. Furthermore, the composition of the intestinal microbiota could maintain a stable state similar to that in healthy mice. CONCLUSION: These findings indicate that Lm. reuteri-fermented yogurt could alleviate intestinal barrier damage, inhibit ETEC growth and maintain the stability of the intestinal microbiota during ETEC infection. © 2023 Society of Chemical Industry.

Modulating Ligand-Exchange Dynamics on Metal-Organic Polyhedra for Reversible Sorting and Hybridization of Miktoarm Star Polymers.

The precise synthesis of miktoarm star polymers (MSPs) remains one of the great challenges in synthetic chemistry due to the difficulty in locating appropriate structural templates and polymer grafting/growing strategies with high selectivity and efficiency. Herein, ≈2 nm metal-organic polyhedra (MOPs), constructed from the coordination of isophthalic acid (IPA) and Cu2+ , are applied as templates for the precise synthesis of 24-arm MSPs for their unique logarithmic ligand-exchange dynamics. Six different polymers are prepared with IPA as an end group and they further coordinated with Cu2+ to afford the corresponding 24-arm star homo-polymers. MSPs can be obtained by mixing targeted homo-arm star polymers in solutions upon thermal annealing. The compositions of MSPs can be facilely and precisely tuned by the recipe of the star polymer mixtures used. Interestingly, the obtained MSPs can be sorted into homo-arm star polymers through a typical solvent extraction procedure. The hybridization and sorting process can be reversibly conducted through the cycle of thermal annealing and solvent treatment. The complex coordination framework not only opens new avenues for the facile and precise synthesis of MSPs and MOPs with hybrid functionalities, but also provides the capability to design sustainable polymer systems.

The radiomics-based tumor heterogeneity adds incremental value to the existing prognostic models for predicting outcome in localized clear cell renal cell carcinoma: a multicenter study.

PURPOSE: Tumor heterogeneity, which is associated with poor outcomes, has not been exhibited in the University of California, Los Angeles, Integrated Staging System (UISS), and the Stage, Size, Grade and Necrosis (SSIGN) scores. Radiomics allows an in-depth characterization of heterogeneity across the tumor, but its incremental value to the existing prognostic models for clear cell renal cell carcinoma (ccRCC) outcome is unknown. The purpose of this study was to evaluate the association between the radiomics-based tumor heterogeneity and postoperative risk of recurrence in localized ccRCC, and to assess its incremental value to UISS and SSIGN. METHODS: A multicenter 866 ccRCC patients derived from 12 Chinese hospitals were studied. The endpoint was recurrence-free survival (RFS). A CT-based radiomics signature (RS) was developed and assessed in the whole cohort and in the subgroups stratified by UISS and SSIGN. Two combined nomograms, the R-UISS (combining RS and UISS) and R-SSIGN (combining RS and SSIGN), were developed. The incremental value of RS to UISS and SSIGN in RFS prediction was evaluated. R statistical software was used for statistics. RESULTS: Patients with low radiomics scores were 4.44 times more likely to experience recurrence than those with high radiomics scores (P<0.001). Stratified analysis suggested the association is significant among low- and intermediate-risk patients identified by UISS and SSIGN. The R-UISS and R-SSIGN showed better predictive capability than UISS and SSIGN did with higher C-indices (R-UISS vs. UISS, 0.74 vs. 0.64; R-SSIGN vs. SSIGN, 0.78 vs. 0.76) and higher clinical net benefit. CONCLUSIONS: The radiomics-based tumor heterogeneity can predict outcome and add incremental value to the existing prognostic models in localized ccRCC patients. Incorporating radiomics-based tumor heterogeneity in ccRCC prognostic models may provide the opportunity to better surveillance and adjuvant clinical trial design.