Effects of Maternal Smoke Exposure on Endoplasmic Reticulum Stress and Autophagy in the Lungs of Offspring Mice.

BACKGROUND: Cigarette smoke (CS) induces autophagy and endoplasmic reticulum (ER) stress in the lungs. Research suggests that maternal exposure to CS during pregnancy leads to decreased lung function in offspring. However, the effects of maternal CS exposure on lung autophagy and ER stress in offspring during pregnancy remain unclear. METHODS: C57BL/6J female mice were divided into the AA (air treatment during both pre-pregnancy and pregnancy), AS (air treatment during pre-pregnancy and CS treatment during pregnancy), SA (CS treatment during pre-pregnancy and air treatment during pregnancy), and SS (CS treatment during both pre-pregnancy and pregnancy) groups. The male offspring mice were selected to the study and euthanized 49 days after birth for the study. Hematoxylin and eosin (HE) staining was employed to observe pathological alterations, while transmission electron microscopy (TEM) was utilized to examine ultrastructure and autophagic vesicles. Additionally, the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method was applied to identify apoptosis in lung tissues. Immunofluorescence, Real-Time PCR, and Western Blot analyses were conducted to assess the expression of ER stress and autophagy-related markers in lung tissues. RESULTS: The findings revealed that exposure to CS heightened the extent of pathological damage and the abundance of autophagosomes in the lungs of offspring mice. TUNEL results indicated an increased fluorescence intensity in the AS, SA and SS groups, with the most significant in AS and SS groups. Furthermore, CS exposure augmented the fluorescence intensity and expression of ER stress and autophagy-related proteins. The expression of C/EBP-homologous protein (CHOP) exhibited no discernible difference between the SA and SS groups but showed a significant increase in the AS group. Conversely, the expression levels of glucose-regulated protein 78 (GRP78), Caspase-12, Beclin-1, and microtubule-associated protein 1 light chain 3 (LC3) exhibited no significant difference between the AS and SA groups, whereas they were significantly upregulated in the SS group. CONCLUSIONS: Preconceptional and gestational exposure to CS heightened ER stress and autophagy in the lungs of mouse offspring. However, in mothers who smoked, withdrawal from CS during pregnancy led to a reduction in ER stress and autophagy in the lungs of their offspring.

ECAS correlation with metabolic alterations on FDG-PET imaging in ALS.

Background: Cognitive impairment is observed in up to 50% of patients with amyotrophic lateral sclerosis (ALS). The Edinburgh Cognitive and Behavioral ALS Screen (ECAS) is an ALS-specific multi-domain screening tool. Few studies have examined the relationship between ECAS scores and [18F]fluorodeoxyglucose positron emission tomography ([18F]FDG-PET) findings. Objective: To assess the relationship between ECAS scores and glucose metabolism patterns on [18F]FDG -PET images in ALS. Methods: We collected [18F]FDG-PET images from 65 patients with ALS and 39 healthy controls. ECAS scores were collected on all patients and we calculated the correlation to [18F]FDG-PET in order to investigate the potential links between cognition and glucose metabolism. Results: We observed hypometabolism in the frontal cortex, insula, and limbic system, together with hypermetabolism in the cerebellum in patients with ALS compared to controls. A lower ECAS total score was associated with lower glucose metabolism in the right orbitofrontal gyrus and higher glucose metabolism in lateral occipital, medial occipital, and cerebellar regions, among patients with ALS. Similar results, although less widespread, were observed in the analyses of ECAS ALS-specific scores. Conclusions: The metabolic patterns in [18F]FDG -PET show that changes in the glucose metabolism of corresponding areas are related to cognitive dysfunction in ALS, and can be detected using the ECAS.

Effect of maternal cigarette smoke exposure on COPD progression in offspring mice.

OBJECTIVE: To investigate the impact of maternal smoking on chronic obstructive pulmonary disease (COPD) progression in offspring. METHODS: Using female C57BL/6 J mice, a maternal cigarette smoke exposure (CSE) model was established. Mice were exposed to cigarette smoke for 2 hours/day, 7 days/week, with a minimum 4-hour interval between exposures. Experimental groups included control (Con), pregnancy exposure (AS), pre-pregnancy exposure (SA), and pre-pregnancy + pregnancy exposure (SS). Lung function tests (Penh, PAU, TVb, EF50, Tr) were conducted on male offspring at 7 weeks. Histopathology, electron microscopy, and protein level changes were examined. RESULTS: Lung function tests revealed significant impairments in Penh, PAU, TVb, EF50, and Tr in offspring across all exposure scenarios. Specifically, AS experienced significant lung function impairment and mitochondrial dysfunction in offspring, with noticeable pulmonary lesions and increased apoptosis. SA showed similar or even more severe lung function impairment and cellular apoptosis. SS exhibited the most pronounced effects, with the highest levels of lung dysfunction, mitochondrial damage, and apoptosis. Histopathological analysis showed pulmonary lesions in offspring exposed to maternal CSE. Flow cytometry revealed increased apoptosis and reduced mitochondrial membrane potential in offspring lung cells. Electron microscopy confirmed mitochondrial dysfunction. Upregulation of apoptotic proteins and downregulation of anti-apoptotic protein Bcl-2 were found in offspring lung tissue exposed to maternal CSE. CONCLUSION: Maternal smoking induces impaired lung function, pulmonary lesions, and mitochondrial dysfunction in offspring, regardless of exposure timing and duration. Additionally, it alters expression of apoptosis-related proteins in offspring lung tissue, potentially contributing to COPD susceptibility.

Corrosion Behavior of 20G and TP347H in Molten LiCl-NaCl-KCl Salt.

The corrosion behavior of 20G and TP347H materials was investigated in molten LiCl-NaCl-KCl salt. The corrosion rates of these materials in molten chloride salt are high and are strongly affected by the alloying surface oxide formation. The 20G shows uniform surface corrosion with almost no protective oxide formation on the surface. In contrast, the austenitic steel TP347H exhibits better corrosion resistance in molten chloride salts due to its high Cr content. Owing to the highly corrosive nature of molten chloride salts, the Cl- in molten salt could react with oxides and alloy, inducing intergranular corrosion of austenitic steel in molten chloride salt environments.

Uncertainty estimation- and attention-based semi-supervised models for automatically delineate clinical target volume in CBCT images of breast cancer.

OBJECTIVES: Accurate segmentation of the clinical target volume (CTV) of CBCT images can observe the changes of CTV during patients' radiotherapy, and lay a foundation for the subsequent implementation of adaptive radiotherapy (ART). However, segmentation is challenging due to the poor quality of CBCT images and difficulty in obtaining target volumes. An uncertainty estimation- and attention-based semi-supervised model called residual convolutional block attention-uncertainty aware mean teacher (RCBA-UAMT) was proposed to delineate the CTV in cone-beam computed tomography (CBCT) images of breast cancer automatically. METHODS: A total of 60 patients who undergone radiotherapy after breast-conserving surgery were enrolled in this study, which involved 60 planning CTs and 380 CBCTs. RCBA-UAMT was proposed by integrating residual and attention modules in the backbone network 3D UNet. The attention module can adjust channel and spatial weights of the extracted image features. The proposed design can train the model and segment CBCT images with a small amount of labeled data (5%, 10%, and 20%) and a large amount of unlabeled data. Four types of evaluation metrics, namely, dice similarity coefficient (DSC), Jaccard, average surface distance (ASD), and 95% Hausdorff distance (95HD), are used to assess the model segmentation performance quantitatively. RESULTS: The proposed method achieved average DSC, Jaccard, 95HD, and ASD of 82%, 70%, 8.93, and 1.49 mm for CTV delineation on CBCT images of breast cancer, respectively. Compared with the three classical methods of mean teacher, uncertainty-aware mean-teacher and uncertainty rectified pyramid consistency, DSC and Jaccard increased by 7.89-9.33% and 14.75-16.67%, respectively, while 95HD and ASD decreased by 33.16-67.81% and 36.05-75.57%, respectively. The comparative experiment results of the labeled data with different proportions (5%, 10% and 20%) showed significant differences in the DSC, Jaccard, and 95HD evaluation indexes in the labeled data with 5% versus 10% and 5% versus 20%. Moreover, no significant differences were observed in the labeled data with 10% versus 20% among all evaluation indexes. Therefore, we can use only 10% labeled data to achieve the experimental objective. CONCLUSIONS: Using the proposed RCBA-UAMT, the CTV of breast cancer CBCT images can be delineated reliably with a small amount of labeled data. These delineated images can be used to observe the changes in CTV and lay the foundation for the follow-up implementation of ART.

Airway hillocks are injury-resistant reservoirs of unique plastic stem cells.

Airway hillocks are stratified epithelial structures of unknown function1. Hillocks persist for months and have a unique population of basal stem cells that express genes associated with barrier function and cell adhesion. Hillock basal stem cells continually replenish overlying squamous barrier cells. They exhibit dramatically higher turnover than the abundant, largely quiescent classic pseudostratified airway epithelium. Hillocks resist a remarkably broad spectrum of injuries, including toxins, infection, acid and physical injury because hillock squamous cells shield underlying hillock basal stem cells from injury. Hillock basal stem cells are capable of massive clonal expansion that is sufficient to resurface denuded airway, and eventually regenerate normal airway epithelium with each of its six component cell types. Hillock basal stem cells preferentially stratify and keratinize in the setting of retinoic acid signalling inhibition, a known cause of squamous metaplasia2,3. Here we show that mouse hillock expansion is the cause of vitamin A deficiency-induced squamous metaplasia. Finally, we identify human hillocks whose basal stem cells generate functional squamous barrier structures in culture. The existence of hillocks reframes our understanding of airway epithelial regeneration. Furthermore, we show that hillocks are one origin of 'squamous metaplasia', which is long thought to be a precursor of lung cancer.

Increased FGF-21 Improves Ectopic Lipid Deposition in the Liver and Skeletal Muscle.

Obesity can lead to excessive lipid accumulation in non-adipose tissues, such as the liver and skeletal muscles, leading to ectopic lipid deposition and damaging target organ function through lipotoxicity. FGF-21 is a key factor in regulating lipid metabolism, so we aim to explore whether FGF-21 is involved in improving ectopic lipid deposition. We observed the characteristics of ectopic lipid deposition in the liver and skeletal muscles of obesity-resistant mice, detected the expression of FGF-21 and perilipin, and found that obesity-resistant mice showed a decrease in ectopic lipid deposition in the liver and skeletal muscles and increased expression of FGF-21. After inhibiting the expression of FGF-21, a more severe lipid deposition in liver cells and skeletal muscle cells was found. The results indicate that inhibiting FGF-21 can exacerbate ectopic lipid deposition via regulating lipid droplet synthesis and decomposition, as well as free fatty acid translocation and oxidation. In conclusion, FGF-21 is involved in improving ectopic lipid deposition caused by obesity in the liver and skeletal muscles.

Associated factors leading to misdiagnosis of a combined diagnostic model of different types of strain imaging and conventional ultrasound in evaluation of breast lesions: Selection strategy for using different types of strain imaging in evaluation of breast lesions.

OBJECTIVE: To evaluate the effectiveness of a decision tree that integrates conventional ultrasound (CUS) with two different strain imaging (SI) techniques for diagnosing breast lesions, and to analyze the factors contributing to false negative (FN) and false positive (FP) in the decision tree's outcomes. MATERIALS AND METHODS: Imaging and clinical data of 796 cases in the training set and 351 cases in the validation set were prospectively collected. A decision tree model that combines two types of SI and CUS was constructed, and its diagnostic performance was analyzed. Univariate analysis and multivariate analysis were applied to identify independent risk factors associated with FP and FN results of the decision tree model. RESULTS: Size, shape, margin, vascularity, the types of internal calcifications, EI score and VTI pattern were found to be significantly independently associated with the diagnosis of benign and malignant breast lesions. Therefore, size, shape, margin, vascularity, EI score and VTI pattern were used to construct decision tree models. The Tree (EI+VTI) model had the highest AUC. Both in the training and validation groups, the AUC of Tree (EI+VTI) was significantly higher compared with that of EI, VTI, and BI-RADS (all, P < 0.05). Orientation, posterior acoustic features and the types of internal calcifications were significantly positively associated with misdiagnosis results of Tree (EI+VTI) in evaluation of breast lesions (all P < 0.05). CONCLUSION: The diagnostic model based on a decision tree that integrates two distinct types of SI with CUS enhances the diagnostic accuracy of each method when used individually. This integration lowers the misdiagnosis rate, potentially assisting radiologists in more effective lesion assessments. When applying the decision tree model, attention should be paid to the orientation, posterior acoustic features, and the types of internal calcifications of the lesions.

Sustainable biochar application in anammox process: Unveiling novel pathways for enhanced nitrogen removal and efficient start-up at low temperature.

This study explored the use of biochar to accelerate the establishment of anaerobic ammonium oxidation (anammox) reactors operating at 15 ± 1℃. Incorporating 10 g/L bamboo charcoal in S1 accelerated the start-up of anammox in 87 days, which was significantly shorter than 103 days in S0 (without biochar). After 140 days, S1 exhibited a 10.9 % increase in nitrogen removal efficiency due to a 28.9 % elevation in extracellular polymeric substances, bolstering anammox bacterial resilience. Predominant anammox bacteria (Cadidatus Brocadia and Cadidatus Jettenia) showed relative abundances of 3.19 % and 0.38 % in S1, respectively, which were significantly higher than 0.40 % and 0.05 % in S0. Biochar provides favorable habitats for the enrichment of anammox bacteria and accelerates the establishment of anammox at low temperatures. This finding holds promise for enhancing the efficiency of anammox in cold climates and advancing sustainable wastewater nitrogen removal.

Light-Sheet Microscopic Imaging of Whole-Mouse Vascular Network with Fluorescent Microsphere Perfusion.

Visualizing the whole vascular network system is crucial for understanding the pathogenesis of specific diseases and devising targeted therapeutic interventions. Although the combination of light sheet microscopy and tissue-clearing methods has emerged as a promising approach for investigating the blood vascular network, leveraging the spatial resolution down to the capillary level and the ability to image centimeter-scale samples remains difficult. Especially, as the resolution improves, the issue of photobleaching outside the field of view poses a challenge to image the whole vascular network of adult mice at capillary resolution. Here, we devise a fluorescent microsphere vascular perfusion method to enable labeling of the whole vascular network in adult mice, which overcomes the photobleaching limit during the imaging of large samples. Moreover, by combining the utilization of a large-scale light-sheet microscope and tissue clearing protocols for whole-mouse samples, we achieve the capillary-level imaging resolution (3.2 × 3.2 × 6.5 µm) of the whole vascular network with dimensions of 45 × 15 × 82 mm in adult mice. This method thus holds great potential to deliver mesoscopic resolution images of various tissue organs for whole-animal imaging.

Design, synthesis, and evaluation of novel quindoline derivatives with fork-shaped side chains as RNA G-quadruplex stabilizers for repressing oncogene NRAS translation.

NRAS mutation is the second most common oncogenic factor in cutaneous melanoma. Inhibiting NRAS translation by stabilizing the G-quadruplex (G4) structure with small molecules seems to be a potential strategy for cancer therapy due to the NRAS protein's lack of a druggable pocket. To enhance the effects of previously reported G4 stabilizers quindoline derivatives, we designed and synthesized a novel series of quindoline derivatives with fork-shaped side chains by introducing (alkylamino)alkoxy side chains. Panels of experimental results showed that introducing a fork-shaped (alkylamino)alkoxy side chain could enhance the stabilizing abilities of the ligands against NRAS RNA G-quadruplexes and their anti-melanoma activities. One of them, 10b, exhibited good antitumor activity in the NRAS-mutant melanoma xenograft mouse model, showing the therapeutic potential of this kind of compounds.

Enhanced reduction of graphene oxide via laser-dispersion coupling: Towards large-scale, low-defect graphene for crease-free heat-dissipating membranes in advanced flexible electronics.

The advancement of flexible electronics demands improved components, necessitating heat dissipation membranes (HDMs) to exhibit high thermal conductivity while maintaining structural integrity and performance stability even after extensive deformation. Herein, we have devised a laser-modulated reduction technique for graphene oxide (GO), enabling the fabrication of high-quality, large-scale, low-defect graphene, which yields high-performance HDMs after orderly deposition. The work underscores the crucial role of the laser wavelength and dispersion liquid's coupling intensity in influencing the morphology and properties of graphene. Optimal coupling effect and energy conversion are realized when a laser of 1064 nm wavelength irradiates a triethylene glycol (TEG)/N,N-Dimethylformamide (DMF) dispersion. This unique synergy generates high transient energy, which facilitates the deprotonation process and ensures a swift, comprehensive GO reduction. In contrast to conventional water-based laser reduction methods, the accelerated reaction magnifies the size of the graphene sheets by mitigating the ablation effect. After membrane construction with an ordered structure, the corresponding membrane exhibits a high thermal conductivity of 1632 W m-1 K-1, requiring only ∼1/10 of the total preparation time required by other reported methods. Remarkably, the resulting HDM demonstrates superior resilience against creasing and folding, maintaining excellent smoothness and negligible reduction in thermal conductivity after violent rubbing. The combination of exceptional flexibility and thermal conductivity in HDMs paves the way for long-term practical use in the flexible electronics industry.

High Manganese Content of Lipid NanoMn (LNM) by Microfluidic Technology for Enhancing Anti-Tumor Immunity.

Immunotherapy is a clinically effective method for treating tumors. Manganese can activate the cGAS-STING signaling pathway and induce an anti-tumor immune response. However, its efficacy is hindered by non-specific distribution and low uptake rates. In this study, we employed microfluidic technology to design and develop an innovative preparation process, resulting in the creation of a novel manganese lipid nanoparticle (LNM). The lipid manganese nanoparticle produced in this process boasts a high manganese payload, excellent stability, the capacity for large-scale production, and high batch repeatability. LNM has effectively demonstrated the ability to activate the cGAS-STING signaling pathway, induce the production of pro-inflammatory cytokines, and inhibit tumor development. Notably, LNM does not require combination chemotherapy drugs or other immune activators. Therefore, LNM presents a safe, straightforward, and efficient strategy for anti-tumor immune activation, with the potential for scalable production.

Identification of Hub Genes in Liver Hepatocellular Carcinoma Based on Weighted Gene Co-expression Network Analysis.

Liver hepatocellular carcinoma (LIHC) is a malignant cancer with high incidence and poor prognosis. To investigate the correlation between hub genes and progression of LIHC and to provided potential prognostic markers and therapy targets for LIHC. Our study mainly used The Cancer Genome Atlas (TCGA) LIHC database and the gene expression profiles of GSE54236 from the Gene Expression Omnibus (GEO) to explore the differential co-expression genes between LIHC and normal tissues. The differential co-expression genes were extracted by Weighted Gene Co-expression Network Analysis (WGCNA) and differential gene expression analysis methods. The Genetic Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were carried out to annotate the function of differential genes. Then the hub genes were validated using protein-protein interaction (PPI) network. And the expression level and prognostic analysis were performed. The probable associations between the expression of hub genes and both tumor purity and infiltration of immune cells were explored by TIMER. A total of 68 differential co-expression genes were extracted. These genes were mainly enriched in complement activation (biological process), collagen trimer (cellular component), carbohydrate binding and receptor ligand activity (molecular function) and cytokine - cytokine receptor interaction. Then we demonstrated that the 10 hub genes (CFP, CLEC1B, CLEC4G, CLEC4M, FCN2, FCN3, PAMR1 and TIMD4) were weakly expressed in LIHC tissues, the qRT-PCR results of clinical samples showed that six genes were significantly downregulated in LIHC patients compared with adjacent tissues. Worse overall survival (OS) and disease-free survival (DFS) in LIHC patients were associated with the lower expression of CFP, CLEC1B, FCN3 and TIMD4. Ten hub genes had positive association with tumor purity. CFP, CLEC1B, FCN3 and TIMD4 could serve as novel potential molecular targets for prognosis prediction in LIHC.

[Research on Position Verification of Multi-Leaf Collimator (MLC) and Dose Verification Based on Electronic Portal Imaging Device].

Objective: A quality control (QC) system based on the electronic portal imaging device (EPID) system was used to realize the Multi-Leaf Collimator (MLC) position verification and dose verification functions on Primus and VenusX accelerators. Methods: The MLC positions were calculated by the maximum gradient method of gray values to evaluate the deviation. The dose of images acquired by EPID were reconstructed using the algorithm combining dose calibration and dose calculation. The dose data obtained by EPID and two-dimensional matrix (MapCheck/PTW) were compared with the dose calculated by Pinnacle/TiGRT TPS for γ passing rate analysis. Results: The position error of VenusX MLC was less than 1 mm. The position error of Primus MLC was significantly reduced after being recalibrated under the instructions of EPID. For the dose reconstructed by EPID, the average γ passing rates of Primus were 98.86% and 91.39% under the criteria of 3%/3 mm, 10% threshold and 2%/2 mm, 10% threshold, respectively. The average γ passing rates of VenusX were 98.49% and 91.11%, respectively. Conclusion: The EPID-based accelerator quality control system can improve the efficiency of accelerator quality control and reduce the workload of physicists.

Prognosis Prediction of Diffuse Large B-cell Lymphoma in 18F-FDG PET images Based on Multi-Deep-Learning Models.

Diffuse large B-cell lymphoma (DLBCL), a cancer of B cells, has been one of the most challenging and complicated diseases because of its considerable variation in clinical behavior, response to therapy, and prognosis. Radiomic features from medical images, such as PET images, have become one of the most valuable features for disease classification or prognosis prediction using learning-based methods. In this paper, a new flexible ensemble deep learning model is proposed for the prognosis prediction of the DLBCL in 18F-FDG PET images. This study proposes the multi-R-signature construction through selected pre-trained deep learning models for predicting progression-free survival (PFS) and overall survival (OS). The proposed method is trained and validated on two datasets from different imaging centers. Through analyzing and comparing the results, the prediction models, including Age, Ann abor stage, Bulky disease, SUVmax, TMTV, and multi-R-signature, achieve the almost best PFS prediction performance (C-index: 0.770, 95% CI: 0.705-0.834, with feature adding fusion method and C-index: 0.764, 95% CI: 0.695-0.832, with feature concatenate fusion method) and OS prediction (C-index: 0.770 (0.692-0.848) and 0.771 (0.694-0.849)) on the validation dataset. The developed multiparametric model could achieve accurate survival risk stratification of DLBCL patients. The outcomes of this study will be helpful for the early identification of high-risk DLBCL patients with refractory relapses and for guiding individualized treatment strategies.

Diagnosis of benign and malignant peripheral lung lesions based on a feature model constructed by the random forest algorithm for grayscale and contrast-enhanced ultrasound.

Rationale and objectives: To construct a predictive model for benign and malignant peripheral pulmonary lesions (PPLs) using a random forest algorithm based on grayscale ultrasound and ultrasound contrast, and to evaluate its diagnostic value. Materials and methods: We selected 254 patients with PPLs detected using chest lung computed tomography between October 2021 and July 2023, including 161 malignant and 93 benign lesions. Relevant variables for judging benign and malignant PPLs were screened using logistic regression analysis. A model was constructed using the random forest algorithm, and the test set was verified. Correlations between these relevant variables and the diagnosis of benign and malignant PPLs were evaluated. Results: Age, lesion shape, size, angle between the lesion border and chest wall, boundary clarity, edge regularity, air bronchogram, vascular signs, enhancement patterns, enhancement intensity, homogeneity of enhancement, number of non-enhancing regions, non-enhancing region type, arrival time (AT) of the lesion, lesion-lung AT difference, AT difference ratio, and time to peak were the relevant variables for judging benign and malignant PPLs. Consequently, a model and receiver operating characteristic curve were constructed with an AUC of 0.92 and an accuracy of 88.2%. The test set results showed that the model had good predictive ability. The index with the highest correlation for judging benign and malignant PPLs was the AT difference ratio. Other important factors were lesion size, patient age, and lesion morphology. Conclusion: The random forest algorithm model constructed based on clinical data and ultrasound imaging features has clinical application value for predicting benign and malignant PPLs.

Hypoxia Reversion by Low-Immunogenic Ultra-Acid-Sensitive Comicelles of Protein-Polymer Conjugates Sensitizes Tumors to Photodynamic Therapy.

Hypoxia is characteristic of the tumor microenvironment, which is correlated with resistance to photodynamic therapy (PDT), radiotherapy, chemotherapy, and immunotherapy. Catalase is potentially useful to catalyze the conversion of endogenous H2O2 to O2 for hypoxia reversion. However, the efficient delivery of catalase into the hypoxia regions of tumors is a huge challenge. Here, we report the self-assembly of ultra-acid-sensitive polymer conjugates of catalase and albumin into nanomicelles that are responsive to the acidic tumor microenvironment. The immunogenicity of catalase is mitigated by the presence of albumin, which reduces the cross-linking of catalase with B cell receptors, resulting in improved pharmacokinetics. The ultra acid sensitivity of the nanomicelles makes it possible to efficiently escape the lysosomal degradation after endocytosis and permeate into the interior of tumors to reverse hypoxia in vitro and in vivo. In mice bearing triple-negative breast cancer, the nanomicelles loaded with a photosensitizer effectively accumulate and penetrate into the whole tumors to generate a sufficient amount of O2 to reverse hypoxia, leading to enhanced efficacy of PDT without detectable side effects. These findings provide a general strategy of self-assembly to design low-immunogenic ultra-acid-sensitive comicelles of protein-polymer conjugates to reverse tumor hypoxia, which sensitizes tumors to PDT.

Rubisco and sucrose synthesis and translocation are involved in the regulation of photosynthesis in wheat with different source-sink relationships.

Source-sink relationships influence photosynthesis. So far, the limiting factors for photosynthesis of wheat cultivars with different source-sink relationships have not been determined. We aimed to determine the variation patterns of photosynthetic characteristics of wheat cultivars with different source-sink relationships. In this study, two wheat cultivars with different source-sink relationships were selected for photosynthetic physiological analyses. The results showed that YM25 (source-limited cultivar) had higher photosynthetic efficiency compared to YM1 (sink-limited cultivar). This is mainly due to a stronger photochemical efficiency, electron transfer capacity, and Rubisco carboxylation capacity of YM25. YM25 accumulated less soluble carbohydrates in flag leaves than YM1. This is mainly due to the stronger sucrose synthesis and transport capacity of YM25 by presenting higher sucrose-related enzyme activities and gene expression. A PCA analysis showed that Rubisco was the main factor limiting the photosynthetic capacity of YM25. The soluble sugar accumulation in flag leaves and sink limitation decreased the photosynthetic activity of YM1. Increased N application improved source-sink relationships and increased grain yield and source leaf photosynthetic capacity in both two wheat cultivars. Taken together, our findings suggest that Rubisco and sucrose synthesis and translocation are involved in the regulation of photosynthesis of wheat cultivars with different source-sink relationships and that source and sink limitation effects should be considered in photosynthesis.

Simplified Modular Access to Enantiopure 1,2-Aminoalcohols via Ni-Electrocatalytic Decarboxylative Arylation.

Chiral aminoalcohols are omnipresent in bioactive compounds. Conventional strategies to access this motif involve multiple-step reactions to install the requisite functionalities stereoselectively using conventional polar bond analysis. This study reveals that a simple chiral oxazolidine-based carboxylic acid can be readily transformed to substituted chiral aminoalcohols with high stereochemical control by Ni-electrocatalytic decarboxylative arylation. This general, robust, and scalable coupling can be used to synthesize a variety of medicinally important compounds, avoiding protecting and functional group manipulations, thereby dramatically simplifying their preparation.