Identification of IGF2 promotes skin wound healing by co-expression analysis.

Oral mucosa is an ideal model for studying scarless wound healing. Researchers have shown that the key factors which promote scarless wound healing already exist in basal state of oral mucosa. Thus, to identify the other potential factors in basal state of oral mucosa will benefit to skin wound healing. In this study, we identified eight gene modules enriched in wound healing stages of human skin and oral mucosa through co-expression analysis, among which the module M8 was only module enriched in basal state of oral mucosa, indicating that the genes in module M8 may have key factors mediating scarless wound healing. Through bioinformatic analysis of genes in module M8, we found IGF2 may be the key factor mediating scarless wound healing of oral mucosa. Then, we purified IGF2 protein by prokaryotic expression, and we found that IGF2 could promote the proliferation and migration of HaCaT cells. Moreover, IGF2 promoted wound re-epithelialization and accelerated wound healing in a full-thickness skin wound model. Our findings identified IGF2 as a factor to promote skin wound healing which provide a potential target for wound healing therapy in clinic.

On-Site Melanoma Diagnosis Utilizing a Swellable Microneedle-Assisted Skin Interstitial Fluid Sampling and a Microfluidic Particle Dam for Visual Quantification of S100A1.

Malignant melanoma (MM) is the most aggressive form of skin cancer. The delay in treatment will induce metastasis, resulting in a poor prognosis and even death. Here, a two-step strategy for on-site diagnosis of MM is developed based on the extraction and direct visual quantification of S100A1, a biomarker for melanoma. First, a swellable microneedle is utilized to extract S100A1 in skin interstitial fluid (ISF) with minimal invasion. After elution, antibody-conjugated magnetic microparticles (MMPs) and polystyrene microparticles (PMPs) are introduced. A high expression level of S100A1 gives rise to a robust binding between MMPs and PMPs and reduces the number of free PMPs. By loading the reacted solution into the device with a microfluidic particle dam, the quantity of free PMPs after magnetic separation is displayed with their accumulation length inversely proportional to S100A1 levels. A limit of detection of 18.7 ng mL-1 for S100A1 is achieved. The animal experiment indicates that ISF-based S100A1 quantification using the proposed strategy exhibits a significantly higher sensitivity compared with conventional serum-based detection. In addition, the result is highly comparable with the gold standard enzyme-linked immunosorbent assay based on Lin's concordance correlation coefficient, suggesting the high practicality for routine monitoring of melanoma.

Orchestrating Precision within the Tumor Microenvironment by Biomimetic Nanoprodrugs for Effective Tumor Therapy.

Malignant tumors are still one of the most deadly diseases that threaten human life and health. However, developing new drugs is challenging due to lengthy trials, funding constraints, and regulatory approval procedures. Consequently, researchers have devoted themselves to transforming some clinically approved old drugs into antitumor drugs with certain active ingredients, which have become an attractive alternative. Disulfiram (DSF), an antialcohol medication, can rapidly metabolize in the physiological environment into diethyldithiocarbamate (DTC) which can readily react with Cu2+ ions in situ to form the highly toxic bis(N,N-diethyldithiocarbamate)-copper(II) (CuET) complex. In this study, DSF is loaded into mesoporous dopamine nanocarriers and surface-chelated with tannin and Cu2+ to construct M-MDTC nanoprodrugs under the camouflage of K7 tumor cell membranes. After intravenous injection, M-MDTC nanoprodrugs successfully reach the tumor sites with the help of mediated cell membranes. Under slightly acidic pH and photothermal stimulation conditions, DSF and Cu2+ are simultaneously released, forming a highly toxic CuET to kill tumor cells in situ. The generated CuET can also induce immunogenic cell death of tumor cells, increase the proportion of CD86+ CD80+ cells, and promote dendritic cell maturation. In vitro and in vivo studies of M-MDTC nanoprodrugs have shown excellent tumor-cell-killing ability and solid tumor suppression. This approach enables in situ amplification of chemotherapy in the tumor microenvironment, achieving an effective antitumor treatment.

Synergistic reinforcement of immunogenic cell death and transformation of tumor-associated macrophages via an M1-type macrophage membrane-camouflaged ferrous-supply-regeneration nanoplatform.

The immune system's role in tumor growth and spread has led to the importance of activating immune function in tumor therapy. We present a strategy using an M1-type macrophage membrane-camouflaged ferrous-supply-regeneration nanoplatform (M1mDDTF) to synergistically reinforce immunogenic cell death (ICD) and transform tumor-associated macrophages (TAMs) against tumors. The M1mDDTF nanoparticles consist of doxorubicin-loaded dendritic mesoporous silica nanoparticles chelated with FeIII-tannic acid (FeIIITA) and coated with M1-type macrophage membranes. In the acidic tumor microenvironment, FeIIITA releases Fe2+ and generates ·OH, aided by near infrared irradiation for enhanced doxorubicin release. Furthermore, the M1mDDTF nanoplatform not only directly kills tumor cells but stimulates ICD, which can increase the proportion of CD86+ CD80+ cells and promote dendritic cell maturation. Particularly, the M1mDDTF nanoplatform can also promote the gradual polarization of TAMs into the M1-type and promote tumor cell killing. This study demonstrates the safety and multifunctionality of M1mDDTF nanoparticles, highlighting their potential for clinical tumor treatment. STATEMENT OF SIGNIFICANCE: Malignant tumors are a global concern and a major cause of death. Nanoparticles' passive targeting is ineffective and hindered by reticuloendothelial system clearance. Therefore, enhancing nanoparticle accumulation in tumors while minimizing toxicity is a challenge. Coating nanoparticles with cell membranes enhances biocompatibility, immune evasion, and specific targeting. This approach has led to the development of numerous cell membrane-mimicking nanomaterials with remarkable properties and functions. This study developed an M1-type macrophage membrane-camouflaged ferrous-supply-regeneration nanoplatform, boosting immunogenic cell death and transforming tumor-associated macrophages. Tannic acid in the tumor microenvironment reduced Fe3+ to Fe2+, generating ·OH. M1mDDTF nanosystem induced M1-type macrophage polarization, inhibiting tumor growth and triggering immune cell death. Safe and versatile, these M1mDDTF nanoparticles hold promise for clinical tumor treatment.

Quantifying pesticide emissions for drift deposition in comparative risk and impact assessment.

Estimating emissions of chemical pesticides used in agriculture is an essential component in evaluating the potential toxicity-related impacts on humans and ecosystems in various comparative risk and impact assessment frameworks, such as life cycle assessment, environmental footprinting, absolute environmental sustainability assessment, chemical substitution, and risk prioritization. Emissions related to drift deposition-usually derived from drift experiments-can reach non-target areas, and vary as a function of crop characteristics and application technique. We derive cumulative drift deposition fractions for a wide range of experimental drift functions for use in comparative and mass-balanced approaches. We clarify that cumulative drift deposition fractions require to integrate the underlying drift functions over the relevant deposition area and to correct for the ratio of deposition area to treated field area to arrive at overall mass deposited per unit mass of applied pesticide. Our results show that for most crops, drift deposition fractions from pesticide application are below 0.03 (i.e. 3% of applied mass), except for grapes and fruit trees, where drift fractions can reach 5% when using canon or air blast sprayers. Notably, aerial applications on soybeans can result in significantly higher drift deposition fractions, ranging from 20% to 60%. Additionally, varying the nozzle position can lead to a factor of five differences in pesticide deposition, and establishing buffer zones can effectively reduce drift deposition. To address remaining limitations in deriving cumulative drift deposition fractions, we discuss possible alternative modelling approaches. Our proposed approach can be implemented in different quantitative and comparative assessment frameworks that require emission estimates of agricultural pesticides, in support of reducing chemical pollution and related impacts on human health and the environment.

Comparative analysis of human respiratory syncytial virus evolutionary patterns during the COVID-19 pandemic and pre-pandemic periods.

The COVID-19 pandemic has resulted in the implementation of strict mitigation measures that have impacted the transmission dynamics of human respiratory syncytial virus (HRSV). The measures also have the potential to influence the evolutionary patterns of the virus. In this study, we conducted a comprehensive analysis comparing genomic variations and evolving characteristics of its neutralizing antigens, specifically F and G proteins, before and during the COVID-19 pandemic. Our findings showed that both HRSV A and B exhibited an overall chronological evolutionary pattern. For the sequences obtained during the pandemic period (2019-2022), we observed that the HRSV A distributed in A23 genotype, but formed into three subclusters; whereas the HRSV B sequences were relatively concentrated within genotype B6. Additionally, multiple positively selected sites were detected on F and G proteins but none were located at neutralizing antigenic sites of the F protein. Notably, amino acids within antigenic site III, IV, and V of F protein remained strictly conserved, while some substitutions occurred over time on antigenic site Ø, I, II and VIII; substitution S389P on antigenic site I of HRSV B occurred during the pandemic period with nearly 50% frequency. However, further analysis revealed no substitutions have altered the structural conformations of the antigenic sites, the vial antigenicity has not been changed. We inferred that the intensive public health interventions during the COVID-19 pandemic did not affect the evolutionary mode of HRSV.

A nanometallic conductive composite-hydrogel core-shell microneedle skin patch for real-time monitoring of interstitial glucose levels.

A microneedle-based skin patch system allows the minimally invasive extraction of skin interstitial fluid, which offers hope for the realization of quantitative and non-invasive diagnosis/monitoring of biological/physiological signals (biomarkers) in the human body. This work describes a nanometallic conductive composite-hydrogel core-shell microneedle skin patch that can realize minimally invasive real-time monitoring of physiological signals. The microneedle sensing system contains an inner conductive silver paste core and an outer bioactive hydrogel layer. The inner core is coated with biomarker-specific enzymes while the outer hydrogel layer extracts the biomarkers from the skin interstitial fluid. This patch can be integrated with the commercial signal processing and transmission modules and enable real-time monitoring. Taking glucose as a model biomarker, we confirm the function and potential application of this core-shell microneedle patch for transdermal diagnosis. It is proven that the core-shell microneedle patch can quickly extract skin interstitial fluid within 30 seconds and has a fast and linear response to glucose concentrations from 0 to 21 mM with a correlation coefficient of 0.9970, which may pave the way for the future development of smart wearable devices with minimally invasive transdermal biosensors.

A skin patch integrating swellable microneedles and electrochemical test strips for glucose and alcohol measurement in skin interstitial fluid.

Microneedle (MN)-based diagnostic devices can efficiently access skin interstitial fluid (ISF) for accurate and minimally invasive detection of health-related biomarkers. This work reports a biomarker (i.e., glucose or alcohol) monitoring MN device that is composed of swellable MNs and electrochemical test strip. This device is constructed by adhering MN patch on the electrochemical strips using the chitosan as the connecting layer. The MNs penetrate the skin for extraction of ISF that flows to the backing layer of MNs and is analyzed by the test strip. In the in vitro skin models, this device accurately detects the glucose from 0 mM to 12 mM and alcohol from 0 mM to 20 mM. In vivo experiment shows this MN device is capable of minimally invasive sampling of ISF and analysis of glucose levels to determine the glycemic status of mice.

Wearable patches for transdermal drug delivery.

Transdermal drug delivery systems (TDDs) avoid gastrointestinal degradation and hepatic first-pass metabolism, providing good drug bioavailability and patient compliance. One emerging type of TDDs is the wearable patch worn on the skin surface to deliver medication through the skin. They can generally be grouped into passive and active types, depending on the properties of materials, design principles and integrated devices. This review describes the latest advancement in the development of wearable patches, focusing on the integration of stimulus-responsive materials and electronics. This development is deemed to provide a dosage, temporal, and spatial control of therapeutics delivery.

Efficacy of apatinib+radiotherapy vs radiotherapy alone in patients with advanced multiline therapy failure for non small cell lung cancer with brain metastasis.

OBJECTIVE: Lung cancer is the leading cause of cancer-associated mortality worldwide. Central nervous system (CNS) metastasis is a prevalent and serious complication. The most common treatment for brain metastasis (BM) is still radiation therapy (RT). An increasing number of drugs have been shown to have intracranial activity or to sensitize tumours to radiotherapy. METHODS: Consecutive advanced multiline therapy failure in patients with non-small-cell lung cancer (NSCLC) with BM at the authors' hospital were retrospectively reviewed. Eligible patients were divided into two groups: Apatinib+RT group and RT group. Intracranial progression-free survival (PFS) and overall survival (OS) were analysed using the Kaplan-Meier method. RESULTS: The median intracranial PFS for the RT group and Apatinib+RT group was 5.83 months and 11.81 months (p = 0.034). The median OS for the RT group and Apatinib+RT group was 9.02 months and 13.62 months (p = 0.311). The Apatinib+RT group had a better intracranial PFS, but there were no significant differences between the two arms in OS. The Apatinib+RT group had significantly reduced symptoms caused by BM. CONCLUSION: RT combined with apatinib could help to control intracranial metastases. The Apatinib+RT group had significantly reduced symptoms caused by BM and improved quality of life for patients, the safety of the two treatments was similar. ADVANCES IN KNOWLEDGE: Here, we propose that RT combined with apatinib can significantly relieve brain symptoms and tolerate side-effects without affecting OS in patients with BM following failure of multiline therapy for NSCLC. Of course, this paper is a retrospective origin study, and more powerful evidence is needed to demonstrate.

Bifurcations driven by generalist and specialist predation: mathematical interpretation of Fennoscandia phenomenon.

In this paper, we revisit a predator-prey model with specialist and generalist predators proposed by Hanski et al. (J Anim Ecol 60:353-367, 1991) , where the density of generalist predators is assumed to be a constant. It is shown that the model admits a nilpotent cusp of codimension 4 or a nilpotent focus of codimension 3 for different parameter values. As the parameters vary, the model can undergo cusp type (or focus type) degenerate Bogdanov-Takens bifurcations of codimension 4 (or 3). Our results indicate that generalist predation can induce more complex dynamical behaviors and bifurcation phenomena, such as three small-amplitude limit cycles enclosing one equilibrium, one or two large-amplitude limit cycles enclosing one or three equilibria, three limit cycles appearing in a Hopf bifurcation of codimension 3 and dying in a homoclinic bifurcation of codimension 3. In addition, we show that generalist predation stabilizes the limit cycle driven by specialist predators to a stable equilibrium, which clearly explains the famous Fennoscandia phenomenon.

Tumor Microenvironment-Adaptive Nanoplatform Synergistically Enhances Cascaded Chemodynamic Therapy.

Chemodynamic therapy (CDT), a noninvasive strategy, has emerged as a promising alternative to conventional chemotherapy for treating tumors. However, its therapeutic effect is limited by the amount of H2O2, pH value, the hypoxic environment of tumors, and it has suboptimal tumor-targeting ability. In this study, tumor cell membrane-camouflaged mesoporous Fe3O4 nanoparticles loaded with perfluoropentane (PFP) and glucose oxidase (GOx) are used as a tumor microenvironment-adaptive nanoplatform (M-mFeP@O2-G), which synergistically enhances the antitumor effect of CDT. Mesoporous Fe3O4 nanoparticles are selected as inducers for photothermal and Fenton reactions and as nanocarriers. GOx depletes glucose within tumor cells for starving the cells, while producing H2O2 for subsequent ·OH generation. Moreover, PFP, which can carry O2, relieves hypoxia in tumor cells and provides O2 for the cascade reaction. Finally, the nanoparticles are camouflaged with osteosarcoma cell membranes, endowing the nanoparticles with homologous targeting and immune escape abilities. Both in vivo and in vitro evaluations reveal high synergistic therapeutic efficacy of M-mFeP@O2-G, with a desirable tumor-inhibition rate (90.50%), which indicates the great potential of this platform for clinical treating cancer.

Recent advances on gelatin methacrylate hydrogels with controlled microstructures for tissue engineering.

Hydrogels with high water content and porous structures are excellent 3D scaffolds for various applications in tissue engineering. Gelatin methacryloyl (GelMA) hydrogels with cell responsive RGD and MMP peptide sequences have been widely used in tissue engineering because of their adjustable mechanical properties, good processing performance and excellent biocompatibility. Advanced manufacturing technologies such as 3D printing and electrospinning can achieve precise control of GelMA-based hydrogel microstructures. Different microstructures of GelMA hydrogels, such as microspheres, microfibers, microchannels, microgrooves/microridges and microwells/micropillars have been fabricated and studied to simulate natural extracellular matrix and regulate the proliferation, migration and differentiation of different cells. In this review, recent efforts in GelMA-based hydrogel microstructures are discussed, including their preparation methods, unique characteristics, and specific applications in cell culture and tissue engineering. Finally, the remaining challenges and future direction of microstructured GelMA hydrogels are also suggested. We believe that with these recent advances and numerous ongoing efforts, GelMA-based hydrogels can be precisely fabricated with controlled microstructures, possessing great potentials as universal scaffolds for tissue engineering.

[The nuclear translocation of circRNA CPSF6 promotes apoptosis of trophoblast cells induced by homocysteine].

Objective To investigate the role of circular RNA cleavage and polyadenylation specificity factor 6 (circRNA CPSF6) in the apoptosis of trophoblast cells induced by homocysteine (Hcy) and its mechanism. Methods HTR-8/SVneo human chorionic trophoblast cells were cultured in vitro and divided into control group (0 mmol/L Hcy treatment) and 1 mmol/L Hcy treatment group. Immunofluorescence cytochemical staining was used to detect the expression of caspase-3 in trophoblasts, and Western blot analysis was used to detect the caspase-3 protein level. The mRNA expression level of circRNA CPSF6 was detected by real-time quantitative PCR. Small interfering RNA (siRNA) was used to knock down the expression of circRNA CPSF6 in trophoblast cells. The expressions of caspase-3, caspase-9, Bcl2, and BAX were detected by Western blot analysis. Real-time quantitative PCR was used to detect the expression level of circRNA CPSF6 in the cytoplasm/nucleus of trophoblast cells before and after Hcy treatment. Results Compared with those in the control group, the expressions of caspase-3 and circRNA CPSF6 mRNA in the Hcy treatment group significantly increased. After knocking down circRNA CPSF6, the expression of caspase-3 decreased, and the mitochondrial apoptosis pathway was inhibited. In normal cultured trophoblast cells, circRNA CPSF6 was expressed in large amounts in the cytoplasm, and after Hcy treatment, circRNA CPSF6 was mainly expressed in the nucleus. Conclusion The mitochondrial apoptotic pathway is activated by circRNA CPSF6 nuclear translocation to promote trophoblast apoptosis induced by Hcy.

Biochar-based fertiliser enhances nutrient uptake and transport in rice seedlings.

Biochar-based compound fertilisers (BCF) are gaining increasing attention as they are cost-effectiveness and improve soil fertility and crop yield. However, little is known about the mechanisms by which micron-size BCF particles enhance crop growth. In the present study, Wuyunjing7 rice seedlings were exposed to micron-size particles of wheat straw-based BCF (mBCF) diffused through a 25-µm nylon mesh. The control was fertilised with urea, diammonium phosphate, and potassium chloride to ensure that both treatments received comparables level of N, P, and K. The effects of mBCF on rice seedling growth were evaluated by determining the changes in nitrogen uptake and utilisation via nitrogen content measurements, short-term 15N-NH4+ influx assays, and analyses of transcript-level nutrient transporter gene expression. The shoot biomass of rice seedling treated with mBCF at the rate of 5 mg/ g soil was 33% greater than that for the control. Root and shoot 15N accumulation rates were 44% and 14% higher, respectively, in the mBCF-treated than the control. The mBCF-treated rice seedlings had higher phosphorus, potassium, and iron content than the control. Moreover, the treatments significantly differed in terms of their nutrient transporter gene expression levels. Spectroscopy and microscopy were used to visualise nutrient distributions across transverse root sections. There were relatively higher iron oxide nanoparticle and silicon-based compound concentrations in the roots of the mBCF-treated rice seedlings than in those of the control. The foregoing difference might account for the fact that the growth of the mBCF-treated rice was superior to that of the control. We demonstrated that the mBCF treatment created a more negative electrical potential at the root epidermal cell layer (~ - 160 mV) than the root surface. This potential difference may have been the driving force for mineral nutrient absorption.

Zwitterionic choline phosphate conjugated folate-poly (ethylene glycol): a general decoration of erythrocyte membrane-coated nanoparticles for enhanced tumor-targeting drug delivery.

Erythrocyte membrane nanosystems have become one of the important research directions of disease treatment, especially for tumor treatment, and can enhance the long circulation time of anti-cancer drugs in vivo, and penetrate and accumulate in the tumor site effectively. However, erythrocyte membranes lack targeting properties and it is necessary to provide tumor-targeting function by modifying erythrocyte membranes. In this study, we report on a novel modification method of an erythrocyte membrane nanosystem to target tumors. Specifically, the tumor-targeting molecule folate-poly (ethylene glycol) (FA-PEG) was modified with a zwitterionic 2-(methyl acryloyoxy) ethyl choline phosphate (MCP) by the Michael addition reaction to obtain MCP-modified FA-PEG (MCP-PEG-FA). Based on the strong "N-P" tetravalent electrostatic interaction between MCP and phosphatidyl choline on the erythrocyte membranes, MCP-PEG-FA can be modified on the erythrocyte membrane encapsulated doxorubicin (DOX) loaded poly(lactic-co-glycolic acid) (PLGA) nanosystem to form a tumor-targeting erythrocyte membrane nanosystem (FA-RBC@PLGA-DOX). The results show that MCP-PEG-FA was synthesized and successfully bonded to the erythrocyte membrane nanosystem, and the FA-RBC@PLGA-DOX nanosystem had a better tumor-targeting function and tumor killing effect compared with those of the nanosystems without FA ligand modification. The universal modification method of erythrocyte membranes is successfully provided and can be applied to the treatment of various diseases.

Differences of Circulating CD25hi Bregs and Their Correlations with CD4 Effector and Regulatory T Cells in Autoantibody-Positive T1D Compared with Age-Matched Healthy Individuals.

Circulating CD25hi B cells, a subset of regulatory B cells in humans, are closely related to inflammation and autoimmune diseases. This study is aimed at investigating the alternation of CD25hi Bregs and their correlation with CD4 effector and regulatory T cells in T1D individuals. We included 68 autoantibody-positive T1D and 68 age-matched healthy individuals with peripheral blood mononuclear cells (PBMCs) and assessed them with CD25hi Bregs and CD4 effector or regulatory T cells by flow cytometry. Here, we demonstrate that the frequency of CD25hi Bregs was significantly decreased in T1D subjects (P = 0.0016), but they were not affected by disease status (age at T1D diagnosis or duration) or T1D risk loci (rs2104286 or rs12251307) in IL2RA (all P > 0.05). Moreover, higher IgD (P = 0.043) and lower CD27 (P = 0.0003) expression was observed in CD25hi Bregs of T1D individuals, but not the expression of IgM, CD24, or CD38 (all P > 0.05). Although there was no correlation between CD25hi Bregs and CD4 effector T cell subsets in either T1D or healthy individuals (all P > 0.05), we found a positive correlation between CD25hi Bregs and CD4 Tregs in healthy controls (Sp. r = 0.3544, P = 0.0249), which disappeared in T1D subjects (Sp. r = 0.137, P = 0.401). In conclusion, our results suggest that decreased CD25hi Bregs and alternation of their phenotypes are features of T1D regardless of disease duration and T1D genetic risk loci, and an impaired balance between CD25hi Bregs and CD4 Tregs might contribute to the pathogenesis of T1D.

Development and validation of an interpretable radiomic nomogram for severe radiation proctitis prediction in postoperative cervical cancer patients.

Background: Radiation proctitis is a common complication after radiotherapy for cervical cancer. Unlike simple radiation damage to other organs, radiation proctitis is a complex disease closely related to the microbiota. However, analysis of the gut microbiota is time-consuming and expensive. This study aims to mine rectal information using radiomics and incorporate it into a nomogram model for cheap and fast prediction of severe radiation proctitis prediction in postoperative cervical cancer patients. Methods: The severity of the patient's radiation proctitis was graded according to the RTOG/EORTC criteria. The toxicity grade of radiation proctitis over or equal to grade 2 was set as the model's target. A total of 178 patients with cervical cancer were divided into a training set (n = 124) and a validation set (n = 54). Multivariate logistic regression was used to build the radiomic and non-raidomic models. Results: The radiomics model [AUC=0.6855(0.5174-0.8535)] showed better performance and more net benefit in the validation set than the non-radiomic model [AUC=0.6641(0.4904-0.8378)]. In particular, we applied SHapley Additive exPlanation (SHAP) method for the first time to a radiomics-based logistic regression model to further interpret the radiomic features from case-based and feature-based perspectives. The integrated radiomic model enables the first accurate quantitative assessment of the probability of radiation proctitis in postoperative cervical cancer patients, addressing the limitations of the current qualitative assessment of the plan through dose-volume parameters only. Conclusion: We successfully developed and validated an integrated radiomic model containing rectal information. SHAP analysis of the model suggests that radiomic features have a supporting role in the quantitative assessment of the probability of radiation proctitis in postoperative cervical cancer patients.

OsLSD1.1 is involved in the photosystem II reaction and affects nitrogen allocation in rice.

Nitrogen (N) is an essential nutrient element for plants; however, high N accumulation often leads to a decrease in photosynthetic nitrogen use efficiency (PNUE). In rice (Oryza sativa L.), well-developed aerenchyma is formed to promote oxygen transport from the shoot to the root tips as an adaptation to submerged and oxygen-deficient environment. Total N concentrations were increased in the rice root by changes in O2 levels in the rhizosphere. However, few reports have focused on how aerenchyma formation-related genes participate in photosynthesis and affect nitrogen allocation in rice. In this study, we found that OsLSD1.1, located in the chloroplast, cell membrane, and nucleus, may be involved in the photosystem II reaction and affect chloroplast development. OsLSD1.1 knockout was found to significantly reduce the quantum efficiency of the PSII reaction center (ΦPSII). Furthermore, we observed that the nitrogen accumulation decreased in the grain of OsLSD1.1 mutants. RNA-Seq transcriptome analysis revealed that OsPEPC3, OsPsbR1, OsNRG2, OsNRT1.5A, OsNRT1.7, and OsAMT3;2 were downregulated in m12 compared with N-WT (wild-type Nipponbare), which may be a reason that photosynthesis and nitrogen transport were inhibited. Taken together, our findings demonstrated that OsLSD1.1 may be key in plant growth, photosynthesis, and nitrogen allocation in rice. Our results may provide theoretical support for the discovery of key genes for nitrogen physiological use efficiency.

Differences in Maturation Status and Immune Phenotypes of Circulating Helios+ and Helios- Tregs and Their Disrupted Correlations With Monocyte Subsets in Autoantibody-Positive T1D Individuals.

CD4 Tregs are involved in the regulation of various autoimmune diseases but believed to be highly heterogeneous. Studies have indicated that Helios controls a distinct subset of functional Tregs. However, the immunological changes in circulating Helios+ and Helios- Tregs are not fully explored in type 1 diabetes (T1D). Here, we elucidated the differences in maturation status and immune regulatory phenotypes of Helios+ and Helios- Tregs and their correlations with monocyte subsets in T1D individuals. As CD25-/low FOXP3+ Tregs also represent a subset of functional Tregs, we defined Tregs as FOXP3+CD127-/low and examined circulating Helios+ and Helios- Treg subpopulations in 68 autoantibody-positive T1D individuals and 68 age-matched healthy controls. We found that expression of both FOXP3 and CTLA4 diminished in Helios- Tregs, while the proportion of CD25-/low Tregs increased in Helios+ Tregs of T1D individuals. Although the frequencies of neither Helios+ nor Helios- Tregs were affected by investigated T1D genetic risk loci, Helios+ Tregs correlated with age at T1D diagnosis negatively and disease duration positively. Moreover, the negative correlation between central and effector memory proportions of Helios+ Tregs in healthy controls was disrupted in T1D individuals. Finally, regulatory non-classical and intermediate monocytes also decreased in T1D individuals, and positive correlations between these regulatory monocytes and Helios+/Helios- Treg subsets in healthy controls disappeared in T1D individuals. In conclusion, we demonstrated the alternations in maturation status and immune phenotypes in Helios+ and Helios- Treg subsets and revealed the missing association between these Treg subsets and monocyte subsets in T1D individuals, which might point out another option for elucidating T1D mechanisms.