Characterization of Ocular Morphology in Col4a3-/- Mice as a Murine Model for Alport Syndrome.

Purpose: The purpose of this study was to investigate the ocular morphological characteristics of Col4a3-/- mice as a model of Alport syndrome (AS) and the potential pathogenesis. Methods: The expression of collagen IV at 8, 12, and 21 weeks of age was evaluated by immunohistochemistry in wild-type (WT) and Col4a3-/- mice. Hematoxylin and eosin (H&E) staining and thickness measurements were performed to assess the thickness of anterior lens capsule and retina. Ultrastructure analysis of corneal epithelial basement membrane, anterior lens capsule, internal limiting membrane (ILM), and retinal pigment epithelium (RPE) basement membrane was performed using transmission electron microscopy. Finally, Müller cell activation was evaluated by glial fibrillary acidic protein (GFAP) expression. Results: Collagen IV was downregulated in the corneal epithelial basement membrane and ILM of Col4a3-/- mice. The hemidesmosomes of Col4a3-/- mice corneal epithelium became flat and less electron-dense than those of the WT group. Compared with those of the WT mice, the anterior lens capsules of Col4a3-/- mice were thinner. Abnormal structure was detected at the ILM Col4a3-/- mice, and the basal folds of the RPE basement membrane in Col4a3-/- mice were thicker and shorter. The retinas of Col4a3-/- mice were thinner than those of WT mice, especially within 1000 µm away from the optic nerve. GFAP expression enhanced in each age group of Col4a3-/- mice. Conclusions: Our results suggested that Col4a3-/- mice exhibit ocular anomalies similar to patients with AS. Additionally, Müller cells may be involved in AS retinal anomalies. Translational Relevance: This animal model could provide an opportunity to understand the underlying mechanisms of AS ocular disorders and to investigate potential new treatments.

A bispecific nanosystem activates endogenous natural killer cells in the bone marrow for haematologic malignancies therapy.

Haematologic malignancies commonly arise from the bone marrow lesion, yet there are currently no effective targeted therapies against tumour cells in this location. Here we constructed a bone-marrow-targeting nanosystem, CSF@E-Hn, which is based on haematopoietic-stem-cell-derived nanovesicles adorned with gripper ligands (aPD-L1 and aNKG2D) and encapsulated with colony-stimulating factor (CSF) for the treatment of haematologic malignancies. CSF@E-Hn targets the bone marrow and, thanks to the gripper ligands, pulls together tumour cells and natural killer cells, activating the latter for specific tumour cell targeting and elimination. The therapeutic efficacy was validated in mice bearing acute myeloid leukaemia and multiple myeloma. The comprehensive assessment of the post-treatment bone marrow microenvironment revealed that the integration of CSF into a bone-marrow-targeted nanosystem promoted haematopoietic stem cell differentiation, boosted memory T cell generation and maintained bone homoeostasis, with long-term prevention of relapse. Our nanosystem represents a promising strategy for the treatment of haematologic malignancies.

Gate-Tunable Positive and Negative Photoconductance in Near-Infrared Organic Heterostructures for In-Sensor Computing.

The rapid growth of sensor data in the artificial intelligence often causes significant reductions in processing speed and power efficiency. Addressing this challenge, in-sensor computing is introduced as an advanced sensor architecture that simultaneously senses, memorizes, and processes images at the sensor level. However, this is rarely reported for organic semiconductors that possess inherent flexibility and tunable bandgap. Herein, an organic heterostructure that exhibits a robust photoresponse to near-infrared (NIR) light is introduced, making it ideal for in-sensor computing applications. This heterostructure, consisting of partially overlapping p-type and n-type organic thin films, is compatible with conventional photolithography techniques, allowing for high integration density of up to 520 devices cm-2 with a 5 µm channel length. Importantly, by modulating gate voltage, both positive and negative photoresponses to NIR light (1050 nm) are attained, which establishes a linear correlation between responsivity and gate voltage and consequently enables real-time matrix multiplication within the sensor. As a result, this organic heterostructure facilitates efficient and precise NIR in-sensor computing, including image processing and nondestructive reading and classification, achieving a recognition accuracy of 97.06%. This work serves as a foundation for the development of reconfigurable and multifunctional NIR neuromorphic vision systems.

Scalable Preparation of Ultraselective and Highly Permeable Fully Aromatic Polyamide Nanofiltration Membranes for Antibiotic Desalination.

Membranes are important in the pharmaceutical industry for the separation of antibiotics and salts. However, its widespread adoption has been hindered by limited control of the membrane microstructure (pore architecture and free-volume elements), separation threshold, scalability, and operational stability. In this study, 4,4',4'',4'''-methanetetrayltetrakis(benzene-1,2-diamine) (MTLB) as prepared as a molecular building block for fabricating thin-film composite membranes (TFCMs) via interfacial polymerization. The relatively large molecular size and rigid molecular structure of MTLB, along with its non-coplanar and distorted conformation, produced thin and defect-free selective layers (~27 nm) with ideal microporosities for antibiotic desalination. These structural advantages yielded an unprecedented high performance with a water permeance of 45.2 L m-2 h-1 bar-1 and efficient antibiotic desalination (NaCl/adriamycin selectivity of 422). We demonstrated the feasibility of the industrial scaling of the membrane into a spiral-wound module (with an effective area of 2.0 m2). This module exhibited long-term stability and performance that surpassed those of state-of-the-art membranes used for antibiotic desalination. This study provides a scientific reference for the development of high-performance TFCMs for water purification and desalination in the pharmaceutical industry.

The Crucial Role of SlGSNOR in Regulating Postharvest Tomato Fruit Ripening.

S-nitrosoglutathione reductase (GSNOR) is a well-known regulator in controlling protein S-nitrosylation modification and nitric oxide (NO) homeostasis. Here, a GSNOR inhibitor N6022 and SlGSNOR silencing were applied to investigate the roles of SlGSNOR in tomato fruit postharvest ripening. We found that the application of N6022 and S-nitrosoglutathione (GSNO, a NO donor), and SlGSNOR silencing delayed the transition of fruit skin color by improving total chlorophyll level by 88.57%, 44.78%, and 91.03%, respectively. Meanwhile, total carotenoid and lycopene contents were reduced by these treatments. Concurrently, the activity of chlorophyll biosynthesis enzymes and the expression of related genes were upregulated, and the transcript abundances of total carotenoid bioproduction genes were downregulated, by N6022 and GSNO treatments and SlGSNOR silencing. In addition, fruit softening was postponed by N6022, GSNO, and SlGSNOR silencing, through delaying the decrease of firmness and declining cell wall composition; structure-related enzyme activity; and gene expression levels. Furthermore, N6022, GSNO, and SlGSNOR silencing enhanced the accumulation of titratable acid; ascorbic acid; total phenol; and total flavonoid, but repressed the content of soluble sugar and soluble protein accompanied with the expression pattern changes of nutrition-related genes. In addition, the endogenous NO contents were elevated by 197.55%; 404.59%; and 713.46%, and the endogenous SNOs contents were enhanced by 74.65%; 93.49%; and 94.85%; by N6022 and GSNO treatments and SlGSNOR silencing, respectively. Altogether, these results indicate that SlGSNOR positively promotes tomato postharvest fruit ripening, which may be largely on account of its negative roles in the endogenous NO level.

Ciceribacter sichuanensis sp. nov., a plant growth promoting rhizobacterium isolated from root nodules of soybean in Sichuan, China.

The fast-growing rhizobia-like strains S101T and S153, isolated from root nodules of soybean (Glycine max) in Sichuan, People's Republic of China, underwent characterization using a polyphasic taxonomy approach. The strains exhibited growth at 20-40 °C (optimum, 28 °C), pH 4.0-10.0 (optimum, pH 7.0) and up to 2.0% (w/v) NaCl (optimum, 0.01%) on Yeast Mannitol Agar plates. The 16S rRNA gene of strain S101T showed 98.4% sequence similarity to the closest type strain, Ciceribacter daejeonense L61T. Major cellular fatty acids in strain S101T included summed feature 8 (C18:1ω7c and/or C18:1ω6c) and C19:0 cyclo ω8c. The predominant quinone was ubiquinone-10. The polar lipids of strain S101T included diphosphatidylglycerol, phosphatidylglycerol, phosphatidylmethyl ethanolamine, phosphatidyl ethanolamine, amino phospholipid, unidentified phosphoglycolipid and unidentified amino-containing lipids. The DNA G + C contents of S101T and S153 were 61.1 and 61.3 mol%, respectively. Digital DNA-DNA hybridization relatedness and average nucleotide identity values between S101T and C. daejeonense L61T were 46.2% and 91.4-92.2%, respectively. In addition, strain S101T promoted the growth of soybean and carried nitrogen fixation genes in its genome, hinting at potential applications in sustainable agriculture. We propose that strains S101T and S153 represent a novel species, named Ciceribacter sichuanensis sp. nov., with strain S101T as the type strain (= CGMCC 1.61309 T = JCM 35649 T).

Priority populations' experiences of isolation, quarantine and distancing for COVID-19: protocol for a longitudinal cohort study (Optimise Study).

INTRODUCTION: Longitudinal studies can provide timely and accurate information to evaluate and inform COVID-19 control and mitigation strategies and future pandemic preparedness. The Optimise Study is a multidisciplinary research platform established in the Australian state of Victoria in September 2020 to collect epidemiological, social, psychological and behavioural data from priority populations. It aims to understand changing public attitudes, behaviours and experiences of COVID-19 and inform epidemic modelling and support responsive government policy. METHODS AND ANALYSIS: This protocol paper describes the data collection procedures for the Optimise Study, an ongoing longitudinal cohort of ~1000 Victorian adults and their social networks. Participants are recruited using snowball sampling with a set of seeds and two waves of snowball recruitment. Seeds are purposively selected from priority groups, including recent COVID-19 cases and close contacts and people at heightened risk of infection and/or adverse outcomes of COVID-19 infection and/or public health measures. Participants complete a schedule of monthly quantitative surveys and daily diaries for up to 24 months, plus additional surveys annually for up to 48 months. Cohort participants are recruited for qualitative interviews at key time points to enable in-depth exploration of people's lived experiences. Separately, community representatives are invited to participate in community engagement groups, which review and interpret research findings to inform policy and practice recommendations. ETHICS AND DISSEMINATION: The Optimise longitudinal cohort and qualitative interviews are approved by the Alfred Hospital Human Research Ethics Committee (# 333/20). The Optimise Study CEG is approved by the La Trobe University Human Ethics Committee (# HEC20532). All participants provide informed verbal consent to enter the cohort, with additional consent provided prior to any of the sub studies. Study findings will be disseminated through public website (https://optimisecovid.com.au/study-findings/) and through peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT05323799.

Construction of a cold island network for the urban heat island effect mitigation.

The urban heat island (UHI) effect seriously challenges sustainable urban development strategies and livability. Numerous studies have explored the UHI problem from the perspective of isolated blue and green patches, ignoring the overall function of cold island networks. This study aims to explore the construction method of cold island network by integrating scattered cold island resources, rationally guiding urban planning and construction, and providing effective ideas and methods for improving the urban thermal environment. Taking the central city of Fuzhou as an example, the identification of the cold island core source (CICS) was optimized by applying relative land surface temperature (LST), morphological spatial pattern analysis, and landscape connectivity analysis. The combined resistance surface was constructed based on a spatial principal component analysis. Subsequently, the cold island network was constructed by applying circuit theory and identifying the key nodes. The results showed that the central and eastern parts of the study area experienced the most significant UHI effects and there was a tendency for them to cluster. Overall, 48 core sources, 104 corridors, 89 cooling nodes, and 34 heating nodes were identified. The average LST of the CICSs was 28.43 °C, significantly lower than the average LST of the entire study area (31.50 °C), and the 104 cold corridors were classified into three categories according to their importance. Different targeting measures should be adopted for the cooling and heating nodes to maintain the stability of the cold island network and prevent the formation of a heat network. Finally, we suggest a model for urban cold island network construction and explore methods for mitigating issues with UHI to achieve proactive and organized adaptation and mitigation of thermal environmental risks in urban areas, as well as to encourage sustainable urban development.

Research progress on hydrogel-based drug therapy in melanoma immunotherapy.

Melanoma is one of the most aggressive skin tumors, and conventional treatment modalities are not effective in treating advanced melanoma. Although immunotherapy is an effective treatment for melanoma, it has disadvantages, such as a poor response rate and serious systemic immune-related toxic side effects. The main solution to this problem is the use of biological materials such as hydrogels to reduce these side effects and amplify the immune killing effect against tumor cells. Hydrogels have great advantages as local slow-release drug carriers, including the ability to deliver antitumor drugs directly to the tumor site, enhance the local drug concentration in tumor tissue, reduce systemic drug distribution and exhibit good degradability. Despite these advantages, there has been limited research on the application of hydrogels in melanoma treatment. Therefore, this article provides a comprehensive review of the potential application of hydrogels in melanoma immunotherapy. Hydrogels can serve as carriers for sustained drug delivery, enabling the targeted and localized delivery of drugs with minimal systemic side effects. This approach has the potential to improve the efficacy of immunotherapy for melanoma. Thus, the use of hydrogels as drug delivery vehicles for melanoma immunotherapy has great potential and warrants further exploration. [BMB Reports 2024; 57(2): 71-78].

Abnormal mRNA Splicing Effect of COL4A3 to COL4A5 Unclassified Variants.

Introduction: Genetic diagnosis of Alport syndrome (AS), which results from pathogenic variants in COL4A3, COL4A4, or COL4A5 genes, is hindered by large numbers of unclassified variants detected using next-generation sequencing (NGS). We examined the impact on splicing of variants of uncertain significance in COL4A3 to COL4A5. Methods: Nine unrelated patients with clinical diagnosis or suspicion of AS were enrolled according to the criteria. Their clinical and genetic data were collected. Blood and urine samples were obtained from the patients and their family members. Sanger sequencing was used to confirm the 9 COL4A3 to COL4A5 unclassified variants identified by NGS. COL4A3 to COL4A5 mRNAs from urine were analyzed using targeted reverse transcription polymerase chain reaction and direct sequencing. Results: Nine COL4A3 to COL4A5 unclassified variants were found to alter mRNAs splicing. Skipping of an exon or an exon fragment was induced by variants COL4A3 c.828+5G>A; COL4A4 c.3506-13_3528del; and COL4A5 c.451A>G (p. [Ile151Val]), c.2042-9 T>G, c.2689 G>C (p. [Glu897Gln]) and c.1033-10_1033-2delGGTAATAAA. Retention of an intron fragment was caused by variants COL4A3 c.3211-30G＞T, and COL4A5 c.4316-20T>A and c.1033-10 G>A, respectively. The 9 families in this study obtained genetic diagnosis of AS, including 3 with autosomal recessive AS and 6 with X-linked AS. Conclusions: Our findings demonstrate that urine mRNA analysis facilitates the identification of abnormal splicing of unclassified variants in Alport genes, which provides evidence of routine use of RNA analysis to improve genetic diagnosis of AS.

Corrigendum: RF_phage virion: classification of phage virion proteins with a random forest model.

[This corrects the article DOI: 10.3389/fgene.2022.1103783.].

CaREM1.4 interacts with CaRIN4 to regulate Ralstonia solanacearum tolerance by triggering cell death in pepper.

Remorins, plant-specific proteins, have a significant role in conferring on plants the ability to adapt to adverse environments. However, the precise function of remorins in resistance to biological stress remains largely unknown. Eighteen CaREM genes were identified in pepper genome sequences based on the C-terminal conserved domain that is specific to remorin proteins in this research. Phylogenetic relations, chromosomal localization, motif, gene structures, and promoter regions of these remorins were analyzed and a remorin gene, CaREM1.4, was cloned for further study. The transcription of CaREM1.4 in pepper was induced by infection with Ralstonia solanacearum. Knocking down CaREM1.4 in pepper using virus-induced gene silencing (VIGS) technologies reduced the resistance of pepper plants to R. solanacearum and downregulated the expression of immunity-associated genes. Conversely, transient overexpression of CaREM1.4 in pepper and Nicotiana benthamiana plants triggered hypersensitive response-mediated cell death and upregulated expression of defense-related genes. In addition, CaRIN4-12, which interacted with CaREM1.4 at the plasma membrane and cell nucleus, was knocked down with VIGS, decreasing the susceptibility of Capsicum annuum to R. solanacearum. Furthermore, CaREM1.4 reduced ROS production by interacting with CaRIN4-12 upon co-injection in pepper. Taken together, our findings suggest that CaREM1.4 may function as a positive regulator of the hypersensitive response, and it interacts with CaRIN4-12, which negatively regulates plant immune responses of pepper to R. solanacearum. Our study provides new evidence for comprehending the molecular regulatory network of plant cell death.

Attribution and driving force of nitrogen losses from the Taihu Lake Basin by the InVEST and GeoDetector models.

Quantifying temporal and spatial changes in reactive nitrogen (Nr) losses from a watershed and exploring its main drivers are the key to watershed water quality improvements. Huge Nr losses continue to threaten the safety of the water environment in the Taihu Lake Basin (TLB). Here, the InVEST and GeoDetector models were combined to estimate Nr losses in the TLB from 1990 to 2020 and explore driving forces. Different scenarios for Nr losses were compared, showing that Nr loss peaked at 181.66 × 103 t in 2000. The key factors affecting Nr loss are land use, followed by elevation, soil, and slope factors, and their mean q-values were 0.82, 0.52, 0.51, and 0.48, respectively. The scenario analysis revealed that Nr losses increased under the business-as-usual and economic development scenarios, while ecological conservation, increased nutrient use efficiency, and reduced nutrient application all contribute to a reduction in Nr losses. The findings provide a scientific reference for Nr loss control and future planning in the TLB.

Research on the Sustainable Renewal of Architectural Heritage Sites from the Perspective of Extenics-Using the Example of Tulou Renovations in LantianVillage, Longyan City.

Fujian Tulous in China are important international architectural heritage sites that reflect precious human cultural heritage. Currently, only a small number of Tulou buildings have been listed as world cultural heritage sites, resulting in a lack of attention and financial support for most Tulou buildings. Thus, it is difficult to effectively renovate and repair Tulou buildings to adapt to modern life, and therefore they are facing the severe challenge of abandonment and desolation. Due to the special conditions of Tulou buildings, there are significant limitations in renovation and repair work, with a number of problems such as the lack of innovative renovations. Therefore, through a problem model analysis of a design system for Tulou renovations, in this study, we adopt the methods of divergent tree, conjugate pair, correlative net, implied system, and split-merge chain analyses in extenics to carry out extension transformation and solve the problem and we verify its feasibility using the example of the Tulou renovation projects in Lantian Village, Longyan City. We explore an innovative methodology for scientific renovation of Tulou buildings, and we establish a design system for Tulou building renovations that enriches and supplements original renovation methods; thus, we provide a basis for the repair and reuse of Tulou buildings, to extend their service life and to realize the sustainable development of Tulou buildings. The research results show that extenics can be implemented in innovative renovations of Tulou buildings, and it is concluded that the essence of achieving sustainable renewal in Tulou building renovations is to solve contradictory problems, including contradictions in conditions, objectives, and design. This study verifies the possibility of applying extenics in the design of Tulou building renovations, makes corresponding contributions to the application of extension methods in the renovation and renewal of Tulou buildings, and also contributes to the renovation, renewal, and protection of other types of architectural heritage sites.

The Relationship between Landscape Construction and Bird Diversity: A Bibliometric Analysis.

Urbanization development is the main cause of drastic habitat changes and biodiversity loss, and urban green space construction is one of the effective ways to mitigate biodiversity decay. The proper construction of urban green space landscapes can maintain or increase the resources provided by urban biodiversity, especially bird diversity. This paper is based on 4112 papers published in this research area between 2002 and 2022, and CiteSpace was used to conduct a bibliometric analysis of the research area in terms of the number of articles published, the country or region of publication, core authors, and academic development. The paper systematically reviews the hotspots, history, and frontiers of research on landscape architecture and bird diversity. At the same time, the relationship between landscape construction and bird diversity is discussed in the context of landscape features, vegetation characteristics, and human behavioral activities. The results revealed: (1) research on the association between landscape camping and bird diversity received high priority from 2002 to 2022. Moreover, this research area has become a mature discipline. (2) Throughout the research history, there are four research hotspots (fundamental research on bird communities, influencing factors related to changes in bird community characteristics, research on bird activity rhythms, and ecological and ornamental values of birds), four development stages (2002-2004, 2005-2009, 2010-2015, and 2016-2022), and several research frontiers. (3) Our aim was to reasonably consider the activity characteristics of birds in future landscape construction, and to thoroughly study the landscape construction strategies and management principles for the harmonious coexistence of humans and birds.

Association between dietary inflammatory index and risk of endometriosis: A population-based analysis.

Background and aims: Chronic inflammation plays a significant role in the etiology of endometriosis, which might be affected by dietary intake. This study aimed to investigate the association between dietary inflammatory index (DII) and the risk of endometriosis. Methods: A cross-sectional analysis using data from the National Health and Nutrition Examination Survey (1999-2006) was conducted on 3,410 American participants, among whom 265 reported a diagnosis of endometriosis. DII scores were calculated based on the dietary questionnaire. The association of DII scores with endometriosis was evaluated by adjusted multivariate logistic regression analyzes, which were further investigated in the subgroups. Results: In the fully adjusted models, the odds ratio (OR) for endometriosis participants in the highest and middle tertiles of DII scores were 1.57 [95% confidence interval (CI): 1.14-2.17] and 1.18 (95% CI: 0.84-1.65), compared to the lowest tertile (P trend = 0.007). In subgroup analyzes, the significant positive association between DII scores and the endometriosis risk was also observed in non-obese women (ORtertile3vs1: 1.69, 95% CI: 1.12-2.55; P trend = 0.012), women without diabetes (ORtertile3vs1: 1.62, 95% CI: 1.16-2.27; P trend = 0.005), women with hypertension (ORtertile3vs1: 2.25, 95% CI: 1.31-3.87; P trend = 0.003), parous women (ORtertile3vs1: 1.55, 95% CI: 1.11-2.17; P trend = 0.011), and women using oral contraceptives (ORtertile3vs1: 1.63, 95% CI: 1.15-2.30; P trend = 0.006). Conclusion: This nationally representative study found that increased intake of the pro-inflammatory diet, as a higher DII score, was positively associated with endometriosis risk among American adults. Our results suggested anti-inflammatory dietary interventions may be promising in the prevention of endometriosis. Further prospective studies are necessary to confirm these findings.

Effects of Hydrogen Sulfide on Sugar, Organic Acid, Carotenoid, and Polyphenol Level in Tomato Fruit.

Hydrogen sulfide (H2S) is known to have a positive effect on the postharvest storage of vegetables and fruits, but limited results are available on its influence in fruit flavor quality. Here, we presented the effect of H2S on the flavor quality of tomato fruit during postharvest. H2S decreased the content of fructose, glucose, carotene and lycopene but increased that of soluble protein, organic acid, malic acid and citric acid. These differences were directly associated with the expression of their metabolism-related genes. Moreover, H2S treatment raised the contents of total phenolics, total flavonoids and most phenolic compounds, and up-regulated the expression level of their metabolism-related genes (PAL5, 4CL, CHS1, CHS2, F3H and FLS). However, the effects of the H2S scavenger hypotaurine on the above flavor quality parameters were opposite to that of H2S, thus confirming the role of H2S in tomato flavor quality. Thus, these results provide insight into the significant roles of H2S in tomato fruit quality regulation and implicate the potential application of H2S in reducing the flavor loss of tomato fruit during postharvest.

Inclusion of Cultural and Linguistic Diversity in COVID-19 Public Health Research: Research Design Adaptations to Seek Different Perspectives in Victoria, Australia.

Participation of people from culturally and linguistically diverse (CALD) communities in public health research is often limited by challenges with recruitment, retention and second-language data collection. Consequently, people from CALD communities are at risk of their needs being marginalised in public health interventions. This paper presents intrinsic case analyses of two studies which were adapted to increase the cultural competence of research processes. Both cases were part of the Optimise study, a major mixed methods research study in Australia which provided evidence to inform the Victorian state government's decision-making about COVID-19 public health measures. Case study 1 involved the core Optimise longitudinal cohort study and Case study 2 was the CARE Victorian representative survey, an Optimise sub-study. Both case studies engaged cultural advisors and bilingual staff to adjust the survey measures and research processes to suit target CALD communities. Reflexive processes provided insights into the strengths and weaknesses of the inclusive strategies. Selected survey results are provided, demonstrating variation across CALD communities and in comparison to participants who reported speaking English at home. While in most cases a gradient of disadvantage was evident for CALD communities, some patterns were unexpected. The case studies demonstrate the challenge and value of investing in culturally competent research processes to ensure research guiding policy captures a spectrum of experiences and perspectives.

Increasing Nitrogen Losses Due to Changing Food Consumption Patterns in Bayannur City, China.

Increasing urbanization and affluence have led to changes in food consumption patterns. The application of nitrogen (N) fertilizers ensures food security but also leads to environmental pollution due to N losses, through processes such as acidification, eutrophication, and greenhouse gas emissions. To clarify whether changes in food consumption patterns could increase N losses and to explore sustainable food system pathways, this study integrated the Chinese Food System Dashboard and the Nutrient Flows in Food Chains, Environment and Resources Use model to quantify and compare the link between food consumption and N losses in different agricultural regions using a case study of Bayannur City in the Yellow River Basin from 2000 to 2016. During the study period, Bayannur's food consumption pattern changed from a "high carbohydrate and pork pattern" to a "high fiber and herbivore pattern", which represents a shift from low to high N consumption. The per-capita food consumption decreased by 11.55% from 425.41 kg cap-1, whereas the per-capita N losses increased by 12.42% from 35.60 kg N cap-1. The average share of the plant-oriented and animal-oriented food supply in these losses was 53.39% and 46.61%, respectively. There were differences in the food consumption patterns and N losses in Bayannur's farming, farming-pastoral, and pastoral regions. The changes in N losses were most significant in the pastoral region. The N losses to the environment increased sharply by 112.33% from 22.75 g N cap-1 over the past 16 years. The low level of economic development in Bayannur resulted in a shift in the food consumption pattern to a high N consumption. Four measures to protect food security and reduce the food N cost were proposed: (1) increasing the wheat planting area and maintaining the existing corn one; (2) expanding the scale of high-quality alfalfa planting; (3) enhancing the area of oat grass and wheat replanting; and (4) using modern planting technology.

Risk stratification and molecular heterogeneity of endometrial cancer and expression profile of TIM-3: A retrospective cohort study.

OBJECTIVE: The present study aimed to implement ProMisE classification and risk grouping on a retrospective cohort of 628 patients with endometrial cancer (EC) and determine the molecular heterogeneity across subtypes and subgroups, as well as to investigate the potential beneficiary for TIM-3 checkpoint inhibition in ECs. METHODS: Protein expressions of p53, MMR, TIM-3 and CD8 were measured by immunohistochemistry, and massively parallel sequencing was conducted for 128 cancer-related genes. Patients were categorized into four ProMisE subtypes: MMR-deficient (MMRd), POLE-ultramutated (POLEmut), p53-wild type (p53wt), and p53-abnormal (p53abn), and were subjected to risk classification. RESULTS: 43 (6.9%) patients belonged to POLEmut, 118 (18.8%) to MMRd, 69 (11%) to p53abn, and 398 (63.3%) to p53wt. Compared to the 2016 stratification system, the 2021 ESGO/ESTRO/ESP risk stratification integrated with molecular classification revealed that 11 patients (11/628, 1.8%) were upgraded due to the p53abn signature, whereas 23 patients (23/628, 3.7%) were downgraded due to the POLEmut signature. JAK1 and RAD50 mutations showed higher frequencies in patients with aggressive phenotypes. RAD51B mutation was significantly related to poor RFS of the p53wt subtype but not of the other three molecular subgroups. TIM-3 expression was detected in 30.9% immune cells (ICs) and 29.0% tumor cells (TCs) in ECs, respectively. It was frequently expressed in POLEmut and MMRd ECs as compared to that in the other two molecular subtypes in TCs and ICs. CONCLUSIONS: Our study revealed the molecular heterogeneity across subtypes and subgroups. The new risk stratification system changed the risk grouping of some patients due to the integration of molecular features. RAD51B mutation can further stratify the recurrence risk in the p53wt subtype. Patients with MMRd or POLEmut may benefit most from immunotherapy against TIM-3.