Identification of cell surface markers for acute myeloid leukemia prognosis based on multi-model analysis.

Given the extremely high inter-patient heterogeneity among acute myeloid leukemia (AML), identifying biomarkers for prognostic assessment and therapeutic guidance is crucial. Cell surface markers (CSMs) have been shown to play an important role in AML leukemogenesis and progression. In this study, we evaluate the prognostic potential of all human CSMs in AML patients based on differential gene expression analysis and univariate Cox regression analysis. Utilizing multi-model analysis, including Adaptive LASSO regression, LASSO regression, and Elastic Net, we construct a 9-CSMs prognostic model for risk stratification of AML patients. The predictive value of the 9-CSMs risk score is further confirmed in three independent datasets. Multivariate Cox regression analysis shows that the risk score is an independent prognostic factor for AML patients. AML patients with high 9-CSMs risk scores have shorter overall and event-free survival time than those with lower scores. Notably, our single-cell RNA-seq analysis indicates that patients with high 9-CSMs risk scores exhibit chemotherapy resistance. Further, PI3K inhibitors are identified as potential treatments for these high-risk patients. In conclusion, we construct a 9-CSMs prognostic model which is an independent prognostic factor for the survival of AML patients and has the potential to guide drug therapy.

Differential expression of FSTL1 and its correlation with the pathological process of periodontitis.

AIMS: This study aimed to elucidate the alterations in Follistatin-like protein 1 (FSTL1) and its association with the pathological process of periodontitis. METHODS: This study included 48 patients with periodontitis and 42 healthy controls. The expression level of FSTL1 in the gingiva was determined by RT-qPCR, validated using the dataset GSE16134, and subsequently examined by western blotting. Bioinformatics analysis revealed a single-cell distribution of FSTL1, characteristic of angiogenesis and immune cell infiltration. The expression and distribution of FSTL1, vascular endothelial marker protein CD31 and myeloperoxidase (MPO), the indicator of neutrophil activity, were determined by immunohistochemistry (IHC). A series of correlation analyses was performed to determine the associations between FSTL1 and clinical parameters, including probing depth (PD) and clinical attachment loss (CAL), and their potential role in angiogenesis (CD31) and neutrophil infiltration (MPO). RESULTS: FSTL1 was significantly upregulated in the gingiva of patients with periodontitis compared to their healthy counterparts. In addition, FSTL1 was positively correlated with the clinical parameters PD (r = .5971, p = .0005) and CAL (r = .6078, p = .0004). Bioinformatic analysis and IHC indicated that high FSTL1 expression was significantly correlated with angiogenesis and neutrophil infiltration in periodontitis. Moreover, receiver operating characteristic (ROC) analysis demonstrated that FSTL1 could serve as an independent indicator for evaluating the severity of periodontitis (area under the curve [AUC] = 0.9011, p < .0001). CONCLUSION: This study demonstrated FSTL1 upregulation in periodontitis and its potential contribution to the disease via angiogenesis and neutrophil infiltration.

Bacillus siamensis Improves the Immune Status and Intestinal Health of Weaned Piglets by Improving Their Intestinal Microbiota.

Previous studies on the early interference of gut microbiota by Bacillus siamensis (B. siamensis) in weaned piglets are rarely reported, and the present trial is a preliminary study. This experiment was conducted to investigate the effects of B. siamensis supplementation on the growth performance, serum biochemistry, immune response, fecal short-chain fatty acids and microbiota of weaned piglets. Sixty weaned piglets were randomly divided into a control group (CON) and a B. siamensis group (BS), which were fed a basal diet and the basal diet supplemented with 5 × 1010 CFU B. siamensis per kg, respectively. Each group had 3 replicates and 10 piglets per replicate. The trial lasted for 28 days. The results showed that B. siamensis significantly increased the serum growth hormone (GH) and insulin-like growth factor (IGF) in piglets. Compared with the CON group, the levels of serum immunoglobulin and inflammatory factors in the BS group were significantly improved. In addition, the serum concentrations of zonulin and endotoxin (ET) in the BS group were lower. The dietary addition of B. siamensis significantly increased fecal short-chain fatty acid (SCFA) levels in piglets. Notably, B. siamensis improved the microbial composition by increasing beneficial genera, including Weissella, Lachnospiraceae_NK4A136_group and Bifidobacterium, and decreasing pathogenic genera, including Pantoea, Fusobacterium and Gemella, in piglet feces. Correlation analysis showed that the benefits of dietary B. siamensis supplementation were closely related to its improved microbial composition. In summary, the addition of B. siamensis can improve the immunity function, inflammatory response, gut permeability and SCFA levels of weaned piglets, which may be achieved through the improvement of their microbiota.

The Immunomodulatory effect of exosomes in diabetes: a novel and attractive therapeutic tool in diabetes therapy.

Exosomes carry proteins, metabolites, nucleic acids and lipids from their parent cell of origin. They are derived from cells through exocytosis, are ingested by target cells, and can transfer biological signals between local or distant cells. Therefore, exosomes are often modified in reaction to pathological processes, including infection, cancer, cardiovascular diseases and in response to metabolic perturbations such as obesity and diabetes, all of which involve a significant inflammatory aspect. Here, we discuss how immune cell-derived exosomes origin from neutrophils, T lymphocytes, macrophages impact on the immune reprogramming of diabetes and the associated complications. Besides, exosomes derived from stem cells and their immunomodulatory properties and anti-inflammation effect in diabetes are also reviewed. Moreover, As an important addition to previous reviews, we describes promising directions involving engineered exosomes as well as current challenges of clinical applications in diabetic therapy. Further research on exosomes will explore their potential in translational medicine and provide new avenues for the development of effective clinical diagnostics and therapeutic strategies for immunoregulation of diabetes.

Expression patterns of mechanosensitive ion channel PIEZOs in irreversible pulpitis.

BACKGROUND: Mechanosensitive ion channel PIEZOs have been widely reported to involve inflammation and pain. This study aimed to clarify expression patterns of PIEZOs and their potential relations to irreversible pulpitis. MATERIALS AND METHODS: Normal pulp tissues (n = 29) from patients with impacted third molars and inflamed pulp tissues (n = 23) from patients with irreversible pulpitis were collected. Pain levels were assessed using a numerical rating scale. PIEZO expressions were measured using real-time PCR and then confirmed using GEO datasets GSE77459, immunoblot, and immunohistochemistry staining. Correlations of PIEZO mRNA expression with inflammatory markers, pain markers, or clinical pain levels were evaluated using Spearman's correlation analysis. Univariate analysis was conducted to analyze PIEZO expressions based on pain description and clinical examinations of cold test, percussion, palpation, and bite test. RESULTS: Compared with normal pulp tissues, mRNA expression levels of PIEZO1 were significantly increased in inflamed pulp tissues, while PIEZO2 was significantly decreased, which was further confirmed in GSE77459 and on a protein and histological level. The positive correlation of the mRNA expression levels between PIEZO1 and inflammatory markers, as well as between PIEZO2 and pain markers, was verified. PIEZO2 expression was also positively correlated with pain levels. Besides, irreversible pulpitis patients who reported continuous pain and who detected a positive response to cold stimulus exhibited a higher expression level of PIEZO2 in the inflamed pulp tissues. By contrast, patients reporting pain duration of more than one week showed a higher expression level of PIEZO1. CONCLUSIONS: This study demonstrated the upregulation of PIEZO1 and the downregulation of PIEZO2 in irreversible pulpitis and revealed the potential relation of PIEZO1 and PIEZO2 to inflammation and pain. These findings suggested that PIEZOs might play critical roles in the progression of irreversible pulpitis and paved the way for further investigations aimed at novel therapies of irreversible pulpitis by targeting PIEZOs.

Screening and Diagnosis of Rare Thalassemia Variants: Is Third-Generation Sequencing Enough?

CONTEXT.­: Rare thalassemia subtypes are often undiagnosed because conventional testing methods can only identify 23 common types of α- and ß-thalassemia. OBJECTIVE.­: To assess a comprehensive approach for the screening and diagnosis of rare thalassemia. DESIGN.­: The study cohort included 72 individuals with suspected rare thalassemia variants. Screening was conducted by next-generation sequencing (NGS) combined with third-generation sequencing (TGS) and chromosomal microarray analysis (CMA)/copy number variation sequencing. RESULTS.­: Of the 72 individuals with suspected rare thalassemia, 49 had rare α- or ß-gene variants. NGS combined with gap polymerase chain reaction detected a total of 42 cases, resulting in a positive detection rate of 58.3%. Additionally, 4 α-globin genetic deletions were identified by TGS, which increased the variant detection rate by 5.6%. Two samples with a microdeletion of chromosome 16 or 11 were detected by CMA, which increased the detection rate by 2.8%. For one sample, reanalysis of the NGS and TGS data confirmed the presence of the ß41-42/ßN and ßN/ßN mosaic. The HBB:c.315 + 2delT mutation was initially reported in Guangdong Province, China. Two HBB gene mutations (HBB:c.315 + 5G>C and HBB:c.295G>A) and 4 rare HBA gene deletions (-11.1, -α27.6, -α2.4, and -α21.9) were initially identified in the Zhonshan region. The hematologic phenotypes of all rare cases in this study were clarified. CONCLUSIONS.­: Rare thalassemia variants are more common than previously thought. Despite advancements in TGS, there is still no foolproof method for detection of all types of thalassemia. Thus, a comprehensive approach is necessary for accurate screening and diagnosis of rare thalassemia variants.

Contactless User-Interactive Sensing Display for Human-Human and Human-Machine Interactions.

Creating a large-scale contactless user-interactive sensing display (CUISD) with optimal features is challenging but crucial for efficient human-human or human-machine interactions. This study reports a CUISD based on dynamic alternating current electroluminescence (ACEL) that responds to humidity. Subsecond humidity-induced luminescence is achieved by integrating a highly responsive hydrogel into the ACEL layer. The patterned silver nanofiber electrode and luminescence layer, produced through electrospinning and microfabrication, result in a stretchable, large-scale, high-resolution, multicolor, and dynamic CUISD. The CUISD is implemented for the real-time control of a remote-controlled car, wherein the luminescence signals induced by touchless finger movements are distinguished and encoded to deliver specific commands. Moreover, the distinctive recognition of breathing facilitates the CUISD to serve as a visual signal transmitter for information interaction, which is particularly beneficial for individuals with disabilities. The paradigm shift depicts in this work is expected to reshape the way authors interact with each other and devices, discovering niche applications in virtual/augmented reality and the metaverse.

Modeling the Zigzag Curves of Transition Metal Ions' Charge Transition Levels in Crystals.

Predicting the defect levels of transition metal (TM) dopants in the band gap of crystals is critical in determining the charge states of TM dopants and explaining their electronic and optical properties. By analyzing the calculated charge transition levels and the crystal-field strengths of all the 3d-TM ions in several insulators, we demonstrate that the variation trend of the 3d-TM dopants in a crystal is a scaling of the variation of 3d-electron binding energies (ionization potential) of the free TM ions corrected by adding the contribution of the 3d-orbital's crystal-field splitting. We therefore develop a model to predict the relative location of TM ions' defect levels in the band gap from the defect level and crystal-field splitting of a reference TM ion in the host of concern. The model is applied to predict the defect levels of the series of TM ions in ß-Ga2O3 and ZnO, which have moderate to small band gaps, making some of the levels fall into the conduction or valence bands. These results show that the model may serve as a quick reference for related material design and optimization.

Paternal preconception alcohol consumption increased Angiotensin II-mediated vasoconstriction in male offspring cerebral arteries via oxidative stress-AT1R pathway.

Alcohol consumption is popular worldwidely and closely associated with cardiovascular diseases. Influences of paternal preconception alcohol consumption on offspring cerebral arteries are largely unknown. Male rats were randomly given alcohol or water before being mated with alcohol-naive females to produce alcohol- and control-sired offspring. Middle cerebral artery (MCA) was tested with a Danish Myo Technology wire myograph, patch-clamp, IONOPTIX, immunofluorescence and quantitative PCR. Alcohol consumption enhanced angiotensin II (AngII)-mediated constriction in male offspring MCA mainly via AT1R. PD123,319 only augmented AngII-induced constriction in control offspring. AngII and Bay K8644 induced stronger intracellular calcium transient in vascular smooth muscle cells (VSMCs) from MCA of alcohol offspring. L-type voltage-dependent calcium channel (L-Ca2+ ) current at baseline and after AngII-stimulation was higher in VSMCs. Influence of large-conductance calcium-activated potassium channel (BKC a ) was lower. Caffeine induced stronger constriction and intracellular calcium release in alcohol offspring. Superoxide anion was higher in alcohol MCA than control. Tempol and thenoyltrifluoroacetone alleviated AngII-mediated contractions, while inhibition was significantly higher in alcohol group. The mitochondria were swollen in alcohol MCA. Despite lower Kcnma1 and Prkce expression, many genes expressions were higher in alcohol group. Hypoxia induced reactive oxygen species production and increased AT1R expression in control MCA and rat aorta smooth muscle cell line. In conclusion, this study firstly demonstrated paternal preconception alcohol potentiated AngII-mediated vasoconstriction in offspring MCA via ROS-AT1R. Alcohol consumption increased intracellular calcium via L-Ca2+ channel and endoplasmic reticulum and decreased BKCa function. The present study provided new information for male reproductive health and developmental origin of cerebrovascular diseases.

OsPGL3A encodes a DYW-type pentatricopeptide repeat protein involved in chloroplast RNA processing and regulated chloroplast development.

The chloroplast serves as the primary site of photosynthesis, and its development plays a crucial role in regulating plant growth and morphogenesis. The Pentatricopeptide Repeat Sequence (PPR) proteins constitute a vast protein family that function in the post-transcriptional modification of RNA within plant organelles. In this study, we characterized mutant of rice with pale green leaves (pgl3a). The chlorophyll content of pgl3a at the seedling stage was significantly reduced compared to the wild type (WT). Transmission electron microscopy (TEM) and quantitative PCR analysis revealed that pgl3a exhibited aberrant chloroplast development compared to the wild type (WT), accompanied by significant alterations in gene expression levels associated with chloroplast development and photosynthesis. The Mutmap analysis revealed that a single base deletionin the coding region of Os03g0136700 in pgl3a. By employing CRISPR/Cas9 mediated gene editing, two homozygous cr-pgl3a mutants were generated and exhibited a similar phenotype to pgl3a, thereby confirming that Os03g0136700 was responsible for pgl3a. Consequently, it was designated as OsPGL3A. OsPGL3A belongs to the DYW-type PPR protein family and is localized in chloroplasts. Furthermore, we demonstrated that the RNA editing efficiency of rps8-182 and rpoC2-4106, and the splicing efficiency of ycf3-1 were significantly decreased in pgl3a mutants compared to WT. Collectively, these results indicate that OsPGL3A plays a crucial role in chloroplast development by regulating the editing and splicing of chloroplast genes in rice. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01468-7.

OsWRKY78 regulates panicle exsertion via gibberellin signaling pathway in rice.

Panicle exsertion is one of the crucial agronomic traits in rice (Oryza sativa). Shortening of panicle exsertion often leads to panicle enclosure and severely reduces seed production. Gibberellin (GA) plays important roles in regulating panicle exsertion. However, the underlying mechanism and the relative regulatory network remain elusive. Here, we characterized the oswrky78 mutant showing severe panicle enclosure, and found that the defect of oswrky78 is caused by decreased bioactive GA contents. Biochemical analysis demonstrates that OsWRKY78 can directly activate GA biosynthesis and indirectly suppress GA metabolism. Moreover, we found OsWRKY78 can interact with and be phosphorylated by mitogen-activated protein kinase (MAPK) kinase OsMAPK6, and this phosphorylation can enhance OsWRKY78 stability and is necessary for its biological function. Taken together, these results not only reveal the critical function of OsWRKY78, but also reveal its mechanism via mediating crosstalk between MAPK and the GA signaling pathway in regulating panicle exsertion.

Role of αENaC in root resorption of adjacent teeth due to entirely impacted mandibular third molars.

BACKGROUND: Entirely impacted mandibular third molar (EIM3M) concerns the pathological external root resorption (ERR) of the adjacent mandibular second molar (M2M) and formation of granulation tissue between two molars. The study aimed to clarify the effect of αENaC, a mechano-sensitive molecule, to explore the mechanical mechanism in this scenario. METHODS: The force EIM3M exerted on M2M was proved by finite element analysis. αENaC expressions were tested by real-time polymerase chain reaction (PCR), immunoblotting and immunofluorescence. Inflammatory and epithelial-mesenchymal transition (EMT)-related molecules expressions were also detected by real-time PCR. The correlation was analyzed by Spearman's correlation analysis, and receiver-operator characteristic (ROC) curve was further exhibited. RESULTS: The force was concentrated in the ERR area. αENaC was upregulated, positively correlated with ERR degree and localized to the fibroblasts in ERR granulation tissues. Moreover, αENaC was respectively and positively associated with elevated TNF-α and N-cadherin in ERR granulation tissues. More importantly, ROC analysis verified αENaC as a novel indication of the incidence of this disease. CONCLUSIONS: Our finding revealed the force from EIM3M causing ERR of M2M, and elucidated the expression and localization of αENaC and its positive correlation with inflammation, EMT and disease severity, suggesting a novel indication in this disease.

Efficient Removal of Iodine from Water by a Calix[4]pyrrole-Based Nanofilm.

The efficient removal of radioactive iodine from an aqueous solution is largely dependent on the adsorbent materials employed. In this work, we report a calix[4]pyrrole-based nanofilm and its application for the rapid removal of iodine from water. The nanofilm was synthesized through a confined dynamic condensation of tetra hydrazide calix[4]pyrrole with 1,3,5-tri-(4-formylphenyl) aldehyde at the air/dimethyl sulfoxide (DMSO) interface. The thickness of the obtained nanofilm is ∼35 nm, enabling fast mass transfer and a high ratio of accessible binding sites for iodine. The pseudo-second-order rate constant of the nanofilm for iodine is ∼0.061 g g-1 min-1, 3 orders of magnitude higher than most reported adsorbent materials. Flow-through nanofiltration tests demonstrated that the nanofilm has an adsorption capacity of 1.48 g g-1, a high removal efficiency, and good reusability. The mechanism study revealed that the moieties of Schiff base, pyrrole, and aromatic rings play a key role for binding iodine. We believe this work provides not only a new strategy for the efficient removal of radioactive iodine from water but also new ideas for designing efficient iodine adsorbents.

A Nanofilm-Based Fluorescent Sensor toward Highly Efficient Detection of Ethephon.

Ethephon (ETH) is widely used to promote fruit ripening and improve fruit quality. However, improper use is harmful to human health and to the environmental safety. Therefore, development of the techniques for on-site and at real-time monitoring of ETH is of importance for its safe use. In this work, we developed a nanofilm-based fluorescence film sensor (FFS) and realized highly efficient detection of ETH in vapor phase, where the detection limit (DL) is <0.2 ppb, the response time is less than 10 s, and the interference is almost free. The unusual sensing performance of the sensor was ascribed to the specific binding of the nanofilm to ETH and to its great porosity, which enables efficient adlayer mass transfer, a requirement for high signal-to-noise ratio. Moreover, visualization-based qualitative sensing is also realized. The nanofilm, a key component of the sensor, was prepared at the humid air/DMSO interface. The building blocks used were a specially designed fluorescent o-carborane derivative (CB-2CHO) and a cross-linker BTN possessing three acylhydrazine groups. The nanofilm as prepared is flexible, uniform, thickness tunable, and photochemically super stable. We believe our effort not only addresses the challenging issue of on-site and at real-time detection of ETH but also provides another route for developing new FFSs via sensing film innovation.

Fully Reversible and Super-Fast Photo-Induced Morphological Transformation of Nanofilms for High-Performance UV Detection and Light-Driven Actuators.

Flexible and highly ultraviolet (UV) sensitive materials garner considerable attention in wearable devices, adaptive sensors, and light-driven actuators. Herein, a type of nanofilms with unprecedented fully reversible UV responsiveness are successfully constructed. Building upon this discovery, a new system for ultra-fast, sensitive, and reliable UV detection is developed. The system operates by monitoring the displacement of photoinduced macroscopic motions of the nanofilms based composite membranes. The system exhibits exceptional responsiveness to UV light at 375 nm, achieving remarkable response and recovery times of < 0.3 s. Furthermore, it boasts a wide detection range from 2.85 µW cm-2 to 8.30 mW cm-2, along with robust durability. Qualitative UV sensing is accomplished by observing the shape changes of the composite membranes. Moreover, the composite membrane can serve as sunlight-responsive actuators for artificial flowers and smart switches in practical scenarios. The photo-induced motion is ascribed to the cis-trans isomerization of the acylhydrazone bonds, and the rapid and fully reversible shape transformation is supposed to be a synergistic result of the instability of the cis-isomers acylhydrazone bonds and the rebounding property of the networked nanofilms. These findings present a novel strategy for both quantitative and qualitative UV detection.

Cross-domain attention-guided generative data augmentation for medical image analysis with limited data.

Data augmentation is widely applied to medical image analysis tasks in limited datasets with imbalanced classes and insufficient annotations. However, traditional augmentation techniques cannot supply extra information, making the performance of diagnosis unsatisfactory. GAN-based generative methods have thus been proposed to obtain additional useful information to realize more effective data augmentation; but existing generative data augmentation techniques mainly encounter two problems: (i) Current generative data augmentation lacks of the capability in using cross-domain differential information to extend limited datasets. (ii) The existing generative methods cannot provide effective supervised information in medical image segmentation tasks. To solve these problems, we propose an attention-guided cross-domain tumor image generation model (CDA-GAN) with an information enhancement strategy. The CDA-GAN can generate diverse samples to expand the scale of datasets, improving the performance of medical image diagnosis and treatment tasks. In particular, we incorporate channel attention into a CycleGAN-based cross-domain generation network that captures inter-domain information and generates positive or negative samples of brain tumors. In addition, we propose a semi-supervised spatial attention strategy to guide spatial information of features at the pixel level in tumor generation. Furthermore, we add spectral normalization to prevent the discriminator from mode collapse and stabilize the training procedure. Finally, to resolve an inapplicability problem in the segmentation task, we further propose an application strategy of using this data augmentation model to achieve more accurate medical image segmentation with limited data. Experimental studies on two public brain tumor datasets (BraTS and TCIA) show that the proposed CDA-GAN model greatly outperforms the state-of-the-art generative data augmentation in both practical medical image classification tasks and segmentation tasks; e.g. CDA-GAN is 0.50%, 1.72%, 2.05%, and 0.21% better than the best SOTA baseline in terms of ACC, AUC, Recall, and F1, respectively, in the classification task of BraTS, while its improvements w.r.t. the best SOTA baseline in terms of Dice, Sens, HD95, and mIOU, in the segmentation task of TCIA are 2.50%, 0.90%, 14.96%, and 4.18%, respectively.

Integrated single-cell transcriptomics reveals the hypoxia-induced inflammation-cancer transformation in NASH-derived hepatocellular carcinoma.

Non-alcoholic fatty liver disease (NAFLD) has emerged as the primary risk factor for hepatocellular carcinoma (HCC), owing to improved vaccination rates of Hepatitis B and the increasing prevalence of metabolic syndrome related to obesity. Although the importance of innate and adaptive immune cells has been emphasized, the malignant transformation of hepatocytes and their intricate cellular network with the immune system remain unclear. The study incorporated four single-cell transcriptomic datasets of liver tissues covering healthy and NAFLD-related disease status. To identify the subsets and functions of hepatocytes and macrophages, we employed differential composition analysis, functional enrichment analysis, pseudotime analysis, and scenic analysis. Furthermore, an experimental mouse model for the transformation of nonalcoholic steatohepatitis into hepatocellular carcinoma was established for validation purposes. We defined CYP7A1+ hepatocytes enriched in precancerous lesions as 'Transitional Cells' in the progression from NAFLD to HCC. CYP7A1+ hepatocytes upregulated genes associated with stress response, inflammation and cancer-associated pathways and downregulated the normal hepatocyte signature. We observed that hypoxia activation accompanied the entire process of inflammation-cancer transformation. Hepatocyte-derived HIF1A was gradually activated during the progression of NAFLD disease to adapt to the hypoxic microenvironment and hepatocytes under hypoxic environment led to changes in the metabolism, proliferation and angiogenesis, promoting the occurrence of tumours. Meanwhile, hypoxia induced the polarization of RACK1+ macrophages that enriched in the liver tissues of NASH towards immunosuppressed TREM2+ macrophages. Moreover, immunosuppressive TREM2+ macrophages were recruited by tumour cells through the CCL15-CCR1 axis to enhance immunosuppressive microenvironment and promote NAFLD-related HCC progression. The study provides a deep understanding of the development mechanism of NAFLD-related HCC and offers theoretical support and experimental basis for biological targets, drug research, and clinical application.

OsALB3 Is Required for Chloroplast Development by Promoting the Accumulation of Light-Harvesting Chlorophyll-Binding Proteins in Rice.

ALBINO3 (ALB3) protein functions in the insertion and assembly of thylakoid membrane protein complexes and plays a critical role for chloroplast development in Arabidopsis. However, the biological function of ALB3 homologs in rice, OsALB3, remains elusive. Here, we identified a rice mutant, yellow leaf and lethal1 (yll1), that displayed yellow leaves and died at the seedling stage. The content of chlorophyll in yll1, compared with wild type, was significantly decreased. Transmission electron microscopy observation shows that the chloroplast of yll1 lacks thylakoid membranes. The causal mutation, which is located in OsALB3, was isolated by Mutmap+ combined with a simple mutation filtering process. Knockout of OsALB3 leads to yellow leaves and seedling lethality, mimicking the phenotype of yll1. OsALB3 is widely expressed and OsALB3 is chloroplast-localized. Moreover, the content of light-harvesting chlorophyll-binding proteins in yll1 is reduced. Together, our study demonstrated the essential role of OsALB3 in chloroplast development and provided clues to the possible conserved molecular function of ALB3 in rice.

Epidermal growth factor receptor activation is essential for kidney fibrosis development.

Fibrosis is the progressive accumulation of excess extracellular matrix and can cause organ failure. Fibrosis can affect nearly every organ including kidney and there is no specific treatment currently. Although Epidermal Growth Factor Receptor (EGFR) signaling pathway has been implicated in development of kidney fibrosis, underlying mechanisms by which EGFR itself mediates kidney fibrosis have not been elucidated. We find that EGFR expression increases in interstitial myofibroblasts in human and mouse fibrotic kidneys. Selective EGFR deletion in the fibroblast/pericyte population inhibits interstitial fibrosis in response to unilateral ureteral obstruction, ischemia or nephrotoxins. In vivo and in vitro studies and single-nucleus RNA sequencing analysis demonstrate that EGFR activation does not induce myofibroblast transformation but is necessary for the initial pericyte/fibroblast migration and proliferation prior to subsequent myofibroblast transformation by TGF-ß or other profibrotic factors. These findings may also provide insight into development of fibrosis in other organs and in other conditions.

Seasonal resource selection of free-ranging Zhongwei goats in the semi-arid grassland.

Goats rarely move and forage randomly. They tend to move in ways generally influenced by biotic and abiotic factors, respectively. However, few studies have explored the foraging behaviour of goats in the absence of predation and human disturbance. Based on step selection function modelling framework, Normalised Difference Vegetation Index, vegetation surveys, and Global Positioning System tracking of 124 free-ranging domestic adult male Zhongwei goats over one year (2016-2017) were used to assess how biotic and abiotic environmental factors affected their spatiotemporal distribution, and developed a conceptual model to represent the goats' trade-off between forage quantity and preference at different seasons, in the semi-arid grassland of Loess Plateau of 1 178 hectare. The results showed that spatial distributions of goats responded to spatiotemporal variation of biotic factors rather than abiotic factors of elevation, slope and solar radiation, which indicated that biotic factors were of priority to abiotic factors in the foraging process for the goats. According to the season changing, the goats positively used areas with higher forage quantity in the spring and winter, areas of higher forage quantity and preferred species in summer, and areas of abundance of preferred species in autumn. We developed a model to describe the phenomenon that the goats selected areas with higher preferred species only when the forage quantity was plentiful, otherwise they selected areas with higher forage quantity. Better understanding of the patterns and drivers of spatiotemporal distribution of the goats can improve our ability to predict foraging behaviour of livestock in heterogeneous environment and lead to better management practices and policies for the sustainability of these semi-arid landscapes and associated ecosystem services.