A large-scale retrospective study enabled deep-learning based pathological assessment of frozen procurement kidney biopsies to predict graft loss and guide organ utilization.

Lesion scores on procurement donor biopsies are commonly used to guide organ utilization for deceased-donor kidneys. However, frozen sections present challenges for histological scoring, leading to inter- and intra-observer variability and inappropriate discard. Therefore, we constructed deep-learning based models to recognize kidney tissue compartments in hematoxylin & eosin-stained sections from procurement needle biopsies performed nationwide in years 2011-2020. To do this, we extracted whole-slide abnormality features from 2431 kidneys and correlated with pathologists' scores and transplant outcomes. A Kidney Donor Quality Score (KDQS) was derived and used in combination with recipient demographic and peri-transplant characteristics to predict graft loss or assist organ utilization. The performance on wedge biopsies was additionally evaluated. Our model identified 96% and 91% of normal/sclerotic glomeruli respectively; 94% of arteries/arterial intimal fibrosis; 90% of tubules. Whole-slide features of Sclerotic Glomeruli (GS)%, Arterial Intimal Fibrosis (AIF)%, and Interstitial Space Abnormality (ISA)% demonstrated strong correlations with corresponding pathologists' scores of all 2431 kidneys, but had superior associations with post-transplant estimated glomerular filtration rates in 2033 and graft loss in 1560 kidneys. The combination of KDQS and other factors predicted one- and four-year graft loss in a discovery set of 520 kidneys and a validation set of 1040 kidneys. By using the composite KDQS of 398 discarded kidneys due to "biopsy findings", we suggest that if transplanted, 110 discarded kidneys could have had similar survival to that of other transplanted kidneys. Thus, our composite KDQS and survival prediction models may facilitate risk stratification and organ utilization while potentially reducing unnecessary organ discard.

Investigating the therapeutic effects and mechanisms of Carthamus tinctorius L.-derived nanovesicles in atherosclerosis treatment.

BACKGROUND: Carthamus tinctorius L., a traditional herbal medicine used for atherosclerosis (AS), lacks a clear understanding of its therapeutic mechanisms. This study aimed to investigate the therapeutic effects and mechanisms of Carthamus tinctorius L.-derived nanovesicles (CDNVs) in AS treatment. METHODS: CDNVs were isolated and characterized using improved isolation methods. Transmission electron microscopy, nanoparticle tracking analysis, and protein analysis confirmed their morphology, size, and protein composition. Small RNA sequencing was performed to identify the miRNA profile of CDNVs, and bioinformatics analysis was used to determine their potential biological roles. In vivo biodistribution and toxicity studies were conducted in mice to assess the stability and safety of orally administered CDNVs. The anti-atherosclerotic effects of CDNVs were evaluated in ApoE-/- mice through plaque burden analysis. The protective effects of CDNVs on ox-LDL-treated endothelial cells were assessed through proliferation, apoptosis, reactive oxygen species activation, and monocyte adhesion assays. miRNA and mRNA sequencing of CDNV-treated endothelial cells were performed to explore their regulatory effects and potential target genes. RESULTS: CDNVs were successfully isolated and purified from Carthamus tinctorius L. tissue lysates. They exhibited a saucer-shaped or cup-shaped morphology, with an average particle size of 142.6 ± 0.7 nm, and expressed EV markers CD63 and TSG101. CDNVs contained proteins, small RNAs, and metabolites, including the therapeutic compound HSYA. Small RNA sequencing identified 95 miRNAs, with 10 common miRNAs accounting for 72.63% of the total miRNAs. These miRNAs targeted genes involved in cell adhesion, apoptosis, and cell proliferation, suggesting their relevance in cardiovascular disease. Orally administered CDNVs were stable in the gastrointestinal tract, absorbed into the bloodstream, and accumulated in the liver, lungs, heart, and aorta. They significantly reduced the burden of atherosclerotic plaques in ApoE-/- mice and exhibited superior effects compared to HSYA. In vitro studies demonstrated that CDNVs were taken up by HUVECs, promoted proliferation, attenuated ox-LDL-induced apoptosis and ROS activation, and reduced monocyte adhesion. CDNV treatment resulted in significant changes in miRNA and mRNA expression profiles of HUVECs, with enrichment in inflammation-related genes. CXCL12 was identified as a potential direct target of miR166a-3p. CONCLUSION: CDNVs isolated from Carthamus tinctorius L. tissue lysates represent a promising oral therapeutic option for cardiovascular diseases. The delivery of miRNAs by CDNVs regulates inflammation-related genes, including CXCL12, in HUVECs, suggesting their potential role in modulating endothelial inflammation. These findings provide valuable insights into the therapeutic potential of CDNVs and their miRNAs in cardiovascular disease.

Effect of different injection rates and doses of contrast medium on the image quality of computed tomographic angiography in African grey parrots (Psittacus erithacus).

BACKGROUND: Atherosclerosis is a common cardiovascular disease in parrots but the antemortem diagnosis is challenging. In human medicine, computed tomography angiography (CTA) has been used widely for the diagnosis of atherosclerosis. By adjusting the injection rate and total dose of contrast medium, the image quality can be improved. To test the effects of different injection conditions on the image quality of major arteries, 10 African grey parrots (Psittacus erithacus) were used. Three injection rates (0.3, 0.4, 0.5 mL/s) and three doses (740, 370, 222 mg of iodine/bird) were tested while the other variables of the studies were fixed. RESULT: A higher injection dose led to a significantly higher attenuation, image noise and diameter, with a lower signal-to-noise ratio and contrast-to-noise ratio of the six major arteries. The 370 mg of iodine/bird group showed significantly better subjective image quality. Furthermore, with increasing injection rates, the prevalence of heterogeneity decreased. However, we found an increased risk of injection failure for the 0.5 mL/s groups. CONCLUSION: We recommend a combination of 370 mg of iodine/bird with 0.4 mL/s for clinical use to achieve better image quality for CTA.

Experience of the Wang procedure in treating pectus excavatum in two hundred fifty-six paediatric patients.

INTRODUCTION: To analyze and summarize the orthopaedic effect and application experience of the Wang procedure in the treatment of pectus excavatum in paediatric patients. METHODS: The clinical data of 256 children ranging from 0.83~14 years (4.89±2.83 years) who underwent the Wang procedure for pectus excavatum from January 2017 to September 2020 in our hospital were analyzed retrospectively. A 1~2-cm incision was made in front of the xiphoid, and a tunnel was constructed on the deep surface of the thoracic cage. Steel wires were inserted through the bilateral costal arch and the lower sternum, and a steel bar was placed in the tunnel. The wires were pulled taut and fixed to the bar, and the incision was sutured. RESULTS: All the procedures were performed using one steel bar. The range of the procedure duration, the intra-operative bleeding volume, and the hospitalization stays of the patients were 18 to 45 (24.02±4.89) minutes, one to ten (2.16±1.68) mL, and three to nine days (5.71±1.35 days) respectively. Post-operative pneumothorax occurred in three cases without other complications. All the cases received follow-up for one to 45 months after discharge, during which six cases experienced poor wound healing, removed steel plate in 82 cases, and three cases of pectus excavatum recurrence. CONCLUSIONS: The Wang procedure is a good option for treating pectus excavatum, secondary pectus excavatum, or recurrent pectus excavatum in paediatric patients.

Dynamic transcriptome landscape of Paragonimus proliferus developmental stages in the rat lungs.

Paragonimus proliferus, a lung fluke of the genus Paragonimus, was first reported in Yunnan province, China. P. proliferus can infect Sprague-Dawley (SD) rats and cause lung damage, but there is still no direct evidence of human infection. Until now, there has been a lack of studies on P. proliferus parasitism and development in mammalian lung tissue. The aim of this study was to perform transcriptomic profiling of P. proliferus at different developmental stages. SD rats were infected with P. proliferus metacercariae obtained from crabs; worms isolated from the lungs at different time points as well as metacercariae were subjected to whole transcriptome sequencing. Overall, 34,403 transcripts with the total length of 33,223,828 bp, average length of 965 bp, and N50 of 1833 bp were assembled. Comparative analysis indicated that P. proliferus, similar to other Paragonimus spp., expressed genes related to catabolism, whereas P. proliferus-specific transcripts were related to the maintenance of cellular redox homeostasis, sensitivity to bacteria, and immune response. Transcriptional dynamics analysis revealed that genes involved in the regulation of catabolism and apoptosis had stable expression over the P. proliferus life cycle, whereas those involved in development and immune response showed time-dependent changes. High expression of genes associated with immune response corresponded to that of genes regulating the sensitivity to bacteria and immune protection. We constructed a P. proliferus developmental model, including the development of the body, suckers, blood cells, reproductive and tracheal systems, lymph, skin, cartilage, and other tissues and organs, and an immune response model, which mainly involved T cells and macrophages. Our study provides a foundation for further research into the molecular biology and infection mechanism of P. proliferus.

Correction to: Organic Matter Pollution During the Spring Thaw in Hulun Lake Basin: Contribution of Multiform Human Activities.

In the original publication of the article, there was an error in the name of institution. The incorrect name of institution "Nanjing Institute of Environmental Sciences, Ministry of Environmental Protection, 8, Jiangwangmiao Road, XuanWu District, 210042 Nanjing, People's Republic of China" should be revised to "Nanjing Institute of Environmental Sciences, Ministry of Ecology and Environmental, 8, Jiangwangmiao Road, XuanWu District, 210042 Nanjing, People's Republic of China". The institution was still the same, but the name of the institution was changed.

Organic Matter Pollution During the Spring Thaw in Hulun Lake Basin: Contribution of Multiform Human Activities.

It has recently been reported that plateau lakes have been seriously polluted by organic matter, however, the sources of this organic matter and their relative contributions remain unknown. In this study, to determine the sources and composition of the organic matter in the Hulun Lake basin during the spring-thaw period, a total of twenty-three sampling sites were investigated. Results showed high levels of organic matter pollution in the surface water of Hulun Lake, with an average COD values of 119.35 mg L-1. Organic matter came from natural sources as well as a variety of anthropogenic activities. The direct sources included urbanization, industrial and residential wastewater discharge, and emission from burning fossile fuels. A large indirect source was organic matter from tumbleweed decomposition, which had increased due to desertification caused by overgrazing. The principal component analysis showed that organic matter from Hulun lake shared composition and sources with the upstream sections of the natural tributaries and the downstream section of the artificial tributary. The artificial inflow river contributed more organic matter than the other tributaries. Notably, a large portion of organic matter in Hulun Lake came from decomposing tumbleweed concentrated in the downstream section of one of the natural rivers. New indirect consequences of human activities must be factored into the rule and regulations that protect plateau lake ecosystems alongside the direct effects of established human activities.

EGF-induced C/EBPß participates in EMT by decreasing the expression of miR-203 in esophageal squamous cell carcinoma cells.

Epithelial-mesenchymal transition (EMT) is a developmental program that is associated with esophageal squamous cell carcinoma (ESCC) progression and metastasis. Recently, C/EBPß has been reported to be an EMT inducer in cancer. However, the detailed molecular mechanisms remain unclear. Here, we report for the first time, that the truncated CCAAT-enhancer-binding protein ß (C/EBPß) LIP isoform is abnormally overexpressed and correlated with cancer metastasis in clinical specimens of human ESCC. Furthermore, we demonstrate that C/EBPß LIP mediates epithelial growth factor (EGF)-induced EMT and increases migration and invasion of esophageal cancer cells in a manner that is dependent on miR-203 inactivation. Finally, we identified miR-203 as a direct target of C/EBPß LIP. Disruption of C/EBPß LIP attenuated the EGF-mediated decrease in miR-203, whereas overexpression of C/EBPß LIP alone markedly suppressed miR-203. In addition, we demonstrated that C/EBPß LIP inhibited miR-203 transcription by directly interacting with a conserved distal regulatory element upstream of the miR-203 locus, and in doing so, orchestrated chromatin remodeling. In conclusion, our results have revealed a new regulatory mechanism that involves C/EBPß-LIP-mediated downregulation of miR-203, which plays a key role in EMT and metastasis.

High-Temperature Superconductivity in Single-Unit-Cell FeSe Films on Anatase TiO_{2}(001).

We report on the observation of high-temperature (T_{c}) superconductivity and magnetic vortices in single-unit-cell FeSe films on anatase TiO_{2}(001) substrate by using scanning tunneling microscopy. A systematic study and engineering of interfacial properties has clarified the essential roles of substrate in realizing the high-T_{c} superconductivity, probably via interface-induced electron-phonon coupling enhancement and charge transfer. By visualizing and tuning the oxygen vacancies at the interface, we find their very limited effect on the superconductivity, which excludes interfacial oxygen vacancies as the primary source for charge transfer between the substrate and FeSe films. Our findings have placed severe constraints on any microscopic model for the high-T_{c} superconductivity in FeSe-related heterostructures.

Mapping the Electronic Structure of Each Ingredient Oxide Layer of High-T\{c} Cuprate Superconductor Bi{2}Sr{2}CaCu{2}O{8+δ}.

Understanding the mechanism of high transition temperature (T{c}) superconductivity in cuprates has been hindered by the apparent complexity of their multilayered crystal structure. Using a cryogenic scanning tunneling microscopy (STM), we report on layer-by-layer probing of the electronic structures of all ingredient planes (BiO, SrO, CuO{2}) of Bi{2}Sr{2}CaCu_2}O{8+δ} superconductor prepared by argon-ion bombardment and annealing technique. We show that the well-known pseudogap (PG) feature observed by STM is inherently a property of the BiO planes and thus irrelevant directly to Cooper pairing. The SrO planes exhibit an unexpected van Hove singularity near the Fermi level, while the CuO{2} planes are exclusively characterized by a smaller gap inside the PG. The small gap becomes invisible near T{c}, which we identify as the superconducting gap. The above results constitute severe constraints on any microscopic model for high T{c} superconductivity in cuprates.

Transcriptional regulation of miR-146b by C/EBPß LAP2 in esophageal cancer cells.

Recent clinical study indicated that up-regulation of miR-146b was associated with poor overall survival of patients in esophageal squamous cell carcinoma. However, the underlying mechanism of miR-146b dysregulation remains to be explored. Here we report that miR-146b promotes cell proliferation and inhibits cell apoptosis in esophageal cancer cell lines. Mechanismly, two C/EBPß binding motifs are located in the miR-146b promoter conserved region. Among the three isoforms of C/EBPß, C/EBPß LAP2 positively regulated miR-146b expression and increases miR-146b levels in a dose-dependent manner through transcription activation of miR-146b gene. Together, these results suggest a miR-146b regulatory mechanism involving C/EBPß, which may contribute to the up-regulation of miR-146b in esophageal squamous cell carcinoma.

Exotic Animal Practice in East Asia: A Retrospective Study of Species Distribution and Their Common Diseases at 2 Exotics-only Veterinary Clinics in the East Asia Region.

The objective of this clinical retrospective study was to analyze the prevalence and distribution of different avian and exotic animals presented to 2 exotics-only veterinary hospital in Hong Kong and Taiwan over a 1 year period. Exotic companion mammals, predominated by rabbits (Oryctolagus cuniculus) that were often diagnosed with fractures, were the most commonly presented group of patients in the hospital in Hong Kong while second most of that in Taiwan, with dental disease being commonly presented in the species. This study provided a general overview of avian and exotic patients presented to exotics-only practices in the East Asia region.

Effects of Substrate Composition on the Growth Traits of Grafted Seedling in Macadamia (Macadamia integrifolia) Nuts.

Macadamia nut plantings in China are expanding year by year. In order to breed and promote superior varieties, this study analyzed the effects of different rootstocks and scions on the survival rate of grafted seedlings, and then selected the best substrate composition for plant growth. The results showed that the survival rate of the HAES788 variety as rootstock and Guire No. 1 as scion was the highest, reaching 96%. The optimal grafting time in December was better than that in March. Furthermore, among 16 substrate formulations, T12, T13, T15, and T16 had advantages of agglomerated soil and more well-developed root systems compared to the CK made of loess. The plant height, stem diameter, leaf length, leaf width, and dry weight of the aboveground and underground parts of the grafted seedlings planted in these substrate formulations were significantly higher than those plants planted in the CK. In addition, the substrate formulations T12, T13, T15, and T16 significantly improved the organic matter, total nitrogen, and total potassium content of the substrate soils, but little improvement was observed for total phosphorus content after 13 months. Overall, macadamia grafting times are best in December, with HAES788 and Guire No. 1 being the best rootstock and scion. The optimal substrate formulations are T12, T13, T15, and T16. This study provides a solid foundation for the production of high-quality macadamia plants.

Near-freezing temperature suppresses avocado (Persea americana Mill.) fruit softening and chilling injury by maintaining cell wall and reactive oxygen species metabolism during storage.

To enhance the postharvest quality of avocado (Persea americana Mill.) fruit, this study investigates alterations in cell wall metabolism and reactive oxygen species (ROS) metabolism during near-freezing temperature (NFT) storage, and explores their impact on fruit softening. The fruit was stored at 25 °C, 5 °C, 2 °C, and NFT, respectively. NFT storage retarded firmness loss and chilling injury in comparison with 25 °C, 5 °C, and 2 °C. NFT storage delayed the decrease of ionic-soluble pectin (ISP) and cellulose (CLL) contents by suppressing cell wall degradation enzyme activities. Correlation analysis showed that cell wall degradation enzyme activities were positively correlated to rates of ethylene release and respiration. Moreover, NFT storage maintained higher levels of DPPH and ABTS scavenging abilities, activities of superoxide dismutase, peroxidase, and catalase, as well as ascorbate-glutathione cycle (ascorbic acid, glutathione, glutathione disulfide, ascorbate peroxidase, cycle-related enzymes), thereby inhibited the increase of ROS content, malondialdehyde content, and cell membrane permeability. Fruit firmness and chilling injury were correlated with the contents of hydrogen (H2O2), superoxide anion (O2.-), ISP, and CLL. These results suggested that NFT could suppress fruit softening and chilling injury by inhibiting cell wall degradation through delaying respiration and ethylene production and suppressing ROS production via activation of antioxidant systems, thereby maintaining quality and prolonged storage life during avocado fruit storage.

Identifying spatial variability of water chemical characteristics and groundwater discharge in Hulun Lake integrated remote sensing data and chemical components.

The frozen period interaction of groundwater and lakes is crucial for hydrological properties and aquatic ecology in cold and arid regions. In this study, we investigate the spatial hydrochemical characteristics, influencing factors in the Hulun Lake basin. The hydrochemical type of lake water exhibits Na-HCO3-SO4-Cl, while river shows a primary classification of Na-Ca-HCO3. Groundwater in the eastern and western regions is characterized by Na-SO4-Cl and Na-HCO3, respectively. Silicic acid and ion exchange predominantly influence groundwater chemistry in the western region, whereas evaporation and concentration play a major role in the eastern region. Total dissolved solids, Cl-, and F- emerge as the primary influencing factors of hydrochemical components in the Hulun Lake basin. Ion content decreased from the southern to the northern region, with the lowest value occurring near the Urson River. The high-temperature water body is primarily distributed in the central and southern regions of the lake. Based on characteristic ions and partial characteristics of ice surface temperature, the potential groundwater discharge areas near the inlet of the Xinkai River, the central and southern region are determined. This study reveals the hydrochemical characteristics, vertical ice distribution, and provides a scientific foundation for water resource management in cold and arid regions.

Research on the evaluation method of steam power system operation status based on the theory of deterioration degree and health value.

The evaluation of the steam power system is very important for the operator to understand the operating status of the system, but the lack of consideration of the fuzziness of the complex system and the impact of the indicator parameters on the whole system makes the evaluation difficult. In this paper, an indicator system for evaluating the operation status of the experimental supercharged boiler is established. After discussing several methods of parameter standardization and weight correction, a comprehensive evaluation method based on the deterioration degree and health value is proposed while considering the deviation of the indicator and the fuzziness of the system. The comprehensive evaluation method, the linear weighting method and the fuzzy comprehensive evaluation method are respectively used to evaluate the experimental supercharged boiler. The comparison of the three methods shows that the comprehensive evaluation method is more sensitive to minor anomalies and faults and can draw quantitative health assessment conclusions.

High exogenous humus inhibits greenhouse gas emissions from steppe lakes.

Although freshwater lakes are considered to be an important source of greenhouse gas (GHG) emissions, the potential driving mechanisms of such emissions are not well understood, especially in steppe lakes. In this study, the GHG emission characteristics in Hulun Lake Basin, including Hulun Lake, Beier Lake, Wulannuoer Lake, and their surrounding watersheds were investigated. The average methane (CH4) and nitrous oxide (N2O) emission fluxes released from rivers were 67.84 ± 20.53 and 0.11 ± 0.04 µg m-2·min-1, which were larger than those of lakes, with values of 28.60 ± 13.02 and 0.06 ± 0.02 µg m-2·min-1, respectively. Conversely, the average carbon dioxide (CO2) emission flux from lakes (1816.58 ± 498.98 µg m-2·min-1) was higher than that of rivers of (1795.41 ± 670.49 µg m-2·min-1). The water in Hulun Lake Basin was rich in organic matter and had a high chemical oxygen demand (COD). Three-dimensional fluorescence combined with a parallel factor analysis (3D-EEM-PARAFAC) demonstrated that the organic matter was composed of four humus types (from Component 1 (C1) to Component 4 (C4)), of which, C1 and C4 were terrestrial humus. The fluorescence index (FI) and humification index (HIX) indicated that the organic matter in the water was mainly imported from exogenous humus. The GHG emission fluxes were negatively correlated with these four components, indicating that GHG emissions were mainly affected by the organic matter source and components, and humus was the most important factor that inhibited GHG emissions in steppe lakes. However, the GHG emission flux was relatively high in some areas of the lake, especially in areas with high nutrient levels or where algal blooms occurred, as evidenced by the significantly positive correlations with total nitrogen (TN), total phosphorous (TP), and chlorophyll-a (chl-a) (p < 0.01). The algae-derived organic matter simulated the decomposition of refractory humus, thus, promoting GHG emissions. These findings are crucial for accurately evaluating the GHG emission fluxes, understanding the carbon cycle, and proposing future management strategies for steppe lakes.

Saikosaponin B2 ameliorates depression-induced microglia activation by inhibiting ferroptosis-mediated neuroinflammation and ER stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Saikosaponins B2 (SSB2) is one of the main active components isolated from Radix Bupleuri (Bupleurum chinense DC.), a herb widely used of traditional Chinese medicine. It has been used for the treatment of depression for more than two thousand years. However, the molecular mechanisms remain to be determined. AIM OF THE STUDY: In this study, we evaluated the anti-inflammatory effect and elucidated underlying molecular mechanisms of SSB2 in LPS-induced primary microglia and CUMS-induced mice model of depression. METHOD: The effects of SSB2 treatment were investigated both in vitro and in vivo. The chronic unpredictable mild stimulation (CUMS) procedure was applied to establish the animal model of depression. Behavioural tests were used to evaluate the depressive-like behaviors in CUMS-exposed mice, including sucrose preference test, open field test, tail suspension test, and forced swimming test. The GPX4 gene of microglia was silenced using shRNA, and inflammatory cytokines were determined by Western Blot and immunofluorescence analysis. Endoplasmic reticulum stress and ferroptosis-related markers were detected by qPCR, flow cytometry and confocal microscopy. RESULT: SSB2 reversed depressive-like behaviours in CUMS-exposed mice and relieved central neuroinflammation and ameliorated hippocampal neural damage. SSB2 alleviated LPS-induced activation of microglia through the TLR4/NF-κB pathway. LPS-induced ferroptosis, with increased levels of ROS, intracellular Fe2+, mitochondrial membrane potential, lipid peroxidation, GSH, SLC7A11, FTH, GPX4 and Nrf2, and decreased transcription levels of ACSL4 and TFR1, was attenuated with SSB2 treatment in primary microglia cells. GPX4 knockdown activated ferroptosis, induced endoplasmic reticulum (ER) stress, and abrogated the protective effects of SSB2. Further, SSB2 attenuated ER stress, balanced calcium homeostasis, reduced lipid peroxidation and intracellular Fe2+ content by regulating the level of intracellular Ca2+. CONCLUSIONS: Our study suggested that SSB2 treatment can inhibit ferroptosis, maintain calcium homeostasis, relieve endoplasmic reticulum stress and attenuate central neuroinflammation. SSB2 exhibited anti-ferroptosis and anti-neuroinflammatory effects through the TLR4/NF-κB pathway in a GPX4-dependent manner.

HCK induces macrophage activation to promote renal inflammation and fibrosis via suppression of autophagy.

Renal inflammation and fibrosis are the common pathways leading to progressive chronic kidney disease (CKD). We previously identified hematopoietic cell kinase (HCK) as upregulated in human chronic allograft injury promoting kidney fibrosis; however, the cellular source and molecular mechanisms are unclear. Here, using immunostaining and single cell sequencing data, we show that HCK expression is highly enriched in pro-inflammatory macrophages in diseased kidneys. HCK-knockout (KO) or HCK-inhibitor decreases macrophage M1-like pro-inflammatory polarization, proliferation, and migration in RAW264.7 cells and bone marrow-derived macrophages (BMDM). We identify an interaction between HCK and ATG2A and CBL, two autophagy-related proteins, inhibiting autophagy flux in macrophages. In vivo, both global or myeloid cell specific HCK-KO attenuates renal inflammation and fibrosis with reduces macrophage numbers, pro-inflammatory polarization and migration into unilateral ureteral obstruction (UUO) kidneys and unilateral ischemia reperfusion injury (IRI) models. Finally, we developed a selective boron containing HCK inhibitor which can reduce macrophage pro-inflammatory activity, proliferation, and migration in vitro, and attenuate kidney fibrosis in the UUO mice. The current study elucidates mechanisms downstream of HCK regulating macrophage activation and polarization via autophagy in CKD and identifies that selective HCK inhibitors could be potentially developed as a new therapy for renal fibrosis.

Surgical treatment of a 36-year-old patient with asphyxiating thoracic dysplasia.

Asphyxiating thoracic dysplasia is a rare and dangerous genetic disease. Many children with this disease die early in life of severe hypoxia, and it is extremely rare that they survive to adulthood. We recently treated a 36-year-old patient who had asphyxiating thoracic dysplasia with a special surgical method and achieved satisfactory results. A review of the literature showed that this patient is the oldest surviving person with this condition.