Endothelial Cell-Derived Extracellular Vesicles Promote Aberrant Neutrophil Trafficking and Subsequent Remote Lung Injury.

The development of acute respiratory distress syndrome (ARDS) in sepsis is associated with substantial morbidity and mortality. However, the molecular pathogenesis underlying sepsis-induced ARDS remains elusive. Neutrophil heterogeneity and dysfunction contribute to uncontrolled inflammation in patients with ARDS. A specific subset of neutrophils undergoing reverse transendothelial migration (rTEM), which is characterized by an activated phenotype, is implicated in the systemic dissemination of inflammation. Using single-cell RNA sequencing (scRNA-seq), it identified functionally activated neutrophils exhibiting the rTEM phenotype in the lung of a sepsis mouse model using cecal ligation and puncture. The prevalence of neutrophils with the rTEM phenotype is elevated in the blood of patients with sepsis-associated ARDS and is positively correlated with disease severity. Mechanically, scRNA-seq and proteomic analys revealed that inflamed endothelial cell (EC) released extracellular vesicles (EVs) enriched in karyopherin subunit beta-1 (KPNB1), promoting abluminal-to-luminal neutrophil rTEM. Additionally, EC-derived EVs are elevated and positively correlated with the proportion of rTEM neutrophils in clinical sepsis. Collectively, EC-derived EV is identified as a critical regulator of neutrophil rTEM, providing insights into the contribution of rTEM neutrophils to sepsis-associated lung injury.

A novel model for predicting postoperative liver metastasis in R0 resected pancreatic neuroendocrine tumors: integrating computational pathology and deep learning-radiomics.

BACKGROUND: Postoperative liver metastasis significantly impacts the prognosis of pancreatic neuroendocrine tumor (panNET) patients after R0 resection. Combining computational pathology and deep learning radiomics can enhance the detection of postoperative liver metastasis in panNET patients. METHODS: Clinical data, pathology slides, and radiographic images were collected from 163 panNET patients post-R0 resection at Fudan University Shanghai Cancer Center (FUSCC) and FUSCC Pathology Consultation Center. Digital image analysis and deep learning identified liver metastasis-related features in Ki67-stained whole slide images (WSIs) and enhanced CT scans to create a nomogram. The model's performance was validated in both internal and external test cohorts. RESULTS: Multivariate logistic regression identified nerve infiltration as an independent risk factor for liver metastasis (p < 0.05). The Pathomics score, which was based on a hotspot and the heterogeneous distribution of Ki67 staining, showed improved predictive accuracy for liver metastasis (AUC = 0.799). The deep learning-radiomics (DLR) score achieved an AUC of 0.875. The integrated nomogram, which combines clinical, pathological, and imaging features, demonstrated outstanding performance, with an AUC of 0.985 in the training cohort and 0.961 in the validation cohort. High-risk group had a median recurrence-free survival of 28.5 months compared to 34.7 months for the low-risk group, showing significant correlation with prognosis (p < 0.05). CONCLUSION: A new predictive model that integrates computational pathologic scores and deep learning-radiomics can better predict postoperative liver metastasis in panNET patients, aiding clinicians in developing personalized treatments.

Human liver derived mesenchymal stromal cells ameliorate murine ischemia-induced inflammation through macrophage polarization.

Introduction: The immunomodulatory properties of mesenchymal stromal cells (MSC) have been well-characterized in in-vitro and in-vivo models. We have previously shown that liver MSC (L-MSC) are superior inhibitors of T-cell activation/proliferation, NK cell cytolytic function, and macrophage activation compared to adipose (A-MSC) and bone marrow MSC (BM-MSC) in-vitro. Method: To test these observations in-vivo, we infused these types of MSC into mice with unilateral renal artery stenosis (RAS), an established model of kidney inflammation. Unilateral RAS was induced via laparotomy in 11-week-old, male 129-S1 mice under general anesthesia. Control mice had sham operations. Human L-MSC, AMSC, and BM-MSC (5x105 cells each) or PBS vehicle were injected intra-arterially 2 weeks after surgery. Kidney morphology was studied 2 weeks after infusion using micro-MRI imaging. Renal inflammation, apoptosis, fibrosis, and MSC retention were studied ex-vivo utilizing western blot, immunofluorescence, and immunohistological analyses. Results: The stenotic kidney volume was smaller in all RAS mice, confirming significant injury, and was improved by infusion of all MSC types. All MSC-infused groups had lower levels of plasma renin and proteinuria compared to untreated RAS. Serum creatinine improved in micetreated with BM- and L-MSC. All types of MSC located to and were retained within the stenotic kidneys, but L-MSC retention was significantly higher than A- and BM-MSC. While all groups of MSC-treated mice displayed reduced overall inflammation and macrophage counts, L-MSC showed superior potency in-vivo at localizing to the site of inflammation and inducing M2 (reparative) macrophage polarization to reduce inflammatory changes. Discussion: These in-vivo findings extend our in-vitro studies and suggest that L-MSC possess unique anti-inflammatory properties that may play a role in liver-induced tolerance and lend further support to their use as therapeutic agents for diseases with underlying inflammatory pathophysiology.

Monocarboxylate transporter 4 facilitates Mycobacterium tuberculosis survival through NF-κB p65-mediated interleukin-10 production.

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb) infection, with the highest single-cause mortality. Monocarboxylate transporter 4 (Mct4) transports intracellular lactate outside, but its role in regulating host immune response against Mtb infection remains unknown. Mct4 expression was upregulated in Mtb-infected macrophages and in patients with TB. Mct4 silencing/deficiency significantly decreased Mtb survival in macrophages and in lungs and spleens of mice, while Mct4 overexpression facilitated Mtb survival in macrophages. Furthermore, Mct4 promoted intracellular lactate transport, nuclear factor κB (NF-κB) p65 activation, and interleukin-10 (IL-10) production upon Mtb infection. Mechanistically, IL-10 silencing and IL-10-neutralizing antibody blocked Mct4 overexpressing increased Mtb survival. Replenishing lactate and NF-κB p65 inhibitor JSH23 treatment could inhibit Mct4 overexpressing increased NF-κB p65 activation, IL-10 production, and Mtb survival in macrophages. This study demonstrates that Mct4 promotes Mtb survival through restricting intracellular lactate accumulation to promote NF-κB p65-mediated IL-10 production and suggests Mct4-NF-κB p65-IL-10 axis a potential target for TB treatment.

[Evolution Trend of Water Quality in the Inner Mongolia Section of the Yellow River from 2003 to 2020].

The aim of this study was to comprehensively understand the water environment quality status and its change trend in the Inner Mongolia section of the Yellow River Basin. To analyze the water quality in recent years,the water quality data in the Yellow River basin from 2003 to 2020 were firstly collected from five typical monitoring stations．Various data analysis methods, including principal component analysis, cluster analysis, and a long short-term memory model, were used along with an improved comprehensive water quality identification index to explore the spatiotemporal characteristics of water quality in the Yellow River Basin. The results showed that the overall water quality in the basin has improved and stabilized over time. In terms of temporal variation, there was a distinction between the wet season and dry season, with a better status observed during the wet season due to increased agricultural irrigation and higher water volume. Spatially, the five monitoring sections could be divided into three categories based on strong natural factors that maintained their temporal characteristics during the wet season； however, significant differences were observed during the dry season due to urban water usage patterns. Analysis using LSTM models revealed that ammonia nitrogen will continue to decline and have a decreasing impact on the comprehensive water quality. These findings provide valuable insights for the comprehensive management of water quality in Inner Mongolia's Yellow River Basin.

Rab11b promotes M1-like macrophage polarization by restraining autophagic degradation of NLRP3 in alcohol-associated liver disease.

Macrophage polarization is vital to mounting a host defense or repairing tissue in various liver diseases. Excessive activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome is related to the orchestration of inflammation and alcohol-associated liver disease (ALD) pathology. Rab GTPases play critical roles in regulating vesicular transport. In this study we investigated the role of Rab11b in ALD, aiming to identify effective therapeutic targets. Here, we first demonstrated a decreased expression of Rab11b in macrophages from ALD mice. Knockdown of Rab11b by macrophage-specific adeno-associated virus can alleviate alcohol induced liver inflammation, injury and steatosis. We found that LPS and alcohol stimulation promoted Rab11b transferring from the nucleus to the cytoplasm in bone marrow-derived macrophages (BMDM) cells. Rab11b specifically activated the NLRP3 inflammasome in BMDMs and RAW264.7 cells to induce M1 macrophage polarization. Rab11b overexpression in BMDMs inhibited autophagic flux, leading to the suppression of LC3B-mediated NLRP3 degradation. We conclude that impaired Rab11b could alleviate alcohol-induced liver injury via autophagy-mediated NLRP3 degradation.

A novel nanoplatform-based circCSNK1G3 affects CBX7 protein and promotes glioma cell growth.

Bioenvironmental and biological factors have the potential to contribute to the development of glioma, a type of brain tumor. Recent studies have suggested that a unique circular RNA called circCSNK1G3 could play a role in promoting the growth of glioma cells. It does this by stabilizing a specific microRNA called miR-181 and reducing the expression of a tumor-suppressor gene known as chromobox protein homolog 7 (CBX7). To further investigate circCSNK1G3 and its effects on glioma, we utilized a nanoplatform called adeno-associated virus (AAV)-RNAi.To explore the functional implications of circCSNK1G3, we employed siRNA to silence its expression. Along with these effects, the silencing of circCSNK1G3 led to a depletion of miR-181d and an upregulation of CBX7. When we introduced miR-181d mimics, which artificially increase the levels of miR-181d, the anti-glioma cell activity induced by circCSNK1G3 siRNA was almost completely reversed. Conversely, inhibiting miR-181d mimicked the effects of circCSNK1G3 silencing. Moreover, when we overexpressed circCSNK1G3 in glioma cells, we observed an elevation of miR-181d and a depletion of CBX7. We found that the growth of A172 xenografts (tumors) carrying circCSNK1G3 shRNA was significantly inhibited. In these xenograft tissues, we detected a depletion of circCSNK1G3 and miR-181d, as well as an upregulation of CBX7.

Corrigendum to 'Predicting post-resection recurrence by integrating imaging-based surrogates of distinct vascular patterns of hepatocellular carcinoma' (JHEP Reports 5 [2023] 100806).

[This corrects the article DOI: 10.1016/j.jhepr.2023.100806.].

BIG coordinates auxin and SHORT ROOT to promote asymmetric stem cell divisions in Arabidopsis roots.

KEY MESSAGE: BIG regulates ground tissue formative divisions by bridging the auxin gradient with SHR abundance in Arabidopsis roots. The formative divisions of cortex/endodermis initials (CEIs) and CEI daughter cells (CEIDs) in Arabidopsis roots are coordinately controlled by the longitudinal auxin gradient and the radial SHORT ROOT (SHR) abundance. However, the mechanism underlying this coordination remains poorly understood. In this study, we demonstrate that BIG regulates ground tissue formative divisions by bridging the auxin gradient with SHR abundance. Mutations in BIG gene repressed cell cycle progression, delaying the formative divisions within the ground tissues and impairing the establishment of endodermal and cortical identities. In addition, we uncovered auxin's suppressive effect on BIG expression, triggering CYCLIND6;1 (CYCD6;1) activation in an SHR-dependent fashion. Moreover, the degradation of RETINOBLASTOMA-RELATED (RBR) is jointly regulated by BIG and CYCD6;1. The loss of BIG function led to RBR protein accumulation, detrimentally impacting the SHR/SCARECROW (SCR) protein complex and the CEI/CEID formative divisions. Collectively, these findings shed light on a fundamental mechanism wherein BIG intricately coordinates the interplay between SHR/SCR and auxin, steering ground tissue patterning within Arabidopsis root tissue.

A Cascade C(sp3)-H Annulation Involving C(alkyl),C(alkyl)-Palladacycle Intermediates.

C-H bond functionalization involving C,C-palladacycle intermediates provides a unique platform for developing novel reactions. However, the vast majority of studies have been limited to the transformations of C(aryl),C-palladacycles. In sharp contrast, catalytic reactions involving C(alkyl),C(alkyl)-palladacycles have rarely been reported. Herein, we disclose an unprecedented cascade C(sp3)-H annulation involving C(alkyl),C(alkyl)-palladacycles. In this protocol, alkene-tethered cycloalkenyl bromides undergo intramolecular Heck/C(sp3)-H activation to generate C(alkyl),C(alkyl)-palladacycles, which can be captured by α-bromoacrylic acids to afford tricyclic fused pyridinediones. In addition, this strategy can also be applied to indole-tethered cycloalkenyl bromides to construct pentacyclic fused pyridinediones via suquential Heck dearomatization/C(sp3)-H activation/decarboxylative cyclization. Notably, the removal of α-bromoacrylic acids in the reaction of alkene-tethered cycloalkenyl bromides can build an interesting tricyclic skeleton containing a four-membered ring. Preliminary mechanistic experiments indicate that five-membered C(alkyl),C(alkyl)-palladacycles serve as the key intermediates. Meanwhile, density functional theory (DFT) calculations have provided insights into the reaction pathway.

Increased Pretransplant Inflammatory Biomarkers Predict Death With Function After Kidney Transplantation.

BACKGROUND: Chronic systemic inflammation is associated with mortality in patients with chronic kidney disease, cardiovascular disease, and diabetes. The goal of this study was to examine the relationship between pretransplant inflammatory biomarkers (growth differentiation factor-15 [GDF-15], interleukin-6 [IL-6], soluble tumor necrosis factor receptor-1, monokine induced by gamma interferon/chemokine [C-X-C motif] ligand 9 [MIG/CXCL9], monocyte chemoattractant protein-1, soluble FAS, tumor necrosis factor-α, interleukin-15, and interleukin-1ß) and death with function (DWF) after kidney transplantation (KT). METHODS: We retrospectively measured inflammatory biomarker levels in serum collected up to 1 y before KT (time from blood draw to KT was 130 ±â€…110 d) in recipients transplanted between January 2006 and December 2018. Kaplan-Meier estimation, Cox regression, and Gradient Boosting Machine modeling were used to examine the relationship between inflammatory biomarkers and DWF. RESULTS: Our cohort consisted of 1595 KT recipients, of whom 62.9% were male and 83.2% were non-Hispanic White. Over a mean follow-up of 7.4 ±â€…3.9 y, 21.2% of patients (n = 338) experienced DWF. Patients with the highest quartile levels of GDF-15 (>4766 pg/mL), IL-6 (>6.11 pg/mL), and MIG/CXCL9 (> 5835 pg/mL) had increased rates of DWF, and each predicted mortality independently of the others. When adjusted for clinical factors (age, diabetes, etc), the highest quartile levels of GDF-15 and IL-6 remained independently associated with DWF. Adding inflammatory markers to a clinical Cox model improved the C-statistic for DWF from 0.727 to 0.762 using a Gradient Boosting Machine modeling approach. CONCLUSIONS: These findings suggest that pre-KT serum concentrations of GDF-15, IL-6, and MIG/CXCL9 may help to risk stratify and manage patients undergoing KT and suggests that chronic inflammation may play a role in mortality in KT recipients.

Drawing as a window to emotion with insights from tech-transformed participant images.

This study delves into expressing primary emotions anger, happiness, sadness, and fear through drawings. Moving beyond the well-researched color-emotion link, it explores under-examined aspects like spatial concepts and drawing styles. Employing Python and OpenCV for objective analysis, we make a breakthrough by converting subjective perceptions into measurable data through 728 digital images from 182 university students. For the prominent color chosen for each emotion, the majority of participants chose red for anger (73.11%), yellow for happiness (17.8%), blue for sadness (51.1%), and black for fear (40.7%). Happiness led with the highest saturation (68.52%) and brightness (75.44%) percentages, while fear recorded the lowest in both categories (47.33% saturation, 48.78% brightness). Fear, however, topped in color fill percentage (35.49%), with happiness at the lowest (25.14%). Tangible imagery prevailed (71.43-83.52%), with abstract styles peaking in fear representations (28.57%). Facial expressions were a common element (41.76-49.45%). The study achieved an 81.3% predictive accuracy for anger, higher than the 71.3% overall average. Future research can build on these results by improving technological methods to quantify more aspects of drawing content. Investigating a more comprehensive array of emotions and examining factors influencing emotional drawing styles will further our understanding of visual-emotional communication.

The immunometabolic function of VGLL3 and female-biased autoimmunity.

Autoimmune diseases exhibit a pronounced yet unexplained prevalence among women. Vestigial-like family member 3 (VGLL3), a female-biased factor that promotes autoimmunity, has recently been discovered to assist cells in sensing and adapting to nutritional stress. This role of VGLL3 may confer a selective advantage during the evolution of placental mammals. However, the excessive activation of the VGLL3-mediated energy-sensing pathway can trigger inflammatory cell death and the exposure of self-antigens, leading to the onset of autoimmunity. These observations have raised the intriguing perspective that nutrient sensing serves as a double-edged sword in immune regulation. Mechanistically, VGLL3 intersects with Hippo signaling and activates multiple downstream, immune-associated genes that play roles in metabolic regulation. Understanding the multifaceted roles of VGLL3 in nutrient sensing and immune modulation provides insight into the fundamental question of sexual dimorphism in immunometabolism and sheds light on potential therapeutic targets for autoimmune diseases.

Bear Bile Powder Ameliorates LPS-Induced Acute Lung Injury by Inhibiting CD14 Pathway and Improving Intestinal Flora: Exploration of "Fei (Lung)-Dachang (Large Intestine) Interaction".

OBJECTIVE: To explore the effect of bear bile powder (BBP) on acute lung injury (ALI) and the underlying mechanism. METHODS: The chemical constituents of BBP were analyzed by ultra-high-pressure liquid chromatography-mass spectrometry (UPLC-MS). After 7 days of adaptive feeding, 50 mice were randomly divided into 5 groups by a random number table (n=10): normal control (NC), lipopolysaccharide (LPS), dexamethasone (Dex), low-, and high-dose BBP groups. The dosing cycle was 9 days. On the 12th and 14th days, 20 µL of Staphylococcus aureus solution (bacterial concentration of 1 × 10-7 CFU/mL) was given by nasal drip after 1 h of intragastric administration, and the mice in the NC group was given the same dose of phosphated buffered saline (PBS) solution. On the 16th day, after 1 h intragastric administration, 100 µL of LPS solution (1 mg/mL) was given by tracheal intubation, and the same dose of PBS solution was given to the NC group. Lung tissue was obtained to measure the myeloperoxidase (MPO) activity, the lung wet/dry weight ratio and expressions of CD14 and other related proteins. The lower lobe of the right lung was obtained for pathological examination. The concentrations of inflammatory cytokines including interleukin (IL)-6, tumour necrosis factor α (TNF-α ) and IL-1ß in the bronchoalveolar lavage fluid (BALF) were detected by enzyme linked immunosorbent assay, and the number of neutrophils was counted. The colonic contents of the mice were analyzed by 16 sRNA technique and the contents of short-chain fatty acids (SCFAs) were measured by gas chromatograph-mass spectrometer (GC-MS). RESULTS: UPLC-MS revealed that the chemical components of BBP samples were mainly tauroursodeoxycholic acid and taurochenodeoxycholic acid sodium salt. BBP reduced the activity of MPO, concentrations of inflammatory cytokines, and inhibited the expression of CD14 protein, thus suppressing the activation of NF-κB pathway (P<0.05). The lung histopathological results indicated that BBP significantly reduced the degree of neutrophil infiltration, cell shedding, necrosis, and alveolar cavity depression. Moreover, BBP effectively regulated the composition of the intestinal microflora and increased the production of SCFAs, which contributed to its treatment effect (P<0.05). CONCLUSIONS: BBP alleviates lung injury in ALI mouse through inhibiting activation of NF-κB pathway and decreasing expression of CD14 protein. BBP may promote recovery of ALI by improving the structure of intestinal flora and enhancing metabolic function of intestinal flora.

Tailoring the Size of Reduced Graphene Oxide Sheets to Fabricate Silicon Composite Anodes for Lithium-Ion Batteries.

The integration of a silicon (Si) anode into lithium-ion batteries (LIBs) holds great promise for energy storage, but challenges arise from unstable electrochemical reactions and volume changes during cycling. This study investigates the influence of reduced graphene oxide (rGO) size on the performance of rGO-protected Si composite (Si@rGO) anodes. Two sizes of graphene oxide (GO(L) and GO(S)) are used to synthesize Si@rGO composites with a core-shell structure by spray drying and thermal reduction. Electrochemical evaluations show the advantages of the Si@rGO(S) anode with improved cycle life and cycling efficiency over Si@rGO(L) and pure Si. The Si@rGO(S) anode facilitates the formation of a stable LiF-rich solid electrolyte interface (SEI) after cycling, ensuring enhanced capacity retention and swelling control. Rate capability tests also demonstrate the superior high-power performance of Si@rGO(S) with low and stable resistances in Si@rGO(S) over extended cycles. This study provides critical insights into the tailoring of graphene-protected Si composites, highlighting the critical role of rGO size in shaping structural and electrochemical properties. The Si material wrapped by graphene with an optimal lateral size of graphene emerges as a promising candidate for high-performance LIB anodes, thereby advancing electrochemical energy storage technologies.

Enhancing Escherichia coli Inactivation: Synergistic Mechanism of Ultraviolet Light and High-Voltage Electric Field.

This study investigated the bactericidal effects of ultraviolet (UV) radiation, a high-voltage electric field (HVEF), and their combination on Escherichia coli. The results indicated that UV and combined disinfection were more effective with longer exposure, leading to significant reductions in microbial activity. Specifically, the single UV disinfection alone reduced activity by 3.3 log after 5 min, while combined disinfection achieved a 4.2 log reduction. In contrast, short-term HVEF treatment did not exhibit significant bactericidal effects, only achieving a reduction of 0.17 log in 5 min. Furthermore, prolonged exposure to both UV disinfection and an HVEF was found to damage cell membranes, ultimately causing cell death, while shorter durations did not. Despite rapid cell count decreases, flow cytometry did not detect apoptotic or necrotic cells, likely due to rapid cell rupture. This study suggests that combining UV radiation and an HVEF could be a promising approach for inhibiting bacterial reproduction, with HVEF enhancing UV effects. These findings provide insights for using combined HVEF and UV disinfection in food safety and preservation.

Taurine reduces the risk for metabolic syndrome: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Metabolic syndrome (MetS) is a cluster of interconnected risk factors that significantly increase the likelihood of cardiovascular disease and type 2 diabetes. Taurine has emerged as a potential therapeutic agent for MetS. This meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the effects of taurine supplementation on MetS-related parameters. METHODS: We conducted electronic searches through databases like Embase, PubMed, Web of Science, Cochrane CENTRAL, and ClinicalTrials.gov, encompassing publications up to December 1, 2023. Our analysis focused on established MetS diagnostic criteria, including systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C). Meta-regression explored potential dose-dependent relationships based on the total taurine dose administered during the treatment period. We also assessed secondary outcomes like body composition, lipid profile, and glycemic control. RESULTS: Our analysis included 1024 participants from 25 RCTs. The daily dosage of taurine in the studies ranged from 0.5 g/day to 6 g/day, with follow-up periods varying between 5 and 365 days. Compared to control groups, taurine supplementation demonstrated statistically significant reductions in SBP (weighted mean difference [WMD] = -3.999 mmHg, 95% confidence interval [CI] = -7.293 to -0.706, p = 0.017), DBP (WMD = -1.509 mmHg, 95% CI = -2.479 to -0.539, p = 0.002), FBG (WMD: -5.882 mg/dL, 95% CI: -10.747 to -1.018, p = 0.018), TG (WMD: -18.315 mg/dL, 95% CI: -25.628 to -11.002, p < 0.001), but not in HDL-C (WMD: 0.644 mg/dl, 95% CI: -0.244 to 1.532, p = 0.155). Meta-regression analysis revealed a dose-dependent reduction in DBP (coefficient = -0.0108 mmHg per g, p = 0.0297) and FBG (coefficient = -0.0445 mg/dL per g, p = 0.0273). No significant adverse effects were observed compared to the control group. CONCLUSION: Taurine supplementation exhibits positive effects on multiple MetS-related factors, making it a potential dietary addition for individuals at risk of or already experiencing MetS. Future research may explore dose-optimization strategies and potential long-term benefits of taurine for MetS management.

HIF-1α and adaptor protein LIM and senescent cell antigen-like domains protein 1 axis promotes tubulointerstitial fibrosis by interacting with vimentin in angiotensin II-induced hypertension.

BACKGROUND AND PURPOSE: Activation of the renin-angiotensin system, as a hallmark of hypertension and chronic kidney diseases (CKD) is the key pathophysiological factor contributing to the progression of tubulointerstitial fibrosis. LIM and senescent cell antigen-like domains protein 1 (LIMS1) plays an essential role in controlling of cell behaviour through the formation of complexes with other proteins. Here, the function and regulation of LIMS1 in angiotensin II (Ang II)-induced hypertension and tubulointerstitial fibrosis was investigated. EXPERIMENTAL APPROACH: C57BL/6 mice were treated with Ang II to induce tubulointerstitial fibrosis. Hypoxia-inducible factor-1α (HIF-1α) renal tubular-specific knockout mice or LIMS1 knockdown AAV was used to investigate their effects on Ang II-induced renal interstitial fibrosis. In vitro, HIF-1α or LIMS1 was knocked down or overexpressed in HK2 cells after exposure to Ang II. KEY RESULTS: Increased expression of tubular LIMS1 was observed in human kidney with hypertensive nephropathy and in murine kidney from Ang II-induced hypertension model. Tubular-specific knockdown of LIMS1 ameliorated Ang II-induced tubulointerstitial fibrosis in mice. Furthermore, we demonstrated that LIMS1 was transcriptionally regulated by HIF-1α in tubular cells and that tubular HIF-1α knockout ameliorates LIMS1-mediated tubulointerstitial fibrosis. In addition, LIMS1 promotes Ang II-induced tubulointerstitial fibrosis by interacting with vimentin. CONCLUSION AND IMPLICATIONS: We conclude that HIF-1α transcriptionally regulated LIMS1 plays a central role in Ang II-induced tubulointerstitial fibrosis through interacting with vimentin. Our finding represents a new insight into the mechanism of Ang II-induced tubulointerstitial fibrosis and provides a novel therapeutic target for progression of CKD.

Bioinspired Structures Made of Silicone Nanofilaments for Upcycling Waste Masks to Reusable N95 Respirators.

The increasing demand for personal protective equipment such as single-use masks has led to large amounts of nondegradable plastic waste, aggravating economic and environmental burdens. This study reports a simple and scalable approach for upcycling waste masks via a chemical vapor deposition technique, realizing a trichome-like biomimetic (TLB) N95 respirator with superhydrophobicity (water contact angle ≥150°), N95-level protection, and reusability. The TLB N95 respirator comprising templated silicone nanofilaments with an average diameter of ∼150 nm offers N95-level protection and breathability comparable to those of commercial N95 respirators. The TLB N95 respirator can still maintain its N95-level protection against particulate matter and viruses after 10 disinfection treatment cycles (i.e., ultraviolet irradiation, microwave irradiation, dry heating, and autoclaving), demonstrating durable reusability. The proposed strategy provides new insight into upcycle waste masks, breaking the existing design and preparation concept of reusable masks.

Value of quantitative microsurface structure analysis for evaluating the invasion depth of type 0-II early gastric cancer.

Background and Aim: The microsurface structure reflects the degree of damage to the glands, which is related to the invasion depth of early gastric cancer. To evaluate the diagnostic value of quantitative microsurface structure analysis for estimating the invasion depth of early gastric cancer. Methods: White-light imaging and narrow-band imaging (NBI) endoscopy were used to visualize the lesions of the included patients. The area ratio and depth-predicting score (DPS) of each patient were calculated; meanwhile, each lesion was examined by endoscopic ultrasonography (EUS). Results: Ninety-three patients were included between 2016 and 2019. Microsurface structure is related to the histological differentiation and progression of early gastric cancer. The receiver operating characteristic curve showed that when an area ratio of 80.3% was used as a cut-off value for distinguishing mucosal (M) and submucosal (SM) type 0-II gastric cancers, the sensitivity, specificity, and accuracy were 82.9%, 80.2%, and 91.6%, respectively. The accuracies for distinguishing M/SM differentiated and undifferentiated early gastric cancers were 87.4% and 84.8%, respectively. The accuracy of EUS for distinguishing M/SM early gastric cancer was 74.9%. DPS can only distinguish M-SM1 (SM infiltration <500 µm)/SM (SM infiltration ≥500 µm) with an accuracy of 83.8%. The accuracy of using area ratio for distinguishing 0-II early gastric cancers was better than those of using DPS and EUS (P < 0.05). Conclusion: Quantitative analysis of microsurface structure can be performed to assess M/SM type 0-II gastric cancer and is expected to be effective for judging the invasion depth of gastric cancer.