Clinical evaluation of maxillary sinus floor elevation with or without bone grafts: a systematic review and meta-analysis of randomised controlled trials with trial sequential analysis.

Introduction: Our goal was to systematically review the current evidence comparing the relative effectiveness of two maxillary sinus floor elevation (MSFE) approaches (internal and external) without bone grafts with that of conventional/grafted MSFE in patients undergoing implantation in the posterior maxilla. Material and methods: Medical databases (PubMed/Medline, Embase, Web of Science, and Cochrane Library) were searched for randomised controlled trials published between January 1980 and May 2023. A manual search of implant-related journals was also performed. Studies published in English that reported the clinical outcomes of MSFE with or without bone material were included. The risk of bias was assessed using the Cochrane Handbook Risk Assessment Tool. Meta-analyses and trial sequence analyses were performed on the included trials. Meta-regression analysis was performed using pre-selected covariates to account for substantial heterogeneity. The certainty of evidence for clinical outcomes was assessed using GRADEpro GDT online (Guideline Development Tool). Results: Seventeen studies, including 547 sinuses and 696 implants, were pooled for the meta-analysis. The meta-analysis showed no statistically significant difference between MSFE without bone grafts and conventional MSFE in terms of the implant survival rate in the short term (n = 11, I2 = 0%, risk difference (RD): 0.03, 95% confidence intervals (CI): -0.01-0.07, p = 0.17, required information size (RIS) = 307). Although conventional MSFE had a higher endo-sinus bone gain (n = 13, I2 = 89%, weighted mean difference (WMD): -1.24, 95% CI: -1.91- -0.57, p = 0.0003, RIS = 461), this was not a determining factor in implant survival. No difference in perforation (n = 13, I2 = 0%, RD = 0.03, 95% CI: -0.02-0.09, p = 0.99, RIS = 223) and marginal bone loss (n = 4, I2 = 0%, WMD = 0.05, 95% CI: -0.14-0.23, p = 0.62, no RIS) was detected between the two groups using meta-analysis. The pooled results of the implant stability quotient between the two groups were not robust on sensitivity analysis. Because of the limited studies reporting on the visual analogue scale, surgical time, treatment costs, and bone density, qualitative analysis was conducted for these outcomes. Conclusions: This systematic review revealed that both non-graft and grafted MSFE had high implant survival rates. Owing to the moderate strength of the evidence and short-term follow-up, the results should be interpreted with caution.

Transdermal Delivery of Recombinant Human Growth Hormone by Liposomal Gel for Skin Photoaging Therapy.

Human growth hormone (hGH) has emerged as a promising therapeutic agent to prevent and treat skin photoaging. However, the success of hGH therapy largely lies in the availability of an optimal delivery system that enables the efficient delivery of hGH to the dermal layer of the skin. Here, we report a delivery system of hyaluronic acid/liposome-gel-encapsulated hGH (HA/HL-Gel) that can transdermally deliver hGH into the skin for hGH-based photoaging therapy through the upregulation of collagen type I (collagen-I). Specifically, hGH-liposomes were prepared by ethanol injection and then modified with HA to achieve specific targeting. The best formulation of HA/hGH-liposomes (HA/HL) had a high encapsulation efficiency (about 20%), with a size of 180 ± 1.2 nm. The optimized HA/HL was further incorporated into the carbomer gel to form an HA/HL-Gel. The biological activity of HA/HL on human dermal fibroblasts (HDFs) was confirmed by the elevated expression level of collagen-I through the enhanced local formation of insulin-like growth factor-1 (IGF-1) in the photoaging model. Moreover, HA/HL-Gel reduced ultraviolet (UV)-induced erythema and wrinkle formation. Meanwhile, immunohistochemical staining further showed higher levels of collagen-I in the HA/HL-Gel group compared to other groups tested. Taken together, these results demonstrate that HA/HL-Gel treatment could significantly ameliorate skin photoaging and thus may be used as a clinical potential for antiaging therapy.

Analysis of the global burden of cervical cancer in young women aged 15-44 years old.

BACKGROUND: Understanding the burden of cervical cancer (CC) in young women aged 15-44 years old are essential for formulating effective preventive strategies. METHODS: Utilizing the Global Burden of Disease 2019 Study, we estimated incidence, disability-adjusted life-years (DALYs), years of life lost (YLLs) and years lived with disability (YLDs) due to CC among young women from 1990 to 2019. Additionally, we evaluated the temporal trends using estimated annual percentage changes (EAPCs) during this period. We conducted a decomposition analysis to assess the absolute contributions of three components: population growth, population age structure and epidemiologic changes. RESULTS: Globally, there were 187 609.22 incident cases of CC worldwide, resulting in 2621 917.39 DALYs in 2019. From1990 to 2019, the age-standardized rates were decline, only the age-standardized YLDs rate (EAPC = 0.02; 95% CI: -0.02 to 0.05) showed a stable trend. The largest increase in age-standardized incidence rate (ASIR) and age-standardized YLDs rate observed in the high-middle social demographic index (SDI) quintiles. Population growth and age structure changes were associated with substantial changes in cases of CC, especially in South Asia and East Asia. CONCLUSIONS: Globally, the burden of CC in young women continues to increase, as measured by the absolute number. As populations are growing and age structure changes were associated with substantial changes in cases of CC, governments will face increasing demand for treatment, and support services for CC, especially in South Asia and East Asia.

Photodetachment and Tunneling Dissociation of Cryogenic Double-Rydberg Anions NH4.

The Rydberg radical NH4 and the double Rydberg anion (DRA) NH4- have long aroused researchers' interests due to their potential for exploring the reaction dynamics of the H + NH3 → H2 + NH2 reaction, a prototypical penta-atomic system. In this study, we present high-resolution photodetachment spectroscopy of DRA NH4- and ion-molecule complex H-(NH3). We observed multiple new photodetachment channels of DRA NH4-. The energy level of the excited state (3p 2T2) of the Rydberg radical NH4 was determined to be 15052(94) cm-1, in excellent agreement with the principal Schüler band (15061.61 cm-1). Additionally, we observed the tunneling dissociation of NH4- in a cryogenic ion trap with its dissociation lifetime determined to be 19(2) ms.

CsZnPbBr3/ZnS core/shell perovskite nanocrystals for stable and efficient white light-emitting diodes.

The widespread applicability of perovskite nanocrystals (PeNCs) is impeded by their intrinsic instability. A promising solution is utilizing robust chalcogenides as a protective shell to shield the sensitive luminescent cores from the external environment. However, the inferior structural stability and surface lability of PeNCs usually lead to perovskite phase transition during shell growth. Herein, we introduced smaller Zn ions to partially replace Pb ions in perovskites, which reduces the Pb-X bond length and enhances the Pb-X bond energy for inner lattice stabilization. Simultaneously, extra oleylammonium bromide (OAmBr) was added to protect the labile surface of PeNCs by compensating for the detachment of ligands and the loss of surface Br ions. As a result, the dual strategies enable the epitaxial growth of a ZnS shell and significantly enhance the chemical stability of CsZnPbBr3/ZnS core/shell PeNCs. After three thermal cycles ranging from 300 to 450 K, the core/shell PeNCs retained 70% of their initial photoluminescence (PL) intensity. In stark contrast, the pristine CsPbBr3 PeNCs exhibit complete PL quenching after just the first temperature cycle. For practical applications, the green core/shell PeNCs were integrated with commercially available red-emitting phosphors on a blue-emitting InGaN chip to fabricate a white light-emitting diode (WLED), which demonstrates a high luminous efficacy (LE) of 61.3 lm W-1 and nearly constant Commission Internationale de l'Eclairage (CIE) coordinates under varying operating currents.

ICP-MS based detection method combined with Au NP and Ag NP labeling for bacteremia diagnosis.

Bacteremia, as a serious infectious disease, has an increasing incidence and a high mortality rate. Early diagnosis and early treatment are crucial for improving the cure rate. In this work, we proposed an inductively coupled plasma mass spectrometry (ICP-MS)-based detection method combined with gold nanoparticle (Au NP) and silver nanoparticle (Ag NP) labeling for the simultaneous detection of Salmonella and Escherichia coli (E. coli O157:H7) in human blood samples. Salmonella and E. coli O157:H7 were captured by magnetic beads coupled with anti-8G3 and anti-7C2, and then specifically labeled by Au NP-anti-5H12 and Ag NP-anti-8B1 respectively, which were used as signal probes for ICP-MS detection. Under the optimal experimental conditions, the limits of detection of 164 CFU mL-1 for Salmonella, 220 CFU mL-1for E. coli O157:H7 and the linear ranges of 400-80,000 CFU mL-1Salmonella, 400-60,000 CFU mL-1 E. coli O157:H7 were obtained. The proposed method can realize the simultaneous detection of two types of pathogenic bacteria in human whole blood in 3.5 h, showing great potential for the rapid diagnosis of bacteremia in clinic.

Recent progress in neonatal hyperoxic lung injury.

With the progress in neonatal intensive care, there has been an increase in the survival rates of premature infants. However, this has also led to an increased incidence of neonatal hyperoxia lung injury and bronchopulmonary dysplasia (BPD), whose pathogenesis is believed to be influenced by various prenatal and postnatal factors, although the exact mechanisms remain unclear. Recent studies suggest that multiple mechanisms might be involved in neonatal hyperoxic lung injury and BPD, with sex also possibly playing an important role, and numerous drugs have been proposed and shown promise for improving the treatment outcomes of hyperoxic lung injury. Therefore, this paper aims to analyze and summarize sex differences in neonatal hyperoxic lung injury, potential pathogenesis and treatment progress to provide new ideas for basic and clinical research in this field.

Exploration of anatomical distribution of brain metastasis from breast cancer at first diagnosis assisted by artificial intelligence.

Objectives: This study aimed to explore the spatial distribution of brain metastases (BMs) from breast cancer (BC) and to identify the high-risk sub-structures in BMs that are involved at first diagnosis. Methods: Magnetic resonance imaging (MRI) scans were retrospectively reviewed at our centre. The brain was divided into eight regions according to its anatomy and function, and the volume of each region was calculated. The identification and volume calculation of metastatic brain lesions were accomplished using an automatically segmented 3D BUC-Net model. The observed and expected rates of BMs were compared using 2-tailed proportional hypothesis testing. Results: A total of 250 patients with BC who presented with 1694 BMs were retrospectively identified. The overall observed incidences of the substructures were as follows: cerebellum, 42.1 %; frontal lobe, 20.1 %; occipital lobe, 9.7 %; temporal lobe, 8.0 %; parietal lobe, 13.1 %; thalamus, 4.7 %; brainstem, 0.9 %; and hippocampus, 1.3 %. Compared with the expected rate based on the volume of different brain regions, the cerebellum, occipital lobe, and thalamus were identified as higher risk regions for BMs (P value ≤ 5.6*10-3). Sub-group analysis according to the type of BC indicated that patients with triple-negative BC had a high risk of involvement of the hippocampus and brainstem. Conclusions: Among patients with BC, the cerebellum, occipital lobe and thalamus were identified as higher-risk regions than expected for BMs. The brainstem and hippocampus were high-risk areas of the BMs in triple negative breast cancer. However, further validation of this conclusion requires a larger sample size.

The BioCascade Impactor: A novel device for direct collection of size-fractionated bioaerosols into liquid medium.

The ability to collect size-fractionated airborne particles that contain viable bacteria and fungi directly into liquid medium while also maintaining their viability is critical for assessing exposure risks. In this study, we present the BioCascade impactor, a novel device designed to collect airborne particles into liquid based on their aerodynamic diameter in three sequential stages (>9.74 µm, 3.94-9.74 µm, and 1.38-3.94 µm when operated at 8.5 L/min). Aerosol samples containing microorganisms - either Saccharomyces kudriavzevii or Micrococcus luteus, were used to evaluate the performance of the BioCascade (BC) paired with either the VIable Virus Aerosol Sampler (VIVAS) or a gelatin filter (GF) as stage 4 to collect particles <1.38 µm. Stages 2 and 3 collected the largest fractions of viable S. kudriavzevii when paired with VIVAS (0.468) and GF (0.519), respectively. Stage 3 collected the largest fraction of viable M. luteus particles in both BC+VIVAS (0.791) and BC+GF (0.950) configurations. The distribution function of viable microorganisms was consistent with the size distributions measured by the Aerodynamic Particle Sizer. Testing with both bioaerosol species confirmed no internal loss and no re-aerosolization occurred within the BC. Irrespective of the bioaerosol tested, stages 1, 3 and 4 maintained ≥80% of viability, while stage 2 maintained only 37% and 73% of viable S. kudriavzevii and M. luteus, respectively. The low viability that occurred in stage 2 warrants further investigation. Our work shows that the BC can efficiently size-classify and collect bioaerosols without re-aerosolization and effectively maintain the viability of collected microorganisms.

Evaluation of an automated clinical decision system with deep learning dose prediction and NTCP model for prostate cancer proton therapy.

OBJECTIVE: To evaluate the feasibility of using a deep learning dose prediction approach to identify patients who could benefit most from proton therapy based on the normal tissue complication probability (NTCP) model. Approach: Two 3D UNets were established to predict photon and proton doses. A dataset of 95 patients with localized prostate cancer was randomly partitioned into 55, 10, and 30 for training, validation, and testing, respectively. We selected NTCP models for late rectum bleeding and acute urinary urgency of grade 2 or higher to quantify the benefit of proton therapy. Propagated uncertainties of predicted ΔNTCPs resulting from the dose prediction errors were calculated. Patient selection accuracies for a single endpoint and a composite evaluation were assessed under different ΔNTCP thresholds. Main results: Our deep learning-based dose prediction technique can reduce the time spent on plan comparison from approximately 2 days to as little as 5 seconds. The expanded uncertainty of predicted ΔNTCPs for rectum and bladder endpoints propagated from the dose prediction error were 0.0042 and 0.0016, respectively, which is less than one-third of the acceptable tolerance. The averaged selection accuracies for rectum bleeding, urinary urgency, and composite evaluation were 90%, 93.5%, and 93.5%, respectively. Significance: Our study demonstrates that deep learning dose prediction and NTCP evaluation scheme could distinguish the NTCP differences between photon and proton treatment modalities. In addition, the dose prediction uncertainty does not significantly influence the decision accuracy of NTCP-based patient selection for proton therapy. Therefore, automated deep learning dose prediction and NTCP evaluation schemes can potentially be used to screen large patient populations and to avoid unnecessary delays in the start of prostate cancer radiotherapy in the future.

The impact of volunteer service on moral education performance and mental health of college students.

BACKGROUND: Moral education in colleges and universities is an important part of the talent training system, including moral education curriculum, moral education practice, mental health education. Volunteer service is a public welfare act in which volunteers volunteer their time, knowledge, property, technology, with the ultimate goal of helping others and serving the society without personal compensation. As an innovative form of moral education practice in colleges and universities, college students' voluntary service is of great significance in promoting the reform and innovation of moral education, enhancing the affinity, appeal and influence of moral education, and building a positive psychology for college students. SUBJECTS AND METHODS: As an effective carrier of moral education practice in colleges and universities, voluntary service is helpful to enhance the effectiveness of moral education practice and construct the positive psychology of college students. This project is based on the actual situation of college students participating in volunteer services, and collected the volunteer services of 4545 college students in Zhejiang Province. Through model construction and data modeling, the correlation between college students' participation in volunteer service and their moral education performance and mental health was analyzed, and the basic path and guarantee measures to promote the role of volunteer service in moral education and positive psychological construction were deeply explored. RESULTS: From the correlation analysis of students' voluntary service participation, moral education performance and voluntary service motivation, students' attributes are determined according to their voluntary service participation, so as to predict their moral education performance and mental health level. CONCLUSION: College students' voluntary service is partially positively related to their moral education performance and mental health. In order to improve students' moral education performance and mental health, we can optimize the participation frequency, participation duration, participation ways and type structure of voluntary service, constantly increase the participation frequency of voluntary service, increase the duration of voluntary service, broaden the participation ways of voluntary activities, and enrich the types of voluntary service activities.

Two novel angiotensin-converting enzyme (ACE) and dipeptidyl peptidase IV (DPP-IV) inhibiting peptides from tilapia (Oreochromis mossambicus) skin and their molecular docking mechanism.

In the study, papain was used to hydrolyze tilapia (Oreochromis mossambicus) skin to obtain a tilapia skin hydrolysate (TSH) with dual angiotensin-converting enzyme (ACE) and dipeptidyl peptidase IV (DPP-IV) inhibitory activities. The resulting TSH was sequentially fractionated by ultrafiltration, size exclusion separation chromatography, and reverse-phase high-performance liquid chromatography. Its inhibitory effects on ACE and DPP-IV were determined by commercial reagent kits. Two peptides purified from TSH were identified as Gly-Pro-Leu-Gly-Ala-Leu (GPLGAL) and Lys-Pro-Ala-Gly-Asn (KPAGN) by the ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Inhibitory concentration (IC50) of GPLGAL on ACE and DPP-IV were 117.20 ± 1.69 and 187.10 ± 2.75 µM, respectively. IC50 of KPAGN on ACE and DPP-IV were 137.40 ± 2.33 and 259.20 ± 2.85 µM, respectively. The molecular simulation demonstrated that the binding affinities of GPLGAL to ACE and DPP-IV proteins were -8.5 and -7.4 kcal/mol, respectively, whereas those of KPAGN to ACE and DPP-IV proteins were -7.9 and -6.7 kcal/mol, respectively. GPLGAL interacted with 21 amino acid residues of the ACE active site, whereas KPAGN engaged with 19 amino acid residues. Additionally, GPLGAL interacted with 10 amino acid residues of the DPP-IV active site, whereas KPAGN engaged with 13 amino acid residues. The two peptides predominantly occupied the active sites of ACE (His513, Tyr523, and Ala354) and DPP-IV (Tyr662 and Arg125) through hydrogen bonding. This leads to the deactivation of ACE and DPP-IV. PRACTICAL APPLICATION: Accelerate tilapia skin development and high-value utilization; provide foundation for preparing the peptides with dual ACE and DPP-IV inhibiting activity.

A Video-based Automated Tracking and Analysis System of Plaque Burden in Carotid Artery Using Deep Learning: A Comparison with Senior Sonographers.

BACKGROUND AND OBJECTIVE: The incidence of stroke is rising, and it is the second major cause of mortality and the third leading cause of disability around the globe. The goal of this study was to rapidly and accurately identify carotid plaques and automatically quantify plaque burden using our automated tracking and segmentation US-video system. METHODS: We collected 88 common carotid artery transection videos (11048 frames) with a history of atherosclerosis or risk factors for atherosclerosis, which were randomly divided into training, test, and validation sets using a 6:3:1 ratio. We first trained different segmentation models to segment the carotid intima and adventitia, and calculate the maximum plaque burden automatically. Finally, we statistically analyzed the plaque burden calculated automatically by the best model and the results of manual labeling by senior sonographers. RESULTS: Of the three Artificial Intelligence (AI) models, the Robust Video Matting (RVM) segmentation model's carotid intima and adventitia Dice Coefficients (DC) were the highest, reaching 0.93 and 0.95, respectively. Moreover, the RVM model has shown the strongest correlation coefficient (0.61±0.28) with senior sonographers, and the diagnostic effectiveness between the RVM model and experts was comparable with paired-t test and Bland-Altman analysis [P= 0.632 and ICC 0.01 (95% CI: -0.24~0.27), respectively]. CONCLUSION: Our findings have indicated that the RVM model can be used in ultrasound carotid video. The RVM model can automatically segment and quantify atherosclerotic plaque burden at the same diagnostic level as senior sonographers. The application of AI to carotid videos offers more precise and effective methods to evaluate carotid atherosclerosis in clinical practice.

Aromatic Amino Acids Promote Lipid Metabolism Disorders by Increasing Hepatic Bile Acid Synthesis.

BACKGROUND: Obesity is a progressive metabolic disease that begins with lipid metabolism disorders. Aromatic amino acids (AAAs), including tryptophan, phenylalanine, and tyrosine, have diverse biological activities as nutrients. However, the underlying mechanisms by which AAAs affect lipid metabolism are unclear. OBJECTIVES: This study was designed to investigate the possible roles and underlying molecular mechanisms of AAA in the pathogenesis of lipid metabolism disorders. METHODS: We added an AAA mixture to the high-fat diet (HFD) of mice. Glucose tolerance test was recorded. Protein expression of hepatic bile acid (BA) synthase and mRNA expression of BA metabolism-related genes were determined. Hepatic BA profiles and gut microbial were also determined in mice. RESULTS: The results showed that AAA significantly increased body weight and white adipose tissue, aggravated liver injury, impaired glucose tolerance and intestinal integrity, and significantly increased hepatic BA synthesis by inhibiting intestinal farnesoid X receptor (FXR). Moreover, AAA increased the content of total BA in the liver and altered the hepatic BA profile, with elevated levels of lithocholic acid, glycochenodeoxycholic acid, and glycoursodeoxycholic acid. AAA markedly increased the levels of proteins involved in BA synthesis (cholesterol 7α-hydroxylase and oxysterol 7α-hydroxylase) and inhibited the intestinal FXR. Gut microbial composition also changed, reducing the abundance of some beneficial bacteria, such as Parvibacter and Lactobacillus. CONCLUSIONS: Under HFD conditions, AAAs stimulate BA synthesis in both the classical and alternative pathways, leading to aggravation of liver injury and fat deposition. Excessive intake of AAA disrupts BA metabolism and contributes to the development of lipid metabolism disorders, suggesting that AAA may be a causative agent of lipid metabolism disorders.

Excessive Tryptophan and Phenylalanine Induced Pancreatic Injury and Glycometabolism Disorder in Grower-finisher Pigs.

BACKGROUND: The increase in circulating insulin levels is associated with the onset of type 2 diabetes (T2D), and the levels of branched-chain amino acids and aromatic amino acids (AAAs) are altered in T2D, but whether AAAs play a role in insulin secretion and signaling remains unclear. OBJECTIVES: This study aimed to investigate the effects of different AAAs on pancreatic function and on the use of insulin in finishing pigs. METHODS: A total of 18 healthy finishing pigs (Large White) with average body weight of 100 ± 1.15 kg were randomly allocated to 3 dietary treatments: Con, a normal diet supplemented with 0.68% alanine; Phe, a normal diet supplemented with 1.26% phenylalanine; and Trp, a normal diet supplemented with 0.78% tryptophan. The 3 diets were isonitrogenous. There were 6 replicates in each group. RESULTS: Herein, we investigated the effects of tryptophan and phenylalanine on pancreatic function and the use of insulin in finishing pigs and found that the addition of tryptophan and phenylalanine aggravated pancreatic fat deposition, increased the relative content of saturated fatty acids, especially palmitate (C16:0) and stearate (C18:0), and the resulting lipid toxicity disrupted pancreatic secretory function. We also found that tryptophan and phenylalanine inhibited the growth and secretion of ß-cells, downregulated the gene expression of the PI3K/Akt pathway in the pancreas and liver, and reduced glucose utilization in the liver. CONCLUSIONS: Using fattening pigs as a model, multiorgan combined analysis of the insulin-secreting organ pancreas and the main insulin-acting organ liver, excessive intake of tryptophan and phenylalanine will aggravate pancreatic damage leading to glucose metabolism disorders, providing new evidence for the occurrence and development of T2D.

Elucidating the changes in the heterogeneity and function of radiation-induced cardiac macrophages using single-cell RNA sequencing.

Purpose: A mouse model of irradiation (IR)-induced heart injury was established to investigate the early changes in cardiac function after radiation and the role of cardiac macrophages in this process. Methods: Cardiac function was evaluated by heart-to-tibia ratio, lung-to-heart ratio and echocardiography. Immunofluorescence staining and flow cytometry analysis were used to evaluate the changes of macrophages in the heart. Immune cells from heart tissues were sorted by magnetic beads for single-cell RNA sequencing, and the subsets of macrophages were identified and analyzed. Trajectory analysis was used to explore the differentiation relationship of each macrophage subset. The differentially expressed genes (DEGs) were compared, and the related enriched pathways were identified. Single-cell regulatory network inference and clustering (SCENIC) analysis was performed to identify the potential transcription factors (TFs) which participated in this process. Results: Cardiac function temporarily decreased on Day 7 and returned to normal level on Day 35, accompanied by macrophages decreased and increased respectively. Then, we identified 7 clusters of macrophages by single-cell RNA sequencing and found two kinds of stage specific macrophages: senescence-associated macrophage (Cdkn1ahighC5ar1high) on Day 7 and interferon-associated macrophage (Ccr2highIsg15high) on Day 35. Moreover, we observed cardiac macrophages polarized over these two-time points based on M1/M2 and CCR2/major histocompatibility complex II (MHCII) expression. Finally, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses suggested that macrophages on Day 7 were characterized by an inflammatory senescent phenotype with enhanced chemotaxis and inflammatory factors, while macrophages on Day 35 showed enhanced phagocytosis with reduced inflammation, which was associated with interferon-related pathways. SCENIC analysis showed AP-1 family members were associated with IR-induced macrophages changes. Conclusion: We are the first study to characterize the diversity, features, and evolution of macrophages during the early stages in an IR-induced cardiac injury animal model.

A deep learning-based calculation system for plaque stenosis severity on common carotid artery of ultrasound images.

OBJECTIVES: Assessment of plaque stenosis severity allows better management of carotid source of stroke. Our objective is to create a deep learning (DL) model to segment carotid intima-media thickness and plaque and further automatically calculate plaque stenosis severity on common carotid artery (CCA) transverse section ultrasound images. METHODS: Three hundred and ninety images from 376 individuals were used to train (235/390, 60%), validate (39/390, 10%), and test (116/390, 30%) on a newly proposed CANet model. We also evaluated the model on an external test set of 115 individuals with 122 images acquired from another hospital. Comparative studies were conducted between our CANet model with four state-of-the-art DL models and two experienced sonographers to re-evaluate the present model's performance. RESULTS: On the internal test set, our CANet model outperformed the four comparative models with Dice values of 95.22% versus 90.15%, 87.48%, 90.22%, and 91.56% on lumen-intima (LI) borders and 96.27% versus 91.40%, 88.94%, 91.19%, and 92.88% on media-adventitia (MA) borders. On the external test set, our model still produced excellent results with a Dice value of 92.41%. Good consistency of stenosis severity calculation was observed between CANet model and experienced sonographers, with Intraclass Correlation Coefficient (ICC) of 0.927 and 0.702, Pearson's Correlation Coefficient of 0.928 and 0.704 on internal and external test set, respectively. CONCLUSIONS: Our CANet model achieved excellent performance in the segmentation of carotid IMT and plaques as well as automated calculation of stenosis severity.

Causal effect of gut microbiota and diabetic nephropathy: a Mendelian randomization study.

BACKGROUND: The interaction of dysbiosis of gut microbiota (GM) with diabetic nephropathy (DN) drew our attention and a better understanding of GM on DN might provide potential therapeutic approaches. However, the exact causal effect of GM on DN remains unknown. METHODS: We applied two-sample Mendelian Randomization (MR) analysis, including inverse variance weighted (IVW), MR-Egger methods, etc., to screen the significant bacterial taxa based on the GWAS data. Sensitivity analysis was conducted to assess the robustness of MR results. To identify the most critical factor on DN, Mendelian randomization-Bayesian model averaging (MR-BMA) method was utilized. Then, whether the reverse causality existed was verified by reverse MR analysis. Finally, transcriptome MR analysis was performed to investigate the possible mechanism of GM on DN. RESULTS: At locus-wide significance levels, the results of IVW suggested that order Bacteroidales (odds ratio (OR) = 1.412, 95% confidence interval (CI): 1.025-1.945, P = 0.035), genus Akkermansia (OR = 1.449, 95% CI: 1.120-1.875, P = 0.005), genus Coprococcus 1 (OR = 1.328, 95% CI: 1.066-1.793, P = 0.015), genus Marvinbryantia (OR = 1.353, 95% CI: 1.037-1.777, P = 0.030) and genus Parasutterella (OR = 1.276, 95% CI: 1.022-1.593, P = 0.032) were risk factors for DN. Reversely, genus Eubacterium ventriosum (OR = 0.756, 95% CI: 0.594-0.963, P = 0.023), genus Ruminococcus gauvreauii (OR = 0.663, 95% CI: 0.506-0.870, P = 0.003) and genus Erysipelotrichaceae (UCG003) (OR = 0.801, 95% CI: 0.644-0.997, P = 0.047) were negatively associated with the risk of DN. Among these taxa, genus Ruminococcus gauvreauii played a crucial role in DN. No significant heterogeneity or pleiotropy in the MR result was found. Mapped genes (FDR < 0.05) related to GM had causal effects on DN, while FCGR2B and VNN2 might be potential therapeutic targets. CONCLUSIONS: This work provided new evidence for the causal effect of GM on DN occurrence and potential biomarkers for DN. The significant bacterial taxa in our study provided new insights for the 'gut-kidney' axis, as well as unconventional prevention and treatment strategies for DN.

Anlotinib enhanced CD8+ T cell infiltration via induction of CCL5 improves the efficacy of PD-1/PD-L1 blockade therapy in lung cancer.

Non-small cell lung cancer (NSCLC) is a leading cause of mortality worldwide and requires effective treatment strategies. Recently, the development of a novel multiple-target tyrosine kinase inhibitor, anlotinib, has drawn increasing attention, especially it shows advantages when combined with PD-1/PD-L1 blockade. However, the mechanism by which anlotinib improves immunotherapy and remodeling of the tumor microenvironment remains unclear. In this study, we found that anlotinib combined with PD-1 blockade significantly inhibited tumor growth and reduced tumor weight in a lung cancer xenograft model compared to any single treatment. Both immunofluorescence and flow cytometry analyses revealed that anlotinib induced a CD8+ T cell dominated tumor microenvironment, which might account for its improved role in immunotherapy. Further investigations showed that CCL5-mediated CD8+ T cell recruitment plays a critical role in anlotinib and PD-1 blockade strategies. The depletion of CD8+ T cells abrogated this process. In conclusion, our findings showed that the combination of anlotinib and PD-1 blockade produced promising effects in the treatment of lung cancer, and that the induction of CCL5-mediced CD8+ T cell recruitment by anlotinib provided a novel mechanism of action.

Electroosmotic Sensing of Uncharged Peptides and Differentiating Their Phosphorylated States Using Nanopores.

The correct characterization and identification of different kinds of proteins is crucial for the survival and development of living organisms, and proteomics research promotes the analysis and understanding of future genome functions. Nanopore technique has been proved to accurately identify individual nucleotides. However, accurate and rapid protein sequencing is difficult due to the variability of protein structures that contains more than 20 amino acids, and it remains very challenging especially for uncharged peptides as they can not be electrophoretically driven through the nanopore. Graphene nanopores have the advantages of high accuracy, sensitivity and low cost in identifying protein phosphorylation modifications. Here, by using all-atom molecular dynamics simulations, charged graphene nanopores are employed to electroosmotically capture and sense uncharged peptides. By further mimicking AFM manipulation of single molecules, it is also found that the uncharged peptides and their phosphorylated states could also be differentiated by both the ionic current and pulling force signals during their pulling processes through the nanopore with a slow and constant velocity. The results shows ability of using nanopores to detect and discriminate single amino acid and its phosphorylation, which is essential for the future low-cost and high-throughput sequencing of protein residues and their post-translational modifications.