Diversity in Pyracantha fortuneana fruits maturity stages enables discrepancy in the phenolic compounds, antioxidant activity, and tyrosinase inhibitory activity.

Pyracantha fortuneana (P. fortuneana) fruit is a wild fruit that is popular because of its delicious taste and numerous nutrients, and phenolic compounds are considered to be the main bioactive components in P. fortuneana fruits. However, the relationship between phenolic compounds and their antioxidant and tyrosinase (TYR) inhibitory activities during the ripening process is still unclear. The study compared the influence of the five developmental stages on the accumulation of phenolic compounds, antioxidant activity, and TYR inhibitory activity in the fruits of P. fortuneana. The compounds were identified by offline two-dimensional liquid chromatography-electrochemical detection (2D-LC-ECD) combined with liquid chromatography-tandem mass spectrometry, and the main active ingredients were quantified. The results showed that stage II had higher total phenolic and flavonoid content, as well as higher antioxidant and TYR inhibitory activity, but the total anthocyanin content was lowest at this stage. A total of 30 compounds were identified by 2D-LC-ECD. Orthogonal partial least squares discriminant analysis screened out six major potential markers, including phenolic acids, procyanidins, and flavonoids. In addition, it was found that caffeoylquinic acids, procyanidins, and flavonoids were higher in stage II than in stages I, III, IV, and V, whereas anthocyanins accumulated gradually from stages III to V. Therefore, this study suggests that the changes in antioxidant and TYR inhibitory activities of P. fortuneana during the five developmental stages may be due to the transformation of procyanidins, caffeoylquinic acids, and phenolic glycosides into other forms during the fruit maturation process. Practical Application: Differences in chemical constituents, antioxidant, and tyrosinase inhibitory activities in fruit maturity stages of P. fortuneana were elucidated to provide reference for rational harvesting and utilization of the fruits and their bioactive components. These findings are expected to provide a comprehensive assessment of the bioactive profile and guide the food industrial production.

Meta-analysis of the GALAD model for diagnosing primary hepatocellular carcinoma.

BACKGROUND: Ever since the GALAD (gender-age-Lens culinaris agglutinin-reactive alpha-fetoprotein-alpha-fetoprotein-des-gamma-carboxy prothrombin) logistic regression model was established to diagnose hepatocellular carcinoma (HCC), there has been no high-level evidence that evaluates and summarizes it. OBJECTIVE: This meta-analysis was performed to assess the diagnostic ability of the GALAD model. METHODS: The following databases were systematically searched for original diagnostic studies on HCC: PubMed, Embase, Medline, the Web of Science, Cochrane Library, China National Knowledge Infrastructure Wanfang (China), Wiper and the Chinese BioMedical Literature Database. After screening the search results according to our criteria, the Quality Assessment of Diagnostic Accuracy Studies 2 tool was used to evaluate the methodologic qualities, and statistical software were used to output the statistics. RESULTS: Ultimately, 10 studies were included and analyzed. The results revealed the pooled sensitivity and specificity of the GALAD model to be 0.86 (95% confidence interval [CI]: 0.82, 0.90) and 0.90 (95% CI: 0.87, 0.92), respectively, for all-stage HCC. The area under the curve (AUC) was 0.94. For early-stage HCC, the pooled sensitivity and specificity of the GALAD model were 0.83 (95% CI: 0.78, 0.87) and 0.81 (95% CI: 0.78, 0.83), respectively. The AUC was 0.90. CONCLUSION: This meta-analysis confirmed that the GALAD model has excellent diagnostic performance for early-stage and all-stage HCC and can maintain high sensitivity and specificity in early-stage HCC. Therefore, the GALAD model is qualified for screening early-stage canceration from chronic liver disease.

Ottowia cancrivicina sp. nov., isolated from human stomach.

A Gram-negative, facultative anaerobic, non-motile and rod-shaped bacterium, designated 10c7w1T, was isolated from a human gastrointestinal tract. Colonies on agar plates were small, circular, smooth and beige. The optimal growth conditions were determined to be 37 °C, pH 7.0-7.5 and 0 % (w/v) NaCl. Comparative analysis of complete 16S rRNA gene sequences revealed that strain 10c7w1T showed the highest sequence similarity of 95.8 % to Ottowia beijingensis MCCC 1A01410T, followed by Ottowia thiooxydans (95.2 %) JCM 11629T. The average amino acid identity values between 10c7w1T and O. beijingensis MCCC 1A01410T and O. thiooxydans JCM 11629T were above 60 % (71.4 and 69.5 %). The average nucleotide identity values between strain 10c7w1T and O. beijingensis MCCC 1A01410T and O. thiooxydans JCM 11629T were 76.9 and 72.5 %, respectively. The dominant fatty acids (≥10 %) were straight chain ones, with summed feature 3 (C16 : 1 ω7c/C16 : 1 ω6c), summed feature 8 (C18 : 1 ω7c/C18 : 1 ω6c) and C16 : 00 being the most abundant. Q-8 was the only respiratory quinone. The major polar lipids of strain 10c7w1T were phosphatidylethanolamine, diphosphatidylglycerol and unknown lipids. The DNA G+C content of strain 10c7w1T was 63.6 mol%. On the basis of phylogenetic, phenotypic and chemotaxonomic data, strain 10c7w1T is considered to represent a novel species within the genus Ottowia, for which the name Ottowia cancrivicina sp. nov. is proposed. The type strain is 10c7w1T (=MCCC 1H01399T=KCTC 92200T).

An ultrasound-triggered injectable sodium alginate scaffold loaded with electrospun microspheres for on-demand drug delivery to accelerate bone defect regeneration.

Biological processes, such as bone defects healing are precisely controlled in both time and space. This spatiotemporal characteristic inspires novel therapeutic strategies. The sustained-release systems including hydrogels are commonly utilized in the treatment of bone defect; however, traditional hydrogels often release drugs at a consistent rate, lacking temporal precision. In this study, a hybrid hydrogel has been developed by using sodium alginate, sucrose acetate isobutyrate, and electrospray microspheres as the base materials, and designed with ultrasound response, and on-demand release properties. Sucrose acetate isobutyrate was added to the hybrid hydrogel to prevent burst release. The network structure of the hybrid hydrogel is formed by the interconnection of Ca2+ with the carboxyl groups of sodium alginate. Notably, when the hybrid hydrogel is exposed to ultrasound, the ionic bond can be broken to promote drug release; when ultrasound is turned off, the release returned to a low-release state. This hybrid hydrogel reveals not only injectability, degradability, and good mechanical properties but also shows multiple responses to ultrasound. And it has good biocompatibility and promotes osteogenesis efficiency in vivo. Thus, this hybrid hydrogel provides a promising therapeutic strategy for the treatment of bone defects.

Electrospun membranes of diselenide-containing poly(ester urethane)urea for in situ catalytic generation of nitric oxide.

Nitric oxide (NO) plays an important role as a signalling molecule in the biological system. Organoselenium-coated or grafted biomaterials have the potential to achieve controlled NO release as they can catalyse decomposition of endogenous S-nitrosothiols to NO. However, such biomaterials are often challenged by the loss of the catalytic sites, which can affect the stability in tissue repair applications. In this work, we prepare a diselenide-containing poly(ester urethane)urea (SePEUU) polymer with Se-Se in the backbone, which is further electrospun into fibrous membranes by blending with poly(ester urethane)urea (PEUU) without diselenide bonds. The presence of catalytic sites in the main chain demonstrates stable and long-lasting NO catalytic activity, while the porous structure of the fibrous membranes ensures uniform distribution of the catalytic sites and better contact with the donor-containing solution. PEUU/SePEUU50 in 50/50 mass ratio has a physiologically adapted rate of NO release, with a sustained generation of NO after exposure to PBS at 37 °C for 30 d. PEUU/SePEUU50 has a low hemolysis and protein adsorption, with mechanical properties in the wet state matching those of natural vascular tissues. It can promote the adhesion and proliferation of human umbilical vein endothelial cells in vitro and control the proliferation of vascular smooth muscle cells in the presence of NO generation. This study exhibits the electrospun fibrous membranes have potential for utilizing as hemocompatible biomaterials for regeneration of blood-contacting tissues.

Entropy-Driven Morphology Regulation of MAX Phase Solid Solutions with Enhanced Microwave Absorption and Thermal Insulation Performance.

Morphology regulation and composition design have proved to be effective strategies for the fabrication of desirable microwave absorbers. However, it is still challenging to precisely control the microstructure and components of MAX phases. Herein, an entropy-driven approach, a transition from irregular grains (low entropy) to sheet structure (high entropy), is proposed to modulate the morphology of MAX phases. The theoretical calculation indicates that the morphology evolution can be ascribed to the enlarged energy difference between (11_00) and (0001) facets. The enriched structural defects and optimized morphologies yield significant dipolar polarization, interfacial polarization, multiple reflections, and scattering, which all enhance the electromagnetic wave absorption performance of (V0.25 Ti0.25 Cr0.25 Mo0.25 )2 GaC. Specifically, its minimum reflection loss can reach up to -47.12 dB at 12.13 GHz, and the optimal effective absorption bandwidth is 4.56 GHz (2.03 mm). Meanwhile, (V0.25 Ti0.25 Cr0.25 Mo0.25 )2 GaC shows also pronounced thermal insulation properties affording it good reliability in the harsh working environment. This work offers a novel approach to designing and regulating the morphology of the high entropy MAX phase, and also presents an opportunity to elucidate the relationship between entropy and electromagnetic wave absorption performance.

Methylation of TTC4 interaction with HSP70 inhibits pyroptosis in macrophages of sepsis-induced lung injury by NLRP3 inflammation.

Acute lung injury (ALI) is an acute infectious diseases caused by a variety of factors. The function of TTC4 in sepsis-induced lung injury remains largely unknown. This study aimed to explore the critical role of TTC4 in sepsis-induced lung injury. Mice anaesthetized using pentobarbital sodium and subjected to cecal ligation and puncture (CLP) surgery. TTC4 expression levels in patients with sepsis-induced lung injury were down-regulated. The inhibition of TTC4 gene promoted lung injury in mice model of sepsis. TTC4 gene improved inflammation in vitro model and mice model. TTC4 gene reduced pyroptosis in macrophages of sepsis-induced lung injury by the inhibition of mitochondrial damage. TTC4 gene induced HSP70 expression to reduce NLRP3-induced pyroptosis in macrophages. TTC4 protein interlinked HSP70 protein. The activation of HSP70 reduced the effects of sh-TTC4 in model of sepsis-induced lung injury through mitochondrial damage. m6A-forming enzyme METTL3 reduced TTC4 stability. Our study suggests the m6A forming enzyme METTL3 control TTC4 reduced inflammation and pyroptosis in model of sepsis-induced lung injury through inhibition of mitochondrial damage by HSP70/ROS/NLRP3 signaling pathway, TTC4 gene as an represents a potential therapeutic strategy for the treatment of sepsis-induced lung injury.

Mesencephalic Astrocyte-Derived Neurotrophic Factor (MANF) Alleviates Sepsis-Induced Cardiomyopathy by Inhibiting Pyroptosis.

Background: Sepsis-induced cardiomyopathy (SIC) is a common complication of sepsis accompanied by high prevalence and mortality in sepsis patients. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a neurotrophic factor, and it exerts critical functions in various diseases, including heart diseases, while its effect on SIC remains elusive. Hence, we aimed to investigate the action of MANF on SIC. Methods: This study was under the guidance of Gongli Hospital, Shanghai, China from January 2021 to December 2021. H9c2 cells and mice were induced by LPS to establish SIC in vitro and in vivo models. qRT-PCR and Western blot were used to determine gene and protein expressions. The levels of MANF, Interleukin-1ß (IL-1ß), Interleukin 18 (IL-18), creatine kinase-MB (CK-MB), and cardiac troponin I (cTn I) were detected using ELISA assay. Cell pyroptosis determination was performed by flow cytometry. The DCFDA assay kit was used to determine ROS production. Results: In SIC in vitro model, LPS induced cell pyroptosis (P<0.001) and ROS accumulation (P<0.001). Besides, MANF was decreased in LPS-induced H9c2 cells (P<0.001) and SIC patients (P<0.001). In addition, overexpression of MANF ameliorated SIC-induced injury in H9C2 cells (P<0.001). Furthermore, inhibition of NLRP3 rescued the function of MANF on SIC-induced injury in H9C2 cells (P<0.001). Moreover, enforced MANF suppressed the SIC-induced injury in vivo model (P<0.001). Conclusion: MANF was down-regulated in SIC. Overexpressed MANF ameliorated the SIC injury by inhibiting NLRP3-mediated pyroptosis.

Impact of diabetes itself and glycemic control status on tuberculosis.

Objectives: To explore the impact of diabetes itself and glycemic control status on tuberculosis (TB). Methods: A total of 3393 patients with TB and diabetes mellitus (DM) who were hospitalized in the Public Health Clinical Center of Chengdu from January 1, 2019, to December 31, 2021, were retrospectively included and divided into three groups according to baseline glycemic control status: two groups according to glycemic status at discharge, two groups according to cavity occurrence, three groups according to sputum results, and three groups according to lesion location. The influencing factors and the differences in cavity occurrence, sputum positivity and lesion location among different glycemic control groups or between different glycemic status groups were analyzed. Results: In this TB with DM cohort, most of the subjects were male, with a male to female ratio of 4.54:1, most of them were 45-59 years old, with an average age of 57.44 ± 13.22 years old. Among them, 16.8% (569/3393) had cavities, 52.2% (1770/3393) were sputum positive, 30.4% (1030/3393) had simple intrapulmonary lesions, 68.1% (2311/3393) had both intra and extrapulmonary lesions, only 15.8% (537/3393) had good glycemic control,16.0% (542/3393) and 68.2% (2314/3393) had fair and poor glycemic control, respectively. Compared with the non-cavity group, the sputum-negative group and the extrapulmonary lesion group, the cavity group, sputum-positive group, intrapulmonary lesion group and the intra and extrapulmonary lesion group all had higher fasting plasma glucose (FPG) and glycosylated hemoglobin A 1c (HbA1c) and lower good glycemic control rates at admission (all P<0.001). Another aspect, compared with the good glycemic control group, the poor glycemic control group had a higher cavity occurrence rate, sputum positive rate, and greater proportion of intrapulmonary lesions. Moreover, FPG and HbA1c levels and poor glycemic control were significantly positively correlated with cavity occurrence, sputum positivity, and intrapulmonary lesions and were the main risk factors for TB disease progression. On the other hand, cavity occurrence, sputum positivity, and intrapulmonary lesions were also main risk factors for hyperglycemia and poor glycemic control. Conclusion: Diabetes itself and glycemic control status could impact TB disease. Good glycemic control throughout the whole process is necessary for patients with TB and DM to reduce cavity occurrence and promote sputum negative conversion and lesion absorption.

Effects of mesencephalic astrocyte-derived neurotrophic factor on sepsis-associated acute kidney injury.

BACKGROUND: To determine the protective role of mesencephalic astrocyte-derived neurotrophic factor (MANF) in regulating sepsis-associated acute kidney injury (S-AKI). METHODS: A total of 96 mice were randomly divided into the control group, control+MANF group, S-AKI group, and S-AKI+MANF group. The S-AKI model was established by injecting lipopolysaccharide (LPS) at 10 mg/kg intraperitoneally. MANF (200 µg/kg) was administered to the control+MANF and S-AKI+MANF groups. An equal dose of normal saline was administered daily intraperitoneally in the control and S-AKI groups. Serum and kidney tissue samples were obtained for biochemical analysis. Western blotting was used to detect the protein expression of MANF in the kidney, and enzyme-linked immunosorbent assay (ELISA) was used to determine expression of MANF in the serum, pro-inflammatory cytokines (tumor necrosis factor-α [TNF-α] and interleukin-6 [IL-6]). Serum creatinine (SCr), and blood urea nitrogen (BUN) were examined using an automatic biochemical analyzer. In addition, the kidney tissue was observed for pathological changes by hematoxylin-eosin staining. The comparison between two groups was performed by unpaired Student's t-test, and statistics among multiple groups were carried out using Tukey's post hoc test following one-way analysis of variance (ANOVA). A P-value <0.05 was considered statistically significant. RESULTS: At the early stage of S-AKI, MANF in the kidney tissue was up-regulated, but with the development of the disease, it was down-regulated. Renal function was worsened in the S-AKI group, and TNF-α and IL-6 were elevated. The administration of MANF significantly alleviated the elevated levels of SCr and BUN and inhibited the expression of TNF-α and IL-6 in the kidney. The pathological changes were more extensive in the S-AKI group than in the S-AKI+MANF group. CONCLUSION: MANF treatment may significantly alleviate renal injury, reduce the inflammatory response, and alleviate or reverse kidney tissue damage. MANF may have a protective effect on S-AKI, suggesting a potential treatment for S-AKI.

Flexible Fluorinated Graphene/Poly(vinyl Alcohol) Films toward High Thermal Management Capability.

Graphene is widely used in heat dissipation, owing to its inherently high in-plane thermal conductivity and excellent mechanical properties. However, its poor cross-plane thermal conductivity limits its use in some electronic applications. The electron distribution of graphene and the interaction with the base material can be greatly altered by introducing F, the most electronegative element, giving fluorinated graphene oxide (FG) with a high thermal conductivity. Herein, FG is prepared by grafting F atoms onto the surface of graphene oxide in a low-temperature solid-phase reaction with poly(vinylidene fluoride) as a fluorine source. This method can effectively avoid the use of dangerous substances such as HF and F2. The FG dispersion and aqueous poly(vinyl alcohol) (PVA) solution are sequentially vacuum-filtered to obtain the FG/PVA composite film. After natural drying and hot-pressing, the thermal conductivity of the N-FG/PVA film is enhanced by the hydrogen bond between F of FG and the hydroxyl group of PVA. The in-plane and cross-plane thermal conductivity of an N-FG/PVA film containing 10.4 wt % FG are 7.13 and 1.42 W m-1 k-1, respectively. The film has a tensile strength of 60 MPa and an elongation at a break of 28%, which is promising for the thermal management of flexible electronic devices.

How immune breakthroughs could slow disease progression and improve prognosis in COVID-19 patients: a retrospective study.

Background: Previous infections and vaccinations have produced preexisting immunity, which differs from primary infection in the organism immune response and may lead to different disease severities and prognoses when reinfected. Objectives: The purpose of this retrospective cohort study was to investigate the impact of immune breakthroughs on disease progression and prognosis in patients with COVID-19. Methods: A retrospective cohort study was conducted on 1513 COVID-19 patients in Chengdu Public Health Clinical Medical Center from January 2020 to November 2022. All patients were divided into the no immunity group (primary infection and unvaccinated, n=1102) and the immune breakthrough group (previous infection or vaccination, n=411). The immune breakthrough group was further divided into the natural immunity subgroup (n=73), the acquired immunity subgroup (n=322) and the mixed immunity subgroup (n=16). The differences in clinical and outcome data and T lymphocyte subsets and antibody levels between two groups or between three subgroups were compared by ANOVA, t test and chi-square test, and the relationship between T lymphocyte subsets and antibody levels and the disease progression and prognosis of COVID-19 patients was assessed by univariate analysis and logistic regression analysis. Results: The total critical rate and the total mortality rate were 2.11% and 0.53%, respectively. The immune breakthrough rate was 27.16%. In the no immunity group, the critical rate and the mortality rate were all higher, and the coronavirus negative conversion time was longer than those in the immune breakthrough group. The differences in the critical rate and the coronavirus negative conversion time between the two groups were all statistically significant (3.72% vs. 0.24%, 14.17 vs. 11.90 days, all p<0.001). In addition, in the no immunity group, although lymphocyte counts and T subsets at admission were higher, all of them decreased consistently and significantly and were significantly lower than those in the immune breakthrough group at the same time from the first week to the fourth week after admission (all p<0.01). The total antibody levels and specific Immunoglobulin G (IgG) levels increased gradually and were always significantly lower than those in the immune breakthrough group at the same time from admission to the fourth week after admission (all p<0.001). Moreover, in the natural immunity subgroup, lymphocyte counts and T subsets at admission were the highest, and total antibody levels and specific IgG levels at admission were the lowest. Then, all of them decreased significantly and were the lowest among the three subgroups at the same time from admission to one month after admission (total antibody: from 546.07 to 158.89, IgG: from 6.00 to 3.95) (all p<0.001). Those in the mixed immunity subgroup were followed by those in the acquired immunity subgroup. While lymphocyte counts and T subsets in these two subgroups and total antibody levels (from 830.84 to 1008.21) and specific IgG levels (from 6.23 to 7.51) in the acquired immunity subgroup increased gradually, total antibody levels (from 1100.82 to 908.58) and specific IgG levels (from 7.14 to 6.58) in the mixed immunity subgroup decreased gradually. Furthermore, T lymphocyte subsets and antibody levels were negatively related to disease severity, prognosis and coronavirus negative conversion time. The total antibody, specific IgM and IgG levels showed good utility for predicting critical COVID-19 patients and dead COVID-19 patients. Conclusion: Among patients with COVID-19 patients, immune breakthroughs resulting from previous infection or vaccination, could decelerate disease progression and enhance prognosis by expediting host cellular and humoral immunity to accelerate virus clearance, especially in individuals who have been vaccinated and previously infected. Clinical trial registry: Chinese Clinical Trial Register ChiCTR2000034563.

Gut Microbiota Metabolite 3-Indolepropionic Acid Directly Activates Hepatic Stellate Cells by ROS/JNK/p38 Signaling Pathways.

There has been a growing interest in studying the communication of gut microbial metabolites between the gut and the liver as liver fibrosis progresses. Although 3-Indolepropionic acid (IPA) is regarded as a clinically valuable gut metabolite for the treatment of certain chronic diseases, the effects of oral administration of IPA on hepatic fibrosis in different animal models have been conflicting. While some mechanisms have been proposed to explain these contradictory effects, the direct impact of IPA on hepatic fibrosis remains unclear. In this study, we found that IPA could directly activate LX-2 human hepatic stellate cells in vitro. IPA upregulated the expression of fibrogenic marker genes and promoted the features associated with HSCs activation, including proliferation and contractility. IPA also increased reactive oxygen species (ROS) in mitochondria and the expression of inflammation-related genes in LX-2 cells. However, when a ROS-blocking agent was used, these effects were reduced. p38 and JNK, the downstream signaling cascades of ROS, were found to be required for the activation of LX-2 induced by IPA. These findings suggest that IPA can directly activate hepatic stellate cells through ROS-induced JNK and p38 signaling pathways.

Multimodal imaging diagnosis for bone fibrous dysplasia malignant transformation: A case report.

Fibrous dysplasia of bone (FDB) is a rare benign condition in which fibrous tissue replaces normal bone architecture. FDB rarely undergoes malignant transformation, but there are reports of locally aggressive fibrous dysplasia with cortical destruction and soft tissue extension. Diagnosis of FDB malignant transformation is not easy, especially in monostotic form, because of the overlap in imaging features of locally aggressive fibrous dysplasia and fibrous dysplasia with malignant transformation. The present case study reports a rare case of FDB in a 23-year-old man with polyostotic fibrous dysplasia arising in the left side of the pelvis and lower limb bones with partial transformation to fibrosarcoma. This study explored the multimodal imaging features of FDB malignant transformation, to achieve early detection and improve diagnostic accuracy of local FDB aggressiveness and its malignant transformation.

Surface Functionalization of Electrospun Scaffolds by QK-AG73 Peptide for Enhanced Interaction with Vascular Endothelial Cells.

Rapid endothelialization still remains challenging for blood-contacting biomaterials, especially for long-term, functional, small-diameter vascular grafts. The vascular endothelial growth factor (VEGF)-mimicking QK peptide holds great promise in promoting vascular endothelial cellular activities such as adhesion, spreading, proliferation, and migration. Syndecans are transmembrane proteoglycans that are highly expressed on cell surfaces, including vascular endothelial cells, which can act as docking receptors to provide binding sites for a variety of cellular growth and signaling molecules. Herein, a novel peptide QK-AG73 that coupled the QK domain with the syndecan binding peptide AG73 was proposed, aiming to synergistically enhance the interaction with vascular endothelial cells. In addition, mechanically matched bioactive scaffolds based on poly(l-lactide-co-ε-caprolactone) were successfully prepared by surface functionalization of the covalently combined QK-AG73 peptide. The result showed that the adhesion of human umbilical vein endothelial cells (HUVECs) was increased by approximately 2-fold on QK-AG73-modified surface compared with those modified with a single QK or AG73 peptide. Moreover, surface functionalization of electrospun scaffolds by this QK-AG73 peptide was more efficient in specifically promoting the proliferation of HUVECs and allowing them to grow with an elongated cobblestone-like cell morphology. It was hypothesized that both VEGF receptors and transmembrane syndecan receptors were involved in cellular regulation by the QK-AG73 peptide, which resulted in synergistic improvement of the interactions with vascular endothelial cells and provided a promising strategy to promote endothelialization of small-diameter vascular grafts.

Exploring calcium channel blocker as a candidate drug for Pseudomonas aeruginosa through network pharmacology and experimental validation.

Calcium channel blocker (CCB) is known to possess antibacterial effects. We aimed to apply network pharmacology (docking and protein-protein interaction [PPI] analyses) to predict the potential targets and mechanisms of CCB against Pseudomonas aeruginosa (PA) as well as to verify the effect of these drugs. The chemical structures of three CCBs were obtained through the Drug Bank platform. The potential channel proteins, efflux pump proteins and ion channel proteins of CCB against bacteria were derived from the literature. These proteins were collected through the PDB and Uniprot platform. The binding mode of the docking complexes was simulated by the CB-Dock platform and Discovery Studio 2019 Client software. The PPI network was constructed by the String platform and Cytoscape 3.8.2 platform. GO was explained by the PANTHER platform. The pathway diagram was drawn with the Pathway Builder Tool 2.0 software. The inhibitory effect of CCB on PA was verified through antibacterial experiments. Finally, 76 proteins were obtained: the iron channel protein of PA demonstrated a good docking relationship with all three CCBs, and the optimum binding energy was approximately -9.0 kcal/mol. GO analysis (biological process [BP], cellular component [CC], and molecular function [MF]) of protein genes showed a good docking relationship (optimum binding energy <-8.0 kcal/mol). The MF annotation results indicated that the target of CCB may be present on the PA membrane protein. The ion channel protein PPI enrichment p-value was 6.65e-08, and PfeA showed the strongest correlation. The experimental results suggested that CCB could inhibit the growth of PA. CCB might be an effective and interesting antimicrobial treatment strategy as CCB can potentially inhibit the growth of PA.

A facial depression recognition method based on hybrid multi-head cross attention network.

Introduction: Deep-learn methods based on convolutional neural networks (CNNs) have demonstrated impressive performance in depression analysis. Nevertheless, some critical challenges need to be resolved in these methods: (1) It is still difficult for CNNs to learn long-range inductive biases in the low-level feature extraction of different facial regions because of the spatial locality. (2) It is difficult for a model with only a single attention head to concentrate on various parts of the face simultaneously, leading to less sensitivity to other important facial regions associated with depression. In the case of facial depression recognition, many of the clues come from a few areas of the face simultaneously, e.g., the mouth and eyes. Methods: To address these issues, we present an end-to-end integrated framework called Hybrid Multi-head Cross Attention Network (HMHN), which includes two stages. The first stage consists of the Grid-Wise Attention block (GWA) and Deep Feature Fusion block (DFF) for the low-level visual depression feature learning. In the second stage, we obtain the global representation by encoding high-order interactions among local features with Multi-head Cross Attention block (MAB) and Attention Fusion block (AFB). Results: We experimented on AVEC2013 and AVEC2014 depression datasets. The results of AVEC 2013 (RMSE = 7.38, MAE = 6.05) and AVEC 2014 (RMSE = 7.60, MAE = 6.01) demonstrated the efficacy of our method and outperformed most of the state-of-the-art video-based depression recognition approaches. Discussion: We proposed a deep learning hybrid model for depression recognition by capturing the higher-order interactions between the depression features of multiple facial regions, which can effectively reduce the error in depression recognition and gives great potential for clinical experiments.

Synergistic impacts of Fe/Fe3C and Fe-Nx on high-efficiency microwave-absorbing properties of Fe/Fe3C@NC composites.

The construction of multi-component composites has become an attractive strategy for high-performance microwave absorption through balancing the magnetic and dielectric loss. However, the influences of different components on absorption performance are ambiguous, which has inevitably hampered the widespread applications of microwave absorbents. Herein, we rationally designed the multi-component absorbers of N-doped carbon composited with Fe/Fe3C nanoparticles, and systematically investigated the impacts of Fe/Fe3C nanoparticles and Fe-Nxmoieties on the microwave-absorbing capacities. It is found that the coexisitence of Fe/Fe3C and Fe-Nxis indispensable to realize the strong microwave absorption ability by simultaneously enhancing the dielectric and magnetic loss in the frequency range of 2-18 GHz. As expected, our optimal absorber dispersed in paraffin with a filler loading of 15 wt% exhibits the minimum reflection loss (RLmin) value of -49 dB and the maximum effective absorption bandwidth (BWeff) value of 4.2 GHz at a low thickness. Our work specifies the importance and influence of the coexistence between the Fe-Nxconfigurations and Fe/Fe3C nanoparticles in the carbon-based composites for the superior microwave absorption and inspires the future fabrication of extraordinary materials in the electromagnetic field.

Regulation of a Novel CircTRRAP/miR-761/MAP3K2 CeRNA Cascade in Inflammation, Apoptosis, and Oxidative Stress in Human AC16 Cardiomyocytes under Hypoxia Conditions.

Emerging evidence uncovers the important involvement of circular RNAs (circRNAs) in the dysfunction of cardiomyocytes under hypoxia conditions. However, no studies proved whether circTRRAP (hsa_circ_0081241) can participate in cardiomyocyte injury evoked by hypoxia.A qRT-PCR or immunoblotting method was used to evaluate the expression of circTRRAP, miR-761, and mitogen-activated protein kinase kinase kinase 2 (MAP3K2). The direct relationships of circTRRAP/miR-761 and miR-761/MAP3K2 were confirmed by RNA immunoprecipitation (RIP) assay, dual-luciferase reporter assay, and RNA pull-down assay. The effects of the circTRRAP/miR-761/MAP3K2 axis on cell functional behaviors were examined by 5-ethynyl-2'-deoxyuridine (EdU) assay, CCK-8 assay, and flow cytometry. The production levels of proinflammatory cytokines (IL-1ß, TNF-α, and IL-6) were evaluated by enzyme-linked immunosorbent assay.CircTRRAP and MAP3K2 were overexpressed but miR-761 was downregulated in AC16 cardiomyocytes under hypoxia and in the serum of patients with acute myocardial infarction. Silencing circTRRAP attenuated hypoxia-evoked inflammation, apoptosis, and oxidative stress in human AC16 cardiomyocytes. CircTRRAP targeted miR-761, and miR-761 directly targeted and suppressed MAP3K2. CircTRRAP involved the post-transcriptional regulation of MAP3K2 through miR-761, indicating its competing endogenous RNA (ceRNA) activity. Moreover, miR-761 inhibition abolished the effects of circTRRAP depletion in hypoxia-induced cell injury. MAP3K2 silencing phenocopied miR-761 increase in attenuating hypoxia-evoked cardiomyocyte inflammation, apoptosis, and oxidative stress.Our study demonstrates that circTRRAP can protect AC16 cardiomyocytes from hypoxia-evoked injury through the miR-761/MAP3K2 axis.

Nutritional risk and a high NRS2002 score are closely related to disease progression and poor prognosis in patients with COVID-19.

Background: Organism can lead to excessive nutrient consumption in the infected state and increase nutritional risk, which is detrimental to the control of the infection and can further aggravate the disease. Objectives: To investigate the impact of nutritional risk and the NRS2002 score on disease progression and prognosis in patients with COVID-19. Methods: This was a retrospective cohort study including 1,228 COVID-19 patients, who were divided into a with-nutritional risk group (patients with NRS2002 score ≥ 3) and a without-nutritional risk group (patients with NRS2002 score < 3) according to the NRS2002 score at admission. The differences in clinical and outcome data between the two groups were compared, and the relationship between the NRS2002 score and the disease progression and prognosis of COVID-19 patients was assessed. Results: Of 1,228 COVID-19 patients, including 44 critical illness patients and 1,184 non-critical illness patients, the rate of harboring nutritional risk was 7.90%. Compared with those in the without-nutritional risk group, patients in the with-nutritional risk group had a significantly longer coronavirus negative conversion time, significantly lower serum albumin (ALB), total serum protein (TP) and hemoglobin (HGB) at admission, discharge or 2 weeks, a significantly greater proportion with 3 or more comorbidities, and a significantly higher rate of critical illness and mortality (all p < 0.001). Multiple regression analysis showed that nutritional risk, NRS2002 score and ALB at admission were risk factors for disease severity. In addition, nutritional risk, NRS2002 score and TP at admission were risk factors for prognosis. The NRS2002 score showed the best utility for predicting critical illness and death in COVID-19 patients. Conclusion: Nutritional risk and a high NRS2002 score are closely related to disease progression and poor prognosis in COVID-19 patients. For patients with NRS2002 score > 0.5, early intervention of malnutrition is needed to reduce the occurrence of critical disease. Additionally, for patients with NRS2002 score > 5.5, continuous nutritional support therapy is needs to reduce mortality and improve prognosis.Clinical Trial registration: [https://www.chictr.org.cn/historyversionpub.aspx?regno=ChiCTR2000034563], identifier [Chinese Clinical Trial Register ChiCTR2000034563].