Nanoscopy reveals integrin clustering reliant on kindlin-3 but not talin-1.

Background: Neutrophils are the most abundant leukocytes in human blood, and their recruitment is essential for innate immunity and inflammatory responses. The initial and critical step of neutrophil recruitment is their adhesion to vascular endothelium, which depends on G protein-coupled receptor (GPCR) triggered integrin inside-out signaling that induces β2 integrin activation and clustering on neutrophils. Kindlin-3 and talin-1 are essential regulators for the inside-out signaling induced β2 integrin activation.

Heart failure misdiagnosed as acute cholecystitis: a case report.

Background: Heart failure is a clinical syndrome characterized by decreased cardiac output, leading to systemic organ hypoxia and resulting in dyspnea, pulmonary edema, organ congestion, and pleural effusion. Owing to the diverse clinical manifestations of heart failure, early diagnosis can be challenging, and misdiagnosis may occur occasionally. The use of echocardiography and blood brain natriuretic peptide can aid in obtaining a more accurate diagnosis.

Peceleganan Spray for the Treatment of Skin Wound Infections: A Randomized Clinical Trial.

Importance: Peceleganan spray is a novel topical antimicrobial agent targeted for the treatment of skin wound infections. However, its efficacy and safety remain unclear.

Objective: To assess the safety and efficacy of peceleganan spray for the treatment of wound infections.

A digital twin model incorporating generalized metabolic fluxes to identify and predict chronic kidney disease in type 2 diabetes mellitus.

We have developed a digital twin-based CKD identification and prediction model that leverages generalized metabolic fluxes (GMF) for patients with Type 2 Diabetes Mellitus (T2DM). GMF digital twins utilized basic clinical and physiological biomarkers as inputs for identification and prediction of CKD. We employed four diverse multi-ethnic cohorts (n = 7072): a Singaporean cohort (EVAS, n = 289) and a North American cohort (NHANES, n = 1044) for baseline CKD identification, and two multi-center Singaporean cohorts (CDMD, n = 2119 and SDR, n = 3627) for 3-year CKD prediction and risk stratification.

Multiscale embedded printing of engineered human tissue and organ equivalents.

Creating tissue and organ equivalents with intricate architectures and multiscale functional feature sizes is the first step toward the reconstruction of transplantable human tissues and organs. Existing embedded ink writing approaches are limited by achievable feature sizes ranging from hundreds of microns to tens of millimeters, which hinders their ability to accurately duplicate structures found in various human tissues and organs. In this study, a multiscale embedded printing (MSEP) strategy is developed, in which a stimuli-responsive yield-stress fluid is applied to facilitate the printing process.

3D printing-based full-scale human brain for diverse applications.

Surgery is the most frequent treatment for patients with brain tumors. The construction of full-scale human brain models, which is still challenging to realize via current manufacturing techniques, can effectively train surgeons before brain tumor surgeries. This paper aims to develop a set of three-dimensional (3D) printing approaches to fabricate customized full-scale human brain models for surgery training as well as specialized brain patches for wound healing after surgery.

Sacrificial scaffold-assisted direct ink writing of engineered aortic valve prostheses.

Heart valve disease has become a serious global health problem, which calls for numerous implantable prosthetic valves to fulfill the broader needs of patients. Although current three-dimensional (3D) bioprinting approaches can be used to manufacture customized valve prostheses, they still have some complications, such as limited biocompatibility, constrained structural complexity, and difficulty to make heterogeneous constructs, to name a few. To overcome these challenges, a sacrificial scaffold-assisted direct ink writing approach has been explored and proposed in this work, in which a sacrificial scaffold is printed to temporarily support sinus wall and overhanging leaflets of an aortic valve prosthesis that can be removed easily and mildly without causing any potential damages to the valve prosthesis.

Crosstalk between ferroptosis and steroid hormone signaling in gynecologic cancers.

Ferroptosis is a novel types of regulated cell death and is widely studied in cancers and many other diseases in recent years. It is characterized by iron accumulation and intense lipid peroxidation that ultimately inducing oxidative damage. So far, signaling pathways related to ferroptosis are involved in all aspects of determining cell fate, including oxidative phosphorylation, metal-ion transport, energy metabolism and cholesterol synthesis progress, et al.

Primary ovarian endometrial stromal sarcoma after hysterectomy associated with multiple organ invasion: A case report.

Rationale: Endometrial stromal sarcoma (ESS) is a rare disease in patients with uterine malignancies, accounting for <1%. Low-grade endometrial stromal sarcoma (LGESS) accounts merely 0.2% of gynecologic malignant tumor.

MicroRNA-126 regulates macrophage polarization to prevent the resorption of alveolar bone in diabetic periodontitis.

Objective: This study aims to investigate the effects of microRNA-126 (miR-126) on the macrophage polarization in vitro and alveolar bone resorption in vivo.

Design: The relationship between miR-126 and MEK/ERK kinase 2 (MEKK2) was confirmed by dual-luciferase reporter assay. Real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay or Western blot was used to detect the changes of miR-126, inducible nitric oxide synthase (iNOS), arginase-1 (Arg-1), tumor necrosis factor (TNF)-α, interleukin (IL)-10, MEKK2 and MEKK2-related pathways: mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) in RAW264.

Kindlin2 enables EphB/ephrinB bi-directional signaling to support vascular development.

Direct contact between cells expressing either ephrin ligands or Eph receptor tyrosine kinase produces diverse developmental responses. Transmembrane ephrinB ligands play active roles in transducing bi-directional signals downstream of EphB/ephrinB interaction. However, it has not been well understood how ephrinB relays transcellular signals to neighboring cells and what intracellular effectors are involved.

Cloud-based blockchain technology to identify counterfeits.

Multi-stakeholder and organizational involvement is an integral part of the medicine supply chain. Keeping track of the activities associated with medical products is difficult when the system is complex. Their complexity limits transparency and data provenance.

Structural Basis of β2 Integrin Inside-Out Activation.

β2 integrins are expressed on all leukocytes. Precise regulation of the β2 integrin is critical for leukocyte adhesion and trafficking. In neutrophils, β2 integrins participate in slow rolling.

Automatic Music Classification Model Based on Instantaneous Frequency and CNNs in High Noise Environment.

Automatic music classification has significant research implications because it is the foundation for quick and efficient music resource retrieval and has a wide range of possible applications. In this study, DL is used to extract and categorize musical features, and a DL-based model for music feature extraction and classification is created. In this study, the instantaneous frequency and short-time Fourier transform are used to estimate the sine of a mixed music signal.

Single cell transcriptomics and TCR reconstruction reveal CD4 T cell response to MHC-II-restricted APOB epitope in human cardiovascular disease.

Atherosclerosis is accompanied by a CD4 T cell response to apolipoprotein B (APOB). Major Histocompatibility Complex (MHC)-II tetramers can be used to isolate antigen-specific CD4 T cells by flow sorting. Here, we produce, validate and use an MHC-II tetramer, DRB1*07:01 APOB-p18, to sort APOB-p18-specific cells from peripheral blood mononuclear cell samples from 8 DRB1*07:01+ women with and without subclinical cardiovascular disease (sCVD).

Efficacy and Safety of PL-5 (Peceleganan) Spray for Wound Infections: A Phase IIb Randomized Clinical Trial.

Objective: To assess the safety and efficacy of antimicrobial peptide PL-5 (Peceleganan) spray in the treatment of wound infections.

Background: Antimicrobial peptide PL-5 spray is a novel topical antimicrobial agent.

Methods: We conducted a multicenter, open-label, randomized, controlled phase IIb clinical trial to evaluate the efficacy and safety of PL-5 spray, as compared with silver sulfadiazine, in patients with skin wound infections.

A humanized β integrin knockin mouse reveals localized intra- and extravascular neutrophil integrin activation in vivo.

β integrins are leukocyte-specific adhesion molecules that are essential for leukocyte recruitment. The lack of tools for reporting β integrin activation in mice hindered the study of β integrin-related immune responses in vivo. Here, we generated a humanized β integrin knockin mouse strain by targeting the human β integrin coding sequence into the mouse Itgb2 locus to enable imaging of β integrin activation using the KIM127 (extension) and mAb24 (high-affinity) reporter antibodies.

Molecular mechanisms of leukocyte β2 integrin activation.

Integrins are transmembrane receptors that mediate cell-cell and cell-extracellular matrix adhesion. Although all integrins can undergo activation (affinity change for ligands), the degree of activation is most spectacular for integrins on blood cells. The β2 integrins are exclusively expressed on the surface of all leukocytes including neutrophils, lymphocytes, and monocytes.

Bone Marrow Transplantation Rescues Monocyte Recruitment Defect and Improves Cystic Fibrosis in Mice.

Cystic fibrosis (CF) is an inherited life-threatening disease accompanied by repeated lung infections and multiorgan inflammation that affects tens of thousands of people worldwide. The causative gene, cystic fibrosis transmembrane conductance regulator (CFTR), is mutated in CF patients. CFTR functions in epithelial cells have traditionally been thought to cause the disease symptoms.

Olfactory receptor 2 in vascular macrophages drives atherosclerosis by NLRP3-dependent IL-1 production.

Atherosclerosis is an inflammatory disease of the artery walls and involves immune cells such as macrophages. Olfactory receptors (OLFRs) are G protein–coupled chemoreceptors that have a central role in detecting odorants and the sense of smell. We found that mouse vascular macrophages express the olfactory receptor and all associated trafficking and signaling molecules.

Usage of intermingled skin allografts and autografts in a senior patient with major burn injury.

Mortality rate in older adults following extensive burn injury is extremely high, and management of these patients is challenging. One of the main problems is that autologous split-thickness skin grafts are scarce and the wounds cannot be covered quickly and effectively. Intermingled skin grafting is a low-tech and economic method, which not only maximizes the use of precious autologous skin but also prevents the wounds from infection and consumption.

CD45 pre-exclusion from the tips of T cell microvilli prior to antigen recognition.

The tyrosine phosphatase CD45 is a major gatekeeper for restraining T cell activation. Its exclusion from the immunological synapse (IS) is crucial for T cell receptor (TCR) signal transduction. Here, we use expansion super-resolution microscopy to reveal that CD45 is mostly pre-excluded from the tips of microvilli (MV) on primary T cells prior to antigen encounter.

[Analysis on the diagnosis and treatment of necrotizing fasciitis complicated with sepsis].

Objective: To recognize the characteristics of necrotizing fasciitis patients complicated with sepsis and summarize the experience the treatment.

Methods: A retrospective study was conducted. The clinical data of 57 patients with necrotizing fasciitis complicated with sepsis admitted to Guangdong Provincial People's Hospital from July 2009 to December 2019 was analyzed by collecting such factors as gender, age, complications, infection sites, pathogens, surgery information, treatment options and outcome.

New Atypical Manifestations and Prognostic Factors of Vibrio vulnificus Infection: a 10-Year Retrospective Study.

Vibrio vulnificus (V. vulnificus) infection is rare but potentially fatal. This study explored new atypical manifestations and prognostic factors of V.