Obesity is one of the most serious global health problems, with an incidence that increases yearly and coincides with the development of cancer. Adipose tissue macrophages (ATMs) are particularly important in this context and contribute to linking obesity-related inflammation and tumor progression. However, the functions of ATMs on the progression of obesity-associated cancer remain unclear. In this review, we describe the origins, phenotypes, and functions of ATMs. Subsequently, we summarize the potential mechanisms on the reprogramming of ATMs in the obesity-associated microenvironment, including the direct exchange of dysfunctional metabolites, inordinate cytokines and other signaling mediators, transfer of extracellular vesicle cargo, and variations in the gut microbiota and its metabolites. A better understanding of the properties and functions of ATMs under conditions of obesity will lead to the development of new therapeutic interventions for obesity-related cancer.

Background: Examining the health outcomes of veterans who have completed the United States Veterans Health Administration’s (VHA’s) Traumatic Brain Injury (TBI) Screening and Evaluation Program may aid in the refinement and improvement of clinical care initiatives within the VHA. This study compared self-reported physical functioning, cardiometabolic health conditions, and health care utilization patterns in Million Veteran Program enrollees with TBI Screening and Evaluation Program data (collected between 2007 and 2019), with the goal of enhancing understanding of potentially modifiable health conditions in this population.

Methods: In this observational cohort study, veterans (n=16,452) were grouped based on the diagnostic outcome of the TBI Screening and Evaluation Program: 1) negative TBI screen (Screen^–); 2) positive TBI screen but no confirmed TBI diagnosis [Screen⁺/Comprehensive TBI Evaluation (CTBIE)^–]; or 3) positive TBI screen and confirmed TBI diagnosis (Screen⁺/CTBIE⁺). Chi-square tests and analysis of covariance were used to explore group differences in physical functioning, cardiometabolic health conditions, and health care utilization patterns, and logistic regressions were used to examine predictors of Screen^+/– and CTBIE^+/– group status.

Results: The results showed that veterans in the Screen⁺/CTBIE^– and Screen⁺/CTBIE⁺ groups generally reported poorer levels of physical functioning (P’s<0.001, n_p²=0.02 to 0.03), higher rates of cardiometabolic health conditions (P’s<0.001, φ=0.14 to 0.52), and increased health care utilization (P’s<0.001, φ=0.14 to >0.5) compared with the Screen^– group; however, health outcomes were generally comparable between the Screen⁺/CTBIE^– and Screen⁺/CTBIE⁺ groups. Follow-up analyses confirmed that while physical functioning, hypertension, stroke, healthcare utilization, and prescription medication use reliably distinguished between the Screen^– and Screen⁺ groups (P’s<0.02, OR’s=0.78 to 3.38), only physical functioning distinguished between the Screen⁺/CTBIE^– and Screen⁺/CTBIE⁺ groups (P<0.001, OR=0.99).

Conclusions: The findings suggest that veterans who screen positive for TBI, regardless of whether they are ultimately diagnosed with TBI, are at greater risk for negative health outcomes, signifying that these veterans represent a vulnerable group that may benefit from increased clinical care and prevention efforts.

Osteoarthritis (OA) is the most common type of degenerative joint disease which affects 7% of the global population and more than 500 million people worldwide. One research frontier is the development of hydrogels for OA treatment, which operate either as functional scaffolds of tissue engineering or as delivery vehicles of functional additives. Both approaches address the big challenge: establishing stable integration of such delivery systems or implants. Adhesive hydrogels provide possible solutions to this challenge. However, few studies have described the current advances in using adhesive hydrogel for OA treatment. This review summarizes the commonly used hydrogels with their adhesion mechanisms and components. Additionally, recognizing that OA is a complex disease involving different biological mechanisms, the bioactive therapeutic strategies are also presented. By presenting the adhesive hydrogels in an interdisciplinary way, including both the fields of chemistry and biology, this review will attempt to provide a comprehensive insight for designing novel bioadhesive systems for OA therapy.

Background: Triclosan [5-chloro-2-(2,4-dichlorophenoxy) phenol, TCS], a common antimicrobial additive in many personal care and health care products, is frequently detected in human blood and urine. Therefore, it has been considered an emerging and potentially toxic pollutant in recent years. Long-term exposure to TCS has been suggested to exert endocrine disruption effects, and promote liver fibrogenesis and tumorigenesis. This study was aimed at clarifying the underlying cellular and molecular mechanisms of hepatotoxicity effect of TCS at the initiation stage.

Methods: C57BL/6 mice were exposed to different dosages of TCS for 2 weeks and the organ toxicity was evaluated by various measurements including complete blood count, histological analysis and TCS quantification. Single cell RNA sequencing (scRNA-seq) was then carried out on TCS- or mock-treated mice livers to delineate the TCS-induced hepatotoxicity. The acquired single-cell transcriptomic data were analyzed from different aspects including differential gene expression, transcription factor (TF) regulatory network, pseudotime trajectory, and cellular communication, to systematically dissect the cellular and molecular events after TCS exposure. To verify the TCS-induced liver fibrosis, the expression levels of key fibrogenic proteins were examined by Western blotting, immunofluorescence, Masson’s trichrome and Sirius red stainings. In addition, normal hepatocyte cell MIHA and hepatic stellate cell LX-2 were used as in vitro cell models to experimentally validate the effects of TCS by immunological, proteomic and metabolomic technologies.

Results: We established a relatively short term TCS exposure murine model and found the TCS mainly accumulated in the liver. The scRNA-seq performed on the livers of the TCS-treated and control groups profiled the gene expressions of > 76,000 cells belonging to 13 major cell types. Among these types, hepatocytes and hepatic stellate cells (HSCs) were significantly increased in TCS-treated group. We found that TCS promoted fibrosis-associated proliferation of hepatocytes, in which Gata2 and Mef2c are the key driving TFs. Our data also suggested that TCS induced the proliferation and activation of HSCs, which was experimentally verified in both liver tissue and cell model. In addition, other changes including the dysfunction and capillarization of endothelial cells, an increase of fibrotic characteristics in B plasma cells, and M2 phenotype-skewing of macrophage cells, were also deduced from the scRNA-seq analysis, and these changes are likely to contribute to the progression of liver fibrosis. Lastly, the key differential ligand-receptor pairs involved in cellular communications were identified and we confirmed the role of GAS6_AXL interaction-mediated cellular communication in promoting liver fibrosis.

Conclusions: TCS modulates the cellular activities and fates of several specific cell types (including hepatocytes, HSCs, endothelial cells, B cells, Kupffer cells and liver capsular macrophages) in the liver, and regulates the ligand-receptor interactions between these cells, thereby promoting the proliferation and activation of HSCs, leading to liver fibrosis. Overall, we provide the first comprehensive single-cell atlas of mice livers in response to TCS and delineate the key cellular and molecular processes involved in TCS-induced hepatotoxicity and fibrosis.

Artificial intelligence (AI), a branch of machine learning (ML) has been increasingly employed in the research of trauma in various aspects. Hemorrhage is the most common cause of trauma-related death. To better elucidate the current role of AI and contribute to future development of ML in trauma care, we conducted a review focused on the use of ML in the diagnosis or treatment strategy of traumatic hemorrhage. A literature search was carried out on PubMed and Google scholar. Titles and abstracts were screened and, if deemed appropriate, the full articles were reviewed. We included 89 studies in the review. These studies could be grouped into five areas: 1) prediction of outcomes; 2) risk assessment and injury severity for triage; 3) prediction of transfusions; 4) detection of hemorrhage; and 5) prediction of coagulopathy. Performance analysis of ML in comparison with current standards for trauma care showed that most studies demonstrated the benefits of ML models. However, most studies were retrospective, focused on prediction of mortality, and development of patient outcome scoring systems. Few studies performed model assessment via test datasets obtained from different sources. Prediction models for transfusions and coagulopathy have been developed, but none is in widespread use. AI-enabled ML-driven technology is becoming integral part of the whole course of trauma care. Comparison and application of ML algorithms using different datasets from initial training, testing and validation in prospective and randomized controlled trials are warranted for provision of decision support for individualized patient care as far forward as possible.

A bio-inspired strategy has recently been developed for camouflaging nanocarriers with biomembranes, such as natural cell membranes or subcellular structure-derived membranes. This strategy endows cloaked nanomaterials with improved interfacial properties, superior cell targeting, immune evasion potential, and prolonged duration of systemic circulation. Here, we summarize recent advances in the production and application of exosomal membrane-coated nanomaterials. The structure, properties, and manner in which exosomes communicate with cells are first reviewed. This is followed by a discussion of the types of exosomes and their fabrication methods. We then discuss the applications of biomimetic exosomes and membrane-cloaked nanocarriers in tissue engineering, regenerative medicine, imaging, and the treatment of neurodegenerative diseases. Finally, we appraise the current challenges associated with the clinical translation of biomimetic exosomal membrane-surface-engineered nanovehicles and evaluate the future of this technology.

Background: Emergency front-of-neck airway (eFONA) is a life-saving procedure in "cannot intubate, cannot oxygenate" (CICO). The fastest and most reliable method of eFONA has not been determined. We compared two of the most advocated approaches: surgical cricothyroidotomy and percutaneous cricothyroidotomy, in an obese, in vivo porcine hemorrhage model, designed to introduce real-time physiological feedback, relevant and high provider stress. The primary aim was to determine the fastest method to secure airway. Secondary aims were arterial saturation and partial pressure of oxygen, proxy survival and influence of experience.

Methods: Twelve pigs [(60.3±4.1) kg] were anesthetized and exposed to 25%–35% total blood volume hemorrhage before extubation and randomization to Seldinger technique "percutaneous cricothyroidotomy" (n=6) or scalpel-bougie-tube technique "surgical cricothyroidotomy" (n=6). Specialists in anesthesia and intensive care in a tertiary referral hospital performed the eFONA, simulating an actual CICO-situation.

Results: In surgical cricothyroidotomy vs. percutaneous cricothyroidotomy, the median (interquartile range, IQR) times to secure airway were 109 (IQR 71–130) s and 298 (IQR 128–360) s (P=0.0152), arterial blood saturation (SaO₂) were 74.7 (IQR 46.6–84.2)% and 7.9 (IQR 4.1–15.6)% (P=0.0167), PaO₂ were 7.0 (IQR 4.7–7.7) kPa and 2.0 (IQR 1.1–2.9) kPa (P=0.0667), and times of cardiac arrest (proxy survival) were 137–233 s, 190 (IQR 143–229) s, from CICO. All six animals survived surgical cricothyroidotomy, and two of six (33%) animals survived percutaneous cricothyroidotomy. Years in anesthesia, 13.5 (IQR 7.5–21.3), did not influence time to secure airway.

Conclusions: eFONA by surgical cricothyroidotomy was faster and had increased oxygenation and survival, when performed under stress by board certified anesthesiologists, and may be an indication of preferred method in situations with hemorrhage and CICO, in obese patients.