Physiological and biochemical processes across tissues of the body are regulated in response to the high demands of intense physical activity in several occupations, such as firefighting, law enforcement, military, and sports. A better understanding of such processes can ultimately help improve human performance and prevent illnesses in the work environment.

To study regulatory processes in intense physical activity simulating real-life conditions, we performed a multi-omics analysis of 3 biofluids (blood plasma, urine, and saliva) collected from 11 wildland firefighters before and after a 45 min, intense exercise regimen. Omics profiles post- vs. pre-exercise were compared by Student’s t-test followed by pathway analysis and comparison between the different omics modalities.

Our multi-omics analysis identified and quantified 3835 proteins, 730 lipids and 182 metabolites combining the 3 different types of samples. The blood plasma analysis revealed signatures of tissue damage and acute repair response accompanied by enhanced carbon metabolism to meet energy demands. The urine analysis showed a strong, concomitant regulation of 6 out of 8 identified proteins from the renin-angiotensin system supporting increased excretion of catabolites, reabsorption of nutrients and maintenance of fluid balance. In saliva, we observed a decrease in 3 pro-inflammatory cytokines and an increase in 8 antimicrobial peptides. A systematic literature review identified 6 papers that support an altered susceptibility to respiratory infection.

This study shows simultaneous regulatory signatures in biofluids indicative of homeostatic maintenance during intense physical activity with possible effects on increased infection susceptibility, suggesting that caution against respiratory diseases could benefit workers on highly physical demanding jobs.

Hypoxic-ischemic injury is a common pathological dysfunction in clinical settings. Mitochondria are sensitive organelles that are readily damaged following ischemia and hypoxia. Dynamin-related protein 1 (Drp1) regulates mitochondrial quality and cellular functions via its oligomeric changes and multiple modifications, which plays a role in mediating the induction of multiple organ damage during hypoxic-ischemic injury. However, there is active controversy and gaps in knowledge regarding the modification, protein interaction, and functions of Drp1, which both hinder and promote development of Drp1 as a novel therapeutic target. Here, we summarize recent findings on the oligomeric changes, modification types, and protein interactions of Drp1 in various hypoxic-ischemic diseases, as well as the Drp1-mediated regulation of mitochondrial quality and cell functions following ischemia and hypoxia. Additionally, potential clinical translation prospects for targeting Drp1 are discussed. This review provides new ideas and targets for proactive interventions on multiple organ damage induced by various hypoxic-ischemic diseases.

Most bone-related injuries to grassroots troops are caused by training or accidental injuries. To establish preventive measures to reduce all kinds of trauma and improve the combat effectiveness of grassroots troops, it is imperative to develop new strategies and scafolds to promote bone regeneration.

In this study, a porous piezoelectric hydrogel bone scafold was fabricated by incorporating polydopamine (PDA)-modified ceramic hydroxyapatite (PDA-hydroxyapatite, PHA) and PDA-modified barium titanate (PDA-BaTiO₃, PBT) nanoparticles into a chitosan/gelatin (Cs/Gel) matrix. The physical and chemical properties of the Cs/Gel/PHA scafold with 0–10 wt% PBT were analyzed. Cell and animal experiments were performed to characterize the immunomodulatory, angiogenic, and osteogenic capabilities of the piezoelectric hydrogel scafold in vitro and in vivo.

The incorporation of BaTiO₃ into the scafold improved its mechanical properties and increased self-generated electricity. Due to their endogenous piezoelectric stimulation and bioactive constituents, the prepared Cs/Gel/PHA/PBT hydrogels exhibited cytocompatibility as well as immunomodulatory, angiogenic, and osteogenic capabilities; they not only effectively induced macrophage polarization to M2 phenotype but also promoted the migration, tube formation, and angiogenic differentiation of human umbilical vein endothelial cells (HUVECs) and facilitated the migration, osteo-differentiation, and extracellular matrix (ECM) mineralization of MC3T3-E1 cells. The in vivo evaluations showed that these piezoelectric hydrogels with versatile capabilities significantly facilitated new bone formation in a rat large-sized cranial injury model. The underlying molecular mechanism can be partly attributed to the immunomodulation of the Cs/Gel/PHA/PBT hydrogels as shown via transcriptome sequencing analysis, and the PI3K/Akt signaling axis plays an important role in regulating macrophage M2 polarization.

The piezoelectric Cs/Gel/PHA/PBT hydrogels developed here with favorable immunomodulation, angiogenesis, and osteogenesis functions may be used as a substitute in periosteum injuries, thereby offering the novel strategy of applying piezoelectric stimulation in bone tissue engineering for the enhancement of combat efectiveness in grassroots troops.

The respiratory system's complex cellular heterogeneity presents unique challenges to researchers in this field. Although bulk RNA sequencing and single-cell RNA sequencing (scRNA-seq) have provided insights into cell types and heterogeneity in the respiratory system, the relevant specific spatial localization and cellular interactions have not been clearly elucidated. Spatial transcriptomics (ST) has filled this gap and has been widely used in respiratory studies. This review focuses on the latest iterative technology of ST in recent years, summarizing how ST can be applied to the physiological and pathological processes of the respiratory system, with emphasis on the lungs. Finally, the current challenges and potential development directions are proposed, including high-throughput full-length transcriptome, integration of multi-omics, temporal and spatial omics, bioinformatics analysis, etc. These viewpoints are expected to advance the study of systematic mechanisms, including respiratory studies.

Skin wounds are characterized by injury to the skin due to trauma, tearing, cuts, or contusions. As such injuries are common to all human groups, they may at times represent a serious socioeconomic burden. Currently, increasing numbers of studies have focused on the role of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) in skin wound repair. As a cell-free therapy, MSC-derived EVs have shown significant application potential in the field of wound repair as a more stable and safer option than conventional cell therapy. Treatment based on MSC-derived EVs can significantly promote the repair of damaged substructures, including the regeneration of vessels, nerves, and hair follicles. In addition, MSC-derived EVs can inhibit scar formation by affecting angiogenesis-related and anti-fibrotic pathways in promoting macrophage polarization, wound angiogenesis, cell proliferation, and cell migration, and by inhibiting excessive extracellular matrix production. Additionally, these structures can serve as a scaffold for components used in wound repair, and they can be developed into bioengineered EVs to support trauma repair. Through the formulation of standardized culture, isolation, purification, and drug delivery strategies, exploration of the detailed mechanism of EVs will allow them to be used as clinical treatments for wound repair. In conclusion, MSC-derived EV-based therapies have important application prospects in wound repair. Here we provide a comprehensive overview of their current status, application potential, and associated drawbacks.

Since 2015, stroke has become the leading cause of death and disability in China, posing a significant threat to the health of its citizens as a major chronic non-communicable disease. According to the China Stroke High-risk Population Screening and Intervention Program, an estimated 17.8 million [95% confidence interval (CI) 17.6–18.0 million] adults in China had experienced a stroke in 2020, with 3.4 million (95%CI 3.3–3.5 million) experiencing their first-ever stroke and another 2.3 million (95%CI 2.2–2.4 million) dying as a result. Additionally, approximately 12.5% (95%CI 12.4%–12.5%) of stroke survivors were left disabled, as defined by a modified Rankin Scale score greater than 1, equating to 2.2 million (95%CI 2.1–2.2 million) stroke-related disabilities in 2020. As the population ages and the prevalence of risk factors like diabetes, hypertension, and hyperlipidemia continues to rise and remains poorly controlled, the burden of stroke in China is also increasing. A large national epidemiological survey initiated by the China Hypertension League in 2017 showed that the prevalence of hypertension was 24.7%; the awareness, treatment, and control rates in hypertensive patients were: 60.1%, 42.5%, and 25.4%, respectively. A nationally representative sample of the Chinese mainland population showed that the weighted prevalence of total diabetes diagnosed by the American Diabetes Association criteria was 12.8%, suggesting there are 120 million adults with diabetes in China, and the awareness, treatment, and control rates in diabetic patients were: 43.3%, 49.0%, and 49.4%, respectively. The "Sixth National Health Service Statistical Survey Report in 2018" showed that the proportion of the obese population in China was 37.4%, an increase of 7.2 points from 2013. Data from 1599 hospitals in the Hospital Quality Monitoring System and Bigdata Observatory Platform for Stroke of China (BOSC) showed that a total of 3,418,432 stroke cases [mean age±standard error (SE) was (65.700±0.006) years, and 59.1% were male] were admitted during 2020. Of those, over 80.0% (81.9%) were ischemic stroke (IS), 14.9% were intracerebral hemorrhage (ICH) strokes, and 3.1% were subarachnoid hemorrhage (SAH) strokes. The mean±SE of hospitalization expenditures was Chinese Yuan (CNY) (16,975.6±16.3), ranging from (13,310.1±12.8) in IS to (81,369.8±260.7) in SAH, and out-of-pocket expenses were (5788.9±8.6), ranging from (4449.0±6.6) in IS to (30,778.2±156.8) in SAH. It was estimated that the medical cost of hospitalization for stroke in 2020 was CNY 58.0 billion, of which the patient pays approximately CNY 19.8 billion. In-hospital death/discharge against medical advice rate was 9.2% (95%CI 9.2%–9.2%), ranging from 6.4% (95%CI 6.4%–6.5%) for IS to 21.8% (95%CI 21.8%–21.9%) for ICH. From 2019 to 2020, the information about 188,648 patients with acute IS receiving intravenous thrombolytic therapy (IVT), 49,845 patients receiving mechanical thrombectomy (MT), and 14,087 patients receiving bridging (IVT+MT) were collected through BOSC. The incidence of intracranial hemorrhage during treatment was 3.2% (95%CI 3.2%–3.3%), 7.7% (95%CI 7.5%–8.0%), and 12.9% (95%CI 12.3%–13.4%), respectively. And in-hospital death/discharge against medical advice rate was 8.9% (95%CI 8.8%–9.0%), 16.5% (95%CI 16.2%–16.9%), and 16.8% (95%CI 16.2%–17.4%), respectively. A prospective nationwide hospital-based study was conducted at 231 stroke base hospitals (Level III) from 31 provinces in China through BOSC from January 2019 to December 2020 and 136,282 stroke patients were included and finished 12-month follow-up. Of those, over 86.9% were IS, 10.8% were ICH strokes, and 2.3% were SAH strokes. The disability rate [%(95%CI)] in survivors of stroke at 3-month and 12-month was 14.8% (95%CI 14.6%–15.0%) and 14.0% (95%CI 13.8%–14.2%), respectively. The mortality rate [%(95%CI)] of stroke at 3-month and 12-month was 4.2% (95%CI 4.1%–4.3%) and 8.5% (95%CI 8.4%–8.6%), respectively. The recurrence rate [%(95%CI)] of stroke at 3-month and 12-month was 3.6% (95%CI 3.5%–3.7%) and 5.6% (95%CI 5.4%–5.7%), respectively. The Healthy China 2030 Stroke Action Plan was launched as part of this review, and the above data provide valuable guidelines for future stroke prevention and treatment efforts in China.

Clustered regulatory interspaced short palindromic repeats (CRISPR) has changed biomedical research and provided entirely new models to analyze every aspect of biomedical sciences during the last decade. In the study of cancer, the CRISPR/CRISPR-associated protein (Cas) system opens new avenues into issues that were once unknown in our knowledge of the non-coding genome, tumor heterogeneity, and precision medicines. CRISPR/Cas-based gene-editing technology now allows for the precise and permanent targeting of mutations and provides an opportunity to target small non-coding RNAs such as microRNAs (miRNAs). However, the development of effective and safe cancer gene editing therapy is highly dependent on proper design to be innocuous to normal cells and prevent introducing other abnormalities. This study aims to highlight the cutting-edge approaches in cancer-gene editing therapy based on the CRISPR/Cas technology to target miRNAs in cancer therapy. Furthermore, we highlight the potential challenges in CRISPR/Cas-mediated miRNA gene editing and offer advanced strategies to overcome them.

Integrated traditional Chinese medicine (TCM) and Western medicine (WM) is a new medical science grounded in the knowledge bases of both TCM and WM, which then forms a unique modern medical system in China. Integrated TCM and WM has a long history in China, and has made important achievements in the process of clinical diagnosis and treatment. However, the methodological defects in currently published clinical practice guidelines (CPGs) limit its development. The organic integration of TCM and WM is a deeper integration of TCM and WM. To realize the progression of "integration" to "organic integration", a targeted and standardized guideline development methodology is needed. Therefore, the purpose of this study is to establish a standardized development procedure for clinical practice guidelines for the organic integration of TCM and WM to promote the systematic integration of TCM and WM research results into clinical practice guidelines in order to achieve optimal results as the whole is greater than the sum of the parts.

Signifcant advancements have been made in recent years in the development of highly sophisticated skin organoids. Serving as three-dimensional (3D) models that mimic human skin, these organoids have evolved into complex structures and are increasingly recognized as efective alternatives to traditional culture models and human skin due to their ability to overcome the limitations of two-dimensional (2D) systems and ethical concerns. The inherent plasticity of skin organoids allows for their construction into physiological and pathological models, enabling the study of skin development and dynamic changes. This review provides an overview of the pivotal work in the progression from 3D layered epidermis to cyst-like skin organoids with appendages. Furthermore, it highlights the latest advancements in organoid construction facilitated by state-of-the-art engineering techniques, such as 3D printing and microfuidic devices. The review also summarizes and discusses the diverse applications of skin organoids in developmental biology, disease modelling, regenerative medicine, and personalized medicine, while considering their prospects and limitations.