Although the health care sector is dedicated to promoting health, it paradoxically contributes to climate change by burning fossil fuels, a major source of greenhouse gas emissions and air pollutants. Its energy-intensive facilities, extensive supply chains, and massive waste production account for approximately 4.6% of global net emissions. In this contradictory position, the promotion of health is undermined by the resulting environmental degradation, leading to rising global temperatures, heat waves, air pollution, intensified droughts and precipitation, and more frequent and severe extreme weather events. Ironically, the health care sector contributes to the chronic medical conditions it aims to address, such as respiratory, cardiovascular, and heat-related diseases; atopic conditions; adverse pregnancy outcomes; and vector-borne diseases. Vulnerable populations, including children, older adults, individuals with chronic medical conditions, ethnic minorities, and socioeconomically marginalized communities, who are already affected by systemic inequities, bear a disproportionate burden of these climate-driven health outcomes. This article reviews the negative impact of the health care sector on human health and global equity, identifies sources of emissions, and outlines actionable procurement measures the medical sector can adopt to lessen its carbon footprint.

In advanced cancer, associations among changes in body composition, cardiac wasting and prior cardiotoxic anticancer therapy have not been investigated.

Using bioelectrical impedance analysis (BIA), body composition was measured in 206 patients with mostly advanced cancer without known cardiovascular disease or infection (stage III/IV: 84%, prior cardiotoxic anticancer therapy: 55%). Left ventricular (LV) mass was assessed by transthoracic echocardiography and grouped by presence of cardiac wasting according to previously established sex-specific thresholds for LV mass adjusted for height² (<61 g/m² for women, <57 g/m² for men). BIA measurements (indexed to height²) included fat mass index (FMI), fat-free mass index (FFMI), skeletal muscle mass index (SMMI), visceral fat index (VFI), total body water index (TBWI) and extracellular water index (ECWI).

Patients with cancer and cardiac wasting (n = 88) were younger (57±15 vs 62±13 years) and more often women (68% vs 29%) compared to those without cardiac wasting (n = 118). Patients with cardiac wasting had significantly lower FMI (-12%), FFMI (-14%), SMMI (-16%), VFI (-46%), TBWI (-13%) and ECWI (-14%). For women, FFMI was significantly associated with LV mass/height² (r = 0.41) and VFI for men (r = 0.40). In the multivariable linear regression analysis, FFMI was the strongest significant predictor of cardiac wasting, with no significant interaction by sex or previous cardiotoxic therapy.

Cardiac wasting in advanced cancer is associated with lower FFMI and VFI independent of prior cardiotoxic therapy.

Elevated systolic blood pressure (SBP) is associated with paradoxically lower mortality in heart failure with reduced ejection fraction (HFrEF), but whether this reflects underlying pathophysiology or residual confounding remains uncertain. Because higher SBP is also a risk factor for kidney failure, we tested the hypothesis that a higher risk of kidney failure despite lower mortality would support a pathophysiological explanation for this mortality paradox.

We assembled a propensity score-matched cohort of 59,834 patients with HFrEF, hypertension, and no baseline kidney failure. The 29,917 pairs with SBP ≥130 versus <130 mmHg were balanced on 77 baseline characteristics. Outcomes were two-year all-cause mortality and incident kidney failure. Cox regression estimated associations of SBP ≥130 mmHg with outcomes, and restricted cubic splines assessed nonlinearity across the SBP continuum.

All-cause mortality occurred in 24.9% of patients with SBP <130 mmHg and 23.0% of patients with SBP ≥130 mmHg (HR associated with SBP ≥130 mmHg, 0.91; 95% CI, 0.88-0.94). Corresponding rates for kidney failure were 1.0% and 1.5% (HR, 1.44; 95% CI, 1.24-1.66). SBP had a nonlinear association with mortality (P<0.001 for nonlinearity), with progressively higher risk at SBP below 130 mmHg but no higher risk above 130 mmHg. The association with kidney failure was linear (P=0.68 for nonlinearity) with progressively higher risk above 130 mmHg.

In patients with HFrEF, elevated SBP is associated with lower mortality but a higher risk of kidney failure. These opposing cardiac and renal associations support a pathophysiological explanation for the inverse relationship between SBP and mortality in HFrEF.

Desmin-related cardiomyopathy (DRC) is an inherited disorder characterized by progressive conduction abnormalities, arrhythmias, and heart failure. Although desmin aggregation is a defining pathological feature, the downstream signaling mechanisms driving disease progression remain poorly understood. In this study, whole-exome sequencing identified a heterozygous DES p.S13F variant in a multigenerational pedigree with a highly penetrant cardiac phenotype, and its pathogenic mechanisms were investigated using clinical data, zebrafish and mouse models, and cellular experiments. DES p.S13F expression induced desmin aggregation, cytoskeletal-associated protein abnormalities, mitochondrial dysfunction, oxidative stress, cardiomyocyte apoptosis, and adverse cardiac remodeling. Transcriptomic and protein analyses consistently revealed impaired canonical Notch signaling, with reduced NICD1 abundance in DES p.S13F-expressing mouse hearts and cardiomyocytes, providing a biochemical readout supporting impaired canonical NOTCH1 activation. Pharmacological Notch inhibition aggravated cardiac and cellular abnormalities, whereas Jagged1-mediated pathway activation ameliorated cardiac phenotypes in zebrafish and partially restored cytoskeletal-associated protein abundance while attenuating oxidative stress and apoptosis in DES p.S13F-expressing cardiomyocytes. Genetic NICD1 overexpression produced concordant protective effects, further supporting the functional involvement of canonical Notch signaling. Collectively, these findings identify Notch signaling insufficiency as a functionally relevant disease-modifying mechanism in DES p.S13F-associated cardiomyopathy and suggest that restoration of canonical Notch signaling may represent a potential therapeutic strategy for desmin-related cardiomyopathy.

Aging is accompanied by a decline in circulating ketone bodies and progressive cardiac dysfunction, yet whether dietary ketone repletion counteracts cardiac aging in a sex-specific manner remains unclear. Here, we first investigated the associations between plasma ketone bodies and cardiac function in a human cohort, comprising 120 adults (44.78 ± 10.97 years; 66 male/54 female) and 121 aged individuals (69.59 ± 6.88 years; 75 male/46 female). And, we then evaluated the therapeutic potential of an 8-week ketogenic diet (KD) in physiologically aged mice (22 months, both sexes), which were daily supplemented with either chow diet (3.79 kcal/g, Aged group) or KD (7.24 kcal/g, Aged+KD group). In humans, circulating β-hydroxybutyrate (β-HB) levels were significantly lower in aged human individuals and positively correlated with key parameters of cardiac function, including ejection fraction (EF), fractional shortening (FS) and the ratio of early to late diastolic filling velocity (E/A ratio). In aged mice, 8-week KD supplementation elevated cardiac β-HB concentrations and attenuated cardiac remodeling in both sexes. Notably, KD improved systolic/diastolic function (e.g., EF, FS and E/A ratio), preserved mitochondrial function, reduced myocardial lipid accumulation, and ameliorated systemic dyslipidemia equivalently in both sexes. Mechanistically, KD suppressed CD36 membrane translocation and MAPK activation, whereas CD36 upregulation abolished these protective effects, establishing a causal role of the CD36/MAPK pathway in KD-mediated cardioprotection. Altogether, these findings identify β-HB as a biomarker of cardiac aging and show that KD rescues age-related cardiomyopathies through CD36-MAPK-mediated lipid metabolic regulation, with equivalent benefits in both sexes.

Cuproptosis is a copper ion-dependent form of regulated cell death discovered in 2022. Its mechanism lies in the binding of copper to acylated proteins in the tricarboxylic acid cycle, thereby triggering proteotoxic stress. Natural products, with their structural diversity and good biocompatibility, are gradually becoming regulators of cuproptosis.

To systematically clarify the mechanisms by which natural products regulate cuproptosis, identify its core targets, and evaluate its therapeutic potential, with a particular focus on cancer therapy and neurodegenerative diseases.

Literature from PubMed and CNKI up to August 1, 2026 was retrieved using keywords including "cuproptosis", "copper ionophore", and "natural product", etc.; studies on natural product intervention in cuproptosis in tumors, neurodegenerative diseases, and cardiovascular diseases were screened and included, and the molecular mechanisms, regulatory modes, and therapeutic prospects were comprehensively analyzed.

The core cuproptosis axis involves FDX1-mediated reduction of Cu²⁺ to Cu⁺, binding of Cu⁺ to lipoylated DLAT, and mitochondrial dysfunction. This axis is tightly controlled by copper homeostasis proteins (SLC31A1, ATP7A/B). Natural products bifunctionally modulate cuproptosis. Specifically, they induce tumor cell cuproptosis by elevating intracellular copper or disrupting copper metabolism, and protect normal cells via copper chelation or FDX1 inhibition. Such strategies benefit tumor drug resistance reversal and neuroprotection in neurodegenerative diseases, but their development is restricted by unclear mechanisms, poor druggability and insufficient clinical translation.

Natural products are versatile modulators of cuproptosis with dual utility as probes and lead compounds. Future work should identify direct targets, improve druggability, and enable clinical translation.

Non-small cell lung cancer (NSCLC) accounts for the vast majority of lung cancer cases and remains a therapeutic challenge due to drug resistance, adverse effects, and metabolic plasticity. Icariin (ICR), a principal bioactive flavonoid from Epimedium, exhibits promising antitumor properties; however, its precise role in modulating cancer energy metabolism remains poorly understood. This study aimed to investigate whether ICR synergistically inhibits glycolysis and mitochondrial metabolism, and whether these effects are associated with the HIF-1α/LONP1 signaling axis in NSCLC.

In vitro functional assays were performed to evaluate cell proliferation, migration, invasion, apoptosis, and cell cycle progression in NSCLC cell lines. Integrative proteomics, targeted metabolomics, and Western blotting were employed to assess ICR-associated changes in HIF-1α, glycolytic enzymes (HK2, LDHA), and mitochondrial proteins (LONP1, TFAM, MTCO2). The in vivo antitumor efficacy and underlying metabolic mechanisms were validated using an A549 cell-derived xenograft model in nude mice.

ICR significantly suppressed proliferation, migration, and invasion while promoting apoptosis and G0/G1 cell cycle arrest in NSCLC cells. Multi-omics and biochemical analyses revealed that ICR attenuated both aerobic glycolysis and mitochondrial oxidative phosphorylation, accompanied by downregulation of HIF-1α, HK2, LDHA, LONP1, TFAM, and MTCO2. In vivo xenograft experiments confirmed that ICR treatment markedly inhibited tumor growth and modulated the expression of these key metabolic regulators, with no significant body weight loss observed.

This study demonstrates that ICR simultaneously suppresses glycolysis and mitochondrial energy metabolism, with these effects being associated with downregulation of the HIF-1α/LONP1 axis. These findings provide a novel mechanistic rationale and experimental foundation for metabolism-targeted therapeutic strategies in NSCLC.

Benzodiazepines (BZDs) remain among the most frequently prescribed psychotropic drugs in older adults, despite well-documented risks and guideline recommendations for short-term use. This study analyzed BZD prescribing trends among individuals aged ≥ 65 years in Catalonia, Spain, between 2018 and 2022.

A retrospective drug utilization study was conducted using anonymized electronic health records from the SIDIAP (Information System for Research in Primary Care) database, covering approximately 80% of the Catalan population. All patients aged ≥ 65 years with at least one BZD prescription were included. Data were analyzed by sex, age group, onset of action, and duration of effect. Utilization was expressed in defined daily doses per 1000 inhabitants per day.

The study included 463,446 older adults (68.2% women; mean age 77.1 ± 8.0 years) with 1,731,408 BZD prescriptions. Rapid-onset BZDs accounted for 51.9% and intermediate-onset for 45.2% of prescriptions; slow-onset drugs were 2.95%. Intermediate-acting BZDs predominated by duration (47.6%), followed by short-acting BZDs (31.9%) and long-acting BZDs (20.4%). Women had higher use than men across all age groups (e.g., short-acting < 75 years: 233.6 vs 106.6 defined daily doses per 1000 inhabitants per day). Median treatment duration was longest for intermediate-acting BZDs (219 days, interquartile range 59-365) and intermediate-onset BZDs (221 days, interquartile range 59-365).

Benzodiazepine prescribing among Catalan older adults remains high, dominated by rapid-onset and short-acting to intermediate-acting agents, with widespread long-term use. These findings highlight the need for structured medication reviews, deprescribing programs, and prescriber education to reduce inappropriate BZD exposure in this population.