Poor sleep quality and chronic psychosocial stress are interrelated risk factors for hypertension, metabolic disease, and neuropsychiatric disorders. Sleep apnea (SA) is a respiratory disorder that disrupts sleep, affecting ~1 billion adults worldwide. However, the origins of SA remain incompletely understood. Clinically, activation of the stress pathways is often considered a consequence of SA rather than a causal factor. Here, we combined preclinical experiments with Mendelian randomization (MR) analysis to show that chronic psychosocial stress is a primary driver of SA onset. In adult rats, 3 wk of social isolation (SI; single housing) activated the stress response, augmented apneas during natural sleep, and increased the ventilatory responses to O2 and CO2 challenges. In supine anesthetized rats, obstructive apneas with O2 desaturations were 5 times more frequent in SI males than in controls, with no effect in females. SI-related anomalies in airway motor control contribute to the problem. SI also induced increased blood pressure and augmented fat gain, especially in males. In humans, MR analysis using genome-wide association studies of multiple stress-related neurological disorders from European cohorts (~100,000 to 1,096,458 participants) revealed significant effects of loneliness on the risk of SA, independent of adiposity. Together, these results challenge the conventional view of stress as merely a consequence of SA and instead position it as a possible cause. These results open the door to a paradigm shift, recognizing psychosocial stress as a risk factor paves the way for alternative avenues in basic mechanistic research, as well as in preventive and therapeutic strategies.

Linking the distinctive structural and functional properties of lipids belonging to different signaling classes is a frontier of physiology. The present minireview focuses on the endocannabinoidome phospholipase NAPE-PLD, which has bile acids (BAs) as structural cofactors at membrane interface and generates bioactive N-acylethanolamines (NAEs) that promote pleiotropic effects. NAPE-PLD is thus at the crossroads of both their physiological functions, an area of ongoing research. The wide internal channel of NAPE-PLD facilitates the transmembrane transport of pyridoxal 5'-phosphate (PLP) and can support the activity of PLP-dependent enzymes in mitochondria, peroxisome and other subcellular compartments. Recent insights demonstrate that drugs and agents that stabilize NAPE-PLD can control blood pressure, vascular resistance and cardiovascular morbidity in clinics, offering new perspectives on the interaction between NAEs and BAs in cardiometabolic and neurological disorders.

Flexible optical tactile sensors hold great promise for wearable electronics and robotic perception; however, existing devices typically face a trade-off among wide sensing range, simple readout, and dynamic slip recognition. Here, we propose a single-element flexible optical fiber sensor based on an asymmetric 3D S-tapered polymer optical fiber embedded in polydimethylsiloxane (PDMS). Leveraging geometry-dependent curvature modulation, normal pressure is transduced into optical intensity variations, while slip direction is intrinsically encoded into distinguishable temporal waveforms. A deformation-optical loss model is established via finite element simulations and optical analyses to elucidate the underlying sensing mechanism. The sensor delivers a pressure sensitivity of 1.55 MPa-1 across a broad linear range of 0-299 kPa, exhibiting an ultrafast response time (<1 ms) and robust cyclic stability over 3,000 loading/unloading cycles. Furthermore, the device demonstrates reliable tensile strain sensing and unambiguous slip-direction discrimination. Its practical utility is validated through applications in radial pulse monitoring, finger-joint motion tracking, and tactile slip perception. This work presents a streamlined paradigm for integrating wide-range pressure sensing and directional slip recognition within a single flexible optical fiber, paving the way for advanced, low-complexity tactile interfaces.

Tedizolid phosphate (TP) and ciprofloxacin (CIP) represent orally effective antibiotics that are often administered in combination for hospitalized patients with complicated or mixed infections, aiming to provide wide antimicrobial coverage. This study describes, for the first time, the establishment of an environmentally sustainable reversed-phase HPLC approach for the simultaneous bioanalysis of TP and CIP in human plasma. The developed chromatographic method allowed for rapid separation within 4 min employing a methanol-water mobile phase, thereby reducing solvent consumption and improving environmental sustainability. The method was validated according to the validation parameters investigated in the present study, with reference to the US FDA Bioanalytical Method Validation Guidance. Excellent linearity was achieved over concentration ranges of 5-90 µg/mL (TP) and 5-80 µg/mL (CIP) in pure samples, and 0.5-30 µg/mL (TP) and 0.5-10 µg/mL (CIP) in human plasma. LOD/LOQ values were 1.60/4.86 µg/mL for TP and 1.58/4.78 µg/mL for CIP in pure samples, and 0.16/0.49 µg/mL for TP and 0.10/0.31 µg/mL for CIP in spiked human plasma. The proposed method was characterized by adequate sensitivity and demonstrated strong performance in terms of accuracy, precision, specificity, and robustness. Furthermore, it proved effective in assessing the forced degradation of TP and CIP under diverse stress conditions, confirming its capability as a stability-indicating approach. The environmental impact of the method was comprehensively evaluated using multiple established greenness and blueness assessment tools, confirming its favorable environmental profile. Overall, the developed approach presents a rapid, highly accurate, and environmentally sustainable strategy for the simultaneous bioanalysis of TP and CIP in bulk drugs, pharmaceutical formulations, and human plasma.

Obesity-related obstructive sleep apnea (OSA) is common, clinically heterogeneous, and tightly linked to cardiometabolic dysfunction, impaired daytime function, and reduced quality of life. Positive airway pressure (PAP) remains the standard device-based treatment for moderate-to-severe disease because it immediately stabilizes the upper airway, but it does not directly reverse the obesity that drives disease in many patients and its long-term effectiveness is often constrained by adherence. This narrative, non-systematic review synthesizes direct OSA-specific randomized evidence, indirect obesity-trial evidence, and mechanistic literature to clarify what is established, what is inferred, and what remains hypothetical. The clinical evidence for incretin therapy in OSA is promising but uneven. Direct OSA-specific randomized evidence is concentrated in liraglutide and tirzepatide: SCALE Sleep Apnea established proof of concept that pharmacologic weight loss can improve the primary apnea-hypopnea index (AHI) outcome, whereas in SURMOUNT-OSA change in AHI was the primary endpoint. Reductions in body weight, sleep apnea-specific hypoxic burden, selected patient-reported sleep outcomes, hsCRP, and systolic blood pressure were reported as key secondary or additional secondary findings, supporting a broader disease-burden signal but not proving long-term cardiovascular event reduction. Discordant vascular-imaging evidence further cautions that GLP-1-mediated weight loss should not be assumed to reproduce all vascular effects of PAP or to prove cardiovascular event reduction. Semaglutide provides important indirect obesity and cardiometabolic evidence, but direct OSA-specific outcome data remain limited; evidence from other incretin agents also remains largely indirect because most trials were designed for obesity or cardiometabolic endpoints rather than sleep outcomes. The most parsimonious mechanistic interpretation is weight-loss-mediated anatomical unloading. This interpretation is supported by non-incretin weight-loss imaging studies and upper-airway physiology, but it has not yet been directly confirmed by serial upper-airway imaging, Pcrit measurement, or physiological endotyping within incretin-treated OSA cohorts. This narrative review organizes the field into three evidence tiers: direct OSA-specific randomized trials, indirect obesity-trial evidence relevant to OSA, and mechanistic extrapolation. We argue that the current evidence is strong enough to position incretin therapy as a disease-modifying adjunct for selected patients with obesity-driven, anatomically dominant OSA, but not yet strong enough to support class-wide claims, routine PAP replacement, or confident attribution of benefit to direct modulation of non-anatomical endotypes.

ZMA001 is a novel human IgG1 monoclonal antibody (mAb) specifically designed to target the N-terminal region of transmembrane lysyl-tRNA synthetase 1 (KARS1), an enzyme implicated in the pathobiology of pulmonary arterial hypertension. The study aimed to develop a bioanalytical method to quantify ZMA001 in human sera to support a phase 1 clinical trial (NCT05967299). An indirect Electrochemiluminescence Immunoassay (ECLIA) method was developed employing KARS1 antigen as the capture reagent and SULFOTAG goat antihuman antibody as the secondary antibody. The method was subsequently validated in accordance with relevant guidelines, including those of the International Council for Harmonization (ICH). The assay's quantification range was established at 0.5-50 µg/mL. The assay was accurate, precise, and selective for the determination of ZMA001 concentrations in human serum. Results revealed that ZMA001 was stable at room temperature for over 4 hours and could withstand multiple freeze-thaw cycles. No prozone/hook effect was apparent in the assay range. Based on preliminary pharmacokinetic data, the average maximum concentration is 41.8 μg/mL while the half-life is about 9.9 days. The method provides a rapid and sensitive approach for the quantitative assessment of ZMA001 in human serum and is well-suited for use in ongoing and future clinical studies.

Complete blood counts are central to clinical practice but require invasive sampling and centralized laboratory analysis. Optical-resolution photoacoustic microscopy provides intrinsic specificity to red blood cells (RBCs) through hemoglobin absorption. However, conventional implementations typically depend on bulky acoustic coupling schemes that hinder clinical translation. Here, we present a compact and integrable, label-free optoacoustic platform that combines optical-resolution excitation in an epi-illumination geometry with a transparent silicon-photonics acoustic detector (SPADE) featuring a wide acoustic acceptance angle that enables detection without strict optical-acoustic co-alignment. System performance was first characterized using optoacoustic point sources and subsequently evaluated in controlled RBC flow experiments within a tapered glass-capillary microfluidic phantom, as well as in vivo measurements of superficial inner-lip capillaries in human volunteers. The transparent SPADE preserved tight optical focusing (≤ 4 µm) and provided an acoustic bandwidth exceeding 100 MHz with a noise-equivalent pressure of approximately 2.3 mPa/Hz[1] ᐟ[2]. Single-RBC transients were robustly detected in the phantom across varying flow conditions, while in vivo measurements at multiple capillary sites yielded reproducible transient signals consistent with individual RBC passages. These results establish a practical framework for stable, fixed-position optoacoustic detection of individual RBCs in superficial human capillaries, demonstrating the potential of transparent SPADE-based systems for non-invasive blood analysis.

Mixed-pathogen infective endocarditis is uncommon and may be difficult to recognize when the clinical course is prolonged and nonspecific. We report a case of mixed Candida albicans and Brucella melitensis native aortic valve endocarditis in a 37-year-old previously healthy man who presented with five months of intermittent fever, chills, anorexia, fatigue, 7 kg weight loss, progressive dyspnea, and intermittent chest pain. Physical examination revealed fever, sinus tachycardia, wide pulse pressure, elevated jugular venous pressure, bibasilar crackles, and a loud early diastolic murmur. Laboratory testing was notable for leukocytosis, anemia, mild thrombocytosis, and elevated inflammatory markers. A transthoracic echocardiogram demonstrated severe aortic regurgitation with a large 19 mm aortic valve vegetation causing holodiastolic flow reversal in the descending thoracic aorta. A transesophageal echocardiogram revealed two large mobile vegetations causing severe leaflet malcoaptation with possible periannular extension. A cardiac CT scan revealed thickening of the aortic root consistent with abscess formation. Blood cultures were positive for Candida albicans and Brucella melitensis. Brucella serology was positive, with an agglutination titer of 1:640. The patient developed pulmonary edema requiring an urgent Bentall procedure with a mechanical composite graft. Valve tissue cultures were positive for Candida albicans, and histopathology from the resected valve was consistent with acute-phase infective endocarditis with features of necrosis, fibrin, and debris. The patient was placed on postoperative antifungal treatment with caspofungin followed by fluconazole suppression, and on Brucella-directed treatment with doxycycline, rifampin, and levofloxacin for a planned six-month course of therapy. A postoperative whole-body PET/CT scan using fluorine-18 fluorodeoxyglucose (18F-FDG) did not demonstrate any residual cardiac infection or extracardiac infectious foci. The patient was doing well clinically at the three-month follow-up, with no signs or symptoms of heart failure and no evidence of relapse or recurrence of fever. This is a rare case of destructive native aortic valve endocarditis with mixed fungal and zoonotic bacterial etiologies that required urgent surgical source control and prolonged combined antimicrobial therapy.