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Human serum albumin (HSA) is the frontline antioxidant protein in blood with established anti-inflammatory and anticoagulation functions. Here, we report that COVID-19-induced oxidative stress inflicts structural damages to HSA and is linked with mortality outcome in critically ill patients. We recruited 39 patients who were followed up for a median of 12.5 days (1–35 days), among them 23 had died. Analyzing blood samples from patients and healthy individuals (n=11), we provide evidence that neutrophils are major sources of oxidative stress in blood and that hydrogen peroxide is highly accumulated in plasmas of non-survivors. We then analyzed electron paramagnetic resonance spectra of spin-labeled fatty acids (SLFAs) bound with HSA in whole blood of control, survivor, and non-survivor subjects (n=10–11). Non-survivors’ HSA showed dramatically reduced protein packing order parameter, faster SLFA correlational rotational time, and smaller S/W ratio (strong-binding/weak-binding sites within HSA), all reflecting remarkably fluid protein microenvironments. Following loading/unloading of 16-DSA, we show that the transport function of HSA may be impaired in severe patients. Stratified at the means, Kaplan–Meier survival analysis indicated that lower values of S/W ratio and accumulated H 2 O 2 in plasma significantly predicted in-hospital mortality (S/W≤0.15, 81.8% (18/22) vs. S/W>0.15, 18.2% (4/22), p=0.023; plasma [H 2 O 2 ]>8.6 μM, 65.2% (15/23) vs. 34.8% (8/23), p=0.043). When we combined these two parameters as the ratio ((S/W)/[H 2 O 2 ]) to derive a risk score, the resultant risk score lower than the mean (<0.019) predicted mortality with high fidelity (95.5% (21/22) vs. 4.5% (1/22), log-rank χ 2 =12.1, p=4.9×10 −4 ). The derived parameters may provide a surrogate marker to assess new candidates for COVID-19 treatments targeting HSA replacements and/or oxidative stress.

Breast cancer remains the most frequently diagnosed malignancy and the primary cause of cancer-related death among women globally. As per the BI-RADS atlas, category 4 lesions generally require histopathological assessment through biopsy rather than follow-up imaging. Nevertheless, many lesions initially classified as BI-RADS 4A and 4B on ultrasound are subsequently found to be benign. This contributes to a high rate of unnecessary biopsies, increasing healthcare costs and significant psychological burden for patients. Among the 172 lesions (130 BI-RADS 4A and 42 BI-RADS 4B), 61 (35.5%) were malignant. MRI accurately identified all malignant lesions and correctly diagnosed 103 out of 111 benign lesions (92.8%). MRI increased the positive predictive value from 35.5% (61/172) to 88.4% (61/69) and reduced false-positive ultrasound findings-those leading to unnecessary biopsies-by 92.8%. MRI also downgraded 103 lesions (59.9%) to lower BI-RADS categories. The combined protocol achieved 100% sensitivity, 92.8% specificity, 88.4% PPV, 100% NPV, and 95.3% overall accuracy. Additionally, MRI identified five suspicious lesions (2.9%) not visualized on ultrasound, four of which were malignant. MRI demonstrates robust efficacy in downgrading BI-RADS 4A and 4B lesions identified on ultrasound, significantly reducing unnecessary biopsies and mitigating patient anxiety and psychological burden, while ensuring complete detection of malignant lesions. However, its high sensitivity may reveal additional suspicious findings that warrant further evaluation.

Background: This study aimed at investigating the prolonged effects of glucocorticoids and bisphosphonates on bone. Methods: Six-to-eight-month-old skeletally mature male Sprague Dawley rats were randomized to receive a cancer therapy combination of zoledronic acid (ZA = 0.13 mg/kg) and dexamethasone (DX = 3.8 mg/kg) (treatment group, n = 10) or sterile phosphate buffer saline solution (control group, n = 10). The rats received weekly intraperitoneal injections for 8 weeks, which were stopped 6 weeks before euthanasia. Mineralized bone samples were characterized by three-point bending tests, micro-CT imaging, X-ray diffraction (XRD), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). Bone collagen was assessed using tensile tests on the demineralized bones and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy on mineralized and demineralized bones. Results: The samples in the treatment group showed increased tibial cortical thickness, mineral crystal size, and toughness. Analyses of demineralized tibiae revealed decreased collagen tensile strength in the experimental group. The spectroscopic and TGA/DSC analyses showed that the ZA + DX treatment increased the collagen amide I 1660/1690 cm−1 area ratio and collagen denaturalization temperature, indicating a higher level of collagen cross-linking. Conclusions: Bisphosphonates and glucocorticoids led to prolonged changes in the mechanical properties of bone as a result of increased cortical thickness, increased crystal size, and the deterioration of collagen quality.