Browse Articles

Understanding and simulating border ownership centered segmentation

High-Dose Influenza Vaccine Effectiveness against Hospitalization in Older Adults

El Niño modulated Holocene hydroclimate extremes as a dipolar pattern of droughts in northeastern China and floods in southwestern China

Oral Semaglutide in Adults with Overweight or Obesity

Evaluate lymphovascular space invasion in endometrial cancer using diffusion-weighted imaging-based habitat imaging

High-Dose Influenza Vaccine to Reduce Hospitalizations

Therapeutic vaccines can challenge pancreatic cancer before it takes hold

A skin-permeable polymer for non-invasive transdermal insulin delivery

Abstract Non-invasive skin permeation is widely used for convenient transdermal delivery of small-molecule therapeutics (less than 500 Da) with appropriate hydrophobicities 1 . However, it has long been deemed infeasible for large molecules—particularly polymers, proteins and peptides 2,3 —due to the formidable barrier posed by the skin structure. Here we show that the fast skin-permeable polyzwitterion poly[2-( N -oxide- N,N -dimethylamino)ethyl methacrylate] (OP) can efficiently penetrate the stratum corneum, viable epidermis and dermis into circulation. OP is protonated to be cationic and is therefore enriched in the acidic sebum and paracellular stratum corneum lipids containing fatty acids, and subsequently diffuses through the intercorneocyte lipid lamella. Beneath the stratum corneum, at the normal physiological pH, OP becomes a neutral polyzwitterion, ‘hopping’ on cell membranes, enabling its efficient migration through the epidermis and dermis and ultimately entering dermal lymphatic vessels and systemic circulation. As a result, OP-conjugated insulin efficiently permeates through the skin into the blood circulation; transdermal administration of OP-conjugated insulin at a dose of 116 U kg −1 into mice with type 1 diabetes quickly lowers their blood glucose levels to the normal range, and a transdermal dose of 29 U kg −1 normalizes the blood glucose levels of diabetic minipigs. Thus, the skin-permeable polymer may enable non-invasive transdermal delivery of insulin, relieving patients with diabetes from subcutaneous injections and potentially facilitating patient-friendly use of other protein- and peptide-based therapeutics through transdermal delivery.

Association of glycemic variability with oxidative stress and AGE accumulation in type 2 diabetes

Abstract Oxidative stress and advanced glycation end products (AGEs) could promote vascular aging in type 2 diabetes mellitus (T2DM), but their relationship with glycemic variability remains unclear. We conducted a cross-sectional study of 68 patients with T2DM who underwent continuous glucose monitoring (CGM). Short-, intermediate-, and long-term glycemic variability were assessed using the % coefficient of variation of glucose (%CV), mean of daily differences (MODD), and HbA1c variability over the prior 2 years, respectively. Oxidative stress was measured by the diacron-reactive oxygen metabolites (d-ROMs) test, and AGE accumulation by skin autofluorescence (SAF). Multivariate analyses identified female sex, %CV, MODD, and nephropathy stage as independent correlates of d-ROMs (adjusted R 2  = 0.436). Duration of diabetes, MODD, urinary albumin-to-creatinine ratio, and macroangiopathy were independently associated with SAF (adjusted R 2  = 0.265). This study suggests that short- and intermediate-term glycemic variability correlate with oxidative stress and AGE accumulation, which may be associated with vascular complications in T2DM.

Disitamab Vedotin plus Toripalimab in HER2-Expressing Advanced Urothelial Cancer

2-Bit reconfigurable microstrip antenna with independently controlled hybrid slots for polarization and frequency switching

Disitamab Vedotin plus Toripalimab — New Players in Urothelial Carcinoma

Nuclear clocks could use electrical signals to keep time

False positive results obtained with latex agglutination identification of Staphylococcus aureus caused by Macrococcus caseolyticus and Mammaliicoccus fleurettii

Case 35-2025: A 5-Year-Old Boy with Fever and Rash

Physically consistent joint prediction of porosity and shale volume via core-calibrated deep learning in well-consolidated sandstones

Aortic Intramural Hematoma

Machine learning-driven multi-objective optimization of straight-blade paddle mixers for efficient mixing in melt-cast explosives systems

Decisional conflict among Chinese family caregivers prior to ECMO initiation: a cross-sectional study

Laser-based conversion electron Mössbauer spectroscopy of 229ThO2

Abstract The exceptionally low-energy 229 Th nuclear isomeric state is expected to provide several new and powerful applications 1,2 , including the construction of a robust and portable solid-state nuclear clock 3 , perhaps contributing to a redefinition of the second 4 , exploration of nuclear superradiance 5,6 and tests of fundamental physics 7–10 . Further, analogous to the capabilities of traditional Mössbauer spectroscopy, the sensitivity of the nucleus to its environment can be used to realize laser Mössbauer spectroscopy and, with it, new types of strain and temperature sensors 3,11 and a new probe of the solid-state environment 12,13 , all with excellent sensitivity. However, current models for examining the nuclear transition in a solid require the use of a high-bandgap, vacuum ultraviolet (VUV) transmissive host, severely limiting the applicability of these techniques. Here we report the first, to the authors’ knowledge, demonstration of laser-induced conversion electron Mössbauer spectroscopy (CEMS) of the 229 Th isomer in a thin ThO 2 sample whose bandgap (approximately 6 eV) is considerably smaller than the nuclear isomeric state energy (8.4 eV). Unlike fluorescence spectroscopy of the 229 Th isomeric transition, this technique is compatible with materials whose bandgap is less than the nuclear transition energy, opening a wider class of systems to study and the potential of a conversion-electron-based nuclear clock.