Activated platelet-rich plasma (aPRP) reduces inflammation and promotes regeneration in osteoarthritic knee joints. It may exert therapeutic effects on osteoarthritic chondrocytes (OACs) compared with healthy chondrocytes (HCs) by promoting cell proliferation, reducing autophagy-related vesicles and inhibiting apoptosis through modulation of intracellular signaling pathways. The aim of this study was therefore to evaluate cell viability, apoptotic fate, extracellular matrix protein expression (collagen type II (COL2A1) and aggrecan (ACAN)), autophagy-related vesicle production, and growth factor profiles, including TGF-β and PDGF-BB, in HCs and OACs.

Aging paradoxically leads to both a decline in skeletal muscle mitochondrial function and a shift in muscle composition that favors fibers rich in mitochondria. Yet the biological rationale and mechanism underlying this phenomenon remain largely unknown. Here we show that synthesis of the mitochondrial membrane lipid, cardiolipin, causally links mitochondrial dysfunction to fiber-type adaptations in aging mouse and human skeletal muscle. By mimicking the aging decline of skeletal muscle cardiolipin levels in young mice using inducible tissue-specific cardiolipin synthase 1 (Crls1) deletion, we could reproduce key aging hallmarks, including the shift from glycolytic to oxidative fibers. This shift is mediated by mitochondria-to-nucleus signaling through the nuclear receptor, estrogen-related receptor γ, which promotes reactive oxygen species-sensitive glucose uptake and enhanced glycolytic rerouting to sustain antioxidant defenses. Restoring Crls1 expression in adult Crls1 knockout mice reestablishes cardiolipin levels, initiates reversal of muscle atrophy and fully rescues premature mortality. These findings reveal how changes in a mitochondrial membrane lipid cell autonomously orchestrate fiber-type adaptations in aging and myopathies.

The application of a fully autonomous artificial pancreas faces fundamental constraints from the bulky mechanical drives of conventional insulin pumps and the spatially separated glucose sensing unit. Herein, we report a wearable closed-loop insulin micropump that enables a miniaturized artificial pancreas for diabetes treatment. It seamlessly integrates an electrochemical micropump with an optical glucose-responsive microneedle (MN) sensor. The core actuation module features a novel semi-dry sandwich electrode configuration combined with a highly elastic latex membrane and a groove-type epoxy sealing architecture. This structural paradigm shift effectively eliminates bulk fluid flow and ensures robust hermeticity for precise, electrolysis-gas-driven, microliter-scale dosing with a precision of 0.5 μL. For continuous glucose monitoring, a polyvinylpyrrolidone/polyvinyl alcohol (PVP/PVA) hydrogel MN array functionalized with 9-anthracene boronic acid (9-ANB) is employed. The specific binding of interstitial glucose triggers measurable fluorescence quenching, which is precisely digitized by an integrated XYZ true-color sensor (detection range: 0-600 mg/dL). Comprehensive in vitro and in vivo evaluations demonstrate the platform's predictable, programmable delivery kinetics and excellent biocompatibility. In type 1 diabetic mouse models, a smartphone-controlled system by autonomously and effectively suppressed postprandial glycemic spikes, maintaining glycemic fluctuations within 25 mg/dL. This highly integrated, miniaturized design offers a compelling paradigm shift for next-generation, patient-friendly diabetes management systems.

The regeneration of tendon-to-bone interface remains a significant clinical challenge due to the highly complex structure, composition, cell population, and mechanical properties of the interface. In this study, polylactic acid (PLA), polycaprolactone (PCL) and type I collagen (Col1) were used as raw materials to prepare a tendon-to-bone interface biomimetic scaffold through electrospinning technology. The nanofiber scaffold features an aligned-to-random bilayer structure mimicking the native ten-don-to-bone interface. Furthermore, when loaded with exosomes derived from bone marrow-derived mesenchymal stem cells (BMSC-Exos), the biomimetic scaffold synergistically promotes ten-don-to-bone regeneration. Our results demonstrate that the biomimetic scaffold is biocompatible and promotes cells adhesion, proliferation, and differentiation. In vivo experiments using a rat tendon-to-bone injury model demonstrated that PLA/PCL/COL1&BMSC-Exos scaffold significantly increased fibro-cartilage thickness, improved collagen fiber alignment, and enhanced biomechanical properties, with concurrent improvement in gait performance. The biomimetic scaffold represented a promising therapeutic approach for addressing tendon-to-bone healing and advancing clinical practices in ten-don-to-bone regeneration.

Women constitute the majority of the health workforce globally and in Tanzania, yet remain underrepresented in leadership roles, particularly at higher levels. Despite national commitments to gender equality and various supportive policies, analysis of gender representation in health sector leadership in Tanzania is limited. This study presents the analysis of gender representation in leadership across three healthcare levels of Tanzania's health system, Regional Health Management Teams (RHMTs), Council Health Management Teams (CHMTs), and Health Facility Management Teams (HFMTs). This study used secondary data collected by a government ministry in 2022 from 20 out of 26 regions of mainland Tanzania, representing over two-thirds of the country's regions. The analysis examined 9,120 leadership positions. Descriptive statistics were done using Excel. Results show that while gender representation is nearing parity overall for less powerful roles, notable disparities remain based on role and level of seniority. The highest proportion of women is found in HFMTs at 48.9%, followed by a decline at the CHMTs level to 41.5%, and further to 39.5% in the RHMTs. This trend is similarly evident in leadership roles such as Medical Officers In-Charge, where women represent 29.8% at the HFMT level, but their presence drops to 17.6% among District Medical Officers and just 11.1% among Regional Medical Officers. Gender representation also varies geographically and by facility type, with lower-level facilities generally showing more equitable gender distributions. The findings reflect the ongoing need for gender-transformative leadership strategies, including targeted mentorship, equitable promotion practices, and inclusive workplace cultures.

While proteins are built from 20 canonical amino acids, it is interesting to explore whether proteins can be formed from significantly reduced amino acid alphabets. Our bioinformatics survey of UniProt (more than 250 m sequences) revealed that proteins composed of reduced amino acid alphabets are extremely rare among existing proteins. Next, we used computational protein design to design proteins 100 amino acid residues in length composed of all 1013 possible alphabets of 2-10 early amino acids (Ala, Asp, Glu, Gly, Ile, Leu, Pro, Ser, Thr, and Val). Our findings show that small amino acid alphabets preferred simple helices or helix bundles, while larger amino acid alphabets allowed for the design of more complex structures. We verified a protein composed of 8 amino acid types (Ala, Asp, Gly, Leu, Val, Ser, Thr, and Pro) finding it adopts the β-sheet-rich fibronectin type III domain architecture. However, attempts to experimentally verify designs composed of 6 and 4 amino acid types were unsuccessful. Furthermore, we show by computational experiment with experimental validation that inverse folding models, namely ProteinMPNNsol, can stabilize a designed protein within the same eight-amino-acid alphabet. Ultimately, our results show that globular proteins may have formed early in evolution using a minimal amino acid alphabet and that it is possible to design such proteins with interesting properties for biotechnology and synthetic biology.

BteA is a cytotoxic effector translocated into host cells via the type III secretion system (T3SS) of Bordetella. The T3SS gatekeeper protein BopN controls BteA translocation, yet the BteA region mediating this regulation remains unknown. Here, we demonstrate that BteA interacts with BopN through its C-terminal region, and this interaction is required for efficient translocation into host cells. Using a CyaA-based translocation assay, we showed that BteA comprising the N-terminal 448 amino acids (BteA-N448) and BteA with a deletion of amino acids 249-448 (BteA-∆249-448) were translocated in a BopN-dependent manner, whereas BteA comprising the N-terminal 248 amino acids (BteA-N248) was translocated independently of BopN. Pull-down assays confirmed that BteA-N448 and BteA-Δ249-448 physically interact with BopN, whereas BteA-N248 does not. ColabFold-based structure prediction identified candidate interface residues, and subsequent mutagenesis revealed that simultaneous alanine substitution of aspartate 263 (D263) and phenylalanine 340 (F340) abolished BopN-dependent translocation. Our results demonstrated that the amino acid residues D263 and F340 in BteA play important roles in BopN-mediated translocation control. Furthermore, the C-terminal 14-amino-acid region of BteA was strongly suggested to be involved in this regulation. The present study provides new insights into the effector-gatekeeper network that controls T3SS-mediated pathogenicity in Bordetella.