Rheumatoid arthritis (RA) is an autoimmune disease with features of synovial inflammation, cartilage erosion, bone destruction, and pain and is currently lacking a satisfactory treatment strategy. Dihydroartemisinin (DHA), the active metabolite of artemisinin, has exhibited outstanding suppressive effects on RA without obvious side effects. However, the underlying mechanisms remain unclear, which limits its further clinical application. The purpose of this study is to reveal the pharmacodynamic mechanism of DHA against RA by means of a combination of single-cell RNA sequencing (RNA-seq), proteomics, as well as transcriptomics both in vivo and in vitro. In our results, DHA effectively reduced the degree of redness, swelling, and pain in RA rats and dramatically changed the synovial tissue microenvironment under the pathological state. Within this microenvironment, fibroblasts, macrophages, B cells, and endothelial cells were the major affected cell types, primarily through DHA targeting the extracellular matrix (ECM) structural constituent signaling pathway. In addition, we confirmed that DHA regulated the ECM by modulating matrix metalloproteinase 2 (MMP2) and MMP3 in the synovial tissue of RA rats. Moreover, DHA induced apoptosis in MH7A cells, further validating the bioinformatics data. In conclusion, DHA effectively reduced the inflammatory response and improved the immune microenvironment in synovial tissue by inhibiting MMP2 and MMP3. Our findings provide a basis for the application of DHA in the treatment of RA.

Intermittent fasting (IF) is a convenient dietary intervention for multiple diseases, including type 2 diabetes. However, whether it can be used as a long-term antidiabetic approach is still unknown. Here, we confirm that IF alone is beneficial for both moderate and severe diabetic mice, but its antidiabetic effects clearly diminish at later stages, especially for severe diabetic db/db mice, which have obviously impaired autophagy. We found that static magnetic fields can directly promote actin assembly and boost IF-induced autophagy. Consequently, the pancreatic islet and liver were improved, and the antidiabetic effects of IF were boosted. In fact, at later stages, combined static magnetic field and IF could reduce the blood glucose level of moderate type 2 diabetic mice by 40.5% (P < 0.001) and severe type 2 diabetes by 34.4% (P < 0.05), when IF alone no longer has significant blood glucose reduction effects. Therefore, although IF is generally beneficial for diabetes, our data reveal its insufficiency for late-stage diabetes, which can be compensated by a simple, noninvasive, long-lasting, and nonpharmacological strategy for effective long-term diabetic control.

Hydrogels have emerged as appealing prospects for wound healing due to their superior biocompatible qualities. However, the integration of antibacterial active substances into hydrogels for effective wound repair remains challenging. Here, we present a novel double-network hydrogel for nasal mucosal injury repair with antibacterial and self-healing capabilities. This hydrogel is the result of mixing aldehyde polyethylene glycol (PEG) and a carboxymethyl chitosan (CMCS)-based hydrogel with a photocured methylacrylate gelatin (GelMA) hydrogel to envelop mesenchymal stem cell exosomes (MSC-Exos). CMCS is rich in amino groups and facilitates antibacterial repair. Given the dynamically reversible Schiff base connections between the amino group of chitosan and the aldehyde group of modified PEG, the hydrogel can be easily injected into the lesion site because of its excellent injection and shear thinning properties. GelMA introduces an additional network layer for the hydrogel, which enhances its strength and extends the duration of stem cell exosomes on the wound surface. On the basis of these characteristics, we provide evidence that this compound hydrogel can substantially increase cell proliferation and regeneration, inhibit scar hyperplasia, and stimulate angiogenesis in rabbit nasal septum mucosa trauma models. These results suggest that MSC exosome-loaded hydrogels (ME-Gel) have substantial clinical potential for the repair and regeneration of nasal mucosa after surgery or trauma.

A series of new targets containing 3 chiral elements of central, orientational, and turbo chirality have been designed and synthesized asymmetrically. The absolute configurations and conformations of these types of chirality were concurrently controlled by using chiral sulfonimine auxiliary and unambiguously determined by x-ray diffraction analysis. These targets include alpha unnatural amino acid derivatives, which may play an important role for drug design, discovery, and development. Three propellers of turbo framework are covalently connected to a chiral C(sp³) center via C(sp²)–C(sp³) bonding along with a C–N axis, while one of them is orientated away from the same carbon chiral center. The turbo or propeller chirality is characterized by 2 types of molecular arrangements of propellers, clockwise (PPP) and counterclockwise (MMM), respectively. The turbo stereogenicity was found to depend on the center chirality of sulfonimine auxiliary instead of the chiral C(sp³) center, i.e., (S)- and (R)-sulfinyl centers led to the asymmetric formation of PPP- and MMM-configurations, respectively. Computational studies were conducted on relative energies for rotational barriers of a turbo target along the C–N anchor and the transition pathway between 2 enantiomers meeting our experimental observations. This work is anticipated to have a broad impact on chemical, biomedical, and materials sciences in the future.

The interaction between organic and inorganic components in metal hybrid perovskites fundamentally determines the intrinsic optoelectronic performance. However, the underlying interaction sites have still remained elusive, especially for those non-hydrogen-bonded hybrid perovskites, thus largely impeding materials precise design with targeted properties. Herein, high pressure is utilized to elucidate the interaction mechanism between organic and inorganic components in the as-synthesized one-dimensional hybrid metal halide (DBU)PbBr₃ (DBU = 1,8-diazabicyclo [5.4.0] undec-7-ene). The interaction sites are identified to be the N from DBU and the Br from inorganic framework by the indicative of enhanced Raman mode under high pressure. The change in interaction strength is indeed derived from the pressure modulation on both distance and spatial arrangement of the nearest Br and N, rather than traditional hydrogen-bonding effect. Furthermore, the enhanced interaction increased charge transfer, resulting in a cyan emission with photoluminescence quantum yields (PLQYs) of 86.6%. The enhanced cyan emission is particularly important for underwater communication due to the much less attenuation in water than at other wavelength emissions. This study provides deep insights into the underlying photophysical mechanism of non-hydrogen-bonded hybrid metal halides and is expected to impart innovative construction with superior performance.

Microneedles have shown considerable potential in treating ocular diseases, yet enhancing their architecture and functionality to improve therapeutic efficacy poses marked challenges. Here, inspired by the antioxidant strategy of blueberries and the wet adhesive mechanism of clingfish, we construct hierarchical and multifunctional microneedles. These microneedles possess both wet adhesive and antioxidant properties, making them highly effective for ocular wound healing. Constructed using polyacrylic acid-N-hydroxysuccinimide-based hydrogel with hexagonal structures, these generated microneedles ensure strong adhesion in wet environments. Furthermore, by incorporating proanthocyanidins (pAc) into the tips, the microneedle is imparted with excellent competence to scavenge reactive oxygen species (ROS). In the rat model of ocular alkali burns, the designed microneedle not only exhibited robust adhesion and desirable antioxidant properties in the moist ocular environment but also facilitated sustained drug release and effective treatment. These results suggest that our bioinspired microneedles with multifunctional properties offer substantial advancement over conventional approaches, positioning them as promising candidates for versatile wound healing applications.

Activation of mitochondrial function and heat production in adipose tissue by the modification of dietary fat is a promising strategy against obesity. However, as an important source of lipids for ketogenic and daily diets, the function of fats extracted from different adipose tissue sites was largely unknown. In this study, we illustrated the function of fats extracted from adipose tissues with different “beigeing” properties in the ketogenic diet and identified lipid profiles of fats that facilitate energy expenditure. We found that the anti-obesity effect of ketogenic diets was potentiated by using “beigeing” fat [porcine subcutaneous adipose tissue (SAT)] as a major energy-providing ingredient. Through lipidomic analyses, phosphatidylserine (PS) was identified as a functional lipid activating thermogenesis in adipose tissue. Moreover, in vivo studies showed that PS induces adipose tissue thermogenesis and alleviates diet-induced obesity in mice. In vitro studies showed that PS promotes UCP1 expression and lipolysis of adipocytes. Mechanistically, PS promoted mitochondrial function in adipocytes via the ADCY3-cAMP-PKA-PGC1α pathway. In addition, PS-PGC1a binding may affect the stability of the PGC1α protein, which further augments PS-induced thermogenesis. These results demonstrated the efficacy of dietary SAT fats in diminishing lipid accumulation and the underlying molecular mechanism of PS in enhancing UCP1 expression and mitochondrial function. Thus, our findings suggest that as dietary fat, “beigeing” fat provides more beneficial lipids that contribute to the improvement of mitochondrial function, including PS, which may become a novel, nonpharmacological therapy to increase energy expenditure and counteract obesity and its related diseases.

Layered structure oxides have emerged as highly promising cathode materials for lithium-ion batteries. In these cathode materials, volume variation related to anisotropic lattice strain during Li⁺ insertion/extraction, however, can induce critical structural instability and electrochemical degradation upon cycling. Despite extensive research efforts, solving the issues of lattice strain and mechanical fatigue remains a challenge. This perspective aims to establish the “structure–property relationship” between the degradation mechanism of the layered oxide cathode due to lattice strain and the structural evolution during cycling. By addressing these issues, we aim to guide the improvement of electrochemical performance, thereby facilitating the widespread adoption of these materials in future high-energy density lithium-ion batteries.

Triple-negative breast cancer (TNBC) is currently the worst prognostic subtype of breast cancer, and there is no effective treatment other than chemotherapy. Processing of precursors 1 (POP1) is the most substantially up-regulated RNA-binding protein (RBP) in TNBC. However, the role of POP1 in TNBC remains clarified. A series of molecular biological experiments in vitro and in vivo and clinical correlation analyses were conducted to clarify the biological function and regulatory mechanism of POP1 in TNBC. Here, we identified that POP1 is significantly up-regulated in TNBC and associated with poor prognosis. We further demonstrate that POP1 promotes the cell cycle and proliferation of TNBC in vitro and vivo. Mechanistically, POP1 directly binds to the coding sequence (CDS) region of CDKN1A mRNA and degrades it. The degradation process depends on the N6-methyladenosine (m6A) modification at the 497th site of CDKN1A and the recognition of this modification by YTH N6-methyladenosine RNA binding protein 2 (YTHDF2). Moreover, the m6A inhibitor STM2457 potently impaired the proliferation of POP1-overexpressed TNBC cells and improved the sensitivity to paclitaxel. In summary, our findings reveal the pivotal role of POP1 in promoting TNBC proliferation by degrading the mRNA of CDKN1A and that inhibition of m6A with STM2457 is a promising therapeutic strategy for TNBC.

Advanced sensing devices based on metasurfaces have emerged as a revolutionary platform for innovative label-free biosensors, holding promise for early diagnostics and the detection of low-concentration analytes. Here, we developed a chip-based ultrasensitive terahertz (THz) metasensor, leveraging a quasi-bound state in the continuum (q-BIC) to address the challenges associated with intricate operations in trace biochemical detection. The metasensor design features an open-ring resonator metasurface, which supports magnetic dipole q-BIC combining functionalized gold nanoparticles (AuNPs) bound with a specific antibody. The substantial enhancement in THz–analyte interactions, facilitated by the potent near-field enhancement enabled by the q-BICs, results in a substantial boost in biosensor sensitivity by up to 560 GHz/refractive index units. This methodology allows for the detection of conjugated antibody–AuNPs for cardiac troponin I at concentrations as low as 0.5 pg/ml. These discoveries deliver valuable insight for AuNP-based trace biomolecule sensing and pave the path for the development of chip-scale biosensors with profound light–matter interactions.