Self-assembly of a ruthenium-based cGAS-STING photoactivator for carrier-free cancer immunotherapy.

The cGAS (cyclic GMP-AMP synthase)-STING (stimulator of interferon genes) pathway promotes antitumor immune responses by sensing cytosolic DNA fragments leaked from nucleus and mitochondria. Herein, we designed a highly charged ruthenium photosensitizer (Ru1) with a ß-carboline alkaloid derivative as the ligand for photo-activating of the cGAS-STING pathway. Due to the formation of multiple non-covalent intermolecular interactions, Ru1 can self-assemble into carrier-free nanoparticles (NPs). By incorporating the triphenylphosphine substituents, Ru1 can target and photo-damage mitochondrial DNA (mtDNA) to cause the cytoplasmic DNA leakage to activate the cGAS-STING pathway. Finally, Ru1 NPs show potent antitumor effects and elicit intense immune responses in vivo. In conclusion, we report the first self-assembling mtDNA-targeted photosensitizer, which can effectively activate the cGAS-STING pathway, thus providing innovations for the design of new photo-immunotherapeutic agents.

UiO-66/PIM-1 Mixed-Matrix Membrane for Hexane Isomer Separation.

The separation of high-octane dibranched alkanes from naphtha is critical in the refining of gasoline. To date, research on the membrane-based separation of alkane isomers has been limited, with a particular paucity of investigations into mixed-matrix membranes. Herein, the continuous and dense UiO-66/PIM-1 mixed-matrix membrane, which was prepared through precise control of the interfacial structure, was first applied to the differentiation of C6 alkane isomers. Due to the synergistic combination of UiO-66 with differential adsorption capabilities for alkanes and PIM-1 that possesses a cross-linkable structure, the resulting UiO-66/PIM-1-(20) membrane demonstrated remarkable separation performance and high stability. Pervaporation measurements showed that the mass fraction of 2,2-dimethylbutane in the feed side was increased from 50.0 to 75.8 wt % while an excellent flux of 1700 g m-2 h-1 was maintained over a continuous 40 h period. The UiO-66/PIM-1-(20) membrane, characterized by its facile replication and processing, shows potential for large-scale fabrication. This study offers a new approach to the membrane separation of alkane isomers.

Analysis of changes in social isolation, loneliness, or both, and subsequent cognitive function among older adults: Findings from a nationwide cohort study.

INTRODUCTION: The study aimed to investigate the associations of changes in social isolation, loneliness, or both, with cognitive function. METHODS: Data were from 7299 older adults in the Chinese Longitudinal Healthy Longevity Survey. We defined four change patterns (no, incident, transient, and persistent) for social isolation and loneliness, and created nine-category variable to represent the joint changes. Tobit regression models and Cox models were performed. RESULTS: Incident, transient, and persistent social isolation or loneliness may accelerate cognitive decline (p < 0.05). Incident, transient, and persistent social isolation were associated with higher cognitive impairment risk, while only persistent loneliness was associated with higher cognitive impairment risk (p < 0.001). Notably, short-term or persistent social isolation was associated with accelerated cognitive decline and incident cognitive impairment, regardless of different loneliness change status (p < 0.05). DISCUSSION: Short-term or persistent social isolation and persistent loneliness may be a salient risk factor for cognitive decline and cognitive impairment. HIGHLIGHTS: Incident, transient, and persistent social isolation were associated with accelerated cognitive decline and higher cognitive impairment risk. Persistent loneliness was associated with accelerated cognitive decline and higher cognitive impairment risk. Short-term or persistent social isolation with concurrent different loneliness change status accelerated cognitive decline and higher cognitive impairment risk.

Stabilization of Ni-containing Keggin-type polyoxometalates with variable oxidation states as novel catalysts for electrochemical water oxidation.

The development of new recyclable and inexpensive electrochemically active species for water oxidation catalysis is the most crucial step for future utilization of renewables. Particularly, transition metal complexes containing internal multiple, cooperative metal centers to couple with redox catalysts in the inorganic Keggin-type polyoxometalate (POM) framework at high potential or under extreme pH conditions would be promising candidates. However, most reported Ni-containing POMs have been highly unstable towards hydrolytic decomposition, which precludes them from application as water oxidation catalysts (WOCs). Here, we have prepared new tri-Ni-containing POMs with variable oxidation states by charge tailored synthetic strategies for the first time and developed them as recyclable POMs for water oxidation catalysts. In addition, by implanting corresponding POM anions into the positively charged MIL-101(Cr) metal-organic framework (MOF), the entrapped Ni2+/Ni3+ species can show complete recyclability for water oxidation catalysis without encountering uncontrolled hydrolysis of the POM framework. As a result, a low onset potential of approximately 1.46 V vs. NHE for water oxidation with stable WOC performance is recorded. Based on this study, rational design and stabilization of other POM-electrocatalysts containing different multiple transition metal centres could be made possible.

Metabolic obesity phenotypes and all-cause mortality among the Chinese oldest-old population: a prospective cohort study.

BACKGROUND: The obesity paradox has been reported among older adults. However, whether the favorable effect of obesity is dependent on metabolic status remains largely unknown. We aimed to explore the association of metabolic obesity phenotypes and their changes with all-cause mortality among the Chinese oldest-old population. METHODS: This prospective cohort study included 1207 Chinese oldest old (mean age: 91.8 years). Metabolic obesity phenotypes were determined by central obesity and metabolic status, and participants were classified into metabolically healthy obesity (MHO), metabolically unhealthy obesity (MUO), metabolically healthy non-obesity (MHN), and metabolically unhealthy non-obesity (MUN). The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated by Cox regression models. RESULTS: During 5.3 years of follow-up, 640 deaths were documented. Compared with non-obesity, obesity was associated with a decreased mortality risk among participants with metabolically healthy (HR, 0.75; 95% CI, 0.63-0.91) while this association was insignificant among metabolically unhealthy. Compared to MHO, MHN (HR, 1.27; 95% CI, 1.06-1.53) and MUN (HR, 1.49; 95% CI, 1.10-2.02) were significantly associated with an increased mortality risk. Compared to those with stable MHO, those transited from MHO to MUO demonstrated a higher mortality risk (HR, 1.81; 95% CI, 1.06-3.11). CONCLUSIONS: MHO predicts better survival among the Chinese oldest-old population. These findings suggest that ensuring optimal management of metabolic health is beneficial and taking caution in weight loss based on the individual body weight for the metabolically healthy oldest-old adults.

Applying dynamic contrast-enhanced MRI tracer kinetic models to differentiate benign and malignant soft tissue tumors.

BACKGROUND: To explore the potential of different quantitative dynamic contrast-enhanced (qDCE)-MRI tracer kinetic (TK) models and qDCE parameters in discriminating benign from malignant soft tissue tumors (STTs). METHODS: This research included 92 patients (41females, 51 males; age range 16-86 years, mean age 51.24 years) with STTs. The qDCE parameters (Ktrans, Kep, Ve, Vp, F, PS, MTT and E) for regions of interest of STTs were estimated by using the following TK models: Tofts (TOFTS), Extended Tofts (EXTOFTS), adiabatic tissue homogeneity (ATH), conventional compartmental (CC), and distributed parameter (DP). We established a comprehensive model combining the morphologic features, time-signal intensity curve shape, and optimal qDCE parameters. The capacities to identify benign and malignant STTs was evaluated using the area under the curve (AUC), degree of accuracy, and the analysis of the decision curve. RESULTS: TOFTS-Ktrans, EXTOFTS-Ktrans, EXTOFTS-Vp, CC-Vp and DP-Vp demonstrated good diagnostic performance among the qDCE parameters. Compared with the other TK models, the DP model has a higher AUC and a greater level of accuracy. The comprehensive model (AUC, 0.936, 0.884-0.988) demonstrated superiority in discriminating benign and malignant STTs, outperforming the qDCE models (AUC, 0.899-0.915) and the traditional imaging model (AUC, 0.802, 0.712-0.891) alone. CONCLUSIONS: Various TK models successfully distinguish benign from malignant STTs. The comprehensive model is a noninvasive approach incorporating morphological imaging aspects and qDCE parameters, and shows significant potential for further development.

CeO2/Co heterostructure encapsulated in hollow necklace-like carbon fiber as an advanced host material for high-performance lithium-sulfur batteries.

The shuttle effect of lithium polysulfides (LiPSs) and the sluggish reaction kinetics of LiPSs conversion pose serious challenges to the commercial feasibility of lithium-sulfur (Li-S) batteries. To address these obstacles, herein, we construct CeO2/Co heterostructures in hollow necklace-like carbon fibers (CeO2/Co-CNFs) as the cathode host material for Li-S batteries. The specific surface area of fibers is significantly enhanced by using a template, thereby promoting the utilization efficiency of sulfur. Meanwhile, CeO2/Co-CNFs show strong conductivity, effective adsorption to LiPSs, and robust catalytic activity for LiPSs conversion. As a result, the Li-S battery with CeO2/Co-CNFs displays 961 mAh g-1 at 0.2 C, with an 86 % capacity retention rate after 100 cycles. At 2.0 C current density, the composite cathode maintains an initial discharge capacity of 782 mAh g-1, with a mere 0.044 % capacity loss per cycle. Furthermore, in situations with limited electrolytes, high sulfur loading, and high areal mass loading, the composite cathode can provide a high areal capacity of 6.2 mg cm-2 over 100 cycles. This work provides a useful approach for investigating high-performance Li-S battery cathodes.

Novel green/red oxyfluoride phosphors with excellent optical properties for near-UV excited white light emitting diode.

Novel eye-sensitive Ba3Nb2O2F12(H2O)2:Tb3+ green and Ba3Nb2O2F12(H2O)2:Mn4+ red oxyfluoride phosphors with extremely strong absorption in the UV region were designed and synthesized by simple co-precipitation strategy. Particularly, Tb3+ ions were doped in this matrix for the first time, which greatly improves their absorption efficiency in the near ultraviolet region (367 nm) and emits sharp green light (544 nm). In addition, the Ba3Nb2O2F12(H2O)2:Mn4+ red phosphors have strong zero phonon line (ZPL) emission at 625 nm, which is conducive to improving the sensitivity of human eye and color purity. Meanwhile, the optical properties of the red phosphor are significantly enhanced via doping K+ cations as charge compensators. Crystal field environment and nephelauxetic effect of the as-prepared phosphors before and after K+ cation doping were systematically analyzed. Moreover, these synthesized red/green phosphors have good thermal stability and moisture resistance. Remarkably, the as-prepared Ba3Nb2O2F12(H2O)2:5%Mn4+ or K0.9Ba2.1Nb2O2F12(H2O)2:5%Mn4+ red phosphors can be directly mixed with the as-synthesized Ba3Nb2O2F12(H2O)2:13%Tb3+ green phosphor coating on 365 nm near-ultraviolet LED chip to package WLED devices with excellent electroluminescence performance. These findings are conducive to opening an avenue for screening the unique structure of optical materials.

Preliminary exploration of animal models of congenital choledochal cysts.

BACKGROUND: Various animal models have been used to explore the pathogenesis of choledochal cysts (CCs), but with little convincing results. Current surgical techniques can achieve satisfactory outcomes for treatment of CCs. Consequently, recent studies have focused more on clinical issues rather than basic research. Therefore, we need appropriate animal models to further basic research. AIM: To establish an appropriate animal model that may contribute to the investigation of the pathogenesis of CCs. METHODS: Eighty-four specific pathogen-free female Sprague-Dawley rats were randomly allocated to a surgical group, sham surgical group, or control group. A rat model of CC was established by partial ligation of the bile duct. The reliability of the model was confirmed by measurements of serum biochemical indices, morphology of common bile ducts of the rats as well as molecular biology experiments in rat and human tissues. RESULTS: Dilation classified as mild (diameter, ≥ 1 mm to < 3 mm), moderate (≥ 3 mm to < 10 mm), and severe (≥ 10 mm) was observed in 17, 17, and 2 rats in the surgical group, respectively, while no dilation was observed in the control and sham surgical groups. Serum levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, and total bile acids were significantly elevated in the surgical group as compared to the control group 7 d after surgery, while direct bilirubin, total bilirubin, and gamma-glutamyltransferase were further increased 14 d after surgery. Most of the biochemical indices gradually decreased to normal ranges 28 d after surgery. The protein expression trend of signal transducer and activator of transcription 3 in rat model was consistent with the human CC tissues. CONCLUSION: The model of partial ligation of the bile duct of juvenile rats could morphologically simulate the cystic or fusiform CC, which may contribute to investigating the pathogenesis of CC.

Control of Zeolite Local Polarity toward Efficient Xenon/Krypton Separation.

The inherent inertness and striking physicochemical similarities of krypton and xenon pose significant challenges to their separation. Reported herein is the efficient xenon capture and xenon/krypton adsorptive separation by transition metal-free zeolites under ambient conditions. The polarized environment of zeolite, denoted as local polarity, can be tuned by changing the topology, framework composition, and counter-cations, which in turn correlates with the guest-host interaction and separation performance. Chabazite zeolite with a framework Si/Al ratio of 2.5 and Ca2+ as the counter-cations, namely, Ca-CHA-2.5, is developed as a state-of-the-art zeolite adsorbent, showing remarkable performance, i.e., high dynamic xenon uptake, high xenon/krypton separation selectivity, and good recyclability, in the adsorptive separation of the xenon/krypton mixture. Grand Canonical Monte Carlo simulation reveals that extraframework Ca2+ cations act as the primary binding sites for xenon and can stabilize xenon molecules together with the chabazite framework, whereas krypton molecules are stabilized by weak guest-host interaction with the zeolite framework.

Large-scale array for radio astronomy on the farside (LARAF).

At the Royal Society meeting in 2023, we have mainly presented our lunar orbit array concept called DSL, and also briefly introduced a concept of a lunar surface array, LARAF. As the DSL concept had been presented before, in this article, we introduce the LARAF. We propose to build an array in the far side of the Moon, with a master station which handles the data collection and processing, and 20 stations with maximum baseline of 10 km. Each station consists of 12 membrane antenna units, and the stations are connected to the master station by power line and optical fibre. The array will make interferometric observation in the 0.1-50 MHz band during the lunar night, powered by regenerated fuel cells. The whole array can be carried to the lunar surface with a heavy rocket mission, and deployed with a rover in eight months. Such an array would be an important step in the long-term development of lunar-based ultralong wavelength radio astronomy. It has a sufficiently high sensitivity to observe many radio sources in the sky, though still short of the dark age fluctuations. We discuss the possible options in the power supply, data communication, deployment etc. This article is part of a discussion meeting issue 'Astronomy from the Moon: the next decades (part 2)'.

Inhibition of anlotinib-induced autophagy attenuates invasion and migration by regulating epithelial-mesenchymal transition and cytoskeletal rearrangement through ATG5 in human osteosarcoma cells

Abstract The cure rates for osteosarcoma have remained unchanged in the past three decades, especially for patients with pulmonary metastasis. Thus, a new and effective treatment for metastatic osteosarcoma is urgently needed. Anlotinib has been reported to have antitumor effects on advanced osteosarcoma. However, both the effect of anlotinib on autophagy in osteosarcoma and the mechanism of anlotinib-mediated autophagy in pulmonary metastasis are unclear. The effect of anlotinib treatment on the metastasis of osteosarcoma was investigated by transwell assays, wound healing assays, and animal experiments. Related proteins were detected by western blotting after anlotinib treatment, ATG5 silencing, or ATG5 overexpression. Immunofluorescence staining and transmission electron microscopy were used to detect alterations in autophagy and the cytoskeleton. Anlotinib inhibited the migration and invasion of osteosarcoma cells but promoted autophagy and increased ATG5 expression. Furthermore, the decreases in invasion and migration induced by anlotinib treatment were enhanced by ATG5 silencing. In addition, Y-27632 inhibited cytoskeletal rearrangement, which was rescued by ATG5 overexpression. ATG5 overexpression enhanced epithelial-mesenchymal transition (EMT). Mechanistically, anlotinib-induced autophagy promoted migration and invasion by activating EMT and cytoskeletal rearrangement through ATG5 both in vitro and in vivo. Our results demonstrated that anlotinib can induce protective autophagy in osteosarcoma cells and that inhibition of anlotinib-induced autophagy enhanced the inhibitory effects of anlotinib on osteosarcoma metastasis. Thus, the therapeutic effect of anlotinib treatment can be improved by combination treatment with autophagy inhibitors, which provides a new direction for the treatment of metastatic osteosarcoma.

Inhibition of anlotinib-induced autophagy attenuates invasion and migration by regulating epithelial-mesenchymal transition and cytoskeletal rearrangement through ATG5 in human osteosarcoma cells.

The cure rates for osteosarcoma have remained unchanged in the past three decades, especially for patients with pulmonary metastasis. Thus, a new and effective treatment for metastatic osteosarcoma is urgently needed. Anlotinib has been reported to have antitumor effects on advanced osteosarcoma. However, both the effect of anlotinib on autophagy in osteosarcoma and the mechanism of anlotinib-mediated autophagy in pulmonary metastasis are unclear. The effect of anlotinib treatment on the metastasis of osteosarcoma was investigated by transwell assays, wound healing assays, and animal experiments. Related proteins were detected by western blotting after anlotinib treatment, ATG5 silencing, or ATG5 overexpression. Immunofluorescence staining and transmission electron microscopy were used to detect alterations in autophagy and the cytoskeleton. Anlotinib inhibited the migration and invasion of osteosarcoma cells but promoted autophagy and increased ATG5 expression. Furthermore, the decreases in invasion and migration induced by anlotinib treatment were enhanced by ATG5 silencing. In addition, Y-27632 inhibited cytoskeletal rearrangement, which was rescued by ATG5 overexpression. ATG5 overexpression enhanced epithelial-mesenchymal transition (EMT). Mechanistically, anlotinib-induced autophagy promoted migration and invasion by activating EMT and cytoskeletal rearrangement through ATG5 both in vitro and in vivo. Our results demonstrated that anlotinib can induce protective autophagy in osteosarcoma cells and that inhibition of anlotinib-induced autophagy enhanced the inhibitory effects of anlotinib on osteosarcoma metastasis. Thus, the therapeutic effect of anlotinib treatment can be improved by combination treatment with autophagy inhibitors, which provides a new direction for the treatment of metastatic osteosarcoma.

Schottky heterojunction CeO2@MXene nanosheets with synergistic type I and type II PDT for anti-osteosarcoma.

Photodynamic therapy (PDT) has shown great potential for tumor treatment as the method is noninvasive, highly selective, and causes minimal side effects. However, conventional type II PDT, which relies on 1O2, presents poor therapeutic efficacy for hypoxic tumors due to its reliance on oxygen. Here, CeO2/Ti3C2-MXene (CeO2@MXene) hybrids were successfully designed by growing CeO2in situ using Ti3C2-MXene (MXene) nanosheets. CeO2@MXene serves as a reduction-oxidation (REDOX) center due to the presence of Ce in the lattice of CeO2 nanoparticles. This REDOX center reacts with H2O2 to generate oxygen and weakens the hypoxic tumor cell environment, achieving type II PDT. At the same time, many other ROS (such as ⋅O2- and ⋅OH) can be produced via a type I photodynamic mechanism (electron transfer process). The CeO2@MXene heterojunction performs nanoenzymatic functions for synergistic type I and type II PDT, which improves cancer treatment.

Dual-Confinement Effect of Nanocages@Nanotubes Suppresses Polysulfide Shuttle Effect for High-Performance Lithium-Sulfur Batteries.

The shuttle effect of lithium polysulfides (LiPSs) severely hinders the development and commercialization of lithium-sulfur batteries, and the design of high-conductive carbon fiber-host material has become a key solution to suppress the shuttle effect. In this work, a unique Co/CoN-carbon nanocages@TiO2-carbon nanotubes structure (NC@TiO2-CNTs) is constructed using an electrospinning and nitriding process. Lithium-sulfur batteries using NC@TiO2-CNTs as cathode host materials exhibit high sulfur utilization (1527 mAh g-1 at 0.2 C) and can still maintain a discharge capacity of 663 mAh g-1 at a high current density of 5 C, and the capacity loss is only 0.056% per cycle during 500 cycles at 1 C. It is worth noting that even under extreme conditions (sulfur-loading = 90%, surface-loading = 5.0 mg cm-2 (S), and E/S = 6.63 µL mg-1), the lithium-sulfur batteries can still provide a reversible capacity of 4 mAh cm-2. Throughdensity functional theory calculations, it has been found that the Co/CoN heterostructures can adsorb and catalyze LiPSs conversion effectively. Simultaneously, the TiO2 can adsorb LiPSs and transfer Li+ selectively, achieving dual confinement for the shuttle effect of LiPSs (nanocages and nanotubes). The new findings provide a new performance enhancement strategy for the commercialization of lithium-sulfur batteries.

Osteoclast Cancer Cell Metabolic Cross-talk Confers PARP Inhibitor Resistance in Bone Metastatic Breast Cancer.

The majority of patients with late-stage breast cancer develop distal bone metastases. The bone microenvironment can affect response to therapy, and uncovering the underlying mechanisms could help identify improved strategies for treating bone metastatic breast cancer. Here, we observed that osteoclasts reduced the sensitivity of breast cancer cells to DNA damaging agents, including cisplatin and the PARP inhibitor (PARPi) olaparib. Metabolic profiling identified elevated glutamine production by osteoclasts. Glutamine supplementation enhanced the survival of breast cancer cells treated with DNA damaging agents, while blocking glutamine uptake increased sensitivity and suppressed bone metastasis. GPX4, the critical enzyme responsible for glutathione oxidation, was upregulated in cancer cells following PARPi treatment through stress-induced ATF4-dependent transcriptional programming. Increased glutamine uptake and GPX4 upregulation concertedly enhanced glutathione metabolism in cancer cells to help neutralize oxidative stress and generate PARPi resistance. Analysis of paired patient samples of primary breast tumors and bone metastases revealed significant induction of GPX4 in bone metastases. Combination therapy utilizing PARPi and zoledronate, which blocks osteoclast activity and thereby reduces the microenvironmental glutamine supply, generated a synergistic effect in reducing bone metastasis. These results identify a role for glutamine production by bone-resident cells in supporting metastatic cancer cells to overcome oxidative stress and develop resistance to DNA-damaging therapies. SIGNIFICANCE: Metabolic interaction between osteoclasts and tumor cells contributes to resistance to DNA-damaging agents, which can be blocked by combination treatment with PARP and osteoclast inhibitors to reduce bone metastatic burden.

Precise Confinement and Position Distribution of Atomic Cu and Zn in ZSM-5 for CO2 Hydrogenation to Methanol.

CuZn-based catalysts are widely used in CO2 hydrogenation, which may effectively convert CO2 to methanol and alleviate CO2 emission issues. The precise design of a model catalyst with a clear atomic structure is crucial in studying the relationship between structure and catalytic activity. In this work, a one-pot strategy was used to synthesize CuZn@ZSM-5 catalysts with approximately two Cu atoms and one Zn atom per unit cell. Atomic Cu and Zn species are confirmed to be located in the [54.6.102] and [62.104] tilings, respectively, by using magic-angle spinning nuclear magnetic resonance spectroscopy (MAS NMR), synchrotron X-ray powder diffraction (SXRD) and high-signal-to-noise-ratio annular dark field scanning transmission electron microscopy (High SNR ADF-STEM). Catalytic hydrogenation of CO2 to methanol was used as a model reaction to investigate the activity of the catalyst with confined active species. Compared to the Cu@ZSM-5, Zn@ZSM-5 and their mixture, the CuZn@ZSM-5 catalyst with a close Cu-Zn distance of 4.5 Å achieves a comparable methanol space-time yield (STY) of 92.0 mgmethanol·gcatal-1·h-1 at 533 K and 4 MPa with high stability. This method is able to confine one to three metal atoms in the zeolite channel and avoid migration and agglomeration of the atoms during the reaction, which maintains the stability of the catalyst and provides an efficient way for adjustment of the type and number of metal atoms along with the distances between them in zeolites.

Associations of Muscle Strength with Central Aspects of Pain: Data from the Knee Pain and Related Health in the Community (KPIC) Cohort.

Knee pain is associated with lower muscle strength, and both contribute to disability. Peripheral and central neurological mechanisms contribute to OA pain. Understanding the relative contributions of pain mechanisms to muscle strength might help future treatments. The Knee Pain and related health In the Community (KPIC) cohort provided baseline and year 1 data from people with early knee pain (n = 219) for longitudinal analyses. A cross-sectional analysis was performed with baseline data from people with established knee pain (n = 103) and comparative data from people without knee pain (n = 98). Quadriceps and handgrip strength indicated local and general muscle weakness, respectively. The indices of peripheral nociceptive drive were knee radiographic and ultrasound scores. The indices associated with central pain mechanisms were Pressure Pain detection Threshold (PPT) distal to the knee, and a validated self-report Central Aspects of Pain Factor (CAPF). The associations were explored using correlation and multivariable regression. Weaker quadriceps strength was associated with both high CAPF and low PPT at baseline. Year 1 quadriceps weakness was predicted by higher baseline CAPF (ß = -0.28 (95% CI: -0.55, -0.01), p = 0.040). Weaker baseline and year 1 handgrip strength was also associated with higher baseline CAPF. Weaker baseline quadriceps strength was associated with radiographic scores in bivariate but not adjusted analyses. Quadriceps strength was not significantly associated with total ultrasound scores. Central pain mechanisms might contribute to muscle weakness, both locally and remote from the knee.

Subtractive Nanopore Engineered MXene Photonic Nanomedicine with Enhanced Capability of Photothermia and Drug Delivery for Synergistic Treatment of Osteosarcoma.

Two-dimensional (2D) nanomaterials as drug carriers and photosensitizers have emerged as a promising antitumor strategy. However, our understanding of 2D antitumor nanomaterials is limited to intrinsic properties or additive modification of different materials. Subtractive structural engineering of 2D nanomaterials for better antitumor efficacy is largely overlooked. Here, subtractively engineered 2D MXenes with uniformly distributed nanopores are synthesized. The nanoporous defects endowed MXene with enhanced surface plasmon resonance effect for better optical absorbance performance and strong exciton-phonon coupling for higher photothermal conversion efficiency. In addition, porous structure improves the binding ability between drug and unsaturated bonds, thus promoting drug-loading capacity and reducing uncontrolled drug release. Furthermore, the porous structure provides adhesion sites for filopodia, thereby promoting the cellular internalization of the drug. Clinically, osteosarcoma is the most common bone malignancy routinely treated with doxorubicin-based chemotherapy. There have been no significant treatment advances in the past decade. As a proof-of-concept, nanoporous MXene loaded with doxorubicin is developed for treating human osteosarcoma cells. The porous MXene platform results in a higher amount of doxorubicin-loading, faster near-infrared (NIR)-controlled doxorubicin release, higher photothermal efficacy under NIR irradiation, and increased cell adhesion and internalization. This facile method pioneers a new paradigm for enhancing 2D material functions and is attractive for tumor treatment.

Exosomes combined with biosynthesized cellulose conduits improve peripheral nerve regeneration.

Peripheral nerve injury is one of the more common forms of peripheral nerve disorders, and the most severe type of peripheral nerve injury is a defect with a gap. Biosynthetic cellulose membrane (BCM) is a commonly used material for repair and ligation of nerve defects with gaps. Meanwhile, exosomes from mesenchymal stem cells can promote cell growth and proliferation. We envision combining exosomes with BCMs to leverage the advantages of both to promote repair of peripheral nerve injury. Prepared exosomes were added to BCMs to form exosome-loaded BCMs (EXO-BCM) that were used for nerve repair in a rat model of sciatic nerve defects with gaps. We evaluated the repair activity using a pawprint experiment, measurement and statistical analyses of sciatica function index and thermal latency of paw withdrawal, and quantitation of the number and diameter of regenerated nerve fibers. Results indicated that EXO-BCM produced comprehensive and durable repair of peripheral nerve defects that were similar to those for autologous nerve transplantation, the gold standard for nerve defect repair. EXO-BCM is not predicted to cause donor site morbidity to the patient, in contrast to autologous nerve transplantation. Together these results indicate that an approach using EXO-BCM represents a promising alternative to autologous nerve transplantation, and could have broad applications for repair of nerve defects.