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The occurrence of osteoarthritis (OA) is highly correlated with the reduction of joint lubrication performance, in which persistent excessive inflammation and irreversible destruction of cartilage dominate the mechanism. The inadequate response to monotherapy methods, suboptimal efficacy caused by undesirable bioavailability, short retention, and lack of stimulus-responsiveness, are few unresolved issues. Herein, we report a pH-responsive metal-organic framework (MOF), namely, MIL-101-NH 2 , for the co-delivery of anti-inflammatory drug curcumin (CCM) and small interfering RNA (siRNA) for hypoxia inducible factor (HIF-2α). CCM and siRNA were loaded via encapsulation and surface coordination ability of MIL-101-NH 2 . Our vitro tests showed that MIL-101-NH 2 protected siRNA from nuclease degradation by lysosomal escape. The pH-responsive MIL-101-NH 2 gradually collapsed in an acidic OA microenvironment to release the CCM payloads to down-regulate the level of pro-inflammatory cytokines, and to release the siRNA payloads to cleave the target HIF-2α mRNA for gene-silencing therapy, ultimately exhibiting the synergetic therapeutic efficacy by silencing HIF-2α genes accompanied by inhibiting the inflammation response and cartilage degeneration of OA. The hybrid material reported herein exhibited promising potential performance for OA therapy as supported by both in vitro and in vivo studies and may offer an efficacious therapeutic strategy for OA utilizing MOFs as host materials.

Intervertebral disc degeneration (IVDD) is driven by persistent inflammation–oxidative stress that disrupts annulus fibrosus (AF) homeostasis. Guided by network pharmacology and docking, we prioritized the NF‐κB–LCN2 axis as a druggable target of wedelolactone (WDL). To achieve targeted modulation, we engineered a dual‐network ROS‐responsive hydrogel (WPG) in which a phenylboronic‐ester/PVA redox‐cleavable network interpenetrates a covalently crosslinked GelMA–elastin matrix, enabling mechanically robust yet stimulus‐triggered WDL release. WDL suppressed NF‐κB activation and downregulated LCN2 in both macrophages and AF cells. Conditioned‐medium co‐culture demonstrated that WDL disrupts macrophage‐derived LCN2‐mediated paracrine amplification, breaking the self‐sustaining inflammatory loop. Bulk RNA‐seq across both cell types revealed coordinated downregulation of NF‐κB – driven chemokine cascades and restoration of adhesion and ECM gene programs following WPG treatment. In a rat AF‐defect model, intradiscal WPG administration preserved disc height and T 2 ‐weighted MRI signal, reduced MMP13 while increasing Collagen I and Aggrecan expression, suppressed nuclear P‐p65 and LCN2, and improved segment biomechanics—without eliciting adverse hematological or organ responses. Collectively, these findings establish that aligning molecular targeting (NF‐κB–LCN2 modulation) with the pathophysiological context via ROS‐gated delivery provides a synergistic strategy for AF repair and attenuation of IVDD progression.

The occurrence of osteoarthritis (OA) is highly correlated with the reduction of joint lubrication performance, in which persistent excessive inflammation and irreversible destruction of cartilage dominate the mechanism. The inadequate response to monotherapy methods, suboptimal efficacy caused by undesirable bioavailability, short retention, and lack of stimulus-responsiveness, are few unresolved issues. Herein, we report a pH-responsive metal-organic framework (MOF), namely, MIL-101-NH.sub.2, for the co-delivery of anti-inflammatory drug curcumin (CCM) and small interfering RNA (siRNA) for hypoxia inducible factor (HIF-2[alpha]). CCM and siRNA were loaded via encapsulation and surface coordination ability of MIL-101-NH.sub.2. Our vitro tests showed that MIL-101-NH.sub.2 protected siRNA from nuclease degradation by lysosomal escape. The pH-responsive MIL-101-NH.sub.2 gradually collapsed in an acidic OA microenvironment to release the CCM payloads to down-regulate the level of pro-inflammatory cytokines, and to release the siRNA payloads to cleave the target HIF-2[alpha] mRNA for gene-silencing therapy, ultimately exhibiting the synergetic therapeutic efficacy by silencing HIF-2[alpha] genes accompanied by inhibiting the inflammation response and cartilage degeneration of OA. The hybrid material reported herein exhibited promising potential performance for OA therapy as supported by both in vitro and in vivo studies and may offer an efficacious therapeutic strategy for OA utilizing MOFs as host materials.

The Venus A-Valve is the first commercially approved transcatheter aortic valve in China that now holds the largest market share. [...]patients being sent to Venus’ core laboratory can be considered as representative. The perimeter of aortic annulus was smaller than the lower bound of the sizing chart of Venus A-Valve (53 mm) in 0.1% (2/1822) of patients and greater than the upper bound (91 mm) in 7.4% (135/1822) of patients. The major findings are (a) at a mean age of 73 years, the proportion of BAV morphology in this cohort was 54%, higher than similar registries of more elderly patients in industrialized countries. (b) Type 0 subtype accounted for over 40% of BAV in China, different from the type 1 dominance seen in other registries. (c) The volume of aortic leaflet calcification was higher in Chinese patients. (d) BAV patients had a relatively larger anatomy and higher calcification volume than tricuspid aortic valve, but their annulus was less elliptical in the current cohort. (e) Type 0 subtype had a smaller but less elliptical aortic annulus and less calcification than type 1 subtype. (f) Regional differences exist in aortic root dimensions and calcification burden in China. [7] Whether it may bring clinical benefits comparing with devices of higher conformability, along with a tailored treatment strategy and device design taking characteristics of Chinese patients into consideration, warrants further research studies.

Seasonal variations in the transports of total alkalinity (TAlk) and dissolved inorganic carbon (DIC) from the Lower Changjiang (Yangtze) River/Estuary to the East China Sea were investigated based on a series of field surveys in 2015–2017, including monthly samplings at Datong Station and seasonal mapping cruises in the Changjiang Estuary and the adjacent northwestern East China Sea. In comparison with historical data sets, the Changjiang TAlk flux varied around a nearly stable average over the past 55 years. This is much different from some American rivers, where TAlk export fluxes increased for a century long. To assess effects of riverine carbonate inputs on coastal carbonate chemistry, we compared several cases showing freshwater‐dilution‐induced decline in coastal aragonite saturation state (Ωarag), including rainwater dilution and riverine water dilution. Without riverine carbonate inputs, the effect of a unit of salinity decrease (due to rainwater dilution) on Ωarag was expected to be counteracted by a DIC removal of 10 μmol/kg relative to the baseline value along relevant conservative mixing line, when coastal Ωarag was close to a critical value of 1.5. Considering terrestrial carbonate inputs from Changjiang, however, the freshwater‐dilution‐induced coastal Ωarag suppression decreased by 12%. Our data also showed that more than 10% of wet‐season DIC flux discharged from the Changjiang Estuary was sequestered by biological activities in nearshore areas, while the TAlk flux was rarely affected. This biological alteration effectively transformed the terrestrial carbonate system from a feature of DIC:TAlk >1.0 to the usual seawater feature of DIC:TAlk <0.9. Plain Language Summary Changjiang (Yangtze River) serves as the second largest carbonate contributor to the ocean among the world large rivers. We examined riverine/estuarine transport fluxes of total alkalinity (TAlk) and dissolved inorganic carbon (DIC) in the continuum from the Lower Changjiang to its estuary and to the adjacent northwestern East China Sea. In comparison with historical data, the Changjiang TAlk flux varied around a nearly stable average over the past 55 years, which was much different from the American case of century‐long TAlk increase in some rivers. We also assessed effects of riverine carbonate inputs on the coastal carbonate chemistry. Results suggest that terrestrial carbonate inputs decreased the freshwater‐dilution‐induced carbonate mineral suppression in coastal zones. Based on field data, we estimated that more than 10% of wet‐season DIC flux discharged from the Changjiang Estuary was sequestered by biological activities in nearshore areas, while the TAlk flux was rarely affected. We explained how biological drawdown of riverine DIC transformed the terrestrial feature of DIC:TAlk ratio higher than 1.0 to the usual seawater feature of DIC:TAlk ratio less than 0.9, supporting Alfred C. Redfield's argument on “the influence of organisms on the composition of seawater” in the 1960s or earlier. Key Points Changjiang (Yangtze River) export flux of total alkalinity varied around a nearly stable average over the past 55 years Terrestrial carbonate input from Changjiang decreased the freshwater‐dilution‐induced coastal aragonite saturation state suppression by 12% More than 10% of wet‐season DIC flux discharged from Changjiang was sequestered in coastal zones, while the TAlk flux was rarely affected

Gradient cemented carbides with the surface depleted in cubic phases were prepared following normal powder metallurgical pro-cedures.Gradient zone formation and the influence of nitrogen introduction methods on the microstructure and performance of the alloys were investigated.The results show that the simple one-step vacuum sintering technique is doable for producing gradient cemented carbides.Gradient structure formation is attributed to the gradient in nitrogen activity during sintering,but is independent from nitrogen introduced methods.A uniform carbon distribution is found throughout the materials.Moreover,the transverse rupture strength of the cemented carbides can be increased by a gradient layer.Different nitrogen carriers give the alloys distinguishing microstructure and mechanical properties,and a gradient alloy with ultrafine-TiC0.5N0.5 is found optimal.

INTRODUCTIONMicroneurosurgery made its debut in the early 1960s. It became popular in the medical field and became a primary operation method in neurosurgery since it improved the efficacy of neurosurgery with a less surgery-related injury. Over the past five decades, the accumulation of experience of microsurgery, improvement of microsurgery techniques, refined micro-instruments, and advanced preoperative diagnostic imaging allowed the evolution of microneurosurgery techniques and further reduced surgery-related trauma.