General Synthesis of Composition-Tunable High-Entropy Amorphous Oxides Toward High Efficiency Oxygen Evolution Reaction.

High-entropy materials have attracted much attention in the electrocatalysis field due to their unique structure, high chemical activity, and compositional tunability. However, the harsh and complex synthetic methods limit the application of such materials. Herein, a universal non-equilibrium liquid-phase synthesis strategy is reported to prepare high-entropy amorphous oxide nanoparticles (HEAO-NPs), and the composition of HEAO-NPs can be precisely controlled from tri- to ten-component. The non-equilibrium synthesis environment provided by an excessively strong reducing agent overcomes the difference in the reduction potentials of various metal ions, resulting in the formation of HEAO-NPs with a nearly equimolar ratio. The oxygen evolution reaction (OER) performance of HEAO-NPs is further improved by adjusting the composition and optimizing the electronic structure. The Fe16Co32Ni32Mn10Cu10BOy exhibits a smaller overpotential (only 259 mV at 10 mA cm-2) and higher stability in OER compared with commercial RuO2. The amorphous high-entropy structure with an optimized concentration of iron makes the binding energy of CoNi shift to a higher direction, promotes the generation of high-valence active intermediates, and accelerates the OER kinetic process. The HEAO-NPs have promising application potential in the field of catalysis, biology, and energy storage, and this work provides a general synthesis method for composition-controllable high-entropy materials.

Methyltransferase Like-3-Mediated N6-Methyladenosine Modification of Long Noncoding RNA Hepatocyte Nuclear Factor 1a Antisense RNA 1/Hepatocyte Nuclear Factor 4a Antisense RNA 1 Regulates Cytochrome P450 Enzyme Expression.

Interindividual variations in the expression and activity of cytochrome P450 enzymes (CYPs) led to lower therapeutic efficacy or adverse drug events. We previously demonstrated that CYPs are regulated by the long noncoding RNAs (lncRNAs) hepatocyte nuclear factor 1a antisense RNA 1 (HNF1A-AS1) and HNF4A-AS1 via transcription factors (TFs) including hepatocyte nuclear factor 1a (HNF1A), hepatocyte nuclear factor 4a (HNF4A), and pregnane X receptor (PXR). However, the upstream mechanisms regulating HNF1A-AS1 and HNF4A-AS1 are poorly understood. N6-methyladenosine (m6A) is a prevalent epitranscriptomic modification in mammalian RNA. Therefore, the aim of this study was to investigate whether m6A modification regulates the expression of HNF1A-AS1 and HNF4A-AS1 and affects CYP expression in HepG2 and Huh7 cells. The methyltransferase-like 3 (METTL3) inhibitor, STM2457, significantly suppressed the expression of HNF1A-AS1 and induced HNF4A-AS1 expression. Consistent with this, a loss-of-function assay of METTL3 in the cell lines resulted in the downregulation of HNF1A-AS1 and its downstream HNF1A, PXR, and CYPs at the RNA level, as well as the downregulation of some CYPs proteins, and upregulation of HNF4A-AS1. The results of gain-of-function experiments showed the opposite trend. Mechanistically, subsequent RNA stability experiments confirmed that METTL3 affected the stability of both lncRNAs, but in opposite ways; that is, METTL3 reduced HNF1A-AS1 stability and increased HNF4A-AS1 stability. Rescue experiments confirmed that the regulation of METTL3 on TFs and CYPs may require the involvement of these two lncRNAs. Altogether, our study demonstrates that METTL3 is involved in TFs-mediated CYP expression by affecting HNF1A-AS1/HNF4A-AS1 stability. SIGNIFICANCE STATEMENT: Although the impact of long noncoding RNAs (lncRNAs) including hepatocyte nuclear factor 1a antisense RNA 1 (HNF1A-AS1) and hepatocyte nuclear factor 4a antisense RNA 1 (HNF4A-AS1) on the downstream transcription factor (TF) and cytochrome P450 enzyme (CYP) expression is well studied, the upstream regulation of these two lncRNAs by methyltransferase-like 3 (METTL3) remains unexplored. This study reveals that METTL3 is involved in the regulation of lncRNA-TF-CYP expression by affecting the stability of HNF1A-AS1 and HNF4A-AS1 in HepG2 and Huh7 cells.

Mn(II)-Based Metal Halide with Near-Unity Quantum Yield for White LEDs and High-Resolution X-ray Imaging.

Metal halides have drawn great interest as luminescent materials and scintillators due to their outstanding optical properties. Exploring new types of phosphors with easy production processes, excellent photophysical properties, high light yields, and environmentally friendly compositions is crucial and quite challenging. Herein, a novel Mn(II)-based metal halide (4-BTP)2MnBr4 was produced using a facile solvent evaporation method, which exhibited a strong green emission peaking at 524 nm from the d-d transition of tetrahedral-coordinated Mn2+ ion and a near-unity quantum yield. The prepared white light-emitting diode device has a wide color gamut of 100.7% NTSC with CIE chromaticity coordinates of (0.32, 0.32). In addition, (4-BTP)2MnBr4 demonstrates excellent characteristics in X-ray scintillation, including a high light yield of 98 000 photons/MeV, a sensitive detection limit of 37.4 nGy/s, excellent resistance to radiation damage, and successful demonstration of X-ray imaging with high resolution at 21.3 lp/mm, revealing the potential for application in diagnostic X-ray medical imaging and industry radiation detection.

Ultralong Red Room-Temperature Phosphorescence of 2D Organic-Inorganic Metal Halide Perovskites for Afterglow Red LEDs and X-ray Scintillation Applications.

Organic-inorganic metal hybrid perovskites (OIHPs) have emerged as a promising class of materials for next-generation optoelectronic applications. However, the realization of red and near-infrared (NIR) room-temperature phosphorescence (RTP) in these materials remains limited. In this study, a very strong red RTP emission centered at 610 nm is achieved by doping Mn2+ ions into Cd-based 2D OIHPs. Notably, the optimized B-EACC:Mn2+ exhibited a high quantum yield of 44.11%, an ultralong lifetime of up to 378 ms, and excellent stability against high temperatures and various solvents, surpassing most reported counterparts of 2D OIHPs. Moreover, the B-EACC:Mn2+ can be used as a red emitter for coating an ultraviolet light-emitting diode chip, exhibiting an observable afterglow to the naked eye for approximately 4 s. In addition, the B-EACC:Mn2+ demonstrates interesting characteristics under X-ray excitation, exhibiting X-ray response at radiation doses in the range of 34.75-278 µGy s-1. This work suggests the infinite possibility of doping guest ions to realize red RTP in 2D OIHPs, promoting the development of long-persistent phosphorescent emitters for multifunctional light-emitting applications.

Human umbilical cord mesenchymal stem cell exosome-derived miR-874-3p targeting RIPK1/PGAM5 attenuates kidney tubular epithelial cell damage.

BACKGROUND: Kidney insults due to various pathogenic factors, such as trauma, infection, and inflammation, can cause tubular epithelial cell injury and death, leading to acute kidney injury and the transformation of acute kidney injury to chronic kidney disease. There is no definitive treatment available. In previous studies, human umbilical cord mesenchymal stem cells have been shown to promote kidney injury. In this preclinical study, we investigate the role and mechanism of human umbilical cord mesenchymal stem cell exosomes (HucMSC-Exos) on the repair of renal tubular epithelial cells after injury. METHODS: C57BL/6 mice underwent unilateral ureteral obstruction, and epithelial cell injury was induced in HK-2 cells by cisplatin. HucMSC-Exos were assessed in vivo and in vitro. The extent of renal cell injury, activation of necroptosis pathway, and mitochondrial quality-control-related factors were determined in different groups. We also analyzed the possible regulatory effector molecules in HucMSC-Exos by transcriptomics. RESULTS: HucMSC-Exo inhibited necroptosis after renal tubular epithelial cell injury and promoted the dephosphorylation of the S637 site of the Drp1 gene by reducing the expression of PGAM5. This subsequently inhibited mitochondrial fission and maintained mitochondrial functional homeostasis, mitigating renal injury and promoting repair. In addition, HucMSC-Exo displayed a regulatory role by targeting RIPK1 through miR-874-3p. CONCLUSION: The collective findings of the present study demonstrate that HucMSC-Exos can regulate necroptosis through miR-874-3p to attenuate renal tubular epithelial cell injury and enhance repair, providing new therapeutic modalities and ideas for the treatment of AKI and the process of AKI to CKD transformation to mitigate renal damage.

Human umbilical cord mesenchymal stem cell exosomes alleviate acute kidney injury by inhibiting pyroptosis in rats and NRK-52E cells.

Human umbilical cord mesenchymal stem cells (hucMSCs) have been shown to improve kidney injury. Exosomes have been indicated to be important mediators of renal protection in MSC therapy. In spite of this, the mechanism remains unclear. Our study investigated how exosomes derived from hucMSCs (hucMSC-Ex) improve acute kidney injury (AKI). Exosomes were extracted by using an ultracentrifugation technique and identified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot. Twenty-four male SD rats were randomly divided into four groups: sham group, sham + hucMSC-Ex group, ischemia-reperfusion injury (IRI) group, and IRI + hucMSC-Ex group. In vitro, we treated rat proximal renal tubular epithelial cell line (NRK-52E) with cisplatin to mimic in vivo models of AKI. The NRK-52E cells were treated with or without 160 µg/mL hucMSC-Ex, and 1 µg/mL cisplatin was added after 9 h. Cells were harvested after 24 h. In the IRI group, the levels of serum creatinine (Scr) and blood urea nitrogen (BUN) were increased; renal tubules were dilated, epithelial cells were vacuolated, and collagen fibers were deposited in the renal interstitium. After treatment with cisplatin, the NRK-52E cells displayed pyroptotic morphology characterized by pyroptotic bodies. The protein expression levels of fibronectin, α-smooth muscle actin (α-SMA), vimentin, gasdermin D (GSDMD), caspase-1, interleukin-1 (IL-1ß) and NLRP3 in IRI tissues and in cisplatin treatment NRK-52E cells were significantly upregulated. However, after the hucMSC-Ex intervention, kidney injury was effectively improved in vivo and in vitro. The current study shows that pyroptosis is involved in AKI and that hucMSC-Ex improves AKI by inhibiting pyroptosis.

Long Noncoding RNAs Hepatocyte Nuclear Factor 4A Antisense RNA 1 and Hepatocyte Nuclear Factor 1A Antisense RNA 1 Are Involved in Ritonavir-Induced Cytotoxicity in Hepatoma Cells.

Ritonavir (RTV), a pharmacoenhancer used in anti-HIV regimens, can induce liver damage. RTV is primarily metabolized by cytochrome P450 3A4 (CYP3A4) in the liver. HNF4A antisense RNA 1 (HNF4A-AS1) and HNF1A antisense RNA 1 (HNF1A-AS1) are long noncoding RNAs that regulate the expression of pregnane X receptor (PXR) and CYP3A4. This study investigated the role and underlying mechanisms of HNF4A-AS1 and HNF1A-AS1 in RTV-induced hepatotoxicity. HNF4A-AS1 and HNF1A-AS1 were knocked down by small hairpin RNAs in Huh7 and HepG2 cells. Lactate dehydrogenase and reactive oxygen species assays were performed to assess RTV-induced hepatotoxicity. Chromatin immunoprecipitation quantitative real-time polymerase chain reaction was used to detect PXR enrichment and histone modifications in the CYP3A4 promoter. HNF4A-AS1 knockdown increased PXR and CYP3A4 expression and exacerbated RTV-induced cytotoxicity, whereas HNF1A-AS1 knockdown generated the opposite phenotype. Mechanistically, enrichment of PXR and trimethylation of histone 3 lysine 4 (H3K4me3) in the CYP3A4 promoter was increased, and trimethylation of histone 3 lysine 27 (H3K27me3) was decreased after HNF4A-AS1 knockdown. However, PXR and H3K4me3 enrichment decreased after HNF1A-AS1 knockdown. Alterations in RTV-induced hepatotoxicity caused by decreasing HNF4A-AS1 or HNF1A-AS1 were reversed by knockdown or overexpression of PXR. Increased susceptibility to RTV-induced liver injury caused by the PXR activator rifampicin was attenuated by HNF4A-AS1 overexpression or HNF1A-AS1 knockdown. Taken together, these results revealed that HNF4A-AS1 and HNF1A-AS1 modulated RTV-induced hepatotoxicity by regulating CYP3A4 expression, primarily by affecting the binding of PXR and histone modification status in the CYP3A4 promoter. SIGNIFICANCE STATEMENT: HNF4A-AS1 and HNF1A-AS1, transcribed separately from neighboring antisense genes of the human transcription factor genes HNF4A and HNF1A, were identified as long noncoding RNAs that can affect RTV-induced hepatotoxicity and susceptibility to RTV-induced hepatotoxicity caused by rifampicin exposure, mainly by affecting the expression of CY3A4 via alterations in PXR enrichment and histone modification status in the CYP3A4 promoter. This discovery provides directions for further research on the mechanisms of RTV-induced liver injury.

The association of chemical composition particularly the heavy metals with the oxidative potential of ambient PM2.5 in a megacity (Guangzhou) of southern China.

Atmospheric fine particulate matters (PM2.5) can cause adverse health effects through the generation of reactive oxygen species (ROS), which is normally characterized by the oxidative potential (OP). However, the particulate components that are mainly responsible for the ROS-induced OP remain controversial and warrant further investigation, especially in megacities where high exposure exists and particulate composition is complex. In this study, we measured the OP of PM2.5 using the dithiothreitol (DTT) assay with and without chelation of metals in a megacity in southern China, Guangzhou, in January and April. We explored the correlations between OP and various chemical components in PM2.5, including water-soluble ions, organic carbon (OC), elemental carbon (EC), and metal elements. There are strong correlations between OPDTTv (volume-normalized) and concentrations of PM2.5, OC, and EC, while the correlations between OPDTTm (mass-normalized) and mass-normalized water-soluble ions, OC, EC or metal elements are weak. The OP values with chelation were reduced by ∼90%, indicating that water-soluble heavy metals were the major contributors to OP of PM2.5 in Guangzhou. On the other hand, correlations between OPDTTm and OC improved significantly after the chelation of heavy metals, implying that OC explains the variance of OPDTTm although its contribution to OP is much smaller than that of heavy metals. We postulate that there might be synergetic effects between water-soluble heavy metals (which contribute most to OP) and OC (which explains the variance of OP) in ROS generation by PM2.5. The findings of the current study provide a better understanding on the critical components in PM2.5 and potential synergism that might be responsible for health effects in urban areas.

Human ucMSCs seeded in a decellularized kidney scaffold attenuate renal fibrosis by reducing epithelial-mesenchymal transition via the TGF-ß/Smad signaling pathway.

BACKGROUND: Renal fibrosis occurs largely through epithelial-mesenchymal transition (EMT). This study explored the beneficial effects of a human umbilical cord mesenchymal stem cell-loaded decellularized kidney scaffold (ucMSC-DKS) on renal fibrosis in a rodent model of post-transplantation renal failure, and the underlying mechanism. METHODS: Rat-derived DKSs were examined after preparation, and then recellularized with human ucMSCs to prepare cell-loaded patches. A rat model of renal failure was established after subtotal nephrectomy (STN). The cell patches were transplanted to remnant kidneys. Changes in renal function, histology, EMT, and proteins related to the transforming growth factor-ß (TGF-ß)/Smad signaling pathway in the remnant kidneys were examined 8 weeks after surgery, compared with non-cell patch controls. RESULTS: The DKSs were acellular and porous, with rich cytokine and major extracellular matrix components. The ucMSCs were distributed uniformly in the DKSs. Renal function was improved, renal fibrosis and EMT were reduced, and the TGF-ß/Smad signaling pathway was inhibited compared with controls at 8 weeks after ucMSC-DKS patch transplantation. CONCLUSIONS: The ucMSC-DKS restores renal function and reduces fibrosis by reducing EMT via the TGF-ß/Smad signaling pathway in rats that have undergone STN. It provides an alternative for renal fibrosis treatment.

The influence of lumbar vertebra and cage related factors on cage-endplate contact after lumbar interbody fusion: An in-vitro experimental study.

Lumbar interbody fusion (LIF) using interbody cages is an established treatment for lumbar degenerative disc disease, but fusion results are known to be affected by risk factors such as bone mineral density (BMD), endplate geometry and cage position. At present, direct measurement of endplate-cage contact variables that affect LIF have not been fully identified. The aim of this study was to use cadaveric experiments to investigate the dependency between BMD, endplate geometry, cage parameters like type, orientation, position, and contact variables like stress and area. One vertebral body specimen from each of the five lumbar positions was harvested from five male donors. The lower half of each vertebra was potted and placed in a material testing machine (Instron 8874). A spinal cage was clamped to the machine then lowered to bring it into contact against the superior endplate. A lockable ball-joint was used to rotate the cage such that its inferior surface was congruent with the local endplate surface. A pressure sensor (Tekscan) was placed between the cage and endplate to record contact area and the peak and average contact pressures. Axial compression of 400 N was performed for five positions using a straight cage, and in one anterior position using a curved cage. The linear mixed model was utilised to perform data analyses for experimental results with statistical significance set at p < 0.05. The results indicated two trends toward significance for contact area, one for volumetric BMD (vBMD) of the vertebra (p = 0.081), and another for predicted contact area (p = 0.057). Peak contact pressure correlated significantly with vBMD (p = 0.041), and there was a trend between average contact pressure and lateral position of cage (p = 0.051). In addition, predicted contact area correlated significantly with cage orientation (p < 0.001). These results indicated that high vBMD of vertebra and a medially positioned cage led to higher contact pressures. Logically, low vBMD of vertebra and transverse cage orientation increased the contact area between the cage and endplate. In conclusion, the study identified significant influence of vBMD of vertebra, cage position and orientation on cage-endplate contact which may help to inform cage selection and design for LIF.

A retrospective study differentiating nontuberculous mycobacterial pulmonary disease from pulmonary tuberculosis on computed tomography using radiomics and machine learning algorithms.

OBJECTIVE: To evaluate the effectiveness of a machine learning based on computed tomography (CT) radiomics to distinguish nontuberculous mycobacterial pulmonary disease (NTM-PD) from pulmonary tuberculosis (PTB). METHODS: In this retrospective analysis, medical records of 99 individuals afflicted with NTM-PD and 285 individuals with PTB in Zhejiang Chinese and Western Medicine Integrated Hospital were examined. Random numbers generated by a computer were utilized to stratify the study cohort, with 80% designated as the training cohort and 20% as the validation cohort. A total of 2153 radiomics features were extracted using Python (Pyradiomics package) to analyse the CT characteristics of the large disease areas. The identification of significant factors was conducted through the least absolute shrinkage and selection operator (LASSO) regression. The following four supervised learning classifier models were developed: random forest (RF), support vector machine (SVM), logistic regression (LR), and extreme gradient boosting (XGBoost). For assessment and comparison of the predictive performance among these models, receiver-operating characteristic (ROC) curves and the areas under the ROC curves (AUCs) were employed. RESULTS: The Student's t-test, Levene test, and LASSO algorithm collectively selected 23 optimal features. ROC analysis was then conducted, with the respective AUC values of the XGBoost, LR, SVM, and RF models recorded to be 1, 0.9044, 0.8868, and 0.7982 in the training cohort. In the validation cohort, the respective AUC values of the XGBoost, LR, SVM, and RF models were 0.8358, 0.8085, 0.87739, and 0.7759. The DeLong test results noted the lack of remarkable variation across the models. CONCLUSION: The CT radiomics features can help distinguish between NTM-PD and PTB. Among the four classifiers, SVM showed a stable performance in effectively identifying these two diseases.

Molecular dynamics simulation of the effect of temperature on the conformation of ubiquitin protein.

CONTENT: Ubiquitin, a ubiquitous small protein found in all living organisms, is crucial for tagging proteins earmarked for degradation and holds pivotal importance in biomedicine. Protein functionality is intricately linked to its structure. To comprehend the impact of diverse temperatures on ubiquitin protein structure, our study delved into the energy landscape, hydrogen bonding, and overall structural stability of ubiquitin protein at varying temperatures. Through meticulous analysis of root mean square deviation and root mean square fluctuation, we validated the robustness of the simulation conditions employed. Within our simulated system, the bonding energy and electrostatic potential energy exhibited linear augmentation, while the van der Waals energy demonstrated a linear decline. Additionally, our findings highlighted that the α-Helix secondary structure of the ubiquitin protein gradually transitions toward helix destabilization under high-temperature conditions. The secondary structure of ubiquitin protein experiences distinct changes under varying temperatures. The outcomes of our molecular simulations offer a theoretical framework that enhances our comprehension of how temperature impacts the structural stability of ubiquitin protein. These insights contribute not only to a deeper understanding of iniquity's behavior but also hold broader implications in the realm of biomedicine and beyond. METHODS: All the MD simulations were performed using the GROMACS software with GROMOS96 force field and SPC for water. The ubiquitin protein was put in the center of a cubic box with a length of 8 nm, a setting that allowed > 0.8 nm in the minimal distance between the protein surface and the box wall. To remove the possible coordinate collision of the configurations, in the beginning, the steepest descent method was used until the maximum force between atoms was under 100 kJ/mol·nm with a 0.01 nm step size. Minimization was followed by 30 ps of position-restrained MD simulation. The protein was restrained to its initial position, and the solvent was freely equilibrated. The product phase was obtained with the whole system simulated for 10 ns without any restraint using an integral time step of 1 fs with different temperatures. The cutoff for short-range electronic interaction was set to 1.5 nm. The long-range interactions were treated with a particle-mesh Ewald (PME) method with a grid width of 1.2 nm.

The necroptosis-mediated imbalance of mitochondrial dynamics is involved in DEHP-induced toxicity to immature testes via the PGAM5-DRP1 interaction.

Di-(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer that has been shown to impair male reproduction, but the potential mechanism underlying testicular injury caused by DEHP remains unclear. In vivo, rats were gavaged consecutively from postnatal day (PND) 21 to PND 31 with 0, 250, or 500 mg/kg DEHP for 10 days, and impaired mitochondria and increased necroptosis were observed in immature testes. In vitro, the GC-1 and GC-2 cell lines were exposed to monoethylhexyl phthalate (MEHP) at 100, 200 and 400 µM for 24 h, and this exposure induced oxidative stress damage, necroptosis and mitochondrial injury. Necroptosis and mitochondrial fission were inhibited by the reactive oxygen species (ROS) inhibitor acetylcysteine, and the imbalanced mitochondrial dynamics were rescued by the RIPK1 inhibitor necrostatin-1. Colocalization and co-IP analyses confirmed an interaction between dynamin-related protein 1 (DRP1) and phosphoglycerate mutase 5 (PGAM5), indicating that PGAM5 dephosphorylates DRP1 at serine 637 to induce mitochondrial fragmentation and thereby induces germ cell damage. Drug prediction with Connectivity Map (cMap) identified sulforaphane as a therapeutic drug. In summary, our findings indicate that DEHP triggers necroptosis and mitochondrial injury via a ROS storm in immature testes and that the PGAM5-DRP1 interaction is involved in this process.

Exosomes From Human Umbilical Cord Stem Cells Suppress Macrophage-to-myofibroblast Transition, Alleviating Renal Fibrosis.

Renal fibrosis, a progressive scarring of the kidney, lacks effective treatment. Human umbilical cord mesenchymal stem cell-derived exosomes (HucMSC-Exos) hold promise for treating kidney diseases due to their anti-inflammatory properties. This study investigates their potential to lessen renal fibrosis by targeting macrophage-to-myofibroblast transformation (MMT), a key driver of fibrosis. We employed a mouse model of unilateral ureteral obstruction (UUO) and cultured cells exposed to transforming growth factor-ß (TGF-ß) to mimic MMT. HucMSC-Exos were administered to UUO mice, and their effects on kidney function and fibrosis were assessed. Additionally, RNA sequencing and cellular analysis were performed to elucidate the mechanisms by which HucMSC-Exos inhibit MMT. HucMSC-Exos treatment significantly reduced kidney damage and fibrosis in UUO mice. They downregulated markers of fibrosis (Collagen I, vimentin, alpha-smooth muscle actin) and suppressed MMT (α-SMA + F4/80 + cells). Furthermore, ARNTL, a specific molecule, emerged as a potential target of HucMSC-Exos in hindering MMT and consequently preventing fibrosis. HucMSC-Exos effectively lessen renal fibrosis by suppressing MMT, suggesting a novel therapeutic strategy for managing kidney damage and fibrosis.

Achieving Ultralong Room-Temperature Phosphorescence in Two-Dimensional Metal Halide Perovskites by Alkyl Chain Engineering.

Two-dimensional (2D) metal halide perovskites with highly efficient ultralong room-temperature phosphorescence (URTP) are rare due to their uncertain structures and complicated intermolecular interactions. Herein, by varying the alkyl length of organic units, we synthesized two single-component 2D metal hybrid perovskites, i.e., B-MACC and B-EACC, with obvious URTP emission. In particular, B-EACC exhibits a green-yellow URTP emission with an ultralong lifetime (579 ms) and a high efficiency (14.86%). It is found that the molecular packing of B-EA+ cations because of the presence one more carbon in the alkyl chain affords strong hydrogen bonding and π-π stacking interactions, which immobilizes and reduces the triplet exciton quenching. Moreover, B-MACC and B-EACC with space-time dual-resolved characteristics can be utilized for dynamic information encryption and optical logic gate applications. This study is the first to disclose the relation between the characteristics of molecular packing and the resultant URTP of 2D metal hybrid perovskites, significantly advancing the development of next-generation URTP materials for versatile applications.

HucMSC exosomes attenuate partial bladder outlet obstruction-induced renal injury and cell proliferation via the Wnt/ß-catenin pathway.

Bladder outlet obstruction (BOO) can cause serious complications including kidney damage; nevertheless, there are currently no animal models for studying BOO-induced kidney damage. Mesenchymal stem cells (MSCs) are widely used in therapeutic studies of renal fibrosis. However, MSC-derived exosomes show improved safety profile and more controllable characteristics compared with those of MSCs. Herein, we established a kidney injury mouse model of partial bladder outlet obstruction (PBOO) and evaluated the effects of human umbilical cord MSC-derived exosomes (hucMSC-Exos) on PBOO-induced reflux kidney injury in this model. Exosomes were isolated from a hucMSC-conditioned medium, purified by ultracentrifugation, and examined. Living image was performed to indicate the distribution of hucMSC-Exos. The PBOO-treated mice interacted with PBS (phosphate-buffered saline) or hucMSC-Exos. Morphologic changes and expression of interstitial-fibrosis-related, cell proliferation and Wnt/ß-catenin signaling-pathway indices were evaluated. At 7 days after induction of PBOO, structural destruction of renal tubules was observed. Expression of the interstitial markers and the cellular-proliferation index increased significantly in the PBOO group compared with the control group. The isolated exosomes were 30-150 nm in diameter, showing a round shape and bilayer membrane structure with CD63, TSG101, Alix expressed, enriched in the kidney of the PBOO group. Administering hucMSC-Exos to post-PBOO mice reversed renal injury and suppressed expression of Wnt/ß-catenin signaling pathway-related proteins. hucMSC-Exos inhibited PBOO-induced kidney injury and cellular proliferation and suppressed the Wnt/ß-catenin signaling pathway. Our findings will spur the development of novel hucMSC-Exo-mediated therapies for treating patients with renal fibrosis.

Additively manufactured controlled porous orthopedic joint replacement designs to reduce bone stress shielding: a systematic review.

BACKGROUND: Total joint replacements are an established treatment for patients suffering from reduced mobility and pain due to severe joint damage. Aseptic loosening due to stress shielding is currently one of the main reasons for revision surgery. As this phenomenon is related to a mismatch in mechanical properties between implant and bone, stiffness reduction of implants has been of major interest in new implant designs. Facilitated by modern additive manufacturing technologies, the introduction of porosity into implant materials has been shown to enable significant stiffness reduction; however, whether these devices mitigate stress-shielding associated complications or device failure remains poorly understood. METHODS: In this systematic review, a broad literature search was conducted in six databases (Scopus, Web of Science, Medline, Embase, Compendex, and Inspec) aiming to identify current design approaches to target stress shielding through controlled porous structures. The search keywords included 'lattice,' 'implant,' 'additive manufacturing,' and 'stress shielding.' RESULTS: After the screening of 2530 articles, a total of 46 studies were included in this review. Studies focusing on hip, knee, and shoulder replacements were found. Three porous design strategies were identified, specifically uniform, graded, and optimized designs. The latter included personalized design approaches targeting stress shielding based on patient-specific data. All studies reported a reduction of stress shielding achieved by the presented design. CONCLUSION: Not all studies used quantitative measures to describe the improvements, and the main stress shielding measures chosen varied between studies. However, due to the nature of the optimization approaches, optimized designs were found to be the most promising. Besides the stiffness reduction, other factors such as mechanical strength can be considered in the design on a patient-specific level. While it was found that controlled porous designs are overall promising to reduce stress shielding, further research and clinical evidence are needed to determine the most superior design approach for total joint replacement implants.

Influence of the geometric and material properties of lumbar endplate on lumbar interbody fusion failure: a systematic review.

BACKGROUND: Lumbar interbody fusion (LIF) is an established surgical intervention for patients with leg and back pain secondary to disc herniation or degeneration. Interbody fusion involves removal of the herniated or degenerated disc and insertion of interbody devices with bone grafts into the remaining cavity. Extensive research has been conducted on operative complications such as a failure of fusion or non-union of the vertebral bodies. Multiple factors including surgical, implant, and patient factors influencing the rate of complications have been identified. Patient factors include age, sex, osteoporosis, and patient anatomy. Complications can also be influenced by the interbody cage design. The geometry of the bony endplates as well as their corresponding material properties guides the design of interbody cages, which vary considerably across patients with spinal disorders. However, studies on the effects of such variations on the rate of complications are limited. Therefore, this study aimed to perform a systematic review of lumbar endplate geometry and material property factors in LIF failure. METHODS: Search keywords included 'factor/cause for spinal fusion failure/cage subsidence/cage migration/non-union', 'lumbar', and 'interbody' in electronic databases PubMed and Scopus with no limits on year of publication. RESULTS: In total, 1341 articles were reviewed, and 29 articles were deemed suitable for inclusion. Adverse events after LIF, such as cage subsidence, cage migration, and non-union, resulted in fusion failure; hence, risk factors for adverse events after LIF, notably those associated with lumbar endplate geometry and material properties, were also associated with fusion failure. Those risk factors were associated with shape, concavity, bone mineral density and stiffness of endplate, segmental disc angle, and intervertebral disc height. CONCLUSIONS: This review demonstrated that decreased contact areas between the cage and endplate, thin and weak bony endplate as well as spinal diseases such as spondylolisthesis and osteoporosis are important causes of adverse events after LIF. These findings will facilitate the selection and design of LIF cages, including customised implants based on patient endplate properties.

Theoretical Mechanism on the Cellulose Regeneration from a Cellulose/EmimOAc Mixture in Anti-Solvents.

The experiments on cellulose dissolution/regeneration have made some achievements to some extent, but the mechanism of cellulose regeneration in ionic liquids (ILs) and anti-solvent mixtures remains elusive. In this work, the cellulose regeneration mechanism in different anti-solvents, and at different temperatures and concentrations, has been studied with molecular dynamics (MD) simulations. The IL considered is 1-ethyl-3-methylimidazolium acetate (EmimOAc). In addition, to investigate the microcosmic effects of ILs and anti-solvents, EmimOAc-nH2O (n = 0-6) clusters have been optimized by Density Functional Theory (DFT) calculations. It can be found that water is beneficial to the regeneration of cellulose due to its strong polarity. The interactions between ILs and cellulose will become strong with the increase in temperature. The H-bonds of cellulose chains would increase with the rising concentrations of anti-solvents. The interaction energies between cellulose and the anions of ILs are stronger than that of cations. Furthermore, the anti-solvents possess a strong affinity for ILs, cation-anion pairs are dissociated to form H-bonds with anti-solvents, and the H-bonds between cellulose and ILs are destroyed to promote cellulose regeneration.