What Matters to Fabrication of Type II Porous Liquids: A Case Study on Metallocages and Bulky Ionic Liquid?

Porosity in bulky solvents can be created by the methods of dispersing and dissolving porous hosts or by their chemical adornment. And the ensuing liquids with cavities offer requisite high gas uptakes. Intriguingly, metal-organic cages (MOCs) as discrete nanoporous hosts have been utilized recently as soluble entities to obtain a series of interesting type II porous liquids (PLs). Yet, factors affecting the fabrication of type II PLs have not been disclosed. Herein, three metallocages (NUT-101, ZrT-1-NH2, and ZrT-1) with the same zirconocene nodes but different organic ligands are chosen as porous hosts and a polyethylene-glycol (PEG) linked bis-imidazolium based IL, IL(NTf2), is used as a bulky solvent. It is revealed for the first time that the generation of type II PL depends upon the flexibility of MOCs and the interaction between MOCs and solvent molecules. The maximum solubility is observed with NUT-101 (5%) in IL(NTf2) while ZrT-1-NH2 and ZrT-1 remain least soluble (0.5% and 0.2%). As a result, PL-NUT-101-5% with most intrinsic cavities shows higher CO2 uptake (0.576 mmol g-1) than PL-ZrT-1-NH2-0.5% and PL-ZrT-1-0.2% as well as those reported type II PLs.

Transformation of Type III to Type II Porous Liquids by Tuning Surface Rigidity of Rhodium(II)-Based Metal-Organic Polyhedra for CO2 Cycloaddition.

Porous liquids (PLs), a summation of porous hosts and bulky solvents bestowing permanent cavities, are the prominent emerging materials. Despite great efforts, exploration of porous hosts and bulky solvents is still needed to develop new PL systems. Metal-organic polyhedra (MOPs) with discrete molecular architectures can be considered as porous hosts; however, many of them are insoluble entities. Here we report the transformation of type III PL to type II PLs by tuning the surface rigidity of insoluble MOP, Rh24 L24 , in a bulky ionic liquid (IL). Functionalization of N-donor molecules on Rh-Rh axial sites ensue their solubilization in bulky IL which confer type II PLs. Experimental and theoretical studies reveal the bulkiness of IL as per the cage apertures, and the cause of their dissolution as well. The obtained PLs, capturing more CO2 than neat solvent, have depicted higher catalytic activity for CO2 cycloaddition compared to individual MOPs and IL.

N6-methyladenosine-modified TRAF1 promotes sunitinib resistance by regulating apoptosis and angiogenesis in a METTL14-dependent manner in renal cell carcinoma.

BACKGROUND: Sunitinib resistance can be classified into primary and secondary resistance. While accumulating research has indicated several underlying factors contributing to sunitinib resistance, the precise mechanisms in renal cell carcinoma are still unclear. METHODS: RNA sequencing and m6A sequencing were used to screen for functional genes involved in sunitinib resistance. In vitro and in vivo experiments were carried out and patient samples and clinical information were obtained for clinical analysis. RESULTS: We identified a tumor necrosis factor receptor-associated factor, TRAF1, that was significantly increased in sunitinib-resistant cells, resistant cell-derived xenograft (CDX-R) models and clinical patients with sunitinib resistance. Silencing TRAF1 increased sunitinib-induced apoptotic and antiangiogenic effects. Mechanistically, the upregulated level of TRAF1 in sunitinib-resistant cells was derived from increased TRAF1 RNA stability, which was caused by an increased level of N6-methyladenosine (m6A) in a METTL14-dependent manner. Moreover, in vivo adeno-associated virus 9 (AAV9) -mediated transduction of TRAF1 suppressed the sunitinib-induced apoptotic and antiangiogenic effects in the CDX models, whereas knockdown of TRAF1 effectively resensitized the sunitinib-resistant CDXs to sunitinib treatment. CONCLUSIONS: Overexpression of TRAF1 promotes sunitinib resistance by modulating apoptotic and angiogenic pathways in a METTL14-dependent manner. Targeting TRAF1 and its pathways may be a novel pharmaceutical intervention for sunitinib-treated patients.

Metal ion-mediated carbon dot nanoprobe for fluorescent turn-on sensing of N-acetyl-l-cysteine.

In this work, carbon dots (CDs) was easily synthesized from aspartic acid through a pyrolysis method. Based on their favourable fluorescence properties, CDs were utilized to design a metal ion-mediated fluorescent probe for N-acetyl-l-cysteine (NAC) detection. The fluorescence intensity of CDs was firstly quenched by manganese ions (Mn2+ ) through static quenching effect and subsequently restored by NAC via the combination with Mn2+ due to the coordination effect. Therefore, the fluorescent turn-on sensing of NAC was actuated based on the fluorescence quenching stimulated by Mn2+ and recovery induced by coordination. The fluorescence recovery efficiencies showed a proportional range to the concentration of NAC in the range 0.04-5 mmol L-1 and the detection limit was 0.03 mmol L-1 . Furthermore, this metal ion-mediated fluorescent nanoprobe was applied to human urine sample detection and the standard recovery rates were located in the range 97.62-102.34%. This was the first time that Mn2+ was used to construct a fluorescent nanoprobe for NAC. Compared with other heavy metal ions, Mn2+ with good biosecurity prevented the risk of application, which made the nanoprobe green and biopractical. The facile synthesis of CDs and novel metal ion-mediated sensing mode made it a promising method for pharmaceutical analysis.

Research on a Silicon Gyroscope Interface Circuit Based on Closed-Loop Controlled Drive Loop.

The existing analysis methods for the silicon gyroscope drive loop, such as the perturbation method and period average method, cannot analyze the dynamic characteristics of the system. In this work, a linearized amplitude control model of the silicon gyroscope drive loop was established to analyze the stability and set-up time of the drive loop, and the vibration conditions of the silicon gyro were obtained. According to the above results, a new silicon gyroscope interface circuit was designed, using a 0.35 µm Bipolar-CMOS-DMOS (BCD) process, and the chip area was 4.5 mm × 4.0 mm. The application-specific integrated circuit (ASIC) of the silicon gyroscope was tested in combination with the sensitive structure with a zero stability of 1.14°/hr (Allen). The test results for the ASIC and the whole machine prove the correctness of the theoretical model, which reflects the effectiveness of the stability optimization of the closed-loop controlled drive loop of the silicon gyroscope circuit.

Porous Liquids Responsive to Light.

A porous liquid is a unique liquid medium that combines the cavity of porous solids with the fluidity of liquids. This special characteristic offers potential in various applications. Here we report a type II photoresponsive porous ionic liquid (PPIL) from dissolving a photoresponsive metal-organic polyhedron (PMOP, constructed from dicopper and azobenzene-containing carboxylate) in a polyethylene-glycol-functionalized bulky ionic liquid (IL). Owing to favorable ion interactions, bulky IL molecules encircle outside PMOP, and the inter cavities are maintained. The azobenzene moieties can be isomerized freely in the PPILs to expose and shelter active sites upon visible and UV light irradiation. Hence, the adsorption capacity of PPILs is controllable by light irradiation, and the change in CO2 uptake is up to 30 % compared to neat IL. This study may inspire the development of new adsorption process regulated by light instead of pressure and temperature swing adsorption.

Oncometabolite L-2-hydroxyglurate directly induces vasculogenic mimicry through PHLDB2 in renal cell carcinoma.

Metabolism reprograming is a hallmark of cancer and plays an important role in tumor progression. The aberrant metabolism in renal cell carcinoma (RCC) leads to accumulation of the oncometabolite L-2-hydroxyglurate (L-2HG). L-2HG has been reported to inhibit the activity of some α-ketoglutarate-dependent dioxygenases such as TET enzymes, which mediate epigenetic alteration, including DNA and histone demethylation. However, the detailed functions of L-2HG in renal cell carcinoma have not been investigated thoroughly. In our study, we found that L-2HG was significantly elevated in tumor tissues compared to adjacent tissues. Furthermore, we demonstrated that L-2HG promoted vasculogenic mimicry (VM) in renal cancer cell lines through reducing the expression of PHLDB2. A mechanism study revealed that activation of the ERK1/2 pathway was involved in L-2HG-induced VM formation. In conclusion, these findings highlighted the pathogenic link between L-2HG and VM and suggested a novel therapeutic target for RCC.

First-principles materials simulation and design for alkali and alkaline metal ion batteries accelerated by machine learning.

The challenge of regeneration of batteries requires a performance improvement in the alkali/alkaline metal ion battery (AMIB) materials, whereas the traditional research paradigm fully based on experiments and theoretical simulations needs massive research and development investment. During the last decade, machine learning (ML) has made breakthroughs in many complex disciplines, which testifies to their high processing speed and ability to capture relationships. Inspired by these achievements, ML has also been introduced to bring a new paradigm for shortening the development of AMIB materials. In this Perspective, the focus will be on how this new ML technology solves the key problems of redox potentials, ionic conductivity and stability parameters in first-principles materials' simulation and design for AMIBs. It is found that ML not only accelerates the property prediction, but also gives physicochemical insights into AMIB materials' design. In addition, the final part of this paper summarizes current achievements and looks forward to the progress of a novel paradigm in direct/inverse design with the increasing number of databases, skills, and ML technologies for AMIBs.

TREM2 regulates obesity-induced insulin resistance via adipose tissue remodeling in mice of high-fat feeding.

BACKGROUND: Adipose tissue remodeling plays a significant role in obesity-induced insulin resistance. Published studies reported that level of trigger receptor expressed on myeloid cells 2 (TREM2) in adipose tissue is up-regulated in animal models of obesity. This study aims to investigate whether TREM2 regulates obesity-induced insulin resistance via modulating adipose tissue remodeling in mice of high-fat diet (HFD). METHODS: Wild-type (WT) and TREM2-/- mice were both fed with a controlled-fat diet (CFD) or HFD for 12 weeks and studied for obesity and insulin resistance. Meanwhile, epididymal adipose tissue (EAT) was examined for morphological and pathological changes to determine adipose tissue remodeling. After that, adipocyte-derived MCP-1 was measured in adipocytes, adipose tissue and circulation. Next, inflammatory cytokines were determined in adipose tissue macrophages (ATM). At last, livers were analyzed for hepatic steatosis. RESULTS: TREM2-/- mice on HFD had increased obesity and insulin resistance compared with WT counterparts. Adipose tissue from TREM2-/- mice exhibited reduced mass but greater adipocyte hypertrophy and increased adipocyte death. Besides, adipocyte-derived MCP-1 was down-regulated in TREM2-/- mice, and circulating MCP-1 level was lower than that of WT mice. Furthermore, TREM2-/- mice displayed reduced infiltration of F4/80+CD11c+ macrophages into adipose tissue, which was unable to form crown-like structures (CLS) to clean dead adipocytes and cellular contents. Also, TREM2 deficiency augmented inflammatory response of adipose tissue macrophages in HFD mice. In addition, TREM2-/- mice demonstrated more severe hepatic steatosis than WT counterparts under HFD feeding. CONCLUSIONS: Trigger receptor expressed on myeloid cells 2 may function as a feedback mechanism to curb obesity-induced insulin resistance via regulating adipose tissue remodeling.

Strategies for computational design and discovery of two-dimensional transition-metal-free materials for electro-catalysis applications.

In this perspective, we review two new strategies for computational design and discovery of two-dimensional (2D) transition-metal (TM) free electro-catalysts for the oxygen reduction reaction (ORR) and the nitrogen reduction reaction (NRR). The "2D binary compound" strategy for designing ORR electro-catalysts shows promising applications, which benefits from abundant intrinsic catalytic sites for the adsorption of reaction intermediates. And with the "activated B site" strategy for designing NRR electro-catalysts, several novel NRR electro-catalysts with extremely low limiting potential are developed. Computational-simulation-driven material design from a bottom-up method could not only provide rational strategies, but also accelerate the discovery of novel materials.

Periodic current oscillation catalyzed by δ-MnO2 nanosheets.

The oxygen evolution reaction (OER) is of wide interest for both fuel and hydrometallurgy applications. Different types of nanoscale MnO2 , varying from nanosheets to nanoneedles, are synthesized and assembled on the anode to investigate their catalytic effect on the nonlinear kinetics of the MnO2 -catalyzed OER at high current. For δ-MnO2 nanosheets, periodic current oscillations (PCO) occurr and occupy up to 40 % of the total energy consumption. The PCO can help to reduce the energy consumption under constant current conditions. Its amplitude could be twice of that for the previously reported MnO2 grown by an in situ electrochemical method. If the amount of γ-MnO2 nanoneedles increases, the oscillation disappears. For different Mn oxides, the rate constants of H2 O2 decomposition differ, resulting in changes in oscillation features. The results of this study may enable new ideas to improve the efficiency of industrial electrolysis and charging-discharging of supercapacitors.

[Bone morphogenetic protein-2-encupsulated PEG-grafted-poly-lactic acid-polycaprolactone nanoparticles promote bone repair].

OBJECTIVE: To explore the efficacy of a novel tissue engineered bone in repairing bone defects using poly-lactic acid-polycaprolactone (PLA-PCL) scaffolding seeded with PEG-bone morphogenetic protein-2 (BMP-2) transfected rBMSCs (rabbit bone marrow stromal cells). METHODS: rBMSCs were harvested, transfected with PEG/BMP-2 or liposome/BMP-2 and then implanted into PLA-PCL tissue engineered bone. The protein level of BMP-2 was assessed by Western blot and immunohistochemistry. Enzyme-linked immunosorbent assay (ELISA) was employed to measure the amount of BMP-2 in culture media. The mRNA levels of BMP-2 and osteocalcin were assayed quantitatively by real-time polymerase chain reaction (PCR). The middle portion of bilateral radius in New Zealand rabbits was excised and implanted with tissue engineered bone. And the modified areas were monitored by radiology, hematoxylin-eosin staining and immunohistochemical staining of BMP-2. RESULTS: PEG-BMP-2 nanoparticles (NPs) and BMP-2 loaded PEG-PLA-PCL tissue engineered bones were successfully constructed. The novel PEG-PLA-PCL NPs/DNA complex was superior for transfecting BMP-2 in rBMSCs compared to traditional liposomes. Moreover, the mRNA level of osteocalcin and alkaline phosphatase activity also increased after a transfection of BMP-2 encapsulated NPs. CONCLUSION: PEG-PLA-PCL NPs/BMP-2 complex facilitates bone repair so that it provides theoretic rationales for potential clinical treatments.

Aerodynamic evaluation of surgical design for the stenosis correction of airway.

Introduction: Congenital tracheal stenosis (CTS) is a rare but life-threatening disease that can lead to respiratory dysfunction in children. Obstructive sleep apnea syndrome (OSAS) in children is characterized by prolonged partial upper airway obstruction and/or intermittent complete obstruction. Both of the diseases require surgical intervention. Although respective treatments of these two diseases are clear, there is a lack of literature discussing the surgical treatment of patients with CTS complicated by OSAS. Methods: We conducted a patient-specific study of patient with CTS complicated by OSAS. Computer-aided design was used to simulate surgical correction under different surgical sequences. Computational fluid dynamics was used to compare the outcomes of different sequences. Results: Aerodynamic parameters, pressure drop, velocity streamlines, wall shear stress (WSS), and the ratio of airflow distribution and energy loss rate were evaluated. An obvious interaction was found between the two diseases in different surgical sequences. The order of correction for CTS or OSAS greatly affected the aerodynamic parameters and turbulence flows downstream of tracheal stenosis and upstream of epiglottis. The CTS and OSAS had mutual influences on each other on the aerodynamic parameters, such as pressure drops and WSS. Discussion: When evaluating the priority of surgical urgency of CTS and OSAS, surgeons need to pay attention to the state of both CTS and OSAS and the physiological conditions of patients. The aerodynamic performance of the uneven airflow distribution and the potential impact caused by the correction of CTS should be considered in surgical planning and clinical management.

N, S, Br co-doped carbon dots: One-step synthesis and fluorescent detection of 6-mercaptopurine in tablet.

Scheme of synthesis of N, S, Br-CDs and fluorescent detection of 6-MP.Image 1.

The identification of a N6-methyladenosin-modifed immune pattern to predict immunotherapy response and survival in urothelial carcinoma.

BACKGROUND: Dysregulation of the immune system and N6-methyladenosine (m6A) contribute to immune therapy resistance and cancer progression in urothelial carcinoma (UC). This study aims to identify immune-related molecules, that are m6A-modified, and that are associated with tumor progression, poor prognosis, and immunotherapy response. METHODS: We identified prognostic immune genes (PIGs) using Cox analysis and random survival forest variable hunting algorithm (RSF-VH) on immune genes retrieved from the Immunology Database and Analysis Portal database (ImmPort). The RM2Target database and MeRIP-seq analysis, combined with a hypergeometric test, assessed m6A methylation in these PIGs. We analyzed the correlation between the immune pattern and prognosis, as well as their association with clinical factors in multiple datasets. Moreover, we explored the interplay between immune patterns, tumor immune cell infiltration, and m6A regulators. RESULTS: 28 PIGs were identified, of which the 10 most significant were termed methylated prognostic immune genes (MPIGs). These MPIGs were used to create an immune pattern score. Kaplan-Meier and Cox analyses indicated this pattern as an independent risk factor for UC. We observed significant associations between the immune pattern, tumor progression, and immune cell infiltration. Differential expression analysis showed correlations with m6A regulators expression. This immune pattern proved effective in predicting immunotherapy response in UC in real-world settings. CONCLUSION: The study identified a m6A-modified immune pattern in UC, offering prognostic and therapeutic response predictions. This emphasizes that immune genes may influence tumor immune status and progression through m6A modifications.

A high-performance organic thin-film transistor with Parylene/PMMA bilayer insulation based on P3HT.

This work introduces a pioneering approach in the development of organic thin-film transistors (OTFTs), featuring a double-layer dielectric structure that combines poly(para-xylylene)s (Parylene) and poly(methyl methacrylate) (PMMA) to leverage the high insulation properties and high surface polarity of Parylene with the low insulation properties and low surface polarity of PMMA. This combination results in devices that showcase significantly enhanced electrical performance, including superior charge carrier mobility, increased current on/off ratios, and greater transconductance. Utilizing poly(3-hexylthiophene) (P3HT) for the active layer, the study demonstrates the advantage of the dual dielectric layers in minimizing hysteresis in the transfer curve, thereby facilitating the systematic growth of the organic active layer and enhancing electrical conductivity over single-layer alternatives. The superior performance of the Parylene/PMMA double-layer insulating structure opens new avenues for the advancement of organic electronics, presenting methodologies for performance optimization and expanding the application spectrum of OTFTs.

TR4 worsen urosepsis by regulating GSDMD.

BACKGROUND: Urosepsis is a life-threatening organ disease in which pathogenic microorganisms in the urine enter the blood through the vessels, causing an imbalance in the immune response to infection. The aim of this study was to elucidate the role of testicular orphan receptor 4 (TR4) in urosepsis. METHODS: The role of TR4 in the progression and prognosis of urosepsis was confirmed by analyzing data from online databases and clinical human samples. To mimic urosepsis, we injected E. coli bacteria into the renal pelvis of mice to create a urosepsis model. Hematoxylin and eosin staining was used to observe histopathological changes in urosepsis. The effects of the upregulation or downregulation of TR4 on macrophage pyroptosis were verified in vitro. Chromatin immunoprecipitation assay was used to verify the effect of TR4 on Gasdermin D (GSDMD) transcription. RESULTS: TR4 was more highly expressed in the nonsurviving group than in the surviving group. Furthermore, overexpressing TR4 promoted inflammatory cytokine expression, and knocking down TR4 attenuated inflammatory cytokine expression. Mechanistically, TR4 promoted pyroptosis by regulating the expression of GSDMD in urosepsis. Furthermore, we also found that TR4 knockdown protected mice from urosepsis induced by the E. coli. CONCLUSIONS: TR4 functions as a key regulator of urosepsis by mediating pyroptosis, which regulates GSDMD expression. Targeting TR4 may be a potential strategy for urosepsis treatment.

The effect of SO2 on CO2 capture in zeolitic imidazolate frameworks.

The CO2 capture performance of four zeolitic imidazolate frameworks (ZIFs), ZIF-10, ZIF-71, ZIF-68 and ZIF-69, was investigated in the presence of SO2 using molecular simulations. Our results show that SO2 is preferentially adsorbed over CO2. However, it also shows a cooperative effect on CO2 adsorption. In ZIF-10 and ZIF-71, the SO2 presence was found to have almost no effect on CO2 adsorption. In ZIF-68 and ZIF-69, although the two ZIFs adsorbed large amounts of SO2, the decrease in CO2 uptake was relatively small due to the cooperative interaction between the SO2 and CO2 molecules.

The Impact of COVID-19 on the Prevalence, Mortality, and Associated Risk Factors for Mortality in Patients with Hip Fractures: A Meta-Analysis.

OBJECTIVE: This study aimed to assess (1) the prevalence of COVID-19 in patients with hip fracture; (2) the mortality rate of patients with hip fracture associated with COVID-19; (3) risk factors associated with mortality in patients with hip fracture; and (4) the effects of COVID-19 on surgical outcomes of patients with hip fracture. DESIGN: Meta-analysis. SETTING AND PARTICIPANTS: Patients with hip fractures during COVID-19. METHODS: PubMed, Web of Science, and Embase were systematically reviewed. The outcomes included the prevalence of COVID-19, case fatality rate, 30-day mortality, cause of death, risk factors associated with the mortality of patients with hip fracture, time to surgery, surgical time, and length of hospitalization. Risk ratio or weight mean difference with 95% confidence intervals were used to pool the estimates. RESULTS: A total of 60 studies were included in this meta-analysis. The pooled estimate showed that the prevalence of COVID-19 was 21% in patents with hip fractures. Patients with hip fracture with COVID-19 had an increased 30-day mortality risk compared with those without the infection. The main causes of death were respiratory failure, COVID-19-associated pneumonia, multiorgan failure, and non-COVID-19 pneumonia. The hospitalization was longer in patients with COVID-19 when compared with those without the infection, but was shorter in patients during the pandemic period. The surgery time and time to surgery were not significantly different between patients during or before the pandemic period and in those with or without COVID-19. CONCLUSIONS AND IMPLICATIONS: The 30-day mortality rate was significantly higher in patients with hip fracture with COVID-19 infection than those without. Patients with COVID-19 had a higher all-cause mortality rate than those without. This information can be used by the medical community to guide the management of patients with hip fracture with COVID-19.

MOF-GRU: A MOFid-Aided Deep Learning Model for Predicting the Gas Separation Performance of Metal-Organic Frameworks.

The remarkable versatility of metal-organic frameworks (MOFs) stems from their rich chemical information, leading to numerous successful applications. However, identifying optimal MOFs for specific tasks necessitates a thorough assessment of their chemical attributes. Conventional machine learning approaches for MOF prediction have relied on intricate chemical and structural details, hampering rapid evaluations. Drawing inspiration from recent advancements exemplified by Snurr et al., wherein a text string was used to represent a MOF (MOFid), we introduce a MOFid-aided deep learning model, named the MOF-GRU model. This model, founded on natural language processing principles and utilizing the gated recurrent unit architecture, leverages the serialized text string representation of metal-organic frameworks (MOFs) to forecast gas separation performance. Through a focused study on CH4/N2 separation, we substantiate the efficacy of this approach. Comparative assessments against traditional machine learning techniques underscore our model's superior predictive accuracy and its capacity to handle extensive data sets adeptly. The MOF-GRU model remarkably uncovers latent structure-performance relationships with only MOF sequences, obviating the necessity for intricate three-dimensional (3D) structural information. Overall, this model's judicious design empowers efficient data utilization, thereby hastening the discovery of high-performance materials tailored for gas separation applications.