Abnormal coagulation after hepatectomy in patients with normal preoperative coagulation function.

BACKGROUND: To explore the risk factors for postoperative abnormal coagulation (PAC) and establish a predictive model for patients with normal preoperative coagulation function who underwent hepatectomy. MATERIALS AND METHODS: A total of 661 patients with normal preoperative coagulation function who underwent hepatectomy between January 2015 and December 2021 at the First Affiliated Hospital of Sun Yat-sen University were divided into two groups: the postoperative abnormal coagulation group (PAC group, n = 362) and the normal coagulation group (non-PAC group, n = 299). Univariate and multivariate logistic analyses were used to identify the risk factors for PAC. RESULTS: The incidence of PAC in 661 patients who underwent hepatectomy was 54.8% (362/661). The least absolute shrinkage and selection operator (LASSO) method was used for multivariate logistic regression analysis. The preoperative international normalized ratio (INR), intraoperative succinyl gelatin infusion and major hepatectomy were found to be independent risk factors for PAC. A nomogram for predicting the PAC after hepatectomy was constructed. The model presented a receiver operating characteristic (ROC) curve of 0.742 (95% confidence interval (CI): 0.697-0.786) in the training cohort. The validation set demonstrated a promising ROC of 0.711 (95% CI: 0.639-0.783), and the calibration curve closely approximated the true incidence. Decision curve analysis (DCA) was performed to assess the clinical usefulness of the predictive model. The risk of PAC increased when the preoperative international normalized ratio (INR) was greater than 1.025 and the volume of intraoperative succinyl gelatin infusion was greater than 1500 ml. CONCLUSION: The PAC is closely related to the preoperative INR, intraoperative succinyl gelatin infusion and major hepatectomy. A three-factor prediction model was successfully established for predicting the PAC after hepatectomy.

An Amphiphilic Cell-Penetrating Macrocycle for Efficient Cytosolic Delivery of Proteins, DNA, and CRISPR Cas9.

The discovery of safe platforms that can circumvent the endocytic pathway is of great significance for biological therapeutics that are usually degraded during endocytosis. Here we show that a self-assembled and dynamic macrocycle can passively diffuse through the cell membrane and deliver a broad range of biologics, including proteins, CRISPR Cas9, and ssDNA, directly to the cytosol while retaining their bioactivity. Cell-penetrating macrocycle CPM can be easily prepared from the room temperature condensation of diketopyrrolopyrrole lactams with diamines. We attribute the high cellular permeability of CPM to its amphiphilic nature and chameleonic properties. It adopts conformations that partially bury polar groups and expose hydrophobic side chains, thus self-assembling into micellar-like structures. Its superior fluorescence makes CPM trackable inside cells where it follows the endomembrane system. CPM outperformed commercial reagents for biologics delivery and showed high RNA knockdown efficiency of CRISPR Cas9. We envisage that this macrocycle will be an ideal starting point to design and synthesize biomimetic macrocyclic tags that can readily facilitate the interaction and uptake of biomolecules and overcome endosomal digestion.

Industrial Separation Challenges: How Does Supramolecular Chemistry Help?

The chemical industry and the chemical processes underscoring it are under intense scrutiny as the demands for the transition to more sustainable and environmentally friendly practices are increasing. Traditional industrial separation systems, such as thermally driven distillation for hydrocarbon purification, are energy intensive. The development of more energy efficient separation technologies is thus emerging as a critical need, as is the creation of new materials that may permit a transition away from classic distillation-based separations. In this Perspective, we focus on porous organic cages and macrocycles that can adsorb guest molecules selectively through various host-guest interactions and permit molecular sieving behavior at the molecular level. Specifically, we summarize the recent advances where receptor-based adsorbent materials have been shown to be effective for industrially relevant hydrocarbon separations, highlighting the underlying host-guest interactions that impart selectivity and permit the observed separations. This approach to sustainable separations is currently in its infancy. Nevertheless, several receptor-based adsorbent materials with extrinsic/intrinsic voids or special functional groups have been reported in recent years that can selectively capture various targeted guest molecules. We believe that the understanding of the interactions that drive selectivity at a molecular level accruing from these initial systems will permit an ever-more-effective "bottom-up" design of tailored molecular sieves that, in due course, will allow adsorbent material-based approaches to separations to transition from the laboratory into an industrial setting.

Caging the Hofmeister Effect by a Biomimetic Supramolecular Receptor.

The effect of anions on the solubility and function of proteins was recognized in 1888 and is now termed the Hofmeister effect. Numerous synthetic receptors are known that overcome the associated anion recognition bias. However, we are unaware of a synthetic host being used to overcome Hofmeister effect perturbations to natural proteins. Here, we report a protonated small molecule cage complex that acts as an exo-receptor and displays non-Hofmeister solubility behavior, with only the chloride complex remaining soluble in aqueous media. This cage allows for the activity of lysozyme to be retained under conditions where anion-induced precipitation would otherwise cause it to be lost. To our knowledge, this is the first time a synthetic anion receptor is used to overcome the Hofmeister effect in a biological system.

Fluorine-Boosted Kinetic and Selective Molecular Sieving of C6 Derivatives.

Porous molecular sorbents have excellent selectivity towards hydrocarbon separation with energy saving techniques. However, to realize commercialization, molecular sieving processes should be faster and more efficient compared to extended frameworks. In this work, we show that utilizing fluorine to improve the hydrophobic profile of leaning pillararenes affords a substantial kinetic selective adsorption of benzene over cyclohexane (20 : 1 for benzene). The crystal structure shows a porous macrocycle that acts as a perfect match for benzene in both the intrinsic and extrinsic cavities with strong interactions in the solid state. The fluorinated leaning pillararene surpasses all reported organic molecular sieves and is comparable to the extended metal-organic frameworks that were previously employed for this separation such as UIO-66. Most importantly, this sieving system outperformed the well-known zeolitic imidazolate frameworks under low pressure, which opens the door to new generations of molecular sieves that can compete with extended frameworks for more sustainable hydrocarbon separation.

Institution Publication Feature Analysis Based on Time-Series Clustering.

Based on the time series of articles obtained from the literature, we propose three analysis methods to deeply examine the characteristics of these articles. This method can be used to analyze the construction and development of various disciplines in institutions, and to explore the features of the publications in important periodicals in the disciplines. By defining the concepts and methods relevant to research and discipline innovation, we propose three methods for analyzing the characteristics of agency publications: numerical distribution, trend, and correlation network analyses. The time series of the issuance of articles in 30 important journals in the field of management sciences were taken, and the new analysis methods were used to discover some valuable results. The results showed that by using the proposed methods to analyze the characteristics of institution publications, not only did we find similar levels of discipline development or similar trends in institutions, achieving a more reasonable division of the academic levels, but we also determined the preferences of the journals selected by the institutions, which provides a reference for subject construction and development.

Combination of optimized tissue engineering bone implantation with heel-strike like mechanical loading to repair segmental bone defect in New Zealand rabbits.

In this study, effects of combining optimized tissue engineering bone (TEB) implantation with heel-strike like mechanical loading to repair segmental bone defect in New Zealand rabbits were investigated. Physiological characteristics of bone marrow mesenchymal stem cells (BMMSCs), compact bone cells (CBCs), and bone marrow and compact bone coculture cells (BMMSC-CBCs) were compared to select the optimal seed cells for optimized TEB construction. Rabbits with segmental bone defects were treated in different ways (cancellous bone scaffold for group A, cancellous bone scaffold and mechanical loading for group B, optimized TEB for group C, optimized TEB and mechanical loading for group D, n = 4), and the bone repair were compared. BMMSC-CBCs showed better proliferation capacity than CBCs (p < 0.01) and stronger osteogenic differentiation ability than BMMSCs (p < 0.05). Heel-strike like mechanical loading improved proliferation and osteogenic differentiation ability and expression levels of TGFß1 as well as BMP2 of seed cells in vitro (p < 0.05). At week 12 post-operation, group D showed the best bone repair, followed by groups B and C, while group A finished last (p < 0.05). During week 4 to 12 post-operation, group D peaked in terms of expression levels of TGFß1, BMP2, and OCN, followed by groups B and C, while group A finished last (p < 0.05). Thus, BMMSC-CBCs showed good proliferation and osteogenic differentiation ability, and they were thought to be better as seed cells than BMMSCs and CBCs. The optimized TEB implantation combined with heel-strike like mechanical loading had a synergistic effect on bone defect healing, and enhanced expression of TGFß1 and BMP2 played an important role in this process.

Omega-3 polyunsaturated fatty acid attenuates traumatic brain injury-induced neuronal apoptosis by inducing autophagy through the upregulation of SIRT1-mediated deacetylation of Beclin-1.

BACKGROUND: Enhancing autophagy after traumatic brain injury (TBI) may decrease the expression of neuronal apoptosis-related molecules. Autophagy-mediated neuronal survival is regulated by the sirtuin family of proteins (SIRT). Omega-3 polyunsaturated fatty acids (ω-3 PUFA) are known to have antioxidative and anti-inflammatory effects. We previously demonstrated that ω-3 PUFA supplementation attenuated neuronal apoptosis by modulating the neuroinflammatory response through SIRT1-mediated deacetylation of the HMGB1/NF-κB pathway, leading to neuroprotective effects following experimental traumatic brain injury (TBI). However, no studies have elucidated if the neuroprotective effects of ω-3 PUFAs against TBI-induced neuronal apoptosis are modulated by SIRT1-mediated deacetylation of the autophagy pathway. METHODS: The Feeney DM TBI model was adopted to induce TBI rats. Modified neurological severity scores, the rotarod test, brain water content, and Nissl staining were employed to determine the neuroprotective effects of ω-3 PUFA supplementation. Immunofluorescent staining and western blot analysis were used to detect Beclin-1 nuclear translocation and autophagy pathway activation. The impact of SIRT1 deacetylase activity on Beclin-1 acetylation and the interaction between cytoplasmic Beclin-1 and Bcl-2 were assessed to evaluate the neuroprotective effects of ω-3 PUFAs and to determine if these effects were dependent on SIRT1-mediated deacetylation of the autophagy pathway in order to gain further insight into the mechanisms underlying the development of neuroprotection after TBI. RESULTS: ω-3 PUFA supplementation protected neurons against TBI-induced neuronal apoptosis via enhancement of the autophagy pathway. We also found that treatment with ω-3 PUFA significantly increased the NAD+/NADH ratio and SIRT1 activity following TBI. In addition, ω-3 PUFA supplementation increased Beclin-1 deacetylation and its nuclear export and induced direct interactions between cytoplasmic Beclin-1 and Bcl-2 by increasing SIRT1 activity following TBI. These events led to the inhibition of neuronal apoptosis and to neuroprotective effects through enhancing autophagy after TBI, possibly due to elevated SIRT1. CONCLUSIONS: ω-3 PUFA supplementation attenuated TBI-induced neuronal apoptosis by inducing the autophagy pathway through the upregulation of SIRT1-mediated deacetylation of Beclin-1.

Valproic acid attenuates traumatic spinal cord injury-induced inflammation via STAT1 and NF-κB pathway dependent of HDAC3.

BACKGROUND: Microglial polarization with M1/M2 phenotype shifts and the subsequent neuroinflammatory responses are vital contributing factors for spinal cord injury (SCI)-induced secondary injury. Nuclear factor-κB (NF-κB) is considered the central transcription factor of inflammatory mediators, which plays a crucial role in microglial activation. Lysine acetylation of STAT1 seems necessary for NF-kB pathway activity, as it is regulated by histone deacetylases (HDACs). There have been no studies that have explained if HDAC inhibition by valproic acid (VPA) affects the NF-κB pathway via acetylation of STAT1 dependent of HDAC activity in the microglia-mediated central inflammation following SCI. We investigated the potential molecular mechanisms that focus on the phenotypic transition of microglia and the STAT1-mediated NF-κB acetylation after a VPA treatment. METHODS: The Basso-Beattie-Bresnahan locomotion scale, the inclined plane test, the blood-spinal cord barrier, and Nissl staining were employed to determine the neuroprotective effects of VPA treatment after SCI. Assessment of microglia polarization and pro-inflammatory markers, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and interferon (INF)-γ was used to evaluate the neuroinflammatory responses and the anti-inflammatory effects of VPA treatment. Immunofluorescent staining and Western blot analysis were used to detect HDAC3 nuclear translocation, activity, and NF-κB signaling pathway activation to evaluate the effects of VPA treatment. The impact of STAT1 acetylation on NF-kB pathway and the interaction between STAT1 and NF-kB were assessed to evaluate anti-inflammation effects of VPA treatment and also whether these effects were dependent on a STAT1/NF-κB pathway to gain further insight into the mechanisms underlying the development of the neuroinflammatory response after SCI. RESULTS: The results showed that the VPA treatment promoted the phenotypic shift of microglia from M1 to M2 phenotype and inhibited microglial activation, thus reducing the SCI-induced inflammatory factors. The VPA treatment upregulation of the acetylation of STAT1/NF-κB pathway was likely caused by the HDAC3 translocation to the nucleus and activity. These results indicated that the treatment with the VPA suppressed the expression and the activity of HDAC3 and enhanced STAT1, as well as NF-κB p65 acetylation following a SCI. The acetylation status of NF-kB p65 and the complex with NF-κB p65 and STAT1 inhibited the NF-kB p65 transcriptional activity and attenuated the microglia-mediated central inflammatory response following SCI. CONCLUSIONS: These results suggested that the VPA treatment attenuated the inflammatory response by modulating microglia polarization through STAT1-mediated acetylation of the NF-κB pathway, dependent of HDAC3 activity. These effects led to neuroprotective effects following SCI.

Long-Term Results of Surgical Atrial Fibrillation Radiofrequency Ablation: Comparison of Two Methods.

BACKGROUND: This retrospective study aimed to evaluate the long-term results of two kinds of surgical atrial fibrillation radiofrequency ablations in concomitant cardiac operations. METHODS: We enrolled 129 patients from January 2006 to December 2015 and performed cardiac operations concomitantly with surgical atrial fibrillation. The patients were divided into a biatrial MAZE group (94 patients) and a left atrial MAZE group (35 patients). A preoperative baseline was compared with intraoperative and postoperative data. Similarly, complications and follow-up results were compared. A matching process based on propensity-score was performed to equalise the potential prognostic factors in both groups and to formulate a balanced 2:1 matched cohort study. RESULTS: There were four deaths (4.3%) in the biatrial MAZE group and one death in left atrial MAZE group due to multiple organ failures followed by low cardiac output. No permanent pacemaker implantations were used in either group. The sinus rhythm maintenance rates at the 6-month, 1-year, 6-year and 8-year follow-ups between the biatrial MAZE group and the left atrial MAZE group were not significantly different (84.7%, 83.3%, 67.3%, and 58.8% vs. 84.9%, 77.4%, 61.1%, and 50%, p>0.05). Similarly, between the propensity-score matched groups, there were no significant differences. CONCLUSION: The left atrial MAZE ablation for the patients with mitral valve diseases who needed open cardiac operation was safe and effective when compared with the biatrial MAZE ablation group.

Synthesis, Structures, and Photophysical Properties of Optically Stable 1,16-Diphenyl-3,14-diaryl-Substituted Tetrahydrobenzo[5]helicenediol Derivatives: Enantioselective Recognition toward Tryptophan Methyl Esters.

Starting from commercially available 7-methoxytetralone, 1,16-diphenyl-3,14-dibromotetrahydrobenzo[5]helicenediol (Br-H[5]HOL) was conveniently prepared, which underwent efficient resolution to give the optically stable enantiomeric diols in gram scale by HPLC with semipreparative chiral columns. The absolute configurations of the diols were determined by the circular dichroism (CD) spectra and X-ray crystal structure. By Suzuki-Miyaura cross-coupling reactions, a series of enantiopure π-extended 1,16-diphenyl-3,14-diaryltetrahydrobenzo[5]helicenediol derivatives (Ar-H[5]HOL) were further synthesized in high yields. The enantiomeric Ar-H[5]HOL exhibited almost identical absorption and emission spectra but showed mirror-image CD spectra and mirror-image circularly polarized luminescence properties. Moreover, it was also found that aryl substituents at the 3,14-positions could extend the chiral environment of the helical skeletons, which led to efficient enantioselective recognition of the enantiomers of tryptophan methyl esters.

Randomized, controlled trial comparing laryngeal mask versus endotracheal intubation during neonatal resuscitation---a secondary publication.

BACKGROUND: This study aimed to study the feasibility, efficacy and safety of using laryngeal mask (LM) ventilation compared with endotracheal intubation (ETI) during neonatal resuscitation. METHODS: Neonates with a heart rate below 60 beats per minute despite 30 s of face mask ventilation were assigned quasi-randomly (odd/even birth date) to LM (n = 36) or ETI (n = 32) ventilation. Differences in first attempt insertion success, insertion time, Apgar score, resuscitation outcome, and adverse effects were compared. RESULTS: There were no significant differences in first attempt at successful insertion (LM, 94.4 % vs. ETI, 90.6 %), insertion time (LM, 7.58 ± 1.16 s vs. ETI, 7.89 ± 1.52 s), Apgar score at 1 and 5 min, response time, ventilation time, successful resuscitation (LM, 86.1 % vs. ETI,  96.9 %), and adverse events (LM, n =3 vs. ETI, n =4) between groups. CONCLUSIONS: Laryngeal mask ventilation is an effective alternative to endotracheal intubation during resuscitation of depressed newborns who do not respond to face-mask ventilation. During an emergency, laryngeal mask ventilation may be a preferred technique for medical staff who are unable to acquire or maintain endotracheal intubation skills. TRIAL REGISTRATION: Current Controlled Trials ChiCTR-IOQ-15006488. Registered on 2 June 2015.

A Non-Intrusive Pressure Sensor by Detecting Multiple Longitudinal Waves.

Pressure vessels are widely used in industrial fields, and some of them are safety-critical components in the system-for example, those which contain flammable or explosive material. Therefore, the pressure of these vessels becomes one of the critical measurements for operational management. In the paper, we introduce a new approach to the design of non-intrusive pressure sensors, based on ultrasonic waves. The model of this sensor is built based upon the travel-time change of the critically refracted longitudinal wave (LCR wave) and the reflected longitudinal waves with the pressure. To evaluate the model, experiments are carried out to compare the proposed model with other existing models. The results show that the proposed model can improve the accuracy compared to models based on a single wave.

Engineering of Methionine Adenosyltransferase toward Mitigated Product Inhibition for Efficient Production of S-Adenosylmethionine.

S-Adenosylmethionine (SAM) is a crucial metabolic intermediate playing irreplaceable roles in organismal activities. However, the synthesis of SAM by methionine adenosyltransferase (MAT) is hindered by low conversion due to severe product inhibition. Herein structure-guided semirational engineering was conducted on MAT from Escherichia coli (EcMAT) to mitigate the product inhibitory effect. Compared with the wild-type EcMAT, the best variant E56Q/Q105R exhibited an 8.13-fold increase in half maximal inhibitory concentration and a 4.46-fold increase in conversion (150 mM ATP and l-methionine), leading to a SAM titer of 47.02 g/L. Another variant, E56N/Q105R, showed superior thermostability with an impressive 85.30-fold increase in half-life (50 °C) value. Furthermore, molecular dynamics (MD) simulation results demonstrate that the alleviation in product inhibitory effect could be attributed to facilitated product release. This study offers molecular insights into the mitigated product inhibition, and provides valuable guidance for engineering MAT toward enhanced catalytic performance.

Smart touchless human-machine interaction based on crystalline porous cages.

The rise of touchless technology, driven by the recent pandemic, has transformed human-machine interaction (HMI). Projections indicate a substantial growth in the touchless technology market, nearly tripling from $13.6 billion in 2021 to an estimated $37.6 billion by 2026. In response to the pandemic-driven shift towards touchless technology, here we show an organic cage-based humidity sensor with remarkable humidity responsiveness, forming the basis for advanced touchless platforms in potential future HMI systems. This cage sensor boasts an ultrafast response/recovery time (1 s/3 s) and exceptional stability (over 800 cycles) across relative humidity (RH) changes from 11% to 95%. The crystal structure's 3D pore network and luxuriant water-absorbing functional groups both inside and outside of the cage contribute synergistically to superior humidity sensing. Demonstrating versatility, we showcase this cage in smart touchless control screens and touchless password managers, presenting cost-effective and easily processable applications of molecularly porous materials in touchless HMI.

Flaring Inflammation and ER Stress by an Organelle-Specific Fluorescent Cage.

The endoplasmic reticulum (ER) plays an important role in protein synthesis and its disruption can cause protein unfolding and misfolding. Accumulation of such proteins leads to ER stress, which ultimately promotes many diseases. Routine screening of ER activity in immune cells can flag serious conditions at early stages, but the current clinically used bio-probes have limitations. Herein, an ER-specific fluorophore based on a biocompatible benzothiadiazole-imine cage (BTD-cage) with excellent photophysical properties is developed. The cage outperforms commercially available ER stains in long-term live cell imaging with no fading or photobleaching over time. The cage is responsive to different levels of ER stress where its fluorescence increases accordingly. Incorporating the bio-probe into an immune disorder model, a 6-, 21-, and 48-fold increase in intensity is shown in THP-1, Raw 246.7, and Jurkat cells, respectively (within 15 min). These results strongly support that this system can be used for rapid visual and selective detection of ER stress. It is envisaged that tailoring molecular interactions and molecular recognition using supramolecular improved fluorophores can expand the library of biological probes for enhanced selectivity and targetability toward cellular organelles.

Engineering of Methionine Adenosyltransferase Reveals Key Roles of Electrostatic Interactions in Enhanced Catalytic Activity.

As an important dietary supplement, S-adenosylmethionine (SAM) is currently synthesized by methionine adenosyltransferase (MAT) using ATP and methionine as substrates. However, the activity of MAT is severely inhibited by product inhibition, which limits the industrial production of SAM. Here, MAT from Bacteroides fragilis (BfMAT), exhibiting relatively low product inhibition and moderate specific activity, was identified by gene mining. Based on molecular docking, residues within 5 Å of ATP in BfMAT were subjected to mutagenesis for enhanced catalytic activity. Triple variants M3-1 (E42M/E55L/K290I), M3-2 (E42R/E55L/K290I), and M3-3 (E42C/E55L/K290I) with specific activities of 1.83, 1.81, and 1.94 U/mg were obtained, which were 110.5-125.6% higher than that of the wild type (WT). Furthermore, compared with WT, the Km values of M3-1 and M3-3 were decreased by 31.4% and 60.6%, leading to significant improvement in catalytic efficiency (kcat/Km) by 322.5% and 681.1%. All triple variants showed shifted optimal pH from 8.0 to 7.5. Moreover, interaction analysis suggests that the enhanced catalytic efficiency may be attributed to the decreased electrostatic interactions between ATP and the mutation sites (E42, E55, and K290). Based on MD simulation, coulomb energy and binding free energy analysis further reveal the importance of electrostatic interactions for catalytic activity of BfMAT, which could be an efficient strategy for improving catalytic performance of MATs.

A nomogram for predicting acute kidney injury following hepatectomy: A propensity score matching analysis.

STUDY OBJECTIVE: The low central venous pressure (LCVP) technique is a key technique in hepatectomy, but its impact on acute kidney injury (AKI) is unclear. The purpose of this study was to explore risk factors (in particular LCVP time) for AKI following hepatectomy. DESIGN: A retrospective case-control study with propensity score matching. SETTING: Operating room. PATIENTS: A total of 1949 patients who underwent hepatectomy were studied. INTERVENTIONS: The patients were grouped with or without AKI within 7 days after surgery. Univariable and multivariable analyses were performed, including recognized intraoperative predictors. The final result is represented as a nomogram. MEASUREMENTS: Preoperative, intraoperative and postoperative data were collected. LCVP is monitored directly through a central venous catheter via the right internal jugular vein. MAIN RESULTS: AKI occurred in 148 patients (7.59%). Surgery time, minimum SBP, furosemide administration and norepinephrine were identified as independent risk factors. The area under the curve for the receiver operating characteristic curves was 0.726 (95% CI 0.668-0.783). CONCLUSION: Intraoperative parameters can be used to predict the probability of postoperative AKI. Although AKI increases the length of stay, it may not increase in-hospital mortality. LCVP time was not confirmed to be a risk factor for AKI.

LDC7559 inhibits microglial activation and GSDMD-dependent pyroptosis after subarachnoid hemorrhage.

Mounting evidence indicates that inhibition of microglial activation and neuronal pyroptosis plays important roles in brain function recovery after subarachnoid hemorrhage (SAH). LDC7559 is a newly discovered gasdermin D (GSDMD) inhibitor. Previous studies have demonstrated that LDC7559 could inhibit microglial proliferation and pyroptosis. However, the beneficial effects of LDC7559 on SAH remain obscure. Based on this background, we investigated the potential role and the mechanism of LDC7559 on SAH-induced brain damage both in vivo and in vitro. The findings revealed that microglial activation and neuronal pyroptosis were evidently increased after SAH, which could be markedly suppressed by LDC7559 both in vivo and in vitro. Meanwhile, LDC7559 treatment reduced neuronal apoptosis and improved behavior function. Mechanistically, LDC7559 decreased the levels of GSDMD and cleaved GSDMD after SAH. In contrast, nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome activation by nigericin increased GSDMD-mediated pyroptosis and abated the beneficial effects of LDC7559 on SAH-induced brain damage. However, LDC7559 treatment did not significantly affect the expression of NLRP3 after SAH. Taken together, LDC7559 might suppress neuronal pyroptosis and microglial activation after SAH by inhibiting GSDMD, thereby promoting brain functional recovery.

Polycage membranes for precise molecular separation and catalysis.

The evolution of the chemical and pharmaceutical industry requires effective and less energy-intensive separation technologies. Engineering smart materials at a large scale with tunable properties for molecular separation is a challenging step to materialize this goal. Herein, we report thin film composite membranes prepared by the interfacial polymerization of porous organic cages (POCs) (RCC3 and tren cages). Ultrathin crosslinked polycage selective layers (thickness as low as 9.5 nm) are obtained with high permeance and strict molecular sieving for nanofiltration. A dual function is achieved by combining molecular separation and catalysis. This is demonstrated by impregnating the cages with highly catalytically active Pd nanoclusters ( ~ 0.7 nm). While the membrane promotes a precise molecular separation, its catalytic activity enables surface self-cleaning, by reacting with any potentially adsorbed dye and recovering the original performance. This strategy opens opportunities for the development of other smart membranes combining different functions and well-tailored abilities.