Development of target-based cell membrane affinity ultrafiltration technology for a simplified approach to discovering potential bioactive compounds in natural products.

Target-based drug discovery technology based on cell membrane targets has gained significant traction and has been steadily advancing. However, current methods still face certain limitations that need to be addressed. One of the challenges is the laborious preparation process of screening materials, which can be time-consuming and resource-intensive. Additionally, there is a potential issue of non-specific adsorption caused by carrier materials, which can result in false-positive results and compromise the accuracy of the screening process. To address these challenges, this paper proposes a target-based cell membrane affinity ultrafiltration technology for active ingredient discovery in natural products. In this technique, the cell membranes of human lung adenocarcinoma epithelial cells (A549) with a high expression of epidermal growth factor receptor (EGFR) were incubated with candidate drugs and then transferred to an ultrafiltration tube. Through centrifugation, components that interacted with EGFR were retained in the ultrafiltration tube as "EGFR-ligand" complex, while the components that did not interact with EGFR were separated. After thorough washing and eluting, the components interacting with EGFR were dissociated and further identified using LC-MS, enabling the discovery of bioactive compounds. Moreover, the target-based cell membrane affinity ultrafiltration technology exhibited commendable binding capacity and selectivity. Ultimately, this technology successfully screened and identified two major components from the Curcumae Rhizoma-Sparganii Rhizoma (CS) herb pair extracts, which were further validated for their potential anti-tumor activity through pharmacological experiments. By eliminating the need for laborious preparation of screening materials and the potential non-specific adsorption caused by carriers, the development of target-based cell membrane affinity ultrafiltration technology provides a simplified approach and method for bioactive compounds discovery in natural sources.

Harnessing the Synergistic Interplay between Atomic-scale Vacancies and Ligand Effect to Optimize the Oxygen Reduction Activity and Tolerance Performance.

Defect engineering is an effective strategy for regulating the electrocatalysis of nanomaterials, yet it is seldom considered for modulating Pt-based electrocatalysts for the oxygen reduction reaction (ORR). In this study, we designed Ni-doped vacancy-rich Pt nanoparticles anchored on nitrogen-doped graphene (Vac-NiPt NPs/NG) with a low Pt loading of 3.5 wt.% and a Ni/Pt ratio of 0.038:1. Physical characterizations confirmed the presence of abundant atomic-scale vacancies in the Pt NPs induces long-range lattice distortions, and the Ni dopant generates a ligand effect resulting in electronic transfer from Ni to Pt. Experimental results and theoretical calculations indicated that atomic-scale vacancies mainly contributed the tolerance performances towards CO and CH3OH, the ligand effect derived from a tiny of Ni dopant accelerated the transformation from *O to *OH species, thereby improved the ORR activity without compromising the tolerance capabilities. Benefiting from the synergistic interplay between atomic-scale vacancies and ligand effect, as-prepared Vac-NiPt NPs/NG exhibited improved ORR activity, sufficient tolerance capabilities, and excellent durability. This study offers a new avenue for modulating the electrocatalytic activity of metal-based nanomaterials.

Insights into the Superior Bioavailability of Biogenic Sulfur from the View of Its Unique Properties: The Key Role of Trace Organic Substances.

Elemental sulfur (S0) is widely utilized in environmental pollution control, while its low bioavailability has become a bottleneck for S0-based biotechnologies. Biogenic sulfur (bio-S0) has been demonstrated to have superior bioavailability, while little is known about its mechanisms thus far. This study investigated the bioavailability and relevant properties of bio-S0 based on the denitrifying activity of Thiobacillus denitrificans with chemical sulfur (chem-S0) as the control. It was found that the conversion rate and removal efficiency of nitrate in the bio-S0 system were 2.23 and 2.04 times those of the chem-S0 system. Bio-S0 was not pure orthorhombic sulfur [S: 96.88 ± 0.25% (w/w)]. Trace organic substances detected on the bio-S0 surface were revealed to contribute to its hydrophilicity, resulting in better dispersibility in the aqueous liquid. In addition, the adhesion force of T. denitrificans on bio-S0 was 1.54 times that of chem-S0, endowing a higher bacterial adhesion efficiency on the sulfur particle. The weaker intermolecular binding force due to the low crystallinity of bio-S0 led to enhanced cellular uptake by attached bacteria. The mechanisms for the superior bioavailability of bio-S0 were further proposed. This study provides a comprehensive view of the superior bioavailability of bio-S0 and is beneficial to developing high-quality sulfur resources.

A Conformational Restriction Strategy for the Control of CRISPR/Cas Gene Editing with Photoactivatable Guide RNAs.

The CRISPR/Cas system is one of the most powerful tools for gene editing. However, approaches for precise control of genome editing and regulatory events are still desirable. Here, we report the spatiotemporal and efficient control of CRISPR/Cas9- and Cas12a-mediated editing with conformationally restricted guide RNAs (gRNAs). This approach relied on only two or three pre-installed photo-labile substituents followed by an intramolecular cyclization, representing a robust synthetic method in comparison to the heavily modified linear gRNAs that often require extensive screening and time-consuming optimization. This tactic could direct the precise cleavage of the genes encoding green fluorescent protein (GFP) and the vascular endothelial growth factor A (VEGFA) protein within a predefined cutting region without notable editing leakage in live cells. We also achieved light-mediated myostatin (MSTN) gene editing in embryos, wherein a new bow-knot-type gRNA was constructed with excellent OFF/ON switch efficiency. Overall, our work provides a significant new strategy in CRISPR/Cas editing with modified circular gRNAs to precisely manipulate where and when genes are edited.

Synergistic Regulation Effect of Nitrate and Calcium Ions for Highly Luminescent and Robust α-CsPbI3 Perovskite.

The α-CsPbI3 nanocrystals (NCs) easily transform into yellow non-perovskite, accompanying with declining photoelectric properties that restricting their practical applications in diverse fields. Herein, the highly luminescent and robust α-CsPbI3 NCs is achieved through engineering the lattice symmetry of perovskite, enabled by the synergistic effect of NO3- ion passivation and Ca2+ ion doping. The introduced NO3- ions enhance the phase-change energy barrier and the surface steric hindrance, thus promoting the formation of α-CsPbI3 NCs with hyper-symmetric crystal structure, while the Ca2+ ion doping contributes to improving their lattice symmetry by significant regulation of the tolerance factor. As a result, the obtained α-CsPbI3 NCs display an outstanding photoluminescence quantum yield of 96.6%, together with the reduced defect state density and eminent conductivity. Most importantly, the as-engineered α-CsPbI3 NCs exhibit excellent stability under ambient conditions for 9 months and UV illumination for 32 h. It displays brilliant thermal stability, maintaining luminous intensity for 15 min under 140 °C, and performing desired durability and reversibility, evidenced by 160 °C cyclic test and 120 °C reversibility test. Given enhanced robustness, the as-engineered α-CsPbI3 NCs based light-emitting-diode devices are constructed, exhibiting a power efficiency of 105.3 lm W-1 and the excellent working stability for 18 h.

Stratification patterns of anammox granular sludge bed: Linking particle size distribution to microbial activity and community.

Anammox granular sludge processes are an attractive and efficient biotechnology in the field of wastewater treatment. In this study, the stratification patterns of anammox granular sludge bed (GSB) at steady states were illustrated and its relationship to microbial activity and community were systematically investigated under different nitrogen loading rates (NLRs). Morphological observation and quantitive particle size distribution analysis demonstrated that the GSB at low NLR was mainly composed of micro and fine granules with a big difference between bottom and top sludge layers. But at high NLR, the volumetric mean diameter (VMD) of GSB increased with the size distribution width (Span) declined forming a more homogeneous and coarse granules population. The particle size distribution parameters of GSB could be fast characterized by the optical lightness (L*) parameter (r = -0.771, p < 0.01, n = 16) and held a significant correlation with the nitrogen removal rate (NRR) of anammox system (r > 0.9, p < 0.05). The microbial spatial distribution patterns of different sludge layers were further investigated by high-throughput sequencing. The microbial community α-diversity index and microbial abundance matrix proved that the community structure tend to coverage at high NLR. Significant difference of the relative abundance of microbial community was detected under different NLRs. The VMD of GSB held a significant correlation with the relative abundance of AnAOB (r = 0.556, p < 0.01, n = 16) and other common accompanying bacteria (Denitratisoma and Chloroflexi). This study proved that the apparent particle size distribution patterns of GSB could be a potential auxiliary indicator to reflect the microbial activity and community, which can facilitate the innovative process monitor of anammox system based on visual features.

ROS/JNK-mediated lysosomal injury in rat intestinal epithelial-6 cells during heat stress.

Injury to the intestinal epithelial cells and loss of the intestinal barrier are critical to heatstroke. To reveal the mechanism through which heatstroke leads to intestinal epithelial injury, the relationship between reactive oxygen species (ROS), c-Jun NH2-terminal kinase (JNK), and lysosomes were studied in intestinal epithelial cells subjected to heat stress. Cells of heat stress groups were incubated at 43 °C for 1 h, then incubated at 37 °C as indicated. Control group cells were incubated at 37 °C. Cell-counting kit-8 assay was used to assess cell viability. Cells were labeled with 2'-7'dichlorofluorescin diacetate and acridine orange (AO) staining, respectively, the total ROS and AO were detected by confocal laser scanning microscopy and flow cytometry. Apoptosis was analyzed by flow cytometry using annexin V-fluorescein isothiocyanate/prodium iodide staining, the expressions of mitogen-activated protein kinases were detected by western blotting. Heat stress induced apoptosis and inhibited cell viability, the production of ROS, and lysosomal injury in IEC-6 cells. After pretreatment with the lysosomal cathepsin inhibitor E64, the JNK inhibitor SP600125, or the ROS scavenger NAC, the effect of heat stress on apoptosis or lysosomal injury was significantly attenuated. In conclusion, heat stress induced apoptosis, lysosomal injury, and the accumulation of ROS in IEC-6 cells; mechanistically, this occurred through the ROS-induced activation of JNK signaling, which mediated the lysosomal injury and ultimately apoptosis.

The removal of veterinary antibiotics in the high-rate anaerobic bioreactor: continuous and batch studies.

Veterinary antibiotics in swine wastewater has drawn great public attention. The removal processes of sulfamethizole (SMZ), enrofloxacin (ENR) and chlortetracycline (CTC) were investigated in the high-rate anaerobic process. The continuous experiments demonstrated that in 3 L working volume and with the organic loading rate 5 kg/(m3·d) rised to 20 kg/(m3·d), the average removal efficiencies of the high-rate anaerobic bioreactor for SMZ, ENR and CTC were 0, 54 and 100%, respectively. By using fixed-bed adsorption models, the saturation time of SMZ, ENR and CTC were 4 hydraulic retention time (HRT) (24 h), 8 HRT (48 h) and 372 HRT (2,232 h). In the batch experiments, the adsorption and biodegradation characteristics of anaerobic granular sludge were determined. In the high-rate anaerobic bioreactor, SMZ removal process mainly relied on the adsorption but it was very weak; ENR removal process was based on the adsorption and biodegradation; CTC removal process was based to a large extent on the adsorption because of the big capacity of AnGS. These results were helpful to create a rational basis for designing more suitable treatment systems as feasible barriers to the release of antibiotics into the environment.

Role of Extracellular Polymeric Substances in a Methane Based Membrane Biofilm Reactor Reducing Vanadate.

For the first time, we demonstrated vanadate (V(V)) reduction in a membrane biofilm reactor (MBfR) using CH4 as the sole electron donor. The V(V)-reducing capability of the biofilm kept increasing, with complete removal of V(V) achieved when the influent surface loading of V(V) was 363 mg m-2 day-1. Almost all V(V) was reduced to V(IV) precipitates, which is confirmed by a scanning electron microscope coupled to energy dispersive X-ray spectroscopy (SEM-EDS) and X-ray photoelectron spectroscopy (XPS). Microbial community analysis revealed that denitrifiers Methylomonas and Denitratisoma might be the main genera responsible for V(V) reduction. The constant enrichment of Methylophilus suggests that the intermediate (i.e., methanol) from CH4 metabolism might be used as the electron carriers for V(V) bioreduction. Intrusion of V(V) (2-5 mg/L, at the surface loading of 150-378 mg m-2 day-1) into the biofilm stimulated the secretion of extracellular polymeric substances (EPS), but high loading of V(V) (10 mg/L, at the surface loading of 668 mg m-2 day-1) decreased the amount of EPS. Metagenomic prediction analysis established the strong correlation between the secretion of EPS and the microbial metabolism associated with V(V) reduction, tricarboxylic acid cycle (TCA) cycle, methane oxidation, and ATP production, and EPS might relieve the oxidative stress induced by high loading of V(V). Colorimetric determination and a three-dimensional excitation-emission matrix (3D-EEM) showed that tryptophan and humic acid-like substances might play important roles in microbial cell protection and V(V) binding. Fourier transform infrared (FTIR) spectroscopy identified hydroxyl (-OH) and carboxyl (COO-) groups in EPS as the candidate functional groups for binding V(V).

Chemical control of CRISPR/Cpf1 editing via orthogonal activation and deactivation of crosslinked crRNA.

Through the integration of CRISPR/Cpf1 with optogenetics and a reduction-responsive motif, we have developed a photoactivatable cross-linked crRNA that enables precise genome editing upon light exposure. This system also allows for termination of editing activity through external application of reducing agent. The dual-stimuli-responsive CRISPR/Cpf1 editing process operates in a unique OFF → ON → OFF sequence, making it a valuable tool for investigating time-sensitive biological events.

The evolution of calcified anaerobic granular sludge bed informs the deep insight into its agglomeration process.

Calcium-induced agglomeration of anaerobic granular sludge bed (AGSB) has become a critical factor in performance decline of calcified anaerobic reactors. However, the agglomeration process of AGSB and the underlying mechanisms remain unclear and elusive. This study delved into the evolution of calcified AGSB, and four typical states of normal AGSB (Nor-AGSB), calcified dispersed AGSB (Dis-AGSB), calcified dimeric AGSB (Dim-AGSB), and calcified polymeric AGSB (Pol-AGSB) were characterized. It was found that the minimum transport velocity of Dis-AGSB was 3.14-3.79 times higher than that of Nor-AGSB, and surpassed both the superficial velocity and the bubble-induced wake velocity. This led to the sedimentation of AGS at the bottom of reactor, resulting in stable contacts with each other. Solid fillers between AGS, namely cement, were observed within Dim-AGSB and Pol-AGSB, and could be classified as tightly- and loosely- bonded cement (T- and L-cement). Further analysis revealed that T-cement was rich in extracellular polymeric substances and intertwining pili/flagella, serving as the primary driving force for robust inter-AGS adhesion. While the L-cement was primarily in the form of calcite precipitation, and blocked the convective mass transfer pathways in Pol-AGSB, leading to the decreased convective mass transfer capacity. The critical distance between calcite and AGS was further revealed as 5.33 nm to form stable initial adhesion. Consequently, the agglomeration mechanism involving the evolution of AGSB was proposed as calcium-induced sedimentation, calcium-induced adhesion, and calcium-induced stasis in order. This study is expected to offer deep insight into the calcium-induced agglomeration especially from the overlooked perspective of AGSB, and provides feasible control strategies to manage the pressing calcification issues in engineering applications.

Strategies for enhancing non-small cell lung cancer treatment: Integrating Chinese herbal medicines with epidermal growth factor receptor-tyrosine kinase inhibitors therapy.

Non-small cell lung cancer (NSCLC) poses a global health threat, and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) such as gefitinib, afatinib, and osimertinib have achieved significant success in clinical treatment. However, the emergence of resistance limits the long-term efficacy of these treatments, necessitating urgent exploration of novel EGFR-TKIs. This review provides an in-depth summary and exploration of the resistance mechanisms associated with EGFR-TKIs, with a specific focus on representative drugs like gefitinib, afatinib, and osimertinib. Additionally, the review introduces a therapeutic strategy involving the combination of Chinese herbal medicines (CHMs) and chemotherapy drugs, highlighting the potential role of CHMs in overcoming NSCLC resistance. Through systematic analysis, we elucidate the primary resistance mechanisms of EGFR-TKIs in NSCLC treatment, emphasizing CHMs as potential treatment medicines and providing a fresh perspective for the development of next-generation EGFR-TKIs. This comprehensive review aims to guide the application of CHMs in combination therapy for NSCLC management, fostering the development of more effective and comprehensive treatment modalities to ultimately enhance patient outcomes.

Oxygen-induced evolution of anammox granular sludge explains its unique responses during preservation.

Anammox granular sludge (AnGS) preservation is indispensable for the application of anammox technology. Oxygen is a common and crucial factor for anammox, yet its long-term effects on AnGS during preservation remain incomplete clarification. This study investigated the effect of oxygen on AnGS in two simulated preservation systems with open and sealed conditions, and the mechanism was discussed. The results showed that the open system was in an oxidized state with an average dissolved oxygen (DO) concentration and oxidation-reduction potential (ORP) of (3.10 ± 1.36) mg·L-1 and (112.58 ± 46.78) mV, while a reduced state for the sealed system with no detected DO and a lower average ORP of (-153.96 ± 64.32) mV. Both systems showed declines in AnGS activity, while with different responses of AnGS demonstrated by the evolution in terms of granular morphology and structure, bacterial communities, bacteria survival, and bacteria antioxidation. In the open system, reactive oxygen species were generated and destroyed the unsaturated fatty acids in the cell membrane, further leading to the destructed cell structure and declined activity. However, in the sealed system, AnAOB tended to enter a dormant state after long-term preservation, contributing to better conditions in granular morphology and structure, higher AnAOB abundance, and higher live cell ratio. The findings of this study are expected to offer vital information and guidelines for the preservation technologies of AnGS.

Risk factors for and outcomes of heatstroke-related intracerebral hemorrhage.

Some patients with heatstroke also experience intracerebral hemorrhage (ICH). However, clinical case reports of heatstroke-induced ICH are rare. The risk factors for cerebral hemorrhage after heatstroke remain unknown. The present study evaluated the clinical characteristics and risk factors of patients with heatstroke-related ICH. In this retrospective observational study, we collected data on all ICHs after heatstroke occurred between 2012 and 2022. The characteristics of patients with heatstroke-induced ICH were described. The risk factors for cerebral hemorrhage after heatstroke were examined using logistic regression analysis. In total, 177 patients were included in this study, and 11 patients with ICH secondary to heatstroke were identified. Variables with P values of <.05 in univariate models, comparing the cerebral hemorrhage and control groups, included heatstroke cause, temperature, heart rate, respiratory rate, vasopressor use, mechanical ventilation use, Acute Physiology and Chronic Health Evaluation II, total bilirubin, creatinine, platelet count, prothrombin time, procalcitonin, creatine kinase, disseminated intravascular coagulation (DIC) occurrence, and DIC score. Multivariate logistic regression showed that heatstroke patients with higher DIC scores (odds ratio, 18.402, 95% confidence interval, 1.384-244.763, P = .027) and higher creatine kinase levels (odds ratio, 1.021, 95% confidence interval, 1.002-1.041, P = .033) were at a higher risk of developing ICH. The death rate was higher in the cerebral hemorrhage group than in the control group (P = .042). Heatstroke-related cerebral hemorrhage may be associated with elevated creatinine levels and DIC severity (International Society on Thrombosis and Hemostasis score) after heatstroke, and heatstroke with cerebral hemorrhage may accelerate death.

Development and clinical application of a liquid chromatography-tandem mass spectrometry-based assay to quantify eight tyrosine kinase inhibitors in human plasma.

Introduction: Tyrosine kinase inhibitors (TKIs) are widely used in tumor treatment. The detection of these medicines by liquid chromatography-tandem mass spectrometry (LC-MS/MS) can avoid the interference of structurally similar compounds. Objectives: This study aimed to develop and validate a new LC-MS/MS assay for the quantification of eight tyrosine kinase inhibitors in human plasma and to preliminarily evaluate the clinical utility of the therapeutic drug monitoring method. Methods: Plasma samples were prepared by simple protein precipitation and separated using an ultra-high-performance reversed phase column. Detection was achieved using a triple quadrupole mass spectrometer in the positive ionization mode. The assay was validated against standard guidelines. We reviewed and analyzed the results of 268 plasma samples obtained from patients administered imatinib and other TKIs collected from January 2020 to November 2021 at Zhongshan Hospital. The analytes were separated and quantified within 3.5 min. Results: The newly developed method demonstrated linearity for the detected drug concentration in the range of 20 to 2000 ng/ml for gefitinib (r2 = 0.991) and crizotinib (r2 = 0.992), 50 to 5000 ng/ml for nilotinib (r2 = 0.991) and imatinib (r2 = 0.995), 1500-150,000 ng/ml for vemurafenib (r2 = 0.998), 1000-100,000 ng/ml for pazopanib (r2 = 0.993), 0.5-100 ng/ml for axitinib (r2 = 0.992) and 5-500 ng/ml for sunitinib (r2 = 0.991) and N-desethyl sunitinib (r2 = 0.998). The lower limit of quantification (LLOQ) was 20 ng/ml for gefitinib and crizotinib, 50 ng/ml for nilotinib and imatinib, 1500 ng/ml for vemurafenib, 1000 ng/ml for pazopanib, 0.5, and 5 ng/ml for sunitinib and N-desethyl sunitinib, respectively. Specificity, precision, accuracy, and stability were tested, and met the requirements of the guidelines. At the same dose, there was no significant difference in plasma drug concentration between the original imatinib medicine and the generic medicine after patent expiration. Conclusion: We developed a sensitive and reliable method for the quantification of eight TKIs.

Organic matter release characteristics of brown rice: A promising solid carbon source with unique dual-enzyme system for wastewater treatment.

Solid carbon source (SCS) has attracted increasing research interests considering its merits of sustainable organic matter release capacity, safe transportation, easy management, and no need for frequent addition. In this study, the organic matter release capacities of five selected natural (milled rice and brown rice) and synthetic (PLA, PHA, PCL) SCSs were systematically investigated. The results showed that brown rice was the preferable SCS with high COD release potential, release rate and maximum accumulation of 309.2 mg-COD/g-SCS, 581.3 mg-COD/L·d and 6183.3 mg-COD/L, respectively. The cost for COD supply of brown rice stood at $1.0/kg-COD with considerable economic viability. The organic matter release process of brown rice could be well depicted by Hixson-Crowell model with a rate constant of -1.10. The addition of activated sludge could enhance the organic matter release of brown rice, evidenced by the increased release of VFAs with a proportion up to 97.1 % in the total organic matter. Moreover, the mass flow of carbon showed that the addition of activated sludge could improve the carbon utilization rate, and the peak value could achieve 45.4 % in 12 days. The unique dual-enzyme system, consisting of exogenous hydrolase from microorganisms in activated sludge and the endogenous amylase from brown rice, was supposed to be the main reason for the superior carbon release capacity of brown rice over other SCSs. This study was expected to offer an economic and effective SCS for the biological treatment of low-carbon wastewater.

Ecological distribution of anaerobic granular sludge towards efficient anaerobic reactor.

Anaerobic reactors often underperform compared to expectations. To identify the key factors, an ecological anaerobic reactor (EAR) with vertical partitions was developed and compared to a physical anaerobic reactor (PAR) as the control. It was observed that EAR achieved a much higher organic loading rate (OLR) compared to PAR (>100 vs 45 kg/m3·d). The different vertical distribution characteristics of anaerobic granular sludge could be ascribed to two vertical distribution patterns dominated in EAR and PAR, i.e., ecological and physical distributions. It was revealed that ecological distribution was formed by the habitat selection, resulting in promoted substrate availability and higher OLR. While physical distribution was mainly affected by hydraulic selection via granule settleability, causing declined substrate availability and lower OLR. Consequently, the promoted ecological distribution and weakened hydraulic selection in EAR contributed to its good performance. Overall, these findings could offer novel concepts for the development of reactors towards high performance.

The culprit for the declining performance of anaerobic reactors caused by calcification: Bioavailability deterioration.

Calcification is a critical challenge for achieving anaerobic reactors' high-efficiency. However, the aggregation caused by calcification at both granular sludge and reactor levels remain to be fully understood. Herein, this study investigated the characteristics of calcification in an anaerobic reactor (RH) operated with high calcium-containing wastewater for over 200-day. It was found that the COD removal efficiency in RH dropped from 98.00 ± 2.06% to 41.29 ± 3.79%, which was much lower than that of 95.50 ± 1.55% in the control reactor. Morphological analysis revealed that the high influent calcium caused granular sludge aggregation, which would further led to the rapid deterioration in bioavailability, as confirmed by both mass transfer tests and theoretical simulations. Moving forward, statistical analysis showed that the proportion of bioavailability deterioration zones in RH system (61.68%) was similar to the decreased COD removal efficiency (57.87%), proving that bioavailability deterioration was the culprit for the performance decline of anaerobic reactor.

Synergistic regulation effect of magnesium and acetate ions on structural rigidity for synthesizing an efficient and robust CsPbI3 perovskite toward red light-emitting devices.

The structure of CsPbI3 nanocrystals (NCs) with excellent photoelectric properties easily collapses, which hinders their application in light-emitting diodes (LEDs). Herein, we accomplished the synthesis of efficient and stable CsPbI3 NCs by regulating structural rigidity under the synergistic effect of Mg2+ and AcO- ions. The introduced AcO- and Mg2+ ions increase surface steric hindrance and defect formation energy, which enhances the structural rigidity of the perovskite. As a result, the CsPbI3 NCs display an outstanding photoluminescence quantum yield of 95.7%, in conjunction with reduced defect state density, balanced carrier injection, and distinguished conductivity. Remarkably, the modified CsPbI3 NCs exhibit excellent stability under ambient conditions for 180 days and can even survive when the temperature reaches 150 °C. Given their enhanced structural rigidity, LEDs made from these modified CsPbI3 NCs exhibit a maximum luminance and an EQE of 3281 cd m-2 and 13.2%, respectively, which are significantly improved compared with those of unmodified CsPbI3 NC LEDs.

Endothelial glycocalyx injury is involved in heatstroke-associated coagulopathy and protected by N-acetylcysteine.

Introduction: Damage to endothelial glycocalyx (EGCX) can lead to coagulation disorders in sepsis. Heat stroke (HS) resembles sepsis in many aspects; however, it is unclear whether EGCX injury is involved in its pathophysiology. The purpose of this study was to examine the relationship between the damage of EGCX and the development of coagulation disorders during HS. Methods: We retrospectively collected 159 HS patients and analyzed coagulation characteristics and prognosis of HS patients with or without disseminated intravascular coagulation (DIC). We also replicated a rat HS model and measured coagulation indexes, pulmonary capillary EGCX injury in HS rats. Finally, we evaluated the effect of the antioxidant N-acetylcysteine (NAC) on HS-initiated EGCX injury and coagulation disorders. Results: Clinical data showed that HS patients complicated with DIC had a higher risk of death than HS patients without DIC. In a rat HS model, we found that rats subjected to heat stress developed hypercoagulability and platelet activation at the core body temperature of 43°C, just before the onset of HS. At 24 h of HS, the rats showed a consumptive hypo-coagulation state. The pulmonary capillary EGCX started to shed at 0 h of HS and became more severe at 24 h of HS. Importantly, pretreatment with NAC substantially alleviated EGCX damage and reversed the hypo-coagulation state in HS rats. Mechanically, HS initiated reactive oxidative species (ROS) generation, while ROS could directly cause EGCX damage. Critically, NAC protected against EGCX injury by attenuating ROS production in heat-stressed or hydrogen peroxide (H2O2)-stimulated endothelial cells. Discussion: Our results indicate that the poor prognosis of HS patients correlates with severe coagulation disorders, coagulation abnormalities in HS rats are associated with the damage of EGCX, and NAC improves HS-induced coagulopathy, probably through its protection against EGCX injury by preventing ROS generation.