Cold granular targets slow the bulk freezing of an impacting droplet.

When making contact with an undercooled target, a drop freezes. The colder the target is, the more rapid the freezing is supposed to be. In this research, we explore the impact of droplets on cold granular material. As the undercooling degree increases, the bulk freezing of the droplet is delayed by at least an order of magnitude. The postponement of the overall solidification is accompanied by substantial changes in dynamics, including the spreading-retraction process, satellite drop generation, and cratering in the target. The solidification of the wetted pores in the granular target primarily causes these effects. The freezing process over the pore dimension occurs rapidly enough to match the characteristic timescales of impact dynamics at moderate undercooling degrees. As a result, the hydrophilic impact appears "hydrophobic," and the dimension of the solidified droplet shrinks. A monolayer of cold grains on a surface can reproduce these consequences. Our research presents a potential approach to regulate solidified morphology for subfreezing drop impacts. It additionally sheds light on the impact scenario of strong coupling between the dynamics and solidification.

Correlation between ferroptosis and adriamycin resistance in breast cancer regulated by transferrin receptor and its molecular mechanism.

Breast cancer is the most prevalent malignant tumor in women. Adriamycin (ADR) is a primary chemotherapy drug, but resistance limits its effectiveness. Ferroptosis, a newly identified cell death mechanism, involves the transferrin receptor (TFRC), closely linked with tumor cells. This study aimed to explore TFRC and ferroptosis's role in breast cancer drug resistance. Bioinformatics analysis showed that TFRC was significantly downregulated in drug-resistant cell lines, and patients with low TFRC expression might demonstrate a poor chemotherapeutic response to standard treatment. High expression of TFRC was positively correlated with most of the ferroptosis-related driver genes. The research findings indicate that ferroptosis markers were higher in breast cancer tissues than in normal ones. In chemotherapy-sensitive cases, Ferrous ion (Fe2+ ) and malondialdehyde (MDA) levels were higher than in resistant cases (all p < .05). TFRC expression was higher in breast cancer than in normal tissue, especially in the sensitive group (all p < .05). Cytological experiments showed increased hydrogen peroxide (H2 O2 ) after ADR treatment in both sensitive and resistant cells, with varying MDA changes (all p < .05). Elevating TFRC increased Fe2+ and MDA in ADR-resistant cells, enhancing their sensitivity to ADR. However, TFRC upregulation combined with ADR increased proliferation and invasiveness in resistant cell lines (all p < .05). In conclusion, ADR resistance to breast cancer is related to the regulation of iron ion-mediated ferroptosis by TFRC. Upregulation of TFRC in ADR-resistant breast cancer cells activates ferroptosis and reverses ADR chemotherapy resistance of breast cancer.

MST1 knockdown inhibits osteoarthritis progression through Parkin-mediated mitophagy and Nrf2/NF-κB signalling pathway.

Osteoarthritis (OA) is a complicated disease that involves apoptosis and mitophagy. MST1 is a pro-apoptotic factor. Hence, decreasing its expression plays an anti-apoptotic effect. This study aims to investigate the protective effect of MST1 inhibition on OA and the underlying processes. Immunofluorescence (IF) was used to detect MST1 expression in cartilage tissue. Western Blot, ELISA and IF were used to analyse the expression of inflammation, extracellular matrix (ECM) degradation, apoptosis and mitophagy-associated proteins. MST1 expression in chondrocytes was inhibited using siRNA and shRNA in vitro and in vivo. Haematoxylin-Eosin, Safranin O-Fast Green and alcian blue staining were used to evaluate the therapeutic effect of inhibiting MST1. This study discovered that the expression of MST1 was higher in OA patients. Inhibition of MST1 reduced inflammation, ECM degradation and apoptosis and enhanced mitophagy in vitro. MST1 inhibition slows OA progression in vivo. Inhibiting MST1 suppressed apoptosis, inflammation and ECM degradation via promoting Parkin-mediated mitophagy and the Nrf2-NF-κB axis. The results suggest that MST1 is a possible therapeutic target for the treatment of osteoarthritis as its inhibition delays the progression of OA through the Nrf2-NF-κB axis and mitophagy.

Smart Physical-Based Transdermal Drug Delivery System:Towards Intelligence and Controlled Release.

Transdermal drug delivery systems based on physical principles have provided a stable, efficient, and safe strategy for disease therapy. However, the intelligent device with real-time control and precise drug release is required to enhance treatment efficacy and improve patient compliance. This review summarizes the recent developments, application scenarios, and drug release characteristics of smart transdermal drug delivery systems fabricated with physical principle. Special attention is paid to the progress of intelligent design and concepts in of physical-based transdermal drug delivery technologies for real-time monitoring and precise drug release. In addition, facing with the needs of clinical treatment and personalized medicine, the recent progress and trend of physical enhancement are further highlighted for transdermal drug delivery systems in combination with pharmaceutical dosage forms to achieve better transdermal effects and facilitate the development of smart medical devices. Finally, the next generation and future application scenarios of smart physical-based transdermal drug delivery systems are discussed, a particular focus in vaccine delivery and tumor treatment.

Direct Assembly of Bioactive Nanoparticles Constructed from Polyphenol-Nanoengineered Albumin.

Albumin nanoparticles are widely used in biomedicine due to their safety, low immunogenicity, and prolonged circulation. However, incorporating therapeutic molecules into these carriers faces challenges due to limited binding sites, restricting drug conjugation efficiency. We introduce a universal nanocarrier platform (X-UNP) using polyphenol-based engineering to incorporate phenolic moieties into albumin nanoparticles. Integration of catechol or galloyl groups significantly enhances drug binding and broadens the drug conjugation possibilities. Our study presents a library of X-UNP nanoparticles with improved drug-loading efficiency, achieving up to 96% across 10 clinically used drugs, surpassing conventional methods. Notably, ibuprofen-UNP nanoparticles exhibit a 5-fold increase in half-life compared with free ibuprofen, enhancing in vivo analgesic and anti-inflammatory effectiveness. This research establishes a versatile platform for protein-based nanosized materials accommodating various therapeutic agents in biotechnological applications.

Design and tribological performance of graphene nanofluids dispersed by dragging effect of bicomponent gelator.

Nanofluids have excellent lubrication and high thermal conductivity. However, the agglomeration and sedimentation produced by the large surface energy of nanoparticles in base liquid threaten the long-term dispersion stability and impact the wide application of nanofluid. In this work, based on the self-assemble behavior and continuous network structure formed by low molecular weight organic gelator, the uniform clusters were formed through regulating the kinetics behavior in the gelling process. The dragging effect was demonstrated by oleic acid - sodium dodecyl sulfate (OA-SDS) bicomponent gelator and graphene oxide (GO) nanosheets. The results showed that GO nanofluids dispersed by OA-SDS were stable for more than 12 months. The well-dispersed GO nanofluid exhibited better anti-friction and anti-wear properties under both immersion and electrostatic minimum quantity lubrication conditions. Moreover, the lower contact angle, surface tension and droplet size of nanofluids after charging improved the wettability on the frictional interface. The GO adsorption film formed on the friction interface protected the tribochemical reaction film of iron oxide and prevented the occurrence of sintering of base oil.

Inferring the genetic effects of serum homocysteine and vitamin B levels on autism spectral disorder through Mendelian randomization.

PURPOSE: The previous studies have suggested that serum homocysteine (Hcy) and vitamin B levels are potentially related to autism spectrum disorder (ASD). However, the causality between their concentrations and ASD risk remains unclear. To elucidate this genetic association, we used a Mendelian randomization (MR) design. METHODS: For this MR analysis, 47 single-nucleotide polymorphisms (SNPs)-13 related to Hcy, 13 to folate, 14 to vitamin B6, and 7 to vitamin B12-were obtained from a large-scale Genome-Wide Association Studies (GWAS) database and employed as instrumental variables (IVs). Our study used three approaches to calculate the MR estimates, including inverse-variance weighted (IVW) method, MR-Egger method, and weighted median (WM) method. Among these, the IVW method served as our primary MR method. False discovery rate (FDR) was implemented to correct for multiple comparisons. We also performed a series of sensitivity analyses, including Cochran's Q test, MR-Egger's intercept, MR-PRESSO, leave-one-out analysis, and the funnel plot. RESULTS: Univariable Mendelian randomization (UVMR) analysis revealed a statistical association between serum vitamin B12 levels and ASD risk (OR = 1.68, 95% CI 1.12-2.52, P = 0.01) using the IVW method. However, neither the WM method (OR = 1.57, 95% CI 0.93-2.66, P = 0.09) nor the MR-Egger method (OR = 2.33, 95% CI 0.48-11.19, P = 0.34) was significantly association with higher levels of serum vitamin B12 and ASD risk. Additionally, we found no evidence of causal relationships between serum levels of vitamin B6, folate, Hcy, and ASD risk. After correcting for the FDR, the causality between serum vitamin B12 levels and ASD risk remained significant (q value = 0.0270). Multivariate Mendelian randomization (MVMR) analysis indicated an independent association between elevated serum vitamin B12 levels and the risk of ASD (OR = 1.74, 95% CI 1.03-2.95, P = 0.03) using the IVW method, but this finding was inconsistent when using the WM method (OR = 1.73, 95% CI 0.89-3.36, P = 0.11) and MR-Egger method (OR = 1.60, 95% CI 0.95-2.71, P = 0.08). Furthermore, no causal associations were observed for serum levels of vitamin B6 and folate in MVMR analysis. Sensitivity analyses confirmed that these results were reliable. CONCLUSION: Our study indicated that elevated serum vitamin B12 levels might increase the risk of ASD. The potential implications of our results for ASD risk warrant validation in randomized clinical trials.

Computed tomography and guidelines-based human-machine fusion model for predicting resectability of the pancreatic cancer.

BACKGROUND AND AIM: The study aims to develop a hybrid machine learning model for predicting resectability of the pancreatic cancer, which is based on computed tomography (CT) and National Comprehensive Cancer Network (NCCN) guidelines. METHOD: We retrospectively studied 349 patients. One hundred seventy-one cases from Center 1 and 92 cases from Center 2 were used as the primary training cohort, and 66 cases from Center 3 and 20 cases from Center 4 were used as the independent test dataset. Semi-automatic module of ITK-SNAP software was used to assist CT image segmentation to obtain three-dimensional (3D) imaging region of interest (ROI). There were 788 handcrafted features extracted for 3D ROI using PyRadiomics. The optimal feature subset consists of three features screened by three feature selection methods as the input of the SVM to construct the conventional radiomics-based predictive model (cRad). 3D ROI was used to unify the resolution by 3D spline interpolation method for constructing the 3D tumor imaging tensor. Using 3D tumor image tensor as input, 3D kernelled support tensor machine-based predictive model (KSTM), and 3D ResNet-based deep learning predictive model (ResNet) were constructed. Multi-classifier fusion ML model is constructed by fusing cRad, KSTM, and ResNet using multi-classifier fusion strategy. Two experts with more than 10 years of clinical experience were invited to reevaluate each patient based on their CECT following the NCCN guidelines to obtain resectable, unresectable, and borderline resectable diagnoses. The three results were converted into probability values of 0.25, 0.75, and 0.50, respectively, according to the traditional empirical method. Then it is used as an independent classifier and integrated with multi-classifier fusion machine learning (ML) model to obtain the human-machine fusion ML model (HMfML). RESULTS: Multi-classifier fusion ML model's area under receiver operating characteristic curve (AUC; 0.8610), predictive accuracy (ACC: 80.23%), sensitivity (SEN: 78.95%), and specificity (SPE: 80.60%) is better than cRad, KSTM, and ResNet-based single-classifier models and their two-classifier fusion models. This means that three different models have mined complementary CECT feature expression from different perspectives and can be integrated through CFS-ER, so that the fusion model has better performance. HMfML's AUC (0.8845), ACC (82.56%), SEN (84.21%), SPE (82.09%). This means that ML models might learn extra information from CECT that experts cannot distinguish, thus complementing expert experience and improving the performance of hybrid ML models. CONCLUSION: HMfML can predict PC resectability with high accuracy.

Improving the level of the cytidine biosynthesis in E. coli through atmospheric room temperature plasma mutagenesis and metabolic engineering.

AIMS: Cytidine, as an important commercial precursor in the chemical synthesis of antiviral and antitumor drugs, is in great demand in the market. Therefore, the purpose of this study is to build a microbial cell factory with high cytidine production. METHODS AND RESULTS: A mutant E. coli NXBG-11-F34 with high tolerance to uridine monophosphate structural analogs and good genetic stability was obtained by atmospheric room temperature plasma (ARTP) mutagenesis combined with high-throughput screening. Then, the udk and rihA genes involved in cytidine catabolism were knocked out by CRISPR/Cas9 gene editing technology, and the recombinant strain E. coli NXBG-13 was constructed. The titer, yield, and productivity of cytidine fermented in a 5 l bioreactor were 15.7 g l-1, 0.164 g g-1, and 0.327 g l-1 h-1, respectively. Transcriptome analysis of the original strain and the recombinant strain E. coli NXBG-13 showed that the gene expression profiles of the two strains changed significantly, and the cytidine de novo pathway gene of the recombinant strain was up-regulated significantly. CONCLUSIONS: ARTP mutagenesis combined with metabolic engineering is an effective method to construct cytidine-producing strains.

Clinical comparative analysis of 3D printing-assisted extracorporeal pre-fenestration and Castor integrated branch stent techniques in treating type B aortic dissections with inadequate proximal landing zones.

BACKGROUND: This study aims to compare the clinical effects of two distinct surgical approaches, namely 3D printing-assisted extracorporeal pre-fenestration and Castor integrated branch stent techniques, in treating patients with Stanford type B aortic dissections (TBAD) characterized by inadequate proximal landing zones. METHODS: A retrospective analysis was conducted on 84 patients with type B aortic dissection (TBAD) who underwent thoracic endovascular aortic repair (TEVAR) with left subclavian artery (LSA) reconstruction at our center from January 2022 to July 2023. Based on the different surgical approaches, the patients were divided into two groups: the group assisted by 3D printing for extracorporeal pre-fenestration (n = 44) and the group using the castor integrated branch stent (n = 40). Clinical indicators: including general patient information, operative time, surgical success rate, intraoperative and postoperative complication rates, re-intervention rate, and mortality, as well as postoperative aortic remodeling, were compared between the two groups. The endpoint of this study is the post-TEVAR mortality rate in patients. RESULTS: The surgical success rate and device deployment success rate were 100% in both groups, with no statistically significant difference (P > 0.05). However, the group assisted by 3D printing for extracorporeal pre-fenestration had a significantly longer operative time (184.20 ± 54.857 min) compared to the group using the castor integrated branch stent (152.75 ± 33.068 min), with a statistically significant difference (t = 3.215, p = 0.002, P < 0.05). Moreover, the incidence of postoperative cerebral infarction and beak sign was significantly lower in the group assisted by 3D printing for extracorporeal pre-fenestration compared to the castor-integrated branch stent group, demonstrating statistical significance. There were no significant differences between the two groups in terms of other postoperative complication rates and aortic remodeling (P > 0.05). Notably, computed tomography angiography images revealed the expansion of the vascular true lumen and the reduction of the false lumen at three specified levels of the thoracic aorta. The follow-up duration did not show any statistically significant difference between the two groups (10.59 ± 4.52 vs. 9.08 ± 4.35 months, t = 1.561, p = 0.122 > 0.05). Throughout the follow-up period, neither group experienced new endoleaks, spinal cord injuries, nor limb ischemia. In the castor-integrated branch stent group, one patient developed a new distal dissection, prompting further follow-up. Additionally, there was one case of mortality due to COVID-19 in each group. There were no statistically significant differences between the two groups in terms of re-intervention rate and survival rate (P > 0.05). CONCLUSION: Both 3D printing-assisted extracorporeal pre-fenestration TEVAR and castor-integrated branch stent techniques demonstrate good safety and efficacy in treating Stanford type B aortic dissection with inadequate proximal anchoring. The 3D printing-assisted extracorporeal pre-fenestration TEVAR technique has a lower incidence of postoperative cerebral infarction and beak sign, while the castor-integrated branch stent technique has advantages in operative time.

Discovery of novel coumarin-based KRAS-G12C inhibitors from virtual screening and Rational structural optimization.

KRAS-G12C inhibitors has been made significant progress in the treatment of KRAS-G12C mutant cancers, but their clinical application is limited due to the adaptive resistance, motivating development of novel structural inhibitors. Herein, series of coumarin derivatives as KRAS-G12C inhibitors were found through virtual screening and rational structural optimization. Especially, K45 exhibited strong antiproliferative potency on NCI-H23 and NCI-H358 cancer cells harboring KRAS-G12C with the IC50 values of 0.77 µM and 1.50 µM, which was 15 and 11 times as potent as positive drug ARS1620, respectively. Furthermore, K45 reduced the phosphorylation of KRAS downstream effectors ERK and AKT by reducing the active form of KRAS (KRAS GTP) in NCI-H23 cells. In addition, K45 induced cell apoptosis by increasing the expression of anti-apoptotic protein BAD and BAX in NCI-H23 cells. Docking studies displayed that the 3-naphthylmethoxy moiety of K45 extended into the cryptic pocket formed by the residues Gln99 and Val9, which enhanced the interaction with the KRAS-G12C protein. These results indicated that K45 was a potent KRAS-G12C inhibitor worthy of further study.

Axial Symptoms and Spinal-pelvic Parameters After Degenerative Lumbar Spondylolisthesis.

Context: Degenerative spondylolisthesis (DS) is a prevalent degenerative condition affecting the lumbar spine. Local spinal parameters play a pivotal role in surgical complications and in the QoL that adults with spinal deformities experience. Treatment can effectively alleviate radicular symptoms, but it doesn't significantly mitigate postoperative axial symptoms (AS). Objective: The study intended to investigate the correlation between postoperative axial symptoms (AS) and spinal-pelvic parameters for patients with DS of the lumbar spine. Design: The research team conducted a prospective cohort study. Setting: The study took place at the Huai'an Hospital of Huai'an City in the Huai'an District of Huai'an City in JiangSu Province, China. Participants: Participants were 120 patients with DS who had been admitted to the department of orthopedics at the hospital between January 2016 and December 2022 and 120 healthy volunteers during the same period. Intervention: The research team created two groups, each with 120 participants: (1) the intervention group with DS who received posterior laminar decompression + pedicle-screw internal fixation + intervertebral-space bone grafting and fusion, and (2) the control group, the healthy volunteers. Outcome Measures: The research team: (1) measured both group's spinal-pelvic parameters at baseline and at 6 months postintervention, (2) evaluated both group's motor functions at baseline and at 6 months postintervention, using the Japanese Orthopedic Association (OAS) scale and the Oswestry Disability Index (ODI), (3) examined the intervention group's postoperative AS, and (4) analyzed the correlation between the intervention group's spinal-pelvic parameters and its postoperative AS and motor function. Results: At 6 months postintervention, the intervention group's spinal-pelvic parameters-lumbar lordosis (LL) and sacral slope (SS) were significantly lower-and-pelvic incidence (PI), pelvic tilt (PT), thoracic kyphosis (TK), segmental lumbar lordosis (SLL), and sagittal vertical axis (SVA) were significantly higher than those of the control group (all P = .000). The intervention group's JOA and ODI scores were significantly lower than those of the control group postintervention (both P = .000). Postintervention compared to the non-AS group, the AS group's LL (P = .000), PI (P = .000), and SS (P = .020) were significantly lower and PT (P = .002), TK (P = .000), SLL (P = .002), and SVA (P = .000) were significantly higher. Postoperative AS was negatively correlated with LL, PI, SS, and positively correlated with PT, TK, SLL, and SVA (all P = .000). The JOA and ODI scores were positively correlated with LL, PI, and SS, and negatively correlated with PT, TK, SLL, and SVA (all P = .000). Conclusions: Postoperative AS in patients with DS is significantly correlated with spinal-pelvic parameters, providing convincing evidence for the evaluation of postoperative dysfunction. However, generalizing to other patients is limited due to the small sample size, which might have resulted in bias in spinal-pelvic parameters. Hence, ongoing trials with large samples are warranted.

Acquired risk factors and incident atrial fibrillation according to age and genetic predisposition.

BACKGROUND AND AIMS: Atrial fibrillation (AF) is the most common sustained arrhythmia in adults. Investigations of risk factor profiles for AF according to age and genetic risk groups are essential to promote individualized strategies for the prevention and control of AF. METHODS: A total of 409 661 participants (mean age, 56 years; 46% men) free of AF at baseline and with complete information about risk factors were included from the UK Biobank cohort. The hazard ratios and population-attributable risk (PAR) percentages of incident AF associated with 23 risk factors were examined, including 3 social factors, 7 health behaviours, 6 cardiometabolic factors, 6 clinical comorbidities, and the genetic risk score (GRS), across 3 age groups (40-49, 50-59, and 60-69 years) and 3 genetic risk groups (low, moderate, and high GRS). RESULTS: After a follow-up of 5 027 587 person-years, 23 847 participants developed AF. Most cardiometabolic factors and clinical comorbidities showed a significant interaction with age, whereby the associations were generally strengthened in younger groups (Pinteraction < .002). However, only low LDL cholesterol, renal dysfunction, and cardiovascular disease showed a significant interaction with genetic risk, and the associations with these factors were stronger in lower genetic risk groups (Pinteraction < .002). Cardiometabolic factors consistently accounted for the largest number of incident AF cases across all age groups (PAR: 36.2%-38.9%) and genetic risk groups (34.0%-41.9%), with hypertension and overweight/obesity being the two leading modifiable factors. Health behaviours (PAR: 11.5% vs. 8.7%) and genetic risk factors (19.1% vs. 14.3%) contributed to more AF cases in the 40-49 years group than in the 60-69 years group, while the contribution of clinical comorbidities remained relatively stable across different age groups. The AF risk attributable to overall cardiometabolic factors (PAR: 41.9% in the low genetic risk group and 34.0% in the high genetic risk group) and clinical comorbidities (24.7% and 15.9%) decreased with increasing genetic risk. The impact of social factors on AF was relatively low across the groups by age and genetic risk. CONCLUSIONS: This study provided comprehensive information about age- and genetic predisposition-related risk factor profiles for AF in a cohort of UK adults. Prioritizing risk factors according to age and genetic risk stratifications may help to achieve precise and efficient prevention of AF.

Self-Supervised Joint Learning for pCLE Image Denoising.

Probe-based confocal laser endoscopy (pCLE) has emerged as a powerful tool for disease diagnosis, yet it faces challenges such as the formation of hexagonal patterns in images due to the inherent characteristics of fiber bundles. Recent advancements in deep learning offer promise in image denoising, but the acquisition of clean-noisy image pairs for training networks across all potential scenarios can be prohibitively costly. Few studies have explored training denoising networks on such pairs. Here, we propose an innovative self-supervised denoising method. Our approach integrates noise prediction networks, image quality assessment networks, and denoising networks in a collaborative, jointly trained manner. Compared to prior self-supervised denoising methods, our approach yields superior results on pCLE images and fluorescence microscopy images. In summary, our novel self-supervised denoising technique enhances image quality in pCLE diagnosis by leveraging the synergy of noise prediction, image quality assessment, and denoising networks, surpassing previous methods on both pCLE and fluorescence microscopy images.

Study on Microstructure and High Temperature Stability of WTaVTiZrx Refractory High Entropy Alloy Prepared by Laser Cladding.

The extremely harsh environment of the high temperature plasma imposes strict requirements on the construction materials of the first wall in a fusion reactor. In this work, a refractory alloy system, WTaVTiZrx, with low activation and high entropy, was theoretically designed based on semi-empirical formula and produced using a laser cladding method. The effects of Zr proportions on the metallographic microstructure, phase composition, and alloy chemistry of a high-entropy alloy cladding layer were investigated using a metallographic microscope, XRD (X-ray diffraction), SEM (scanning electron microscope), and EDS (energy dispersive spectrometer), respectively. The high-entropy alloys have a single-phase BCC structure, and the cladding layers exhibit a typical dendritic microstructure feature. The evolution of microstructure and mechanical properties of the high-entropy alloys, with respect to annealing temperature, was studied to reveal the performance stability of the alloy at a high temperature. The microstructure of the annealed samples at 900 °C for 5-10 h did not show significant changes compared to the as-cast samples, and the microhardness increased to 988.52 HV, which was higher than that of the as-cast samples (725.08 HV). When annealed at 1100 °C for 5 h, the microstructure remained unchanged, and the microhardness increased. However, after annealing for 10 h, black substances appeared in the microstructure, and the microhardness decreased, but it was still higher than the matrix. When annealed at 1200 °C for 5-10 h, the microhardness did not increase significantly compared to the as-cast samples, and after annealing for 10 h, the microhardness was even lower than that of the as-cast samples. The phase of the high entropy alloy did not change significantly after high-temperature annealing, indicating good phase stability at high temperatures. After annealing for 10 h, the microhardness was lower than that of the as-cast samples. The phase of the high entropy alloy remained unchanged after high-temperature annealing, demonstrating good phase stability at high temperatures.

Metal-Phenolic Nanocloaks on Cancer Cells Potentiate STING Pathway Activation for Synergistic Cancer Immunotherapy.

Due to the presence of natural neoantigens, autologous tumor cells hold great promise as personalized therapeutic vaccines. Yet autologous tumor cell vaccines require multi-step production that frequently leads to the loss of immunoreactive antigens, causing insufficient immune activation and significantly hampering their clinical applications. Herein, we introduce a novel whole-cell cancer vaccine by cloaking cancer cells with lipopolysaccharide-decorated manganese(II)-phenolic networks (MnTA nanocloaks) to evoke tumor-specific immune response for highly efficacious synergistic cancer immunotherapy. The natural polyphenols coordinate with Mn2+ and immediately adhere to the surface of individual cancer cells, thereby forming a nanocloak and encapsulating tumor neoantigens. Subsequent decoration with lipopolysaccharide induces internalization by dendritic cells, where Mn2+ ions are released in the cytosol, further facilitating the activation of the stimulator of the interferon genes (STING) pathway. Highly effective tumor suppression was observed by combining the nanocloaked cancer cell treatment with anti-programmed cell death ligand 1 (anti-PD-L1) antibodies-mediated immune checkpoint blockade therapy. Our work demonstrates a universal yet simple strategy to engineer a cell-based nanobiohybrid system for enhanced cancer immunotherapy.

Measurement of CO2 Isotopologue Ratios Using a Hollow Waveguide-Based Mid-Infrared Dispersion Spectrometer.

We demonstrate for the first time the measurement of CO2 isotope ratios (13C/12C and 18O/16O) in a hollow waveguide (HWG) fiber using a mid-infrared heterodyne phase-sensitive dispersion spectrometer (HPSDS). A 4.329 µm interband cascade laser is used to target the absorption lines of three CO2 isotopes (13C16O2, 18O12C16O, and 12C16O2) in a 1 m long and 1 mm inner diameter HWG fiber. The detection limits are 0.29 ppm, 65.78 ppb, and 14.65 ppm with an integration time of 218 s for 13C16O2, 18O12C16O, and 12C16O2, respectively, at a modulation frequency of 160 MHz and a pressure of 230 mbar. The measurement precisions of δ13C and δ18O are 0.89 and 0.88 ‰, respectively, corresponding to an integration time of 167 s. An experimental comparison between a HPSDS and a built wavelength modulation system with second-harmonic detection (WMS-2f) is conducted. The results show that compared to the WMS-2f, the developed HPSDS exhibits a greater linear dynamic range and excellent long-term stability. This work aims to demonstrate a detection technique of CO2 isotope dispersion spectroscopy with a large dynamic range for relevant applications focusing on samples with high concentrations of CO2 (% volume fraction), such as respiratory analysis in medical diagnostics.

Elamipretide alleviates pyroptosis in traumatically injured spinal cord by inhibiting cPLA2-induced lysosomal membrane permeabilization.

Spinal cord injury (SCI) is a devastating injury that may result in permanent motor impairment. The active ingredients of medications are unable to reach the affected area due to the blood‒brain barrier. Elamipretide (SS-31) is a new and innovative aromatic cationic peptide. Because of its alternating aromatic and cationic groups, it freely crosses the blood‒brain barrier. It is also believed to decrease inflammation and protect against a variety of neurological illnesses. This study explored the therapeutic value of SS-31 in functional recovery after SCI and its possible underlying mechanism. A spinal cord contusion injury model as well as the Basso Mouse Scale, footprint assessment, and inclined plane test were employed to assess how well individuals could function following SCI. The area of glial scarring, the number of dendrites, and the number of synapses after SCI were confirmed by HE, Masson, MAP2, and Syn staining. Western blotting, immunofluorescence, and enzyme-linked immunosorbent assays were employed to examine the expression levels of pyroptosis-, autophagy-, lysosomal membrane permeabilization (LMP)- and MAPK signalling-related proteins. The outcomes showed that SS-31 inhibited pyroptosis, enhanced autophagy and attenuated LMP in SCI. Mechanistically, we applied AAV vectors to upregulate Pla2g4A in vivo and found that SS-31 enhanced autophagy and attenuated pyroptosis and LMP by inhibiting phosphorylation of cPLA2. Ultimately, we applied asiatic acid (a p38-MAPK agonist) to test whether SS-31 regulated cPLA2 partially through the MAPK-P38 signalling pathway. Our group is the first to suggest that SS-31 promotes functional recovery partially by inhibiting cPLA2-mediated autophagy impairment and preventing LMP and pyroptosis after SCI, which may have potential clinical application value.

Tunable Crystallinity and Electron Conduction in Wavy 2D Conjugated Metal-Organic Frameworks via Halogen Substitution.

Currently, most reported 2D conjugated metal-organic frameworks (2D c-MOFs) are based on planar polycyclic aromatic hydrocarbons (PAHs) with symmetrical functional groups, limiting the possibility of introducing additional substituents to fine-tune the crystallinity and electrical properties. Herein, a novel class of wavy 2D c-MOFs with highly substituted, core-twisted hexahydroxy-hexa-cata-benzocoronenes (HH-cHBCs) as ligands is reported. By tailoring the substitution of the c-HBC ligands with electron-withdrawing groups (EWGs), such as fluorine, chlorine, and bromine, it is demonstrated that the crystallinity and electrical conductivity at the molecular level can be tuned. The theoretical calculations demonstrate that F-substitution leads to a more reversible coordination bonding between HH-cHBCs and copper metal center, due to smaller atomic size and stronger electron-withdrawing effect. As a result, the achieved F-substituted 2D c-MOF exhibits superior crystallinity, comprising ribbon-like single crystals up to tens of micrometers in length. Moreover, the F-substituted 2D c-MOF displays higher electrical conductivity (two orders of magnitude) and higher charge carrier mobility (almost three times) than the Cl-substituted one. This work provides a new molecular design strategy for the development of wavy 2D c-MOFs and opens a new route for tailoring the coordination reversibility by ligand substitution toward increased crystallinity and superior electric conductivity.

Methane detection with a near-infrared heterodyne phase-sensitive dispersion spectrometer at a stronger frequency modulation using direct injection-current dithering.

Heterodyne phase-sensitive dispersion spectrometer (HPSDS) retrieves the concentration of gas samples by measuring the refractive index fluctuations near the molecular resonance. Compared to previous HPSDS studies focusing on pure intensity modulation, it is attractive to investigate the performance of HPSDS sensor based on a distributed feedback (DFB) laser under conditions where frequency modulation is much higher than intensity modulation. In this work, we report the implementation of a near-infrared HPSDS for methane detection based on the direct modulation of a DFB laser. The performance of our HPSDS is assessed using the characteristic absorption peak of methane near 1653.7 nm. Long-time measurements show that our HPSDS has a detection limit (MDL) of 1.22 ppm at standard atmospheric pressure and room temperature. In the same experimental conditions, we have experimentally compared HPSDS to wavelength modulation spectroscopy (WMS) to evaluate the dynamical range, long-term stability, and precision limits of the two methods.