Co-delivery of paclitaxel and curcumin loaded solid lipid nanoparticles for improved targeting of lung cancer: In vitro and in vivo investigation.

The objective of this study was to develop nanotechnology-mediated paclitaxel (PAC) and curcumin (CUR) co-loaded solid lipid nanoparticles (PAC-CUR-SLNs) for the treatment of lung cancer, which is a leading cause of death worldwide. Around 85 % cases of lungs cancer constitute non-small cell lung cancer (NSCLC). PAC-CUR-SLNs were prepared via high pressure homogenization. The in vitro drug release of PAC-CUR-SLNs was checked followed by their in vitro cytotoxic investigation using adenocarcinomic human alveolar basal epithelial cells (A549) cell lines. Anticancer effects along with side effects of the synergistic delivery of PAC-CUR-SLNs were studied in vivo, using BALB/c mice. PAC-CUR-SLNs were nano sized (190 nm), homogeneously disseminated particles with %IE of both PAC and CUR above 94 %. PAC-CUR-SLNs released PAC and CUR in a controlled fashion when compared with free drug suspensions. The cytotoxicity of PAC-CUR-SLNs was higher than individual drug-loaded SLNs and pure drugs. Moreover, the co-delivery displayed synergistic effect, indicating potential of PAC-CUR-SLNs in lung cancer treatment. In vivo tumor investigation of PAC-CUR-SLNs exhibited 12-fold reduced tumor volume and almost no change in body weight of BALB/c mice, when compared with the experimental groups including control group. The inhibition of tumor rate on day 28 was 82.7 % in the PAC-CUR-SLNs group, which was significantly higher than the pure drugs and monotherapies. It can be concluded that, encapsulating the co-loaded antitumor drugs like PAC-CUR in SLNs may help in improved targeting of the tumor with enhanced anticancer effect.

The genomic history and global migration of a windborne pest.

Many insect pests, including the brown planthopper (BPH), undergo windborne migration that is challenging to observe and track. It remains controversial about their migration patterns and largely unknown regarding the underlying genetic basis. By analyzing 360 whole genomes from around the globe, we clarify the genetic sources of worldwide BPHs and illuminate a landscape of BPH migration showing that East Asian populations perform closed-circuit journeys between Indochina and the Far East, while populations of Malay Archipelago and South Asia undergo one-way migration to Indochina. We further find round-trip migration accelerates population differentiation, with highly diverged regions enriching in a gene desert chromosome that is simultaneously the speciation hotspot between BPH and related species. This study not only shows the power of applying genomic approaches to demystify the migration in windborne migrants but also enhances our understanding of how seasonal movements affect speciation and evolution in insects.

The impacts of national centralized drug procurement policy on drug utilization of medical institutions: an empirical study in a county-level hospital in China.

PURPOSE: Under the background of the regular implementation of the National Centralized Drug Procurement (NCDP) policy, this study aimed to assess the impacts of the NCDP policy on drug utilization of county-level medical institutions, and probe into the influencing factors of the changes in drug utilization. METHOD: A pre-post study was applied using inpatient data from a county-level medical institution in Nanjing. Drug utilization behavior of medical institutions of 88 most commonly used policy-related drugs (by generic name, including bid-winning and bid-non-winning brands) was analyzed, and the substitution of bid-winning brands for brand-name drugs after policy intervention was evaluated. RESULTS: After policy intervention, 43.18% of policy-related drugs realized the substitution of bid-winning brands for bid-non-winning brands (6.82% of complete substitution, 36.36% of partial substitution). Meanwhile, 40.90% of policy-related drugs failed to realize brand substitution. Multiple factors affected brand substitution, including: (1) Policy effect: brand substitution was more obvious after the intervention of the first and third round of NCDP. (2) Drug market competition: the greater the price reduction of bid-non-winning brands, the more the drugs for the same indication, the more likely that medical institutions keep using the same brands as they did before policy intervention. (3) Previous drug utilization of medical institutions: brand substitution was more obvious in drugs with large number of prescriptions and weak preference for brand-name drugs. CONCLUSION: The NCDP policy promoted the substitution of bid-winning brands for bid-non-winning brands. However, the NCDP policy remained to be further implemented in county-level medical institutions. Policy implememtation efforts, drug market competition and drug utilization of medical institutions would affect the implementation of the NCDP policy.

Deep learning-aided 3D proxy-bridged region-growing framework for multi-organ segmentation.

Accurate multi-organ segmentation in 3D CT images is imperative for enhancing computer-aided diagnosis and radiotherapy planning. However, current deep learning-based methods for 3D multi-organ segmentation face challenges such as the need for labor-intensive manual pixel-level annotations and high hardware resource demands, especially regarding GPU resources. To address these issues, we propose a 3D proxy-bridged region-growing framework specifically designed for the segmentation of the liver and spleen. Specifically, a key slice is selected from each 3D volume according to the corresponding intensity histogram. Subsequently, a deep learning model is employed to pinpoint the semantic central patch on this key slice, to calculate the growing seed. To counteract the impact of noise, segmentation of the liver and spleen is conducted on superpixel images created through proxy-bridging strategy. The segmentation process is then extended to adjacent slices by applying the same methodology iteratively, culminating in the comprehensive segmentation results. Experimental results demonstrate that the proposed framework accomplishes segmentation of the liver and spleen with an average Dice Similarity Coefficient of approximately 0.93 and a Jaccard Similarity Coefficient of around 0.88. These outcomes substantiate the framework's capability to achieve performance on par with that of deep learning methods, albeit requiring less guidance information and lower GPU resources.

Outcomes of Excimer Laser Ablation Combined with Drug-coated Balloon in Atherosclerotic Lesions of the Popliteal Artery.

BACKGROUND: The treatment of atherosclerotic lesions in the popliteal artery is challenging. This study aims to investigate the efficacy and safety of excimer laser ablation (ELA) combined with drug-coated balloon (DCB) for these lesions. METHODS: From June 2019 to December 2021, data of patients who underwent ELA combined with DCB in the popliteal artery were retrospectively reviewed. Demographics, lesion characteristics, periprocedural complications, and follow-up information were analyzed. The primary endpoint was primary patency. Secondary endpoints included major amputation-free survival rate, technical success, bailout stenting, clinically-driven target lesion reintervention, improvement of ankle-brachial index (ABI), and Rutherford class. RESULTS: A total of 61 patients were enrolled. The mean age was 73.4 ± 11.7 years. 20 (32.8%) patients had stenotic lesions, while 41 (67.2%) patients had chronic total occlusions. The mean length of these lesions was 7.3 ± 2.8 cm. Procedure technical success rate was 95.1%. Bailout stent was performed in 3 (4.9%) patients. Intraprocedural distal embolization occurred in 3 (4.9%) patients, while flow limiting dissections occurred in 3 (4.9%) patients. The mean ABI was significantly improved from 0.45 ± 0.13 at baseline to 0.90 ± 0.12 after ELA, 0.88 ± 0.11 at 6 months and 0.85 ± 0.12 at 12 months during the follow-up period. The median follow-up time was 28.2 ± 6.1 months. Reintervention was performed in 5 (8.2%) patients. The 2-year primary patency was 83.5%. CONCLUSIONS: ELA combined with DCB is a safe and effective strategy in the treatment of popliteal artery atherosclerotic lesions with low rates of bail-out stenting and high primary patency.

Integrated serum pharmacochemistry and network pharmacology to explore the mechanism of Yi-Shan-Hong formula in alleviating chronic liver injury.

BACKGROUND: Chronic liver injury (CLI) is a complex condition that requires effective therapeutic interventions. The Yi-Shan-Hong (YSH) formula is an empirically derived remedy that has shown effectiveness and safety in the management of chronic liver damage. However, the bioactive components and multifaceted mechanisms of YSH remain inadequately understood. PURPOSE: To examine the bioactive compounds and functional processes that contribute to the therapeutic benefits of YSH against CLI. METHODS: Serum pharmacochemistry and network pharmacology were employed to identify active compounds and possible targets of YSH in CLI. In addition, YSH was also given in three doses to d-(+)-galactosamine hydrochloride (D-GalN) -induced CLI rats to test its therapeutic efficacy. RESULTS: The analysis of serum samples successfully detected 25 compounds from YSH. Searches on the databases resulted in 277 genes as being correlated with chemicals in YSH, and 397 genes associated with CLI. In vivo experiments revealed that YSH displayed a notable therapeutic impact on liver injury caused by d-GalN. This was evidenced by enhanced liver function and histopathological improvements, reduced oxidative stress response, proinflammatory factors, and fibrosis levels. Importantly, no discernible adverse effects were observed. Furthermore, the administration of YSH treatment reversed the activation of AKT phosphorylation caused by d-GalN, aligning with the findings of the network pharmacology study. CONCLUSION: These findings provide preclinical evidence of YSH's therapeutic value in CLI and highlight its hepatoprotective action via the PI3K/AKT signaling pathway.

High-content analysis identified synergistic drug interactions between INK128, an mTOR inhibitor, and HDAC inhibitors in a non-small cell lung cancer cell line.

BACKGROUND: The development of drug resistance is a major cause of cancer therapy failures. To inhibit drug resistance, multiple drugs are often treated together as a combinatorial therapy. In particular, synergistic drug combinations, which kill cancer cells at a lower concentration, guarantee a better prognosis and fewer side effects in cancer patients. Many studies have sought out synergistic combinations by small-scale function-based targeted growth assays or large-scale nontargeted growth assays, but their discoveries are always challenging due to technical problems such as a large number of possible test combinations. METHODS: To address this issue, we carried out a medium-scale optical drug synergy screening in a non-small cell lung cancer cell line and further investigated individual drug interactions in combination drug responses by high-content image analysis. Optical high-content analysis of cellular responses has recently attracted much interest in the field of drug discovery, functional genomics, and toxicology. Here, we adopted a similar approach to study combinatorial drug responses. RESULTS: By examining all possible combinations of 12 drug compounds in 6 different drug classes, such as mTOR inhibitors, HDAC inhibitors, HSP90 inhibitors, MT inhibitors, DNA inhibitors, and proteasome inhibitors, we successfully identified synergism between INK128, an mTOR inhibitor, and HDAC inhibitors, which has also been reported elsewhere. Our high-content analysis further showed that HDAC inhibitors, HSP90 inhibitors, and proteasome inhibitors played a dominant role in combinatorial drug responses when they were mixed with MT inhibitors, DNA inhibitors, or mTOR inhibitors, suggesting that recessive drugs could be less prioritized as components of multidrug cocktails. CONCLUSIONS: In conclusion, our optical drug screening platform efficiently identified synergistic drug combinations in a non-small cell lung cancer cell line, and our high-content analysis further revealed how individual drugs in the drug mix interact with each other to generate combinatorial drug response.

Engineering design and application of large-scale oil-based drilling cuttings treatment project.

Thermal phase separation technology is a new comprehensive treatment technology, which heats oil-based cuttings to a certain temperature to vaporize oil and water components. Based on a large oil-based drilling cuttings comprehensive utilization project, the engineering design and application effect of thermal phase separation technology were analysed. The practice shows that thermal phase separation technology can reduce the oil content of purified residue to 0.1-0.2%, the average recovery rate of base oil is 94.12% and the annual recovery of base oil is about 4800 t; the purified residue does not have corrosive, leaching toxicity and other dangerous characteristics, and can be used for making bricks or building materials. Thermal phase separation technology is a comprehensive utilization and treatment technology with excellent engineering and environmental benefits, which has a high promotion value.

Burkholderia cenocepacia epigenetic regulator M.BceJIV simultaneously engages two DNA recognition sequences for methylation.

Burkholderia cenocepacia is an opportunistic and infective bacterium containing an orphan DNA methyltransferase (M.BceJIV) with roles in regulating gene expression and motility of the bacterium. M.BceJIV recognizes a GTWWAC motif (where W can be an adenine or a thymine) and methylates the N6 of the adenine at the fifth base position (GTWWAC). Here, we present a high-resolution crystal structure of M.BceJIV/DNA/sinefungin ternary complex and allied biochemical, computational, and thermodynamic analyses. Remarkably, the structure shows not one, but two DNA substrates bound to the M.BceJIV dimer, wherein each monomer contributes to the recognition of two recognition sequences. This unexpected mode of DNA binding and methylation has not been observed previously and sets a new precedent for a DNA methyltransferase. We also show that methylation at two recognition sequences occurs independently, and that GTWWAC motifs are enriched in intergenic regions of a strain of B. cenocepacia's genome. We further computationally assess the interactions underlying the affinities of different ligands (SAM, SAH, and sinefungin) for M.BceJIV, as a step towards developing selective inhibitors for limiting B. cenocepacia infection.

Analytical challenges in omics research on asthma and allergy: A National Institute of Allergy and Infectious Diseases workshop.

Studies of asthma and allergy are generating increasing volumes of omics data for analysis and interpretation. The National Institute of Allergy and Infectious Diseases (NIAID) assembled a workshop comprising investigators studying asthma and allergic diseases using omics approaches, omics investigators from outside the field, and NIAID medical and scientific officers to discuss the following areas in asthma and allergy research: genomics, epigenomics, transcriptomics, microbiomics, metabolomics, proteomics, lipidomics, integrative omics, systems biology, and causal inference. Current states of the art, present challenges, novel and emerging strategies, and priorities for progress were presented and discussed for each area. This workshop report summarizes the major points and conclusions from this NIAID workshop. As a group, the investigators underscored the imperatives for rigorous analytic frameworks, integration of different omics data types, cross-disciplinary interaction, strategies for overcoming current limitations, and the overarching goal to improve scientific understanding and care of asthma and allergic diseases.

Endovascular Strategies and Outcomes for Aberrant Splenic Artery Aneurysms.

OBJECTIVES: Aberrant splenic artery aneurysms (ASAAs) located at the splenomesenteric trunk (SMT) and the celiacomesenteric trunk have a close anatomical relationship with the superior mesenteric artery (SMA). The aim of this study was to review our institutional experience of endovascular treatment for ASAAs and evaluate the long-term outcomes. METHODS: A retrospective review of patients with ASAAs who underwent endovascular treatment between December 2006 and December 2022 was performed. The demographics of the patients, aneurysm characteristics, treatment strategies, perioperative and long-term outcomes, and complications were analyzed. RESULTS: A total of 29 patients with ASAAs were endovascularly treated at our institution. The SMT variant occurred in the majority of the patients. All ASAAs were characterized by eccentric growth and extremely short inflow arteries. Only 1 patient's inflow artery of the aneurysm exceeded 1 cm in length. Thirteen patients were treated by coil embolization alone. Four patients received bare stent-assisted coil embolization. A combination of coil embolization and covered stent placement across the orifice of the aberrant splenic artery was performed in the remaining 12 cases. Coil migration into the SMA occurred in 2 patients during the operation. Technical success was achieved in all patients. With a median duration of 63 (34-101) months of follow-up, no intestinal ischemia, aneurysm-related death, aneurysm rupture, or sac enlargement occurred. Three cases of aneurysm sac reperfusion were observed, and 1 patient underwent reintervention with secondary embolization. Asymptomatic occlusion of the covered stent was detected in 1 patient at 2 years. CONCLUSIONS: Endovascular treatment is a safe, effective, and durable option for ASAAs. Inflow embolization might be difficult to achieve in ASAAs and poses a high risk of coil migration into the SMA. Long-term observation indicates that reasonable use of the covered stent could achieve reliable inflow artery exclusion in ASAAs without intestinal complications. CLINICAL IMPACT: Aberrant splenic artery aneurysm (ASAA) is an extremely rare entity. This study reported a large sample size of ASAAs treated by endovascular techniques with long-term follow-up. The ASAA was characterized by an extremely short inflow artery and a close anatomical relationship with the superior mesenteric artery (SMA). Endovascular treatment is a safe, effective, and durable option for ASAAs. Inflow embolization might be difficult to achieve in ASAAs and pose a high risk of coil migration into the SMA. Long-term observation indicates that reasonable use of the covered stent could achieve reliable inflow artery exclusion in ASAAs without intestinal complications.

mEnrich-seq: methylation-guided enrichment sequencing of bacterial taxa of interest from microbiome.

Metagenomics has enabled the comprehensive study of microbiomes. However, many applications would benefit from a method that sequences specific bacterial taxa of interest, but not most background taxa. We developed mEnrich-seq (in which 'm' stands for methylation and seq for sequencing) for enriching taxa of interest from metagenomic DNA before sequencing. The core idea is to exploit the self versus nonself differentiation by natural bacterial DNA methylation and rationally choose methylation-sensitive restriction enzymes, individually or in combination, to deplete host and background taxa while enriching targeted taxa. This idea is integrated with library preparation procedures and applied in several applications to enrich (up to 117-fold) pathogenic or beneficial bacteria from human urine and fecal samples, including species that are hard to culture or of low abundance. We assessed 4,601 bacterial strains with mapped methylomes so far and showed broad applicability of mEnrich-seq. mEnrich-seq provides microbiome researchers with a versatile and cost-effective approach for selective sequencing of diverse taxa of interest.

Pathologic complete response prediction in breast cancer lesion segmentation and neoadjuvant therapy.

Objectives: Predicting whether axillary lymph nodes could achieve pathologic Complete Response (pCR) after breast cancer patients receive neoadjuvant chemotherapy helps make a quick follow-up treatment plan. This paper presents a novel method to achieve this prediction with the most effective medical imaging method, Dynamic Contrast-enhanced Magnetic Resonance Imaging (DCE-MRI). Methods: In order to get an accurate prediction, we first proposed a two-step lesion segmentation method to extract the breast cancer lesion region from DCE-MRI images. With the segmented breast cancer lesion region, we then used a multi-modal fusion model to predict the probability of axillary lymph nodes achieving pCR. Results: We collected 361 breast cancer samples from two hospitals to train and test the proposed segmentation model and the multi-modal fusion model. Both segmentation and prediction models obtained high accuracy. Conclusion: The results show that our method is effective in both the segmentation task and the pCR prediction task. It suggests that the presented methods, especially the multi-modal fusion model, can be used for the prediction of treatment response in breast cancer, given data from noninvasive methods only.

Precise Therapeutic Targeting of Distinct NRXN1+/- Mutations.

As genetic studies continue to identify risk loci that are significantly associated with risk for neuropsychiatric disease, a critical unanswered question is the extent to which diverse mutations--sometimes impacting the same gene-- will require tailored therapeutic strategies. Here we consider this in the context of rare neuropsychiatric disorder-associated copy number variants (2p16.3) resulting in heterozygous deletions in NRXN1, a pre-synaptic cell adhesion protein that serves as a critical synaptic organizer in the brain. Complex patterns of NRXN1 alternative splicing are fundamental to establishing diverse neurocircuitry, vary between the cell types of the brain, and are differentially impacted by unique (non-recurrent) deletions. We contrast the cell-type-specific impact of patient-specific mutations in NRXN1 using human induced pluripotent stem cells, finding that perturbations in NRXN1 splicing result in divergent cell-type-specific synaptic outcomes. Via distinct loss-of-function (LOF) and gain-of-function (GOF) mechanisms, NRXN1+/- deletions cause decreased synaptic activity in glutamatergic neurons, yet increased synaptic activity in GABAergic neurons. Stratification of patients by LOF and GOF mechanisms will facilitate individualized restoration of NRXN1 isoform repertoires; towards this, antisense oligonucleotides knockdown mutant isoform expression and alters synaptic transcriptional signatures, while treatment with ß-estradiol rescues synaptic function in glutamatergic neurons. Given the increasing number of mutations predicted to engender both LOF and GOF mechanisms in brain disease, our findings add nuance to future considerations of precision medicine.

Combination of Kaempferol and Docetaxel Induces Autophagy in Prostate Cancer Cells In Vitro and In Vivo.

Docetaxel is a first-line chemotherapy drug used to treat advanced prostate cancer, but patients who have used it often face the challenges of drug resistance and side effects. Kaempferol is a naturally occurring flavonol; our previous studies have confirmed that it has excellent anti-prostate activity. To investigate the anti-prostate cancer effects of docetaxel in combination with kaempferol, we conducted experiments at the cellular and whole-animal level. Plate cloning assays showed that the combination of docetaxel and kaempferol had a synergistic effect in inhibiting the proliferation of prostate cancer cells. The combination of these two compounds was found to induce autophagy in prostate cancer cells via transmission electron microscopy, and changes in the expression of autophagy-related proteins via Western blot assays also confirmed the occurrence of autophagy at the molecular level. We also confirmed the anti-prostate cancer effect of docetaxel in combination with kaempferol in vivo by establishing a mouse xenograft prostate cancer model. Autophagy-related proteins were also examined in mouse tumor tissues and verified the presence of autophagy in mouse tumor tissues. The above cellular and animal data suggest that docetaxel in combination with kaempferol has significant anti-prostate cancer effects and that it works by inducing autophagy in cells.

An artificial intelligence-based ecological index for prognostic evaluation of colorectal cancer.

BACKGROUND AND OBJECTIVE: In the tumor microenvironment (TME), the dynamic interaction between tumor cells and immune cells plays a critical role in predicting the prognosis of colorectal cancer. This study introduces a novel approach based on artificial intelligence (AI) and immunohistochemistry (IHC)-stained whole-slide images (WSIs) of colorectal cancer (CRC) patients to quantitatively assess the spatial associations between tumor cells and immune cells. To achieve this, we employ the Morisita-Horn ecological index (Mor-index), which allows for a comprehensive analysis of the spatial distribution patterns between tumor cells and immune cells within the TME. MATERIALS AND METHODS: In this study, we employed a combination of deep learning technology and traditional computer segmentation methods to accurately segment the tumor nuclei, immune nuclei, and stroma nuclei within the tumor regions of IHC-stained WSIs. The Mor-index was used to assess the spatial association between tumor cells and immune cells in TME of CRC patients by obtaining the results of cell nuclei segmentation. A discovery cohort (N = 432) and validation cohort (N = 137) were used to evaluate the prognostic value of the Mor-index for overall survival (OS). RESULTS: The efficacy of our method was demonstrated through experiments conducted on two datasets comprising a total of 569 patients. Compared to other studies, our method is not only superior to the QuPath tool but also produces better segmentation results with an accuracy of 0.85. Mor-index was quantified automatically by our method. Survival analysis indicated that the higher Mor-index correlated with better OS in the discovery cohorts (HR for high vs. low 0.49, 95% CI 0.27-0.77, P = 0.0014) and validation cohort (0.21, 0.10-0.46, < 0.0001). CONCLUSION: This study provided a novel AI-based approach to segmenting various nuclei in the TME. The Mor-index can reflect the immune status of CRC patients and is associated with favorable survival. Thus, Mor-index can potentially make a significant role in aiding clinical prognosis and decision-making.

Predictors of Return to Work After Thoracic Endovascular Aortic Repair in Patients With Type B Aortic Dissection.

OBJECTIVE: Type B aortic dissection (TBAD) is a life-threatening condition, and it takes heavy burden to family and society. Return to work (RTW) not only means patients' physical health but also demonstrates their mental well-being. Thoracic endovascular aortic repair (TEVAR) has been successful in treatment of TBAD patients. However, less studies have addressed on the social functional recovery of TBAD after TEVAR, especially for RTW. METHODS: From January 1, 2017 to January 1, 2021, TBAD patients who underwent TEVAR and completed a 12-month follow-up were retrospectively enrolled. Primary outcome was RTW. Patients' demographic, sociological, and clinical characteristics, and so on were recorded to analyze and demonstrate independent risk factors for RTW. RESULTS: Four hundred thirty-two TBAD patients (388 males) were enrolled with a mean age of 48.3±8.9 years (ranged from 19 to 60 years). The 12-month cumulative RTW rate was 62.7% (95% confidence interval [CI]: 57.2%-67.8%). Age <50 years (odds ratio [OR]=3.675, 95% CI: 1.436-9.405) was identified as independent protective factors for RTW, while preoperative job as manual workers (OR=0.101, 95% CI: 0.029-0.353), average annual income, <30 000 Chinese Yuan (CNY) [<4400 US dollar], (OR=0.186, 95% CI: 0.054-0.637), complicated TBAD (malperfusion) (OR=0.246, 95% CI: 0.092-0.659), and distal stent graft-induced new entry (SINE) (OR=0.218, 95% CI: 0.083-0.575, p=0.002) were identified as independent risk factors. CONCLUSION: Approximately 64% of our patients were able to RTW in the 12 months post-TEVAR for TBAD. Younger patients, patients with less physically demanding jobs, and patients with less complex surgeries were more likely to RTW. Based on these results, more can be done to facilitate the patient's ability and willingness to RTW after TEVAR. CLINICAL IMPACT: Type B aortic dissection (TBAD) is a life-threatening condition that poses significant burden on both individuals and society. The ability to return to work (RTW) not only reflects the patient's physical health but also indicates their mental well-being. Therefore, identifying risk factors for RTW and promoting the reintegration of TBAD patients into the workforce is crucial in clinical practice.To our knowledge, this study is the first to elucidate and predict the RTW outcomes of TBAD patients who underwent thoracic endovascular aortic repair (TEVAR).

Bioactive Molecules against Rheumatoid Arthritis by Suppressing Pyroptosis.

Rheumatoid arthritis is an inflammatory disease, and pyroptosis is a form of death associated with an inflammatory response. Pyroptosis, which occurs in synovial and osteoblastic cells, can exacerbate the development of rheumatoid arthritis. The inhibition of pyroptosis of these cells can, therefore, clearly be used as a therapeutic strategy against rheumatoid arthritis. Here, we have summarized the current status of progress in the treatment of rheumatoid arthritis by targeting cellular pyroptosis. We have identified seven compounds, including a cyclic RNA, a microRNA, a peptide, and a cytokine (protein), that may influence the progression of rheumatoid arthritis by regulating the initiation of pyroptosis. All of these compounds have been shown to have anti-rheumatoid effects in vitro and/or in vivo and have the potential to be developed as anti-rheumatoid agents. These findings may help to accelerate the development of anti-rheumatoid arthritis drugs.

Evaluation of the lower extremity blood supply in no-option critical limb ischemia patients with stem cell transplantation by time maximum intensity projection CT perfusion: A single-centre prospective study.

OBJECTIVES: Cell therapy has had satisfactory safety and efficacy outcomes for no-option critical limb ischaemia (NO-CLI) patients. In the current study, we aimed to compare the image quality of ischaemic lower limb blood vessels shown on volumetric CT-based time maximum intensity projection CT perfusion (t-MIP CTP) versus single-phase CTA (sCTA). We also tried to quantify the blood flow of the ischaemic lower extremity based on the t-MIP technique, not only to precisely show the dynamic change in blood flow from before to after cell therapy but also to detect any relationship between this change and patient prognosis. METHODS: A total of 31 patients with thromboangiitis obliterans (TAO)-induced NO-CLI who had been referred from the department of vascular surgery to undergo autologous stem cell transplantation into a single limb from January 2020 to March 2021 were prospectively enrolled in this study. Preoperative sCTA or t-MIP CTP and postoperative 1-month t-MIP CTP were performed in all patients. Clinical outcomes, including the 1-month ankle-brachial index (ABI) and 3-month CLI status, were also analysed. Image quality, including objective scores (attenuation, signal-to-noise ratio [SNR] and contrast-to-noise ratio [CNR]), subjective scores and collateral scores, was compared between preoperative sCTA and t-MIP CTP. Vascular volume was calculated as the total volume (mL) of lower limb arteries within the scanning range. All images and calculations were performed by 2 separate radiologists. Receiver operating characteristic curves were drawn to reveal the sensitivity and specificity of vascular volume and ABI in predicting prognosis. RESULTS: Both sCTA and t-MIP CTP images exhibited good quality for diagnosis. t-MIP CTP images showed significantly higher attenuation, SNR and CNR in all arterial segments (popliteal artery, anterior tibial artery, posterior tibial artery and peroneal artery). In subjective and collateral score evaluations, t-MIP CTP images were also significantly better than sCTA images (both p < .05). At 1 month after transplantation, both vascular volume and ABI showed significant improvement (both p < .01). At 3 months after transplantation, 38.71% of patients (12/31) achieved CLI relief (Rutherford class < 4). Through the receiver operating characteristic (ROC) curve, the 1-month vascular volume increase ratio showed better ability to predict the 3-month prognosis (radiologist 1: AUC, 0.757; sensitivity, 0.750; specificity, 0.840; radiologist 2: AUC, 0.803; sensitivity, 0.500; specificity, 1.000) than the 1-month ABI increase ratio (AUC, 0.607; sensitivity, 0.230; specificity, 0.820) or 1-month ABI (AUC, 0.410; sensitivity, 0.080; specificity, 0.580). CONCLUSION: t-MIP CTP showed significantly higher-quality images of ischaemic limb vascularity than sCTA. t-MIP CTP can reveal the anatomical information of collaterals more accurately, which is of great importance for NO-CLI patients undergoing cell transplantation. The 1-month vascular volume increase ratio can predict the 3-month prognosis more precisely on this basis.

First-principles study on the structure and electronic properties of M2CSx (M = Sc, Ti, Y, Zr and Hf, x = 1, 2).

Two-dimensional (2D) transition metal carbides/nitrides, known as MXenes, have attracted extensive attention due to their rich elemental composition and diverse surface chemistry. In this study, the crystal structure, electronic, mechanical, and electronic transport properties of M2CSx (M = Sc, Ti, Y, Zr, and Hf, x = 1, 2) were investigated by density functional theory (DFT). Our results showed that the studied M2CSx except Y2CS2 are thermodynamically, dynamically, thermally, and mechanically stable. The p-d hybridization between the M-d state and the C/S-p state of M2CS is stronger than that of the corresponding M2CS2. However, the antibonding state would appear near the Fermi level and thus reduce the thermal stability of the material due to the introduction of sulfur vacancies in the Y-free MXenes studied. In contrast, sulfur vacancies would significantly enhance the bonding states of Y-C and Y-S bonds and improve the stability of Y2CSx. This provides an explanation for the experimentally observed formation of non-stoichiometric Ti2CS1.2. The room-temperature electron mobilities of semiconductor Sc2CS (Y2CS) along the x and y directions were determined to be 232.59 (818.51) and 628.22 (552.55) cm2 V-1 s-1, and the room-temperature hole mobilities are only 88.32 (1.64) and 61.75 (17.80) cm2 V-1 s-1. This work is expected to provide theoretical insights for the preparation and application of S-terminated MXenes.