Exploratory and confirmatory factor analysis of the sensitivity to punishment and sensitivity to reward questionnaire-revised and its psychometric evaluation among Chinese person with substance use disorder.

The Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ) is a self-report tool widely used to assess individuals' level of reinforcement sensitivity. Drug addiction is strongly associated with reinforcement sensitivity, but there is a lack of measurement tools to assess reinforcement sensitivity in drug users, necessitating the revision and application of the SPSRQ among drug users. This study recruited 819 drug users (mean age = 34.74; 56.41% female) from five compulsory rehabilitation centers in Hunan Province, China. The applicability of the SPSRQ among person with substance use disorder was assessed by conducting reliability analyses and validity analyses, with retesting performed by 127 individuals after 6 weeks. Exploratory factor analysis for the SPSRQ showed a stable two-factor structure in person with substance use disorder. Confirmatory factor analysis indicated acceptable goodness of fit indexes for the two-factor structure. The SPSRQ also demonstrated good reliability and convergent and discriminant validity evidence. The two-factor structure of the SPSRQ also demonstrated measurement invariance across gender. Further comparative analysis found that the degree of reward sensitivity was higher for males than for females. Generally, the SPSRQ has shown evidence of good reliability and validity in Chinese drug-dependent populations, and it is suitable for research and application with Chinese person with substance use disorder. These findings about the personality traits of people with substance use disorder provide a solid basis for further research.

Facile Synthesis of a Multifunctional Porous Organic Polymer Nanosonosensitizer (mHM@HMME) for Enhanced Cancer Sonodynamic Therapy.

Sonodynamic therapy (SDT), which involves the activation of sonosensitizers to generate cytotoxic reactive oxygen species under ultrasound irradiation, is a promising noninvasive modality for cancer treatment. However, the clinical translational application of SDT is impeded by the lack of efficient sonosensitizers, the inefficient accumulation of sonosensitizers at tumor sites, and the complicated immunosuppressive tumor microenvironment. Herein, we developed a facilely synthesized multifunctional porous organic polymer nanosonosensitizer (mHM@HMME) for enhanced SDT. Specifically, mHM@HMME nanosonosensitizers were prepared by incorporating chemotherapeutic mitoxantrone into the one-step synthesis process of disulfide bond containing porous organic polymers, followed by loading with organic sonosensitizer (HMME) and camouflaging with a cancer cell membrane. Due to the cancer cell membrane camouflage, this multifunctional mHM@HMME nanosonosensitizer showed prolonged blood circulation and tumor targeting aggregation. Under ultrasound irradiation, the mHM@HMME nanosonosensitizer exhibited a satisfactory SDT performance both in vitro and in vivo. Moreover, the potent SDT combined with glutathione-responsive drug release in tumor cells induced robust immunogenic cell death to enhance the antitumor effect of SDT in turn. Overall, this facilely synthesized multifunctional mHM@HMME nanosonosensitizer shows great potential application in enhanced SDT.

A Study to Analyse the Feasibility and Effectiveness of Left Bundle Branch Area Pacing Used in Young Children.

This study aimed to investigate the feasibility and effectiveness of left bundle branch area pacing (LBBaP) in young children. From September 2020 to May 2021, a total of 31 children (≤ 7 years) with complete atrioventricular block were included. All patients were scheduled to undergo LBBaP. Pacing parameters, and cardiac function and synchrony were evaluated during follow-up. LBBaP succeeded in 21 children (3.3 ± 2.1 years old), with a success rate of 70.9%. LBBaP failed in nine children, who eventually received right ventricular septal pacing (RVSP). The average postoperative QRS duration in patients of LBBaP group was narrower than that of RVSP group: 100.9 ± 9.1 versus 114.2 ± 11.9 ms (P = 0.002). The median follow-up duration was 12 [interquartile range (IQR) 6-15] months. At last time of follow-up, the capture threshold of ventricular electrode in patients of LBBaP group were significantly lower than that of RVSP group (0.70 ± 0.25 versus 1.39 ± 0.94 V, P = 0.011). The echo-left ventricular ejection fraction (LVEF) in patients in the LBBaP group was better than that in the RVSP group (66.1 ± 3.3 versus 63.1 ± 2.2%, P = 0.025). LBBaP can be safely and effectively administered in young children. Satisfactory pacing parameters, and narrow QRS durations were obtained.

Defect-induced deep red luminescence of CaGdAlO4-type layered perovskites: multi-cationic sites partial/full substitution and application in pc-LED and plant lighting.

A series of CaGdAlO4-type layered perovskite phosphors showing deep red luminescence (λem = 711 nm, λex = 338 nm) were synthesized via a solid-state reaction. A comprehensive analysis performed via photoluminescence, X-ray photoelectron spectroscopy, thermoluminescence, and fluorescence decay revealed that the deep red luminescence is related to oxygen defects and particularly oxygen interstitials. The defect-related luminescence was effectively regulated through partial substitution of multi-cationic sites (the Ca2+ site with Mg2+, Sr2+, and Ba2+; the Gd3+ site with La3+, Y3+, and Lu3+) and full substitution of Gd3+ with Y3+. Remarkably, a 383.3% stronger luminescence was obtained through partial substitution with Lu3+, and the quantum yield of luminescence reached 28.74%, which is higher than those values of most previously reported self-luminescent systems. A pc-LED device was fabricated using this phosphor, and the device was shown to have potential application in indoor plant cultivation.

Evaluation of a rail logistics transmission system for the transportation of blood components within a medical centre.

BACKGROUND AND OBJECTIVES: Rail logistics transmission systems (RLTSs) are commonly used for the transportation of blood samples, pathological specimens and other medical materials in many hospitals, as they are rapid, secure, cost-effective and intelligent. However, few studies have evaluated blood component transportation from blood banks to the patient care areas of hospitals using RLTS. In this study, we evaluate the RLTS used for the transportation of blood components within a medical centre. MATERIALS AND METHODS: The dispatch of blood components, including packed red blood cells (pRBCs), fresh frozen plasma (FFP), cryoprecipitate and platelet units, from a blood bank to critical care areas or general wards was done using RLTS. Parameters such as the delivery time, temperature, physical integrity and blood component quality were evaluated via analytical testing using specimens obtained before and after transportation by RLTS. RESULTS: The turnaround time and temperature of all tested blood units via RLTS transportation were able to meet the clinical demands of blood component delivery (median time: 323 s [118-668 s]; temperature variation: 4.5-8.9°C for pRBCs and FFP and 21.5-23.5°C for cryoprecipitate and platelet units). Furthermore, parameters of pRBC quality, including the haemolysis index and potassium and lactate dehydrogenase levels in plasma, were not significantly different before and after transportation through RLTS. Similarly, RLTS transportation affected neither the basic coagulation test results in FFP and cryoprecipitate specimens nor platelet aggregation and activation markers in apheresis platelet specimens. CONCLUSION: Hospital-wide delivery of blood components via RLTS seems to be safe, reliable and cost-effective and does not have any negative impact on blood quality. Therefore, the establishment of standard criteria, protocols and guidelines based on further studies is needed.

SLC25A51 promotes tumor growth through sustaining mitochondria acetylation homeostasis and proline biogenesis.

Solute carrier family 25 member 51 (SLC25A51) was recently identified as the mammalian mitochondrial NAD+ transporter essential for mitochondria functions. However, the role of SLC25A51 in human disease, such as cancer, remains undefined. Here, we report that SLC25A51 is upregulated in multiple cancers, which promotes cancer cells proliferation. Loss of SLC25A51 elevates the mitochondrial proteins acetylation levels due to SIRT3 dysfunctions, leading to the impairment of P5CS enzymatic activity, which is the key enzyme in proline biogenesis, and the reduction in proline contents. Notably, we find fludarabine phosphate, an FDA-approved drug, is able to bind with and inhibit SLC25A51 functions, causing mitochondrial NAD+ decrease and proteins hyperacetylation, which could further synergize with aspirin to reinforce the anti-tumor efficacy. Our study reveals that SLC25A51 is an attractive anti-cancer target, and provides a novel drug combination of fludarabine phosphate with aspirin as a potential cancer therapy strategy.

Automatic knowledge extraction from Chinese electronic medical records and rheumatoid arthritis knowledge graph construction.

Background: Knowledge graphs are a powerful tool for organizing knowledge, processing information and integrating scattered information, effectively visualizing the relationships among entities and supporting further intelligent applications. One of the critical tasks in building knowledge graphs is knowledge extraction. The existing knowledge extraction models in the Chinese medical domain usually require high-quality and large-scale manually labeled corpora for model training. In this study, we investigate rheumatoid arthritis (RA)-related Chinese electronic medical records (CEMRs) and address the automatic knowledge extraction task with a small number of annotated samples from CEMRs, from which an authoritative RA knowledge graph is constructed. Methods: After constructing the domain ontology of RA and completing manual labeling, we propose the MC-bidirectional encoder representation from transformers-bidirectional long short-term memory-conditional random field (BERT-BiLSTM-CRF) model for the named entity recognition (NER) task and the MC-BERT + feedforward neural network (FFNN) model for the entity extraction task. The pretrained language model (MC-BERT) is trained with many unlabeled medical data and fine-tuned using other medical domain datasets. We apply the established model to automatically label the remaining CEMRs, and then an RA knowledge graph is constructed based on the entities and entity relations, a preliminary assessment is conducted, and an intelligent application is presented. Results: The proposed model achieved better performance than that of other widely used models in knowledge extraction tasks, with mean F1 scores of 92.96% in entity recognition and 95.29% in relation extraction. This study preliminarily confirmed that using a pretrained medical language model could solve the problem that knowledge extraction from CEMRs requires a large number of manual annotations. An RA knowledge graph based on the above identified entities and extracted relations from 1,986 CEMRs was constructed. Experts verified the effectiveness of the constructed RA knowledge graph. Conclusions: In this paper, an RA knowledge graph based on CEMRs was established, the processes of data annotation, automatic knowledge extraction, and knowledge graph construction were described, and a preliminary assessment and an application were presented. The study demonstrated the viability of a pretrained language model combined with a deep neural network for knowledge extraction tasks from CEMRs based on a small number of manually annotated samples.

Sustained release of alginate hydrogel containing antimicrobial peptide Chol-37(F34-R) in vitro and its effect on wound healing in murine model of Pseudomonas aeruginosa infection.

BACKGROUND: Antibiotic resistance is a significant public health concern around the globe. Antimicrobial peptides exhibit broad-spectrum and efficient antibacterial activity with an added advantage of low drug resistance. The higher water content and 3D network structure of the hydrogels are beneficial for maintaining antimicrobial peptide activity and help to prevent degradation. The antimicrobial peptide released from hydrogels also hasten the local wound healing by promoting epithelial tissue regeneration and granulation tissue formation. OBJECTIVE: This study aimed at developing sodium alginate based hydrogel loaded with a novel antimicrobial peptide Chol-37(F34-R) and to investigate the characteristics in vitro and in vivo as an alternative antibacterial wound dressing to treat infectious wounds. METHODS: Hydrogels were developed and optimized by varying the concentrations of crosslinkers and subjected to various characterization tests like cross-sectional morphology, swelling index, percent water contents, water retention ratio, drug release and antibacterial activity in vitro, and Pseudomonas aeruginosa infected wound mice model in vivo. RESULTS: The results indicated that the hydrogel C proved superior in terms of cross-sectional morphology having uniformly sized interconnected pores, a good swelling index, with the capacity to retain a higher quantity of water. Furthermore, the optimized hydrogel has been found to exert a significant antimicrobial activity against bacteria and was also found to prevent bacterial infiltration into the wound site due to forming an impermeable barrier between the wound bed and external environment. The optimized hydrogel was found to significantly hasten skin regeneration in animal models when compared to other treatments in addition to strong inhibitory effect on the release of pro-inflammatory cytokines (interleukin-1ß and tumor necrosis factor-α). CONCLUSIONS: Our results suggest that sodium alginate -based hydrogels loaded with Chol-37(F34-R) hold the potential to be used as an alternative to conventional antibiotics in treating infectious skin wounds.

Using Semantic Text Similarity calculation for question matching in a rheumatoid arthritis question-answering system.

Background: When users inquire about knowledge in a certain field using the internet, the intelligent question-answering system based on frequently asked questions (FAQs) provides numerous concise and accurate answers that have been manually verified. However, there are few specific question-answering systems for chronic diseases, such as rheumatoid arthritis, and the related technology to construct a question-answering system about chronic diseases is not sufficiently mature. Methods: Our research embedded the classification information of the question into the sentence vector based on the bidirectional encoder representations from transformers (BERT) language model. First of all, we calculated the similarity using edit distance to recall the candidate set of similar questions. Then, we took advantage of the BERT pretraining model to map the sentence information to the corresponding embedding representation. Finally, each dimensional feature of the sentence was obtained by passing a sentence vector through the multihead attention layer and the fully connected feedforward layer. The features that were stitched and fused were used for the semantic similarity calculation. Results: Our improved model achieved a Top-1 precision of 0.551, Top-3 precision of 0.767, and Top-5 precision of 0.813 on 176 testing question sentences. In the analysis of the actual application effect of the model, we found that our model performed well in understanding the actual intention of users. Conclusions: Our deep learning model takes into account the background and classifications of questions and combines the efficiency of deep learning technology and the comprehensibility of semantics. The model enables the deep meaning of the user's question to be better understood by the intelligent question answering system, and answers that are more relevant to the original query are provided.

Ablation of Ventricular Preexcitation to Cure Preexcitation-Induced Dilated Cardiomyopathy in Infants: Diagnosis and Outcome.

BACKGROUND: To investigate the clinical features of preexcitation-induced dilated cardiomyopathy in infants and evaluate safety and efficacy of radiofrequency ablation (RFCA) in these patients. METHODS: This study included 10 infants (4 males and 6 females) with mean age of 6.78±3.14 months, mean weight of 8.11±1.71 kg, and mean left ventricular ejection fraction (LVEF) was 32.6±10.34%. Tachycardiomyopathy has been excluded and all patients were refractory to the drugs. All of these 10 patients underwent RFCA. RESULTS: All the accessory pathways in these patients were located on right free wall and the acute success rate was 100%. No complication associated with the procedure occurred. In one case preexcitation recurred and was ablated successfully during the second attempt. There were 3 patients with mild cardiac dysfunction (LVEF, 40≤LVEF<50%), 3 with moderate (30≤LVEF<40%), and 4 with severe cardiac dysfunction (LVEF<30%, the ages were 3, 6, 7, and 10 months, respectively). The time for LVEF normalization was 1 week, 1 to 3 months, and ≥3 months, respectively. In 3 of the 4 severe cardiac dysfunction patients, the LVEF normalized at 3, 6, and 12 months after ablation, the LVEF of the remaining case did not recover at 3 months and is still being followed. CONCLUSIONS: Ventricular preexcitation could lead to severe cardiac dysfunction during infancy. RFCA may be a safe and effective treatment option in right free wall accessory pathways, even in infants with cardiac dysfunction. Cases of more severe cardiac dysfunction might require a longer time for LVEF recovery after RFCA.

KAT8 acetylation-controlled lipolysis affects the invasive and migratory potential of colorectal cancer cells.

Epigenetic mechanisms involved in gene expression play an essential role in various cellular processes, including lipid metabolism. Lysine acetyltransferase 8 (KAT8), a histone acetyltransferase, has been reported to mediate de novo lipogenesis by acetylating fatty acid synthase. However, the effect of KAT8 on lipolysis is unclear. Here, we report a novel mechanism of KAT8 on lipolysis involving in its acetylation by general control non-repressed protein 5 (GCN5) and its deacetylation by Sirtuin 6 (SIRT6). KAT8 acetylation at K168/175 residues attenuates the binding activity of KAT8 and inhibits the recruitment of RNA pol II to the promoter region of the lipolysis-related genes adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), subsequently down-regulating lipolysis to affect the invasive and migratory potential of colorectal cancer cells. Our findings uncover a novel mechanism that KAT8 acetylation-controlled lipolysis affects invasive and migratory potential in colorectal cancer cells.

Enhancement of the chemical stability of nanoemulsions loaded with curcumin by unsaturated mannuronate oligosaccharide.

Unsaturated mannuronate oligosaccharide (MOS) is an acidic oligosaccharide prepared from alginate-derived polymannuronate by enzymatic depolymerization, followed by double bond formation between C-4 and C-5 at the nonreducing end. In this study, MOS was used as a stabilizer to fabricate O/W nanoemulsions loaded with curcumin (MOS-CUR) for the first time. The results revealed that the MOS-CUR showed small droplet sizes and narrow size distributions and was slightly more stable than normal oil-in-water (O/W) curcumin nanoemulsions (water-CUR). Additionally, MOS can improve the superoxide anion scavenging ability and iron ion reducing ability of the curcumin nanoemulsion system. Although the digestion behaviour of MOS-CUR and water-CUR was similar, the bioavailability of curcumin in MOS-CUR was significantly higher than that in water-CUR. All these results indicated that MOS could be used as a stabilizer for preparing nanoemulsions to easily encapsulate labile nutrients and to enhance the bioavailability and antioxidant capacity of these nutrients.

Soy protein isolate-polyguluronate nanoparticles loaded with resveratrol for effective treatment of colitis.

Polyguluronate (PG) is an acidic homopolymer of α-(1,4)-l-guluronate separated from alginate. In this study, PG was first grafted with soy protein isolate (SPI) through the Maillard reaction to obtain a new glycoprotein (SPI-PG). Then, this novel glycoprotein was used to prepare nanoparticles to encapsulate the resveratrol (RES). Our results showed that SPI-PG-RES had better pH stability, storage stability and ionic stability than SPI-RES. In vitro digestion experiments showed that the RES bioavailability of SPI-PG-RES was much higher than that of free RES and SPI-RES. Furthermore, the in vitro antioxidant capacity of SPI-PG-RES was much stronger than that of free RES and SPI-RES. In addition, SPI-PG-RES was more effective in preventing the symptoms of DSS-induced colitis than RES and SPI-RES. These results suggested that the protein nanoparticles prepared using SPI-PG were a stable and effective hydrophobic polyphenol carrier and could be applied to food-grade components in functional foods and nutritional supplements.

Comparison of ventricular synchrony in children with left bundle branch area pacing and right ventricular septal pacing.

OBJECTIVE: This study aimed to determine the ideal pacing site in children by comparing the postoperative ventricular synchrony in children with left bundle branch area pacing and those with right ventricular septal pacing. METHODS: This retrospective study included children with complete atrioventricular block who underwent permanent pacemaker implantation from March 2019 to August 2021. Patients were grouped according to their ventricular pacing site, the left bundle branch area pacing group and the right ventricular septal pacing group. Two-dimensional speckle tracking echocardiography was used to evaluate the ventricular synchrony. RESULTS: Forty-eight children (median age, 2.7 years; interquartile range, 1.7-4.6 years) were included. The paced QRS duration in the left bundle branch area pacing group was significantly narrower than that in the right ventricular septal pacing group (100.2 ± 9.3 versus 115.4 ± 15.1 ms, p = 0.001). The median follow-up duration was 1.5 years (interquartile range, 1-2 years). At the last follow-up, the average capture threshold of the ventricular electrode in the left bundle branch area pacing group was lower than that in the right ventricular septal pacing group (0.79 ± 0.18 versus 1.20 ± 0.56 V, p = 0.008). The left ventricular intraventricular synchrony parameters in the left bundle branch area pacing group were better than those in the right ventricular septal pacing group (e.g. standard deviation of the time to peak longitudinal strain, 37.4 ± 4.3 versus 46.6 ± 8.2 ms, p = 0.000). The average interventricular mechanical delay time in the left bundle branch area pacing group was significantly shorter than that in the right ventricular septal pacing group (36.4 ± 14.2 versus 52.5 ± 22.7 ms, p = 0.016). CONCLUSION: Compared with right ventricular septal pacing, left bundle branch area pacing in children produces a narrower QRS duration and better pacing and ventricular synchrony parameters postoperatively.

Analysis of the influencing factors associated with dyssynchrony and cardiac dysfunction in children with ventricular pre-excitation.

OBJECTIVE: To investigate the correlation between ventricular pre-excitation-related dyssynchrony, on cardiac dysfunction, and recovery. METHODS AND RESULTS: This study included 76 children (39 boys and 37 girls) with a median age of 5.25 (2.67-10.75) years. The patients with pre-excitation-related cardiac dysfunction (cardiac dysfunction group, n = 34) had a longer standard deviation of the time-to-peak systolic strain of the left ventricle and larger difference between the maximum and minimum times-to-peak systolic strain than those with a normal cardiac function (normal function group, n = 42) (51.77 ± 24.70 ms versus 33.29 ± 9.48 ms, p < 0.05; 185.82 ± 92.51 ms versus 111.93 ± 34.27 ms, p < 0.05, respectively). The cardiac dysfunction group had a maximum time-to-peak systolic strain at the basal segments of the anterior and posterior septa and the normal function group at the basal segments of anterolateral and posterolateral walls. The prevalence of ventricular septal dyssynchrony in the cardiac dysfunction group was significantly higher than that in the normal function group (94.1% (32/34) versus 7.7% (3/42), p < 0.05). The patients with ventricular septal dyssynchrony (n = 35) had a significantly higher prevalence of intra-left ventricular systolic dyssynchrony than those with ventricular septal synchrony (n = 41) (57.1% (20/35) versus 14.6% (6/41), p < 0.05). During follow-up after pathway ablation, the patients who recovered from intra-left ventricular dyssynchrony (n = 29) had a shorter left ventricular ejection fraction recovery time than those who did not (n = 5) (χ2 = 5.94, p < 0.05). Among the patients who recovered, 93.1% (27/29) had a normalised standard deviation of the time-to-peak systolic strain and difference between the maximum and minimum times-to-peak systolic strain within 1 month after ablation. CONCLUSION: Ventricular pre-excitation may cause ventricular septal dyssynchrony; thus, attention must be paid to intra-left ventricular dyssynchrony and cardiac dysfunction. Whether intra-left ventricular systolic dyssynchrony can resolve within 1 month may be a new early predictor of patient prognosis.

Left ventricular pacing in the treatment of pediatric cardiac dysfunction caused by idiopathic complete left bundle branch block.

OBJECTIVE: This study aimed to investigate the feasibility and effectiveness of transthoracic epicardial dual-chamber pacemaker implantation in the treatment of cardiac dysfunction caused by idiopathic complete left bundle branch block (CLBBB) in children. METHODS: Nine children diagnosed with cardiac dysfunction due to idiopathic CLBBB were included in this study. All patients underwent transthoracic epicardial dual-chamber pacemaker implantation. Cardiac function was evaluated using echocardiography during the follow-up. Additionally, intraventricular synchronization parameters were assessed using two-dimensional speckle tracking echocardiography (STE). RESULTS: Nine children (mean age, 3.0 ± 2.6 years) were included in this study. The median follow-up duration was 2 (interquartile range, 1-3) years. The cardiac function of all patients recovered to normal levels within 1 year postoperatively. The postoperative QRS duration on electrocardiography (142 ± 21 ms) was significantly shorter than that at baseline (106 ± 12 ms) (p < .05). Cardiac dyssynchrony in patients who manifested preoperatively achieved complete correction after pacemaker implantation. The comparison of preoperative and postoperative (last follow-up visit) synchronization parameters were as follows: longitudinal standard deviation of the time to peak strain, 99.0 ± 41.9 versus 36.8 ± 5.0 ms (p = .004); delay time of peak longitudinal strain, 252.2 ± 131.4 versus 35.0 ± 22.9 ms (p = .002); and longitudinal systolic dyssynchrony index, 2.8 ± 0.8% versus 1.0 ± 0.3% (p = .001), respectively. CONCLUSION: Transthoracic epicardial dual-chamber pacemaker implantation (with left atrial sensing and left ventricular single-site pacing) can be used for the treatment of cardiac dysfunction caused by idiopathic CLBBB in children.

Tumor microenvironment-activated Nb2C quantum dots/lactate oxidase nanocatalyst mediates lactate consumption and macrophage repolarization for enhanced chemodynamic therapy.

Chemodynamic therapy (CDT), which takes advantages of CDT agents to selectively induce tumor cells apoptosis via Fenton or Fenton-like reactions, is considered to have great potential for tumor-specific treatment. However, the therapeutic outcome of CDT still faces the challenges of the lack of efficient CDT agents and insufficient supply of endogenous H2O2. Herein, to explore highly efficient CDT agents as well as increase the H2O2 content at tumor sites to enhance the efficiency of CDT, a red blood cell (RBC) membrane encapsulated Nb2C quantum dots/lactate oxidase (LOD) nanocatalyst (Nb2C QDs/LOD@RBC) was proposed. Nb2C quantum dots are quite prospective as efficient CDT agents in CDT application due to the intrinsic merits such as abundant active catalytic sites, satisfactory hydrophilicity, and good biocompatibility. The encapsulation of Nb2C QDs and LOD into RBC membrane was to prolong the in vivo circulation time of the nanocatalyst and increase its tumor sites accumulation. The accumulated Nb2C QDs/LOD@RBC nanocatalyst could efficiently convert the endogenous H2O2 into ·OH, while the overexpressed lactate could be catalyzed into H2O2 by LOD to replenish the depletion of H2O2. The cascaded reaction between Nb2C quantum dots and LOD eventually enhanced the CDT effect of Nb2C QDs/LOD@RBC nanocatalyst for tumors growth inhibition. Moreover, the consumption of lactate at tumor sites induced by Nb2C QDs/LOD@RBC nanocatalyst leads to the increased infiltration of antitumoral M1 tumor-associated macrophages, which alleviated the immunosuppression of the tumor microenvironment and further maximized the therapeutic outcome of CDT. Taken together, the Nb2C QDs/LOD@RBC nanocatalyst provides a promising paradigm for tumor inhibition via catalytic cascaded reaction between Nb2C quantum dots and LOD.

Surgical procedure long terms recognition from Chinese literature incorporating structural feature.

With rapid development of technologies in medical diagnosis and treatment, the novel and complicated concepts and usages of clinical terms especially of surgical procedures have become common in daily routine. Expected to be performed in an operating room and accompanied by an incision based on expert discretion, surgical procedures imply clinical understanding of diagnosis, examination, testing, equipment, drugs and symptoms, etc., but terms expressing surgical procedures are difficult to recognize since the terms are highly distinctive due to long morphological length and complex linguistics phenomena. To achieve higher recognition performance and overcome the challenge of the absence of natural delimiters in Chinese sentences, we propose a Named Entity Recognition (NER) model named Structural-SoftLexicon-Bi-LSTM-CRF (SSBC) empowered by pre-trained model BERT. In particular, we pre-trained a lexicon embedding over large-scale medical corpus to better leverage domain-specific structural knowledge. With input additionally augmented by BERT, rich multigranular information and structural term information is transferred from Structural-SoftLexicon to downstream model Bi-LSTM-CRF. Therefore, we could get a global optimal prediction of input sequence. We evaluate our model on a self-built corpus and results show that SSBC with pre-trained model outperforms other state-of-the-art benchmarks, surpassing at most 3.77% in F1 score. This study hopefully would benefit Diagnostic Related Groups (DRGs) and Diagnosis Intervention Package (DIP) grouping system, medical records statistics and analysis, Medicare payment system, etc.

Cytoplasmic SIRT6-mediated ACSL5 deacetylation impedes nonalcoholic fatty liver disease by facilitating hepatic fatty acid oxidation.

Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive hepatic lipid accumulation, which can progress to nonalcoholic steatohepatitis (NASH). Histone deacetylase Sirtuin 6 (SIRT6) regulates NAFLD by regulating metabolism-related gene expression, but an extrachromosomal role for SIRT6 in NAFLD development remains elusive. We investigated whether SIRT6 functions on NAFLD in the cytoplasm. We found that SIRT6 binds saturated fatty acids, especially palmitic acid. This binding leads to its nuclear export, where it deacetylates long-chain acyl-CoA synthase 5 (ACSL5), thereby facilitating fatty acid oxidation. High-fat diet-induced NAFLD is suppressed by ACSL5 hepatic overexpression but is exacerbated by its depletion. As confirmation, overexpression of a deacetylated ACSL5 mimic attenuated NAFLD in Sirt6 liver-specific knockout mice. Moreover, NASH-hepatic tissues from both patients and diet-fed mice exhibited significantly reduced cytoplasmic SIRT6 levels and increased ACSL5 acetylation. The SIRT6/ACSL5 signaling pathway has a critical role in NAFLD progression and might constitute an avenue for therapeutic intervention.

Degradable Multifunctional Porphyrin-Based Porous Organic Polymer Nanosonosensitizer for Tumor-Specific Sonodynamic, Chemo- and Immunotherapy.

Sonodynamic therapy (SDT) benefiting from its intrinsic merits, such as noninvasiveness and deep tissue penetrability, is receiving increasing considerable attention in reactive oxygen species (ROS)-based tumor treatment. However, current sonosensitizers usually suffer from low tumor lesion accumulation, insufficient ROS generation efficiency under ultrasound, and non-biodegradability, which seriously impede the therapeutic outcomes. Additionally, it is difficult that SDT alone can completely eradicate tumors because of the complex and immunosuppressive tumor microenvironment (TME). Herein, we simultaneously employ sonosensitive porphyrin building blocks and glutathione (GSH)-responsive disulfide bonds to construct a novel degradable multifunctional porphyrin-based hollow porous organic polymer (POP) nanosonosensitizer (H-Pys-HA@M/R), which combine SDT, "on-demand" chemotherapy, and immunotherapy. Taking the unique advantages of POPs with designable structures and high specific surface area, this H-Pys-HA@M/R nanosonosensitizer can achieve tumor target accumulation, GSH-triggered drug release, and low-frequency ultrasound-activating ROS generation with encouraging results. Furthermore, this multifunctional nanosonosensitizer can effectively evoke immunogenic cell death (ICD) response through the combination of SDT and chemotherapy for both primary and distal tumor growth suppression. Meanwhile, H-Pys-HA@M/R exhibits favorable biodegradation and biosafety. Therefore, this study provides a new strategy for reasonably designing and constructing POP-related sonosensitizers combining SDT/chemotherapy/immunotherapy triple treatment modalities to eradicate malignant tumors.