Prediction of Ablation Rate for High-Intensity Focused Ultrasound Therapy of Adenomyosis in MR Images Based on Multi-model Fusion.

This study aimed to develop a model based on radiomics and deep learning features to predict the ablation rate in patients with adenomyosis undergoing high-intensity focused ultrasound (HIFU) therapy. A total of 119 patients with adenomyosis who received HIFU therapy were retrospectively analyzed. Participants were included in the training and testing queues in a 7:3 ratio. Radiomics features were extracted from T2-weighted imaging (T2WI) images, and VGG-19 was used to extract advanced deep features. An ensemble model based on multi-model fusion for predicting the efficacy of HIFU in adenomyosis was proposed, which consists of four base classifiers and was evaluated using accuracy, precision, recall, F-score, and area under the receiver operating characteristic curve (AUC). The predictive performance of the combined model combining radiomics and deep learning features outperformed the radiomics and deep learning feature models alone, with accuracy of 0.848 and 0.814 in training and test sets, and AUC of 0.916 and 0.861, respectively. Compared with the base classifiers that make up the multi-model fusion model, the fusion model also exhibited better prediction performance. The fusion model incorporating both radiomics and deep learning features had certain predictive value for the ablation rate of adenomyosis under HIFU therapy and could help select patients with adenomyosis who would benefit from HIFU therapy.

Source analysis and health risk assessment of polycyclic aromatic hydrocarbon (PAHs) in total suspended particulate matter (TSP) from Bengbu, China.

The polycyclic aromatic hydrocarbon (PAH) concentrations in total suspended particulate matter (TSP) samples collected from October, 2021 to September, 2022 were analyzed to clarify the pollution characteristics and sources of 16 PAHs in the atmospheric TSP in Bengbu City. The ρ(PAHs) concentrations ranged from 1.71 to 43.85 ng/m3 and higher concentrations were detected in winter, followed by spring, autumn, and summer. The positive matrix factorization analysis revealed that, in spring and summer, PAH pollution was caused mainly by industrial emissions, gasoline and diesel fuel combustion, whereas in autumn and winter, it was coal, biomass and natural gas combustion. The cluster and potential source factor analyses showed that long-range transport was a significant factor. During spring, autumn, and winter, the northern and northwestern regions had a significant impact, whereas the coastal area south of Bengbu had the greatest influence in summer. The health risk assessment revealed that the annual total carcinogenic equivalent concentration values for PAHs varied from 0.0159 to 7.437 ng/m3, which was classified as moderate. Furthermore, the annual incremental lifetime cancer risk values ranged from 1.431 × 10-4 to 3.671 × 10-3 for adults and from 6.823 × 10-5 to 1.749 × 10-3 for children, which were higher than the standard.

Multitask prediction models for serous ovarian cancer by preoperative CT image assessments based on radiomics.

Objective: High-grade serous ovarian cancer (HGSOC) has the highest mortality rate among female reproductive system tumors. Accurate preoperative assessment is crucial for treatment planning. This study aims to develop multitask prediction models for HGSOC using radiomics analysis based on preoperative CT images. Methods: This study enrolled 112 patients diagnosed with HGSOC. Laboratory findings, including serum levels of CA125, HE-4, and NLR, were collected. Radiomic features were extracted from manually delineated ROI on CT images by two radiologists. Classification models were developed using selected optimal feature sets to predict R0 resection, lymph node invasion, and distant metastasis status. Model evaluation was conducted by quantifying receiver operating curves (ROC), calculating the area under the curve (AUC), De Long's test. Results: The radiomics models applied to CT images demonstrated superior performance in the testing set compared to the clinical models. The area under the curve (AUC) values for the combined model in predicting R0 resection were 0.913 and 0.881 in the training and testing datasets, respectively. De Long's test indicated significant differences between the combined and clinical models in the testing set (p = 0.003). For predicting lymph node invasion, the AUCs of the combined model were 0.868 and 0.800 in the training and testing datasets, respectively. The results also revealed significant differences between the combined and clinical models in the testing set (p = 0.002). The combined model for predicting distant metastasis achieved AUCs of 0.872 and 0.796 in the training and test datasets, respectively. The combined model displayed excellent agreement between observed and predicted results in predicting R0 resection, while the radiomics model demonstrated better calibration than both the clinical model and combined model in predicting lymph node invasion and distant metastasis. The decision curve analysis (DCA) for predicting R0 resection favored the combined model over both the clinical and radiomics models, whereas for predicting lymph node invasion and distant metastasis, DCA favored the radiomics model over both the clinical model and combined model. Conclusion: The identified radiomics signature holds potential value in preoperatively evaluating the R0, lymph node invasion and distant metastasis in patients with HGSC. The radiomics nomogram demonstrated the incremental value of clinical predictors for surgical outcome and metastasis estimation.

MRI Plain Scan: A Tool in the Management of Cervical Cancer during Pregnancy.

OBJECTIVE: The purpose of this study was to assess the diagnostic value of magnetic resonance imaging (MRI) in staging and treatment of cervical cancer in pregnancy, and to evaluate the benefit of apparent diffusion coefficient (ADC) during neoadjuvant chemotherapy management. MATERIALS AND METHODS: This was a retrospective cohort study. Patients were divided into two groups according to the stage of cervical cancer. The mean term of pregnancy at the time of the diagnosis was the early second trimester (range 10-27 weeks) and the median age was 33 years (range 26-40 years). The abdominal and pelvic MRI images and clinical data of these patients were reviewed. Tumor size, local tumor spread, and nodal involvement were evaluated using an MRI dataset. The treatment and follow-up imaging were analyzed as well, and the ADC was measured before and after the chemotherapy. RESULTS: 16 patients with histopathologically confirmed cervical cancer during pregnancy were retrospectively enrolled. 7 patients were diagnosed with local cervical cancer (FIGO stage IAI) and designated as early stage group, as the lesion was invisible on MRI. In this group, pregnancies were allowed to continue until cesarean delivery (CD) at 38-41 weeks. The other 9 patients presenting with local or extensive cervical cancer (FIGO stage IB2-IIA2) were designated as the advanced-stage group. The lesion could be measured and analyzed on MRI. They were treated with neoadjuvant chemotherapy in pregnancy. Among them, 6 patients underwent TP regimen (paclitaxel 135~175 mg/m2 plus cisplatin 70~75 mg/m2), while 3 patients received TC regimen (paclitaxel 135~175 mg/m2 plus carboplatin AUC=5). NACT was performed for 1 to 2 courses before surgery. ADC demonstrated significant differences before and after chemotherapy administered during pregnancy (1.06 ± 0.12 sec/mm2 vs. 1.34 ± 0.21 sec/mm2). CONCLUSION: MRI has been found to be helpful in staging cervical cancer in pregnancy. Patients with stage IA confirmed by MRI can choose conservative treatment and continue the pregnancy until term birth. MRI can dynamically monitor the efficacy of chemotherapy for patients with stage IB and above during pregnancy. ADC value can have a potential role in the evaluation of chemotherapy efficacy.

Intratumoral and peritumoral MRI radiomics nomogram for predicting parametrial invasion in patients with early-stage cervical adenocarcinoma and adenosquamous carcinoma.

OBJECTIVE: To develop a comprehensive nomogram based on MRI intra- and peritumoral radiomics signatures and independent risk factors for predicting parametrial invasion (PMI) in patients with early-stage cervical adenocarcinoma (AC) and adenosquamous carcinoma (ASC). METHODS: A total of 460 patients with IB to IIB cervical AC and ASC who underwent preoperative MRI examination and radical trachelectomy/hysterectomy were retrospectively enrolled and divided into primary, internal validation, and external validation cohorts. The original (Ori) and wavelet (Wav)-transform features were extracted from the volumetric region of interest of the tumour (ROI-T) and 3mm- and 5mm-peritumoral rings (ROI-3 and ROI-5), respectively. Then the Ori and Ori-Wav feature-based radiomics signatures from the tumour (RST) and 3 mm- and 5 mm-peritumoral regions (RS3 and RS5) were independently built and their diagnostic performances were compared to select the optimal ones. Finally, the nomogram was developed by integrating optimal intra- and peritumoral signatures and clinical independent risk factors based on multivariable logistic regression analysis. RESULTS: FIGO stage, disruption of the cervical stromal ring on MRI (DCSRMR), parametrial invasion on MRI (PMIMR), and serum CA-125 were identified as independent risk factors. The nomogram constructed by integrating independent risk factors, Ori-Wav feature-based RST, and RS5 yielded AUCs of 0.874 (0.810-0.922), 0.885 (0.834-0.924), and 0.966 (0.887-0.995) for predicting PMI in the primary, internal and external validation cohorts, respectively. Furthermore, the nomogram was superior to radiomics signatures and clinical model for predicting PMI in three cohorts. CONCLUSION: The nomogram can preoperatively, accurately, and noninvasively predict PMI in patients with early-stage cervical AC and ASC. CLINICAL RELEVANCE STATEMENT: The nomogram can preoperatively, accurately, and noninvasively predict PMI and facilitate precise treatment decisions regarding chemoradiotherapy or radical hysterectomy in patients with early-stage cervical AC and ASC. KEY POINTS: The accurate preoperative prediction of PMI in early-stage cervical AC and ASC can facilitate precise treatment decisions regarding chemoradiotherapy or radical hysterectomy. The nomogram integrating independent risk factors, Ori-Wav feature-based RST, and RS5 can preoperatively, accurately, and noninvasively predict PMI in early-stage cervical AC and ASC. The nomogram was superior to radiomics signatures and clinical model for predicting PMI in early-stage cervical AC and ASC.

Weakly supervised segmentation of uterus by scribble labeling on endometrial cancer MR images.

Uterine segmentation of endometrial cancer MR images can be a valuable diagnostic tool for gynecologists. However, uterine segmentation based on deep learning relies on artificial pixel-level annotation, which is time-consuming, laborious and subjective. To reduce the dependence on pixel-level annotation, a method of weakly supervised uterine segmentation on endometrial cancer MRI slices is proposed, which only requires scribble label and is enhanced by pseudo-label technology, exponential geodesic distance loss and input disturbance strategy. Specifically, the limitations caused by the shortage of supervision are addressed by dynamically mixing the two outputs of the dual branch network to generate pseudo-labels, expanding supervision information and promoting mutual supervision training. On the other hand, considering the large difference of grayscale intensity between the uterus and surrounding tissues, the exponential geodesic distance loss is introduced to enhance the ability of the network to capture the edge of the uterus. Input disturbance strategies are incorporated to adapt to the flexible and variable characteristics of the uterus and further improve the segmentation performance of the network. The proposed method is evaluated on MRI images from 135 cases of endometrial cancer. Compared with other four weakly supervised segmentation methods, the performance of the proposed method is the best, whose mean DI, HD95, Recall, Precision, ADP are 92.8%, 11.632, 92.7%, 93.6%, 6.5% and increasing by 2.1%, 9.144, 0.6%, 2.4%, 2.9% respectively. The experimental results demonstrate that the proposed method is more effective than other weakly supervised methods and achieves similar performance as those fully supervised.

Prenatal Magnetic Resonance Imaging helps Discover Cerebellar Dysplasia or Malformations in Foetuses.

OBJECTIVE: This study aimed to characterize and assess the diagnostic value of prenatal magnetic resonance (MR) imaging in detecting fetal cerebellar hypoplasia/dysplasia and developmental malformations. METHODS: Reports of suspected intracranial abnormalities were retrospectively collected on ultrasound screening (US), and MR images of fetuses were reviewed at our institution over a 5-year period on picture archiving and communication system (PACS) servers. Two experienced radiologists recorded major abnormalities and coexisting abnormalities at the reading of the census. The results of the MRI were compared against the US in each case. RESULTS: For prenatal MR imaging, we enlisted a total of 121 patients (mean gestational week, 24.5 ± 4.7 weeks). This included 28 cases with normal findings of MR imaging, 62 cases with findings of cerebellar hypoplasia or dysplasia, and the remaining 31 cases with other abnormities findings. Cerebral malformations cases included agenesis of the corpus callosum, cerebral hemorrhage, hydrocephalus, holoprosencephaly, ventriculomegaly, and brainstem/gyri malformation. Cerebellar abnormalities included vermis absence, cerebellar tonsil hernia, Dandy-Walker malformation, Blake's pouch cysts, arachnoid cysts, and intracranial hemorrhage. Other systemic malformation cases included tethered cord syndromes (9 cases), cleft lip and palate (1 case), club foot (1 case), and cardiac malformation (1 case). In 12 cases (24.5%), compared to the US, MR imaging proved the value of confirming the diagnosis and/or even yielded more findings on abnormalities. CONCLUSION: Prenatal MR imaging can better visualize systemic malformations coexisting with cerebellar abnormalities. MR imaging, a complementary means to the US, can aid in prenatal counseling and treatment selection for term delivery.

IFNγ synergies with cold atmospheric plasma in triggering colorectal cancer cell ferroptosis via the IFNγ/IFNR2/APC/TCF4/GPX4 axis.

Colorectal cancer accounts for the second most common cancer-related lethality. Intestinal stem cells are responsible for enteric homeostasis maintenance that, once being transformed, become colorectal cancer stem cells. Arresting cancer stemness represents an innovative strategy for colorectal cancer management. Using intestinal stem cell organoids as the primary model, we screened common inflammatory cytokines to identify key players targeting cancer stemness. We also explored the downstream signaling that drives the functionalities of the identified cytokine through both experimental investigations and computational predictions. As the results, we identified IFNγ as the key cytokine capable of arresting intestinal stem cells via the IFNγ/IFNGR2/APC/TCF4/GPX4 axis, proposed its role in killing colorectal cancer stem cells via triggering GPX4-dependent ferroptosis, and demonstrated its synergistic anti-cancer effect with cold atmospheric plasma in killing colorectal cancer cells that is worthy to be experimentally validated.

Complex Blood Supply Patterns in Cesarean Scar Pregnancy: Insights from Digital Subtraction Angiography Imaging.

BACKGROUND Understanding the blood supply pattern of cesarean scar pregnancy (CSP) can effectively help to determine the best choice of treatment. The aim of this study was to investigate the blood supply pattern and outcomes of patients with CSP through digital subtraction angiography (DSA) imaging. MATERIAL AND METHODS This was a retrospective cohort study. Patients were divided into 2 groups according to the type of CSP. The DSA images of these patients were reviewed, including the type of blood supply, dominant vessel, and collateral blood supply to the gestational sac. The clinical outcomes were analyzed between the 2 groups. RESULTS Thirty-seven patients with type I and 29 patients with type II CSP were enrolled in this study. Type II CSP showed a higher proportion of rich blood supply than type I (44.83% vs 29.72%, P>0.05). Compared with type II CSP, type I CSP tended to have bilateral dominant blood supply predominance (67.57% vs 41.38%, P<0.05). The incidence of collateral blood supply was 5.41% in the type I CSP group and 31.03% in the type II CSP group (P<0.05). In the type II CSP group, multiple collateral blood vessels were found in 4 patients. The superior vesicle artery was the most common source of collateral blood supply in both groups. Two patients with type II CSP suffered massive bleeding during surgery after uterine artery embolization (UAE). None of the patients received a hysterectomy. CONCLUSIONS UAE is safe and effective for both types of CSP. The blood supply pattern is more complex and abnormal in type II CSP. More attention should be paid to the collateral blood supply to achieve complete embolization during the UAE procedure in the case of type II CSP.

Deep Learning Nomogram for the Identification of Deep Stromal Invasion in Patients With Early-Stage Cervical Adenocarcinoma and Adenosquamous Carcinoma: A Multicenter Study.

BACKGROUND: Deep stromal invasion (DSI) is one of the predominant risk factors that determined the types of radical hysterectomy (RH). Thus, the accurate assessment of DSI in cervical adenocarcinoma (AC)/adenosquamous carcinoma (ASC) can facilitate optimal therapy decision. PURPOSE: To develop a nomogram to identify DSI in cervical AC/ASC. STUDY TYPE: Retrospective. POPULATION: Six hundred and fifty patients (mean age of 48.2 years) were collected from center 1 (primary cohort, 536), centers 2 and 3 (external validation cohorts 1 and 2, 62 and 52). FIELD STRENGTH/SEQUENCE: 5-T, T2-weighted imaging (T2WI, SE/FSE), diffusion-weighted imaging (DWI, EPI), and contrast-enhanced T1-weighted imaging (CE-T1WI, VIBE/LAVA). ASSESSMENT: The DSI was defined as the outer 1/3 stromal invasion on pathology. The region of interest (ROI) contained the tumor and 3 mm peritumoral area. The ROIs of T2WI, DWI, and CE-T1WI were separately imported into Resnet18 to calculate the DL scores (TDS, DDS, and CDS). The clinical characteristics were retrieved from medical records or MRI data assessment. The clinical model and nomogram were constructed by integrating clinical independent risk factors only and further combining DL scores based on primary cohort and were validated in two external validation cohorts. STATISTICAL TESTS: Student's t-test, Mann-Whitney U test, or Chi-squared test were used to compare differences in continuous or categorical variables between DSI-positive and DSI-negative groups. DeLong test was used to compare AU-ROC values of DL scores, clinical model, and nomogram. RESULTS: The nomogram integrating menopause, disruption of cervical stromal ring (DCSRMR), DDS, and TDS achieved AU-ROCs of 0.933, 0.807, and 0.817 in evaluating DSI in primary and external validation cohorts. The nomogram had superior diagnostic ability to clinical model and DL scores in primary cohort (all P < 0.0125 [0.05/4]) and CDS (P = 0.009) in external validation cohort 2. DATA CONCLUSION: The nomogram achieved good performance for evaluating DSI in cervical AC/ASC. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Pharmacological mechanism of quercetin in the treatment of colorectal cancer by network pharmacology and molecular simulation.

Colorectal cancer is a serious threat to people's life due to its high incidence and high mortality. Quercetin can effectively treat colorectal carcinoma (CRC), but its exact mechanism of action is still unclear. Then quercetin-related target genes were obtained from Swiss Target Prediction database and Similarity Ensemble Approach (SEA) database, and CRC-related target genes were obtained from GeneCards database, respectively. Common target genes were obtained by FunRich software. String software was used to construct a protein-protein interaction (PPI) network. R package was used for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Molecular docking, molecular dynamics (MD) simulation and post-dynamics simulation were used to explore the binding stability of quercetin to key targets. In total, 103 and 141 target information of quercetin were obtained from the Swiss Target Prediction database and SEA database, respectively. 1,649 CRC-related genes were obtained from GeneCards database. FunRich software was used to draw venny map and obtain 36 intersection targets of quercetin and CRC. String software was used to construct the PPI network. The core genes were AKT1, EGFR, MMP9, KDR, MET and PTK2. There were 532 items related to biological processes, 14 items related to cellular components, and 43 items related to molecular functions among the key target GO enrichment items. KEGG enrichment pathways of key targets involved cancer pathways, PI3K-Akt signal pathway, etc. The results of molecular docking, MD simulation and post-dynamics simulation showed they had a good affinity and formed a stable effect. So quercetin may play an important role in the treatment of CRC by acting on AKT1, EGFR, MMP9, KDR, MET and PTK2 to affect the development of CRC.Communicated by Ramaswamy H. Sarma.

Effect of post-extubation high-flow nasal cannula combined with respiratory training versus conventional oxygen therapy on postoperative pulmonary complications in patients after major abdominal surgery: protocol for a single-centre randomized controlled trial.

BACKGROUND: Nearly 234 million patients undergo surgery each year, and 1.3 million among them develop complications. Patients undergoing major upper abdominal surgery (operation time > 2 h) have a really high incidence of postoperative pulmonary complications (PPCs). The occurrence of PPCs seriously affects the outcomes of patients. High-flow nasal cannula (HFNC) is as effective as noninvasive ventilation (NIV) in preventing postoperative hypoxaemia and respiratory failure. Respiratory training using positive expiratory pressure (PEP) Acapella (Choice) has been shown to help patients with rapid recovery from postoperative atelectasis. However, no relevant randomized controlled studies have been conducted to clarify the effect of HFNC combined with respiratory training in the prevention of PPCs. This study aims to investigate whether the use of HFNC combined with respiratory training could reduce the incidence of PPCs within 7 days after major upper abdominal surgery compared to that with conventional oxygen therapy (COT). METHODS: This is a randomized controlled single-centre trial. A total of 328 patients who undergo major abdominal surgery will be included. Subjects who fulfil the eligible criteria will be randomly assigned into the combination treatment group (Group A) or COT group (Group B) after extubation. The interventions will begin within 30 min of extubation. Patients in Group A will receive HFNC for at least 48 h and respiratory training three times a day for at least 72 h. Patients in Group B will receive oxygen therapy through a nasal catheter or mask for at least 48 h. Our primary endpoint is the incidence of PPCs within 7 days, and the secondary outcome measures include 28-day mortality, reintubation rate, length of hospital stay, and all-cause mortality within 1 year. DISCUSSION: This trial would help provide evidence on the effectivity of applying HFNC combined with respiratory training for the prevention of PPCs in patients undergoing major upper abdominal surgery. The objective of this study is to determine the optimal treatment approach to improve the prognosis of patients undergoing surgery. TRIAL REGISTRATION: ChiCTR2100047146. Registered on 8 June 2021. Retrospectively registered.

Formation of Amorphous Iron-Calcium Phosphate with High Stability.

Amorphous iron-calcium phosphate (Fe-ACP) plays a vital role in the mechanical properties of teeth of some rodents, which are very hard, but its formation process and synthetic route remain unknown. Here, the synthesis and characterization of an iron-bearing amorphous calcium phosphate in the presence of ammonium iron citrate (AIC) are reported. The iron is distributed homogeneously on the nanometer scale in the resulting particles. The prepared Fe-ACP particles can be highly stable in aqueous media, including water, simulated body fluid, and acetate buffer solution (pH 4). In vitro study demonstrates that these particles have good biocompatibility and osteogenic properties. Subsequently, Spark Plasma Sintering (SPS) is utilized to consolidate the initial Fe-ACP powders. The results show that the hardness of the ceramics increases with the increase of iron content, but an excess of iron leads to a rapid decline in hardness. Calcium iron phosphate ceramics with a hardness of 4 GPa can be achieved, which is higher than that of human enamel. Furthermore, the ceramics composed of iron-calcium phosphates show enhanced acid resistance. This study provides a novel route to prepare Fe-ACP, and presents the potential role of Fe-ACP in biomineralization and as starting material to fabricate acid-resistant high-performance bioceramics.

Clinical Value of Platelets and Coagulation Parameters in Predicting the Severity of Delta Variant SARS-CoV-2.

INTRODUCTION: The present study aimed to analyze the clinical features and laboratory markers of patients with Delta variant SARS-CoV-2 and explore the role of platelet in predicting the severity of Delta. METHODS: This retrospective, observational study was conducted on 863 patients laboratory-confirmed Delta variant SARS-CoV-2. These cases were sub-classified based on disease severity into mild (n = 304), moderate (n = 537), and severe (n = 22). A series of laboratory findings and clinical data were collected and analyzed during hospitalization. RESULTS: Of 863 hospitalized patients with Delta, the median age was 38 years (interquartile range, 30-51 years) and 471 (54.58%) were male. The most common clinical symptoms mainly included cough, fever, pharyngalgia, expectoration, dyspnea, fatigue, and headache, and the commonest comorbidities were hypertension and diabetes. Among the hematological variables, neutrophil count, red blood cell count, and hemoglobin, were found to be statistically significant with regard to subcategories based of disease severity (p < 0.05). Among coagulation parameters, there was a statistically significant difference in D-dimer, fibrinogen, international normalized ratio, and prothrombin time (p < 0.05). Statistically significant differences were observed in platelet markers including platelet count, large platelet count, and plateletcrit (p < 0.05). Additionally, there was strong correlation between platelet and other parameters with disease severity. Logistical regression analysis and ROC curves showed that D-dimer was a single best marker of disease severity (p = 0.005, p < 0.0001); however, platelet (p = 0.009, p = 0.002) and plateletcrit (p = 0.002, p = 0.001) could also predict severe disease. Platelet was identified as an independent risk factor for severe Delta. CONCLUSION: Low platelet may be a marker of disease severity in Delta variant SARS-CoV-2 and may contribute to determine the severity of patients infected with Delta.

Elastin-Derived VGVAPG Fragment Decorated Cell-Penetrating Peptide with Improved Gene Delivery Efficacy.

Cell-penetrating peptides (CPPs) are attractive non-viral gene delivery vectors due to their high transfection capacity and safety. Previously, we have shown that cell-penetrating peptide RALA can be a promising gene delivery vector for chronic wound regeneration application. In this study, we engineered a novel peptide called RALA-E by introducing elastin-derived VGVAPG fragment into RALA, in order to target the elastin-binding protein on the cell surface and thus improve delivery efficacy of RALA. The transfection efficiency of RALA-E was evaluated by transfecting the HEK-293T and HeLa cell lines cells with RALA-E/pDNA complexes and the flow-cytometry results showed that RALA-E significantly increased the transfection efficiency by nearly 20% in both cell lines compared to RALA. Inhibition of pDNA transfection on HEK-293T cells via chlorpromazine, genistein and mßCD showed that the inhibition extent in transfection efficiency was much less for RALA-E group compared to RALA group. In addition, RALA-E/miR-146a complexes showed up to 90% uptake efficiency in macrophages, and can escape from the endosome and enter the nucleus to inhibit the expression of inflammation genes. Therefore, the developed RALA-E peptide has high potential as a safe and efficient vector for gene therapy application.

Three-dimensional quantitative structural-activity relationship and molecular dynamics study of multivariate substituted 4-oxyquinazoline HDAC6 inhibitors.

3D-QSAR models were established by collecting 46 multivariate-substituted 4-oxyquinazoline HDAC6 inhibitors. The relationship of molecular structure and inhibitory activity was studied by comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA). The results showed the models established by CoMFA (q2 = 0.590, r2 = 0.965) and CoMSIA (q2 = 0.594, r2 = 0.931) had good prediction ability. At the same time, 3D-QSAR models met the internal verification, external verification and AD test. Ten new compounds were designed based on CoMFA and CoMSIA contour maps and their pharmacokinetic/toxic properties (ADME/T) were evaluated. It was found that most compounds have well safety profile and pharmacokinetic property. Then, we explored the interaction between HDAC6 and compounds by molecular docking. The results showed that the binding mode of the new compounds with HDAC6 was the same as the template compound 46, and the hydrogen bond and hydrophobic bond played a vital role in the binding process. Molecular dynamics simulation results showed that residues Ser531, His574 and Tyr745 played key roles in the binding process. All newly designed compounds had lower energy gap and binding energy than compound 46 according to DFT analysis and free energy analysis. This study provided a theoretical reference for designing compounds of higher activity and a new idea for the development of novel HDAC6 inhibitors.

Familial mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode syndrome: Three case reports.

BACKGROUND: Mitochondrial encephalomyopathy (ME) is a multisystem metabolic disease that primarily affects the central nervous system and skeletal muscle. It is caused by mutations in mitochondrial or nuclear DNA, resulting in abnormal mitochondrial structure and function and insufficient ATP synthesis. The most common subtype is mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episode (MELAS) syndrome. In recent years, reports of MELAS syndrome have increased but familial cases are rare. CASE SUMMARY: We report a case of familial MELAS syndrome. Cases 2 and 3 are sisters and case 1 is their nephew. All are short in stature and showed stroke-like episodes with rapid onset and no obvious symptoms such as paroxysmal headache, aphasia, or blurred vision. After admission, blood lactate levels were significantly higher than normal. The patients underwent magnetic resonance imaging of the head. Cases 1 and 2 were considered to have ME, whereas case 3 was considered to have a space-occupying lesion in the left temporal lobe. Pathological evaluation showed no obvious tumor cells in the brain lesions of case 3. Muscle biopsy or genetic test results were consistent with ME. The patients were diagnosed with MELAS syndrome and their symptoms improved with intravenous infusions of coenzyme Q10, coenzyme A, vitamin B, and vitamin C. At the 6 mo follow-up, there was no recurrence or progression. CONCLUSION: When a patient has MELAS syndrome, familial MELAS syndrome should be considered if related family members have similar symptoms.

Microwave-Induced Deep Catalytic Oxidation of NO Using Molecular-Sieve-Supported Oxygen-Vacancy-Enriched Fe-Mn Bimetal Oxides.

A novel microwave (MW) catalytic oxidation denitrification method was developed, which can deeply oxidize NO into nitrate/nitrite with little NO2 yield. A molecular-sieve-supported oxygen-vacancy-enriched Fe2O3-MnO2 catalyst (Ov-Fe-Mn@MOS) was fabricated. Physicochemical properties of the catalyst were revealed by various characterization methods. MW irradiation was superior to the conventional heating method in NO oxidation (90.5 vs 70.6%), and MW empowered the catalyst with excellent low-temperature activity (100-200 °C) and good resistance to H2O and SO2. Ion chromatography analysis demonstrated that the amount of nitrate/nitrite accounted for over 90.0% of the N products, but the main product gradually varied from nitrate to nitrite as the reaction proceeded because of the switching of the main reaction path of NO removal. Mechanism analyses clarified that NO oxidation was a non-radical catalytic reaction: (i) the chemisorbed NO on ≡Mn(IV) reacted with O2* to produce nitrate and (ii) the excited NO* due to MW irradiation reacted with the active O* generated from Ov···O2 to form nitrite. Density functional theory calculations combined with electron paramagnetic resonance tests revealed the promotional effects of Fe2O3 in (i) boosting the Ov's quantity; (ii) facilitating O2 adsorption; (iii) increasing the nitrite formation; and (iv) alleviating the suppression of SO2.

Suprasellar cistern tuberculoma presenting as unilateral ocular motility disorder and ptosis: A case report.

BACKGROUND: Intracranial tuberculoma is a rare and serious type of tuberculosis, which mostly occurs in the frontoparietal and cerebellar hemispheres, with predominance in the gray-white matter junction area, while tuberculomas only in the cistern are extremely rare with only a few reported cases in the literature. We describe a unique case of isolated tuberculoma in the suprasellar cistern, with only right ocular motility disorder and upper eyelid ptosis. CASE SUMMARY: A 5-year-old boy without any medical history presented with right ocular motility disorder and upper eyelid ptosis one month ago. He had no history of fever, headache, vomiting, convulsions, or limb weakness. Neurological examination showed right third cranial nerve palsy with restrictions of eye movements and ptosis, pupil dilation and negative light reflex. Imaging suggested a space-occupying lesion in the suprasellar cistern with calcification and ring-enhancement. Moreover, no Mycobacterium tuberculosis was found in cerebrospinal fluid by polymerase chain reaction (PCR). The lesion was initially diagnosed as a tumor, while postoperative pathology combined with PCR indicated tuberculoma. The patient continued postoperative anti-tuberculosis treatment. At present, the patient's condition is stable and the symptoms are partially relieved compared with those before surgery. CONCLUSION: This case confirmed that isolated intracranial tuberculoma can occur in the suprasellar cistern. Therefore, for space-occupying lesions in the suprasellar cistern, tuberculoma should be included in the differential diagnosis even if there is no history or indication of tuberculosis infection.

Thermal-Switchable, Trifunctional Ceramic-Hydrogel Nanocomposites Enable Full-Lifecycle Security in Practical Battery Systems.

Thermal runaway (TR) failures of large-format lithium-ion battery systems related to fires and explosions have become a growing concern. Here, we design a smart ceramic-hydrogel nanocomposite that provides integrated thermal management, cooling, and fire insulation functionalities and enables full-lifecycle security. The glass-ceramic nanobelt sponges exhibit high mechanical flexibility with 80% reversible compressibility and high fatigue resistance, which can firmly couple with the polymer-nanoparticle hydrogels and form thermal-switchable nanocomposites. In the operating mode, the high enthalpy of the nanocomposites enables efficient thermal management, thereby preventing local temperature spikes and overheating under extremely fast charging conditions. In the case of mechanical or thermal abuse, the stored water can be immediately released, leaving behind a highly flexible ceramic matrix with low thermal conductivity (42 mW m-1 K-1 at 200 °C) and high-temperature resistance (up to 1300 °C), thus effectively cooling the TR battery and alleviating the devastating TR propagation. The versatility, self-adaptivity, environmental friendliness, and manufacturing scalability make this material highly attractive for practical safety assurance applications.