Integrated Transcriptomic Landscape and Deep Learning Based Survival Prediction in Uterine Sarcomas.

Purpose: The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the USs. Materials and Methods: Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients. Results: A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), 3 adenosarcomas, 2 carcinosarcomas, and 1 uterine tumor resembling an ovarian sex-cord tumor (UTROSCT). ESS (including high-grade ESS and low-grade ESS) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A - PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uDEGs were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named MMN-MIL showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804. Conclusion: USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients.

High performance molecular iodine optical reference using an unsaturated vapor cell.

We describe a high-performance molecular iodine optical frequency reference that is referenced to the R(56)32-0: a1 hyperfine transition of molecular iodine based on modulation transfer spectroscopy. We design an unsaturated iodine vapor cell with a gas pressure equivalent to the saturation pressure at -17 °C. Using this cell, we developed a compact, frequency-stabilized laser. The iodine cell operates at room temperature and is not actively temperature stabilized. We demonstrate a laser with fractional frequency instability of 1.4 × 10-14 at 1 s and 1.7 × 10-15 at 104 s. To our knowledge, the level of frequency instability at 104 s is comparable to the previously reported best results for an iodine stabilized laser. These results suggest that using an unsaturated iodine vapor cell is a valid approach for the development of long-term, stable iodine-based optical references.

Prognostic value and distribution pattern of tumor infiltrating lymphocytes and their subsets in distant metastases of advanced breast cancer.

BACKGROUND: There are significant correlations between the levels of tumor infiltrating lymphocytes (TILs) and the prognosis of primary breast cancer. While little is known about immunological mechanisms in the distant metastasis of advanced breast cancer. PATIENTS AND METHODS: A total of 106 patients with advanced metastatic breast cancer were enrolled in this study between 2016 and 2022. Hematoxylin and eosin staining and immunohistochemistry were used to assess the densities of stromal TILs (sTILs), intratumoral TILs (iTILs) and invasive marginal TILs (imTILs) and CD4+, CD8+, CD20+, FOXP3+ TILs in the primary tumor and metastasis (bone, lung, liver, and distant lymph node) of advanced breast cancer. RESULTS: Higher levels of sTILs at metastatic sites were associated with better progression-free survival (PFS), postmetastasis survival (PMS) and overall survival (OS) (p = .026, .001 and .005, respectively). The levels of iTILs were significantly lower than those of sTILs and imTILs in both primary tumor (p< .001, both) and metastasis (p< .001, both). The level of CD4+ T cells was higher than those of CD8+ T cells and CD20+ B cells in both primary tumor (p < .001) and metastasis (p < .001). The levels of sTILs (p=0. 001) and imTILs (p< .001) in the primary tumor were generally higher than those in the metastasis. CONCLUSION: The levels of TILs and their subsets can predict the survival and prognosis of patients with advanced breast cancer. The distributions of TILs and their subsets are similar between the primary tumor and metastasis. The metastases have a lower degree of lymphocytes infiltration than its corresponding primary tumor.

A virtual biopsy study of microsatellite instability in gastric cancer based on deep learning radiomics.

OBJECTIVES: This study aims to develop and validate a virtual biopsy model to predict microsatellite instability (MSI) status in preoperative gastric cancer (GC) patients based on clinical information and the radiomics of deep learning algorithms. METHODS: A total of 223 GC patients with MSI status detected by postoperative immunohistochemical staining (IHC) were retrospectively recruited and randomly assigned to the training (n = 167) and testing (n = 56) sets in a 3:1 ratio. In the training set, 982 high-throughput radiomic features were extracted from preoperative abdominal dynamic contrast-enhanced CT (CECT) and screened. According to the deep learning multilayer perceptron (MLP), 15 optimal features were optimized to establish the radiomic feature score (Rad-score), and LASSO regression was used to screen out clinically independent predictors. Based on logistic regression, the Rad-score and clinically independent predictors were integrated to build the clinical radiomics model and visualized as a nomogram and independently verified in the testing set. The performance and clinical applicability of hybrid model in identifying MSI status were evaluated by the area under the receiver operating characteristic (AUC) curve, calibration curve, and decision curve (DCA). RESULTS: The AUCs of the clinical image model in training set and testing set were 0.883 [95% CI: 0.822-0.945] and 0.802 [95% CI: 0.666-0.937], respectively. This hybrid model showed good consistency in the calibration curve and clinical applicability in the DCA curve, respectively. CONCLUSIONS: Using preoperative imaging and clinical information, we developed a deep-learning-based radiomics model for the non-invasive evaluation of MSI in GC patients. This model maybe can potentially support clinical treatment decision making for GC patients.

Osthole, an ingredient from Cnidium monnieri, reduces the pyroptosis and apoptosis in bronchial epithelial cells.

Osthole is the prominent active ingredient isolated from Cnidium. The role of osthole in chronic obstructive pulmonary disease (COPD) was investigated herein. Bronchial epithelial 16HBE cells were exposed to cigarette smoke extract (CSE) to generate injury models. The concentration of CSE had an inverse correlation with cell viability. Osthole suppressed inflammation, oxidative stress, apoptosis, and pyroptosis in 16HBE cells, along with a decrease in RIPK2 level. RIPK2 overexpression reversed the effects of osthole on the abovementioned aspects. This study found that the osthole could reduce RIPK2 level, inhibit pyroptosis, and alleviate the damage in 16HBE cells under CSE stimulation.

Time delay interferometry with a transfer oscillator.

In this work, we experimentally perform time delay interferometry by using a transfer oscillator, which is capable of reducing the laser frequency noise and the clock noise simultaneously in the post processing. The iodine frequency reference is coherently downconverted to the microwave frequency using a laser frequency comb. The residual noise of the downconversion network is 5 × 10-6Hz/Hz1/2 at 0.7 mHz, and 4 × 10-6Hz/Hz1/2 at 0.1 Hz, indicating high homology between the optical frequency and the microwave frequency. We carry out time delay interferometry with the aid of the electrical delay module, which can introduce large time delays. The results show that the laser frequency noise and the clock noise can be reduced simultaneously by ten and three orders of magnitude, respectively, in the frequency band from 0.1 mHz to 0.1 Hz. The performance of the noise reduction can reach 6 × 10-8Hz/Hz1/2 at 0.1 mHz, and 7 × 10-7Hz/Hz1/2 at 1 mHz, meeting the requirements of the space-borne gravitational wave detection. Our work will be able to offer an alternative method for the frequency comb-based time delay interferometry in the future space-borne gravitational wave detectors.

Screen-printed electrode-based biosensors modified with functional nucleic acid probes and their applications in this pandemic age: a review.

Electrochemical methodology has probably been the most used sensing platform in the past few years as they provide superior advantages. In particular, screen-printed electrode (SPE)-based sensing applications stand out as they provide extraordinary miniaturized but robust and user-friendly detection system. In this context, we are focusing on the modification of SPE with functional nucleic acid probes and nanostructures to improve the electrochemical detection performance in versatile sensing applications, particularly in the fight against the COVID-19 pandemic. Aptamers are immobilized on the electrode surface to detect non-nucleic acid targets and complementary probes to recognize and capture nucleic acid targets. In a step further, SPE-based biosensors with the modification of self-assembled DNA nanostructures are emphasized as they offer great potential for the interface engineering of the electrode surface and promote the excellent performance of various interface reactions. By equipping with a portable potentiostat and a smartphone monitoring device, the realization of this SPE-based miniaturized diagnostic system for the further requirement of fast and POC detection is revealed. Finally, more novel and excellent works are previewed and future perspectives in this field are mentioned.

Association of multiple tumor markers with newly diagnosed gastric cancer patients: a retrospective study.

Background: The purpose of this paper was to explore the correlation between multiple tumor markers and newly diagnosed gastric cancer. Methods: We selected 268 newly diagnosed patients with gastric cancer and 209 healthy subjects for correlation research. The detection of multiple tumor markers was based on protein chips and the results were statistically analyzed using SPSS. Results: We concluded that gastric cancer was significantly related to gender, age, alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), carbohydrate antigen 199 (CA199), and carbohydrate antigen 242 (CA242) positive levels (P < 0.001). After CA199 and CA242 were stratified by gender, the male odds ratio (OR) was 30.400 and 31.242, respectively, while the female OR was 3.424. After CA125 was stratified by age in patients over 54 years old with gastric cancer, the risk of occurrence in the CA125-positive population was 16.673 times that of the CA125-negative patients. Among patients 54 years old and younger, being CA125-positive was not a risk factor for gastric cancer (P = 0.082). AFP, CEA, CA125, CA199, and CA242 positive levels during the M1 stage were statistically significant when compared with the M0 stage and control group (P < 0.001), but the AFP (P = 0.045) and CA125 (P = 0.752) positive levels were not statistically significant when compared with the M0 stage and control group. The combined detection sensitivity of multiple tumor markers was 44.78%. Conclusion: Our research shows that gastric cancer is associated with age, gender, and the positive levels of AFP, CEA, CA125, CA199, and CA242. The positive levels of AFP and CA125 were related to the distant metastasis of gastric cancer. To a certain extent, the combined detection sensitivity can be used for the initial screening of gastric cancer.

Factors influencing resident and tourist outdoor thermal comfort: A comparative study in China's cold region.

Thermal comfort and environmental health in scenic open spaces, a communication bridge between tourists and their environment, are prerequisites for tourism activities. In this study, scenic open spaces in an urban area of Xi'an, China were selected. Thermal perception (thermal sensation, comfort and acceptability) of residents and tourists were investigated through meteorological measurement and questionnaire survey. Physiological equivalent temperature (PET) was used to determine thermal benchmarks of all visitors to the site. Variables that influence individual thermal perception assessment (physical, individual, society and psychology) were measured and compared. Finally, a series of strategies and suggestions were proposed based on meteorological characteristics and influencing factors of thermal perception from perspectives of designers and scenic spot managers. Results show that: 1) Neutral PET (NPET) of respondents were 17.3 °C (residents) and 15.5 °C (tourists). Neutral PET ranges (NPETR) were 8.9-25.8 °C (residents) and 7.2-23.8 °C (tourists). Preferred PET values were 20.1 °C (residents) and 19.7 °C (tourists). Thermal acceptability ranges (TAR) were 6.3-37.8 °C (residents) and 0.5-39.9 °C (tourists). 2) In winter, physical factors were primary influencers of residents' thermal perception, followed by social factors, while tourists' thermal perception was mainly influenced by physical factors. In spring, physical factors were still the primary influencers for residents, followed by individual factors. Physical factors were also dominant for tourists, followed by psychological. In summer, physical factors were the major influencing factors for residents and tourists' thermal perceptions.

Applications of electrochemical biosensors based on functional antibody-modified screen-printed electrodes: a review.

The detection of biomolecular analytes is of great importance in clinical, environmental, and argo-food areas, among which the electrochemical methodology is attracting much attention. In particular, screen-printed electrode (SPE)-based sensing applications have exhibited potential possibility for on-site detection, especially for fast clinical biomarker detection, since they provide a miniaturized but robust and portable electrode detection system. In this context, we focused on the modification of SPE with functional antibodies to improve the electrochemical detection performance in versatile sensing applications, particularly for COVID-19 detection. These antibodies were immobilized onto the electrode surface via various methodologies, through which the powerful potential from the modification of SPE was revealed. Finally, more novel and excellent works on the biomolecular modification of SPE and the prospects of this technology from its state-of-art status to commercialization are previewed and future perspectives in this field are mentioned.

Enzyme-responsive micellar JQ1 induces enhanced BET protein inhibition and immunotherapy of malignant tumors.

Bromodomain and extra-terminal (BET) proteins are attractive targets for treating various malignancies including melanoma. The inhibition of BET bromodomains, e.g. with JQ1, is found to downregulate the expression of both c-MYC oncoprotein and programmed cell death ligand 1 (PD-L1), which play a crucial role in tumor growth and the immunosuppressive tumor microenvironment, respectively. The BET bromodomain inhibitors like JQ1 though exhibiting high selectivity and affinity show usually low bioavailability and efficacy in vivo due to fast clearance and inferior uptake by tumor cells. The therapeutic effect of JQ1 might further be lowered by drug resistance. Here, enzyme-responsive micellar JQ1 (mJQ1) was fabricated from a poly(ethylene glycol)-b-poly(L-tyrosine) copolypeptide to enhance JQ1 delivery and the immunotherapy of malignant melanoma. The in vitro results showed that mJQ1 induced clearly better repression of c-MYC and PD-L1 proteins, cell cycle arrest, cell inhibition, and apoptotic activity than free JQ1 in B16F10 cancer cells. The intratumoral administration of mJQ1 at 2.5 mg of JQ1 equiv. per kg was found to show better inhibition of B16F10 tumors in C57BL/6 mice than the intraperitoneal administration of free JQ1 at 50 mg kg-1. In particular, when combined with radiotherapy, mJQ1 effectively suppressed tumor growth and brought about strong local and systemic antitumor immunity as evidenced by elevated CD8+ T cells and increased ratios of CD8+ T cells to Tregs, affording significantly improved survival of B16F10 tumor-bearing mice than their JQ1 counterparts and marked growth suppression of distant tumors. The great potency of enzyme-responsive micellar JQ1 makes it interesting for immunotherapy of various tumors.

Contrast-Enhanced Ultrasound Guided Transoral Core Needle Biopsy: A Novel, Safe and Well-Tolerated Procedure for Obtaining High-Quality Tissue in Patients with Oral Cancer.

The aim of the prospective study described here was to compare the tolerability, safety and diagnostic value of contrast-enhanced ultrasound-guided transoral core needle biopsy (CEUS-CNB) with that of conventional US-guided transoral CNB (US-CNB) and standard incisional biopsy in patients with oral masses. Between June 2017 and November 2019, consecutive patients with oral masses referred for biopsy were randomly assigned to undergo incisional biopsy, US-CNB or CEUS-CNB. Procedure time, intra­operative blood loss volume, diagnostic performance and pain level before and after the procedure assessed by visual analogue score (VAS) were recorded and compared among the three procedures. Finally, 238 patients with pathology confirmation were analyzed: 80 patients underwent incisional biopsy, 78 patients US-CNB and 80 patients CEUS-CNB. In this study, no significant difference was found in biopsy time between CEUS-CNB, US-CNB and incisional biopsy (75 ± 11 s vs. 73.6 ± 12 s vs. 77 ± 13 s, p = 0.24). CEUS-CNB achieved the highest sensitivity (CEUS-CNB: 100%, US-CNB: 88.5%, incisional biopsy: 84.3%), negative predictive value (CEUS-CNB: 100%, US-CNB: 81.3%, incisional biopsy: 78.4%) and accuracy (CEUS-CNB: 100%, US-CNB: 92.3%, incisional biopsy: 90%). The VAS score for incision biopsy was higher (p = 0.01) and the amount of bleeding was larger (p < 0.001), yet there was no significant difference between CEUS-CNB and US-CNB. Our results indicate CEUS-guided transoral CNB is an efficient, safe and well-tolerated procedure, with biopsy time comparable to and diagnostic performance better than those of conventional US-guided transoral CNB and incisional biopsy.

A tetrahedral DNA nanostructure-decorated electrochemical platform for simple and ultrasensitive EGFR genotyping of plasma ctDNA.

Genotyping of the epidermal growth factor receptor (EGFR) mutation status is of great importance in the screening of appropriate patients with advanced non-small cell lung carcinoma (NSCLC) to receive superior tyrosine kinase inhibitor (TKIs) therapy. Yet conventional assays are generally costly with a relatively long turnaround time for obtaining results, which can lead to a bottleneck for immediately starting TKI therapy in late-staged patients. In this study, we propose an on-site electrochemical platform for sensitive simultaneous genotyping of the two major EGFR mutations (19del and L858R) through plasma ctDNA based on tetrahedral DNA nanostructure decorated screen-printed electrodes (SPE). Linear-after-the-exponential (LATE)-PCR combined with the amplification refractory mutation system (ARMS) was adopted to produce abundant biotin-labeled single-stranded DNA with high amplification efficiency and specificity. Disposable SPE decorated with self-assembled tetrahedral nanostructured DNA probes that showed ordered orientation and good target accessibility enabled the highly efficient hybridization of the specific amplicons through a sandwich-type and quantitatively translated the interfacial hybridization event into electrochemical signals via enzymatic amplification. Taking advantage of the ARMS-based LATE-PCR and the tetrahedral nanostructure-decorated SPE platform, we achieved the accurate detection of around 30 pg DNA of 19del or L858R, or as low as 0.1% of them in the presence of wild-type DNA. Moreover, the EGFR mutation profiles of 13 NSCLC patients we enlisted were accurately genotyped by our electrochemical platform, the results of which were in good agreement with those of commercial genetic detection methods.

Comparative Study of the Decomposition Mechanism and Kinetics of Biimidazole-Based Energetic Explosives.

It is well known that imidazoles, possessing two or more nitro substituents, are potential candidates for highly energetic explosives with detonation parameters comparable to those of 1,3,5-trinitro-1,3,5-triazacyclohexane (RDX) and 1,3,5,7-tetranitro-1,3,5,7-tetraazacyclooctane. 4,4',5,5'-Tetranitro-2,2'-bi-imidazole (TNBI) is a typical imidazole explosive with energy equivalent to that of RDX but suffers from low sensitivity (impact sensitivity 7 J). 1,1'-Diamino-4,4',5,5'-tetranitro-2,2'-biimidazole (DATNBI), a derivative of TNBI, possesses two -NH2 groups and has a higher detonation velocity (9063 m s-1) and lower impact sensitivity of 15 J, which indicates great potential for future applications. Examination of the thermal decomposition mechanism and kinetics of TNBI and DATNBI gives a more comprehensive view of the influence that the -NH2 group has on the sensitivity and storage safety of the energetic explosive-based TNBI molecular skeleton. Herein, the thermal decomposition mechanism is studied, showing that detachment of -NH2 groups from DATNBI generates 1-diamino-4,4',5,5'-tetranitro-2,2'-biimidazole (ATNBI) and TNBI and induces self-decomposition. Although the decomposition peak temperature of DATNBI is significantly lower than that of TNBI at the same heating rate; its self-accelerating decomposition temperature (50 kg) is only 4 K lower. Therefore, the -NH2 group displays good ability of reducing sensitivity but has no influence on storage safety of DATNBI.

Preliminary study of real-time three-dimensional contrast-enhanced ultrasound of sentinel lymph nodes in breast cancer.

PURPOSE: To investigate the clinical value of real-time three-dimensional contrast-enhanced ultrasound (3D-CEUS) in the detection of sentinel lymph nodes (SLNs) and drainage lymphatics in breast cancer patients. METHOD: The prospective study was performed in women with pathology-confirmed T1/2 breast cancer between June 2016 and December 2017 who underwent sentinel lymph node biopsy and 3D-CEUS. The number, size, location, enhancement pattern of SLNs, and the lymphatic drainage patterns were reviewed. The routes, location of SLNs, and lymph channels (LCs) on the surface were marked. All patients underwent blue dye-guided sentinel lymph node biopsy (SLNB) finally. RESULTS: According to the postoperative pathology findings and the blue dye staining of the lymphatic drainage routes, there are six patterns of lymphatic drainage routes and the coincidence rate of the 3D-CEUS was 97.4%; the sensitivity, specificity, positive predictive value, negative predictive value, the LN detection rate, and the correct diagnosis rate of the 3D-CEUS were 75%, 93.0%, 81.8%, 89.9%, 95.3%, and 87.7%, respectively. CONCLUSION: 3D-CEUS is a new feasible and useful approach to detect the SLNs and LCs. 3D-CEUS can accurately localize the LCs and SLNs and estimate the presence of metastatic lymph nodes. KEY POINTS: • The three-dimensional contrast-enhanced ultrasound can detect the sentinel lymph nodes. • The three-dimensional contrast-enhanced ultrasound can show the stereo direction of sentinel lymph nodes and lymph drainage routes. • The three-dimensional contrast-enhanced ultrasound can accurately localize the LCs and SLNs and estimate the presence of metastatic lymph nodes.

How Pre-operative Sentinel Lymph Node Contrast-Enhanced Ultrasound Helps Intra-operative Sentinel Lymph Node Biopsy in Breast Cancer: Initial Experience.

We aimed to evaluate the value of sentinel lymph node contrast-enhanced ultrasound (SLN-CEUS) and surface tracing for the biopsy of intra-operative sentinel lymph nodes (SLNs). Between June 2015 and December 2017, a total of 453 patients with early invasive breast cancer were recruited. Patients received an intradermal injection of microbubble contrast agent around the areola on the day before surgery. The locations and sizes of lymphatic channels (LCs) and SLNs were marked on the body surface using gentian violet. Then, injection of double blue dye was performed half an hour before surgery. We compared the pathway of LCs and the location of SLNs obtained from SLN-CEUS and blue dye during surgery. Among the 453 patients, the mean numbers of LCs and SLNs detected by SLN-CEUS were 1.42 and 1.72, respectively, and the coincidence rate was 98.2% compared with blue dye during surgery. The median distance from the SLN to skin measured by pre-operative CEUS and blue dye was 1.95 ± 0.69 and 2.03 ± 0.87 cm (p = 0.35). There were three SLN enhancement in our research, including homogeneous enhancement, inhomogeneous enhancement and no enhancement, with the sensitivity, specificity, positive predictive value and negative predictive value of SLN-CEUS for the diagnosis of SLNs being 96.82%, 91.91%, 87.54% and 98.01%, respectively. SLN-CEUS with skin marking can identify the pathway of LCs and the location of the SLN before surgery, measure the distance from the SLN to skin and determine if the SLN is metastatic. SLN-CEUS can be used as an effective complement to the blue dye method.

[Analysis of intestinal patients' flora changes with severe pneumonia based on 16SrDNA sequencing technology].

OBJECTIVE: To investigate the characteristics of gut microbiota dysbosis in patients with severe pneumonia using 16SrDNA sequencing. METHODS: A prospective observational research was conducted. The stool samples retained by natural defecation or enema within 2 days after hospital were collected from 16 patients with severe pneumonia admitted to department of intensive care unit (ICU) of General Hospital of Ningxia Medical University from June to December in 2018 and 10 persons for physical exam were enrolled as the healthy control group. The 16SrDNA sequencing technology was used to detect fecal flora and analyze biological information. RESULTS: (1) 1 015 475 effective sequences were obtained from the stool samples from the severe pneumonia group and the healthy control group. Using 16SrDNA method, it was found that the average effective length of the sample sequence was 458.35 bp and the average sequence number of the total samples was 39 056.73. (2) Analysis of α diversity of gut microbiota showed that, compared with the healthy control group, the Ace index, Chao index and the Shannon index of gut microbiota diversity in the severe pneumonia group were significantly decreased [Ace index: 167.23 (143.14, 211.26) vs. 227.71 (214.53, 247.05), Chao index: 152.38 (138.09, 182.54) vs. 228.25 (215.49, 248.95), Shannon index: 2.37 (1.68, 2.89) vs. 3.39 (3.03, 3.63), all P < 0.01], and the Simpson index was significantly increased [0.21 (0.11, 0.33) vs. 0.07 (0.06, 0.12), P < 0.01], which indicated the gut microbiota diversity of the severe pneumonia group was decreased. (3) Analysis of ß diversity of gut microbiota, principal coordinate analysis (PCoA) showed that gut microbiota structural with the healthy control group was similar, while that in the severe pneumonia group was different. Adonis analysis showed that the structural of the gut microflora revealing significant differences between the severe pneumonia group and the healthy control group (R2 = 0.061, P = 0.05). (4) Analysis of phylum difference gut microflora showed that, compared with the healthy control group, the proportion of Firmicutes in severe pneumonia group was decreased [27.36 (18.12, 39.28)% vs. 52.25 (38.36, 63.82)%, P = 0.02], the proportions of Actinobacterias, Synergistetes and Fusobacterias were increased [2.30 (0.30, 4.80)% vs. 0.02 (0.00, 0.06)%, 0.36 (< 0.01, 0.57)% vs. < 0.01 (< 0.01, < 0.01)%, 0.01 (< 0.01, 0.08)% vs. < 0.01 (< 0.01, < 0.01)%, all P < 0.05]. (5) Analysis of genus difference gut microflora showed that, the proportions of Bifidobacterium, Ruminococcus, Pseudobutyrivibrio, Coprococcus, Lachnospira and Prevotella in the severe pneumonia group were significantly lower than those in healthy control group [0.18 (0.01, 0.25)% vs. 3.40 (0.46, 5.78)%, 0.01 (< 0.01, 0.29)% vs. 2.26 (0.84, 4.86)%, 0.01 (< 0.01, 0.02)% vs. 2.73 (1.87, 5.74)%, 0.02 (< 0.01, 0.07)% vs. 0.80 (0.50, 2.32)%, < 0.01 (< 0.01, < 0.01)% vs. 0.88 (0.33, 2.08)%, 0.02 (< 0.01, 0.31)% vs. 7.74 (0.07, 36.27)%, all P < 0.05]; the proportions of Escherichia and Enterococcus in the severe pneumonia group were higher than those in healthy control group, but there was no difference between the two groups [2.00 (0.57, 10.23)% vs. 1.16 (0.23, 2.68)%, 0.02 (< 0.01, 0.42)% vs. < 0.01 (< 0.01, 0.04)%, both P > 0.05]; the proportions of Fusobacterium and Staphylococcus in severe pneumonia group were significantly higher than those in healthy control group [0.01 (< 0.01, 0.08)% vs. < 0.01 (< 0.01, < 0.01)%, 0.01 (< 0.01, 0.02)% vs. < 0.01 (< 0.01, < 0.01)%, both P < 0.05]. CONCLUSIONS: Gut microbiota dysbiosis in patients with severe pneumonia shows that the abundance and diversity decrease, structure of intestinal flora changes, and beneficial symbiotic bacteria decrease and pathogenic bacteria increase, which may be associated with the occurrence and development of severe pneumonia.

5-Amino-1H-1,2,4-triazole-3-carbohydrazide and its applications in the synthesis of energetic salts: a new strategy for constructing the nitrogen-rich cation based on the energetic moiety combination.

Nitrogen-rich cation 5-amino-1H-1,2,4-triazole-3-carbohydrazide and its derivatives were synthesized by a new molecular design strategy based on the energetic moiety combination. All derivatives were fully characterized by vibrational spectroscopy (IR), multinuclear (1H, 13C) NMR spectroscopy, elemental analysis, differential scanning calorimetry (DSC), and impact and friction-sensitivity tests. The structures of compounds 1-4, 7 and 8 were further confirmed by single-crystal X-ray diffraction and six different types of crystal packing were surprisingly discovered. The results show that the extensive hydrogen bonding interactions between the cations and anions lead to a complex 3D network, which contribute greatly to the high density, insensitivity and thermal stability of the 5-amino-1H-1,2,4-triazole-3-carbohydrazide salts. It is also found that the cationic form of 5-amino-1H-1,2,4-triazole-3-carbohydrazide can decrease the sensitivity and elevate the nitrogen content of the target salts effectively. Some of these salts exhibit reasonable physical properties, such as good thermal stability (up to 407 °C) and reasonable impact sensitivities (IS = 5-80 J). In addition, theoretical detonation properties of the energetic salts obtained with EXPLO 5 (version 6.02) confirm them as competitively energetic compounds comparable to those of RDX or HMX.

Gem-dinitromethyl-substituted Energetic Metal-Organic Framework based on 1,2,3-Triazole from in situ Controllable Synthesis.

Synthesizing energetic metal-organic frameworks at ambient temperature and pressure has been always a challenge in the research area of energetic materials. In this work, through in situ controllable synthesis, energetic metal-organic framework gem-dinitromethyl-substituted dipotassium 4,5-bis(dinitromethyl)-1,2,3-triazole with a "cage-like" crystal packing was obtained and characterized. Most importantly, for the first time, we found that it could be successfully afforded with a catalytic effect of trifluoroacetic acid. This new compound exhibited its high density (2.04 g cm-3 ) at ambient temperature, superior detonation velocity (8715 m s-1 ) to that of lead azide (5877 m s-1 ) and comparable to that of RDX (8748 m s-1 ). Its detonation products are mainly N2 (48.1 %), suggesting it is also a green energetic material. The above-mentioned performance indicates its potential applications in detonator devices as lead-free primary explosive.

Dual-modal photoacoustic and magnetic resonance tracking of tendon stem cells with PLGA/iron oxide microparticles in vitro.

Reliable cell tracking is essential to understand the fate of stem cells following implantation, and thus promote the clinical application of stem cell therapy. Dual or multiple modal imaging modalities mediated by different types of multifunctional contrast agent are generally needed for efficient cell tracking. Here, we created a new contrast agent-PLGA/iron oxide microparticles (PLGA/IO MPs) and characterized the morphology, structure and function of enhancing both photoacoustic (PA) and magnetic resonance imaging (MRI). Both PA and MRI signal increased with increased Fe concentration of PLGA/IO MPs. Fluorescent staining, Prussian blue staining and transmission electron microscope (TEM) certified that PLGA/IO MPs were successfully encapsulated in the labeled TSCs. The established PLGA/IO MPs demonstrated superior ability of dual-modal PA/MRI tracking of TSCs without cytotoxicity at relatively lower Fe concentrations (50, 100 and 200 µg/mL). The optimal Fe concentration of PLGA/IO MPs was determined to be 100 µg/mL, thus laying a foundation for the further study of dual-modal PA/MRI tracking of TSCs in vivo and promoting the repair of injured tendon.