Neural topic models with survival supervision: Jointly predicting time-to-event outcomes and learning how clinical features relate.

We present a neural network framework for learning a survival model to predict a time-to-event outcome while simultaneously learning a topic model that reveals feature relationships. In particular, we model each subject as a distribution over "topics", where a topic could, for instance, correspond to an age group, a disorder, or a disease. The presence of a topic in a subject means that specific clinical features are more likely to appear for the subject. Topics encode information about related features and are learned in a supervised manner to predict a time-to-event outcome. Our framework supports combining many different topic and survival models; training the resulting joint survival-topic model readily scales to large datasets using standard neural net optimizers with minibatch gradient descent. For example, a special case is to combine LDA with a Cox model, in which case a subject's distribution over topics serves as the input feature vector to the Cox model. We explain how to address practical implementation issues that arise when applying these neural survival-supervised topic models to clinical data, including how to visualize results to assist clinical interpretation. We study the effectiveness of our proposed framework on seven clinical datasets on predicting time until death as well as hospital ICU length of stay, where we find that neural survival-supervised topic models achieve competitive accuracy with existing approaches while yielding interpretable clinical topics that explain feature relationships. Our code is available at: https://github.com/georgehc/survival-topics.

Regulation of Glandular Size and Phytoalexin Biosynthesis by a Negative Feedback Loop in Cotton.

Plants have evolved diverse defense mechanisms encompassing physical and chemical barriers. Cotton pigment glands are known for containing various defense metabolites, but the precise regulation of gland size to modulate defense compound levels remains enigmatic. Here, it is discovered that the VQ domain-containing protein JAVL negatively regulates pigment gland size and the biosynthesis of defense compounds, while the MYC2-like transcription factor GoPGF has the opposite effect. Notably, GoPGF directly activates the expression of JAVL, whereas JAVL suppresses GoPGF transcription, establishing a negative feedback loop that maintains the expression homeostasis between GoPGF and JAVL. Furthermore, it is observed that JAVL negatively regulates jasmonate levels by inhibiting the expression of jasmonate biosynthetic genes and interacting with GoPGF to attenuate its activation effects, thereby maintaining homeostatic regulation of jasmonate levels. The increased expression ratio of GoPGF to JAVL leads to enlarged pigment glands and elevated jasmonates and defense compounds, enhancing insect and pathogen resistance in cotton. These findings unveil a new mechanism for regulating gland size and secondary metabolites biosynthesis, providing innovative strategies for strengthening plant defense.

Valence and coordination form transition of tungsten ions in molten alkali chlorides.

This study examined the possibility of deep significance for the reduction of low-valence tungsten to inhibit disproportionation reactions in various molten alkali chlorides. Electrolysis and electrochemical tests of tungsten carbide were carried out in molten LiCl, LiCl-KCl, NaCl-KCl, NaCl-CsCl, and KCl-CsCl. One finding was that the reduction valence of tungsten ions decreased as the radius of the solvent alkali ion increased. This phenomenon may be viewed from the dissolution of tungsten carbide and the existence and deposition of tungsten ions. The mechanism of tungsten ion reduction and the stable configuration of tungsten ion groups were confirmed via a detailed study of the computational calculation. The increase in the radius of the solvent alkali ion was conducive to the dissolution of tungsten from tungsten carbide in the form of low valence state. Other results also indicated that W(II) ion groups first deposited on the cathode. They had the advantages of smaller coordination numbers and faster diffusion combined. Morphological and composition analysis results of the products are also presented.

Trace removal of benzene vapour using double-walled metal-dipyrazolate frameworks.

In principle, porous physisorbents are attractive candidates for the removal of volatile organic compounds such as benzene by virtue of their low energy for the capture and release of this pollutant. Unfortunately, many physisorbents exhibit weak sorbate-sorbent interactions, resulting in poor selectivity and low uptake when volatile organic compounds are present at trace concentrations. Herein, we report that a family of double-walled metal-dipyrazolate frameworks, BUT-53 to BUT-58, exhibit benzene uptakes at 298 K of 2.47-3.28 mmol g-1 at <10 Pa. Breakthrough experiments revealed that BUT-55, a supramolecular isomer of the metal-organic framework Co(BDP) (H2BDP = 1,4-di(1H-pyrazol-4-yl)benzene), captures trace levels of benzene, producing an air stream with benzene content below acceptable limits. Furthermore, BUT-55 can be regenerated with mild heating. Insight into the performance of BUT-55 comes from the crystal structure of the benzene-loaded phase (C6H6@BUT-55) and density functional theory calculations, which reveal that C-H···X interactions drive the tight binding of benzene. Our results demonstrate that BUT-55 is a recyclable physisorbent that exhibits high affinity and adsorption capacity towards benzene, making it a candidate for environmental remediation of benzene-contaminated gas mixtures.

A Practice of Reticular Chemistry: Construction of a Robust Mesoporous Palladium Metal-Organic Framework via Metal Metathesis.

Constructing stable palladium(II)-based metal-organic frameworks (MOFs) would unlock more opportunities for MOF chemistry, particularly toward applications in catalysis. However, their availability is limited by synthetic challenges due to the inertness of the Pd-ligand coordination bond, as well as the strong tendency of the Pd(II) source to be reduced under typical solvothermal conditions. Under the guidance of reticular chemistry, herein, we present the first example of an azolate Pd-MOF, BUT-33(Pd), obtained via a deuterated solvent-assisted metal metathesis. BUT-33(Pd) retains the underlying sodalite network and mesoporosity of the template BUT-33(Ni) and shows excellent chemical stability (resistance to an 8 M NaOH aqueous solution). With rich Pd(II) sites in the atomically precise distribution, it also demonstrates good performances as a heterogeneous Pd(II) catalyst in a wide application scope, including Suzuki/Heck coupling reactions and photocatalytic CO2 reduction to CH4. This work highlights a feasible approach to reticularly construct noble metal based MOFs via metal metathesis, in which various merits, including high chemical stability, large pores, and tunable functions, have been integrated for addressing challenging tasks.

MiR-301a promotes embryonic stem cell differentiation to cardiomyocytes.

BACKGROUND: Cardiovascular disease is the leading cause of death worldwide. Tissue repair after pathological injury in the heart remains a major challenge due to the limited regenerative ability of cardiomyocytes in adults. Stem cell-derived cardiomyocytes provide a promising source for the cell transplantation-based treatment of injured hearts. AIM: To explore the function and mechanisms of miR-301a in regulating cardiomyocyte differentiation of mouse embryonic stem (mES) cells, and provide experimental evidence for applying miR-301a to the cardiomyocyte differentiation induction from stem cells. METHODS: mES cells with or without overexpression of miR-301a were applied for all functional assays. The hanging drop technique was applied to form embryoid bodies from mES cells. Cardiac markers including GATA-4, TBX5, MEF2C, and α-actinin were used to determine cardiomyocyte differentiation from mES cells. RESULTS: High expression of miR-301a was detected in the heart from late embryonic to neonatal mice. Overexpression of miR-301a in mES cells significantly induced the expression of cardiac transcription factors, thereby promoting cardiomyocyte differentiation and beating cardiomyocyte clone formation. PTEN is a target gene of miR-301a in cardiomyocytes. PTEN-regulated PI3K-AKT-mTOR-Stat3 signaling showed involvement in regulating miR-301a-promoted cardiomyocyte differentiation from mES cells. CONCLUSION: MiR-301a is capable of promoting embryonic stem cell differentiation to cardiomyocytes.

HistoQC: An Open-Source Quality Control Tool for Digital Pathology Slides.

PURPOSE: Digital pathology (DP), referring to the digitization of tissue slides, is beginning to change the landscape of clinical diagnostic workflows and has engendered active research within the area of computational pathology. One of the challenges in DP is the presence of artefacts and batch effects, unintentionally introduced during both routine slide preparation (eg, staining, tissue folding) and digitization (eg, blurriness, variations in contrast and hue). Manual review of glass and digital slides is laborious, qualitative, and subject to intra- and inter-reader variability. Therefore, there is a critical need for a reproducible automated approach of precisely localizing artefacts to identify slides that need to be reproduced or regions that should be avoided during computational analysis. METHODS: Here we present HistoQC, a tool for rapidly performing quality control to not only identify and delineate artefacts but also discover cohort-level outliers (eg, slides stained darker or lighter than others in the cohort). This open-source tool employs a combination of image metrics (eg, color histograms, brightness, contrast), features (eg, edge detectors), and supervised classifiers (eg, pen detection) to identify artefact-free regions on digitized slides. These regions and metrics are presented to the user via an interactive graphical user interface, facilitating artefact detection through real-time visualization and filtering. These same metrics afford users the opportunity to explicitly define acceptable tolerances for their workflows. RESULTS: The output of HistoQC on 450 slides from The Cancer Genome Atlas was reviewed by two pathologists and found to be suitable for computational analysis more than 95% of the time. CONCLUSION: These results suggest that HistoQC could provide an automated, quantifiable, quality control process for identifying artefacts and measuring slide quality, in turn helping to improve both the repeatability and robustness of DP workflows.

In-orbit operation of an atomic clock based on laser-cooled 87Rb atoms.

Atomic clocks based on laser-cooled atoms are widely used as primary frequency standards. Deploying such cold atom clocks (CACs) in space is foreseen to have many applications. Here we present tests of a CAC operating in space. In orbital microgravity, the atoms are cooled, trapped, launched, and finally detected after being interrogated by a microwave field using the Ramsey method. Perturbing influences from the orbital environment on the atoms such as varying magnetic fields and the passage of the spacecraft through Earth's radiation belt are also controlled and mitigated. With appropriate parameters settings, closed-loop locking of the CAC is realized in orbit and an estimated short-term frequency stability close to 3.0 × 10-13τ-1/2 has been attained. The demonstration of the long-term operation of cold atom clock in orbit opens possibility on the applications of space-based cold atom sensors.

The Fast Spiking Subpopulation of Striatal Neurons Coding for Temporal Cognition of Movements.

Background: Timing dysfunctions occur in a number of neurological and psychiatric disorders such as Parkinson's disease, obsessive-compulsive disorder, autism and attention-deficit-hyperactivity disorder. Several lines of evidence show that disrupted timing processing is involved in specific fronto-striatal abnormalities. The striatum encodes reinforcement learning and procedural motion, and consequently is required to represent temporal information precisely, which then guides actions in proper sequence. Previous studies highlighted the temporal scaling property of timing-relevant striatal neurons; however, it is still unknown how this is accomplished over short temporal latencies, such as the sub-seconds to seconds range. Methods: We designed a task with a series of timing behaviors that required rats to reproduce a fixed duration with robust action. Using chronic multichannel electrode arrays, we recorded neural activity from dorso-medial striatum in 4 rats performing the task and identified modulation response of each neuron to different events. Cell type classification was performed according to a multi-criteria clustering analysis. Results: Dorso-medial striatal neurons (n = 557) were recorded, of which 113 single units were considered as timing-relevant neurons, especially the fast-spiking subpopulation that had trial-to-trial ramping up or ramping down firing modulation during the time estimation period. Furthermore, these timing-relevant striatal neurons had to calibrate the spread of their firing pattern by rewarded experience to express the timing behavior accurately. Conclusion: Our data suggests that the dynamic activities of timing-relevant units encode information about the current duration and recent outcomes, which is needed to predict and drive the following action. These results reveal the potential mechanism of time calibration in a short temporal resolution, which may help to explain the neural basis of motor coordination affected by certain physiological or pathological conditions.

Variation Trend and Driving Factors of Greenhouse Gas Emissions from Chinese Magnesium Production.

As the largest magnesium producer in the world, China is facing a great challenge of greenhouse gas (GHG) emissions reduction. In this paper, the variation trend and driving factors of GHG emissions from Chinese magnesium production were evaluated and the measures of technology and policy for effectively mitigating GHG emissions were provided. First, the energy-related and process-oriented GHG inventory is compiled for magnesium production in China. Then, the driving forces for the changes of the energy-related emission were analyzed by the method of Logarithmic Mean Divisia Index (LMDI) decomposition. Results demonstrated that Chinese magnesium output from 2003 to 2013 increased by 125%, whereas GHG emissions only increased by 16%. The emissions caused by the fuels consumption decline most significantly (from 28.4 to 6.6 t CO2eq/t Mg) among all the emission sources. The energy intensity and the energy structure were the main offsetting factors for the increase of GHG emissions, while the scale of production and the international market demand were the main contributors for the total increase. Considering the improvement of technology application and more stringent policy measures, the annual GHG emissions from Chinese primary magnesium production will be controlled within 22 million tons by 2020.

Inhibition of Alveolar Macrophage Pyroptosis Reduces Lipopolysaccharide-induced Acute Lung Injury in Mice.

BACKGROUND: Pyroptosis is the term for caspase-1-dependent cell death associated with pro-inflammatory cytokines. The role of alveolar macrophage (AM) pyroptosis in the pathogenesis of the acute lung injury and acute respiratory distress syndrome (ALI/ARDS) remains unclear. METHODS: C57BL/6 wild-type mice were assigned to sham, lipopolysaccharide (LPS) + vehicle, LPS + acetyl-tyrosyl-valyl- alanyl-aspartyl-chloromethylketone (Ac-YVAD-CMK) and LPS + Z-Asp-Glu-Val-Asp-fluoromethylketone groups. Mice were given intraperitoneal (IP) injections of LPS. Drugs were IP injected 1 h before LPS administration. Mice were sacrificed 16 h after LPS administration, and AMs were isolated. Western blot analysis for active caspase-1 and cleaved caspase-3, evaluation of lung injury and a cytokine release analysis were performed. AMs were treated with LPS and adenosine triphosphate (ATP); caspase-1-dependent cell death was evaluated using flow cytometry; the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) pyroptosomes were examined by immunofluorescence. RESULTS: The expression of activated caspase-1 in AMs was enhanced following LPS challenge compared with the sham group. In the ex vivo study, the caspase-1/propidium iodide-positive cells, caspase-1 specks and ASC pyroptosomes were up-regulated in AMs following LPS/ATP stimulation. The specific caspase-1 inhibitor Ac-YVAD-CMK inhibited the activation of caspase-1 and pyroptotic cell death. Ac-YVAD-CMK also reduced the lung injury, pulmonary edema and total protein in bronchoalveolar lavage fluid (BALF). In addition, Ac-YVAD-CMK significantly inhibited interleukin-α2 (IL-1α2) release both in serum and BALF and reduced the levels of IL-18, tumor necrosis factor-α± (TNF-α±), High Mobility Group Box 1 (HMGB1) in BALF during LPS-induced ALI/ARDS. CONCLUSIONS: This study reported AM pyroptosis during LPS-induced ALI/ARDS in mice and has demonstrated that Ac-YVAD-CMK can prevent AM-induced pyroptosis and lung injury. These preliminary findings may form the basis for further studies to evaluate this pathway as a target for prevention or reduction of ALI/ARDS.

Inhibition of Alveolar Macrophage Pyroptosis Reduces Lipopolysaccharide-induced Acute Lung Injury in Mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Pyroptosis is the term for caspase-1-dependent cell death associated with pro-inflammatory cytokines. The role of alveolar macrophage (AM) pyroptosis in the pathogenesis of the acute lung injury and acute respiratory distress syndrome (ALI/ARDS) remains unclear.</p><p><b>METHODS</b>C57BL/6 wild-type mice were assigned to sham, lipopolysaccharide (LPS) + vehicle, LPS + acetyl-tyrosyl-valyl- alanyl-aspartyl-chloromethylketone (Ac-YVAD-CMK) and LPS + Z-Asp-Glu-Val-Asp-fluoromethylketone groups. Mice were given intraperitoneal (IP) injections of LPS. Drugs were IP injected 1 h before LPS administration. Mice were sacrificed 16 h after LPS administration, and AMs were isolated. Western blot analysis for active caspase-1 and cleaved caspase-3, evaluation of lung injury and a cytokine release analysis were performed. AMs were treated with LPS and adenosine triphosphate (ATP); caspase-1-dependent cell death was evaluated using flow cytometry; the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) pyroptosomes were examined by immunofluorescence.</p><p><b>RESULTS</b>The expression of activated caspase-1 in AMs was enhanced following LPS challenge compared with the sham group. In the ex vivo study, the caspase-1/propidium iodide-positive cells, caspase-1 specks and ASC pyroptosomes were up-regulated in AMs following LPS/ATP stimulation. The specific caspase-1 inhibitor Ac-YVAD-CMK inhibited the activation of caspase-1 and pyroptotic cell death. Ac-YVAD-CMK also reduced the lung injury, pulmonary edema and total protein in bronchoalveolar lavage fluid (BALF). In addition, Ac-YVAD-CMK significantly inhibited interleukin-α2 (IL-1α2) release both in serum and BALF and reduced the levels of IL-18, tumor necrosis factor-α± (TNF-α±), High Mobility Group Box 1 (HMGB1) in BALF during LPS-induced ALI/ARDS.</p><p><b>CONCLUSIONS</b>This study reported AM pyroptosis during LPS-induced ALI/ARDS in mice and has demonstrated that Ac-YVAD-CMK can prevent AM-induced pyroptosis and lung injury. These preliminary findings may form the basis for further studies to evaluate this pathway as a target for prevention or reduction of ALI/ARDS.</p>

[Survey on public medications satisfaction in Guangdong Province].

OBJECTIVE: To analyze the influencing factors, and explore effective measures to improve the public medication satisfaction in Guangdong Province according to the survey on public medications satisfaction. METHODS: Information was collected through questionnaire survey supplemented by interview survey. Data were analyzed by SPSS 19.0 and Microsoft Excel 2003. RESULTS: The average public satisfaction of the seven items including the overall impression of pharmacy, the pharmacist professional quality, the waiting time of getting or buying drug, the attitude of the staffs, the drug labeling and instructions, drug prices and drug reliability scored 7.10, 6.76, 6.43, 6.57, 7.22, 5.52, 6.69 (out of 10), respectively. CONCLUSION: For low satisfaction and items that the public pay more attention to, countermeasures to improve satisfaction is proposed. On the premise of guaranteeing drug reliability, it is necessary to regulate drug prices positively, and improve the quality of pharmacy services and the professional quality of the pharmacists.

[Determination of film thickness, component and content based on glass surface by using XRF spectrometry].

Film thickness, component and content based on glass surface were determined by using XRF technic, measure condition and instrument work condition in every layer were set and adjusted for the best measure effect for every element. Background fundamental parameter (BG-FP) method was built up. Measure results with this method were consistent with the actual preparation course and the method could fit to production application.

[The element determination of six samples of petal powders by using XRF spectrometry].

Elements and contents in three kinds of petal powders of white and red rose, carnation, and butterfly orchis were determined by using XRF technic, and the data for every group were compared and analysed. The results indicated that all powders contain no toxic elements determined but have lots of normal elements and trace elements, such as Fe, Cu, Zn, Mn, Ni, Si, Sr, and Rb. The same sort of powder had approximately equivalent elements but their contents are different, and the element content of the white sort. was higher than the red one.

[Construct Mxi1 mutation gene expression vector from leukemia cell line KG1].

OBJECTIVE: To construct the eukaryotic expression vector for Max interacting protein 1 (Mxi1). METHODS: The full length cDNA of Mxi1 gene obtained from fetal lymphocyte and KG1 cells were inserted into plasmid pDs-red2-N1 respectively to generate pDs-red2-N1/Mri1 (wild/mutation type). Then the recombinant vector was transfected into Cos-7 cells via liposome. 48 hours post transfection, mRNA of Mri1 gene was detected by RT-PCR and Mxi1 protein expression was detected by flow cytometry and fluorescence microscope in the Cos-7 cells. RESULTS: The eukaryotic expression vector of Mxi1 was constructed and transfected into eukaryotic cells successfully. The expression of red fluorescence protein in the transfected Cos-7 cells was observed under fluorescence microscope which implied the expression of Mxi1. The transfect efficiency of both wild and mutation type were in a high level in 3 days after transfected, which lasted to 6 d. RT-PCR amplified the total RNA extracted from the transfected Cos-7 cells could find increased mRNA level of Mxi1 gene. CONCLUSION: We successfully constructed the eukaryote expression vector for Mri1 gene; Cos-7 cells transfected with the vector via liposome could express Mxi1 protein. These could be useful for the further study of the Myc gene modulation.

[Characterization and analysis of direction extraction and precipitation of cerium loading organic phase by oxalic acid solution].

In the condition of sodium hydroxide saponification, the test results using direction extraction and precipitation of cerium from P507 loading organic phase by oxalic acid solution were studied. Infared (IR) spectrum, X-ray diffraction (XRD), transmission electron microscope (TEM) and thermogravimetry (TG-DSC) were used to study and characterize organic cerium precipitates and the final calcined products. The results showed that organic cerium precipitates and final calcined products were spheric organic cerium coordination and spheric cube CeO2 crystal, respectively, showing their morphologies were successive. IR made out that the structures of organic cerium precipitates and final calcined products were different. TG-DSC indicated that the final calcined products weightlessness was 3.5% and chemical composing was CeO2 x 1/3H2O.

[Detection of lymph node micrometastasis for patients with extrahepatic cholangiocarcinoma and its prognostic significance].

OBJECTIVE: To observe the expression of antibodies of cytokeratin 19 and 20 in lymph node micrometastasis in patients with extrahepatic cholangiocarcinoma (EHCC), evaluate the prognostic significance of lymph node (LN) micrometastasis and study the correlation between lymph node micrometastasis and clinicopathological features, CA19-9 and CEA. METHODS: A total of 279 lymph nodes was intra-operatively collected from 59 EHCC patients and routine histological examination performed. Immunohistochemical staining was performed on all samples by the murine antibodies of anti-CK19 and anti-CK20 respectively. Then the micrometastasis was identified microscopically according to the color of cells. The results were analyzed according to clinical, pathological and follow-up data. And the relation of micrometastasis with clinical pathological factors and its impact upon survival rate were analyzed. RESULTS: Among 59 EHCC patients, 14 (23.72%) LN metastasis were found with HE staining and 21 micrometastases with CK staining. The incidence of nodal involvement in 59 EHCC patients increased from 5.37% (15/279) by HE staining to 13.98% (39/279) by CK staining. Among 45 patients not positive for LN metastases with HE staining, CK staining was positive in 7 patients and the incidence of micrometastasis was 15.56%. The preoperative serum CA19-9 levels in patients with LN micrometastasis was higher than that those without LN metastasis (P < 0.05). And there was a positive correlation between occult nodal micrometastasis and serum concentrations of CA19-9 (r(s) = 0.371, P < 0.05). The histological type and lymphatic vessel infiltration of tumor were the most importance factors for LN micrometastasis through Logistic regression analysis (P < 0.05). CONCLUSION: The CK immunohistochemical staining can detect the micrometastases in HE negative LN. And LN micrometastasis can more accurately predict the prognosis of EHCC patients.

[XPS study on the influence of calcination conditions to cerium ion valence].

For the system of Ce(NO3)2.6H2O and urea solution during homogeneous precipitation method, X-ray diffraction (XRD), infrared spectrum (IR) and especially X-ray photoelectron spectroscopy (XPS) were used to study and characterize the product structure, variety of cerium ion valence, compound surface character and kernel electronic configurations. The results of XRD and IR showed that calcination temperature had a great effect on the cerium ion valence. The products are orthorhombic Ce2 O(CO3)2.H2O with valence III by using homogeneous precipitation method directly. When heated from the temperature 200 degrees C to 250 degrees C, the product of CeO(CO3)2.H2O with valence VI was finally changed into stable CeO2 with valence IV. XPS was used to study the surface character and kernel electronic configurations of the three different compounds through fine scanning of O(1s), Ce(3d) and Ce(4d) apices, and the results approved that the compounds with different valences are caused by the different valence electronic configurations of the products.