KDGene: knowledge graph completion for disease gene prediction using interactional tensor decomposition.

The accurate identification of disease-associated genes is crucial for understanding the molecular mechanisms underlying various diseases. Most current methods focus on constructing biological networks and utilizing machine learning, particularly deep learning, to identify disease genes. However, these methods overlook complex relations among entities in biological knowledge graphs. Such information has been successfully applied in other areas of life science research, demonstrating their effectiveness. Knowledge graph embedding methods can learn the semantic information of different relations within the knowledge graphs. Nonetheless, the performance of existing representation learning techniques, when applied to domain-specific biological data, remains suboptimal. To solve these problems, we construct a biological knowledge graph centered on diseases and genes, and develop an end-to-end knowledge graph completion framework for disease gene prediction using interactional tensor decomposition named KDGene. KDGene incorporates an interaction module that bridges entity and relation embeddings within tensor decomposition, aiming to improve the representation of semantically similar concepts in specific domains and enhance the ability to accurately predict disease genes. Experimental results show that KDGene significantly outperforms state-of-the-art algorithms, whether existing disease gene prediction methods or knowledge graph embedding methods for general domains. Moreover, the comprehensive biological analysis of the predicted results further validates KDGene's capability to accurately identify new candidate genes. This work proposes a scalable knowledge graph completion framework to identify disease candidate genes, from which the results are promising to provide valuable references for further wet experiments. Data and source codes are available at https://github.com/2020MEAI/KDGene.

Prognostic significance of limited resection in pathologic stage I lung adenocarcinoma with spread through air spaces.

Background: Tumor spread through air spaces (STAS) is now recognized as tumor invasion. However, the association between STAS and procedure-specific outcomes (limited resection and lobectomy) in patients with pathologic stage I lung adenocarcinoma (ADC) is still under investigation. Methods: To investigate whether limited resection predicts poorer survival in such patients, we retrospectively analyzed the clinicopathologic features of a large cohort of 1,566 patients with stage I ADC from 2017 to 2020 and classified them according to STAS status and surgical method. Kaplan-Meier, Cox hazard proportional regression, and propensity score matching (PSM) were adopted for prognostic evaluation. Results: STAS-positive patients had worse recurrence-free survival (RFS) (P<0.001). There was no significant difference in RFS and overall survival (OS) between limited resection and lobectomy, neither for the STAS-negative nor STAS-positive group before matching. After matching, limited resection was found to achieve comparable RFS to lobectomy in STAS-positive patients with pathologic I, IA, or IB stage tumor, (P=0.816, P=0.576, P=0.281, respectively), but worse OS in stage I and stage IB patients (P=0.029, P=0.010, respectively). Furthermore, in multivariable analysis, limited resection was not an independent prognostic factor of RFS or OS. Instead, the high-grade histological subtype was the only independent prognostic factor for RFS (P=0.001). In the subgroup analysis, adjuvant chemotherapy (ACT) did not improve the outcomes of stage IB STAS-positive patients. Conclusions: Limited resection was associated with worse survival than lobectomy in stage I STAS-positive patients, but not in stage IA STAS-positive patients.

Unplanned reoperation after pulmonary surgery: Rate, risk factors and early outcomes at a single center.

Background: Unplanned reoperation is a potential risk factor for worse prognoses and reflects the quality of surgical treatment. This study compared the short-term outcomes between patients with and without reoperation and identified clinical factors predicting reoperation within 90 days following pulmonary surgery. Methods: Consecutive patients undergoing pulmonary resection from January 2012 to August 2021 at our institution were retrospectively reviewed. Clinical and operation-related data were collected and analyzed. Kaplan‒Meier, Cox hazard proportional regression, and propensity score matching were adopted for prognostic evaluation. Results: A total of 90263 patients were included: 247 (0.27%) patients required reoperation within 90 days. Patients undergoing unplanned reoperation had higher mortality and more postoperative complications than the nonreoperation group. Reoperation within 24 h was associated with reduced odds of mortality relative to reoperation beyond 24 h. Independent risk factors for unplanned reoperation were male sex, benign lung disease, specific surgical locations, lobectomy, and pneumonectomy. A history of smoking, pulmonary tuberculosis, intraoperative pleural adhesion, and postoperative complications were also identified as predisposing factors. The most common complication was hemorrhage in 75.7% (187 of 247). Conclusion: Our study found that unplanned reoperation was a rare but serious event that increased the risk of postoperative complications and mortality. We identified several risk factors that could be used to stratify patients according to their reoperation risk and suggest that high-risk patients should receive more intensive monitoring and preventive measures. Moreover, our study indicated that reoperating within 24 h could improve the outcomes for patients who needed reoperation.

Metal-Free Amino(hetero)arylation and Aminosulfonylation of Alkenes Enabled by Photoinduced Energy Transfer.

ß-(Hetero)arylethylamines are privileged structural motifs found in many high-value organic molecules, including pharmaceuticals and natural products. To construct these important molecular skeletons, previous methods are mainly achieved by amino(hetero)arylation reaction with the aid of transition metals and preactivated substrates. Herein, we report a metal-free and photoinduced intermolecular amino(hetero)arylation reaction for the single-step installation of both (hetero)aryl and iminyl groups across alkenes in an efficient and regioselective manner. This method shows broad scope (up to 124 examples) and excellent tolerance of various olefins─from the simplest ethylene to complex multisubstituted alkenes can all participate in the reaction. Furthermore, aminosulfonylation of alkenes can be also conducted in the presence of sodium bisulfite as the SO2 source.

Sulfur fertilization and water management ensure phytoremediation coupled with argo-production by mediating rhizosphere microbiota in the Oryza sativa L.-Sedum alfredii Hance rotation system.

Sulfur (S) fertilizers, water management and crop rotation are important agronomic practices, related to soil heavy metal bioavailability. However, the mechanisms of microbial interactions remain unclear. Herein, we investigated how S fertilizers (S0 and Na2SO4) and water management affected plant growth, soil cadmium (Cd) bioavailability, and rhizospheric bacterial communities in the Oryza sativa L. (rice)-Sedum alfredii Hance (S. alfredii) rotation system through 16S rRNA gene sequencing and ICP-MS analysis. During rice cultivation, continuous flooding (CF) was better than alternating wetting and drying (AWD). CF treatment decreased soil Cd bioavailability by the promotion of insoluble metal sulfide production and soil pH, thus lowering Cd accumulation in grains. S application recruited more S-reducing bacteria in the rhizosphere of rice, whilst Pseudomonas promoted metal sulfide production and rice growth. During S. alfredii cultivation, S fertilizer recruited S-oxidizing and metal-activating bacteria in the rhizosphere. Thiobacillus may oxidize metal sulfides and enhance Cd and S absorption into S. alfredii. Notably, S oxidation decreased soil pH and elevated Cd content, thereby promoting S. alfredii growth and Cd absorption. These findings showed rhizosphere bacteria were involved in Cd uptake and accumulation in the rice-S. alfredii rotation system, thus providing useful information for phytoremediation coupled with argo-production.

Characteristics of bacterial communities in rhizosphere and bulk soil in Fe-deficient citrus growing in coastal saline-alkali land.

Aims: Citruses often occur with imbalance in iron nutrition in coastal saline-alkali lands, which severely limits the yield and quality of the fruit. In the rhizosphere, the salt content plays a crucial role in reducing uptake of iron, as well as the activity and abundance of bacteria. However, few studies have explored how salt content affects the effectiveness of iron and the community structure of bacteria across different vertical spatial scales. Methods: We investigated the citrus rhizosphere (0-30 cm) and bulk (0-60 cm) soil microenvironments of the coastal saline soil were analyzed using the 16S rRNA amplicon and inductively coupled plasma-optical emission spectroscopy. Results: We found that the nutrient-related elements in the rhizosphere and bulk soil decreased with increasing soil depth, while the salinity-related elements showed the opposite trend. The nutrient-related element content in the rhizosphere was higher than that in the bulk, whereas the salinity-alkaline-related element content was lower than that in the bulk. The structure and diversity of bacterial communities are affected by the rhizosphere and soil depth. In the bulk, there are enriched bacteria such as WB1-A12, Nitrospiraceae and Anaerolineae that are tolerant to salt-alkali stress. In the rhizosphere, bacteria that promote plant nutrient absorption and secretion of iron carriers, such as Pseudomonas, Streptomyces, and Duganella, are prominent. Conclusions: The soil depth and rhizosphere affect soil nutrients and saline alkali-related factors. Changes in soil depth and rhizosphere determine the structure and diversity of bacterial communities. Rhizosphere enhances iron absorption promoting bacteria to alleviate iron deficiency stress in saline-alkali soils. Our results indicate that citrus roots maybe can resist the stress of iron deficiency in saline-alkali soils by enhancing iron absorption promoting bacteria.

3D deep learning versus the current methods for predicting tumor invasiveness of lung adenocarcinoma based on high-resolution computed tomography images.

Background: Different pathological subtypes of lung adenocarcinoma lead to different treatment decisions and prognoses, and it is clinically important to distinguish invasive lung adenocarcinoma from preinvasive adenocarcinoma (adenocarcinoma in situ and minimally invasive adenocarcinoma). This study aims to investigate the performance of the deep learning approach based on high-resolution computed tomography (HRCT) images in the classification of tumor invasiveness and compare it with the performances of currently available approaches. Methods: In this study, we used a deep learning approach based on 3D conventional networks to automatically predict the invasiveness of pulmonary nodules. A total of 901 early-stage non-small cell lung cancer patients who underwent surgical treatment at Shanghai Chest Hospital between November 2015 and March 2017 were retrospectively included and randomly assigned to a training set (n=814) or testing set 1 (n=87). We subsequently included 116 patients who underwent surgical treatment and intraoperative frozen section between April 2019 and January 2020 to form testing set 2. We compared the performance of our deep learning approach in predicting tumor invasiveness with that of intraoperative frozen section analysis and human experts (radiologists and surgeons). Results: The deep learning approach yielded an area under the receiver operating characteristic curve (AUC) of 0.946 for distinguishing preinvasive adenocarcinoma from invasive lung adenocarcinoma in the testing set 1, which is significantly higher than the AUCs of human experts (P<0.05). In testing set 2, the deep learning approach distinguished invasive adenocarcinoma from preinvasive adenocarcinoma with an AUC of 0.862, which is higher than that of frozen section analysis (0.755, P=0.043), senior thoracic surgeons (0.720, P=0.006), radiologists (0.766, P>0.05) and junior thoracic surgeons (0.768, P>0.05). Conclusions: We developed a deep learning model that achieved comparable performance to intraoperative frozen section analysis in determining tumor invasiveness. The proposed method may contribute to clinical decisions related to the extent of surgical resection.

Biofortification Technology for the Remediation of Cadmium-Contaminated Farmland by the Hyperaccumulator Sedum alfredii under Crop Rotation and Relay Cropping Mode.

Soil cadmium (Cd) extraction for hyperaccumulators is one of the most important technologies for the remediation of Cd-contaminated farmland soil. However, a phytoremediation model using a single hyperaccumulator cannot guarantee normal agricultural production in contaminated areas. To solve this problem, a combination of efficient remediation and safe production has been developed. Based on two-period field experiments, this study explored the effect of biofortification on soil Cd remediation using the fruit tree Sedum alfredii Hance and oil sunflower crop rotation and relay cropping mode. BioA and BioB treatments could markedly improve the efficiency of Cd extraction and remediation, and the maximum increase in Cd accumulation was 243.29%. When BioB treatment was combined with papaya-S. alfredii and oil sunflower crop rotation and relay cropping mode, the highest soil Cd removal rate in the two periods was 40.84%, whereas the Cd concentration of papaya fruit was lower than safety production standards (0.05 mg/kg). These results demonstrate that biofortification measures can significantly improve the Cd extraction effect of S. alfredii crop rotation and relay cropping restoration modes, which has guiding significance for Cd pollution remediation and safe production in farmland.

Regulable cross-coupling of alcohols and benzothiazoles via a noble-metal-free photocatalyst under visible light.

Here, we realize a regulable cross-coupling reaction using alcohols as alkylating reagents to functionalize benzothiazoles. Two types of cross-coupling products are obtained with the highest isolated yields of up to 99% and 90% for alkyl- and acetyl-derived benzothiazoles, respectively, which opens up a broad research prospect for expanding alcohols as alkylating reagents.

Role of SaPCR2 in Zn Uptake in the Root Elongation Zone of the Zn/Cd Hyperaccumulator Sedum alfredii.

Zn pollution is a potential toxicant for agriculture and the environment. Sedum alfredii is a Zn/Cd hyperaccumulator found in China and has been proven as a useful resource for the phytoremediation of Zn-contaminated sites. However, the molecular mechanism of Zn uptake in S. alfredii is limited. In this study, the function of SaPCR2 on Zn uptake in S. alfredii was identified by gene expression analysis, yeast function assays, Zn accumulation and root morphology analysis in transgenic lines to further elucidate the mechanisms of uptake and translocation of Zn in S. alfredii. The results showed that SaPCR2 was highly expressed in the root elongation zone of the hyperaccumulating ecotype (HE) S. alfredii, and high Zn exposure downregulated the expression of SaPCR2 in the HE S. alfredii root. The heterologous expression of SaPCR2 in yeast suggested that SaPCR2 was responsible for Zn influx. The overexpression of SaPCR2 in the non-hyperaccumulating ecotype (NHE) S. alfredii significantly increased the root uptake of Zn, but did not influence Mn, Cu or Fe. SR-µ-XRF technology showed that more Zn was distributed in the vascular buddle tissues, as well as in the cortex and epidermis in the transgenic lines. Root morphology was also altered after SaPCR2 overexpression, and a severe inhibition was observed. In the transgenic lines, the meristematic and elongation zones of the root were lower compared to the WT, and Zn accumulation in meristem cells was also reduced. These results indicate that SaPCR2 is responsible for Zn uptake, and mainly functions in the root elongation zone. This research on SaPCR2 could provide a theoretical basis for the use of genetic engineering technology in the modification of crops for their safe production and biological enhancement.

Computed tomography versus frozen sections for distinguishing lung adenocarcinoma: A cohort study of concordance rate.

BACKGROUND: Computed tomography (CT) imaging can help to predict the pathological invasiveness of early-stage lung adenocarcinoma and guide surgical resection. This retrospective study investigated whether CT imaging could distinguish pre-invasive lung adenocarcinoma from IAC. It also compared final pathology prediction accuracy between CT imaging and intraoperative frozen section analysis. METHODS: This study included 2093 patients with early-stage peripheral lung adenocarcinoma who underwent CT imaging and intraoperative frozen section analysis between March 2013 and November 2014. Nodules were classified as ground-glass (GGNs), part-solid (PSNs), and solid nodules according to CT findings; they were classified as pre-IAC and IAC according to final pathology. Univariate, multivariate, and receiver operating characteristic (ROC) curve analyses were performed to evaluate whether CT imaging could distinguish pre-IAC from IAC. The concordance rates of CT imaging and intraoperative frozen section analyses with final pathology were also compared to determine their accuracies. RESULTS: Multivariate analysis identified tumor size as an independent distinguishing factor. ROC curve analyses showed that the optimal cut-off sizes for distinguishing pre-IAC from IAC for GGNs, PSNs, and solid nodules were 10.79, 11.48, and 11.45 mm, respectively. The concordance rate of CT imaging with final pathology was significantly greater than the concordance rate of intraoperative frozen section analysis with final pathology (P = 0.041). CONCLUSION: CT imaging could distinguish pre-IAC from IAC in patients with early-stage lung adenocarcinoma. Because of its accuracy in predicting final pathology, CT imaging could contribute to decisions associated with surgical extent. Multicenter standardized trials are needed to confirm the findings in this study.

Identification and characterization of a novel elastase inhibitor from Hirudinaria manillensis.

A large number of protease inhibitors have been found from leeches, which are essential in various physiological and biological processes. In the curret study, a novel elastase inhibitor was purified and characterized from the leech of Hirudinaria manillensis, which was named HMEI-A. Primary structure analysis showed that HMEI-A belonged to a new family of proteins. HMEI-A exerted inhibitory effects on elastase and showed potent abilities to inhibit elastase with an inhibition constant (Ki) of 1.69 × 10-8 mol·L-1. Further study showed that HMEI-A inhibited the formation of neutrophil extracellular trap (NET). These results suggested that HMEI-A from the leech of H. manillensis is a novel elastase inhibitor which can suppress NET formation. It may play a significant role in blood-sucking of leeches and is a potential candidate as an anti-inflammatory agent.

Multicomponent Synthesis of α-Branched Tertiary and Secondary Amines by Photocatalytic Hydrogen Atom Transfer Strategy.

A multicomponent carbonyl alkylative amination reaction is described. A variety of N-arylamines, aldehydes, and hydrocarbons have been examined as reaction substrates using tetrabutylammonium decatungstate as photocatalyst, providing the corresponding α-branched tertiary and secondary amines in good to moderate yields. The reaction proceeds through the generation of alkyl radicals by a light-promoted hydrogen atom transfer process followed by free radical addition to iminium ions generated in situ.

Temporal metabolic and transcriptomic characteristics crossing islets and liver reveal dynamic pathophysiology in diet-induced diabetes.

To investigate the molecular mechanisms underlying islet dysfunction and insulin resistance in diet-induced diabetes, we conducted temporal RNA sequencing of tissues responsible for insulin secretion (islets) and action (liver) every 4 weeks in mice on high-fat (HFD) or chow diet for 24 weeks, linking to longitudinal profile of metabolic characteristics. The diverse responses of α, ß, and δ cells to glucose and palmitate indicated HFD-induced dynamic deterioration of islet function from dysregulation to failure. Insulin resistance developed with variable time course in different tissues. Weighted gene co-expression network analysis and Ingenuity Pathway Analysis implicated islets and liver jointly programmed ß-cell compensatory adaption via cell proliferation at early phase and irreversible islet dysfunction by inappropriate immune response at later stage, and identified interconnected molecules including growth differentiation factor 15. Frequencies of T cell subpopulation showed an early decrement in Tregs followed by increases in Th1 and Th17 cells during progression to diabetes.

Selective photoredox decarboxylation of α-ketoacids to allylic ketones and 1,4-dicarbonyl compounds dependent on cobaloxime catalysis.

A photoredox/cobaloxime co-catalyzed coupling reaction of α-ketoacids and methacrylates to obtain allylic ketones is described. Without the cobaloxime catalyst, 1,4-dicarbonyl compounds are generated. The cobaloxime catalyst enables dehydrogenation to generate the formation of new olefins. The generality, good substrate scope and mild conditions are good features in the photoredox/cobaloxime catalysis protocol, and this method will provide new opportunities for the functionalization of more olefins.

Photoinduced synthesis of fluorinated dibenz[b,e]azepines via radical triggered cyclization.

A simple, mild and efficient approach to access fluorinated dibenz[b,e]azepines via visible-light photoredox catalysis is presented. Inexpensive and commercially available fluoroalkyl anhydrides in concert with pyridine N-oxide are employed as the source of the fluoroalkyl radicals. A one-pot process involving the trifluoroacetylation of unprotected secondary benzyl amines followed by radical cyclization could also afford the desired fluorinated dibenz[b,e]azepines.

Analysis of Cloud-Resolving Model Simulations for Scale Dependence of Convective Momentum Transport.

We use 3-D cloud-resolving model (CRM) simulations of two mesoscale convective systems at mid-latitudes and a simple statistical ensemble method to diagnose the scale dependency of convective momentum transport (CMT) and CMT-related properties, and evaluate a parameterization scheme for convection-induced pressure gradient (CIPG) developed by Gregory et al. (GKI97). GKI97 relates CIPG to a constant coefficient multiplied by mass flux and vertical mean wind shear. CRM results show that mass fluxes and CMT exhibit strong scale dependency in temporal evolution and vertical structure. The prevalent understandings of CMT characteristics in terms of upgradient/downgradient transport are applicable to updrafts but not downdrafts across a wide range of grid spacings (4-512 km). For the small-to-median grid spacings (4~64 km), GKI97 reproduces some aspects of CIPG scale dependency except for underestimating the variations of CIPG as grid spacing decreases. However, for large grid spacings (128~512 km), GKI97 might even less adequately parameterize CIPG because it omits the contribution from either the nonlinear shear or buoyancy forcings. Further diagnosis of CRM results suggests that inclusion of nonlinear shear forcing in GKI97 is needed for the large grid spacings, and use of the three-updraft and one downdraft approach proposed in an earlier study may help a modified GKI97 capture more variations of CIPG as grid spacing decreases for the small-to-median grid spacings. Further, the optimal coefficients used in GKI97 seems insensitive to grid spacings, but they might be different for updrafts and downdrafts, for different MCS types, and for zonal and meridional components.

Differences in the Hydrological Cycle and Sensitivity Between Multiscale Modeling Frameworks with and without a Higher-order Turbulence Closure.

Current conventional global climate models (GCMs) produce a weak increase in global mean precipitation with anthropogenic warming in comparison with the lower-tropospheric moisture increases. The motive of this study is to understand the differences in the hydrological sensitivity between two multiscale modeling frameworks (MMFs) that arise from the different treatments of turbulence and low clouds in order to aid to the understanding of the model spread among conventional GCMs. We compare the hydrological sensitivity and its energetic constraint from MMFs with (SPCAM-IPHOC) or without (SPCAM) an advanced higher-order turbulence closure. SPCAM-IPHOC simulates higher global hydrological sensitivity for the slow response but lower sensitivity for the fast response than SPCAM. Their differences are comparable to the spreads of conventional GCMs. The higher sensitivity in SPCAM-IPHOC is associated with the higher ratio of the changes in latent heating to those in net atmospheric radiative cooling, which is further related to a stronger decrease in the Bowen ratio with warming than in SPCAM. The higher sensitivity of cloud radiative cooling resulting from the lack of low clouds in SPCAM is another major factor in contributing to the lower precipitation sensitivity. The two MMFs differ greatly in the hydrological sensitivity over the tropical lands, where the simulated sensitivity of surface sensible heat fluxes to surface warming and CO2 increase in SPCAM-IPHOC is weaker than in SPCAM. The difference in divergences of dry static energy flux simulated by the two MMFs also contributes to the difference in land precipitation sensitivity between the two models.

Evaluation of a general circulation model by the CERES Flux-by-cloud type simulator.

In this work, we use the Clouds and the Earth's Radiant Energy System (CERES) FluxByCloudTyp data product, which calculates TOA shortwave and longwave fluxes for cloud categories defined by cloud optical depth (τ) and cloud top pressure (pc ), to evaluate the HadGEM2-A model with a simulator. The CERES Flux-by-cloud type simulator is comprised of a cloud generator that produces subcolumns with profiles of binary cloud fraction, a cloud property simulator that determines the (τ, pc ) cloud type for each subcolumn, and a radiative transfer model that calculates TOA fluxes. The identification of duplicate atmospheric profiles reduces the number of radiative transfer calculations required by approximately 97.6%. In the Southern Great Plains region in JFD (January, February, and December) 2008, the simulator shows that simulated cloud tops are higher in altitude than observed, but also have higher values of OLR than observed, leading to a compensating error that results in an average value of OLR that is close to observed. When the simulator is applied to the Southeast Pacific stratocumulus region in JJA 2008, the simulated cloud tops are primarily low in altitude; however, the clouds tend to be less numerous, and have higher optical depths than are observed. In addition to the increase in albedo that comes from having too many clouds with higher optical depth, the HadGEM2-A albedo is higher than observed for those cloud types that occur most frequently. The simulator is also applied to the entire 60° N - 60° S region, and it is found that there are fewer clouds than observed for most cloud types, but there are also higher albedos for most cloud types, which represents a compensating error in terms of the shortwave radiative budget.