Prognostic Factors in COVID-19 Pneumonia with Severe Acute Respiratory Distress Syndrome: An Observational Study

Purpose: To identify prognostic factors in patients with coronavirus disease 2019 (COVID-19)-associated severe acute respiratory distress syndrome (ARDS). Methods: In this study, we included 45 patients with COVID-19-associated ARDS hospitalized at The First Affiliated Hospital of Yangtze University in Jingzhou, Hubei, China, between January 22, 2020, and March 6, 2020. Clinical data and outcomes were reviewed and analyzed according to the Berlin definition. Findings: Men were more likely to develop severe ARDS than women (11 [91.7%] vs. 1 [8.3%]). Factors associated with severe ARDS included sex (male) (hazard ratio [HR], 13.75;95% confidence interval [CI], 1.45 - 130.24), neutrophil count (HR, 55.00;95% CI, 5.02 - 602.15), lymphocyte count (HR, 40.00;95% CI, 4.83 - 331.00), prothrombin time (HR, 12.14;95% CI, 1.19 - 123.62), D-dimer (HR, 11.00;95% CI, 1.16 - 103.94), total bilirubin levels (HR, 5.00;95% CI, 0.93 - 26.79), albumin (HR, 17.5;95% CI, 2.67 - 114.85), blood urea nitrogen levels (HR, 28.60;95% CI, 2.89 - 283.06), lactate dehydrogenase levels (HR, 6.00;95% CI, 1.17 - 30.73), and C-reactive protein levels (HR, 15.87;95% CI, 2.40 - 111.11). Conclusion: Laboratory indicators, such as neutrophil count and lymphocyte count, could play an important role in the diagnosis of severe ARDS and guide clinical decision-making for patients with ARDS.

CiteOpinion: Evidence-based Evaluation Tool for Academic Contributions of Research Papers Based on Citing Sentences

Purpose:To uncover the evaluation information on the academic contribution of research papers cited by peers based on the content cited by citing papers,and to provide an evidencebased tool for evaluating the academic value of cited papers.Design/methodology/approach:CiteOpinion uses a deep learning model to automatically extract citing sentences from representative citing papers;it starts with an analysis on the citing sentences,then it identifies major academic contribution points of the cited paper,positive/negative evaluations from citing authors and the changes in the subjects of subsequent citing authors by means of Recognizing Categories of Moves(problems,methods,conclusions,etc.),and sentiment analysis and topic clustering.Findings:Citing sentences in a citing paper contain substantial evidences useful for academic evaluation.They can also be used to objectively and authentically reveal the nature and degree of contribution of the cited paper reflected by citation,beyond simple citation statistics.Practical implications:The evidence-based evaluation tool CiteOpinion can provide an objective and in-depth academic value evaluation basis for the representative papers of scientific researchers,research teams,and institutions.Originality/value:No other similar practical tool is found in papers retrieved.Research limitations:There are difficulties in acquiring full text of citing papers.There is a need to refine the calculation based on the sentiment scores of citing sentences.Currently,the tool is only used for academic contribution evaluation,while its value in policy studies,technical application,and promotion of science is not yet tested.

The E3 ubiquitin ligase CSIT1 regulates critical sterility-inducing temperature by ribosome-associated quality control to safeguard two-line hybrid breeding in rice

Two-line hybrid breeding can fully utilize heterosis in crops.In thermo-sensitive genic male sterile(TGMS)lines,low critical sterility-inducing temperature(CSIT)is vital to safeguard the production of two-line hybrid seeds in rice(Oryza sativa),but the molecular mechanism determining CSIT is unclear.Here,we report the cloning of CSIT1,which encodes an E3 ubiquitin ligase,and show that CSIT1 modulates the CSIT of thermo-sensitive genic male sterility 5(tms5)-based TGMS lines through ribosome-associated quality control(RQC).Biochemical assays demonstrated that CSIT1 binds to the 80S ribosomes and ubiquitinates abnormal nascent polypeptides for degradation in the RQC process.Loss of CSIT1 function inhibits the possible damage of tms5 to the ubiquitination system and protein translation,resulting in enhanced accumulation of anther-related proteins such as catalase to suppress abnormal accumulation of reactive oxygen species and premature programmed cell death in the tapetum,thereby leading to a much higher CSIT in the tms5-based TGMS lines.Taken together,our findings reveal a regulatory mechanism of CSIT,providing new insights into RQC and potential targets for future two-line hybrid breeding.

Intrinsic chemiluminescence production from the degradation of haloaromatic pollutants during environmentally-friendly advanced oxidation processes:Mechanism,structure-activity relationship and potential applications

The ubiquitous distribution of halogenated aromatic compounds(XAr) coupled with their carcinogenicity has raised public concerns on their potential risks to both human health and the ecosystem. Recently, advanced oxidation processes(AOPs) have been considered as an"environmentally-friendly" technology for the remediation and destruction of such recalcitrant and highly toxic XAr. During our study on the mechanism of metal-independent production of hydroxyl radicals(UOH) by halogenated quinones and H_2O_2, we found, unexpectedly, that an unprecedented UOH-dependent two-step intrinsic chemiluminescene(CL) can be produced by H_2O_2 and tetrachloro-p-benzoquinone, the major carcinogenic metabolite of the widely used wood preservative pentachlorophenol. Further investigations showed that, in all UOH-generating systems, CL can also be produced not only by pentachlorophenol and all other halogenated phenols, but also by all XAr tested. A systematic structure–activity relationship study for all 19 chlorophenolic congeners showed that the CL increased with an increasing number of Cl-substitution in general. More importantly, a relatively good correlation was observed between the formation of quinoid/semiquinone radical intermediates and CL generation. Based on these results, we propose that UOH-dependent formation of quinoid intermediates and electronically excited carbonyl species is responsible for this unusual CL production; and a rapid, sensitive,simple, and effective CL method was developed not only to detect and quantify trace amount of XAr, but also to provide useful information for predicting the toxicity or monitoring real-time degradation kinetics of XAr. These findings may have broad chemical, environmental and biological implications for future studies on halogenated aromatic persistent organic pollutants.

Methylesterification of cell-wall pectin controls the diurnal flower-opening times in rice

Flowers are the core reproductive organ of plants, and flowering is essential for cross-pollination. Diurnal flower-opening time is thus a key trait influencing reproductive isolation, hybrid breeding, and thermostability in plants. However, the molecular mechanisms controlling this trait remain unknown. Here, we report that rice Diurnal Flower Opening Time 1 (DFOT1) modulates pectin methylesterase (PME) activity to regulate pectin methylesterification levels of the lodicule cell walls, which affect lodicule swelling to control diurnal flower-opening time. DFOT1 is specifically expressed in the lodicules, and its expression gradually increases with the approach to flowering but decreases with flowering. Importantly, a knockout of DFOT1 showed earlier diurnal flower opening. We demonstrate that DFOT1 interacts directly with multiple PMEs to promote their activity. Knockout of PME40 also resulted in early diurnal flower opening, whereas overexpression of PME42 delayed diurnal flower opening. Lower PME activity was observed to be associated with higher levels of pectin methylesterification and the softening of cell walls in lodicules, which contribute to the absorption of water by lodicules and cause them to swell, thus promoting early diurnal flower opening. Higher PME activity had the opposite effect. Collectively, our work uncovers a molecular mechanism underlying the regulation of diurnal flower-opening time in rice, which would help reduce the costs of hybrid breeding and improve the heat tolerance of flowering plants by avoiding higher temperatures at anthesis.

Ubiquitinome Profiling Reveals the Landscape of Ubiquitination Regulation in Rice Young Panicles

Ubiquitination,an essential post-transcriptional modification(PTM),plays a vital role in nearly every biological process,including development and growth.Despite its functions in plant reproductive development,its targets in rice panicles remain unclear.In this study,we used proteome-wide profiling of lysine ubiquitination in rice(O.sativa ssp.indica)young panicles.We created the largest ubiquitinome dataset in rice to date,identifying 1638 lysine ubiquitination sites on916 unique proteins.We detected three conserved ubiquitination motifs,noting that acidic glutamic acid(E)and aspartic acid(D)were most frequently present around ubiquitinated lysine.Enrichment analysis of Gene Ontology(GO)annotations and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways of these ubiquitinated proteins revealed that ubiquitination plays an important role in fundamental cellular processes in rice young panicles.Interestingly,enrichment analysis of protein domains indicated that ubiquitination was enriched on a variety of receptorlike kinases and cytoplasmic tyrosine and serine-threonine kinases.Furthermore,we analyzed the crosstalk between ubiquitination,acetylation,and succinylation,and constructed a potential protein interaction network within our rice ubiquitinome.Moreover,we identified ubiquitinated proteins related to pollen and grain development,indicating that ubiquitination may play a critical role in the physiological functions in young panicles.Taken together,we reported the most comprehensive lysine ubiquitinome in rice so far,and used it to reveal the functional role of lysine ubiquitination in rice young panicles.

Lysosomal Hydrolase Cathepsin D Non-proteolytically Modulates Dendritic Morphology in Drosophila

The main lysosomal protease cathepsin D(cathD)is essential for maintaining tissue homeostasis via its degradative function,and its loss leads to ceroid accumulation in the mammalian nervous system,which results in progressive neurodegeneration.Increasing evidence implies non-proteolytic roles of cathD in regulating various biological processes such as apoptosis,cell proliferation,and migration.Along these lines,we here showed that cathD is required for modulating dendritic architecture in the nervous system independent of its traditional degradative function.Upon cathD depletion,class I and class III arborization(da)neurons in Drosophila larvae exhibited aberrant dendritic morphology,including overbranching,aberrant turning,and elongation defects.Reintroduction of wild-type cathD or its proteolyticallyinactive mutant dramatically abolished these morphological defects.Moreover,cathD knockdown also led to dendritic defects in the adult mushroom bodies,suggesting that cathD-mediated processes are required in both the peripheral and central nervous systems.Taken together,our results demonstrate a critical role of cathD in shaping dendritic architecture independent of its proteolytic function.