Multi-omics analysis revealed that the protein kinase MoKin1 affected the cellular response to endoplasmic reticulum stress in the rice blast fungus, Magnaporthe oryzae.

BACKGROUND: Previous studies have shown that protein kinase MoKin1 played an important role in the growth, conidiation, germination and pathogenicity in rice blast fungus, Magnaporthe oryzae. ΔMokin1 mutant showed significant phenotypic defects and significantly reduced pathogenicity. However, the internal mechanism of how MoKin1 affected the development of physiology and biochemistry remained unclear in M. oryzae. RESULT: This study adopted a multi-omics approach to comprehensively analyze MoKin1 function, and the results showed that MoKin1 affected the cellular response to endoplasmic reticulum stress (ER stress). Proteomic analysis revealed that the downregulated proteins in ΔMokin1 mutant were enriched mainly in the response to ER stress triggered by the unfolded protein. Loss of MoKin1 prevented the ER stress signal from reaching the nucleus. Therefore, the phosphorylation of various proteins regulating the transcription of ER stress-related genes and mRNA translation was significantly downregulated. The insensitivity to ER stress led to metabolic disorders, resulting in a significant shortage of carbohydrates and a low energy supply, which also resulted in severe phenotypic defects in ΔMokin1 mutant. Analysis of MoKin1-interacting proteins indicated that MoKin1 really took participate in the response to ER stress. CONCLUSION: Our results showed the important role of protein kinase MoKin1 in regulating cellular response to ER stress, providing a new research direction to reveal the mechanism of MoKin1 affecting pathogenic formation, and to provide theoretical support for the new biological target sites searching and bio-pesticides developing.

Br-Vacancies Induced Variable Ranging Hopping Conduction in High-Order Topological Insulator Bi4Br4.

The defects have a remarkable influence on the electronic structures and the electric transport behaviors of the matter, providing the additional means to engineering their physical properties. In this work, a comprehensive study on the effect of Br-vacancies on the electronic structures and transport behaviors in the high-order topological insulator Bi4Br4 is performed by the combined techniques of the scanning tunneling microscopy (STM), angle-resolved photoemission spectroscopy (ARPES), and physical properties measurement system along with the first-principle calculations. The STM results show the defects on the cleaved surface of a single crystal and reveal that the defects are correlated to the Br-vacancies with the support of the simulated STM images. The role of the Br-vacancies in the modulation of the band structures has been identified by ARPES spectra and the calculated energy-momentum dispersion. The relationship between the Br-vacancies and the semiconducting-like transport behaviors at low temperature has been established, implying a Mott variable ranging hopping conduction in Bi4Br4. The work not only resolves the unclear transport behaviors in this matter, but also paves a way to modulate the electric conduction path by the defects engineering.

CAR-NK cells for acute myeloid leukemia immunotherapy: past, present and future.

Acute myeloid leukemia (AML) is a deadly disease and the most common leukemia in adult with clonal heterogeneity and abnormity in myeloid lineages, which has been recognized with high morbidity and mortality attributes to the recurrence and resistance to chemotherapy. Numerous literatures have indicated the encouraging progress in allogeneic hematopoietic stem cell transplantation (allo-HSCT) and chimeric antigen receptor-transduced T (CAR-T) cells. However, the outcomes of recurrent and refractory AML (r/rAML) patients with current strategies are still unsatisfactory, which largely due to the matching restriction as well as adverse reactions, including graft-versus-host disease (GvHD), neurotoxicity and cytokine release syndrome (CRS). State-of-the-art literatures have indicated CAR-transduced NK (CAR-NK) cells for the management of diverse hematologic malignancies including AML, which are recognized as novel weapons for reinforcing the specificity and cytotoxicity of autogenous and allogeneic "off-the-shelf" NK cells dispense with prior sensitization. Therefore, in this review, we mainly focus on the latest updates of alternative cell sources, therapeutic targets, CAR-modification and delivery strategies, standardization and productization, together with prospective and challenges of CAR-NK cell-based cytotherapy, which will collectively benefit the further development of novel treatment paradigms for combating AML via both CAR-dependent and NK cell receptor-dependent signaling cascades in future.

Vertical Stress Induced Anomalous Spectral Shift of 13.17° Moiré Superlattice in Twist Bilayer Graphene.

The electronic states of the twist bilayer graphene (TBG) moiré superlattice are usually regulated by the rotation angle, applied electric field, applied magnetic field, carrier concentration and applied stress, and thus exhibit novel physical properties. Squeezing, that is, applying vertical compressive stress to the graphene layers, has profound significance in regulating the photoelectric properties of the moiré superlattice and constructing optical nanodevices. This paper presents the photoelectric properties of a TBG moiré superlattice with a twist angle of 13.17° and tunability under vertical stress. Interlayer distance decreases nonlinearly with compressive stress from 0 to 10 GPa, giving rise to weakened interlayer coupling compared to a Bernal-stacked graphene bilayer and an enhanced repulsive effect between the layers. The calculated Bloch wave functions show a strong dependence on stress. With the increase in stress, the band gaps of the system present a nonlinear increase, which induces and enhances the interlayer charge transfer and leads to the redshift of the absorption spectrum of the moiré superlattice system. By analyzing the differences in the Bloch wave function and charge density differences, we explain the nature of the physical mechanism of photoelectric property change in a stress-regulated twist superlattice system. This study provides a theoretical basis for the identification of piezoelectric properties and the stress regulation of photoelectric devices based on TBG, and also provides a feasible method for regulating the performance of TBG.

Transcriptome Analysis of Protein Kinase MoCK2, which Affects Acetyl-CoA Metabolism and Import of CK2-Interacting Mitochondrial Proteins into Mitochondria in the Rice Blast Fungus Magnaporthe oryzae.

The rice pathogen Magnaporthe oryzae causes severe losses to rice production. Previous studies have shown that the protein kinase MoCK2 is essential for pathogenesis, and this ubiquitous eukaryotic protein kinase might affect several processes in the fungus that are needed for infection. To better understand which cellular processes are affected by MoCK2 activity, we performed a detailed transcriptome sequencing analysis of deletions of the MoCK2 b1 and b2 components in relation to the background strain Ku80 and connected this analysis with the abundance of substrates for proteins in a previous pulldown of the essential CKa subunit of CK2 to estimate the effects on proteins directly interacting with CK2. The results showed that MoCK2 seriously affected carbohydrate metabolism, fatty acid metabolism, amino acid metabolism, and the related transporters and reduced acetyl-CoA production. CK2 phosphorylation can affect the folding of proteins and especially the effective formation of protein complexes by intrinsically disordered or mitochondrial import by destabilizing soluble alpha helices. The upregulated genes found in the pulldown of the b1 and b2 mutants indicate that proteins directly interacting with CK2 are compensatorily upregulated depending on their pulldown. A similar correlation was found for mitochondrial proteins. Taken together, the classes of proteins and the changes in regulation in the b1 and b2 mutants suggest that CK2 has a central role in mitochondrial metabolism, secondary metabolism, and reactive oxygen species (ROS) resistance, in addition to its previously suggested role in the formation of new ribosomes, all of which are processes central to efficient nonself responses as innate immunity. IMPORTANCE The protein kinase CK2 is highly expressed and essential for plants, animals, and fungi, affecting fatty acid-related metabolism. In addition, it directly affects the import of essential mitochondrial proteins into mitochondria. These effects mean that CK2 is essential for lipid metabolism and mitochondrial function and, as shown previously, is crucial for making new translation machinery proteins. Taken together, our new results combined with previously reported results indicate that CK2 is an essential protein necessary for the capacities to launch efficient innate immunity responses and withstand the negative effects of such responses necessary for general resistance against invading bacteria and viruses as well as to interact with plants, withstand plant immunity responses, and kill plant cells.

Sleep quality status, anxiety, and depression status of nurses in infectious disease department.

Objective: To investigate the current status of sleep quality and influencing factors of clinical nurses in infectious disease hospitals, and to provide basis and reference for improving their sleep status and providing psychological support. Methods: Using convenience sampling method, clinical nurses from a tertiary hospital for infectious diseases were selected as the survey subjects in September 2021. General information questionnaire, Pittsburgh Sleep Quality Questionnaire (PSQI), Generalized Anxiety Disorder Scale (GAD-7), Depression Screening Scale (PHQ-9) were used for questionnaire surveys, and multiple linear regression was used to analyze the impact of decreased sleep quality in clinical nurses factor. Results: A total of 460 questionnaires were returned, of which 442 were valid, effective rate is 96.09%. The Pittsburgh sleep quality index (PSQI) score of 442 clinical nurses was 7.07 ± 2.14, of which 60 (13.57%) had sleep disorders; the Generalized Anxiety Disorder Scale (GAD-7) score was 4.77 ± 3.50, of which 182 (41.18%) had varying degrees of anxiety; The score of PHQ-9 was 5.95 ± 3.79, of which 187 (42.31%) had different degrees of depressive symptoms. The stepwise multiple linear regression analysis which involved PHQ-9 and GAD-7 scores showed that: both the PHQ-9 score and the GAD-7 score were positively correlated with the sleep quality score, and the PHQ-9 score increased every time 1 point, sleep quality score increased by 0.239 points; GAD-7 score increased by 1 point, sleep quality score increased by 0.150 points. The overall model test (F = 109.760, P < 0.001) regression model is meaningful. Conclusion: Decreased sleep quality is common among clinical nurses in infectious disease hospitals, and the sleep status of nurses is positively correlated with anxiety and depression. Nursing managers pay attention to sleep quality of clinical nurses in infectious disease hospitals and carry out effective interventions to improve the sleep quality of nurses.

Decoding the multidimensional signatures of resident and expanded natural killer cells generated from perinatal blood.

Natural killer (NK) cells are lymphocytes and play a pivotal role in innate and adaptive immune responses against infections and malignancies. Longitudinal studies have indicated the feasibility of perinatal blood for large-scale NK cell generation, yet the systematic and detailed comparations of the signatures of resident and expanded NK cells (rNKs, eNKs) are largely obscure. Herein, we harvested rNKs from umbilical cord blood (rUC-NKs) and placental blood (rP-NKs) as well as the corresponding eNKs (eUC-NKs, eP-NKs). Furthermore, the biological properties and transcriptomic signatures including cellular subpopulations, cytotoxicity, gene expression profiling, genetic characteristics, signaling pathways and gene set-related biological process were investigated. The enriched rNKs and eNKs exhibited diversity in biomarker expression pattern, and eNKs with higher percentages of NKG2D+, NKG2A+, NKp44+ and NKp46+ subsets. rNKs or eNKs with different origins showed more similarities in transcriptomic signatures than those with the same origin. Our data revealed multifaceted similarities and differences of the indicated rNKs and pNKs both at the cellular and molecular levels. Our findings provide new references for further dissecting the efficacy and molecular mechanisms of rNKs and eNKs, which will collectively benefit the fundamental and translational studies of NK cell-based immunotherapy.

[Clinical Significance of Pretransplant Serum Ferritin Level in Patients with Prolonged Thrombocytopenia after Allogeneic Hematopoietic Stem Cell Transplantation].

OBJECTIVE: To investigate the correlation between pretransplant serum ferritin (SF) level and prolonged or prolonged isolated thrombocytopenia (PT) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: The clinical data of 35 patients with PT after allo-HSCT were retrospectively analyzed, and 35 patients were matched according to age and sex as a controls from 424 allo-HSCT patients with normal platelet count. The serum ferritin level before the transplantation was analyzed. The potential risk factors were analyzed by chi-square test and Fisher's exact test as well as univariate and multivariate logistic regression. The survival curve was estimated by the Kaplan-Meier model to explore its clinical significance. In addition, ROC curve was used to verify the predictive power of SF. RESULTS: Compared with control group, the SF level in the PT group before transplantation significantly increased (P=0.001). Multivariate analysis results showed that SF level before transplantation was a risk factor for prolonged thrombocytopenia after HSCT, and patients with SF≥1000 ng / ml showed a higher risk of death (P=0.014). ROC curve showed that SF level could be used as a predictor of prolonged thrombocytopenia after allo-HSCT. CONCLUSION: The SF level before allo-HSCT relates with occurrence and prognosis of PT in patients after allo-HSCT. Detection of SF level can provide guidance for the intervention of prolonged thrombocytopenia after HSCT.

Rare earth ions-enhanced gold nanoclusters as fluorescent sensor array for the detection and discrimination of phosphate anions.

The discrimination and detection of phosphate anions have attracted extensive attention due to their important roles in various biological processes. Compared with sensors to detect one individual phosphate at a time, sensor arrays are able to discriminate multiple phosphates simultaneously. In this study, we developed a rare earth ions enhanced AuNCs-based sensor array to achieve facile and rapid identification of phosphate anions (PPi, ADP and ATP). The rare earth ions (i. e., Ce3+ , Gd3+ , Tm3+ and Yb3+ ) can significantly enhance the fluorescence of AuNCs through aggregation-induced emission effect. And the subsequent addition of phosphate anions can recover the fluorescence of the AuNCs-rare earth ions assembly. Thanks to the different numbers of phosphate group and different steric hindrance effects of phosphate anions, the recovery fluorescence of AuNCs-rare earth ions assembly induced by PPi, ADP or ATP are respectively distinct. Thus the sensor array composed of AuNCs and different rare earth ions is able to distinguish those phosphate anions. Finally, the sensor array was successfully demonstrated to identify the phosphates in blind samples.

Immune Thrombocytopenia Plasma-Derived Exosomes Impaired Megakaryocyte and Platelet Production through an Apoptosis Pathway.

Reduced megakaryocyte (MK) apoptosis and insufficient platelet production play important roles in the pathogenesis of immune thrombocytopenia (ITP). The contribution of plasma-derived exosomes to the decreased platelet count in ITP has not been entirely understood. Here, we found the percentage of apoptotic MKs in patients with ITP was significantly lower than those in healthy volunteers. In the presence of ITP plasma-derived exosomes (ITP-Exo), the apoptosis of MKs was reduced during the process of MK differentiation in vitro, which contributed to the reduced platelet production by Bcl-xL/caspase signaling. Furthermore, in vivo study demonstrated that ITP-Exo administration led to significantly delayed platelet recovery in mice after 3.5 Gy of irradiation. All these findings indicated that ITP-Exo, as a regulator of platelet production, impaired MK apoptosis and platelet production through Bcl-xL/caspase signaling, unveiling new mechanisms for reduced platelet count in ITP.

The prognostic value of plasma fibrinogen level in patients with acute myeloid leukemia: a systematic review and meta-analysis.

Increasing evidence has revealed that plasma fibrinogen levels may serve as prognostic indicators in patients with acute myeloid leukemia (AML), yet the exact association is still elusive. We conducted a systematic review and meta-analysis of all available studies concerning the relationship between plasma fibrinogen level and survival in AML patients. The pooled hazard ratio (HR) and 95% confidence intervals (CIs) for overall survival (OS) were calculated to evaluate the effect. A random-effect model was applied and the robustness of the pooled results was confirmed by subgroup and sensitivity analysis. A total of 9 studies were eligible to assess the association between plasma fibrinogen level and prognosis in AML. Among these investigations above, 5 studies adopted OS as their outcome indicator and were selected for the final meta-analysis. The pooled result suggested that plasma fibrinogen level was significantly relevant to increased mortality risk in AML patients (HR = 1.21, 95% CI: 1.01-1.44, p = .000, I2=85.4%). In conclusion, high plasma fibrinogen level may independently predict worse OS in patients with AML.

Intra-specific comparison of mitochondrial genomes reveals host gene fragment exchange via intron mobility in Tremella fuciformis.

BACKGROUND: Mitochondrial genomic sequences are known to be variable. Comparative analyses of mitochondrial genomes can reveal the nature and extent of their variation. RESULTS: Draft mitochondrial genomes of 16 Tremella fuciformis isolates (TF01-TF16) were assembled from Illumina and PacBio sequencing data. Mitochondrial DNA contigs were extracted and assembled into complete circular molecules, ranging from 35,104 bp to 49,044 bp in size. All mtDNAs contained the same set of 41 conserved genes with identical gene order. Comparative analyses revealed that introns and intergenic regions were variable, whereas genic regions (including coding sequences, tRNA, and rRNA genes) were conserved. Among 24 introns detected, 11 were in protein-coding genes, 3 in tRNA genes, and the other 10 in rRNA genes. In addition, two mobile fragments were found in intergenic regions. Interestingly, six introns containing N-terminal duplication of the host genes were found in five conserved protein-coding gene sequences. Comparison of genes with and without these introns gave rise to the following proposed model: gene fragment exchange with other species can occur via gain or loss of introns with N-terminal duplication of the host genes. CONCLUSIONS: Our findings suggest a novel mechanism of fungal mitochondrial gene evolution: partial foreign gene replacement though intron mobility.

The Dependence of Implicit Solvent Model Parameters and Electronic Absorption Spectra and Photoinduced Charge Transfer.

In this work, the relationship between multiple solvent parameters and charge transfer index was analyzed by multi-factor multi-variate partial least squares regression (PLSR). The charge transfer of the molecule is visualized by the analysis of the excited state wave function. Hydrogen bond basicity and surface tension can significantly affect charge transfer by studying the solvation model parameters and charge transfer index. Finally, a method in which a solvent regulates charge transfer strength and migration length is proposed.

Efficacy and Safety of Eculizumab in the Treatment of Transplant-Associated Thrombotic Microangiopathy: A Systematic Review and Meta-Analysis.

Background: Transplant-associated thrombotic microangiopathy (TA-TMA) is a dangerous and life-threatening complication in patients undergoing hematopoietic stem cell transplantation (HSCT). Eculizumab has been used in the treatment of TA-TMA, and several studies have confirmed the benefit of Eculizumab in patients with TA-TMA. However, the results remain controversial. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of Eculizumab for TA-TMA. Materials and Methods: We searched PubMed and Embase for studies on the efficacy and safety of Eculizumab in TA-TMA patients. Efficacy outcomes consisted of overall response rate (ORR), complete response rate (CRR), and survival rate at the last follow-up (SR). Safety outcomes were adverse events (AEs), including infection, sepsis, impaired liver function, infusion reactions, and death. Results: A total of 116 patients from six studies were subjected to meta-analysis. The pooled estimates of ORR, CRR, and SR for TA-TMA patients were 71% (95% CI: 58-82%), 32% (95% CI: 11-56%), and 52% (95% CI: 40-65%), respectively. Only one patient presented with a severe rash, and infection was the most common AEs. The main causes of death were infection and GvHD. Conclusion: Current evidence suggests that Eculizumab improves SR and ORR in patients with TA-TMA and that Eculizumab is well tolerated. However, the number of studies is limited, and the findings are based mainly on data from observational studies. Higher quality randomized controlled trials and more extensive prospective cohort studies are needed.

Circulating Heme Oxygenase-1 and Complement Activation in Transplant-Associated Thrombotic Microangiopathy.

Transplant-associated thrombotic microangiopathy (TA-TMA) is a severe complication in patients after hematopoietic stem cell transplantation. The pathogenesis of TA-TMA is still unclear. Previous studies showed that complement activation plays an important role in the development of TA-TMA. However, no data showed which kind of complement component triggers this process. In this study we found that heme oxygenase-1, which could induce decay-accelerating factor (DAF) and inhibit the membrane-attack complex, was significantly decreased in patients with TA-TMA. DAF levels in the TA-TMA group were in line with the levels in the myocardial infarction group but were lower than levels in the healthy, noncomplication, infection, and graft-versus-host disease groups (P < .05). Human umbilical vein endothelial cells (HUVECs) incubated with TA-TMA plasma showed lower DAF levels compared with that incubated with normal human plasma. Notably, treatment with N-acetylcysteine (NAC), a drug against oxidation, increased the level of DAF. NAC could also inhibit complement activation in HUVECs incubated with TA-TMA plasma. Taken together, we propose that NAC represents a new potential therapy for patients facing TA-TMA.

Temporal and spatial transcriptomic and microRNA dynamics of CAM photosynthesis in pineapple.

The altered carbon assimilation pathway of crassulacean acid metabolism (CAM) photosynthesis results in an up to 80% higher water-use efficiency than C3 photosynthesis in plants making it a potentially useful pathway for engineering crop plants with improved drought tolerance. Here we surveyed detailed temporal (diel time course) and spatial (across a leaf gradient) gene and microRNA (miRNA) expression patterns in the obligate CAM plant pineapple [Ananas comosus (L.) Merr.]. The high-resolution transcriptome atlas allowed us to distinguish between CAM-related and non-CAM gene copies. A differential gene co-expression network across green and white leaf diel datasets identified genes with circadian oscillation, CAM-related functions, and source-sink relations. Gene co-expression clusters containing CAM pathway genes are enriched with clock-associated cis-elements, suggesting circadian regulation of CAM. About 20% of pineapple microRNAs have diel expression patterns, with several that target key CAM-related genes. Expression and physiology data provide a model for CAM-specific carbohydrate flux and long-distance hexose transport. Together these resources provide a list of candidate genes for targeted engineering of CAM into C3 photosynthesis crop species.

The pineapple genome and the evolution of CAM photosynthesis.

Pineapple (Ananas comosus (L.) Merr.) is the most economically valuable crop possessing crassulacean acid metabolism (CAM), a photosynthetic carbon assimilation pathway with high water-use efficiency, and the second most important tropical fruit. We sequenced the genomes of pineapple varieties F153 and MD2 and a wild pineapple relative, Ananas bracteatus accession CB5. The pineapple genome has one fewer ancient whole-genome duplication event than sequenced grass genomes and a conserved karyotype with seven chromosomes from before the ρ duplication event. The pineapple lineage has transitioned from C3 photosynthesis to CAM, with CAM-related genes exhibiting a diel expression pattern in photosynthetic tissues. CAM pathway genes were enriched with cis-regulatory elements associated with the regulation of circadian clock genes, providing the first cis-regulatory link between CAM and circadian clock regulation. Pineapple CAM photosynthesis evolved by the reconfiguration of pathways in C3 plants, through the regulatory neofunctionalization of preexisting genes and not through the acquisition of neofunctionalized genes via whole-genome or tandem gene duplication.

Origin and domestication of papaya Yh chromosome.

Sex in papaya is controlled by a pair of nascent sex chromosomes. Females are XX, and two slightly different Y chromosomes distinguish males (XY) and hermaphrodites (XY(h)). The hermaphrodite-specific region of the Y(h) chromosome (HSY) and its X chromosome counterpart were sequenced and analyzed previously. We now report the sequence of the entire male-specific region of the Y (MSY). We used a BAC-by-BAC approach to sequence the MSY and resequence the Y regions of 24 wild males and the Y(h) regions of 12 cultivated hermaphrodites. The MSY and HSY regions have highly similar gene content and structure, and only 0.4% sequence divergence. The MSY sequences from wild males include three distinct haplotypes, associated with the populations' geographic locations, but gene flow is detected for other genomic regions. The Y(h) sequence is highly similar to one Y haplotype (MSY3) found only in wild dioecious populations from the north Pacific region of Costa Rica. The low MSY3-Y(h) divergence supports the hypothesis that hermaphrodite papaya is a product of human domestication. We estimate that Y(h) arose only ∼ 4000 yr ago, well after crop plant domestication in Mesoamerica >6200 yr ago but coinciding with the rise of the Maya civilization. The Y(h) chromosome has lower nucleotide diversity than the Y, or the genome regions that are not fully sex-linked, consistent with a domestication bottleneck. The identification of the ancestral MSY3 haplotype will expedite investigation of the mutation leading to the domestication of the hermaphrodite Y(h) chromosome. In turn, this mutation should identify the gene that was affected by the carpel-suppressing mutation that was involved in the evolution of males.