Functional characterization of NOD1 from golden pompano Trachinotus ovatus.

Fish rely on innate immune system for immunity, and nucleotide-binding oligomerization domain-like receptors (NLRs) are a vital group of receptor for recognition. In the present study, NOD1 gene was cloned and characterized from golden pompano Trachinotus ovatus, a commercially important aquaculture fish species. The ORF of T. ovatus NOD1 was 2820 bp long, encoding 939 amino acid residues with a highly conserved domains containing CARD-NACHT-LRRs. Phylogenetic analysis revealed that the T. ovatus NOD1 clustered with those of fish and separated from those of birds and mammals. T. ovatus NOD1 has wide tissue distribution with the highest expression in gills. Bacterial challenges (Streptococcus agalactiae and Vibrio alginolyticus) significantly up-regulated the expression of NOD1 with different response time. The results of T. ovatus NOD1 ligand recognition and signaling pathway analysis revealed that T. ovatus NOD1 could recognize iE-DAP at the concentration of ≧ 100 ng/mL and able to activate NF-κB signaling pathway. This study confirmed that NOD1 play a crucial role in the innate immunity of T. ovatus. The findings of this study improve our understanding on the immune function of NOD1 in teleost, especially T. ovatus.

Regulation of PhoB on biofilm formation and hemolysin gene hlyA and ciaR of Streptococcus agalactiae.

PhoB is a response regulator protein that plays a key role in the PhoBR two-component signal transduction system. In this study, we used transcriptome and proteomics techniques to evaluate the detect the gene network regulated by PhoB of Streptococcus agalactiae. The results showed that expression of biofilm formation and virulence-related genes were changed after phoB deficiency. Crystal violet and CLSM assay confirmed that the deletion of the phoB increased the thickness of S. agalactiae biofilm. The results of lacZ reporter and the bacterial one-hybridization method showed that PhoB could directly bind to the promoter regions of hemolysin A and ciaR genes but not to the promoter regions of cylE and hemolysin III. Through the construction of an 18-base pair deoxyribose nucleic acid (DNA) random fragment library and the bacterial one-hybridization system, it was found that the conservative sequence of PhoB binding was TTGGAGAA(G/T). Our research has uncovered the virulence potential of the PhoBR two-component system of S. agalactiae. The findings of this study provide the theoretical foundation for in-depth research on the pathogenic mechanism of S. agalactiae.

Low-Cost Preparation of High-Performance Na-B-H-S Electrolyte for All-Solid-State Sodium-Ion Batteries.

All-solid-state sodium-ion batteries have the potential to improve safety and mitigate the cost bottlenecks of the current lithium-ion battery system if a high-performance electrolyte with cost advantages can be easily synthesized. In this study, a one-step dehydrogenation-assisted strategy to synthesize the novel thio-borohydride (Na-B-H-S) electrolyte is proposed, in which both raw material cost and preparation temperature are significantly reduced. By using sodium borohydride (NaBH4 ) instead of B as a starting material, B atoms can be readily released from NaBH4 with much less energy and thus became more available to generate thio-borohydride. The synthesized Na-B-H-S (NaBH4 /Na-B-S) electrolyte exhibits excellent compatibility with current cathode materials, including FeF3 (1.0-4.5 V), Na3 V2 (PO4 )3 (2.0-4.0 V), and S (1.2-2.8 V). This novel Na-B-H-S electrolyte will take a place in mainstream electrolytes because of its advantages in preparation, cost, and compatibility with various cathode materials.

Molecular characterization of complement regulatory factor CD46 in Trachinotus ovatus and its role in the antimicrobial immune responses and complement regulation.

CD46, as a cofactor of complement I factor, not only regulates the complement system but also functions as a pathogen receptor and is involved in controlling early pathogen infection through autophagy. In this study, a new CD46 gene (ToCD46) was identified from golden pompano (Trachinotus ovatus), which showed higher sequence homology with other teleosts CD46. Homology comparison showed that ToCD46 had higher sequence homology (46.95-52.85%) with other teleosts CD46 and lower homology with mammal. Tissue expression profile analysis showed that ToCD46 was generally expressed in all tissues with the highest expression level in liver, followed by head kidney, and showed different patterns of up-regulation in immune-related tissues after stimulation by Streptococcus agalactiae and Vibrio alginolyticus. The hemolytic activity analysis and apoptosis assay showed that rToCD46 decreased the hemolytic activity of serum of golden pompano and effectively inhibited the damage of A549 cells, suggesting that ToCD46 might be involved in the regulation of complement activation of golden pompano. In vitro antibacterial experiments showed that rToCD46 had antibacterial activity against gram negative bacteria V. alginolyticus but no effect on positive bacteria S. agalactiae. These results suggest that ToCD46 may be involved in the immune response of golden pompano to pathogens, which will provide important basic information for elucidating the evolutionary history of the complement system of golden pompano.

The high expression of glial cell line-derived neurotrophic factor receptor alpha â ¡ (GFRA2) as a predictor of poor prognosis in gastric cancer patients: A survival and regression analysis approach.

Gastric cancer has high mortality rates worldwide. Therefore, there is a need to identify prognostic biomarkers. This study evaluated the association between GFRA2 expression levels with clinicopathological features and prognosis in gastric cancer using data extracted from The Cancer Genome Atlas (TCGA) database and a series of algorithms. Survival analysis was performed using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were used to analyze the association between different clinical features and survival. Single-sample gene set enrichment analysis (GSEA) was used to examine the correlation between GFRA2 expression and immune infiltration. The results showed that the expression of GFRA2 in tumor samples was significantly lower than that in normal samples. High expression of GFRA2 was significantly associated with histological type, histologic grade, and worse overall survival, disease-specific survival, and progression-free survival. The univariate Cox analysis showed that the expression of GFRA2 was significantly correlated with T stage, N stage, M stage, and age. The multivariate analysis identified GFRA2 expression as an independent prognostic factor for gastric cancer. GSEA showed that GFRA2 might regulate the calcium signaling pathway, focus adhesion, olfactory conduction, the extracellular matrix glycoproteins, and response to the Leishmania parasitic infection. GFRA2 showed a significant moderate positive correlation with the infiltration of mast cells. In summary, a high expression of GFRA2 may contribute to poor survival in gastric cancer patients and could be used as a potential prognostic biomarker.

Promotion of the Nucleation of Ultrafine Ni-Rich Layered Oxide Primary Particles by an Atomic Layer-Deposited Thin Film for Enhanced Mechanical Stability.

Understanding the atomistic mechanisms of non-equilibrium processes during solid-state synthesis, such as nucleation and grain structure formation of a layered oxide phase, is a critical challenge for developing promising cathode materials such as Ni-rich layered oxide for Li-ion batteries. In this study, we found that the aluminum oxide coating layer transforms into lithium aluminate as an intermediate, which has favorable low interfacial energies with the layered oxide to promote the nucleation of the latter. The fast and uniform nucleation and formation of the layered oxide phase at relatively low temperatures were evidenced using solid-state nuclear magnetic resonance and in situ synchrotron X-ray diffraction. The resulting Ni-rich layered oxide cathode has fine primary particles, as visualized by three-dimensional tomography constructed using a focused-ion beam and scanning electron microscopy. The densely packed fine primary particles enable the excellent mechanical strength of the secondary particles, as demonstrated by in situ compression tests. This strategy provides a new approach for developing next-generation, high-strength battery materials.

Humeral and cellular immune responses to SARS-CoV-2 vaccination in patients on peritoneal dialysis.

BACKGROUND: Patients with chronic kidney disease are at high risk for coronavirus disease 2019. Little is known about immune response to severe acute respiratory syndrome coronavirus 2 vaccination in patients on peritoneal dialysis (PD). METHOD: We prospectively enrolled 306 PD patients receiving two doses of vaccines (ChAdOx1-S: 283, mRNA-1273: 23) from July 2021 at a medical center. Humeral and cellular immune responses were assessed by anti-spike IgG concentration and blood T cell interferon-γ production 30 days after vaccination. Antibody ≥0.8 U/mL and interferon-γ ≥ 100 mIU/mL were defined as positive. Antibody was also measured in 604 non-dialysis volunteers (ChAdOx1-S: 244, mRNA-1273: 360) for comparison. RESULT: PD patients had less adverse events after vaccinations than volunteers. After the first dose of vaccine, the median antibody concentrations were 8.5 U/mL and 50.4 U/mL in ChAdOx1-S group and mRNA-1273 group of PD patients, and 66.6 U/mL and 195.3 U/mL in ChAdOx1-S group and mRNA-1273 group of volunteers, respectively. And after the second dose of vaccine, the median antibody concentrations were 344.8 U/mL and 9941.0 U/mL in ChAdOx1-S group and mRNA-1273 group of PD patients, and 620.3 U/mL and 3845.0 U/mL in ChAdOx1-S group and mRNA-1273 group of volunteers, respectively. The median IFN-γ concentration was 182.8 mIU/mL in ChAdOx1-S group, which was substantially lower than the median concentration 476.8 mIU/mL in mRNA-1273 group of PD patients. CONCLUSION: Both vaccines were safe and resulted in comparable antibody seroconversion in PD patients when compared with volunteers. However, mRNA-1273 vaccine induced significantly higher antibody and T cell response than ChAdOx1-S in PD patients. Booster doses are recommended for PD patients after two doses of ChAdOx1-S vaccination.

Fat mass as an important predictor of persistent hypertension in patients with primary aldosteronism after adrenalectomy.

Aldosterone excess is present in obesity and is associated with involvement in the pathogenesis of obesity. We evaluate the impact of body obesity as measured by body composition monitor (BCM) on clinical outcomes in patients with unilateral primary aldosteronism (uPA) after adrenalectomy. The BCM device was used to assess body composition before and after adrenalectomy. We used fat mass (FM) and body mass index (BMI) to classify obesity and divided obesity into three groups: clinical overweight (BMI (kg/m2) ≥25); normal weight obesity (NWO, FM (%) ≥ 35 for women, >25 for men & BMI < 25); and no obesity (FM < 35 for women, <25 for men & BMI < 25). A total of 130 unilateral PA (uPA) patients received adrenalectomy, and 27 EH patients were identified; uPA patients with hypertension remission were found to have lower FM (p = 0.046), BMI (p < 0.001), and lower prevalence of overweight (p = 0.001). In the logistic regression model, patients with clinical overweight (OR = 2.9, p = 0.007), NWO (OR = 3.04, p = 0.041) and longer HTN duration (years, OR = 1.065, p = 0.013) were at the risk of persistent hypertension after adrenalectomy. Obesity status was strongly associated with persistent hypertension in uPA patients after adrenalectomy. However, patients in the NWO group also carried higher risk of persistent hypertension. Therefore, assessment of pre-obesity and overweight in uPA patients are extremely important, especially in those who have normal BMI.

Comparative accuracy of biomarkers for the prediction of hospital-acquired acute kidney injury: a systematic review and meta-analysis.

BACKGROUND: Several biomarkers have been proposed to predict the occurrence of acute kidney injury (AKI); however, their efficacy varies between different trials. The aim of this study was to compare the predictive performance of different candidate biomarkers for AKI. METHODS: In this systematic review, we searched PubMed, Medline, Embase, and the Cochrane Library for papers published up to August 15, 2022. We selected all studies of adults (> 18 years) that reported the predictive performance of damage biomarkers (neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid-binding protein (L-FABP)), inflammatory biomarker (interleukin-18 (IL-18)), and stress biomarker (tissue inhibitor of metalloproteinases-2 × insulin-like growth factor-binding protein-7 (TIMP-2 × IGFBP-7)) for the occurrence of AKI. We performed pairwise meta-analyses to calculate odds ratios (ORs) and 95% confidence intervals (CIs) individually. Hierarchical summary receiver operating characteristic curves (HSROCs) were used to summarize the pooled test performance, and the Grading of Recommendations, Assessment, Development and Evaluations criteria were used to appraise the quality of evidence. RESULTS: We identified 242 published relevant studies from 1,803 screened abstracts, of which 110 studies with 38,725 patients were included in this meta-analysis. Urinary NGAL/creatinine (diagnostic odds ratio [DOR] 16.2, 95% CI 10.1-25.9), urinary NGAL (DOR 13.8, 95% CI 10.2-18.8), and serum NGAL (DOR 12.6, 95% CI 9.3-17.3) had the best diagnostic accuracy for the risk of AKI. In subgroup analyses, urinary NGAL, urinary NGAL/creatinine, and serum NGAL had better diagnostic accuracy for AKI than urinary IL-18 in non-critically ill patients. However, all of the biomarkers had similar diagnostic accuracy in critically ill patients. In the setting of medical and non-sepsis patients, urinary NGAL had better predictive performance than urinary IL-18, urinary L-FABP, and urinary TIMP-2 × IGFBP-7: 0.3. In the surgical patients, urinary NGAL/creatinine and urinary KIM-1 had the best diagnostic accuracy. The HSROC values of urinary NGAL/creatinine, urinary NGAL, and serum NGAL were 91.4%, 85.2%, and 84.7%, respectively. CONCLUSIONS: Biomarkers containing NGAL had the best predictive accuracy for the occurrence of AKI, regardless of whether or not the values were adjusted by urinary creatinine, and especially in medically treated patients. However, the predictive performance of urinary NGAL was limited in surgical patients, and urinary NGAL/creatinine seemed to be the most accurate biomarkers in these patients. All of the biomarkers had similar predictive performance in critically ill patients. Trial registration CRD42020207883 , October 06, 2020.

Positive Correlation of Peripheral CD8+ T Lymphocytes with Immune-Related Adverse Events and Combinational Prognostic Value in Advanced Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICIs) therapy has revolutionized the treatment patterns of non-small cell lung cancer (NSCLC). However, patients treated with ICIs may experience immune-related adverse events (irAEs). Markers that could predict the onset of irAEs are still unclear. Here, we report the possible correlation of baseline peripheral lymphocytes with irAEs and clinical outcomes in advanced NSCLC patients receiving ICIs. A total of 109 advanced NSCLC patients treated with ICIs from April 2017 to January 2021 were analyzed retrospectively. Logistic and Cox regression analyses was applied to evaluate independent risk factors for irAEs, progression-free survival (PFS), and overall survival (OS). Among these patients, 55 (50.5%) patients experienced irAEs. The level of CD8+ T lymphocytes at baseline was the independent risk factor for the onset of irAEs (p = 0.008). A higher level of CD8+ T lymphocytes was associated with longer PFS (11.0 months vs. 3.0 months, p < 0.001) and OS (27.9 months vs. 11.7 months, p = 0.014). Furthermore, patients who had higher baseline CD8+ T lymphocytes and experienced irAEs had a longer PFS (18.4 months vs. 2.2 months, p < 0.001) and OS (32.8 months vs. 9.0 months, p = 0.001) than those who had lower CD8+ T lymphocytes and no irAEs. Our study highlights the value of baseline peripheral CD8+ T lymphocytes as a predictive factor for irAEs in advanced NSCLC patients receiving ICIs. In addition, patients who have higher baseline CD8+ T lymphocytes and experience irAEs would have a superior PFS and OS.

A deep learning-based precision and automatic kidney segmentation system using efficient feature pyramid networks in computed tomography images.

This paper proposes an encoder-decoder architecture for kidney segmentation. A hyperparameter optimization process is implemented, including the development of a model architecture, selecting a windowing method and a loss function, and data augmentation. The model consists of EfficientNet-B5 as the encoder and a feature pyramid network as the decoder that yields the best performance with a Dice score of 0.969 on the 2019 Kidney and Kidney Tumor Segmentation Challenge dataset. The proposed model is tested with different voxel spacing, anatomical planes, and kidney and tumor volumes. Moreover, case studies are conducted to analyze segmentation outliers. Finally, five-fold cross-validation and the 3D-IRCAD-01 dataset are used to evaluate the developed model in terms of the following evaluation metrics: the Dice score, recall, precision, and the Intersection over Union score. A new development and application of artificial intelligence algorithms to solve image analysis and interpretation will be demonstrated in this paper. Overall, our experiment results show that the proposed kidney segmentation solutions in CT images can be significantly applied to clinical needs to assist surgeons in surgical planning. It enables the calculation of the total kidney volume for kidney function estimation in ADPKD and supports radiologists or doctors in disease diagnoses and disease progression.

Angiotensin II Receptor Blocker Associated With Less Outcome Risk in Patients With Acute Kidney Disease.

Objective: The aim of this study was to explore the respective use of angiotensin-converting-enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs) on the outcomes of patients who could be weaned from dialysis-requiring acute kidney injury (AKI-D). Methods: This case-control study enrolled 41,731 patients who were weaned from AKI-D for at least 7 days from Taiwan's National Health Insurance Administration. We further grouped AKI-D patients according to ACEi and ARB use to evaluate subsequent risks of all-cause mortality and re-dialysis. The outcomes included the all-cause mortality and new-onset of end-stage kidney disease (ESKD; re-dialysis) following withdraw from AKI-D. Results: A total of 17,141 (41.1%) patients surviving AKI-D could be weaned from dialysis for at least 7 days. The overall events of mortality were 366 (48.9%) in ACEi users, 659 (52.1%) in ARB users, and 6,261 (41.3%) in ACEi/ARB nonusers, during a mean follow-up period of 1.01 years after weaning from AKI-D. In regard to all-cause of mortality, pre-dialysis ARB users had lower incidence than ACEi users [hazard ratio (HR 0.82), p = 0.017]. Compared with ACEi/ARB nonusers, continuing ARB users had a significantly low risk of long-term all-cause mortality (adjusted hazard ratio 0.51, p = 0.013) after propensity score matching. However, new users of ACEi at the acute kidney disease (AKD) period had a higher risk of re-dialysis after weaning than ACEi/ARB nonusers (aHR 1.82, p < 0.001), whereas neither ACEi nor ARB users confronted significantly increased risks of hyperkalemia after weaning. Conclusions: Compared with patients without ACEi/ARB, those continuing to use ARB before the event and after weaning had low all-cause mortality, while new users of ACEi at AKD had increased risk of re-dialysis. AKI-D patients continuing to use ACEi or ARB did not have higher risk of hyperkalemia. Future prospective randomized trials are expected to confirm these findings.

A deep learning-based precision volume calculation approach for kidney and tumor segmentation on computed tomography images.

Previously, doctors interpreted computed tomography (CT) images based on their experience in diagnosing kidney diseases. However, with the rapid increase in CT images, such interpretations were required considerable time and effort, producing inconsistent results. Several novel neural network models were proposed to automatically identify kidney or tumor areas in CT images for solving this problem. In most of these models, only the neural network structure was modified to improve accuracy. However, data pre-processing was also a crucial step in improving the results. This study systematically discussed the necessary pre-processing methods before processing medical images in a neural network model. The experimental results were shown that the proposed pre-processing methods or models significantly improve the accuracy rate compared with the case without data pre-processing. Specifically, the dice score was improved from 0.9436 to 0.9648 for kidney segmentation and 0.7294 for all types of tumor detections. The performance was suitable for clinical applications with lower computational resources based on the proposed medical image processing methods and deep learning models. The cost efficiency and effectiveness were also achieved for automatic kidney volume calculation and tumor detection accurately.

Nomenclature and diagnostic criteria for acute kidney injury - 2020 consensus of the Taiwan AKI-task force.

Acute kidney injury (AKI) is a common syndrome that has a significant impact on prognosis in various clinical settings. To evaluate whether new evidence supports changing the current definition/classification/staging systems for AKI suggested by the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 Clinical Practice Guideline, the Taiwan AKI-TASK Force, composed of 64 experts in various disciplines, systematically reviewed the literature and proposed recommendations about the current nomenclature and diagnostic criteria for AKI. The Taiwan Acute Kidney Injury (TW-AKI) Consensus 2020 was established following the principles of evidence-based medicine to investigate topics covered in AKI guidelines. The Taiwan AKI-TASK Force determined that patients with AKI have a higher risk of developing chronic kidney disease, end-stage renal disease, and death. After a comprehensive review, the TASK Force recommended using novel biomarkers, imaging examinations, renal biopsy, and body fluid assessment in the diagnosis of AKI. Clinical issues with regards to the definitions of baseline serum creatinine (sCr) level and renal recovery, as well as the use of biomarkers to predict renal recovery are also discussed in this consensus. Although the present classification systems using sCr and urine output for the diagnosis of AKI are not perfect, there is not enough evidence to change the current criteria in clinical practice. Future research should investigate and clarify the roles of the aforementioned tools in clinical practice for AKI.

Long-term mortality and cardiovascular events in patients with unilateral primary aldosteronism after targeted treatments.

OBJECTIVE: Long-term outcomes (especially mortality and/or major cardiovascular events (MACE)) of the unilateral primary aldosteronism (uPA) patients who underwent medical or surgery-targeted treatment, relative to those with essential hypertension (EH), have been scarcely reported. DESIGN AND SETTINGS: Using the prospectively designed observational Taiwan Primary Aldosteronism Investigation cohort, we identified 858 uPA cases among 1220 primary aldosteronism patients and another 1210 EH controls. EXPOSURES: Operated uPA patients were grouped via their 1-year post-therapy statuses. RESULTS: Primary Aldosteronism Surgical Outcome clinical complete success (hypertension remission) was achieved in 272 (49.9%) of 545 surgically treated uPA patients. After follow-up for 6.3 ± 4.0 years, both hypertension-remissive (hazard ratio (HR): 0.54; P < 0.001) and not-cured (HR: 0.61; P < 0.001) uPA patients showed a lower risk of all-cause mortality than that of EH controls; whereas the not-cured group had a higher risk of incident MACE (sub-hazard ratio (sHR), 1.41; P = 0.037) but similar atrial fibrillation (Af) and congestive heart failure (CHF). Mineralocorticoid receptor antagonist (MRA)-treated uPA patients had higher risks of MACE (sHR: 1.38; P = 0.033), Af (sHR:1.62, P = 0.049), and CHF (sHR: 1.44; P = 0.048) than those of EH controls, with mortality as a competing risk. Using inverse probability of treatment-weighted matching and counting adrenalectomy as a time-varying factor, treatment with adrenalectomy was associated with lower risks of all-cause mortality (HR: 0.57; P = 0.035), MACE (HR: 0.67; P = 0.037), and CHF (HR: 0.49; P = 0.005) compared to those of MRA therapy. CONCLUSIONS: Adrenalectomy, independent of post-surgical hypertension remission, was associated with lower all-cause mortality of uPA patients, compared to that of EH patients. We further documented a more beneficial effect of adrenalectomy over MRA treatment on long-term mortality, MACE, and CHF in uPA patients.

Proteomic Analysis of Generative and Vegetative Nuclei Reveals Molecular Characteristics of Pollen Cell Differentiation in Lily.

In plants, the cell fates of a vegetative cell (VC) and generative cell (GC) are determined after the asymmetric division of the haploid microspore. The VC exits the cell cycle and grows a pollen tube, while the GC undergoes further mitosis to produce two sperm cells for double fertilization. However, our understanding of the mechanisms underlying their fate differentiation remains limited. One major advantage of the nuclear proteome analysis is that it is the only method currently able to uncover the systemic differences between VC and GC due to GC being engulfed within the cytoplasm of VC, limiting the use of transcriptome. Here, we obtained pure preparations of the vegetative cell nuclei (VNs) and generative cell nuclei (GNs) from germinating lily pollens. Utilizing these high-purity VNs and GNs, we compared the differential nucleoproteins between them using state-of-the-art quantitative proteomic techniques. We identified 720 different amount proteins (DAPs) and grouped the results in 11 fate differentiation categories. Among them, we identified 29 transcription factors (TFs) and 10 cell fate determinants. Significant differences were found in the molecular activities of vegetative and reproductive nuclei. The TFs in VN mainly participate in pollen tube development. In comparison, the TFs in GN are mainly involved in cell differentiation and male gametogenesis. The identified novel TFs may play an important role in cell fate differentiation. Our data also indicate differences in nuclear pore complexes and epigenetic modifications: more nucleoporins synthesized in VN; more histone variants and chaperones; and structural maintenance of chromosome (SMC) proteins, chromatin remodelers, and DNA methylation-related proteins expressed in GN. The VC has active macromolecular metabolism and mRNA processing, while GC has active nucleic acid metabolism and translation. Moreover, the members of unfolded protein response (UPR) and programmed cell death accumulate in VN, and DNA damage repair is active in GN. Differences in the stress response of DAPs in VN vs. GN were also found. This study provides a further understanding of pollen cell differentiation mechanisms and also a sound basis for future studies of the molecular mechanisms behind cell fate differentiation.

Pemetrexed-Platinum With or Without Bevacizumab for Chinese Chemo-Naive Advanced Lung Adenocarcinoma Patients: A Real-World Study.

Despite recent advances in the treatment of advanced non-small-cell lung cancer (NSCLC), bevacizumab plus platinum-based doublet chemotherapy remains a commonly used first-line regimen. This study was conducted to compare the efficacy and safety of pemetrexed-platinum with or without bevacizumab in Chinese chemo-naive advanced lung adenocarcinoma patients in a real-world setting. We retrospectively collected 100 patients who received pemetrexed-platinum with or without bevacizumab (PP, n = 46; Bev+PP, n = 54) until disease progression or unacceptable toxicity. Clinical characteristics of patients were balanced, except for the proportion of stage IV b+c (Bev+PP and PP: 67.4 vs. 37.0%, p = 0.0066). Bev+PP significantly improved the objective response rate (ORR, 65 vs. 30%, p = 0.0004) and progression-free survival (PFS, 7.4 vs. 6.8 months, p = 0.009), but not overall survival (OS, 17.5 vs. 15.0 months, p = 0.553) compared with PP. Treatment (p = 0.001), gender (p = 0.008), adrenal metastasis (p = 0.001), and liver metastasis (p = 0.013) were independent risk factors for PFS. Patients with adrenal metastasis tended to be at the highest risk of not benefiting from bevacizumab addition (HR [95% CI]: 2.244 [0.6495-7.753]). The safety profile was acceptable, and grade ≥3 toxicity occurred similarly. This study showed that pemetrexed-platinum plus bevacizumab was effective compared to chemotherapy alone in Chinese patients with advanced NSCLC.

Angiotensin II Receptor Blockers but Not Angiotensin-Converting Enzyme Inhibitors Are Associated With a Reduced Risk of Acute Kidney Injury After Major Surgery.

Objective: We investigated the respective effects of preoperative angiotensin-converting-enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) on the incidence of postoperative acute kidney injury (AKI) and mortality. Methods: In this nested case-control study, we enrolled 20,276 patients who received major surgery. We collected their baseline demographic data, comorbidities and prescribed medication, the outcomes of postoperative AKI and mortality. AKI was defined by the criteria suggested by KDIGO (Kidney disease: Improving Global Outcome). Logistic regression was used to assess the impact of exposure to ACEIs or ARBs. Results: Compared with patients without ACEI/ARB, patient who received ARBs had a significantly lower risk for postoperative AKI (adjusted odds ratio (OR) 0.82, p = 0.007). However, ACEI users had a higher risk for postoperative AKI than ARB users (OR 1.30, p = 0.027), whereas the risk for postoperative AKI was not significantly different between the ACEI users and patients without ACEI/ARB (OR 1.07, p = 0.49). Compared with patients without ACEI/ARB, both ACEI and ARB users were associated with a reduced risk of long-term all-cause mortality following surgery (OR 0.47, p = 0.002 and 0.60, p < 0.001 in ACEI and ARB users, respectively), without increasing the risk of hyperkalemia during the index hospitalization (p = 0.20). The risk of long-term all-cause mortality following surgery in ACEIs and ARBs users did not differ significantly (OR 0.74, p = 0.27). Furthermore, the higher the defined daily dose of ARB, the better the protection against AKI provided. Conclusion: Our study revealed that preoperative use of ARBs was associated with reduced postoperative AKI, which is better in high quantity, whereas preoperative use of ACEIs or ARBs were both associated with reduced mortality and did not increase the risk of hyperkalemia.

The Role of Calcium/Calcium-Dependent Protein Kinases Signal Pathway in Pollen Tube Growth.

Pollen tube (PT) growth as a key step for successful fertilization is essential for angiosperm survival and especially vital for grain yield in cereals. The process of PT growth is regulated by many complex and delicate signaling pathways. Among them, the calcium/calcium-dependent protein kinases (Ca2+/CPKs) signal pathway has become one research focus, as Ca2+ ion is a well-known essential signal molecule for PT growth, which can be instantly sensed and transduced by CPKs to control myriad biological processes. In this review, we summarize the recent progress in understanding the Ca2+/CPKs signal pathway governing PT growth. We also discuss how this pathway regulates PT growth and how reactive oxygen species (ROS) and cyclic nucleotide are integrated by Ca2+ signaling networks.

The calcium-dependent protein kinase ZmCDPK7 functions in heat-stress tolerance in maize.

Global warming poses a serious threat to crops. Calcium-dependent protein kinases (CDPKs)/CPKs play vital roles in plant stress responses, but their exact roles in plant thermotolerance remains elusive. Here, we explored the roles of heat-induced ZmCDPK7 in thermotolerance in maize. ZmCDPK7-overexpressing maize plants displayed higher thermotolerance, photosynthetic rates, and antioxidant enzyme activity but lower H2 O2 and malondialdehyde (MDA) contents than wild-type plants under heat stress. ZmCDPK7-knockdown plants displayed the opposite patterns. ZmCDPK7 is attached to the plasma membrane but can translocate to the cytosol under heat stress. ZmCDPK7 interacts with the small heat shock protein sHSP17.4, phosphorylates sHSP17.4 at Ser-44 and the respiratory burst oxidase homolog RBOHB at Ser-99, and upregulates their expression. Site-directed mutagenesis of sHSP17.4 to generate a Ser-44-Ala substitution reduced ZmCDPK7's enhancement of catalase activity but enhanced ZmCDPK7's suppression of MDA accumulation in heat-stressed maize protoplasts. sHSP17.4, ZmCDPK7, and RBOHB were less strongly upregulated in response to heat stress in the abscisic acid-deficient mutant vp5 versus the wild type. Pretreatment with an RBOH inhibitor suppressed sHSP17.4 and ZmCDPK7 expression. Therefore, abscisic acid-induced ZmCDPK7 functions both upstream and downstream of RBOH and participates in thermotolerance in maize by mediating the phosphorylation of sHSP17.4, which might be essential for its chaperone function.