Comparison of Recovery Effect for Sufentanil vs. Remifentanil Anesthesia in Elderly Patients Undergoing Curative Resection for Hepatocellular Carcinoma.

INTRODUCTION: The aim of this work is to evaluate the clinical efficacy and safety of sufentanil vs. remifentanil anesthesia in elderly patients undergoing curative resection for hepatocellular carcinoma (HCC). METHODS: Medical records of elderly patients aged ≥ 65 years who received curative resection for HCC between January 2017 and December 2020 were retrospectively reviewed. The patients were divided into either the sufentanil group or the remifentanil group according to the method of analgesia used. Vital signs including mean arterial pressure (MAP), heart rate (HR), and arterial oxygen saturation (SpO2), distribution of T-cell subsets (CD3, CD4, and CD8 lymphocytes), distribution of the stress response index [cortisol (COR), interleukin (IL)-6, C-reactive protein (CRP), and glucose (GLU)] were recorded prior to anesthesia (T0), after induction of anesthesia (T1), at the end of surgery (T2), 24 h after surgery (T3), and 72 h after surgery (T4). Postoperative adverse events were collected. RESULTS: Repeated measure analysis of variance (ANOVA) showed that after controlling for baseline patient demographic and treatment characteristics as covariates, both between- and within-group effects were significant (all P < 0.01), and the interaction between time and treatments was also significant (all P < 0.01) in the vital signs (MAP, HR, and SpO2), distribution of T-cell subsets (CD3, CD4, and CD8 lymphocytes), and distribution of the stress response index (COR, IL-6, CRP, and GLU), indicating that sufentanil led to stable hemodynamic and respiratory functions, lower reduction of T-lymphocyte subsets, and stable stress response indices compared to remifentanil. There is no significant difference in adverse reactions between the two groups (P = 0.72). CONCLUSIONS: Sufentanil was associated with improved hemodynamic and respiratory function, less stress response, less inhibition of cellular immunity, and similar adverse reactions compared with remifentanil.

Functional characterization of three maize SIZ/PIAS-type SUMO E3 ligases.

SUMOylation is a critical post-translational modification that regulates the nature and activity of protein substrates. The reaction is usually enhanced by a SIZ/PIAS-type of SUMO E3 ligase, but the functions of its homologs in maize have not yet been reported. In this study, we functionally characterized three members of this family of SUMO ligases, ZmSIZ1a, ZmSIZ1b, and ZmSIZ1c, from Zea mays. These maize SIZ1 homologs harbor conserved domains and structures with AtSIZ1, suggesting that they are potential functional SUMO ligases, which is supported by further biochemical data. The expression of these maize SIZ1 genes was detectable ubiquitously in different maize tissues and was usually induced by abiotic stresses. Expression of ZmSIZ1 members complements the leaf developmental defects of the AtSIZ1 mutant, suggesting their conserved function in development regulation. Interestingly, overexpression of ZmSIZ1c, but not ZmSIZ1a or ZmSIZ1b, in the wild-type Arabidopsis resulted in early flowering, implying that these members differ in terms of flowering control. Besides, overexpression of these ZmSIZ1 genes also improved salt tolerance in Arabidopsis. Collectively, our functional characterization of the ZmSIZ1 members provides hints for further investigation on the functions of SUMOylation in the development and stress responses in maize.

Application of etomidate and propofol mixture in hematoma removal in patients with intracranial epidural hematoma.

OBJECTIVE: To innvestigate the application of etomidate and propofol mixture in the evacuation of hematoma in patients with epidural hematoma. METHODS: 98 patients with epidural hematoma were randomly divided into two groups: the joint group (n=49, anesthesia induction with etomidate and propofol) and the etomidate group (n=49, anesthesia induction with etomidate) using a random number table. Hemodynamics, stress response and cerebral oxygen metabolism were compared between the two groups at T0 (pre-anesthesia induction), T1 (after endotracheal intubation), T2 (10 min after the beginning of the operation) and T3 (the end of the operation). Adverse reactions were also analyzed. RESULTS: Compared with T0, the mean arterial pressure (MAP) at T1, T2 and T3 in the joint group decreased first and then increased, and the MAP at T1 was significantly lower than that in the etomidate group (P<0.05). Compared with T0, blood oxygen saturation of internal jugular vein bulb (SjvO2) increased in T1-T3 groups, and SjvO2 in the joint group was higher than that in the etomidate group (all P<0.05). Compared with T0, cerebral oxygen uptake rate (CERO2) in the T1-T3 groups decreased significantly, and CERO2 at T3 in the joint group was higher than that in the etomidate group (all P<0.05). Compared with T0, the levels of cortisol and superoxide dismutase (SOD) at T3 in the two groups were significantly lower, but those in the etomidate group were higher than those in the combination group (all P<0.05). There was no significant difference in the incidence of postoperative anesthesia-related adverse reactions between the two groups (P>0.05). CONCLUSION: Etomidate has less effect on hemodynamics and stress reaction during intravenous anesthesia, but its combination with propofol can improve cerebral oxygen metabolism to a certain extent with fewer adverse reactions.

A SUMO ligase OsMMS21 regulates rice development and auxin response.

SUMOylation, which transfers the Small Ubiquitin-related Modifier (SUMO) polypeptides to target proteins, regulates diverse cellular processes in eukaryotes. The SUMO conjugation reaction is usually promoted by SUMO E3 ligases, but the molecular functions of this type of enzymes remain unclear in cereal crops. Here, OsMMS21, a SUMO E3 ligase, was functionally characterized in rice (Oryza sativa). Bioinformatics analysis showed that OsMMS21 harbors a conserved SP-RING domain that is essential for the activity of SUMO ligases. Biochemical data indicated that this protein is auto-SUMOylated. Besides, overexpression of OsMMS21 rescued the developmental defects of the AtMMS21 mutant, supporting that OsMMS21 is a functional homolog of the Arabidopsis SUMO ligase AtMMS21. The OsMMS21 rice T-DNA mutant displays a short-root and dwarfism phenotype. RNA-seq data revealed that the expression levels of many genes involved in signaling transduction of hormones, including auxin, are altered in the OsMMS21 mutant. Further results under the auxin treatment showed that the OsMMS21 mutant is insensitive to auxin. Collectively, our results demonstrated the molecular features of OsMMS21 and uncovered the roles of this SUMO ligase in development and auxin response, providing hints for further studies on protein SUMOylation in rice.

Functional characterization of a chloroplast-localized Mn2+(Ca2+)/H+ antiporter, ZmmCCHA1 from Zea mays ssp. mexicana L.

The annual Zea mays ssp. mexicana L. is a member of the teosinte group and a close wild relative of maize. Thus, Zea mays ssp. mexicana L. can be effectively used in maize breeding. AtCCHA1 is a Mn2+ and/or Ca2+/H+ antiporter localized in chloroplasts in Arabidopsis. In this study, its homolog from Zea mays ssp. mexicana L., ZmmCCHA1, was isolated and characterized. The transcriptional level of ZmmCCHA1 in Zea mays ssp. mexicana L. was repressed in response to excessive Ca2+ or Mn2+. Heterologous functional complementation assays using yeast mutants showed that ZmmCCHA1 mediates Ca2+ and Mn2+ transport. The ZmmCCHA1 protein was localized in the chloroplasts when expressed in tobacco leaves. Furthermore, ectopic overexpression of ZmmCCHA1 in the Arabidopsis ccha1 mutant rescued the mutant defects on growth and the photosynthetic proteins in the thylakoid membranes. Moreover, the photosynthetic phenotypes of Arabidopsis ccha1 mutant at steady-state were greatly but not completely complemented by the overexpression of ZmmCCHA1. In addition, overexpressing the ZmmCCHA1 rescued the sensitives of PSII in the Arabidopsis ccha1 mutant to Mn2+ deficiency or high Ca2+ condition. These results indicate that the isolated ZmmCCHA1 is the homolog of AtCCHA1 and plays a conserved role in maintaining the Mn2+ and/or Ca2+ homeostasis in chloroplasts which is critical for the function of PSII in photosynthesis.

Functional characterization of DiMMS21, a SUMO ligase from Desmodium intortum.

SUMOylation is an important protein modification that regulates the properties of substrate proteins in a variety of cellular processes. SUMOylation is catalyzed via a cascade of enzymes and is usually stimulated by SUMO E3 ligases. However, the molecular functions and regulatory mechanisms of SUMOylation in forage crops are unknown. Here, we isolated and functionally characterized DiMMS21, a homolog of the Arabidopsis thaliana SUMO ligase AtMMS21, from the forage legume Desmodium intortum. DiMMS21 is expressed ubiquitously in various D. intortum organs and its encoded protein is found in the cytoplasm and nucleus. Bioinformatics analysis indicated that DiMMS21 contains a conserved SP-RING domain that is required for its activity. Biochemical evidence supports the notion that this protein is a functional SUMO ligase. When expressed in an Arabidopsis mms21 mutant, DiMMS21 completely rescued the defects in root, leaf, and silique development. The results from cotyledon greening and marker gene expression suggested that DiMMS21 can only partially complements the role of AtMMS21 in abscisic acid (ABA) responses. In summary, we characterized the molecular features of DiMMS21 and uncovered potential roles of this SUMO ligase in development and ABA responses, increasing our understanding on the function of SUMOylation in forage crops.

A SUMO ligase AtMMS21 regulates activity of the 26S proteasome in root development.

The 26S proteasome is a multi-subunit protease controlling most of the cytosolic and nuclear protein turnover, regulating many cellular events in eukaryotes. However, functional modification on this complex remains unclear. Here, we showed a novel mechanism that a SUMO ligase AtMMS21 regulates activity of the 26S proteasome in root development of Arabidopsis. Our in vitro and in vivo data supported that AtMMS21 interacts with RPT2a, a subunit of the 26S proteasome. The mutants of AtMMS21 and RPT2a display similar developmental defect of roots, suggesting their association in this process. In addition, RPT2a is modified by SUMO3, potentially related to AtMMS21. During development, the activity of the 26S proteasome is lower in both mutants of AtMMS21 and RPT2a, compared with that of wild type. Furthermore, the protein level but not the RNA level of RPT2a is decreased in the absence of AtMMS21, implying stability regulation of the proteasome complex through the AtMMS21-RPT2a interaction. Taken together, the current study would improve our understanding on the regulatory mechanism of the 26S proteasome via protein modification in root development.

A SUMO Ligase AtMMS21 Regulates the Stability of the Chromatin Remodeler BRAHMA in Root Development.

Chromatin remodeling is essential for gene expression regulation in plant development and response to stresses. Brahma (BRM) is a conserved ATPase in the SWI/SNF chromatin remodeling complex and is involved in various biological processes in plant cells, but the regulation mechanism on BRM protein remains unclear. Here, we report that BRM interacts with AtMMS21, a SUMO ligase in Arabidopsis (Arabidopsis thaliana). The interaction was confirmed in different approaches in vivo and in vitro. The mutants of BRM and AtMMS21 displayed a similar defect in root development. In the mms21-1 mutant, the protein level of BRM-GFP was significantly lower than that in wild type, but the RNA level of BRM did not change. Biochemical evidence indicated that BRM was modified by SUMO3, and the reaction was enhanced by AtMMS21. Furthermore, overexpression of wild-type AtMMS21 but not the mutated AtMMS21 without SUMO ligase activity was able to recover the stability of BRM in mms21-1 Overexpression of BRM in mms21-1 partially rescued the developmental defect of roots. Taken together, these results supported that AtMMS21 regulates the protein stability of BRM in root development.

Jasmonate complements the function of Arabidopsis lipoxygenase3 in salinity stress response.

The functions of jasmonic acid (JA) in various stress responses have been uncovered in details, but its role in salt tolerance remains unclear. Here, we characterize the function of Arabidopsis lipoxygenase3 (LOX3), an enzyme involved in JA synthesis, in salt stress response. The transcriptional analysis indicated that LOX3 was dramatically induced under salt treatment. Compared with wild type, the lox3 mutant exhibited hypersensitivity to salt stress in germination and different developmental stages. Interestingly, methyl jasmonate (MeJA) rescued the salt sensitivity phenotypes of the lox3 mutant, suggesting the impairment of salinity response in the mutant may be mediated by JA. Furthermore, the lateral root number of the lox3 mutant was similar with that in wild type under normal condition, but less than that in wild type during salt treatment, and this lateral root sensitivity phenotype was also complemented by exogenous MeJA. In addition, the measurement of oxylipins in the lox3 mutant and the analysis on germination of the JA receptor coi1 mutant under salt stress supported that JA may regulate the early response to salinity. In conclusion, we characterized the novel function of LOX3 in salinity stress response, and found that the salt hypersensitivity of the lox3 mutant can be complemented by MeJA, providing new evidence for the association between JA and salt tolerance.

OsAGSW1, an ABC1-like kinase gene, is involved in the regulation of grain size and weight in rice.

Grain shape and weight are two determining agronomic traits of rice yield. ABC1 (Activity of bc1 complex) is a newly found atypical kinase in plants. Here, we report on an ABC1 protein kinase gene, OsAGSW1 (ABC1-like kinase related to Grain size and Weight). Expression of OsAGSW1-GFP in rice revealed that OsAGSW1 is localized to the chloroplasts in rice. Analysis of OsAGSW1 promoter::ß-glucuronidase transgenic rice indicated that this gene was highly expressed in vascular bundles in shoot, hull and caryopsis. Furthermore, OsAGSW1-RNAi and overexpressed transgenic rice lines were generated. Stable transgenic lines overexpressing OsAGSW1 exhibited a phenotype with a significant increase in grain size, grain weight, grain filling rate and 1000-grain weight compared with the wild-type and RNAi transgenic plants. Microscopy analysis showed that spikelet hulls just before heading were different in the OsAGSW1-overexpressed plants compared with wild-type and OsAGSW1 RNAi rice. Further cytological analysis showed that the number of external parenchyma cells in rice hulls of OsAGSW1-overexpressed plants increased, leading to wider and longer spikelet hulls than those of the wild-type and OsAGSW1-RNAi plants. The vascular cross-sectional area in lemma, carpopodium and ovules also strikingly increased and area of both xylem and phloem were enlarged in the OsAGSW1-overexpressed plants. Thus, our results demonstrated that OsAGSW1 plays an important role in seed shape and size of rice by regulating the number of external parenchyma cells and the development of vascular bundles, providing a new insight into the functions of ABC1 genes in plants.

SUMO E3 ligase AtMMS21 is required for normal meiosis and gametophyte development in Arabidopsis.

BACKGROUND: MMS21 is a SUMO E3 ligase that is conserved in eukaryotes, and has previously been shown to be required for DNA repair and maintenance of chromosome integrity. Loss of the Arabidopsis MMS21 causes defective meristems and dwarf phenotypes. RESULTS: Here, we show a role for AtMMS21 during gametophyte development. AtMMS21 deficient plants are semisterile with shorter mature siliques and abortive seeds. The mms21-1 mutant shows reduced pollen number, and viability, and germination and abnormal pollen tube growth. Embryo sac development is also compromised in the mutant. During meiosis, chromosome mis-segregation and fragmentation is observed, and the products of meiosis are frequently dyads or irregular tetrads. Several transcripts for meiotic genes related to chromosome maintenance and behavior are altered. Moreover, accumulation of SUMO-protein conjugates in the mms21-1 pollen grains is distinct from that in wild-type. CONCLUSIONS: Thus, these results suggest that AtMMS21 mediated SUMOylation may stabilize the expression and accumulation of meiotic proteins and affect gametophyte development.

AtMMS21 regulates DNA damage response and homologous recombination repair in Arabidopsis.

DNA damage is a significant problem in living organisms and DNA repair pathways have been evolved in different species to maintain genomic stability. Here we demonstrated the molecular function of AtMMS21, a component of SMC5/6 complex, in plant DNA damage response. Compared with wild type, the AtMMS21 mutant plants show hypersensitivity in the DNA damaging treatments by MMS, cisplatin and gamma radiation. However, mms21-1 is not sensitive to replication blocking agents hydroxyurea and aphidicolin. The expression of a DNA damage response gene PARP2 is upregulated in mms21-1 under normal condition, suggesting that this signaling pathway is constitutively activated in the mutant. Depletion of ATAXIA-TELANGIECTASIA MUTATED (ATM) in mms21-1 enhances its root growth defect phenotype, indicating that ATM and AtMMS21 may play additive roles in DNA damage pathway. The analysis of homologous recombination frequency showed that the number of recombination events is reduced in mms21-1 mutant. Conclusively, we provided evidence that AtMMS21 plays an important role in homologous recombination for DNA damage repair.

Arabidopsis CPR5 independently regulates seed germination and postgermination arrest of development through LOX pathway and ABA signaling.

The phytohormone abscisic acid (ABA) and the lipoxygenases (LOXs) pathway play important roles in seed germination and seedling growth and development. Here, we reported on the functional characterization of Arabidopsis CPR5 in the ABA signaling and LOX pathways. The cpr5 mutant was hypersensitive to ABA in the seed germination, cotyledon greening and root growth, whereas transgenic plants overexpressing CPR5 were insensitive. Genetic analysis demonstrated that CPR5 gene may be located downstream of the ABI1 in the ABA signaling pathway. However, the cpr5 mutant showed an ABA independent drought-resistant phenotype. It was also found that the cpr5 mutant was hypersensitive to NDGA and NDGA treatment aggravated the ABA-induced delay in the seed germination and cotyledon greening. Taken together, these results suggest that the CPR5 plays a regulatory role in the regulation of seed germination and early seedling growth through ABA and LOX pathways independently.