GTP Binding Protein Gtr1 Cooperating with ASF1 Regulates Asexual Development in Stemphylium eturmiunum.

The Gtr1 protein was a member of the RagA subfamily of the Ras-like small GTPase superfamily and involved in phosphate acquisition, ribosome biogenesis and epigenetic control of gene expression in yeast. However, Gtr1 regulation sexual or asexual development in filamentous fungi is barely accepted. In the study, SeGtr1, identified from Stemphylium eturmiunum, could manipulate mycelial growth, nuclear distribution of mycelium and the morphology of conidia in Segtr1 silenced strains compared with its overexpression transformants, while the sexual activity of Segtr1 silenced strains were unchanged. SeASF1, a H3/H4 chaperone, participated in nucleosome assembly/disassembly, DNA replication and transcriptional regulation. Our experiments showed that deletion Seasf1 mutants produced the hyphal fusion and abnormal conidia. Notably, we characterized that Segtr1 was down-regulated in Se∆asf1 mutants and Seasf1 was also down-regulated in SiSegtr1 strains. We further confirmed that SeGtr1 interacted with SeASF1 or SeH4 in vivo and vitro, respectively. Thus, SeGtr1 can cooperate with SeASF1 to modulate asexual development in Stemphylium eturmiunum.

The application of patient-centered care bundle significantly reduces incidence of perioperative respiratory complications in hip fracture patients aged 80 and over.

This study was designed as a pilot test to analyze the effect of patient-centered care (PCC) bundle intervention on perioperative respiratory complications and other outcomes in hip fracture patients aged ≥80. Between Jan 2018 and Dec 2019, 198 patients comprised the routine care group and 187 comprised the PCC bundle group. After propensity score matching, 151 remained in each group. Incidence of perioperative respiratory complications in the PCC bundle group was significantly lower than in the routine care group (all P < 0.05). Furthermore, significant reductions were observed in surgery delay, length of stay, incidence of arrhythmia, hypoproteinemia, and electrolyte disturbance (all P < 0.05) in the PCC bundle group. Age-Adjusted Charlson Comorbidity Index score was related, but only weakly, to length of stay and the number of perioperative complications. These results suggested that the PCC bundle might be a more suitable care modality for patients ≥80 with hip fracture.

DA-LSTM-VAE: Dual-Stage Attention-Based LSTM-VAE for KPI Anomaly Detection.

To ensure the normal operation of the system, the enterprise's operations engineer will monitor the system through the KPI (key performance indicator). For example, web page visits, server memory utilization, etc. KPI anomaly detection is a core technology, which is of great significance for rapid fault detection and repair. This paper proposes a novel dual-stage attention-based LSTM-VAE (DA-LSTM-VAE) model for KPI anomaly detection. Firstly, in order to capture time correlation in KPI data, long-short-term memory (LSTM) units are used to replace traditional neurons in the variational autoencoder (VAE). Then, in order to improve the effect of KPI anomaly detection, an attention mechanism is introduced into the input stage of the encoder and decoder, respectively. During the input stage of the encoder, a time attention mechanism is adopted to assign different weights to different time points, which can adaptively select important input sequences to avoid the influence of noise in the data. During the input stage of the decoder, a feature attention mechanism is adopted to adaptively select important latent variable representations, which can capture the long-term dependence of time series better. In addition, this paper proposes an adaptive threshold method based on anomaly scores measured by reconstruction probability, which can minimize false positives and false negatives and avoid adjustment of the threshold manually. Experimental results in a public dataset show that the proposed method in this paper outperforms other baseline methods.

Log Sequence Anomaly Detection Method Based on Contrastive Adversarial Training and Dual Feature Extraction.

The log messages generated in the system reflect the state of the system at all times. The realization of autonomous detection of abnormalities in log messages can help operators find abnormalities in time and provide a basis for analyzing the causes of abnormalities. First, this paper proposes a log sequence anomaly detection method based on contrastive adversarial training and dual feature extraction. This method uses BERT (Bidirectional Encoder Representations from Transformers) and VAE (Variational Auto-Encoder) to extract the semantic features and statistical features of the log sequence, respectively, and the dual features are combined to perform anomaly detection on the log sequence, with a novel contrastive adversarial training method also used to train the model. In addition, this paper introduces the method of obtaining statistical features of log sequence and the method of combining semantic features with statistical features. Furthermore, the specific process of contrastive adversarial training is described. Finally, an experimental comparison is carried out, and the experimental results show that the method in this paper is better than the contrasted log sequence anomaly detection method.

Phytophthora capsici PcFtsZ2 Is Required for Asexual Development and Plant Infection.

In bacteria, FtsZ proteins form a Z ring that is the initial step preceding septal fission. FtsZ proteins enable the division of mitochondria in early eukaryotes and are present in some kingdoms but have been lost in animals, fungi, and plants. Here, we have identified two Phytophthora capsici ortholog genes of Escherichia coli FtsZs, designated PcFtsZ1 and PcFtsZ2. Overexpression of PcFtsZ2 in E. coli fully complemented the overexpression phenotype of EcFtsZ. In contrast, overexpression of PcFtsZ1 in E. coli had minimal impact on cell division and separation. Thus, we focused on evaluating the impact of altered expression of PcFtsZ2 in P. capsici, as it exhibited the strongest phenotype. PcFtsZ2 was expressed at the highest levels in mycelia, sporangia, and germinating cysts, as well as in late infection. PcFtsZ2 mis-expression lines showed aberrant asexual growth and development of P. capsici. Alterations in the expression of PcFtsZ2 changed the distribution of mitochondria in hyphae and sporangia and, also, affected the number, size, and shape of actin plaques. Silencing of PcFtsZ2 restrained growth and development of invasive structures, especially cysts and sporangia, substantially inhibiting the ability of transformants to cause blight lesions. In overexpressed transformant lines, cyst and sporangial germination rates were only half that of controls, but hyphal growth from direct germination of sporangia was more rapid than controls. These transformant lines were only slightly impaired in virulence relative to controls. This study emphasizes the essential role of the evolutionarily conserved FtsZ2 proteins in affecting cytoskeleton dynamics.

An Autonomous Path Planning Model for Unmanned Ships Based on Deep Reinforcement Learning.

Deep reinforcement learning (DRL) has excellent performance in continuous control problems and it is widely used in path planning and other fields. An autonomous path planning model based on DRL is proposed to realize the intelligent path planning of unmanned ships in the unknown environment. The model utilizes the deep deterministic policy gradient (DDPG) algorithm, through the continuous interaction with the environment and the use of historical experience data; the agent learns the optimal action strategy in a simulation environment. The navigation rules and the ship's encounter situation are transformed into a navigation restricted area, so as to achieve the purpose of planned path safety in order to ensure the validity and accuracy of the model. Ship data provided by ship automatic identification system (AIS) are used to train this path planning model. Subsequently, the improved DRL is obtained by combining DDPG with the artificial potential field. Finally, the path planning model is integrated into the electronic chart platform for experiments. Through the establishment of comparative experiments, the results show that the improved model can achieve autonomous path planning, and it has good convergence speed and stability.

Crystal structure and expression patterns of prolyl 4-hydroxylases from Phytophthora capsici.

Prolyl 4-hydroxylases (P4Hs) are members of the Fe2+ and 2-oxoglutarate- dependent oxygenases family, which play central roles in the collagen stabilization, hypoxia sensing, and translational regulation in eukaryotes. Thus far, nothing is known about the role of P4Hs in development and pathogenesis in oomycetes. Here we show that the Phytophthora capsici genome contains five putative prolyl 4-hydroxylases. In mycelia, all P4Hs were downregulated in response to hypoxia, but the expression of PcP4H1 was most affected. Strikingly, Pc4H1 was upregulated more than 110 fold at the onset of infection, and Pc4H5 was upregulated seven fold, while the expression of other P4H's were unchanged. Similar to well-characterized P4H proteins, the crystallographic structure of PcP4H1 contains a highly conserved double-stranded ß-helix core fold and catalytic residues. However, the binding affinity of 2-oxoglutarate to PcP4H1 is very low. The extended C-terminal α-helix bundle and longer ß2-ß3 disordered substrate binding loop may help in confirming the peptide target of this enzyme.

Disturbance in biosynthesis of arachidonic acid impairs the sexual development of the onion blight pathogen Stemphylium eturmiunum.

The formation of sexual fruiting bodies for plant pathogenic fungi is a key strategy to propagate their progenies upon environmental stresses. Stemphylium eturmiunum is an opportunistic plant pathogen fungus causing blight in onion. This self-fertilizing filamentous ascomycete persists in the soil by forming pseudothecia, the sexual fruiting body which helps the fungus survive in harsh environments. However, the regulatory mechanism of pseudothecial formation remains unknown. To uncover the mechanism for pseudothecial formation so as to find a practical measure to control the propagation of this onion pathogen, we tentatively used DNA methyltransferase inhibitor 5-azacytidine (5-AC) to treat S. eturmiunum. 5-AC treatment silenced the gene-encoding monoacylglycerol lipase (magl) concomitant with the presence of the inheritable fluffy phenotype and defectiveness in pseudothecial development. Moreover, the silence of magl also resulted in a reduction of arachidonic acid (AA) formation from 27 ± 3.1 µg/g to 9.5 ± 1.5 µg/g. To correlate the biosynthesis of AA and pseudothecial formation, we created magl knockdown and overexpression strains. Knockdown of magl reduced AA to 11 ± 2.4 µg/g, which subsequently disabled pseudothecial formation. In parallel, overexpression of magl increased AA to 37 ± 3.4 µg/g, which also impaired pseudothecial formation. Furthermore, exogenous addition of AA to the culture of magl-silenced or magl knockdown strains rescued the pseudothecial formation but failed in the gpr1 knockdown strain of S. eturmiunum, which implicates the involvement of AA in signal transduction via a putative G protein-coupled receptor 1. Thus, AA at a cellular level of 27 ± 3.1 µg/g is essential for sexual development of S. eturmiunum. Disturbance in the biosynthesis of AA by up- and down-regulating the expression of magl disables the pseudothecial development. The specific requirement for AA in pseudothecial development by S. eturmiunum provides a hint to curb this onion pathogen: to impede pseudothecial formation by application of AA.

Crystal structure of the RxLR effector PcRxLR12 from Phytophthora capsici.

RxLR genes are a prominent class of effectors in oomycetes, and almost half of these proteins contain a conserved sequence motif termed the WY domain, that may exist singly, or as divergent tandem repeats in different effectors. Here we describe the crystal structure of PcRxLR12 (63-488) from Phytophthora capsici at 3.0 Šresolution. The structure consists of five tandemly arrayed WY-domains linked to each other by short connecting helices. Superposition of the WY-2 domain on the other four domains of PcRxLR12, show that the first α-helix termed the K motif, and Loop 3 which connects α3 and α4 are the key regions of structural divergence between the WY domains. A similar pattern was observed when WY-2 was superposed on the 11 WY domains from other oomycete effectors. We also note that an added connecting helix between WY domains in some RXLR effectors, ensures that the WY domains are oriented in the same direction.

Microwave ablation versus hepatic resection for the treatment of hepatocellular carcinoma and oesophageal variceal bleeding in cirrhotic patients.

PURPOSE: The aim of this study was to compare the results of microwave ablation (MWA) and hepatic resection (HR) when combined with pericardial devascularisation plus splenectomy (PCDV) for the treatment of patients with cirrhosis complicated by small hepatocellular carcinoma (HCC) and oesophageal variceal bleeding (EVB). MATERIALS AND METHODS: Between 2001 and 2013, 73 patients (median age 53.2 years, 67% male) with small HCC and concomitant EVB who underwent MWA or HR for HCC and PCDV for cirrhotic portal hypertension were selected retrospectively for inclusion in this study. The overall survival curves and recurrence-free survival curves were calculated using the Kaplan-Meier method and compared using log-rank tests. Multivariate analysis was performed using the Cox regression model. RESULTS: The 1-, 3- and 5-year overall survival rates were 95.2%, 71.4% and 38.1% and 96.7%, 53.3% and 43.3% for the HR and MWA groups, respectively; these did not differ significantly between the two groups. However, patients in the HR group had more post-operative complications (52.3% vs. 13.7%; p = 0.002). Multivariate analysis identified albumin and bilirubin levels and tumour size to be statistically significant and independent prognostic factors for overall survival, while BCLC stage was associated with poor recurrence-free survival. Furthermore, albumin levels were shown to be an independent predictive factor for post-operative complications. CONCLUSIONS: For patients with small HCC and concomitant EVB, MWA plus PCDV may reduce the incidence of post-operative complications relative to and provide similar therapeutic benefits as HR plus PCDV, especially for patients with low albumin levels.

Optimal staging system for predicting the prognosis of patients with hepatocellular carcinoma in China: a retrospective study.

BACKGROUND: Several staging systems have been developed to evaluate patients with hepatocellular carcinoma (HCC), including the China Staging System (CS), the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system, and seventh edition; the Barcelona Clinic Liver Cancer (BCLC) staging system, and Cancer of the Liver Italian Program (CLIP) staging system. The optimal staging system for to evaluate patients in China with HCC has not been determined. This study was designed to determine the optimal staging system for predicting patient prognosis by comparing the performances of these four staging systems in a cohort of Chinese patients with HCC. METHODS: This study enrolled 307 consecutive Chinese patients with HCC in Shandong Province. The performances of the CS, TNM, BCLC, and CLIP staging systems were compared and ranked using a concordance index. Predictors of survival were identified using univariate and multivariate Cox model analyses. RESULTS: The mean overall survival of the patient cohort was 12.08 ± 11.87 months. Independent predictors of survival included tumor size, number of lesions, tumor thromboses, cirrhosis, serum albumin level and serum total bilirubin level. Compared with the other three staging systems, the CS staging system showed optimal performance as an independent predictor of patient survival. The BCLC staging system showed the poorest performance; its treatment algorithm was not suitable for patients in this study. CONCLUSIONS: CS was the most suitable staging system for predicting survival of patients with HCC in China.

Characterization of Cell-Death-Inducing Members of the Pectate Lyase Gene Family in Phytophthora capsici and Their Contributions to Infection of Pepper.

Pectate lyases (PL) play a critical role in pectin degradation. PL have been extensively studied in major bacterial and fungal pathogens of a wide range of plant species. However, the contribution of PL to infection by oomycete pathogens remains largely unknown. Here, we cloned 22 full-length pectate lyase (PcPL) genes from a highly aggressive strain of Phytophthora capsici SD33. Of these, PVX agroinfiltration revealed that 12 PcPL genes were found to be highly induced during infection of pepper by SD33 but the induction level was twofold less in a mildly aggressive strain, YN07. The four genes with the highest transcript levels as measured by by quantitative reverse-transcription polymerase chain reaction (PcPL1, PcPL15, PcPL16, and PcPL20) also produced a severe cell death response following transient expression in pepper leaves but the other eight PcPL genes did not. Overexpression of these four genes increased the virulence of SD33 on pepper slightly, and increased it more substantially during infection of tobacco. Overexpression of the genes in YN07 restored its aggressiveness to near that of SD33. Gene silencing experiments with the 12 PcPL genes produced diverse patterns of silencing of PcPL genes, from which it could be inferred from regression analysis that PcPL1, PcPL16, and PcPL20 could account for nearly all of the contributions of the PcPL genes to virulence.

New insight into the history of domesticated apple: secondary contribution of the European wild apple to the genome of cultivated varieties.

The apple is the most common and culturally important fruit crop of temperate areas. The elucidation of its origin and domestication history is therefore of great interest. The wild Central Asian species Malus sieversii has previously been identified as the main contributor to the genome of the cultivated apple (Malus domestica), on the basis of morphological, molecular, and historical evidence. The possible contribution of other wild species present along the Silk Route running from Asia to Western Europe remains a matter of debate, particularly with respect to the contribution of the European wild apple. We used microsatellite markers and an unprecedented large sampling of five Malus species throughout Eurasia (839 accessions from China to Spain) to show that multiple species have contributed to the genetic makeup of domesticated apples. The wild European crabapple M. sylvestris, in particular, was a major secondary contributor. Bidirectional gene flow between the domesticated apple and the European crabapple resulted in the current M. domestica being genetically more closely related to this species than to its Central Asian progenitor, M. sieversii. We found no evidence of a domestication bottleneck or clonal population structure in apples, despite the use of vegetative propagation by grafting. We show that the evolution of domesticated apples occurred over a long time period and involved more than one wild species. Our results support the view that self-incompatibility, a long lifespan, and cultural practices such as selection from open-pollinated seeds have facilitated introgression from wild relatives and the maintenance of genetic variation during domestication. This combination of processes may account for the diversification of several long-lived perennial crops, yielding domestication patterns different from those observed for annual species.

Characterization of necrosis-inducing NLP proteins in Phytophthora capsici.

BACKGROUND: Effector proteins function not only as toxins to induce plant cell death, but also enable pathogens to suppress or evade plant defense responses. NLP-like proteins are considered to be effector proteins, and they have been isolated from bacteria, fungi, and oomycete plant pathogens. There is increasing evidence that NLPs have the ability to induce cell death and ethylene accumulation in plants. RESULTS: We evaluated the expression patterns of 11 targeted PcNLP genes by qRT-PCR at different time points after infection by P. capsici. Several PcNLP genes were strongly expressed at the early stages in the infection process, but the expression of other PcNLP genes gradually increased to a maximum at late stages of infection. The genes PcNLP2, PcNLP6 and PcNLP14 showed the highest expression levels during infection by P. capsici. The necrosis-inducing activity of all targeted PcNLP genes was evaluated using heterologous expression by PVX agroinfection of Capsicum annuum and Nicotiana benthamiana and by Western blot analysis. The members of the PcNLP family can induce chlorosis or necrosis during infection of pepper and tobacco leaves, but the chlorotic or necrotic response caused by PcNLP genes was stronger in pepper leaves than in tobacco leaves. Moreover, PcNLP2, PcNLP6, and PcNLP14 caused the largest chlorotic or necrotic areas in both host plants, indicating that these three genes contribute to strong virulence during infection by P. capsici. This was confirmed through functional evaluation of their silenced transformants. In addition, we further verified that four conserved residues are putatively active sites in PcNLP1 by site-directed mutagenesis. CONCLUSIONS: Each targeted PcNLP gene affects cells or tissues differently depending upon the stage of infection. Most PcNLP genes could trigger necrotic or chlorotic responses when expressed in the host C. annuum and the non-host N. benthamiana. Individual PcNLP genes have different phytotoxic effects, and PcNLP2, PcNLP6, and PcNLP14 may play important roles in symptom development and may be crucial for virulence, necrosis-inducing activity, or cell death during infection by P. capsici.

Multifaceted cytoprotection by synthetic polyacetylenes inspired by the ginseng-derived natural product, panaxytriol.

We describe herein the discovery of a series of panaxytriol (PXT)-derived polyacetylene small molecules with promising cytoprotective activity. In mouse xenograft models, we have demonstrated the capacity of our synthetic analogs to mitigate a range of cancer therapeutic agent-induced toxicities, including body weight loss, lethality, neurotoxicity, and hematotoxicity. Our PXT analogs have also been found to reduce radiation-induced body weight loss and lethality in mouse models. Moreover, several PXT analogs appear to exhibit moderate in vivo antiinflammatory activity as well as in vitro immunoenhancing capabilities. These compounds appear to derive their activity through induction of cancer preventive phase 2 enzymes. The studies described herein suggest that coadministration of a PXT-derived agent with cancer chemotherapeutics or radiation therapy may serve to mitigate a range of therapy-associated toxicities.

Characterization and phylogenetic analysis of the mating-type loci in the asexual ascomycete genus Ulocladium.

The genus Ulocladium is thought to be strictly asexual. Mating-type (MAT) loci regulate sexual reproduction in fungi and their study may help to explain the apparent lack of sexual reproduction in Ulocladium. We sequenced the full length of two MAT genes in 26 Ulocladium species and characterized the entire MAT idiomorphs plus flanking regions of Ulocladium botrytis. The MAT1-1 ORF encodes a protein with an alpha-box motif by the MAT1-1-1 gene and the MAT1-2 ORF encodes a protein with an HMG box motif by the MAT1-2-1 gene. Both MAT1-1-1 and MAT1-2-1 genes were detected in a single strain of every species. Moreover, the results of RT-PCR revealed that both MAT genes are expressed in all 26 Ulocladium species. This demonstrates that MAT genes of Ulocladium species might be functional and that they have the potential for sexual reproduction. Phylogenies based on MAT genes were compared with GAPDH and Alt a 1 phylograms in Ulocladium using maximum parsimony (MP) and Bayesian analysis. The MAT genealogies and the non-MAT trees displayed different topologies, indicating that MAT genes are unsuitable phylogenetic markers at the species level in Ulocladium. Furthermore, the conflicting topologies between MAT1-1-1 and MAT1-2-1 phylogeny indicate separate evolutionary events for the two MAT genes. However, the intergeneric phylogeny of four closely allied genera (Ulocladium, Alternaria, Cochliobolus, Stemphylium) based on MAT alignments demonstrated that MAT genes are suitable for phylogenetic analysis among allied genera.

Three New Species of Apiospora (Amphisphaeriales, Apiosporaceae) on Indocalamus longiauritus, Adinandra glischroloma and Machilus nanmu from Hainan and Fujian, China.

Apiospora is widely distributed throughout the world, and most of its hosts are Poaceae. In this study, Arthrinium-like strains were isolated from non-Poaceae in the Hainan and Fujian provinces of China. Based on the combined DNA sequence data of the internal transcriptional spacer (ITS), partial large subunit nuclear rDNA (LSU), translation extension factor 1-α gene (TEF1-α) and ß-tubulin (TUB2), the collected Apiospora specimens were compared with known species, and three new species were identified. Based on morphological and molecular phylogenetic analyses, Apiospora adinandrae sp. nov., A. bawanglingensis sp. nov. and A. machili sp. nov. are described and illustrated.

Three new species of Pestalotiopsis (Amphisphaeriales, Sporocadaceae) were identified by morphology and multigene phylogeny from Hainan and Yunnan, China.

Pestalotiopsis fungi are widely distributed all over the world, mainly as plant pathogens, endophytes or saprobes from multiple hosts. In this study, the sequence data analysis based on internal transcribed spacer (ITS), partial beta-tubulin (tub2) and partial regions of translation elongation factor 1 alpha (tef1α) combined with morphological characteristics was used to identify strains isolated from the diseased leaves of Aporosadioica and Rhaphiolepisindica, as well as some rotted leaves from Yunnan and Hainan Provinces in China as three new species, viz., Pestalotiopsisaporosae-dioicae sp. nov., P.nannuoensis sp. nov. and P.rhaphiolepidis sp. nov.

Phylogeny, Taxonomy and Morphological Characteristics of Apiospora (Amphisphaeriales, Apiosporaceae).

Apiospora is widely distributed throughout the world, and usually identified as endophytes, pathogens or saprobes. In this study, six strains were isolated from Bambusaceae sp., Prunus armeniaca, Salix babylonica and saprophytic leaves in Shandong Province, China. Three new species were identified based on a multi-locus gene phylogenetic analysis using a combined dataset of ITS, LSU, TEF1α and TUB2 in conjunction with morphological assessments. Apiospora armeniaca sp. nov., Apiospora babylonica sp. nov., and Apiospora jinanensis sp. nov. have been comprehensively described and illustrated, representing significant additions to the existing taxonomy.

Association of frailty with adverse outcomes in surgically treated geriatric patients with hip fracture: A meta-analysis and trial sequential analysis.

OBJECTIVE: Some studies have associated frailty and prognostic outcomes in geriatric hip fracture patients, but whether frailty can predict postoperative outcomes remains controversial. This review aims to assess the relationship between frailty and adverse postoperative outcomes in geriatric patients with hip fracture. METHODS: Based on electronic databases, including PubMed, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature, the Cochrane Library, Chinese National Knowledge Infrastructure, and WanFang Data, we systematically searched for studies that investigated the association between frailty and adverse outcomes among patients aged 60 or over after hip fracture surgery. Stata 17.0 and Trial Sequential Analysis viewer software were used to obtain pooled estimates and verify whether the sample size was sufficient and the evidence robust. RESULTS: Twenty-one studies involving 49,196 patients were included for quantitative analysis. Compared with nonfrail patients, frail patients had a higher risk of inpatient mortality (risk ratio [RR] = 1.93, 95% confidence interval [CI]: 1.66-2.23), 30-day mortality (RR = 2.13, 95% CI: 1.23-3.70), and 1-year mortality (RR = 2.44, 95% CI: 1.47-4.04). Frailty can significantly predict postoperative complications (RR = 1.76, 95% CI: 1.38-2.23), including delirium, pneumonia, cardiac complications, urinary tract infection, and surgical site infection; the association between frailty and deep venous thrombosis/pulmonary embolism and acute kidney injury needs further analysis. Trial sequential analysis showed that the findings regarding mortality were reliable and robust. CONCLUSION: This meta-analysis provides detailed information indicating that frailty is a substantial predictor of mortality and selected postoperative complications.