Development of a Recombinase-Aided Amplification Assay for the Rapid Detection of Candida auris.

Candida auris (C. auris) was first discovered in Japan in 2009 and has since spread worldwide. It exhibits strong transmission ability, high multidrug resistance, blood infectivity, and mortality rates. Traditional diagnostic techniques for C. auris have shortcomings, leading to difficulty in its timely diagnosis and identification. Therefore, timely and accurate diagnostic assays for clinical samples are crucial. We developed a novel, rapid recombinase-aided amplification (RAA) assay targeting the 18S rRNA, ITS1, 5.8S rRNA, ITS2, and 28S rRNA genes for C. auris identification. This assay can rapidly amplify DNA at 39 °C in 20 min. The analytical sensitivity and specificity were evaluated. From 241 clinical samples collected from pediatric inpatients, none were detected as C. auris-positive. We then prepared simulated clinical samples by adding 10-fold serial dilutions of C. auris into the samples to test the RAA assay's efficacy and compared it with that of real-time PCR. The assay demonstrated an analytical sensitivity of 10 copies/µL and an analytical specificity of 100%. The lower detection limit of the RAA assay for simulated clinical samples was 101 CFU/mL, which was better than that of real-time PCR (102-103 CFU/mL), demonstrating that the RAA assay may have a better detection efficacy for clinical samples. In summary, the RAA assay has high sensitivity, specificity, and detection efficacy. This assay is a potential new method for detecting C. auris, with simple reaction condition requirements, thus helping to manage C. auris epidemics.

Metabolomics analysis reveals the metabolite profiles of Rheum tanguticum grown under different altitudinal gradients.

BACKGROUND: Plant growth and quality are often affected by environmental factors, including geographical location, climate, and soil. In this study, we describe the effect of altitudinal differences on the growth and active ingredients in Rheum tanguticum Maxim. ex Balf. (R. tanguticum), a traditional Chinese medicinal herb known for its laxative properties. RESULTS: The results showed that plants grown at lower altitudes had better growth performances than those in higher altitude areas. The yield varied by 2.45-23.68 times with altitude, reaching a maximum of 102.01 t/ha. In addition, total anthraquinone and total sennoside contents decreased with increasing altitude, whereas total tannins increased with increasing altitude. The total anthraquinone content of the indicator compound reached 5.15% at five experimental sites, which exceeded the Chinese Pharmacopoeia standard by 70.87%. The content of the other two categories of active ingredients reached a maximum value of 0.94% (total sennosides) and 2.65% (total tannins). Redundancy analysis revealed that annual rainfall, annual average temperature, annual sunshine hours, and pH significantly affected growth and active ingredients. Moreover, key metabolites, such as flavonoids, amino acids and their derivatives, phenolic acids, lipids, and terpenes, were differentially expressed between samples from low- and high-altitude cultivation areas. These metabolites were enriched in the flavonoid and flavonol biosynthetic pathway and the monoterpene biosynthetic pathway. CONCLUSIONS: These results suggest that high anthraquinone content was observed in the lowest-latitude cultivation area due to low rainfall and alkaline soil pH. Key metabolites were significantly upregulated in high-latitude cultivation areas. These results provide a scientific basis for quality control and the systematic cultivation of R. tanguticum.

Interface-Engineered NiFe/Ni-S Nanoparticles for Reliable Alkaline Oxygen Production at Industrial Current: A Sulfur Source Confinement Strategy.

Using powder-based ink appears to be the most suitable candidate for commercializing the membrane electrode assembly (MEA), while research on the powder-based NPM catalyst for anion exchange membrane water electrolyzer (AEMWE) is currently insufficient, especially at high current density. Herein, a sulfur source (NiFe Layered double hydroxide adsorbed SO 4 2 - ${\mathrm{SO}}_4^{2 - }$ ) confinement strategy is developed to integrate Ni3S2 onto the surface of amorphous/crystalline NiFe alloy nanoparticles (denoted NiFe/Ni-S), achieving advanced control over the sulfidation process for the formation of metal sulfides. The constructed interface under the sulfur source confinement strategy generates abundant active sites that increase electron transport at the electrode-electrolyte interface and improve ability over an extended period at a high current density. Consequently, the constructed NiFe/Ni-S delivers an ultra-low overpotential of 239 mV at 10 mA cm-2 and 0.66 mA cm ECSA - 2 ${\mathrm{cm}}_{{\mathrm{ECSA}}}^{ - 2}$ under an overpotential of 300 mV. The AEMWE with NiFe/Ni-S anode exhibits a cell voltage of 1.664 V @ 0.5 A cm-2 and a 400 h stability at 1.0 A cm-2.

Exploring the role of ubiquitin regulatory X domain family proteins in cancers: bioinformatics insights, mechanisms, and implications for therapy.

UBXD family (UBXDF), a group of proteins containing ubiquitin regulatory X (UBX) domains, play a crucial role in the imbalance of proliferation and apoptotic in cancer. In this study, we summarised bioinformatics proof on multi-omics databases and literature on UBXDF's effects on cancer. Bioinformatics analysis revealed that Fas-associated factor 1 (FAF1) has the largest number of gene alterations in the UBXD family and has been linked to survival and cancer progression in many cancers. UBXDF may affect tumour microenvironment (TME) and drugtherapy and should be investigated in the future. We also summarised the experimental evidence of the mechanism of UBXDF in cancer, both in vitro and in vivo, as well as its application in clinical and targeted drugs. We compared bioinformatics and literature to provide a multi-omics insight into UBXDF in cancers, review proof and mechanism of UBXDF effects on cancers, and prospect future research directions in-depth. We hope that this paper will be helpful for direct cancer-related UBXDF studies.

CRISPR-Cas9 mediated genome editing of Kluyveromyces marxianus for iterative, multiplexed gene disruption and pathway integration.

Kluyveromyces marxianus, a thermotolerant, fast-growing, Crabtree-negative yeast, is a promising chassis for the manufacture of various bioproducts. Although several genome editing tools are available for this yeast, these tools still require refinement to enable more convenient and efficient genetic modification. In this study, we engineered the K. marxianus NBRC 104275 strain by impairing the nonhomologous end joining and enhancing the homologous recombination machinery, which resulted in improved homology-directed repair effective on homology arms of up to 40 bp in length. Additionally, we simplified the CRISPR-Cas9 editing system by constructing a strain for integrative expression of Cas9 nuclease and plasmids bearing different selection markers for gRNA expression, thereby facilitating iterative genome editing without the need for plasmid curing. We demonstrated that tRNA was more effective than the hammerhead ribozyme for processing gRNA primary transcripts, and readily assembled tRNA-gRNA arrays were used for multiplexed editing of at least four targets. This editing tool was further employed for simultaneous scarless in vivo assembly of a 12-kb cassette from three fragments and marker-free integration for expressing a fusion variant of fatty acid synthase, as well as the integration of genes for starch hydrolysis. Together, the genome editing tool developed in this study makes K. marxianus more amenable to genetic modification and will facilitate more extensive engineering of this nonconventional yeast for chemical production.

Identification and validation of m6A-associated ferroptosis genes in renal clear cell carcinoma.

Urinary cancer is synonymous with clear cell renal cell carcinoma (ccRCC). Unfortunately, existing treatments for this illness are ineffective and unpromising. Finding novel ccRCC biomarkers is crucial to creating successful treatments. The Cancer Genome Atlas provided clear cell renal cell carcinoma transcriptome data. Functional enrichment analysis was performed on ccRCC and control samples' differentially expressed N6-methyladenosine RNA methylation and ferroptosis-related genes (DEMFRGs). Machine learning was used to find and model ccRCC patients' predicted genes. A nomogram was created for clear cell renal cell carcinoma patients. Prognostic genes were enriched. We examined patients' immune profiles by risk score. Our prognostic genes predicted ccRCC treatment drugs. We found 37 DEMFRGs by comparing 1913 differentially expressed ccRCC genes to 202 m6A RNA methylation FRGs. Functional enrichment analysis showed that hypoxia-induced cell death and metabolism pathways were the most differentially expressed methylation functional regulating genes. Five prognostic genes were found by machine learning: TRIB3, CHAC1, NNMT, EGFR, and SLC1A4. An advanced renal cell carcinoma nomogram with age and risk score accurately predicted the outcome. These five prognostic genes were linked to various cancers. Immunological cell number and checkpoint expression differed between high- and low-risk groups. The risk model successfully predicted immunotherapy outcome, showing high-risk individuals had poor results. NIACIN, TAE-684, ROCILETINIB, and others treat ccRCC. We found ccRCC prognostic genes that work. This discovery may lead to new ccRCC treatments.

Crystalline MnCO3@Amorphous MnOx Composite as Cathode Material for High-Performance Aqueous Zinc-Ion Batteries.

Rechargeable aqueous zinc-ion batteries (RAZIBs) have received extensive attention because of their advantages of low cost, high safety, and nontoxicity. However, problems such as dissolution of the active cathode material, dendrites/passivation of the zinc anode, and slow reaction kinetics hindered their further applications. In this work, a crystalline/amorphous composite-type material composed of crystalline MnCO3 and amorphous MnOx was prepared and used as the cathode material for RAZIBs. The MnCO3@amorphous MnOx (MnCO3@A-MnOx) composite possesses the merits of both the pure crystalline phase of MnCO3 and the amorphous phase of MnOx, which can deliver better electrochemical performance than the corresponding single component in repeated cycles. In addition, crystalline MnCO3 undergoes a complex phase transition to the active MnO2 during the first charge process, providing the composite with a stable structure and additional electrochemical capacity. The electrochemical measurement results indicate that the MnCO3@A-MnOx electrode can display high reversible discharge capacity at 0.1 A g-1, excellent rate performance at 5.0 A g-1, and long cycling stability over 2000 cycles, showing great potential as a cathode material for high-performance RAZIBs.

Measurement of the absorption cross-sections of sulfur compounds in the 180-270 nm region considering nonlinear effects.

Sulfur compounds (SO2, CS2, H2S and OCS) are common toxic pollutants in the atmospheric environment, and the absorption spectroscopy technique can indeed help to realize online monitoring of their concentrations. However, nonlinear effects that occur during absorption spectroscopy measurements have a serious impact on the measurement of the absorption cross-sections (ACSs) of sulfur compounds, leading to serious deviations in both the substance absorption properties and concentrations obtained based on ACS analysis. In this paper, the maximum effective ACSs of sulfur compounds in the linear region are obtained by considering the influence of nonlinear effects and eliminating interference factors such as oxygen and photolysis. In addition, the nonlinear effects are found to be greatly attenuated in spectra with broad band absorption characteristics by comparing the oscillatory absorption spectra before and after the differential treatment and by comparing the change in the oscillatory ACS with the broad band ACS. The experimental results show that the effective ACSs of SO2, CS2, H2S, and OCS with a resolution of 0.23 nm are 14.15 × 10-18 cm2 per molecule, 5.61 × 10-16 cm2 per molecule, 7.09 × 10-18 cm2 per molecule, and 3.20 × 10-19 cm2 per molecule, respectively. So far, it is the largest ACS obtained at room temperature and atmospheric pressure, which is of great significance for online measurement of sulfur compounds.

Autistic traits and ARFID-associated eating behaviors in preschoolers: Mediating effects of sensory processing patterns.

OBJECTIVE: This study aimed to examine the association between autistic traits and Avoidant Restrictive Food Intake Disorder (ARFID)-associated eating behaviors in preschool-age children and investigated whether this association was mediated by sensory processing patterns. METHOD: A cross-sectional, parent-reported study was conducted between July 2022 and March 2023 among 503 preschoolers aged 4-6 years in China. Parents provided assessments of their children's autistic traits using the Social Responsiveness Scale, sensory processing patterns using the Short Sensory Profile 2, and ARFID-associated eating behaviors using the Nine Items ARFID Screen. The mediation model based on ordinary least squares regression was employed to test the mediating effects of sensory processing patterns between autistic traits and ARFID-associated eating behaviors. RESULTS: The results indicated significant associations among autistic traits, ARFID-associated eating behaviors, and sensory processing patterns. Moreover, mediation analyses revealed that sensory processing patterns played a partial mediating role in the relationship between autistic traits and ARFID-associated eating behaviors. Specifically, autistic traits were observed to weaken ARFID-associated eating behaviors, particularly picky eating and poor appetite, through Registration, while simultaneously fostering them through Sensitivity and Avoiding. DISCUSSION: Our study is limited to some extent by the inability to draw longitudinal conclusions from cross-sectional data. Nevertheless, it underscores the significance of early identification and intervention for food avoidance/restriction behaviors due to sensory processing abnormalities in children with heightened autistic traits. This proactive approach may contribute to mitigating ARFID-associated eating behaviors that might drive clinical symptoms of ARFID.

Autistic traits and eating behaviors in Chinese preschoolers: Role of sensory profiles and home environment.

OBJECTIVE: This study aims to 1) explore the association between autistic traits and eating behaviors in Chinese preschoolers; 2) explore the mediating role of sensory processing patterns on the relation of autistic traits and eating-related behaviors; and 3) examine home nurturing environment as a moderator between autistic traits and eating-related behaviors. We hypothesize that there is a significant association between autistic traits and eating behaviors, which is mediated by sensory processing patterns and moderated by the home nurturing environment. METHOD: 509 children aged 3-4 years participated in this cross-sectional research. They were assessed using the Social Responsiveness Scale-Second Edition (SRS-2) for autistic traits, the Chinese Preschoolers' Eating Behavior Questionnaire (CPEBQ) for eating-related behaviors, the Short Sensory Profile-Second Edition (SSP-2) for sensory processing patterns, and the Children Home Nurture Environment Questionnaire (CHNEQ) for home nurturing environment. Mediation regression analyses were used to examine the role of sensory processing patterns, while moderation analyses to examine the role of home nurturing environment. RESULTS: We observed a positive association between autistic traits and eating behavior problems among typically developed children. Sensory processing patterns significantly mediated the impact of autistic traits on children's eating-related behaviors and home nurturing environment also moderated this relationship. DISCUSSION: Our research suggests that Chinese preschoolers with higher autistic traits may face more eating challenges when they possess more heightened sensory processing patterns, while living in supportive home environments helps to improve their eating behaviors. These findings contribute to the understanding of how and to what extent eating problems are influenced by autistic traits, and they offer insight into the alleviation of eating problems from the perspectives of sensory patterns and family nurturing environments.

Application of Human Acellular Dermal Matrix with Skin Graft for Lacunar Soft-Tissue Defect of Lateral Heel after Calcaneal Fracture.

OBJECTIVE: To investigate the clinical effect of human acellular dermal matrix (HADM) combined with split-thickness skin graft in repairing lacunar soft tissue defects of the lateral heel after calcaneal fracture. METHODS: From June 2018 to October 2020, providers repaired 11 cases of lacunar soft tissue defects at the lateral part of the heel using HADM combined with split-thickness skin graft. After thorough debridement, the HADM was trimmed and filled into the lacunar defect area. Once the wound was covered, a split-thickness skin graft and negative-pressure wound therapy were applied. Providers evaluated the appearance, scar, ductility of the skin graft site, appearance of the donor site, healing time, and any reoperation at follow-up. RESULTS: Of the 11 cases, 8 patients achieved successful wound healing by primary intention. Three patients showed partial necrosis in the edge of the skin graft, but the wound healed after standard wound care. Evaluation at 6 and 12 months after surgery showed that all patients had wound healing and mild local scarring; there was no obvious pigmentation or scar formation in the donor skin area. The average healing time was 37.5 days (range, 24-43 days). CONCLUSIONS: The HADM combined with split-thickness skin graft is a simple and effective reconstruction method for lacunar soft tissue defect of the lateral heel after calcaneal fracture. In this small sample, the combination demonstrated few infections, minor scar formation, few donor site complications, and relatively short hospital stays.

Homeostatic Solid Solution in Layered Transition-Metal Oxide Cathodes of Sodium-Ion Batteries.

Two-phase transformation reaction is ubiquitous in solid-state electrochemistry; however, it usually involves inferior structure rearrangement upon extraction and insertion of large-sized Na+, thus leading to severe local strain, cracks, and capacity decay in sodium-ion batteries (SIBs). Here, a homeostatic solid solution reaction is reported in the layered cathode material P'2-Na0.653Ni0.081Mn0.799Ti0.120O2 during sodiation and desodiation. It is induced by the synergistic incorporation of Ni and Ti for the reinforced O(2p)-Mn(3d-eg*) hybridization, which leads to mitigated Jahn-Teller distortion of MnO6 octahedra, contracted transition-metal oxide slabs, and enlarged Na layer spacings. The thermodynamically favorable solid solution pathway rewards the SIBs with excellent cycling stability (87.2% capacity retention after 500 cycles) and rate performance (100.5 mA h g-1 at 2500 mA g-1). The demonstrated reaction pathway will open a new avenue for rational designing of cathode materials for SIBs and beyond.

Synthesis of isobutanol using acetate as sole carbon source in Escherichia coli.

BACKGROUND: With concerns about depletion of fossil fuel and environmental pollution, synthesis of biofuels such as isobutanol from low-cost substrate by microbial cell factories has attracted more and more attention. As one of the most promising carbon sources instead of food resources, acetate can be utilized by versatile microbes and converted into numerous valuable chemicals. RESULTS: An isobutanol synthetic pathway using acetate as sole carbon source was constructed in E. coli. Pyruvate was designed to be generated via acetyl-CoA by pyruvate-ferredoxin oxidoreductase YdbK or anaplerotic pathway. Overexpression of transhydrogenase and NAD kinase increased the isobutanol titer of recombinant E. coli from 121.21 mg/L to 131.5 mg/L under batch cultivation. Further optimization of acetate supplement concentration achieved 157.05 mg/L isobutanol accumulation in WY002, representing the highest isobutanol titer by using acetate as sole carbon source. CONCLUSIONS: The utilization of acetate as carbon source for microbial production of valuable chemicals such as isobutanol could reduce the consumption of food-based substrates and save production cost. Engineering strategies applied in this study will provide a useful reference for microbial production of pyruvate derived chemical compounds from acetate.

Molecular epidemiological and genetic characterization of pseudorabies virus in Guangxi, China.

Pseudorabies virus (PRV) is an important pathogen that can cause harm to the pig population. Since 2011, there have been a number of large-scale outbreaks of pseudorabies on Chinese farms where animals had been vaccinated with the Bartha-K61 vaccine. In order to understand the epidemiological trend and genetic variations of PRV in Guangxi province, China, 819 tissue samples were collected from swine farms where PRV infection was suspected from 2013 to 2019, and these were tested for infectious wild strains of PRV. The results showed a positive rate of PRV in Guangxi province of 28.21% (231/819). Thirty-six wild-type PRV strains were successfully isolated from PRV-positive tissue samples, and a genetic evolutionary analysis was performed based on the gB, gC, gD, gE, and TK genes. Thirty of the PRV strains were found to be closely related to the Chinese variant strains HeN1-China-2012 and HLJ8-China-2013. In addition, five PRV strains were genetically related to Chinese classical strains, and one isolate was a recombinant of the PRV variant and the vaccine strain Bartha-K61. Amino acid sequence analysis showed that all 36 PRV strains had characteristic variant sites in the amino acid sequences of the gB, gC, gD, and gE proteins. Pathogenicity analysis showed that, compared to classical PRV strains, the PRV variant strains were more pathogenic in mice and had a lower LD50. Taken together, our results show that wild-type PRV infections are common on pig farms in Guangxi province of China and that the dominant prevalent strains were those of the PRV variants. The PRV variant strains also had increased pathogenicity in mice. Our data will provide a useful reference for understanding the prevalence and genetic evolution of PRV in China.

Soluble Protein Content, Bioactive Compounds and the Antioxidant Activity in Seeds of Ten Rheum tanguticum Lines from Qinghai-Tibet Plateau.

Rheum tanguticum (Rh. tanguticum) is a Chinese medicinal plant traditionally used in the treatment of constipation. As a byproduct, the seeds of this plant are rich in nutrients and phytochemicals. This study aimed to determine and assess seed germination ability, seed physical characteristics, soluble protein content, chemical constituents and antioxidant capacity from different breeding lines, to promote the development and utilization of seed resources. Significant differences were observed for the soluble protein content and antioxidant assays among the ten lines. The contents of aloe-emodin, rhein and catechins accumulated in seeds were extremely low and significantly different from those in roots. In contrast, emodin and chrysophanol were abundant in seeds, and significant differences were observed between seeds and roots. It was found that associations between gallic acid and catechins were not significant for either soluble protein or antioxidant capacity. There was a significantly positive correlation between the contents of four anthraquinones (aloe-emodin, rhein, emodin and chrysophanol) and soluble protein. Seeds have potent antioxidative capacity and relatively high levels of soluble protein content. The rich chemical composition of seeds can be widely used in the medical industry for further development.

Programmed Death of Injured Pseudomonas aeruginosa on Mechano-Bactericidal Surfaces.

Mechano-bactericidal surfaces deliver lethal effects to contacting bacteria. Until now, cell death has been attributed to the mechanical stress imparted to the bacterial cell envelope by the surface nanostructures; however, the process of bacterial death encountering nanostructured surfaces has not been fully illuminated. Here, we perform an in-depth investigation of the mechano-bactericidal action of black silicon (bSi) surfaces toward Gram-negative bacteria Pseudomonas aeruginosa. We discover that the mechanical injury is not sufficient to kill the bacteria immediately due to the survival of the inner plasma membrane. Instead, such sublethal mechanical injury leads to apoptosis-like death (ALD) in affected bacteria. In addition, when the mechanical stress is removed, the self-accumulated reactive oxygen species (ROS) incur poststress ALD in damaged cells in a nonstressed environment, revealing that the mechano-bactericidal actions have sustained physiological effects on the bacterium. This work creates a new facet and can introduce many new regulation tools to this field.

[Guidelines for prevention and treatment of colorectal adenoma with integrated Chinese and western medicine].

The Guidelines for prevention and treatment of colorectal adenoma with integrated Chinese and western medicine are put forward by Nanjing University of Chinese Medicine and approved by China Association of Chinese Medicine. According to the formulation processes and methods of relevant clinical practice guidelines, the experts in clinical medicine and methodology were organized to discuss the key problems to be addressed in the clinical prevention and treatment of colorectal adenoma(CRA) and provided answers following the evidence-based medicine method, so as to provide guidance for clinical decision-making. CRA is the major precancerous disease of colorectal cancer. Although the prevention and treatment with integrated Chinese and western medicine have been applied to the clinical practice of CRA, there is still a lack of high-quality guidelines. Four basic questions, 15 clinical questions, and 10 outcome indicators were determined by literature research and Delphi questionnaire. The relevant randomized controlled trial(RCT) was retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, Web of Science, and 2 clinical trial registries, and finally several RCTs meeting the inclusion criteria were included. The data extracted from the RCT was imported into RevMan 5.3 for evidence synthesis, and the evidence was evaluated based on the Grading of Recommendations, Assessment, Development, and Evaluations(GRADE). The final recommendations were formed by the nominal group method based on the evidence summary table. The guidelines involve the diagnosis, screening, treatment with integrated Chinese and western medicine, prevention, and follow-up of colorectal adenoma, providing options for the clinical prevention and treatment of CRA.

Sex Differences in Anatomical Rich-Club and Structural-Functional Coupling in the Human Brain Network.

Structural and functional differences between the brains of female and male adults have been well documented. However, potential sex differences in the patterns of rich-club organization and the coupling between their structural connectivity (SC) and functional connectivity (FC) remain to be determined. In this study, functional magnetic resonance imaging and diffusion tensor imaging techniques were combined to examine sex differences in rich-club organization. Females had a stronger SC-FC coupling than males. Moreover, stronger SC-FC coupling in the females was primarily located in feeder connections and non-rich-club nodes of the left inferior frontal gyrus and inferior parietal lobe and the right superior frontal gyrus and superior parietal gyrus, whereas higher coupling strength in males was primarily located in rich-club connections and rich-club node of the right insula, and non-rich-club nodes of the left hippocampus and the right parahippocampal gyrus. Sex-specific patterns in correlations were also shown between SC-FC coupling and cognitive function, including working memory and reasoning ability. The topological changes in rich-club organization provide novel insight into sex-specific effects on white matter connections that underlie a potential network mechanism of sex-based differences in cognitive function.

An mALBI-Child-Pugh-based nomogram for predicting post-hepatectomy liver failure grade B-C in patients with huge hepatocellular carcinoma: a multi-institutional study.

OBJECTIVE: Post-hepatectomy liver failure (PHLF) is a severe complication in patients with hepatocellular carcinoma (HCC) who underwent hepatectomy. This study aims to develop a nomogram of PHLF grade B-C in patients with huge HCC (diameter ≥ 10 cm). METHODS: We retrospectively collected clinical information of 514 and 97 patients who underwent hepatectomy for huge HCC at two medical centers between 2016 and 2021. Univariate and multivariate analysis were carried out to screen the independent risk factors of PHLF grade B-C, which were visualized as a nomogram. RESULTS: Three Hundred Forty Three Thousand One Hundred Seventy One  and 97 HCC patients were included in the training cohort, internal validation cohort, and external validation cohort, with probabilities of PHLF grade B-C of 15.1%, 12.9%, and 22.7%, respectively. Pre-operative modified albumin-bilirubin (mALBI) grade (p < 0.001), Child-Pugh classification (p = 0.044), international normalized ratio (INR) (p = 0.005), cirrhosis (p = 0.019), and intraoperative blood loss (p = 0.004) were found to be independently associated with PHLF grade B-C in the training cohort. All the five independent factors were considered in the establishment of the nomogram model. In the internal validation cohort and external validation cohort, the area under receiver operating characteristic curve for the nomogram in PHLF grade B-C prediction reached 0.823 and 0.740, respectively. Divided into different risk groups according to the optimal cut-off value, patients in the high-risk group reported significantly higher frequency of PHLF grade B-C than those in the low-risk group, both in the training cohort and the validation cohort (p < 0.001). CONCLUSIONS: The proposed noninvasive nomogram based on mALBI-Child-Pugh and three other indicators achieved optimal prediction performance of PHLF grade B-C in patients with huge HCC.

Transcription Factor IAA27 Positively Regulates P Uptake through Promoted Adventitious Root Development in Apple Plants.

Phosphate (P) deficiency severely limits the growth and production of plants. Adventitious root development plays an essential role in responding to low phosphorus stress for apple plants. However, the molecular mechanisms regulating adventitious root growth and development in response to low phosphorus stress have remained elusive. In this study, a mutation (C-T) in the coding region of the apple AUXIN/INDOLE-3-ACETIC ACID 27 (IAA27) gene was identified. MdIAA27T-overexpressing transgenic apple improved the tolerance to phosphorus deficiency, which grew longer and denser adventitious roots and presented higher phosphorous content than the control plants under low phosphorus conditions, while the overexpression of MdIAA27C displayed the opposite trend. Moreover, the heterologous overexpression of MdIAA27 in tobacco yielded the same results, supporting the aforementioned findings. In vitro and in vivo assays showed that MdIAA27 directly interacted with AUXIN RESPONSE FACTOR (ARF8), ARF26 and ARF27, which regulated Small Auxin-Up RNA 76 (MdSAUR76) and lateral organ boundaries domain 16 (MdLBD16) transcription. The mutation in IAA27 resulted in altered interaction modes, which in turn promoted the release of positive ARFs to upregulate SAUR76 and LBD16 expression in low phosphorus conditions. Altogether, our studies provide insights into how the allelic variation of IAA27 affects adventitious root development in response to low phosphorus stress.