Engineering and functional analysis of yeast with a monotypic 40S ribosome subunit.

Emerging evidence reveals that ribosomes are not monolithic but dynamic machines with heterogeneous protein compositions that can reshape ribosomal translational abilities and cellular adaptation to environmental changes. Duplications of ribosomal protein (RP) genes are ubiquitous among organisms and are believed to affect cell function through paralog-specific regulation (e.g., by generating heterogeneous ribosomes) and/or gene dose amplification. However, direct evaluations of their impacts on cell function remain elusive due to the highly heterogeneous cellular RP pool. Here, we engineered a yeast with homogeneous 40S RP paralog compositions, designated homo-40S, by deleting the entire set of alternative duplicated genes encoding yeast 40S RP paralogs. Homo-40S displayed mild growth defects along with high sensitivity to the translation inhibitor paromomycin and a significantly increased stop codon readthrough. Moreover, doubling of the remaining RP paralogous genes in homo-40S rescued these phenotypes markedly, although not fully, compared to the wild-type phenotype, indicating that the dose of 40S RP genes together with the heterogeneity of the contents was vital for maintaining normal translational functionalities and growth robustness. Additional experiments revealed that homo-40S improved paromomycin tolerance via acquisition of bypass mutations or evolved to be diploid to generate fast-growing derivatives, highlighting the mutational robustness of engineered yeast to accommodate environmental and genetic changes. In summary, our work demonstrated that duplicated RP paralogs impart robustness and phenotypic plasticity through both gene dose amplification and paralog-specific regulation, paving the way for the direct study of ribosome biology through monotypic ribosomes with a homogeneous composition of specific RP paralogs.

Trinitarian Design of Gradient Artificial Interphase Enables Colossal Granular Li Deposits for Stable Li-Metal Batteries.

The cycling lifespan of Li-metal batteries is compromised by the unstable solid electrolyte interphase (SEI) and the continuous Li dendrites, restricting their practical implementations. Given these challenges, establishing an artificial SEI holds promise. Herein, a trinitarian gradient interphase is innovatively designed through composite coatings of magnesium fluoride (MgF2), N-hexadecyltrimethylammonium chloride (CTAC), and polyvinylidene fluoride-hexafluoropropylene copolymer (PVDF-HFP) on Li-metal anode (LMA). Specifically, the MgF2/CTAC/PVDF-HFP SEI spontaneously forms a lithium fluoride (LiF)-rich PVDF-HFP-based SEI, along with lithium-magnesium (Li-Mg) alloy substrate as lithiophilic electronic conductor and positively charged CTAC during plating. Noticeably, the Li-Mg alloy homogenizes the distribution of electric field and reduce the internal resistance, while the electronically insulated LiF/PVDF-HFP composite SEI offers fast ion-conducting and mechanical flexibility, accommodating the volumetric expansion and ensuring stable Li-ion flux. Additionally, CTAC at the dendritic tip is pivotal for mitigating dendrites through its electrostatic shield mechanism. Innovatively, this trinitarian synergistic mechanism, which facilitates colossal granular Li deposits, constructs a dendrite-free LMA, leading to stable cycling performances in practical Li||LFP, popular Li||NCM811, and promising Li||S full cells. This work demonstrates the design of multifunctional composite SEI for comprehensive Li protection, thereby inspiring further advancements in artificial SEI engineering for alkali-metal batteries.

A bacteriophage against Citrobacter braakii and its synergistic effect with antibiotics.

A bacteriophage BD49 specific for Citrobacter braakii was screened out and purified by double-layer plate method. It consists of a polyhedral head of 93.1 ± 1.2 nm long and 72.9 ± 4.2 nm wide, tail fibers, collar, sheath and baseplate. The bacteriophage was identified by morphology observed with transmission electron microscope (TEM), whole genome sequencing carried out by Illumina next generation sequencing (NGS) technique, and gene annotation based on Clusters of Orthologous Groups of proteins (COG) database. It was identified primarily as a member of Caudovirales by morphology and further determined as Caudovirales, Myoviridae, and Citrobacter bacteriophage by alignment of its whole genome sequence with the NCBI database and establishment of phylogenetic tree. The bacteriophage showed good environmental suitability with optimal multiplicity of infection (MOI) of 0.01, proliferation time of 80 min, optimum living temperature of 30-40 °C, and living pH of 5-10. In addition, it exhibited synergistic effect with ciprofloxacin against C. braakii in antibacterial tests.

Large-scale pathway reconstruction and colorimetric screening accelerate cellular metabolism engineering.

The capability to manipulate and analyze hard-wired metabolic pathways sets the pace at which we can engineer cellular metabolism. Here, we present a framework to extensively rewrite the central metabolic pathway for malonyl-CoA biosynthesis in yeast and readily assess malonyl-CoA output based on pathway-scale DNA reconstruction in combination with colorimetric screening (Pracs). We applied Pracs to generate and test millions of enzyme variants by introducing genetic mutations into the whole set of genes encoding the malonyl-CoA biosynthetic pathway and identified hundreds of beneficial enzyme mutants with increased malonyl-CoA output. Furthermore, the synthetic pathways reconstructed by randomly integrating these beneficial enzyme variants generated vast phenotypic diversity, with some displaying higher production of malonyl-CoA as well as other metabolites, such as carotenoids and betaxanthin, thus demonstrating the generic utility of Pracs to efficiently orchestrate central metabolism to optimize the production of different chemicals in various metabolic pathways. Pracs will be broadly useful to advance our ability to understand and engineer cellular metabolism.

miR-21-5p in extracellular vesicles obtained from adipose tissue-derived stromal cells facilitates tubular epithelial cell repair in acute kidney injury.

BACKGROUND AIMS: Acute kidney injury (AKI) is often associated with poor patient outcomes. Extracellular vesicles (EVs) have a marked therapeutic effect on renal recovery. This study sought to explore the functional mechanism of EVs from adipose tissue-derived stromal cells (ADSCs) in tubular epithelial cell (TEC) repair in AKI. METHODS: ADSCs were cultured and EVs were isolated and identified. In vivo and in vitro AKI models were established using lipopolysaccharide (LPS). RESULTS: EVs increased human kidney 2 (HK-2) cell viability; decreased terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells and levels of kidney injury molecule 1, cleaved caspase-1, apoptosis-associated speck-like protein containing a CARD, gasdermin D-N, IL-18 and IL-1ß; and elevated pro-caspase-1. EVs carried miR-21-5p into LPS-induced HK-2 cells. Silencing miR-21-5p partly eliminated the ability of EVs to suppress HK-2 cell pyroptosis and inflammation. miR-21-5p targeted toll-like receptor 4 (TLR4) and inhibited TEC pyroptosis and inflammation after AKI by inhibiting TLR4. TLR4 overexpression blocked the inhibitory effects of EVs on TEC pyroptosis and inflammation. EVs suppressed the nuclear factor-κB/NOD-like receptor family pyrin domain-containing 3 (NF-κB/NLRP3) pathway via miR-21-5p/TLR4. Finally, AKI mouse models were established and in vivo assays verified that ADSC-EVs reduced TEC pyroptosis and inflammatory response and potentiated cell repair by mediating miR-21-5p in AKI mice. CONCLUSIONS: ADSC-EVs inhibited inflammation and TEC pyroptosis and promoted TEC repair in AKI by mediating miR-21-5p to target TLR4 and inhibiting the NF-κB/NLRP3 pathway.

Enhancing Uranium Removal with a Titanium-Incorporated Zirconium-Based Metal-Organic Framework.

The urgent need to efficiently and rapidly decontaminate uranium contamination in aquatic environments underscores its significance for ecological preservation and environmental restoration. Herein, a series of titanium-doped zirconium-based metal-organic frameworks were meticulously synthesized through a stepwise process. The resultant hybrid bimetallic materials, denoted as NU-Zr-n%Ti, exhibited remarkable efficiency in eliminating uranium (U (VI)) from aqueous solution. Batch experiments were executed to comprehensively assess the adsorption capabilities of NU-Zr-n%Ti. Notably, the hybrid materials exhibited a substantial increase in adsorption capacity for U (VI) compared to the parent NU-1000 framework. Remarkably, the optimized NU-Zr-15%Ti displayed a noteworthy adsorption capacity (∼118 mg g-1) along with exceptionally rapid kinetics at pH 4.0, surpassing that of pristine NU-1000 by a factor of 10. This heightened selectivity for U (VI) persisted even when diverse ions exist. The dominant mechanisms driving this high adsorption capacity were identified as the robust electrostatic attraction between the negatively charged surface of NU-Zr-15%Ti and positively charged U (VI) species as well as surface complexation. Consequently, NU-Zr-15%Ti emerges as a promising contender for addressing uranium-laden wastewater treatment and disposal due to its favorable sequestration performance.

Radiomic features from dynamic susceptibility contrast perfusion-weighted imaging improve the three-class prediction of molecular subtypes in patients with adult diffuse gliomas.

OBJECTIVES: To investigate whether radiomic features extracted from dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) can improve the prediction of the molecular subtypes of adult diffuse gliomas, and to further develop and validate a multimodal radiomic model by integrating radiomic features from conventional and perfusion MRI. METHODS: We extracted 1197 radiomic features from each sequence of conventional MRI and DSC-PWI, respectively. The Boruta algorithm was used for feature selection and combination, and a three-class random forest method was applied to construct the models. We also constructed a combined model by integrating radiomic features and clinical metrics. The models' diagnostic performance for discriminating the molecular subtypes (IDH wild type [IDHwt], IDH mutant and 1p/19q-noncodeleted [IDHmut-noncodel], and IDH mutant and 1p/19q-codeleted [IDHmut-codel]) was compared using AUCs in the validation set. RESULTS: We included 272 patients (training set, n = 166; validation set, n = 106) with grade II-IV gliomas (mean age, 48.7 years; range, 19-77 years). The proportions of the molecular subtypes were 66.2% IDHwt, 15.1% IDHmut-noncodel, and 18.8% IDHmut-codel. Nineteen radiomic features (13 from conventional MRI and 6 from DSC-PWI) were selected to build the multimodal radiomic model. In the validation set, the multimodal radiomic model showed better performance than the conventional radiomic model did in predicting the IDHwt and IDHmut-codel subtypes, which was comparable to the conventional radiomic model in predicting the IDHmut-noncodel subtype. The multimodal radiomic model yielded similar performance as the combined model in predicting the three molecular subtypes. CONCLUSIONS: Adding DSC-PWI to conventional MRI can improve molecular subtype prediction in patients with diffuse gliomas. KEY POINTS: • The multimodal radiomic model outperformed conventional MRI when predicting both the IDH wild type and IDH mutant and 1p/19q-codeleted subtypes of gliomas. • The multimodal radiomic model showed comparable performance to the combined model in the prediction of the three molecular subtypes. • Radiomic features from T1-weighted gadolinium contrast-enhanced and relative cerebral blood volume images played an important role in the prediction of molecular subtypes.

Image-based deep learning identifies glioblastoma risk groups with genomic and transcriptomic heterogeneity: a multi-center study.

OBJECTIVES: To develop and validate a deep learning imaging signature (DLIS) for risk stratification in patients with multiforme (GBM), and to investigate the biological pathways and genetic alterations underlying the DLIS. METHODS: The DLIS was developed from multi-parametric MRI based on a training set (n = 600) and validated on an internal validation set (n = 164), an external test set 1 (n = 100), an external test set 2 (n = 161), and a public TCIA set (n = 88). A co-profiling framework based on a radiogenomics analysis dataset (n = 127) using multiscale high-dimensional data, including imaging, transcriptome, and genome, was established to uncover the biological pathways and genetic alterations underpinning the DLIS. RESULTS: The DLIS was associated with survival (log-rank p < 0.001) and was an independent predictor (p < 0.001). The integrated nomogram incorporating the DLIS achieved improved C indices than the clinicomolecular nomogram (net reclassification improvement 0.39, p < 0.001). DLIS significantly correlated with core pathways of GBM (apoptosis and cell cycle-related P53 and RB pathways, and cell proliferation-related RTK pathway), as well as key genetic alterations (del_CDNK2A). The prognostic value of DLIS-correlated genes was externally confirmed on TCGA/CGGA sets (p < 0.01). CONCLUSIONS: Our study offers a biologically interpretable deep learning predictor of survival outcomes in patients with GBM, which is crucial for better understanding GBM patient's prognosis and guiding individualized treatment. KEY POINTS: • MRI-based deep learning imaging signature (DLIS) stratifies GBM into risk groups with distinct molecular characteristics. • DLIS is associated with P53, RB, and RTK pathways and del_CDNK2A mutation. • The prognostic value of DLIS-correlated pathway genes is externally demonstrated.

A collaborative diffusion mechanism of multiple atoms during Cu-Ag bimetal surface reconstruction.

The reconstruction of bimetals under reaction conditions is critical for precisely controlling the catalytic performance of bimetallic catalysts. The surface diffusion mechanisms of Cu@Ag nanoparticles before and after CO adsorption were studied in this work. The diffusion patterns with the lowest energy barrier were determined by using ab initio molecular dynamics and meta-dynamics simulations. The effects of nanoparticle size, surface species and CO adsorption were taken into account. We present a mechanism of multiple atom collaborative diffusion during Cu@Ag bimetal reconstruction: surface atoms diffuse outward to form adatoms first, with nearby atoms occupying the original position of the outward diffused atom, and the outward diffusion can accelerate the inward diffusion of nearby surface atoms. The surface diffusion mechanisms of Cu@Ag under a CO atmosphere are different from those of Pd@Au that we previously presented, due to the different diffusion abilities of metal atoms. Our study provides a potential strategy to control the beginning of reconstruction to change the stability of bimetals under reaction conditions.

Independent and interactive associations between greenness and ambient pollutants on novel glycolipid metabolism biomarkers: A national repeated measurement study.

This study aims to investigate the independent and interactive effects of greenness and ambient pollutants on novel glycolipid metabolism biomarkers. A repeated national cohort study was conducted among 5085 adults from 150 counties/districts across China, with levels of novel glycolipid metabolism biomarkers of TyG index, TG/HDL-c, TC/HDL-c, and non-HDL-c measured. Exposure levels of greenness and ambient pollutants (including PM1, PM2.5, PM10, and NO2) for each participant were determined based on their residential location. Linear mixed-effect and interactive models were used to evaluate the independent and interactive effects between greenness and ambient pollutants on the four novel glycolipid metabolism biomarkers. In the main models, the changes [ß (95% CIs)] of TyG index, TG/HDL-c, TC/HDL-c, and non-HDL-c were -0.021 (-0.036, -0.007), -0.120 (-0.175, -0.066), -0.092 (-0.122, -0.062), and -0.445 (-1.370, 0.480) for every 0.1 increase in NDVI, and were 0.004 (0.003, 0.005), 0.014 (0.009, 0.019), 0.009 (0.006, 0.011), and 0.067 (-0.019, 0.154) for every 1 µg/m3 increase in PM1. Results of interactive analyses demonstrated that individuals living in low-polluted areas could get greater benefits from greenness than those living in highly-polluted areas. Additionally, the results of mediation analyses revealed that PM2.5 mediated 14.40% of the association between greenness and the TyG index. Further research is needed to validate our findings.

Effects of air pollution and residential greenness on sleep disorder: A 8-year nationwide cohort study.

BACKGROUND: Sleep disorder influencing the quality of life, however, its contributing factors have not been fully identified yet. Recently the potential effects of environmental exposures like air pollution and greenness on sleep disorder have attracted attention, but the evidence in China is limited, particularly in the middle-aged and elderly. METHODS: We conducted a nationwide prospective study that included 21,878 Chinese citizens aged 45 years or above. For each participant, the 3-year averaged exposure concentrations of air pollutants (including PM10, PM2.5, PM1, NO2) and greenness (assessed by NDVI) were estimated based on residential address. We used mixed-effects logistic models to examine the associations of sustained air pollutants and greenness exposures with the occurrence of sleep disorder, and used linear mixed-effects models to assess the associations with sleep duration. Specifically, interaction effects models were employed to identify potential modificators of the above associations. RESULTS: A total of 39,580 survey responses were received, with the overall occurrence rate of sleep disorder was 25.7%. A 10 µg/m3 increment in PM10 and PM2.5 were associated with increased occurrence of sleep disorder at 2% (aOR = 1.02, 95%CI:1.01, 1.04) and 7% (aOR = 1.07, 95%CI: 1.04, 1.11), and were associated with reduced sleep duration by 0.07 (95% CI: 0.08, 0.05) and 0.04 (95% CI: 0.05, 0.03) hours, respectively. Residential greenness appears to the potential protective factor for sleep disorder, that a 0.1 higher of the NDVI was associated a 9% (aOR = 0.91, 95%CI: 0.86, 0.96) decreased occurrence of sleep disorder and 0.09 h (95% CI: 0.05, 0.13) longer of sleep duration. Age and residence were identified as modificators of the above significant associations. CONCLUSION: Sustained exposure to air pollutants can increase the occurrence of sleep disorder and can reduce sleep duration, while exposure to higher levels of greenness can protect sleep health from the side effects of air pollutants.

Coevolution of ribosomal RNA expansion segment 7L and assembly factor Noc2p specializes the ribosome biogenesis pathway between Saccharomyces cerevisiae and Candida albicans.

Ribosomes of different species share an evolutionarily conserved core, exhibiting flexible shells formed partially by the addition of species-specific ribosomal RNAs (rRNAs) with largely unexplored functions. In this study, we showed that by swapping the Saccharomyces cerevisiae 25S rRNA genes with non-S. cerevisiae homologs, species-specific rRNA variations caused moderate to severe pre-rRNA processing defects. Specifically, rRNA substitution by the Candida albicans caused severe growth defects and deficient pre-rRNA processing. We observed that such defects could be attributed primarily to variations in expansion segment 7L (ES7L) and could be restored by an assembly factor Noc2p mutant (Noc2p-K384R). We showed that swapping ES7L attenuated the incorporation of Noc2p and other proteins (Erb1p, Rrp1p, Rpl6p and Rpl7p) into pre-ribosomes, and this effect could be compensated for by Noc2p-K384R. Furthermore, replacement of Noc2p with ortholog from C. albicans could also enhance the incorporation of Noc2p and the above proteins into pre-ribosomes and consequently restore normal growth. Taken together, our findings help to elucidate the roles played by the species-specific rRNA variations in ribosomal biogenesis and further provide evidence that coevolution of rRNA expansion segments and cognate assembly factors specialized the ribosome biogenesis pathway, providing further insights into the function and evolution of ribosome.

The dynamic nexus: exploring the interplay of BMI before, during, and after pregnancy with Metabolic Syndrome (MetS) risk in Chinese lactating women.

BACKGROUND AND AIM: The health implications of BMI and MetS in lactating women are significant. This study aims to investigate the relationship between risk of Mets in lactation and BMI in four stages: pre-pregnancy, prenatal period, 42 days postpartum, and current lactation. METHODS AND RESULTS: A total of 1870 Lactating Women within 2 years after delivery were included from "China Child and Lactating Mother Nutrition Health Surveillance (2016-2017)". Logistic regression model and Restricted cubic spline (RCS) were used to estimate the relationship between BMI and risk of MetS. ROC analysis was used to determine the threshold for the risk of MetS. Chain mediating effect analysis was used to verify the mediating effect. BMI of MetS group in all stages were higher than non-MetS group (P < 0.0001). There were significant positive correlations between BMI in each stage and ORs of MetS during lactation (P < 0.05). The best cut-off values for BMI in the four stages were 23.47, 30.49, 26.04 and 25.47 kg/m2. The non-linear spline test at BMI in 42 days postpartum, current and MetS in lactation was statistically significant (P non-linear = 0.0223, 0.0003). The mediation effect of all chains have to work through lactation BMI. The total indirect effect accounted for 80.95% of the total effect. CONCLUSIONS: The risk of MetS in lactating women is due to a high BMI base before pregnancy and postpartum. High BMI in all stages of pregnancy and postpartum were risk factors for MetS in lactation. BMI during lactation plays a key role in the risk of MetS.

Exposures to ambient air pollutants increase prevalence of sleep disorder in adults: Evidence from Wuhan Chronic Disease Cohort Study (WCDCS).

BACKGROUND: Sleep disorder contributes to memory dysfunction and chronic diseases. Clear evidence of environment disturbance, such as residential noise, are associated with an increased risk of sleep disorder. However, not enough studies have been conducted on association between residential air pollutants and sleep disorder. We sought to determine whether exposures to residential air pollutants associated with risk of sleep disorder among adults. METHODS: Using the dataset of the Wuhan Chronic Disease Cohort Study (WCDCS), we investigated the prevalence of sleep disorder and five sleep disorder symptoms in the study. The data of air pollutants (including PM10, PM2.5, NO2, SO2 and O3) were obtained from 10 air quality monitoring stations in Wuhan. We utilized logistic regression model to evaluate the associations of five types of air pollutants with odds ratio (OR) of sleep disorder and symptoms. The potential moderating effects of socio-demographic factors in the associations were explored using the interaction effects model. RESULTS: Of the study participants, 52.1 % had sleep disorder. Exposures to higher concentrations of air pollutants were associated with increased prevalence of sleep disorder. For example, per interquartile range (IQR) increases in concentrations of PM10, PM2.5 or SO2 corresponded to the increase of sleep disorder increased prevalence at 14.7 % (adjusted odds ratio (aOR) = 1.147, 95 %CI:1.062, 1.240), 8.9 % (aOR = 1.089, 95 %CI: 1.003, 1.182) and 15.8 % (aOR = 1.158, 95 %CI: 1.065, 1.260). For symptoms specific analyses, significant linkages of PM10, PM2.5, SO2 with difficulty in falling asleep, wake up after falling asleep and early awaken were observed. Moderating effects of age and place of residence on the linkages of PM10 with increased prevalence of sleep disorder were identified. CONCLUSION: Higher level of air pollution exposure could increase the prevalence of sleep disorder. Middle-aged and elderly population, as well as the rural residents are more likely to suffer from sleep disorder.

A Strategy for Studying Environmental Engineering: Simple Hydrothermal Synthesis of Flower-Shaped Stannous Sulfide Nanomaterials for Efficient Cataluminescence Sensing of Diethyl Ether.

In this work, flower-like stannous sulfide (SnS) nanomaterials are synthesized using a hydrothermal method and used as sensitive materials for cataluminescence (CTL)-based detection of diethyl ether. Gas sensors based on SnS nanomaterials are prepared, and the SnS nanomaterials exhibit excellent gas-sensitive behavior towards ether. High sensitivity to ether is achieved at a relatively low operating temperature (153 °C) compared to other common sensors. The response time is 3 s and the recovery time is 8 s. The CTL intensity shows a good linear relationship (R2 = 0.9931) with a detection limit of 0.15 ppm and the concentration of ether in the range of 1.5-60 ppm. The proposed CTL sensor shows good selectivity towards ether. In addition, a highly stable signal is obtained with a relative standard deviation of 1.5%. This study indicates that the SnS-based sensor has excellent gas-sensitive performance and shows potential for applications in the detection of ether.

Chaihu Shugan San promotes gastric motility in rats with functional dyspepsia by regulating Drp-1-mediated ICC mitophagy.

CONTEXT: Chaihu Shugan San (CHSGS) was effective in the treatment of functional dyspepsia (FD). OBJECTIVE: To investigate the mechanism of CHSGS in FD through dynamin-related protein 1 (Drp-1)-mediated interstitial cells of cajal (ICC) mitophagy. MATERIALS AND METHODS: Forty Sprague-Dawley (SD) rats were randomly divided into control, model, mdivi-1, mdivi-1 + CHSGS and CHSGS groups. Tail-clamping stimulation was used to establish the FD model. Mdivi-1 + CHSGS and CHSGS groups were given CHSGS aqueous solution (4.8 g/kg) by gavage twice a day. Mdivi-1 (25 mg/kg) was injected intraperitoneally once every other week for 4 w. Mitochondrial damage was observed by corresponding kits and related protein expressions were assessed by Immunofluorescence and (or) Western Blot. RESULTS: Compared with the mean value of the control group, superoxide dismutase (SOD) and citrate synthase (CS) in the model group were decreased by 11% and 35%; malondialdehyde (MDA) and reactive oxygen species (ROS) were increased by 1.2- and 2.8-times; ckit fluorescence and protein expressions were decreased by 85% and 51%, co-localization expression of LC3 and voltage dependent anion channel 1 (VDAC1), Drp-1 and translocase of the outer mitochondrial membrane 20 (Tom20) were increased by 10.1- and 5.4-times; protein expressions of Drp-1, Beclin-1, and LC3 were increased by 0.5-, 1.4-, and 2.5-times whereas p62 was decreased by 43%. After mdivi-1 and (or) CHSGS intervention, the above situation has been improved. DISCUSSION AND CONCLUSION: CHSGS could improve mitochondrial damage and promote gastric motility in FD rats by regulating Drp-1-mediated ICC mitophagy.

Clinical experience in laparoscopic treatment of gallbladder perforation.

Aim: We herein present our clinical experience in laparoscopic surgery for gallbladder perforation (GBP). Materials and Methods: Retrospective analysis was performed on the clinical data of 44 patients who diagnosed with GBP from January 2015 to November 2020. Results: The mean age of the 44 patients was 64.0 years and the female-to-male ratio was 20:24. The most common type of GBP was Type II, followed by Type I and Type III (31:9:4). 72.7% of the patients were diagnosed with GBP at the time of surgery. Laparoscopic surgery was performed for 38 (86.4%) patients, with a conversion rate of 13.2%. The mean length of hospital stays was 7.8 days. The mortality and morbidity rates were 2.3% and 11.4%, respectively. Conclusions: Pre-operative diagnosis of GBP is difficult. Laparoscopic surgery is safe, feasible and effective for patients with GBP.

Predicting 1p/19q co-deletion status from magnetic resonance imaging using deep learning in adult-type diffuse lower-grade gliomas: a discovery and validation study.

Determination of 1p/19q co-deletion status is important for the classification, prognostication, and personalized therapy in diffuse lower-grade gliomas (LGG). We developed and validated a deep learning imaging signature (DLIS) from preoperative magnetic resonance imaging (MRI) for predicting the 1p/19q status in patients with LGG. The DLIS was constructed on a training dataset (n = 330) and validated on both an internal validation dataset (n = 123) and a public TCIA dataset (n = 102). The receiver operating characteristic (ROC) analysis and precision recall curves (PRC) were used to measure the classification performance. The area under ROC curves (AUC) of the DLIS was 0.999 for training dataset, 0.986 for validation dataset, and 0.983 for testing dataset. The F1-score of the prediction model was 0.992 for training dataset, 0.940 for validation dataset, and 0.925 for testing dataset. Our data suggests that DLIS could be used to predict the 1p/19q status from preoperative imaging in patients with LGG. The imaging-based deep learning has the potential to be a noninvasive tool predictive of molecular markers in adult diffuse gliomas.

Regulation of mitophagy through HIF-1α/miR-140-5p/PARKIN axis in acute kidney injury.

Mitochondria homeostasis plays an important role in acute kidney injury (AKI). In this study, we aimed at identifying the mechanism of mitophagy regulation in AKI. Activation of mitophagy after ischemic kidney injury was visualized with increased expression of LC3, PINK1, PARKIN expression and with a subsequent decline in p62 levels. Immuohistochemistry staining showed higher LC3 levels in ischemic kidney injury mice. Further, differential expression of PARKIN targeting miRNAs revealed that miR-140-5p was significantly downregulated followed by ischemic kidney injury. miR-140-5p mimics suppressed PARKIN expressions and their mitochondrial translocation. Further, miR-140-5p mimics under hypoxia prevented mitophagosome formation. These effects on hypoxia-induced PARKIN expression and LC3/TOMM20 levels were reversed by antagomiR miR-140-5p treatment. Dual-luciferase reporter assay revealed that miR-140-5p had significant interaction with 3'UTR of PARKIN. Our findings show that HIF-1α is bound to miR-140-5p promoter and down regulates its expression and thereby promotes mitophagy process under hypoxic conditions. These results cumulatively show that HIF-1α regulates mitophagy during AKI through the regulation of miR-140-5p/PARKIN axis.

Genome-Wide Association Study of Kernel Black Point Resistance in Chinese Wheat Landraces.

Black point (BP) disease of wheat has become a noticeable problem in China. The symptoms are spots that are brown to black in color around the wheat kernel embryo or in the endosperm, resulting in a significant reduction of wheat grain quality. Here, we evaluated 272 Chinese wheat landraces for BP reaction and performed a genome-wide association study to identify BP resistance quantitative trait loci (QTLs) in five field environments without artificial inoculation. The BP incidence data showed continuous distributions and had low to moderate correlations between environments (r = 0.094 to 0.314). Among the 272 landraces, 11 had 0.1 to 4.9%, 144 had 5 to 14.9%, 100 had 15 to 29.9%, and 17 had >30% incidence. We found three resistant accessions: WH094 (3.33%), AS661463 (2.67%), and AS661231 (2.67%), which can be used in breeding programs to enhance BP resistance. We identified 11 QTLs, which explained 8.22 to 10.99% phenotypic BP variation, and mapped them to eight wheat chromosomes. Three of the QTLs were novel. The molecular markers for the BP resistance could facilitate molecular breeding for developing BP-resistant cultivars.