Transcriptome screening identifies TIPARP as an antiviral host factor against the Getah virus.

IMPORTANCE: Alphaviruses threaten public health continuously, and Getah virus (GETV) is a re-emerging alphavirus that can potentially infect humans. Approved antiviral drugs and vaccines against alphaviruses are few available, but several host antiviral factors have been reported. Here, we used GETV as a model of alphaviruses to screen for additional host factors. Tetrachlorodibenzo-p-dioxin-inducible poly(ADP ribose) polymerase was identified to inhibit GETV replication by inducing ubiquitination of the glycoprotein E2, causing its degradation by recruiting the E3 ubiquitin ligase membrane-associated RING-CH8 (MARCH8). Using GETV as a model virus, focusing on the relationship between viral structural proteins and host factors to screen antiviral host factors provides new insights for antiviral studies on alphaviruses.

Scalable batch-correction approach for integrating large-scale single-cell transcriptomes.

Integration of accumulative large-scale single-cell transcriptomes requires scalable batch-correction approaches. Here we propose Fugue, a simple and efficient batch-correction method that is scalable for integrating super large-scale single-cell transcriptomes from diverse sources. The core idea of the method is to encode batch information as trainable parameters and add it to single-cell expression profile; subsequently, a contrastive learning approach is used to learn feature representation of the additive expression profile. We demonstrate the scalability of Fugue by integrating all single cells obtained from the Human Cell Atlas. We benchmark Fugue against current state-of-the-art methods and show that Fugue consistently achieves improved performance in terms of data alignment and clustering preservation. Our study will facilitate the integration of single-cell transcriptomes at increasingly large scale.

A universal approach for integrating super large-scale single-cell transcriptomes by exploring gene rankings.

Advancement in single-cell RNA sequencing leads to exponential accumulation of single-cell expression data. However, there is still lack of tools that could integrate these unlimited accumulations of single-cell expression data. Here, we presented a universal approach iSEEEK for integrating super large-scale single-cell expression via exploring expression rankings of top-expressing genes. We developed iSEEEK with 11.9 million single cells. We demonstrated the efficiency of iSEEEK with canonical single-cell downstream tasks on five heterogenous datasets encompassing human and mouse samples. iSEEEK achieved good clustering performance benchmarked against well-annotated cell labels. In addition, iSEEEK could transfer its knowledge learned from large-scale expression data on new dataset that was not involved in its development. iSEEEK enables identification of gene-gene interaction networks that are characteristic of specific cell types. Our study presents a simple and yet effective method to integrate super large-scale single-cell transcriptomes and would facilitate translational single-cell research from bench to bedside.

Time-Lapse Macro Imaging with Dissolution Tests for Exploring the Interrelationship Between Disintegration and Dissolution Behaviors of Solid Dosages.

OBJECTIVE: This study aims to establish a Flow-through Visualization Dissolution System (FVDS) that combines time-lapse macro-imaging and a flow-through cell to simultaneously elucidate dissolution and disintegration profiles. METHODS: Three cefaclor extended-release tablets (CEC-1, CEC-2, CEC-3) from different manufacturers were subjected to dissolution tests using both the US Pharmacopeia basket method and the FVDS method. Two dissolution media plans were implemented in FVDS: i) Plan I involved dissolution in pH1.0 medium for 12 h; ii) Plan II initiated dissolution in pH1.0 medium for 1 h, followed by pH6.8 phosphate buffer for 11 h. The resulting dissolution data were fitted using classic mathematical models. Pixel information was further extracted from images obtained using FVDS and plotted over time. RESULTS: The basket method showed the cumulative dissolution of all three tablets in pH1.0, pH4.0 and water reached 80% within 6 h, but remained below 60% in the pH6.8 medium. The f2 values indicated CEC-2 was similar to CEC-1 in the pH4.0 medium, pH6.8 medium and water. Using FVDS with medium plan II, the cumulative dissolution of CEC-1 and CEC-2 reached about 80% showing similarity, while no similarity was observed between CEC-3 and CEC-1. The f2 factor of the percentage area change profiles also showed consistent results in the dissolution profile of medium plan II. However, FVDS with medium plan I cannot distinguish between CEC-2 and CEC-3. CONCLUSION: FVDS offers an alternative to traditional dissolution methods by integrating imaging analysis as a complementary tool to disintegration and dissolution testing methods.

Lower serum creatinine to cystatin C ratio associated with increased incidence of frailty in community-dwelling elderly men but not in elderly women.

BACKGROUND: Sarcopenia has been reported to play an important role in frailty syndrome. The serum creatinine/serum cystatin C ratio (Scr/Cys C ratio) has recently been recognized as a valuable indicator for assessing sarcopenia. However, few studies have examined the association between serum creatinine/serum cystatin C ratio and frailty. The objective of this study is to investigate the relationship between the serum creatinine/serum cystatin C ratio and frailty among older adults residing in the community. METHODS AND MATERIALS: A Total of 1926 community-dwelling older adults aged ≥ 60 years in the 2011 waves of the China Health and Retirement Longitudinal Study (CHARLS) were included. The participants' frailty status was determined using a 39 item frailty index (FI), which classified individuals as "robust" (FI ≤ 0.1), "pre-frailty" (0.1 < FI < 0.25), or "frailty" (FI ≥ 0.25). The Scr/Cys C ratio was determined by dividing the serum creatinine level (mg/dL) by the cystatin C level (mg/L). The one-way analysis of variance(ANOVA) and Chi-squared test (χ2)were applied to compare the differences between the 3 groups. Both linear regression and logistic regression models were used to further investigate the relationship between Scr/Cys C ratio and frailty. RESULTS: After adjusting for potential confounding factors, the study revealed that participants in the Q1 quartile of Scr/Cys C ratio had increased odds of frailty (Q1vs.Q4: OR = 1.880, 95% CI 1.126-3.139, p = 0.016) compared with those in the Q4 quartile group. In fully adjusted logistic regression models, male participants in the Q2 quartile of Scr/Cys C ratio were significantly correlated with higher odds of pre-frailty (Q2 vs.Q4: OR = 1.693, 95%CI 1.040-2.758, p = 0.034). However, this correlation was not observed in females (OR = 0.984, 95% CI 0.589-1.642, p = 0.950,). Additionally, the study observed an increase in both the frailty index and the incidence of frailty as age increased in both males and females. CONCLUSION: Among community-dwelling older adults, lower Serum creatinine to cystatin C ratio were found to be associated with increased odds of frailty prevalence in males.

Transient Receptor Potential Channels in Sensory Mechanisms of the Lower Urinary Tract.

BACKGROUND: Urine storage and excretion require a network of interactions in the urinary tract and the central nervous system, which is mediated by a reservoir of water in the bladder and the outlet to the bladder neck, urethra, and external urethral sphincter. Through communicating and coordinating each other, micturition system eventually showed a switch-like activity pattern. SUMMARY: At cervicothoracic and lumbosacral spine, the spinal reflex pathway of the lower urinary tract (LUT) received mechanosensory input from the urothelium to regulate the bladder contraction activity, thereby controlled urination voluntarily. Impairment of above-mentioned any level could result in lower urinary tract dysfunction, placed a huge burden on patients and society. Specific expression of purinergic receptors and transient receptor potential (TRP) channels are thought to play an important role in urinary excretion in the LUT. KEY MESSAGES: This article reviewed the knowledge about the voiding reflex and described the role and function of TRP channels during voiding.

Observation of Electronic Nematicity Driven by the Three-Dimensional Charge Density Wave in Kagome Lattice KV3Sb5.

Kagome superconductors AV3Sb5 (A = K, Rb, Cs) provide a fertile playground for studying intriguing phenomena, including nontrivial band topology, superconductivity, giant anomalous Hall effect, and charge density wave (CDW). Recently, a C2 symmetric nematic phase prior to the superconducting state in AV3Sb5 drew enormous attention due to its potential inheritance of the symmetry of the unusual superconductivity. However, direct evidence of the rotation symmetry breaking of the electronic structure in the CDW state from the reciprocal space is still rare, and the underlying mechanism remains ambiguous. The observation shows unconventional unidirectionality, indicative of rotation symmetry breaking from six-fold to two-fold. The interlayer coupling between adjacent planes with π-phase offset in the 2 × 2 × 2 CDW phase leads to the preferred two-fold symmetric electronic structure. These rarely observed unidirectional back-folded bands in KV3Sb5 may provide important insights into its peculiar charge order and superconductivity.

Clinicopathological and genetic characteristics of gastric neuroendocrine tumour (NET) G3 and comparisons with neuroendocrine carcinoma and NET G2.

AIMS: To characterise the clinicopathological and genetic characteristics of gastric neuroendocrine tumour G3 (gNET G3) and to compare them with those of gastric neuroendocrine carcinoma (gNEC) and gNET G2. METHODS AND RESULTS: A total of 115 gastric neuroendocrine neoplasms (NENs) were included, of which gNET G3 was different from gNET G1/G2 in terms of tumour location (P = 0.029), number (P = 0.003), size (P = 0.010), the Ki67 index (P < 0.001), lymph node metastasis (P < 0.001) and TNM stage (P = 0.011), and different from gNEC/gastric mixed neuroendocrine-non-neuroendocrine neoplasm (gMiNEN) in terms of tumour size (P = 0.010) and the Ki67 index (P = 0.001). High-resolution copy number (CN) profiling and validation experiments showed CN gains and high expression of DLL3 in gNET G3. Hierarchical clustering analysis based on CN characteristics showed that gNET G3 was separated from gNEC but mixed with gNET G2. In gene set enrichment analysis, eight pathways were significantly enriched in gNEC when comparing gNET G3 and gNEC (P < 0.05), while no pathways were enriched when comparing gNET G3 and gNET G2. Whole-exome sequencing and validation experiments showed nonsense mutation of TP53 in one gNET G3, with wild-type staining for p53. In gNEC, TP53 mutations were detected in four of eight cases, and abnormal expression of p53 was detected in all cases. CONCLUSION: Gastric NET G3 is a distinct entity with unique genetic characteristics, which are different from those of gNEC than gNET G2. Our results provide insight into some molecular alterations that may contribute to the development and progression of gNET G3 and serve as potential therapeutic targets.

Leucobacter edaphi sp. nov., a highly chromate-tolerant bacterium isolated from chromium containing chemical plant soil.

A Gram-positive, aerobic, rod-shaped non-motile, non-sporulating bacterium, designated CSA2T, was isolated from chromium-containing soils collected from a chemical plant. The 16S rRNA gene sequence of strain CSA2T showed the highest homology with Leucobacter chromiireducens subsp. solipictus (97.85%), Leucobacter chromiireducens subsp. chromiireducens (97.85%). The digital DNA-DNA hybridization (dDDH), average nucleotide identity (ANI) and the amino acid identity (AAI) values among strains CSA2T and the selected Leucobacter species were 20.6-23.4% (dDDH), 72.67-78.03% (ANI) and 66.39-76.16% (AAI), falling below the recommended thresholds for species delimitation. The principal fatty acids were anteiso-C15:0, iso-C16:0 and anteiso-C17:0. The polar lipids were phosphatidylglycerol, diphosphatidylglycerol and an unknown glycolipid. The major menaquinones detected were MK-10 and MK-11. The cell-wall amino acids included 2,4-diaminobutyric acid, threonine, glutamic acid, alanine and glycine. Based on molecular feature, phenotypic and chemotaxonomic, strain CSA2T was considered to be a novel species of the genus Leucobacter., and the name Leucobacter edaphi sp. nov. is proposed. The type strain is CSA2T (= JCM 34360T = CGMCC 1.18747T).

Ochrobactrum chromiisoli sp. nov., Isolated from Chromium-Contaminated Soil.

A Gram-stain-negative, non-spore-forming, flagellated, motile, aerobic, rod-shaped bacteria strain, designated YY2XT, was isolated from chromium-contaminated soil. Phylogenetic analysis based on 16S rRNA gene, recA gene, and whole genome indicated that the strain represented a new member of the genus Ochrobactrum, family Brucellaceae, class Alphaproteobacteria. The phylogenetic trees based on 16 s rRNA gene, revealed that Falsochrobactrum ovis DSM26720T (96.7%), Ochrobactrum gallinifaecis DSM15295T (96.2%), and Pseudochrobactrum asaccharolyticum DSM25619T (96.2%) are the most closely related phylogenetic neighbors of strain YY2XT. The draft genome of YY2XT was approximately 4,650,646 bp in size with a G + C content of 53.0 mol%. Average nucleotide identity and digital DNA-DNA hybridization values among strain YY2XT and the selected Brucellaceae species were 71.4-83.1% and 13.5-42.7%, which are below the recommended cut-off values for species delineation. Growth of strain YY2XT occurred within pH 5-10 (optimum, pH 7-8), 4 â„ƒ-42 °C (optimum, 30 °C), and NaCl concentrations of 0.0-6.0% (optimum, 1.0%). Major quinone system was ubiquinone 10, the major fatty acids were C16:0, C18:1ω7c, and C16:1ω7c and the major polyamines were spermidine and putrescine. Major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, phosphatidylmonomethylethanolamine, phosphatidylethanolamine, and four undefined lipids. On the basis of the phenotypic, genotypic and chemotaxonomic traits, strain YY2XT was considered to represent a novel species of the genus Ochrobactrum, for which the name Ochrobactrum chromiisoli sp. nov. is proposed. The type strain is YY2XT (= CCTCC AB 2023035T = JCM 36000T).

Study on the Influence of the Preparation Method of Konjac Glucomannan-Silica Aerogels on the Microstructure, Thermal Insulation, and Flame-Retardant Properties.

Natural polysaccharides with high viscosity, good thermal stability, and biocompatibility can improve the mechanical properties of inorganic silica aerogels and enhance their application safety. However, the effects of the preparation methods of polysaccharide-silica aerogels on their microstructure and application properties have not been systematically studied. To better investigate the effect of the microstructure on the properties of aerogel materials, two aerogels with different structures were prepared using Konjac glucomannan (KGM) and tetraethoxysilane (TEOS) via physical blending (KTB) and co-precursor methods (KTC), respectively. The structural differences between the KTB and KTC aerogels were characterized, and the thermal insulation and fire-retardant properties were further investigated. The compressive strength of the KTC aerogels with a cross-linked interpenetrating network (IPN) structure was three times higher than that of the KTB aerogels, while their thermal conductivity was 1/3 of that of the KTB aerogels. The maximum limiting oxygen index (LOI) of the KTC aerogels was 1.4 times, the low peak heat release rate (PHRR) was reduced by 61.45%, and the lowest total heat release (THR) was reduced by 41.35% compared with the KTB aerogels. The results showed that the KTC aerogels with the IPN have better mechanical properties, thermal insulation, and fire-retardant properties than the simple physically blending KTB aerogels. This may be due to the stronger hydrogen-bonding interactions between KGM and silica molecules in the KTC aerogels under the unique forcing effect of the IPN, thus enhancing their structural stability and achieving complementary properties. This work will provide new ideas for the microstructure design of aerogels and the research of new thermal insulation and fire-retardant aerogels.

Circular RNA circ_0040823 inhibits the proliferation of acute myeloid leukemia cells and induces apoptosis by regulating miR-516b/PTEN.

OBJECTIVE: Endogenous circular RNAs (circRNAs) and microRNAs (miRNAs) have been shown to regulate the pathogenesis of acute myeloid leukemia (AML). The current study aimed to identify the role of circRNA 0040823 (circ_0040823) in AML. METHODS: Microarray datasets were analyzed to identify differentially expressed circRNAs in AML patients. Peripheral blood samples were obtained from healthy volunteers and AML patients for the measurement of circ_0040823 and miR-516b levels. The overexpression or knockdown of a target gene in AML cells was achieved by the transfection with lentiviral vectors or small interfering RNAs. BALB/c nude mice were inoculated with AML cells and monitored for tumor growth. Dual-luciferase reporter assay, RNA immunoprecipitation, and RNA pull-down assay were used to determine the binding relationship between circRNA and miRNA. RESULTS: circ_0040823 was significantly downregulated in AML patients and leukemia cells. Overexpression of circ_0040823 inhibited AML cell proliferation, and induced apoptosis and cell cycle arrest. Upregulation of circ_0040823 also repressed the growth of xenograft tumors in vivo. circ_0040823 acted as a miR-516b sponge and regulated key cellular events in leukemia cells via downregulating miR-516b. Moreover, tumor suppressor phosphatase and tensin homolog (PTEN) was a downstream target of miR-516b. The inhibition of miR-516b impaired the proliferation capacity of leukemia cells and induced apoptosis, while PTEN deficiency attenuated these effects. CONCLUSION: This study showed that circ_0040823 inhibited proliferation and induced apoptosis of AML cells by sponging miR-516b, thereby diminishing the regulatory effect of miR-516b on PTEN. These findings identified circ_0040823/miR-516b/PTEN as a new therapeutic target for AML.

Prognostic Characteristics of Patients With Colorectal Cancer Who Have Benign Mesenteric Lymph Node Enlargement: A Multi-institutional Cohort Study.

BACKGROUND: The characteristics of patients with colorectal cancer who have benign mesenteric lymph node enlargement are not well documented. OBJECTIVE: The aim of this study is to assess the clinical and prognostic significance of benign mesenteric lymph node enlargement in patients with colorectal cancer. DESIGN: This is a prospective cohort study. SETTING: This study was conducted at multitertiary institutions. PATIENTS: We included 601 patients with stage 0, I, and II colorectal cancer in Tianjin, Shandong, and Zhejiang from January 2010 to April 2014. Patients underwent curative surgery and were separated into 2 groups by the presence of benign mesenteric lymph node enlargement: the enlargement group (n = 275) and the control group (n = 326). MAIN OUTCOME MEASURES: Univariate log rank and multivariate Cox regression analyses were constructed to identify risk factors for recurrence and mortality. RESULTS: The risk of recurrence in the enlargement group after curative resection was significantly lower than in the control group, with the 1-, 3-, and 5-year disease-free survival rates being 97.1%, 91.6%, and 86.9% in the enlargement group and 95.7%, 86.2%, and 78.2% in the control group (p = 0.004). The postoperative 1-, 3-, and 5-year overall survival rates were 99.6%, 94.9%, and 90.5% in the enlargement group and 99.4%, 91.4%, and 82.1% in the control group (p = 0.001). Patients in the enlargement group had a higher percentage of patients at a younger age, family tumor history, right-sided tumors, and larger tumor size compared with the control group. For patients in the enlargement group, no significant correlation was observed between the number of enlarged lymph nodes and disease-free survival or overall survival (p = 0.113 and 0.386). Adjusted Cox regression model showed that benign mesenteric lymph node enlargement was an independent prognostic risk factor for both disease-free survival (HR, 0.587; 95% CI, 0.399-0.861; p = 0.007) and overall survival (HR, 0.506; 95% CI, 0.328-0.779; p = 0.002). LIMITATIONS: No immunological results could be compared with clinicopathological findings. CONCLUSIONS: The study indicates that benign mesenteric lymph node enlargement can be a useful positive factor in predicting recurrence and long-term survival concerning patients with colorectal cancer. See Video Abstract at http://links.lww.com/DCR/B785. CARACTERSTICAS PRONSTICAS DE LOS PACIENTES PORTADORES DE CNCER COLORRECTAL CON AGRANDAMIENTO BENIGNO DE LOS GANGLIOS LINFTICOS MESENTRICOS UN ESTUDIO DE COHORTE MULTIINSTITUCIONAL: ANTECEDENTES:Las características de los pacientes portadores de cáncer colorrectal con agrandamiento benigno de los ganglios linfáticos mesentéricos no se encuentran bien documentados.OBJETIVO:El objetivo de este estudio es evaluar la importancia clínica y pronóstica del agrandamiento benigno de los ganglios linfáticos mesentéricos en pacientes con cáncer colorrectal.DISEÑO:Este es un estudio de cohorte de tipo prospectivo.AJUSTE:Este estudio se llevó a cabo en instituciones de educación superior.PACIENTES:Incluimos a 601 pacientes con cáncer colorrectal en estadio 0, I, II en Tianjin, Shandong y Zhejiang desde enero de 2010 hasta abril de 2014. Los pacientes fueron sometidos a cirugía curativa y fueron separaron en dos grupos tomando en cuenta la presencia del agrandamiento benigno de los ganglios linfáticos mesentéricos: grupo con agrandamiento (n = 275) y grupo control (n = 326).PRINCIPALES MEDIDAS DE RESULTADO:Se construyeron análisis de rango logarítmico de una variante y de regresión de Cox con variante múltiple para identificar los factores de riesgo de recurrencia y mortalidad.RESULTADOS:El riesgo de recurrencia en el grupo con agrandamiento tras la resección curativa fue significativamente menor que en el grupo de control, con tasas de periodo libre de enfermedad a los 1, 3 y 5 años de 97,1, 91,6, y 86,9% en el grupo de agrandamiento y con tasas de 95,7, 86,2, y 78,2% en el grupo control respectivamente (p = 0,004). Las tasas postoperatorias de supervivencia general a los 1, 3 y 5 años fueron 99,6, 94,9, y 90,5% en el grupo de agrandamiento y de 99,4, 91,4, y 82,1% en el grupo de control, respectivamente (p = 0,001). Los pacientes del grupo con agrandamiento tenían un porcentaje más elevado de menor edad, antecedente familiar tumoral, tumores del lado derecho y de mayor tamaño tumoral con respecto al grupo de control. Para los pacientes con agrandamiento, no se observó una correlación significativa entre el número de ganglios linfáticos agrandados y el periodo libre de enfermedad o la supervivencia general (p = 0,113 y 0,386). El modelo de regresión de Cox ajustado mostró que el agrandamiento benigno de los ganglios linfáticos mesentéricos era un factor de riesgo pronóstico independiente tanto para la supervivencia libre de enfermedad (cociente de riesgo 0,587; IC del 95%: 0,399-0,861; p = 0,007) como para la supervivencia global (cociente de riesgo 0,506; IC del 95%: 0,328- 0,779; p = 0,002).LIMITACIONES:No fue posible comparar los resultados inmunológicos con los hallazgos clínico-patológicos.CONCLUSIONES:El estudio indica que el agrandamiento benigno de los ganglios linfáticos mesentéricos puede ser un factor positivo útil para predecir la recurrencia y la supervivencia a largo plazo en pacientes con cáncer colorrectal. Consulte Video Resumen en http://links.lww.com/DCR/B785. (Traducción-Dr. Osvaldo Gauto).

The prognostic value of N6-methyladenosine RBM15 regulators in lung adenocarcinoma.

N6-methyladenosine (m6A) is the most common internal modification in mammalian mRNAs while RNA-binding motif protein 15 (RBM15) is an important methyltransferase in m6A modification. Increasing evidences have shown that RBM15 has a close correlation with lung cancer. However, specific functions of RBM15 in lung adenocarcinoma (LUAD) are limited. RBM15 expression was analyzed in human LUAD tissues and matched healthy lung tissue. RBM15 was knocked down via siRNA in A549 and H1734 cells. The relationships between RBM15 with cellular functions characteristics and mRNA m6A levels were explored. We performed functional characterization in A549 and H1734 cells lines to elucidate the molecular role of RBM15. Results found that RBM15 was up-regulated in the LUAD tissue and cells, which was linked to poor survival of LUAD patients. RBM15 can be knocked down via siRNA in A549, which leads to the exploration of the associations between RBM15 with cell characteristics. In vivo, RBM15 knockdown could decrease the methylation level, reduce proliferation, accelerate apoptosis and inhibit tumor growth. Our research shows that RBM15 facilitates LUAC cell progression by m6A demethylation. However, it is necessary to conduct further researches on potential downstream molecular mechanisms and m6A modification of RBM15 activity in LUAC.

Adaptive Recognition of Bioacoustic Signals in Smart Aquaculture Engineering Based on r-Sigmoid and Higher-Order Cumulants.

In recent years, interest in aquaculture acoustic signal has risen since the development of precision agriculture technology. Underwater acoustic signals are known to be noisy, especially as they are inevitably mixed with a large amount of environmental background noise, causing severe interference in the extraction of signal features and the revelation of internal laws. Furthermore, interference adds a considerable burden on the transmission, storage, and processing of data. A signal recognition curve (SRC) algorithm is proposed based on higher-order cumulants (HOC) and a recognition-sigmoid function for feature extraction of target signals. The signal data of interest can be accurately identified using the SRC. The analysis and verification of the algorithm are carried out in this study. The results show that when the SNR is greater than 7 dB, the SRC algorithm is effective, and the performance improvement is maximized when the SNR is 11 dB. Furthermore, the SRC algorithm has shown better flexibility and robustness in application.

Exosome-delivered miR-221/222 exacerbates tumor liver metastasis by targeting SPINT1 in colorectal cancer.

MicroRNAs (miRNAs) are involved in the progression of many cancers through largely unelucidated mechanisms. The results of our present study identified a gene cluster, miR-221/222, that is constitutively upregulated in serum exosome samples of patients with colorectal carcinoma (CRC) with liver metastasis (LM); this upregulation predicts a poor overall survival rate. Using an in vitro cell coculture model, we demonstrated that CRC exosomes harboring miR-221/222 activate liver hepatocyte growth factor (HGF) by suppressing SPINT1 expression. Importantly, miR-221/222 plays a key role in forming a favorable premetastatic niche (PMN) that leads to the aggressive nature of CRC, which was further shown through in vivo studies. Overall, our results show that exosomal miR-221/222 promotes CRC progression and may serve as a novel prognostic marker and therapeutic target for CRC with LM.

Development of an AI system for accurately diagnose hepatocellular carcinoma from computed tomography imaging data.

BACKGROUND AND AIMS: Computed tomography (CT) scan is frequently used to detect hepatocellular carcinoma (HCC) in routine clinical practice. The aim of this study is to develop a deep-learning AI system to improve the diagnostic accuracy of HCC by analysing liver CT imaging data. METHODS: We developed a deep-learning AI system by training on CT images from 7512 patients at Henan Provincial Peoples' Hospital. Its performance was validated on one internal test set (Henan Provincial Peoples' Hospital, n = 385) and one external test set (Henan Provincial Cancer Hospital, n = 556). The area under the receiver-operating characteristic curve (AUROC) was used as the primary classification metric. Accuracy, sensitivity, specificity, precision, negative predictive value and F1 metric were used to measure the performance of AI systems and radiologists. RESULTS: AI system achieved high performance in identifying HCC patients, with AUROC of 0.887 (95% CI 0.855-0.919) on the internal test set and 0.883 (95% CI 0.855-0.911) on the external test set. For internal test set, accuracy was 81.0% (76.8-84.8%), sensitivity was 78.4% (72.4-83.7%), specificity was 84.4% (78.0-89.6%) and F1 (harmonic average of precision and recall rate) was 0.824. For external test set, accuracy was 81.3% (77.8-84.5%), sensitivity was 89.4% (85.0-92.8%), specificity was 74.0% (68.5-78.9%) and F1 was 0.819. Compared with radiologists, AI system achieved comparable accuracy and F1 metric on internal test set (0.853 versus 0.818, P = 0.107; 0.863 vs. 0.824, P = 0.082) and external test set (0.805 vs. 0.793, P = 0.663; 0.810 vs. 0.814, P = 0.866). The predicted HCC risk scores by AI system in HCC patients with multiple tumours and high fibrosis stage were higher than those with solitary tumour and low fibrosis stage (tumour number: 0.197 vs. 0.138, P = 0.006; fibrosis stage: 0.183 vs. 0.127, P < 0.001). Radiologists' review showed that the accuracy of saliency heatmaps predicted by algorithms was 92.1% (95% CI: 89.2-95.0%). CONCLUSIONS: AI system achieved high performance in the detection of HCC compared with a group of specialised radiologists. Further investigation by prospective clinical trials was necessitated to verify this model.

Emergence and adaptive evolution of influenza D virus.

As a novel member of the Orthomyxoviridae, influenza D virus (IDV) was firstly isolated from swine. However, cattle were found to serve as its primary reservoir. The study of IDV emergence can shed light into the dynamics of zoonotic infections and interspecies transmission. Although there is an increasing number of strains and sequenced IDV strains, their origin, epidemiology and evolutionary dynamics remain unclear. In this study, we reconstruct the diversity and evolutionary dynamics of IDVs. Molecular detection of swine tissue samples shows that six IDV positive samples were identified in the Eastern China. Phylogenetic analyses suggest three major IDV lineages designated as D/Japan, D/OK and D/660 as well as intermediate lineages. IDVs show strong association with geographical location indicating a high level of local transmission, which suggests IDVs tend to establish a local lineage of in situ evolution. In addition, the D/OK lineage widely circulates in swine in Eastern China, and all of the Chinese virus isolates form a distinct sub-clade (D/China sub-lineage). Furthermore, we identified important amino acids in the HEF gene under positive selection that might affect its receptor binding cavity relevant for its broader cell tropism. The combined results highlight that more attention should be paid to the potential threat of IDV to livestock and farming in China.

Multiple Magnetic Topological Phases in Bulk van der Waals Crystal MnSb_{4}Te_{7}.

The magnetic van der Waals crystals MnBi_{2}Te_{4}/(Bi_{2}Te_{3})_{n} have drawn significant attention due to their rich topological properties and the tunability by external magnetic field. Although the MnBi_{2}Te_{4}/(Bi_{2}Te_{3})_{n} family have been intensively studied in the past few years, their close relatives, the MnSb_{2}Te_{4}/(Sb_{2}Te_{3})_{n} family, remain much less explored. In this work, combining magnetotransport measurements, angle-resolved photoemission spectroscopy, and first principles calculations, we find that MnSb_{4}Te_{7}, the n=1 member of the MnSb_{2}Te_{4}/(Sb_{2}Te_{3})_{n} family, is a magnetic topological system with versatile topological phases that can be manipulated by both carrier doping and magnetic field. Our calculations unveil that its A-type antiferromagnetic (AFM) ground state stays in a Z_{2} AFM topological insulator phase, which can be converted to an inversion-symmetry-protected axion insulator phase when in the ferromagnetic (FM) state. Moreover, when this system in the FM phase is slightly carrier doped on either the electron or hole side, it becomes a Weyl semimetal with multiple Weyl nodes in the highest valence bands and lowest conduction bands, which are manifested by the measured notable anomalous Hall effect. Our work thus introduces a new magnetic topological material with different topological phases that are highly tunable by carrier doping or magnetic field.

Emergence of New van Hove Singularities in the Charge Density Wave State of a Topological Kagome Metal RbV_{3}Sb_{5}.

Quantum materials with layered kagome structures have drawn considerable attention due to their unique lattice geometry, which gives rise to flat bands together with Dirac-like dispersions. Recently, vanadium-based materials with layered kagome structures were discovered to be topological metals, which exhibit charge density wave (CDW) properties, significant anomalous Hall effect, and unusual superconductivity at low temperatures. Here, we employ angle-resolved photoemission spectroscopy to investigate the electronic structure evolution upon the CDW transition in a vanadium-based kagome material RbV_{3}Sb_{5}. The CDW phase transition gives rise to a partial energy gap opening at the boundary of the Brillouin zone and, most importantly, the emergence of new van Hove singularities associated with large density of states, which are absent in the normal phase and might be related to the superconductivity observed at lower temperatures. Our work sheds light on the microscopic mechanisms for the formation of the CDW and superconducting states in these topological kagome metals.