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Alcohol-associated liver disease (ALD) is a worldwide health problem, of which the effective treatment is still lacking. Both detrimental and protective roles of adipose tissue have been implicated in ALD. Although alcohol increases adipose tissue lipolysis to promote alcohol-induced liver injury, alcohol also activates brown adipose tissue (BAT) thermogenesis as an adaptive response in protecting against alcohol-induced liver injury. Moreover, aging and obesity are also risk factors for ALD. In the present study, we investigated the effects of autophagy receptor protein SQSTM1/p62 on adipose tissue and obesity in alcohol-induced liver injury in both young and aged mice.Young and aged whole-body SQSTM1/p62 knockout (KO) and their age-matched wild-type (WT) mice were subjected to chronic plus binge (Gao-binge) alcohol feeding. Blood, adipose and liver tissues were collected for biochemical and histologic analysis.Aged but not young SQSTM1/p62 KO mice had significantly increased body weight and fat mass compared with the matched WT mice. Gao-binge alcohol feeding induced white adipose atrophy and decreased levels of SQSTM1/p62 levels in adipose tissue in aged WT mice. SQSTM1/p62 KO aged mice were resistant to Gao-binge alcohol-induced white adipose atrophy. Alcohol feeding increased the expression of thermogenic genes in WT mouse BAT, which was significantly blunted in SQSTM1/p62 KO aged mice. Alcohol-fed aged SQSTM1/p62 KO mice showed significantly higher levels of serum alanine aminotransferase, hepatic triglyceride, and inflammation compared with young and aged WT mice fed with alcohol. Alcohol-fed SQSTM1/p62 KO mice also increased secretion of proinflammatory and angiogenic adipokines that may promote alcohol-induced liver injury.Loss of SQSTM1/p62 in aged mice leads to obesity and impairs alcohol-induced BAT adaptation, resulting in exacerbated alcohol-induced liver injury in mice.

Sellaphora tanghongquii sp. nov. is described from epilithic samples taken from river systems in Southern China. The morphology of the new species is described based on light microscopy (LM) and scanning electron microscopy (SEM), and detailed ecological information is provided. This species has diagnostic features consistent with the genus Sellaphora, including small and linear valves, undulate and filiform raphe, and the presence of internal hymenate occlusions. Compared to morphologically similar species, we found that the new species is the most similar to S. constrictum in valve size and outline, raphe structure, and the external arrangement of the striae. However, S. tanghongquii sp. nov. has the following outstanding features which distinguish from similar species: 1) the valve striae are uniseriate externally and biseriate internally, 2) the shape of areolae are mostly square to elliptical, partly round, oval or irregularly shaped, composed of 2–4 small holes inside externally and round, elliptical, C-shaped, or irregularly shaped internally, 3) undulate valves with a slight constriction near the central portion of the valve, and 4) the presence of a row of separated and small pores on the valve mantle. The species appears to be best assigned to the group of species with axial grooves, which includes the generitype of Sellaphora. The discovery of this new diatom species increases the known biodiversity of the southern regions in China.

We report for the first time the complete genome sequence of a novel amalgavirus, tentatively designated as 'lily amalgavirus 1' (LAV-1), isolated from Lilium spp. in China. LAV-1 is a 3448-nt double-stranded RNA virus that encodes two putative proteins. Open reading frame 1 (ORF1) encodes a 394-aa protein with unknown function. ORF2 encodes a putative RNA-dependent RNA polymerase (RdRp) of 895 aa. The two ORFs putatively encode a '1 + 2' fusion protein generated by a '+1' programmed ribosomal frameshift (PRF). BLASTp analysis revealed that the complete genome sequence of LAV-1 shares 48.23-59.80% sequence identity (query sequence coverage77%) with those of members of the genus Amalgavirus, with the highest nucleotide sequence identity of 59.80% with that of Allium cepa amalgavirus 1 (query sequence coverage, 87%). The genome structure, phylogenetic relationships, and sequence similarities to other plant amalgaviruses suggest that LAV-1 is a new member of the genus Amalgavirus.

BACKGROUND AND AIMS: Increased megamitochondria formation and impaired mitophagy in hepatocytes have been linked to the pathogenesis of alcohol-associated liver disease (ALD). This study aims to determine the mechanisms by which alcohol consumption increases megamitochondria formation in the pathogenesis of ALD. APPROACH AND RESULTS: Human alcoholic hepatitis (AH) liver samples were used for electron microscopy, histology, and biochemical analysis. Liver-specific dynamin-related protein 1 (DRP1; gene name DNM1L, an essential gene regulating mitochondria fission) knockout (L-DRP1 KO) mice and wild-type mice were subjected to chronic plus binge alcohol feeding. Both human AH and alcohol-fed mice had decreased hepatic DRP1 with increased accumulation of hepatic megamitochondria. Mechanistic studies revealed that alcohol feeding decreased DRP1 by impairing transcription factor EB–mediated induction of DNM1L. L-DRP1 KO mice had increased megamitochondria and decreased mitophagy with increased liver injury and inflammation, which were further exacerbated by alcohol feeding. Seahorse flux and unbiased metabolomics analysis showed alcohol intake increased mitochondria oxygen consumption and hepatic nicotinamide adenine dinucleotide (NAD(+)), acylcarnitine, and ketone levels, which were attenuated in L-DRP1 KO mice, suggesting that loss of hepatic DRP1 leads to maladaptation to alcohol-induced metabolic stress. RNA-sequencing and real-time quantitative PCR analysis revealed increased gene expression of the cGAS–stimulator of interferon genes (STING)–interferon pathway in L-DRP1 KO mice regardless of alcohol feeding. Alcohol-fed L-DRP1 KO mice had increased cytosolic mtDNA and mitochondrial dysfunction leading to increased activation of cGAS-STING-interferon signaling pathways and liver injury. CONCLUSION: Alcohol consumption decreases hepatic DRP1 resulting in increased megamitochondria and mitochondrial maladaptation that promotes AH by mitochondria-mediated inflammation and cell injury.

Here, a novel mycovirus, tentatively designated as "Botryosphaeria dothidea fusarivirus 2" (BdFV2), was discovered in Botryosphaeria dothidea strain JZ-3. The complete genome sequence is 6,271 nucleotides (nt) in length, excluding the poly(A) tail, and contains two putative open reading frames (ORFs). The larger ORF1 encodes a polypeptide of 1,552 amino acids (aa) with conserved RNA-dependent RNA polymerase (RdRp) domains and a viral helicase domain. The ORF1-encoded polypeptide shares 19.47-78.70% sequence identity with those of other fusariviruses and shares the highest sequence identity (78.70%) with the corresponding protein aa sequences of Neofusicoccum luteum fusarivirus 1 (NlFV1) isolate CBS110299. The small ORF2 encodes a hypothetical protein with 479 aa, which is predicted to contain a chromosome segregation protein SMC domain of unknown function. Sequence alignments and phylogenetic analysis indicated that BdFV2 is a distinct member of the recently established family Fusariviridae. BdFV2 appears to be a novel fusarivirus infecting a pathogenic B. dothidea strain that causes pear ring rot disease.

One new species, Placoneis modaomensis, found in freshwater environment from tributary of the Pearl River which lies in Modaomen Channel, Zhuhai County, Guangdong Province, China, is described based on light and scanning electron microscope observations. P. modaomensis sp. nov. has the morphological features that are typical for the genus, including external terminal raphe fissures curve to the opposite sides and areolae with internal volate occlusions. The new species is similar to P. amphibola (Cleve) E.J. Cox, P. amphiboliformis (Metzeltin, Lange-Bertalot & Soninkhishig) Vishnyakov, P. parvapolonica Lange-Bertalot & Wojtal, P. clementispronina Lange-Bertalot & Wojtal and P. nanoclementis Lange-Bertalot & Wojtal in the shape of the valves and having course striae but it can be easily distinguished by the two main morphological characteristics: external central raphe endings bent in the opposite directions, and areolae covered by volate occlusions externally. The latter feature appears to be new for taxa assigned to the genus Placoneis. Data on the associated diatom flora and its ecology are also given. These findings increase our understanding about the morphology of Placoneis in general and its and distribution of the genus in China.

Gomphocymbellopsis guijiangensis Y.-L. Li, sp. nov. (Figs 1–17) Description: LM (Figs 1–8): Valves lanceolate with broadly rounded apices, slightly dorsiventral and heteropolar, commonly asymmetrical about the apical axis with a moderately inflated central portion gradually tapering to the head pole and foot pole. Dorsal and ventral margins similarly arched. Valve length 30.0–36.0 μm, valve width 8.0–13.5 μm, valve length/width ratio varying between 2.6–4.3, median 3.5 (n = 30). Raphe slightly lateral, occasionally appearing slightly reverse-lateral near the central ends, narrowing and becoming filiform towards the distal ends. External central raphe ends deflected gently towards the ventral side, appearing as slightly inflated central pores. External terminal raphe fissures hooked and deflected towards dorsal margin. Axial area very narrow, moderately curved, not or slightly expanded proximally, approximately in the median line of the valve. Central area lacking or not well defined, with one markedly shortened stria near the valve centre. Striae nearly parallel around the valve centre, becoming slightly radiate towards the poles, indistinctly punctate, more widely spaced near the markedly shortened stria, density 7–9 in 10 µm in the middle portion, up to 8–11 in 10 µm towards the ends. Individual areolae not visible. SEM: Valve exterior (Figs 9–13): Striae biseriate, occasionally uniseriate adjacent to the axial area, almost parallel in the middle, slightly radiate towards both ends (Figs 9–13). Areolae round to elliptical, 60–80 in 10 μm (Figs 10–13). Apical pore fields present at head pole and foot pole on the mantle, entire (not bisected) and clearly physically separated and morphologically distinct from the areolae (Figs 9–12). Three external, round to elliptical stigma openings present on the ventral side (Figs 10, 13). Valve interior (Figs 14–17): Striae formed by biseriate, rounded-elliptical areolae delimited by slightly oblique orientated vimines (Figs 14–17). The internal raphe slit continuous, without an intermissio (Figs 14, 17). Terminal raphe ends offset, bent slightly towards the dorsal margin, and terminating in small, knob-like helictoglossae adjacent to the shortened striae (Figs 14–16). Three internal, elliptical or slit-like stigma openings present on the ventral side (Figs 14, 17). Type:— CHINA. Guangxi Province: Guijiang River, freshwater, 24°15′23.89478″ N, 110°46′2.05771″ E, elevation 97.495 m a.s.l., 1st July 2021, rock scraping samples collected by Prof. Yan-Ling Li (Holotype GJ 2021070101 in Coll. Yan-Ling Li, Yunnan University, Kunming, China = Fig. 1; Isotype YUNGL20220120, Harbin Normal University, Harbin, China). Etymology:— guijiangensis, referring to the type locality from which the new species was obtained. Ecology: — Gomphocymbellopsis guijiangensis was found in a low altitude freshwater lake with moderately alkaline pH (8.35), dissolved oxygen of 7.94 mg /L, and conductivity of 181.5 μS/cm.At the type locality G. guijiangensis was uncommon (Achnanthidium biasolettianum (Grunow) Lange-Bertalot (1999) (74.7 %), Cymbella turgidula Grunow (in Schmidt 1875: 9) (8.2 %), Navicula cryptotenella Lange-Bertalot (Krammer & Lange-Bertalot 1985: 43) (7.4 %), Nitzschia palea (Kützing) W. Smith (1856: 89) (4.0 %), Gomphonema pumilum (Grunow) E. Reichardt & Lange-Bertalot (1991: 528) (1.6 %), G. minutiforme Lange-Bertalot & E. Reichardt (1993: 61) (0.8 %), Aulacoseira granulata (Ehrenberg) Simonsen (1979: 58) (0.5 %), C. tumida (Brébisson) Van Heurck (1880: 64) (0.5 %), Fragilaria tenera (W. Smith) Lange-Bertalot (1980: 746) (0.5 %), F. capucina Desmazières (1830: 453) (0.4 %), Planothidium lanceolata (Brébisson ex Kützing) Lange-Bertalot (1999: 287) (0.3 %), G. parvulum (Kützing) Kützing (1849: 65) (0.3 %), Synedra ulna (Nitzsch) Ehrenberg (1832: 87) (0.3 %), Psammothidium curtissimum (Carter) Aboal (Aboal et al. 2003) (0.1 %), and one unidentified species of Sellaphora C. Mereschkowsky (1902). A second species was found in sediments of the Jianghan Plain (Figs 18–25) that is a putative additional new species of Gomphocymbellopsis. Specimens of this species have only been observed with LM to date. Specimens are 16.5–25.5 µm long and 4.5–6.0 µm wide. They have a length/width ratio that varies between 3.4–5.3, with a median of 4.6. The raphe is lateral and slightly undulate. The axial area is narrow, becoming laterally expanded at the rectangular central area. Striae are radiate, becoming parallel at the apices. Stria density 8–14 in 10 µm in the center of the valves, up to 9–13 in 10 µm towards the ends. No stigmata have been observed. These specimens appear similar in general overall construction of G. guijiangensis but SEM observations are needed to confirm its systematic placement., Published as part of Guo, Ji-Shu, Ni, Hong-Ping, Li, Yu-Jie, Kociolek, John Patrick & Li, Yan-Ling, 2023, Gomphocymbellopsis guijiangensis sp. nov. (Cymbellaceae; Bacillariophyta), a new species from Guangxi Province with comments on associated specimens from Hubei Province, China, pp. 204-212 in Phytotaxa 594 (3) on pages 205-208, DOI: 10.11646/phytotaxa.594.3.4, http://zenodo.org/record/7901243, {"references":["Lange-Bertalot, H. (1999) Neue Kombinationen von Taxa aus Achnanthes Bory (sensu lato). In: Lange-Bertalot, H. (Ed.) Iconographia Diatomologica. Annotated Diatom Micrographs. Vol. 6. Phytogeography-Diversity-Taxonomy. Koeltz Scientific Books, Konigstein, Germany, 304 pp.","Schmidt, A. (1875) Atlas der Diatomaceen-kunde. Series I (Heft 3). pls. 9 - 12. https: // doi. org / 10.5962 / bhl. title. 64396","Krammer, K. & Lange-Bertalot, H. (1985) Naviculaceae: Neue und wenig bekannte Taxa, neue Kombinationen und Synonyme sowie Bemerkungen zu einigen Gattungen. Bibliotheca Diatomologica 9: 5 - 230.","Smith, W. (1856) A synopsis of the British Diatomaceae: with remarks on their structure, functions and distribution; and instructions for collecting and preserving specimens. Vol. 2. London, pp. 1 - 107.","Reichardt, E. & Lange-Bertalot, H. (1991) Taxonomische Revision des Artencomplexes um Gomphonema angustum-G. dichotomum - G. intricatum - G. vibrio und ahnliche Taxa (Bacillariophyceae). Nova Hedwigia 53 (3 - 4): 519 - 544.","Simonsen, R. (1979) The diatom system: ideas on phylogeny. Bacillaria 2: 9 - 71.","Van Heurck, H. (1880) Synopsis des Diatomees de Belgique Atlas. Vol. 3. pp. 1 - 30.","Lange-Bertalot, H. (1980) Zur systematischen Bewertung der bandformigen Kolonien bei Navicula und Fragilaria. Kriterien fur die Vereinigung von Synedra (subgen. Synedra) Ehrenberg mit Fragilaria Lyngbye. Nova Hedwigia 33: 723 - 787.","Desmazieres, J. B. H. J. (1830) Plantes Cryptogames du nord de la France. pp. 451 - 500.","Kutzing, F. T. (1849) Species algarum. Lipsiae, F. A. Brockhaus, 922 pp.","Ehrenberg, C. G. (1832) Uber die Entwicklung und Lebensdauer der Infusionsthiere; nebst ferneren Beitragen zu einer Vergleichung ihrer organischen Systeme. Abhandlungen der Koniglichen Akademie der Wissenschaften zu Berlin 1831: 1 - 154.","Aboal, M., Alvarez Cobelas, M., Cambra, J. & Ector, L. (2003) Floristic list of non-marine diatoms (Bacillariophyceae) of Iberian Peninsula, Balearic Islands and Canary Islands. In: Witkowski, A, (Ed.) Diatom Monographs Vol. 4. A. R. G. Gantner Verlag K. G., 639 pp.","Mereschkowsky, C. (1902) On Sellaphora, a new genus of Diatoms. Annals and Magazine of Natural History 9 (51): 185 - 195. https: // doi. org / 10.1080 / 00222930208678565"]}

Anti-PD-1 therapy has shown promising outcomes in the treatment of different types of cancer. It is of fundamental interest to analyze the efficacy of anti-PD-1 therapy in cancer patients infected with hepatitis B virus (HBV) since the comorbidity of HBV and cancer is widely documented. We designed a multicenter retrospective study to evaluate the efficacy of anti-PD-1 therapy on non-liver cancer patients infected with HBV. We found anti-PD-1 therapy achieved much better outcomes in HBV+ non-liver cancer patients than their HBV– counterparts. We performed single-cell RNA sequencing (scRNA-seq) on peripheral blood mononuclear cells (PBMCs) from esophageal squamous cell carcinoma (ESCC) patients. We found both cytotoxicity score of T cells and MHC score of B cells significantly increased after anti-PD-1 therapy in HBV+ ESCC patients. We also identified CX3CR1high TEFF, a subset of CD8+ TEFF, associated with better clinical outcome in HBV+ ESCC patients. Lastly, we found CD8+ TEFF from HBV+ ESCC patients showing higher fraction of Exhaustionhi T than their HBV– counterpart. In summary, anti-PD-1 therapy on HBV+ non-liver cancer patients is safe and achieves better outcomes than that on HBV– non-liver cancer patients, potentially because HBV+ patients had higher fraction of Exhaustionhi T, which made them more efficiently respond to anti-PD-1 therapy.

Fluid-attenuated inversion recovery vascular hyperintensity (FVH) is frequently observed in patients with acute ischemic stroke (AIS). FVH is associated with functional outcome at 3 months in AIS patients receiving endovascular thrombectomy. In the present study, we assessed whether FVH predicted early neurological deterioration (END) and hemorrhagic transformation (HT) within 72 h in AIS patients receiving endovascular thrombectomy. We retrospectively analyzed 104 patients with acute internal-carotid-artery or proximal middle-cerebral-artery occlusion within 16 h after symptom onset. Before thrombectomy, all patients underwent brain magnetic resonance imaging. END was defined as an increase of 4 points or more from baseline National Institutes of Health Stroke Scale (NIHSS) during 72 h following onset. HT was assessed by brain computed tomography. Statistical analyses were performed to predict END and HT. The proportion of high FVH score, high American Society of Intervention and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) grade in non-END group was higher than that in END group (p 0.001, p 0.001, respectively). FVH score was positively correlated with ASITN/SIR grade (r = 0.461, p 0.001). FVH score was a predictor factor for END (adjusted OR, 13.552; 95% CI, 2.408-76.260; p = 0.003), while FVH score was not a predictor factor for HT. Furthermore, NIHSS at admission (adjusted OR, 1.112; 95% CI, 1.006-1.228; p = 0.038) and high-density lipoprotein cholesterol (adjusted OR, 18.865; 95% CI, 2.998-118.683; p = 0.002) were predictor factors for HT. To assess FVH score before thrombectomy might be useful for predicting END in AIS patients receiving endovascular thrombectomy.

Classic T cell subsets are defined by a small set of cell surface markers, while single-cell RNA sequencing (scRNA-seq) clusters cells using genome-wide gene expression profiles. The relationship between scRNA-seq clustered populations (scCPops) and cell surface marker–defined classic T cell subsets remains unclear. In this article, we integrated six bead-enriched T cell subsets with 62,235 single-cell transcriptomes from human PBMCs and clustered them into nine scCPops. Bead-enriched CD4+/CD45RA+/CD25− naive T and CD8+/CD45RA+ naive T cells were mainly clustered into their scCPop counterparts, while cells from the other T cell subsets were assigned to multiple scCPops, including mucosal-associated invariant T cells and NKT cells. The multiple T cell subsets forming one scCPop exhibit similar expression patterns, but not vice versa, indicating scCPop is a more homogeneous cell population with similar cell states. Interestingly, we discovered and named IFN signaling–associated gene (ISAG) high T (ISAGhi T) cells, a T cell subpopulation that highly expressed ISAGs. We further enriched ISAGhi T cells from human PBMCs by FACS of BST2 for scRNA-seq analyses. The ISAGhi T cell cluster disappeared on t-distributed stochastic neighbor embedding plot after removing ISAGs, whereas the ISAGhi T cell cluster showed up by analysis of ISAGs alone, indicating ISAGs are the major contributor of the ISAGhi T cell cluster. BST2+ and BST2− T cells showing different efficiencies of T cell activation indicate that a high level of ISAGs may contribute to quick immune responses.

A novel plant virus with a double-stranded (ds) RNA genome was detected in Lilium spp. in China by high-throughput sequencing, tentatively named “Lily amalgavirus 2” (LAV2). The genomic RNA of LAV2 is 3432 nucleotides (nt) and encodes a large fusion protein with 1053 amino acids (aa). It encodes two open reading frames (ORFs). The two ORFs putatively encode a ‘1 + 2’ fusion protein generated by a ‘+1’ programmed ribosomal frameshift (PRF). ORF1 encodes a 386-aa protein with unknown function, ORF2 overlaps ORF1 by 350 nt and encodes a 783-aa protein consists of a conserved sequence, which is RNA-dependent RNA polymerase (RdRp). The ‘+1’ ribosomal frameshifting motif sequence, UUU_CGN, which was highly conserved among known Amalgaviruses, was also found in LAV2. Sequence analysis suggested that it shared 46.04%-51.59% complete nucleotide sequence identity with those members of the genus Amalgavirus and had the highest identity (51.59%) to Lily amalgavirus 1 (accession no. OM782323). Phylogenetic analysis based on the RdRp amino acid sequences showed that LAV2 clustered with Amalgavirus. Overall, our data suggest that LAV2 is a new member of the genus Amalgavirus.

Soil bacteria are a crucial component of forest soil biodiversity and play important functions in numerous ecosystem processes. Hence, studying the variation of diversity and composition of soil bacteria between latitude gradients and the driving factors responsible for these differences is important for understanding the changes of soil bacteria. We used Illumina MiSeq sequencing of bacterial 16S rRNA to investigate the distribution pattern and driving factors of bacterial diversity and composition in temperate forest soils at three different latitudes in northeast China, with samples taken at low, middle and high latitude. Each sample area was located at a distance of 1,200 km. Our results indicate that the soil bacterial diversity decreased with increasing latitude. Members of the phyla Acidobacteria and Proteobacteria were the dominant in all investigated soils, the highest relative abundances of these phyla were: Acidobacteria and Proteobacteria in high-latitude forest, Rokubacteria and Actinobacteria in low-latitude forest. The dominant bacterial genera in the three different latitude forests were Candidatus_Solibacter, Bryobacter, Roseiarcus and Granulicella. Mean average temperature, soil pH and total nitrogen content were the key environmental factors shaping the soil bacterial diversity and composition in different latitudes of these temperate forests. The results of this study contribute to a deeper understanding and better predictions the latitudinal pattern of soil biodiversity.

Additional file 1: Supplementary Figure 1. (A) Boxplot show the relative abundance and difference of nine phyla of bacteria among four groups of laying hens. Wilcoxon rank-sum test: *, P < 0.05; **, P < 0.01, ***, P < 0.001; ****, P < 0.0001. (B) Five-fold cross-validation with five repeats were used to evaluate the importance of indicator bacterial genera, including HE versus HP, YE versus YP, HE versus YE, HP versus YP.

Alternative polyadenylation (APA) plays an important role in posttranscriptional gene regulation such as transcript stability and translation efficiency. However, our knowledge about APA dynamics at the single-cell level is largely unexplored. Here, we developed single-cell polyadenylation sequencing, a strand-specific approach for sequencing the 3′ end of transcripts, to investigate the landscape of APA at the single-cell level. By analyzing several cell lines, we found many genes using multiple polyA sites in bulk data are prone to use only one polyA site in each single cell. Interestingly, cell cycle genes were significantly enriched in genes with high variation in polyA site usages. Furthermore, the 414 genes showing a polyA site usage switch after cell synchronization enriched cell cycle genes, while the differentially expressed genes after cell synchronization did not enrich cell cycle genes. We further identified 812 genes showing polyA site usage changes between neighboring cell cycles, which were grouped into six clusters, with cell phase-specific functional categories enriched in each cluster. Deletion of one polyA site in MSL1 and SCCPDH results in slower and faster cell cycle progression, respectively, supporting polyA site usage switch played an important role in cell cycle. These results indicate that APA is an important layer for cell cycle regulation.

Diaporthe species are significant pathogens, saprobes, and endophytes, with comprehensive host association and geographic distribution. These fungi cause severe dieback, cankers, leaf spots, blights, and stem-end rot of fruits on different plant hosts. This study, explored the occurrence, diversity and pathogenicity of Diaporthe spp. associated with Actinidia chinensis and A. deliciosa in the main kiwifruit production areas of China. Diaporthe isolates (284) derived from 106 diseased leaf and branch samples were examined. Multi-locus phylogenetic analyses and morphology of 43 representative isolates revealed that seven Diaporthe species were obtained, including D. alangii, D. compactum, D. eres, D. hongkongensis, D. sojae, D. tectonae, and D. unshiuensis. Pathogenicity tests were performed on kiwifruit fruits, leaves and branches. Koch’s postulates confirmed all species were pathogenic. D. alangii and D. tectonae were the most aggressive species, followed by D. eres, D. sojae, D. hongkongensis, D. unshiuensis, and D. compactum. Host range evaluation showed that the seven Diaporthe species could also infect apricot, apple, peach, pear, and plum. This is the first report of D. alangii, D. compactum, D. sojae, D. tectonae, and D. unshiuensis infecting kiwifruit in China, increasing understanding of the Diaporthe complex causing diseases of kiwifruit plants, to assist effective disease management.

Sellaphora tanghongquii Y.-L. Li sp. nov. (Figs 2–26) Description:— LM (Figs 2–20): Valves broadly linear, margins weakly undulate, slightly constricted near the middle, with round ends. Length 24.5–45.5 μm, width 9.0–11.0 μm, length/width ratio varying between 2.7–4.1, median 3.3 (n = 30). Raphe filiform, lateral and undulate towards the distal and proximal ends. The terminal raphe ends slightly hooked and deflected to the same side. The central raphe ends relatively straight and tipped with slightly inflated pores. Axial area narrow and undulate following the raphe. Central area oval or elliptical, occupying 1/5–1/3 the valve width. Striae radiate more strongly towards the poles, sparser and shorter around the valve center, density 14–17 in 10 µm in the middle portion, up to 22 in 10 µm towards the ends. In some specimens, a longitudinal ridge adjacent to the trough can be seen (see arrow in Figs 3–4). Areolae not visible. SEM: Valves external (Figs 21–23): Raphe undulate with central raphe ends slightly dilated with drop-shaped pores and slightly deflected towards the same side (Figs 21, 23), terminal fissures hooked, deflected towards the opposite side of the valve, terminating onto the mantle (Figs 21, 22). The axial area has shallow troughs on both sides, extending to the apical area and becoming progressively shallower (arrow A in Fig. 21), slightly expanded at the apical area (Figs 21, 22), with wavy edges near the middle region (Fig. 23). Striae uniseriate, slightly radiate throughout, and extending onto the mantle (Figs 21–23). Areolae are mostly square and elliptical, partly round, oval, or irregularly shaped along the axial area and central area. Compared with the areolae from the longitudinal ridge to the edge of the mantle (type I: 47–55 in 10 µm), the areolae from the longitudinal ridge to the trough (type II: 42–46 in 10 µm) are smaller (arrow B in Fig. 21). Each areola has almost 2–4 small holes internally (Figs 21–23). A row of separated and small pores is present along with the mantle (arrow C in Fig. 21). Polar bars are absent. Valves internal (Figs 24–26): Axial area straight and slightly expanded near the central area. Internal raphe straight, discontinuous with intermission. Central raphe ends not expanded, bending towards the same direction (Figs 24, 26). Terminal raphe ends offset, terminating in elongated and straight helictoglossae (Figs 24, 25). The apical area of the valve has a pore-like pit, and the striae in the apical area are covered by hymenate occlusions (Fig. 25). Striae are biseriate, slightly radiate, formed by round, elliptical, C-shaped, or irregularly shaped areolae (107–150 in 10 µm) delimited by slightly oblique orientated vimines (Figs 24–26). Type:— CHINA. Guangxi Zhuang Autonomous Region: the Gui River, GR 17, elevation 78 m asl., 24°15′33′′ N, 110°45′51′′ E, Dr. Hong-Qu Tang, 29th July 2021 (Holotype GR202172902! in Coll. Hong-Qu Tang, Jinan University, Guangzhou, China = Fig. 2). Etymology:— tanghongquii, honors Dr. Hong-Qu Tang, the collector of the type sample., Published as part of Ni, Hong-Ping, Guo, Ji-Shu, Tang, Zheng-Bin, Huang, Ying-Yan, Kociolek, John Patrick & Li, Yan-Ling, 2022, Sellaphora tanghongquii sp. nov. (Bacillariophyta, Sellaphoraceae), a new diatom species from the Southern China, pp. 103-114 in Phytotaxa 573 (1) on pages 106-108, DOI: 10.11646/phytotaxa.573.1.6, http://zenodo.org/record/7329529

Sellaphora tanghongquii Y.-L. Li sp. nov. (Figs 2–26) Description:— LM (Figs 2–20): Valves broadly linear, margins weakly undulate, slightly constricted near the middle, with round ends. Length 24.5–45.5 μm, width 9.0–11.0 μm, length/width ratio varying between 2.7–4.1, median 3.3 (n = 30). Raphe filiform, lateral and undulate towards the distal and proximal ends. The terminal raphe ends slightly hooked and deflected to the same side. The central raphe ends relatively straight and tipped with slightly inflated pores. Axial area narrow and undulate following the raphe. Central area oval or elliptical, occupying 1/5–1/3 the valve width. Striae radiate more strongly towards the poles, sparser and shorter around the valve center, density 14–17 in 10 µm in the middle portion, up to 22 in 10 µm towards the ends. In some specimens, a longitudinal ridge adjacent to the trough can be seen (see arrow in Figs 3–4). Areolae not visible. SEM: Valves external (Figs 21–23): Raphe undulate with central raphe ends slightly dilated with drop-shaped pores and slightly deflected towards the same side (Figs 21, 23), terminal fissures hooked, deflected towards the opposite side of the valve, terminating onto the mantle (Figs 21, 22). The axial area has shallow troughs on both sides, extending to the apical area and becoming progressively shallower (arrow A in Fig. 21), slightly expanded at the apical area (Figs 21, 22), with wavy edges near the middle region (Fig. 23). Striae uniseriate, slightly radiate throughout, and extending onto the mantle (Figs 21–23). Areolae are mostly square and elliptical, partly round, oval, or irregularly shaped along the axial area and central area. Compared with the areolae from the longitudinal ridge to the edge of the mantle (type I: 47–55 in 10 µm), the areolae from the longitudinal ridge to the trough (type II: 42–46 in 10 µm) are smaller (arrow B in Fig. 21). Each areola has almost 2–4 small holes internally (Figs 21–23). A row of separated and small pores is present along with the mantle (arrow C in Fig. 21). Polar bars are absent. Valves internal (Figs 24–26): Axial area straight and slightly expanded near the central area. Internal raphe straight, discontinuous with intermission. Central raphe ends not expanded, bending towards the same direction (Figs 24, 26). Terminal raphe ends offset, terminating in elongated and straight helictoglossae (Figs 24, 25). The apical area of the valve has a pore-like pit, and the striae in the apical area are covered by hymenate occlusions (Fig. 25). Striae are biseriate, slightly radiate, formed by round, elliptical, C-shaped, or irregularly shaped areolae (107–150 in 10 µm) delimited by slightly oblique orientated vimines (Figs 24–26). Type:— CHINA. Guangxi Zhuang Autonomous Region: the Gui River, GR 17, elevation 78 m asl., 24°15′33′′ N, 110°45′51′′ E, Dr. Hong-Qu Tang, 29th July 2021 (Holotype GR202172902! in Coll. Hong-Qu Tang, Jinan University, Guangzhou, China = Fig. 2). Etymology:— tanghongquii, honors Dr. Hong-Qu Tang, the collector of the type sample.

Crossbreeding, mutation breeding, and traditional transgenic breeding take much time to improve desirable characters/traits. CRISPR/Cas-mediated genome editing (GE) is a game-changing tool that can create variation in desired traits, such as biotic and abiotic resistance, increase quality and yield in less time with easy applications, high efficiency, and low cost in producing the targeted edits for rapid improvement of crop plants. Plant pathogens and the severe environment cause considerable crop losses worldwide. GE approaches have emerged and opened new doors for breeding multiple-resistance crop varieties. Here, we have summarized recent advances in CRISPR/Cas-mediated GE for resistance against biotic and abiotic stresses in a crop molecular breeding program that includes the modification and improvement of genes response to biotic stresses induced by fungus, virus, and bacterial pathogens. We also discussed in depth the application of CRISPR/Cas for abiotic stresses (herbicide, drought, heat, and cold) in plants. In addition, we discussed the limitations and future challenges faced by breeders using GE tools for crop improvement and suggested directions for future improvements in GE for agricultural applications, providing novel ideas to create super cultivars with broad resistance to biotic and abiotic stress.

Here, we describe a novel mycovirus, tentatively designated as "Botryosphaeria dothidea mitovirus 3" (BdMV3), isolated from Botryosphaeria dothidea strain FJ, which causes pear ring rot disease in Fujian Province, China. The complete genome nucleotide sequence of BdMV3 is 2538 nt in length and contains a single 2070-nt open reading frame (ORF) encoding a putative RNA-dependent RNA polymerase (RdRp) of 689 amino acids (aa) using the fungal mitochondrial genetic code. BLASTp analysis revealed that the RdRp of BdMV3 shares 28.91%-69.36% sequence identity (query sequence coverage more than 90%) with those of members of the genus Mitovirus, with the highest sequence identity of 69.36% and 68.79% to the corresponding RdRp aa sequences of Rhizoctonia solani mitovirus 10 and Macrophomina phaseolina mitovirus 4, respectively. Phylogenetic analysis based on RdRp aa sequences indicated that BdMV3 is a new member of the genus Mitovirus in the family Mitoviridae.

T cell activation is a key event in adaptive immunity. However, factors affecting T cell activation have not been systematically analyzed. Here, we analyzed stimulated CD4 T cells with anti-CD3/CD28 under several conditions to explore the factors affecting T cell activation. We defined stimulated T overlapped with resting T on UMAP as inert T. Inert T expressed activated T specific genes and cytokines, indicating it is a special functional state. Stimulated T derived from peripheral CD4 T has higher fraction of effector T (TEFF) while stimulated T derived from CD4 TNhas higher fraction of proliferation T and interferon highly expressed T (IFNhiT). CD4 T was more likely to differentiate into TEFFand less likely to differentiate into heat shock protein specific T (HSPhiT) and IFNhiT in the presence of CD8 T. Interestingly,CXCR4lowT responded to stimulation more efficiently thanCXCR4hiT. These information facilitates we design stimulation to obtain ideal activated T.

Viroids have been found to naturally infect only plants, resulting in big losses for some crops, but whether viroids or viroid-like RNAs naturally infect non-plant hosts remains unknown. Here we report the existence of a set of exogenous, single-stranded circular RNAs, ranging in size between 157-450 nucleotides (nt), isolated from the fungus Botryosphaeria dothidea and nominated Botryosphaeria dothidea circular RNAs (BdcRNAs). BdcRNA(s) replicate autonomously in the nucleus via a rolling-circle replication mechanism following symmetric pathways with distribution patterns depending on strand polarity and species. BdcRNAs can modulate to different degrees specific biological traits (e.g., alter morphology, decrease growth rate, attenuate virulence, and increase or decrease tolerance to osmotic stress and oxidative stress) of the host fungus by regulating related metabolic pathways. Overall, BdcRNA(s) have genome characteristics similar to those of viroids and exhibit pathogenic effects on the fungal hosts. These novel viroid-like RNAs infecting fungi are proposed to be termed as mycoviroids. BdcRNA(s) may be regarded as additional inhabitants at the frontier of life in terms of genomic complexity, and represent a new class of acellular entities endowed with regulatory functions, and novel epigenomic carriers of biological information.Significance statementSeveral viroids have been transfected into unicellular and filamentous fungi to assess whether they can replicate, but no natural infections of fungi with viroid or viroid-like RNAs have been reported before. Here we describe a set of exogenous circular RNAs (cRNAs) in a phytopathogenic fungus. These cRNAs display molecular and biological features which might represent a new class of viroid-like cRNAs endowed with regulatory functions, and novel epigenomic carriers of biological information. This is the first report of infectious viroid-like RNAs (or exogenous small cRNAs) in a life kingdom (fungi) other than plants. We also present a subcellular analysis of cRNAs in a fungus for the first time and provide useful understanding in how cRNAs replicate, move, and are distributed in fungal cells.

Anti-PD1 therapy has shown promising outcomes in different types of cancer. It is valuable to analyze whether the efficacy of anti-PD1 therapy has been impacted in cancer patients infected with hepatitis B virus (HBV) since the comorbidity of HBV and cancer cannot be neglected. We designed a multicenter retrospective study to evaluate the efficacy of anti-PD1 therapy on non-liver cancer patients infected with HBV. In addition, we performed single-cell RNA-seq (scRNA-seq) on peripheral blood mononuclear cells (PBMCs) from esophageal squamous cell carcinoma (ESCC) patients to compare the responses of HBV + ESCC patients and HBV- ESCC patients to anti-PD1 therapy. We found anti-PD1 therapy achieved better outcomes in HBV + non-liver cancer patients than their HBV- counterparts. Further analysis showed cytotoxicity of T cells and antigen presentation capacity of B cells significantly increased after anti-PD1 therapy in the 2 HBV + ESCC patients. We also identified CX3CR1high TEFF, a subset of CD8+ TEFF, associated with better clinical outcome of HBV + patients. Lastly, we found CD8+ TEFF from HBV + patients have higher fraction of Exhaustionhi T and lower cytotoxicity score than their HBV- counterpart. In summary, Anti-PD1 therapy on HBV + non-liver patients is safe and achieves better outcomes than that on HBV- non-liver patients, potentially because HBV + patients had stronger immunosuppression which made them more efficiently respond to anti-PD1 therapy.

BackgroundPortal hypertension monitoring is important throughout the natural course of cirrhosis. Hepatic venous pressure gradient (HVPG), regarded as the golden standard, is limited by invasiveness and technical difficulties. Portal hypertension is increasingly being assessed non-invasively, and hematological indices, imaging data, and statistical or computational models are studied to surrogate HVPG. This paper discusses the existing non-invasive methods based on measurement principles and reviews the methodological developments in the last 20 years.MethodsFirst, we used VOSviewer to learn the architecture of this field. The publications about the non-invasive assessment of portal hypertension were retrieved from the Web of Science Core Collection (WoSCC). VOSviewer 1.6.17.0 was used to analyze and visualize these publications, including the annual trend, the study hotspots, the significant articles, authors, journals, and organizations in this field. Next, according to the cluster analysis result of the keywords, we further retrieved and classified the related studies to discuss.ResultsA total of 1,088 articles or review articles about our topic were retrieved from WoSCC. From 2000 to 2022, the number of publications is generally growing. “World Journal of Gastroenterology” published the most articles (n = 43), while “Journal of Hepatology” had the highest citations. “Liver fibrosis” published in 2005 was the most influential manuscript. Among the 20,558 cited references of 1,088 retrieved manuscripts, the most cited was a study on liver stiffness measurement from 2007. The highest-yielding country was the United States, followed by China and Italy. “Berzigotti, Annalisa” was the most prolific author and had the most cooperation partners. Four study directions emerged from the keyword clustering: (1) the evaluation based on fibrosis; (2) the evaluation based on hemodynamic factors; (3) the evaluation through elastography; and (4) the evaluation of variceal bleeding.ConclusionThe non-invasive assessment of portal hypertension is mainly based on two principles: fibrosis and hemodynamics. Liver fibrosis is the major initiator of cirrhotic PH, while hemodynamic factors reflect secondary alteration of splanchnic blood flow. Blood tests, US (including DUS and CEUS), CT, and magnetic resonance imaging (MRI) support the non-invasive assessment of PH by providing both hemodynamic and fibrotic information. Elastography, mainly USE, is the most important method of PH monitoring.

Fungi are generally thought to live in host plants with a single lifestyle, being parasitism, commensalism, or mutualism. The former, known as phytopathogenic fungi, cause various plant diseases that result in significant losses every year; while the latter, such as endophytic fungi, can confer fitness to the host plants. It is unclear whether biological factors can modulate the parasitic and mutualistic traits of a fungus. In this study, we isolated and characterized a mycovirus from an endophytic strain of the fungus Pestalotiopsis theae, a pathogen of tea (Camellia sinensis). Based on molecular analysis, we tentatively designated the mycovirus as Pestalotiopsis theae chrysovirus-1 (PtCV1), a novel member of the family Chrysoviridae, genus Alphachrysovirus. PtCV1 has four double-stranded (ds) RNAs as its genome, ranging from 0.9 to 3.4 kbp in size, encapsidated in isometric particles. PtCV1 significantly reduced the growth rates of its host fungus in vitro (ANOVA; P-value

In this study, a novel positive-sense single-stranded RNA (+ssRNA) mycovirus, tentatively named Colletotrichum fructicola RNA virus 1 (CfRV1), was identified in the phytopathogenic fungus Colletotrichum fructicola. CfRV1 has seven genomic components, encoding seven proteins from open reading frames (ORFs) flanked by highly conserved untranslated regions (UTRs). Proteins encoded by ORFs 1, 2, 3, 5, and 6 are more similar to the putative RNA-dependent RNA polymerase (RdRp), hypothetical protein (P2), methyltransferase, and two hypothetical proteins of Hadaka virus 1 (HadV1), a capsidless 10- or 11-segmented +ssRNA virus, while proteins encoded by ORFs 4 and 7 showed no detectable similarity to any known proteins. Notably, proteins encoded by ORFs 1 to 3 also share considerably high similarity with the corresponding proteins of polymycoviruses. Phylogenetic analysis conducted based on the amino acid sequence of CfRV1 RdRp and related viruses placed CfRV1 and HadV1 together in the same clade, close to polymycoviruses and astroviruses. CfRV1-infected C. fructicola strains demonstrate a moderately attenuated growth rate and virulence compared to uninfected isolates. CfRV1 is capsidless and potentially encapsulated in vesicles inside fungal cells, as revealed by transmission electron microscopy. CfRV1 and HadV1 are +ssRNA mycoviruses closely related to polymycoviruses and astroviruses, represent a new linkage between +ssRNA viruses and the intermediate double-stranded RNA (dsRNA) polymycoviruses, and expand our understanding of virus diversity, taxonomy, evolution, and biological traits. IMPORTANCE A scenario proposing that dsRNA viruses evolved from +ssRNA viruses is still considered controversial due to intergroup knowledge gaps in virus diversity. Recently, polymycoviruses and hadakaviruses were found as intermediate dsRNA and +ssRNA stages, respectively, between +ssRNA and dsRNA viruses. Here, we identified a novel +ssRNA mycovirus, Colletotrichum fructicola RNA virus 1 (CfRV1), isolated from Colletotrichum fructicola in China. CfRV1 is phylogenetically related to the 10- or 11-segmented Hadaka virus 1 (HadV1) but consists of only seven genomic segments encoding two novel proteins. CfRV1 is naked and may be encapsulated in vesicles inside fungal cells, representing a potential novel lifestyle for multisegmented RNA viruses. CfRV1 and HadV1 are intermediate +ssRNA mycoviruses in the linkage between +ssRNA viruses and the intermediate dsRNA polymycoviruses and expand our understanding of virus diversity, taxonomy, and evolution.

In this study, a novel positive-sense single-stranded RNA (+ssRNA) mycovirus, tentatively named Colletotrichum fructicola RNA virus 1 (CfRV1), was identified in the phytopathogenic fungus Colletotrichum fructicola. CfRV1 has seven genomic components, encoding seven proteins from open reading frames (ORFs) flanked by highly conserved untranslated regions (UTRs). Proteins encoded by ORFs 1, 2, 3, 5, and 6 are more similar to the putative RNA-dependent RNA polymerase (RdRp), hypothetical protein (P2), methyltransferase, and two hypothetical proteins of Hadaka virus 1 (HadV1), a capsidless 10- or 11-segmented +ssRNA virus, while proteins encoded by ORFs 4 and 7 showed no detectable similarity to any known proteins. Notably, proteins encoded by ORFs 1 to 3 also share considerably high similarity with the corresponding proteins of polymycoviruses. Phylogenetic analysis conducted based on the amino acid sequence of CfRV1 RdRp and related viruses placed CfRV1 and HadV1 together in the same clade, close to polymycoviruses and astroviruses. CfRV1-infected C. fructicola strains demonstrate a moderately attenuated growth rate and virulence compared to uninfected isolates. CfRV1 is capsidless and potentially encapsulated in vesicles inside fungal cells, as revealed by transmission electron microscopy. CfRV1 and HadV1 are +ssRNA mycoviruses closely related to polymycoviruses and astroviruses, represent a new linkage between +ssRNA viruses and the intermediate double-stranded RNA (dsRNA) polymycoviruses, and expand our understanding of virus diversity, taxonomy, evolution, and biological traits. IMPORTANCE A scenario proposing that dsRNA viruses evolved from +ssRNA viruses is still considered controversial due to intergroup knowledge gaps in virus diversity. Recently, polymycoviruses and hadakaviruses were found as intermediate dsRNA and +ssRNA stages, respectively, between +ssRNA and dsRNA viruses. Here, we identified a novel +ssRNA mycovirus, Colletotrichum fructicola RNA virus 1 (CfRV1), isolated from Colletotrichum fructicola in China. CfRV1 is phylogenetically related to the 10- or 11-segmented Hadaka virus 1 (HadV1) but consists of only seven genomic segments encoding two novel proteins. CfRV1 is naked and may be encapsulated in vesicles inside fungal cells, representing a potential novel lifestyle for multisegmented RNA viruses. CfRV1 and HadV1 are intermediate +ssRNA mycoviruses in the linkage between +ssRNA viruses and the intermediate dsRNA polymycoviruses and expand our understanding of virus diversity, taxonomy, and evolution.

We report firstly the complete genome sequence of a novel amalgavirus, tentatively designated as ‘Lily amalgavirus 1’(LAV-1), isolated from Lilium spp.in China. LAV-1 is a 3448-nt double-stranded RNA virus. It codes two putative proteins, open reading frame 1(ORF1) is 394 aa in length with unknown function. ORF2 encodes a putative RNA-dependent RNA polymerase (RdRp) of 895 aa. Two ORFs form a ‘1 + 2’ fusion protein translated in ‘+1’ programmed ribosomal frame shift (PRF). BLASTp analysis revealed that the complete genome sequence of LAV-1 shares 48.23%–59.80% sequence identity (query sequence coverage more than 77%) with those of members of the genus Amalgavirus, with the highest nucleotide sequence identity of 59.80% with that of Allium cepa amalgavirus 1 (query sequence coverage 87%). The genome structure, phylogenetic relationships, and sequence similarities to other plant amalgaviruses suggest that LAV-1 is a new member of the genus Amalgavirus.

Pear chlorotic leaf spot (PCLS) is a recently emerged disease of commercially cultivated sandy pear (Pyrus pyrifolia) trees in central and southern China. By integrating high-throughput sequencing and conventional Sanger sequencing of reverse-transcription (RT)-PCR products, a novel emaravirus infecting pear trees was identified and molecularly characterized. The virus was provisionally named pear chlorotic leaf spot-associated virus (PCLSaV). PCLSaV shows the typical molecular features of members of the genus Emaravirus in the family Fimoviridae. It has a genome composed of at least five negative-sense RNA segments, with each containing a single open reading frame and two complementary 13-nucleotide stretches at the 5′ and 3′ termini. PCLSaV shows a close phylogenetic relationship with recognized emaraviruses but forms a separate clade. Moreover, double-membrane-bound bodies were observed in PCLSaV-infected tissues and in extracts of PCLSaV-infected leaves. For the first time, our study revealed the profile distribution of viral RNA reads from the RNA-seq libraries of three samples along the RNA1 to RNA5 of an emaravirus. Field surveys combined with specific RT-PCR assays revealed the presence of PCLSaV in almost all PCLS-diseased pear samples, strongly supporting the association of the virus with the PCLS disease. This study revealed the first emaravirus infecting pear trees and its association with a severe pear chlorotic leaf disease.

Although mammalian genomes are diploid, previous studies extensively investigated the average chromatin architectures without considering the differences between homologous chromosomes. We generated Hi-C, ChIP-seq, and RNA-seq data sets from CD4 T cells of B6, Cast, and hybrid mice, to investigate the diploid chromatin organization and epigenetic regulation. Our data indicate that inter-chromosomal interaction patterns between homologous chromosomes are similar, and the similarity is highly correlated with their allelic coexpression levels. Reconstruction of the 3D nucleus revealed that distances of the homologous chromosomes to the center of nucleus are almost the same. The inter-chromosomal interactions at centromere ends are significantly weaker than those at telomere ends, suggesting that they are located in different regions within the chromosome territories. The majority of A|B compartments or topologically associated domains (TADs) are consistent between B6 and Cast. We found 58% of the haploids in hybrids maintain their parental compartment status at B6/Cast divergent compartments owing to cis effect. About 95% of the trans-effected B6/Cast divergent compartments converge to the same compartment status potentially because of a shared cellular environment. We showed the differentially expressed genes between the two haploids in hybrid were associated with either genetic or epigenetic effects. In summary, our multi-omics data from the hybrid mice provided haploid-specific information on the 3D nuclear architecture and a rich resource for further understanding the epigenetic regulation of haploid-specific gene expression.

It has been reported that squash leaf curl China virus (SLCCNV) infects some Cucurbitaceae crops except for melon (Cucumis melo L.). A new disease of melon exhibiting severe leaf curl and dwarfing was observed in Hainan Province of China. In this study, the pathogen was identified as SLCCNV through biological and molecular characterization. The isolate (SLCCNV-HN) possess a bipartite genome, DNA-A (HM566112.1) with the highest nucleotide identity (99%) to SLCCNV-Hn (MF062251.1) pumpkin and SLCCNV-Hn61 (AM260205.1) squash isolates from China, whereas DNA-B (HM566113.1) with the highest nucleotide identity (99%) to SLCCNV-Hn (MF062252.1). Phylogenetic analyses based on the full-length SLCCNV-HN DNA-A and -B sequences indicated that SLCCNV-HN melon isolate is clustered with SLCCNV-Hn pumpkin, SLCCNV-Hn61 and SLCCNV-SY squash isolates from southern China, forming an independent cluster. Infectious clone of SLCCNV-HN was constructed and the melon plants were inoculated and the infection rate is 100%, the systemic symptoms in melon showed identical to those of melon plants infected in fields. Additionally, melon plants transmission of this virus by Bemisia tabaci with a transmission rate of 95% (19/20) showed leaf curl and dwarf symptoms 15 days post transmission, thereby fulfilling Koch's postulates. Analysis of genomic organization and phylogenetic trees indicated that SLCCNV-HN melon isolate belongs to the Begomovirus genus. To the best of our knowledge, this is the first characterization of melon-infecting SLCCNV through its genome, infectious clone and transmission.

Bo-Wen Zhang,1 Ni-Hong Pang,2 Ren-Ai Xu,1 Gao-Er Qu,3 Cong-Rong Tang1 1Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Pharmacy, The Third Affiliated Hospital of Shanghai University (Wenzhou People’s Hospital), Wenzhou, People’s Republic of China; 3Department of Pharmacy, Health Service Community of Yueqing Third People’s Hospital, Wenzhou, People’s Republic of ChinaCorrespondence: Cong-Rong Tang, Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China, Tel +86 13867722688, Email 13867722688@163.comObjective: To evaluate the effect of axitinib on buspirone metabolism in vitro and in vivo.Methods: A microsome incubation assay was performed to study the effect and mechanism of axitinib on buspirone metabolizing. In vivo, buspirone was administered with or without axitinib to Sprague–Dawley rats. Plasma samples were collected and subjected to ultra-performance liquid chromatography–tandem mass spectrometry.Results: In both human liver microsomes (HLMs) and rat liver microsomes (RLMs), axitinib (100 μM) decreased buspirone hydroxylation and N-dealkylation by > 85%. Axitinib inhibited buspirone hydroxylation and N-dealkylation, with an IC50 of 15.76 and 9.74 for RLMs, and 10.63 and 9.902 for HLMs. Axitinib showed noncompetitive inhibition of both 6′-hydroxylation and N-dealkylation. Moreover, coadministration of axitinib and buspirone led to an increase in the maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) of buspirone by 4.3- and 5.3-fold, respectively, compared with the control group.Conclusion: Axitinib inhibited buspirone metabolism in vivo and in vitro, which increases the risk of the side effects of buspirone in the clinic. When coadministered with axitinib, a lower dosage of buspirone should be defined to avoid a toxic response. Axitinib is suspected to function as an inhibitor of CYP3A4.Keywords: buspirone, axitinib, drug-drug interactions, liver microsomes, noncompetitive inhibition

Viral seed transmission causes the spread of many plant viral diseases.

Apple rubbery wood virus 2 (ARWV-2) and citrus virus A (CiVA) belong to a recently approved family Phenuiviridae in the order Bunyavirales and possess negative-sense single-stranded RNA genomes. In this study, the genome sequence of three ARWV-2 isolates (S17E2, LYC2, and LYXS) and a CiVA isolate (CiVA-P) infecting pear trees grown in China were characterized using high-throughput sequencing combined with conventional reverse-transcription PCR (RT-PCR) assays. The genome-wide nt sequence identities were above 93.6% among the ARWV-2 isolates and above 93% among CiVA isolates. Sequence comparisons showed that sequence diversity occurred in the 5′ untranslated region of the ARWV-2 genome and the intergenic region of the CiVA genome. For the first time, this study revealed that ARWV-2 proteins Ma and Mb displayed a plasmodesma subcellular localization, and the MP of CiVA locates in cell periphery and can interact with the viral NP in bimolecular fluorescence complementation assays. RT-PCR tests disclosed that ARWV-2 widely occurs, while CiVA has a low incidence in pear trees grown in China. This study presents the first complete genome sequences and incidences of ARWV-2 and CiVA from pear trees and the obtained results extend our knowledge of the viral pathogens of pear grown in China.

Journal of high energy physics 05(5), 007 (2023). doi:10.1007/JHEP05(2023)007, The collective behavior of $ {\textrm{K}}_{\textrm{S}}^0 $ and $ \Lambda /\overline{\Lambda} $ strange hadrons is studied by measuring the elliptic azimuthal anisotropy (v$_{2}$) using the scalar-product and multiparticle correlation methods. Proton-lead (pPb) collisions at a nucleon-nucleon center-of-mass energy $ \sqrt{s_{\textrm{NN}}} $ = 8.16 TeV and lead-lead (PbPb) collisions at $ \sqrt{s_{\textrm{NN}}} $ = 5.02 TeV collected by the CMS experiment at the LHC are investigated. Nonflow effects in the pPb collisions are studied by using a subevent cumulant analysis and by excluding events where a jet with transverse momentum greater than 20 GeV is present. The strange hadron v$_{2}$ values extracted in pPb collisions via the four- and six-particle correlation method are found to be nearly identical, suggesting the collective behavior. Comparisons of the pPb and PbPb results for both strange hadrons and charged particles illustrate how event-by-event flow fluctuations depend on the system size.[graphic not available: see fulltext], Published by SISSA, [Trieste]

Pear chlorotic leaf spot associated virus (PCLSaV) belongs to the genus Emaravirus and possesses a genome composed of five negative-sense single-stranded RNA (-ssRNA) segments. This study developed a SYBR green-based reverse transcription quantitative PCR (RT-qPCR) assay for the detection of PCLSaV infecting pear trees. A set of two primers q5-F2/q5-R2 designed based on the viral RNA5 sequences showed high specificity and feasibility for PCLSaV detection. The standard curve was established. RT-qPCR assays showed that PCLSaV content was greatly higher in diseased branch and symptomatic leaf samples than that in un-diseased branch and asymptomatic leaf samples. The RT-qPCR was reliability in the detection of the virus in field and in-vitro cultured pear samples. This technique would be useful for the supervision of the viral disease and the certification of pear planting materials.

Due to the overload of IP semantics, the traditional TCP/IP network has a number of problems in scalability, mobility, and security. In this context, information-centric networking (ICN) is proposed to solve these problems. To reduce the cost of deployment and smoothly evolve, the ICN architecture needs to be compatible with existing IP infrastructure. However, the rigid underlying IP routing regulation limits the data transmission efficiency of ICN. In this paper, we propose a novel multipath transmission scheme by utilizing the characteristics and functions of ICN to enhance data transmission. The process of multipath transmission can be regarded as a service, and a multipath transmission service ID (MPSID) is assigned. By using the ICN routers bound to the MPSID as relay nodes, multiple parallel paths between the data source and the receiver are constructed. Moreover, we design a path management mechanism, including path selection and path switching. It can determine the initial path based on historical transmission information and switch to other optimal paths according to the congestion degree during transmission. The experimental results show that our proposed method can improve the average throughput and reduce the average flow completion time and the average chunk completion time.

Chinese jujube (Ziziphus jujuba Mill.) is a widely grown fruit crop at Aksu in Xinjiang Uygur Autonomous Region of China. Viral disease-like symptoms are common on jujube plants. Here, for the first time, we report a virus tentatively named persimmon ampelovirus jujube isolate (PAmpV-Ju) infecting jujube plants. The virus was identified using high-throughput sequencing from a jujube plant (ID: AKS15) and molecularly related to viruses in the family Closteroviridae. The genomic sequences of two PAmpV-Ju variants named AKS15-20 and AKS15-17 were determined by RT-PCR amplifications. The genome structure of PAmpV-Ju was identical to that of a recently reported persimmon ampelovirus (PAmpV) and consisted of seven open reading frames. The genomes of AKS15-20 and AKS15-17 shared 83.7% nt identity with each other, and the highest nt sequence identity of 79% with two variants of PAmpV. The incidence of PAmpV-Ju on Aksu jujube plants was evaluated by RT-PCR assays. The phylogenetic analysis of amplified partial sequences coding for polymerase, HSP70h, and CP revealed two phylogenetic clades represented by AKS15-20 and AKS15-17. Our study provides important evidence for understanding viruses infecting jujube plants and establishing efficient measures to prevent virus spread.

Alternative polyadenylation (APA) plays an important role in post-transcriptional gene regulation such as transcript stability and translation efficiency. However, our knowledge about APA dynamics at single cell level is largely unexplored. Here we developed single cell polyadenylation sequencing (scPolyA-seq), a strand-specific approach for sequencing 3’ end of transcripts, to investigate the landscape of APA at single cell level. By analyzing several cell lines, we found many genes using multiple polyA sites in bulk data are prone to use only one polyA site in each single cell. Interestingly, cell cycle was significantly enriched in genes showing high variation of polyA site usages. We further identified 414 genes showing polyA site usage switch after cell synchronization. Genes showing cell cycle associated polyA site usage switch were grouped into 6 clusters, with cell phase specific functional categories enriched in each cluster. Furthermore, scPolyA-seq could facilitate study of APA in various biological processes.

Eleven new 9,19-cycloartane triterpenes (1-9, 11-12) and one undescribed lanostane-type aglycone (10) were identified from the aerial parts of

Apple stem pitting virus (ASPV) is an important causal agent of pear diseases. Nowadays, the infection status and molecular characteristics of the virus in old pear trees have never been investigated. In this study, we provide the first complete genome sequence of an ASPV isolate LYC from an over 300-year-old tree of a local Pyrus bretschneideri cultivar ‘Chili’ specifically grown at Laiyang area in China. ASPV-LYC possesses a chimeric genome consisting of 9 273 nucleotides excluding a poly(A) tail at its 3’ end and harboring a recombination region in its open reading frame (ORF1) with Aurora-1 and KL9 identified as the major and minor parents. Western blot analysis with antisera against recombinant coat proteins (CPs) of three ASPV isolates from pear indicates that ASPV-LYC is serologically related to these ASPV isolates, but with differential activities. Further biological tests on indicator plants of Pyronia veitchii show that ASPV-LYC can induce serious leaf and stem symptoms as other ASPV isolates. The results provide an important information for understanding molecular evolution of ASPV and suggest a need to prevent dissemination of the isolate among pear trees.

Cabozantinib is a multityrosine kinase inhibitor and has a wide range of applications in the clinic, whose metabolism is predominately dependent on CYP3A4. This study was performed to characterize the enzymatic properties of 29 CYP3A4 alleles toward cabozantinib and the functional changes of five selected alleles (the wild-type, CYP3A4.2.8.14 and .15) toward cabozantinib in the presence of ketoconazole. Cabozantinib, 1-100 μM, with/without the presence of ketoconazole and CYP3A4 enzymes in the incubation system went through 30 min incubation at 37 °C, and the concentrations of cabozantinib N-oxide were quantified by UPLC-MS/MS to calculate the corresponding kinetic parameters of each variant. Collectively, without the presence of ketoconazole, most variants displayed defective enzymatic activities in different degrees, and only CYP3A4.14 and .15 showed significantly augmented enzymatic activities. With the presence of ketoconazole, five tested CYP3A4 alleles, even CYP3A4.14 and .15, exhibited obvious reductions in intrinsic clearance. Besides, we compared cabozantinib with regorafenib in relative clearance to confirm that CYP3A4 has the property of substrate specificity. As the first study of CYP3A4 genetic polymorphisms toward cabozantinib, our observations can provide prediction of an individual's capability in response to cabozantinib and guidance for medication and treatment of cabozantinib.

Aim Regorafenib is a tyrosine kinase inhibitor that is mainly metabolized by CYP3A4. The genetic polymorphism of CYP3A4 would contribute to differences in metabolism of regorafenib. Previously, we had discovered several novel CYP3A4 variants. However, the catalytic characteristics of these 27 CYP3A4 variants on oxidizing regorafenib have not being determined. The purpose of this study was to investigate the catalytic characteristics of 27 CYP3A4 protein variants on the oxidative metabolism of regorafenib in vitro. Method Wild-type CYP3A4.1 or other variants was incubated with 0.5-20 μmol/L regorafenib for 30 minutes. After sample processing, regorafenib-N-oxide, a primary metabolite, was detected by ultra-performance liquid chromatography-tandem mass spectrometry system. Result CYP3A4.20 had no detectable enzyme activity compared with wild-type CYP3A4.1; five variants (CYP3A4.5, .16, .19, .24, .29) exhibited similar clearance value with CYP3A4.1; four variants (CYP3A4.14, .15, .28, .31) displayed increased enzymatic activities, while remaining variants showed markedly decreased intrinsic clearance values. Conclusion This study is the first to investigate the function of 27 CYP3A4 protein variants on the metabolism of regorafenib in vitro, and it may provide some valuable information for further research in clinic.

In vitro culture of sand pear (Pyrus pyrifolia) cv. Huanghua (HH) infected with apple stem grooving virus (ASGV) was conducted and the titer and variant mutations of the virus in sub-culture were analyzed. The results showed that ASGV could replicate stably in 20 successive sub-cultures. The 500 bp PCR products of ASGV in each sub-culture were cloned and used for single-strand conformation polymorphism analysis. The results demonstrated that there was a dominant molecular variant of ASGV in vitro and that the variant structure of ASGV is stable in sub-culturing. The rate of the main haplotype in the 20 passages was from 78.0% to 95.7%. To clarify the origin of subordinate haplotypes, the error rate of our RT-PCR assay (5.4× 10−4/nt) was computed and the results indicated that the mutations which appeared in sub-passages were acquired from artificial operation and not produced by viral replication.