PanDepth, an ultrafast and efficient genomic tool for coverage calculation.

Coverage quantification is required in many sequencing datasets within the field of genomics research. However, most existing tools fail to provide comprehensive statistical results and exhibit limited performance gains from multithreading. Here, we present PanDepth, an ultra-fast and efficient tool for calculating coverage and depth from sequencing alignments. PanDepth outperforms other tools in computation time and memory efficiency for both BAM and CRAM-format alignment files from sequencing data, regardless of read length. It employs chromosome parallel computation and optimized data structures, resulting in ultrafast computation speeds and memory efficiency. It accepts sorted or unsorted BAM and CRAM-format alignment files as well as GTF, GFF and BED-formatted interval files or a specific window size. When provided with a reference genome sequence and the option to enable GC content calculation, PanDepth includes GC content statistics, enhancing the accuracy and reliability of copy number variation analysis. Overall, PanDepth is a powerful tool that accelerates scientific discovery in genomics research.

The genetic status and rescue measure for a geographically isolated population of Amur tigers.

The Amur tiger is currently confronted with challenges of anthropogenic development, leading to its population becoming fragmented into two geographically isolated groups: smaller and larger ones. Small and isolated populations frequently face a greater extinction risk, yet the small tiger population's genetic status and survival potential have not been assessed. Here, a total of 210 samples of suspected Amur tiger feces were collected from this small population, and the genetic background and population survival potentials were assessed by using 14 microsatellite loci. Our results demonstrated that the mean number of alleles in all loci was 3.7 and expected heterozygosity was 0.6, indicating a comparatively lower level of population genetic diversity compared to previously reported studies on other subspecies. The genetic estimates of effective population size (Ne) and the Ne/N ratio were merely 7.6 and 0.152, respectively, representing lower values in comparison to the Amur tiger population in Sikhote-Alin (the larger group). However, multiple methods have indicated the possibility of genetic divergence within our isolated population under study. Meanwhile, the maximum kinship recorded was 0.441, and the mean inbreeding coefficient stood at 0.0868, both of which are higher than those observed in other endangered species, such as the African lion and the grey wolf. Additionally, we have identified a significant risk of future extinction if the lethal equivalents were to reach 6.26, which is higher than that of other large carnivores. Further, our simulation results indicated that an increase in the number of breeding females would enhance the prospects of this population. In summary, our findings provide a critical theoretical basis for further bailout strategies concerning Amur tigers.

Identification of prognostic models for glycosylation-related subtypes and tumor microenvironment infiltration characteristics in clear cell renal cell cancer.

Background: One of the most fatal forms of cancer of the urinary system, renal cell carcinoma (RCC), significantly negatively impacts human health. Recent research reveals that abnormal glycosylation contributes to the growth and spread of tumors. However, there is no information on the function of genes related to glycosylation in RCC. Methods: In this study, we created a technique that can be used to guide the choice of immunotherapy and chemotherapy regimens for RCC patients while predicting their survival prognosis. The Cancer Genome Atlas (TCGA) provided us with patient information, while the GeneCards database allowed us to collect genes involved in glycosylation. GSE29609 was used as external validation to assess the accuracy of prognostic models. The "ConsensusClusterPlus" program created molecular subtypes based on genes relevant to glycosylation discovered using differential expression analysis and univariate Cox analysis. We examined immune cell infiltration as measured by estimate, CIBERSORT, TIMER, and ssGSEA algorithms, Tumor Immune Dysfunction and Exclusion (TIDE) and exclusion of tumour stemness indices (TSIs) based on glycosylation-related molecular subtypes and risk profiles. Stratification, somatic mutation, nomogram creation, and chemotherapy response prediction were carried out based on risk factors. Results: We built and verified 16 gene signatures associated with the prognosis of ccRCC patients, which are independent prognostic variables, and identified glycosylation-related genes by bioinformatics research. Cluster 2 is associated with lower human leukocyte antigen expression, worse overall survival, higher immunological checkpoints, and higher immune escape scores. In addition, cluster 2 had significantly better angiogenic activity, mesenchymal EMT, and stem ability scores. Higher immune checkpoint genes and human leukocyte antigens are associated with lower overall survival and a higher risk score. Higher estimated and immune scores, lesser tumor purity, lower mesenchymal EMT, and higher stem scores were all characteristics of the high-risk group. High amounts of tumor-infiltrating lymphocytes, a high mutation load, and a high copy number alteration frequency were present in the high-risk group.Discussion.According to our research, the 16-gene prognostic signature may be helpful in predicting prognosis and developing individualized treatments for patients with renal clear cell carcinoma, which may result in new personalized management options for these patients.

Microcapsules of mesoporous silica and cyclodextrin modified loaded with nonanal and decanal for effective control of Sitotroga cerealella in grain storage environments.

BACKGROUND: The Angoumois grain moth, Sitotroga cerealella, is a destructive pest of maize, wheat, and rice, causing economic losses and threatening food security. This study aimed to develop and characterize microcapsules of mesoporous silica nanospheres (MSN) and cyclodextrin-modified mesoporous silica nanospheres (CDMSN) containing two aldehydes, nonanal and decanal, found in plant essential oils, to assess their attractiveness to S. cerealella populations. RESULTS: Microcapsules with 2:1 ratio of nonanal and decanal exhibited an average encapsulation efficiency of 39.82% for MSN loaded with nonanal and decanal (MSN-ND) and 46.10% for CDMSN loaded with nonanal and decanal (CDMSN-ND). They have an elliptical shape with particle sizes of 115 nm for MSN and 175 nm for CDMSN. Gas chromatography-mass spectrometry analysis revealed in vitro release of nonanal in MSN at 96.24% and decanal at 96.42% by the 36th day. CDMSN showed releases of 93.83% for nonanal and 93.74% for decanal by the 50th day. CDMSN-ND attracted adult S. cerealella for 43 days, while MSN-ND remained effective for 29 days. In mass trapping assays in simulated grain warehouse, both MSN-ND and CDMSN-ND trapped over 50% of the adult population within 7 days, significantly reducing grain infestation rates below 10% by inhibiting F1 adult emergence. At temperatures ranging from 20 °C to 35 °C, both microcapsules exhibited significant and effective attraction rates for S. cerealella. Stored wheat seeds treated with CDMSN and CDMSN-ND over 1 year showed no significant differences in key germination parameters. CONCLUSION: Microencapsulated nonanal and decanal offer a promising, sustainable approach for controlling S. cerealella infestation in stored grains, contributing to global food security. © 2024 Society of Chemical Industry.

RNA-binding protein DND1 participates in migration, invasion, and EMT of prostate cancer cells by degrading CLIC4.

Dead-End 1 (DND1) is an RNA-binding protein (RBP) with regulatory functions in multiple cancers, including gastric and colorectal. Nevertheless, the role that DND1 plays in prostatic cancer (PCa) as well as the hidden molecular mechanism is still obscure. The gene expression of DND1 and survival analyses in PCa were analyzed by the UALCAN database. Expression of DND1 and chloride intracellular channel 4 (CLIC4) were detected by qRT-PCR and western blot analysis. The Cell Counting Kit-8 assay and EDU staining were employed for the estimation of cell viability. The capabilities of cells to migrate and invade were appraised by the wound healing assay as well as the Transwell assay, while epithelial-mesenchymal transition (EMT) was measured by immunofluorescence and western blot assay. The interaction of DND1 and CLIC4 was predicted by PCTA, linkedomics, and RPISeq databases. It was discovered that DND1 expression was elevated in PCa cells. DND1 silencing had suppressive impacts on cells' proliferative, migrative, and invasive capabilities as well as EMT in DU145 and 22Rv1 cells. Mechanistically, bioinformatic analysis demonstrated that DND1 was negatively correlated with CLIC4 and that DND1 protein could bind to CLIC4 mRNA. Additionally, the CLIC4 level was reduced in PCa cells. CLIC4 depletion countervailed the suppressive impacts of DND1 deficiency on the capabilities of DU145 and 22Rv1 cells to proliferate, migrate, and invade as well as the process of EMT. These results suggested that DND1 silencing repressed the proliferation, migration, invasion, and EMT in PCa by regulating the mRNA level of CLIC4.

Preliminary study of the effect of gut microbiota on the development of prostatitis.

BACKGROUND: Dysbacteriosis of intestinal tract may cause systemic inflammation, making distant anatomical locations more susceptible to illness. Recent research has demonstrated that the microbiome can affect both prostatitis and the inflammation of the prostate that is linked to prostate cancer. It is still unclear, though, whether this relationship indicates causation. We conducted a Mendelian randomization investigation on two samples to fully uncover gut microbiota's potential genetic causal role in prostatitis. METHOD: Prostatitis (1859 prostatitis cases and 72,799 controls) was utilized as the outcome, while SNPs highly linked with 196 microbial taxa (18 340 people) were chosen as instrumental factors. Random effects, inverse variance weighting, weighted medians, and MR-Egger were used to analyze causal effects. The Cochran's Q test, funnel plot, leave-one-out analysis, and MR-Egger intercept test were all used in the sensitivity analysis. RESULTS: A causal effect in lowering the incidence of prostatitis is anticipated for five gut microorganisms (Methanobacteria, Methanobacteriaceae, Erysipelatoclostridium, Parasutterella, and Slackia; P < 0.05). Four gut bacteria, including Faecalibacterium, LachnospiraceaeUCG004, Sutterella, and Gastranaerophilales, are predicted to play a causal role in increasing the risk of prostatitis (P < 0.05). There were no discernible estimates of pleiotropy or heterogeneity. CONCLUSION: Our investigation established the genetic links between nine gut microorganisms and prostatitis, which may offer fresh perspectives and a theoretical framework for the future prevention and management of prostatitis.

Transposable elements cause the loss of self-incompatibility in citrus.

Self-incompatibility (SI) is a widespread prezygotic mechanism for flowering plants to avoid inbreeding depression and promote genetic diversity. Citrus has an S-RNase-based SI system, which was frequently lost during evolution. We previously identified a single nucleotide mutation in Sm-RNase, which is responsible for the loss of SI in mandarin and its hybrids. However, little is known about other mechanisms responsible for conversion of SI to self-compatibility (SC) and we identify a completely different mechanism widely utilized by citrus. Here, we found a 786-bp miniature inverted-repeat transposable element (MITE) insertion in the promoter region of the FhiS2-RNase in Fortunella hindsii Swingle (a model plant for citrus gene function), which does not contain the Sm-RNase allele but are still SC. We demonstrate that this MITE plays a pivotal role in the loss of SI in citrus, providing evidence that this MITE insertion prevents expression of the S-RNase; moreover, transgenic experiments show that deletion of this 786-bp MITE insertion recovers the expression of FhiS2-RNase and restores SI. This study identifies the first evidence for a role for MITEs at the S-locus affecting the SI phenotype. A family-wide survey of the S-locus revealed that MITE insertions occur frequently adjacent to S-RNase alleles in different citrus genera, but only certain MITEs appear to be responsible for the loss of SI. Our study provides evidence that insertion of MITEs into a promoter region can alter a breeding strategy and suggests that this phenomenon may be broadly responsible for SC in species with the S-RNase system.

Multi-omics analyses reveal the importance of chromoplast plastoglobules in carotenoid accumulation in citrus fruit.

Chromoplasts act as a metabolic sink for carotenoids, in which plastoglobules serve as versatile lipoprotein particles. PGs in chloroplasts have been characterized. However, the features of PGs from non-photosynthetic plastids are poorly understood. We found that the development of chromoplast plastoglobules (CPGs) in globular and crystalloid chromoplasts of citrus is associated with alterations in carotenoid storage. Using Nycodenz density gradient ultracentrifugation, an efficient protocol for isolating highly purified CPGs from sweet orange (Citrus sinensis) pulp was established. Forty-four proteins were defined as likely comprise the core proteome of CPGs using comparative proteomics analysis. Lipidome analysis of different chromoplast microcompartments revealed that the nonpolar microenvironment within CPGs was modified by 35 triacylglycerides, two sitosterol esters, and one stigmasterol ester. Manipulation of the CPG-localized gene CsELT1 (esterase/lipase/thioesterase) in citrus calli resulted in increased lipids and carotenoids, which is further evidence that the nonpolar microenvironment of CPGs contributes to carotenoid accumulation and storage in the chromoplasts. This multi-feature analysis of CPGs sheds new light on the role of chromoplasts in carotenoid metabolism, paving the way for manipulating carotenoid content in citrus fruit and other crops.

Phase Ib study of anti-EGFR antibody (SCT200) in combination with anti-PD-1 antibody (SCT-I10A) for patients with RAS/BRAF wild-type metastatic colorectal cancer.

OBJECTIVE: This study evaluated the safety and efficacy of an anti-epidermal growth factor receptor (EGFR) antibody (SCT200) and an anti-programmed cell death 1 (PD-1) antibody (SCT-I10A) as third-line or subsequent therapies in patients with rat sarcoma viral oncogene (RAS)/v-raf murine sarcoma viral oncogene homolog B (BRAF) wild-type (wt) metastatic colorectal cancer (mCRC). METHODS: We conducted a multicenter, open-label, phase Ib clinical trial. Patients with histologically confirmed RAS/BRAF wt mCRC with more than two lines of treatment were enrolled and treated with SCT-I10A and SCT200. The primary endpoints were the objective response rate (ORR) and safety. The secondary endpoints included disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). RESULTS: Twenty-one patients were enrolled in the study through January 28, 2023. The ORR was 28.57% and the DCR was 85.71% (18/21). The median PFS and OS were 4.14 and 12.84 months, respectively. The treatment-related adverse events (TRAEs) were tolerable. Moreover, compared with the monotherapy cohort from our previous phase I study evaluating SCT200 for RAS/BRAF wt mCRC in a third-line setting, no significant improvements in PFS and OS were observed in the combination group. CONCLUSIONS: SCT200 combined with SCT-I10A demonstrated promising efficacy in previously treated RAS/BRAF wt mCRC patients with an acceptable safety profile. Further head-to-head studies with larger sample sizes are needed to validate whether the efficacy and safety of combined anti-EGFR and anti-PD-1 therapy are superior to anti-EGFR monotherapy in the third-line setting. (Registration No. NCT04229537).

Risk factors and predictors of urogenous sepsis after percutaneous nephrolithotomy for idiopathic calcium oxalate nephrolithiasis.

Background: The aim of this study was to use bioinformatics approaches to screen and identify the key genes of idiopathic calcium oxalate nephrolithiasis, and explore its potential molecular mechanism. Methods: The GSE73680 kidney stone data set was downloaded from the Gene Expression Omnibus (GEO). R software (The R Foundation for Statistical Computing) was used to screen differentially expressed genes. GeneMANIA and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) databases were used to analyze related genes interacting with crucial genes, and a protein-protein interaction (PPI) network was constructed. The differential genes were then subjected to the Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database. The clinical data of 156 patients who received percutaneous nephrolithotomy (PCNL) therapy at our facility between January 2013 and December 2017 were retrospectively analyzed. The various parameters associated with postoperative urogenous sepsis were identified using multivariable logistic regression analysis. Results: The study discovered one differentially expressed gene was nucleotide-binding oligomerization domain-containing protein 2 (NOD2). GO and KEGG analysis showed that NOD2 might affect the occurrence of idiopathic calcium oxalate kidney stones by affecting inflammation, receptor expression, immune environment, necrosis, apoptosis, and other pathways. The clinical parameter of patients who participated in the study, including preoperative urinary white blood cell (WBC) count, preoperative urinary nitrite, stone diameter, operation time, WBC count, and WBC D values, were statistically different between the systemic inflammatory response syndrome (SIRS) group and the urosepsis group. According to multivariate logistic regression analysis, the preoperative urine nitrite, calculus diameter, blood WBC, and NOD2 expression 3 hours after surgery were all independently associated with the urosepsis development. Conclusions: Preoperative urinary nitrite positive status, postoperative WBC count ≥2.98×109/L 3 hours after operation, stone diameter >6 cm, and low expression of NOD2 in renal papillary tissue are more likely to cause the urinary source of idiopathic calcium oxalate nephrolithiasis after PCNL urogenous sepsis. These parameters also offer a viable treatment paradigm for the perioperative management of PCNL in treating idiopathic calcium oxalate kidney stones.

SlZF3 regulates tomato plant height by directly repressing SlGA20ox4 in the gibberellic acid biosynthesis pathway.

Plant height is an important target trait for crop genetic improvement. Our previous work has identified a salt-tolerant C2H2 zinc finger, SlZF3, and its overexpression lines also showed a semi-dwarf phenotype, but the molecular mechanism remains to be elucidated. Here, we characterized the dwarf phenotype in detail. The dwarfism is caused by a decrease in stem internode cell elongation and deficiency of bioactive gibberellic acids (GAs), and can be rescued by exogenous GA3 treatment. Gene expression assays detected reduced expression of genes in the GA biosynthesis pathway of the overexpression lines, including SlGA20ox4. Several protein-DNA interaction methods confirmed that SlZF3 can directly bind to the SlGA20ox4 promoter and inhibit its expression, and the interaction can also occur for SlKS and SlKO. Overexpression of SlGA20ox4 in the SlZF3-overexpressing line can recover the dwarf phenotype. Therefore, SlZF3 regulates plant height by directly repressing genes in the tomato GA biosynthesis pathway.

A 21-bp InDel in the promoter of STP1 selected during tomato improvement accounts for soluble solid content in fruits.

Domestication and improvement are important processes that generate the variation in genome and phonotypes underlying crop improvement. Unfortunately, during selection for certain attributes, other valuable traits may be inadvertently discarded. One example is the decline in fruit soluble solids content (SSC) during tomato breeding. Several genetic loci for SSC have been identified, but few reports on the underlying mechanisms are available. In this study we performed a genome-wide association study (GWAS) for SSC of the red-ripe fruits in a population consisting of 481 tomato accessions with large natural variations and found a new quantitative trait locus, STP1, encoding a sugar transporter protein. The causal variation of STP1, a 21-bp InDel located in the promoter region 1124 bp upstream of the start codon, alters its expression. STP1 Insertion accessions with an 21-bp insertion have higher SSC than STP1 Deletion accessions with the 21-bp deletion. Knockout of STP1 in TS-23 with high SSC using CRISPR/Cas9 greatly decreased SSC in fruits. In vivo and in vitro assays demonstrated that ZAT10-LIKE, a zinc finger protein transcription factor (ZFP TF), can specifically bind to the promoter of STP1 Insertion to enhance STP1 expression, but not to the promoter of STP1 Deletion , leading to lower fruit SSC in modern tomatoes. Diversity analysis revealed that STP1 was selected during tomato improvement. Taking these results together, we identified a naturally occurring causal variation underlying SSC in tomato, and a new role for ZFP TFs in regulating sugar transporters. The findings enrich our understanding of tomato evolution and domestication, and provide a genetic basis for genome design for improving fruit taste.

Diallyl Trisulfide, a Biologically Active Component of Garlic Essential Oil, Decreases Male Fertility in Sitotroga cerealella by Impairing Dimorphic Spermatogenesis, Sperm Motility and Lipid Homeostasis.

Diallyl trisulfide (DAT) is a biologically active component of garlic essential oil and exhibits multi-targeted activity against many organisms. The current study tested the capacity of DAT to decrease the male fertility of Sitotroga cerealella. The effects on testis morphology, sperm number, motility, and lipid homeostasis were observed in adult males fumigated with DAT at a dose of 0.01 µL/L in air. The results indicated that the DAT significantly decreased the dimorphic sperm number. Meanwhile, the ultrastructural analysis of the sperm showed that the DAT caused malformed and aberrant structures of mitochondrial derivatives of dimorphic sperm. Additionally, the lipid homeostasis and ATP contents in the male adults were significantly decreased after treatment. Moreover, the total sperm motility was reduced, while the wave-propagation velocity, amplitude, frequency, and wavelength were significantly decreased compared with the controls. Overall, this study reported, for the first time, that DAT impairs energy metabolism, inhibits dimorphic spermatogenesis, and decreases sperm motility, while these abnormalities in sperm lead to adult-male infertility.

Individual automatic detection and identification of big cats with the combination of different body parts.

The development of facial recognition technology has become an increasingly powerful tool in wild animal individual recognition. In this paper, we develop an automatic detection and recognition method with the combinations of body features of big cats based on the deep convolutional neural network (CNN). We collected dataset including 12 244 images from 47 individual Amur tigers (Panthera tigris altaica) at the Siberian Tiger Park by mobile phones and digital camera and 1940 images and videos of 12 individual wild Amur leopard (Panthera pardus orientalis) by infrared cameras. First, the single shot multibox detector algorithm is used to perform the automatic detection process of feature regions in each image. For the different feature regions of the image, like face stripe or spots, CNNs and multi-layer perceptron models were applied to automatically identify tiger and leopard individuals, independently. Our results show that the identification accuracy of Amur tiger can reach up to 93.27% for face front, 93.33% for right body stripe, and 93.46% for left body stripe. Furthermore, the combination of right face, left body stripe, and right body stripe achieves the highest accuracy rate, up to 95.55%. Consequently, the combination of different body parts can improve the individual identification accuracy. However, it is not the higher the number of body parts, the higher the accuracy rate. The combination model with 3 body parts has the highest accuracy. The identification accuracy of Amur leopard can reach up to 86.90% for face front, 89.13% for left body spots, and 88.33% for right body spots. The accuracy of different body parts combination is lower than the independent part. For wild Amur leopard, the combination of face with body spot part is not helpful for the improvement of identification accuracy. The most effective identification part is still the independent left or right body spot part. It can be applied in long-term monitoring of big cats, including big data analysis for animal behavior, and be helpful for the individual identification of other wildlife species.

Induced mutation in ELONGATED HYPOCOTYL5 abolishes anthocyanin accumulation in the hypocotyl of pepper.

KEY MESSAGE: The causal gene, CaHY5 of a chemical induced green-hypocotyl mutant was identified by molecular mapping. CaHY5 regulates anthocyanin accumulation by directly binding to the promoter of genes in anthocyanin pathway. Morphological markers at seedling stage are useful indicators for F1 hybrid seeds screening. Pepper is a worldwide vegetable with diverse uses, and F1 hybrids are popular in the pepper industry. Hypocotyl color is a useful marker to identify F1 hybrid seeds. However, most pepper accessions have purple hypocotyl caused by anthocyanin accumulation, while green hypocotyl pepper accessions are rare. In this study, we identified a green hypocotyl mutant (e1898) from a pepper ethylmethanesulfonate (EMS) mutant library. By combining bulked segregant RNA-seq (BSR), genome resequencing and recombinant analysis, it was found that CaHY5 is the causal gene of this mutant. Virus-induced gene silencing (VIGS) of CaHY5 resulted in the decrease of anthocyanin accumulation in pepper hypocotyls. RNA-seq data showed that many genes related to anthocyanin biosynthesis and transport decreased significantly in the mutant. Yeast one-hybrid (Y1H) assays showed that CaHY5 can bind to the promoter of CaF3H, CaF3'5'H, CaDFR, CaANS and CaGST, which are important genes in anthocyanin biosynthesis or transport. Our results indicate that CaHY5 directly regulates anthocyanin biosynthesis and transport, thus governing anthocyanin accumulation in pepper hypocotyl. The mutant and gene identified in this work shall be valuable in the purity control of hybrid pepper seeds.

Loss-of-function of SAWTOOTH 1 affects leaf dorsiventrality genes to promote leafy heads in lettuce.

The mechanisms underlying leafy heads in vegetables are poorly understood. Here, we cloned a quantitative trait locus (QTL) controlling leafy heads in lettuce (Lactuca sativa). The QTL encodes a transcription factor, SAWTOOTH 1 (LsSAW1), which has a BEL1-like homeodomain and is a homolog of Arabidopsis thaliana. A 1-bp deletion in Lssaw1 contributes to the development of leafy heads. Laser-capture microdissection and RNA-sequencing showed that LsSAW1 regulates leaf dorsiventrality and loss-of-function of Lssaw1 downregulates the expression of many adaxial genes but upregulates abaxial genes. LsSAW1 binds to the promoter region of the adaxial gene ASYMMETRIC LEAVES 1 (LsAS1) to upregulate its expression. Overexpression of LsAS1 compromised the effects of Lssaw1 on heading. LsSAW1 also binds to the promoter region of the abaxial gene YABBY 1 (LsYAB1), but downregulates its expression. Overexpression of LsYAB1 led to bending leaves in LsSAW1 genotypes. LsSAW1 directly interacts with KNOTTED 1 (LsKN1), which is necessary for leafy heads in lettuce. RNA-seq data showed that LsSAW1 and LsKN1 exert antagonistic effects on the expression of thousands of genes. LsSAW1 compromises the ability of LsKN1 to repress LsAS1. Our results suggest that downregulation or loss-of-function of adaxial genes and upregulation of abaxial genes allow for the development of leafy heads.

Disruption of the lipolysis pathway results in stem cell death through a sterile immunity-like pathway in adult Drosophila.

We previously showed that the Arf1-mediated lipolysis pathway sustains stem cells and cancer stem cells (CSCs); its ablation resulted in necrosis of stem cells and CSCs, which further triggers a systemic antitumor immune response. Here we show that knocking down Arf1 in intestinal stem cells (ISCs) causes metabolic stress, which promotes the expression and translocation of ISC-produced damage-associated molecular patterns (DAMPs; Pretaporter [Prtp] and calreticulin [Calr]). DAMPs regulate macroglobulin complement-related (Mcr) expression and secretion. The secreted Mcr influences the expression and localization of enterocyte (EC)-produced Draper (Drpr) and LRP1 receptors (pattern recognition receptors [PRRs]) to activate autophagy in ECs for ATP production. The secreted ATP possibly feeds back to kill ISCs by activating inflammasome-like pyroptosis. We identify an evolutionarily conserved pathway that sustains stem cells and CSCs, and its ablation results in an immunogenic cascade that promotes death of stem cells and CSCs as well as antitumor immunity.

Long non-coding RNA MIR22HG suppresses cell proliferation and promotes apoptosis in prostate cancer cells by sponging microRNA-9-3p.

The present study was designed to discuss long non-coding RNA (lncRNA) MIR22HG expression in prostate cancer and to address its effect on prostate cancer cells. MIR22HG and microRNA (miR)-9-3p expressions in prostate cancer cells were examined with the use of quantitative real-time PCR (qRT-PCR). Cell counting kit (CCK)-8, colony formation, and TUNEL were conducted to determine cell viability and apoptosis. Immunofluorescence was employed for the detection of Ki67 expression, and western blotting was applied for the examination of apoptosis-related proteins. The relationship of MIR22HG and miR-9-3p was verified employing luciferase reporter assay. Indeed, low MIR22HG expression was discovered in prostate cancer cells. Subsequently, in vitro loss-of-function studies revealed that MIR22HG overexpression suppressed cell proliferation but promoted cell apoptosis, accompanied with a reduction in Ki67 and Bcl-2 expressions, as well as an elevation in Bax and cleaved caspase 3 expressions. In addition, MIR22HG was identified as a sponge of miR-9-3p and the impacts of MIR22HG overexpression on cell proliferation and apoptosis were partly hindered by miR-9-3p overexpression. In summary, MIR22HG acts as an anticancer gene in prostate cancer via inhibiting cell proliferation and promoting apoptosis by sponging miR-9-3p. This article may provide a novel insight into the treatment of prostate cancer.