Integrated analyses reveal the diagnostic and predictive values of COL5A2 and association with immune environment in Crohn's disease.

The pathogenesis of Crohn's disease (CD) involves abnormal immune cell infiltration and dysregulated immune response. Therefore, thorough research on immune cell abnormalities in CD is crucial for improved treatment of this disease. Single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data of CD were obtained from the Gene Expression Omnibus (GEO) database. Cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT), weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) networks evaluated the proportion of immune infiltrating cells, constructed co-expression network and identified key genes, respectively. Based on the dataset (GSE134809), 15 cell clusters were defined and labeled as different cell types. Among the 11 modules, the yellow module had the closest relationship with plasma cells (cluster 5). Confirmed using RNA sequencing and IHC assay, the expression of COL5A2 in CD samples was higher than that in control samples. Furthermore, the COL5A2 protein expression remarkably decreased in the group of patients who responded to anti-tumor necrosis factor (TNF) treatments, compared to the non-response group. The comprehensive analyses described here provided novel insight into the landscape of CD-associated immune environment. In addition, COL5A2 were identified as potential diagnostic indicators for CD, as well as promising predictive markers for CD patients.

Contrast enhancement method in aero thermal radiation images based on cyclic multi-scale illumination self-similarity and gradient perception regularization.

In aerospace, the effects of thermal radiation severely affect the imaging quality of infrared (IR) detectors, which blur the scene information. Existing methods can effectively remove the intensity bias caused by the thermal radiation effect, but they have limitations in the ability of enhancing contrast and correcting local dense intensity or global dense intensity. To address the limitations, we propose a contrast enhancement method based on cyclic multi-scale illumination self-similarity and gradient perception regularization solver (CMIS-GPR). First, we conceive to correct for intensity bias by amplifying gradient. Specifically, we propose a gradient perception regularization (GPR) solver to correct intensity bias by directly decomposing degraded image into a pair of high contrast images, which do not contain intensity bias and exhibit inverted intensity directions. However, we find that the GPR fails for dense intensity area due to small gradient of the scene. Second, to cope with the cases of dense intensity, we regard the dense intensity bias as the sum of multiple slight intensity bias. Then, we construct a cyclic multi-scale illumination self-similarity (CMIS) model by using multi-scale Gaussian filters and structural similarity prior to removing the dense intensity layer by layer. The result acts as coarse correction for GPR, which does not need to be overly concerned with whether the result has intensity residuals or not. Finally, the coarse corrected result is input to the GPR module to further correct residual intensity bias by enhancing contrast. Extensive experiments in real and simulated data have demonstrated the superiority of the proposed method.

Global patterns of human-wildlife spatial associations and implications for differentiating conservation strategies.

Understanding the global patterns of human and wildlife spatial associations is essential for pragmatic conservation implementation, yet analytical foundations and indicator-based assessments that would further this understanding are lacking. We integrated the global distributions of 30,664 terrestrial vertebrates and human pressures to map human-nature index (HNI) categories that indicate the extent and intensity of human-wildlife interactions. Along the 2 dimensions of biodiversity and human activity, the HNI allowed placement of terrestrial areas worldwide in one of 4 HNI categories: anthropic (human-dominated areas), wildlife-dominated (little human influence and rich in wildlife), co-occurring (substantial presence of humans and wildlife), and harsh-environment (limited presence of humans and wildlife) areas. The HNI varied considerably among taxonomic groups, and the leading driver of HNI was global climate patterns. Co-occurring regions were the most prevalent (35.9%), and wildlife-dominated and anthropic regions encompassed 26.45% and 6.50% of land area, respectively. Our results highlight the necessity for customizing conservation strategies to regions based on human-wildlife spatial associations and the distribution of existing protected area networks. Human activity and biodiversity should be integrated for complementary strategies to support conservation toward ambitious and pragmatic 30×30 goals.

Patrones globales de las asociaciones espaciales entre humanos y fauna y las implicaciones para la diferenciación de las estrategias de conservación Resumen Es esencial entender los patrones globales de asociaciones entre humanos y fauna para la implementación pragmática de la conservación. Aun así, son muy pocos los fundamentos analíticos y las evaluaciones basadas en indicadores que incrementarían este conocimiento. Integramos la distribución global de 30,664 vertebrados terrestres y presiones humanas para mapear las categorías del índice de naturaleza humana (INH) que indican la extensión e intensidad de las interacciones humano­fauna. El INH permitió la colocación de áreas terrestres en todo el mundo en las dos dimensiones de la biodiversidad y las actividades humanas dentro de una de las cuatro categorías del INH: áreas antrópicas (dominadas por humanos), dominadas por fauna (poca influencia humana y rica en fauna), co­ocurrentes (presencia sustancial de humanos y fauna) y de ambiente severo (presencia limitada de humanos y fauna). El INH varió considerablemente entre los taxones, y el factor principal fueron los patrones climáticos mundiales. Las regiones co­ocurrentes fueron las más frecuentes (35.9%) las regiones antrópicas y dominadas por fauna englobaron el 26.45% y 6.50% del área terrestre respectivamente. Nuestros resultados enfatizan la necesidad de personalizar las estrategias de conservación acorde a la región con base en las asociaciones espaciales entre humanos y fauna y la distribución de las redes existentes de áreas protegidas. La actividad humana y la biodiversidad deberían estar integradas para las estrategias complementarias para respaldar a la conservación hacia los objetivos ambiciosos y pragmáticos de 30 para el 30.

Systemic inflammation response index predicts the postoperative recurrence of chronic rhinosinusitis with nasal polyps: a retrospective study in the Chinese population.

PURPOSE: Endoscopic sinus surgery (ESS) is now frequently used to treat chronic sinusitis with nasal polyps (CRSwNP), but postoperative recurrence plagues many patients. We aimed to assess the value of the systemic inflammation response index (SIRI) and the systemic immune-inflammatory index (SII) for the prediction of postoperative recurrence in patients with CRSwNP. METHODS: A total of 143 patients with CRSwNP and 76 age- and sex-matched healthy subjects were enrolled. Patients were divided into the recurrence group and the non-recurrence group according to the recurrence of CRSwNP. Univariate and multivariate analyses showed independent risk factors for the recurrence. A receiver operating characteristic curve analysis was conducted to assess the predictive accuracy of the variables and determine the optimal cut-off values. Finally, a survival analysis was conducted. RESULTS: Univariate analysis revealed that age, sex, CRP, EOS, SIRI, SII, NLR, ELR, and Lund-Mackay CT scores were significant predictors of the recurrence of CRSwNP. Multivariate analysis confirmed that SIRI (OR = 1.310, p < 0.001) and Lund-Mackay CT scores (OR = 1.396, p < 0.001) were independent predictors. SIRI (AUC = 0.761, 95% CI: 0.685-0.836) had a certain value in predicting the recurrence of CRSwNP. CONCLUSION: SIRI is a potential predictive marker of the postoperative recurrence of CRSwNP.

Inhibition and Mechanism of Citral on Bacillus cereus Vegetative Cells, Spores, and Biofilms.

Bacillus cereus causes food poisoning by producing toxins that cause diarrhea and vomiting and, in severe cases, endocarditis, meningitis, and other diseases. It also tends to form biofilms and spores that lead to contamination of the food production environment. Citral is a potent natural antibacterial agent, but its antibacterial activity against B. cereus has not been extensively studied. In this study, we first determined the minimum inhibitory concentrations and minimum bactericidal concentrations, growth curves, killing effect in different media, membrane potential, intracellular adenosine triphosphate (ATP), reactive oxygen species levels, and morphology of vegetative cells, followed by germination rate, morphology, germination state of spores, and finally biofilm clearance effect. The results showed that the minimum inhibitory concentrations and minimum bactericidal concentrations of citral against bacteria ranged from 100 to 800 µg/mL. The lag phase of bacteria was effectively prolonged by citral, and the growth rate of bacteria was slowed down. Bacteria in Luria-Bertani broth were reduced to below the detection limit by citral at 800 µg/mL within 0.5 h. Bacteria in rice were reduced to 3 log CFU/g by citral at 4000 µg/mL within 0.5 h. After treatment with citral, intracellular ATP concentration was reduced, membrane potential was altered, intracellular reactive oxygen species concentration was increased, and normal cell morphology was altered. After treatment with citral at 400 µg/mL, spore germination rate was reduced to 16.71%, spore morphology was affected, and spore germination state was altered. It also had a good effect on biofilm removal. The present study showed that citral had good bacteriostatic activity against B. cereus vegetative cells and its spores and also had a good clearance effect on its biofilm. Citral has the potential to be used as a bacteriostatic substance for the control of B. cereus in food industry production.

Comprehensive Genomic Profiling of NF2-Mutated Kidney Tumors Reveals Potential Targets for Therapy.

Genomic alterations (GA) in NF2 tumor-suppressor gene have been associated with aggressive behavior in kidney tumors. We used comprehensive genomic profiling (CGP) to evaluate the frequencies of NF2 GA in histologic subtypes of kidney tumors and co-occurring GA in other genes and biomarkers. Advanced kidney tumors included 1875 clear cell (ccRCC), 405 papillary (pRCC), 108 chromophobe (chRCC), 171 sarcomatoid (sRCC), 61 collecting duct (cdRCC), 49 medullary (mRCC), 134 unclassified (uRCC), 906 urothelial carcinoma of renal pelvis (UC), and 147 Wilms tumors underwent hybrid-capture based CGP to evaluate all classes of GA. 192 (4.9%) of kidney tumors featured NF2 GA which were predominantly structural variant mutations (89%), followed by copy number alterations (9%). Gender and age were similar between NF2-mutant (NF2mut) and NF2-wild type (NF2wt) cohorts with male preponderance. NF2 GA frequency was highest in cdRCC (30%), sRCC (21%), uRCC (15%), and pRCC (12%) while lowest in ccRCC (3%), UC (3%) Wilms tumor (1%), and chRCC (0%). NF2 mutational status was associated with loss of Ch 22 (P < .001). NF2mut RCC harbored co-occurring GA including CDKN2A, CDKN2B, SETD2, and BAP1. VHL, PBRM1, PTEN, and FGFR3 GA were significantly more frequent in NF2wt than in NF2mut tumors. MTOR pathway GAs were uncommon in NF2mut tumors. No NF2 mutated RCC featured MSI-high or high TMB. sRCC was associated with high PD-L1 expression. PD-L1 SP142 tumoral (P = .04) and immune cells (P = .013) were more frequent in NF2mut as compared to NF2wt group. Among histologic subtypes of RCC, cdRCC, sRCC, pRCC, and uRCC are enriched in NF2 GA. Co-occurrent GA in CDKN2A/B, SETD2, and BAP1 may represent potential therapeutic targets. Higher level of PD-L1 expression in NF2mut cohort suggests that these tumors might be sensitive to immune checkpoint inhibitor therapies.

The ubiquitin ligase Peli1 negatively regulates T cell activation and prevents autoimmunity.

T cell activation is subject to tight regulation to avoid inappropriate responses to self antigens. Here we show that genetic deficiency in the ubiquitin ligase Peli1 caused hyperactivation of T cells and rendered T cells refractory to suppression by regulatory T cells and transforming growth factor-ß (TGF-ß). As a result, Peli1-deficient mice spontaneously developed autoimmunity characterized by multiorgan inflammation and autoantibody production. Peli1 deficiency resulted in the nuclear accumulation of c-Rel, a member of the NF-κB family of transcription factors with pivotal roles in T cell activation. Peli1 negatively regulated c-Rel by mediating its Lys48 (K48) ubiquitination. Our results identify Peli1 as a critical factor in the maintenance of peripheral T cell tolerance and demonstrate a previously unknown mechanism of c-Rel regulation.

Strong non-uniformity correction algorithm based on spectral shaping statistics and LMS.

The existence of non-uniformity in infrared detector output images is a widespread problem that significantly degrades image quality. Existing scene-based non-uniformity correction algorithms typically struggle to balance strong non-uniformity correction with scene adaptability. To address this issue, we propose a novel scene-based algorithm that leverages the frequency characteristics of the non-uniformity, combine and improve single-frame stripe removal, multi-scale statistics, and least mean square (LMS) methods. Following the "coarse-to-fine" correction process, the coarse correction stage introduces an adaptive progressive correction strategy based on Laplacian pyramids. By improving 1-D guided filtering and high-pass filtering to shape high-frequency sub-bands, non-uniformity can be well separated from the scene, effectively suppressing ghosting. In the fine correction stage, we optimize the expected image estimation and spatio-temporal adaptive learning rates based on guided filtering LMS method. To validate the efficacy of our algorithm, we conduct extensive simulation and real experiments, demonstrating its adaptability to various scene conditions and its effectiveness in correcting strong non-uniformity.

Gaps in mammal conservation in China: An analysis with a framework based on minimum area requirements.

Climate change, habitat loss, and human disturbance are major threats to biodiversity. Protecting habitats plays a pivotal role in biodiversity conservation, and there is a global imperative to establish an effective system of protected areas (PAs) to implement habitat conservation and halt biodiversity decline. However, the protected patch size of habitat for a species is just as important for biodiversity conservation as the expansion of areas already under protection. In China, conservation management is often carried out based on administrative divisions. Therefore, here, an analytical conservation management framework was developed based on administrative divisions to assess whether the current network of PAs can effectively meet species' conservation needs using the minimum area requirements (MARs) of species as criteria for medium and large-sized mammals in China. This study found that the MAR of medium and large-sized mammals was larger in the northwest and smaller in the southeast, while taking the Hu line as the dividing line. Precipitation seasonality, elevation, annual mean temperature, and annual precipitation are the main environmental factors driving the distribution of a species MAR. Compared with MAR for each species, the maximum protected patch size of habitat is severely undersized in most provinces where those species primarily distribute, and this is particularly true for large carnivores and threatened species. The densely populated provinces of eastern China are particularly affected by this. The present study's framework can identify the provinces needing to expand PAs or implement other effective area-based conservation measures and habitat restoration. This analytical framework is also relevant for biodiversity conservation in different taxa and regions around the globe.

High efficient electrochemical biosensor based on exonuclease-â ¢-assisted dual-recycling amplification for ultrasensitive detection of kanamycin.

A target-triggered and exonuclease-Ⅲ-assisted strand displacement, dual-recycling amplification reaction-based biosensor was developed for the rapid, ultrasensitive and accurate detection of kanamycin. The robust profiling platform was constructed using high conductive MXene/VS2 for the electrode surface modification and high active CeCu2O4 bimetallic nanoparticles as nanozyme to improve the sensitivity as well as the catalytic signal amplification of the biosensor. Using the dual supplementary recycling of primer DNA and hairpin DNA, the electrochemical platform could accurately detect kanamycin to as low as 0.6 pM from the range of 5 pM to 5 µM. By profiling five other antibiotics, this platform exhibited high specificity, enhanced repeatability and reproducibility. Based on these intrinsic characteristics and by utilizing milk and water samples, the as-designed biosensor offers a remarkable strategy for antibiotic detection due to its favorable analytical accuracy and reliability, thereby demonstrating potential application prospect for various antibiotic biosensing in food quality control, water contamination detection and biological safety analysis.

A chromosome-scale genome sequence of sudangrass (Sorghum sudanense) highlights the genome evolution and regulation of dhurrin biosynthesis.

KEY MESSAGE: Sudangrass is more similar to US commercial sorghums than to cultivated sorghums from Africa sequence-wise and contain significantly lower dhurrin than sorghums. CYP79A1 is linked to dhurrin content in sorghum. Sudangrass [Sorghum sudanense (Piper) Stapf] is a hybrid between grain sorghum and its wild relative S. bicolor ssp. verticilliflorum and is grown as a forage crop due to its high biomass production and low dhurrin content compared to sorghum. In this study, we sequenced the sudangrass genome and showed that the assembled genome was 715.95 Mb with 35,243 protein-coding genes. Phylogenetic analysis with whole genome proteomes demonstrated that the sudangrass genome was more similar to US commercial sorghums than to its wild relatives and cultivated sorghums from Africa. We confirmed that at seedling stage, sudangrass accessions contained significantly lower dhurrin as measured by hydrocyanic acid potential (HCN-p) than cultivated sorghum accessions. Genome-wide association study identified a QTL most tightly associated with HCN-p and the linked SNPs were located in the 3' UTR of Sobic.001G012300 which encodes CYP79A1, the enzyme that catalyzes the first step of dhurrin biosynthesis. As in other grasses such as maize and rice, we also found that copia/gypsy long terminal repeat (LTR) retrotransposons were more abundant in cultivated than in wild sorghums, implying that crop domestication in the grasses was accompanied by increased copia/gypsy LTR retrotransposon insertions in the genomes.

Probing Regio- and Enantioselectivity in the Formal [2 + 2] Cycloaddition of C(1)-Alkyl Ammonium Enolates with ß- and α,ß-Substituted Trifluoromethylenones.

The isothiourea-catalyzed regio- and enantioselective formal [2 + 2] cycloaddition of C(1)-alkyl and C(1)-unsubstituted ammonium enolates with ß- and α,ß-substituted trifluoromethylenones has been developed. In all cases, preferential [2 + 2]-cycloaddition over the alternative [4 + 2]-cycloaddition is observed, giving ß-lactones with excellent diastereo- and enantioselectivity (34 examples, up to >95:5 dr, >99:1 er). The regioselectivity of the process was dictated by the nature of the substituents on both reaction components. Solely [2 + 2] cycloaddition products are observed when using α,ß-substituted trifluoromethylenones or α-trialkylsilyl acetic acid derivatives; both [2 + 2] and [4 + 2] cycloaddition products are observed when using ß-substituted trifluoromethylenones and α-alkyl-α-trialkylsilyl acetic acids as reactants, with the [2 + 2] cycloaddition as the major reaction product. The beneficial role of the α-silyl substituent within the acid component in this protocol has been demonstrated by control experiments.

Synthesis of fused quinazolinones via visible light induced cyclization of 2-aminobenzaldehydes with tetrahydroisoquinolines.

This study reports a novel method for the synthesis of fused quinazolinones by visible-light-induced cyclization of 2-aminobenzaldehydes and tetrahydroisoquinolines. The reaction is easily carried out by irradiation with a blue LED in the presence of 9-fluorenone and air. A broad substrate scope with good tolerance of functionalities was observed under the optimized reaction conditions. Moreover, using 2-aminophenone as the substrate and under similar reaction conditions, the same product was obtained when a carbon was removed. The bio-active naturally occurring alkaloid rutaecarpine could be obtained by this strategy. The success of the reaction on the gram-scale and the further transformation of the substrate demonstrated the synthetic practicability of this reaction.

Enhancing infrared imaging systems with temperature-dependent nonuniformity correction via single-frame and inter-frame structural similarity.

Temperature-dependent nonuniformity in infrared images significantly impacts image quality, necessitating effective solutions for intensity nonuniformity. Existing variational models primarily rely on gradient prior constraints from single-frame images, resulting in limitations due to insufficient exploitation of intensity characteristics in both single-frame and inter-frame images. This paper introduces what we believe to be a novel variational model for nonuniformity correction (NUC) that leverages single-frame and inter-frame structural similarity (SISB). This approach capitalizes on the structural similarities between the corrected image, intensity bias map, and degraded image, facilitating efficient suppression of intensity nonuniformity in real-world scenarios. The proposed method diverges fundamentally from existing strategies and demonstrates superior performance in comparison with state-of-the-art correction models.

"Growing fibroadenoma": Are there clinical and pathological features predicting a phyllodes tumor on surgical excision?

In cases of growth of FA on imaging, core needle biopsies (CNB) are often performed to rule out phyllodes tumor (PT). We aim to focus on "growing FAs" and to identify clinical and histopathologic features that are likely to predict a PT on excision. Thirty-four FAs with radiologic documentation of growth were included. Various clinical and pathological features such as age, body mass index (BMI), lesion size, and growth rate were recorded. On excision, 17 cases (50 %) were FAs, whereas 16 (47 %) were re-classified as benign PT despite only 19 % being suspicious for PT on CNB. PT patients were older (mean age 42.6) than those with FAs (mean age 28.2), p = 0.0002. All false negative cases demonstrated intracanalicular growth. Mitotic rate was the most significant histologic feature in PT on excision compared to others, such as lesion circumscription and stromal cellularity. Recognition and careful counting of mitotic rate, especially with intracanalicular patterns in growing FAs, can potentially prevent missing a PT on CNB. In patients with "growing FAs" who are ≥40 years of age, excision may be recommended due to the high likelihood of PT diagnosis on excision and high false negative rate on CNB.

MMR Deficiency Defines Distinct Molecular Subtype of Breast Cancer with Histone Proteomic Networks.

Mismatch repair (MMR) alterations are important prognostic and predictive biomarkers in a variety of cancer subtypes, including colorectal and endometrial. However, in breast cancer (BC), the distinction and clinical significance of MMR are largely unknown. This may be due in part to the fact that genetic alterations in MMR genes are rare and only seen to occur in around 3% of BCs. In the present study, we analyzed TCGA data using a multi-sample protein-protein interaction (PPI) analysis tool, Proteinarium, and showed a distinct separation between specific MMR-deficient and -intact networks in a cohort of 994 BC patients. In the PPI networks specific to MMR deficiency, highly connected clusters of histone genes were identified. We also found the distribution of MMR-deficient BC to be more prevalent in HER2-enriched and triple-negative (TN) BC subtypes compared to luminal BCs. We recommend defining MMR-deficient BC by next-generation sequencing (NGS) when any somatic mutation is detected in one of the seven MMR genes.

Genome-wide association mapping identifies an SNF4 ortholog that impacts biomass and sugar yield in sorghum and sugarcane.

Sorghum is a feed/industrial crop in developed countries and a staple food elsewhere in the world. This study evaluated the sorghum mini core collection for days to 50% flowering (DF), biomass, plant height (PH), soluble solid content (SSC), and juice weight (JW), and the sorghum reference set for DF and PH, in 7-12 testing environments. We also performed genome-wide association mapping with 6 094 317 and 265 500 single nucleotide polymorphism markers in the mini core collection and the reference set, respectively. In the mini core panel we identified three quantitative trait loci for DF, two for JW, one for PH, and one for biomass. In the reference set panel we identified another quantitative trait locus for PH on chromosome 6 that was also associated with biomass, DF, JW, and SSC in the mini core panel. Transgenic studies of three genes selected from the locus revealed that Sobic.006G061100 (SbSNF4-2) increased biomass, SSC, JW, and PH when overexpressed in both sorghum and sugarcane, and delayed flowering in transgenic sorghum. SbSNF4-2 encodes a γ subunit of the evolutionarily conserved AMPK/SNF1/SnRK1 heterotrimeric complexes. SbSNF4-2 and its orthologs will be valuable in genetic enhancement of biomass and sugar yield in plants.

A novel chromosome 2q24.3-q32.1 microdeletion in a fetus with multiple malformations.

BACKGROUND: Terminal or interstitial deletion of chromosome 2q is rarely reported but clinically significant, which can result in developmental malformations and psychomotor retardation in humans. In the present study, we analyzed this deletion to comprehensively clarify the relationship between phenotype and microdeletion region. METHODS: We collected clinical records of the fetus and summarized patient symptoms. Subsequently, genomic DNA was extracted from fetal tissue or peripheral blood collected from parents. In addition, whole-exome sequencing (WES) and copy number variation sequencing (CNV-seq) were performed. RESULTS: The fetus presented a previously unreported interstitial deletion of 2q24.3-q32.1. WES and CNV-seq revealed a de novo 18.46 Mb deletion at 2q24.3-q32.1, a region involving 94 protein-coding genes, including HOXD13, MAP3K20, DLX1, DLX2, SCN2A, and SCN1A. The fetus had upper and lower limb malformations, including camptodactyly and syndactyly, along with congenital cardiac defects. CONCLUSION: Herein, we report a fetus with a novel microdeletion of chromosome 2q24.3-q32.1, likely a heterozygous pathogenic variant. Haploinsufficiency of HOXD13 might be related to limb deformity in the fetus.

Heterozygous pathogenic variants in CWF19L1 in a Chinese family with spinocerebellar ataxia, autosomal recessive 17.

BACKGROUND: CWF19L1 is responsible for spinocerebellar ataxia, autosomal recessive 17, which presents with cerebellar ataxia, and atrophy. Here, we report novel compound heterozygous variants of CWF19L1 in a Chinese family with progressive ataxia and mental retardation of unknown etiology by analyzing clinical characteristics and genetic variations. METHODS: Clinical profiles and genomic DNA extracts of family members were collected. Whole-exome and Sanger sequencing were performed to detect associated genetic variants. Pathogenicity prediction and conservation analysis of the identified variants were performed using bioinformatics tools. RESULTS: We identified heterozygous variants at the invariant +2 position (c.1555_c.1557delGAG in exon 14 and c.1070G > T in exon 11) of the CWF19L1 gene. Two novel heterozygous variants of the CWF19L1 gene were identified in the CWF19L1 gene associated with autosomal recessive cerebellar ataxia. CONCLUSION: Our results suggest that CWF19L1 variants may be a novel cause of recessive ataxia with developmental delay. Whole-exome sequencing is an efficient tool for screening variants associated with the disease. This case report may help diagnose and identify the causes of other ataxias, leading to novel therapies, especially in China. This finding enriches the variant spectrum of the CWF19L1 gene and lays the foundation for future studies on the correlation between genotype and phenotype.

First report of Rhizopus oryzae causing rhizome rot on ginger in China.

Ginger (Zingiber officinale Rosc.) is a herbal plant, widely grown in China for its medicinal and culinary purposes. In July 2020, a new rhizome rot disease was observed on ginger in Laiwu, Shandong Province, China. The disease symptoms were observed on both above-ground and underground plant parts. The above ground stems and leaves becoming withered and yellow, and water-soaked symptoms were observed on the collar region. The diseased rhizomes were poorly developed with brown lesion and eventually they would rot, without offensive odors. Disease incidence was estimated at approximately 5% across the survey area. To isolate the pathogen, tissues from 30 rhizomes were cut from the border between diseased and healthy tissue, surface sterilized in 75% alcohol for 15 s, soaked in 0.1% mercuric chloride for 1 min, washed with sterile distilled water three times, and plated on potato dextrose agar (PDA) at 25°C for 2-3 days. Twenty nine fungal isolates with similar morphological characteristics were obtained and pure cultures were obtained using single spore isolation. The colony of AQJ-1, a representative isolate, on PDA was cottony, fluffy, white, and beige coloration on the reverse side at first, and subsequently many black sporangia were produced. The sporangia were black, sub-globose, and 45.2-181.7 µm (n = 50) in diameter. The sporangiospores were unequal, globose or sub-globose, about 3.2-8.7 × 4.6-12.3µm (n = 50) in diameter. For the molecular characterization, genomic DNA was extracted by modified CTAB method (Niu et al., 2008). Internal transcribed spacer (ITS) region and translation elongation factor 1-alpha (EF-1α) gene were amplified using the primer pairs ITS1/ITS4 (White et al., 1990) and MEF10/MEF4 (Abe et al., 2007), respectively. The ITS and EF-1α sequences of isolate AQJ-1 were submitted to GenBank (MN606288 and MN735220, respectively). The BLASTn analysis of the sequences showed 99%-100% similarity to the sequences of R. oryzae strain CBS 120.12 (MH854609, AB281529, respectively). Therefore, based on morphological and molecular characteristics, isolate AQJ-1 was identified as R. oryzae. For pathogenicity tests, thirty ginger seedlings (Laiwu Big Ginger) were grown for 30 days in plastic pots and removed from the pots and the rhizomes washed in running tap water. The rhizomes of fifteen ginger seedlings were attached to a 7 mm agar disk from a plate containing 2-day-old mycelium, and the other fifteen seedlings were attached to agar disk without mycelium as control. Then the inoculated and control seedlings were planted in pots and were kept in separate chambers in a greenhouse at 25±2 °C. After 14 days, the same symptoms of rhizome rot were observed in all inoculated plants as previously described, and no symptoms were observed on the control plants. The pathogen was re-isolated from symptomatic tissues, and was identified as R. oryzae, which full-filled the Koch's postulates. To our knowledge, this is the first report of R. oryzae causing rhizome rot on ginger in China. This disease may pose a potential threat to ginger production in China.