Plexin B3 guides axons to cross the midline in vivo.

During the development of neural circuits, axons are guided by a variety of molecular cues to navigate through the brain and establish precise connections with correct partners at the right time and place. Many axon guidance cues have been identified and they play pleiotropic roles in not only axon guidance but also axon fasciculation, axon pruning, and synaptogenesis as well as cell migration, angiogenesis, and bone formation. In search of receptors for Sema3E in axon guidance, we unexpectedly found that Plexin B3 is highly expressed in retinal ganglion cells of zebrafish embryos when retinal axons are crossing the midline to form the chiasm. Plexin B3 has been characterized to be related to neurodevelopmental disorders. However, the investigation of its pathological mechanisms is hampered by the lack of appropriate animal model. We provide evidence that Plexin B3 is critical for axon guidance in vivo. Plexin B3 might function as a receptor for Sema3E while Neuropilin1 could be a co-receptor. The intracellular domain of Plexin B3 is required for Semaphorin signaling transduction. Our data suggest that zebrafish could be an ideal animal model for investigating the role and mechanisms of Sema3E and Plexin B3 in vivo.

A high-throughput method for quantifying Drosophila fecundity.

Measurements of Drosophila fecundity are used in a wide variety of studies, such as investigations of stem cell biology, nutrition, behavior, and toxicology. In addition, because fecundity assays are performed on live flies, they are suitable for longitudinal studies such as investigations of aging or prolonged chemical exposure. However, standard Drosophila fecundity assays have been difficult to perform in a high-throughput manner because experimental factors such as the physiological state of the flies and environmental cues must be carefully controlled to achieve consistent results. In addition, exposing flies to a large number of different experimental conditions (such as chemical additives in the diet) and manually counting the number of eggs laid to determine the impact on fecundity is time-consuming. We have overcome these challenges by combining a new multiwell fly culture strategy with a novel 3D-printed fly transfer device to rapidly and accurately transfer flies from one plate to another; the RoboCam, a low-cost, custom built robotic camera to capture images of the wells automatically; and an image segmentation pipeline to automatically identify and quantify eggs. We show that this method is compatible with robust and consistent egg laying throughout the assay period; and demonstrate that the automated pipeline for quantifying fecundity is very accurate (r2 = 0.98 for the correlation between the automated egg counts and the ground truth) In addition, we show that this method can be used to efficiently detect the effects on fecundity induced by dietary exposure to chemicals. Taken together, this strategy substantially increases the efficiency and reproducibility of high throughput egg laying assays that require exposing flies to multiple different media conditions.

Targeting IL-12 family cytokines: A potential strategy for type 1 and type 2 diabetes mellitus.

Diabetes is a common metabolic disease characterized by an imbalance in blood glucose levels. The pathogenesis of diabetes involves the essential role of cytokines, particularly the IL-12 family cytokines. These cytokines, which have a similar structure, play multiple roles in regulating the immune response. Recent studies have emphasized the importance of IL-12 family cytokines in the development of both type 1 and type 2 diabetes mellitus. As a result, they hold promise as potential therapeutic targets for the treatment of these conditions. This review focuses on the potential of targeting IL-12 family cytokines for diabetes therapy based on their roles in the pathogenesis of both types of diabetes. We have summarized various therapies that target IL-12 family cytokines, including drug therapy, combination therapy, cell therapy, gene therapy, cytokine engineering therapy, and gut microbiota modulation. By analyzing the advantages and disadvantages of these therapies, we have evaluated their feasibility for clinical application and proposed possible solutions to overcome any challenges. In conclusion, targeting IL-12 family cytokines for diabetes therapy provides updated insights into their potential benefits, such as controlling inflammation, preserving islet ß cells, reversing the onset of diabetes, and impeding the development of diabetic complications.

First Report of Apiospora arundinis Causing Leaf Spot on Polygonatum cyrtonema Hua in China.

Polygonatum cyrtonema Hua, which is a perennial herb of Liliaceae, can be used as clinical Chinese medicine for treating diabetes and asthma. It is widely cultivated in China, with 700 ha planted in Tonggu County, Jiangxi province (Chen et al. 2022). In June 2022, leaf spot symptoms were observed on P. cyrtonema in Tonggu county (28°71'42″N, 114°56'19″E), and the disease incidence was estimated to be above 35%. In the early stages of infection, small brown spots appear on the edge or tip of the leaves. As the lesion matures, the spots gradually expand to form wedge-shaped or elliptic to irregular lesions with brown edges and yellow halos. To identify the pathogen species, leaf pieces (5 × 5 mm) from the lesion borders were surface sterilized in 75% ethanol for 30 s, followed by 2% NaClO for 2 min, then rinsed with sterile distilled water for 3 times and dried with sterile filter paper. The tissues were placed on potato dextrose agar (PDA) and incubated at 25°C. Pure cultures were obtained by monosporic isolation, and the representative isolates, HJYB2-1, HJYB2-2 were used for morphological studies and phylogenetic analyses. Colonies on PDA of the two isolates were white with fluffy aerial mycelia. The hyphae were smooth, hyaline, and branched. The conidiophores were hyaline or pale brown and produced conidiogenous cells. The conidiogenous cells were pale brown, smooth, and ampulliform, 5.8-11.7 × 3.0-4.9 µm (n=50). The conidia were brown, smooth, and ellipsoidal to spherical, 4.7-7.3 × 2.3-4.5 µm (n=50). Morphological features were similar to Apiospora arundinis species complex (Crous et al. 2013, Pintos et al. 2021). For molecular identification, the ITS, TUB2 and TEF 1-α genes were amplified with the primer pairs ITS1/ITS4, T1/Bt-2b and EF1-728F/EF-2 (White et al. 1990), respectively. The generated sequences were deposited in GenBank with accession numbers OR229623, OR229624 (ITS), OR260104, OR260105 (TUB2), and OR290789, OR290790 (TEF1-α). Maximum likelihood and Bayesian posterior probability analyses using IQtree v. 1.6.8 and Mr. Bayes v. 3.2.6 with the concatenated sequences placed HJYB2-1 and HJYB2-2 in the clade of A. arundinis. The two isolates were identified as A. arundinis based on morphological and multilocus phylogenetic analyses. For pathogenicity testing, healthy leaves of six P. cyrtonema plants (five leaves each, n=30) in the field were pin-pricked with a sterile needle and inoculated with 100 µL spore suspension on the wound (1×106 conidia per mL). Healthy leaves of another three P. cyrtonema plants (five leaves each, n=15) in the field were pin-pricked with a sterile needle, inoculated with sterile distilled water and served as the control. All the inoculated leaves were covered with plastic bags to keep a high-humidity environment with a temperature of about 28℃. The test was repeated three times. More than 90% of inoculated leaves showed similar symptoms to those observed in the field, whereas control leaves were asymptomatic for 7 days. Apiospora arundinis was reisolated from the leaf lesions on the inoculated plants. No pathogenic fungus was isolated from the control leaves. A. arundinis has been reported causing disease on Camellia sinensis (Thangaraj et al. 2019), Prunus persica (Ji et al. 2020), Saccharum officinarum (Liao et al. 2022) but has not previously been reported causing disease on P. cyrtonema. To our knowledge, this is the first report that A. arundinis can cause leaf spot on P. cyrtonema in China. Our result should help with future monitoring and control of this disease.

First Report of Polygonatum cyrtonema Hua Root Rot Caused by Trichoderma virens in China.

Polygonatum cyrtonema Hua is a traditional Chinese medicine, which has anti-oxidant, anti-inflammatory, immunomodulatory, and other pharmacological effects (Lu et al. 2023). In June 2022, A disease of root rot was observed on P. cyrtonema plants in Tonggu County (28°63'89″N, 114°48'07″E), Jiangxi Province, China. The disease incidence was approximately 30% in a surveyed area of 3 hectares, which contained approximately 20,000 plants. Initially, the above-ground parts of the plants did not show any obvious symptoms. However, the underground roots exhibited red-brown spots that gradually expanded and sunken areas appeared, and the diseased plants presented leaf chlorosis and red-brown discoloration of the tubers, eventually leading to plant death. To identify the pathogen, symptomatic root tissues (0.5×0.5×0.5cm) from the lesion margin surface were sterilized with 75% ethanol for 30s, 3% NaClO for 3 min followed by rinsing three times with sterile water. The sterile root pieces were placed on potato dextrose agar (PDA) and incubated at 25℃. Thirteen pure fungal isolates with the same morphological characteristics were obtained by monosporic isolation from 20 pieces of roots, and the representative isolates, HJGF1-1, HJGF1-2 were used for morphological studies and phylogenetic analyses. Initially, the two colonies on PDA appeared white with cotton-shaped aerial hyphae, which later turned light green to green and formed concentric rings. At the end of the conidiophores, 3 to 6 pear-shaped branches are irregularly gathered, and the angles between the branches are acute. The conidia were mostly solitary ellipsoid or obovate with the size of (3.7-5.9) × (3.6-4.5) µm (n=100). These morphological characteristics are consistent with the description of a Trichoderma spp. (Kamala et al. 2015). For molecular identification, the internal transcribed spacer (ITS), translation elongation factor 1-alpha (TEF-1α) and RNA polymerase II second largest subunit (RPB2) sequences were PCR amplified using primer pairs of ITS1/ITS4 (White et al. 1990), EF1-728F/EF1-986R (Carbone et al. 1999), and RPB2-5F2/RPB2-7cR (O'Donnell et al. 2022), respectively. BLAST analysis showed that the ITS, TEF-1α and RPB2 sequences of isolates HJGF1-1 (GenBank accession nos. OR229621, OR290791, OR334600) and HJGF1-2 (GenBank accession nos. OR229622, OR290792, OR334600) showed 99%-100% identity with multiple GenBank sequences of Trichoderma virens. A phylogenetic tree based on concatenated sequences of ITS, TEF-1α and RPB2 using maximum-likelihood analyses revealed that the two isolates HJGF1-1 and HJGF1-2 were in the same clade with T. virens strains. The two isolates were identified as T. virens based on the morphological characteristics and molecular phylogeny. To test pathogenicity, ten healthy P. cyrtonema plants (one tuber each, 5 tubers per isolate, n=10) in the field were pin-pricked with a sterile needle and pour-inoculated with 5 mL spore suspension per tuber (1× 107 conidia/ mL) with a temperature of about 28℃. Another five tubers were were pin-pricked with a sterile needle, inoculated with sterile water and served as controls. The resulting symptoms were similar to those on the original infected plants in the field, and control tubers remained symptomless fourteen days after inoculation. T. virens was reisolated from the diseased tubers, nevertheless no pathogenic fungus was isolated from the control tubers. T. virens has been reported causing disease on tulip bulb (Lou et al. 2003) but has not previously been reported causing disease on P. cyrtonema. Although several species of Trichoderma are known to be beneficial microorganisms, the beneficial fungus may have had an evolutionary period of interaction with plants in which it behaved as a plant pathogen (Poveda et al. 2022). To our knowledge, this is the first report of T. virens infecting P. cyrtonema in China. This result may expanded the etiological study of T. virens and the control strategy of P. cyrtonema root rot.

Diagnostic and therapeutic effects of fluorescence cystoscopy and narrow-band imaging in bladder cancer: a systematic review and network meta-analysis.

BACKGROUND: This review aims to compare the efficacies of fluorescence cystoscopy, narrow-band imaging (NBI), and white light cystoscopy in the treatment and diagnosis of bladder cancer. METHODS: The authors searched PubMed, EMbase, Web of Science, and the Cochrane Library from January 1990 to April 2022. A total of 26 randomized controlled studies and 22 prospective single-arm studies were selected. Most patients had nonmuscle-invasive bladder cancer. The study protocol has been registered at PROSPERO. RESULTS: In the pairwise meta-analysis, 5-aminolevulinic acid (5-ALA) reduced the short-term and long-term recurrence rates of bladder cancer compared with white light cystoscopy (WLC); however, no statistical difference was observed in intermediate-term recurrence rates (RR=0.79, 95% CI: 0.57-1.09). Hexaminolevulinic acid and NBI reduced short-term, intermediate-term, and long-term recurrence rates. The sensitivity of 5-ALA, hexaminolevulinic acid, NBI, and WLC for bladder cancer were 0.89 (95% CI: 0.81-0.94), 0.96 (95% CI: 0.92-0.98), 0.96 (95% CI: 0.92-0.98), and 0.75 (95% CI: 0.70-0.79), respectively; however, only NBI had the same specificity as WLC (0.74 vs. 0.74). Compared with WLC, 5-ALA improved the detection rate of carcinoma in situ and Ta stage bladder cancer but had no advantage in T1 stage tumors (OR=2.39, 95% CI:0.79-7.19). Hexaminolevulinic acid and NBI improved the detection rates of all nonmuscular-invasive bladder cancers. In the network meta-analysis, there was no significant difference in either recurrence or detection rates between 5-ALA, hexaminolevulinic acid, and NBI. CONCLUSION: Fluorescence cystoscopy and NBI are advantageous for treating and diagnosing patients with nonmuscle-invasive bladder cancer.

Listening to plant's Esperanto via root exudates: reprogramming the functional expression of plant growth-promoting rhizobacteria.

Rhizomicrobiome plays important roles in plant growth and health, contributing to the sustainable development of agriculture. Plants recruit and assemble the rhizomicrobiome to satisfy their functional requirements, which is widely recognized as the 'cry for help' theory, but the intrinsic mechanisms are still limited. In this study, we revealed a novel mechanism by which plants reprogram the functional expression of inhabited rhizobacteria, in addition to the de novo recruitment of soil microbes, to satisfy different functional requirements as plants grow. This might be an efficient and low-cost strategy and a substantial extension to the rhizomicrobiome recruitment theory. We found that the plant regulated the sequential expression of genes related to biocontrol and plant growth promotion in two well-studied rhizobacteria Bacillus velezensis SQR9 and Pseudomonas protegens CHA0 through root exudate succession across the plant developmental stages. Sixteen key chemicals in root exudates were identified to significantly regulate the rhizobacterial functional gene expression by high-throughput qPCR. This study not only deepens our understanding of the interaction between the plant-rhizosphere microbiome, but also provides a novel strategy to regulate and balance the different functional expression of the rhizomicrobiome to improve plant health and growth.

The Relationship Between Systemic Immune Inflammatory Index and Prognosis of Patients With Non-Small Cell Lung Cancer: A Meta-Analysis and Systematic Review.

Background: The relationship between systemic immune inflammation index (SII) and the prognosis of cancer has always been a subject of intense interest. However, the prognostic value of SII in non-small cell lung cancer (NSCLC) patients remains a controversial topic. Objective: To evaluate the effect of SII index on prognosis of NSCLC. Methods: We conducted a comprehensive search of PubMed, EMBASE, and the Cochrane Library databases to determine correlation between SII index, clinicopathological features, overall survival (OS), and progression-free survival (PFS). Odds ratio (ORs) and 95% confidence interval (CIs) were used to assess the connection between SII and clinicopathological parameters, and HRs and 95% CIs were used to assess the connection between SII and survival. Results: Seventeen studies with 8,877 cases were included in the analysis. Compared with NSCLC patients with low SII level, patients with NSCLC with high SII level had a poor OS (HR = 1.75, 95% CI, 1.50-2.00; P < 0.001) and had a poor PFS (HR = 1.61, 95% CI, 1.25-1.96; P < 0.001). In addition, patients with higher pathological stage (II-III) had higher SII levels (OR = 2.32, 95% CI, 2.06-2.62; P < 0.001). Conclusions: The SII index is a promising prognostic biomarker for NSCLC and may help clinicians choose appropriate NSCLC treatments.

DNAJC5 promotes hepatocellular carcinoma cells proliferation though regulating SKP2 mediated p27 degradation.

DNAJC5 (DnaJ heat shock protein family (Hsp40) member C5), also known as cysteine tandem protein (CSPα), is important for maintaining the normal function of nerve tissues, but its oncogenic function remains unknown. Here, we report a unique mechanism underlying the oncogenic function of DNAJC5. DNAJC5 protein expression is highly detectable in human hepatocellular carcinoma (HCC) tissues and is strongly related to a poor prognosis among HCC patients. DNAJC5 overexpression promotes HCC cell proliferation and reduced the ratio of cells in G1 phase of the cell cycle. Furthermore, DNAJC5 interacts with SKP2 and enhances the degradation of p27 (a cyclin-dependent kinase inhibitor1B) by promoting formation of the SKP2-p27 complex. In contrast, DNAJC5 knockdown rescues the SKP2-mediated decrease in p27 protein levels. These results reveal that the DNAJC5-SKP2-p27 pathway is a novel mechanism for the oncogenic function of DNAJC5 in HCC.

The seasonal development dynamics of the yak hair cycle transcriptome.

BACKGROUND: Mammalian hair play an important role in mammals' ability to adapt to changing climatic environments. The seasonal circulation of yak hair helps them adapt to high altitude but the regulation mechanisms of the proliferation and differentiation of hair follicles (HFs) cells during development are still unknown. Here, using time series data for transcriptome and hormone contents, we systematically analyzed the mechanism regulating the periodic expression of hair development in the yak and reviewed how different combinations of genetic pathways regulate HFs development and cycling. RESULTS: This study used high-throughput RNA sequencing to provide a detailed description of global gene expression in 15 samples from five developmental time points during the yak hair cycle. According to clustering analysis, we found that these 15 samples could be significantly grouped into three phases, which represent different developmental periods in the hair cycle. A total of 2316 genes were identified in these three consecutive developmental periods and their expression patterns could be divided into 9 clusters. In the anagen, genes involved in activating hair follicle growth are highly expressed, such as the WNT pathway, FGF pathway, and some genes related to hair follicle differentiation. In the catagen, genes that inhibit differentiation and promote hair follicle cell apoptosis are highly expressed, such as BMP4, and Wise. In the telogen, genes that inhibit hair follicle activity are highly expressed, such as DKK1 and BMP1. Through co-expression analysis, we revealed a number of modular hub genes highly associated with hormones, such as SLF2, BOP1 and DPP8. They may play unique roles in hormonal regulation of events associated with the hair cycle. CONCLUSIONS: Our results revealed the expression pattern and molecular mechanisms of the seasonal hair cycle in the yak. The findings will be valuable in further understanding the alpine adaptation mechanism in the yak, which is important in order to make full use of yak hair resources and promote the economic development of pastoral plateau areas.

The N-terminal domain of the non-receptor tyrosine kinase ABL confers protein instability and suppresses tumorigenesis.

Chromosome translocation can lead to chimeric proteins that may become oncogenic drivers. A classic example is the fusion of the BCR activator of RhoGEF and GTPase and the ABL proto-oncogene nonreceptor tyrosine kinase, a result of a chromosome abnormality (Philadelphia chromosome) that causes leukemia. To unravel the mechanism underlying BCR-ABL-mediated tumorigenesis, here we compared the stability of ABL and the BCR-ABL fusion. Using protein degradation, cell proliferation, 5-ethynyl-2-deoxyuridine, and apoptosis assays, along with xenograft tumor analysis, we found that the N-terminal segment of ABL, which is lost in the BCR-ABL fusion, confers degradation capacity that is promoted by SMAD-specific E3 ubiquitin protein ligase 1. We further demonstrate that the N-terminal deletion renders ABL more stable and stimulates cell growth and tumorigenesis. The findings of our study suggest that altered protein stability may contribute to chromosome translocation-induced cancer development.

The sequence and de novo assembly of the wild yak genome.

Vulnerable populations of wild yak (Bos mutus), the wild ancestral species of domestic yak, survive in extremely cold, harsh and oxygen-poor regions of the Qinghai-Tibetan Plateau (QTP) and adjacent high-altitude regions. In this study, we sequenced and assembled its genome de novo. In total, six different insert-size libraries were sequenced, and 662 Gb of clean data were generated. The assembled wild yak genome is 2.83 Gb in length, with an N50 contig size of 63.2 kb and a scaffold size of 16.3 Mb. BUSCO assessment indicated that 93.8% of the highly conserved mammal genes were completely present in the genome assembly. Annotation of the wild yak genome assembly identified 1.41 Gb (49.65%) of repetitive sequences and a total of 22,910 protein-coding genes, including 20,660 (90.18%) annotated with functional terms. This first construction of the wild yak genome provides a variable genetic resource that will facilitate further study of the genetic diversity of bovine species and accelerate yak breeding efforts.