An induced mutation of ABC-transporter component VraF(K84E) contributes to vancomycin resistance and virulence in Staphylococcus aureus strain MW2.

Staphylococcus aureus is a notorious pathogen responsible for various severe diseases. Due to the emergence of drug-resistant strains, the prevention and treatment of S. aureus infections have become increasingly challenging. Vancomycin is considered to be one of the last-resort drugs for treating most methicillin-resistant S. aureus (MRSA), so it is of great significance to further reveal the mechanism of vancomycin resistance. VraFG is one of the few important ABC (ATP-binding cassette) transporters in S. aureus that can form TCS (two-component systems)/ABC transporter modules. ABC transporters can couple the energy released from ATP hydrolysis to translocate solutes across the cell membrane. In this study, we obtained a strain with decreased vancomycin susceptibility after serial passaging and selection. Subsequently, whole-genome sequencing was performed on this laboratory-derived strain MWA2 and a novel single point mutation was discovered in vraF gene, leading to decreased sensitivity to vancomycin and daptomycin. Furthermore, the mutation reduces autolysis of S. aureus and downregulates the expression of lytM, isaA, and atlA. Additionally, we observed that the mutant has a less net negative surface charge than wild-type strain. We also noted an increase in the expression of the dlt operon and mprF gene, which are associated with cell surface charge and serve to hinder the binding of cationic peptides by promoting electrostatic repulsion. Moreover, this mutation has been shown to enhance hemolytic activity, expand subcutaneous abscesses, reflecting an increased virulence. This study confirms the impact of a point mutation of VraF on S. aureus antibiotic resistance and virulence, contributing to a broader understanding of ABC transporter function and providing new targets for treating S. aureus infections.

The role of regulatory T cells in vitiligo and therapeutic advances: a mini-review.

BACKGROUND: Regulatory T cells (Tregs) play vital roles in controlling immune reactions and maintaining immune tolerance in the body. The targeted destruction of epidermal melanocytes by activated CD8+T cells is a key event in the development of vitiligo. However, Tregs may exert immunosuppressive effects on CD8+T cells, which could be beneficial in treating vitiligo. METHODS: A comprehensive search of PubMed and Web of Science was conducted to gather information on Tregs and vitiligo. RESULTS: In vitiligo, there is a decrease in Treg numbers and impaired Treg functions, along with potential damage to Treg-related signaling pathways. Increasing Treg numbers and enhancing Treg function could lead to immunosuppressive effects on CD8+T cells. Recent research progress on Tregs in vitiligo has been summarized, highlighting various Treg-related therapies being investigated for clinical use. The current status of Treg-related therapeutic strategies and potential future directions for vitiligo treatment are also discussed. CONCLUSIONS: A deeper understanding of Tregs will be crucial for advancing Treg-related drug discovery and treatment development in vitiligo.

Genetic Variability of CYP4F2, CYP2D6, CYP2E1, and ACE in the Chinese Yi Population.

Genetic polymorphisms of very important pharmacogenes (VIP) are a significant factor contributing to inter-individual variability in drug therapy. The purpose of this study was to identify significantly different loci in the Yi population and to enrich their pharmacogenomic information. 54 VIP variants were selected from the Pharmacogenomics Knowledge Base (PharmGKB) and genotyped in 200 Yi individuals. Then, we compared their genotype distribution between the Yi population and the other 26 populations using the χ2 test. Compared with the other 26 populations, the genotype frequencies of 4 single nucleotide polymorphisms (SNPs), rs2108622 (CYP4F2), rs1065852 (CYP2D6), rs2070676 (CYP2E1), and rs4291 (ACE), had significant differences in the Yi population. For example, the TT genotype frequency of rs2108622 (8.1%) was higher than that of African populations, and the AA genotype frequency of rs1065852 (27.3%) was higher than that of other populations except East Asians. We also found that the Yi populations differed the least from East Asians and the most from Africans. Furthermore, the differences in these variants might be related to the effectiveness and toxicity risk of using warfarin, iloperidone, cisplatin cyclophosphamide, and other drugs in the Yi population. Our data complement the pharmacogenomic information of the Yi population and provide theoretical guidance for their personalized treatment.

Tumor-specific enhanced NIR-II photoacoustic imaging via photothermal and low-pH coactivated AuNR@PNIPAM-VAA nanogel.

BACKGROUND: Properly designed second near-infrared (NIR-II) nanoplatform that is responsive tumor microenvironment can intelligently distinguish between normal and cancerous tissues to achieve better targeting efficiency. Conventional photoacoustic nanoprobes are always "on", and tumor microenvironment-responsive nanoprobe can minimize the influence of endogenous chromophore background signals. Therefore, the development of nanoprobe that can respond to internal tumor microenvironment and external stimulus shows great application potential for the photoacoustic diagnosis of tumor. RESULTS: In this work, a low-pH-triggered thermal-responsive volume phase transition nanogel gold nanorod@poly(n-isopropylacrylamide)-vinyl acetic acid (AuNR@PNIPAM-VAA) was constructed for photoacoustic detection of tumor. Via an external near-infrared photothermal switch, the absorption of AuNR@PNIPAM-VAA nanogel in the tumor microenvironment can be dynamically regulated, so that AuNR@PNIPAM-VAA nanogel produces switchable photoacoustic signals in the NIR-II window for tumor-specific enhanced photoacoustic imaging. In vitro results show that at pH 5.8, the absorption and photoacoustic signal amplitude of AuNR@PNIPAM-VAA nanogel in NIR-II increases up obviously after photothermal modulating, while they remain slightly change at pH 7.4. Quantitative calculation presents that photoacoustic signal amplitude of AuNR@PNIPAM-VAA nanogel at 1064 nm has ~ 1.6 folds enhancement as temperature increases from 37.5 °C to 45 °C in simulative tumor microenvironment. In vivo results show that the prepared AuNR@PNIPAM-VAA nanogel can achieve enhanced NIR-II photoacoustic imaging for selective tumor detection through dynamically responding to thermal field, which can be precisely controlled by external light. CONCLUSIONS: This work will offer a viable strategy for the tumor-specific photoacoustic imaging using NIR light to regulate the thermal field and target the low pH tumor microenvironment, which is expected to realize accurate and dynamic monitoring of tumor diagnosis and treatment.

A novel insight of degradation ibuprofen in aqueous by catalytic ozonation with supported catalyst: Supports effect on ozone mass transfer.

Catalytic ozonation is an effective wastewater purification process. However, the low ozone mass transfer in packed bubble columns leads to low ozone utilization efficiency (OUE), poor organic degradation performance, and high energy consumption. Therefore, there is an urgent need to develop efficient supported catalysts that can enhance mass transfer and performance. However, the reaction mechanism of the support on ozone mass transfer remains unclear, which hinders the development of catalytic ozonation applications. In this study, lava rocks (LR)-supported catalysts, specifically CuMn2O4@LR and MnO2Co3O4@LR, were proposed for catalytic ozonation of IBP degradation due to their superior catalytic activity, stability, and high OUE. Addition of CuMn2O4@LR or MnO2Co3O4@LR increased IBP removal efficiency from 85% to 91% or 88%, and reduced energy consumption from 2.86 to 2.14 kWh/m3 or 2.60 kWh/m3, respectively. This improvement was attributed to LR-supported catalysts enhancing mass transfer and promoting O3 decomposition to generate •OH and •O2-, leading to IBP degradation. Furthermore, this study investigated the effects of ozone dose, supporter sizes, and catalyst components on ozone-liquid mass transfer. The results revealed that the size of the supporter influenced stacked porosity and consequently affected ozone mass transfer. Larger-sized LR (kLa= 0.172 min-1) exhibited better mass transfer compared to smaller-sized supports. Based on these findings, it was concluded that both CuMn2O4@LR and MnO2Co3O4@LR are potential catalysts for catalytic ozonation in residual IBP degradation of pharmaceutical wastewater, and LR showed good credibility as a catalyst supporter. Understanding the effects of supporters and active components on ozone mass transfer provides a fundamental principle for designing supported catalysts in catalytic ozonation applications.

The Therapeutic Effects of Baicalein on the Hepatopulmonary Syndrome in the Rat Model of Chronic Common Bile Duct Ligation.

Background and Aims: Hepatopulmonary syndrome (HPS) is characterized by arterial oxygenation defects due to pulmonary vascular dilation in liver disease. To date, liver transplantation remains the only effective treatment for HPS. This study aimed to explore the preventative role of baicalein in HPS development. Methods: Sixty male rats were randomly assigned to three groups: sham, common bile duct ligation (CBDL), and baicalein, receiving intraperitoneal injections of baicalein (40 mg·kg-1·d-1, diluted in saline) for 21 days. Survival rate, liver and kidney function, and bile acid metabolism levels were evaluated. Liver and lung angiogenesis and hepatic glycogen staining were assessed, and the expression of relevant proteins was evaluated by immunohistochemistry. Results: Baicalein improved survival rates and hypoxemia in rats post-CBDL, reducing angiogenic protein levels and enhancing glucose homeostasis. Compared to the untreated group, baicalein suppressed the expression of vascular endothelial growth factor, placental growth factors, matrix metalloprotease 9 and C-X-C motif chemokine 2, and it increased the expression of glycemic regulatory proteins, including dipeptidyl peptidase-4, sirtuin 1, peroxisome proliferator-activated receptor gamma co-activator 1α, and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3. Conclusion: Baicalein significantly improves hepatic function and hypoxia in HPS rats by attenuating pathological angiogenesis in the liver and lungs, showing promise as a treatment for HPS.

Enhancing Orbital Interaction in Spinel LiNi0.5Mn1.5O4 Cathode for High-Voltage and High-Rate Li-Ion Batteries.

High voltage cobalt-free spinel LiNi0.5Mn1.5O4 (LNMO) is well organized as a high-power cathode material for lithium (Li)-ion batteries, however, the weak interaction between the 3d orbital of the transition metal (TM) ions and the 2p orbital of oxygen (O) leads to the instability of crystal structural, hindering the long-term stable cycling of LNMO cathode especially at high temperatures. Here, a design strategy of orbital interaction is initiated to strengthen TM 3d-O 2p framework in P-doped LNMO (P-LNMO) by choosing phytic acid as P dopant, which can realize more uniform doping compared to regular phosphate. The results show that the enhancement of TM 3d-O 2p orbital interaction in P-LNMO can suppress the Jahn-Teller effect and subsequent dissolution of Mn, as well as lowers the energy barrier for Li ion insertion/extraction kinetics. As a result, superior electrochemical performances including high discharge capacity, stable cycling behavior and enhanced rate capability of P-LNMO are obtained. Significantly, the P-LNMO pouch cell shows great cycling stability with 97.4% capacity retention after 100 cycles.

Predicting Survival Using Whole-Liver MRI Radiomics in Patients with Hepatocellular Carcinoma After TACE Refractoriness.

PURPOSE: To develop a model based on whole-liver radiomics features of pre-treatment enhanced MRI for predicting the prognosis of hepatocellular carcinoma (HCC) patients undergoing continued transarterial chemoembolization (TACE) after TACE-resistance. MATERIALS AND METHODS: Data from 111 TACE-resistant HCC patients between January 2014 and March 2018 were retrospectively collected. At a ratio of 7:3, patients were randomly assigned to developing and validation cohorts. The whole-liver were manually segmented, and the radiomics signature was extracted. The tumor and liver radiomics score (TLrad-score) was calculated. Models were trained by machine learning algorithms and their predictive efficacies were compared. RESULTS: Tumor stage, tumor burden, body mass index, alpha-fetoprotein, and vascular invasion were revealed as independent risk factors for survival. The model trained by Random Forest algorithms based on tumor burden, whole-liver radiomics signature, and clinical features had the highest predictive efficacy, with c-index values of 0.85 and 0.80 and areas under the ROC curve of 0.96 and 0.83 in the developing cohort and validation cohort, respectively. In the high-rad-score group (TLrad-score > - 0.34), the median overall survival (mOS) was significantly shorter than in the low-rad-score group (17 m vs. 37 m, p < 0.001). A shorter mOS was observed in patients with high tumor burden compared to those with low tumor burden (14 m vs. 29 m, p = 0.007). CONCLUSION: The combined radiomics model from whole-liver signatures may effectively predict survival for HCC patients continuing TACE after TACE refractoriness. The TLrad-score and tumor burden are potential prognostic markers for TACE therapy following TACE-resistance.

All-Silicon Polarization-Insensitive Metamaterial Absorber in the Terahertz Range.

All-silicon terahertz absorbers have attracted considerable interest. We present a design and numerical study of an all-silicon polarization-insensitive terahertz metamaterial absorber. The meta-atoms of the metamaterial absorber are square silicon rings which can be viewed as gratings. By properly optimizing the structure of the meta-atom, we achieve a broadband absorptivity that is above 90% ranging from 0.77 THz to 2.53 THz, with a relative bandwidth of 106.7%. Impedance matching reduces the reflection of the terahertz waves and the (0, ±1)-order diffraction induce the strong absorption. The absorption of this absorber is insensitive to the polarization of the terahertz wave and has a large incident angle tolerance of up to 60 degrees. The all-silicon metamaterial absorber proposed here provides an effective way to obtain broadband absorption in the terahertz regime. Metamaterial absorbers have outstanding applications in terahertz communication and imaging.

Can artemisinin and its derivatives treat malaria in a host-directed manner?

Malaria is caused by an apicomplexan protozoan parasite, Plasmodium, and is transmitted through vectors. It remains a substantial health burden, especially in developing countries, leading to significant socioeconomic losses. Although the World Health Organization (WHO) has approved various antimalarial medications in the past two decades, the increasing resistance to these medications has worsened the situation. The development of drug resistance stems from genetic diversity among Plasmodium strains, impeding eradication efforts. Consequently, exploring innovative technologies and strategies for developing effective medications based on the host is crucial. Artemisinin and its derivatives (artemisinins) have been recommended by the WHO for treating malaria owing to their known effectiveness in killing the parasite. However, their potential to target the host for malaria treatment has not been investigated. This article concisely reviews the application of host-directed therapeutics, potential drug candidates targeting the host for treating malaria, and usage of artemisinins in numerous diseases. It underscores the importance of host-directed interventions for individuals susceptible to malaria, suggests the potential utility of artemisinins in host-directed malaria treatments, and posits that the modulation of host proteins with artemisinins may offer a means of intervening in host-parasite interactions. Further studies focusing on the host-targeting perspective of artemisinins can provide new insights into the mechanisms of artemisinin resistance and offer a unique opportunity for new antimalarial drug discovery.

Clinical value of neutrophil to lymphocyte ratio and ultrasonic parameters in the diagnosis of bladder outlet obstruction in benign prostatic hyperplasia.

AIM: This study aimed to investigate the clinical significance of neutrophil-to-lymphocyte ratio and ultrasonic parameters in diagnosing bladder outlet obstruction in patients with benign prostatic hyperplasia. MATERIAL: Between September 2022 and January 2024, a total of 106 patients with benign prostatic hyperplasia were collected from Hongqi Hospital affiliated to Mudanjiang Medical University followed by urodynamic testing. The patients were categorized into three groups based on the International Prostate Symptom Score: mild (45 cases), moderate (36 cases), and severe (25 cases). Thirty-five healthy men were recruited at the hospital as a control group. All patients had blood tests and ultrasound scans. RESULTS: Neutrophil-to-lymphocyte ratio, detrusor wall thickness, detrusor muscle elastic modulus, internal gland elastic modulus, intravesical prostatic protrusion, and post-voiding residual volume were significantly correlated with the bladder outlet obstruction stage and showed good diagnostic efficiency（all P＜0.05）. There was no statistically significant difference observed in the external gland elastic modulus between the experimental group and the control group (P>0.05). CONCLUSIONS: The neutrophil-to-lymphocyte ratio, detrusor wall thickness, elastic modulus of the detrusor and glandular gland may hold clinical significance for diagnosing bladder outlet obstruction resulting from benign prostatic hyperplasia.

Clinical, pathological, and molecular features of central nervous system tumors with BCOR internal tandem duplication.

Central nervous system tumor with BCOR internal tandem duplication (CNS tumor with BCOR-ITD) constitutes a molecularly distinct entity, characterized by internal tandem duplication within exon 15 of the BCOR transcriptional co-repressor gene (BCOR-ITD). The current study aimed to elucidate the clinical, pathological, and molecular attributes of CNS tumors with BCOR-ITD and explore their putative cellular origin. This study cohort comprised four pediatric cases, aged 23 months to 13 years at initial presentation. Magnetic resonance imaging revealed large, well-circumscribed intra-CNS masses localized heterogeneously throughout the CNS. Microscopically, tumors were composed of spindle to ovoid cells, exhibiting perivascular pseudorosettes and palisading necrosis, but lacking microvascular proliferation. Immunohistochemical staining showed diffuse tumor cell expression of BCOR, CD56, CD99, vimentin, and the stem cell markers PAX6, SOX2, CD133 and Nestin, alongside focal positivity for Olig-2, S100, SOX10, Syn and NeuN. Molecularly, all cases harbored BCOR-ITDs ranging from 87 to 119 base pairs in length, including one case with two distinct ITDs. Notably, the ITDs were interrupted by unique 1-3 bp insertions in all cases. In summary, CNS tumors with BCOR-ITD exhibit characteristic clinical, pathological, and molecular features detectable through BCOR immunohistochemistry and confirmatory molecular analyses. Their expression of stem cell markers raises the possibility of an origin from neuroepithelial stem cells rather than representing true embryonal neoplasms.

Zeolitic imidazolate framework-encapsulated zinc porphyrin photoresponsive nanozyme for colorimetric/fluorescent dual-mode sensing of glyphosate.

A novel zeolitic imidazolate framework-encapsulated zinc porphyrin (ZnTCPP@ZIF-90) photoresponsive nanozyme is proposed for the colorimetric/fluorescent dual-mode visual sensing of glyphosate (Gly). ZnTCPP@ZIF-90 exhibits photoresponsive oxidase-like activity and fluorescence quenching behavior. Meanwhile, the outer ZIF-90 layer can be selectively destroyed by Gly, causing the release of free ZnTCPP, resulting in the enhanced enzyme-like activity as well as fluorescence emission. The constructed ZnTCPP@ZIF-90 was successfully used for the colorimetric/fluorescent dual-mode detection of Gly. Additionally, the colorimetric and fluorescent images information captured by the smartphone were converted to color intensity (HSV/RGB values), with limits of detection of 0.27 µg/mL and 0.19 µg/mL, respectively. The proposed dual-mode sensor exhibits excellent selectivity and reliability for detecting Gly, and can be successfully applied to the analysis of real samples such as tap water, lake water, and fruit washing water. The current research efforts are expected to provide new perspectives for designing highly active photoresponsive nanozymes and their stimuli-responsive sensing systems, paving the way for their applications in portable dual-mode chemical sensing and environmental monitoring.

Astrocyte atrophy induced by L-PGDS/PGD2/Src signaling dysfunction in the central amygdala mediates postpartum depression.

BACKGROUND: Postpartum depression (PPD) is a serious psychiatric disorder that has significantly adverse impacts on maternal health. Metabolic abnormalities in the brain are associated with numerous neurological disorders, yet the specific metabolic signaling pathways and brain regions involved in PPD remain unelucidated. METHODS: We performed behavioral test in the virgin and postpartum mice. We used mass spectrometry imaging (MSI) and targeted metabolomics analyses to investigate the metabolic alternation in the brain of GABAAR Delta-subunit-deficient (Gabrd-/-) postpartum mice, a specific preclinical animal model of PPD. Next, we performed mechanism studies including qPCR, Western blot, immunofluorescence staining, electron microscopy and primary astrocyte culture. In the specific knockdown and rescue experiments, we injected the adeno-associated virus into the central amygdala (CeA) of female mice. RESULTS: We identified that prostaglandin D2 (PGD2) downregulation in the CeA was the most outstanding alternation in PPD, and then validated that lipocalin-type prostaglandin D synthase (L-PGDS)/PGD2 downregulation plays a causal role in depressive behaviors derived from PPD in both wild-type and Gabrd-/- mice. Furthermore, we verified that L-PGDS/PGD2 signaling dysfunction-induced astrocytes atrophy is mediated by Src phosphorylation both in vitro and in vivo. LIMITATIONS: L-PGDS/PGD2 signaling dysfunction may be only responsible for the depressive behavior rather than maternal behaviors in the PPD, and it remains to be seen whether this mechanism is applicable to all depression types. CONCLUSION: Our study identified abnormalities in the L-PGDS/PGD2 signaling in the CeA, which inhibited Src phosphorylation and induced astrocyte atrophy, ultimately resulting in the development of PPD in mice.

Carfilzomib activates ER stress and JNK/p38 MAPK signaling to promote apoptosis in hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC) is one of the most prevalent and deadly cancers in the world, which is frequently diagnosed at a late stage. HCC patients have a poor prognosis due to the lack of an efficacious therapeutic strategy. Approved drug repurposing is a way for accelerating drug discovery and can significantly reduce the cost of drug development. Carfilzomib (CFZ) is a second-generation proteasome inhibitor, which is highly efficacious against multiple myeloma and has been reported to possess potential antitumor activities against multiple cancers. However, the underlying mechanism of CFZ on HCC is still unclear. Here, we show that CFZ inhibits the proliferation of HCC cells through cell cycle arrest at the G2/M phase and suppresses the migration and invasion of HCC cells by inhibiting epithelial-mesenchymal transition. We also find that CFZ promotes reactive oxygen species production to induce endoplasmic reticulum (ER) stress and activate JNK/p38 MAPK signaling in HCC cells, thus inducing cell death in HCC cells. Moreover, CFZ significantly inhibits HCC cell growth in a xenograft mouse model. Collectively, our study elucidates that CFZ impairs mitochondrial function and activates ER stress and JNK/p38 MAPK signaling, thus inhibiting HCC cell and tumor growth. This indicates that CFZ has the potential as a therapeutic drug for HCC.

Fixing the Huai River: Technology of Labor Formation in Maoist China, 1950-53.

This article contributes to the large-scale engineering scholarship by revealing the labor practices involved and the state's role in shaping them. It provides a history of labor formation through earthwork technology in China's 1950s Huai River Control Project. The Communist Party's approach to engineering and labor differed from its Nationalist predecessor's. The party mobilized millions of peasants to dig and move an astronomical amount of soil in a few years. This herculean feat was made possible by promoting "work methods" to encourage peasants' self-Taylorization. The campaign aimed to cultivate a habit to work efficiently in mass-scale collaboration under external instructions. Through promoting work methods, state-appointed cadres assumed a tutelage role that allowed them to replace labor foremen. A hierarchical cadre-laborer relationship emerged from the same labor process that changed the nation's landscape.

Gradually Self-Strengthen DNA Supramolecular Hydrogels.

The dynamic mechanical strength of the extracellular matrix (ECM) has been demonstrated to play important role in determining the cell behavior. Growing evidences suggest that the gradual stiffening process of the matrix is particularly decisive during tissue development and wound healing. Herein, a novel strategy to prepare hydrogels with gradually enhanced mechanical strength is provided. Such hydrogels could maintain the dynamic properties at their initial states, such as self-healing and shear-thinning properties. With subsequent slow covalent crosslinking, the stability and mechanical properties would be gradually improved. This method is useful for sequence programmability and oxidation strategies, which has provided an alternated tool to study cell behavior during dynamic increase in mechanical strength of ECM.

Strong Yet Tough Transparent Paper with Superb Foldability.

Transparent paper manufactured from wood fibers is emerging as a promising, cost-effective, and carbon-neutral alternatives to plastics. However, fully exploring their mechanical properties is one of the most pressing challenges. In this work, a strong yet tough transparent paper with superior folding endurance is prepared by rationally altering the native fiber structure. Microwave-assisted choline chloride/lactic acid deep eutectic solvent (DES) pulping is first utilized to isolate wood fibers from spruce wood. During this process, the S1 layer within the fibers is partially disrupted, forming protruding microfibrils that play a crucial role in enhancing cellulose accessibility. Subsequently, carboxymethylation treatment is applied to yield uniformly swollen carboxymethylated wood fibers (CM fibers), which improves the interaction between CM fibers during papermaking. The as-prepared transparent paper not only shows a 90% light transmittance (550 nm) but also exhibits impressive mechanical properties, including a folding endurance of over 26 000, a tensile strength of 248.4 MPa, and a toughness of 15.6 MJ m-3. This work provides a promising route for manufacturing transparent paper with superior mechanical properties from wood fibers and can extend their use in areas normally dominated by high-performance nonrenewable plastics.

The construction of a novel prognostic prediction model for glioma based on GWAS-identified prognostic-related risk loci.

Backgrounds: Glioma is a highly malignant brain tumor with a grim prognosis. Genetic factors play a role in glioma development. While some susceptibility loci associated with glioma have been identified, the risk loci associated with prognosis have received less attention. This study aims to identify risk loci associated with glioma prognosis and establish a prognostic prediction model for glioma patients in the Chinese Han population. Methods: A genome-wide association study (GWAS) was conducted to identify risk loci in 484 adult patients with glioma. Cox regression analysis was performed to assess the association between GWAS-risk loci and overall survival as well as progression-free survival in glioma. The prognostic model was constructed using LASSO Cox regression analysis and multivariate Cox regression analysis. The nomogram model was constructed based on the single nucleotide polymorphism (SNP) classifier and clinical indicators, enabling the prediction of survival rates at 1-year, 2-year, and 3-year intervals. Additionally, the receiver operator characteristic (ROC) curve was employed to evaluate the prediction value of the nomogram. Finally, functional enrichment and tumor-infiltrating immune analyses were conducted to examine the biological functions of the associated genes. Results: Our study found suggestive evidence that a total of 57 SNPs were correlated with glioma prognosis (p < 5 × 10-5). Subsequently, we identified 25 SNPs with the most significant impact on glioma prognosis and developed a prognostic model based on these SNPs. The 25 SNP-based classifier and clinical factors (including age, gender, surgery, and chemotherapy) were identified as independent prognostic risk factors. Subsequently, we constructed a prognostic nomogram based on independent prognostic factors to predict individualized survival. ROC analyses further showed that the prediction accuracy of the nomogram (AUC = 0.956) comprising the 25 SNP-based classifier and clinical factors was significantly superior to that of each individual variable. Conclusion: We identified a SNP classifier and clinical indicators that can predict the prognosis of glioma patients and established a prognostic prediction model in the Chinese Han population. This study offers valuable insights for clinical practice, enabling improved evaluation of patients' prognosis and informing treatment options.

First report of cucumber green mottle mosaic virus infecting Cynanchum rostellatum in China.

Cucumber green mottle mosaic virus (CGMMV) was first discovered on cucumber in the United Kingdom in 1935 (Ainsworth, 1935), and has spread worldwide except to Antarctica (Jones, 2021). Given its extensive damage, it is considered an important pathogen on global cucurbit plants and fruit crops. In China, CGMMV was first reported on pumpkin in Guangxi Province in 2003 (Qin et al., 2005), and occurred on 34 plants species across 23 provinces (Liu et al., 2016). Cynanchum rostellatum is a member of the family Apocynaceae. In July 2021, leaves of C. rostellatum exhibiting virus-like symptoms (yellowing, severe crinkling, deformation) were observed and collected in Liaoning Province, China. Aphids were also observed on the leaves and stems (Fig. S1) of the plants and were collected. Total RNA was extracted from diseased leaves following the CTAB method, followed by the depletion of ribosomal RNAs (rRNA) with TIANSeq rRNA Depletion Kit (Tiangen, China). The RNAs were, then processed into a DNBSEQ LncRNA-Seq library, and sequenced on the MGISEQ-2000 platform at BGI Genomics (Wuhan, China). A total of 106.98 M clean reads were obtained after data filtering using SOAPnuke software (BGI, China). The clean reads were assembled into contigs using CLC Genomics Workbench 11 (Qiagen, USA) and Trinity v2.0.6 (Haas et al., 2013). A contig (4,760 reads, average coverage:73.76) of 6,391 nucleotides was found to share the highest sequence identity (99.83%) with CGMMV isolate GDLZ (MK933286), irrespective of other virus-like contigs related to Polerovirus and Totivirus. Based on the genome of GDLZ isolate, seven specific primers (Table S1) were designed to amplify the full viral genomic sequences using a PrimeScriptTM One-Step RT-PCR Kit. Seven expected amplicons were obtained, cloned, and sequenced. The complete genome was determined to be 6,423 nucleotides (GenBank accession number OR854819) in length and designated as LNMJ isolate. LNMJ shared 96.8%-99.7% nucleotide sequence identities with CGMMV isolates from China. Phylogenetic analysis based on the complete genome sequences showed that LNMJ clustered together with CGMMV isolates hn (GenBank accession number KC851866), GDLZ (GenBank accession number MK933286), and JD8 (GenBank accession number KM873784) from China. The specific primers LM-TJ-3F/3R were designed to determine the virus-symptom association for LNMJ, and all twelve symptomatic C. rostellatum plants collected from fields tested positive for LNMJ. Two out of six randomly selected aphids from the diseased plants also tested positive. To further prove its infectivity, LNMJ was inoculated mechanically onto ten healthy Nicotiana benthamiana plants, and the results indicated a high infection rate of 80% (8/10), at 30 days post-inoculation despite no distinct symptoms observed. To our knowledge, this is the first report of the natural infection of C. rostellatum plants with CGMMV. C. rostellatum is a widespread herb in China (Wei et al., 2019) and more surveys are needed to determine the distribution of CGMMV. The habitats of C. rostellatum span diverse agroecological zones, and thus our study underscores the potential spillover of CGMMV to neighboring crops as a significant risk.