First report of Lasiodipilodia theobromae Causing leaf spot of Agave sisalana in GuangXi, China.

Agave sisalana, as an excellent fiber producing plant, is mainly planted in Guangxi Province, China. In November 2023, a foliar disease occured on A. sisalana at Liangjiang Town (108.3593 W, 23.4723 N), Wuming District, Nanning in GuangXi, China. Approximately 50 to 60% of the plants (n=200) had obvious leaf spots on more than 70% of the leaves. On the leaves of sisal, circular or irregularly shaped yellow brown spots can be seen, sunken, with no halo on the edges. As time goes on, the lesion gradually expands to the entire blade of the sword (Figure 1A, 1B). To identify the disease etiology, ten agave leaves were collected from GuangXi. Symptomatic midribs were cut into 3×3 mm pieces, surface sterilized with 75 % ethanol for 20 s, rinsed with sterilized distilled water three times, air dried on sterile filter paper, plated on photo dextrose agar (PDA) medium, and incubated at 28 ℃ in the dark. Five isolates (JM01, JM02, JM03, JM05, JM06) with similar morphology were obtained. Colonies on PDA medium were white to grayish-white with atrial mycelia growing initially upward and then forming clusters (Figure 1E). After five days, mycelia turned grayish black. Immature conidia were initially hyaline, aseptate, and ellipsoid. Mature conidia were dark brown, one septate, longitudinal striate, and 22.1 to 26.3×10.2 to 14.9 µm (Figure 1F). Morphologically , the isolates were identified as Lasiodiplodia theobromae (Alves et al. 2008). For molecular identification, genome DNA of five representative isolate was extracted using the Fungi Genomic DNA Purification kit. The internal transcribed spacer (ITS) region of rDNA and translation elongation factor 1-alpha (TEF-1α) and ß-tublin (TUB) gene were amplified with primer pairs ITS1/ITS4 (White et al. 1990), EF1-728F/EF1-986R (Carbone and Kohn 1999), and Bt2a/Bt2b (Glass and Donaldson 1995), respectively, and sequenced. The ITS (PP209594), TEF-1α (PP234629), and TUB (PP234628) sequences of representative isolate JM01 were deposited in GeneBank. BLAST searches showed >99% nucleotide identity to sequences of L. theobromae (ITS, 99.26% to NR111174; TEF-1α, 99.69% to MM840490; TUB, 98.92% to MN172230). Phylogenetic analysis using maximum likelihood based on the combined ITS, TEF-1α, and TUB sequences of the isolates and reference sequences of Lasiodiplodias spp. from GenBank indicated the isolates obtained in this study formed a clade strongly supported based on bootstrap values to the ex-type isolate CBS164.96 sequences of L.theobromae (Figure 2). To test pathogenicity, JM01 was tested by inoculation leaves of one year old agave plants, the epidermis at the inoculation site, 10, 15 and 20 cm below to the crown, was wiped with a 75% alcohol cotton ball, washed three times with sterile water, and punctured (5 mm diameter) with a sterile inoculation needle. A 5 mm block of each isolate cultured on PDA for 3 days was attached to the inoculation site. Controls were inoculated with sterile PDA. The inoculation area was covered with plastic wrap. All plants were kept in a controlled greenhouse at 27℃, 80% relative humidity, and natural daylight, and watered weekly. Each treatment was repeated three times. Remove the block one day later. Three days after inoculation, all inoculated had typical symptoms,but control were healthy (Figure 1C, 1D). Fungal isolates were only recovered from symptomatic stems and were morphologically identical to L. theobromae, completing Koch's postulates. L. Theobromae has been reported as the cause of leaf rot on A. angustifolia in Mexico (Reyes-García et al. 2023). To our knowledge, this is the first report of L. theobromae causing leaf spot on A. sisalana in GuangXi, China. L. theobromae is primarily a plant pathogen that causes rotting and dieback in fruits and plants in tropical and subtropical regions (Puttanna 1967). This study is useful to focus on management strategies for leaf rot disease by L. theobromae of A. sisalana.

Recent Advances in Sample Preparation and Chromatographic/Mass Spectrometric Techniques for Detecting Polycyclic Aromatic Hydrocarbons in Edible Oils: 2010 to Present.

Polycyclic aromatic hydrocarbons are considered to be potentially genotoxic and carcinogenic to humans. For non-smoking populations, food is the main source of polycyclic aromatic hydrocarbons exposure. Due to their lipophilic nature, oils and fats rank among the food items with the highest polycyclic aromatic hydrocarbon content. Consequently, the detection of polycyclic aromatic hydrocarbons in edible oils is critical for the promotion of human health. This paper reviews sample pretreatment methods, such as liquid-phase-based extraction methods, adsorbent-based extraction methods, and the QuEChERS (quick, easy, cheap, effective, rugged, and safe) method, combined with detection techniques like mass spectrometry and chromatography-based techniques for accurate quantification of polycyclic aromatic hydrocarbons in edible oils since 2010. An overview on the advances of the methods discussed herein, along with a commentary addition of current challenges and prospects, will guide researchers to focus on developing more effective detection methods and control measures to reduce the potential risks and hazards posed by polycyclic aromatic hydrocarbons.

Characteristics of the HIV/AIDS Epidemic among People Aged ≥ 50 Years in China during 2018-2021.

Objective: This study aimed to determine the current epidemiological status of PLWHA aged ≥ 50 years in China from 2018 to 2021. It also aimed to recommend targeted interventions for the prevention and treatment of HIV/AIDS in elderly patients. Methods: Data on newly reported cases of PLWHA, aged ≥ 50 years in China from 2018 to 2021, were collected using the CRIMS. Trend tests and spatial analyses were also conducted. Results: Between 2018 and 2021, 237,724 HIV/AIDS cases were reported among patients aged ≥ 50 years in China. The main transmission route was heterosexual transmission (91.24%). Commercial heterosexual transmission (CHC) was the primary mode of transmission among males, while non-marital non-CHC ([NMNCHC]; 60.59%) was the prevalent route in women. The proportion of patients with CHC decreased over time ( Z = 67.716, P < 0.01), while that of patients with NMNCHC increased ( Z = 153.05, P < 0.01). The sex ratio varied among the different modes of infection, and it peaked at 17.65 for CHC. The spatial analysis indicated spatial clustering, and the high-high clustering areas were mainly distributed in the southwestern and central-southern provinces. Conclusion: In China, PLWHA, aged ≥ 50 years, were predominantly infected through heterosexual transmission. The primary modes of infection were CHC and NMNCHC. There were variations in the sex ratio among different age groups, infected through various sexual behaviors. HIV/AIDS cases exhibited spatial clustering. Based on these results, the expansion of HIV testing, treatment, and integrated behavioral interventions in high-risk populations is recommended to enhance disease detection in key regions.

Synergistic effect of mesenchymal stem cell-derived extracellular vesicle and miR-137 alleviates autism-like behaviors by modulating the NF-κB pathway.

Autism spectrum disorder (ASD) is a multifaceted neurodevelopmental disorder predominant in childhood. Despite existing treatments, the benefits are still limited. This study explored the effectiveness of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) loaded with miR-137 in enhancing autism-like behaviors and mitigating neuroinflammation. Utilizing BTBR mice as an autism model, the study demonstrated that intranasal administration of MSC-miR137-EVs ameliorates autism-like behaviors and inhibits pro-inflammatory factors via the TLR4/NF-κB pathway. In vitro evaluation of LPS-activated BV2 cells revealed that MSC-miR137-EVs target the TLR4/NF-κB pathway through miR-137 inhibits proinflammatory M1 microglia. Moreover, bioinformatics analysis identified that MSC-EVs are rich in miR-146a-5p, which targets the TRAF6/NF-κB signaling pathway. In summary, the findings suggest that the integration of MSC-EVs with miR-137 may be a promising therapeutic strategy for ASD, which is worthy of clinical adoption.

Postoperative cognitive dysfunction in heart transplantation recipients.

OBJECTIVE: This study aimed to investigate the occurrence and risk factors of postoperative neurocognitive disorder (NCD) in patients who underwent heart transplantation. METHODS: Seventy-six heart transplant patients were analyzed for clinical data including gender, age, height, weight, education level, left ventricular ejection fraction (LVEF), stroke volume (SV), transplantation duration, and pretransplant medical history. Cognitive function was assessed using the mini-mental status examination (MMSE) and Montreal cognitive assessment (MoCA) scales. Patients were categorized into cognitively normal and impaired groups based on the presence or absence of cognitive dysfunction, and their cognitive function scores were compared. Multivariate logistic regression was used to identify independent risk factors for cognitive impairment in postoperative cardiac transplant patients. RESULTS: Cognitive dysfunction was observed in 48 out of 76 heart transplant patients, representing an incidence of 63.2%. Cognitive impairment in heart transplant recipients predominantly affected multiple cognitive domains. Logistic regression analysis identified age (OR = 1.057, 95% CI 1.002-1.115), gender (OR = .200, 95% CI .044-.919), education level (OR = .728, 95% CI .600-.883), LVEF (OR = .891, 95% CI .820-.969), and history of diabetes (OR = 7.674, 95% CI 1.317-44.733) as independent risk factors for postoperative NCD in heart transplant recipients (P < .05). CONCLUSION: The study found a high incidence of postoperative NCD in heart transplant patients, with gender, age, education level, LVEF, and diabetes history being significant risk factors. Early identification and intervention targeting these risk factors may help prevent NCD in postheart transplant patients and improve long-term outcomes.

Defining and benchmarking open problems in single-cell analysis.

With the growing number of single-cell analysis tools, benchmarks are increasingly important to guide analysis and method development. However, a lack of standardisation and extensibility in current benchmarks limits their usability, longevity, and relevance to the community. We present Open Problems, a living, extensible, community-guided benchmarking platform including 10 current single-cell tasks that we envision will raise standards for the selection, evaluation, and development of methods in single-cell analysis.

Resveratrol regulates Thoc5 to improve maternal immune activation-induced autism-like behaviors in adult mouse offspring.

Maternal infection during pregnancy is an important cause of autism spectrum disorder (ASD) in offspring, and inflammatory infiltration caused by maternal immune activation (MIA) can cause neurodevelopmental disorders in the fetus. Medicine food homologous (MFH) refers to a traditional Chinese medicine (TCM) concept, which effectively combines food functions and medicinal effects. However, no previous study has screened, predicted, and validated the potential targets of MFH herbs for treating ASD. Therefore, in this study, we used comprehensive bioinformatics methods to screen and analyze MFH herbs and drug targets on a large scale, and identified resveratrol and Thoc5 as the best small molecular ingredient and drug target, respectively, for the treatment of MIA-induced ASD. Additionally, the results of in vitro experiments revealed that resveratrol increased the expression of Thoc5 and effectively inhibited lipopolysaccharide-induced inflammatory factor production by BV2 cells. Moreover, in vivo, resveratrol increased the expression of Thoc5 and effectively inhibited placental and fetal brain inflammation in MIA pregnancy mice, and improved ASD-like behaviors in offspring.

Association between TyG index trajectory and new-onset lean NAFLD: a longitudinal study.

Objective: The purpose of this manuscript is to identify longitudinal trajectories of changes in triglyceride glucose (TyG) index and investigate the association of TyG index trajectories with risk of lean nonalcoholic fatty liver disease (NAFLD). Methods: Using data from 1,109 participants in the Health Management Cohort longitudinal study, we used Latent Class Growth Modeling (LCGM) to develop TyG index trajectories. Using a Cox proportional hazard model, the relationship between TyG index trajectories and incident lean NAFLD was analyzed. Restricted cubic splines (RCS) were used to visually display the dose-response association between TyG index and lean NAFLD. We also deployed machine learning (ML) via Light Gradient Boosting Machine (LightGBM) to predict lean NAFLD, validated by receiver operating characteristic curves (ROCs). The LightGBM model was used to create an online tool for medical use. In addition, NAFLD was assessed by abdominal ultrasound after excluding other liver fat causes. Results: The median age of the population was 46.6 years, and 440 (39.68%) of the participants were men. Three distinct TyG index trajectories were identified: "low stable" (TyG index ranged from 7.66 to 7.71, n=206, 18.5%), "moderate stable" (TyG index ranged from 8.11 to 8.15, n=542, 48.8%), and "high stable" (TyG index ranged from 8.61 to 8.67, n=363, 32.7%). Using a "low stable" trajectory as a reference, a "high stable" trajectory was associated with an increased risk of lean-NAFLD (HR: 2.668, 95% CI: 1.098-6.484). After adjusting for baseline age, WC, SBP, BMI, and ALT, HR increased slightly in "moderate stable" and "high stable" trajectories to 1.767 (95% CI:0.730-4.275) and 2.668 (95% CI:1.098-6.484), respectively. RCS analysis showed a significant nonlinear dose-response relationship between TyG index and lean NAFLD risk (χ2 = 11.5, P=0.003). The LightGBM model demonstrated high accuracy (Train AUC 0.870, Test AUC 0.766). An online tool based on our model was developed to assist clinicians in assessing lean NAFLD risk. Conclusion: The TyG index serves as a promising noninvasive marker for lean NAFLD, with significant implications for clinical practice and public health policy.

Mechanistic and biophysical characterization of polymyxin resistance response regulator PmrA in Acinetobacter baumannii.

Introduction: Acinetobacter baumannii PmrAB is a crucial two-component regulatory system (TCS) that plays a vital role in conferring resistance to polymyxin. PmrA, a response regulator belonging to the OmpR/PhoB family, is composed of a C-terminal DNA-binding effector domain and an N-terminal receiver domain. The receiver domain can be phosphorylated by PmrB, a transmembrane sensor histidine kinase that interacts with PmrA. Once phosphorylated, PmrA undergoes a conformational change, resulting in the formation of a symmetric dimer in the receiver domain. This conformational change facilitates the recognition of promoter DNA by the DNA-binding domain of PmrA, leading to the activation of adaptive responses. Methods: X-ray crystallography was carried out to solve the structure of PmrA receiver domain. Electrophoretic mobility shift assay and Isothermal titration calorimetry were recruited to validate the interaction between the recombinant PmrA protein and target DNA. Field-emission scanning electron microscopy (FE-SEM) was employed to characterize the surface morphology of A. baumannii in both the PmrA knockout and mutation strains. Results: The receiver domain of PmrA follows the canonical α5ß5 response regulator assembly, which undergoes dimerization upon phosphorylation and activation. Beryllium trifluoride is utilized as an aspartate phosphorylation mimic in this process. Mutations involved in phosphorylation and dimerization significantly affected the expression of downstream pmrC and naxD genes. This impact resulted in an enhanced cell surface smoothness with fewer modifications, ultimately contributing to a decrease in colistin (polymyxin E) and polymyxin B resistance. Additionally, a conservative direct-repeat DNA PmrA binding sequence TTTAAGNNNNNTTTAAG was identified at the promoter region of the pmrC and naxD gene. These findings provide structural insights into the PmrA receiver domain and reveal the mechanism of polymyxin resistance, suggesting that PmrA could be a potential drug target to reverse polymyxin resistance in Acinetobacter baumannii.

Yigansan ameliorates maternal immune activation-induced autism-like behaviours by regulating the IL-17A/TRAF6/MMP9 pathway: Network analysis and experimental validation.

BACKGROUND: Maternal immune activation (MIA) is a significant factor inducing to autism spectrum disorder (ASD) in offspring. The fundamental principle underlying MIA is that inflammation during pregnancy impedes fetal brain development and triggers behavioural alterations in offspring. The intricate pathogenesis of ASD renders drug treatment effects unsatisfactory. Traditional Chinese medicine has strong potential due to its multiple therapeutic targets. Yigansan, composed of seven herbs, is one of the few that has been proven to be effective in treating neuro-psychiatric disorders among numerous traditional Chinese medicine compounds, but its therapeutic effect on ASD remains unknown. HYPOTHESIS: Yigansan improves MIA-induced ASD-like behaviours in offspring by regulating the IL-17 signalling pathway. METHODS: Pregnant C57BL/6J mice were intraperitoneally injected with poly(I:C) to construct MIA models and offspring ASD models. Network analysis identified that the IL-17A/TRAF6/MMP9 pathway is a crucial pathway, and molecular docking confirmed the binding affinity between the monomer of Yigansan and target proteins. qRT-PCR and Western blot were used to detect the expression levels of inflammatory factors and pathway proteins, immunofluorescence was used to detect the distribution of IL-17A, and behavioural tests were used to evaluate the ASD-like behaviours of offspring. RESULTS: We demonstrated that Yigansan can effectively alleviate MIA-induced neuroinflammation of adult offspring by regulating the IL-17A/TRAF6/MMP9 pathway, and the expression of IL-17A was reduced in the prefrontal cortex. Importantly, ASD-like behaviours have been significantly improved. Moreover, we identified that quercetin is the effective monomer for Yigansan to exert therapeutic effects. CONCLUSION: Overall, this study was firstly to corroborate the positive therapeutic effect of Yigansan in the treatment of ASD. We elucidated the relevant molecular mechanism and regulatory pathway involved, determined the optimal therapeutic dose and effective monomer, providing new solutions for the challenges of drug therapy for ASD.

CTAT-LR-fusion: accurate fusion transcript identification from long and short read isoform sequencing at bulk or single cell resolution.

Gene fusions are found as cancer drivers in diverse adult and pediatric cancers. Accurate detection of fusion transcripts is essential in cancer clinical diagnostics, prognostics, and for guiding therapeutic development. Most currently available methods for fusion transcript detection are compatible with Illumina RNA-seq involving highly accurate short read sequences. Recent advances in long read isoform sequencing enable the detection of fusion transcripts at unprecedented resolution in bulk and single cell samples. Here we developed a new computational tool CTAT-LR-fusion to detect fusion transcripts from long read RNA-seq with or without companion short reads, with applications to bulk or single cell transcriptomes. We demonstrate that CTAT-LR-fusion exceeds fusion detection accuracy of alternative methods as benchmarked with simulated and real long read RNA-seq. Using short and long read RNA-seq, we further apply CTAT-LR-fusion to bulk transcriptomes of nine tumor cell lines, and to tumor single cells derived from a melanoma sample and three metastatic high grade serous ovarian carcinoma samples. In both bulk and in single cell RNA-seq, long isoform reads yielded higher sensitivity for fusion detection than short reads with notable exceptions. By combining short and long reads in CTAT-LR-fusion, we are able to further maximize detection of fusion splicing isoforms and fusion-expressing tumor cells. CTAT-LR-fusion is available at https://github.com/TrinityCTAT/CTAT-LR-fusion/wiki.

GABA in the anterior cingulate cortex mediates the association of white matter hyperintensities with executive function: a magnetic resonance spectroscopy study.

White matter hyperintensities (WMH) and gamma-aminobutyric acid (GABA) are associated with executive function. Multiple studies suggested cortical alterations mediate WMH-related cognitive decline. The aim of this study was to investigate the crucial role of cortical GABA in the WMH patients. In the 87 WMH patients (46 mild and 41 moderate to severe) examined in this study, GABA levels in the anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC) assessed by the Meshcher-Garwood point resolved spectroscopy (MEGA-PRESS) sequence, WMH volume and executive function were compared between the two groups. Partial correlation and mediation analyses were carried out to examine the GABA levels in mediating the association between WMH volume and executive function. Patients with moderate to severe WMH had lower GABA+/Cr in the ACC (p = 0.034) and worse executive function (p = 0.004) than mild WMH patients. In all WMH cases, the GABA+/Cr levels in the ACC mediated the negative correlation between WMH and executive function (ab: effect = -0.020, BootSE = 0.010, 95% CI: -0.042 to -0.004). This finding suggested GABA+/Cr levels in the ACC might serve as a protective factor or potential target for preventing the occurrence and progression of executive function decline in WMH people.

The relationship between major life events and non-suicidal self-injury among college students: the effect of rumination and body image.

Background: Non-suicidal self-injury (NSSI) poses a growing risk to public health worldwide. While numerous studies have identified major life events as key risk factors for NSSI, the mechanisms by which emotional and cognitive problems mediate or moderate this relationship remain unclear. To enhance the understanding of this field, we will draw upon the cascade theory of self-injury and the benefits and barriers model, to examine the relationship between major life events and NSSI, as well as the effect of rumination and body image. Methods: A sample of 2,717 college students (Mage = 19.81 years; SD = 1.09) participated in this study and anonymously completed the questionnaires. The moderated mediation model were conducted using Model 4 and Model 15 of the Process macro program in SPSS. Results: The results showed that rumination mediated the positive relationship between major life events and NSSI. Furthermore, body image was found to moderate both the relationship between major life events and NSSI, as well as the relationship between rumination and NSSI. Conclusion: The current findings suggest that rumination is an important mediator in the relationship between major life events and NSSI among college students. Teachers, parents, and researchers should recognize the important role of body image self-perceptions of college students and actively promote a healthy and accurate body image.

Sequence Analysis of the Plastomes of Two Tibetan Medicinal Plants of the Family Papaveraceae.

BACKGROUND: With the rapid development of next-generation sequencing technology, more plants plastomes have been sequenced, further advancing species identification and phylogenetic studies. However, there are a few studies on the genetic and phylogenetic analysis of the plastomes of Dicranostigma lactucoides Hook. f. et Thoms. and Hypecoum leptocarpum Hook. f. et Thoms. METHODS: In this study, we sequenced and analyzed the plastomes of Dicranostigma lactucoides Hook. f. et Thoms. and Hypecoum leptocarpum Hook. f. et Thoms., and conducted a phylogenetic analysis using 13 related species. RESULTS: The results showed that the plastomes of both D. lactucoides and H. leptocarpum had a typical tetrad structure, with sizes of 166,819 bp and 163,282 bp, respectively. We annotated 133 genes for D. lactucoides and 120 genes for H. leptocarpum. A total of 72 and 43 simple repetitive sequences were detected in D. lactucoides and H. leptocarpum, respectively. Codon preference analysis showed that the relative usage frequency of codons and the relative abundance of synonymous codons used were the same for both plastomes. Nucleotide polymorphism analysis identified seven variant loci with high nucleotide diversity (Pi) values, all located in the large single copy (LSC) region. Inverted repeat (IR) boundary analysis revealed differences in gene types and locations on both sides of the boundary, except for the small single copy/inverted repeat a (SSC/IRa) boundary. The phylogenetic analysis showed the species clustered into two major groups, one with five genera (Hypecoum, Corydalis, Papaver, Meconopsis, and Dicranostigma) and the other with two genera (Coreanomecon; and Hylomecon). CONCLUSIONS: Comparative analysis of the plastome genomic characteristics and phylogeny of D. lactucoides and H. leptocarpum laid the foundation for identifying the above two species and the phylogenetic study and comprehensive exploitation of the Papaveraceae.