Analysis of binding and authentic virus-neutralizing activities of immune sera induced by various monkeypox virus antigens.

Monkeypox cases continue to increase globally, and there is an urgent need to develop a highly effective vaccine against monkeypox. This study investigated the binding and authentic-virus neutralizing activities of sera from mice immunized with EEV (extracellularly enveloped viruses) antigens B6R and A35R, and IMV (intrinsic material viruses) antigens M1R, A29L, E8L, and H3L against monkeypox virus. The results showed that immunizations of A35R and E8L could only induce lower titers of binding antibodies, in contrast, immunization of M1R induced the highest titers of binding antibodies, while immunization of B6R, H3L, and A29L induced moderate titers of binding antibodies. For the live monkeypox virus neutralization assay, the results showed that immunization with two doses of EEV antigen B6R did not effectively induce humoral immune responses to neutralize monkeypox live virus, immunization with EEV-A35R only induced weak monkeypox-neutralizing antibodies. In contrast, the immunization of the four types of monkeypox virus IMV antigens can all induce neutralizing antibodies against authentic monkeypox virus, among them, A29L and H3L induced the highest neutralizing antibody titers. The results of this study provide important references for the selection of antigens in the development of the next generation of monkeypox vaccines.

First report of Stagonosporopsis cucurbitacearum Causing Gummy Stem Blight on Trichosanthes kirilowii Maxim. in China.

Trichosanthes kirilowii Maxim. (Cucurbitaceae), one of the Chinese herbal medicines, is an economically important crop in Anhui Province, China. In recent years, gummy stem blight disease, a major disease of cucurbits, was widespread in many T. kirilowii plantations. The initial symptoms on the naturally infected stems appeared as dark brown water-soaked lesions, and as the disease progressed, vines of T. kirilowii gradually withered. On leaves, brown water-soaked lesions were visible initially, and then lesions enlarged and coalesced, resulting in extensive necrosis of leaves. On fruit, lesions covered with the white mycelium were nearly circular and tan to brown initially. Subsequently, the diseased fruit turned black and rotten commonly known as fruit rot or black rot. A Stagonosporopsis-like organism was consistently isolated from symptomatic stems, leaves and fruits. Fungal isolates were initially white and later turned dark grey or black with woolly to floccose aerial mycelium on PDA medium. Twenty-four isolates from different plantations were selected for further morphological studies. Pycnidia and conidia were formed after inoculating on cucumber fruit for 3 days. Pycnidia were globose to sub-globose, brown, ostiolate and 106.7 to 213.6 µm (average 160.1 µm, n = 50) in diameter. Conidia were hyaline, ellipsoidal, aseptate or one-septate, slightly constricted at the septa, 6.1 to 13.6 × 3.5 to 4.8 µm (average 9.9 × 4.1 µm, n = 50), and contained two or more oil drops. Three different loci of the genomic DNA, including the nuclear ribosome DNA internal transcribed spacer (ITS), RNA polymerase II second-largest subunit (RPB2), and ß-tubulin (TUB2) genes., were amplified using primers ITS1/ITS4 (White et al. 1990), RBP2DF/RBP2DR (Lawrence et al. 2013), and T1/ß-Sandy-R (O' Donnell and Cigelnik 1997; Stukenbrock et al. 2012), respectively and sequenced. A phylogenetic tree was built based on analysis of ITS, RPB2, and TUB2 sequences that deposited in GenBank (MW485497-MW485502 for ITS, MW531661-MW531666 for RPB2, and MW531667-MW531672 for TUB2), using the maximum likelihood method. The phylogenetic tree showed that the isolates fell into a single clade with S. cucurbitacearum. On the basis of morphological and molecular characteristics, the isolates obtained from T. kirilowii were identified as Stagonosporopsis cucurbitacearum. Pathogenicity tests were carried out on stems and leaves of 4-week-old T. kirilowii seedlings and on immature fruit collected from adult T. kirilowii plants. The epidermis, previously injured with a syringe needle, was inoculated with 5-mm-diameter mycelial plugs, and the inoculated areas were then wrapped in water-soaked cotton. Controls were similarly inoculated with agar plugs. The diameters of lesions were measured in two perpendicular directions. Re-isolations from the stem and leaf lesions were performed on the PDA medium. Stagonosporopsis cucurbitacearum, was re-identified based on its colony and conidial characteristics and, therefore, completed Koch's postulates. Gummy stem blight caused by S. cucurbitacearum has been reported in a wide range of hosts, including cucumber, luffa, pumpkin, gourd, muskmelon, cantaloupe, and watermelon (Jiang et al. 2015; Keinath 2011; Zhao et al. 2019). To our knowledge, this is the first report of gummy Stem blight disease on T. kirilowii caused by S. cucurbitacearum in China. The research provides a basis for the development and implementation of effective management strategies. Pathogenicity tests were carried out on stems and leaves of 4-week-old T. kirilowii seedlings and on immature fruits collected from adult T. kirilowii plants. The epidermis, previously injured with a syringe needle, was inoculated with 5-mm-diameter mycelial plugs, and the inoculated areas were then wrapped in water-soaked cotton. Controls were treated similarly but inoculated with agar plugs. Diameters of lesions were measured in two mutually perpendicular directions. Reisolations from the lesions were performed on PDA medium, and was re-identified based on its colony and conidial characteristics to complete Koch's postulates. Gummy stem blight caused by S. cucurbitacearum have been reported in a wide range of hosts, including cucumber, luffa, pumpkin, gourd, muskmelon, cantaloupe, and watermelon (Jiang et al. 2015; Keinath 2011; Zhao et al. 2019). To our knowledge, this is the first report of gummy Stem blight disease on T. kirilowii caused by S. cucurbitacearum in China. The research provides a basis for the development and implementation of effective management strategies.

Benserazide, a cystathionine beta-synthase (CBS) inhibitor, potentially enhances the anticancer effects of paclitaxel via inhibiting the S-sulfhydration of SIRT1 and the HIF1-α/VEGF pathway.

Cancer targeted therapy is essential to minimize damage to normal cells and improve treatment outcomes. The elevated activity of Cystathionine beta-synthase (CBS), an enzyme responsible for producing endogenous hydrogen sulfide (H2S), plays a significant role in promoting tumor growth, invasiveness, and metastatic potential. Consequently, the selective inhibition of CBS could represent a promising therapeutic strategy for cancer. Currently, there is much interest in combining paclitaxel with other drugs for cancer treatment. This study aimed to investigate the efficacy of combining benserazide, a CBS inhibitor, with paclitaxel in treating tumors. Firstly, we demonstrated CBS is indeed involved in the progression of multiple cancers. Then it was observed that the total binding free energy between the protein and the small molecule is -98.241 kJ/mol. The release of H2S in the group treated with 100 µM benserazide was reduced by approximately 90% compared to the negative control, and the thermal denaturation curve of the complex protein shifted to the right, suggesting that benserazide binds to and blocks the CBS protein. Next, it was found that compared to paclitaxel monotherapy, the combination of benserazide with paclitaxel demonstrated stronger antitumor activity in KYSE450, A549, and HCT8 cells, accompanied by reduced cell viability, cell migration and invasion, as well as diminished angiogenic and lymphangiogenic capabilities. In vivo studies showed that the combined administration of benserazide and paclitaxel significantly reduced the volume and weight of axillary lymph nodes in comparison to the control group and single administration group. Further mechanistic studies revealed that the combination of benserazide and paclitaxel significantly suppressed the S-sulfhydration of SIRT1 protein, thereby inhibiting the expression of SIRT1 protein and activating SIRT1 downstream Notch1/Hes1 signaling pathway in KYSE450, A549, and HCT8 cells. Meanwhile, we observed that benserazide combined with paclitaxel induced a more significant downregulation of HIF-1α, VEGF-A, VEGF-C, and VEGF-D proteins expression levels in KYSE450, A549, and HCT8 cells compared to paclitaxel alone. These findings indicated that benserazide enhances the anticancer effects of paclitaxel via inhibiting the S-sulfhydration of SIRT1 and down-regulating HIF-1α/VEGF signaling pathway. This study suggests that benserazide may have potential as a chemosensitizer in cancer treatment.

Characterization of Quantitative Trait Loci for Leaf Rust Resistance from CI 13227 in Three Winter Wheat Populations.

Leaf rust is a widespread foliar wheat disease causing substantial yield losses worldwide. Slow-rusting is "adult plant" resistance that significantly slows epidemic development and thereby reduces yield loss. Wheat accession CI 13227 was previously characterized as having slow-rusting resistance. To validate the quantitative trait loci (QTL) and develop diagnostic markers for slow rusting resistance in CI 13227, a new population of recombinant inbred lines (RILs) of CI 13227 × Everest was evaluated for latent period (LP), final severity (FS), area under disease progress curve (AUDPC), and infection type (IT) in greenhouses and genotyped using genotyping-by-sequencing (GBS). Four QTL were identified on chromosome arms 2BL, 2DS, 3BS, and 7BL, explaining 6.82 to 28.45% of the phenotypic variance for these traits. Seven kompetitive allele specific polymorphism (KASP) markers previously reported to be linked to the QTL in two other CI 13227 populations were validated. In addition, the previously reported QLr.hwwg-7AL was remapped to 2BL (renamed QLr.hwwg-2BL) after adding new markers in this study. Phenotypic data showed that the RILs harboring two or three of the QTL had a significantly longer LP. QLr.hwwg-2DS on 2DS showed a major effect on all rust resistance traits and was finely mapped to a 2.7 Mb interval by two newly developed flanking markers from exome capture. Three disease-resistance genes and two transporter genes were identified as the putative candidates for QLr.hwwg-2DS. The validated QTL can be used as slow rusting resistance resources and the markers developed in this study will be useful for marker-assisted selection.

Human Amniotic Epithelial Stem Cells Alleviate Autoimmune Premature Ovarian Insufficiency in Mice by Targeting Granulosa Cells via AKT/ERK Pathways.

Autoimmune factors play an important role in premature ovarian insufficiency (POI). Human amniotic epithelial stem cells (hAESCs) have recently shown promising treatment effects on chemotherapy-induced POI. However, the therapeutic efficacy and underlying mechanisms of hAESCs in autoimmune POI remain to be investigated. In this study, we showed for the first time that intravenous transplantation of hAESCs could reside in the ovary of zona pellucida 3 peptide (pZP3) induced autoimmune POI mice model for at least 4 weeks. hAESCs could improve ovarian function and fertility, alleviate inflammation and reduce apoptosis of granulosa cells (GCs) in autoimmune POI mice. The transcriptome analysis of mice ovaries and in vitro co-cultivation experiments suggest that activation of the AKT and ERK pathways may be the key mechanism in the therapeutic effect of hAESCs. Our work provides the theoretical and experimental foundation for optimizing the administration of hAESCs, as well as the clinical application of hAESCs in autoimmune POI patients.

Reprogramming exosomes for immunity-remodeled photodynamic therapy against non-small cell lung cancer.

Traditional treatments against advanced non-small cell lung cancer (NSCLC) with high morbidity and mortality continue to be dissatisfactory. Given this situation, there is an urgent requirement for alternative modalities that provide lower invasiveness, superior clinical effectiveness, and minimal adverse effects. The combination of photodynamic therapy (PDT) and immunotherapy gradually become a promising approach for high-grade malignant NSCLC. Nevertheless, owing to the absence of precise drug delivery techniques as well as the hypoxic and immunosuppressive characteristics of the tumor microenvironment (TME), the efficacy of this combination therapy approach is less than ideal. In this study, we construct a novel nanoplatform that indocyanine green (ICG), a photosensitizer, loads into hollow manganese dioxide (MnO2) nanospheres (NPs) (ICG@MnO2), and then encapsulated in PD-L1 monoclonal antibodies (anti-PD-L1) reprogrammed exosomes (named ICG@MnO2@Exo-anti-PD-L1), to effectively modulate the TME to oppose NSCLC by the synergy of PDT and immunotherapy modalities. The ICG@MnO2@Exo-anti-PD-L1 NPs are precisely delivered to the tumor sites by targeting specially PD-L1 highly expressed cancer cells to controllably release anti-PD-L1 in the acidic TME, thereby activating T cell response. Subsequently, upon endocytic uptake by cancer cells, MnO2 catalyzes the conversion of H2O2 to O2, thereby alleviating tumor hypoxia. Meanwhile, ICG further utilizes O2 to produce singlet oxygen (1O2) to kill tumor cells under 808 nm near-infrared (NIR) irradiation. Furthermore, a high level of intratumoral H2O2 reduces MnO2 to Mn2+, which remodels the immune microenvironment by polarizing macrophages from M2 to M1, further driving T cells. Taken together, the current study suggests that the ICG@MnO2@Exo-anti-PD-L1 NPs could act as a novel drug delivery platform for achieving multimodal therapy in treating NSCLC.

Cognitive diagnostic assessment: A Q-matrix constraint-based neural network method.

Cognitive diagnosis is a crucial element of intelligent education that aims to assess the proficiency of specific skills or traits in students at a refined level and provide insights into their strengths and weaknesses for personalized learning. Researchers have developed numerous cognitive diagnostic models. However, previous studies indicate that diagnostic accuracy can be significantly influenced by the appropriateness of the model and the sample size. Thus, designing a general model that can adapt to different assumptions and sample sizes remains a considerable challenge. Artificial neural networks have been proposed as a promising approach in some studies. In this paper, we propose a cognitive diagnosis model of a neural network constrained by a Q-matrix and named QNN. Specifically, we employ the Q-matrix to determine the connections between neurons and the width and depth of the neural network. Moreover, to reduce the human effort in the training algorithm, we designed a self-organizing map-based cognitive diagnosis training framework called SOM-NN, which enables the QNN to be trained unsupervised. Extensive experimental results on simulated and real datasets demonstrate that our approaches are effective in both accuracy and interpretability. Notably, under unsupervised conditions, our approach has significant advantages on small sample datasets with high levels of guessing and slipping, especially on the pattern-wise agreement rates. This work bridges the gap between psychometrics and machine learning and provides a realistic and implementable reference solution for classroom instructional assessment and the cold start of personalized and adaptive assessment systems.

Efficient single-cycle mid-infrared femtosecond laser pulse generation by spectrally temporally cascaded optical parametric amplification with pump energy recycling.

We proposed spectrally temporally cascaded optical parametric amplification (STOPA) using pump energy recycling to simultaneously increase spectral bandwidth and conversion efficiency in optical parametric amplification (OPA). Using BiB3O6 and KTiOAsO4 nonlinear crystals, near-single-cycle mid-infrared (MIR) pulses with maximum energy conversion efficiencies exceeding 25% were obtained in simulations. We successfully demonstrated sub-two-cycle, CEP-stable pulse generation at 1.8 µm using a four-step STOPA system in the experiment. This method provides a solution to solve the limitations of the gain bandwidth of nonlinear crystals and the low conversion efficiency in broadband OPA systems, which is helpful for intense attosecond pulse generation and strong laser field physics studies.

The step-by-step assembly mechanism of secreted flavivirus NS1 tetramer and hexamer captured at atomic resolution.

Flaviviruses encode a conserved, membrane-associated nonstructural protein 1 (NS1) with replication and immune evasion functions. The current knowledge of secreted NS1 (sNS1) oligomers is based on several low-resolution structures, thus hindering the development of drugs and vaccines against flaviviruses. Here, we revealed that recombinant sNS1 from flaviviruses exists in a dynamic equilibrium of dimer-tetramer-hexamer states. Two DENV4 hexameric NS1 structures and several tetrameric NS1 structures from multiple flaviviruses were solved at atomic resolution by cryo-EM. The stacking of the tetrameric NS1 and hexameric NS1 is facilitated by the hydrophobic ß-roll and connector domains. Additionally, a triacylglycerol molecule located within the central cavity may play a role in stabilizing the hexamer. Based on differentiated interactions between the dimeric NS1, two distinct hexamer models (head-to-head and side-to-side hexamer) and the step-by-step assembly mechanisms of NS1 dimer into hexamer were proposed. We believe that our study sheds light on the understanding of the NS1 oligomerization and contributes to NS1-based therapies.

Impact of inter-lesion distance and first-pass isolation on outcomes of pulmonary venous isolation for paroxysmal atrial fibrillation.

BACKGROUND: Contiguity of ablation lesions is a critical determinant of success for paroxysmal atrial fibrillation (PAF) ablation. Evidence supports maintaining an inter-lesional distance (ILD) ≤ 6 mm during pulmonary venous isolation (PVI). Meanwhile, first-pass isolation (FPI) on PVI outcome in follow-up was not deeply studied. The impact of ILD and FPI on PAF ablation outcomes was investigated. METHODS: Consecutive PAF patients who underwent first-time antral PVI were recruited. Coordinates of ablation points were extracted from the electro-anatomical mapping system and analyzed using custom-developed software to determine the ILD. A gap is defined as ILD greater than 6 mm. FPI was defined as the achievement of PVI by encircling the ipsilateral veins while simultaneously recording their electrical activity using a multipolar catheter. The primary endpoint was freedom from documented atrial arrhythmias including AF, atrial tachycardia (AT), or atrial flutter (AFL) lasting longer than 30 s during follow-up. RESULTS: A total of 105 patients underwent first-time antral PVI. During 13.3 ± 0.6 months of follow-up, atrial arrhythmias recurrence was noted in 22.9% of the patients. Atrial arrhythmia recurrence was significantly higher in patients with more gaps (> 2) (37.0% versus 11.9%, P < 0.01), and the number of gaps was an independent predictor of AF/AT/AFL recurrence. (Hazard ratio [HR] 1.20, 95% CI 1.03-1.40, P = 0.02). The group with FPI for at least one ipsilateral pair of PVs exhibited a decreased number of gaps (2.0 versus 7.0, P < 0.01) and demonstrated a significant correlation with a reduction of recurrence (HR 0.26, 95% CI 0.09-0.71, P = 0.01). Among 16 patients who underwent repeat ablation, the number of gaps during the index PVI was associated with PV reconnection (PVR) (P < 0.01). CONCLUSIONS: Gaps created during PVI are a modifiable determinant of AF/AT/AFL recurrence, and avoidance of gaps is crucial to improve clinical outcomes of PAF ablation. In addition, FPI exhibited a strong predictive capability for clinical success in patients with PAF.

The roles of adenosine signaling in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with multiple etiological factors. Immune disorder contributes to SLE development and is an important clinical manifestation of SLE patients. Immune dysfunction is characterized by abnormal of B cells, T cells, monocyte-macrophages and dendritic cells (DCs), in both quantity and quality. Adenosine is a critical factor for human immune homeostasis, which acts as an immunosuppressive signal and can prevent the hyperactivity of human immune system. Adenosine levels are significant decreased in serum from SLE patients. Adenosine level is regulated by the CD39, CD73 and adenosine deaminase (ADA). CD39/CD73/ADA catalyzed the cascade enzymatic reaction, which contained the adenosine generation and degradation. Adenosine affects the function of various immune cells via bind to the adenosine receptors, which are expressed on the cell surface. This review aims to export the changes of immune cells and adenosine signal pathway in SLE, as well as the effect of adenosine signal pathway in SLE development.

Contralateral approach using microscope and tubular retractor system for ipsilateral decompression of lumbar degenerative lateral recess stenosis associated with narrow spinal canal.

Objective: To summarize the clinical effect of a single-center retrospective analysis of the contralateral approach with a microscope and tubular retractor system for ipsilateral decompression in patients with lumbar lateral recess stenosis and a narrow spinal canal. Methods: A total of 25 patients who underwent ipsilateral decompression surgery via a contralateral approach with microscope and tubular retractor system, performed by one surgeon at a single center were retrospectively examined. The width of the lamina fenestration was compared with the preoperative distance from the root of the spinous process to the dorsal articular facet, the bilateral articular facet change in the suprapedicle notch section on CT scan, and with the changes in transverse and sagittal diameters of the canal area on MRI. Clinical efficacy was assessed using the Japanese Orthopedic Association (JOA), Visual Analog Scale (VAS), and Oswestry Disability Index (ODI) scores. Results: In total, 25 patients were treated and the mean intraoperative time was 82.04 ± 12.48 min. There was no nerve injury, cerebrospinal fluid leakage, and infection complications. The postoperative CT revealed that the width of the contralateral laminar fenestration was less than the distance from the root of the spinous process to the dorsal articular facet. The residual widths of the ipsilateral articular facet and contralateral articular facet were greater than 2/3 of the preoperative articular facet width. The transverse and sagittal diameter of canal were significantly increased. The mean follow-up period was 12-16 months, and no recurrence or reoperation incidence were found at the last follow-up. When compared to pre-surgery, the ODI, VAS, and JOA scores were significantly improved after surgery (p < 0.05). Conclusion: Based on our single-center retrospective observation of 25 cases and combined with previous literature, the contralateral approach with a microscope and tubular retractor system for ipsilateral decompression in patients with lumbar lateral recess stenosis and a narrow spinal canal can reduce damage to the articular processes, and probably more conducive to the postoperative stability of the lumbar spine. This was a single center retrospective analysis with a small sample size and lacked randomized controlled trials (RCTs). However, larger-scale, multicenter RTCs are required for additional validation.

Revealing the Na storage behavior of graphite anodes in low-concentration imidazole-based electrolytes.

The thermodynamic instability of Na+-intercalated compounds is an important factor limiting the application of graphite anodes in sodium-ion batteries. Although solvent co-intercalation is recognized as a simple and effective strategy, the challenge lies in the lack of durable electrolytes. Herein, we successfully apply low-concentration imidazole-based electrolytes to graphite anodes for sodium-ion batteries. Specifically, low concentrations ensure high ionic conductivity while saving on costs. Methylimidazole molecules can be co-intercalated with Na+, and a small amount of unreleased solvated Na+ serves the dual purpose of providing support to the graphite layer and preventing peeling off. The interphase formed in imidazole is more uniform and dense compared with that in ether electrolytes, which reduces side reactions and the risk of internal short circuits. The obtained battery demonstrates a long cycle life of 1800 cycles with a capacity retention of 84.6%. This success extends to other imidazole-based solvents such as 1-propylimidazole and 1-butylimidazole.

Utilizing transcriptomics and proteomics to unravel key genes and proteins of Oryza sativa seedlings mediated by selenium in response to cadmium stress.

BACKGROUND: Cadmium (Cd) pollution has declined crop yields and quality. Selenium (Se) is a beneficial mineral element that protects plants from oxidative damage, thereby improving crop tolerance to heavy metals. The molecular mechanism of Se-induced Cd tolerance in rice (Oryza sativa) is not yet understood. This study aimed to elucidate the beneficial mechanism of Se (1 mg/kg) in alleviating Cd toxicity in rice seedlings. RESULTS: Exogenous selenium addition significantly improved the toxic effect of cadmium stress on rice seedlings, increasing plant height and fresh weight by 20.53% and 34.48%, respectively, and increasing chlorophyll and carotenoid content by 16.68% and 15.26%, respectively. Moreover, the MDA, ·OH, and protein carbonyl levels induced by cadmium stress were reduced by 47.65%, 67.57%, and 56.43%, respectively. Cell wall metabolism, energy cycling, and enzymatic and non-enzymatic antioxidant systems in rice seedlings were significantly enhanced. Transcriptome analysis showed that the expressions of key functional genes psbQ, psbO, psaG, psaD, atpG, and PetH were significantly up-regulated under low-concentration Se treatment, which enhanced the energy metabolism process of photosystem I and photosystem II in rice seedlings. At the same time, the up-regulation of LHCA, LHCB family, and C4H1, PRX, and atp6 functional genes improved the ability of photon capture and heavy metal ion binding in plants. Combined with proteome analysis, the expression of functional proteins OsGSTF1, OsGSTU11, OsG6PDH4, OsDHAB1, CP29, and CabE was significantly up-regulated under Se, which enhanced photosynthesis and anti-oxidative stress mechanism in rice seedlings. At the same time, it regulates the plant hormone signal transduction pathway. It up-regulates the expression response process of IAA, ABA, and JAZ to activate the synergistic effect between each cell rapidly and jointly maintain the homeostasis balance. CONCLUSION: Our results revealed the regulation process of Se-mediated critical metabolic pathways, functional genes, and proteins in rice under cadmium stress. They provided insights into the expression rules and dynamic response process of the Se-mediated plant resistance mechanism. This study provided the theoretical basis and technical support for crop safety in cropland ecosystems and cadmium-contaminated areas.

Could ceftriaxone be a viable alternative to penicillin for the treatment of ocular syphilis?

This study was conducted to compare the effectiveness of ceftriaxone with that of aqueous crystalline penicillin G in treating ocular syphilis. We conducted a retrospective study from 2010 to 2021. Syphilis patients were administered either ceftriaxone (2 g intravenously daily for 14 days) or aqueous crystalline penicillin G [4 million units (MU) intravenously every 4 h for 14 days] as therapeutic interventions. Subsequently, we utilized these two groups to assess the serological results, cerebrospinal fluid analysis, and visual acuity at time intervals spanning 3 to 6 months post-treatment. A total of 205 patients were included, with 34 assigned to the ceftriaxone group and 171 to the penicillin group. The median age of patients was 56 years, with an interquartile range of 49-62 years, and 137 of them (66.8%) were male. Between 3 and 6 months after treatment, 13 patients (38.2%) in the ceftriaxone group and 82 patients (48.0%) in the penicillin group demonstrated effective treatment based on the clinical and laboratory parameters. The crude odds ratio (OR) was 0.672 (95% confidence interval [CI]: 0.316-1.428, P = 0.301), indicating no significant difference in effectiveness between the two groups. Thirty patients (17.5%) in the penicillin group and six patients (17.6%) in the ceftriaxone group did not experience successful outcomes. Notably, no serious adverse effects were reported in both the groups. There was no significant difference in the effectiveness of ceftriaxone and aqueous crystalline penicillin G in treating ocular syphilis. The administration of ceftriaxone without requiring hospitalization presents a convenient and safe alternative treatment option for ocular syphilis.

The Adjuvant Efficacy of Angong Niuhuang Pill in the Treatment of Viral Encephalitis: A Meta-Analysis of Randomized Controlled Trials.

This meta-analysis aims to evaluate the efficacy of Angong Niuhuang Pill (ANP) as an adjuvant therapy in the treatment of viral encephalitis. Seven databases (PubMed, Cochrane Library, Embase, SinoMed, CNKI, VIP and WanFang) were included for literature retrieval from inception to July 2023. Randomized controlled trials comparing ANP plus conventional therapy with conventional therapy alone were eligible. Pooled effect sizes and 95% confidence intervals (CIs) were calculated for evaluating efficacy and safety. Sensitivity analysis and publication bias assessments were performed for analyzing the inconclusiveness of findings. 13 studies involving 1045 cases were included for meta-analysis. Adjuvant treatment with ANP increased the probability of the total effective rate by 17% compared with conventional treatment (Risk ratios (RR) = 1.17, 95%CI [1.08, 1.27]). The disappearance time of clinical syndromes and signs was significantly decreased after adjuvant treatment with ANP, including the time of defervescence (weighted mean difference (WMD) = -1.59, 95%CI [-2.09, -1.09]), the time of consciousness recovery (WMD = -1.79, 95%CI [-2.06, -1.51]), the time of headache disappearance (WMD = -1.51, 95%CI [-1.93, -1.08]), the time of tic disappearance (WMD = -1.88, 95%CI [-2.39, -1.36]). The adjuvant efficacy of ANP for treating viral encephalitis (VE) appears to improve the total effective rate and shorten the disappearance time of clinical syndromes. More high-quality randomized controlled trials (RCTs) are needed to support our findings.

A glutathione S-transferase from Thinopyrum ponticum confers Fhb7 resistance to Fusarium head blight in wheat.

Fusarium head blight (FHB), mainly incited by Fusarium graminearum Schwabe, has caused great losses in grain yield and quality of wheat globally. Fhb7, a major gene from 7E chromosome of Thinopyrum ponticum, confers broad resistance to multiple Fusarium species in wheat, and has recently been cloned and identified as encoding a glutathione S-transferase (GST). However, some recent reports raised doubt about if GST is the causal gene of Fhb7. To resolve the discrepancy and validate the gene function of GST in wheat, we phenotyped Fhb7 near-isogenic lines (Jimai22-Fhb7 vs Jimai22) and GST over-expressed lines for FHB resistance. Jimai22-Fhb7 showed significantly higher FHB resistance with a lower percentage of symptomatic spikelets (PSS), Fusarium-damaged kernel (FDK) and Deoxynivalenol (DON) content than susceptible Jimai22 in three experiments. All the positive GST transgenic lines driven by either the maize ubiquitin promoter (MubiP) or its native promoter (NP) with high gene expression in the wheat cultivar 'Fielder' showed high FHB resistance. Only one MubiP-driven transgenic line showed low GST expression and similar susceptibility as Fielder, suggesting high GST expression confers Fhb7 resistance to FHB. Knockout of GST in Jimai22-Fhb7 line using CRISPR-Cas9-based gene-editing showed significantly higher FHB susceptibility compared with the non-edited control plants. Therefore, we confirmed GST as the causal gene of Fhb7 for FHB resistance. Considering its major effect on FHB resistance, pyramiding Fhb7 with other QTLs has a great potential to create highly FHB-resistant wheat cultivars.

Association analysis between an epigenetic risk score and blood pressure.

Background: Epigenome-wide association studies have revealed multiple DNA methylation sites (CpGs) associated with alcohol consumption, an important lifestyle risk factor for cardiovascular diseases. Results: We generated an alcohol consumption epigenetic risk score (ERS) based on previously reported 144 alcohol-associated CpGs and examined the association of the ERS with systolic blood pressure (SBP), diastolic blood pressure (DBP), and hypertension (HTN) in 3,898 Framingham Heart Study (FHS) participants. We found an association of alcohol intake with the ERS in the meta-analysis with 0.09 units higher ERS per drink consumed per day (p < 0.0001). Cross-sectional analyses in FHS revealed that a one-unit increment of the ERS was associated with 1.93 mm Hg higher SBP (p = 4.64E-07), 0.68 mm Hg higher DBP (p = 0.006), and an odds ratio of 1.78 for HTN (p < 2E-16). Meta-analysis of the cross-sectional association of the ERS with BP traits in eight independent external cohorts (n = 11,544) showed similar relationships with blood pressure levels, i.e., a one-unit increase in ERS was associated with 0.74 (p = 0.002) and 0.50 (p = 0.0006) mm Hg higher SBP and DBP, but could not confirm the association with hypertension. Longitudinal analyses in FHS (n = 3,260) and five independent external cohorts (n = 4,021) showed that the baseline ERS was not associated with a change in blood pressure over time or with incident HTN. Conclusions: Our findings provide proof-of-concept that utilizing an ERS is a useful approach to capture the recent health consequences of lifestyle behaviors such as alcohol consumption.

Dasatinib-induced pleural effusions, pericardial effusion and pulmonary arterial hypertension: a case report.

Background: Pleural effusion, pericardial effusion, and pulmonary arterial hypertension have been shown to have potential associations with the use of dasatinib in adults. However, due to the limited data regarding the efficacy and safety of tyrosine kinase inhibitors (TKIs) in pediatric patients necessities reliance on clinical experience gained from treating adults. Case Description: We present a case of a 12-year-old female patient with chronic myelogenous leukemia (CML) who developed significant right-sided pleural effusion, moderate pericardial effusion, and pulmonary arterial hypertension during dasatinib therapy. Dasatinib was promptly discontinued upon identification of these adverse events. This was followed by the use of bosentan for pulmonary hypertension, furosemide and spironolactone diuretics, prednisone anti-inflammatory, and especially a bold attempt to improve pulmonary endothelial permeability with acetyl cysteine aerosolization. At the same time, according to the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) data reported by the patient and combined with the actual situation, the appropriate TKI was selected for the patient to continue the CML treatment. Conclusions: FAERS data gathered on OpenVigil indicates that the signal associated with pericardial effusion is stronger among individuals under the age of 18 when imatinib is used instead of dasatinib (exactly the reverse of the results in the adult group). However, this does not imply that dasatinib is safer for the smaller group. In our situation, dasatinib-induced adverse effects include pericardial effusion. As a result, while administering TKIs to pediatric patients, we still need to increase monitoring-particularly for pulmonary and cardiovascular toxicity-and take swift action in the event that a major adverse reaction occurs. In addition, it is important to report these adverse effects as much as possible in order to give pediatric patients utilizing TKIs more helpful information.