Superantigen-fused T cell engagers for tumor antigen-mediated robust T cell activation and tumor cell killing.

Inadequate T cell activation has severely limited the success of T cell engager (TCE) therapy, especially in solid tumors. Enhancing T cell activity while maintaining the tumor specificity of TCEs is the key to improving their clinical efficacy. However, currently, there needs to be more effective strategies in clinical practice. Here, we design novel superantigen-fused TCEs that display robust tumor antigen-mediated T cell activation effects. These innovative drugs are not only armed with the powerful T cell activation ability of superantigens but also retain the dependence of TCEs on tumor antigens, realizing the ingenious combination of the advantages of two existing drugs. Superantigen-fused TCEs have been preliminarily proven to have good (>30-fold more potent) and specific (>25-fold more potent) antitumor activity in vitro and in vivo. Surprisingly, they can also induce the activation of T cell chemotaxis signals, which may promote T cell infiltration and further provide an additional guarantee for improving TCE efficacy in solid tumors. Overall, this proof-of-concept provides a potential strategy for improving the clinical efficacy of TCEs.

Guluronic acid disaccharide inhibits reactive oxygen species production and amyloid-ß oligomer formation.

In general, Cu(II) is the critical factor in catalyzing reactive oxygen species (ROS) production and accelerating amyloid-ß (Aß) oligomer formation in Alzheimer's disease (AD). Natural chelating agents with good biocompatibility and appropriate binding affinity with Cu(II) have emerged as potential candidates for AD therapy. Herein, we tested the capability of guluronic acid disaccharide (Di-GA), a natural chelating agent with the moderate association affinity to Cu(II), in inhibiting ROS production and Aß oligomer formation. The results showed that Di-GA was capable of chelating with Cu(II) and reducing ROS production, even in solutions containing Fe(II), Zn(II), and Aß. In addition, Di-GA can also capture Cu(II) from Cu-Aß complexes and decrease Aß oligomer formation. The cellular results confirmed that Di-GA prevented SH-SY5Y cells from ROS and Aß oligomer damage by reducing the injury of ROS and Aß oligomers on cell membrane and decreasing their intracellular damage on mitochondria. Notably, the slightly higher efficiency of Di-GA in chelating with Cu(I) than Cu(II) can be benefit for its in vivo applications, as Cu(I) is not only the most active but also the special intermediate specie during ROS production process. All of these results proved that Di-GA could be a promising marine drug candidate in reducing copper-related ROS damage and Aß oligomer toxicity associated with AD.

Adequate water supply enhances seedling growth and metabolism in Festuca kryloviana: insights from physiological and transcriptomic analys.

BACKGROUND: Festuca kryloviana is a significant native grass species in the Qinghai Lake region, and its low emergence rate is a primary factor limiting the successful establishment of cultivated grasslands. The region's arid and low-rainfall climate characteristics result in reduced soil moisture content at the surface. Despite the recognized impact of water availability on plant growth, the specific role of moisture in seedling development remains not fully elucidated. This study aims to investigate the germination rate and seedling growth velocity of F. kryloviana seeds under varying moisture conditions, and to integrate physiological and transcriptomic analyses of seedlings under these conditions to reveal the mechanisms by which water influences seedling development. RESULTS: The emergence rate of F. kryloviana seedlings exhibited an initial increase followed by a decrease with increasing moisture content. The highest emergence rate, reaching 75%, was observed under 20% soil moisture conditions. By the eighth day of the experiment, the lengths of the plumules and radicles under the optimal emergence rate (full water, FW) were 21.82% and 10.87% longer, respectively, than those under closely matching the soil moisture content during the background survey (stress water, SW). The differential development of seedlings under varying moisture regimes is attributed to sugar metabolism within the seeds and the accumulation of abscisic acid (ABA). At FW conditions, enhanced sugar metabolism, which generates more energy for seedling development, is facilitated by higher activities of α-amylase, sucrose synthase, and trehalose-6-phosphate synthase compared to SW conditions. This is reflected at the transcriptomic level with upregulated expression of the α-amylase (AMY2) gene and trehalose-6-phosphate synthase (TPS6), while genes associated with ABA signaling and transduction are downregulated. Additionally, under FW conditions, the expression of genes related to the chloroplast thylakoid photosystems, such as photosystem II (PSII) and photosystem I (PSI), is upregulated, enhancing the seedlings' light-capturing ability and photosynthetic efficiency, thereby improving their autotrophic capacity. Furthermore, FW treatment enhances the expression of the non-enzymatic antioxidant system, promoting metabolism within the seeds. In contrast, SW treatment increases the activity of the enzymatic antioxidant system, including peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT), to cope with water stress. CONCLUSIONS: Our experiment systematically evaluated the impact of moisture conditions on the growth and development of F. kryloviana seedlings. Physiological and transcriptomic data collectively indicate that adequate water (20%) supply enhances seedling growth and development by reducing ABA levels and increasing α-amylase activity within seeds, thereby boosting sugar metabolism and promoting the growth of seedling, which in turn leads to an improved emergence rate. Considering water management in future cultivation practices may be a crucial strategy for enhancing the successful establishment of F. kryloviana in grassland ecosystems.

Human papillomavirus prevalence and genotype distribution in Liaocheng men between 2016 and 2022.

Human papillomavirus (HPV) infection can lead to HPV-related cancer in men, including the anus, penile, and oropharyngeal cancers and precancerous lesions. This study retrospectively investigated HPV prevalence and genotype distribution in Liaocheng men between 2016 and 2022. The total HPV positive rate was 64.87% (2388/3681, 95% confidence interval [CI]: 63.32%-66.40%), where high risk (HR)-HPV and low risk (LR)-HPV accounted for 42.49% (1564/3681, 95% CI: 40.90%-44.09%) and 69.71% (2566/3681, 95% CI: 68.20%-71.17%), respectively. The mixed HPV infection rate of two and more genotypes was 35.72%. The infection rate of HR-HPV increased with the number of positive cases annually from 2016 (16.91%) to 2022 (46.59%). The most common HR-HPV genotypes were HPV16 (11.60%), HPV52 (6.95%), and HPV59 (6.28%), whereas the least common HR-HPV was HPV26. The most common LR-HPV genotypes were HPV6 (56.99%), HPV11 (23.79%), and HPV43 (6.37%). The 9 v HPV vaccine preventable for LR-HPV and HR-HPV accounted for 80.78% and 30.40%, respectively, in this study. Most HPV-positive patients aged 1-86 were in the 30-39 age group. This study confirmed that HPV prevalence in Liaocheng men was common and diverse. HPV16, HPV52, and HPV59 are widely distributed in Liaocheng men, and the male HR-HPV infection rate remained high in this region. Regarding public health and cancer prevention, it is recommended and effective to include the HPV vaccination in the national vaccination program for men.

Transmission chains of the first local outbreak cause by Delta VariantB.1.617.2 COVID-19 in Guangzhou, Southern China.

BACKGROUND: The first local outbreak of Delta Variant B.1.617.2 COVID-19 of China occurred in Guangzhou city, south China, in May 2021. This study analyzed the transmission chains and local cluster characteristics of this outbreak, intended to provide information support for the development and adjustment of local prevention and control strategies. METHODS: The transmission chains and local cluster characteristics of 161 local cases in the outbreak were described and analyzed. Incubation period, serial interval and generation time were calculated using the exact time of exposure and symptom onset date of the cases. The daily number of reported cases and the estimated generation time were used to estimate the effective reproduction number (Rt). RESULTS: We identified 7 superspreading events who had more than 5 next generation cases and their infected cases infected 70.81%(114/161) of all the cases transmission. Dining and family exposure were the main transmission routes in the outbreak, with 29.19% exposed through dining and 32.30% exposed through family places. Through further analysis of the outbreak, the estimated mean incubation period was 4.22 (95%CI: 3.66-4.94) days, the estimated mean generation time was 2.60 (95%CI: 1.96-3.11) days, and the estimated Rt was 3.29 (95%CI: 2.25-5.07). CONCLUSIONS: Classification and dynamically adjusted prevention and control measures had been carried out according to analysis of transmission chains and epidemical risk levels, including promoting nucleic acid screening at different regions and different risk levels, dividing closed-off area, controlled area according to the risk of infection, raising the requirements of leaving Guangzhou. By the above control measures, Guangzhou effectively control the outbreak within 28 days without implementing a large-scale lockdown policy.

Mir-204-5p alleviates mitochondrial dysfunction by targeting IGFBP5 in diabetic cataract.

BACKGROUND: Cataract contributes to visual impairment worldwide, and diabetes mellitus accelerates the formation and progression of cataract. Here we found that the expression level of miR-204-5p was diminished in the lens epithelium with anterior lens capsule of cataract patients compared to normal donors, and decreased more obviously in those of diabetic cataract (DC) patients. However, the contribution and mechanism of miR-204-5p during DC development remain elusive. METHODS AND RESULT: The mitochondrial membrane potential (MMP) was reduced in the lens epithelium with anterior lens capsule of DC patients and the H2O2-induced human lens epithelial cell (HLEC) cataract model, suggesting impaired mitochondrial functional capacity. Consistently, miR-204-5p knockdown by the specific inhibitor also attenuated the MMP in HLECs. Using bioinformatics and a luciferase assay, further by immunofluorescence staining and Western blot, we identified IGFBP5, an insulin-like growth factor binding protein, as a direct target of miR-204-5p in HLECs. IGFBP5 expression was upregulated in the lens epithelium with anterior lens capsule of DC patients and in the HLEC cataract model, and IGFBP5 knockdown could reverse the mitochondrial dysfunction in the HLEC cataract model. CONCLUSIONS: Our results demonstrate that miR-204-5p maintains mitochondrial functional integrity through repressing IGFBP5, and reveal IGFBP5 may be a new therapeutic target and prognostic factor for DC.

Yield stress Measurement of municipal sludge: A comprehensive evaluation of testing methods and concentration effects using a rotational rheometer.

Accurate prediction and measurement of yield stress are crucial for optimizing sludge treatment and disposal. However, the differences and applicability of various methods for measuring yield stress are subjects of ongoing debate. Meanwhile, literature on measuring sludge yield stress is limited to low solid concentrations (TS <10%), understanding and studying the yield stress of medium to high solid concentration sludge is crucial due to increasingly stringent standards for sludge treatment and disposal. So, this study employed a rotational rheometer to measure sludge yield stress across a wide range of TS (4-50%) using steady shear, dynamic oscillatory shear, and transient shear. The study derived significant conclusions by comparing and summarizing the applicability and limitations of each testing method: Dynamic oscillatory shear methods, including G'-σ curve method, γ-σ curve method, and G**γc method can measure sludge yield stress ranging from 4% to 40% TS, while other methods are restricted to low or limited solid concentrations; The G' = G″ method, utilizing the intersection of G' and G″ curves, consistently yields the highest value for yield stress when 4%≤ TS ≤ 12%; The rotational rheometer cannot measure sludge yield stress when the solid concentration exceeds 40% TS; The relationship between sludge yield stress and solid concentration is stronger as a power-law for TS ≤ 25%, transitioning to linear for higher concentrations (28%≤ TS <40%). This study systematically explores the applicability and limitations of various measurement methods for characterizing sludge yield stress across a wide range of solid concentrations, providing valuable guidance for scientific measurement and highlighting challenging research issues.

Effects of meteorological factors on influenza transmissibility by virus type/subtype.

BACKGROUND: Quantitative evidence on the impact of meteorological factors on influenza transmissibility across different virus types/subtypes is scarce, and no previous studies have reported the effect of hourly temperature variability (HTV) on influenza transmissibility. Herein, we explored the associations between meteorological factors and influenza transmissibility according to the influenza type and subtype in Guangzhou, a subtropical city in China. METHODS: We collected influenza surveillance and meteorological data of Guangzhou between October 2010 and December 2019. Influenza transmissibility was measured using the instantaneous effective reproductive number (Rt). A gamma regression with a log link combined with a distributed lag non-linear model was used to assess the associations of daily meteorological factors with Rt by influenza types/subtypes. RESULTS: The exposure-response relationship between ambient temperature and Rt was non-linear, with elevated transmissibility at low and high temperatures. Influenza transmissibility increased as HTV increased when HTV < around 4.5 °C. A non-linear association was observed between absolute humidity and Rt, with increased transmissibility at low absolute humidity and at around 19 g/m3. Relative humidity had a U-shaped association with influenza transmissibility. The associations between meteorological factors and influenza transmissibility varied according to the influenza type and subtype: elevated transmissibility was observed at high ambient temperatures for influenza A(H3N2), but not for influenza A(H1N1)pdm09; transmissibility of influenza A(H1N1)pdm09 increased as HTV increased when HTV < around 4.5 °C, but the transmissibility decreased with HTV when HTV < 2.5 °C and 3.0 °C for influenza A(H3N2) and B, respectively; positive association of Rt with absolute humidity was witnessed for influenza A(H3N2) even when absolute humidity was larger than 19 g/m3, which was different from that for influenza A(H1N1)pdm09 and influenza B. CONCLUSIONS: Temperature variability has an impact on influenza transmissibility. Ambient temperature, temperature variability, and humidity influence the transmissibility of different influenza types/subtypes discrepantly. Our findings have important implications for improving preparedness for influenza epidemics, especially under climate change conditions.

Optimization of Flavonoid Extraction from Abelmoschus manihot Flowers Using Ultrasonic Techniques: Predictive Modeling through Response Surface Methodology and Deep Neural Network and Biological Activity Assessment.

Understanding the optimal extraction methods for flavonoids from Abelmoschus manihot flowers (AMF) is crucial for unlocking their potential benefits. This study aimed to optimize the efficiency of flavonoid extraction from AMF. After comparing extraction methods, the ultrasonic cell crusher demonstrated superior performance over conventional techniques. Four key factors-solid-to-liquid ratio (1:10 to 1:50 g·mL-1), ethanol concentration (55% to 95%), ultrasonic time (10 to 50 min), and ultrasonic power (5% to 25% of 900 W)-were investigated and normalized using the entropy weight method. This led to a comprehensive evaluation (CE). Optimization of extraction conditions for the ultrasonic cell crusher was achieved through response surface methodology and a deep neural network model, resulting in optimal parameters: ethanol volume fraction of 66%, solid-to-liquid ratio of 1:21 g/mL, extraction efficiency of 9%, and extraction duration of 35 min, yielding a CE value of 23.14 (RSD < 1%). Additionally, the inhibitory effects of the optimized extracts against Streptococcus mutans (S. mutans) were assessed. The results revealed that AMF extract (AMFE) exhibits inhibitory effects on S. mutans, with concomitant inhibition of sucrase and lactate dehydrogenase (LDH). The MIC of AMFE against planktonic S. mutans is 3 mg/mL, with an MBC of 6 mg/mL. Within the concentration range of 1/8 MIC to 2 MIC of AMFE, the activities of sucrase and LDH decreased by 318.934 U/mg prot and 61.844 U/mg prot, respectively. The antioxidant activity of AMFE was assessed using the potassium ferricyanide reduction and phosphomolybdenum methods. Additionally, the effect of AMFE on DPPH, ABTS, and ·OH free radical scavenging abilities was determined. The concentrations at which AMFE exhibited over 90% scavenging rate for ABTS and DPPH free radicals were found to be 0.125 mg/mL and 2 mg/mL, respectively.

The Dynamic Evolution Model of the Chemical and Carbon Isotopic Composition of C1-3 during the Hydrocarbon Generation Process.

A new approach is presented in this paper for the dynamic modeling of the chemical and isotopic evolution of C1-3 during the hydrocarbon generation process. Based on systematic data obtained from published papers for the pyrolysis of various hydrocarbon sources (type I kerogen/source rock, type II kerogen/source rock, type III kerogen/source rock, crude oil, and asphalt, etc.), the empirical evolution framework of the chemical and isotopic composition of C1-3 during the hydrocarbon generation process was built. Although the empirical framework was built only by fitting a large amount of pyrolysis data, the chemical and isotopic composition of C1-3 derived from the pyrolysis experiments all follow evolution laws, convincing us that it is applicable to the thermal evolution process of various hydrocarbon sources. Based on the simplified formula of the isotopic composition of mixed natural gas at different maturities (δ13Cmixed), δ13Cmixed = X×niA×δ13CiA+Y×niB×δ13CiBX×niA+Y×niB, it can be derived that the cumulative isotopic composition of alkane generated in a certain maturity interval can be expressed by the integral of the product of the instantaneous isotopic composition and instantaneous yield at a certain maturity point, and then divided by the cumulative yield of alkane generated in the corresponding maturity interval. Thus, the cumulative isotopic composition (A(X)), cumulative yield (B(X)), instantaneous isotope (C(X)), and instantaneous yield (D(x)) in the dynamic model, comply with the following formula during the maturity interval of (X0~X). A(X) = ∫X0XCX×DXdxB(X), where A(X) and B(X) can be obtained by the fitting of pyrolysis data, and D(x) can also be obtained from the derivation of B(X). The dynamic model was applied on the pyrolysis data of Pingliang Shale to illustrate the quantitative evolution of the cumulative yield, instantaneous yield, cumulative isotope, and instantaneous isotope of C1-3 with increasing maturity. The dynamic model can quantify the yield of methane, ethane, and propane, as well as δ13C1, δ13C2, and δ13C3, respectively, during the hydrocarbon generation process. This model is of great significance for evaluating the natural gas resources of hydrocarbon source rock of different maturities and for identifying the origin and evolutionary process of hydrocarbons by chemical and isotopic data. Moreover, this model provides an approach to study the dynamic evolution of the isotope series of C1-3 (including reversed isotopic series), which is promising for revealing the mechanism responsible for isotopic reversal when combined with post-generation studies.

Tannic acid alleviates ETEC K88-induced intestinal damage through regulating the p62-keap1-Nrf2 and TLR4-NF-κB-NLRP3 pathway in IPEC-J2 cells.

BACKGROUND: Tannic acid (TA), a naturally occurring polyphenol, has shown diverse potential in preventing intestinal damage in piglet diarrhea induced by Enterotoxigenic Escherichia coli (ETEC) K88. However, the protective effect of TA on ETEC k88 infection-induced post-weaning diarrhea and its potential mechanism has not been well elucidated. Therefore, an animal trial was carried out to investigate the effects of dietary supplementation with TA on the intestinal diarrhea of weaned piglets challenged with ETEC K88. In addition, porcine intestinal epithelial cells were used as an in vitro model to explore the mechanism through which TA alleviates intestinal oxidative damage and inflammation. RESULTS: The results indicated that TA supplementation (2 and 4 g kg-1) reduced diarrhea rate, enzyme activity (diamine oxidase [DAO] and Malondialdehyde [MAD]) and serum inflammatory cytokines concentration (TNF-α and IL-1ß) (P < 0.05) compared to the Infection group (IG), group in vivo. In vitro, TA treatment effectively alleviated ETEC-induced cytotoxicity, increased the expression of ZO-1, occludin and claudin-1 at both mRNA and protein levels. Moreover, TA pre-treatment increased the activity of antioxidant enzymes (such as T-SOD) and decreased serum cytokine levels (TNF-α and IL-1ß). Furthermore, TA increased cellular antioxidant capacity by activating the Nrf2 signaling pathway and decreased inflammatory response by down-regulating the expression of TLR4, MyD88, NF-kB and NLRP3. CONCLUSION: The present study showed that TA reduced the diarrhea rate of weaned piglets by restoring the intestinal mucosal mechanical barrier function, alleviating oxidative stress and inflammation. The underlying mechanism was achieved by modulating the p62-keap1-Nrf2 and TLR4-NF-κB-NLRP3 pathway. © 2024 Society of Chemical Industry.

[Research progress on DNMT3A gene expression in Acute myeloid leukemia].

DNA methylation is an important epigenetic regulatory mechanism which plays a crucial role in cell differentiation and development. Its function is closely related to DNA methyltransferase 3 alpha (DNMT3A), which can affect gene expression and stem cell differentiation. The mutation rate of the DNMT3A gene is relatively high in Acute myeloid leukemia (AML), but its type and pathogenic mechanism are not yet clear. Further research on DNMT3A may help to identify its pathogenic targets and provide a basis for precise treatment of AML. This article has provided a review for the research progress on the expression of the DNMT3A gene in AML.

The role of grid management in community risk governance: a case study in Yuelu, China.

Objective: In this study, we aim to provide a comprehensive analysis of the effectiveness of the risk prevention and control mechanism within the grid management model for community risk prevention. We emphasize the importance of thoroughly examining the risk prevention and control mechanism to enhance risk management efforts in urban communities, particularly in response to unforeseen outbreaks such as COVID-19. Methods: Case studies are widely acknowledged as one of the most effective approaches to examine governance in China. In this study, the "Yuelu Model" serves as an illustrative example to demonstrate the application and effectiveness of grid management in community risk governance. To ensure the validity of the case study, it is imperative to adhere to the principle of representativeness. The collection of case data involves a combination of primary and secondary sources, and supplementary information is obtained through follow-up investigations conducted via WeChat, telephone, and other means, thereby enhancing the comprehensiveness and accuracy of the data. Results: Our analysis reveals significant findings regarding the impact of the grid management model, fulfilling a triple role as a "Social Safety Valve" in the management process: (1) Community stress reduction function, (2) Community alarm function, and (3) Community integration function. Furthermore, we explore the adaptability of the grid management mechanism in addressing community risks, highlighting its effectiveness and potential for broader application. Discussion: The findings of this study suggest that: Firstly, it is crucial to establish a shared information repository among different departments on a big data platform. Secondly, a dynamic government public information internal network should be established through collaborative efforts among multiple departments. Thirdly, implementing a regular (or periodic) early warning mechanism is essential. Lastly, the establishment of a high-quality talent team for power grid management is highly recommended. Our research provides valuable insights to enhance community risk governance.

Legume-grass mixtures improve biological nitrogen fixation and nitrogen transfer by promoting nodulation and altering root conformation in different ecological regions of the Qinghai-Tibet Plateau.

Introduction: Biological nitrogen fixation (BNF) plays a crucial role in nitrogen utilization in agroecosystems. Functional characteristics of plants (grasses vs. legumes) affect BNF. However, little is still known about how ecological zones and cropping patterns affect legume nitrogen fixation. This study's objective was to assess the effects of different cropping systems on aboveground dry matter, interspecific relationships, nodulation characteristics, root conformation, soil physicochemistry, BNF, and nitrogen transfer in three ecological zones and determine the main factors affecting nitrogen derived from the atmosphere (Ndfa) and nitrogen transferred (Ntransfer). Methods: The 15N labeling method was applied. Oats (Avena sativa L.), forage peas (Pisum sativum L.), common vetch (Vicia sativa L.), and fava beans (Vicia faba L.) were grown in monocultures and mixtures (YS: oats and forage peas; YJ: oats and common vetch; YC: oats and fava beans) in three ecological regions (HZ: Huangshui Valley; GN: Sanjiangyuan District; MY: Qilian Mountains Basin) in a split-plot design. Results: The results showed that mixing significantly promoted legume nodulation, optimized the configuration of the root system, increased aboveground dry matter, and enhanced nitrogen fixation in different ecological regions. The percentage of nitrogen derived from the atmosphere (%Ndfa) and percentage of nitrogen transferred (%Ntransfer) of legumes grown with different legume types and in different ecological zones were significantly different, but mixed cropping significantly increased the %Ndfa of the legumes. Factors affecting Ndfa included the cropping pattern, the ecological zone (R), the root nodule number, pH, ammonium-nitrogen, nitrate-nitrogen, microbial nitrogen mass (MBN), plant nitrogen content (N%), and aboveground dry biomass. Factors affecting Ntransfer included R, temperature, altitude, root surface area, nitrogen-fixing enzyme activity, organic matter, total soil nitrogen, MBN, and N%. Discussion: We concluded that mixed cropping is beneficial for BNF and that mixed cropping of legumes is a sustainable and effective forage management practice on the Tibetan Plateau.

Research hotspots and frontiers of alcohol and epilepsy: A bibliometric analysis.

PURPOSE: Alcohol is implicated in epileptogenesis and seizures attack. An increasing number of studies about alcohol and epilepsy have been published. We aimed to assess research trends and hot spots in the field of alcohol and epilepsy. PATIENTS AND METHODS: Literature concerning alcohol and epilepsy was systemically searched through the Web of Science database. Collaborative maps were quantitatively analyzed by using the VOSviewer and CiteSpace tools. RESULTS: A total of 1578 papers about the field of alcohol and epilepsy were taken into analysis, which was written by 6840 authors from 2153 institutions in 85 countries, published in 676 journals, and cited 79 667 references from 10 750 journals. The United States was the leading country and had close ties with others. The University of Toronto was the most productive institution. Alcoholism-clinical and experimental research was the fastest-growing journal. Richard J. Bodnar was the author contributing the most literature. Analysis of keywords showed epilepsy, alcohol, seizures, alcohol withdrawal, and management were common themes. CONCLUSION: The presented study conducted the first bibliometric analysis of the field of alcohol and epilepsy, which will provide insights into the latest progress, evolution paths, frontier research hot spots, and future research trends in the field.

Variation and interrelationships in the growth, yield, and lodging of oat under different planting densities.

Background: Oat is a dual-purpose cereal used for grain and forage. The demand of oat has been increasing as the understanding of the nutritional, ecological, and economic values of oat increased. However, the frequent lodging during the growing period severely affect the high yielding potential and the quality of the grain and forage of oat. Methods: Therefore, we used the lodging-resistant variety LENA and the lodging-sensitive variety QY2 as materials, implementing four different planting densities: 2.25×106 plants/ha (D1), 4.5×106 plants/ha (D2), 6.75×106 plants/ha (D3), and 9×106 plants/ha (D4). At the appropriate growth and development stages, we assessed agronomic traits, mechanical characteristics, biochemical compositions, yield and its components. The study investigated the impact of planting density on the growth, lodging, and yield of oat, as well as their interrelationships. Additionally, we identified the optimal planting density to establish a robust crop structure. The research aims to contribute to the high-yield and high-quality cultivation of oat. Results: We observed that with increasing planting density, plant height, grass and grain yields of both varieties first increased and then decreased; root fresh weight, stem diameter, stem wall thickness, stem puncture strength, breaking strength, compressive strength, lignin and crude fiber contents, and yield components decreased; whereas the lodging rate and lodging coefficient increased. Planting density affects lodging by regulating plant height, height of center of gravity, stem wall thickness, internode length, and root fresh weight of oat. Additionally, it can impact stem mechanical strength by modulating the synthesis of lignin and crude fiber, which in turn affecting lodging resistance. Plant height, height of center of gravity, stem wall thickness, internode length, root fresh weight, breaking strength, compressive strength, lignin and crude fiber content, single-plant weight, grain yield and 1,000-grain weight can serve as important indicators for evaluating oat stem lodging resistance. We also noted that planting density affected grain yield both directly and indirectly (by affecting lodging); high density increased lodging rate and decreased grain yield, mainly by reducing 1,000-grain weight. Nonetheless, there was no significant relationship between lodging and grass yield. As appropriate planting density can increase the yield while maintaining good lodging resistance, in this study, 4.5×106 plants/ha (D2) was found to be the best planting density for oat in terms of lodging resistance and grass and grain yield. These findings can be used as a reference for oat planting.

A Transcriptome Reveals the Mechanism of Nitrogen Regulation in Tillering.

Nitrogen (N) application significantly increases tiller numbers and is accompanied by changes in endogenous hormone content. We treated seedlings of Festuca kirilowii-a perennial forage grass-with nitrogen, determined the endogenous hormone content in the tiller buds, and performed a transcriptome analysis. The application of N reduced GA3, ABA, and 5-DS content and increased ZT and IAA content. By screening DEGs in the transcriptome results, we obtained DEGs annotated to 25 GO entries and 8 KEGG pathways associated with endogenous hormones. Most of these GO entries and KEGG pathways were associated with IAA, GAS, and ABA. We conducted a validation analysis of hormone-related DEGs using qRT-PCR to demonstrate that nitrogen controls the content of endogenous hormones by regulating the expression of these DEGs, which further affects tillering in F. kirilowii.

TTYH3 promotes the malignant progression of oral squamous cell carcinoma SCC-9 cells by regulating tumor-associated macrophage polarization.

OBJECTIVE: This study was designed to investigate the biological role and the reaction mechanism of Tweety family member 3 (TTYH3) in oral squamous cell carcinoma (OSCC). DESIGN: The mRNA and protein expressions of TTYH3 were assessed with RT-qPCR and western blot. After silencing TTYH3 expression, the proliferation of OSCC cells were detected using cell counting kit-8 (CCK-8) assay, 5-ethynyl-2'-deoxyuridine (EdU) staining and colony formation assay. Cell migration and invasion were detected using wound healing and transwell. Gelatin zymography protease assay was used to detect matrix metalloproteinase-2 (MMP2) and matrix metalloproteinase-2 (MMP9) activity and western blot was used to detect the expressions of proteins associated with proliferation and epithelial-mesenchymal transition (EMT). The mRNA expression of TTYH3 in THP-1-derived macrophage was detected using real-time reverse transcriptase-polymerase chain reaction (RT-qPCR). The number of CD86-positive cells and CD206-positive cells was detected using immunofluorescence assay. RT-qPCR was used to detect the expressions of M2 markers arginase 1 (ARG1), chitinase-like 3 (YM1) and mannose receptor C-type 1 (MRC1). RESULTS: In this study, it was found that TTYH3 expression was upregulated in OSCC cell lines and TTYH3 knockdown could inhibit the proliferation, migration, invasion and EMT process in OSCC via suppressing M2 polarization of tumor-associated macrophages. CONCLUSIONS: Collectively, TTYH3 facilitated the progression of OSCC through the regulation of tumor-associated macrophages polarization.

Genetics of causal relationships between circulating inflammatory proteins and postherpetic neuralgia: a bidirectional Mendelian randomization study.

Objective: According to data from several observational studies, there is a strong association between circulating inflammatory cytokines and postherpetic neuralgia (PHN), but it is not clear whether this association is causal or confounding; therefore, the main aim of the present study was to analyze whether circulating inflammatory proteins have a bidirectional relationship with PHN at the genetic inheritance level using a Mendelian randomization (MR) study. Methods: The Genome-Wide Association Study (GWAS) database was used for our analysis. We gathered data on inflammation-related genetic variation from three GWASs of human cytokines. These proteins included 91 circulating inflammatory proteins, tumor necrosis factor-alpha (TNF-α), macrophage inflammatory protein 1b (MIP-1b), and CXC chemokine 13 (CXCL13). The PHN dataset was obtained from the FinnGen biobank analysis round 5, and consisted of 1,413 cases and 275,212 controls. We conducted a two-sample bidirectional MR study using the TwoSampleMR and MRPRESSO R packages (version R.4.3.1). Our main analytical method was inverse variance weighting (IVW), and we performed sensitivity analyses to assess heterogeneity and pleiotropy, as well as the potential influence of individual SNPs, to validate our findings. Results: According to our forward analysis, five circulating inflammatory proteins were causally associated with the development of PHN: interleukin (IL)-18 was positively associated with PHN, and IL-13, fibroblast growth factor 19 (FGF-19), MIP-1b, and stem cell growth factor (SCF) showed reverse causality with PHN. Conversely, we found that PHN was closely associated with 12 inflammatory cytokines, but no significant correlation was found among the other inflammatory factors. Among them, only IL-18 had a bidirectional causal relationship with PHN. Conclusion: Our research advances the current understanding of the role of certain inflammatory biomarker pathways in the development of PHN. Additional verification is required to evaluate the viability of these proteins as targeted inflammatory factors for PHN-based treatments.