Integrated physiological, transcriptomic and metabolomic analyses reveal the mechanism of peanut kernel weight reduction under waterlogging stress.

Waterlogging stress (WS) hinders kernel development and directly reduces peanut yield; however, the mechanism of kernel filling in response to WS remains unknown. The waterlogging-sensitive variety Huayu 39 was subjected to WS for 3 days at 7 days after the gynophores touched the ground (DAG). We found that WS affected kernel filling at 14, 21, and 28 DAG. WS decreased the average filling rate and kernel dry weight, while transcriptome sequencing and widely targeted metabolomic analysis revealed that WS inhibited the gene expression in starch and sucrose metabolism, which reduced sucrose input and transformation ability. Additionally, genes related to ethylene and melatonin synthesis and the accumulation of tryptophan and methionine were upregulated in response to WS. WS upregulated the expression of the gene encoding tryptophan decarboxylase (AhTDC), and overexpression of AhTDC in Arabidopsis significantly reduced the seed length, width, and weight. Therefore, WS reduced the kernel-filling rate, leading to a reduction in the 100-kernel weight. This survey informs the development of measures that alleviate the negative impact of WS on peanut yield and quality and provides a basis for exploring high-yield and high-quality cultivation, molecular-assisted breeding, and waterlogging prevention in peanut farming.

An E7-retinoblastoma protein pathway mechanism may account for the higher carcinogenic ability of HPV16 over HPV58 in cervical cancer.

Background: Among human papillomavirus (HPV) type, HPV16 displays the strongest carcinogenic capacity for cervical cancer, but the mechanism underlying this phenomenon remains unclear. We investigated the effect and the underlying mechanism of HPV16 on higher carcinogenic capacity than HPV58. Methods: We collected 4,030 cervical exfoliated cell samples for genotyping HPV using HybriBio's proprietary flow-through hybridization technique, liquid-based cytology (LBC), colposcopy, and biopsies if indicated. Four plasmids containing E6 and E7 of HPV16 and 58 were constructed and transfected into 293T and U2OS cells. We detected the cell phenotype using Cell Counting Kit 8 (CCK8) assay, Transwell assay, flow cytometry, and apoptosis assay; the expression of retinoblastoma protein (Rb) and phosphorylated Rb (pRb) was determined via Western blot; and the cell activity was determined via a zebrafish model treated with or without roscovitine. Results: The positive rates of HPV16 and 58 were, respectively, 18.9% and 19.7% in the ≤ low-grade squamous intraepithelial lesion (LSIL) group, 49.5% and 19.6% (P<0.001) in the high-grade squamous intraepithelial lesion (HSIL) group, 65.3% and 9.0% (P<0.001) in the cancer group. In vitro, both 293T and U2OS cells with overexpressed HPV16 E6 and E7 displayed significantly higher cell proliferation, faster cell invasion, decreased cell apoptosis, and accelerated cell cycle from G1 phase to S phase compared to those with overexpressed HPV58 E6 and E7 (all P values <0.05). Rb loss of function was observed in cells with HPV16 E7 overexpression, while a greater level of phosphorylated Rb was observed in cells with HPV58 E7 overexpression. Roscovitine restored Rb expression and decreased the cell activity in zebrafish. Conclusions: HPV16 possesses a stronger carcinogenic ability than does HPV 58, and the mechanism underlying this effect may be the impairment of the E7-Rb pathway.

Celastrol ameliorates hypoxic-ischemic brain injury in neonatal rats by reducing oxidative stress and inflammation.

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) is caused by perinatal hypoxia and subsequent reductions in cerebral blood flow and is one of the leading causes of severe disability or death in newborns. Despite its prevalence, we currently lack an effective drug therapy to combat HIE. Celastrol (Cel) is a pentacyclic triterpene extracted from Tripterygium Wilfordi that can protect against oxidative stress, inflammation, and cancer. However, whether Cel can alleviate neonatal hypoxic-ischemic (HI) brain damage remains unclear. METHODS: Here, we established both in vitro and in vivo models of HI brain damage using CoCl2-treated PC12 cells and neonatal rats, respectively, and explored the neuroprotective effects of Cel in these models. RESULTS: Analyses revealed that Cel administration reduced brain infarction size, microglia activation, levels of inflammation factors, and levels of oxidative stress markers by upregulating levels of p-AMPKα, Nrf2, HO-1, and by downregulating levels of TXNIP and NLRP3. Conversely, these beneficial effects of Cel on HI brain damage were largely inhibited by AMPKα inhibitor Compound C and its siRNA. CONCLUSIONS: We present compelling evidence that Cel decreases inflammation and oxidative stress through the AMPKα/Nrf2/TXNIP signaling pathway, thereby alleviating neonatal HI brain injury. Cel therefore represents a promising therapeutic agent for treating HIE. IMPACT: We firstly report that celastrol can ameliorate neonatal hypoxic-ischemic brain injury both in in vivo and in vitro, which represents a promising therapeutic agent for treating related brain injuries. Celastrol activates the AMPKα/Nrf2/TXNIP signaling pathway to relieve oxidative stress and inflammation and thereby alleviates neonatal hypoxic-ischemic brain injury.

Alveolar bone retention following treatment of dilacerated labial inversely impacted maxillary central incisors-a retrospective study.

The root of late-dental-age labial inversely impacted maxillary central incisors (LIIMCIs) typically develops to severe dilacerated morphology. Therefore, reliable posttreatment periodontal estimates of orthodontic treatment prognosis would be critical to the treatment value of impacted incisors. This study aims to analyze further changes in dimensions of the alveolar bone following the closed-eruption treatment of late-dental-age dilacerated LIIMCIs. Cone beam computed tomography (CBCT) scanning data of 16 patients with unilateral dilacerated late-dental-age LIIMCIs were collected, including the pretreatment (T1) and at the 2.23 ± 0.78 years follow-up stage (T2) respectively. Patients underwent closed-eruption treatments to bring the impacted incisor into the dental arch. Dolphin imaging software was used to measure alveolar bone height labially, palatally, and proximally to the site at T1 and T2, as well as alveolar bone thicknesses at 0, 2, 4, 6 and 8 mm below the initial measurement plane (IMP). The alveolar bone heights on the impacted and contralateral sides increased from T1 to T2 (p < 0.05). Alveolar bone growth on both sides had no significant difference. In T2, the mean values of labial and distal alveolar heights on the contralateral sides were greater than on the impacted sides (p < 0.05). The mean values of total alveolar bone thicknesses on the impacted sides in T1 were significantly smaller than those on the contralateral sides in IMP-0, 2, 4, 6, 8 (p < 0.05). The total thicknesses on the impacted sides in T2 increased and were significantly greater than on the contralateral sides (p < 0.05), except for the thickness in IMP-0. The closed-eruption treatment of dilacerated late-dental-age LIIMCIs results in no significant changes to alveolar bone height, except on the labial and distal sides, with increased alveolar bone thickness, suggesting that this approach may be viable first choice therapy for non-extraction orthodontic cases.

Curcumin Improves Neurogenesis in Alzheimer's Disease Mice via the Upregulation of Wnt/ß-Catenin and BDNF.

Adult neurogenesis in the dentate gyrus (DG) is impaired during Alzheimer's disease (AD) progression. Curcumin has been reported to reduce cell apoptosis and stimulate neurogenesis. This study aimed to investigate the influence of curcumin on adult neurogenesis in AD mice and its potential mechanism. Two-month-old male C57BL/6J mice were injected with soluble ß-amyloid (Aß1-42) using lateral ventricle stereolocalization to establish AD models. An immunofluorescence assay, including bromodeoxyuridine (BrdU), doublecortin (DCX), and neuron-specific nuclear antigen (NeuN), was used to detect hippocampal neurogenesis. Western blot and an enzyme-linked immunosorbent assay (ELISA) were used to test the expression of related proteins and the secretion of brain-derived neurotrophic factor (BDNF). A Morris water maze was used to detect the cognitive function of the mice. Our results showed that curcumin administration (100 mg/kg) rescued the impaired neurogenesis of Aß1-42 mice, shown as enhanced BrdU+/DCX+ and BrdU+/NeuN+ cells in DG. In addition, curcumin regulated the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) -mediated glycogen synthase kinase-3ß (GSK3ß) /Wingless/Integrated (Wnt)/ß-catenin pathway and cyclic adenosine monophosphate response element-binding protein (CREB)/BDNF in Aß1-42 mice. Inhibiting Wnt/ß-catenin and depriving BDNF could reverse both the upregulated neurogenesis and cognitive function of curcumin-treated Aß1-42 mice. In conclusion, our study indicates that curcumin, through targeting PI3K/Akt, regulates GSK3ß/Wnt/ß-catenin and CREB/BDNF pathways, improving the adult neurogenesis of AD mice.

Active metabolomics identify potential functional metabolites for preeclampsia prevention.

BACKGROUND: Preeclampsia (PE) is a leading cause of maternal and fetal morbidity and mortality, with limited effective clinical treatment options. Active metabolomics offers a promising approach to uncover metabolic changes in PE and identify potential biomarkers or therapeutic targets. This study performed untargeted metabolomics using LC-MS to compare serum samples from preeclampsia and normal pregnancies. METHODS: We performed untargeted metabolomics using liquid chromatography-mass spectrometry (LC-MS) to compare serum samples from PE patients and normal pregnancies. We analyzed the alterations in metabolites and conducted functional experiments to assess the effects of LysoPE(16:0) on trophoblast cell invasion and migration. Mechanistic studies were performed to explore the potential targeting of GSK-3ß by LysoPE(16:0). RESULTS: Our metabolomics analysis revealed significant alterations in several metabolites, including lysophosphatidylcholines and organic acids. Notably, LysoPE(16:0) was found to be downregulated in the serum of PE patients. Functional experiments demonstrated that LysoPE(16:0) could promote trophoblast cell invasion and migration. Mechanistic studies suggest that the protective effect of LysoPE(16:0) against PE might be mediated through the modulation of the GSK-3ß/ß-Catenin pathway, with LysoPE(16:0) potentially targeting the GSK-3ß protein. CONCLUSIONS: Our findings highlight the potential role of LysoPE(16:0) in the pathophysiology of PE and its ability to modulate the GSK-3ß/ß-Catenin pathway. These results provide new insights into the metabolic changes associated with PE and suggest that LysoPE(16:0) could serve as a promising biomarker or therapeutic target for the prevention and treatment of PE.

A whole-exome sequencing study of patent foramen ovale: investigating genetic variants and their association with cardiovascular disorders.

Background: Patent foramen ovale (PFO) has a genetic predisposition and is closely associated with cryptogenic stroke (CS), migraine, decompression sickness, and hypoxemia. Identifying PFO-related mutant genes through whole-exome sequencing (WES) can help in the early recognition of cardiovascular genetic risk factors, guide timely clinical intervention, and reduce the occurrence of cardiovascular events. Methods: We analyzed mutant genes from ClinVar and OMIM databases. WES was performed on 25 PFO patients from Zhejiang Provincial Hospital of Chinese Medicine. Pathogenicity of variants was evaluated using American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology. (AMP) guidelines. Results: In ClinVar (4 Feb 2023), 113 coding gene mutations were found, including 83 associated with PFO. From OMIM (18 Apr 2023), 184 gene mutations were analyzed, with 110 mutant coding genes. WES identified pathogenic mutations in two of 25 PFO patients (8%). LDLR, SDHC, and NKX2-5 genes were linked to PFO and primarily involved in myocardial tissue function. NKX2-5 may play a crucial role in PFO development, interacting with NOTCH1, GATA4, MYH6, SCN5A signaling pathways regulating cardiomyocyte characteristics. Conclusion: We identified pathogenic mutations in LDLR, SDHC, and NKX2-5 genes, implying their role in PFO development. Functional enrichment analysis revealed NKX2-5's interaction with signaling pathways regulating cardiomyocyte function. These findings enhance our understanding of PFO's genetic basis, suggesting potential therapeutic targets for future research.

Stratified Treatment in Pediatric Anaplastic Large Cell Lymphoma: Result of a Prospective Open-Label Multiple-Institution Study.

Purpose: The risk stratification of pediatric anaplastic large cell lymphoma (ALCL) has not been standardized. In this study, new risk factors were included to establish a new risk stratification system for ALCL, and its feasibility in clinical practice was explored. Materials and Methods: On the basis of the non-Hodgkin's lymphoma Berlin-Frankfurt-Munster 95 (NHL-BFM-95) protocol, patients with minimal disseminated disease (MDD), high-risk tumor site (multiple bone, skin, liver, and lung involvement), and small cell/lymphohistiocytic (SC/LH) pathological subtype were enrolled in risk stratification. Patients were treated with a modified NHL-BFM-95 protocol combined with an anaplastic lymphoma kinase inhibitor or vinblastine (VBL). Results: A total of 136 patients were enrolled in this study. The median age was 8.8 years. The 3-year event-free survival (EFS) and overall survival of the entire cohort were 77.7% [95% Confidence Interval (CI), 69.0%-83.9%] and 92.3% (95% CI,86.1%-95.8%), respectively. The 3-year EFS rates of low-risk group (R1), intermediate-risk group (R2), and high-risk group (R3) patients were 100%, 89.5% (95% CI, 76.5%-95.5%, and 67.9% (95% CI, 55.4%-77.6%), respectively. The prognosis of patients with MDD (+), stage IV cancer, SC/LH lymphoma, and high-risk sites was poor, and the 3-year EFS rates were 45.3% (95% CI, 68.6%-19.0%), 65.7% (95% CI, 47.6%-78.9%), 55.7% (95% CI, 26.2%-77.5%), and 70.7% (95% CI, 48.6%-84.6%), respectively. At the end of follow-up, one of the 5 patients who received maintenance therapy with VBL relapsed, and seven patients receiving ALK inhibitor maintenance therapy did not experience relapse. Conclusion: This study has confirmed the poor prognostic of MDD (+) ，high risk site and SC/LH ,but patients with SC/LH lymphoma and MDD (+) at diagnosis still need to receive better treatment (ClinicalTrials.gov number, NCT03971305).

H2O2-triggered CO release based on porphyrinic covalent organic polymers for photodynamic/gas synergistic therapy.

A novel H2O2-responsive carbon monoxide nanogenerator was designed by effectively encapsulating a manganese carbonyl prodrug into porphyrinic covalent organic polymers for realizing the combined CO gas and photodynamic therapy under near infrared light irradiation.

[Research progress in raw and processed Raphani Semen and prediction of quality markers].

Raphani Semen, with both edible and medicinal values, is a typical Chinese herbal medicine with different effects before and after processing. The raw helps ascending and the cooked helps descending. This paper comprehensively summarizes the differences in chemical constituents and pharmacological effects between raw and processed Raphani Semen that are reported in recent years. Based on the principle of quality markers(Q-markers) of traditional Chinese medicines, the chemical constituent sources, chemical constituent detection techniques, and correlation between bidirectional regulatory efficacy and chemical constituents are compared between raw and processed Raphani Semen. The results suggest that sulforaphene and glucoraphanin could be used as candidate Q-markers of raw and processed Raphani Semen, respectively. This review is expected to provide a reference for further research on the processing, new drug development, and improvement of safety and effectiveness of Raphani Semen in clinical application.

Above- and belowground phenology responses of subtropical Chinese fir (Cunninghamia lanceolata) to soil warming, precipitation exclusion and their interaction.

Plant phenology plays an important role in nutrient cycling and carbon balance in forest ecosystems, but its response to the interaction of global warming and precipitation reduction remains unclear. In this study, an experiment with factorial soil warming (ambient, ambient +5 °C) and precipitation exclusion (ambient, ambient -50 %) was conducted in a subtropical Chinese fir (Cunninghamia lanceolata) plantation. We investigated the effects of soil warming, precipitation exclusion, and their interactions on Chinese fir phenology involving tree height and fine root growth. In the meantime, the impact of tree height growth and related climatic factors on fine root production was also assessed. The results showed that: (1) more variable phenology responses were observed in fine root growth than in tree height growth to the climatic treatments; the duration of fine root growth and tree height growth was significantly reduced by the precipitation exclusion and warming treatment, respectively; phenology differences of fine root and tree height growth caused by the solo warming and precipitation exclusion treatment were further enhanced by the combined treatment; and despite the greater inter-annual phenology stability of tree height growth than that of fine root growth, both of them showed insignificant response to all the climate treatments; (2) asynchrony of phenology between tree height and fine root growth was significantly enlarged by solo warming and precipitation exclusion treatments, and further enlarged by the combined treatment; (3) fine root production was significantly and positively correlated with air, and soil temperature, and tree height growth as well, which was altered by warming and precipitation exclusion treatments. Our results demonstrated that climatic changes significantly and differently alter phenology of, and extend the phenology asynchrony between, above and below ground plant components, and also highlight the climate-sensitive and variable nature of root phenology. Overall, these phenology responses to climatic change may weaken the close link between fine root production and tree height growth, which may result in temporal mismatch between nutrient demand and supply in Chinese fir plantation.

Tailoring the Electrochemical Responses of MOF-74 Via Dual-Defect Engineering for Superior Energy Storage.

Rationally designed defects in a crystal can confer unique properties. This study showcases a novel dual-defects engineering strategy to tailor the electrochemical response of metal-organic framework (MOF) materials used for electrochemical energy storage. Salicylic acid (SA) is identified as an effective modulator to control MOF-74 growth and induce structural defects, and cobalt cation doping is adopted for introducing a second type of defect. The resulting dual-defects engineered bimetallic MOF exhibits a discharging capacity of 218.6 mAh g-1, 4.4 times that of the pristine MOF-74, and significantly improved cycling stability. Moreover, the engineered MOF-74(Ni0.675Co0.325)-8//Zn aqueous battery shows top energy/power density performances for Ni-Zn batteries (266.5 Wh kg-1, 17.22 kW kg-1). Comprehensive investigations reveal that engineered defects modify the local coordination environment and promote the in situ electrochemical reconfiguration during operation to significantly boost the electrochemical activity. This work suggests that rational tailoring of the defects within the MOF crystal is an effective strategy to manipulate the coordination environment of the metal centers and the corresponding electrochemical reconfiguration for electrochemical applications.

Analysis of factors influencing family farms' adoption of green prevention and control techniques on an integrative framework of the TPB and NAM.

The application of green prevention and control techniques (GCTs) is a vital measure for improving the quality of agricultural products and enhancing the safety of the ecological environment and agricultural production. However, realistically, limited by the small-scale, part-time and decentralized business model, the adoption of GCTs by family farms in China faces practical problems such as insufficient internal transformation force and ability, as well as low external supervision efficiency. To reveal the directions of promoting family farms' GCTs adoption behavior, we establish a comprehensive theoretical model through the application of a novel integrated approach combining two dominant psychological theories of behavior change: the Theory of Planned Behavior (TPB) and the Norm Activation Model (NAM). We apply this framework to targeted research of vegetable growers in Henan Province in China using survey data (sample n = 653) analyzed through structural equation modeling (SEM). The integrated TPB-NAM model provides insight into both internal motivation and external environmental conditions for farmers' predicted adoption of GCTs. First, internal motivation, value cognition and personal norms are all driving factors affecting the GCTs behavioral intention of vegetable family farms. When GCTs are driven by the dual motivations of "self-interest" (personal norms) and "others-interest" (value cognition), personal norms can be activated by two factors: awareness of consequences and responsibility attribution. Furthermore, social norms, capital endowment and government regulation are the pressure and obstacle factors affecting the GCTs application of vegetable family farms. Social norms can indirectly affect the application of GCTs by forming personal norms. In addition, there are differences between the influencing factors and mechanism of GCTs adoption behavior intention of family farms of different sizes. Based on this, we propose some specific policy suggestions from three aspects: enhance value cognition, improve environmental awareness and responsibility perception, fill in the shortcomings of capital endowment, and implement differentiated incentive and restraint policies.

Epidemiological characteristics and behaviors of online broadcast suicidality in China: implications for targeted prevention strategies.

Objectives: Suicide is a global health concern, exacerbated by stigma around mental illnesses. Online platforms like Twitter and Sina Weibo have seen a rise in "online broadcast suicide," where individuals share suicidal thoughts and actions. However, there is limited understanding of the epidemiological characteristics, particularly in China. This study aims to analyze the demographics and behaviors of individuals engaging in online broadcast suicide in China to inform targeted prevention strategies. Methods: A total of 525 incidents were identified through systematic retrieval of relevant news reports from online sources. Subsequently, a content analysis was performed on these reports to extract detailed information on the characteristics of each individual incident. Results: Among the incidents analyzed, the male-to-female ratio was 1:1.6, with an average age of 23.1 ± 5.9 years. Approximately 71.9% took place in Southern China. Unemployment was reported in 15.0% of incidents. Relationship breakup (62.3%) was cited as the leading cause of suicide. Wrist cutting (58.2%) emerged as the predominant suicide method, and home (36.2%) was the most common location for these tragic events. Instant messaging apps were the primary platforms (54.7%) for conveying suicidal thoughts and actions. Additionally, among the 525 incidents examined, 12.0% disclosed having a mental disorder, and 7.6% had a history of prior suicide attempts. Significant variations were observed across age, gender, region, and occupation categories. Conclusion: This study emphasizes the importance of developing suicide prevention programs for internet users. Besides, interventions should be customized to meet the specific needs of various populations.

Cholesterol neutralized vemurafenib treatment by promoting melanoma stem-like cells via its metabolite 27-hydroxycholesterol.

Vemurafenib has been used as first-line therapy for unresectable or metastatic melanoma with BRAFV600E mutation. However, overall survival is still limited due to treatment resistance after about one year. Therefore, identifying new therapeutic targets for melanoma is crucial for improving clinical outcomes. In the present study, we found that lowering intracellular cholesterol by knocking down DHCR24, the limiting synthetase, impaired tumor cell proliferation and migration and abrogated the ability to xenotransplant tumors. More importantly, administration of DHCR24 or cholesterol mediated resistance to vemurafenib and promoted the growth of melanoma spheroids. Mechanistically, we identified that 27-hydroxycholesterol (27HC), a primary metabolite of cholesterol synthesized by the enzyme cytochrome P450 27A1 (CYP27A1), reproduces the phenotypes induced by DHCR24 or cholesterol administration and activates Rap1-PI3K/AKT signaling. Accordingly, CYP27A1 is highly expressed in melanoma patients and upregulated by DHCR24 induction. Dafadine-A, a CYP27A1 inhibitor, attenuates cholesterol-induced growth of melanoma spheroids and abrogates the resistance property of vemurafenib-resistant melanoma cells. Finally, we confirmed that the effects of cholesterol on melanoma resistance require its metabolite 27HC through CYP27A1 catalysis, and that 27HC further upregulates Rap1A/Rap1B expression and increases AKT phosphorylation. Thus, our results suggest that targeting 27HC may be a useful strategy to overcome treatment resistance in metastatic melanoma.

Sexual Harassment Among Chinese Psychiatrists and Its Impact on Quality of Life: A Cross-Sectional Survey.

Objectives: Sexual harassment (SH) is a prevalent issue in various professional fields worldwide. The current study aims to investigate the incidence of SH targeting psychiatrists in China and explore its impact on quality of life (QOL). Methods: A consecutive recruitment of 1093 psychiatrists was conducted from 6 hospitals in China. The recorded data included participants' socio-demographic characteristics, experiences of workplace SH within the previous year, and their QOL. SH comprised verbal harassment, physical harassment, and displaying of sexual organs. The Chinese version of the World Health Organization Quality of Life Brief Version (WHOQOL-BREF) was employed to assess QOL. We compared the demographic characteristics and QOL between the SH group and the non-SH group. Multiple logistic regression analysis was used to identify independent demographic correlates of SH. Results: In total, 13.8% (n = 151) of the psychiatrists reported SH, with 5.8% reporting it once, 4.4% reporting it twice, and 3.6% reporting it three times or more. Psychiatrists who had encountered SH exhibited lower QOL across social, psychological, physical, and environmental domains. Multiple logistic regression analysis revealed that young physicians and those with shorter work experience had a higher likelihood of experiencing SH. Conclusion: The high prevalence of SH among Chinese psychiatrists is of concern. Given its detrimental effects on the well-being of physicians and the quality of medical care they provide, it is crucial to develop specialized employee training programs for this population to effectively manage workplace SH.