Molecular identification of a putative novel varicosavirus in Agastache rugosa in China.

A putative novel virus was identified in Agastache rugosa in China and tentatively named "Agastache rugosa-associated varicosavirus" (ARaVV). The nearly complete genome sequence of ARaVV was obtained through RNA sequencing (RNA-seq) and subsequent RT-PCR. The ARaVV genome consists of two negative-sense single-stranded RNA segments that are 6428 and 3862 nucleotides (nt) in size, respectively. RNA1 encodes a large polymerase (L), and RNA2 encodes a putative nucleocapsid protein (N), protein 2 (P2), and protein 3 (P3). The L protein shared the highest amino acid (aa) sequence identity (51.3%) with Erysimum virus 1 (EryV1, BK061766.1). The N, P2, and P3 shared the highest aa sequence identity (33.1%, 14.0%, and 24.2%) with Leucanthemum virus 1, Raphanus virus 1, and Spinach virus 1, respectively. Phylogenetic analysis based on amino acid sequences of the L protein showed that ARaVV clustered in a clade with the varicosaviruses, indicating that ARaVV is a putative new member of the genus Varicosavirus.

A comprehensive review on pharmacokinetic mechanism of herb-herb/drug interactions in Chinese herbal formula.

Oral administration of Chinese Herbal Medicine (CHM) faces various challenges in reaching the target organs including absorption and conversion in the gastrointestinal tract, hepatic metabolism via the portal vein, and eventual systemic circulation. During this process, factors such as gut microbes, physical or chemical barriers, metabolic enzymes, and transporters play crucial roles. Particularly, interactions between different herbs in CHM have been observed both in vitro and in vivo. In vitro, interactions typically manifest as detectable physical or chemical changes, such as facilitating solubilization or producing precipitates when decoctions of multiple herbs are administered. In vivo, such interactions cause alterations in the ADME (absorption, distribution, metabolism, and excretion) profile on metabolic enzymes or transporters in the body, leading to competition, antagonism, inhibition, or activation. These interactions ultimately contribute to differences in the therapeutic and pharmacological effects of multi-herb formulas in CHM. Over the past two thousand years, China has cultivated profound expertise and solid theoretical frameworks over the scientific use of herbs. The combination of multiple herbs in one decoction has been frequently employed to synergistically enhance therapeutic efficacy or mitigate toxic and side effects in clinical settings. Additionally combining herbs with increased toxicity or decreased effect is also regarded as a remedy, a practice that should be approached with caution according to Traditional Chinese Medicine (TCM) physicians. Such historical records and practices serve as a foundation for predicting favorable multi-herb combinations and their potential risks. However, systematic data that are available to support the clinical practice and the exploration of novel herbal formulas remain limited. Therefore, this review aims to summarize the pharmacokinetic interactions and mechanisms of herb-herb or herb-drug combinations from existing works, and to offer guidance as well as evidence for optimizing CHM and developing new medicines with CHM characteristics.

An improved YOLOv7 model based on Swin Transformer and Trident Pyramid Networks for accurate tomato detection.

Accurate fruit detection is crucial for automated fruit picking. However, real-world scenarios, influenced by complex environmental factors such as illumination variations, occlusion, and overlap, pose significant challenges to accurate fruit detection. These challenges subsequently impact the commercialization of fruit harvesting robots. A tomato detection model named YOLO-SwinTF, based on YOLOv7, is proposed to address these challenges. Integrating Swin Transformer (ST) blocks into the backbone network enables the model to capture global information by modeling long-range visual dependencies. Trident Pyramid Networks (TPN) are introduced to overcome the limitations of PANet's focus on communication-based processing. TPN incorporates multiple self-processing (SP) modules within existing top-down and bottom-up architectures, allowing feature maps to generate new findings for communication. In addition, Focaler-IoU is introduced to reconstruct the original intersection-over-union (IoU) loss to allow the loss function to adjust its focus based on the distribution of difficult and easy samples. The proposed model is evaluated on a tomato dataset, and the experimental results demonstrated that the proposed model's detection recall, precision, F1 score, and AP reach 96.27%, 96.17%, 96.22%, and 98.67%, respectively. These represent improvements of 1.64%, 0.92%, 1.28%, and 0.88% compared to the original YOLOv7 model. When compared to other state-of-the-art detection methods, this approach achieves superior performance in terms of accuracy while maintaining comparable detection speed. In addition, the proposed model exhibits strong robustness under various lighting and occlusion conditions, demonstrating its significant potential in tomato detection.

Combining Network Pharmacology and Transcriptomics to Investigate the Mechanisms of Yujiang Paidu Decoction in the Treatment of Chronic Rhinosinusitis with Nasal Polyps.

Background: Yujiang Paidu Decoction (YJPD) has demonstrated clinical efficacy in the treatment of chronic rhinosinusitis. However, the effects and mechanisms of the YJPD on chronic rhinosinusitis with nasal polyps (CRSwNP) remain unclear. Purpose: This study aimed to elucidate the potential mechanism of action of YJPD in the treatment of CRSwNP based on network pharmacology, transcriptomics and experiments. Methods: A CRSwNP mouse model was established using ovalbumin (OVA) and staphylococcus aureus enterotoxin B (SEB) for 12 weeks and the human nasal epithelial cell (HNEpC) model was induced with IL-13 in vitro. Behavioral tests, scanning electron microscopy (SEM), micro-CT and pathological change of nasal tissues were observed to investigate the therapeutic effects of YJPD. Network pharmacology and transcriptomics were launched to explore the pharmacological mechanisms of YJPD in CRSwNP treatment. Finally, an ELISA, immunofluorescence, RT-qPCR, Western blotting and Tunel were performed for validation. Results: Different doses of YJPD intervention effectively alleviated rubbing and sneezing symptoms in CRSwNP mice. Additionally, YJPD significantly reduced abnormal serological markers, structural damage of the nasal mucosa, inflammatory cell infiltration, goblet cell increases, and inhibited OVA-specific IgE levels and the secretion of Th2 cytokines such as IL-4, IL-5, and IL-13. Moreover, transcriptomics and network pharmacology analyses indicated that YJPD may exert anti-inflammatory and anti-apoptotic effects by inhibiting the MAPK/AP-1 signaling pathway. The experimental findings supported this conclusion, which was further corroborated by similar results observed in IL13-induced HNEpCs in vitro. Conclusion: YJPD could alleviate inflammatory status and epithelial apoptosis by inhibiting aberrant activation of MAPK/AP-1 signaling pathway. This finding provides a strong basis for using YJPD as a potential treatment in CRSwNP.

Influence of Liquid Nitrogen Pre-Freezing and Drying Methods on the Collagen Content, Physical Properties, and Flavor of Fish Swim Bladder.

Fish swim bladder (FSB) is a type of traditional nutraceutical, but the lack of high-quality drying methods limits its premium market development. In order to obtain optimal-quality dried FSBs from Chinese longsnout catfish, the effects of liquid nitrogen pre-freezing (LNF) and drying on the physical properties and flavor of FSB were evaluated. Four methods were used for FSB drying, including natural air-drying (ND), hot-air-drying (HD), LNF combined with freeze-drying (LN-FD), and LNF combined with HD (LN-HD). Color, collagen content, rehydration ratio, textural properties, and flavor characteristics (by GC-IMS, E-nose, and E-tongue) were measured to clarify the differences among four dried FSBs. The results showed that ND cannot effectively remove moisture from FSB as the final product showed a stronger sourness in taste. HD led to a decrease in the collagen content and the collapse of the fiber structure in FSB. Compared to HD, LN-HD showed a higher collagen content (0.56 g/g) and a different flavor fingerprint. FSB treated by LN-FD had better physical qualities in terms of an attractive color, a high collagen content (0.79 g/g), low shrinkage, a higher rehydration ratio (2.85), and a soft texture, while also possessing richer characteristic flavors. The application of LN-FD may help the optimization of the nutrition level, rehydration ability, mouthfeel, and flavor of dried FSB.

The Effect of a Caffeine and Nicotine Combination on Nicotine Withdrawal Syndrome in Mice.

Nicotine dependence is an important cause of excessive exposure to tobacco combustion compounds in most smokers. Nicotine replacement therapy is the main method to treat nicotine dependence, but it still has its shortcomings, such as the inability to mitigate withdrawal effects and limited applicability. It has been hypothesized that a combination of low-dose nicotine and caffeine could achieve the same psychological stimulation effect as a high dose of nicotine without causing nicotine withdrawal effects. To establish a model of nicotine dependence, male C57BL/6J mice were subcutaneously injected four times a day with nicotine (2 mg/kg) for 15 days and fed with water containing nicotine at the same time. They were randomly divided into four groups. After 24 h of withdrawal, different groups were injected with saline, nicotine (0.25 mg/kg or 0.1 mg/kg), or nicotine (0.1 mg/kg) and caffeine (20 mg/kg). Behavioral and physiological changes were evaluated by an assessment of physical signs, open field tests, elevated plus maze experiments, forced swimming tests, hot plate tests, and new-object-recognition tests. The changes in dopamine release in the prefrontal cortex (PFC) and ventral tegmental area (VTA) in the midbrain were analyzed using ELISA. The results showed that a combination of caffeine and nicotine could effectively relieve nicotine withdrawal syndrome, increase movement ability and pain thresholds, reduce anxiety and depression, enhance memory and cognitive ability, and increase the level of dopamine release in the PFC and VTA. Thus, caffeine combined with nicotine has potential as a stable and effective treatment option to help humans with smoking cessation.

Mitochondrial-Derived Peptide MOTS-c Suppresses Ovarian Cancer Progression by Attenuating USP7-Mediated LARS1 Deubiquitination.

Mitochondrial-nuclear communication plays a vital role in maintaining cellular homeostasis. MOTS-c, a short peptide derived from the 12S rRNA of mitochondrial DNA, has been suggested as a retrograde mitochondrial signal. Although recent clinical studies have suggested a possible link between MOTS-c and human cancer, the role of MOTS-c in tumorigenesis has yet to be investigated. Here, MOTS-c levels are found to be reduced in both serum and tumor tissues from ovarian cancer (OC) patients, which are associated with poor patients' prognosis. Exogenous MOTS-c inhibits the proliferation, migration and invasion of OC cells, and induces cell cycle arrest and apoptosis. Mechanistically, MOTS-c interacts with LARS1 and promotes its ubiquitination and proteasomal degradation. In addition, USP7 was identified as a deubiquitinase of LARS1, and MOTS-c can attenuates USP7-mediated LARS1 deubiquitination by competing with USP7 for binding to LARS1. Besides, LARS1 was found to be increased and play an important oncogenic function in OC. More importantly, MOTS-c displays a marked anti-tumor effect on OC growth without systemic toxicity in vivo. In conclusion, this study reveals a crucial role of MOTS-c in OC and provides a possibility for MOTS-c as a therapeutic target for the treatment of this manlignacy.

Exploring the key flavor compounds and aroma profiles in traditionally fermented golden pompano (Trachinotus ovatus): Perspective from molecular sensory science.

Fermented golden pompano (Trachinotus ovatus) has a distinctive flavor, but the key flavor compounds and aroma profiles remains unclear. Thus, a molecular sensory science approach was used to investigate flavor and key aromatic compounds. The fermentation process enhanced the overall flavor, as evidenced by sensory evaluation and electronic nose (E-nose) analyses. A total of 48 aroma compounds were identified at different fermentation stages. Among them, 11 key aroma compounds were identified by flavor dilution (FD) factors ≥8 and odor activity values (OAVs) ≥ 1. Aroma recombination model successfully reproduces the characteristic floral and fruity aromas of fermented golden pompano. Omission experiments identified hexanal, decanal, 1-octen-3-ol, limonene, and isovaleric acid as significant contributors to the overall aroma profile. This study elucidates flavor dynamic modulation and key aromatic compounds during golden pompano fermentation, to provide a theoretical reference for the targeting process regulation of the product.

Efficacy and safety of fentanyl inhalant for the treatment of breakthrough cancer pain: a multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Breakthrough cancer pain (BTcP) has a negative impact on patients' quality of life, general activities, and is related to worse clinical outcomes. Fentanyl inhalant is a hand-held combination drug-device delivery system providing rapid, multi-dose (25µg/dose) administration of fentanyl via inhalation of a thermally generated aerosol. This multicenter, randomized, placebo-controlled, multiple-crossover, double-blind study evaluated the efficacy, safety, and tolerability of fentanyl inhalant in treating BTcP in opioid-tolerant patients. METHODS: The trial was conducted in opioid-tolerant cancer patients with 1 ~ 4 BTcP outbursts per day. Each patient was treated and observed for 6 episodes of BTcP (4 with fentanyl inhalant, 2 with placebo). During each episode of targeted BTcP, patients were allowed up to six inhalations, with an interval of at least 4 min between doses. Primary outcome was the time-weighted sum of PID (pain intensity difference) scores at 30 min (SPID30). RESULTS: A total of 335 BTcP episodes in 59 patients were treated. The mean SPID30 was -97.4 ± 48.43 for fentanyl inhalant-treated episodes, and -64.6 ± 40.25 for placebo-treated episodes (p < 0.001). Significant differences in PID for episodes treated with fentanyl inhalant versus placebo was seen as early as 4 min and maintained for up to 60 min. The percentage of episodes reported PI (pain intensity) scores ≤ 3, a ≥ 33% or ≥ 50% reduction in PI scores at 30 min, PR30 (pain relief scores at 30 min) and SPID60 favored fentanyl inhalant over placebo. Only 4.4% of BTcP episodes required rescue medication in fentanyl inhalant group. Most AEs were of mild or moderate severity and typical of opioid drugs. CONCLUSION: Treatment with fentanyl inhalant was shown to be a promising therapeutic option for BTcP, with significant pain relief starting very soon after dosing. Confirmation of effectiveness requires a larger phase III trial. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05531422 registered on 6 September 2022 after major amendment, NCT04713189 registered on 14 January 2021.

ITRAQ Based Proteomics Reveals the Potential Mechanism of Placental Injury Induced by Prenatal Stress.

Maternal stress experienced during prenatal development is recognized as a significant risk factor for neurodevelopmental and neuropsychiatric disorders across the offspring's lifespan. The placental barrier serves a crucial function in safeguarding the fetus from detrimental exposures during gestation. However, previous investigations have not yet comprehensively elucidated the extensive connections between prenatal stress and the expression of placental proteins. In this study, we used iTRAQ-based quantitative proteomics to elucidate the placental adaptive mechanisms of pregnant rats in response to fear-induced stress. Our results showed that during pregnancy, exposure to fear-induced stress led to a pathological hypercoagulable state in the mother's body. Placental circulation was also disrupted, significantly reducing placental efficiency and blood oxygen saturation in newborn rats. Proteomic analyses showed that most of the DEPs were annotated to the PI3K-Akt and ECM-receptor interaction signaling pathway. In addition, the expressions of CDC37, HSP90ß, AKT, p-AKT and p-mTOR were down-regulated significantly in the placenta. Our results demonstrated that prenatal fear-induced stress led to inhibition of the cellular signal transduction of placental PI3K/AKT/mTOR, which affected biological processes such as rRNA processing, translation, protein folding, protein stability, and oxygen transport in the placenta. These abnormalities in biological functions could potentially damage the barrier function of the placenta and thereby result in abnormal development in the offspring.

Association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and diabetic kidney disease in patients with diabetes in the United States: a cross-sectional study.

BACKGROUND: This paper investigated the link between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and diabetic kidney disease (DKD) in adult diabetic patients and identified the optimal NHHR value for impacting DKD. METHODS: This cross-sectional research made use of records from the National Health and Nutrition Examination Survey (NHANES) executed between 2005 and 2016. The link of NHHR to DKD risk was analyzed by logistic regression and restricted cubic spline (RCS) models. The stability and reliability of the results were assessed by subgroup analysis and sensitivity analysis. RESULTS: In total, 4,177 participants were involved. As a continuous variable, NHHR was markedly connected to an increased risk of DKD (OR 1.07, 95% CI 1.02, 1.12, P < 0.01). When NHHR was grouped in quartiles, relative to the reference set, the highest NHHR group was also linked to a heightened risk of DKD (OR 1.23, 95% CI 1.01, 1.50, P < 0.05). The outcome of RCS show a "J" shaped correlation between NHHR and DKD risk (P for nonlinear = 0.0136). The risk of developing DKD was the lowest when NHHR equals 2.66. Subgroup analysis revealed that the link of NHHR to DKD persisted in participants aged below 40, females, non-smokers, and those without hyperuricemia. Sensitivity analysis demonstrated a certain robustness in this association. CONCLUSION: A meaningful link is present between NHHR and DKD. An NHHR value of around 2.66 could represent the ideal cutoff for assessing DKD risk.

A causal relationship between bone mineral density and breast cancer risk: a mendelian randomization study based on east Asian population.

BACKGROUND: Breast cancer (BC) poses significant burdens on women globally. While past research suggests a potential link between bone mineral density (BMD) and BC risk, findings remain inconsistent. Our study aims to elucidate the causal relationship between BMD and BC in East Asians using bidirectional Mendelian randomization (MR). METHODS: Genetic association data for bone mineral density T-scores (BMD-T) and Z-scores (BMD-Z) (Sample size = 92,615) and BC from two different sources (Sample size1 = 98,283; Sample size2 = 79,550) were collected from publicly available genome-wide association studies (GWAS). Single-nucleotide polymorphisms (SNPs) associated with BMD-T and BMD-Z as phenotype-related instrumental variables (IVs) were used, with BC as the outcome. As the primary means of causal inference, the inverse variance weighted (IVW) approach was employed. Heterogeneity analysis was conducted using Cochran's Q test, while MR-Egger regression analysis was implemented to assess the pleiotropic effects of the IVs. Sensitivity analyses were performed using methods such as MR-Egger, weighted median, and weighted mode to analyze the robustness and reliability of the results. The MR-PRESSO method and the RadialMR were used to detect and remove outliers. The PhenoScanner V2 website was utilized to exclude confounding factors shared between BMD and BC. Besides, the Bonferroni correction was also used to adjust the significance threshold. Then, the meta-analysis method was applied to combine the MR analysis results from the two BC sources. Finally, a reverse MR analysis was conducted. RESULTS: The results of the IVW method were consolidated through meta-analysis, revealing a positive correlation between genetically predicted BMD-T ([Formula: see text], [Formula: see text], [Formula: see text]) and BMD-Z ([Formula: see text],[Formula: see text], [Formula: see text]) with increased BC risk. The Cochran's [Formula: see text] test and MR-Egger regression suggested that neither of these causal relationships was affected by heterogeneity or horizontal pleiotropy. The sensitivity analyses supported the IVW results, indicating the robustness of the findings. Reverse MR analysis showed no causal relationship between BC and BMD. CONCLUSION: Our MR study results provide evidence for the causal relationship between BMD and BC risk in East Asian populations, suggesting that BMD screening is of great significance in detecting and preventing BC.

The Use of Water Sac Dilation in Resecting Parapharyngeal Space Benign Tumor via Transoral Approach.

OBJECTIVES: To evaluate the effectiveness of employing the water sac dilation (WSD) method during endoscopy-assisted transoral resection of parapharyngeal space benign tumor (PSBT). METHODS: Between February 2017 and January 2022, a total of 32 patients diagnosed with PSBT were included in this prospective study and were randomly allocated into two groups: the WSD group and the control group. Tumors of the WSD group patients were all dissected using the WSD method. RESULTS: The final numbers of studied patients in WSD group and control group were 17 and 15, respectively. The basic information was comparable between these two groups of patients. All these patients successfully underwent tumor resection via transoral approach. The operation time, intraoperative blood loss, drainage volume on the first postoperative day, drainage duration, and the total drainage volume in the WSD group patients were significantly lower than those in the control group patients (all p < 0.05). No surgical complications occurred, and no residual tumor or recurrence could be identified at 6 months after surgery in both groups of patients. CONCLUSION: The application of the WSD method in endoscopy-assisted transoral resection of PSBT effectively attenuated intraoperative injury, improved surgical efficiency, and accelerated postoperative recovery. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Efficacy and safety of standard BEACOPP regimen versus ABVD regimen for treatment of advanced Hodgkin's lymphoma.

INTRODUCTION: The current treatment regimens for Hodgkin's lymphoma (HL) are associated with high incidences of adverse events. PURPOSE: This study aimed to compare the efficacy and safety of doxorubicin + bleomycin + vincristine + dacarbazine (ABVD) and standard bleomycin + etoposide + doxorubicin + cyclophosphamide + vincristine + procarbazine + prednisone (BEACOPP) chemotherapy in the treatment of advanced stage HL. METHODS: This multicenter, randomized, parallel, open, positive control noninferiority trial was conducted from 2016 to 2019 and comprised 93 subjects who were randomized in a 1:1 ratio between the treatment (BEACOPP; n = 44) and control (ABVD; n = 49) groups. RESULTS: The primary efficacy endpoint of this trial was the objective response rate (ORR) after eight cycles of chemotherapy, which was 100.00% (36/36) in the treatment group and 95.74% (45/49) in the control group. The incidence of adverse reactions was 100% in both groups. Significant differences (P < 0.05) in the incidences of grade 3 (39/44 [88.64%] vs. 23/49 [46.94%]) and grade 4 (27/44 [61.36%] vs. 8/49 [16.94%]) adverse events were observed between the treatment and control groups, respectively. However, most of these reactions were manageable, with no serious consequences, and were reversible after discontinuation of the treatment. CONCLUSION: Both regimens had a similar ORR and were associated with a high number of adverse events. The ABVD regimen was better tolerated and safer than the standard BEACOPP regimen. This study indicates that the standard BEACOPP regimen may be considered as a treatment option for patients with advanced HL.

Hesperidin PLGA nanoparticles potentiate the efficacy of aPD-1 in treating triple negative breast cancer by regulating CCL2 and ADPN expression in cancer-associated adipocytes.

Triple negative breast cancer (TNBC) represents a heterogeneous subtype of breast cancer characterized by an unfavorable prognosis due to its aggressive biology. Cancer-associated adipocytes (CAAs) play an active role in tumor development, invasion and metastasis, and response to treatment by secreting various cytokines. CAAs secrete CCL2 and ADPN which significantly affect the efficacy of aPD-1 in treating breast cancer. Our recent research has demonstrated that Hesperidin, a natural phenolic compound, significantly inhibits CCL2, elevates ADPN secreted by CAAs in vitro and in vivo, remodels the immune microenvironment, and potentiates the efficacy of aPD-1 in triple-negative breast cancer. We used Oil red staining, Bodipy 493/503 staining and quantitative real-time PCR to verify the formation of CAAs. ELISA was used to detect levels of CCL2, ADPN secreted by CAAs. Changes in the number of immune cells in mouse tumor tissues were detected using flow cytometry and immunofluorescence. Our data suggest that Hesperidin PLGA nanoparticles significantly reduced CCL2 and increased ADPN secreted by CAAs, which concurrently decreased the recruitment of M2 macrophages, Tregs and MDSCs while increased the infiltration of CD8+T cells, M1 macrophages and DCs into tumor, thus significantly potentiated the efficacy of aPD-1 in vivo. This study provides a new combined strategy for the clinical treatment of triple-negative breast cancer by interfering with CCL2, ADPN secreted by CAAs to enhance the efficacy of immunotherapy.

Accurate prediction and intelligent control of COD and other parameters removal from pharmaceutical wastewater using electrocoagulation coupled with catalytic ozonation process.

In this study, we employed the response surface method (RSM) and the long short-term memory (LSTM) model to optimize operational parameters and predict chemical oxygen demand (COD) removal in the electrocoagulation-catalytic ozonation process (ECOP) for pharmaceutical wastewater treatment. Through RSM simulation, we quantified the effects of reaction time, ozone dose, current density, and catalyst packed rate on COD removal. Then, the optimal conditions for achieving a COD removal efficiency exceeding 50% were identified. After evaluating ECOP performance under optimized conditions, LSTM predicted COD removal (56.4%), close to real results (54.6%) with a 0.2% error. LSTM outperformed RSM in predictive capacity for COD removal. In response to the initial COD concentration and effluent discharge standards, intelligent adjustment of operating parameters becomes feasible, facilitating precise control of the ECOP performance based on this LSTM model. This intelligent control strategy holds promise for enhancing the efficiency of ECOP in real pharmaceutical wastewater treatment scenarios. PRACTITIONER POINTS: This study utilized the response surface method (RSM) and the long short-term memory (LSTM) model for pharmaceutical wastewater treatment optimization. LSTM predicted COD removal (56.4%) closely matched experimental results (54.6%), with a minimal error of 0.2%. LSTM demonstrated superior predictive capacity, enabling intelligent parameter adjustments for enhanced process control. Intelligent control strategy based on LSTM holds promise for improving electrocoagulation-catalytic ozonation process efficiency in pharmaceutical wastewater treatment.

Identification of signature genes and immune infiltration analysis in thyroid cancer based on PANoptosis related genes.

Background: Thyroid cancer is the most common malignancy of the endocrine system. PANoptosis is a specific form of inflammatory cell death. It mainly includes pyroptosis, apoptosis and necrotic apoptosis. There is increasing evidence that PANoptosis plays a crucial role in tumour development. However, no pathogenic mechanism associated with PANoptosis in thyroid cancer has been identified. Methods: Based on the currently identified PANoptosis genes, a dataset of thyroid cancer patients from the GEO database was analysed. To screen the common differentially expressed genes of thyroid cancer and PANoptosis. To analyse the functional characteristics of PANoptosis-related genes (PRGs) and screen key expression pathways. The prognostic model was established by LASSO regression and key genes were identified. The association between hub genes and immune cells was evaluated based on the CIBERSORT algorithm. Predictive models were validated by validation datasets, immunohistochemistry as well as drug-gene interactions were explored. Results: The results showed that eight key genes (NUAK2, TNFRSF10B, TNFRSF10C, TNFRSF12A, UNC5B, and PMAIP1) exhibited good diagnostic performance in differentiating between thyroid cancer patients and controls. These key genes were associated with macrophages, CD4+ T cells and neutrophils. In addition, PRGs were mainly enriched in the immunomodulatory pathway and TNF signalling pathway. The predictive performance of the model was confirmed in the validation dataset. The DGIdb database reveals 36 potential therapeutic target drugs for thyroid cancer. Conclusion: Our study suggests that PANoptosis may be involved in immune dysregulation in thyroid cancer by regulating macrophages, CD4+ T cells and activated T and B cells and TNF signalling pathways. This study suggests potential targets and mechanisms for thyroid cancer development.

Hyperconjugation-Driven Isodesmic Reaction of Indoles and Anilines: Reaction Discovery, Mechanism Study, and Antitumor Application.

Isodesmic reactions, in which chemical bonds are redistributed between substrates and products, provide a general and powerful strategy for both biological and chemical synthesis. However, most isodesmic reactions involve either metathesis or functional-group transfer. Here, we serendipitously discovered a novel isodesmic reaction of indoles and anilines that proceeds intramolecularly under weakly acidic conditions. In this process, the five-membered ring of the indole motif is broken and a new indole motif is constructed on the aniline side, accompanied by the formation of a new aniline motif. Mechanistic studies revealed the pivotal role of σ→π* hyperconjugation on the nitrogen atom of the indole motif in driving this unusual isodesmic reaction. Furthermore, we successfully synthesized a diverse series of polycyclic indole derivatives; among quinolines, potential antitumor agents were identified using cellular and in vivo experiments, thereby demonstrating the synthetic utility of the developed methodology.

Score Images as a Modality: Enhancing Symbolic Music Understanding through Large-Scale Multimodal Pre-Training.

Symbolic music understanding is a critical challenge in artificial intelligence. While traditional symbolic music representations like MIDI capture essential musical elements, they often lack the nuanced expression in music scores. Leveraging the advancements in multimodal pre-training, particularly in visual-language pre-training, we propose a groundbreaking approach: the Score Images as a Modality (SIM) model. This model integrates music score images alongside MIDI data for enhanced symbolic music understanding. We also introduce novel pre-training tasks, including masked bar-attribute modeling and score-MIDI matching. These tasks enable the SIM model to capture music structures and align visual and symbolic representations effectively. Additionally, we present a meticulously curated dataset of matched score images and MIDI representations optimized for training the SIM model. Through experimental validation, we demonstrate the efficacy of our approach in advancing symbolic music understanding.