The Effects of Nitrogen Fertilizer on the Aroma of Fresh Tea Leaves from Camellia sinensis cv. Jin Xuan in Summer and Autumn.

Nitrogen fertilization level and harvesting season significantly impact tea aroma quality. In this study, we analyzed the volatile organic compounds of fresh Jin Xuan (JX) tea leaves under different nitrogen application levels (N0, N150, N300, N450) during summer and autumn. A total of 49 volatile components were identified by gas chromatography-mass spectrometry (GC-MS). Notably, (E)-2-hexenal, linalool, and geraniol were the main contributors to the aroma of fresh JX leaves. The no-nitrogen treatment (N0) presented the greatest quantity and variety of volatiles in both seasons. A greater difference in volatile compounds was observed between nitrogen treatments in summer vs. autumn. The N0 treatment had a greater total volatile concentration in summer, while the opposite was observed in the nitrogen application treatments (N150, N300, N450). Summer treatments appeared best suited to black tea production. The concentration of herbaceous aroma-type volatiles was higher in summer, while the concentration of floral volatiles was higher in autumn. Volatile concentrations were highest in the N0 and N450 treatments in autumn and appeared suitable for making black tea and oolong tea. Overall, this research provides valuable insights into how variations in N application rates across different harvesting seasons impact the aroma characteristics of tea leaves.

Development and validation of a deep learning-based model to predict response and survival of T790M mutant non-small cell lung cancer patients in early clinical phase trials using electronic medical record and pharmacokinetic data.

Background: Epidermal growth factor receptor (EGFR) T790M mutation is the standard predictive biomarker for third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment. While not all T790M-positive patients respond to third-generation EGFR-TKIs and have a good prognosis, it necessitates novel tools to supplement EGFR genotype detection for predicting efficacy and stratifying EGFR-mutant patients with various prognoses. Mixture-of-experts (MoE) is designed to disassemble a large model into many small models. Meanwhile, it is also a model ensembling method that can better capture multiple patterns of intrinsic subgroups of enrolled patients. Therefore, the combination of MoE and Cox algorithm has the potential to predict efficacy and stratify survival in non-small cell lung cancer (NSCLC) patients with EGFR mutations. Methods: We utilized the electronic medical record (EMR) and pharmacokinetic parameters of 326 T790M-mutated NSCLC patients, including 283 patients treated with Abivertinib in phase I (n=177, for training) and II (n=106, for validation) clinical trials and an additional validation cohort 2 comprising 43 patients treated with BPI-7711. Furthermore, 18 patients underwent whole-exome sequencing for biological interpretation of CoxMoE. We evaluated the predictive performance for therapeutic response using the area under the curve (AUC) and the Concordance index (C-index) for progression-free survival (PFS). Results: CoxMoE exhibited AUCs of 0.73-0.83 for predicting efficacy defined by best overall response (BoR) and achieved C-index values of 0.64-0.65 for PFS prediction in training and validating cohorts. The PFS of 198 patients with a low risk [median, 6.0 (range, 1.0-23.3) months in the abivertinib treated cohort; median 16.5 (range, 1.4-27.4) months in BPI-7711 treated cohort] of being non-responder increased by 43% [hazard ratio (HR), 0.56; 95% confidence interval (CI), 0.40-0.78; P=0.0013] and 50% (HR, 0; 95% CI, 0-0; P=0.01) compared to those at high-risk [median, 4.2 (range, 1.0-35) months in the abivertinib treated cohort; median, 11.0 (range, 1.4-25.1) months in BPI-7711 treated cohort]. Additionally, activated partial thromboplastin time (APTT), creatinine clearance (Ccr), monocyte, and steady-state plasma trough concentration utilited to construct model were found significantly associated with drug resistance and aggressive tumor pathways. A robust correlation was observed between APTT and Ccr with PFS (log-rank test; P<0.01) and treatment response (Wilcoxon test; P<0.05), respectively. Conclusions: CoxMoE offers a valuable approach for patient selection by forecasting therapeutic response and PFS utilizing laboratory tests and pharmacokinetic parameters in the setting of early-phase clinical trials. Simultaneously, CoxMoE could predict the efficacy of third-generation EGFR-TKI non-invasively for T790M-positive NSCLC patients, thereby complementing existing EGFR genotype detection.

Bioinformatics analysis and experimental verification of the cancer-promoting effect of DHODH in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a malignant tumor of the urinary system. To explore the potential mechanisms of DHODH in ccRCC, we analyzed its molecular characteristics using public databases. TCGA pan-cancer dataset was used to analyze DHODH expression in different cancer types and TCGA ccRCC dataset was used to assess differential expression, prognosis correlation, immune infiltration, single-gene, and functional enrichment due to DHODH. The GSCALite and CellMiner databases were employed to explore drugs and perform molecular docking analysis with DHODH. Protein-protein interaction networks and ceRNA regulatory networks of DHODH were constructed using multiple databases. The effect of DHODH on ccRCC was confirmed in vitro. DHODH was highly expressed in ccRCC. Immune infiltration analysis revealed that DHODH may be involved in regulating the infiltration of immunosuppressive cells such as Tregs. Notably, DHODH influenced ccRCC progression by forming regulatory networks with molecules, such as hsa-miR-26b-5p and UMPS and significantly enhanced the malignant characteristics of ccRCC cells. Several drugs, such as lapatinib, silmitasertib, itraconazole, and dasatinib, were sensitive to DHODH expression and exhibited strong molecular binding with it. Thus, DHODH may promote ccRCC progression and is a candidate effective therapeutic target for ccRCC.

Use of a 3D-printed body surface percutaneous puncture guide plate in vertebroplasty for osteoporotic vertebral compression fractures.

BACKGROUND: Percutaneous vertebroplasty (PVP) has been used widely to treat osteoporotic vertebral compression fractures (OVCFs). However, it has many disadvantages, such as excessive radiation exposure, long operation times, and high cement leakage rates. This study was conducted to explore the clinical effects and safety of the use of a three-dimensional (3D)-printed body-surface guide plate to aid PVP for the treatment of OVCFs. METHODS: This prospective cohort study was conducted with patients with OVCFs presenting between October 2020 and June 2021. Fifty patients underwent traditional PVP (group T) and 47 patients underwent PVP aided by 3D-printed body-surface guide plates (3D group). The following clinical and adverse events were compared between groups: the puncture positioning, puncture, fluoroscopy exposure and total operation times; changes in vertebral height and the Cobb angle after surgery relative to baseline; preoperative and postoperative visual analog scale and Oswestry disability index scores; and perioperative complications (bone cement leakage, neurological impairment, vertebral infection, and cardiopulmonary complications. RESULTS: The puncture, adjustment, fluoroscopy, and total operation times were shorter in the 3D group than in group T. Visual analog scale and Oswestry disability index scores improved significantly after surgery, with significant differences between groups (both p < 0.05). At the last follow-up examination, the vertebral midline height and Cobb angle did not differ between groups. The incidence of complications was significantly lower in the 3D group than in group T (p < 0.05). CONCLUSION: The use of 3D-printed body-surface guide plates can simplify and optimize PVP, shortening the operative time, improving the success rate, reducing surgical complications, and overall improving the safety of PVP.

Facing small and biased data dilemma in drug discovery with enhanced federated learning approaches.

Artificial intelligence (AI) models usually require large amounts of high-quality training data, which is in striking contrast to the situation of small and biased data faced by current drug discovery pipelines. The concept of federated learning has been proposed to utilize distributed data from different sources without leaking sensitive information of the data. This emerging decentralized machine learning paradigm is expected to dramatically improve the success rate of AI-powered drug discovery. Here, we simulated the federated learning process with different property and activity datasets from different sources, among which overlapping molecules with high or low biases exist in the recorded values. Beyond the benefit of gaining more data, we also demonstrated that federated training has a regularization effect superior to centralized training on the pooled datasets with high biases. Moreover, different network architectures for clients and aggregation algorithms for coordinators have been compared on the performance of federated learning, where personalized federated learning shows promising results. Our work demonstrates the applicability of federated learning in predicting drug-related properties and highlights its promising role in addressing the small and biased data dilemma in drug discovery.

Outcome of one-stage percutaneous endoscopic debridement and lavage combined with percutaneous pedicle screw fixation for lumbar pyogenic spondylodiscitis.

BACKGROUND: This study assessed the therapeutic effect of one-stage percutaneous endoscopic debridement and lavage (PEDL) combined with percutaneous pedicle screw fixation (PPSF) in the treatment of lumbar pyogenic spondylodiscitis. METHODS: From March 2017 to October 2019, 51 patients diagnosed with pyogenic spondylodiscitis underwent PPSF followed by PEDL in our department. Biopsy specimens were examined for microorganisms and evaluated histopathologically. Clinical outcomes were assessed by physical examination, routine serological testing, visual analogue scale (VAS), Oswestry Disability Index (ODI) and imaging studies. RESULTS: Of the enrolled patients, the operation time ranged from 90 min to 114 min every level with an average of 102 min, and the average drainage time ranged from 6 days to 10 days with an average of 7.4 days. All patients who complained of lower back pain symptoms were more relieved than before surgery. Causative pathogens were identified in 20 of 51 biopsy specimens; Staphylococcus aureus was the most prevalent. However, there were eight patients with postoperative complications. The mean follow-up was 25.0 ± 3.8 (range: 20-32) months. Inflammatory markers showed that infection was controlled. The VAS and ODI improved significantly. At the last follow-up, magnetic resonance imaging showed that the infected lesions had disappeared. CONCLUSION: PEDL supplementing PPSF may be useful for patients with single-level lumbar pyogenic spondylodiscitis, as it is minimally invasive, especially for patients who cannot undergo conventional open surgery due to poor health or advanced age.

Efficacy of air purifier therapy for patients with allergic asthma

Objectives: This study aimed to evaluate the efficacy of air purifier therapy for patients with allergic asthma. Methods: Thirty-eight subjects were categorized under two groups namely treatment group and control group. All subjects were under 18 years of age and they had been clinically diagnosed with allergic asthma. The treatment group used high efficiency particulate air (HEPA) purifiers for six consecutive months, and the control group did not use the air filters. Particulate matter (PM) data and dust samples (from bedding and a static point) were collected from the subjects’ bedrooms before they started using the air purifiers and each month thereafter. Simultaneously, the subjects were asked to complete a questionnaire for the Asthma Control Test (ACT) or Childhood Asthma Control Test (C-ACT). Fractional exhaled nitric oxide (FENO) tests were performed at the start and end of the study. The concentrations of Der p1 and Der f1 were measured in the dust samples. Results: (1) After utilizing the air purifier, the concentrations of house dust mite (HDM) allergens (Der p1+ Der f1) in the dust samples decreased. In addition, the PMindoor/outdoor values significantly decreased. (2) The ACT and C-ACT scores in the treatment group maintained a steady significant upward trend. (3) At the end of the study, the FENO levels in both groups were lower, although the differences were not significant. Conclusions: It is witnessed that HEPA air purifiers can decrease indoor HDM allergen and PM levels and improve the quality of life for allergic asthma patients (AU)

Development of a High-speed Mental Spelling System Combining Eye Tracking and SSVEP-based BCI with High Scalability.

Hybrid brain-computer interfaces (BCIs) have been proved to be more effective in mental control. In this study, a hybrid BCI speller system combining steady-state visual evoked potentials (SSVEPs) and eye tracking has been proposed. In this system, the eye tracker was used to detect eye gaze position for a 3×3 block selection, after that classification of the command was achieved through filter bank canonical correlation analysis (FBCCA) method. Results showed that the 40-classes hybrid speller system outperformed the SSVEP-only method, achieved a mean accuracy of 92.1% and a mean information transfer rate (ITR) of 180.8 bits/min during online experiments, and the scalability of the proposed system also has been tested with larger number of commands.

[Acupuncture combined with local anesthesia for percutaneous vertebroplasty].

OBJECTIVE: To observe the analgesic and sedative effects of acupuncture combined with local anesthesia for percutaneous vertebroplasty (PVP). METHODS: Sixty patients of single segmental osteoporotic vertebral compression fractures who were prepared to receive PVP were randomly divided into an observation group, a control 1 group, a control 2 group, 20 cases in each group. The patients in the observation group were treated with electroacupuncture (EA) at Hegu (LI 4), Neiguan (PC 6) and Zusanli (ST 36) 20 min before operation; during operation, EA was given combined with regular anesthesia. The patients in the control 1 group were treated with intramuscular injection of parecoxib sodium (40 mg), combined with regular anesthesia. The patients in the control 2 group were treated with intravenous injection of dezocine (5 mg), combined with regular anesthesia. Visual analogue scale (VAS) and Ramesy sedation score were compared among the three groups. RESULTS: In the observation group and control 2 group, the VAS during puncture and bone cement placement was higher than that before acupuncture (all P<0.01); the VAS during bone cement placement was higher than that before puncture (P<0.05, P<0.01); the VAS after operation was lower than that during puncture and bone cement placement (P<0.05, P<0.01). In the control 1 group, the VAS during puncture and bone cement placement and after operation was higher than that before acupuncture (P<0.01, P<0.05), the VAS after operation was lower than that during puncture and bone cement placement (P<0.05, P<0.01). There was no significant difference in VAS and Ramesy score among three groups at all time points (all P>0.05). CONCLUSION: Compared with local anesthesia and analgesics, acupuncture combined with local anesthesia has similar analgesic and sedative effect for PVP, which could be considered a better method for PVP anesthesia.