Active Discovery of the Allosteric Inhibitor Targeting Botrytis cinerea Chitinase Based on Neural Relational Inference for Food Preservation.

Currently, allosteric inhibitors have emerged as an effective strategy in the development of preservatives against the drug-resistant Botrytis cinerea (B. cinerea). However, their passively driven development efficiency has proven challenging to meet the practical demands. Here, leveraging the deep learning Neural Relational Inference (NRI) framework, we actively identified an allosteric inhibitor targeting B. cinerea Chitinase, namely, 2-acetonaphthone. 2-Acetonaphthone binds to the crucial domain of Chitinase, forming the strong interaction with the allosteric sites. Throughout the interaction process, 2-acetonaphthone diminished the overall connectivity of the protein, inducing conformational changes. These findings align with the results obtained from Chitinase activity experiments, revealing an IC50 value of 67.6 µg/mL. Moreover, 2-acetonaphthone exhibited outstanding anti-B. cinerea activity by inhibiting Chitinase. In the gray mold infection model, 2-acetonaphthone significantly extended the preservation time of cherry tomatoes, positioning it as a promising preservative for fruit storage.

Percutaneous coronary intervention leads to microplastics entering the blood: Interventional devices are a major source.

Microplastics (MPs) is an emerging pollutant potentially harmful to health. Medical practices using plastic devices, such as percutaneous coronary interventions (PCI), may result in MPs entering into the blood. The purpose of this study was to quantify the effect of PCI on microplastic levels in patients' blood. Laser direct infrared (LDIR) was used to detect MPs in the blood of 23 patients before and after PCI. MPs in the water in which devices used in PCI were washed were also examined. The concentration of MPs in the blood was significantly elevated (93.57 ± 35.95 vs. 4.96 ± 3.40 particles/10 mL of blood, P < 0.001) after PCI compared to before, and the increased MPs were polyamide (PA), polyethylene (PE), polyurethane (PU), and polyethylene terephthalate (PET), which was consistent with the types of MPs detected in the device washing water. The maximum diameter of MPs in blood before PCI was 50 µm, whereas after PCI it was 213 µm, and even 336 µm in device washing water. These findings indicated that PCI will cause MPs to enter the blood, and devices used during PCI were a major source, a range of medical practices that use plastic devices may be a new route for MPs to enter the human body.

Tumor recurrence and survival prognosis in patients with advanced gastric cancer after radical resection with radiotherapy and chemotherapy.

BACKGROUND: Advanced gastric cancer is a common malignancy that is often diagnosed at an advanced stage and is still at risk of recurrence after radical surgical treatment. Chemoradiotherapy, as one of the important treatment methods for gastric cancer, is of great significance for improving the survival rate of patients. However, the tumor recurrence and survival prognosis of gastric cancer patients after radiotherapy and chemotherapy are still uncertain. AIM: To analyze the tumor recurrence after radical radiotherapy and chemotherapy for advanced gastric cancer and provide more in-depth guidance for clinicians. METHODS: A retrospective analysis was performed on 171 patients with gastric cancer who received postoperative adjuvant radiotherapy and chemotherapy in our hospital from 2021 to 2023. The Kaplan-Meier method was used to calculate the recurrence rate and survival rate; the log-rank method was used to analyze the single-factor prognosis; and the Cox model was used to analyze the prognosis associated with multiple factors. RESULTS: The median follow-up time of the whole group was 63 months, and the follow-up rate was 93.6%. Stage II and III patients accounted for 31.0% and 66.7%, respectively. The incidences of Grade 3 and above acute gastrointestinal reactions and hematological adverse reactions were 8.8% and 9.9%, respectively. A total of 166 patients completed the entire chemoradiotherapy regimen, during which no adverse reaction-related deaths occurred. In terms of the recurrence pattern, 17 patients had local recurrence, 29 patients had distant metastasis, and 12 patients had peritoneal implantation metastasis. The 1-year, 3-year, and 5-year overall survival (OS) rates were 83.7%, 66.3%, and 60.0%, respectively. The 1-year, 3-year, and 5-year disease-free survival rates were 75.5%, 62.7%, and 56.5%, respectively. Multivariate analysis revealed that T stage, peripheral nerve invasion, and the lymph node metastasis rate (LNR) were independent prognostic factors for OS. CONCLUSION: Postoperative intensity-modulated radiotherapy combined with chemotherapy for gastric cancer treatment is well tolerated and has acceptable adverse effects, which is beneficial for local tumor control and can improve the long-term survival of patients. The LNR was an independent prognostic factor for OS. For patients with a high risk of local recurrence, postoperative adjuvant chemoradiation should be considered.

Immobilized PAD4 enzyme on magnetic nanoparticles for screening natural inhibitors from traditional Chinese medicines.

Dysregulation of peptidyl arginine deiminase 4 (PAD4) is involved in a variety of diseases including rheumatoid arthritis (RA) and Alzheimer's disease (AD), and it has emerged as potential and promising therapeutic target. However, no PAD4 inhibitor is ready for clinical use. Immobilized enzyme screening technology has gained increasing attention due to its low cost, reusability, easy separation from the reaction mixture, and resistance to changes in environmental conditions. In this study, PAD4 was immobilized on the magnetic nanoparticles (MNP) to prolong its activity stability, and a simple and rapid screening strategy of traditional Chinese medicine inhibitors based on immobilized PAD4 was established. The PAD4 enzyme was immobilized on magnetic nanoparticles (MNP) via Schiff base reaction using glutaraldehyde (GA) as crosslinking agent. Compared with free PAD4, the resulting MNP@GA@PAD4 exhibited an enhanced tolerance to temperature and storage stability, and its reusability was greatly improved with 66 % of initial enzyme activity after being recycled 10 times. The inhibitory activity of the immobilized PAD4 was assessed using two known PAD4 inhibitors GSK484 and BB-Cl-amidine. The semi-maximum inhibitory concentrations (IC50) of GSK484 and BB-Cl-amidine for MNP@GA@PAD4 were 1.00 and 0.97 µM, respectively, for free PAD4 were 0.64 and 0.85 µM, respectively. Finally, the MNP@GA@PAD4 was employed to rapid screen of natural PAD4 inhibitors from forty traditional Chinese medicines (TCMs). Under the same conditions, the controlled experiment was conducted with free PAD4. The screening results of TCMs inhibitors on MNP@GA@PAD4 and free PAD4 were similar, the alcohol extracts of Cinnamomi Cortex and Caryophylli Flos had significant inhibitory effects on PAD4 enzyme activity. The IC50 values of Cinnamomi Cortex extract for MNP@GA@PAD4 and free PAD4 were determined as 27 and 48 µg/mL, respectively. The IC50 values of Caryophylli Flos extracts for MNP@GA@PAD4 and free PAD4 were determined as 48 and 32 µg/mL, respectively. For the first time, this study proposed a method to immobilize PAD4 on magnetic materials, and developed a rapid, reusable and feasible strategy to screening natural PAD4 inhibitors from TCMs.

Intrathecal topotecan with systemic checkpoint inhibitor therapy for gastroesophageal cancer with leptomeningeal involvement: two case reports and review of the literature.

Background: Leptomeningeal metastases (LM) in gastroesophageal (GE) malignancies are exceedingly rare. Historically, treatment for LM has included steroids, radiation, chemotherapy, and intrathecal (IT) chemotherapy. However, the outcomes in GE malignancies with LM remain poor. Unfortunately, clinical trials in GE malignancies have traditionally excluded those with LM, limiting advances in therapeutic strategies. Given that LM poses potentially devastating neurologic and psychologic sequelae, there is an urgent need for more effective treatments. Case Description: Patient 1 is a 44-year-old woman with localized esophageal adenocarcinoma who undergoes neoadjuvant chemoradiation followed by esophagectomy. Seven months following surgery, she develops ataxia, weakness, and nausea/vomiting. Magnetic resonance imaging (MRI) reveals intracranial disease that is subsequently successfully resected and then treated with gamma knife (GK) radiation. Pathology confirms metastases. Three months later she is found to have LM. She receives palliative whole brain radiation therapy as well as focal radiation to the spine. Following this she transitioned to concurrent IT topotecan plus intravenous (IV) ipilumumab/nivolumab with durable response beyond 14 months. Patient 2 is a 71-year-old man with de novo metastatic esophageal adenocarcinoma with durable response to 5-fluorouracil plus irinotecan. Asymptomatic intracranial metastases are detected on surveillance scans 2 years after initial diagnosis for which he receives GK. Follow up MRI identifies new LM. As such, to treat the LM, he was transitioned to IT topotecan and IV pembrolizumab with good response for 6 months until death from a gastrointestinal bleed. Conclusions: We present two cases of LM in patients with GE adenocarcinoma who had longer survival than what has been reported. They were treated with combination IT topotecan and IV checkpoint inhibition. Further studies evaluating the central nervous system tumor immune-microenvironment can help expand our understanding of how this combination has worked well in our patients and how to care for others with similar scenarios.

Percutaneous ablation versus robotic­assisted partial nephrectomy for cT1 renal cell carcinoma: an evidence-based analysis of comparative outcomes.

This investigation sought to conduct a comprehensive meta-analysis to assess the comparative effectiveness and safety of percutaneous ablation (PCA) versus robotic-assisted partial nephrectomy (RAPN) among individuals diagnosed with cT1 renal tumors. This study rigorously followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to conduct a systematic review and meta-analysis. A systematic search was carried out in the PubMed, Embase, Web of Science, and Cochrane Library databases, focusing on studies published in English through February 2024. We focused on evaluating primary outcomes, specifically perioperative outcomes, functional outcomes, and oncological outcomes. In this analysis, data from 1534 patients across 13 studies were evaluated. PCA was found to have advantageous outcomes in comparison to RAPN regarding hospital stay durations, with a Weighted Mean Difference (WMD) of - 2.03 days (95% Confidence Interval [CI]: -3.78 to - 0.27; p = 0.02), operative times (WMD: -106.75 min; 95% CI: - 170.78 to - 42.72; p = 0.001), and overall complication rates (Odds Ratio [OR]: 0.61; 95% CI: 0.42 to 0.89; p = 0.01). Conversely, PCA showed a higher incidence of local recurrence compared to RAPN, with an OR of 3.20 (95% CI: 1.91 to 5.35; p < 0.00001). Moreover, there were no statistically significant differences between the two treatments in terms of major complications, declines in estimated glomerular filtration rates (eGFR), variations in creatinine levels, overall survival rates, and recurrence-free survival. While PCA exhibits higher local recurrence rates than RAPN, it also presents significant advantages, such as shorter hospital stays, decreased operative durations, and lower complication rates. This juxtaposition underscores the urgent need for further, more rigorous research to substantiate these findings.

Association between IL-2 Receptor and Severe Coronary Artery Calcification in Patients with Coronary Artery Disease.

Background: Coronary artery calcification (CAC) is a crucial marker for coronary atherosclerosis, and the extent of CAC is closely linked to the incidence and progression of cardiovascular diseases. The interleukin-2 (IL-2) receptor (IL-2R), which plays a critical role in mediating the proliferation and differentiation of immune cells, may also be involved in the development of CAC. The study aimed to investigate the relationship between IL-2R and CAC, with the goal of providing new insights into cardiovascular diseases. Methods: In this study, we enrolled 606 patients diagnosed with coronary artery disease to assess CAC. Based on coronary artery calcification score (CACS), patients were divided into two groups: the non-severe CAC group (CACS ≤ 400 Agatston units, AU) and the severe CAC group (CACS > 400 AU). Results: The results showed that IL-2R levels were significantly higher in patients with severe CAC compared to those with non-severe CAC (383 vs. 352 pg/mL, p = 0.002). Moreover, the level of IL-2R was positively correlated with the severity of CAC, independent of other clinical risk factors. According to Receiver Operating Characteristic (ROC) curve, the IL-2R prediction model demonstrated a good capability in distinguishing severe CAC with the Area Under the Curve (AUC) value of 0.726. Conclusions: Our study suggests that IL-2R is independently associated with the occurrence of severe CAC in coronary artery disease (CAD) patients. Additionally, IL-2R may play a crucial role in the development of advanced atherosclerosis. Consequently, therapeutic strategies targeting the IL-2/IL-2R pathway may be effective in preventing or treating CAD.

Outcomes and Pattern of Care for Spinal Myxopapillary Ependymoma in the Modern Era-A Population-Based Observational Study.

(1) Background: Myxopapillary ependymoma (MPE) is a rare tumor of the spine, typically slow-growing and low-grade. Optimal management strategies remain unclear due to limited evidence given the low incidence of the disease. (2) Methods: We analyzed data from 1197 patients with spinal MPE from the Surveillance, Epidemiology, and End Results (SEER) database (2000-2020). Patient demographics, treatment modalities, and survival outcomes were examined using statistical analyses. (3) Results: Most patients were White (89.9%) with a median age at diagnosis of 42 years. Surgical resection was performed in 95% of cases. The estimated 10-year overall survival was 91.4%. Younger age (hazard ratio (HR) = 1.09, p < 0.001) and receipt of surgery (HR = 0.43, p = 0.007) were associated with improved survival. Surprisingly, male sex was associated with worse survival (HR = 1.86, p = 0.008) and a younger age at diagnosis compared to females. (4) Conclusions: This study, the largest of its kind, underscores the importance of surgical resection in managing spinal MPE. The unexpected association between male sex and worse survival warrants further investigation into potential sex-specific pathophysiological factors influencing prognosis. Despite limitations, our findings contribute valuable insights for guiding clinical management strategies for spinal MPE.

Perineural Invasion as a Risk Factor For Soft Tissue Progression in Patients With Metastatic Castration-Resistant Prostate Cancer After Abiraterone Resistance.

BACKGROUND: Prostate cancer presents with soft tissue progression (STP) is highly aggressive. We analyzed the risk factor for STP in patients with metastatic castration-resistant prostate cancer (mCRPC) who developed abiraterone acetate (AA) resistance. METHODS: This retrospective study included patients with mCRPC who received AA between February 2018 and July 2022. STP was defined as recurrent lesions in situ, multiple regional lymph node metastases (mLNM), or visceral metastases. Clinical features of patients with STP were analyzed, and risk factors for STP were further investigated. RESULTS: Sixty-three patients (mean age, 75.0 years; median follow-up time, 22.3 months) were included in this study. Twenty-three patients (36.5%) presented STP during follow up, the overall survival (OS) after STP was 4.6 months. The serum neuron-specific enolase (NSE) were significantly elevated in patients with STP. Biopsies for 8 patients with STP showed neuroendocrine prostate cancer (NEPC, n = 5) was the major pathological types. Further analysis showed that perineural invasion (PNI) in primary tumor were the independent risk factors (HR = 3.145, P = 0.020) for STP, and PNI was related to the aggressiveness of tumor. Patients with PNI showed shorter castration-resistant progression free survival (median, 23.73 months vs. 25.59 months) and STP progression free survival (median, 19.7 months vs. not reached) compared with patients without PNI. CONCLUSIONS: STP showed extremely poor prognoses in patients with mCRPC after AA resistance, NEPC is the main pathological type of STP, and PNI in primary tumor was an independent risk factor for STP and indicated poor prognosis of prostate cancer.

Perovskite photodetector-based laser absorption spectroscopy for gas detection.

A gas detection method based on CH3NH3PbI3 (MAPbI3) and poly (3,4-ethylenedioxythiophene): poly (4-styrene sulfonate) (PEDOT:PSS) composite photodetectors (PDs) is proposed. The operation of the PD primarily relies on the photoelectric effect within the visible light band. Our study involves constructing a gas detection system based on tunable diode laser spectroscopy (TDLAS) and MAPbI3/PEDOT:PSS PD, and O2 was selected as the target analyte. The system has achieved a minimum detection limit (MDL) of 0.12% and a normalized noise equivalent absorption coefficient (NNEA) of 8.83 × 10-11 cm-1⋅W⋅Hz-1/2. Furthermore, the Allan deviation analysis results indicate that the system can obtain sensitivity levels as low as 0.058% over an averaging time of 328 seconds. This marks the first use of MAPbI3/PEDOT:PSS PD in gas detection based on TDLAS. Despite the detector's performance leaves much to be desired, this innovation offers a new approach to developing spectral based gas detection system.

Efficacy and safety of robotic vs. laparoscopic gastrectomy for patients with gastric cancer: systematic review and meta-analysis.

BACKGROUND: The emergence of robotic surgical systems compensated for the technological shortcomings of laparoscopic approaches. However, whether robotic gastrectomy (RG) has better perioperative outcomes and survival than laparoscopic gastrectomy (LG) for gastric cancer is still unclear but increasingly drawing attention. MATERIALS AND METHODS: In this systematic review and meta-analysis, we searched the PubMed, EMBASE, Web of Science, and Cochrane Library as of January 20, 2024 and referenced list of eligible articles for all published studies comparing RG and LG for patients with gastric cancer, Data on study characteristics, individual characteristics, and outcome parameters were extracted. The quality of studies was assessed using the Revised Cochrane risk-of-bias 2 tool and the risk of bias in non-randomized studies of interventions tool. The main outcome measures were overall survival (OS) and disease-free survival (DFS). RESULTS: We identified 3641 articles, of which 72 studies (30081 patients) were included in the meta-analysis. Compared with LG, RG was associated with higher OS [hazard ratio (HR)=0.89, 95% CI=0.83 to 0.96), lower rate of overall postoperative complications [odds ratio (OR)=0.77, 95% CI=0.71 to 0.84], longer operating time [mean difference (MD)=35.53, 95% CI=29.23 to 41.83], less estimated blood loss (MD=-37.45, 95% CI=-46.24 to -28.67), a higher number of retrieved lymph nodes (MD=1.88, 95% CI=0.77 to 3.00), faster postoperative recovery, and lower rate of conversion (OR=0.44, 95% CI=0.36 to 0.55). Mortality and DFS were not significantly different between the two groups. The subgroup of meta-analysis results also showed the advantages of robotic surgery over laparoscopic surgery in intracorporeal reconstruction, total gastrectomy, Ⅰ/Ⅱ stage, and BMI≥25, especially for patients with stage Ⅰ/Ⅱ, there is better overall survival and disease-free survival. CONCLUSION: Our findings point to robotic surgery having great benefits compared with laparoscopic surgery in gastric cancer. Our study may help inform decision-making in applying robotic surgical systems to clinical treatment.

Genome-wide identification and phylogenetic analysis of the tetraspanin gene family in lepidopteran insects and expression profiling analysis in Helicoverpa armigera.

The tetraspanin gene family encodes cell-surface proteins that span the membrane 4 times and play critical roles in a wide range of biological processes across numerous organisms. Recent findings highlight the involvement of a tetraspanin of the lepidopteran pest Helicoverpa armigera in resistance to Bacillus thuringiensis Cry insecticidal proteins, which are extensively used in transgenic crops. Thus, a better understanding of lepidopteran tetraspanins is urgently needed. In the current study, genome scanning in 10 lepidopteran species identified a total of 283 sequences encoding potential tetraspanins. Based on conserved cysteine patterns in the large extracellular loop and their phylogenetic relationships, these tetraspanins were classified into 8 subfamilies (TspA to TspH). Six ancestral introns were identified within lepidopteran tetraspanin genes. Tetraspanins in TspA, TspB, TspC, and TspD subfamilies exhibit highly similar gene organization, while tetraspanins in the remaining 4 subfamilies exhibited variation in intron loss and/or gain during evolution. Analysis of chromosomal distribution revealed a lepidopteran-specific cluster of 10 to 11 tetraspanins, likely formed by tandem duplication events. Selective pressure analysis indicated negative selection across all orthologous groups, with ω values ranging between 0.004 and 0.362. However, positive selection was identified at 18 sites within TspB5, TspC5, TspE3, and TspF10. Furthermore, spatiotemporal expression analysis of H. armigera tetraspanins demonstrated variable expression levels across different developmental stages and tissues, suggesting diverse functions of tetraspanin members in this globally important insect pest. Our findings establish a solid foundation for subsequent functional investigations of tetraspanins in lepidopteran species.

The Role of TLR7 and TLR9 in the Pathogenesis of Systemic Sclerosis.

The bleomycin-induced scleroderma model is a well-established and dependable method for creating a mouse model of SSc (systemic sclerosis). In the field of skin connective tissue diseases, increasing evidence from clinical and animal experiments suggests that TLRs (Toll-like receptors) play an important role in several diseases. This study aimed to determine the role of TLR7 (Toll-like receptor 7) and TLR9 (Toll-like receptor 9) in the mechanisms of immune abnormalities and fibrosis in SSc. This study used TLR7-KO mice (TLR7-knockout mice with a balb/c background) and TLR9-KO mice (TLR9-knockout mice with a balb/c background) as well as WT mice (wild-type balb/c mice). All three kinds of mice were induced by BLM (bleomycin) in a scleroderma model as the experimental group; meanwhile, WT mice treated with PBS (phosphate-buffered saline) were used as the control group. We analyzed the fibrotic phenotype and the immunological abnormality phenotype of TLR7-deficient and TLR9-deficient mice in the SSc disease model using flow cytometry, RT-PCR (reverse transcription-polymerase chain reaction), a histological examination, and IHC (immunohistochemical staining). In a mouse model of SSc disease, the deletion of TLR7 attenuated skin and lung fibrosis, while the deletion of TLR9 exacerbated skin and lung fibrosis. The deletion of TLR7 resulted in a relative decrease in the infiltration and expression of various pro-inflammatory and fibrotic cells and cytokines in the skin. On the other hand, the deletion of TLR9 resulted in a relative increase in the infiltration and expression of various pro-inflammatory and cytokine-inhibiting cells and cytokines in the skin. Under the influence of pDCs (plasmacytoid dendritic cells), the balances of Beff/Breg (IL-6 + CD19 + B cell/IL-10 + CD19 + B cell), Th17/Treg (IL-17A + CD4 + T cell/Foxp3 + CD25 + CD4 + T cell), M1/M2 (CD86 + macrophage/CD206 + macrophage), and Th1/Th2 (TNFα + CD3 + CD4 + T cell/IL-4 + CD3 + CD4 + T cell) were biased towards the suppression of inflammation and fibrosis as a result of the TLR7 deletion. Comparatively, the balance was biased towards promoting inflammation and fibrosis due to the TLR9 deletion. In the SSc model, TLR7 promoted inflammation and fibrosis progression, while TLR9 played a protective role. These results suggest that TLR7 and TLR9 play opposite roles in triggering SSc to produce immune system abnormalities and skin fibrosis.

Incrementally Adapting Pretrained Model Using Network Prior for Multi-Focus Image Fusion.

Multi-focus image fusion can fuse the clear parts of two or more source images captured at the same scene with different focal lengths into an all-in-focus image. On the one hand, previous supervised learning-based multi-focus image fusion methods relying on synthetic datasets have a clear distribution shift with real scenarios. On the other hand, unsupervised learning-based multi-focus image fusion methods can well adapt to the observed images but lack the general knowledge of defocus blur that can be learned from paired data. To avoid the problems of existing methods, this paper presents a novel multi-focus image fusion model by considering both the general knowledge brought by the supervised pretrained backbone and the extrinsic priors optimized on specific testing sample to improve the performance of image fusion. To be specific, the Incremental Network Prior Adaptation (INPA) framework is proposed to incrementally integrate features extracted from the pretrained strong baselines into a tiny prior network (6.9% parameters of the backbone network) to boost the performance for test samples. We evaluate our method on both synthetic and real-world public datasets (Lytro, MFI-WHU, and Real-MFF) and show that our method outperforms existing supervised learning-based methods and unsupervised learning based methods.

Robust Model Free Adaptive Predictive Control for Wastewater Treatment Process With Packet Dropouts.

External disturbances and packet dropouts will lead to poor control performance for the wastewater treatment process (WWTP). To address this issue, a robust model-free adaptive predictive control (RMFAPC) strategy with a packet dropout compensation mechanism (PDCM) is proposed for WWTP. First, a dynamic linearization approach (DLA), relying only on perturbed process data, is employed to approximate the system dynamics. Second, a predictive control strategy is introduced to avoid a short-sighted control decision, and an extended state observer (ESO) is used to attenuate the disturbance effectively. Furthermore, a PDCM strategy is designed to handle the packet dropout problem, and the stability of RMFAPC is rigorously analyzed. Finally, the correctness and effectiveness of RMFAPC are verified through extensive simulations. The simulation results indicate that RMFAPC can significantly reduce IAE by 0.0223 and 0.1976 in two scenarios, regardless of whether the expected value remains constant or varies. This comparison to MFAPC demonstrates the superior robustness of RMFAPC against disturbances. The ablation experiment on PDCM further confirms its capability in handling the packet dropout problem.

Stereotactic radiosurgery for prostate cancer spine metastases: local control and fracture risk using a simultaneous integrated boost approach.

OBJECTIVE: Variation exists in approaches to delivery of spine stereotactic radiosurgery (SSRS). Here, the authors describe outcomes following single-fraction SSRS performed using a simultaneous integrated boost for the treatment of prostate cancer spine metastases. METHODS: Health records of patients with prostate cancer spine metastases treated with single-fraction SSRS at the authors' institution were reviewed. Treatment was uniform, with 16 Gy to the clinical tumor volume and 18 Gy to the gross tumor volume. The primary endpoint was local recurrence, with secondary endpoints including vertebral fracture and overall survival. Univariate and multivariate competing risk regression models made using the Fine and Gray method were used to identify factors predictive of local recurrence, considering death to be a competing event for local recurrence. RESULTS: A total of 87 targets involving 108 vertebrae in 68 patients were included, with a median follow-up of 22.5 months per treated target. The 1-, 2-, and 4-year cumulative incidence rates of local failure for all targets were 4.6%, 8.4%, and 19%, respectively. The presence of epidural disease (subdistribution hazard ratio [sHR] 5.43, p = 0.04) and SSRS as reirradiation (sHR 16.5, p = 0.02) emerged as significant predictors of local failure in a multivariate model. Hormone sensitivity did not predict local control. Vertebral fracture incidence rates leading to symptoms or requiring intervention at 1, 2, and 4 years were 1.1%, 3.7%, and 8.4%, respectively. In an exploratory analysis of patterns of failure, 3 (25%) failures occurred in the epidural space and only 1 (8%) occurred clearly in the clinical tumor volume. There were several lesions for which the precise location of failure with regard to target volumes was unclear. CONCLUSIONS: High rates of local control were observed, particularly for radiotherapy-naïve lesions without epidural disease. Hormone sensitivity was not predictive of local control in this cohort and fracture risk was low. Further research is needed to better predict which patients are at high risk of recurrence and who might benefit from treatment escalation.

Study on regulating AQP1, AQP3, AQP4, 5-HT, NOS1 in slow transit constipation rats by Liqi Tongbian mixture.

BACKGROUND: Liqi Tongbian is a traditional Chinese medicine (TCM) preparation that contains herbs that may treat slow transit constipation (STC). Atractylodes macrocephala, Astragalus membranaceus, Fructus aurantii, radish seed, uncooked Polygonum multiflorum, and Agastache rugosa were included in the formula for their unique qualities. The control of water transfer in the colon is greatly influenced by aquaporin 3 (AQP3). OBJECTIVES: Based on this, the Liqi Tongbian mixture was used to detect the concentrations of aquaporins (AQPs), 5-HT and nitrix oxide synthase 1 (NOS1) in STC rats, and explore its effect, in order to provide a theoretical basis for the remedy of STC with TCM. MATERIAL AND METHODS: Zhejiang University of Traditional Chinese Medicine provided 32 three-week-old Sprague Dawley rats of SPF-grade. The pairs licensed under SYXK (Zhejiang) 2021-0012 were kept at 20-25°C and humidity of 50-65%. The compound diphenoxylate caused constipation in the control, model, Liqi laxative (LQTB), and mosapride groups. The Liqi laxative rats were administered a mixture of traditional Chinese herbs after modeling, while mosapride was given to the other group. The levels of 5-HT, NOS1 and AQPs were tested in the feces and intestinal tissues. RESULTS: Comparing the condition of rat feces, it was found that the model group had significantly lower overall bulk, score and particles within 24 h compared to the control group. In comparison to mosapride, LQTB performed better. The model group had higher levels of 5-HT and NOS1 in intestinal tissue, while the LQTB and mosapride groups had decreased levels of these AQPs. LQTB had lower levels of AQP1, AQP3 and AQP4 than mosapride, while the model group had higher levels of these AQPs. CONCLUSIONS: Liqi Tongbian mixture works better than mosapride in improving constipation symptoms in rats with STC, and its mechanism is related to regulating the level of intestinal AQPs and neurotransmitters.

Variation in TaSPL6-D confers salinity tolerance in bread wheat by activating TaHKT1;5-D while preserving yield-related traits.

Na+ exclusion from above-ground tissues via the Na+-selective transporter HKT1;5 is a major salt-tolerance mechanism in crops. Using the expression genome-wide association study and yeast-one-hybrid screening, we identified TaSPL6-D, a transcriptional suppressor of TaHKT1;5-D in bread wheat. SPL6 also targeted HKT1;5 in rice and Brachypodium. A 47-bp insertion in the first exon of TaSPL6-D resulted in a truncated peptide, TaSPL6-DIn, disrupting TaHKT1;5-D repression exhibited by TaSPL6-DDel. Overexpressing TaSPL6-DDel, but not TaSPL6-DIn, led to inhibited TaHKT1;5-D expression and increased salt sensitivity. Knockout of TaSPL6-DDel in two wheat genotypes enhanced salinity tolerance, which was attenuated by a further TaHKT1;5-D knockdown. Spike development was preserved in Taspl6-dd mutants but not in Taspl6-aabbdd mutants. TaSPL6-DIn was mainly present in landraces, and molecular-assisted introduction of TaSPL6-DIn from a landrace into a leading wheat cultivar successfully improved yield on saline soils. The SPL6-HKT1;5 module offers a target for the molecular breeding of salt-tolerant crops.

Repeat it without me: Crowdsourcing the T1 mapping common ground via the ISMRM reproducibility challenge.

PURPOSE: T1 mapping is a widely used quantitative MRI technique, but its tissue-specific values remain inconsistent across protocols, sites, and vendors. The ISMRM Reproducible Research and Quantitative MR study groups jointly launched a challenge to assess the reproducibility of a well-established inversion-recovery T1 mapping technique, using acquisition details from a seminal T1 mapping paper on a standardized phantom and in human brains. METHODS: The challenge used the acquisition protocol from Barral et al. (2010). Researchers collected T1 mapping data on the ISMRM/NIST phantom and/or in human brains. Data submission, pipeline development, and analysis were conducted using open-source platforms. Intersubmission and intrasubmission comparisons were performed. RESULTS: Eighteen submissions (39 phantom and 56 human datasets) on scanners by three MRI vendors were collected at 3 T (except one, at 0.35 T). The mean coefficient of variation was 6.1% for intersubmission phantom measurements, and 2.9% for intrasubmission measurements. For humans, the intersubmission/intrasubmission coefficient of variation was 5.9/3.2% in the genu and 16/6.9% in the cortex. An interactive dashboard for data visualization was also developed: https://rrsg2020.dashboards.neurolibre.org. CONCLUSION: The T1 intersubmission variability was twice as high as the intrasubmission variability in both phantoms and human brains, indicating that the acquisition details in the original paper were insufficient to reproduce a quantitative MRI protocol. This study reports the inherent uncertainty in T1 measures across independent research groups, bringing us one step closer to a practical clinical baseline of T1 variations in vivo.