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Abstract Background Quadriceps training is necessary in function and activity of daily living for patients with knee osteoarthritis (KOA). However, it did not reduce the rate of surgical treatment for end-stage KOA in the long term. This may be related to brain structure changes and maladaptive plasticity in KOA patients. Transcranial Magnetic Stimulation (TMS) could enhance the functional connectivity of brain regions and improves maladaptive plasticity. However, the synergistic effect of the combination of the two for treat KOA is still unclear. Therefore, the purpose of this study is to investigate whether the High-Frequency rTMS combined with quadriceps strength training can improve the pain and function in KOA more effectively than quadriceps training alone and explore the mechanism of action. Methods This study is an assessor-blind, sham-controlled, randomized controlled trial involving 12 weeks of intervention and 6 months follow-up. 148 participants with KOA will receive usual care management and be randomized into four subgroups equally, including quadriceps strength training, high-frequency rTMS training, sham rTMS and quadriceps strength training, high-frequency rTMS and quadriceps strength training. The rehabilitation interventions will be carried out 5 days per week for a total of 12 weeks. All outcomes will be measured at baseline, 4 weeks, 8 weeks, and 12 weeks during the intervention and 1 month, 3 months and 6 months during the follow-up period. The effectiveness outcomes will be included visual analog scale, isokinetic knee muscle strength, Knee Injury and Osteoarthritis Outcome score and 36-Item Short-Form Health Survey score; The act mechanism outcomes will be included motor evoked potential, grey matter density, white matter, subcortical nuclei volumes, cortical thickness and functional connectivity by MRI. Two-way of variance with repeated measures will be used to test the group and time effect for outcome measures. Discussion The study will be the first protocol to examine whether there are synergistic effects following high-frequency rTMS combined with quadriceps strength training for treat KOA and clarify the mechanism of action. High-frequency rTMS can be added into the training program for KOA patients if it is proven effective. Trial registration Chinese Clinical Trial Registry ChiCTR2300067617. Registered on Jan.13,2023.

A novel metal-free synthesis of 3-substituted isocoumarins through a sequential O-acylation/Wittig reaction has been established. The readily accessible (2-carboxybenzyl)-triphenylphosphonium bromide and diverse chlorides produced various 1H-isochromen-1-one in the presence of triethylamine, employing sequential O-acylation and an intramolecular Wittig reaction of acid anhydride. Reactions using these facile conditions have exhibited high functional group tolerance and excellent yields (up to 90%). Moreover, the fluorescence properties of isocoumarin derivatives were evaluated at the theoretical and experimental levels to determine their potential application in fluorescent materials. These derivatives have good photoluminescence in THF with a large Stokes shift and an absolute fluorescence quantum yield of up to 14%.

Winter jujube is susceptible to cold stress during cold storage, resulting in quality deterioration. Shelf life of winter jujube after cold storage has not been investigated. This study investigated the effects of 1.0 μL L−1 1-methylcyclopropene (1-MCP) fumigation treatment for 24 h on the quality characteristics of jujube fruits (Zizyphus jujuba Mill. cv. Dalidongzao) during cold storage. The jujubes from the early experimental stage (0 d) were stored at room temperature (20 ± 1 °C) to estimate the shelf life. The remaining jujubes were transferred to cold storage at 0 ± 1 °C and were removed during the middle (40 d) and the later (60 d) stages of the experiment. The decay rate, firmness, color, titratable acidity, total phenolics and flavonoids, antioxidant activity, and antioxidant enzyme activity of winter jujube were measured every 3 days until the end of shelf life. The results indicated that the application of 1-MCP treatment extended the time for jujube to exceed a decay rate of more than 10 % by three days after 40 and 60 days of cold storage. 1-MCP treatment effectively retard the decrease of total phenolic and flavonoid content in jujube, and maintain high free radical scavenging ability and antioxidant enzyme activity throughout shelf life storage.

BackgroundThis study aims to compare the outcomes of active surveillance (AS) in low-risk papillary thyroid carcinoma (PTC) patients with different tumor sizes and lymph node metastasis status, in order to establish appropriate management strategies. By analyzing these results, this study provides valuable insights for the effective management of such patients, addressing the issues and challenges associated with AS in practical clinical practice.MethodsThe study utilized the SEER database supported by the National Cancer Institute of the United States, extracting data of PTC diagnosed between 2000 and 2015. Statistical analyses were conducted using inverse probability weighting (IPTW) and propensity score matching (PSM), including Kaplan-Meier survival curves and Cox regression models, to evaluate the impact of different tumor sizes and lymph node metastasis status on thyroid cancer-specific survival (TCSS).ResultsA total of 57,000 PTC patients were included, with most covariates having standardized mean differences below 10% after IPTW and PSM adjustments. The TCSS of PTC with a diameter smaller than 13mm is significantly better than that of tumors with a diameter larger than 13mm, regardless of the presence of lymph node metastasis. Among PTC cases with a diameter smaller than 13mm, the TCSS of patients is similar, regardless of the presence of lymph node metastasis. However, in PTC cases with a diameter larger than 13mm, the presence of lateral neck lymph node metastasis (N1b stage) significantly impacts the TCSS, although the absolute impact on TCSS rate is minimal.ConclusionThe treatment strategy of AS is safe for patients with T1a stage papillary thyroid microcarcinoma (PTMC). However, for patients with T1b stage, if the tumor diameter exceeds 13mm or there is lymph node metastasis in the lateral neck region, the TCSS will be significantly affected. Nevertheless, the absolute impact on survival is relatively small.

Abstract Background Associations of drugs with diseases provide important information for expediting drug development. Due to the number of known drug-disease associations is still insufficient, and considering that inferring associations between them through traditional in vitro experiments is time-consuming and costly. Therefore, more accurate and reliable computational methods urgent need to be developed to predict potential associations of drugs with diseases. Methods In this study, we present the model called weighted graph regularized collaborative non-negative matrix factorization for drug-disease association prediction (WNMFDDA). More specifically, we first calculated the drug similarity and disease similarity based on the chemical structures of drugs and medical description information of diseases, respectively. Then, to extend the model to work for new drugs and diseases, weighted $$K$$ K nearest neighbor was used as a preprocessing step to reconstruct the interaction score profiles of drugs with diseases. Finally, a graph regularized non-negative matrix factorization model was used to identify potential associations between drug and disease. Results During the cross-validation process, WNMFDDA achieved the AUC values of 0.939 and 0.952 on Fdataset and Cdataset under ten-fold cross validation, respectively, which outperforms other competing prediction methods. Moreover, case studies for several drugs and diseases were carried out to further verify the predictive performance of WNMFDDA. As a result, 13(Doxorubicin), 13(Amiodarone), 12(Obesity) and 12(Asthma) of the top 15 corresponding candidate diseases or drugs were confirmed by existing databases. Conclusions The experimental results adequately demonstrated that WNMFDDA is a very effective method for drug-disease association prediction. We believe that WNMFDDA is helpful for relevant biomedical researchers in follow-up studies.

The electromagnetic interference (EMI) from pulsed electromagnetic field (PEMF) on pacemakers is unignorable in modern power grids and healthcare environments, but there is limited study on the interaction mechanisms and protective measures. In this paper, an in-vitro human chest model for pacemaker implantation is made by using pork tissues immersed in 0.9% sodium chloride solution. The effect of PEMFs generated by the switching actions of common electrical equipment and low-frequency medical equipment on pacemakers is simulated by using fast-front current sources. The pulse forming line theory is employed for analyzing the waveform compression of PEMFs in human thoracic cavity. Further, the parameterized bio-electromagnetic transient model of pacemaker in combination with biological tissues is established in finite element software. The results show that pacemaker malfunctions including pacing inhibition and P pulmonale occur under PEMF. The “Window effect” in subcutaneous pouch under PEMF is found by changing the winding of pacemaker leads in the pouch. Based on the research finding, a protective strategy by using composite materials to shield the window area is proposed. The theoretical feasibility of this protective measure is confirmed by simulation, where the intensity of pacemaker EMI could be reduced by 80 dB when the composite materials shielding is used. Finally, a safe distance is developed for pacemaker wearers in electrical and medical environments.

Abstract Purpose c-Type cytochromes are essential for extracellular electron transfer (EET) in electroactive microorganisms. The expression of appropriate c-type cytochromes is an important feature of these microorganisms in response to different extracellular electron acceptors. However, how these diverse c-type cytochromes are tightly regulated is still poorly understood. Methods In this study, we identified the high co-fitness genes that potentially work with different c-type cytochromes by using genome-wide co-fitness analysis. We also constructed and studied the co-fitness networks that composed of c-type cytochromes and the top 20 high co-fitness genes of them. Results We found that high co-fitness genes of c-type cytochromes were enriched in signal transduction processes in Shewanella oneidensis MR-1 cells. We then checked the top 20 co-fitness proteins for each of the 41 c-type cytochromes and identified the corresponding signal proteins for different c-type cytochromes. In particular, through the analysis of the high co-fitness signal protein for CymA, we further confirmed the cooperation between signal proteins and c-type cytochromes and identified a novel signal protein that is putatively involved in the regulation of CymA. In addition, we showed that these signal proteins form two signal transduction modules. Conclusion Taken together, these findings provide novel insights into the coordinated utilization of different c-type cytochromes under diverse conditions.

The curing stage is of great importance in flavor formation during Chinese bacon processing. Ultrasound-assisted curing plays an essential role in the Lipid oxidation of meat products. In this study, GC–MS and electronic nose were used to analyze the influence of different power ultrasonic-assisted curing on the flavor formation of Chinese bacon. Through the analysis of phospholipid and lipase, the fundamental precursors of ultrasonic on the flavor of Chinese bacon were determined. It was found that there were differences in the flavor contour description of Chinese bacon between the ultrasonic treatment group, mainly due to the change in the W1W sensor. A total of 28 volatile compounds were detected by GC–MS, and the aldehyde content increased with ultrasonic power. PC and PE are the main flavor precursors in the curing process. This study provides a theoretical basis for improving the curing technology of Chinese bacon.