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Abstract Background Knee osteoarthritis (KOA) was characterized by pain and limited joint function, which seriously affected the quality of life of patients. The vast majority of KOA was closely related to degeneration of the patellofemoral joint and abnormal patellar movement trajectory. Tissue-bone homeostasis manipulation (TBHM) could correct abnormal patellar movement trajectory on the basis of loosening soft tissue. However, there was little strong evidence to verify its efficacy on the patients with KOA. The study objective was to explore the efficacy of the TBHM on gait and knee function in the patients with KOA. Methods Sixty KOA patients were randomly assigned to either the joint mobilization (n = 30) or TBHM (n = 30) group. The joint mobilization group received joint mobilization, while the TBHM group received TBHM. For two groups, the patients participated in 30 min rehabilitation sessions thrice per week for 12 weeks. The primary outcome was biomechanical gait outcomes during walking, including step length, step velocity, double support, knee range of motion (ROM), and knee adduction moment (KAM). The secondary outcomes were the Western Ontario and McMaster Index (WOMAC) and 36-Item short- form health survey (SF-36), which reflected improvements in knee function and quality of life, respectively. At baseline and 12 weeks, evaluations were conducted and compared between groups. Results After a 12-week intervention, significant group differences were observed in KAM (p = 0.018), WOMAC-Pain (p = 0.043) and WOMAC-Stiffness (p = 0.026). A noteworthy finding was the presence of a significant interaction effect between group and time specifically observed in step velocity during gait (p = 0.046), WOMAC-Function (p = 0.013) and SF-36 (p = 0.027). Further analysis revealed a significant difference in step velocity (p = 0.034), WOMAC-Function (p = 0.025) and SF-36 (p = 0.042) during post-assessment between the two groups. Moreover, a significant time effect was observed across all outcomes of the two groups (p

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.

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.

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%.

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.

A new efficient synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines via sequential Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution reaction has been developed. The three-component Passerini reactions of 2-azidobenzaldehydes 1, benzoic acid (2), and isocyanides 3 produced the azide intermediates 4, which were treated sequentially with triphenylphosphine, isocyanates (or CS2), and secondary amines to give polysubstituted 3,4-dihydroquinazolines 8 and 4H-3,1-benzothiazines 11 in good overall yields through consecutive Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution reactions.

While floral signaling plays a central role in the reproductive success of all animal‐pollinated plants, it may also attract herbivores eager to feed on flowers. False nectaries with glossy surfaces reflecting incident light may produce signals that attract floral visitors guiding their movements to and within the flower. Whether false nectaries also attract herbivores that lower the reproductive success of natural populations requires attention. In this study, we focus on Parnassia wightiana, a subalpine species with a whorl of staminodes that act as false nectaries attracting bees, flies, and herbivorous beetles. We tested the functions of staminodes using controlled manipulative experiments under field and lab conditions. We found a significant decrease in pollinator visits, and subsequent seed set, in flowers in which we removed staminodes or staminode apices confirming the function of these organs. In our natural populations, we found that a beetle, Nonarthra variabilis (Alticinae; Chrysomelidae), chews first on staminode apices, then it eats the entire staminodes and other flower parts, but rarely feeds on ovaries. Additional experiments suggested these beetles preferred staminodes to ovaries. Our results suggest this is a case of selective florivory, in which staminodes play a dual role, attracting pollinators and herbivores at the same time causing the attractive dilemma. Although selective florivory by beetles did not directly damage fruits, it influenced plant‐pollinator interactions, decreasing reproductive success in plant populations. Our study highlights the importance of plant‐pollinator‐herbivore interactions in selecting floral traits. [ABSTRACT FROM AUTHOR]

Alcoholic liver disease (ALD) is regarded as one of the main global health problems. Accumulated evidence indicates that fruit-derived polyphenols can lower the risk of ALD, this attributed to their strong antioxidant capacities. Thinned immature kiwifruits (TIK) are the major agro-byproducts in the production of kiwifruits, which have abundantly valuable polyphenols. However, knowledge about the protective effects of polyphenol-enriched extract from TIK against ALD is still lacking, which ultimately restricts their application as value-added functional products. To promote their potential applications, phenolic compounds from TIK and their corresponding mature fruits were compared, and their protective effects against ALD were studied in the present study. The findings revealed that TIK possessed extremely high levels of total phenolics (116.39 ± 1.51 mg GAE/g DW) and total flavonoids (33.88 ± 0.59 mg RE/g DW), which were about 7.4 times and 4.8 times greater than those of their corresponding mature fruits, respectively. Furthermore, the level of major phenolic components in TIK was measured to be 29,558.19 ± 1170.58 μg/g DW, which was about 5.4 times greater than that of mature fruits. In particular, neochlorogenic acid, epicatechin, procyanidin B1, and procyanidin B2 were found as the predominant polyphenols in TIK. In addition, TIK exerted stronger in vitro antioxidant and anti-inflammatory effects than those of mature fruits, which was probably because of their higher levels of polyphenols. Most importantly, compared with mature fruits, TIK exhibited superior hepatoprotective effects on alcohol-induced liver damage in mice. The administration of polyphenol-enriched extract from TIK (YK) could increase the body weight of mice, reduce the serum levels of ALP, AST, and ALT, lower the levels of hepatic TG and TC, and diminish lipid droplet accumulation and hepatic tissue damage. In addition, the treatment of YK could also significantly restore the levels of antioxidant enzymes (e.g., SOD and CAT) in the liver and lower the levels of hepatic proinflammatory cytokines (e.g., IL-6, IL-1β, and TNF-α), indicating that YK could effectively ameliorate ALD in mice by reducing hepatic oxidative stress and hepatic inflammation. Collectively, our findings can provide sufficient evidence for the development of TIK and their extracts as high value-added functional products for the intervention of ALD. [ABSTRACT FROM AUTHOR]

Discarded unripe kiwifruits (DUKs) are regarded as the major agro-byproducts in the production of kiwifruits, which have abundantly valuable secondary metabolites. Nevertheless, owing to the limited knowledge about the differences in phytochemicals and bioactivity between DUKs and mature kiwifruits, the utilization of DUKs in the food industry remains scarce. Hence, to promote their food applications, the phenolic compounds and bioactivity of discarded unripe, mature, and overripe fruits from three red-fleshed kiwifruit cultivars were studied and compared. The results revealed that the levels of total phenolics, total flavonoids, and total procyanidins in kiwifruits varied significantly by maturity stage. In addition, our findings demonstrated that DUKs possessed much higher contents of valuable phenolic compounds (e.g., chlorogenic acid (CHA), neochlorogenic acid (NCHA), gallic acid (GA), protocatechuic acid (PA), procyanidin B1 (ProcB1), procyanidin B2 (ProcB2), procyanidin C1 (ProcC1), quercetin 3-O-glucoside (QueG), and quercetin 3-O-rhamnoside (QueR)) than mature and overripe kiwifruits. Furthermore, DUKs exerted much stronger in vitro antioxidant capacity, inhibitory effects on α-glucosidase, and anti-inflammatory activity than mature and overripe kiwifruits, which were mainly attributed to their higher contents of total polyphenols and individual phenolic components, such as GA, CHA, NCHA, PA, ProcB1, ProcB2, ProcC1, and QueR. Overall, these findings provide sufficient evidence for the development and utilization of DUKs in the food/functional food industry. [ABSTRACT FROM AUTHOR]

Increasing evidences suggest that miRNAs play a key role in the occurrence and progression of many complex human diseases. Therefore, targeting dysregulated miRNAs with small molecule drugs in the clinical has become a new treatment. Nevertheless, it is high cost and time-consuming for identifying miRNAs-targeted with drugs by biological experiments. Thus, more reliable computational method for identification associations of drugs with miRNAs urgently need to be developed. In this study, we proposed an efficient method, called GNMFDMA, to predict potential associations of drug with miRNA by combining graph Laplacian regularization with non-negative matrix factorization. We first calculated the overall similarity matrices of drugs and miRNAs according to the collected different biological information. Subsequently, the new drug-miRNA association adjacency matrix was reformulated based on the K nearest neighbor profiles so as to put right the false negative associations. Finally, graph Laplacian regularization collaborative non-negative matrix factorization was used to calculate the association scores of drugs with miRNAs. In the cross validation, GNMFDMA obtains AUC of 0.9193, which outperformed the existing methods. In addition, case studies on three common drugs (i.e., 5-Aza-CdR, 5-FU and Gemcitabine), 30, 31 and 34 of the top-50 associations inferred by GNMFDMA were verified. These results reveal that GNMFDMA is a reliable and efficient computational approach for identifying the potential drug-miRNA associations.

Accumulating evidence indicated that the interaction between lncRNA and miRNA is crucial for gene regulation, which can regulate gene transcription, further affecting the occurrence and development of many complex diseases. Accurate identification of interactions between lncRNAs and miRNAs is helpful for the diagnosis and therapeutics of complex diseases. However, the number of known interactions of lncRNA with miRNA is still very limited, and identifying their interactions through biological experiments is time-consuming and expensive. There is an urgent need to develop more accurate and efficient computational methods to infer lncRNA–miRNA interactions. In this work, we developed a matrix completion approach based on structural perturbation to infer lncRNA–miRNA interactions (SPCMLMI). Specifically, we first calculated the similarities of lncRNA and miRNA, including the lncRNA expression profile similarity, miRNA expression profile similarity, lncRNA sequence similarity, and miRNA sequence similarity. Second, a bilayer network was constructed by integrating the known interaction network, lncRNA similarity network, and miRNA similarity network. Finally, a structural perturbation-based matrix completion method was used to predict potential interactions of lncRNA with miRNA. To evaluate the prediction performance of SPCMLMI, five-fold cross validation and a series of comparison experiments were implemented. SPCMLMI achieved AUCs of 0.8984 and 0.9891 on two different datasets, which is superior to other compared methods. Case studies for lncRNA XIST and miRNA hsa-mir-195–5-p further confirmed the effectiveness of our method in inferring lncRNA–miRNA interactions. Furthermore, we found that the structural consistency of the bilayer network was higher than that of other related networks. The results suggest that SPCMLMI can be used as a useful tool to predict interactions between lncRNAs and miRNAs.