Newly identified peptide Nigrocin-OA27 inhibits UVB induced melanin production via the MITF/TYR pathway.

Melasma is a common skin disease induced by an increase in the content of melanin in the skin, which also causes serious physical and mental harm to patients. In this research, a novel peptide (Nigrocin-OA27) from Odorrana andersonii is shown to exert a whitening effect on C57 mice pigmentation model. The peptide also demonstrated non-toxic and antioxidant capacity, and can significantly reduce melanin content in B16 cells. Topical application effectively delivered Nigrocin-OA27 to skin's epidermal and dermal layers and exhibited significant preventive and whitening effects on the UVB-induced ear pigmentation model in C57 mice. The whitening mechanism of Nigrocin-OA27 may be related to reduced levels of the microphthalmia-associated transcription factor and the key enzyme for melanogenesis-tyrosinase (TYR). Nigrocin-OA27 also inhibited the catalytic activity by adhering to the active core of TYR, thereby reducing melanin formation and deposition. In conclusion, Nigrocin-OA27 may be a potentially effective external agent to treat melasma by inhibiting aberrant skin melanin synthesis.

Hydrogel Loaded with Peptide-Containing Nanocomplexes: Symphonic Cooperation of Photothermal Antimicrobial Nanoparticles and Prohealing Peptides for the Treatment of Infected Wounds.

Current treatment for chronic infectious wounds is limited due to severe drug resistance in certain bacteria. Therefore, the development of new composite hydrogels with nonantibiotic antibacterial and pro-wound repair is important. Here, we present a photothermal antibacterial composite hydrogel fabricated with a coating of Fe2+ cross-linked carboxymethyl chitosan (FeCMCS) following the incorporation of melanin nanoparticles (MNPs) and the CyRL-QN15 peptide. Various physical and photothermal properties of the hydrogel were characterized. Cell proliferation, migration, cycle, and free-radical scavenging activity were assessed, and the antimicrobial properties of the hydrogel were probed by photothermal therapy. The effects of the hydrogel were validated in a model of methicillin-resistant Staphylococcus aureus (MRSA) infection with full-thickness injury. This effect was further confirmed by changes in cytokines associated with inflammation, re-epithelialization, and angiogenesis on the seventh day after wound formation. The MNPs demonstrated robust photothermal conversion capabilities. The composite hydrogel (MNPs/CyRL-QN15/FeCMCS) promoted keratinocyte and fibroblast proliferation and migration while exhibiting high antibacterial efficacy, effectively killing more than 95% of Gram-positive and Gram-negative bacteria. In vivo study using an MRSA-infected full-thickness injury model demonstrated good therapeutic efficacy of the hydrogel in promoting regeneration and remodeling of chronically infected wounds by alleviating inflammatory response and accelerating re-epithelialization and collagen deposition. The MNPs/CyRL-QN15/FeCMCS hydrogel showed excellent antibacterial and prohealing effects on infected wounds, indicating potential as a promising candidate for wound healing promotion.

SNRPB promotes the progression of hepatocellular carcinoma via regulating cell cycle, oxidative stress, and ferroptosis.

Small Nuclear Ribonucleoprotein Polypeptides B and B1 (SNRPB) have been linked to multiple human cancers. However, the mechanism of SNRPB in hepatocellular carcinoma (HCC) and whether SNRPB has a synergistic effect with sorafenib in the treatment of HCC remain unclear. In this study, bioinformatic analysis found that SNRPB was an independent prognostic factor for HCC that exerted a critical effect on the progression of HCC. SNRPB was linked with immune checkpoints, cell cycle, oxidative stress and ferroptosis in HCC. Single cell sequencing analysis found that HCC cell subset with high expression of SNRPB, accounted for a higher proportion in HCC cells with higher stages, had higher expression levels of the genes which promote cell cycle, inhibit oxidative stress and ferroptosis, and had higher cell cycle score, lower oxidative stress score and ferroptosis score. Single-sample gene set enrichment analysis (ssGSEA) analysis found that 17 oxidative stress pathways and 68 oxidative stress-ferroptosis related genes were significantly correlated with SNRPB risk scores. SNRPB knockdown induced cell cycle G2/M arrest and restrained cell proliferation, while downregulated the expression of CDK1, CDK4, and CyclinB1. The combined treatment (SNRPB knockdown+sorafenib) significantly inhibited tumor growth. In addition, the expression of SLC7A11, which is closely-related to ferroptosis, decreased significantly in vitro and in vivo. Therefore, SNRPB may promote HCC progression by regulating immune checkpoints, cell cycle, oxidative stress and ferroptosis, while its downregulation inhibits cell proliferation, which enhances the therapeutic effect of sorafenib, providing a novel basis for the development of HCC therapies.

ASD2023: towards the integrating landscapes of allosteric knowledgebase.

Allosteric regulation, induced by perturbations at an allosteric site topographically distinct from the orthosteric site, is one of the most direct and efficient ways to fine-tune macromolecular function. The Allosteric Database (ASD; accessible online at http://mdl.shsmu.edu.cn/ASD) has been systematically developed since 2009 to provide comprehensive information on allosteric regulation. In recent years, allostery has seen sustained growth and wide-ranging applications in life sciences, from basic research to new therapeutics development, while also elucidating emerging obstacles across allosteric research stages. To overcome these challenges and maintain high-quality data center services, novel features were curated in the ASD2023 update: (i) 66 589 potential allosteric sites, covering > 80% of the human proteome and constituting the human allosteric pocketome; (ii) 748 allosteric protein-protein interaction (PPI) modulators with clear mechanisms, aiding protein machine studies and PPI-targeted drug discovery; (iii) 'Allosteric Hit-to-Lead,' a pioneering dataset providing panoramic views from 87 well-defined allosteric hits to 6565 leads and (iv) 456 dualsteric modulators for exploring the simultaneous regulation of allosteric and orthosteric sites. Meanwhile, ASD2023 maintains a significant growth of foundational allosteric data. Based on these efforts, the allosteric knowledgebase is progressively evolving towards an integrated landscape, facilitating advancements in allosteric target identification, mechanistic exploration and drug discovery.

A simple, sensitive and colorimetric assay for Pseudomonas aeruginosa infection analysis.

Skin and soft tissue infections caused by Pseudomonas aeruginosa are common acquired diseases in postpartum care. Many methods have been developed in recent years for detecting P. aeruginosa, but they are criticized for the drawbacks of labor-intensiveness, complicated operation and high cost. Here, a simple, sensitive and colorimetric assay for P. aeruginosa detection is described. The approach displays a green color for positive samples and colorless for target-free samples. The approach exhibits a wide detection range and a low limit of detection of 45 CFU/ml. Thus, the developed ligation-initiated multiple-signal amplification method may be used for on-site testing of pathogenic bacteria and assist in the early diagnosis of postpartum care skin infections.

Interactions between phenanthrene and polystyrene micro/nano plastics: Implications for rice (Oryza sativa L.) toxicity.

Micro/nano plastics (MPs/NPs) are widely distributed and are one of the global pollutants of current concern. Micro/nano plastics can adsorb a variety of persistent organic pollutants, and different particle sizes and surface charges affect the biological effects of MPs/NPs. Therefore, how the compound pollution of MPs/NPs with different particle sizes and organic pollutants produces toxic effects on plants needs to be further studied. We investigated the toxic effects of phenanthrene (Phe) and amino-modified PS (PS-NH2) with two particle sizes (50 nm, 5 µm) on rice. The stress mechanism of PS-NH2 was different between the two particle sizes. Moreover, 50 nm PS-NH2 inhibited stomatal conductance and transpiration rate, reduced photosynthetic rate, significantly enriched GO functions such as "DNA repair" and "DNA double-strand break," and caused severe DNA damage in rice. Notably, 5 µm PS-NH2 affected the gene expression of "photosynthetic lighting" and "photosynthetic antenna protein" in rice, decreased chlorophyll content, and inhibited rice growth. The toxicity of 50 nm PS-NH2 was stronger. In addition, we found that Phe reduced the toxicity of PS-NH2 with different particle sizes, and the relief effect of 50 nm PS-NH2+Phe was more evident. Further, 50 nm PS-NH2+Phe alleviated the toxicity by stimulating the activities of antioxidant enzymes, reducing oxidative damage to chloroplasts, and inhibiting photosynthesis. However, 5 µm PS-NH2+Phe can reduce the stress by reducing the degree of membrane lipid peroxidation, activating metabolic pathways related to the cell wall and cell membrane formation, and plant antitoxin biosynthesis. The results contribute to the understanding of the mechanism of toxicity of MPs/NPs and polycyclic aromatic hydrocarbons (PAHs) to crops.

Molecular mechanisms of toxicity and detoxification in rice (Oryza sativa L.) exposed to polystyrene nanoplastics.

Nanoplastics (NPs) are an emerging threat to higher plants in terrestrial ecosystems. However, the molecular of NP-related phytotoxicity remains unclear. In the present study, rice seedlings were exposed to polystyrene (PS, 50 nm) NPs at 0, 50, 100, and 200 mg/L under hydroponic conditions to investigate the induced physiological indices and transcriptional mechanisms. We found that 50, 100, and 200 mg/L PS significantly reduced root (53.05%, 49.61%, and 57.58%, respectively) and shoot (54.63%, 61.56%, and 62.64%, respectively) biomass as compared with the control seedlings. The activities of antioxidant enzymes, including catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), and ascorbate peroxidase (APX), were significantly activated in all PS treatment groups, indicating that PS inhibited plant growth and induced oxidative stress. Transcriptome analyses showed that PS modulated the expression of the genes involved in cell detoxification, active oxygen metabolism, mitogen-activated protein kinase (MAPK), and plant hormone transduction pathways. Our study provides new insights into phytotoxicity by demonstrating the potential underlying toxicity of PS NPs in higher plants.

Toxicological effects and transcriptome mechanisms of rice (Oryza sativa L.) under stress of quinclorac and polystyrene nanoplastics.

The absorption and accumulation of nanoplastics (NPs) by plants is currently attracting considerable attention. NPs also tend to adsorb surrounding organic pollutants, such as pesticides, which can damage plants. However, molecular mechanisms underlying the phytotoxicity of NPs are not sufficiently researched. Therefore, we analyzed the toxicological effects of 50 mg/L polystyrene NPs (PS 50 nm) and 5 mg/L the herbicide quinolinic (QNC) on rice (Oryza sativa L.) using 7-day hydroponic experiments, explaining the corresponding mechanisms by transcriptome analysis. The main conclusion is that all treatments inhibit rice growth and activate the antioxidant level. Compared with CK, the inhibition rates of PS, QNC, and PS+QNC on rice shoot length were 3.95%, 6.68%, and 11.43%, respectively. The gene ontology (GO) term photosynthesis was significantly enriched by QNC, and the combination PS+QNC significantly enriched the GO terms of amino sugar and nucleotide sugar metabolisms. The chemicals QNC and PS+QNC significantly affected the Kyoto Encyclopedia of Genes and Genomes (KEGG) of the MAPK signaling pathway, plant hormone signal transduction, and plant-pathogen interaction. Our findings provide a new understanding of the phytotoxic mechanisms and environmental impacts of the interactions between NPs and pesticides. It also provides insights into the impact of NPs and pesticides on plants in the agricultural system.

Effects of Electrical Pulse Width and Output Irradiance on Intense Pulse Light Inactivation.

The effects of electrical pulse width and output irradiance on the inactivation effect of intense pulse light (IPL) are studied in this paper. The measured radiant efficiency of pulsed xenon lamp can be more than 50%, and its irradiance can reach levels 100-times greater than that of a low-pressure mercury lamp. Staphylococcus aureus is used in inactivation experiments. When the irradiance and dose are both constant, there is no significant difference in inactivation efficiency when the pulse width is changed. However, a narrow pulse width corresponding to high irradiance at the same single-pulsed dose displays better inactivation effect. Experimental results are compared between the xenon lamp and low-pressure mercury lamp. The reduction factor (RF) value of the xenon lamp is more than 1.0 higher under the condition of both the same dose and irradiance. In order to achieve the same RF value, the dose of continuous-wave light must be at least three-times greater than that of pulsed light. The spectral action of the pulsed light is also studied. It is confirmed that UVC plays a major role across the whole spectrum. The experimental results show that extreme high-pulsed irradiance presents the main contributing factor behind the excellent bactericidal effect of IPL.

Effects of individual and combined polystyrene nanoplastics and phenanthrene on the enzymology, physiology, and transcriptome parameters of rice (Oryza sativa L.).

Owing to their wide distribution, easy production, and resistance to degradation, microplastics (MPs) represent a globally emerging group of pollutants of concern. Furthermore, their decomposition can result in the generation of nanoplastics (NPs), which cause further environmental issues. Currently, the impact of the combination of these plastics with other organic pollutants on crop growth remains poorly investigated. In this study, a hydroponic experiment was conducted for seven days to evaluate the effects of 50 nm, 50 mg/L polystyrene (PS), and 1 mg/L phenanthrene (Phe) on the growth of rice plants. The results revealed that both Phe and PS inhibited growth and improved the antioxidant potential of rice. Relative to Phe alone, exposure to a combination of PS and Phe reduced Phe accumulation in the roots and shoots by 67.73% and 36.84%, respectively, and decreased the pressure on the antioxidant system. Exposure to Phe alone destroyed the photosynthetic system of rice plant leaves, whereas a combination of PS and Phe alleviated this damage. Gene Ontology (GO) analysis of the rice transcriptomes revealed that detoxification genes and phenylalanine metabolism were suppressed under exposure to Phe, which consequently diminished the antioxidant capacity and polysaccharide synthesis in rice plants. Kyoto Encyclopaedia of Genes and Genomes (KEGG) transcriptome analysis revealed that the combined presence of both PS and Phe improved photosynthesis and energy metabolism and alleviated the toxic effects of Phe by altering the carbon fixation pathway and hormone signal transduction in rice plants. The combination of PS and Phe also prevented Phe-associated damage to rice growth. These findings improve our understanding of the effects of MP/NPs and polycyclic aromatic hydrocarbons on crops.

Posterior cruciate ligament reconstruction with independent internal brace reinforcement: surgical technique and clinical outcomes with a minimum two year follow-up.

PURPOSE: We developed an augmentation technique for PCL reconstruction with independent internal brace reinforcement and evaluated the functional outcome after PCL reconstruction employing autologous hamstrings augmented with an internal brace system for patients with isolated or combined grade 3 posterior instability who were treated with this technique. METHODS: From January 2016 to January 2018, patients with isolated or combined grade 3 PCL tears who underwent single-bundle PCL reconstruction using autologous hamstrings augmented with independent internal braces were studied. The function of the operated knee was evaluated according to the International Knee Documentation Committee (IKDC) score, Lysholm score, and Tegner activity score. The patients were asked the level of returned to their previous sport. Posterior knee laxity was examined with a KT-1000 arthrometer, and data on range of motion (ROM), re-operation, and other complications were collected. RESULTS: A total of 33 consecutive patients who received single-bundle PCL reconstruction using autologous hamstrings augmented with independent internal braces with a minimum two years follow-up were included in this study. Two patients had undergone this procedure during the study period and were not included in this study (one had combined bone fractures, and one patient had previous meniscus surgery). Thirty-one patients were available for final analysis. The mean follow-up was 45.35 ± 10.88 months (range 29-66 months). The average IKDC subjective knee evaluation scores from 51.65 ± 12.35 to 84.52 ± 6.42, the Lysholm score from 53.90 ± 11.86 to 85.68 ± 4.99, and the Tegner score from 2.81 ± 0.79 to 6.71 ± 1.83 (P < 0.05 for all). The mean total posterior side-to-side difference in knee laxity, assessed using a KT-1000 arthrometer, decreased from 12.13 ± 2.66 mm pre-operatively to 1.87 ± 0.56 mm post-operatively at 70° (P < 0.05). Most patients (29/31) had normal or near normal knee ROM post-operatively; two patients revealed a 6-15° loss of knee flexion compared with the contralateral knee. Twenty-nine patients (93.55%) returned to a normal daily exercise level. Twenty-three patients (74.19%) returned to competitive sports with high-level sports (Tegner score of 6 or above; eleven patients (35.48%) reported to be on the same level as well as the Tegner level); six patients (19.35%) returned to recreational sports (Tegner score of 4 or 5). Two patients had Tegner scores of 2 and 3, indicating poor function level. No patient needed PCL revision surgery during the follow-up period. CONCLUSION: Single-bundle PCL reconstruction with internal brace augmentation for PCL injury exhibited satisfactory posterior stability and clinical outcomes in patients with isolated or combined grade 3 PCL injuries at a minimum two year follow-up.

Effects of polystyrene nanoplastics with different functional groups on rice (Oryza sativa L.) seedlings: Combined transcriptome, enzymology, and physiology.

Plastic particles originate from the daily use of plastics and have become a new form of pollutant. However, the effects of nanoplastics (NPs) on higher plants remain largely unclear, thus requiring further research. In this study, rice plants were exposed to polystyrene (PS) NPs with different functional groups to determine their toxicity. The presence of NPs reduced the biomass and photosynthetic capacity of rice. Compared with control (CK), the heights of rice plants exposed to no-modified PS, carboxyl-modified PS (PS-COOH) and amino-modified PS (PS-NH2) groups decreased by 13.59%, 26.61%, and 42.71%, while the dry shoot weight decreased by 47.46%, 50.09%, and 71.04%, respectively. All treatments activated the antioxidant levels of rice and reduced photosynthesis. Transcriptome analysis showed that NPs induced the expression of genes related to antioxidant enzyme activity in rice roots. Rice could partially reduce the xenobiotic toxicity caused by external sources by regulating phenylpropane biosynthesis and the processes involved in cell detoxification. PS mainly affected the process of RNA metabolism, while PS-COOH mainly affected ion transport, and PS-NH2 mainly affected the synthesis of macromolecular protein, which had different effects on rice growth.

[Comparative study of transosseous suture and suture anchor technique in medial patellofemoral ligament double bundle reconstruction].

OBJECTIVE: To investigate the effectiveness of transosseous suture in medial patellofemoral ligament (MPFL) double bundle reconstruction. METHODS: The clinical data of 75 patients with recurrent patella dislocation who met the selection criteria between January 2014 and December 2017 were retrospectively analyzed. All of them were treated with MPFL double bundle reconstruction, and divided into study group (39 cases, using new transosseous suture technique) and control group (36 cases, using traditional suture anchor fixation) depending on the intraoperative fixation technique. There was no significant difference in gender, age, body mass index, affected knee side, preoperative tibial tuberosity-trochlear groove distance, Insall-Salvati ratio, knee range of motion, Kujala score, International Knee Documentation Committee (IKDC) score, congruence angle, and tilt angle between the two groups ( P>0.05). The operation time, intraoperative blood loss, hospital stay, and postoperative complications were recorded and compared between the two groups. Kujala score, IKDC score, and knee range of motion were used to evaluate the functional improvement of patients before and after operation. The congruence angle and tilt angle were measured on X-ray films. RESULTS: There was no significant difference in operation time, intraoperative blood loss, and hospital stay between the two groups ( P>0.05). Patients in both groups were followed up 24-36 months, with an average of 29.4 months. There was no complication such as incision infection, fat liquefaction, patellar redislocation, and prepatellar pain during follow-up. At last follow-up, the Kujala score, IKDC score, knee range of motion, congruence angle, and tilt angle of two groups significantly improved when compared with those before operation ( P<0.05), while there was no significant difference between the two groups ( P>0.05). CONCLUSION: The application of suture anchor or transosseous suture to complete MPFL double bundle reconstruction can restore patellar stability, and there is no significant difference in the short-term effectiveness between them.

[Acupuncture combined with western medication in treatment of type 2 diabetes mellitus with angina pectoris of coronary heart disease: a randomized controlled study].

OBJECTIVE: To compare the therapeutic effect on type 2 diabetes mellitus (T2DM) complicated with angina pectoris of coronary heart disease between the combined therapy of acupuncture and western medication and the simple administration of western medication. METHODS: A total of 134 patients with T2DM and angina pectoris of coronary heart disease were randomly divided into two groups, i.e. an acupuncture plus medication group (67 cases, 3 cases dropped off) and a medication group (67 cases, 4 cases dropped off). The routine western medication was used according to symptoms in the patients of both groups. In the acupuncture plus medication group, on the base of medication, acupuncture was applied to Jianshi (PC 5), Quchi (LI 11), Neiguan (PC 6), etc. The needles were retained for 20 min in each treatment and 3 treatments of acupuncture were required weekly. The treatment was given consecutively for 8 weeks in the two groups. Separately, before and after treatment, the symptom scores of TCM were observed and the indexes were detected, including glycolipid metabolism [fasting plasma glucose (FPG), 2-h plasma glucose (2hPG), glucosylated hemoglobin (HbA1c), triacylglycerol (TG) and total cholesterol (TC)], islet ß cell function [homeostasis model assessment-ß (HOMA-ß), homeostasis model assessment-IR (HOMA-IR), fasting insulin (FINS) and insulin sensitivity index (ISI)], cardiac function indexes [cardiac output (CO), early diastolic peak velocity/late diastolic peak velocity (E/A), left ventricular end diastolic diameter (LVEDD) and left ventricular ejection fraction (LVEF)], as well as electrocardiogram QT dispersion (QTd). Besides, the clinical therapeutic effects were compared between the two groups. RESULTS: After treatment, the TCM symptom scores and the values of FPG, 2hPG, HbA1c, TG, TC, HOMA-IR, FINS, E/A and LVEDD as well as QTd were all lower than those before treatment in the two groups (P<0.05), and the levels of the above-mentioned indexes in the acupuncture plus medication group were all lower than those in the medication group (P<0.05). The values of HOMA-ß, ISI, CO and LVEF after treatment were higher than those before treatment in the two groups (P<0.05), and the levels of the above-mentioned indexes in the acupuncture plus medication group were all higher than those in the medication group (P<0.05). The total effective rate was 93.8% (60/64) in the acupuncture plus medication group, higher than 79.4% (50/63) in the medication group (P<0.05). CONCLUSION: The combined therapy of acupuncture and medication is effective in treatment of T2DM complicated with angina pectoris of coronary heart disease. Such therapy effectively improves glucolipid metabolism, islet ß cell function, cardiac function and myocardial blood supply. Its curative effect is better than the simple administration of western medicine.

A Unified Fourth-Order Tensor-Based Smart Community System.

Empowered by the ubiquitous sensing capabilities of Internet of Things (IoT) technologies, smart communities could benefit our daily life in many aspects. Various smart community studies and practices have been conducted, especially in China thanks to the government's support. However, most intelligent systems are designed and built individually by different manufacturers in diverging platforms with different functionalities. Therefore, multiple individual systems must be deployed in a smart community to have a set of functions, which could lead to hardware waste, high energy consumption and high deployment cost. More importantly, current smart community systems mainly focus on the technologies involved, while the effects of human activity are neglected. In this paper, a fourth-order tensor model representing object, time, location and human activity is proposed for human-centered smart communities, based on which a unified smart community system is designed. Thanks to the powerful data management abilities of a high-order tensor, multiple functions can be integrated into our system. In addition, since the tensor model embeds human activity information, complex functions could be implemented by exploring the effects of human activity. Two exemplary applications are presented to demonstrate the flexibility of the proposed unified fourth-order tensor-based smart community system.

The effect of femoral head size on edge loading in metal-on-metal hip joint replacement under dynamic separation conditions.

Edge loading that occurs in hip joint replacements due to dynamic separation of the joint bearings has been shown to cause severe wear for meal-on-metal bearings. In the present study, the multibody dynamics model for metal-on-metal (MoM) hip joints with a medial-lateral translational mismatch in the centers of rotation of the cup and head has been developed to predict the dynamic separation and contact force of edge loading under gait loading conditions. The effects of larger head diameters (28-55 mm), in combination with the translational mismatch (0-4 mm) and varied cup inclination angles (45°-65°), on edge loading of MoM bearings have been computationally investigated. For the given translational mismatch, increasing head diameters results in negligible effects on the dynamic separation, contact force and severity of edge loading. Increasing head size also leads to increased offset loading torque which has been found to reach at the level that may cause cup loosening under larger translational mismatch at 4 mm. The result highlights the importance of the cup inclination angle of 45° and a lower translational mismatch to avoid severe edge loading.

Erlotinib as Neoadjuvant Therapy in Stage IIIA (N2) EGFR Mutation-Positive Non-Small Cell Lung Cancer: A Prospective, Single-Arm, Phase II Study.

LESSONS LEARNED: The findings of this prospective, single-arm, phase II study showed that neoadjuvant erlotinib was well tolerated and might improve the radical resection rate in patients with stage IIIA-N2 epidermal growth factor receptor mutation-positive non-small cell lung cancer (NSCLC).Erlotinib shows promise as a neoadjuvant therapy option in this patient population.Next-generation sequencing may be useful for predicting outcomes with preoperative tyrosine kinase inhibitors (TKIs) in patients with NSCLC.Large-scale randomized controlled trials investigating the role of TKIs in perioperative therapy, combining neoadjuvant and adjuvant treatments to enhance personalized therapy for patients in this precision medicine era, are warranted. BACKGROUND: Information on epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) as neoadjuvant therapy in non-small cell lung cancer (NSCLC) is scarce. We evaluated whether neoadjuvant erlotinib improves operability and survival in patients with stage IIIA-N2 EGFR mutation-positive NSCLC. METHODS: We conducted a prospective, single-arm, phase II study. Patients received erlotinib 150 mg per day for 56 days in the neoadjuvant period. The primary endpoint was the radical resection rate. RESULTS: Nineteen patients were included in the final analysis. After erlotinib treatment, 14 patients underwent surgery. The radical resection rate was 68.4% (13/19) with a 21.1% (4/19) rate of pathological downstaging. The objective response rate was 42.1%; 89.5% (17/19) of patients achieved disease control, with a 10.3-month median disease-free survival among patients who underwent surgery. Among all 19 patients who received neoadjuvant therapy, median progression-free survival (PFS) and overall survival were 11.2 and 51.6 months, respectively. Adverse events (AEs) occurred in 36.8% (7/19) of patients, with the most common AE being rash (26.3%); 15.8% experienced grade 3/4 AEs. Quality of life (QoL) improvements were observed after treatment with erlotinib for almost all QoL assessments. Effects of TP53 mutation on prognosis were evaluated in eight patients with adequate tissue samples. Next-generation sequencing revealed that most patients had a TP53 gene mutation (7/8) in addition to an EGFR mutation. No TP53 mutation, or very low abundance, was associated with longer PFS (36 and 38 months, respectively), whereas high abundance was associated with short PFS (8 months). CONCLUSION: Neoadjuvant erlotinib was well tolerated and may improve the radical resection rate in this patient population. Next-generation sequencing may predict outcomes with preoperative TKIs.

Research on Fault Extraction Method of Variational Mode Decomposition Based on Immunized Fruit Fly Optimization Algorithm.

In recent years, a new method of fault diagnosis, named variational mode decomposition (VMD), has been widely used in industrial production, but the decomposition accuracy of VMD is determined by two parameters, which are respectively the decomposition layer number k and the penalty factor α, if the parameters are not properly selected, there will be over-decomposition or under-decomposition. In order to find an approach to determine the parameters adaptively, a method to optimize VMD by using the immune fruit fly optimization algorithm (IFOA) is proposed in this paper. In this method, permutation entropy is used as the fitness function, firstly, the immune fruit fly optimization algorithm is used to search the combined parameters of k and α in VMD, searching for the best combination parameters of k and α by iteration, and then uses the combined parameters to perform VMD, finally, the center frequency is determined through frequency spectrum analysis. The method mentioned is applied to the fault extraction of a simulated signal and a measured signal of a wind turbine gearbox, and the fault frequency is successfully extracted. Using ensemble empirical mode decomposition (EEMD) and singular spectrum decomposition (SSD) to compare with the proposed method, which validated feasibility of the proposed method.

A New Fuzzy Logic Classifier Based on Multiscale Permutation Entropy and Its Application in Bearing Fault Diagnosis.

The self-organizing fuzzy (SOF) logic classifier is an efficient and non-parametric classifier. Its classification process is divided into an offline training stage, an online training stage, and a testing stage. Representative samples of different categories are obtained through the first two stages, and these representative samples are called prototypes. However, in the testing stage, the classification of testing samples is completely dependent on the prototype with the maximum similarity, without considering the influence of other prototypes on the classification decision of testing samples. Aiming at the testing stage, this paper proposed a new SOF classifier based on the harmonic mean difference (HMDSOF). In the testing stage of HMDSOF, firstly, each prototype was sorted in descending order according to the similarity between each prototype in the same category and the testing sample. Secondly, multiple local mean vectors of the prototypes after sorting were calculated. Finally, the testing sample was classified into the category with the smallest harmonic mean difference. Based on the above new method, in this paper, the multiscale permutation entropy (MPE) was used to extract fault features, linear discriminant analysis (LDA) was used to reduce the dimension of fault features, and the proposed HMDSOF was further used to classify the features. At the end of this paper, the proposed fault diagnosis method was applied to the diagnosis examples of two groups of different rolling bearings. The results verify the superiority and generalization of the proposed fault diagnosis method.

Modified Singular Spectrum Decomposition and Its Application to Composite Fault Diagnosis of Gearboxes.

Under the strong noise environment, the composite fault signal of gearbox is weak, which makes it difficult to extract fault features. For this problem, based on noise-assisted method, we propose a novel method called Modified Singular Spectrum Decomposition (MSSD). Singular Spectrum Decomposition (SSD) has many advantages such as high decomposition precision and strong ability to restrain mode mixing, etc. However, the ability of SSD to extract a weak signal is not ideal, the decomposition results usually contain a lot of redundant noise and mode mixing caused by intermittency, which is also a troubling problem. In order to improve the decomposition efficiency and make up for the defects of SSD, the new method MSSD adds an adaptive and particular noise in every SSD decomposition stage for each trial, and in addition, whenever the input signal is decomposed to obtain an intrinsic module function (IMF), a unique residual is obtained. After multiple decomposition, the average value of the residual is used as input to the next stage, until the residual cannot continue to decompose, which means that the residual component has, at most, one extreme value. Finally, analyzing simulated signals to explain the advantages of MSSD compared to ensemble empirical mode decomposition (EEMD) and complete ensemble local mean decomposition with adaptive noise (CEEMDAN). In order to further prove the effectiveness of MSSD, this new method, MSSD, is applied to the fault diagnosis of an engineering gearbox test stand in an actual engineer project case. The final results show that MSSD can extract more fault feature information, and mode mixing has been improved and suffers less interference compared to SSD.