Repair System Research Articles

Generation of SOX2ZsGreen reporter authentic porcine induced pluripotent stem cells

The transcription factor SOX2 plays a crucial role in pluripotency during embryogenesis. In this study, we successfully generated porcine induced pluripotent stem cells (piPSC) by transducing porcine fetal fibroblasts with doxycycline-inducible reprogramming lentiviral vectors. To enhance the utility of these piPSCs, we used a CRISPR/Cas9-based homology-directed repair (HDR) system to introduce a nls-zsGreen reporter in-frame and before the stop codon of the SOX2 coding sequence. The incorporation of the zsGreen reporter offers a novel opportunity for real-time monitoring of SOX2 expression and aiding in the characterization of piPSC lines.

Novel role of circRNAs in the drug resistance of gastric cancer: regulatory mechanisms and future for cancer therapy.

Cancer, including gastric cancer, has become a serious disease that jeopardizes public life. Currently, the main treatment methods are surgery, radiation therapy, and chemotherapy. One of the primary causes of death for patients with gastric cancer is drug resistance. Several mechanisms of anticancer drugs resistance have been reported, including changes in drugs transport and metabolism, mutations in drug targets, changes in DNA repair systems, inhibition of cell apoptosis and autophagy, gastric cancer stem cells, invasion and migration. It is becoming more widely known that non-coding RNAs, like circRNAs, play a critical role in the resistance of drugs used to treat gastric cancer. CircRNAs have a unique structure and function that is related to gastric cancer resistance, cell proliferation, apoptosis, autophagy, DNA repair systems, migration, and invasion. A clear understanding of the molecular mechanism of circRNAs mediated the resistance of gastric cancer drugs will open a new window for the treatment and management of gastric cancer. Therefore, in this review, we will summarize the current mechanism of drug resistance, and finally discuss the molecular mechanism of circRNAs in regulating the development of drug resistance in gastric cancer.

Strengthening of RC Beam with GFRP Composites in Shear N. B. Bhopale

The rehabilitation, repair and strengthening of existing reinforced concrete (RC) structures is essential due to factors such as aging, steel reinforcement corrosion, construction/design defects, increased service loads demand, seismic events, and advancements in design guidelines. Fiber-reinforced polymers (FRP) are now being recognized as a promising material for the rehabilitation of such structures, through strengthening or repairing. In buildings and bridges, RC sections are commonly found in the form of beams and girders. Shear failure of RC beams is particularly due to its sudden occurrence without warning. Therefore, the utilization of externally bonded (EB) FRP composites for shear strengthening of RC beams has gathered popularity as a structural enhancement technique, primarily due to advantages of FRP composites, such as high strength-to- weight ratio and exceptional corrosion resistance. In addition, FRP repair systems give a cost-saving choice to traditional repair methods and materials. A study was performed to analyse the shear characteristics of RC beams enhanced with continuous glass fiber-reinforced polymer (GFRP) sheets. Reinforced concrete beams externally bonded GFRP sheets subjected to failure using a symmetrical two-point concentrated static loading system. The experimental data obtained included load, deflection, and failure modes of each beam, along with the effect of the number of GFRP layers on the beams The failures observed in strengthened beams typically commence with the debonding of the FRP sheets, followed by brittle shear failure. The shear capacities of these beams were higher than that of the control beam.

On Reliability of Repairable Hot Double Redundant System with Arbitrarily Distributed Life- and Repair Times of Its Elements

The article introduces the concept of Marked Markov processes, which are used to study a repairable hot double redundant system with a single repair facility. It is assumed that components’ life- and repair times follow arbitrary distributions. The proposed approach allows for calculating the system’s reliability function, and its mean lifetime, as well as conducting the sensitivity analysis to the shape of input distributions. The new method was validated with numerical examples by comparing it with previously obtained analytical results and showed high accuracy.

A decoupling estimation method for baseline load of photovoltaic user clusters based on multidimensional abnormal data restoration

Abstract With the widespread installation of distributed photovoltaics, their fluctuation characteristics with weather changes have posed significant challenges to baseline load estimation. In addition, due to measurement and collection anomalies, it is easy to cause continuous missing and abnormal data collection. To address the issue of low baseline estimation accuracy caused by distributed photovoltaic fluctuation characteristics and abnormal data collection, this paper proposes a photovoltaic user cluster baseline load decoupling estimation method based on multi-dimensional abnormal data repair. Firstly, a multidimensional anomaly data repair system is established based on extreme learning machines and multi-step prediction. Secondly, using the repaired data for baseline estimation, photovoltaic users and non-photovoltaic users are decoupled and separated. Long short-term memory neural network estimation models are used for non-photovoltaic users, and baseline load estimation methods based on weather type analysis are used for photovoltaic users. Finally, the baseline results are accumulated. The simulation results show that compared with the direct estimation method of baseline load, the accuracy of decoupling estimation has improved by 33.7%.

Biomechanical Evaluation of an Atraumatic Polymer-assisted Peripheral Nerve Repair System Compared with Conventional Neurorrhaphy Techniques.

Microsuturing, the gold standard for peripheral nerve repair, can create tension and damage at the repair site, potentially impacting regeneration and causing neuroma formation. A sutureless and atraumatic polymer-assisted system was developed to address this challenge and support peripheral nerve repair. The system is based on a biocompatible and biodegradable biosynthetic polymer and consists of a coaptation chamber and a light-activated polymer for securing to the nerve. In this study, we compare the system's biomechanical performance and mechanism of action to microsutures and fibrin repairs. The system's fixation force was compared with microsutures and fibrin glue, and evaluated across various nerve diameters through tensile testing. Tension and tissue morphology at the repair site were assessed using finite element modeling and scanning electron microscopy. The fixation force of the polymer-assisted repair was equivalent to microsutures and superior to fibrin glue. This force increased linearly with nerve diameter, highlighting the correlation between polymer surface contact area and performance. Finite element modeling analysis showed stress concentration at the repair site for microsuture repairs, whereas the polymer-assisted repair dissipated stress along the nerve, away from the repair site. Morphological analysis revealed nerve alignment with no tissue trauma for the polymer-assisted repair, unlike microsutures. The mechanical performance of the polymer-assisted coaptation system is suitable for peripheral nerve repair. The achieved fixation forces are equivalent to those of microsutures and superior to fibrin glue, minimizing stress concentration at the repair site and avoiding trauma to the severed nerve ends.

Repair Bond Strength of Composite Resin to Dental Ceramic Using Various Surface Treatments: An In Vitro Study

Abstract Aim: This research aims to evaluate and compare the effect of various surface treatments and adhesive types on the bond strength between composite resin and two types of ceramic materials. Materials and Methods: A total of 98 disk-shaped of 10 mm diameter and 4 mm thickness were fabricated for each of the zirconia (H. C. Starck) and lithium disilicate (IPS E-Max computer-aided design), which were implanted individually in the acrylic resin mold leaving one surface exposed. The disks in each group were sub-divided according to the surface treatments into seven groups (n = 14): [hydrofluoric acid (HF, 9.5%), air abrasion, bur, laser, HF + bur, HF + air abrasion, HF + laser]. Each sub-group was further divided into two groups (n = 7) according to the type of adhesive used for the repairing procedure [G-Premio Bond universal adhesive group and intraoral repair kit (BISCO) group]. Each adhesive was applied depending on manufacturer instructions and, then, the composite cylinder (4 mm in diameter and 4 mm in height) was built on the pre-determined treated ceramic surface area by the addition of rubber mold. Then the samples were stored in distal water for 24 h. After that, all groups were submitted to a shear bond test using an Instron testing machine (TSTM 02500; Elista Ltd., Istanbul, Turkey) at 0.5 mm/min a crosshead speed. The data were analyzed by three-way analysis of variance and Tukey post hoc test at (P ≤ 0.05). Results: The HF + air abrasion groups registered the higher bond strength but with no statistically significant difference from groups of HF + bur. While the laser groups showed the lowest mean bond strength. Generally, E-Max registered significantly higher bond strength in comparison to zirconia. Finally, the BISCO repair system registered a significantly higher bond strength value in comparison to G-Premio. Conclusion: Combined surface treatment of HF + air abrasion with an intraoral repair kit can provide a promising method for repairing cracked ceramic restorations. However, repairing lithium disilicate is more predictable and successful than zirconia.

A pilot study of chlorambucil in pre-treated metastatic pancreatic adenocarcinoma patients bearing germline BRCA or other DNA damage repair system variants

BackgorundPancreatic adenocarcinoma remains a malignancy with a grim prognosis and scarce personalized treatment options. Pathogenic variants of DNA damage repair (DDR) genes are emerging as molecular targets, as they confer a higher sensitivity to DNA-damaging agents. This study aimed at assessing the activity of chlorambucil as salvage therapy in metastatic pancreatic cancer patients bearing a germline pathogenetic variant or variant of uncertain significance on a DDR-related gene. MethodsPlatinum-pretreated metastatic pancreatic cancer patients harbouring a germline variant on a DDR gene received chlorambucil at a daily oral dose of 6 mg/m2 for 42 every 56 days for the first cycle and for 14 every 28 days for the following cycles, until disease progression or unacceptable toxicity. The primary endpoint was 6-month progression-free survival rate (PFS-6). Median progression-free survival (PFS) and overall survival (OS) were secondarily described. ResultsTwenty patients were enrolled between December 2020 and September 2022. PFS-6 was 5%, median PFS and OS were 1.6 months and 3.0 months, respectively. Grade-3 adverse events were observed in 25% of patients, while no Grade-4 toxicity was reported. ConclusionsSingle agent chlorambucil did not show sufficient signal of activity to warrant its further investigation in metastatic pancreatic cancer patients bearing a DDR-related germline alteration.

Fluorescence capturing behaviour of cyanobacterial resilience: Insights into UV-exposed ecosystems and its environmental applications.

Cyanobacteria are resilient microorganisms and thrive in environments exposed to UV radiation, ranging from ocean surfaces to scorching hot springs and dry expanses. 'Cyanobacterial Resilience' refers to their ability to withstand UV radiation, revealing intricate genomic secrets and adaptive mechanisms ensuring survival. These mechanisms include metabolic adaptations, robust DNA repair systems and UV-protective compounds such as Scytonemin and Mycosporine, vital for shielding against UV radiation survival. Cyanobacteria are crucial pioneers in UV-exposed ecosystems, highlighting their resilience and adaptability. Some cyanobacteria exhibit luminescence, emitting blue-green light due to phycobiliproteins, while bioluminescence in cyanobacteria, if it occurs, involves different compounds rather than luciferins and luciferase enzymes. This luminescence holds promise for various biotechnological applications, such as biosensors, imaging probes and carbon sequestration, for participating in photocatalytic processes for water purification and CO2 conversion, and contributes to solar simulation studies to advance photosynthesis and renewable energy technologies. The versatile applications of these materials highlight their ecological importance and potential in addressing global challenges. In conclusion, 'Cyanobacterial Resilience' highlights the remarkable adaptation strategies of cyanobacteria in UV-exposed environments. It emphasises their role as pioneers and innovators in biological and technological domains, providing insights into their enduring impact on ecosystems and scientific advancement.

Emergency Supply Alternatives for a Storage Facility of a Repairable Multi-Component System

This paper studies a continuous-review stochastic replenishment model for a multi-component system with regular and emergency orders. The system consists of N parallel and independent components, each of which has a finite life span. In addition, there is a warehouse with a limited stock of new components. Each broken component is replaced by a new component from the stock. When no component is available, an emergency supply is ordered. The stock is managed according to an ((s,S),(0,Qe)) policy, which is a combination of an (s,S) policy for the regular order and a (0,Qe) policy for the emergency order. The regular order is delivered after an exponentially distributed lead time, whereas the emergency order is delivered immediately. We study three sub-policies for emergency orders, which differ from each other in size and in relation to the regular order. Applying the results from queueing theory and phase-type properties, we derive the optimal thresholds for each sub-policy and then compare the economic benefit of each one.

Single G-quadruplex-based fluorescence method for the uracil-DNA glycosylase inhibitor screening

Uracil-DNA glycosylase (UDG) plays a pivotal role in the base repair system. Through bioinformatics, we found that the expression of the UDG enzyme in many cancer cells is increased, and its high expression is not conducive to the prognosis of lung cancer patients. The development of analytical techniques for the quantification of UDG activity and the identification of UDG inhibitors is of paramount importance. We found that when the T base in the G4 loop region mutated to uracil, the G4 structure was not disrupted and still retained the characteristics of a G4 structure (emitting strong fluorescence after binding with ThT (Thioflavin T). Inspired by this phenomenon, we developed a detection method for UDG and its inhibitors utilizing a single DNA strand engineered to form a G-quadruplex structure, containing uracil residues within the loop region, designated as G4-dU. The inclusion of uracil-DNA glycosylase (UDG) in the assay environment induces the removal of uracil, resulting in the formation of apurinic sites (AP) within the G4-dU sequence. Subsequent thermal denaturation leads to strand cleavage at AP sites, precluding the reformation of the G-quadruplex configuration and abrogating fluorescence emission. The detection process in this study can be completed in only 30 min to 1 h, offers a straightforward, expedient, and efficacious modality for assessing UDG activity and UDG inhibitor potency, thereby facilitating the discovery of novel therapeutic agents for cancer treatment.

Involvement of PG1037 in the repair of 8-oxo-7,8-dihydroguanine caused by oxidative stress in Porphyromonas gingivalis.

The PG1037 gene is part of the uvrA-PG1037-pcrA operon in Porphyromonas gingivalis. It encodes for a protein of unknown function upregulated under hydrogen peroxide (H2O2)-induced oxidative stress. Bioinformatic analysis shows that PG1037 has a zinc-finger motif, two peroxidase motifs, and one cytidylate kinase domain. The aim of this study is to characterize further the role of the PG1037 recombinant protein in the unique 8-oxoG repair system in P. gingivalis. PG1037 recombinant proteins with deletions in the zinc-finger or peroxidase motifs were created. Electrophoretic mobility shift assays were used to evaluate the ability of the recombinant proteins to bind 8-oxoG-containing oligonucleotides. Zinc binding, peroxidase, and Fenton reaction assays were used to assess the functional roles of the rPG1037 protein. A bacterial adenylate cyclase two-bride assay was used to identify the partner protein of PG1037 in the repair of 8-oxoG. The recombinant PG1037 (rPG1037) protein carrying an N-terminal His-tag demonstrated an ability to recognize and bind 8-oxoG-containing oligonucleotide. In contrast to the wild-type rPG1037 protein, the zinc-finger motif deletion resulted in the loss of zinc and 8-oxoG binding activities. A deletion of the peroxidase motif-1 showed a decrease in peroxidase activity. Using a bacterial adenylate cyclase two-hybrid system, there was no observed protein-protein interaction of PG1037 with UvrA (PG1036), PcrA (PG1038), or mismatch repair system proteins. Taken together, the results show that PG1037 is an important member of a novel mechanism that recognizes and repairs oxidative stress-induced DNA damage in P. gingivalis.

C-terminal residues of DNA polymerase β and E3 ligase required for ubiquitin-linked proteolysis of oxidative DNA-protein crosslinks

Free radicals produce in DNA a large variety of base and deoxyribose lesions that are corrected by the base excision DNA repair (BER) system. However, the C1′-oxidized abasic residue 2-deoxyribonolactone (dL) traps DNA repair lyases in covalent DNA-protein crosslinks (DPC), including the core BER enzyme DNA polymerase beta (Polβ). Polβ-DPC are rapidly processed in mammalian cells by proteasome-dependent digestion. Blocking the proteasome causes oxidative Polβ-DPC to accumulate in a ubiquitylated form, and this accumulation is toxic to human cells. In the current study, we investigated the mechanism of Polβ-DPC processing in cells exposed to the dL-inducing oxidant 1,10-copper-ortho-phenanthroline. Alanine substitution of either or both of two Polβ C-terminal residues, lysine-206 and lysine-244, enhanced the accumulation of mutant Polβ-DPC relative to the wild-type protein, and removal of the mutant DPC was diminished. Substitution of the N-terminal lysines 41, 61, and 81 did not affect Polβ-DPC processing. For Polβ with the C-terminal lysine substitutions, the amount of ubiquitin in the stabilized DPC was lowered by ∼40 % relative to wild-type Polβ. Suppression of the HECT domain-containing E3 ubiquitin ligase TRIP12 augmented the formation of oxidative Polβ-DPC and prevented Polβ-DPC removal in oxidant-treated cells. Consistent with the toxicity of accumulated oxidative Polβ-DPC, TRIP12 knockdown increased oxidant-mediated cytotoxicity. Thus, ubiquitylation of lysine-206 and lysine-244 by TRIP12 is necessary for digestion of Polβ-DPC by the proteasome as the rapid first steps of DPC repair to prevent their cytotoxic accumulation. Understanding how DPC formed with Polβ or other AP lyases are repaired in vivo is an important step in revealing how cells cope with the toxic potential of such adducts.

Error-Prone DNA Synthesis on Click-Ligated Templates.

Click ligation is a technology of joining DNA fragments based on azide-alkyne cycloaddition. In the most common variant, click ligation introduces a 4-methyl-1,2,3-triazole (trz) group instead of the phosphodiester bond between two adjacent nucleosides. While this linkage is believed to be biocompatible, little is known about the possibility of its recognition by DNA repair systems or its potential for DNA polymerase stalling and miscoding. Here we report that trz linkage is resistant to several human and bacterial endonucleases involved in DNA repair. At the same time, it strongly blocks some DNA polymerases (Pfu, DNA polymeraseβ) while allowing bypass by others (phage RB69 polymerase, Klenow fragment). All polymerases, except for DNA polymeraseβ, showed high frequency of misinsertion at the trz site, incorporating dAMP instead of the next complementary nucleotide. Thus, click ligation can be expected to produce a large amount of errors if used in custom gene synthesis.

Injectable and self-healing sulfated hyaluronic acid/gelatin hydrogel as dual drug delivery system for circumferential tracheal repair

Stem cell-based therapies show promise for clinically addressing circumferential tracheal defects (CTD) through tissue engineering. However, creating a tissue-engineered tracheal tube possesses a healthy cartilage matrix and intact tube structure remains a challenge. A solution lies in the use of an injectable hydrogel with shape adaptability and chondrogenic capacity, serving as a practical and dependable platform for tubular tracheal cartilage regeneration. In this study, we developed an injectable hydrogel using modified natural polymers-hydrazide-grafted gelatin (Gelatin-ADH) and aldehyde-modified hyaluronic acid with sulfated groups (HA-CHO-SO3) via Schiff Base interaction. Additionally, aldehyde-modified β-cyclodextrin (β-CD-CHO) was introduced into the network during hydrogel formation. The negative sulfated groups and hydrophobic cavities of β-cyclodextrin facilitated the efficient encapsulation and sustained release of transforming growth factor-β1 (TGF-β1) and kartogenin (KGN) within our hydrogel. This synergistically promoted the chondrogenesis of loaded bone marrow stem cells (BMSCs). Subsequently, we employed this TGF-β1, KGN, and BMSCs loaded hydrogel to form a cartilage ring. This ring was then assembled into an engineered tracheal cartilage tube using our previously reported ring-to-tube strategy. Our results demonstrated that the engineered tracheal cartilage tube effectively repaired CTD in a rabbit model. Hence, this study introduces a novel hydrogel with significant clinical application potential for tracheal tissue engineering.

Open vs. Percutaneous Achilles Tendon Repair: Experience of Single Orthopedic Institute with Long-Term Follow-Up.

Background and Objectives: There are numerous techniques for the surgical treatment of Achilles tendon lesions described in the literature, and it is possible to distinguish repair techniques as either open surgery or percutaneous repair techniques. Both approaches have advantages and disadvantages. With this retrospective study, we aim to analyze the incidence of re-ruptures and other complications, return to sport and overall quality of life at a long-term follow-up in the treatment of acute ATRs, comparing the results of percutaneous repair with those of open repair. Materials and Methods: This is a retrospective study on a consecutive series of patients with complete tear of the AT who were managed through a surgical approach by the Operative Unit of Orthopaedics and Traumatology of Sant'Anna University Hospital (Ferrara, Emilia-Romagna, Italy) between April 2014 and December 2021. Patients were treated with a percutaneous or an open technique according to the surgeon's preference without randomization. Results: We considered 155 patients who met the established inclusion criteria. Of these, 103 (66.45%) patients underwent percutaneous treatment with the Tenolig® system, and 52 (33.55%) underwent open surgery, with an average ATRS in the first group of 92.5 compared to an average ATRS value of 82 in patients treated with the open technique. Conclusions: In our experience, following overlapping rehabilitation protocols in all patients included, we observed that the Tenolig® repair system led to a better ATRS at long-term follow-up, with comparable complication rates to open surgery.

MXene‐Based Responsive Hydrogels and Applications in Wound Healing

AbstractIn recent years, stimulation‐responsive hydrogels have emerged as a promising vehicle for wound management and drug delivery. However, due to their limited therapeutic effect, there is an urgent need to develop new hydrogel systems that can achieve effective wound treatment. MXenes have been widely used in diagnostic, antimicrobial, and electrochemical sensing applications, and are increasingly being investigated for their potential in wound therapy. In this review, we present a comprehensive overview of responsive MXene‐based hydrogels systems for wound repair, including their synthesis methods, structures, surface modification strategies, biomedical applications, cytotoxicity, and biocompatibility. We also discuss the opportunities and challenges that responsive MXene‐based hydrogels are likely to face in the future. Overall, this review will be a useful resource for researchers and practitioners working on the development and application of responsive MXene‐based hydrogels for wound treatment.

Tricarboxylic Acid Cycle Relationships with Non-Metabolic Processes: A Short Story with DNA Repair and Its Consequences on Cancer Therapy Resistance.

Metabolic changes involving the tricarboxylic acid (TCA) cycle have been linked to different non-metabolic cell processes. Among them, apart from cancer and immunity, emerges the DNA damage response (DDR) and specifically DNA damage repair. The oncometabolites succinate, fumarate and 2-hydroxyglutarate (2HG) increase reactive oxygen species levels and create pseudohypoxia conditions that induce DNA damage and/or inhibit DNA repair. Additionally, by influencing DDR modulation, they establish direct relationships with DNA repair on at least four different pathways. The AlkB pathway deals with the removal of N-alkylation DNA and RNA damage that is inhibited by fumarate and 2HG. The MGMT pathway acts in the removal of O-alkylation DNA damage, and it is inhibited by the silencing of the MGMT gene promoter by 2HG and succinate. The other two pathways deal with the repair of double-strand breaks (DSBs) but with opposite effects: the FH pathway, which uses fumarate to help with the repair of this damage, and the chromatin remodeling pathway, in which oncometabolites inhibit its repair by impairing the homologous recombination repair (HRR) system. Since oncometabolites inhibit DNA repair, their removal from tumor cells will not always generate a positive response in cancer therapy. In fact, their presence contributes to longer survival and/or sensitization against tumor therapy in some cancer patients.

Quercetin and its derivatives from lotus (Nelumbo nucifera) seedpod extract combat radioresistance by suppressing ACSL4.

Radioresistance poses a significant obstacle in cancer treatment. Lotus seedpod extract (LSE) has demonstrated anticancer effects in various cancer cells. However, its potential against radioresistant tumors remains unclear. In this study, we aimed to investigate the effect of LSE on radioresistant breast cancer cells, explore the underlying mechanism, and identify the major constituents responsible for its cytotoxic effect. LSE, extracted using 70% ethanol, exhibited selective cytotoxic effects against radioresistant breast cancer cells compared with their parental cells. Chemical analysis identified quercetin and its derivatives, hyperoside and miquelianin, as the major constituents responsible for these selective effects. Notably, quercetin displayed the most potent cytotoxicity against radioresistant breast cancer cells compared with hyperoside and miquelianin. Further investigation revealed that these compounds inhibited the activation of DNA repair systems, leading to the accumulation of DNA damage and the induction of apoptosis. Importantly, they efficiently suppressed the expression of ACSL4, a factor previously associated with radioresistance. In an in vivo study, quercetin exhibited a significant suppression of tumor growth in radioresistant tumor-bearing mice. Taken together, our findings highlight the potential of LSE and its major constituents, quercetin and its derivatives, in overcoming radioresistance in breast cancer. This study provides compelling evidence to support the use of LSE as a medicinal source for the future adjunctive therapy to combat radioresistance in breast cancers.

Benchmarking and Categorizing the Performance of Neural Program Repair Systems for Java

Recent years have seen a rise in neural program repair systems in the software engineering community, which adopt advanced deep learning techniques to automatically fix bugs. Having a comprehensive understanding of existing systems can facilitate new improvements in this area and provide practical instructions for users. However, we observe two potential weaknesses in the current evaluation of NPR systems: ① published systems are trained with varying data, and ② NPR systems are roughly evaluated through the number of totally fixed bugs. Questions such as “what types of bugs are repairable for current systems” cannot be answered yet. Consequently, researchers can not make target improvements in this area and users have no idea of the real affair of existing systems. In this paper, we perform a systematic evaluation of the existing nine state-of-the-art NPR systems. To perform a fair and detailed comparison, we (1) build a new benchmark and framework that supports training and validating the nine systems with unified data, and (2) evaluate retrained systems with detailed performance analysis, especially on the effectiveness and the efficiency. We believe our benchmark tool and evaluation results could offer practitioners the real affairs of current NPR systems and the implications of further facilitating the improvements of NPR.