RIG-I modulates Src-mediated AKT activation to restrain leukemic stemness.

Retinoic acid (RA)-inducible gene I (RIG-I) is highly upregulated and functionally implicated in the RA-induced maturation of acute myeloid leukemia (AML) blasts. However, the underlying mechanism and the biological relevance of RIG-I expression to the maintenance of leukemogenic potential are poorly understood. Here, we show that RIG-I, without priming by foreign RNA, inhibits the Src-facilitated activation of AKT-mTOR in AML cells. Moreover, in a group of primary human AML blasts, RIG-I reduction renders the Src family kinases hyperactive in promoting AKT activation. Mechanistically, a PxxP motif in RIG-I, upon the N-terminal CARDs' association with the Src SH1 domain, competes with the AKT PxxP motif for recognizing the Src SH3 domain. In accordance, mutating PxxP motif prevents Rig-I from inhibiting AKT activation, cytokine-stimulated myeloid progenitor proliferation, and in vivo repopulating capacity of leukemia cells. Collectively, our data suggest an antileukemia activity of RIG-I via competitively inhibiting Src/AKT association.

Cisplatin plus paclitaxel chemotherapy with or without bevacizumab in postmenopausal women with previously untreated advanced cervical cancer: a retrospective study.

BACKGROUND: The aim of this study was to assess the survival outcomes of cisplatin-paclitaxel chemotherapy plus bevacizumab (CPB) versus cisplatin-paclitaxel chemotherapy alone (CPA) in postmenopausal women with previously untreated advanced cervical cancer (CC). METHODS: Consecutive postmenopausal women who experienced CPB or CPA were identified retrospectively from our medical centre during 2015-2019. Follow-up visits occurred 1 and 3 months after starting CPB or CPA. Afterwards, this assessment was conducted every 3 months for 1 year and then yearly thereafter. The primary endpoints were overall survival (OS) and progression-free survival (PFS); secondary endpoints were the frequency and severity of adverse events (AEs). RESULTS: Two hundred forty-six postmenopausal women were included (CPB, n = 124; CPA, n = 122). The median follow-up for the entire cohort was 24 months (range, 2-32). At the final follow-up, a significant difference was detected in terms of median OS (16.4 months [95% CI, 15.3-17.1] for CPB vs. 12.3 months [95% CI, 10.2-13.5] for CPA; hazard ratio (HR) 0.69, 95% CI, 0.49-0.99; p = 0.001), and the median PFS was longer in the CPB group than in the CPA group (9.2 months [95% CI, 8.3-10.7] vs. 7.9 months (95% CI, 6.1-8.6) (HR 0.62, 95% CI, 0.47-0.82; p < 0.001). There were significant differences in the number of AEs between the groups (hypertension grade ≥ 2 [p < 0.001], neutropenia grade ≥ 4 [p < 0.001], and thrombosis/embolism grade ≥ 3 [p = 0.030]). CONCLUSIONS: Among postmenopausal women with previously untreated advanced CC, those who received CPB experienced superior survival benefits compared to those who received CPA. The safety profile for CPB was controllable despite the long duration of CPB use.

Nivolumab plus ipilimumab versus nivolumab in individuals with treatment-naive programmed death-ligand 1 positive metastatic soft tissue sarcomas: a multicentre retrospective study.

BACKGROUND: Currently, the choice of treatment for individuals with metastatic soft tissue sarcomas (MSTS) presents a significant challenge to clinicians. The aim of this retrospective study was to assess the efficacy and safety of nivolumab plus ipilimumab (NPI) versus nivolumab alone (NIV) in individuals with treatment-naive programmed death-ligand 1 (PD-L1) positive MSTS. METHODS: Prospectively maintained databases were reviewed from 2013 to 2018 to assess individuals with treatment-naive PD-L1 MSTS who received NPI (nivolumab 3 mg/kg and ipilimumab 1 mg/kg every 3 weeks for 4 doses followed by nivolumab 3 mg/kg every 2 weeks) or NIV (3 mg/kg every 2 weeks) until disease progression, withdrawal, unendurable [AEs], or death. The co-primary endpoints were overall survival (OS) and progression-free survival (PFS). RESULTS: The median follow-up was 16.0 months (IQR 14.4-18.5) after targeted intervention. The median OS was 12.2 months (95% confidence interval [CI], 6.1-13.7) and 9.2 months (95% CI, 4.2-11.5) for the NPI and NIV groups, respectively (hazard ratio [HR] 0.49, 95% CI, 0.33-0.73; p=0.0002); the median PFS was 4.1 months (95% CI, 3.2-4.5) and 2.2 months (95% CI, 1.1-3.4) for the NPI and NIV groups, respectively (HR 0.51, 95% CI, 0.36-0.71; p< 0.0001). Key grade 3-5 AEs occurred more frequently in the NPI group than in the NIV group (94 [72.9%] for NPI vs. 35 [27.1%], p< 0.001). CONCLUSIONS: For treatment-naive PD-L1 positive MSTS, NPI seems to be less tolerated but has a greater survival advantage than NIV as the primary therapy.

An efficient Screening System in Yeast to Select a Hyperactive piggyBac Transposase for Mammalian Applications.

As non-viral transgenic vectors, the piggyBac transposon system represents an attractive tool for gene delivery to achieve a long-term gene expression in immunotherapy applications due to its large cargo capacity, its lack of a trace of transposon and of genotoxic potential, and its highly engineered structure. However, further improvements in transpose activity are required for industrialization and clinical applications. Herein, we established a one-plasmid effective screening system and a two-step high-throughput screening process in yeast to isolate hyperactive mutants for mammalian cell applications. By applying this screening system, 15 hyperactive piggyBac transposases that exhibited higher transpose activity compared with optimized hyPBase in yeast and four mutants that showed higher transpose activity in mammalian cells were selected among 3000 hyPBase mutants. The most hyperactive transposase, bz-hyPBase, with four mutation sites showed an ability to yield high-efficiency editing in Chinese hamster ovarian carcinoma (CHO) cells and T cells, indicating that they could be expanded for gene therapy approaches. Finally, we tested the potential of this screening system in other versions of piggyBac transposase.

Engineered CAR T cells targeting mesothelin by piggyBac transposon system for the treatment of pancreatic cancer.

Patients with pancreatic cancer have a poor prognosis largely due to the poor efficacy of the available treatment modalities. In this study, we engineered mesothelin-targeting chimeric antigen receptor T cells (mesoCAR T) using the piggyBac transposon based plasmid electroporation technique for specific targeting of pancreatic cancer cells expressing mesothelin. In vitro, mesoCAR T cells exhibited rapid and robust killing effect against ASPC1 cells with high expression levels of mesothelin with high production of IFN-γ; the cytotoxic effect on PANC1 cells with low expressions of mesothelin was relatively attenuated. In the ASPC1 xenograft mice model, mesoCAR T cells significantly suppressed the tumor growth accompanied with higher-level IFN-γ secretion as compared to control T cells. Besides, more mesoCAR T cells differentiated into memory T cells after tumor remission, whilst causing minimal lesions in major organs. Our study suggests promising efficacy of piggyBac transposon-based mesoCAR T cell therapy for pancreatic cancer, which is a potential candidate for clinical translation.

The effects of threshing and redrying on bacterial communities that inhabit the surface of tobacco leaves.

Before being subjected to the aging process, raw tobacco leaves (TLs) must be threshed and redried. We propose that threshing and redrying affect the bacterial communities that inhabit the TL surface, thereby influencing the aging process. However, these effects remain unclear. In this study, Illumina sequencing was applied to analyze the bacterial communities on both raw and redried TLs. Shannon's diversity value decreased from 3.38 to 2.52 after the threshing and redrying processes, indicating a large reduction in TL bacterial diversity. The bacterial communities also largely differed between raw TLs and redried TLs. On unaged raw TLs, Proteobacteria was the most dominant phylum (56.15%), followed by Firmicutes (38.99%). In contrast, on unaged redried TLs, Firmicutes (76.49%) was the most dominant phylum, followed by Proteobacteria (21.30%). Thus, the dominant genus Proteobacteria, which includes Sphingomonas, Stenotrophomonas, and Pantoea, decreased after the threshing and redrying processes, while the dominant genus Firmicutes, which includes Bacillus and Lactococcus, increased. Changes in the bacterial communities between raw and redried TLs were also noted after 1 year of aging. The relative abundance of dominant Proteobacteria taxa on raw TLs decreased from 56.15 to 16.92%, while the relative abundance of Firmicutes taxa increased from 38.99 to 79.10%. However, small changes were observed on redried TLs after 1 year of aging, with a slight decrease in Proteobacteria (21.30 to 17.64%) and a small increase in Firmicutes (76.49 to 79.10%). Based on these results, Firmicutes taxa may have a higher tolerance for extreme environments (such as high temperature or low moisture) than Proteobacteria bacteria. This study is the first report to examine the effects of threshing and redrying on bacterial communities that inhabit TLs.

Degradation of phytosterols in tobacco waste extract by a novel Paenibacillus sp.

Phytosterols have been demonstrated to be precursors of polycyclic aromatic hydrocarbons (PAHs) formed during biomass pyrolysis. Here, a novel Paenibacillus sp. was evaluated for its ability to degrade phytosterols in tobacco waste extract (TWE). The optimal conditions for cell growth and stigmasterol (a representative of phytosterols) degradation were 37 °C, pH 7.0, 1.0 g/L yeast extract, and 6.0 g/L glucose. Paenibacillus sp. could degrade stigmasterol under high concentrations of glucose (up to 130 g/L) and tolerate wide pH (5.0-9.0) and temperature (25-42 °C) ranges. The new strain could degrade stigmasterol completely into CO2 and H2 O, and no intermediate steroids were detected during the degradation process. Phytosterol degradation in TWE was demonstrated by high-performance liquid chromatography-tandem mass spectrometry. Under optimal conditions (37 °C, pH 7.0, with the exponential-phase cells), the total degradation ratio of phytosterols reached 38.5% in TWE, including 45.2% of stigmasterol, 37.4% of ß-sitosterol, 27.3% of campesterol, and 28.7% of cholesterol. These results showed that Paenibacillus sp. is a candidate for phytosterol degradation in TWE and other biomass and is potentially useful in reducing the PAHs generated from biomass pyrolysis.

Placental Expressions of CDKN1C and KCNQ1OT1 in Monozygotic Twins with Selective Intrauterine Growth Restriction.

CDKN1C and KCNQ1OT1 are imprinted genes that might be potential regulators of placental development. This study investigated placental expressions of CDKN1C and KCNQ1OT1 in monozygotic twins with and without selective intrauterine growth restriction (sIUGR). Seventeen sIUGR and fifteen normal monozygotic(MZ) twin pairs were examined. Placental mRNA expressions of CDKN1C and KCNQ1OT1 were detected by real-time fluorescent quantitative PCR. CDKN1C protein expression was detected by immunohistochemical assay and Western-blotting. In the sIUGR group, smaller fetuses had a smaller share of the placenta, and CDKN1C protein expression was significantly increased while KCNQ1OT1 mRNA expression was significantly decreased. The CDKN1C/KCNQ1OT1 mRNA ratio was lower in the larger fetus than in the smaller fetus (p < .05). In the control group, CDKN1C protein expression showed no difference between larger and smaller fetuses, while KCNQ1OT1 mRNA expression was significantly lower in the larger fetus, and the CDKN1C/KCNQ1OT1 mRNA ratio was higher in the larger fetus than in the smaller fetus (p < .05). Our findings showed that pathogenesis of sIUGR may be related to the co-effect of the up-regulated protein expression of CDKN1C and down-regulated mRNA expression of KCNQ1OT1 in the placenta.

Accuracy of using computer-aided rapid prototyping templates for mandible reconstruction with an iliac crest graft.

BACKGROUND: This study aimed to evaluate the accuracy of surgical outcomes in free iliac crest mandibular reconstructions that were carried out with virtual surgical plans and rapid prototyping templates. METHODS: This study evaluated eight patients who underwent mandibular osteotomy and reconstruction with free iliac crest grafts using virtual surgical planning and designed guiding templates. Operations were performed using the prefabricated guiding templates. Postoperative three-dimensional computer models were overlaid and compared with the preoperatively designed models in the same coordinate system. RESULTS: Compared to the virtual osteotomy, the mean error of distance of the actual mandibular osteotomy was 2.06 ± 0.86 mm. When compared to the virtual harvested grafts, the mean error volume of the actual harvested grafts was 1412.22 ± 439.24 mm3 (9.12% ± 2.84%). The mean error between the volume of the actual harvested grafts and the shaped grafts was 2094.35 ± 929.12 mm3 (12.40% ± 5.50%). CONCLUSIONS: The use of computer-aided rapid prototyping templates for virtual surgical planning appears to positively influence the accuracy of mandibular reconstruction.

Digital surgical templates for managing high-energy zygomaticomaxillary complex injuries associated with orbital volume change: a quantitative assessment.

PURPOSE: This study sought to introduce 3-dimensional (3D) virtual surgical planning and digital rapid-prototyping templates for zygomaticomaxillary complex (ZMC) injuries associated with orbital volume change and to evaluate the surgical outcomes quantitatively. PATIENTS AND METHODS: Eight patients who underwent open reduction and fixation for a ZMC injury with orbital volume change were studied. Computed tomographic (CT) scan of the zygomaticomaxillary area was performed before the operation in each case. Scanned data were converted into 3D models using Mimics software (Materialise, Brussels, Belgium) for surgical designs. Virtual surgical reductions and correlated guiding templates were designed using Mimics and Magics software (Materialise). The operations were performed with the help of prefabricated templates to reduce the fractures. A postoperative CT scan of each patient was obtained within 2 weeks after surgery, and quantitative measurements were made to assess the surgical outcomes. Preoperative volumes of the bilateral orbits were compared, and concordance with postoperative volumes of the bilateral orbits was assessed. Twenty-one pairs of distances from 7 marker points to 3 reference planes were measured to assess postoperative facial symmetry. RESULTS: Volumes of the injured orbits were significantly different from volumes of the uninjured orbits preoperatively (P < .05), whereas bilateral orbital volumes showed no statistically significant difference postoperatively (P > .05). In addition, 19 of the 21 pairs of bilateral distances showed no significant difference postoperatively (P > .05). CONCLUSIONS: Quantitative assessment showed that digitally designed, rapid-prototyping templates for ZMC fractures have a positive impact on restoring facial symmetry and concordance of bilateral orbital volumes.

Study on the mechanism of Gualou Xiebai Guizhi decoction (GLXBGZD) in the treatment of coronary heart disease based on network pharmacology.

BACKGROUND: This study aims to analyze the mechanism of Gualou Xiebai Guizhi decoction (GLXBGZD) in treating coronary heart disease (CHD) utilizing network pharmacology. METHODS: The GLXBGZD effective components were searched on the pharmacological database platform of the Traditional Chinese Medicine Systems Pharmacol, and its potential target was predicted. The Online Mendelian Inheritance obtained CHD disease target in Man and GeneCards database. The Venn map of the intersection target for GLXBGZD and CHD was constructed by using Venn online website. The "drug-component-target-disease" network map was constructed by Cytoscape 3.7.2 software. The DAVID online platform was used to analyze the function of Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) at the intersection of targets of drugs and diseases. RESULTS: A total of 27 articles were searched for GLXBGZD, including 111 potential targets, 5521 disease targets, 100 drug and disease intersection targets. The core target network map shows that Interleukin (IL)-6, TNF, vascular endothelial growth factor (VEGFA), TP53, EGF, JUN, MAPK1, Catalase (CAT), and prostaglandin-endoperoxide synthase 2 (PTGS2) may be the key targets in CHD therapy. GO functional enrichment analysis revealed that the biological functions of GLXBGZD involved biological processes such as response to drugs, positive regulation of nitric oxide biosynthesis process, and response to hypoxia. KEGG pathway enrichment analysis showed that GLXBGZD might participate in CHD treatment through Hypoxia-inducible factor-1 (HIF-1), Tumor necrosis factor (TNF), PhosphoInositide-3 Kinase--Threonine protein kinase (PI3K-Akt), and the calcium signal pathway. CONCLUSIONS: This study reveals that the GLXBGZD mechanism in CHD treatment has the characteristics of multi-components, multi-targets, and multi-pathways, which provides a theoretical basis for its clinical application and subsequent experimental verification.

A novel method of 3D printing locating guide for abutment screw removal in cement-retained implant-supported prostheses.

Background/purpose: Cement-retained restorations have the advantages of passive fit, less complexity of clinical and laboratory methods, cost, esthetics, and dimensional stability over screw-retained restorations, especially in multiple abutment implant-supported prostheses. A common and difficult technical problem with cement-retained implant prostheses is abutment screw loosening. Three-dimensional (3D) printing is a technology that has been rapidly developed and has become widely accepted in dentistry. The aim of this study was to establish a novel method of using 3D implant planning guide to locate the abutment screw in cement-retained implant prosthesis. Materials and methods: Six standard gypsum complete denture models were used to locate the abutment screw. An implant analog (4.5 mm in diameter and 12 mm in length) was placed in the drilling hole (5 mm in diameter and 14 mm in depth). After scanning with a 3D scanner, the 3D printing software was used to design the abutment screw location guide, which was printed by a resin-based 3D printer. Results: A total of 30 abutment screws were located and removed using the guide. The locating guide's actual diameter was 2.4 mm. The drilling point was accurate and precise, and no excessive loss of the abutment was noticed. Conclusion: The guide would help the dentist in locating the abutment screw access channel, resulting in a more precise and accurate drilling point. The guide for locating the abutment screw enhances the accuracy of screw channel access and reduces damage to the crown and abutment.

Risk factors for thoracolumbar pain following percutaneous vertebroplasty for osteoporotic vertebral compression fractures.

OBJECTIVE: To explore possible risk factors for poor outcomes following percutaneous vertebroplasty (PV) for painful osteoporotic compression fractures of thoracolumbar vertebra. METHODS: This was a retrospective review of data from patients who underwent PV at our institution over a ten-year period to evaluate the association between possible risk factors and thoracolumbar pain (T11-L2). According to the difference between pre- and post-operative visual analogue scale (VAS) scores for pain, patients were separated into poor relief (PR; <4) and good relief (GR; ≥4) of pain. RESULTS: Of the 750 patients identified, 630 (PR group, n =310; GR group, n = 320) fulfilled the eligibility criteria. Multivariate binary logistic analysis showed that bone mineral density (BMD), >2 fractured vertebral bodies, maldistribution of bone cement, <5 ml bone cement injected into a single vertebral body and thoracolumbar fascia injury prior to surgery were independent risk factors associated with thoracolumbar pain following PV. CONCLUSION: Although prospective controlled studies are required to confirm our results, this review suggests that the above factors should be taken into account when selecting patients for PV.

Revision of failed metal-on-metal total hip arthroplasty using cemented arthroplasty: a mean 10-year follow-up of 157 consecutive patients.

OBJECTIVE: This study was performed to assess the outcomes of Asian patients who underwent conversion from metal-on-metal total hip arthroplasty (MoM-THA) to cemented THA (CTHA). METHODS: One hundred and fifty-seven consecutive patients (157 hips) who underwent CTHA following primary MoM-THA from January 2005 to February 2015 were retrospectively analysed. The primary endpoints were the clinical outcomes. Follow-ups occurred at 3 months, 6 months, 1 year, 2 years, and then every 2 years following revision of MoM-THA. RESULTS: The mean follow-up after conversion was 10 years (range, 5-14 years). Statistically significant improvements in the mean Harris hip score were observed between the preoperative and final follow-up evaluations (62.71 ± 13.85 vs. 84.03 ± 16.21, respectively). The major orthopaedic complication rate was 16.5% (26/157). Six (3.8%) patients underwent revision at a mean of 3.5 ± 1.3 years after conversion, predominantly because of prosthesis loosening or recurrent dislocation. Nine (5.7%) patients developed prosthesis loosening at a mean of 2.6 ± 1.1 years following conversion, two of whom requested revision surgery. Eleven (7.0%) patients developed prosthesis dislocation, four of whom requested revision surgery. CONCLUSION: CTHA may yield favourable functional outcomes and a reduced rate of major orthopaedic complications.

Effectiveness of Direct Pulp Capping Bioactive Materials in Dentin Regeneration: A Systematic Review.

BACKGROUND: Regenerative endodontics aims to restore normal pulp function in necrotic and infected teeth, restoring protective functions, such as innate pulp immunity, pulp repair through mineralization, and pulp sensibility. The aim of this systematic review was to assess the dentin regeneration efficacy of direct pulp capping (DPC) biomaterials. METHODS: The literature published between 2005 and 2021 was searched by using PubMed, Web of Science, Science Direct, Google Scholar, and Scopus databases. Clinical controlled trials, randomized controlled trials, and animal studies investigating DPC outcomes or comparing different capping materials after pulp exposure were included in this systematic review. Three independent authors performed the searches, and information was extracted by using a structured data format. RESULTS: A total of forty studies (21 from humans and 19 from animals) were included in this systemic review. Histological examinations showed complete/partial/incomplete dentin bridge/reparative dentin formation during the pulp healing process at different follow-up periods, using different capping materials. CONCLUSIONS: Mineral trioxide aggregate (MTA) and Biodentine can induce dentin regeneration when applied over exposed pulp. This systematic review can conclude that MTA and its variants have better efficacy in the DPC procedure for dentin regeneration.

Accuracy of half-way mucosa-supported implant guides for edentulous jaws: a retrospective study with a median follow-up of 2 years.

OBJECTIVE: To assess the accuracy of half-way digital mucosa-supported implant guides (HDMIGs) for edentulous jaws. METHODS: Ninety-five consecutive patients (859 implants) with edentulous jaws who underwent implant placement using an HDMIG from July 2012 to June 2018 were retrospectively identified. The primary endpoint was implant-related complications (nerve injury and unexpected perforation), and the secondary endpoints were the faciolingual distance, mesiodistal distance, buccolingual angle, and mesiodistal angle. Follow-ups occurred at 1 month, 2 months, and then every 2 months following implant placement. RESULTS: Twenty-seven (28.4%) patients met the exclusion criteria, leaving 68 eligible patients (636 implants) for the final analysis. The median follow-up was 24 months (range, 18-27 months). No patients developed nerve injury, revision, or unexpected perforation. At the final follow-up, the mean faciolingual distance was 0.65 ± 0.16 mm, the mean mesiodistal distance was 1.16 ± 0.61 mm, the mean buccolingual angle was 4.04° ± 2.26°, and the mean mesiodistal angle was 3.75° ± 2.56°. In the comparison of the first month after surgery and the last follow-up, no significant differences were detected in any of the four measured variables. CONCLUSION: Use of an HDMIG may be a convenient and safe method to ensure correct implantation.

PHILOS Plate Plus Oblique Insertion of Autologous Fibula for 2-Part Proximal Humerus Fractures With Medial Column Disruption: A Retrospective Study.

INTRODUCTION: The aim of this retrospective study was to evaluate the outcomes of older patients with 2-part proximal humerus fractures (PHFs) with medial column disruption stabilized using a proximal humeral internal locking system (PHILOS) plate plus oblique insertion of autologous fibula as a primary procedure. MATERIALS AND METHODS: Data involving 112 patients (112 shoulders) sustaining 2-part PHFs with medial column disruption treated with PHILOS plate plus oblique insertion of autologous fibula as a primary procedure during 2012-2019 were identified. The median follow-up was 36 months (range: 11.2-43.5 months). The primary endpoint was the Constant scores and American Shoulder and Elbow Surgeons (ASES) scores. The secondary endpoint was the main orthopedic complication rate. RESULTS: The median Constant and ASES scores were 78 (range, 52-95) and 77 (range, 62-96) at the final follow-up, respectively. The main orthopedic complication rate was 10.7% (12/112). Twelve orthopedic complications in 8 patients were detected, and they involved loss of reduction, varus collapse, aseptic loosening, mal-union, revision, and intolerable shoulder pain. Of these complications, 3 (2.6%) involved loss of reduction, 2 (1.7%) involved varus collapse, 3 (2.6%) involved aseptic loosening, 1 (0.8%) involved mal-union, 2 (1.7%) required revision surgery, and 1 (0.8%) presented intolerable shoulder pain. CONCLUSION: PHILOS plate plus oblique insertion of autologous fibula as a primary procedure may yield good functional outcomes and a low rate of the main orthopedic complications.

An "all-in-one" strategy based on the organic molecule DCN-4CQA for effective NIR-fluorescence-imaging-guided dual phototherapy.

Dual phototherapy combining photodynamic therapy (PDT) and photothermal therapy (PTT) is considered to be a more effective therapeutic method against cancer than single treatment. Therefore, the development of a single material with both near-infrared (NIR)-laser-triggered PDT and PTT abilities is highly desirable but remains a great challenge. A design philosophy for photosensitizers for integrated PDT and PTT treatment has been put forward: (1) a high molar extinction coefficient in the NIR region; (2) suitable LUMO and T1 energy levels to regulate intersystem crossing for effective singlet oxygen (1O2) generation for PDT; and (3) the suppression of fluorescence emission to enhance the process of nonradiative transition with appropriate chemical modifications. Herein, an "all-in-one" functional material, di-cyan substituted 5,12-dibutylquinacridone (DCN-4CQA), for diagnosis and therapy was obtained. DCN-4CQA possesses dual-functional phototherapeutic activity and NIR fluorescence and it was produced via a facile synthesis process from the classic organic photoelectric material quinacridone. We then prepared smart water-soluble nanoparticles (NPs), DCN-4CQA/F127, using Pluronic® 127 (F127) as a drug carrier. The NPs exhibited excellent biocompatibility, robust photostability, NIR fluorescence, a high photothermal conversion efficiency (η = 47.3%), and sufficient 1O2 generation (ΦΔ = 24.3%) under NIR laser irradiation. Remarkably, the DCN-4CQA/F127 NPs significantly inhibited tumor growth in mice subjected to NIR laser irradiation. This study provides a new route for the development of highly efficient, low-cytotoxicity photosensitizers for fluorescence-imaging-guided PTT/PDT.

Traditional versus mirror three-dimensional printing technology for isolated acetabular fractures: a retrospective study with a median follow-up of 25 months.

OBJECTIVE: To assess the outcomes of traditional three-dimensional (3D) printing technology (TPT) versus mirror 3D printing technology (MTT) in treating isolated acetabular fractures (IAFs). METHODS: Consecutive patients with an IAF treated by either TPT or MTT at our tertiary medical centre from 2012 to 2018 were retrospectively reviewed. Follow-up was performed 1, 3, 6, and 12 months postoperatively and annually thereafter. The primary outcome was the Harris hip score (HHS), and the secondary outcomes were major intraoperative variables and key orthopaedic complications. RESULTS: One hundred fourteen eligible patients (114 hips) with an IAF (TPT, n = 56; MTT, n = 58) were evaluated. The median follow-up was 25 months (range, 21-28 months). At the last follow-up, the mean HHS was 82.46 ±14.70 for TPT and 86.30 ± 13.26 for MTT with a statistically significant difference. Significant differences were also detected in the major intraoperative variables (operation time, intraoperative blood loss, number of fluoroscopic screenings, and anatomical reduction number) and the major orthopaedic complications (loosening, implant failure, and heterotopic ossification). CONCLUSION: Compared with TPT, MTT tends to produce accurate IAF reduction and may result in better intraoperative variables and a lower rate of major orthopaedic complications.

Evaluation of Nonviral piggyBac and lentiviral Vector in Functions of CD19chimeric Antigen Receptor T Cells and Their Antitumor Activity for CD19+ Tumor Cells.

Nonviral transposon piggyBac (PB) and lentiviral (LV) vectors have been used to deliver chimeric antigen receptor (CAR) to T cells. To understand the differences in the effects of PB and LV on CAR T-cell functions, a CAR targeting CD19 was cloned into PB and LV vectors, and the resulting pbCAR and lvCAR were delivered to T cells to generate CD19pbCAR and CD19lvCAR T cells. Both CD19CAR T-cell types were strongly cytotoxic and secreted high IFN-γ levels when incubated with Raji cells. TNF-α increased in CD19pbCAR T cells, whereas IL-10 increased in CD19lvCAR T cells. CD19pbCAR and CD19lvCAR T cells showed similar strong anti-tumor activity in Raji cell-induced mouse models, slightly reducing mouse weight while enhancing mouse survival. High, but not low or moderate, concentrations of CD19pbCAR T cells significantly inhibited Raji cell-induced tumor growth in vivo. These CD19pbCAR T cells were distributed mostly in mesenteric lymph nodes, bone marrow of the femur, spleen, kidneys, and lungs, specifically accumulating at CD19-rich sites and CD19-positive tumors, with CAR copy number being increased on day 7. These results indicate that pbCAR has its specific activities and functions in pbCAR T cells, making it a valuable tool for CAR T-cell immunotherapy.