Systemic treatment options for non-small cell lung cancer after failure of previous immune checkpoint inhibitors: a bayesian network meta-analysis based on randomized controlled trials.

BACKGROUND: Although immune checkpoint inhibitors (ICIs) have brought survival benefits to non-small cell lung cancer (NSCLC), disease progression still occurs, and there is no consensus on the treatment options for these patients. We designed a network meta-analysis (NMA) to evaluate systemic treatment options for NSCLC after failure of ICIs. METHODS: PubMed, Embase, Web of Science and Cochrane Library databases were searched, then literature screening was followed by NMA. We included all Phase II and III randomized controlled trials (RCTs). Progression-free survival (PFS) and overall survival (OS) used hazard ratio (HR) for evaluation. Objective response rate (ORR) and adverse events (AEs) used odds ratio (OR) and relative risk (RR) effect sizes, respectively. R software was applied to compare the Bayesian NMA results. RESULTS: We finally included 6 studies. 1322 patients received ICI plus Chemotherapy (ICI + Chemo), ICI plus Anti-angiogenic monoclonal antibody (ICI + Antiangio-Ab), ICI plus Tyrosine kinase inhibitor (ICI + TKI), Tyrosine kinase inhibitor plus Chemotherapy (TKI + Chemo), Standard of Care (SOC), Chemotherapy (Chemo). TKI + Chemo is associated with longer PFS, higher ORR (surface under cumulative ranking curve [SUCRA], 99.7%, 88.2%), ICI + TKI achieved the longest OS (SUCRA, 82.7%). ICI + Antiangio-Ab was granted the highest safety rating for adverse events (AEs) of any grade, AEs greater than or equal to grade 3 and AEs of any grade leading to discontinuation of treatment (SUCRA, 95%, 82%, 93%). CONCLUSIONS: For NSCLC after failure of ICIs, TKI + Chemo was associated with longer PFS and higher ORR, while ICI + TKI was associated with the longest OS. In terms of safety, ICI + Antiangio-Ab was the highest.

pH sensor based on tilted fiber Bragg grating surface plasmon resonance with a polyaniline reaction deposition film layer.

In this paper, we propose a surface plasmon resonance (SPR) fiber-optic pH sensor combined with a tilted fiber Bragg grating (TFBG) by continuously coating gold and polyaniline (PANI) onto the surface of a TFBG. The micron-scale thickness polyaniline film provides the sensor with good sensitivity, and it achieves accurate measurement of pH values ranging from 2 to 12 by utilizing the pH-responsive mechanism of PANI and the surface plasmon resonance characteristics. Experimental results show that within the 2-12 pH range, the sensitivity of the TFBG surface plasmon resonance pH sensor based on PANI coating is 0.50335 nm/pH, and results demonstrate, a linear correlation coefficient between wavelength and pH value reaching 0.96614. This indicates significant potential for future engineering applications in real-world pH measurement using this sensor.

Endoscopically-assisted extraction of broken roots or fragments within the mandibular canal: a retrospective case series study.

PURPOSE: To assess the impact of endoscope-assisted fractured roots or fragments extraction within the mandibular canal, along with quantitative sensory testing (QST) alterations in the inferior alveolar nerve (IAN). METHODS: Six patients with lower lip numbness following mandibular third molar extraction were selected. All patients had broken roots or fragments within the mandibular canal that were extracted under real-time endoscopic assistance. Follow-up assessments were conducted on postoperative days 1, 7, and 35, including a standardized QST of the lower lip skin. RESULTS: The average surgical duration was 32.5 min, with the IAN exposed in all cases. Two of the patient exhibited complete recovery of lower lip numbness, three experienced symptom improvement, and one patient remained unaffected 35 days after the surgery. Preoperative QST results showed that the mechanical detection and pain thresholds on the affected side were significantly higher than those on the healthy side, but improved significantly by postoperative day 7 in five patients, and returned to baseline in two patients on day 35. There were no significant differences in the remaining QST parameters. CONCLUSIONS: All endoscopic surgical procedures were successfully completed without any additional postoperative complications. There were no cases of deterioration of IAN injury, and lower lip numbness recovered in the majority of cases. Endoscopy allowed direct visualization and examination of the affected nerve, facilitating a comprehensive analysis of the IAN.

Endoscopic visualization of the inferior alveolar nerve associated with somatosensory changes after impacted mandibular third molar extraction.

The aim of this study is to assess the relationship between somatosensory functional changes and inferior alveolar nerve (IAN) exposure after impacted mandibular third molars (M3M) removal. We recruited 35 patients who underwent impacted M3M extraction near the IAN. The M3Ms were extracted by combined endoscopy, piezosurgery, and contra-angle high-speed turbine handpiece. All IAN canal perforations and exposed regions were recorded and measured by endoscopy after extraction and on cone-beam computed tomography (CBCT) images before extraction. The patients were followed up 1, 7, and 35 days after surgery. A standardized quantitative sensory testing (QST) battery was performed on the lower lip skin. All of 35 cases had exposed IAN on CBCT images, 5 of which had no exposed IAN under endoscopy. For the other 30 cases, the endoscopy-measured IAN length and width were shorter than the CBCT measurements (P < 0.001). The warm and mechanical detection thresholds (MDT) on the operation side were significantly higher than the contralateral side after surgery (P < 0.05). Thermal sensory limen, MDT, and cold pain threshold were strongly correlated with the exposed IAN length and MDT also with the exposed IAN width one day after surgery. In conclusion, it was found that not all exposed IAN in CBCT images were real exposure after surgery. The intraoperative exposed IAN endoscopic measurements were smaller than by CBCT and strongly correlated with some QST parameters.

Comparison of Composition, Free-Radical-Scavenging Capacity, and Antibiosis of Fresh and Dry Leave Aqueous Extract from Michelia shiluensis.

Numerous plants of medicinal value grow on Hainan Island (China). Given the lack of knowledge on the phytochemical and pharmacological properties of Michelia shiluensis Chun and Y. F. Wu (M. shiluensis), the application of natural antioxidants and antimicrobials in the food industry has attracted increasing interest. This study aimed to compare the chemical composition, free-radical-scavenging capacity, and antibiosis of aqueous extracts of the fresh and dried leaves of M. shiluensis. The aqueous extract of the leaves of M. shiluensis was obtained using steam distillation, and its chemical components were separated and identified via gas chromatography-mass spectrometry (GC-MS). The free-radical-scavenging capacity and antibiosis were determined. Further, 28 and 20 compounds were isolated from the fresh leaf aqueous extract of M. shiluensis (MSFLAE) and dried leaf aqueous extract of M. shiluensis (MSDLAE), respectively. The free-radical-scavenging capacity of MSFLAE and MSDLAE was determined by the 2,2-diphenyl-1 picrylhydrazyl (DPPH) method, which was 43.43% and 38.74%, respectively. The scavenging capacity of MSFLAE and MSDLAE determined by the 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonate (ABTS)) method was 46.90% and 25.99%, respectively. The iron ion reduction capacity of MSFLAE and MSDLAE was determined by the ferric-reducing antioxidant power (FRAP) method as 94.7 and 62.9 µmol Fe2⁺/L, respectively. This indicated that the two leaf aqueous extracts had a certain free-radical-scavenging capacity, and the capacity of MSFLAE was higher than that of MSDLAE. The antibiosis of the two leaf aqueous extracts on the three foodborne pathogenic bacteria was low, but the antimicrobial effects on Gram-positive bacteria were better than those on Gram-negative bacteria. The antibiosis of MSFLAE on Escherichia coli and Staphylococcus aureus was greater than that of MSDLAE. Finally, MSFLAE and MSDLAE both had certain free-radical-scavenging capacities and antibiosis, confirming that the use of this plant in the research and development of natural antioxidants and antibacterial agents was reasonable. Plant aqueous extracts are an essential source of related phytochemistry and have immense pharmacological potential.

Slim the face or not: 3D change of facial soft and hard tissues after third molars extraction: a pilot study.

BACKGROUND: Whether slim the face or not after removed third molars is the concern of some orthodontic treatment candidates. The aim of this article is to explore the volume changes of facial soft and hard tissues after third molars extraction, as well as develop a reproducible clinical protocol to precisely assess facial soft tissue volume change. METHODS: A non-randomized, non-blind, self-controlled pilot study was conducted. 24 adults aged 18-30 had ipsilateral third molars extracted. The body weight change was controlled within 2 kg. Structured light scans were taken under a standardized procedure pre-extraction (T0), three (T1), and six (T2) months post-extraction; CBCTs were taken at T0 and T2. The projection method was proposed to measure the soft tissue volume (STV) and the soft tissue volume change (STVC) by the Geomagic software. The hard tissue volume change (HTVC) was measured in the Dragonfly software. RESULTS: The final sample size is 23, including 5 males (age 26.6 ± 2.5 years) and 18 females (age 27.3 ± 2.5 years). The HTVC was - 2.33 ± 0.46ml on the extraction side. On the extraction side, the STV decreased by 1.396 (95% CI: 0.323-2.470) ml (P < 0.05) at T1, and increased by 1.753 (95% CI: -0.01-3.507) ml (P = 0.05) at T2. T2 and T0 had no difference (P > 0.05). The inter and intra-raters ICC of the projection method was 0.959 and 0.974. There was no correlation between the STVC and HTVC (P > 0.05). CONCLUSIONS: After ipsilateral wisdom teeth extraction, the volume of hard tissue on the extraction side reduces, and the volume of facial soft tissue does not change evidently. However, further research with large sample size is still needed. The STV measurement has excellent repeatability. It can be extended to other interested areas, including forehead, nose, paranasal, upper lip, lower lip and chin, which is meaningful in the field of orthodontics and orthopedics. TRIAL REGISTRATION: ChiCTR, ChiCTR1800018305 (11/09/2018), http://www.chictr.org.cn/showproj.aspx?proj=28868 .

Predictive factors for open reduction of flexion-type supracondylar fracture of humerus in children.

OBJECTIVE: The incidence of open reduction and internal fixation (ORIF) in flexion-type supracondylar humerus fractures (SCHF) in children is significantly higher than that of extension-type fractures. This study aimed to identify risk factors for ORIF in flexion-type SCHF. METHODS: One hundred seventy-one patients with Wilkins type III flexion-type SCHF from January 2012 to December 2021 were retrospectively enrolled in a tertiary paediatric hospital. Patients were divided into ORIF group versus closed reduction and internal fixation (CRIF) group. Then, patients data of age, sex, injury side, obesity, deviation of displacement, fracture level, rotation, nerve injury, and delay from injury to surgery were reviewed. Univariate analysis and multivariate logistic regression were used to identify independent risk factors and odds ratios (OR) of ORIF. RESULTS: Overall, 171 children with type III flexion-type SCHF were analyzed (average aged 7.9 ± 2.8 years). Displacement was lateral in 151 cases, medial in 20. 20 cases had combined ulnar nerve injury. The failed closed reduction rate was 20%. Univariate analysis indicated age, distal fracture fragment rotation, and ulnar nerve injury were significantly associated with ORIF. (P = 0.047, P = 0.009, and P = 0.001, respectively). Multivariate logistic regression analysis showed that distal fracture fragment rotation (OR, 3.3; 95%CI:1.1-9.5; P = 0.028) and ulnar nerve injury (OR, 6.4; 95%CI:2.3-18.3; P = 0.001) were independent risk factors; however, the age was not an independent one (OR, 1.5; 95%CI:0.6-3.5; P = 0.397) for ORIF in the Wilkins type III flexion-type SCHF. CONCLUSION: Distal fracture fragment malrotation on initial x-rays and ulnar nerve injury were significant risk factors for ORIF in Wilkins type III flexion-type SCHF. Surgeons should prepare tourniquets or other open reduction instruments when treating these types of fractures. LEVEL OF EVIDENCE: Level IV.

Analysis of the location and trajectory of the Kirschner wires in the fixation of extension-type supracondylar fracture of the humerus by 3D computational simulation.

BACKGROUND: Closed reduction and percutaneous pinning is still a preference for the treatment of supracondylar humerus fractures in children. However, no reports have shown the pin trajectory and the characteristics of the entry point so far. So we established a computational simulation model of the elbow to observe the trajectory of pinning for supracondylar humerus fractures. METHODS: We reconstructed an adult elbow computationally and simulated pin placement through lateral and medial pinning. Pin trajectories were traced after placement and after the addition of the skin profile; the relative entry points of the pins were determined. We used the center of the dorsal olecranon inflection as an anatomic reference for the entry points of lateral pinning. Four quadrants were established based on the center of the dorsal olecranon inflection: upper medial quadrant, upper lateral quadrant, lower medial quadrant, and lower lateral quadrant (LLQ). RESULTS: The maximum angle of pinning through the lateral column was 64° ± 3°. The minimum angles of pinning through the lateral column and middle column were 37° ± 3° and 20° ± 2°, respectively. The range of safe angle pinning through the medial column was between 18° ± 2° and 57° ± 3° to avoid penetration of the olecranon fossa and the cortex of the medial column. The entry points of lateral pinning were within the lateral half of the LLQ, and the lateral one-third of the LLQ contained all entry points of the pins through the lateral column and minor points of the pins through the middle column. The exit points of the medial pinning were within the lateral fringe of the metaphyseal-diaphyseal junction region; entering from the inferior two-thirds of the medial epicondyle could lead to the exit points in the proximal half of the metaphyseal-diaphyseal junction region laterally. DISCUSSION: For lateral pinning, the entry points would be within the lateral half of the LLQ. For the pins through the lateral column, the entry points should be within the lateral one-third of the LLQ. For medial pinning, entering from the inferior two-thirds of the medial epicondyle would lead to a more proximal exit.

Transcriptome Analysis Revealing the Interaction of Abscisic Acid and Cell Wall Modifications during the Flower Opening and Closing Process of Nymphaea lotus.

As a tropical flower, Nymphaea lotus is a typical night-blooming waterlily used in water gardening. Its petals are rich in aromatic substances that can be used to extract essential oils and as flower tea. However, the short life of the flower seriously affects the development of its cut flowers. At present, neither the mechanism behind the night-opening waterlily flower's opening and closing nor the difference between day-opening and night-opening waterlily flowers' opening and closing mechanisms are clear. In this study, endogenous hormone contents of closed (CP) and open (OP) petals were measured, and transcriptome analysis of CP and OP petals was carried out to determine the signal transduction pathway and metabolic pathway that affect flower opening and closing. ABA and cell wall modification were selected as the most significant factors regulating flowering. We used qRT-PCR to identify the genes involved in the regulation of flower opening in waterlilies. Finally, by comparing the related pathways with those of the diurnal type, the obvious difference between them was found to be their hormonal regulation pathways. In conclusion, the endogenous ABA hormone may interact with the cell wall modification pathway to induce the flowering of N. lotus. Our data provide a new direction for the discovery of key factors regulating the flower opening and closing of N. lotus and provide basic theoretical guidance for future horticultural applications.

Implications of Virtual CBCT-Based Immediate Implant Planning for Maxillary and Mandibular First Molars.

The purpose of his study was to investigate the projected ridge-implant dimensions derived from virtual superimposition of implants on intact first molars mimicking immediate implantation in the mandible (Md1) and maxilla (Mx1) using cone-beam computed tomography (CBCT). The CBCT records of 41 patients (19 males and 22 females) with Md1 or Mx1 were collected. Ten-millimeter-long cylindrical implants with different diameters were virtually positioned at prosthetically ideal angles into interradicular septum using CBCT software. Radiographic alveolar ridge height (ARH), alveolar ridge width (ARW), gap distance, and vertical distance from the implant platform to the alveolar crest were measured. Twenty Mx1s (48.8%) and 21 Md1s (51.2%) were included. The mean ARH values were 7.13 ± 4.32 and 15.64 ± 1.80 mm for Mx1 and Md1, respectively; 87.8% of mesiobuccal sites had gap distance of >2 mm when 6-mm-diameter implants were used. Increasing implant diameter from 6 to 9 mm decreased the percentage of sites with ARW > 2 mm from 80.5% to 41.5% buccally and from 86.4% to 26.8% lingually. The mean vertical distance from the implant platform to the alveolar crest was 1.41 ± 1.09 mm buccally and 1.11 ± 1.10 mm lingually. Immediate implant placement of first molars, especially in the maxilla, requires stringent presurgical evaluation. Implants no wider than 6 mm placed into the interradicular septum may meet acceptable running room and alveolar plate thickness criteria if the jumping distance is grafted. Further clinical trials are needed to confirm these findings in this virtual study.

WISP-2, an upregulated gene in hip cartilage from the DDH model rats, induces chondrocyte apoptosis through PPARγ in vitro.

Chondrocyte apoptosis plays an important role in the developmental dysplasia of the hip (DDH) development. It has been found that WNT1 inducible signaling pathway protein 2 (WISP-2) and peroxisome proliferator-activated receptor γ (PPARγ) are involved in cell apoptosis. In this study, we performed the straight-leg swaddling DDH rat model and we found that cartilage degradation and chondrocyte apoptosis were remarkably increased in DDH rats in vivo. Moreover, we found that WISP-2 was upregulated in hip acetabular cartilage of DDH rats compared to control rats. Next, the effects of WISP-2 on chondrocyte apoptosis and its possible underlying mechanism were examined in vitro. The lentivirus-mediated gain- and loss-of-function experiments of WISP-2 and peroxisome proliferator-activated receptor γ (PPARγ) for cell viability and apoptosis were performed in primary rat chondrocytes. The results showed that the overexpression of WISP-2 induced chondrocyte apoptosis, and knockdown of WISP-2 could suppress the chondrocyte apoptosis induced by advanced glycation end products (AGE). Additionally, WISP-2 could negatively regulate the expression of PPARγ in chondrocytes. Moreover, the knockdown of PPARγ promoted chondrocyte apoptosis and overexpression of PPARγ abated the increased apoptosis and decreased cell viability of chondrocytes induced by WISP-2. This study demonstrated that WISP-2 might contribute to chondrocyte apoptosis of hip acetabular cartilage through regulating PPARγ expression and activation, which may play an important role in the development of DDH.

Development of acetabular anteversion in children with normal hips and those with developmental dysplasia of the hip: a cross-sectional study using magnetic resonance imaging.

Background and purpose - Acetabular anteversion (AA) is related to hip function. Most previous studies were based on radiographic investigations that determine osseous acetabular anteversion (OAA). But children's acetabulum is mostly composed of cartilage; the cartilaginous acetabular anteversion (CAA) represents the real anteversion of the acetabulum. We measured OAA and CAA in children of various ages using MRI, and compared the developmental patterns between children with normal hips and those with developmental dysplasia of the hip (DDH).Patients and methods - The OAA and CAA were measured on MRI cross-sections of the hips in 293 children with normal hips (average age 8 years), and in 196 children with DDH (average age 34 months). Developmental patterns of OAA and CAA in children with normal hips were determined through age-based cross-sectional analysis. Differences in OAA and CAA between children with normal hips and those with DDH were compared.Results - Normal OAA increased from mean 8.7° (SD 3.2) to 12° (3.0) during the first 2 years of life and remained unchanged until 9 years of age. From 9 to 16 years, the OAA showed a minimal increase of 2°-3°. The normal CAA increased rapidly from a mean of 12° (3.1) to 15° (2.7) within the first 2 years of life, and remained constant at 15° (SD 3.4) until 16 years of age. The age-matched average OAA in the normal and DDH cases was 11° (3.2) and 15° (3.0), respectively (p < 0.001). The age-matched average CAA in normal and DDH cases was 17° (4.2) and 23° (4.5), respectively (p < 0.001). Similarly, there was a significant difference in OAA and CAA between the uninvolved hips in unilateral DDH and normal cases (p < 0.001).Interpretation - The CAA was fully formed at birth in normal children, and remained unchanged until adulthood, whereas the OAA increased with age. The OAA and CAA were both over-anteverted in DDH children. MRI evaluation is of importance in children during skeletal development when planning hip surgery.

Polyoxometalate-Derived Multi-Component X/W2 C@X,N-C (X=Co, Si, Ge, B, and P) Nanoelectrocatalysts for Efficient Triiodide Reduction in Dye-Sensitized Solar Cells.

Multi-component tungsten carbide-based hybrid materials featuring different heteroatom dopants coated with X,N dual-doped carbon layers (X/W2 C@X,N-C, XWXNC) were prepared by selecting Keggin-type polyoxometalates (POMs) (NH4 )n [XW12 O40 ] (X=Co, Si, Ge, B, and P) and dicyandiamide (DCA) as precursors. The electrocatalytic activity of these nanocomposites as counter electrode (CE) catalysts for dye-sensitized solar cells (DSSCs) was systematically investigated. Structure characterizations show that X,N heteroatoms were successfully introduced into the W2 C and carbon frameworks. The obtained X,N dual-doped carbon layers were modified and loaded with W2 C nanoparticles, promoting the improvement of catalytic performance by a synergistic effect. The consequence of photoelectric conversion efficiency (PCE) is CoWCoNC (6.68 %)>SiWSiNC (6.56 %)>GeWGeNC (6.49 %)>BWBNC (6.45 %)>PWPNC (6.20 %)>WNC (6.05 %). With the increase in electronegativity of the dopants, the photovoltaic performance decreases in a reverse order. This work provides a shortcut to the rational design of highly efficient and cost-effective catalysts for DSSCs.

Polyoxometalates in dye-sensitized solar cells.

Dye-sensitized solar cells (DSSCs) are the third generation of photovoltaic cells developed by Grätzel and O'Regan. They have the characteristics of low cost, simple manufacturing process, tunable optical properties, and higher photoelectric conversion efficiency (PCE). With an ever increasing energy crisis, there is an urgent need to develop highly efficient, environmentally benign, and energy-saving cell materials. Polyoxometalates (POMs), a kind of molecular inorganic quasi-semiconductor, are promising candidates for use in different parts of DSSCs due to their excellent photosensitivity, redox, and catalytic properties, as well as their relative stability. Following a brief introduction to the development of DSSCs and the potential virtues of POMs in DSSCs, we attempt to make some generalizations about the energy level regulation of POMs that is the underlying theoretical basis for their application in DSSCs, and then we summarize the research progress of POMs in DSSCs in recent years. This is organized in terms of the properties of POMs, namely, electron acceptor, photosensitivity, redox and catalysis, based on the accumulation of our research into POMs over many years. Meanwhile, in view of the fact that the properties of POMs depend primarily on their electronic structural diversity, we keep this point in mind throughout the article with a view to revealing their structure-property relationships. Finally we provide a short summary and remarks on the future outlook. This review may be of interest to synthetic chemists devoted to designing POMs with specific structures, and researchers engaged in the extension of POMs to photoelectric materials.

High-Throughput Sequencing Analysis of Microbial Profiles in the Dry Socket.

PURPOSE: The aim of this study was to explore and describe the microbial profiles of dry socket (DS) and identify the key microbial population as a possible disease-related factor. MATERIALS AND METHODS: Bacterial samples were collected from patients who underwent surgical mandibular third molar extraction and were divided in 3 groups: the disease (D) group composed of patients who were diagnosed with DS; the treated (T) group composed of patients from the D group who received treatment; and the control (C) group composed of patients who did not have adverse reactions after tooth extraction. Bacterial DNA was extracted and the V3 and V4 hypervariable regions of the bacterial 16S rRNA gene were amplified and subjected to sequencing. Sequence data were analyzed using alpha and beta diversity indices. RESULTS: In total, 772,169 high-quality sequences were detected from 31 samples. Using a 97% similarity level, 531 operational taxonomic units were detected. In addition, 10 phyla, 23 classes, 38 orders, 63 families, and 116 genera were found. Composition of the microbial community in the D group differed considerably from that of the T and C groups. Furthermore, a specific microbial pattern, which included Parvimonas, Peptostreptococcus, Prevotella, Fusobacterium, Slackia, Oribacterium, and Solobacterium species, appeared abundantly in the D group compared with the T and C groups. Moreover, Parvimonas, Peptostreptococcus, Prevotella, and Fusobacterium species had important roles in discriminating the D group from the other 2 groups. CONCLUSION: These results suggest differences in the microbial community composition among DSs, normal-healing sockets, and post-treated sockets. These results provide better insight into the development of DS and enhance the understanding of DS. Nonetheless, further studies are necessary to investigate and confirm how these differential bacteria contribute to the development of the disease.

A comparative biomechanical study on different fixation techniques in the management of transverse metaphyseal-diaphyseal junction fractures of the distal humerus in children.

BACKGROUND: Metaphyseal-diaphyseal junction (MDJ) fractures of the distal humerus are problematic to reduce and more susceptible to post-operative complications. This biomechanical study was designed to compare Kirschner wires (KW), lateral external fixation, and elastic stable intramedullary nails (ESIN) in simulated transverse MDJ fractures of various heights. METHOD: Sagittally oblique, transverse MDJ fractures were created in fourth-generation composite bone models at three levels: high, mid, and low fractures, respectively, and then fixed with either Kirschner wires, lateral external fixation (EF), or ESIN respectively and tested in extension, flexion, valgus, varus, internal, and external rotations. RESULTS: In the high fractures, ESIN had better overall stiffness than the other techniques. In the mid groups, three crossed pinning (1-medial and 2-lateral pins) had the best overall stiffness, followed by two crossed pinning (1-medial and 1-lateral pins). In the low fractures, three crossed pinning was superior to all other techniques. Two crossed pinning and three -lateral pinning techniques yielded comparable stiffness in the low fracture model. CONCLUSIONS: From a biomechanical perspective, ESIN provides the best overall stability for fractures located in the upper region of the MDJ, while percutaneous pinning is superior in stabilizing fractures of the lower region. Two lateral and one medial pins make the most stable crossed pinning construct for these fractures.

MicroRNA-140 suppresses osteosarcoma tumor growth by enhancing anti-tumor immune response and blocking mTOR signaling.

Immune checkpoint blockade is proved to be a promising therapeutic strategy against several human malignancies. MicroRNAs (miRNAs) are ∼22 nucleotide RNAs that play important roles in regulating gene expression, either suppressing its translation or speeding up its degradation. In this study, we demonstrated that miR-140 acts as a critical modulator of PD-L1 and is significantly reduced in osteosarcoma (OS). MiR-140 was inversely correlated with PD-L1 and luciferase reporter assay confirmed that miR-140 can direct regulate PD-L1 expression by binding to its 3'UTR. MiR-140 failed to influence tumor growth in nude mice, whereas markedly inhibited tumor growth in the immune-competent C57BL/6J mice. Mechanistically, the tumor-suppressive role of miR-140 was associated with the increased infiltrates of cytotoxic CD8+ T cells and the decreased infiltrates of myeloid-derived suppressive cells and regulatory T cells. Moreover, miR-140 significantly inhibited mTOR signaling and combined miR-140 overexpression with pharmacological inhibition of mTOR signaling showed remarkable synergistic anti-tumor effect. Collectively, our findings indicate that miR-140 exerts anti-OS efficacy by targeting immune checkpoint molecule PD-L1 and can be developed as a novel immunotherapeutic agent for the treatment of OS.

A Reusable N-Doped-Carbon-Coated Mo2 C Composite Counter Electrode for High-Efficiency Dye-Sensitized Solar Cells.

The design and development of efficient and stable nonprecious-metal-based catalysts for counter electrodes (CEs) in dye-sensitized solar cells (DSSCs) has received a great deal of attention. In this work, molybdenum carbide nanoparticles homogeneously distributed in a nitrogen-rich carbon matrix (Mo2 C@NC) have been synthesized from inexpensive raw materials (polyoxometalate and dicyandiamide) by a facile one-step solid-phase synthesis method. The novel Mo2 C@NC hybrid was not only used as a CE in a DSSC, but also showed superior catalytic activity towards I3- /I- as a redox electrolyte. The power conversion efficiency of a DSSC with Mo2 C@NC as the CE was as high as 6.49 %, comparable to that with Pt (6.38 %). The CE was prepared by a drop-coating method, without the addition of another conductive polymer. Most importantly, the method circumvents the problem of the sample falling off from the fluorine-doped tin oxide (FTO), and the CE could be repeatedly reused with unchanged efficiency. Therefore, it opens the way for the development of platinum-free catalysts with low cost, simple processing, good stability, and high efficiency.

A Strategy for Breaking Polyoxometalate-based MOFs To Obtain High Loading Amounts of Nanosized Polyoxometalate Clusters to Improve the Performance of Dye-sensitized Solar Cells.

Polyoxometalates (POM) have already been confirmed to act as effective electron-transfer mediators for improving the power conversion efficiency (PCE) of dye-sensitized solar cells (DSSCs) based on previous studies. However, the improvement may be limited by the agglomeration of the polyoxoanions. In this paper, the previous synthesis strategy is improved upon by breaking the metal-organic frameworks (MOFs) with POMs as the secondary building units ([Ni(bpp)(H2 O)2 ]3 [P2 W18 O62 ]⋅24 H2 O (1) (bpp=1,3-bis(4-pyridyl)propane) and H6 [Cu3 (H2 O)6 (P2 W18 O62 )2 (3-dpye)6 ]⋅28 H2 O (2) (3-dpye=N,N'-bis(3-pyridinecarboxamide)-1,2-ethane)) to design and synthesize small sized and highly disperse POM nanoparticles by means of compositing with TiO2 , through calcination to remove the organic ligand. TEM and element mapping confirm that P2 W18 O626- (denoted as P2 W18 ) nanoparticles with the diameter of ≈1 nm are uniformly distributed in TiO2 composites. The loading amount (wt. %) of POM in MOFs reaches 75.67 %. The small sized and highly disperse P2 W18 nanoparticles may provide more active sites and specific surface areas for improving the PCE of DSSCs. Finally, the investigations indicate that the PCE of composite P2 W18 ⋅NiO@TiO2 photoanodes is up to 7.56 %, which was 26 % higher than the pristine TiO2 based photoanodes.