Tunability of Photovoltaic Functions via Halogen Substitution [(Ade)2 CdX4](X = Cl, Br): A Class of Three-Dimensional Organic-Inorganic Hybrid Materials.

Two new three-dimensional organic-inorganic hybrid crystalline materials, [(Ade)2 CdCl4] (1) and [(Ade)2 CdBr4] (2), were obtained by the slow evaporation of adenine (Ade) and cadmium chloride in aqueous solution at room temperature with hydrochloric acid and hydrobromic acid used as halogen sources. The structural, thermal, optical, and electrical properties were characterized by single-crystal X-ray diffraction, infrared spectroscopy, thermogravimetric analysis, variable-temperature-variable-frequency dielectric constant analysis, and electrochemical tests. With increasing the substitution of Cl by Br, the composition of the material changed and the space group shifted from P-1 to P21/m, with a significant blue-shift in the fluorescence emission. Changing the temperature induced the deformation of the three-dimensional framework structure formed by hydrogen bonding interactions, leading to dielectric anomalies. Cyclic voltammetry tests showed the good reversibility of the electrolysis process. The structural diversity of the complexes was realized by modulating the halogen composition, and a new method for designing novel organic-inorganic hybrids with controllable photoelectric functionality was proposed.

The Synthesis, Structure, and Dielectric Properties of a One-Dimensional Hydrogen-Bonded DL-α-Phenylglycine Supramolecular Crown-Ether-Based Inclusion Compound.

A novel hydrogen-bonded supramolecular crown-ether-based inclusion compound, [(DL-α-Phenylglycine)(18-crown-6)]+[(CoCl4)0.5]-(1), was obtained via evaporation in a methanolic solution at room temperature using DL-α-phenylglycine, 18-crown-6, cobalt chloride (CoCl2), and hydrochloric acid. Its structure, thermal properties, and electrical properties were characterized via elemental analysis, single-crystal X-ray diffraction, variable-temperature infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, and variable temperature-variable frequency dielectric constant testing. The compound was a monoclinic crystal system in the C2 space group at low temperature (100 K) and room temperature (293 K). Analysis of the single crystal structure showed that [(CoCl4)0.5]- presented an edge-sharing ditetrahedral structure in the disordered state, while the protonated DL-α-phenylglycine molecule in the disordered state and intramolecular hydroxyl group (-OH) underwent dynamic rocking, causing a significant stretching motion of the O-H···Cl-type one-dimensional hydrogen bond chain. This resulted in dielectric anomalies in the three axes of the crystal, thus showing significant dielectric anisotropy.

Risk factors analysis and nomogram construction for blood transfusion in elderly patients with femoral neck fractures undergoing hemiarthroplasty.

INTRODUCTION: Elderly patients with femoral neck fractures (FNFs) undergoing hemiarthroplasty usually have poor physical condition. The main aim of this study was to identify risk factors for blood transfusion in these patients and construct a nomogram to intuitively predict the requirement of transfusion. The secondary purpose was to examine the relationship between blood transfusion and complications within 30 days post-operatively. Our hypothesis was that chronic kidney disease (CKD) and hypoalbuminemia may increase the requirement of transfusion. METHODS: Data of 414 elderly patients undergoing hemiarthroplasty for FNFs were retrospectively collected. Univariate and multiple regression analysis were performed to identify independent risk factors for blood transfusion, which were used to construct a nomogram subsequently. The discrimination and calibration of the nomogram model were assessed with concordance index (C-index), the area under receiver operating characteristic curve (AUC), and calibration curve. Furthermore, the complications of blood transfusion within 30 days post-operatively were also analyzed. RESULTS: Out of 414 patients, 127 (30.7%) received a blood transfusion. Independent risk factors for blood transfusion included CKD, hypoalbuminemia, pre-operative anaemia, general anaesthesia, higher American Society of Anesthesiologists score, more intraoperative blood loss, and longer surgical time. Increased hidden blood loss, deep vein thrombosis, superficial wound infection, and prolonged hospital stays were more common in transfused patients. The C-index of the nomogram model was 0.848 (95% CI = 0.811-0.885), and the AUC value was 0.859. The calibration curve showed a good consistency between the actual transfusion and the predicted probability. DISCUSSION: We observed a transfusion rate of 30.7% in elderly FNF patients undergoing hemiarthroplasty. CKD and hypoalbuminemia were firstly identified as independent risk for blood transfusion. In addition, blood transfusion can increase the occurrence of early post-operative complications. CONCLUSION: Targeted pre-operative intervention, such as optimizing CKD and correcting hypoalbuminemia is essential and highly regarded.

Mitochondria-targeted accumulation of oxygen-irrelevant free radicals for enhanced synergistic low-temperature photothermal and thermodynamic therapy.

BACKGROUND: Although lower temperature (< 45 °C) photothermal therapy (LPTT) have attracted enormous attention in cancer therapy, the therapeutic effect is still unsatisfying when applying LPTT alone. Therefore, combining with other therapies is urgently needed to improve the therapeutic effect of LPTT. Recently reported oxygen-irrelevant free radicals based thermodynamic therapy (TDT) exhibit promising potential for hypoxic tumor treatment. However, overexpression of glutathione (GSH) in cancer cells would potently scavenge the free radicals before their arrival to the specific site and dramatically diminish the therapeutic efficacy. METHODS AND RESULTS: In this work, a core-shell nanoplatform with an appropriate size composed of arginine-glycine-aspartate (RGD) functioned polydopamine (PDA) as a shell and a triphenylphosphonium (TPP) modified hollow mesoporous manganese dioxide (H-mMnO2) as a core was designed and fabricated for the first time. This nanostructure endows a size-controllable hollow cavity mMnO2 and thickness-tunable PDA layers, which effectively prevented the pre-matured release of encapsulated azo initiator 2,2'-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIBI) and revealed pH/NIR dual-responsive release performance. With the mitochondria-targeting ability of TPP, the smart nanocomposites (AIBI@H-mMnO2-TPP@PDA-RGD, AHTPR) could efficiently induce mitochondrial associated apoptosis in cancer cells at relatively low temperatures (< 45 °C) via selectively releasing oxygen-irrelevant free radicals in mitochondria and facilitating the depletion of intracellular GSH, exhibiting the advantages of mitochondria-targeted LPTT/TDT. More importantly, remarkable inhibition of tumor growth was observed in a subcutaneous xenograft model of osteosarcoma (OS) with negligible side effects. CONCLUSIONS: The synergistic therapy efficacy was confirmed by effectively inducing cancer cell death in vitro and completely eradicating the tumors in vivo. Additionally, the excellent biosafety and biocompatibility of the nanoplatforms were confirmed both in vitro and in vivo. Taken together, the current study provides a novel paradigm toward oxygen-independent free-radical-based cancer therapy, especially for the treatment of hypoxic solid tumors.

Amplification of oxidative stress with lycorine and gold-based nanocomposites for synergistic cascade cancer therapy.

BACKGROUND: Despite advances of surgery and neoadjuvant chemotherapy during the past few decades, the therapeutic efficacy of current therapeutic protocol for osteosarcoma (OS) is still seriously compromised by multi-drug resistance and severe side effects. Amplification of intracellular oxidative stress is considered as an effective strategy to induce cancer cell death. The purpose of this study was to develop a novel strategy that can amplify the intracellular oxidative stress for synergistic cascade cancer therapy. METHODS AND RESULTS: A novel nanocomposite, composed of folic acid (FA) modified mesoporous silica-coated gold nanostar (GNS@MSNs-FA) and traditional Chinese medicine lycorine (Ly), was rationally designed and developed. Under near-infrared (NIR) irradiation, the obtained GNS@MSNs-FA/Ly could promote a high level of ROS production via inducing mitochondrial dysfunction and potent endoplasmic reticulum (ER) stress. Moreover, glutathione (GSH) depletion during ER stress could reduce ROS scavenging and further enable efficient amplification of intracellular oxidative stress. Both in vitro and in vivo studies demonstrated that GNS@MSNs-FA/Ly coupled with NIR irradiation exhibited excellent antitumor efficacy without noticeable toxicity in MNNG/HOS tumor-bearing mice. CONCLUSION: All these results demonstrated that GNS@MSNs-FA/Ly coupled with NIR irradiation could dramatically amplify the intra-tumoral oxidative stress, exhibiting excellent antitumor ability without obvious systemic toxicity. Taken together, this promising strategy provides a new avenue for the effective cancer synergetic therapy and future clinical translation.

The influence of the steep medial posterior tibial slope on medial meniscus tears in adolescent patients: a retrospective case-control study.

BACKGROUND: Several studies have demonstrated a relationship between the posterior tibial slope (PTS) and meniscal tears in adults. However, little is known about the association between the PTS of the adolescents and medial meniscal tears (MMT). The purpose of this study was to evaluate the association between the PTS and MMT in adolescents, and to determine the optimal cut-off values of PTS for discriminating between the MMT and the control groups. METHODS: Between January 2018 and January 2020, a retrospective case-control study was performed. In this study, isolated MMT adolescent patients with no ligamentous injuries were matched by age and sex to a control group of radiologically normal images. The PTS was defined as the angle between the perpendicular line to proximal tibial cortex (PTC) and the tangent line along the tibial plateau. Then, both the medial posterior tibial slope (MPTS) and lateral posterior tibial slope (LPTS) were measured by plain radiographs on the lateral views. In addition, the optimal cut-off values of PTS were determined by the receiver operating characteristic (ROC) curve analysis. RESULTS: A total of seventy-two patients who met the inclusion criteria were enrolled in the final analysis (36 patients with isolated MMT, 36 controls). The MPTS was greater in the knees with isolated MMT (10.7° ± 2.1°) than that of the control group (8.8° ± 1.7°), showing significant difference (P<0.001). However, there was no significant difference regarding the LPTS between the isolated MMT and controls (11.5 ± 3.4 vs 10.9 ± 2.6, p>0.05). In the ROC curve analysis, the calculated cutoff value of the MPTS discriminating between the groups was 10.3°, with a sensitivity of 73.3% and specificity of 78.9%. CONCLUSIONS: This study demonstrated that steep MPTS is associated with MMT, and MPTS≥10.3° was identified to be a risk factor for MMT in adolescents.

Prevalence and risk factors of surgical site infection after closed isolated patella fracture surgery: A prospective cohort study.

PURPOSE: Surgical site infection (SSI) after patella fracture surgery could be devastating and challenging. There is no large sample size study to investigate the prevalence and risk factors of it. The purpose of this study was to address this clinical issue. METHODS: A total of 820 patients who underwent patella fracture surgery between October 2014 and December 2018, were included. Demographic data, fracture type, injury mechanism, pre-operative stay, surgery-related variables, and pre-operative laboratory indexes were obtained from a prospective database. The optimum cutoff value of surgery duration was detected by receiver operating characteristic analysis. Univariate analysis and multivariate analysis were performed to determine the risk factors. RESULTS: A total of 17 patients developed SSI after patella fracture surgery, indicating a prevalence of 2.1%, with 11 cases (1.3%) for superficial infection and six cases (0.8%) for deep infection. After adjustment of multiple variables, current smoking, (OR, 18.6, CI, 3.5-99.0); albumin < 35 g/L, (OR, 7.4, CI, 1.1-52.3); diabetes mellitus, (OR, 8.8, CI, 1.3-59.4) and surgery duration > 79.5 minutes, (OR, 13.2, CI, 1.5-117.3) were identified to be independent risk factors of SSI after patella fracture surgery (p < 0.05). CONCLUSION: The prevalence of SSI in patients with closed isolated patella fracture was 2.1%, with 1.3% for superficial and 0.8% for deep infection. We recommend individualized risk stratification and targeted interventions for patients with risk factors (current smoking, albumin < 35 g/L, diabetes mellitus, and surgery duration > 79.5 minutes).

Arthroscopic evaluation for tibial plateau fractures on the incidence and types of cruciate ligamentous injuries following closed reduction and internal fixation.

PURPOSE: To evaluate the overall incidence and types of anterior cruciate ligament (ACL) injuries and posterior cruciate ligament (PCL) injuries associated with tibial plateau fractures (TPFs) following closed reduction and internal fixation (CRIF), and to identify the relationship between the incidence and types of cruciate ligamentous injuries with Schatzker classification and "three-column" classification. METHODS: From January 2016 to January 2018, 185 patients with closed TPFs who underwent CRIF were included in this retrospective study. All patients were performed with arthroscopic examination after CRIF, and then, the incidence and types of cruciate ligamentous injuries were recorded and evaluated. RESULTS: The overall incidence rates of cruciate ligamentous injuries associated with TPFs were 37.3% with 21.6% of these being ACL injuries and 15.7% had PCL injuries. Importantly, patients with fractures in "two-column" fractures have a significantly higher incidence rate of ACL avulsion fracture and PCL complete tears (P < 0.05) than other fracture types, especially involving anteromedial and posterior column fractures. In addition, the incidence of PCL partial tears in patients with three-column involvement was 11.8%, which was higher than other fracture patterns based on three-column classification system (P < 0.05). In the current study, Schatzker IV was most commonly associated with ACL injuries, occurring in 48.1% of our series. Furthermore, PCL injuries occurred at a significantly higher incidence in Schatzker VI with 34.5% than other fracture types (P < 0.05). Statistical analysis revealed that there was a significant difference between Schatzker classification and incidence of injury to the ACL (P < 0.05) and PCL (P < 0.05). Of note, avulsion fracture was the most common types of ACL injuries which was observed in 45% ACL injuries, while partial tear was the most common types of PCL injuries. However, no significant relationship was identified between the types of cruciate ligamentous injuries and Schatzker classification (P > 0.05). CONCLUSIONS: In the recognition of concomitant cruciate ligamentous injuries associated with TPFs based on Schatzker classification and three-column classification, orthopaedic trauma surgeons may better guide optimal surgical protocols for patients.

Changes in patellar height and posterior tibial slope angle following uniplanar medial opening wedge high tibial osteotomy using a novel wedge-shaped spacer implanation concurrent with proximal partial fibulectomy.

PURPOSE: The purpose of this study was to evaluate changes of patellar height and posterior tibial slope angle following uniplanar medial opening wedge high tibial osteotomy using a novel wedge-shaped spacer implanation concurrent with proximal partial fibulectomy. METHODS: All patients who underwent uniplanar medial opening wedge high tibial osteotomy using a novel wedge-shaped spacer implanation concurrent with proximal partial fibulectomy between January 2017 and February 2019 were included and assessed retrospectively. Radiological assessment was made in terms of the changes in patellar height and posterior tibial slope angle between pre-operative and post-operative radiographs. RESULTS: Thirty-five patients (9 males and 26 females) with a mean age of 57.3 years (range 50.8-64.2 years) were enrolled in this study protocol and demonstrated decreased posterior tibial slope angle post-operatively (9.7° ± 2.5° pre-operatively and 7.3° ± 1.8° post-operatively, P < 0.001). Patellar height was unchanged significantly post-operatively (Caton-Deschamps: 0.83 ± 0.12 pre-operatively and 0.82 ± 0.09 post-operatively, P > 0.05). CONCLUSIONS: Uniplanar medial opening wedge high tibial osteotomy using a novel wedge-shaped spacer implanation concurrent with proximal partial fibulectomy can decrease posterior tibial slope and maintain the patellar height.

Long-term outcomes after partial patellectomy in comminuted fractures - a clinical study.

PURPOSE: The purpose of this study was to evaluate the long-term clinical and radiographic outcomes of partial patellectomy (PP) in patients with patella comminuted distal pole fractures. METHODS: Seventeen patients who were diagnosed with patella comminuted distal pole fractures and underwent PP procedures were retrospectively included between January 1995 and January 2005. We collected patient demographics and data on the mechanism of injury, time to surgery, fracture type, follow-up time, and post-operative complications (infection, patellofemoral arthritis, and stiffness). At the final follow-up, functional outcome was evaluated by the range of motion (ROM) and the Bostman Scoring System. Quadriceps strength was evaluated by using an isokinetic dynamometer to measure peak torque, and patellar height was evaluated by the Insall-Salvati (IS) ratio in lateral knee radiographs. The average follow-up period was 14.6 years (range, 11-19 years). RESULTS: We analyzed 17 patients (AO/OTA 34-A1), with an average age of 59.8 years (range, 43-76 years). According to the Bostman grading scales, final functional outcomes were excellent in 11 (64.7%) and good in six (35.3%) patients. All patients had full knee extension, and the average ROM was 125.1° (range, 121.4-129.3°). The average peak torque of the injured knee was 103.2 ± 9.7 Nm, and that of the uninjured opposite side was 108.3 ± 7.6 Nm, with no significant difference (p > 0.05). Furthermore, no postoperative complications, such as infection, posttraumatic osteoarthritis, or stiffness, were observed. Compared to the uninjured knee, the IS ratio of the injured knee was 0.76 ± 0.13, indicating that the patellar height was decreased, which meant patella baja. CONCLUSIONS: The PP procedure for patella comminuted distal pole fractures is a safe, simple, and reliable technique that can provide good long-term clinical outcomes even with decreased patellar height and could be a satisfactory alternative treatment option when anatomical reduction is difficult.

Three-dimensional-printed intercalary prosthesis for the reconstruction of large bone defect after joint-preserving tumor resection.

BACKGROUND: Joint-preserving intercalary tumor resection can result in better proprioception and a more normal joint function after reconstruction. However, most reported reconstruction techniques are usually associated with frequent complications. Therefore, the approach of reconstruction following joint-preserving tumor resection warrants further study. METHODS: Between September 2016 and October 2018, 12 patients with metaphyseal malignant bone tumors around the knee joint were treated by joint-preserving intercalary resections with the aid of three-dimensional (3D)-printed osteotomy guide plates and reconstructions using 3D-printed intercalary prostheses. We assessed the accuracy of the resection by comparing the cross sections at the resection plane with 3D-printed matching surface of the prostheses. The functional outcomes, complications and oncological status were also evaluated. RESULTS: All patients were observed for 7 to 32 months with an average follow-up of 22.5 months. The achieved resection was accurate, with accurate matching between the residual bone and prosthesis. The mean MSTS score was 28 (range, 26-30). Superficial infection occurred in two patients. Local recurrence was observed in one patient, while pulmonary metastasis was identified in one patient. CONCLUSIONS: The personalized osteotomy guide plate and prosthesis based on 3D printing technique facilitate joint-preserving tumor resection and functional reconstruction. However, longer follow-up and larger sample size are required to clarify its long-term outcomes. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Prognostic value of prognostic nutritional index and systemic immune-inflammation index in patients with osteosarcoma.

The aim of this study was to evaluate the relationship between prognostic nutritional index (PNI) and systemic immune-inflammation index (SII) and clinical features and prognosis of osteosarcoma patients. We retrospectively investigated 126 patients with surgery for osteosarcoma between 2012 and 2018 at our hospital. The preoperative PNI was calculated as albumin level (g/L) + 5 × total lymphocyte count (10 9 /L). The SII was defined as platelet × neutrophil/lymphocyte counts. The optimal cut-off values for PNI and SII were evaluated with receiver operating curve analysis. Clinical features and PNI and SII were tested with the χ 2 test. The effects of PNI and SII on overall survival (OS) was investigated by Kaplan-Meier method and Cox proportional hazards model. A low preoperative PNI was remarkably correlated with tumor size, Enneking stage, pathological fracture, local recurrence, metastasis, and neoadjuvant chemotherapy ( p < 0.05). Whereas, a high SII was significantly associated with tumor size, histological type, Enneking stage, and neoadjuvant chemotherapy ( p < 0.05). There was a significant negative relationship between the PNI and SII ( r = 0.384; p < 0.001). For univariate analyses, the results revealed that tumor size, local recurrence, metastasis, PNI, and SII were predictors of OS ( p < 0.05). In multivariate analyses, local recurrence ( p = 0.010), metastasis ( p < 0.001), PNI ( p < 0.001), and SII ( p = 0.029) as independent prognostic factors were significantly correlated with OS. This study suggested that PNI and SII could be important prognostic parameters for patients with osteosarcoma.

Information spread of emergency events: path searching on social networks.

Emergency has attracted global attentions of government and the public, and it will easily trigger a series of serious social problems if it is not supervised effectively in the dissemination process. In the Internet world, people communicate with each other and form various virtual communities based on social networks, which lead to a complex and fast information spread pattern of emergency events. This paper collects Internet data based on data acquisition and topic detection technology, analyzes the process of information spread on social networks, describes the diffusions and impacts of that information from the perspective of random graph, and finally seeks the key paths through an improved IBF algorithm. Application cases have shown that this algorithm can search the shortest spread paths efficiently, which may help us to guide and control the information dissemination of emergency events on early warning.

Silver nanoparticles modified sulfur-containing POSS polymer membrane substrate for adsorption and surface-enhanced Raman scattering analysis of chrysoidine in food samples.

In analysis of complex samples, the stability and sensitivity of surface-enhanced Raman scattering (SERS) substrates may be compromised by matrix interference. To address this issue, a membrane substrate was prepared for fast enrichment, separation, and detection of chrysoidine all-in-one. The silver nanoparticles modified sulfur-containing POSS polymer (AgNPs/POSS-P-S) SERS membrane substrate was fabricated using polyhedral oligomeric silsesquioxane (POSS) as support materials. Through in-situ growth, AgNPs were uniformly modified on POSS-P-S to ensure the stability and SERS activity of the membrane substrate. The enhancement factor of the malachite green was up to 5.3 × 105. By loading the AgNPs/POSS-P-S on membrane, on the other hand, the SERS membrane substrate can also serve as an adsorption medium for separating chrysoidine from sample matrix. Furthermore, the specific sensing mechanism of AgNPs/POSS-P-S for chrysoidine was investigated and a fast, sensitive, and selective method for its quantification was established, with a linear range of 0.010-2.0 mg/L and the limits of detection at 3.7 µg/L. In addition, the SERS method was successfully applied for the analysis of chrysoidine in beverages and chili products with the recoveries in the range of 83.5%-113.4 % and the relative standard deviations in 3.2%-9.0 %. The proposed AgNPs/POSS-P-S membrane based SRES method has great potential for rapid chrysoidine analysis in food samples.

Iron-Based Nanovehicle Delivering Fin56 for Hyperthermia-Boosted Ferroptosis Therapy Against Osteosarcoma.

Background: Although systemic chemotherapy is a standard approach for osteosarcoma (OS) treatment, its efficacy is limited by the inherent or acquired resistance to apoptosis of tumor cells. Ferroptosis is considered as an effective strategy capable of stimulating alternative pathways of cancer cell demise. The purpose of this study is to develop a novel strategy boosting ferroptotic cascade for synergistic cancer therapy. Methods and Results: A novel nanovehicle composed of arginine-glycine-aspartate (RGD) modified mesoporous silica-coated iron oxide loading Fin56 was rationally prepared (FSR-Fin56). With the RGD-mediated targeting affinity, FSR-Fin56 could achieve selective accumulation and accurate delivery of cargos into cancer cells. Upon exposure to NIR light, the nanovehicle could generate localized hyperthermia and disintegrate to liberate the therapeutic payload. The released Fin56 triggered the degradation of GPX4, while Fe3+ depleted the intracellular GSH pool, producing Fe2+ as a Fenton agent. The local rise in temperature, in conjunction with Fe2+-mediated Fenton reaction, led to a rapid and significant accumulation of ROS, culminating in LPOs and ferroptotic death. The outstanding therapeutic efficacy and safety of the nanovehicle were validated both in vitro and in vivo. Conclusion: The Fin56-loaded FSR nanovehicle could effectively disturb the redox balance in cancer cells. Coupled with NIR laser irradiation, the cooperative CDT and PTT achieved a boosted ferroptosis-inducing therapy. Taken together, this study offers a compelling strategy for cancer treatment, particularly for ferroptosis-sensitive tumors like osteosarcoma.

POLE2 promotes osteosarcoma progression by enhancing the stability of CD44.

Osteosarcoma (OS) is the most prevalent primary malignancy of bone in children and adolescents. It is extremely urgent to develop a new therapy for OS. In this study, the GSE14359 chip from the GEO database was used to screen differentially expressed genes in OS. DNA polymerase epsilon 2 (POLE2) was confirmed to overexpress in OS tissues and cell lines by immunohistochemical staining, qPCR and Western blot. Knockdown of POLE2 inhibited the proliferation and migration of OS cells in vitro, as well as the growth of tumors in vivo, while the apoptosis rate was increased. Bioinformatics analysis revealed that CD44 and Rac signaling pathway were the downstream molecule and pathway of POLE2, which were inhibited by knockdown of POLE2. POLE2 reduced the ubiquitination degradation of CD44 by acting on MDM2. Moreover, knockdown of CD44 inhibited the tumor-promoting effects of POLE2 overexpression on OS cells. In conclusion, POLE2 augmented the expression of CD44 via inhibiting MDM2-mediated ubiquitination, and then activated Rac signaling pathway to influence the progression of OS, indicating that POLE2/CD44 might be potential targets for OS treatment.

Characterizing the tumor microenvironment at the single-cell level reveals a novel immune evasion mechanism in osteosarcoma.

The immune microenvironment extensively participates in tumorigenesis as well as progression in osteosarcoma (OS). However, the landscape and dynamics of immune cells in OS are poorly characterized. By analyzing single-cell RNA sequencing (scRNA-seq) data, which characterize the transcription state at single-cell resolution, we produced an atlas of the immune microenvironment in OS. The results suggested that a cluster of regulatory dendritic cells (DCs) might shape the immunosuppressive microenvironment in OS by recruiting regulatory T cells. We also found that major histocompatibility complex class I (MHC-I) molecules were downregulated in cancer cells. The findings indicated a reduction in tumor immunogenicity in OS, which can be a potential mechanism of tumor immune escape. Of note, CD24 was identified as a novel "don't eat me" signal that contributed to the immune evasion of OS cells. Altogether, our findings provide insights into the immune landscape of OS, suggesting that myeloid-targeted immunotherapy could be a promising approach to treat OS.

Amplification of oxidative stress with a hyperthermia-enhanced chemodynamic process and MTH1 inhibition for sequential tumor nanocatalytic therapy.

During chemodynamic therapy (CDT), tumor cells can adapt to hydroxyl radical (˙OH) invasion by activating DNA damage repairing mechanisms such as initiating mutt homologue 1 (MTH1) to mitigate oxidation-induced DNA lesions. Therefore, a novel sequential nano-catalytic platform MCTP-FA was developed in which ultrasmall cerium oxide nanoparticle (CeO2 NP) decorated dendritic mesoporous silica NPs (DMSN NPs) were used as the core, and after encapsulation of MTH1 inhibitor TH588, folic acid-functionalized polydopamine (PDA) was coated on the periphery. Once endocytosed into the tumor, CeO2 with multivalent elements (Ce3+/4+) could transform H2O2 into highly toxic ˙OH through a Fenton-like reaction to attack DNA as well as eliminating GSH through a redox reaction to amplify oxidative damage. Meanwhile, controllable release of TH588 hindered the MTH1-mediated damage repair process, further aggravating the oxidative damage of DNA. Thanks to the excellent photothermal performance of the PDA shell in the near-infrared (NIR) region, photothermal therapy (PTT) further improved the catalytic activity of Ce3+/4+. The therapeutic strategy of combining PTT, CDT, GSH-consumption and TH588-mediated amplification of DNA damage endows MCTP-FA with powerful tumor inhibition efficacy both in vitro and in vivo.

Comparison of macrofaunal assemblages in temperate seagrass meadows and neighboring seabeds along the southeastern coast of Shandong Peninsula, China.

Comparative study of macrofaunal assemblages in seagrass meadows and neighboring seabeds along the southeastern coast of Shandong Peninsula, China were performed. A total of 136 species were identified, including polychaetes (49 species), crustaceans (28), molluscs (58), and echinoderms (1). Species numbers of macrofauna in seagrass meadows and the neighboring seabeds were 52 and 65, respectively, whereas those in autumn were 90 and 56, respectively. Average macrofaunal abundances in spring in seagrass and neighboring seabeds were 2388.9 and 2516.7 ind./m2, respectively, whereas those in autumn were 11,689.0 and 1733.3 ind./m2, respectively. Ranges of species richness index, evenness index, and Shannon-Wiener index in seagrass meadows and the neighboring seabeds were 1.3-2.7, 0.7-0.9, 2.8-3.8, and 1.04-2.4, 0.5-0.9, 1.6-3.4 during spring, whereas those in autumn were 0.1-4.2, 0.3-0.8, 0.8-3.6 and 1.4-3.5, 0.5-0.9, 2.2-4.5. Bottom water temperature, salinity, sediment chlorophyll a concentration, and water content were the most important environmental factors influencing macrofaunal assemblages.

Oxidative stress induced by berberine-based mitochondria-targeted low temperature photothermal therapy.

Introduction: Mitochondria-targeted low-temperature photothermal therapy (LPTT) is a promising strategy that could maximize anticancer effects and overcome tumor thermal resistance. However, the successful synthesis of mitochondria-targeted nanodrug delivery system for LPTT still faces diverse challenges, such as laborious preparations processes, low drug-loading, and significant systemic toxicity from the carriers. Methods: In this study, we used the tumor-targeting folic acid (FA) and mitochondria-targeting berberine (BBR) derivatives (BD) co-modified polyethylene glycol (PEG)-decorated graphene oxide (GO) to synthesize a novel mitochondria-targeting nanocomposite (GO-PEG-FA/BD), which can effectively accumulate in mitochondria of the osteosarcoma (OS) cells and achieve enhanced mitochondria-targeted LPTT effects with minimal cell toxicity. The mitochondria-targeted LPTT effects were validated both in vitro and vivo. Results: In vitro experiments, the nanocomposites (GO-PEG-FA/BD) could eliminate membrane potential (ΔΨm), deprive the ATP of cancer cells, and increase the levels of reactive oxygen species (ROS), which ultimately induce oxidative stress damage. Furthermore, in vivo results showed that the enhanced mitochondria-targeted LPTT could exert an excellent anti-cancer effect with minimal toxicity. Discussion: Taken together, this study provides a practicable strategy to develop an ingenious nanoplatform for cancer synergetic therapy via mitochondria-targeted LPTT, which hold enormous potential for future clinical translation.