The expansion of MDSCs induced by exosomal PD-L1 promotes the progression of gastric cancer.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are the major factor in gastric cancer (GC) immune evasion. Nevertheless, the molecular process underlying the expansion of MDSCs induced by tumor-derived exosomes (TDEs) remains elusive. METHODS: The levels of exosomal and soluble PD-L1 in ninety GC patients were examined via enzyme-linked immunosorbent assay (ELISA) to determine their prognostic value. To investigate the correlation between exosomal PD-L1 and MDSCs, the percentage of MDSCs in the peripheral blood of 57 GC patients was assessed via flow cytometry. Through ultracentrifugation, the exosomes were separated from the GC cell supernatant and detected via Western blotting, nanoparticle tracking analysis (NTA), and transmission electron microscopy (TEM). The function of exosomal PD-L1 in MDSCs was evaluated via immunofluorescence, Western blotting and flow cytometry in a GC cell-derived xenograft (CDX) model. RESULTS: The overall survival (OS) of GC patients in the high exosomal PD-L1 group was significantly lower than that of patients in the low exosomal PD-L1 group (P = 0.0042); however, there was no significant correlation between soluble PD-L1 and OS in GC patients (P = 0.0501). Furthermore, we found that the expression of exosomal PD-L1 was positively correlated with the proportions of polymorphonuclear MDSCs (PMN-MDSCs, r = 0.4944, P < 0.001) and monocytic MDSCs (M-MDSCs, r = 0.3663, P = 0.005) in GC patients, indicating that exosomal PD-L1 might induce immune suppression by promoting the aggregation of MDSCs. In addition, we found that exosomal PD-L1 might stimulate MDSC proliferation by triggering the IL-6/STAT3 signaling pathway in vitro. The CDX model confirmed that exosomal PD-L1 could stimulate tumor development and MDSC amplification. CONCLUSIONS: Exosomal PD-L1 has the potential to become a prognostic and diagnostic biomarker for GC patients. Mechanistically, MDSCs can be activated by exosomal PD-L1 through IL-6/STAT3 signaling and provide a new strategy against GC through the use of exosomal PD-L1 as a treatment target.

Melatonin prevents bone loss in osteoporotic rats with valproic acid treatment by anti-inflammatory and anti-oxidative stress.

Melatonin (MEL) has shown positive effects in anti-inflammatory and anti-oxidative stress research. This study investigates whether MEL can positively impact bone loss induced by valproic acid (VPA) in rats. The study examines changes in MC3T3-E1 cell viability and osteogenic potential, along with osteoclast differentiation in RAW264.7 cells in the presence of VPA using CCK-8, ALP staining, AR staining, and TRAP staining. In vitro experiments reveal that VPA-induced inhibition of osteogenic differentiation and promotion of osteoclastic differentiation are linked to increased inflammation and oxidative stress. Furthermore, MEL has demonstrated the ability to reduce oxidative stress and inflammation, boost osteogenic differentiation, and inhibit osteoclast differentiation. Animal experiments confirm that MEL significantly increases SOD2 expression and decreases TNF-α expression, leading to the restoration of impaired bone metabolism, enhanced bone strength, and higher bone mineral density. The combined experimental results strongly suggest that MEL can enhance osteogenic activity in the presence of VPA by reducing inflammation and oxidative stress, impeding osteoclast differentiation, and alleviating bone loss in VPA-treated rat models.

Ganoderic Acid A prevents bone loss in lipopolysaccharide-treated male rats by reducing oxidative stress and inflammatory.

Ganoderic Acid A (GAA) has demonstrated beneficial effects in anti-inflammatory and anti-oxidative stress studies. However, it remains unknown whether GAA exerts positive impacts on bone loss induced by lipopolysaccharide (LPS). This study aims to investigate the influence of GAA on bone loss in LPS-treated rats. The study assesses changes in the viability and osteogenic potential of MC3T3-E1 cells, as well as osteoclast differentiation in RAW264.7 cells in the presence of LPS using CCK-8, ALP staining, AR staining, and Tartrate-resistant acid phosphatase (TRAP) staining. In vitro experiments indicate that LPS-induced inhibition of osteoclasts (OC) and Superoxide Dismutase 2 (SOD2) correlates with heightened levels of inflammation and oxidative stress. Furthermore, GAA has displayed the ability to alleviate oxidative stress and inflammation, enhance osteogenic differentiation, and suppress osteoclast differentiation. Animal experiment also proves that GAA notably upregulates SOD2 expression and downregulates TNF-α expression, leading to the restoration of impaired bone metabolism, improved bone strength, and increased bone mineral density. The collective experimental findings strongly suggest that GAA can enhance osteogenic activity in the presence of LPS by reducing inflammation and oxidative stress, hindering osteoclast differentiation, and mitigating bone loss in LPS-treated rat models.

Protocatechualdehyde inhibits iron overload-induced bone loss by inhibiting inflammation and oxidative stress in senile rats.

The accumulating evidence has made it clear that iron overload is a crucial mechanism in bone loss. Protocatechualdehyde (PCA) has also been used to prevent osteoporosis in recent years. Whether PCA can reverse the harmful effects of iron overload on bone mass in aged rats is still unknown. Therefore, this study aimed to assess the role of PCA in iron overload-induced bone loss in senile rats. In the aged rat model, we observed that iron overload affects bone metabolism and bone remodeling, manifested by bone loss and decreased bone mineral density. The administration of PCA effectively mitigated the detrimental effects caused by iron overload, and concomitant reduction in MDA serum levels and elevation of SOD were noted. In addition, PCA-treated rats were observed to have significantly increased bone mass and elevated expression of SIRT3，BMP2，SOD2 and reduced expression of TNF-α in bone tissue. We also observed that PCA was able to reduce oxidative stress and inflammation and restore the imbalance in bone metabolism. When MC3T3-E1 and RAW264.7 cells induced osteoblast and osteoclasts differentiation, PCA intervention could significantly recover the restriction of osteogenic differentiation and up-regulation of osteoclast differentiation treated by iron overload. Further, by detecting changes in ROS, SOD, MDA, expression of SIRT3 and mitochondrial membrane potentials, we confirm that the damage caused to cells by iron overload is associated with decreased SIRT3 activity, and that 3-TYP have similar effects on oxidative stress caused by FAC. In conclusion, PCA can resist iron overload-induced bone damage by improving SIRT3 activity, anti-inflammatory and anti-oxidative stress.

Single-port versus traditional three-port laparoscopic total extraperitoneal inguinal hernia repair: A single-centre, prospective, randomised study.

OBJECTIVE: To explore the efficacy and safety of single-incision laparoscopic (SIL) technique compared with the traditional three-port total extraperitoneal (TEP) technique for inguinal hernia repair. METHODS: This prospective, randomised study involved patients who underwent surgery for inguinal hernia at our hospital from December 2021 to July 2023. Patients were randomly assigned to SIL-TEP or TEP groups based on a computer-generated random number table. Perioperative clinical indicators for the surgical approaches were evaluated. RESULTS: Of the 127 patients eligible for study, 66 were randomised to the SIL-TEP group and 61 to the TEP group. The operation time for SIL-TEP was significantly longer than for TEP but the time to return to normal activities was significantly shorter and short-term pain score was significantly lower. There were no differences between groups in intraoperative blood loss, postoperative hospital stays, pain relief time, hospitalization costs or cosmetic satisfaction scores. CONCLUSION: While SIL-TEP is more challenging than TEP for hernia repair, we found that at our centre it is comparable with regard to overall safety and feasibility. Further studies are needed to validate our findings.

Predominant P3-Type Solid-Solution Phase Transition Enables High-Stability O3-Type Na-Ion Cathodes.

Layered O3-type oxides are one of the most promising cathode materials for Na-ion batteries owing to their high capacity and straightforward synthesis. However, these materials often experience irreversible structure transitions at elevated cutoff voltages, resulting in compromised cycling stability and rate performance. To address such issues, understanding the interplay of the composition, structure, and properties is crucial. Here, we successfully introduced a P-type characteristic into the O3-type layered structure, achieving a P3-dominated solid-solution phase transition upon cycling. This modification facilitated a reversible transformation of the O3-P3-P3' structure with minimal and gradual volume changes. Consequently, the Na0.75Ni0.25Cu0.10Fe0.05Mn0.15Ti0.45O2 cathode exhibited a specific capacity of approximately 113 mAh/g, coupled with exceptional cycling performance (maintaining over 70% capacity retention after 900 cycles). These findings shed light on the composition-structure-property relationships of Na-ion layered oxides, offering valuable insights for the advancement of Na-ion batteries.

Slight Multielement Doping-Induced Structural Order-Disorder Transition for High-Performance Layered Na-Ion Oxide Cathodes.

To realize concurrently the high-energy density and excellent cycling stability, maximum utilization of redox couple, minimization of detrimental phase transition, and structural degradation of O3-type layered oxide cathodes are critical for developing Na-ion batteries. Ni2+/Ni4+ redox couple showing multielectron reaction and higher redox potential is favorable to increase the energy density. However, the Jahn-Teller distortion of Ni3+ generated upon (dis)charging results in a strong anisotropy in the local crystal structure that causes irreversible interlayer bending and chemo-mechanical cracks of the cathode particles, compromising the electrochemical properties eventually. In this work, we show a slight multielement doping strategy that enlarges the amount of active redox components while minimizing the inactive contents. The results show that the uniform distribution of multiple components can help increase the disorder degree of atom arrangement and alleviate the structural changes and detrimental anisotropy cracks. As a proof of concept, a multielement-doped O3-type Na0.9Ni0.25Cu0.05Mg0.05Zn0.05Fe0.05Al0.05Mn0.40Ti0.05Sn0.05O2 oxide is rationally prepared that presents better chemo-mechanical stability and delayed O3-P3 phase transition behavior. Compared to the high Ni-content Na0.9Ni0.35Fe0.2Mn0.45O2 cathode, this as-prepared multielement material delivers a reversible capacity of about 120 mAh/g in the voltage range of 2-4.0 V, superior cycling stability with 90% of capacity retention after 500 cycles, and excellent rate capability (more than 70% of initial capacity at 5.0 C). This work indicates that the multielement doping method is highly suitable for the development of advanced Na-ion layered oxide cathodes.

Manipulating of P2/O3 Composite Sodium Layered Oxide Cathode through Ti Substitution and Synthesis Temperature.

P2/O3 composite sodium layered oxide has emerged as a promising cathode for high-performance Na-ion batteries. However, it has been challenging to regulate accurately the phase ratio of P2/O3 composite due to their high compositional diversity, which brings about some difficulty in manipulating the electrochemical performance of P2/O3 composite. Here, we explore the effect of Ti substitution and the synthesis temperature on the crystal structure and Na storage performance of Na0.8Ni0.4Mn0.6O2. The investigation indicates Ti-substitution and altering synthesis temperature can rationally manipulate the phase ratio of P2/O3 composite, thereby purposefully regulating the cycling and rate performance of P2/O3 composite. Typically, O3-rich Na0.8Ni0.4Mn0.4Ti0.2O2-950 shows excellent cycling stability with a capacity retention of 84% (3C, 700 cycles). By elevating the proportion of P2 phase, Na0.8Ni0.4Mn0.4Ti0.2O2-850 displays concurrently improved rate capability (65% capacity retention at 5 C) and comparable cycling stability. These findings will help guide the rational design of high-performance P2/O3 composite cathodes for sodium-ion batteries.

Enhanced Electrorheological Polishing Efficiency of Alumina-Doped Titanium Dioxide Particles.

Electrorheological (ER) polishing is a novel polishing technology having flexible and tunable characteristics. At present, ER polishing uses ER particles to drive abrasive particles to polish the material surface. Under the action of high-speed centrifugation, the abrasive particles are easily separated from ER particles due to their significantly different ER effect, and this can easily cause the degradation of polishing ability. In this work, alumina-doped titanium dioxide ER polishing particles were developed via a sol-gel method. As a classical abrasive, alumina has higher hardness and can improve the ER effect of titanium dioxide by doping. Thus, alumina-doped titanium dioxide particles simultaneously possess high ER effect and high hardness. No phase separation appears in the polishing process and the result shows that alumina-doped titanium dioxide has a good polishing efficiency for materials with Mohs hardness of 3 and below.

[Prediction of internal fixation failure of femoral trochanteric fracture by external wall morphology].

OBJECTIVE: To investigate the relationship between the shape of the lateral wall and the early failure of internal fixation in the fracture of the femoral trochanteric region(FFT). METHODS: Total 295 patients with femoral trochanteric fracture underwent internal fixation from January 2015 to January 2020 were selected. The patients were divided into two groups according to whether there was early internal fixation failure after surgery, 19 patients in the failure group and 276 patients in the normal group. Gender, affected side, age, AO classification, body mass index(BMI), preoperative hemoglobin, X-ray measurement of lower lateral wall thickness, preoperative internal diseases, intraoperative blood loss, postoperative tip apex distance(TAD), postoperative neck shaft angle, operation time and other data were compared between two groups. The shape of the lateral wall was compared between two groups, and the correlation between the shape of the lateral wall and the early internal fixation failure of femoral trochanteric fracture was analyzed. RESULTS: All patients were followed up for more than 1 year. There was no significant difference between two groups in terms of intraoperative blood loss, operation time, postoperative TAD, and postoperative neck shaft angle(P>0.05). At the latest follow-up, the visual anaglue scale (VAS) of the failure group was higher than that of the normal group(P<0.01), and the Harris score of the failure group was lower than that of normal group(P<0.05). The receiver operator characteristic (ROC) curve between shape of lateral wall and failure of early internal fixation of femoral trochanteric fracture was drawn. The critical value of the midpoint lateral wall thickness was 16.5 mm, and the area under the ROC curve was 0.845;The critical value of average sidewall thickness was 16.5 mm, and the area under ROC curve was 0.838;The critical value of the axial area of the sidewall was 7.5 mm, and the area under the ROC curve was 0.826. CONCLUSION: The shape of the lateral femoral wall measured by CT could be used as a predictive factor for the early failure of internal fixation of femoral trochanteric fractures. For patients at risk, more reasonable surgical plans and postoperative preventive measures should be developed.

Electrorheological Effect of Suspensions of Polyaniline Nanoparticles with Different Morphologies.

Polyaniline (PANI) nanospheres, nanofibers, and nanoplates were prepared using the oxidative polymerization method. Scanning electron microscopy (SEM) was used to observe the three morphologies of PANI, and their structure was tested using infrared spectroscopy, X-ray diffraction, Raman spectroscopy, and X-ray photoelectron spectroscopy. The influence of particle morphology on the electrorheological (ER) effect was studied through rheological experiments and molecular dynamics (MD) simulation. The experimental and simulation results indicate that without applying an electric field, the nanofibers easily form a three-dimensional network structure in the suspension, resulting in yield stress. The three-dimensional network structure of the nanoplate suspension becomes weaker and the PANI nanosphere suspension lacks the ability to form a three-dimensional network structure. After applying an electric field, under the same condition, the yield stress and electric field-induced shear stress increment of PANI nanofibers are the highest, followed by nanoplates, and those of PANI nanospheres are the lowest. This indicates that the ER effect increases with the increase in particle morphology anisotropy. Through three-dimensional visual simulation analysis, it can be concluded that the enhanced ER effect associated with increased particle anisotropy can be attributed to improved stability in the ER chain structure.

[Fixation of anterior pelvic ring fracture with long reconstruction plate combined with MIPPO technique].

OBJECTIVE: To evaluate the efficacy of long reconstruction plate combined with minimally invasive percutaneous plate osteosynthesis(MIPPO) technique in the treatment of unstable pelvic anterior ring fractures. METHODS: From January 2013 to February 2019, 16 patients with unstable pelvic fracture were treated, including 12 males and 4 females, aged from 20 to 60 years(mean 46.5 years). According to Tile classification, there were 4 cases of type B1, 6 cases of type B2, 4 cases of type C1 and 2 cases of type C2. The fracture of all patients was closed, and the time from injury to operation was 7 to 10 days with an average of 6.2 days. The operation time, intraoperative blood loss, fracture reduction quality, fracture healing time, complications and limb function during the final follow-up were evaluated in 16 patients. RESULTS: All 16 patients were followed up for 12 to 23 months (mean 19.1 months). The operation time was 60 to 180 min (mean 107.8 min). The intraoperative blood loss was 120 to 600 ml (mean 368.1 ml). The fracture healing time was 12 to 20 weeks (mean 16.3 weeks). According to Matta criteria, the fracture reduction was excellent in 6 cases, good in 8 cases and fair in 2 cases. One patient suffered from lateral femoral cutaneous nerve injury during the operation, and the lateral thigh sensation decreased after operation, which recovered after 6 months. One patient had pain stimulated by internal fixation at the iliac fossa. The symptoms were improved after the internal fixation was removed. The fractures of 16 patients were healed satisfactorily and there was no internal fixation loosening. Majeed score at the final follow-up was 67 to 95, excellent in 10 cases, good in 4 cases and fair in 2 cases. CONCLUSION: Closed reduction and fixation of pelvic anterior ring fracture with long reconstruction plate combined with MIPPO technique through anterior approach has the advantages of less injury, less bleeding time during operation, saving operation time, high intraoperative safety, high fracture healing rate, early functional exercise after operation, and effective treatment of pelvic anterior ring fracture.

Application of a three-dimensional virtual model to study the effect of fluoroscopic angle on infra-acetabular corridor parameters and screw insertion rates.

PURPOSE: To use three-dimensional (3D) virtual models to study how the parameters and insertion rates of the infra-acetabular corridor (IAC) change under different fluoroscopic angles. METHODS: The pelvis computed tomography data of 187 patients are imported into Mimics software in DICOM format to generate a 3D model. The anterior pelvis plane is used as the reference plane to measure the diameter of the optimum IAC when the pelvis model is tilted forward by 5°, 15°, 25°, 35° and 45°. The diameter of at least 3.5 mm is defined as the cutoff for placing a 3.5 mm screw, the rate of infra-acetabular screw (IAS) insertion is calculated, and the mean length of the IAC and the mean tilt of the corridor axis in relation to the sagittal midline plane (SMP) are measured. RESULTS: The similar diameters of the IAC can be found under fluoroscopy at 5°-35°, with the largest diameter of 4.08 ± 1.84 mm and the highest screw insertion rate of 60.42% at 15° and 25°, whereas the diameter and insertion rate are lowest at 45°. The corridor length increases with increasing fluoroscopic angle, and the angle of the corridor axis to the SMP decreases gradually. CONCLUSION: The conventional fluoroscopic angle of the pelvic inlet is not suitable for the IAS insertion. The parameters of the IAC vary according to a certain rule under different fluoroscopic angles, so a surgeon can select the appropriate fluoroscopic angle in accordance with the type of fracture and the fracture line angle.

[Minimally invasive percutaneous plate internal fixation through anterolateral single incision for the treatment of open distal tibiofibula fractures].

OBJECTIVE: To investigate therapeutic effect of minimally invasive percutaneous plate internal fixation (MIPPO) through a single incision in treating open distal tibiofibula fractures. METHODS: From March 2015 to February 2019, 10 patients with open distal tibiofibula fractures were treated with MIPPO technique through single anterolateral incision, including 8 males and 2 females, aged from 31 to 68 years old. According to Gustilo classification, 6 patients were typeⅠ, 3 patients were typeⅡand 1 patient was type ⅢA. Operative time, intraoperative blood loss and fracture healing were observed, Mazur ankle joint scoring was used to evaluate clinical effect. RESULTS: All patients were followed up from 9 to 24 months. Operative time ranged from 85 to 120 min, intraoperative blood loss ranged from 80 to 200 ml, fracture healing time ranged from 18 to 30 weeks. Nine patients with Gustilo typeⅠandⅡachieved satisfactory healing wound, original wound of 1 patient with Gustilo type ⅢA was poor, and healed by skin flap transplantation at stageⅡ. No steel exposed and infection occurred. According to Mazur ankle scoring at the final following-up, total score was from 61 to 97, and 8 patients got excellent result, 1 good and 1 poor. CONCLUSION: MIPPO technique through anterolateral single incision for the treatment of open distal tibiofibula fractures could protect original medial wound in opertaion, avoid plate exposed through anterolateral extensor tendon to cover internal fixation, and MIPPO technique could protect fracture end blood flow to improve fracture healing rate, and it is a kind of choice.

A new possible megalosauroid theropod from the Middle Jurassic Xintiangou Formation of Chongqing, People's Republic of China and its implication for early tetanuran evolution.

Tetanurae is a special group of theropod dinosaurs that originated by the late Early Jurassic. It includes several early-diverging groups of generally large-bodied predators (megalosauroids, allosauroids, tyrannosauroid coelurosaurs) as well as morphologically disparate small-bodied coelurosaurs, including birds. Aspects of the evolutionary history of tetanurans remain contested, including the topology of their deep phylogenetic divergences (among Megalosauroidea, Allosauroidea and Coelurosauria). We report a new theropod, Yunyangosaurus puanensis gen. et sp. nov., based on a fragmentary specimen recovered from the Middle Jurassic Xintiangou Formation of Chongqing, southwestern China. It shares several features uniquely with some megalosauroids (the clade of megalosaurids + spinosaurids + piatnitzkysaurids), such as prominent rims around the anterior articular surfaces of cervical centra and bifurcated anterior dorsal neural spines (present in piatnitzkysaurids). Nevertheless, it also shows several features that are rare or absent among megalosauroids and more crownward tetanurans, including prominent spinopostyzgopophyseal laminae (also present in non-tetanurans and metriacanthosaurid allosauroids), flat anterior articular surfaces of the cervical centra (also present in piatnitzkysaurids and some earlier-diverging tetanurans), and the presence of a posterior pneumatic foramen or fossa (absent in most tetanurans, but sporadically present in some cervical vertebrae of piatnitzkysaurids). Yunyangosaurus therefore presents a combination of derived and apparently primitive character states that are not seen in other theropods. This suggests that patterns of morphological evolution associated with deep tetanuran divergences were more complex than currently recognized, with implications for understanding the character evolution in theropods.