The Long-Acting Serine Protease Inhibitor mPEG-SPA-MDSPI16 Alleviates LPS-Induced Acute Lung Injury.

Anti-inflammatory drugs have become the second-largest class of common drugs after anti-infective drugs in animal clinical care worldwide and are often combined with other drugs to treat fever and viral diseases caused by various factors. In our previous study, a novel serine protease inhibitor-encoding gene (MDSPI16) with improved anti-inflammatory activity was selected from a constructed suppressive subducted hybridization library of housefly larvae. This protein could easily induce an immune response in animals and had a short half-life, which limited its wide application in the clinic. Thus, in this study, mPEG-succinimidyl propionate (mPEG-SPA, Mw = 5 kDa) was used to molecularly modify the MDSPI16 protein, and the modified product mPEG-SPA-MDSPI16, which strongly inhibited elastase production, was purified. It had good stability and safety, low immunogenicity, and a long half-life, and the IC50 for elastase was 86 nM. mPEG-SPA-MDSPI16 effectively inhibited the expression of neutrophil elastase and decreased ROS levels. Moreover, mPEG-SPA-MDSPI16 exerted anti-inflammatory effects by inhibiting activation of the NF-κB signaling pathway and the MAPK signaling pathway in neutrophils. It also exerted therapeutic effects on a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. In summary, mPEG-SPA-MDSPI16 is a novel anti-inflammatory protein modified with PEG that has the advantages of safety, nontoxicity, improved stability, and strong anti-inflammatory activity in vivo and in vitro and is expected to become an effective anti-inflammatory drug.

Chitosan-based multifunctional hydrogel with bio-adhesion and antioxidant properties for efficient wound hemostasis.

Benefiting from the biocompatibility, adhesiveness, and natural extracellular matrix-mimicking ability, hydrogels have received increasing research in recent years. In this study, a hydrogel system composed of dopamine, quaternized ammoniated chitosan (QCS), and polyvinylpyrrolidone was reported to exhibit fast hemostatic properties in Sprague-Dawley rat tail amputation and liver bleeding models. The results showed that this hydrogel had good hemostatic properties. The designed hydrogel showed high swelling ratios in H2O, PBS, and 0.9 % NaCl solution, indicating its capability to absorb tissue residual exudate and form a stable hydrogel. Compared with the control group, the blood loss in Sprague-Dawley rat tail amputation and liver bleeding were reduced by nearly 78 % and 76 %, respectively. Interestingly, dopamine endowed the hydrogel with antioxidant properties, thus holding a great application promise in inflammatory wounds. Furthermore, the designed hydrogel demonstrated good and reversible adhesion properties (12.23 ± 0.22 kPa-24.31 ± 0.55 kPa), ensuring its firm attachment to bleeding wounds of pig skin in wet environments. This research points out a novel path for designing chitosan-based hydrogels for biomedical applications.

Short- and long-term results of open vs laparoscopic multisegmental resection and anastomosis for synchronous colorectal cancer located in separate segments.

BACKGROUND: It remains unclear whether laparoscopic multisegmental resection and anastomosis (LMRA) is safe and advantageous over traditional open multisegmental resection and anastomosis (OMRA) for treating synchronous colorectal cancer (SCRC) located in separate segments. AIM: To compare the short-term efficacy and long-term prognosis of OMRA as well as LMRA for SCRC located in separate segments. METHODS: Patients with SCRC who underwent surgery between January 2010 and December 2021 at the Cancer Hospital, Chinese Academy of Medical Sciences and the Peking University First Hospital were retrospectively recruited. In accordance with the inclusion and exclusion criteria, 109 patients who received right hemicolectomy together with anterior resection of the rectum or right hemicolectomy and sigmoid colectomy were finally included in the study. Patients were divided into the LMRA and OMRA groups (n = 68 and 41, respectively) according to the surgical method used. The groups were compared regarding the surgical procedure's short-term efficacy and its effect on long-term patient survival. RESULTS: LMRA patients showed markedly less intraoperative blood loss than OMRA patients (100 vs 200 mL, P = 0.006). Compared to OMRA patients, LMRA patients exhibited markedly shorter postoperative first exhaust time (2 vs 3 d, P = 0.001), postoperative first fluid intake time (3 vs 4 d, P = 0.012), and postoperative hospital stay (9 vs 12 d, P = 0.002). The incidence of total postoperative complications (Clavien-Dindo grade: ≥ II) was 2.9% and 17.1% (P = 0.025) in the LMRA and OMRA groups, respectively, while the incidence of anastomotic leakage was 2.9% and 7.3% (P = 0.558) in the LMRA and OMRA groups, respectively. Furthermore, the LMRA group had a higher mean number of lymph nodes dissected than the OMRA group (45.2 vs 37.3, P = 0.020). The 5-year overall survival (OS) and disease-free survival (DFS) rates in OMRA patients were 82.9% and 78.3%, respectively, while these rates in LMRA patients were 78.2% and 72.8%, respectively. Multivariate prognostic analysis revealed that N stage [OS: HR hazard ratio (HR) = 10.161, P = 0.026; DFS: HR = 13.017, P = 0.013], but not the surgical method (LMRA/OMRA) (OS: HR = 0.834, P = 0.749; DFS: HR = 0.812, P = 0.712), was the independent influencing factor in the OS and DFS of patients with SCRC. CONCLUSION: LMRA is safe and feasible for patients with SCRC located in separate segments. Compared to OMRA, the LMRA approach has more advantages related to short-term efficacy.

First principles study of structural and electron properties in scorodite: the bulk and surface.

Scorodite (FeAsO4·2H2O) is an ideal material for the fixation of arsenic that has attracted considerable research interest in recent decades. However, the position of the H atom in the scorodite crystal structure, water molecular configuration, surface morphology, and chemical state of the surface atoms have not been reported. In this work, density functional theory (DFT) is used to optimize the scorodite crystal structure, and the atomic bonding is analyzed. At the same time, a surface model is constructed to calculate the configuration and electronic structure of the surface atoms for different coordination groups. The results show that the tetrahedral [AsO4] and octahedral [FeO4(2H2O)] groups in the scorodite crystal structure have good stability(geometry configuration), and the covalent bond strength between the As atom and the bridged oxygen atom (Ob) is greater than that between the Ob atom and the Fe atom. The water molecules in the crystal structure do not seriously deform and ionize. The configuration of the water molecules remains stable through electrostatic interactions (Ow-Fe) and hydrogen bonding (H-Ob). The Fe atoms on the surface of scorodite can coordinate with OH and H2O, while the As atoms can only form a stable coordination with OH. When an Fe atom on the surface coordinates with two H2O atoms, the Fe atom will shrink to the inside of the bulk. With the increase in the hydroxylation number of the Fe atom, the bonding strength between the Fe atom and the Ob atom decreases. Different surface configurations do not affect the stability(geometry configuration) of the [AsO4] structure. In addition, the surface water molecular layer has a very weak effect on the surface coordination configuration. By contrast, in the surface configuration of the (W + OH) structure, the change in the surface atomic layer spacing is the smallest.

Sex Estimation of Medial Aspect of the Ischiopubic Ramus in Adults Based on Deep Learning.

OBJECTIVES: To investigate the reliability and accuracy of deep learning technology in automatic sex estimation using the 3D reconstructed images of the computed tomography (CT) from the Chinese Han population. METHODS: The pelvic CT images of 700 individuals (350 males and 350 females) of the Chinese Han population aged 20 to 85 years were collected and reconstructed into 3D virtual skeletal models. The feature region images of the medial aspect of the ischiopubic ramus (MIPR) were intercepted. The Inception v4 was adopted as the image recognition model, and two methods of initial learning and transfer learning were used for training. Eighty percent of the individuals' images were randomly selected as the training and validation dataset, and the remaining were used as the test dataset. The left and right sides of the MIPR images were trained separately and combinedly. Subsequently, the models' performance was evaluated by overall accuracy, female accuracy, male accuracy, etc. RESULTS: When both sides of the MIPR images were trained separately with initial learning, the overall accuracy of the right model was 95.7%, the female accuracy and male accuracy were both 95.7%; the overall accuracy of the left model was 92.1%, the female accuracy was 88.6% and the male accuracy was 95.7%. When the left and right MIPR images were combined to train with initial learning, the overall accuracy of the model was 94.6%, the female accuracy was 92.1% and the male accuracy was 97.1%. When the left and right MIPR images were combined to train with transfer learning, the model achieved an overall accuracy of 95.7%, and the female and male accuracies were both 95.7%. CONCLUSIONS: The use of deep learning model of Inception v4 and transfer learning algorithm to construct a sex estimation model for pelvic MIPR images of Chinese Han population has high accuracy and well generalizability in human remains, which can effectively estimate the sex in adults.

Atomic reconstruction and oxygen adsorption behavior of the pyrite (100) surface: a DFT study.

The analysis of the surface chemical behavior of pyrite is highly crucial in the fields of environmental conservation, metal extraction, and flotation separation. In this paper, the mechanism of atomic reconstruction on the pyrite surface and the adsorption behavior of O2 on a reconstructed surface are calculated by density functional theory (DFT). Different reconstruction surfaces were constructed by deleting S and Fe atoms on the (100) surface of pyrite. In addition, the geometric configuration, formation energy, binding energy, cohesion energy, and surface electronic properties of the reconstruction surface were calculated. The adsorption energies and geometric configurations of O2 on different reconstructed surfaces were also determined. The results show that under Fe-poor conditions, the charge of Fe atoms increases, and S atoms form Sn on the reconstructed surface. The binding energy between the Sn and the substrate (ideal surface) is lower, which is similar to the Sn adsorption on the substrate surface with the Fe atom as the site. Sn has high cohesive energy and is resistant to being attacked by oxidants, which leads to structural collapse, and a low affinity for O2. Under S-poor conditions, the -[Fe-S]n- plane structure formed on the reconstructed surface. The -[Fe-S]n- structure stably bonds to the substrate by an Fe-S bond, and exhibits strong binding energy. However, the -[Fe-S]n- structure has low cohesive energy and exhibits thermodynamic instability. In contrast, O2 shows a strong affinity for the -[Fe-S]n- structure, indicating that the deficiency of the S atom promotes the surface oxidation reaction. The mechanism of atomic reconstruction on the surface of pyrite is of utmost importance for understanding its surface chemical behavior.

Microstructure and Phase Evolution Characteristics of the In Situ Synthesis of TiC-Reinforced AZ91D Magnesium Matrix Composites.

TiC-reinforced AZ91D magnesium alloy composites were synthesized through the in situ reaction between an AZ91D melt and Ti-C-Al preforms. The microstructural evolution characteristics and phase transformation were investigated at different melt reaction temperatures (1013, 1033, and 1053 K), with the aim of understanding the in situ formation mechanism of TiC particles from thermodynamic and kinetic perspectives. The results showed that the temperature played a critical role in determining the formation and morphology of TiC. Initially, only the Al3Ti phase was formed through the reaction between Ti and Al when the temperature was 1013 K. With the increase in the melt temperature, the A13Ti's thermodynamic stability decreased, and dissolution and precipitation reactions occurred at higher temperatures (1033 and 1053 K, respectively), contributing to the formation of TiC particles. The formation of the TiC phase was attributed to two factors: Firstly, A13Ti as an intermediate product reacted with carbon and formed TiC with increasing temperature. Secondly, the in situ TiC reaction was promoted due to the increased reaction-driving force provided by the increasing temperature.

Clinical value of microRNA-135a and MMP-13 in colon cancer.

The aim of the present study was to investigate the expression and prognostic value of microRNA-135a (miR-135a) and matrix metalloproteinase-13 (MMP-13) in serum of colon cancer (CC). A total of 117 cases of patients admitted to Sheng Li Oil Field Central Hospital from May 2015 to May 2017 were enrolled in the research group (RG), and 120 cases of subjects undergoing normal health examination were included in the control group (CG). The expression of miR-135 and MMP-13 in peripheral blood of the two groups were compared, and their values were analyzed. It was found that miR-135a was decreased and MMP-13 was increased in the RG (P<0.050), both of which were closely related to the pathological features and prognosis of CC (P<0.050), and was also significantly correlated with CEA (P<0.001). ROC curve analysis showed that both of them had great predictive value for the occurrence, prognosis and death of CC. In conclusion, miR-135a was low expressed in CC, while MMP-13 was increased in CC, suggesting that the combined detection of the two had a good diagnostic effect on the occurrence of CC, and was closely related to the prognosis of CCC patients, which might be an excellent potential indicator for the diagnosis and treatment of CC in the future.