Design of Single-atom Catalysts on C5N2 for Nitrogen Fixation at Ambient Conditions : A First-principles Study.

Single atom catalysts (SACs) exhibit the flexible coordination structure of the active site and high utilization of active atoms, making them promising candidates for nitrogen reduction reaction (NRR) under ambient conditions. By the aid of first-principles calculations based on DFT, we have systematically explored the NRR catalytic behavior of thirteen 4d- and 5d-transition metal atoms anchored on 2D porous graphite carbon nitride C5N2. With high selectivity and outstanding activity, Zr, Nb, Mo, Ta, W and Re-doped C5N2 are identified as potential nominees for NRR. Particularly, Mo@C5N2 possesses an impressive low limiting potential of -0.39 V (corresponding to a very low temperature and atmospheric pressure), featuring the potential determining step involving *N-N transitions to *N-NH via the distal path. The catalytic performance of TM@C5N2 can be well characterized by the adsorption strength of intermediate *N2H. Moreover, there exists a volcanic relationship between the catalytic property UL and the structure descriptor Ψ, which validates the robustness and universality of Ψ, combined with our previous study. This work sheds light on the design of SACs with eminent NRR performance.

Red cell distribution width to total serum calcium ratio and in-hospital mortality risk in patients with acute ischemic stroke: A MIMIC-IV retrospective analysis.

We investigated the relationship among red cell distribution width (RDW), to total serum calcium (TSC) ratio (RCR), and in-hospital mortality in patients with acute ischemic stroke (AIS). This study was a retrospective analysis. The data of 2700 AIS patients was retrospectively analyzed from the Medical Information Mart for Intensive Care database (version IV). The main outcome of interest was in-hospital mortality. A Cox proportional hazards regression model was used to determine whether RCR was independently associated with in-hospital mortality. The Kaplan-Meier method was used to plot the survival curves for RCR. Subgroup analyses were performed to measure the mortality across various subgroups. The area under curve (AUC) of receiver operating characteristic curve (ROC) was calculated to ascertain the quality of RCR as a predictor of in-hospital mortality in patients with AIS. In the multivariate analysis, statistically significant differences were identified in age, ethnicity, length of ICU stay, mechanical ventilation, sequential organ failure assessment (SOFA) score, RDW, hemoglobin, RCR, whether taking anticoagulants, hyperlipidemia, and atrial fibrillation (P < .05). A threshold inflection point value of 1.83 was obtained through a two-piecewise regression model. There was a non-linear relationship between RCR and hospital mortality in patients with AIS. The hazard ratio (HR) and the 95% confidence intervals (CI) on the right and left of the inflection point were 0.93 (0.57-1.51; P = .7660) and 2.96 (1.37-6.42; P = .0060), respectively. The Kaplan-Meier curve indicated that survival rates were higher when RCR was ≤ 1.83 and lower when RDW was > 1.83 after adjustment for age, gender, BMI, ethnicity. The area under curve (AUC) of RCR was 0.715. A higher RCR was associated with an increased risk of in-hospital mortality in patients with AIS.

An oncolytic virus delivering tumor-irrelevant bystander T cell epitopes induces anti-tumor immunity and potentiates cancer immunotherapy.

Tumor-specific T cells are crucial in anti-tumor immunity and act as targets for cancer immunotherapies. However, these cells are numerically scarce and functionally exhausted in the tumor microenvironment (TME), leading to inefficacious immunotherapies in most patients with cancer. By contrast, emerging evidence suggested that tumor-irrelevant bystander T (TBYS) cells are abundant and preserve functional memory properties in the TME. To leverage TBYS cells in the TME to eliminate tumor cells, we engineered oncolytic virus (OV) encoding TBYS epitopes (OV-BYTE) to redirect the antigen specificity of tumor cells to pre-existing TBYS cells, leading to effective tumor inhibition in multiple preclinical models. Mechanistically, OV-BYTE induced epitope spreading of tumor antigens to elicit more diverse tumor-specific T cell responses. Remarkably, the OV-BYTE strategy targeting human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell memory efficiently inhibited tumor progression in a human tumor cell-derived xenograft model, providing important insights into the improvement of cancer immunotherapies in a large population with a history of SARS-CoV-2 infection or coronavirus disease 2019 (COVID-19) vaccination.

The relationship between red cell distribution width, serum calcium ratio, and in-hospital mortality among patients with acute respiratory failure: A retrospective cohort study of the MIMIC-IV database.

To investigate the impact of RDW/CA (the ratio of red cell distribution width to calcium) on in-hospital mortality in patients with acute respiratory failure (ARF). This retrospective cohort study analyzed the data of 6981 ARF patients from the Medical Information Mart for Intensive Care (MIMIC-IV) database 2.0. Critically ill participants between 2008 and 2019 at the Beth Israel Deaconess Medical Center in Boston. The primary outcome of interest was in-hospital mortality. A Cox proportional hazards regression model was used to determine whether the RDW/CA ratio independently correlated with in-hospital mortality. The Kaplan-Meier method was used to plot the survival curves of the RDW/CA. Subgroup analyses were performed to measure the mortality across various subgroups. After adjusting for potential covariates, we found that a higher RDW/CA was associated with an increased risk of in-hospital mortality (HR = 1.17, 95% CI: 1.01-1.35, P = .0365) in ARF patients. A nonlinear relationship was observed between RDW/CA and in-hospital mortality, with an inflection point of 1.97. When RDW/CA ≥ 1.97 was positively correlated with in-hospital mortality in patients with ARF (HR = 1.554, 95% CI: 1.183-2.042, P = .0015). The Kaplan-Meier curve indicated the higher survival rates for RDW/CA < 1.97 and the lower for RDW/CA ≥ 1.97 after adjustment for age, gender, body mass index, and ethnicity. RDW/CA is an independent predictor of in-hospital mortality in patients with ARF. Furthermore, a nonlinear relationship was observed between RDW/CA and in-hospital mortality in patients with ARF.

Prediction of the risk of severe small bowel obstruction and effects of Houpu Paiqi mixture in patients undergoing surgery for small bowel obstruction.

AIM: Small bowel obstruction is a common condition that requires emergency surgery. Slow recovery of bowel function after surgery or the occurrence of one or more complications can exacerbate the disease and result in severe small bowel obstruction (SSBO), significantly impacting recovery. It is characterized by a failure to regain enteral nutrition promptly, requiring long-term intensive care. Therefore, it is necessary to identify factors that predict SSBO, to allow early intervention for patients likely to develop this condition. METHODS: Of the 260 patients who underwent emergency or elective surgery for small bowel obstruction between January 2018 and December 2022, 45 developed SSBO. The least absolute shrinkage and selection operator regression model was applied to optimize factor selection and multivariable logistic regression analysis was used to construct a predictive model. The performance and clinical utility of the nomogram were determined and internal validation was conducted. In addition, the effects of the Houpu Paiqi mixture on postoperative recovery were analyzed by comparing the clinical data of 28 patients who were treated with the mixture and 61patients who did not receive it. RESULTS: The predictors included in the prediction nomogram were age, peritonitis, intestinal resection and anastomosis, complications, operation time, Acute Physiology and Chronic Health Evaluation II score, white blood cell count, and procalcitonin level. The model had an area under the receiver operating characteristic curve of 0.948 (95% confidence interval: 0.814-0.956). Decision curve analysis demonstrated that the SSBO risk nomogram had a good net clinical benefit. In addition, treatment with the Houpu Paiqi mixture reduced postoperative exhaust time, postoperative defecation time, time to first postoperative liquid feed, and length of stay in hospital. CONCLUSIONS: We developed a nomogram that can assist clinicians in identifying patients at greater risk of SSBO, which may aid in early diagnosis and intervention. Additionally, we found that the Houpu Paiqi mixture promoted postoperative recovery.

Comparison and evaluation of L. reuteri and L. rhamnosus-fermented egg yolk on the physicochemical and flavor properties of cookies.

The study aims to explore an effective approach to improve the sensory quality and consumer satisfaction of cookies in the food industry. L. reuteri and L. rhamnosus were chosen to ferment egg yolk and their effects on dough properties and physicochemical properties, flavor, texture, color, and sensory acceptability of cookies were studied. Results show that the utilization of fermented egg yolk significantly decreased baking loss and increased spread factor of cookies. GC-MS analysis indicates different Lactobacillus species enhanced cookie flavor through unique mechanisms. Texture analysis shows cookies prepared with L. rhamnosus-fermented egg yolk had significantly lower hardness (1807.12 g) than control cookies (2028.34 g). Sensory evaluation reveals the L. reuteri-fermented egg yolk significantly improved the overall acceptability of cookies by enhancing appearance, flavor, and mouthfeel scores. These findings have practical implications for food manufacturers seeking to enhance their product's quality and appeal, thereby gaining a competitive edge in the market.

Phosvitin-based hydrogels prepared in AmimCl under magnetic field treatment: Structural characteristics, biological functions, and application in skin wound healing.

Due to the serious bacterial infection of skin and the waste of petroleum-based materials, there is an urgent need to develop natural biodegradable wound dressings with high antibacterial activity. Phosvitin (PSV) has shown its natural antioxidant and antibacterial properties, making it an excellent material for preparing wound healing dressings. In this study, we investigated the effect of magnetic field on the preparation of PSV-Microcrystalline Cellulose (MCC) composite hydrogels in 1-Allyl-3-methylimidazolium chloride (AmimCl) system. The results showed that the prepared hydrogels exhibited homogeneous surface structure, suitable swelling capacity and elasticity modulus, and sufficient thermal stability. The excellent antibacterial and antioxidant activities of hydrogels were mainly resulting from AmimCl and PSV, respectively, and the properties were enhanced after magnetic field treatment. The proteomics analysis indicated that AmimCl can readily penetrate the biological membranes of Staphylococcus aureus (S. aureus), upsetting the metabolism and reducing the virulence. The hydrogels showed great blood compatibility. Compared with the commercial materials, the 5 mT-treated hydrogels presented a comparable wound healing rate in the full-thickness skin injury model. On day 7, the wound healing rate of the 5 mT group reached approximately 84.40 %, which was significantly higher than that of the control group, 72.88 % (P < 0.05). In conclusion, our work provides experience for the development of biodegradable materials combined in ionic liquids and magnetic field, and explores their applications in wound healing dressings.

Photoactivatable Aptamer-CRISPR Nanodevice Enables Precise Profiling of Interferon-Gamma Release in Humanized Mice.

Real-time dynamic imaging of immunoactivation-related cytokines is crucial for evaluating the efficacy of immune checkpoint blockade therapy and optimizing the treatment regimen. We introduce herein a spatiotemporally controlled nanodevice that allows in situ photoactivated imaging of interferon-gamma (IFN-γ) secretion from T cells in vitro and in vivo. The nanodevice is constructed by rational engineering of an aptamer-embedded, UV-cleavable PC-DNA probe and further integration with upconversion nanoparticles- and CRISPR-Cas12a-enhanced fluorescence systems. Using human peripheral blood mononuclear cells (PBMC)-engrafted mouse models, this nanodevice allows for the quantitative imaging of endogenous IFN-γ and its intratumoral dynamics responding to antiprogrammed cell death receptor 1 (anti-PD-1) therapy. This study thus provides a toolbox for boosting the sensitivity and precision of cytokine imaging during immune checkpoint blockade therapy, enlightening research toward imaging-guided tumor therapy.

Association of magnesium sulfate use with mortality in critically ill patients with sepsis: a retrospective propensity score-matched cohort study.

BACKGROUND: Trials have demonstrated lower rates of acute kidney injury in critically ill patients receiving magnesium supplementation, but they have yielded conflicting results regarding mortality. METHODS: This is a retrospective cohort study based on the MIMIC-IV (Medical Information Mart in Intensive Care-IV) database. Adult critically ill patients with sepsis were included in the analysis. The exposure was magnesium sulfate use during ICU stay. The primary outcome was 28-day all-cause mortality. Propensity score matching (PSM) was conducted at a 1:1 ratio. Multivariable analyses were used to adjust for confounders. RESULTS: The pre-matched and propensity score-matched cohorts included 10 999 and 6052 patients, respectively. In the PSM analysis, 28-day all-cause mortality rate was 20.2% (611/3026) in the magnesium sulfate use group and 25.0% (757/3026) in the no use group. Magnesium sulfate use was associated with lower 28-day all-cause mortality (hazard ratio [HR], 0.70; 95% CI, 0.61-0.79; P<0.001). Lower mortality was observed regardless of baseline serum magnesium status: for hypomagnesaemia, HR, 0.64; 95% confidence interval (CI), 0.45-0.93; P=0.020; for normomagnesaemia, HR, 0.70; 95% CI, 0.61-0.80; P<0.001. Magnesium sulfate use was also associated with lower ICU mortality (odds ratio [OR], 0.52; 95% CI, 0.42-0.64; P<0.001), lower in-hospital mortality (OR, 0.65; 95% CI, 0.55-0.77; P<0.001), and renal replacement therapy (OR, 0.67; 95% CI, 0.52-0.87; P=0.002). A sensitivity analysis using the entire cohort also demonstrated lower 28-day all-cause mortality (HR, 0.62; 95% CI, 0.56-0.69; P<0.001). CONCLUSIONS: Magnesium sulfate use was associated with lower mortality in critically ill patients with sepsis. Prospective studies are needed to verify this finding.

Risk factors and prediction model for inpatient surgical site infection after elective abdominal surgery.

BACKGROUND: Surgical site infections (SSIs) are the commonest healthcare-associated infection. In addition to increasing mortality, it also lengthens the hospital stay and raises healthcare expenses. SSIs are challenging to predict, with most models having poor predictability. Therefore, we developed a prediction model for SSI after elective abdominal surgery by identifying risk factors. AIM: To analyse the data on inpatients undergoing elective abdominal surgery to identify risk factors and develop predictive models that will help clinicians assess patients preoperatively. METHODS: We retrospectively analysed the inpatient records of Shaanxi Provincial People's Hospital from January 1, 2018 to January 1, 2021. We included the demographic data of the patients and their haematological test results in our analysis. The attending physicians provided the Nutritional Risk Screening 2002 (NRS 2002) scores. The surgeons and anaesthesiologists manually calculated the National Nosocomial Infections Surveillance (NNIS) scores. Inpatient SSI risk factors were evaluated using univariate analysis and multivariate logistic regression. Nomograms were used in the predictive models. The receiver operating characteristic and area under the curve values were used to measure the specificity and accuracy of the model. RESULTS: A total of 3018 patients met the inclusion criteria. The surgical sites included the uterus (42.2%), the liver (27.6%), the gastrointestinal tract (19.1%), the appendix (5.9%), the kidney (3.7%), and the groin area (1.4%). SSI occurred in 5% of the patients (n = 150). The risk factors associated with SSI were as follows: Age; gender; marital status; place of residence; history of diabetes; surgical season; surgical site; NRS 2002 score; preoperative white blood cell, procalcitonin (PCT), albumin, and low-density lipoprotein cholesterol (LDL) levels; preoperative antibiotic use; anaesthesia method; incision grade; NNIS score; intraoperative blood loss; intraoperative drainage tube placement; surgical operation items. Multivariate logistic regression revealed the following independent risk factors: A history of diabetes [odds ratio (OR) = 5.698, 95% confidence interval (CI): 3.305-9.825, P = 0.001], antibiotic use (OR = 14.977, 95%CI: 2.865-78.299, P = 0.001), an NRS 2002 score of ≥ 3 (OR = 2.426, 95%CI: 1.199-4.909, P = 0.014), general anaesthesia (OR = 3.334, 95%CI: 1.134-9.806, P = 0.029), an NNIS score of ≥ 2 (OR = 2.362, 95%CI: 1.019-5.476, P = 0.045), PCT ≥ 0.05 µg/L (OR = 1.687, 95%CI: 1.056-2.695, P = 0.029), LDL < 3.37 mmol/L (OR = 1.719, 95%CI: 1.039-2.842, P = 0.035), intraoperative blood loss ≥ 200 mL (OR = 29.026, 95%CI: 13.751-61.266, P < 0.001), surgical season (P < 0.05), surgical site (P < 0.05), and incision grade I or III (P < 0.05). The overall area under the receiver operating characteristic curve of the predictive model was 0.926, which is significantly higher than the NNIS score (0.662). CONCLUSION: The patient's condition and haematological test indicators form the bases of our prediction model. It is a novel, efficient, and highly accurate predictive model for preventing postoperative SSI, thereby improving the prognosis in patients undergoing abdominal surgery.

Investigation on physicochemical properties, sensory quality and storage stability of mayonnaise prepared from lactic acid fermented egg yolk.

In this research, the physicochemical properties, sensory quality, and storage stability of mayonnaise prepared from egg yolk fermented for different times (0, 3, 6, and 9 h) have been investigated. Compared with control mayonnaise (3.50 µm and 92.88%), mayonnaise prepared from fermented egg yolk possessed significantly lower particle size (3.32-3.41 µm) and higher emulsion stability (97.26-98.72%). Meanwhile, texture, color, and gas chromatography-mass spectrometry (GC-MS) analysis revealed that the fermented egg yolk significantly enhanced the firmness, consistency and cohesiveness, lightness and redness, and flavor profile of mayonnaise. Sensory evaluation showed that mayonnaise with 3 h-fermented egg yolk exhibited the highest sensory scores. And the microscopic and appearance characteristics revealed that fermented egg yolk endowed mayonnaise with a more stable appearance after 30 days of storage. These results indicated that lactic acid fermentation of egg yolk is a feasible way to improve consumer acceptability and shelf life of mayonnaise.

Bazedoxifene attenuates intestinal injury in sepsis by suppressing the NF-κB/NLRP3 signaling pathways.

Acute inflammatory injury is the primary cause of sepsis, leading to various organ failures. Bazedoxifene (BAZ) has been proven to have anti-inflammatory effects. However, its effects on sepsis-induced intestinal injury are unclear. Here, we demonstrated the beneficial effects of BAZ on intestinal injury and explored the underlying mechanisms using cecal ligation and perforation (CLP)-mediated sepsis mouse model and in vitro cultured intestinal epithelial MODE-K cells. We found that BAZ elevated the survival rate of septic mice and attenuated CLP-triggered intestinal damage. BAZ inhibited intestinal inflammation and restored the impaired intestinal barriers in CLP mice. The mechanistic study in lipopolysaccharide (LPS)/adenosine triphosphate (ATP)-stimulated MODE-K cells showed that BAZ significantly downregulated the expression of NOD-like receptor protein 3 (NLRP3), interleukin-1ß (IL-1ß), caspase-1, and gasdermin D (GSDMD), and markedly reduced the phosphorylation of molecules in the nuclear factor kappa B (NF-κB) pathway. Moreover, BAZ prominently rescued the decreased viability of MODE-K cells and reduced lactate dehydrogenase (LDH) release upon LPS/ATP challenge. However, BAZ did not affect the inflammasome assembly, as evidenced by the lack of changes in ASC (apoptosis speck-like protein containing a CARD) speck formation. Our results suggest that BAZ relieves inflammation and intestinal barrier function disruption by suppressing the NF-κB/NLRP3 signaling pathways. Therefore, BAZ is a potential therapeutic candidate for treating intestinal injury in sepsis.

Betulinaldehyde exhibits effective anti-tumor effects in A549 cells by regulating intracellular autophagy.

It is of great significance to find new effective drugs for an adjuvant therapy targeting lung cancer to improve the survival rate and prognosis of patients with the disease. Previous studies have confirmed that certain Chinese herbal extracts have clear anti-tumor effects, and in our preliminary study, betulinaldehyde was screened for its potential anti-tumor effects. The current study thus aimed to confirm the anti-tumor effect of betulinaldehyde, using in vitro experiments to explore its underlying molecular mechanism. It was found that betulinaldehyde treatment significantly inhibited the viability, proliferation, and migration of A549 cells in a dose-dependent manner. In addition, betulinaldehyde inhibited the activation of Akt, MAPK, and STAT3 signaling pathways in A549 cells in a time-dependent manner. More importantly, betulinaldehyde also decreased the expression level of SQSTM1 protein, increased the expression level of LC3 II, and increased the autophagy flux in A549 cells. The pretreatment of A549 cells with the autophagy inhibitor, 3-methyladenine, could partially negate the anti-tumor effects of betulinaldehyde. These findings suggest that betulinaldehyde could significantly inhibit the oncological activity of A549 cells by regulating the intracellular autophagy level, making it a potentially effective option for the adjuvant therapy used to treat lung cancer in the future.

Calcitonin gene-related peptide ameliorates sepsis-induced intestinal injury by suppressing NLRP3 inflammasome activation.

Intestinal damage has long been viewed as the primary cause of sepsis-induced multiple organ dysfunction syndrome (MODS). Previous studies have demonstrated that calcitonin gene-related peptide (CGRP) exhibits anti-inflammatory and protective effects in mice exposed to endotoxin. This study investigated whether CGRP protects against sepsis-induced intestinal damage and its underlying mechanisms. Using a murine caecal ligation and puncture (CLP) model, we observed elevated serum and intestinal CGRP levels in septic mice. CGRP knockout (KO) mice showed more severe intestinal barrier damage, excessive NLRP3 inflammasome activation and higher levels of inflammation. In vitro, we used lipopolysaccharide (LPS) and adenosine triphosphate (ATP) to activate the NLRP3 inflammasome in MODE-K murine intestinal epithelial cells. CGRP inhibited NF-κB pathway activation; prevented ASC assembly and ROS accumulation; significantly decreased NLRP3, Caspase-1 p10, and IL-1ß levels and LDH release; and increased cell viability. Treatment with an IL-1ß inhibitor or CGRP suppressed p38 MAPK and ERK1/2 pathway activation and increased ZO-1 and Occludin protein levels in LPS+ATP-treated MODE-K cells. Finally, we used the CGRP upstream agonist drug rutaecarpine (RUT) to control endogenous CGRP release in mice, and this drug demonstrated good therapeutic effects on septic intestinal injury. In conclusion, our results suggest that CGRP ameliorates sepsis-induced intestinal damage, providing valuable insights for drug development.

RDW-to-ALB Ratio Is an Independent Predictor for 30-Day All-Cause Mortality in Patients with Acute Ischemic Stroke: A Retrospective Analysis from the MIMIC-IV Database.

Purpose: Previous studies have shown that the peripheral red blood cell distribution width (RDW) and human serum albumin (ALB) were both predictors of the risk and mortality of cerebrovascular diseases, and the ratio of RDW to ALB (RAR) was a combined new index that can predict the prognosis of the cardiovascular and respiration systemic diseases, but its role in cerebrovascular diseases had not been effectively evaluated. This study is aimed at exploring whether RAR can effectively predict the 30-day all-cause mortality of acute ischemic stroke (AIS) patients. Methods: This retrospective cohort study was conducted on AIS patients (age > 18 years) in the intensive care database MIMIC-IV. The RAR was measured based on the red blood cell distribution width and albumin. The main result was 30-day all-cause mortality, and the secondary results were ICU mortality and hospital mortality. Obtain the odds ratio (OR) estimate from the logistic regression model of log-transformed RAR values and mortality. We had used another database for external validation. Results: A total of 1412 patients were enrolled, with an average age of 68.8 ± 15.9, including 708 (50.1%) males. When log-transformed RAR values were used as a continuous variable, as the values increases, the risk of death increases (30-day all-cause mortality OR = 4.02 (2.21, 7.32) P < 0.0001, ICU mortality OR = 3.81 (1.92, 7.54) P = 0.0001, and hospital mortality OR = 3.31 (1.83, 6.00) P < 0.0001), when the values were used as three-category variables and as a trend variable was also positively correlated with each mortality rate. Especially as the categorical variables, a dose-response relationship was clearly observed, that was, as the category of RAR increased (Q1 to Q3), the HR value of the risk of death gradually steadily increased. Such a relationship can also be observed in the external validation database. In the subgroup analysis, we observed an increased risk of death in the patient with hyperlipidemia and low HAS-BLED scores; however, no significant interaction was found in other subgroup analyses (including the diagnostic sequence of AIS). Conclusion: RAR was a predictor of mortality in AIS patients. However, more in-depth research is needed to further analyze and confirm the role of RAR in AIS patients.

Research on the Properties of Zein, Soy Protein Isolate, and Wheat Gluten Protein-Based Films Containing Cellulose Nanocrystals.

Plant protein films are a research hotpot in the current food packaging field for their renewable and bio-compatibility, and further improving the physicochemical properties of plant protein films in combination with biodegradable materials is of great significance. In this study, we selected cellulose nanocrystals (CNC) to modify the protein films with soybean protein isolate (SPI), wheat gluten protein (WGP), and Zein, and the physicochemical properties were studied. The results showed that the hardness and opacity of Zein-based films decreased by 16.61% and 54.12% with the incorporation of CNC, respectively. The SPI-based films performed with lower hardness and higher tensile strength. The thickness and opacity of WGP-based films increased by 39.76% and 214.38% after combination with CNC, respectively. Accordingly, this study showed that CNC could largely modify the physicochemical properties of the plant protein films, which provided a reference for the preparation of modified plant protein films using biodegradable materials.

Sinomenine promotes differentiation of induced pluripotent stem cells into immature dendritic cells with high induction of immune tolerance.

BACKGROUND: Immature dendritic cells (imDCs) play an important role in the induction of donor-specific transplant immunotolerance. However, these cells have limitations, such as rapid maturation and a short lifespan in vivo. In previous studies, induced pluripotent stem cells (iPSCs) differentiated into imDCs, and sinomenine (SN) was used to inhibit the maturation of imDCs. AIM: To study the capacity of SN to maintain iPSC-derived imDCs (SN-iPSCs-imDCs) in an immature state and the mechanism by which SN-iPSCs-imDCs induce immunotolerance. METHODS: In this study, mouse iPSCs were induced to differentiate into imDCs in culture medium without or with SN (iPSCs-imDCs and SN-iPSCs-imDCs). The imDC-related surface markers, endocytotic capacity of fluorescein isothiocyanate-Dextran and apoptosis were analyzed by flow cytometry. The effects of iPSCs-imDCs and SN-iPSCs-imDCs on T-cell stimulatory function, and regulatory T (Treg) cell proliferative function in vitro were analyzed by mixed lymphocyte reaction. Cytokine expression was detected by ELISA. The apoptosis-related proteins of iPSCs-DCs and SN-iPSCs-DCs were analyzed by western blotting. The induced immunotolerance of SN-iPSCs-DCs was evaluated by treating recipient Balb/c skin graft mice. Statistical evaluation of graft survival was performed using Kaplan-Meier curves. RESULTS: Both iPSCs-imDCs and SN-iPSCs-imDCs were successfully obtained, and their biological characteristics and ability to induce immunotolerance were compared. SN-iPSCs-imDCs exhibited higher CD11c levels and lower CD80 and CD86 levels compared with iPSCs-imDCs. Reduced major histocompatibility complex II expression, worse T-cell stimulatory function, higher Treg cell proliferative function and stronger endocytotic capacity were observed with SN-iPSCs-imDCs (P < 0.05). The levels of interleukin (IL)-2, IL-12, interferon-γ in SN-iPSCs-imDCs were lower than those in iPSCs-imDCs, whereas IL-10 and transforming growth factor-ß levels were higher (P < 0.05). The apoptosis rate of these cells was significantly higher (P < 0.05), and the expression levels of cleaved caspase3, Bax and cleaved poly(ADP-ribose) polymerase were higher after treatment with lipopolysaccharides, but Bcl-2 was reduced. In Balb/c mice recipients immunized with iPSCs-imDCs or SN-iPSCs-imDCs 7 d before skin grafting, the SN-iPSCs-imDCs group showed lower ability to inhibit donor-specific CD4+ T-cell proliferation (P < 0.05) and a higher capacity to induce CD4+CD25+FoxP3+ Treg cell proliferation in the spleen (P < 0.05). The survival span of C57bl/6 skin grafts was significantly prolonged in immunized Balb/c recipients with a donor-specific pattern. CONCLUSION: This study demonstrated that SN-iPSCs-imDCs have potential applications in vitro and in vivo for induction of immunotolerance following organ transplantation.

A Novel Method for Preoperative Positioning of Total Ankle Replacement Using 3D Digital Model.

OBJECTIVE: To establish a digital model of the ankle joint through 3D imaging technology and explore the preoperative placement of ankle replacement prostheses. METHODS: Computed tomography images of intact ankle joints from 54 cases in the outpatient and inpatient departments of our hospital were collected; according to the INBONE® total ankle system surgery process, the surgery model and surgical osteotomy were finished using MIMICS based on computer simulation method. The shortest distance was measured between the center point and the anterior, posterior, medial, and lateral, respectively, to ensure the precise position of the ankle replacement prosthesis by digital simulation surgery. The relationship between the two variables was analyzed by bivariate correlation analysis. RESULTS: The dataset of this study included 48 cases of the sub-data set (26 males and 22 females) and included 27 cases of left ankle and 21 cases of right ankle. The average medial malleolar angle was 18.67°± 2.87°, the average amount of bone resection was 12.13 ± 1.86 cm3 , the mid-anterior distance was 1.72 ± 0.19 cm, the mid-posterior distance was 2.00 ± 0.19 cm, the ratio of mid-anterior to mid-posterior was 0.87, the mid-medial distance was 1.26 ± 0.17 cm, the mid-lateral distance was 1.19 ± 0.16 cm, and the ratio of mid-medial to mid-lateral was 1.06. After osteotomy, the anteroposterior diameter was 3.73 ± 0.32 cm, the transverse diameter was 2.46 ± 0.27 cm, and the ratio of anteroposterior diameter to transverse diameter was 1.53. In the bottom view, the shape after osteotomy is rectangular. The mid-anterior distance was strongly negatively correlated with age, the mid-anterior distance and the amount of bone resection, the mid-medial distance and the amount of bone resection, the mid-lateral distance and the amount of bone resection, the mid-lateral distance and the anteroposterior diameter, the anteroposterior diameter and the transverse diameter were all strongly positively correlated. CONCLUSION: The projection point of the lower tibia centerline on the tibial horizontal osteotomy surface is located at a position slightly anterior to the midpoint of the transverse diameter after ankle arthroplasty. The rational positioning of the total ankle replacement is located at both a position slightly anterior to the midpoint of the transverse diameter and midpoint of the anteroposterior diameter, which can be used as a reference method before total ankle arthroplasty surgery.

Lipid nanoparticle-encapsulated mRNA antibody provides long-term protection against SARS-CoV-2 in mice and hamsters.

Monoclonal antibodies represent important weapons in our arsenal to against the COVID-19 pandemic. However, this potential is severely limited by the time-consuming process of developing effective antibodies and the relative high cost of manufacturing. Herein, we present a rapid and cost-effective lipid nanoparticle (LNP) encapsulated-mRNA platform for in vivo delivery of SARS-CoV-2 neutralization antibodies. Two mRNAs encoding the light and heavy chains of a potent SARS-CoV-2 neutralizing antibody HB27, which is currently being evaluated in clinical trials, were encapsulated into clinical grade LNP formulations (named as mRNA-HB27-LNP). In vivo characterization demonstrated that intravenous administration of mRNA-HB27-LNP in mice resulted in a longer circulating half-life compared with the original HB27 antibody in protein format. More importantly, a single prophylactic administration of mRNA-HB27-LNP provided protection against SARS-CoV-2 challenge in mice at 1, 7 and even 63 days post administration. In a close contact transmission model, prophylactic administration of mRNA-HB27-LNP prevented SARS-CoV-2 infection between hamsters in a dose-dependent manner. Overall, our results demonstrate a superior long-term protection against SARS-CoV-2 conferred by a single administration of this unique mRNA antibody, highlighting the potential of this universal platform for antibody-based disease prevention and therapy against COVID-19 as well as a variety of other infectious diseases.