Aluminium-doped Carbon Dots for the Simultaneous Selective Detection of Five Tetracycline Antibiotics.

In this paper, the aluminium-doped carbon dots (Al-CDs) were developed for simultaneous selective detection of five tetracycline antibiotics (TCs), including minocycline (MC), tetracycline (TC), oxytetracycline (OTC), doxycycline (DOC) and chlortetracycline (CTC). With the bright blue fluorescence, Al-CDs displayed excellent stability and showed no obvious fluorescence intensity changes under different ionic strength, acidic or alkaline environment, continuous ultraviolet light illumination, and even longtime storage at room temperature. As adding different antibiotics, the fluorescence of Al-CDs was strongly quenched by five TCs and showed no distinguished changes with the addition of other kinds of antibiotics. The presence of interferential metal ions, anions and small organic molecules imposed no effect on the simultaneous selective detection of five TCs. A good linear relationship was achieved for five TCs in the range of 0-100 µM, and the limit of detection for MC, TC, OTC, DOC, and CTC were 13.91 (0-100 µM), 15.54 (0-100 µM), 14.26 (0-100 µM), 13.48 (0-100 µM) and 13.88 nM (0-100 µM), respectively. Moreover, Al-CDs was successfully used to the detection of five TCs in real samples with recovery ranging from 92.47% to 122.05%, confirming a bright future for the practical applications in the assays of foods, medicines, and environments.

Development and validation of a machine learning-based nomogram for predicting HLA-B27 expression.

BACKGROUND: HLA-B27 positivity is normal in patients undergoing rheumatic diseases. The diagnosis of many diseases requires an HLA-B27 examination. METHODS: This study screened totally 1503 patients who underwent HLA-B27 examination, liver/kidney function tests, and complete blood routine examination in First Affiliated Hospital of Guangxi Medical University. The training cohort included 509 cases with HLA-B27 positivity whereas 611 with HLA-B27 negativity. In addition, validation cohort included 147 cases with HLA-B27 positivity whereas 236 with HLA-B27 negativity. In this study, 3 ML approaches, namely, LASSO, support vector machine (SVM) recursive feature elimination and random forest, were adopted for screening feature variables. Subsequently, to acquire the prediction model, the intersection was selected. Finally, differences among 148 cases with HLA-B27 positivity and negativity suffering from ankylosing spondylitis (AS) were investigated. RESULTS: Six factors, namely red blood cell count, human major compatibility complex, mean platelet volume, albumin/globulin ratio (ALB/GLB), prealbumin, and bicarbonate radical, were chosen with the aim of constructing the diagnostic nomogram using ML methods. For training queue, nomogram curve exhibited the value of area under the curve (AUC) of 0.8254496, and C-value of the model was 0.825. Moreover, nomogram C-value of the validation queue was 0.853, and the AUC value was 0.852675. Furthermore, a significant decrease in the ALB/GLB was noted among cases with HLA-B27 positivity and AS cases. CONCLUSION: To conclude, the proposed ML model can effectively predict HLA-B27 and help doctors in the diagnosis of various immune diseases.

Application of machine learning in prediction of bone cement leakage during single-level thoracolumbar percutaneous vertebroplasty.

BACKGROUND: In the elderly, osteoporotic vertebral compression fractures (OVCFs) of the thoracolumbar vertebra are common, and percutaneous vertebroplasty (PVP) is a common surgical method after fracture. Machine learning (ML) was used in this study to assist clinicians in preventing bone cement leakage during PVP surgery. METHODS: The clinical data of 374 patients with thoracolumbar OVCFs who underwent single-level PVP at The First People's Hospital of Chenzhou were chosen. It included 150 patients with bone cement leakage and 224 patients without it. We screened the feature variables using four ML methods and used the intersection to generate the prediction model. In addition, predictive models were used in the validation cohort. RESULTS: The ML method was used to select five factors to create a Nomogram diagnostic model. The nomogram model's AUC was 0.646667, and its C value was 0.647. The calibration curves revealed a consistent relationship between nomogram predictions and actual probabilities. In 91 randomized samples, the AUC of this nomogram model was 0.7555116. CONCLUSION: In this study, we invented a prediction model for bone cement leakage in single-segment PVP surgery, which can help doctors in performing better surgery with reduced risk.

A naturally evolved mutation (Ser59Gly) in glutamine synthetase confers glufosinate resistance in plants.

Glufosinate is an important and widely used non-selective herbicide active on a wide range of plant species. Evolution of resistance to glufosinate in weedy plant species (including the global weed Eleusine indica) is underway. Here, we established the molecular basis of target site glufosinate resistance in Eleusine indica. Full-length E. indica glutamine synthetase (GS) iso-genes (EiGS1-1, 1-2, 1-3, and EiGS2) were cloned, and expression of EiGS1-1 and EiGS1-2 was higher than that of EiGS2. A novel point mutation resulting in a Ser59Gly substitution in EiGS1-1 was identified in glufosinate-resistant plants. Rice calli and seedlings transformed with the mutant EiGS1-1 gene were resistant to glufosinate. Purified mutant EiGS1-1 expressed in yeast was more tolerant to glufosinate than the wild-type variant. These transgenic results correlate with a more glufosinate-resistant GS in the crude tissue extract of resistant versus susceptible E. indica plants. Structural modelling of the mutant EiGS1-1 revealed that Ser59 is not directly involved in glufosinate binding but is in contact with some important binding residues (e.g. Glu297) and especially with Asp56 that forms an intratoroidal contact interface. Importantly, the same Ser59Gly mutation was also found in geographically isolated glufosinate-resistant populations from Malaysia and China, suggesting parallel evolution of this resistance mutation.

Bio-Inspired Antibacterial Hydrogel Adhesives with High Adhesion Strength.

Traditional adhesives such as cyanoacrylate glue are mostly solvent-based. They are facing the problem of insufficient adhesion to some substrates, and also from the drawback of volatilization and release of small organic molecules in the process of usage. Therefore, a novel adhesive with non-irritating, high adhesive strength, and antibacterial properties is highly required. In this study, a full physically crosslinked zwitterionic poly(betaine sulfonate methacrylate) (PSBMA) hydrogel is proposed. The physical crosslinking interactions endow the hydrogel with good self-healing properties. Furthermore, the pure physical crosslinking hydrogel can form PSBMA powder adhesive after lyophilization and return to the hydrogel state after hydration. The mechanical properties of PSBMA adhesive can be modulated via adjusting the solid content and initiator dosage. Following the cure process similar to that of snail mucus or insect exoskeletons in nature, the adhesion of the PSBMA adhesive is improved at least 100 times than its wet state. In addition, the PSBMA adhesive is easy to be removed due to the dissociation of cross-linked structures in saltwater environments. Moreover, PSBMA adhesive with antifouling properties can effectively prevent the adhesion of proteins and bacteria, which shows potential applications in the assembly of medical devices.

Pulmonary embolism following the third thoracic tuberculosis surgery: A case report and literature review.

BACKGROUND: The study aimed to analyze the clinical effects of pulmonary embolism succeeding a third surgery conducted for multiple recurrences in thoracic tuberculosis (TB). CASE REPORT: A 74-year-old female patient developed thoracic tuberculosis and was subsequently treated in our hospital in March 2019, October 2020, and February 2021. The third surgical intervention included anterolateral thoracic lesion resection, internal fixation, posterior spinal tuberculous sinus resection, and debridement with suture. The operative time was 172 min resulting in a substantial intraoperative blood loss (2321 ml). Postoperative re-examination of chest CTPA indicated a strip filling defect and pulmonary embolism in the external branch of the right middle lobe of the lung. After completing the active treatment, the D-dimer quantification, WBC, CRP, and ESR values were 1261 ng/ml, 7.71 × 109 /L, 74.66 mg/L, and 63 mm, respectively. Chest CTPA re-examination after the treatment showed no signs of pulmonary embolism. CONCLUSION: Patients with a long-term history of multiple operations, high BMI, cerebral infarction, diabetes, and older age group were more likely to develop pulmonary embolism after spinal tuberculosis surgery. Thus, the possibility of postoperative pulmonary embolism should be thoroughly analyzed before any subsequent surgical treatment in patients with recurrent spinal tuberculosis.

Blood transfusion risk prediction in spinal tuberculosis surgery: development and assessment of a novel predictive nomogram.

OBJECTIVE: The present study attempted to predict blood transfusion risk in spinal tuberculosis surgery by using a novel predictive nomogram. METHODS: The study was conducted on the clinical data of 495 patients (167 patients in the transfusion group and 328 patients in the non-transfusion group) who underwent spinal tuberculosis surgery in our hospital from June 2012 to June 2021. The least absolute shrinkage and selection operator (LASSO) and multivariable logistic regression analyses were used to screen out statistically significant parameters, which were included to establish a novel predictive nomogram model. The receiver operating characteristic (ROC) curve, calibration curves, C-index, and decision curve analysis (DCA) were used to evaluate the model. Finally, the nomogram was further assessed through internal validation. RESULTS: The C-index of the nomogram was 0.787 (95% confidence interval: 74.6%-.82.8%). The C-value calculated by internal validation was 0.763. The area under the curve (AUC) of the predictive nomogram was 0.785, and the DCA was 0.01-0.79. CONCLUSION: A nomogram with high accuracy, clinical validity, and reliability was established to predict blood transfusion risk in spinal tuberculosis surgery. Surgeons must prepare preoperative surgical strategies and ensure adequate availability of blood before surgery.

Feasibility of 3.5 mm C2 pedicle screws in children: A computerized tomography analysis.

There have been no studies with large sample sizes on growth of the pedicle of C2 in children. In the present study we measured the pedicle of C2 through computed tomography (CT) imaging in children aged less than 14 years and evaluated the suitability of the 3.5-mm screw for the pedicle in such children. The study was conducted on CT morphometric images of 420 children in our hospital between June 2018 and June 2020. The width (D1), length (D2), height (D3), inclination angle (α), and tail angle (ß) of the C2 pedicle were measured. One-way analysis of variance and Student's t test were used for statistical analyses. The least-square method was used to analyze the curve fitting the trend of anatomical change in the pedicle. The largest degree of goodness of fit determined the best-fitting curve. The size of the pedicle of C2 increased with age. The median ranges of D1, D2, D3, α, and ß were 3.312-5.431 mm, 11.732-23.645 mm, 3.597-8.038 mm, 32.583°-36.640°, and 24.867°-31.567°, respectively. The curves fitting the trends of D1 and D3 were power functions, whereas D2 was fitted by a logarithmic curve. However, no curve fitted α or ß. A 3.5-mm screw can be placed in the pedicle of C2 in children aged more than 1 year. The growth and development trend of this pedicle can provide an anatomical reference for deciding on posterior cervical surgery and for selecting and designing pedicle screws for children.

A Retrospective Study of Factors Associated with Restoration of Thoracic Kyphosis in 43 Patients with Adolescent Idiopathic Scoliosis with Lenke Type 1 Curvature.

BACKGROUND This retrospective study aimed to identify the factors associated with successful surgical correction of thoracic kyphosis (TK) in 43 patients with adolescent idiopathic scoliosis (AIS) with Lenke type 1 curvature, in which the major curve with the largest Cobb angle was mainly in the thoracic region. MATERIAL AND METHODS We collected data from patients with Lenke 1 AIS. The following parameters were measured: Cobb angle, side-bending Cobb angle, cervical lordosis (CL), TK, lumbar lordosis (LL), pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), the sagittal vertical axis (SVA), the center of a C7 plumb line to the center sacral vertical line (C7-CSVL), correction rate, Ponte osteotomy, flexibility, and screw density. Univariate analysis and multivariate logistic regression analyses were performed. RESULTS Among the 43 cases analyzed, the mean postoperative Cobb angle at the last follow-up, C7-CSVL, SVA, CL, TK, LL, PI, SS, and PT were respectively 21.33±9.47°, 10.41±8.45 mm, 19.68±14.33 mm, 16.19±7.45°, 23.12±7.45°, 50.33±11.37°, 49.70±9.83°, 39.42±8.11°, and 10.16±6.63°. Univariate analysis suggested that preoperative TK, preoperative LL, and Ponte osteotomy were statistically significant (P<0.05), and multivariate analysis suggested that preoperative LL and Ponte osteotomy were statistically significant (P<0.05). CONCLUSIONS The results of this study demonstrated that preoperative TK, preoperative LL, and Ponte osteotomy were related factors for maintaining normal TK. Multivariate analysis suggested that preoperative LL and the use of Ponte osteotomy with full-thickness segmental resection of the spinal posterior column resulted in the successful surgical correction of TK in patients with AIS with Lenke type 1 curvature.

A Mechanism Underlying Sex-Associated Differences in Ankylosing Spondylitis: Troponin C2, Fast Skeletal Type (TNNC2) and Calcium Signaling Pathway.

BACKGROUND Ankylosing spondylitis (AS) is a disease that causes pathological changes in the spine and sacroiliac joints. Numerous studies have shown that the characteristics of AS differ between males and females. The purpose of this study was to discover the key molecules that contribute to sex-associated differences in AS, which may provide a new molecular target for personalized treatment. MATERIAL AND METHODS The gene expression profile of GSE39340 was downloaded from the Gene Expression Comprehensive database, and 2 groups (AS vs. No-AS groups and male AS vs. female AS groups) of differentially expressed genes (EDGs) were obtained by GEO2R. The DAVID database was used for DEGs function and enrichment analysis. Based on data in the STRING online database, a protein-protein interaction (PPI) network was constructed in Cytoscape. Hub genes were selected from CytoHubba. With the intersection of the top 30 hub genes of 2 sets of EDGs, genes coexisting with the KEGG-related pathway were found. RESULTS We screened 560 genes between the AS and No-AS groups, and screened 710 genes that were differentially expressed between the male and female AS groups. GO analysis showed that DEGs were mainly co-enriched in molecular functions, including structural constituent of muscle. The KEGG pathway mainly included the structural constituent of muscle. Seven hub genes were obtained. Troponin C2 and fast skeletal type (TNNC2) were the key genes participating in the calcium signaling pathway. CONCLUSIONS This study contributes to understanding the molecular biological mechanism underlying sex-associated differences in AS. TNNC2 and calcium signaling pathway may be new targets for the individualized treatment of AS.

Risk Factors for Recurrent L5-S1 Disc Herniation After Percutaneous Endoscopic Transforaminal Discectomy: A Retrospective Study.

BACKGROUND This retrospective study aimed to investigate the risk factors associated with the recurrence of L5-S1 disc herniation after percutaneous endoscopic transforaminal discectomy (PETD). MATERIAL AND METHODS There were 484 patients L5-S1 disc herniation who underwent PETD who were divided into the recurrence group (n=46) and the non-recurrence group (n=438). Transforaminal endoscopic approaches included modifications of the Yeung endoscopy spine system (YESS) (the intraforaminal intradiscal approach) and the transforaminal endoscopic spine system (TESSYS) (intraforaminal extradiscal approach). Demographic and clinical characteristics and imaging data were analyzed. The two study groups were compared to determine the factors associated with the recurrence of L5-S1 disc herniation. The patients underwent postoperative follow-up for between one and four years. RESULTS At follow-up, 9.504% of patients (46/484) with the recurrence of L5-S1 disc herniation following PETD when compared with the non-recurrence group showed no significant difference for time to return to work, gender, history of diabetes mellitus, trauma, duration of symptoms, smoking and alcohol history, hypertension, location of disc herniation, transverse process length, intervertebral space height, and pelvic incidence angle (P>0.05). However, age, body mass index (BMI), the degree of disc degeneration, sagittal range of motion, lumbar lordosis angle, and sacral slope were significantly associated with the recurrence of L5-S1 disc herniation following PETD (P<0.05). Logistic regression analysis supported these main associations. CONCLUSIONS The recurrence of L5-S1 disc herniation following PETD was significantly associated with increased age and BMI, more severe disc degeneration, increased sagittal range of motion, increased lumbar lordosis, and sacral slope.

In-Depth Analysis on Influencing Factors of Adjacent Segment Degeneration After Cervical Fusion.

BACKGROUND To explore the related influencing factors of adjacent segment degeneration (ASD) after cervical discectomy and fusion (ACDF). MATERIAL AND METHODS A retrospective analysis of 263 patients who underwent ACDF was carried out. Cervical x-ray and magnetic resonance imaging (MRI) were required before operation, after operation, and at the last follow-up. General information and some radiographic parameters of all patients were measured and recorded. According to the imaging data, patients were put into one of two groups: non-ASD group and ASD group. The differences between the two groups were compared by t-test and χ²-test, and the related influencing factors of ASD were analyzed by logistic regression. RESULTS In all, 138 patients had imaging ASD. Comparing the age, the postoperative cervical arc chord distance (po-CACD), and the plate to disc distance (PDD) of the two groups, differences were statistically significant (p<0.05). The gender, the fusion segment number, the pre-CACD, the pre-and-po CACD, the preoperative cervical spinal canal ratio, and the upper and lower disc height (DH) showed no statistical difference between the two groups (p>0.05). The results of logistic regression analysis showed that there were significant correlations in the following characteristics: age, postoperative po-CACD, and the PDD (p<0.05). Of all these characteristics, the correlation of age was the highest (R=1.820). CONCLUSIONS Age, po-CACD, and PDD were risk factors for ASD after ACDF. The older the operation age, the worse the recovery was of postoperative physiological curvature of cervical spine, and a PDD < 5 mm was more likely to lead to ASD.

First-Principles Studies on Transition Metal Doped Mo2B2 as Anode Material for Li-Ion Batteries.

New two-dimensional (2D) transition-metal borides have attracted considerable interest in research on electrode materials for Li-ion batteries (LIBs) owing to their promising properties. In this study, 2D molybdenum boride (Mo2 B2 ) with and without transition metal (TM, TM=Mn, Fe, Co, Ni, Ru, and Pt) atom doping was investigated. Our results indicated that all TM-doped Mo2 B2 samples exhibited excellent electronic conductivity, similar to the intrinsic 2D Mo2 B2 metal behavior, which is highly beneficial for application in LIBs. Moreover, we found that the diffusion energy barriers of Li along paths 1 and 2 for all TM-doped Mo2 B2 samples are smaller than 0.30 and 0.24 eV of the pristine Mo2 B2 . In particular, for 2D Co-doped Mo2 B2 , the diffusion energy barriers of Li along paths 1 and 2 are reduced to 0.14 and 0.11 eV, respectively, making them the lowest Li diffusion barriers in both paths 1 and 2. This indicates that TM doping can improve the electrochemical performance of 2D Mo2 B2 and that Co-doped Mo2 B2 is a promising electrode material for LIBs. Our work not only identifies electrode materials with promising electrochemical performance but also provides guidance for the design of high-performance electrode materials for LIBs.

Chemically Programmed Hydrogels for Spatiotemporal Modulation of the Cardiac Pathological Microenvironment.

After myocardial infarction (MI), sustained ischemic events induce pathological microenvironments characterized by ischemia-hypoxia, oxidative stress, inflammatory responses, matrix remodeling, and fibrous scarring. Conventional clinical therapies lack spatially targeted and temporally responsive modulation of the infarct microenvironment, leading to limited myocardial repair. Engineered hydrogels have a chemically programmed toolbox for minimally invasive localization of the pathological microenvironment and personalized responsive modulation over different pathological periods. Chemically programmed strategies for crosslinking interactions, interfacial binding, and topological microstructures in hydrogels enable minimally invasive implantation and in situ integration tailored to the myocardium. This enhances substance exchange and signal interactions within the infarcted microenvironment. Programmed responsive polymer networks, intelligent micro/nanoplatforms, and biological therapeutic cues contribute to the formation of microenvironment-modulated hydrogels with precise targeting, spatiotemporal control, and on-demand feedback. Therefore, this review summarizes the features of the MI microenvironment and chemically programmed schemes for hydrogels to conform, integrate, and modulate the cardiac pathological microenvironment. Chemically programmed strategies for oxygen-generating, antioxidant, anti-inflammatory, provascular, and electrointegrated hydrogels to stimulate iterative and translational cardiac tissue engineering are discussed.

Enhancing cell cryopreservation with acidic polyamino acids integrated liquid marbles.

Cryopreservation is highly desired for long-term maintenance of the viability of living biosamples, while effective cell cryopreservation still relies heavily on the addition of dimethyl sulfoxide (DMSO) and fetal bovine serum (FBS). However, the intrinsic toxicity of DMSO is still a bottleneck, which could not only cause the clinical side effect but also induce cell genetic variants. In the meantime, the addition of FBS may bring potentially the risk of pathogenic microorganism contamination. The liquid marbles (LMs), a novel biotechnology tool for cell cryopreservation, which not only have a small volume system that facilitated recovery, but the hydrophobic shell also resisted the harm to cells caused by adverse environments. Previous LM-based cell cryopreservation relied heavily on the addition of FBS. In this work, we introduced acidic polyaspartic acid and polyglutamic acid as cryoprotectants to construct LM systems. LMs could burst in an instant to facilitate and achieve ultrarapid recovery process, and the hydrophilic carboxyl groups of the cryoprotectants could form hydrogen bonds with water molecules and further inhibit ice growth/formation to protect cells from cryoinjuries. The L929 cells could be well cryopreserved by acidic polyamino acid-based LMs. This new biotechnology platform is expected to be widely used for cell cryopreservation, which has the potential to propel LMs for the preservation of various functional cells in the future.

Injectable Asymmetric Adhesive-Antifouling Bifunctional Hydrogel for Peritoneal Adhesion Prevention.

Peritoneal adhesion is a common problem after abdominal surgery and can lead to various medical problems. In response to the lack of in situ retention and pro-wound healing properties of existing anti-adhesion barriers, this work reports an injectable adhesive-antifouling bifunctional hydrogel (AAB-hydrogel). This AAB-hydrogel can be constructed by "two-step" injection. The tissue adhesive hydrogel based on gallic acid-modified chitosan and aldehyde-modified dextran is prepared as the bottom hydrogel (B-hydrogel) by Schiff base reaction. The aldehyde-modified zwitterionic dextran/carboxymethyl chitosan-based hydrogel is formed on the B-hydrogel surface as the antifouling top hydrogel (T-hydrogel). The AAB-hydrogel exhibits good bilayer binding and asymmetric properties, including tissue adhesive, antifouling, and antimicrobial properties. To evaluate the anti-adhesion effect in vivo, the prepared hydrogels are injected onto the wound surface of a mouse abdominal wall abrasion-cecum defect model. Results suggest that the AAB-hydrogel has antioxidant capacity and can reduce the postoperative inflammatory response by modulating the macrophage phenotype. Moreover, the AAB-hydrogel could effectively inhibit the formation of postoperative adhesions by reducing protein deposition, and resisting fibroblast adhesions and bacteria attacking. Therefore, AAB-hydrogel is a promising candidate for the prevention of postoperative peritoneal adhesions.

Exploration of the combined role of immune checkpoints and immune cells in the diagnosis and treatment of ankylosing spondylitis: a preliminary study immune checkpoints in ankylosing spondylitis.

OBJECTIVE: Immune checkpoints have emerged as promising therapeutic targets for autoimmune diseases. However, the specific roles of immune checkpoints in the pathophysiology of ankylosing spondylitis (AS) remain unclear. METHODS: Hip ligament samples were obtained from two patient groups: those with AS and femoral head deformity, and those with femoral head necrosis but without AS, undergoing hip arthroplasty. Label-Free Quantification (LFQ) Protein Park Analysis was used to identify the protein composition of the ligaments. Peripheral blood samples of 104 AS patients from public database were used to validate the expression of key proteins. KEGG, GO, and GSVA were employed to explore potential pathways regulated by immune checkpoints in AS progression. xCell was used to calculate cell infiltration levels, LASSO regression was applied to select key cells, and the correlation between immune checkpoints and immune cells was analyzed. Drug sensitivity analysis was conducted to identify potential therapeutic drugs targeting immune checkpoints in AS. The expression of key genes was validated through immunohistochemistry (IHC). RESULTS: HLA-DMB and HLA-DPA1 were downregulated in the ligaments of AS and this has been validated through peripheral blood datasets and IHC. Significant differences in expression were observed in CD8 + Tcm, CD8 + T cells, CD8 + Tem, osteoblasts, Th1 cells, and CD8 + naive T cells in AS. The infiltration levels of CD8 + Tcm and CD8 + naive T cells were significantly positively correlated with the expression levels of HLA-DMB and HLA-DPA1. Immune cell selection using LASSO regression showed good predictive ability for AS, with AUC values of 0.98, 0.81, and 0.75 for the three prediction models, respectively. Furthermore, this study found that HLA-DMB and HLA-DPA1 are involved in Th17 cell differentiation, and both Th17 cell differentiation and the NF-kappa B signaling pathway are activated in the AS group. Drug sensitivity analysis showed that AS patients are more sensitive to drugs such as doramapimod and GSK269962A. CONCLUSION: Immune checkpoints and immune cells could serve as avenues for exploring diagnostic and therapeutic strategies for AS.

Chronological-Programmed Black Phosphorus Hydrogel for Responsive Modulation of the Pathological Microenvironment in Myocardial Infarction.

Electroactive hydrogels have garnered extensive interest as a promising approach to myocardial tissue engineering. However, the challenges of spatiotemporal-specific modulation of individual pathological processes and achieving nontoxic bioresorption still remain. Herein, inspired by the entire postinfarct pathological processes, an injectable conductive bioresorbable black phosphorus nanosheets (BPNSs)-loaded hydrogel (BHGD) was developed via reactive oxide species (ROS)-sensitive disulfide-bridge and photomediated cross-linking reaction. Significantly, the chronologically programmed BHGD hydrogel can achieve graded modulation during the inflammatory, proliferative, and maturation phases of myocardial infarction (MI). More details, during early infarction, the BHGD hydrogel can effectively reduce ROS levels in the MI area, inhibit cellular oxidative stress damage, and promote macrophage M2 polarization, creating a favorable environment for damaged myocardium repair. Meanwhile, the ROS-responsive structure can protect BPNSs from degradation and maintain good conductivity under MI microenvironments. Therefore, the BHGD hydrogel possesses tissue-matched modulus and conductivity in the MI area, facilitating cardiomyocyte maturation and electrical signal exchange, compensating for impaired electrical signaling, and promoting vascularization in infarcted areas in the maturation phase. More importantly, all components of the hydrogel degrade into nontoxic substances without adverse effects on vital organs. Overall, the presented BPNS-loaded hydrogel offers an expandable and safe option for clinical treatment of MI.

Large-Scale Fabrication of Freestanding Polymer Ultrathin Porous Membranes for Transparent Transwell Coculture Systems.

Advancements in cell coculture systems with porous membranes have facilitated the simulation of human-like in vitro microenvironments for diverse biomedical applications. However, conventional Transwell membranes face limitations in low porosity (ca. 6%) and optical opacity due to their large thickness (ca. 10 µm). In this study, we demonstrated a one-step, large-scale fabrication of freestanding polymer ultrathin porous (PUP) membranes with thicknesses of hundreds of nanometers. PUP membranes were produced by using a gap-controlled bar-coating process combined with polymer blend phase separation. They are 20 times thinner than Transwell membranes, possessing 3-fold higher porosity and exhibiting high transparency. These membranes demonstrate outstanding molecular permeability and significantly reduce the cell-cell distance, thereby facilitating efficient signal exchange pathways between cells. This research enables the establishment of a cutting-edge in vitro cell coculture system, enhancing optical transparency, and streamlining the large-scale manufacturing of porous membranes.

Osmotic stress and membrane phase changes during freezing of stallion sperm: mode of action of cryoprotective agents.

The aim of this study was to determine how different membrane-permeable and -impermeable cryoprotective agents modulate tolerance of stallion sperm to osmotic stress and stabilize membranes during cryopreservation. Special emphasis was on hydroxyl ethylene starch (HES), which exposes cells to minimal osmotic stress due to its large molecular weight. Percentages of motile sperm post-thaw were found to be similar when glycerol, sucrose, and HES were used at their optimal concentrations. Percentages of plasma membrane intact sperm after return to isotonic medium were highest for HES. Fourier transform infrared spectroscopy studies were carried out to study subzero membrane phase and permeability behavior. Cryoprotectants were shown to decrease the initial rate of membrane dehydration during freezing, decrease the activation energy for water transport, and increase the total extent of freezing-induced dehydration. Freezing studies with liposomes as a model system showed that only the membrane-permeable cryoprotective agents glycerol and ethylene glycol protected membranes against leakage, whereas egg yolk, sucrose, and HES did not. Differential scanning calorimetry studies showed that sucrose and HES raise the glass transition temperature of the freezing extender and the difference in heat capacity associated with the glass transition. This indicates that these compounds enable formation of a stable glassy matrix at higher subzero temperatures. Sperm cryosurvival rates can be increased by combining different cryoprotectants with different protective functions; membrane permeable cryoprotective agents stabilize membranes and modulate the rate of cellular dehydration, whereas di- and polysaccharides increase the glass transition temperature and facilitate storage and handling at higher subzero temperatures.