Silk Fibroin-Laponite Porous Microspheres as Cell Microcarriers for Osteogenic Differentiation.

Silk fibroin (SF) has garnered significant attention as a natural polymer for fabricating porous scaffolds in various engineering applications. However, the limited osteoinductive property of SF has hindered its efficacy in bone repair applications. In this study, we constructed an SF-based injectable porous microcarrier that is doped with laponite (LAP), containing magnesium ions (Mg2+). The influence of freezing temperatures and concentrations of SF and LAP on the structural parameters of SF-LAP microcarriers was investigated. The SF-LAP microcarrier exhibited a porosity of 76.7 ± 1.2% and a controlled pore size of 24.6 ± 4.0 µm. At the 6 weeks of in vitro degradation test, a mild alkaline level in culture medium containing SF-LAP microcarriers was detected. The release of Mg2+ from the SF-LAP microcarrier was maintained at a concentration within the range of 1.2-2.3 mM during the 6 weeks. The seeded human adipose-derived stem cells in the SF-LAP microcarrier demonstrated a significant enhancement in osteogenic differentiation compared with cells seeded in the pure SF microcarrier, as evidenced by quantitative alkaline phosphatase activity and the expression of osteogenic marker genes. These findings underscore the potential of the SF-LAP microcarrier as an ideal cell carrier in the treatment of bone defects.

Ten-year epidemiology and risk factors of cytomegalovirus infection in hematopoietic stem cell transplantation patients in Taiwan.

BACKGROUND: Cytomegalovirus (CMV) can cause infection and critical diseases in hematopoietic stem cell transplantation (HSCT) recipients. This study aimed to explore the cumulative incidence and risk factors for CMV infection and disease among HSCT recipients in Taiwan. METHODS: This retrospective cohort study using the Taiwan Blood and Marrow Transplantation Registry (TBMTR) included HSCT recipients between 2009 and 2018 in Taiwan. The primary outcome was cumulative incidence of CMV infection or disease at day 100 after HSCT. Secondary outcomes included day 180 cumulative incidence of CMV infection or disease, infection sites, risk factors for CMV infection or disease, survival analysis, and overall survival after CMV infection and disease. RESULTS: There were 4394 HSCT recipients included in the study (2044 auto-HSCT and 2350 allo-HSCT). The cumulative incidence of CMV infection and disease was significantly higher in allo-HSCT than in auto-HSCT patients at day 100 (53.7% vs. 6.0%, P < 0.0001 and 6.1% vs. 0.9%, P < 0.0001). Use of ATG (HR 1.819, p < 0.0001), recipient CMV serostatus positive (HR 2.631, p < 0.0001) and acute GVHD grades ≥ II (HR 1.563, p < 0.0001) were risk factors for CMV infection, while matched donor (HR 0.856, p = 0.0180) and myeloablative conditioning (MAC) (HR 0.674, p < 0.0001) were protective factors. CONCLUSION: The study revealed a significant disparity in terms of the incidence, risk factors, and clinical outcomes of CMV infection and disease between auto and allo-HSCT patients. These findings underscore the importance of considering these factors in the management of HSCT recipients to improve outcomes related to CMV infections.

Omnidirectional Sensor Design for Distributed Laser Measurement Systems.

Distributed laser measurement systems, widely used in high-end equipment such as airplanes, ships, and other manufacturing fields, face challenges in large spatial measurements due to laser plane obstructions and weak intersections. This paper introduces a novel omnidirectional sensor with enhanced adaptability to complex environments and improved measurement accuracy. Initially, an integrated omnidirectional measurement model is established, followed by the analysis of the optical path of the front-end detector, and the design of a signal-conditioning circuit for the photoelectric conversion of the front-end laser signal, Subsequently, a circuit testing platform is established to validate the detection functionality, and the corresponding results indicate that the symmetry of the output waveform is under 10 ns, the response time is under 100 ns, and the maximum detection distance is 22 m. Further, experimental results demonstrate the superiority of omnidirectional sensors over planar ones in complex environments, successfully receiving 360° laser signals. The positional accuracy of the common point to be measured on the top of the omnidirectional sensor is confirmed to exceed 0.05 mm, and the accuracy of the angle of attitude exceeds 0.04°. Using the laser tracker, the measurement accuracy of the system is verified to be better than 0.3 mm. When rotating in the horizontal and pitch directions, the measurement accuracy is better than 0.35 mm and 0.47 mm, respectively, fulfilling the sub-millimeter precision requirement and expanding the application scope of distributed laser measurement systems.

Multimodal feature fusion in deep learning for comprehensive dental condition classification.

BACKGROUND: Dental health issues are on the rise, necessitating prompt and precise diagnosis. Automated dental condition classification can support this need. OBJECTIVE: The study aims to evaluate the effectiveness of deep learning methods and multimodal feature fusion techniques in advancing the field of automated dental condition classification. METHODS AND MATERIALS: A dataset of 11,653 clinically sourced images representing six prevalent dental conditions-caries, calculus, gingivitis, tooth discoloration, ulcers, and hypodontia-was utilized. Features were extracted using five Convolutional Neural Network (CNN) models, then fused into a matrix. Classification models were constructed using Support Vector Machines (SVM) and Naive Bayes classifiers. Evaluation metrics included accuracy, recall rate, precision, and Kappa index. RESULTS: The SVM classifier integrated with feature fusion demonstrated superior performance with a Kappa index of 0.909 and accuracy of 0.925. This significantly surpassed individual CNN models such as EfficientNetB0, which achieved a Kappa of 0.814 and accuracy of 0.847. CONCLUSIONS: The amalgamation of feature fusion with advanced machine learning algorithms can significantly bolster the precision and robustness of dental condition classification systems. Such a method presents a valuable tool for dental professionals, facilitating enhanced diagnostic accuracy and subsequently improved patient outcomes.

Advancing nutrition risk assessment in middle-aged and older individuals with diverse food cultures: A data-driven personalized approach to predict incident hypertension, diabetes and mortality.

BACKGROUND: Personalized nutrition risk assessment is crucial in addressing the association between healthy dietary habits across the life course and the development of disease, functional capacity, and healthy aging, as specific dietary pattern recommendations may not be suitable for diverse food cultures. OBJECTIVE: To develop a data-driven, personalized nutrition risk assessment algorithm linked to incident hypertension, diabetes, and all-cause mortality utilizing the food frequency questionnaire among middle-aged and older individuals. METHODS: A retrospective, population-based cohort study conducted between 1999 and 2015 utilized the nationally representative Taiwan Longitudinal Study on Aging (TLSA) survey to examine personalized dietary risk clusters and their associations with health outcomes. Latent class analysis was performed to derive the dietary diversity clusters among community-dwelling middle-aged and older individuals. Outcomes were defined as new-onset hypertension, diabetes mellitus and all-cause mortality at 4-, 8-, 12- and 16-year follow-ups. RESULTS: Data from 1,811 participants (58.14% males, 43.90% aged 50-64 years) showed that around one-third of participants reported being illiterate, 21.98% widowed, and 51.46% engaging in regular physical exercise. Four dietary diversity clusters were identified: "least diverse", "fish and meat", "dairy, fruit, and vegetable", and "most diverse". The "most diverse" cluster was characterized by a high consumption of protein-rich foods, while the "dairy, fruit, and vegetable" cluster had the highest consumption of dairy products and beans/legumes. The "least diverse" cluster had the lowest intake of protein-rich foods, and dark-colored vegetables and fruits. The "most diverse" cluster had a significantly lower risk of hypertension development at the 4-year (aOR 0.58; p < 0.02) and 8-year (aOR 0.57; p < 0.01) follow-up and diabetes at the 4-year (aOR 0.44; p < 0.03) follow-up. Participants in the "most diverse" clusters exhibited lower risks of 8-year, 12-year, and 16-year mortality than those in the "least diverse" cluster (aOR 0.67, p < 0.05; 0.67, p < 0.03; and 0.50, p < 0.01, respectively). CONCLUSION: The personalized nutrition risk assessment algorithm from the food frequency questionnaire can effectively stratify personal health risks among diverse middle-aged and older individuals, making it a valuable tool in lifestyle modification and intervention studies.

Effect of Hashimoto's thyroiditis on the dual-energy CT quantitative parameters and performance in diagnosing metastatic cervical lymph nodes in patients with papillary thyroid cancer.

BACKGROUND: To evaluate the effect of Hashimoto's thyroiditis (HT) on dual-energy computed tomography (DECT) quantitative parameters of cervical lymph nodes (LNs) in patients with papillary thyroid cancer (PTC), and its effect on the diagnostic performance and threshold of DECT in preoperatively identifying metastatic cervical LNs. METHODS: A total of 479 LNs from 233 PTC patients were classified into four groups: HT+/LN+, HT+/LN-, HT-/LN + and HT-/LN - group. DECT quantitative parameters including iodine concentration (IC), normalized IC (NIC), effective atomic number (Zeff), and slope of the spectral Hounsfield unit curve (λHU) in the arterial phase (AP) and venous phase were compared. Receiver operating characteristic curve analyses were performed to evaluate DECT parameters' diagnostic performance in differentiating metastatic from nonmetastatic LNs in the HT - and HT + groups. RESULTS: The HT+/LN + group exhibited lower values of DECT parameters than the HT-/LN + group (all p < 0.05). Conversely, the HT+/LN - group exhibited higher values of DECT parameters than the HT-/LN - group (all p < 0.05). In the HT + group, if an AP-IC of 1.850 mg/mL was used as the threshold value, then the optimal diagnostic performance (area under the curve, 0.757; sensitivity, 69.4%; specificity, 71.0%) could be obtained. The optimal threshold value of AP-IC in the HT - group was 2.050 mg/mL. In contrast, in the HT - group, AP-NIC demonstrated the highest area under the curve of 0.988, when an optimal threshold of 0.243 was used. The optimal threshold value of AP-NIC was 0.188 in the HT + group. CONCLUSIONS: HT affected DECT quantitative parameters of LNs and subsequent the diagnostic thresholds. When using DECT to diagnose metastatic LNs in patients with PTC, whether HT is coexistent should be clarified considering the different diagnostic thresholds.

The incidences and clinical outcomes of cryptococcosis in Taiwan: A nationwide, population-based study, 2002-2015.

Large-scale epidemiological data on cryptococcosis other than cryptococcal meningitis (CM), human immunodeficiency virus (HIV)- or solid organ transplantation (SOT)-associated cryptococcosis are limited. This study investigated the disease burden of cryptococcosis in Taiwan over 14 years. Incident episodes of cryptococcosis, comorbidities, treatment, and outcomes were captured from Taiwan's National Health Insurance Research Database and National Death Registry between 2002 and 2015. Of 6647 episodes analyzed, the crude incidence rate per 100 000 population increased from 1.48 in 2002 to 2.76 in 2015, which was driven by the growing trend in the non-CM group (0.86-2.12) but not in the CM group (0.62-0.64). The leading three comorbidities were diabetes mellitus (23.62%), malignancy (22.81%), and liver disease (17.42%). HIV accounted for 6.14% of all episodes and was associated with the highest disease-specific incidence rate (269/100 000 population), but the value dropped 16.20% biennially. Within 90 days prior to cohort entry, 30.22% of episodes had systemic corticosteroid use. The in-hospital mortality of all episodes was 10.80%, which varied from 32.64% for cirrhosis and 13.22% for HIV to 6.90% for SOT. CM was associated with a higher in-hospital mortality rate than non-CM (19.15% vs. 6.33%). At diagnosis, only 48.53% of CM episodes were prescribed an amphotericin-based regimen. The incidence rate of cryptococcosis was increasing, especially that other than meningitis and in the non-HIV population. A high index of clinical suspicion is paramount to promptly diagnose, treat, and improve cryptococcosis-related mortality in populations other than those with HIV infection or SOT.

This nationwide study showed that the incidence rate of cryptococcosis doubled from 2002 to 2015. Non-meningeal cryptococcosis and non-HIV/nontransplant (NHNT)-associated cryptococcosis contributed to this increase. Our study highlighted the underestimated burden of cryptococcosis in the NHNT hosts.

ACT001 improved cardiovascular function in septic mice by inhibiting the production of proinflammatory cytokines and the expression of JAK-STAT signaling pathway.

Sepsis is a life-threatening multiple organ dysfunction syndrome (MODS) caused by a microbial infection that leads to high morbidity and mortality worldwide. Sepsis-induced cardiomyopathy (SIC) and coagulopathy promote the progression of adverse outcomes in sepsis. Here, we reported that ACT001, a modified compound of parthenolide, improved the survival of sepsis mice. In this work, we used cecal ligation and puncture (CLP) model to induce SIC. Transthoracic echocardiography and HE staining assays were adopted to evaluate the influence of ACT001 on sepsis-induced cardiac dysfunction. Our results showed that ACT001 significantly improved heart function and reduced SIC. Coagulation accelerates organ damage in sepsis. We found that ACT001 decreased blood clotting in the FeCl3-induced carotid artery thrombosis experiment. ACT001 also reduced the production of neutrophil extracellular traps (NETs). RNA-sequencing of heart tissues revealed that ACT001 significantly downregulated the expression of pro-inflammatory cytokines and the JAK-STAT signaling pathway. These results were confirmed with real-time PCR and ELISA. In summary, we found ACT001 rescued mice from septic shock by protecting the cardiovascular system. This was partially mediated by inhibiting pro-inflammatory cytokine production and down-regulating the JAK-STAT signaling.

Fusion extracted features from deep learning for identification of multiple positioning errors in dental panoramic imaging.

BACKGROUND: Dental panoramic imaging plays a pivotal role in dentistry for diagnosis and treatment planning. However, correctly positioning patients can be challenging for technicians due to the complexity of the imaging equipment and variations in patient anatomy, leading to positioning errors. These errors can compromise image quality and potentially result in misdiagnoses. OBJECTIVE: This research aims to develop and validate a deep learning model capable of accurately and efficiently identifying multiple positioning errors in dental panoramic imaging. METHODS AND MATERIALS: This retrospective study used 552 panoramic images selected from a hospital Picture Archiving and Communication System (PACS). We defined six types of errors (E1-E6) namely, (1) slumped position, (2) chin tipped low, (3) open lip, (4) head turned to one side, (5) head tilted to one side, and (6) tongue against the palate. First, six Convolutional Neural Network (CNN) models were employed to extract image features, which were then fused using transfer learning. Next, a Support Vector Machine (SVM) was applied to create a classifier for multiple positioning errors, using the fused image features. Finally, the classifier performance was evaluated using 3 indices of precision, recall rate, and accuracy. RESULTS: Experimental results show that the fusion of image features with six binary SVM classifiers yielded high accuracy, recall rates, and precision. Specifically, the classifier achieved an accuracy of 0.832 for identifying multiple positioning errors. CONCLUSIONS: This study demonstrates that six SVM classifiers effectively identify multiple positioning errors in dental panoramic imaging. The fusion of extracted image features and the employment of SVM classifiers improve diagnostic precision, suggesting potential enhancements in dental imaging efficiency and diagnostic accuracy. Future research should consider larger datasets and explore real-time clinical application.

The collision-induced dissociation mechanism of sodiated Hex-HexNAc disaccharides.

Determining carbohydrate structures, such as their compositions, linkage positions, and in particular the anomers and stereoisomers, is a great challenge. Isomers of different anomers or stereoisomers have the same sequences of chemical bonds, but have different orientations of some chemical bonds which are difficult to be distinguished by mass spectrometry. Collision-induced dissociation (CID) tandem mass spectroscopy (MS/MS) is a widely used technique for characterizing carbohydrate structures. Understanding the carbohydrate dissociation mechanism is important for obtaining the structural information from MS/MS. In this work, we studied the CID mechanism of galactose-N-acetylgalactosamine (Gal-GalNAc) and glucose-N-acetylglucosamine (Glc-GlcNAc) disaccharides with 1→3 and 1→4 linkages. For Gal-GalNAc disaccharides, the CID mass spectra of sodium ion adducts show significant difference between the α- and ß-anomers of GalNAc at the reducing end, while no difference in the CID mass spectra between two anomers of Glc-GlcNAc disaccharides was found. Quantum chemistry calculations show that for Gal-GalNAc disaccharides, the difference of the dissociation barriers between dehydration and glycosidic bond cleavage is significantly small in the ß-anomer compared to that in the α-anomer; while these differences are similar between the α- and ß-anomers of Glc-GlcNAc disaccharides. These differences can be attributed to the different orientations of hydroxyl and N-acetyl groups located at GalNAc and GlcNAc. The calculation results are consistent with the CID spectra of isotope labelled disaccharides. Our study provides an insight into the CID of 1→3 and 1→4 linked Gal-GalNAc and Glc-GlcNAc disaccharides. This information is useful for determining the anomeric configurations of GalNAc in oligosaccharides.

Nano-SiO2 reinforced alginate-chitosan-gelatin nanocomposite hydrogels with improved physicochemical properties and biological activity.

Alginate (Alg) hydrogels possess desirable advantages for application in tissue engineering; however, they are limited by their weak mechanical properties, poor chronical stability in phosphate buffered saline, and absence of mammalian cell recognition sites, severely restricting their biomedical applications. To overcome these limitations, we integrated Alg hydrogels with nano-silica (SiO2) to produce nano-SiO2 reinforced Alg-chitosan-gelatin nanocomposite hydrogels (Alg/SiO2-CHI-GA NCH) for biomedical purposes, utilizing Chitosan (CHI) and gelatin (GA) in an alternate electrostatic adsorption. Specifically, we investigated the regulatory and promotional effects of the nano-SiO2 on the morphological structure, mechanical properties, thermal stability, rheological properties, swelling, biodegradability, biomineralization and cytocompatibility of the resultant Alg/SiO2-CHI-GA NCH. The experimental findings demonstrate that the constructed Alg/SiO2-CHI-GA NCH exhibited uniform morphology and a regular structure. Upon freeze-drying, the internal cross-sections of the NCH exhibited a honeycomb porous structure. Furthermore, the physicochemical properties and biological activities of the prepared Alg/SiO2-CHI-GA NCH were regulated to some extent by nano-SiO2 content. Notably, nano-SiO2 inclusion enhanced the attachment and viability of MG63 and MC3T3-E1 cells and induced three-dimensional cell growth in ALG/SiO2-CHI-GA NCH. Among the fabricated NCH, Alg/SiO2-CHI-GA NCH with 0.5% and 1.0% (w/v) nano-SiO2 exhibited significant proliferative activity, which is attributable to their high porosity and uniform cell adhesion. Furthermore, the alkaline phosphatase activity in the cells gradually increased with increasing of nano-SiO2 amount, indicating the favorable effect of nano-SiO2 on the osteogenic differentiation of MG63 and MC3T3-E1 cells. Our study findings provide a comprehensive foundation for the structural- and property-related limitations of Alg hydrogels in biomedicine, thereby expanding their potential applications in tissue engineering.

Occurrence and ecological risk assessment of 16 phthalates in surface water of the mainstream of the Yangtze River, China.

Phthalic acid esters (PAEs), a class of typical endocrine disruptors, have received considerable attention due to their widespread applications and adverse effects on biological health. In this study, 30 water samples, along the mainstream of the Yangtze River (YR), were collected from Chongqing (upper stream) to Shanghai (estuary) from May to June in 2019. The total concentrations of 16 targeted PAEs ranged from 0.437 to 20.5 µg/L, with an average of 1.93 µg/L, where dibutyl phthalate (DBP, 0.222-20.2 µg/L), bis (2-ethylhexyl) phthalate (DEHP, 0.254-7.03 µg/L), and diisobutyl phthalate (DIBP, 0.0645-0.621 µg/L) were the most abundant PAEs. According to the pollution level in the YR to assess the ecological risk posed by PAEs, the results showed medium risk level of PAEs in the YR, among which DBP and DEHP posed a high ecological risk to aquatic organisms. The optimal solution for DBP and DEHP is found in ten fitting curves. The PNECSSD of them is 2.50 µg/L and 0.34 µg/L, respectively.

A simple tandem mass spectrometry method for structural identification of pentose oligosaccharides.

Differentiation of stereoisomers that are only dissimilar in the orientation of chemical bonds in space by mass spectrometry remains challenging. Structural determination of carbohydrates by mass spectrometry is difficult, mainly due to the large number of stereoisomers in carbohydrates. Arabinose and xylose are pentose stereoisomers typically present in plant polysaccharides and exist in α- and ß-anomeric configurations of furanose and pyranose forms. Conventional methods used to determine the structures of polysaccharides include hydrolysis of polysaccharides into oligosaccharides followed by identification of these oligosaccharides' structures individually through nuclear magnetic resonance spectroscopy (NMR). Although the sensitivity of mass spectrometry is much higher than that of NMR, conventional mass spectrometry provides only limited useful information on oligosaccharide structure determination, only the linkage positions of glycosidic bonds. In this study, we demonstrated a mass spectrometry method for the identification of linkage positions, anomeric configurations, and monosaccharide stereoisomers of intact oligosaccharides consisting of arabinose and xylose. We separated arabinose and xylose monosaccharides into α-furanose, ß-furanose, α-pyranose, and ß-pyranose forms through high-performance liquid chromatography and obtained the corresponding collision-induced dissociation mass spectra. Using these monosaccharide spectra and a flow chart consisting of the proper CID sequences derived from the dissociation mechanisms of pentose, a simple multi-stage tandem mass spectrometry method for structural identification of intact oligosaccharides consisting of arabinose and xylose was developed. The new mass spectrometry method provides a simple method for determining the structure of polysaccharides consisting of arabinose and xylose. The flow chart can be used in computer coding for automation, an ultimate goal for oligosaccharide structure determination.

Xuanfei Baidu Decoction regulates NETs formation via CXCL2/CXCR2 signaling pathway that is involved in acute lung injury.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening symptoms in Coronavirus Disease 2019 (COVID-19) patients. Xuanfei Baidu Decoction (XFBD) is a recommend first-line traditional Chinese medicine (TCM) formula therapeutic strategy for COVID-19 patients. Prior studies demonstrated the pharmacological roles and mechanisms of XFBD and its derived effective components against inflammation and infections through multiple model systems, which provided the biological explanations for its clinical use. Our previous work revealed that XFBD inhibited macrophages and neutrophils infiltration via PD-1/IL17A signaling pathway. However, the subsequent biological processes are not well elucidated. Here, we proposed a hypothesis that XFBD can regulate the neutrophils-mediated immune responses, including neutrophil extracellular traps (NETs) formation and the generation of platelet-neutrophil aggregates (PNAs) after XFBD administration in lipopolysaccharide (LPS)-induced ALI mice. The mechanism behind it was also firstly explained, that is XFBD regulated NETs formation via CXCL2/CXCR2 axis. Altogether, our findings demonstrated the sequential immune responses of XFBD after inhibiting neutrophils infiltration, as well as shedding light on exploiting the therapy of XFBD targeting neutrophils to ameliorate ALI during the clinical course.

Setting method of exit advance guide signs in mountainous expressway tunnel based on information quantization theory.

Driving behavior in expressway tunnels is more complicated than in common roadbed sections because of differences in illuminance, visual range, speed perception, and reaction time. To explore the setting method of exit advance guide signs in expressway tunnels and improve the effectiveness of drivers' recognition of them, we propose 12 layout forms based on information quantification theory. In experiments, UC-win/Road was used to build a simulation scene, and the recognition reaction time of 12 element combinations of exit advance guide signs of different subjects was collected through an E-Prime simulation experiment. The loading effectiveness of the signs was analyzed based on the subjective workload and comprehensive evaluation scores of different subjects. The results are the following. The width of the exit advance guide sign layout in the tunnel is negatively correlated with the height of Chinese characters and the distance between the characters and the edge of the sign. The larger the height of Chinese characters and the distance between them and the edge of the sign, the smaller the maximum layout width of the sign. Considering the driver's reaction time, subjective workload, sign recognition, amount of sign information, sign accuracy, and sign safety of 12 different information combinations, we suggest that exit advance guide signs in tunnels should be laid out as Chinese/English place name + distance + guide arrow.

Effects of Calcium Ions on the Antimicrobial Activity of Gramicidin A.

Gramicidin A (gA) is a linear antimicrobial peptide that can form a channel and specifically conduct monovalent cations such as H+ across the lipid membrane. The antimicrobial activity of gA is associated with the formation of hydroxyl free radicals and the imbalance of NADH metabolism, possibly a consequence caused by the conductance of cations. The ion conductivity of gramicidin A can be blocked by Ca2+ ions. However, the effect of Ca2+ ions on the antimicrobial activity of gA is unclear. To unveil the role of Ca2+ ions, we examined the effect of Ca2+ ions on the antimicrobial activity of gramicidin A against Staphylococcus aureus (S. aureus). Results showed that the antimicrobial mechanism of gA and antimicrobial activity by Ca2+ ions are concentration-dependent. At the low gA concentration (≤1 µM), the antimicrobial mechanism of gA is mainly associated with the hydroxyl free radical formation and NADH metabolic imbalance. Under this mode, Ca2+ ions can significantly inhibit the hydroxyl free radical formation and NADH metabolic imbalance. On the other hand, at high gA concentration (≥5 µM), gramicidin A acts more likely as a detergent. Gramicidin A not only causes an increase in hydroxyl free radical levels and NAD+/NADH ratios but also induces the destruction of the lipid membrane composition. At this condition, Ca2+ ions can no longer reduce the gA antimicrobial activity but rather enhance the bacterial killing ability of gramicidin A.

Poly(acridan-grafted biphenyl germanium) with High Triplet Energy as a Universal Host for High-Efficiency Thermally Activated Delayed Fluorescence Full-Color Devices and Their Hybrid with Phosphor for White Light Electroluminescence.

Developing an effective host for highly efficient full-color electroluminescence devices through a solution-process is still a challenge at present. Here, we use the σ-π conjugated polymer, poly(acridan grafted biphenyl germanium) P(DMAC-Ge), having the highest triplet energy (ET) 2.86 eV among conjugated polymers as the host in sky-blue phosphorescence, TADFs (blue (B), green (G), and red (R)), and hybrid white (W) PLEDs. Upon doping with a sky-blue phosphor-emitter (Firpic), the resulting device gives the high EQEmax 19.7% with Bmax 24,918 cd/m2. The Ge-containing polymer backbone can provide as a channel for electron transport and charge trap into the guest as manifested by the electroluminescence dynamics. Further introducing the bipolar material DCzPPy as cohost, the devices with a sky-blue phosphor (Firpic) and each of the TADF-guests─B (DMAC-TRZ), G (DACT-II), and R (TPA-DCPP) in the EML─achieve the high maximum EQEs as 19.7%, 19.4%, 21.5% and 3.82% with the emission peaks at 470, 485, 508, and 630 nm, respectively. As the three guests (DMAC-TRZ, Ir-O, Ir-R) are doped together into the emitting layer, we obtain a TADF-phosphor (T-P) hybrid white PLED giving a record-high EQE 22.5% among the solution processed hybrid OLED with CIE (0.34, 0.40) and Bmax 28,945 cd/m2. These results manifest that P(DMAC-Ge) is a potential polymer host for full-color TADF and hybrid white light PLEDs with high performance.

Xuebijing injection inhibited neutrophil extracellular traps to reverse lung injury in sepsis mice via reducing Gasdermin D.

The mortality of sepsis and septic shock remains high worldwide. Neutrophil extracellular traps (NETs) release is a major cause of organ failure and mortality in sepsis. Targeting Gasdermin D (GSDMD) can restrain NETs formation, which is promising for sepsis management. However, no medicine is identified without severe safety concerns for this purpose. Xuebijing injection (XBJ) has been demonstrated to alleviate the clinical symptoms of COVID-19 and sepsis patients, but there are not enough animal studies to reveal its mechanisms in depth. Therefore, we wondered whether XBJ relieved pulmonary damage in sepsis by suppressing NETs formation and adopted a clinically relevant polymicrobial infection model to test this hypothesis. Firstly, XBJ effectively reversed lung injury caused by sepsis and restrained neutrophils recruitment to lung by down-regulating proinflammatory chemokines, such as CSF-3, CXCL-2, and CXCR-2. Strikingly, we found that XBJ significantly reduced the expressions of NETs component proteins, including citrullinated histone H3 (CitH3), myeloperoxidase (MPO), and neutrophil elastase (NE). GSDMD contributes to the production of NETs in sepsis. Notably, XBJ exhibited a reduced effect on the expressions of GSDMD and its upstream regulators. Besides, we also revealed that XBJ reversed NETs formation by inhibiting the expressions of GSDMD-related genes. Collectively, we demonstrated XBJ protected against sepsis-induced lung injury by reversing GSDMD-related pathway to inhibit NETs formation.

Identification of side-reaction products generated during the ammonia-catalyzed release of N-glycans.

N-linked glycosylation is one of the most important post translational modification of proteins. Various analytical techniques are used for the structural identification of the N-glycans released from proteins through various enzymatic and chemical methods. Although very few side-reaction products are generated during the enzymatic release of N-glycans, this method is expensive and suitable only for small quantities of samples. By contrast, chemical methods can be used for large quantities of samples; however, various side-reaction products are generated when chemical methods are used. Recently, the ammonia-catalyzed release of N-glycans from proteins has been reported to be associated with no typical side reactions. In the present study, we discovered a new side reaction: the epimerization of N-acetylglucosamine present at the reducing end of N-glycans to N-acetylmannosamine. The product of this side reaction interfered with the structural identification N-glycans. We propose a simple method that can help identify this artifact N-glycan isomer and eliminate the aforementioned interference. This simple method widens the applicability of ammonia-catalyzed reactions for N-glycan release from proteins, and is also suitable for N-glycans released using any other alkaline solutions.

Collision-induced dissociation of Na+-tagged ketohexoses: experimental and computational studies on fructose.

Collision-induced dissociation tandem mass spectrometry (CID-MSn) and computational investigation at the MP2/6-311+G(d,p) level of theory have been employed to study Na+-tagged fructose, an example of a ketohexose featuring four cyclic isomers: α-fructofuranose (αFruf), ß-fructofuranose (ßFruf), α-fructopyranose (αFrup), and ß-fructopyranose (ßFrup). The four isomers can be separated by high-performance liquid chromatography (HPLC) and they show different mass spectra, indicating that CID-MSn can distinguish the different fructose forms. Based on a simulation using a micro-kinetic model, we have obtained an overview of the mechanisms for the different dissociation pathways. It has been demonstrated that the preference for the C-C cleavage over the competing isomerization of linear fructose is the main reason for the previously reported differences between the CID-MS spectra of aldohexoses and ketohexoses. In addition, the kinetic modeling helped to confirm the assignment of the different measured mass spectra to the different fructose isomers. The previously reported assignment based on the peak intensities in the HPLC chromatogram had left some open questions as the preference for the dehydration channels did not always follow trends previously observed for aldohexoses. Setting up the kinetic model further enabled us to directly compare the computational and experimental results, which indicated that the model can reproduce most trends in the differences between the dissociation pathways of the four cyclic fructose isomers.