Search

Abstract Background Radiation-induced lung injury (RILI) is associated with alveolar epithelial cell death and secondary fibrosis in injured lung. Mesenchymal stem cell (MSC)-derived exosomes have regenerative effect against lung injury and the potential to intervene of RILI. However, their intervention efficacy is limited because they lack lung targeting characters and do not carry sufficient specific effectors. SARS-CoV-2 spike glycoprotein (SARS-CoV-2-S-RBD) binds angiotensin-converting enzyme 2 (ACE2) receptor and mediates interaction with host cells. MiR-486-5p is a multifunctional miRNA with angiogenic and antifibrotic potential and acts as an effector in MSC-derived exosomes. Ferroptosis is a form of cell death associated with radiation injury, its roles and mechanisms in RILI remain unclear. In this study, we developed an engineered MSC-derived exosomes with SARS-CoV-2-S-RBD- and miR-486-5p- modification and investigated their intervention effects on RIPF and action mechanisms via suppression of epithelial cell ferroptosis. Results Adenovirus-mediated gene modification led to miR-486-5p overexpression in human umbilical cord MSC exosomes (p

Abstract Pancreatic cancer is one of the most fatal cancers in the world. A growing number of studies have begun to demonstrate that mitochondria play a key role in tumorigenesis. Our previous study reveals that NDUFS2 (NADH: ubiquinone oxidoreductase core subunit S2), a core subunit of the mitochondrial respiratory chain complex I, is upregulated in Pancreatic adenocarcinoma (PAAD). However, its role in the development of PAAD remains unknown. Here, we showed that NDUFS2 played a critical role in the survival, proliferation and migration of pancreatic cancer cells by inhibiting mitochondrial cell death. Additionally, protein mass spectrometry indicated that the NDUFS2 was interacted with a deubiquitinase, OTUB1. Overexpression of OTUB1 increased NDUFS2 expression at the protein level, while knockdown of OTUB1 restored the effects in vitro. Accordingly, overexpression and knockdown of OTUB1 phenocopied those of NDUFS2 in pancreatic cancer cells, respectively. Mechanically, NDUFS2 was deubiquitinated by OTUB1 via K48-linked polyubiquitin chains, resulted in an elevated protein stability of NDUFS2. Moreover, the growth of OTUB1-overexpressed pancreatic cancer xenograft tumor was promoted in vivo, while the OTUB1-silenced pancreatic cancer xenograft tumor was inhibited in vivo. In conclusion, we revealed that OTUB1 increased the stability of NDUFS2 in PAAD by deubiquitylation and this axis plays a pivotal role in pancreatic cancer tumorigenesis and development.

Tau protein, a microtubule-associated protein, has a high specific expression in neurons and axons. Because traumatic spinal cord injury mainly affects neurons and axons, we speculated that tau protein may be a promising biomarker to reflect the degree of spinal cord injury and prognosis of motor function. In this study, 160 female Sprague-Dawley rats were randomly divided into a sham group, and mild, moderate, and severe spinal cord injury groups. A laminectomy was performed at the T8 level to expose the spinal cord in all groups. A contusion lesion was made with the NYU-MASCIS impactor by dropping a 10 g rod from heights of 12.5 mm (mild), 25 mm (moderate) and 50 mm (severe) upon the exposed dorsal surface of the spinal cord. Tau protein levels were measured in serum and cerebrospinal fluid samples at 1, 6, 12, 24 hours, 3, 7, 14 and 28 days after operation. Locomotor function of all rats was assessed using the Basso, Beattie and Bresnahan locomotor rating scale. Tau protein concentration in the three spinal cord injury groups (both in serum and cerebrospinal fluid) rapidly increased and peaked at 12 hours after spinal cord injury. Statistically significant positive linear correlations were found between tau protein level and spinal cord injury severity in the three spinal cord injury groups, and between the tau protein level and Basso, Beattie, and Bresnahan locomotor rating scale scores. The tau protein level at 12 hours in the three spinal cord injury groups was negatively correlated with Basso, Beattie, and Bresnahan locomotor rating scale scores at 28 days (serum: r = −0.94; cerebrospinal fluid: r = −0.95). Our data suggest that tau protein levels in serum and cerebrospinal fluid might be a promising biomarker for predicting the severity and functional outcome of traumatic spinal cord injury.

Magnesium alloys, acknowledged as the environmentally-friendly engineering material of the 21st century, are ideally suited to fulfill the requirements of lightweight manufacturing. However, the poor plasticity of magnesium alloys hampers their further application. Subsequently, development of nanoparticle-reinforced magnesium matrix composites has been proven to be a promising way to enhance the comprehensive performance of magnesium alloys. The exceptional performance achieved even by very small number of reinforcements stimulated innovation in preparation techniques and in-depth analysis of reinforcement mechanisms. This paper provides a review on key challenges related to their processing, the profound impact of different micro-nanoparticle reinforcements on the microstructure and properties of magnesium matrix composites during solidification and subsequent deformation machining. Additionally, the reinforcement mechanisms of the excellent mechanical performance of the composites are also discussed. This study can provide valuable insights for the understanding of the selection of appropriate reinforcements and processing to optimize the performance nanoparticle-reinforced magnesium matrix composites.

Spinal cord impairment involving motor neuron degeneration and demyelination can cause lifelong disabilities, but effective clinical interventions for restoring neurological functions have yet to be developed. In early spinal cord development, neural progenitors of the motor neuron (pMN) domain, defined by the expression of oligodendrocyte transcription factor 2 (OLIG2), in the ventral spinal cord first generate motor neurons and then switch the fate to produce myelin-forming oligodendrocytes. Given their differentiation potential, pMN progenitors could be a valuable cell source for cell therapy in relevant neurological conditions such as spinal cord injury. However, fast generation and expansion of pMN progenitors in vitro while conserving their differentiation potential has so far been technically challenging. In this study, based on chemical screening, we have developed a new recipe for efficient induction of pMN progenitors from human embryonic stem cells. More importantly, these OLIG2+ pMN progenitors can be stably maintained for multiple passages without losing their ability to produce spinal motor neurons and oligodendrocytes rapidly. Our results suggest that these self-renewing pMN progenitors could potentially be useful as a renewable source of cell transplants for spinal cord injury and demyelinating disorders. [ABSTRACT FROM AUTHOR]

Directed activation of C–H bonds usually occurs through 5-membered metallacycles, which poses limitations of regiochemistry. Herein, the authors use a phosphine oxide-ligated Ni−Al bimetallic catalyst to enable β-C−H bond-involved hydroarylations of alkynes via a rare 7-membered nickelacycle.

Allylic amines are versatile building blocks in organic synthesis and exist in bioactive compounds, but efficient catalytic systems for hydroaminoalkylation of alkynes are needed. Here, the authors report a late transition metal‐catalyzed hydroaminoalkylation of alkynes with N‐sulfonyl amines, providing a series of allylic amines in up to 94% yield.

To address energy shortage and environmental pollution, scientists are working to develop methods for the production, conversion, and storage of new energy sources. The development of thermal energy storage (TES) is considered to be one of the most effective energy conservation and environmental protection strategies for utilizing various renewable energy sources. Energy storage technology can solve the contradiction between energy supply and demand in time and space and also improve energy efficiency. Currently, TES includes mainly sensible heat storage, latent heat storage, and thermochemical energy storage. The latent heat TES based on phase change materials (PCMs) is an efficient technology that is being actively pursued owing to high storage density in a small temperature region, which is essential for accelerating new energy development and improving energy efficiency. In this paper, hydroxyapatite aerogels with self-supporting network structure were prepared via a hydrothermal method using calcium oleate as a precursor. Self-supporting hydroxyapatite-based composite phase change materials were synthesized using the impregnation method. The morphology and thermal properties of the prepared composite phase change materials were characterized and tested by scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, thermogravimetry, and differential scanning calorimetry. The experimental results show that the composite phase change materials of hydroxyapatite aerogels loaded with octadecanol or paraffin have good thermal properties. The measured values of melting enthalpy and solidified enthalpy of the 60% paraffin@HAP composite phase change materials are 85.10 and 85.30 J·g−1, respectively, and its crystallinity is 81.50%. The measured values of melting enthalpy and solidified enthalpy of the 60% octadecanol@HAP composite phase change material are 113.78 and 112.25 J·g−1, respectively, and its crystallinity is 86.20%. In addition, the composite has good thermal and chemical stability. Furthermore, the hydroxyapatite substrate has the advantages of good flame retardancy, corrosion-free characteristics, safety, and environmental protection, which effectively expands the practical application of phase change materials in the field of intelligent thermal insulation textiles and building materials.

Background: Traditional Chinese medicine (TCM) is widely integrated into cancer care in China. An overview in 2011 identified 2384 randomized and non-randomized controlled trials (RCTs, non-RCTs) on TCM for cancer published in the Chinese literature. This article summarizes updated evidence of RCTs on TCM for cancer care. Methods: We searched 4 main Chinese databases: China National Knowledge Infrastructure, Chinese Scientific Journal Database, SinoMed, and Wanfang. RCTs on TCM used in cancer care were analyzed in this bibliometric study. Results: Of 5834 RCTs (477 157 cancer patients), only 62 RCTs were indexed in MEDLINE. The top 3 cancers treated were lung, stomach, and breast cancer. About 4752 RCTs (81.45%) tested TCM combined with conventional treatment, and 1082 RCTs (18.55%) used TCM alone for treating symptoms and side-effects. Herbal medicine was the most frequently used TCM modality (5087 RCTs; 87.20%). The most frequently reported outcome was symptom improvement (3712 RCTs; 63.63%) followed by quality of life (2725 RCTs; 46.71%), and biomarkers (2384 RCTs; 40.86%). The majority of RCTs (4051; 69.44%) concluded there were beneficial effects using either TCM alone or TCM plus conventional treatment compared with conventional treatment. Conclusion: Substantial randomized trials demonstrated different types/stages of cancer were treated by various TCM modalities, alone or in combination with conventional medicine. Further evaluation on the effects and safety of TCM modalities focusing on outcomes such as quality of life is required.

Mitochondrial DNA (mtDNA) encodes vital proteins and RNAs for the normal functioning of the mitochondria. Mutations in mtDNA leading to mitochondrial dysfunction are relevant to a large spectrum of diseases, including fertility disorders. Since mtDNA undergoes rather complex processes during gametogenesis and fertilization, clarification of the changes and functions of mtDNA and its essential impact on gamete quality and fertility during this process is of great significance. Thanks to the emergence and rapid development of gene editing technology, breakthroughs have been made in mitochondrial genome editing (MGE), offering great potential for the treatment of mtDNA-related diseases. In this review, we summarize the features of mitochondria and their unique genome, emphasizing their inheritance patterns; illustrate the role of mtDNA in gametogenesis and fertilization; and discuss potential therapies based on MGE as well as the outlook in this field.

Abstract Inorganic mixed‐halide CsPbX3‐based perovskite solar cells (PeSCs) are emerging as one of the most promising types of PeSCs on account of their thermostability compared to organic–inorganic hybrid counterparts. However, dissatisfactory device performance and high processing temperature impede their development for viable applications. Herein, a facile route is presented for tuning the energy levels and electrical properties of sol–gel‐derived ZnO electron transport material (ETM) via the doping of a classical alkali metal carbonate Cs2CO3. Compared to bare ZnO, Cs2CO3‐doped ZnO possesses more favorable interface energetics in contact with the CsPbI2Br perovskite layer, which can reduce the ohmic loss to a negligible level. The optimized PeSCs achieve an improved open‐circuit voltage of 1.28 V, together with an increase in fill factor and short‐circuit current. The optimized power conversion efficiencies of 16.42% and 14.82% are realized on rigid glass substrate and flexible plastic substrate, respectively. A high thermostability can be simultaneously obtained via defect passivation at the Cs2CO3‐doped ZnO/CsPbI2Br interface, and 81% of the initial efficiency is retained after aging for 200 h at 85 °C.