Structural and functional basis of low-affinity SAM/SAH-binding in the conserved MTase of the multi-segmented Alongshan virus distantly related to canonical unsegmented flaviviruses.

Alongshan virus (ALSV), a newly discovered member of unclassified Flaviviridae family, is able to infect humans. ALSV has a multi-segmented genome organization and is evolutionarily distant from canonical mono-segmented flaviviruses. The virus-encoded methyltransferase (MTase) plays an important role in viral replication. Here we show that ALSV MTase readily binds S-adenosyl-L-methionine (SAM) and S-adenosyl-L-homocysteine (SAH) but exhibits significantly lower affinities than canonical flaviviral MTases. Structures of ALSV MTase in the free and SAM/SAH-bound forms reveal that the viral enzyme possesses a unique loop-element lining side-wall of the SAM/SAH-binding pocket. While the equivalent loop in flaviviral MTases half-covers SAM/SAH, contributing multiple hydrogen-bond interactions; the pocket-lining loop of ALSV MTase is of short-length and high-flexibility, devoid of any physical contacts with SAM/SAH. Subsequent mutagenesis data further corroborate such structural difference affecting SAM/SAH-binding. Finally, we also report the structure of ALSV MTase bound with sinefungin, an SAM-analogue MTase inhibitor. These data have delineated the basis for the low-affinity interaction between ALSV MTase and SAM/SAH and should inform on antiviral drug design.

Development of a bispecific nanobody conjugate broadly neutralizes diverse SARS-CoV-2 variants and structural basis for its broad neutralization.

The continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with increased transmissibility and profound immune-escape capacity makes it an urgent need to develop broad-spectrum therapeutics. Nanobodies have recently attracted extensive attentions due to their excellent biochemical and binding properties. Here, we report two high-affinity nanobodies (Nb-015 and Nb-021) that target non-overlapping epitopes in SARS-CoV-2 S-RBD. Both nanobodies could efficiently neutralize diverse viruses of SARS-CoV-2. The neutralizing mechanisms for the two nanobodies are further delineated by high-resolution nanobody/S-RBD complex structures. In addition, an Fc-based tetravalent nanobody format is constructed by combining Nb-015 and Nb-021. The resultant nanobody conjugate, designated as Nb-X2-Fc, exhibits significantly enhanced breadth and potency against all-tested SARS-CoV-2 variants, including Omicron sub-lineages. These data demonstrate that Nb-X2-Fc could serve as an effective drug candidate for the treatment of SARS-CoV-2 infection, deserving further in-vivo evaluations in the future.

Comparative study on metabolite variations of two rose teas by plant metabolomics and revealing their skin-whitening candidates by spectrum-effect relationship analysis.

INTRODUCTION: Rosa rugosa var. plena Rehd (CBR) and Rosa chinensis cv. "JinBian" (JBR) are two common species used in rose tea among different original species. CBR, the officially documented original plant of the rose species for food and medicinal purposes, is more costly than JBR. With increasing demand for different rose teas, it is meaningful to compare the chemical constituents for their quality control and reveal their skin-whitening components that will provide in-depth insights for the expansion of the rose tea industry. OBJECTIVE: This study aims to reveal the chemical variances between CBR and JBR and determine their skin-whitening components. METHODOLOGY: A strategy obtained by combining MS-based plant-metabolomics with spectrum-effect relationship analysis has been proposed for unveiling chemical differences between CBR and JBR and further exploring their potential skin-whitening components. RESULTS: A total of 2030 metabolites were found that revealed considerable differences between CBR and JBR. The results of bioactivity assay demonstrated that JBR exhibited stronger tyrosinase inhibition activity than CBR. Six potential skin-whitening compounds (di-O-galloyl-HHDP-glucoside, tri-O-galloyl-HHDP-glucoside, spiraeoside, quinic acid, rugosin A, and 1,2,3,6-tetra-O-galloyl-glucose) were discovered as potential tyrosinase inhibitors, via spectrum-effect relationship analysis. This is the first time that di-O-galloyl-HHDP-glucoside, tri-O-galloyl-HHDP-glucoside, rugosin A, and 1,2,3,6-tetra-O-galloyl-glucose have been reported with tyrosinase inhibitory activity. Additionally, molecular docking analysis was used to reveal the inhibition mechanism of these compounds toward tyrosinase. CONCLUSION: The finding of this study will be of great importance for the quality control of the two types of rose teas, and the revealed active ingredients will provide in-depth insights for the expansion of the rose tea industry.

PLS performance analysis of the vertical UWOC system with perfect and imperfect CSI.

Although underwater wireless optical communication (UWOC) receives much interest lately, security issues associated with it get little attention. In this work, it is the first attempt to investigate the physical layer security (PLS) performance of the vertical UWOC system with perfect and imperfect channel state information (CSI). Specifically speaking, the communication between two legitimate peers in the presence of an external eavesdropper is studied from the information-theoretic security perspective. Assuming that turbulence-induced fading over the vertical UWOC links is respectively subject to cascaded lognormal (LN) and Gamma-Gamma (GG) distributions for weak and moderate/strong turbulence conditions, and the angular pointing error is randomized by the Beckmann distribution, the composite cascaded statistical fading models are derived with the comprehensive effects of path loss, underwater turbulence, angular pointing errors, and channel estimation error. On the basis of these models, analysis frameworks of the probability of strictly positive secrecy capacity (SPSC), secrecy outage probability (SOP), and average secrecy capacity (ASC) are further obtained for this UWOC system, which are confirmed by Monte Carlo (MC) simulations. Furthermore, the effects including the number of layers, the level of channel estimation error, the link distance, the location of the eavesdropper, the quality of the main and eavesdropping channels on this system are analyzed for different water conditions. The presented results give valuable insights into the practical aspects of deployment of UWOC networks.

Markedly hypoechoic: a new definition improves the diagnostic performance of thyroid ultrasound.

OBJECTIVES: To determine the contribution of a modified definition of markedly hypoechoic in the differential diagnosis of thyroid nodules. METHODS: A total of 1031 thyroid nodules were included in this retrospective multicenter study. All of the nodules were examined with US before surgery. The US features of the nodules were evaluated, in particular, the classical markedly hypoechoic and modified markedly hypoechoic (decreased or similar echogenicity relative to the adjacent strap muscles). The sensitivity, specificity, and AUC of classical/modified markedly hypoechoic and the corresponding ACR-TIRADS, EU-TIRADS, and C-TIRADS categories were calculated and compared. The inter- and intraobserver variability in the evaluation of the main US features of the nodules was assessed. RESULTS: There were 264 malignant nodules and 767 benign nodules. Compared with classical markedly hypoechoic as a diagnostic criterion for malignancy, using modified markedly hypoechoic as the criterion resulted in a significant increase in sensitivity (28.03% vs. 63.26%) and AUC (0.598 vs. 0.741), despite a significant decrease in specificity (91.53% vs. 84.88%) (p < 0.001 for all). Compared to the AUC of the C-TIRADS with the classical markedly hypoechoic, the AUC of the C-TIRADS with the modified markedly hypoechoic increased from 0.878 to 0.888 (p = 0.01); however, the AUCs of the ACR-TIRADS and EU-TIRADS did not change significantly (p > 0.05 for both). There was substantial interobserver agreement (κ = 0.624) and perfect intraobserver agreement (κ = 0.828) for the modified markedly hypoechoic. CONCLUSION: The modified definition of markedly hypoechoic resulted in a significantly improved diagnostic efficacy in determining malignant thyroid nodules and may improve the diagnostic performance of the C-TIRADS. CLINICAL RELEVANCE STATEMENT: Our study found that, compared with the original definition, modified markedly hypoechoic significantly improved the diagnostic performance in differentiating malignant from benign thyroid nodules and the predictive efficacy of the risk stratification systems. KEY POINTS: • Compared with the classical markedly hypoechoic as a diagnostic criterion for malignancy, the modified markedly hypoechoic resulted in a significant increase in sensitivity and AUC. • The C-TIRADS with the modified markedly hypoechoic achieved higher AUC and specificity than that with the classical markedly hypoechoic (p = 0.01 and < 0.001, respectively).

The urban-rural disparities and factors associated with the utilization of public health services among diabetes patients in China.

BACKGROUND: Basic public health services for diabetes play an essential role in controlling glycemia in patients with diabetes. This study was conducted to understand the urban-rural disparities in the utilization of basic public health services for people with diabetes and the factors influencing them. METHODS: The data were obtained from the 2018 China Health and Retirement Longitudinal Study (CHARLS) with 2976 diabetes patients. Chi-square tests were used to examine the disparities in the utilization of diabetes physical examination and health education between urban and rural areas. Logistic regression was performed to explore the factors associated with the utilization of diabetes public health services. RESULTS: Among all participants, 8.4% used diabetes physical examination in the past year, and 28.4% used diabetes health education services. A significant association with age (OR = 0.64, 95% CI:0.49-0.85; P < 0.05) was found between patients' use of health education services. Compared with diabetes patients living in an urban area, diabetes patients living in a rural area used less diabetes health education. (χ2= 92.39, P < 0.05). Patients' self-reported health status (OR = 2.04, CI:1.24-3.35; P < 0.05) and the use of glucose control (OR = 9.33, CI:6.61-13.16; P < 0.05) were significantly positively associated with the utilization of diabetes physical examination. Patients with higher education levels were more likely to use various kinds of health education services than their peers with lower education levels (OR = 1.64, CI:1.21-2.22; P < 0.05). CONCLUSION: Overall, urban-rural disparities in the utilization of public health services existed. Vulnerable with diabetes, such as those in rural areas, are less available to use diabetes public health services. Providing convenient health service infrastructure facilitates the utilization of basic public health services for diabetes in older patients with diabetes, especially in rural areas.

Nerve Injury-Induced γH2AX Reduction in Primary Sensory Neurons Is Involved in Neuropathic Pain Processing.

Phosphorylation of the serine 139 of the histone variant H2AX (γH2AX) is a DNA damage marker that regulates DNA damage response and various diseases. However, whether γH2AX is involved in neuropathic pain is still unclear. We found the expression of γH2AX and H2AX decreased in mice dorsal root ganglion (DRG) after spared nerve injury (SNI). Ataxia telangiectasia mutated (ATM), which promotes γH2AX, was also down-regulated in DRG after peripheral nerve injury. ATM inhibitor KU55933 decreased the level of γH2AX in ND7/23 cells. The intrathecal injection of KU55933 down-regulated DRG γH2AX expression and significantly induced mechanical allodynia and thermal hyperalgesia in a dose-dependent manner. The inhibition of ATM by siRNA could also decrease the pain threshold. The inhibition of dephosphorylation of γH2AX by protein phosphatase 2A (PP2A) siRNA partially suppressed the down-regulation of γH2AX after SNI and relieved pain behavior. Further exploration of the mechanism revealed that inhibiting ATM by KU55933 up-regulated extracellular-signal regulated kinase (ERK) phosphorylation and down-regulated potassium ion channel genes, such as potassium voltage-gated channel subfamily Q member 2 (Kcnq2) and potassium voltage-gated channel subfamily D member 2 (Kcnd2) in vivo, and KU559333 enhanced sensory neuron excitability in vitro. These preliminary findings imply that the down-regulation of γH2AX may contribute to neuropathic pain.

Identification of a Novel Specific Cucurbitadienol Synthase Allele in Siraitia grosvenorii Correlates with High Catalytic Efficiency.

Mogrosides, the main bioactive compounds isolated from the fruits of Siraitia grosvenorii, are a group of cucurbitane-type triterpenoid glycosides that exhibit a wide range of notable biological activities and are commercially available worldwide as natural sweeteners. However, the extraction cost is high due to their relatively low contents in plants. Therefore, molecular breeding needs to be achieved when conventional plant breeding can hardly improve the quality so far. In this study, the levels of 21 active mogrosides and two precursors in 15 S. grosvenorii varieties were determined by HPLC-MS/MS and GC-MS, respectively. The results showed that the variations in mogroside V content may be caused by the accumulation of cucurbitadienol. Furthermore, a total of four wild-type cucurbitadienol synthase protein variants (50R573L, 50C573L, 50R573Q, and 50C573Q) based on two missense mutation single nucleotide polymorphism (SNP) sites were discovered. An in vitro enzyme reaction analysis indicated that 50R573L had the highest activity, with a specific activity of 10.24 nmol min-1 mg-1. In addition, a site-directed mutant, namely, 50K573L, showed a 33% enhancement of catalytic efficiency compared to wild-type 50R573L. Our findings identify a novel cucurbitadienol synthase allele correlates with high catalytic efficiency. These results are valuable for the molecular breeding of luohanguo.

Factors associated with psychological insulin resistance among patients with type 2 diabetes in China.

Objective: The aim of this study was to understand the psychological insulin resistance status among Chinese patients with type 2 diabetes and investigate its associated factors in these patients. Methods: A multi-stage stratified random sampling was performed to randomly select patients with type 2 diabetes from the eastern, central, and western regions in Shandong Province, China, and 660 valid questionnaires were collected. Psychological insulin resistance was assessed by the scale of My Opinion on Insulin (MOI). Factors associated with psychological insulin resistance were examined in a binary logistic model. Results: Four-fifths of the patients with type 2 diabetes (82.1%) had psychological insulin resistance. Being female (OR = 1.770, 95% CI: 1.063-2.950, p < 0.05), having a monthly income of greater than 4,000 Renminbi (approximately $1,540) (OR = 0.444, 95% CI: 0.216-0.915, p < 0.05), living with type 2 diabetes for 11 years or more (OR = 0.387, 95% CI: 0.238-0.630, p < 0.05), self-rated poor health (OR = 1.706, 95% CI: 1.092-2.664, p < 0.05), and moderate discrimination against type 2 diabetes (OR = 1.924, 95% CI: 1.166-3.175, p < 0.05) were associated with psychological insulin resistance. Conclusions: The prevalence of psychological insulin resistance among Chinese patients with type 2 diabetes is relatively high. Approaches are needed to address the issue of psychological insulin resistance of type 2 diabetes.

Columnar optical-radiative properties and components of aerosols in the Arctic summer from long-term AERONET measurements.

Aerosols as an external factor have an important role in the amplification of Arctic warming, yet the geography of this harsh region has led to a paucity of observations, which has limited our understanding of the Arctic climate. We synthesized the latest decade (2010-2021) of data on the microphysical-optical-radiative properties of aerosols and their multi-component evolution during the Arctic summer, taking into consideration the important role of wildfire burning. Our results are based on continuous observations from eight AERONET sites across the Arctic region, together with a meteorological reanalysis dataset and satellite observations of fires, and utilize a back-trajectory model to track the source of the aerosols. The summer climatological characteristics within the Arctic Circle showed that the aerosols are mainly fine-mode aerosols (fraction >0.95) with a radius of 0.15-0.20 µm, a slight extinction ability (aerosol optical depth âˆ¼ 0.11) with strong scattering (single scattering albedo ∼0.95) and dominant forward scattering (asymmetry factor âˆ¼ 0.68). These optical properties result in significant cooling at the Earth's surface (∼-13 W m-2) and a weak cooling effect at the top of the atmosphere (∼-5 W m-2). Further, we found that Arctic region is severely impacted by wildfire burning events in July and August, which primarily occur in central and eastern Siberia and followed in subpolar North America. The plumes from wildfire transport aerosols to the Arctic atmosphere with the westerly circulation, leading to an increase in fine-mode aerosols containing large amounts of organic carbon, with fraction as high as 97-98 %. Absorptive carbonaceous aerosols also increase synergistically, which could convert the instantaneous direct aerosol radiative effect into a heating effect on the Earth-atmosphere system. This study provides insights into the complex sources of aerosol loading in the Arctic atmosphere in summer and emphasizes the important impacts of the increasingly frequent occurrence of wildfire burning events in recent years.

Nucleoside modification-based flexizymes with versatile activity for tRNA aminoacylation.

Extensive research has focused on genetic code reprogramming using flexizymes (Fxs), ribozymes enabling diverse tRNA acylation. Here we describe a nucleoside-modification strategy for the preparation of flexizyme variants derived from 2'-OMe, 2'-F, and 2'-MOE modifications with unique and versatile activities, enabling the charging of tRNAs with a broad range of substrates. This innovative strategy holds promise for synthetic biology applications, offering a robust pathway to expand the genetic code for diverse substrate incorporation.

Deprivation of methionine inhibits osteosarcoma growth and metastasis via C1orf112-mediated regulation of mitochondrial functions.

Osteosarcoma is a malignant bone tumor that primarily inflicts the youth. It often metastasizes to the lungs after chemotherapy failure, which eventually shortens patients' lives. Thus, there is a dire clinical need to develop a novel therapy to tackle osteosarcoma metastasis. Methionine dependence is a special metabolic characteristic of most malignant tumor cells that may offer a target pathway for such therapy. Herein, we demonstrated that methionine deficiency restricted the growth and metastasis of cultured human osteosarcoma cells. A genetically engineered Salmonella, SGN1, capable of overexpressing an L-methioninase and hydrolyzing methionine led to significant reduction of methionine and S-adenosyl-methionine (SAM) specifically in tumor tissues, drastically restricted the growth and metastasis in subcutaneous xenograft, orthotopic, and tail vein-injected metastatic models, and prolonged the survival of the model animals. SGN1 also sharply suppressed the growth of patient-derived organoid and xenograft. Methionine restriction in the osteosarcoma cells initiated severe mitochondrial dysfunction, as evident in the dysregulated gene expression of respiratory chains, increased mitochondrial ROS generation, reduced ATP production, decreased basal and maximum respiration, and damaged mitochondrial membrane potential. Transcriptomic and molecular analysis revealed the reduction of C1orf112 expression as a primary mechanism underlies methionine deprivation-initiated suppression on the growth and metastasis as well as mitochondrial functions. Collectively, our findings unraveled a molecular linkage between methionine restriction, mitochondrial function, and osteosarcoma growth and metastasis. A pharmacological agent, such as SGN1, that can achieve tumor specific deprivation of methionine may represent a promising modality against the metastasis of osteosarcoma and potentially other types of sarcomas as well.

Application of Polypyrrole-Based Electrochemical Biosensor for the Early Diagnosis of Colorectal Cancer.

Although colorectal cancer (CRC) is easy to treat surgically and can be combined with postoperative chemotherapy, its five-year survival rate is still not optimistic. Therefore, developing sensitive, efficient, and compliant detection technology is essential to diagnose CRC at an early stage, providing more opportunities for effective treatment and intervention. Currently, the widely used clinical CRC detection methods include endoscopy, stool examination, imaging modalities, and tumor biomarker detection; among them, blood biomarkers, a noninvasive strategy for CRC screening, have shown significant potential for early diagnosis, prediction, prognosis, and staging of cancer. As shown by recent studies, electrochemical biosensors have attracted extensive attention for the detection of blood biomarkers because of their advantages of being cost-effective and having sound sensitivity, good versatility, high selectivity, and a fast response. Among these, nano-conductive polymer materials, especially the conductive polymer polypyrrole (PPy), have been broadly applied to improve sensing performance due to their excellent electrical properties and the flexibility of their surface properties, as well as their easy preparation and functionalization and good biocompatibility. This review mainly discusses the characteristics of PPy-based biosensors, their synthetic methods, and their application for the detection of CRC biomarkers. Finally, the opportunities and challenges related to the use of PPy-based sensors for diagnosing CRC are also discussed.

NIR-II Luminescent and Multi-Responsive Rare Earth Nanocrystals for Improved Chemodynamic Therapy.

Chemodynamic therapy (CDT) based on the Fe2+-mediated Fenton reaction can amplify intracellular oxidative stress by producing toxic •OH. However, the high-dose need for Fe2+ delivery in tumors and its significant cytotoxicity to normal tissues set a challenge. Therefore, a controllable delivery to activate the Fenton reaction and enhance Fe2+ tumor accumulation has become an approach to solve this conflict. Herein, we report a rare-earth-nanocrystal (RENC)-based Fe2+ delivery system using light-control techniques and DNA nanotechnology to realize programmable Fe2+ delivery. Ferrocenes, the source of Fe2+, are modified on the surface of RENCs through pH-responsive DNAs, which are further shielded by a PEG layer to elongate blood circulation and "turn off" the cytotoxicity of ferrocene. The up-/down-conversion dual-mode emissions of RENCs endow the delivery system with both capabilities of diagnosis and delivery control. The down-conversion NIR-II fluorescence can locate tumors. Consequently, up-conversion UV light spatiotemporally activates the catalytic activity of Fe2+ by shedding off the protective PEG layer. The exposed ferrocene-DNAs not only can "turn on" Fenton catalytic activity but also respond to tumor acidity, driving cross-linking and enhanced Fe2+ enrichment in tumors by 4.5-fold. Accordingly, this novel design concept will be inspiring for developing CDT nanomedicines in the future.

Changes in aerosol loading before, during and after the COVID-19 pandemic outbreak in China: Effects of anthropogenic and natural aerosol.

Anthropogenic emissions reduced sharply in the short-term during the coronavirus disease pandemic (COVID-19). As COVID-19 is still ongoing, changes in atmospheric aerosol loading over China and the factors of their variations remain unclear. In this study, we used multi-source satellite observations and reanalysis datasets to synergistically analyze the spring (February-May) evolution of aerosol optical depth (AOD) for multiple aerosol types over Eastern China (EC) before, during and after the COVID-19 lockdown period. Regional meteorological effects and the radiative response were also quantitatively assessed. Compared to the same period before COVID-19 (i.e., in 2019), a total decrease of -14.6 % in tropospheric TROPOMI nitrogen dioxide (NO2) and a decrease of -6.8 % in MODIS AOD were observed over EC during the lockdown period (i.e., in 2020). After the lockdown period (i.e., in 2021), anthropogenic emissions returned to previous levels and there was a slight increase (+2.3 %) in AOD over EC. Moreover, changes in aerosol loading have spatial differences. AOD decreased significantly in the North China Plain (-14.0 %, NCP) and Yangtze River Delta (-9.4 %) regions, where anthropogenic aerosol dominated the aerosol loading. Impacted by strong wildfires in Southeast Asia during the lockdown period, carbonaceous AOD increased by +9.1 % in South China, which partially offset the emission reductions. Extreme dust storms swept through the northern region in the period after COVID-19, with an increase of +23.5 % in NCP and + 42.9 % in Northeast China (NEC) for dust AOD. However, unfavorable meteorological conditions overwhelmed the benefits of emission reductions, resulting in a +20.1 % increase in AOD in NEC during the lockdown period. Furthermore, the downward shortwave radiative flux showed a positive anomaly due to the reduced aerosol loading in the atmosphere during the lockdown period. This study highlights that we can benefit from short-term controls for the improvement of air pollution, but we also need to seriously considered the cross-regional transport of natural aerosol and meteorological drivers.

One-Pot Rapid Synthesis of Cu2+-Doped GOD@MOF to Amplify the Antitumor Efficacy of Chemodynamic Therapy.

Chemodynamic therapy (CDT) relies on the transformation of intracellular hydrogen peroxide (H2O2) to hydroxyl radicals (·OH) with higher toxicity under the catalysis of Fenton/Fenton-like reagents, which amplifies the oxidative stress and induces significant cellular apoptosis. However, the CDT efficacy is generally limited by the overexpressed GSH and insufficient endogenous H2O2 in tumors. Co-delivery of Cu2+ and glucose oxidase (GOD) can lead to a Cu2+/Cu+ circulation to realize GSH depletion and amplify the Fenton-like reaction. pH-responsive metal-organic frameworks (MOFs) are the optical choice to deliver Fenton/Fenton-like ions to tumors. However, considering that the aqueous condition is requisite for GOD encapsulation, it is challenging to abundantly dope Cu2+ in ZIF-8 MOF nanoparticles in aqueous conditions due to the ease of precipitation and enlarged crystal size. In this work, a robust one-pot biomimetic mineralization method using excessive ligand precursors in aqueous conditions is developed to synthesize GOD@Cu-ZIF-8. Copper ions abundantly doped to the GOD@Cu-ZIF-8 can eliminate GSH to produce Cu+, which is further proceeded to the Fenton-like reaction in the presence of GOD-catalyzed H2O2. Through breaking the tumor microenvironment homeostasis and producing an enhanced CDT effect, the promising antitumor capability of GOD@Cu-ZIF-8 was evidenced by the experiments both in vitro and in vivo.

The roles and applications of neural stem cells in spinal cord injury repair.

Spinal cord injury (SCI), which has no current cure, places a severe burden on patients. Stem cell-based therapies are considered promising in attempts to repair injured spinal cords; such options include neural stem cells (NSCs). NSCs are multipotent stem cells that differentiate into neuronal and neuroglial lineages. This feature makes NSCs suitable candidates for regenerating injured spinal cords. Many studies have revealed the therapeutic potential of NSCs. In this review, we discuss from an integrated view how NSCs can help SCI repair. We will discuss the sources and therapeutic potential of NSCs, as well as representative pre-clinical studies and clinical trials of NSC-based therapies for SCI repair.

Effect of germination on the main chemical compounds and 5-methyltetrahydrofolate metabolism of different quinoa varieties.

This study determined the content of macronutrients and micronutrients to investigate the nutritional value and health benefits of six varieties of quinoa seeds and sprouts. Germination markedly increased the contents of proteins, reducing sugars, free amino acids, vitamins, and phytochemicals such as phenolic and carotenoid compounds, with variation among different quinoa varieties. Relatively high levels of 5-methyltetrahydrofolate (5-MTHF) were found in 6-day-old quinoa sprouts, especially in the LL-1 variety (1747.25 µg/100 g DW), followed by QL-2 sprouts (1501.67 µg/100 g DW). Furthermore, we examined the relative expression of genes involved in the folate biosynthetic pathway during QL-2 germination. The expression of the ADCS gene was upregulated 28.31-fold in 6-day-old sprouts, greatly facilitating folate synthesis. Pterin synthesis genes regulate the biosynthesis and further accumulation of folate by controlling pterin metabolic flux. Overall, the 6-day-old sprouts were recommended as a functional food with nutritional value and health benefits in dietary supplements.

Electrospun nanofibers for manipulating soft tissue regeneration.

Soft tissue damage is a common clinical problem that affects the lives of a large number of patients all over the world. It is of great importance to develop functional scaffolds to manipulate and promote the repair and regeneration of soft tissues. Owing to their unique composition and structural properties, electrospun nanofibers have attracted much attention for soft tissue regeneration. Electrospun nanofibers can be easily constructed and functionally modified to regulate their composition, morphology, structure, three-dimensional architecture, and biological functions, as well as specific light/electric/magnetic properties. By integrating multiple types of guidance cues, such as topographical and biochemical cues and external stimuli, electrospun nanofiber scaffolds can be used to manipulate cell behaviors and thus facilitate tissue regeneration. In this review article, we have first described the construction of electrospun nanofibers with specific morphology and topography and their capability of modulating cell migration, cell morphology, and stem cell differentiation. We have then discussed the role of electrospun nanofiber scaffolds in promoting the regeneration of different types of soft tissues, including nerves, skin, heart, blood vessels, and cornea, from the point of view of the anatomical structures and physiological regeneration processes of tissues. By presenting and discussing the recent progress of electrospun nanofibers in manipulating soft tissue regeneration, we hope to provide a possible solution and reference for the repair of tissue damage in clinical practice.

Molecular imaging nanoprobes for theranostic applications.

As a non-invasive imaging monitoring method, molecular imaging can provide the location and expression level of disease signature biomolecules in vivo, leading to early diagnosis of relevant diseases, improved treatment strategies, and accurate assessment of treating efficacy. In recent years, a variety of nanosized imaging probes have been developed and intensively investigated in fundamental/translational research and clinical practice. Meanwhile, as an interdisciplinary discipline, this field combines many subjects of chemistry, medicine, biology, radiology, and material science, etc. The successful molecular imaging not only requires advanced imaging equipment, but also the synthesis of efficient imaging probes. However, limited summary has been reported for recent advances of nanoprobes. In this paper, we summarized the recent progress of three common and main types of nanosized molecular imaging probes, including ultrasound (US) imaging nanoprobes, magnetic resonance imaging (MRI) nanoprobes, and computed tomography (CT) imaging nanoprobes. The applications of molecular imaging nanoprobes were discussed in details. Finally, we provided an outlook on the development of next generation molecular imaging nanoprobes.