Upregulation of serine metabolism enzyme PSAT1 predicts poor prognosis and promotes proliferation, metastasis and drug resistance of clear cell renal cell carcinoma.

Serine metabolic reprogramming is known to be associated with oncogenesis and tumor development. The key metabolic enzyme PSAT1 has been identified as a potential prognostic marker for various cancers, but its role in ccRCC remains unkown. In this study, we investigated expression of PSAT1 in ccRCC using the TCGA database and clinical specimens. Our results showed that PSAT1 exhibited lower expression in tumor tissue compared to adjacent normal tissue, but its expression level increased with advancing stages and grades of ccRCC. Patients with elevated expression level of PSAT1 exhibited an unfavorable prognosis. Functional experiments have substantiated that the depletion of PSAT1 shows an effective activity in inhibiting the proliferation, migration and invasion of ccRCC cells, concurrently promoting apoptosis. RNA sequencing analysis has revealed that the attenuation of PSAT1 can diminish tumor resistance to therapeutic drugs. Furthermore, the xenograft model has indicated that the inhibition of PSAT1 can obviously impact the tumorigenic potential of ccRCC and mitigate lung metastasis. Notably, pharmacological targeting PSAT1 by Aminooxyacetic Acid (AOA) or knockdown of PSAT1 increased the susceptibility of sunitinib-resistant cells. Inhibition of PSAT1 increased the sensitivity of drug-resistant tumors to sunitinib in vivo. Collectively, our investigation identifies PSAT1 as an independent prognostic biomarker for advanced ccRCC patients and as a prospective therapeutic target.

Tetherin Suppresses Type I Interferon Signaling by Targeting MAVS for NDP52-Mediated Selective Autophagic Degradation in Human Cells.

Tetherin (BST2/CD317) is an interferon-inducible antiviral factor known for its ability to block the release of enveloped viruses from infected cells. Yet its role in type I interferon (IFN) signaling remains poorly defined. Here, we demonstrate that Tetherin is a negative regulator of RIG-I like receptor (RLR)-mediated type I IFN signaling by targeting MAVS. The induction of Tetherin by type I IFN accelerates MAVS degradation via ubiquitin-dependent selective autophagy in human cells. Moreover, Tetherin recruits E3 ubiquitin ligase MARCH8 to catalyze K27-linked ubiquitin chains on MAVS at lysine 7, which serves as a recognition signal for NDP52-dependent autophagic degradation. Taken together, our findings reveal a negative feedback loop of RLR signaling generated by Tetherin-MARCH8-MAVS-NDP52 axis and provide insights into a better understanding of the crosstalk between selective autophagy and optimal deactivation of type I IFN signaling.

Flower-shaped Ni(OH)2decorated with biomass-derived carbon TPB-1 for asymmetric supercapacitors.

In recent years, notable headway has been made in augmenting supercapacitor functioning through employment of pioneering components, exceptional nanostructures and additional investigation of electrolytes. Nonetheless, achieving superior performance with straightforward techniques remains a significant hurdle. In order to surmount this, an experimental three-dimensional nanospherical pore structure (TPB-20@Ni(OH)2) was designed and prepared. TPB-1 was obtained through carbonisation and activation. TPB-20@Ni(OH)2nanoparticles were synthesized using TPB-1 as the carbon source and nickel chloride hexahydrate as the nickel source. Furthermore, the TPB-20@Ni(OH)2//AC supercapacitor displayed an impressive energy density of 22.1 Wh kg-1. The TPB-20@Ni(OH)2composites exhibited a specific capacity of 978 F-1, which is noteworthy. The exceptional output exhibited by the TPB-20@Ni(OH)2composite derives from its innovative structure, presenting an extensive specific surface area of 237.4 m2g-1and porosity of roughly 4.0 nm. Following 20 000 cycles (at a current density of 1 A g-1), asymmetric supercapacitors assembled from TPB-20@Ni(OH)2//AC retained 80.0% of its initial specific electrostatic capacity, indicating superior electrochemical stability and high electrochemical reversibility.

Synthesis and evaluation of pentacyclic triterpenoids conjugates as novel HBV entry inhibitors targeting NTCP receptor.

Chronic liver diseases caused by hepatitis B virus (HBV) are the accepted main cause leading to liver cirrhosis, hepatic fibrosis, and hepatic carcinoma. Sodium taurocholate cotransporting polypeptide (NTCP), a specific membrane receptor of hepatocytes for triggering HBV infection, is a promising target against HBV entry. In this study, pentacyclic triterpenoids (PTs) including glycyrrhetinic acid (GA), oleanolic acid (OA), ursolic acid (UA) and betulinic acid (BA) were modified via molecular hybridization with podophyllotoxin respectively, and resulted in thirty-two novel conjugates. The anti-HBV activities of conjugates were evaluated in HepG2.2.15 cells. The results showed that 66% of the conjugates exhibited lower toxicity to the host cells and had significant inhibitory effects on the two HBV antigens, especially HBsAg. Notably, the compounds BA-PPT1, BA-PPT3, BA-PPT4, and UA-PPT3 not only inhibited the secretion of HBsAg but also suppressed HBV DNA replication. A significant difference in the binding of active conjugates to NTCP compared to the HBV PreS1 antigen was observed by SPR assays. The mechanism of action was found to be the competitive binding of these compounds to the NTCP 157-165 epitopes, blocking HBV entry into host cells. Molecular docking results indicated that BA-PPT3 interacted with the amino acid residues of the target protein mainly through π-cation, hydrogen bond and hydrophobic interaction, suggesting its potential as a promising HBV entry inhibitor targeting the NTCP receptor.

Optical Genome Mapping Reveals Novel Structural Variants in Lymphoblastic Lymphoma.

BACKGROUND: Accurate histologic and molecular genetic diagnosis is critical for the pathogenesis study of pediatric patients with lymphoblastic lymphoma (LBL). Optical genome mapping (OGM) as all-in-one process allows the detection of most major genomic risk markers, which addresses some of the limitations associated with conventional cytogenomic testing, such as low resolution and throughput, difficulty in ascertaining genomic localization, and orientation of segments in duplication, inversions, and insertions. Here, for the first time, we examined the cytogenetics of 5 children with LBL using OGM. METHODS: OGM was used to analyze 5 samples of pediatric LBL patients treated according to the modified NHL-BFM95 backbone regimen. Whole-exon Sequencing (WES) was used to confirm the existence of structural variants (SVs) identified by OGM with potentially clinical significance on MGI Tech (DNBSEQ-T7) platform. According to the fusion exon sequences revealed by WES, the HBS1L :: AHI1 fusion mRNA in case 4 was amplified by cDNA-based PCR. RESULTS: In total, OGM identified 251 rare variants (67 insertions, 129 deletions, 3 inversion, 25 duplications, 15 intrachromosomal translocations, and 12 interchromosomal translocations) and 229 copy number variants calls (203 gains and 26 losses). Besides all of the reproducible and pathologically significant genomic SVs detected by conventional cytogenetic techniques, OGM identified more SVs with definite or potential pathologic significance that were not detected by traditional methods, including 2 new fusion genes, HBS1L :: AHI1 and GRIK1::NSDHL , which were confirmed by WES and/or Reverse Transcription-Polymerase Chain Reaction. CONCLUSIONS: Our results demonstrate the feasibility of OGM to detect genomic aberrations, which may play an important role in the occurrence and development of lymphomagenesis as an important driving factor.

Comparison of radiological and clinical outcomes of cervical laminoplasty versus lateral mass screw fixation in patients with ossification of the posterior longitudinal ligament.

PURPOSE: This study aimed to compare cervical sagittal parameters and clinical outcomes between patients undergoing cervical laminoplasty(CL) and those undergoing lateral mass screw fixation(LMS). METHODS: We retrospectively studied 67 patients with multilevel ossification of the posterior longitudinal ligament (OPLL) of the cervical spine who underwent lateral mass screw fixation (LMS = 36) and cervical laminoplasty (CL = 31). We analyzed cervical sagittal parameters (C2-7 sagittal vertical axis (C2-7 SVA), C0-2 Cobb angle, C2-7 Cobb angle, C7 slope (C7s), T1 slope (T1s), and spino-cranial angle (SCA)) and clinical outcomes (visual analog scale [VAS], neck disability index [NDI], Japanese Orthopaedic Association [JOA] scores, recovery rate (RR), and minimum clinically significant difference [MCID]). The cervical sagittal parameters at the last follow-up were analyzed by binary logistic regression. Finally, we analyzed the correlation between the cervical sagittal parameters and each clinical outcome at the last follow-up after surgery in both groups. RESULTS: At the follow-up after posterior decompression in both groups, the mean values of C2-C7 SVA, C7s, and T1s in the LMS group were more significant than those in the CL group (P ≤ 0.05). Compared with the preoperative period, C2-C7 SVA, T1s, and SCA gradually increased, and the C2-C7 Cobb angle gradually decreased after surgery (P < 0.05). The improvement in the JOA score and the recovery rate was similar between the two groups, while the improvement in the VAS-N score and NDI score was more significant in the CL group (P = 0.001; P = 0.043). More patients reached MCID in the CL group than in the LMS group (P = 0.036). Binary logistic regression analysis showed that SCA was independently associated with whether patients reached MCID at NDI postoperatively. SCA was positively correlated with cervical NDI and negatively correlated with cervical JOA score at postoperative follow-up in both groups (P < 0.05); C2-7 Cobb angle was negatively correlated with cervical JOA score at postoperative follow-up (P < 0.05). CONCLUSION: CL may be superior to LMS in treating cervical spondylotic myelopathy caused by OPLL. In addition, smaller cervical SCA after posterior decompression may suggest better postoperative outcomes.

Differentiation and immunosuppressive function of CD19+CD24hiCD27+ regulatory B cells are regulated through the miR-29a-3p/NFAT5 pathway.

BACKGROUND: Regulatory B cells (Bregs) is an indispensable element in inducing immune tolerance after liver transplantation. As one of the microRNAs (miRNAs), miR-29a-3p also inhibits translation by degrading the target mRNA, and yet the relationship between Bregs and miR-29a-3p has not yet been fully explored. This study aimed to investigate the impact of miR-29a-3p on the regulation of differentiation and immunosuppressive functions of memory Bregs (mBregs) and ultimately provide potentially effective therapies in inducing immune tolerance after liver transplantation. METHODS: Flow cytometry was employed to determine the levels of Bregs in peripheral blood mononuclear cells. TaqMan low-density array miRNA assays were used to identify the expression of different miRNAs, electroporation transfection was used to induce miR-29a-3p overexpression and knockdown, and dual luciferase reporter assay was used to verify the target gene of miR-29a-3p. RESULTS: In patients experiencing acute rejection after liver transplantation, the proportions and immunosuppressive function of mBregs in the circulating blood were significantly impaired. miR-29a-3p was found to be a regulator of mBregs differentiation. Inhibition of miR-29a-3p, which targeted nuclear factor of activated T cells 5 (NFAT5), resulted in a conspicuous boost in the differentiation and immunosuppressive function of mBregs. The inhibition of miR-29a-3p in CD19+ B cells was capable of raising the expression levels of NFAT5, thereby promoting B cells to differentiate into mBregs. In addition, the observed enhancement of differentiation and immunosuppressive function of mBregs upon miR-29a-3p inhibition was abolished by the knockdown of NFAT5 in B cells. CONCLUSIONS: miR-29a-3p was found to be a crucial regulator for mBregs differentiation and immunosuppressive function. Silencing miR-29a-3p could be a potentially effective therapeutic strategy for inducing immune tolerance after liver transplantation.

Transcriptomic analysis the mechanisms of anti-osteoporosis of desert-living Cistanche herb in ovariectomized rats of postmenopausal osteoporosis.

Desert-living Cistanche herb (DC), as a traditional Chinese medicine for tonifying kidney yang, is often used to treat postmenopausal osteoporosis (PMOP). Total phenylethanoid glycosides are instruction ingredients for discrimination and assay according to the China pharmacopoeia for DC. This research aimed to reveal the anti-osteoporosis mechanism of total phenylethanoid glycosides of DC (PGC) by transcriptomic analysis of ovariectomized rats. Serum levels of BGP were evaluated by ELISA, the bone weight was measured, and transmission electron microscopy was used to examine the ultrastructure of osteoblasts in rats. In addition, micro-CT was used to detect the bone volume (Tb.BS/BV), bone mineral density (Tb.BMD), and bone mineral content (Tb.BMC) in trabecular bone, and the ratio of cortical bone area to total area (Ct.ar/Tt.ar), and the level of bone mineral content (Ct.BMC) in cortical bone. Differential expressed genes (DEGs) after PGC treatment were analyzed by transcriptomics. Then, a bioinformatics analysis of DEGs was carried out through GO enrichment, KEGG enrichment, and selection of the nucleus gene through the protein-protein interaction network. Through qRT-PCR analysis, the DEGs were verified. The analysis results indicated that PGC increased the secretion of osteogenic markers, and ultrastructural characterization of osteoblasts and bone morphology were improved in ovariectomized rats. A total of 269 genes were differentially expressed, including 201 genes that were downregulated and 68 genes that were upregulated between the model group and the PGC group. Bioinformation analysis results prompt the conclusion that PGC could promote the bone metabolism by muscle cell development, myofibril assembly, etc. In addition, our study also found that PGC has a good effect on osteoporosis complicated with cardiomyopathy, and it also provided evidence for the correlation between sarcopenia and osteoporosis.

Hierarchical MOF@AuNP/Hairpin Nanotheranostic for Enhanced Photodynamic Therapy via O2 Self-Supply and Cancer-Related MicroRNA Imaging In Vivo.

Developing a nanotheranostic with a high sensing performance and efficient therapy was significant in cancer diagnosis and treatment. Herein, a Au nanoparticle and hairpin-loaded photosensitive metal-organic framework (PMOF@AuNP/hairpin) nanotheranostic was constructed by growing AuNPs on PMOF in situ and then attaching hairpins. On the one hand, the PMOF@AuNP/hairpin nanotheranostic could effectively transfer O2 into ROS, facilitating efficient PDT. Additionally, the nanotheranostic possessed catalase-like activity, which could effectively catalyze H2O2 to generate O2, thus achieving O2-evolving PDT and significantly enhancing the antitumor effect of PDT in vivo. On the other hand, the nanotheranostic showed a high loading efficiency of hairpins and achieved the sensitive and selective detection of miR-21 both in living cells and in vivo. Moreover, the nanotheranostic could dynamically monitor the miR-21 level. Due to the excellent imaging performance, the nanotheranostic could recognize cancer cells and might provide important information on cancer progression for PDT. The developed PMOF@AuNP/hairpin nanotheranostic provided a useful tool for tumor diagnosis and antitumor therapy.

Hybrid Triboelectric-Electromagnetic-Piezoelectric Wind Energy Harvester toward Wide-Scale IoT Self-Powered Sensing.

Wind energy is the most promising alternative to fossil fuels as a clean, nonpolluting, and renewable source of energy. However, how to achieve stable and efficient harvesting of wind energy has been a major challenge. Here, a triboelectric-electromagnetic-piezoelectric hybrid wind energy harvester (TEP-WEH) based on the cantilever is proposed. The TEP-WEH achieves a power density of 62.79 mW (m3 rpm)-1 at a 3 m s-1 wind speed, attributable to a rational and optimized structural design. In addition, owing to the soft contact strategy of the TENG module, the TEP-WEH provides excellent durability and drivability. The harvester is demonstrated to successfully and continuously light a commercial lighting bulb rated at 5 W and provide an energy supply for self-powered sensing. This work provides an efficient solution for wind energy harvesting and wide-scale self-powered IoT sensing.

Extracellular Vesicle-Conjugated Functional Matrix Hydrogels Prevent Senescence by Exosomal miR-3594-5p-Targeted HIPK2/p53 Pathway for Disc Regeneration.

Nucleus pulposus stem cells (NPSCs) senescence plays a critical role in the progression of intervertebral disc degeneration (IDD). Stem cell-derived extracellular vesicles (EV) alleviate cellular senescence. Whereas, the underlying mechanism remains unclear. Low stability largely limited the administration of EV in vivo. RGD, an arginine-glycine-aspartic acid tripeptide, strongly binds integrins expressed on the EV membranes, allowing RGD to anchor EV and prolong their bioavailability. An RGD-complexed nucleus pulposus matrix hydrogel (RGD-DNP) is developed to enhance the therapeutic effects of small EV (sEV). RGD-DNP prolonged sEV retention in vitro and ex vivo. sEV-RGD-DNP promoted NPSCs migration, decreased the number of SA-ß-gal-positive cells, alleviated cell cycle arrest, and reduced p16, p21, and p53 activation. Small RNA-seq showed that miR-3594-5p is enriched in sEV, and targets the homeodomain-interacting protein kinase 2 (HIPK2)/p53 pathway. The HIPK2 knockdown rescues the impaired therapeutic effects of sEV with downregulated miR-3594-5p. RGD-DNP conjugate with lower amounts of sEV achieved similar disc regeneration with free sEV of higher concentrations in DNP. In conclusion, sEV-RGD-DNP increases sEV bioavailability and relieves NPSCs senescence by targeting the HIPK2/p53 pathway, thereby alleviating IDD. This work achieves better regenerative effects with fewer sEV and consolidates the theoretical basis for sEV application for IDD treatment.

Parents' willingness to vaccinate themselves and their children with the booster vaccine against SARS-CoV-2: A cross-sectional study in Puyang city, China.

We aimed to investigate the hesitancy and willingness of parents to vaccinate themselves and their children with a booster dose against severe acute respiratory syndrome coronavirus 2 and related factors. We conducted a cross-sectional study in Puyang city, China. The information was collected, including demographic characteristics, willingness to receive a booster dose of coronavirus disease 2019 (COVID-19) vaccine, and attitudes and concerns toward COVID-19 and vaccines. Vaccine hesitancy was assessed in individuals completing the first two doses and booster eligible, while vaccine willingness was assessed in those completing the first two doses and not yet booster eligible. Among the participants completing two primary doses while not meeting the booster criteria, 95.4% (1465/1536) and 95.0% (1385/1458) had a willingness to a booster dose of COVID-19 vaccine for themselves and their children, respectively. Among the participants who met the booster criteria, 40.3% had vaccine hesitancy. Vaccine hesitancy and unwillingness tended to occur in people who were younger, less educated, less healthy, and with unsureness of vaccines' efficacy and adverse events (AE). The younger age of children, children in poorer health, and concern about the efficacy and AE of vaccines contributed to the participants' unwillingness to vaccinate their children. We observed a high willingness to the booster dose of COVID-19 vaccine both for the parents and their children, regardless of the eligibility to a booster dose. However, 40% of people had delayed vaccination behaviors. The promotion of scientific knowledge of vaccines' effectiveness and safety is needed, especially for people in poor health and parents with young children. Timely disclosure of AE caused by COVID-19 vaccines and proper aiding offered to people encountering AE are suggested.

Clinical, biological, and outcome features of P2RY8-CRLF2 and CRLF2 over-expression in pediatric B-cell precursor acute lymphoblastic leukemia according to the CCLG-ALL 2008 and 2018 protocol.

OBJECTIVES: CRLF2 alterations are associated with B-cell precursor acute lymphoblastic leukemia (BCP-ALL). This study aimed to explore the clinical, biological, and outcome features of pediatric BCP-ALL with CRLF2 abnormalities. METHODS: This study enrolled 630 childhood BCP-ALLs treated on CCLG-ALL 2008 or 2018 protocol. P2RY8-CRLF2 was determined by Sanger sequencing and CRLF2 expression was evaluated by qRT-PCR. The correlation between clinical, biological features and outcomes with P2RY8-CRLF2 or CRLF2 over-expression were analyzed. RESULTS: P2RY8-CRLF2 and CRLF2 over-expression were found in 3.33% and 5.71% respectively. P2RY8-CRLF2 was associated with male, higher frequency of CD7 expression, high WBC and MRD before consolidation. CRLF2 over-expression showed ETV6-RUNX1- , higher frequency of CD22, CD34, CD66c, CD86 expression, hyperdiploidy and high MRD at early treatment. The lower overall survival (OS) was found in patients with P2RY8-CRLF2 and confined only in IR group. Furthermore, adverse event-free survival and OS of P2RY8-CRLF2 were discovered comparing to those without known fusions or treated on CCLG-ALL 2008 protocol. However, P2RY8-CRLF2 was not confirmed as independent prognostic factors and no prognostic impact of CRLF2 over-expression was found. CONCLUSIONS: These findings indicate P2RY8-CRLF2 identifies a subset of patients with specific features and adverse outcomes that could be improved by risk-directed treatment.

Large-scale and tunable transparent displays based on silver nanoparticles metasurface.

We report a transparent display based on a metasurface of silver nanoparticles (Ag NPs), consisting of a transparent substrate and a layer of Ag NPs deposited by a dielectric film. The Ag NPs metasurface is prepared by a simple and direct annealing process. It presents a deep transmission valley at the wavelength ofλ= 468 nm and enables desired transparent display by projecting the monochromatic image onto the metasurface. We also demonstrate that the formed Ag NPs can be approximated as truncated nanospheres, which have obvious directional scattering properties, and can radiate most of the scattered energy into the backward hemisphere with a relatively large angular beamwidth (the full width at half maximum of the scattered intensity) of ∼90°. Therefore, the fabricated displays possess wide viewing angles and high brightness characteristics. Additionally, the transmission modes can be red-shifted to the wavelength ofλ= 527 nm by controlling the thickness of the deposited dielectric film. This approach using traditional thin film deposition and moderate annealing processing techniques enables simple, low-cost, and scalable fabrication in large areas for transparent displays.

Plasmon mode manipulation based on multi-layer hyperbolic metamaterials.

Metamaterial with hyperbolic dispersion properties can effectively manipulate plasmonic resonances. Here, we designed a hyperbolic metamaterial (HMM) substrate with a near-zero dielectric constant in the near-infrared region to manipulate the plasmon resonance of the nano-antenna (NA). For NA arrays, tuning the equivalent permittivity of HMM substrate by modifying the thickness of Au/diamond, the wavelength range of plasmon resonance can be manipulated. When the size of the NA changes within a certain range, the spectral position of the plasmon resonance will be fixed in a narrow band close to the epsilon-near-zero (ENZ) wavelength and produce a phenomenon similar to "pinning effect." In addition, since the volume plasmon polaritons (VPP) mode is excited, it will couple with the localized surface plasmon (LSP) mode to generate a spectrum splitting. Therefore, the plasmon resonance is significantly affected and can be precisely controlled by designing the HMM substrate.

A systematic meta-analysis of immune signatures in patients with COVID-19.

Currently severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission has been on the rise worldwide. Predicting outcome in COVID-19 remains challenging, and the search for more robust predictors continues. We made a systematic meta-analysis on the current literature from 1 January 2020 to 15 August 2020 that independently evaluated 32 circulatory immunological signatures that were compared between patients with different disease severity was made. Their roles as predictors of disease severity were determined as well. A total of 149 distinct studies that evaluated ten cytokines, four antibodies, four T cells, B cells, NK cells, neutrophils, monocytes, eosinophils and basophils were included. Compared with the non-severe patients of COVID-19, serum levels of Interleukins (IL)-2, IL-2R, IL-4, IL-6, IL-8, IL-10 and tumor necrosis factor α were significantly up-regulated in severe patients, with the largest inter-group differences observed for IL-6 and IL-10. In contrast, IL-5, IL-1ß and Interferon (IFN)-γ did not show significant inter-group difference. Four mediators of T cells count, including CD3+ T, CD4+ T, CD8+ T, CD4+ CD25+ CD127- Treg, together with CD19+ B cells count and CD16+ CD56+ NK cells were all consistently and significantly depressed in severe group than in non-severe group. SARS-CoV-2 specific IgA and IgG antibodies were significantly higher in severe group than in non-severe group, while IgM antibody in the severe patients was slightly lower than those in the non-severe patients, and IgE antibody showed no significant inter-group differences. The combination of cytokines, especially IL-6 and IL-10, and T cell related immune signatures can be used as robust biomarkers to predict disease severity following SARS-CoV-2 infection.

Decoupling environmental impact from economic growth to achieve Sustainable Development Goals in China.

Developing countries, such as China, have achieved unprecedented success in a single Sustainable Development Goal (SDG), which usually leads to trade-offs between the three pillars of sustainability, and even destroys sustainability. Quantifying the degrees of coupling among the pillars is essential to support policymakers' systematic actions to minimize trade-offs and maximize co-benefits between the pillars, and simultaneously achieve all SDGs. However, assessing the degrees of coupling among the pillars for the full SDGs is lacking. Here, we evaluate the progress of the pillars towards the SDGs and quantify the degrees of coupling among them at both national and sub-national levels in China from 2000 to 2015. The results indicate that the degrees of coupling among the pillars were almost constant while the degrees of coupling between the pillars and economic growth declined over time. The degrees of coupling between environmental impact and economic growth accounted for 52%-83% of the SDGs' progress. Reducing the degrees of coupling helps achieve simultaneously economic growth and environmental protection. The higher the degrees of coupling, the lower progress. This trend was universal among all provinces (sub-national level) regardless of their development levels. Our study highlights not only the necessity to track the degrees of coupling among the pillars, but also decoupling environmental impact from economic growth to achieve the SDGs.

Novel Ascorbic Acid Co-Crystal Formulations for Improved Stability.

A series of co-crystals of ascorbic acid were prepared with equimolar amounts of co-crystal formers (CCFs), including isonicotinic acid, nicotinic acid, 3,4-dihydroxybenzoic acid, 2,5-dihydroxybenzoic acid and m-hydroxybenzoic acid, by slow solvent evaporation and solvent-assisted grinding. The co-crystals were characterized by single-crystal X-ray diffraction spectroscopy, powder X-ray diffraction, IR spectroscopy, differential scanning calorimetry and thermogravimetric analysis. Molecular dynamics (MD) simulations further validated the interaction energy and the possible intermolecular hydrogen bonds among VC and CCFs. The co-crystals showed improved stability when exposed to different wavelengths of light, pH and temperatures compared to the free analogue, especially at higher pH (~9) and lower temperature (~4 °C).

A review and meta-analysis of the epidemiology and clinical presentation of coxsackievirus A6 causing hand-foot-mouth disease in China and global implications.

Coxsackievirus A6 (CV-A6) has been associated with increasingly occurred sporadic hand-foot-mouth disease (HFMD) cases and outbreak events in many countries. In order to understand epidemiological characteristics of CV-A6, we collected the information describing HFMD caused by CV-A6 to describe the detection rate, severe rate and onychomadesis rate, which is defined as one or more nails defluvium, caused by CV-A6 from 2007 to 2017. The results showed that there was an outbreak of CV-A6 every other year, and overall trend of the epidemic of CA6-associated HFMD was increasing in China. The detection rate of CV-A6 in other countries was 32.0% (95% CI: 25.0%~40.0%) before 2013 and 28.0% (95% CI: 20.0%~36.0%) after 2013, respectively. Although the severe rate of HFMD caused by CV-A6 was low (0.10%, 95% CI: 0.01%~0.20%), CV-A6 can cause a high incidence of onychomadesis (28.0%, 95%CI: 21.9%-34.3%). Thus, it would be worthwhile to research and develop an effective multivalent vaccine for CV-A6 to achieve a more powerful prevention of HMFD.

The rapid identification of chemical constituents in Fufang Xiling Jiedu capsule, a modern Chinese medicine, by ultra-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry and data mining strategy.

Fufang Xiling Jiedu capsule is an effective Chinese medicine widely used for the treatment of cold and influenza. However, its chemical constituents had not been determined, which entailed a huge obstacle to further pharmacological studies, clinical-safe medication administration, and quality evaluation. To identify the chemical constituents in Fufang Xiling Jiedu capsule, an efficient and systematic approach using ultra-high-performance liquid chromatography coupled with a quadrupole time-of-flight mass spectrometry in conjunction with a data mining strategy was adopted in this study. As a result, 145 compounds were qualitatively identified, including 26 phenolic acids, 46 flavonoids, 39 triterpenes, and 34 other compounds, among which 6 were potentially new and 144 were being reported from Fufang Xiling Jiedu capsule for the first time. This research not only provides useful information for quality control of Fufang Xiling Jiedu capsule and its involved single herbs but also serve as basis data for further study of Fufang Xiling Jiedu capsule in vivo. Moreover, it provides a reference for the characterization of the chemical constituents of other Chinese medicine preparations.