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An efficient electrochemical trifluoromethylation of coumarins using CF3SO2NHNHBoc as the source of the trifluoromethyl group was developed.

Diabetes mellitus is a disease of metabolism, featuring persistent hyperglycaemia due to insufficient insulin secretion or insulin resistance. At present, the generation of new beta cells from autologous cells by ectopic expression of specific transcription factors is a promising treatment for diabetes. The application of this strategy urgently needs safe and effective gene delivery vectors. In this work, a therapeutic plasmid (pNPMN-PBase), combined multiple specific transcription factors Ngn3, Pdx1, Mafa and Neruod1 (NPMN), was firstly constructed. Then, phenylboronic acid (PBA)-functionalized branched polymers (SS-HPT-P) have been proposed to deliver pNPMN-PBasefor the promising treatment of diabetes. SS-HPT-P had good biocompatibility and low cytotoxicity, and could achieve liver-targeted delivery. SS-HPT-P/pNPMN-PBase system can effectively realize the liver delivery of exogenous therapeutic genes, induce the reprogramming of hepatocytes into beta-like cells, reestablish the endogenous insulin-expression system, and alleviate diabetes and its complications. The present study thus provides an effective strategy for the cell replacement therapy of diabetes.

Filtration membranes are widely applied in medical fields. However, these membranes are challenged by bacterial contamination in hospitals, which increases the risk of nosocomial infections. Thus, it is significant to develop antibacterial filtration membranes. In this work, an oxidated dextran (ODex)-based antibacterial coating was designed and constructed on microfiltration (MF) membranes and melt-blown fabrics. Polyhexamethylene guanidine (PHMG) was synthesized as an antibacterial agent, and was fixed by ODex onto filtration membranes. The functionalized MF membranes increased the filtration efficiency for E. coli from 20.9% to 99.9%, and improved the absorption ratio for endotoxin by 59.1%, while the water flow rate still remained as high as 5255 L (h m2)−1. Furthermore, the trapped bacteria were inactivated by the antibacterial coating. For the melt-blown fabrics, the aerosol filtration efficiency was increased from 74.6% to 81.0%, and the antibacterial efficiency was promoted to 92.0%. The present work developed a facile and universal antibacterial functionalization strategy for filtration membranes, which provided a new method for the design and development of various novel antibacterial filtration materials in the medical field.

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) gene editing technology is a promising approach for cancer therapy, and its application practice urgently requires a safe and effective gene carrier. In this work, we focus on the design of a phenylboronic acid (PBA)-functionalized, disulfide bonded branched polyaminoglycoside (SS-HPT-P) as a robust delivery vector of the CRISPR-Cas9 system. SS-HPT-P showed great tumor-targeting performance, reduction-responsive degradability, and gene transfection ability. The typical pCas9-surv (one CRISPR-Cas9 plasmid that targets and knocks out the survivin gene) delivery mediated by SS-HPT-P exhibited gene editing performance in the A549 cell line, confirming the feasibility of SS-HPT-P to effectively deliver the CRISPR-Cas9 system. SS-HPT-P/pCas9-surv could effectively inhibit the proliferation of tumor cells both in vitro and in vivo, suggesting the potential of PBA-functionalized nanocarriers for cancer gene therapy. The present work provides a promising approach for the treatment of malignant tumors.

Global warming is changing the global wave climate, making waves stronger. In this study, we find that the wave climate in the South China Sea (SCS) undergoes an intensifying trend under global warming background, by examining the ERA-5 wave reanalysis data over 1979–2018. Results show a significant increase in most of the SCS, of 0.2% per year in significant wave height (SWH) and 0.15% per year in wave period (WP), but there is no significant change in surface wind speed (WS), which may correspond to the weakening of the Asian monsoon. The increase of the swell is the main characteristic of wave climate change in the SCS. We further examined the possible factors to cause the increasing of SWH, and found that the frequency of gale events occurring in the SCS and its adjacent regions increased over study period. The more frequent gale events can explain the significant increasing tendency of the SWH in the SCS by causing the occurrence of swell. The increasing appearance of gale events is closely related to the intensification of El Nino/Southern Oscillation (ENSO). ENSO activities also can regulate the interannual variability of wave climate in the SCS through the surface wind. Therefore, ENSO activities play an important role in the change of wave climate in the SCS.

Persistent cardiac hypertrophy causes heart failure and sudden death. Gene therapy is a promising intervention for this disease, but is limited by the lack of effective delivery systems. Herein, it is reported that CHO‐PGEA (cholesterol (CHO)‐terminated ethanolamine‐aminated poly(glycidyl methacrylate)) can efficiently condense small RNAs into nanosystems for preventing cardiac hypertrophy. CHO‐PGEA contains two features: 1) lipophilic cholesterol groups enhance transfection efficiency in cardiomyocytes, 2) abundant hydrophilic hydroxyl groups benefit biocompatibility. miR‐182, which is known to downregulate forkhead box O3, is selected as an intervention target and can be blocked by synthetic small RNA inhibitor of miR‐182 (miR‐182‐in). CHO‐PGEA can efficiently deliver miR‐182‐in into hearts. In the mice with aortic coarctation, CHO‐PEGA/miR‐182‐in significantly suppresses cardiac hypertrophy without organ injury. This work demonstrates that CHO‐PGEA/miRNA nanosystems are very promising for RNA‐based therapeutics to treat heart diseases.

Based on satellite altimeter data, it was found that the mesoscale eddy propagates along the continental slope in northern South China Sea. When the mesoscale eddy passed the Dongsha Islands, the propagation speed clearly slowed down. Additionally, the radius increased and strength decreased when the mesoscale eddy touched the Dongsha Islands. Using the analytic expression for the speed of the center of an isolated eddy, it was found that the sudden slowdown of the zonal propagation speed was accompanied by the sudden decrease of the meridional topography gradient, which was the main reason for the slowdown of the propagation speed.

The current chemiluminescence (CL) probes for hydroxyl radical (•OH) are poorly selective owing to a non-specific redox reaction. To the best of our knowledge, there have not been established on the CL probes for •OH using the strong electrophilicity of •OH. In this work, an ultrastrong CL emission is initiated by electrophilic attack of •OH towards rhodamine B (RhB) on the surface of montomorillonite (MMT). The improved CL emissions are attributed to the oriented H-type aggregation of RhB molecules on the surface of MMT by π–π stacking interactions, resulting in an increase in π-electron density of aromatic ring of RhB. The high π-electron density of benzene ring could facilitate the attack of electrophilic •OH towards RhB. In addition, a novel CL probe for •OH with high selectivity and high sensitivity has been established using the electrophilic properties of •OH rather than its common redox properties. The applicability of the proposed CL probe is evaluated by detecting •OH in untreated and gentamicin treated mouse fresh plasma samples. Our findings provide a new strategy to improve the selectivity of CL sensor of •OH.

The utilization of semiconductor quantum dots (QDs) as optical labels for biosensing and biorecognition has made substantial progress. However, the development of a suitable QD-based luminescent probe that is capable of detecting individual reactive oxygen species (ROS) represents a great challenge, mainly because the fluorescence of QDs is quenched by a wide variety of ROS. To overcome this limitation, a novel QD-based turn-on luminescent probe for the specific detection of (.) OH has been designed, and its application in monitoring the endogenous release of (.) OH species in living cells is demonstrated. Metal citrate complexes on the surfaces of the QDs can act as electron donors, injecting electrons into the LUMO of the QDs, while (.) OH can inject holes into the HOMO of the QDs. Accordingly, electron-hole pairs are produced, which could emit strong luminescence by electron-hole recombination. Importantly, this luminescent probe does not respond to other ROS.

Based on simulation, the summer upper-ocean cross-isobath's flow on the Northern South China Sea has been analyzed. East to Xisha water, the cross-isobaths flow mainly onshore, including little offshore flows. On Xisha water, the sea water flows onshore on the north side and is reversed on the other side. The momentum balance shows that the along-isobath's barotropic pressure gradient determines the distribution of the cross-isobath flow. Theoretical analysis shows that the along-isobath's density gradient and the windstress curl are two important factors that determine the along-isobath's sea surface height gradient, which is the main contributor to the barotropic pressure gradient. Numerical experiments demonstrate that the temperature distribution dominates the along-isobath's density gradient and determines the along-isobath's sea surface height gradient.

Synoptic-scale disturbances of latent-heat flux in the South China Sea are examined using Xisha automatic weather station measurements and satellite-derived daily latent heat-flux datasets. The power spectra of observations suggest a synoptic feature with a pronounced energy peak at a period of 4–8 days, comparable with the timescales of the atmospheric synoptic variabilities in the region. The characteristics of the synoptic latent-heat flux variations in summer are remarkably different from those in winter. The amplitudes of significant synoptic oscillations are about 20 and 40 W·m−2 during summer and winter monsoons, respectively. An active monsoon is clearly correlated with positive and negative phases of the synoptic latent-heat flux oscillations in the South China Sea. Using a composite analysis, some fundamental features of the synoptic latent-heat flux variabilities were revealed. In summer, the synoptic-scale latent-heat flux fluctuations are highly correlated with wind speed. While the synoptic variations of winds were removed during summer, the latent-heat anomalies precede about 1 day. In winter, however, they are primarily associated with winds and near-surface air humidity. When the synoptic oscillations of near-surface air humidity are removed, the amplitude of the composite latent-heat flux is reduced by 70%.

Air–sea interaction in the South China Sea (SCS) has direct impacts on the weather and climate of its surrounding areas at various spatiotemporal scales. In situ observation plays a vital role in exploring the dynamic characteristics of the regional circulation and air–sea interaction. Remote sensing and regional modeling are expected to provide high-resolution data for studies of air–sea coupling; however, careful validation and calibration using in situ observations is necessary to ensure the quality of these data. Through a decade of effort, a marine observation network in the SCS has begun to be established, yielding a regional observatory for the air–sea synoptic system. Earlier observations in the SCS were scarce and narrowly focused. Since 2004, an annual series of scientific open cruises during late summer in the SCS has been organized by the South China Sea Institute of Oceanology (SCSIO), carefully designed based on the dynamic characteristics of the oceanic circulation and air–sea interaction in the SCS region. Since 2006, the cruise carried a radiometer and radiosondes on board, marking a new era of marine meteorological observation in the SCS. Fixed stations have been established for long-term and sustained records. Observations obtained through the network have been used to study regional ocean circulation and processes in the marine atmospheric boundary layer. In the future, a great number of multi-institutional, collaborative scientific cruises and observations at fixed stations will be carried out to establish a mesoscale hydrological and marine meteorological observation network in the SCS.

In the past 10 years (2004–2013), annual open cruise during late summer provided new opportunities for comprehensive studies in the Northern South China Sea (NSCS). The 10-year field investigation program was carried out by the South China Sea Institute of Oceanology, Chinese Academy of Sciences (SCSIO, CAS). Measurements included water mass property, ocean circulation, atmospheric structure, and chemical and biological elements. The observation data collected during these open cruises have been intensively used in the studies of marine oceanographic, meteorological, chemical, and biological processes in the NSCS. In this study, comprehensive assessment of data application in oceanographic and meteorological studies is provided: (1) the property and variability of water masses in different layers; (2) the distribution of main currents and three-dimensional structure of mesoscale eddies; and (3) atmospheric structure and its feedback to the ocean. With the continuance of open cruises, it is feasible to construct high-quality, gridded climatological marine meteorological datasets in the NSCS in the near future.

Summary Induced pluripotent stem cells (iPSCs) generated from somatic cells by ectopic expression of reprogramming factors, e.g., POU5F1 (OCT4), KLF4, and SOX2, have great potential for regenerative medicine. However, before they can be used in a clinical setting, the mechanism of reprogramming needs to be better understood. Here, by engineering reprogramming factors to a destabilizing protein domain, we achieved inducible generation of mouse and pig iPSCs. Stability of the fusion protein was precisely regulated by the addition of the cell-permeable small molecule trimethoprim (TMP) in a dose-dependent manner. With these tools, we found that during the early and middle stages of reprogramming, exogenous OCT4 or KLF4 could be omitted, whereas exogenous SOX2 expression at early and middle stages was required for successful reprogramming. Our TMP reprogramming system is useful for defining the stoichiometry and temporal requirements of transcription factors for reprogramming., Graphical Abstract, Highlights • TMP reprogramming system can be used for inducible generation of iPSCs • Stability of reprogramming factors is precisely regulated by TMP • During early/middle stages of reprogramming, exogenous OCT4 or KLF4 can be omitted • During early/middle stages of reprogramming, exogenous SOX2 expression is required, By engineering reprogramming factors to a destabilizing protein domain, Li, Wu, and colleagues achieved inducible generation of iPSCs. Stability of the fusion protein was precisely regulated by small molecule TMP. With these tools, we found that during the early and middle stages of reprogramming, exogenous OCT4 or KLF4 could be omitted, whereas exogenous SOX2 expression at early/middle stages was required for successful reprogramming.

Using an observation data set of temperature and the Simple Ocean Data Assimilation (SODA), the decadal variability of upper ocean heat content (0–400 m; hereafter, OHC) in the South China Sea (SCS) was investigated for the period from 1958 to 2007. Decadal variability was identified as the dominant mode of upper OHC besides the seasonal cycle. According to decreasing or increasing OHC, four periods were chosen to discuss detailed processes behind OHC variability in the SCS; the four periods are 1958–1968, 1969–1981, 1982–1992, and 1993–2003. Results show that advection was the major factor for decreasing (increasing) OHC during 1958–1968 (1968–1981). During 1982–1992 and 1993–2003, the net surface heat flux was the main contributor to the variability of OHC besides the advection. The OHC, advection and net surface heat flux had significant positive trends during 1992–2003. The spatial characteristics of OHC variability and heat budget in the Luzon Strait, west of Luzon Island, and in the Xisha warm eddy region are also discussed.

The prevalence of reactive oxygen species (ROS) production and the enzyme-containing intracellular environment could lead to the fluorescence quenching of bovine serum albumin (BSA)-capped gold nanoclusters (AuNCs). Here we report an efficient strategy to address this issue, where a polymer-like shielding layer is designed to wrap around the Au core to significantly improve the stability of AuNCs against ROS and protease degradation. The key of our design is to covalently incorporate a thiolated AuNC into the BSA-AuNC via carbodiimide-activated coupling, leading to the formation of a AuNC pair inside the cross-linked BSA molecule. The as-designed paired AuNCs in BSA (or BSA-p-AuNCs for short) show improved performances in living cells.

There is currently great interest in developing chemiluminescence (CL) probes that can selectively detect peroxynitrite (ONOO(-)) in living cells. In comparison with other reactive oxygen species (ROS), ONOO(-) can spontaneously decompose into a series of radicals. Notably, the interaction of quantum dots (QDs) with oxidizing/reducing ROS radicals can generate a strong CL emission by electron-transfer annihilation. Herein, we report a novel CL probe that affords the ability to distinguish ONOO(-) from other ROS in living cells. ONOO(-) can activate luminescence of QDs in the absence of excitation source, effectively avoiding background noise and scattering of light from biological matrixes produced by in situ excitation; however, there is no response to other ROS including (1)O2, H2O2, (•)OH, O2(•-), and ClO(-). The outstanding selectivity of the present CL probe leads us to detect the exogenous release of ONOO(-) from 3-morpholinosydnonimine (SIN-1) in living cells. These results suggest that this present probe-based CL provides a promising platform for highly selective and sensitive detection of ONOO(-) in biological systems.

Using surface and aerological meteorological observations obtained at the Xisha Automatic Weather Station and three moored buoys along the continental slope, characteristics of the synoptic-scale disturbances over the northern South China Sea (NSCS) are extensively studied. The power spectra of surface and aerological observations suggest a synoptic feature with a pronounced energy peak at a period of 5–8 d and a weak peak at 3–4 d. The standard deviation of the synoptic temperature component derived at Xisha Station from 1976 to 2011 indicates that the strongest variability normally exists in August all through the whole troposphere. At the interannual scale, it is found that El Nino plays an important role in regulating the synoptic disturbances of atmosphere. The vertical synoptic disturbances have a double active peak following El Nino condition. The first peak usually occurs during the mature phase of El Nino, and the second one occurs in the summer of decay year. Comparing with the summer of developing years, the summer of the decaying year of El Nino has more active and stronger synoptic disturbances, especially for the 5–8 d period variations.

Ag–SrTiO3 nanocrystal photocatalysts were prepared by hydrothermal synthesis method for reducing CO2 to methyl formate (MF) in methanol via ultraviolet irradiation. CO2 was reduced to MF by electrons on conduction band of the photocatalyst. In order to obtain a high rate of MF evolution, we researched and optimized the preparation procedure of Ag–SrTiO3 by changing the Ag dosage, hydrothermal temperature and time. The as synthesized photocatalysts were characterized with X-ray diffraction, UV–Vis absorption spectra, transmission electron microscope, N2 sorption analysis at 77 K and activity evaluation. A catalyst of 7 wt% Ag on SrTiO3 with hydrothermal synthesis at 150 °C and 22 h was found to exhibit the highest photocatalytic activity in MF formation rate of 3,006 μmol/(h g cat), which was more remarkable than that of pristine SrTiO3. When the SrTiO3 is irradiated by UV light of suitable wavelength with sufficient photonic energy (hν), photo-generated electron–hole pairs were created, part of the excited electrons and holes recombined together and radiated out heat, while rest part would react with the reactants near the SrTiO3 surface. It was certain electrons transmitting to the surface of Ag particle that avoided their recombination with holes, resulting in effective extension of the life-span of the electron–hole pairs.

The peptide hormone ghrelin is secreted in the stomach, with unique N-octanoylation at serine 3, which is a requirement for its functionality. These functions include growth hormone release, appetite stimulation, gastrointestinal motility, glucose regulation, and cell proliferation. The enzyme responsible for ghrelin acylation was recently identified as ghrelin O-acyltransferase (GOAT). In this study, porcine GOAT was cloned and characterized. A full-length cDNA of GOAT of 2013 bp was obtained, which included a 70-bp 5' UTR, a 635-bp 3' UTR, and a 1308-bp open reading frame encoding a protein of 415 amino acids. The GOAT and ghrelin mRNAs are co-expressed in stomach, pancreas, and duodenum at high levels. GOAT was also detected in liver, lung, brain, testis, spleen, kidney, heart, muscle, lipid, and ovary. Our results provide an important basis for further research on GOAT function and the relationship between ghrelin and GOAT.