DNAJC24 acts directly with PCNA and promotes malignant progression of LUAD by activating phosphorylation of AKT.

Heat shock proteins (HSPs) are a group of highly conserved proteins found in a wide range of organisms. In recent years, members of the HSP family were overexpressed in various tumors and widely involved in oncogenesis, tumor development, and therapeutic resistance. In our previous study, DNAJC24, a member of the DNAJ/HSP40 family of HSPs, was found to be closely associated with the malignant phenotype of hepatocellular carcinoma. However, its relationship with other malignancies needs to be further explored. Herein, we demonstrated that DNAJC24 exhibited upregulated expression in LUAD tissue samples and predicted poor survival in LUAD patients. The upregulation of DNAJC24 expression promoted proliferation and invasion of LUAD cells in A549 and NCI-H1299 cell lines. Further studies revealed that DNAJC24 could regulate the PI3K/AKT signaling pathway by affecting AKT phosphorylation. In addition, a series of experiments such as Co-IP and mass spectrometry confirmed that DNAJC24 could directly interact with PCNA and promoted the malignant phenotypic transformation of LUAD. In conclusion, our results suggested that DNAJC24 played an important role in the progression of LUAD and may serve as a specific prognostic biomarker for LUAD patients. The DNAJC24/PCNA/AKT axis may be a potential target for future individualized and precise treatment of LUAD patients.

TWF1 induces autophagy and accelerates malignant phenotype in lung adenocarcinoma via inhibiting the cAMP signaling pathway.

Many studies have shown that the actin cytoskeleton plays an essential role in the initiation and progression of cancer. As an actin-binding protein, Twinfilin1 (TWF1) plays an important role in regulating cytoskeleton-related functions. However, little is known about the expression and function of TWF1 in human tumors. The present study aimed to investigate the functional roles and the underlying molecular mechanisms of TWF1 in human lung adenocarcinoma (LUAD). By using bioinformatics databases and tumor tissues, TWF1 expression was found to be higher in LUAD tissues than in adjacent tissues and poor survival was predicted in patients with LUAD. In vitro and in vivo assays indicated that downregulation of TWF1 expression suppressed LUAD cells invasion and migration. Further studies revealed that TWF1 interacted with p62 and was involved in the regulation of autophagy. The molecular mechanisms underlying TWF1 were investigated by RNA-seq analysis and a series of functional experiments. The results showed that downregulation of TWF1 suppressed LUAD progression through the cAMP signaling pathway. Therefore, overexpression of TWF1 in LUAD promoted migration, invasion, and autophagy through the cAMP signaling pathway.

ACOX1 deficiency-induced lipid metabolic disorder facilitates chronic interstitial fibrosis development in renal allografts.

Chronic interstitial fibrosis presents a significant challenge to the long-term survival of transplanted kidneys. Our research has shown that reduced expression of acyl-coenzyme A oxidase 1 (ACOX1), which is the rate-limiting enzyme in the peroxisomal fatty acid ß-oxidation pathway, contributes to the development of fibrosis in renal allografts. ACOX1 deficiency leads to lipid accumulation and excessive oxidation of polyunsaturated fatty acids (PUFAs), which mediate epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM) reorganization respectively, thus causing fibrosis in renal allografts. Furthermore, activation of Toll-like receptor 4 (TLR4)-nuclear factor kappa-B (NF-κB) signaling induced ACOX1 downregulation in a DNA methyltransferase 1 (DNMT1)-dependent manner. Overconsumption of PUFA resulted in endoplasmic reticulum (ER) stress, which played a vital role in facilitating ECM reorganization. Supplementation with PUFAs contributed to delayed fibrosis in a rat model of renal transplantation. The study provides a novel therapeutic approach that can delay chronic interstitial fibrosis in renal allografts by targeting the disorder of lipid metabolism.

Sporophytic control of tapetal development and pollen fertility by a mitogen-activated protein kinase cascade in rice.

Tapetum, the innermost layer of the anther wall, provides essential nutrients and materials for pollen development. Timely degradation of anther tapetal cells is a prerequisite for normal pollen development in flowering plants. Tapetal cells facilitate male gametogenesis by providing cellular contents after highly coordinated programmed cell death (PCD). Tapetal development is regulated by a transcriptional network. However, the signaling pathway(s) involved in this process are poorly understood. In this study, we report that a mitogen-activated protein kinase (MAPK) cascade composed of OsYDA1/OsYDA2-OsMKK4-OsMPK6 plays an important role in tapetal development and male gametophyte fertility. Loss of function of this MAPK cascade leads to anther indehiscence, enlarged tapetum, and aborted pollen grains. Tapetal cells in osmkk4 and osmpk6 mutants exhibit an increased presence of lipid body-like structures within the cytoplasm, which is accompanied by a delayed occurrence of PCD. Expression of a constitutively active version of OsMPK6 (CA-OsMPK6) can rescue the pollen defects in osmkk4 mutants, confirming that OsMPK6 functions downstream of OsMKK4 in this pathway. Genetic crosses also demonstrated that the MAPK cascade sporophyticly regulates pollen development. Our study reveals a novel function of rice MAPK cascade in plant male reproductive biology.

Urbanization can accelerate climate change by increasing soil N2 O emission while reducing CH4 uptake.

Urban land-use change has the potential to affect local to global biogeochemical carbon (C) and nitrogen (N) cycles and associated greenhouse gas (GHG) fluxes. We conducted a meta-analysis to (1) assess the effects of urbanization-induced land-use conversion on soil nitrous oxide (N2 O) and methane (CH4 ) fluxes, (2) quantify direct N2 O emission factors (EFd ) of fertilized urban soils used, for example, as lawns or forests, and (3) identify the key drivers leading to flux changes associated with urbanization. On average, urbanization increases soil N2 O emissions by 153%, to 3.0 kg N ha-1  year-1 , while rates of soil CH4 uptake are reduced by 50%, to 2.0 kg C ha-1  year-1 . The global mean annual N2 O EFd of fertilized lawns and urban forests is 1.4%, suggesting that urban soils can be regional hotspots of N2 O emissions. On a global basis, conversion of land to urban greenspaces has increased soil N2 O emission by 0.46 Tg N2 O-N year-1 and decreased soil CH4 uptake by 0.58 Tg CH4 -C year-1 . Urbanization driven changes in soil N2 O emission and CH4 uptake are associated with changes in soil properties (bulk density, pH, total N content, and C/N ratio), increased temperature, and management practices, especially fertilizer use. Overall, our meta-analysis shows that urbanization increases soil N2 O emissions and reduces the role of soils as a sink for atmospheric CH4 . These effects can be mitigated by avoiding soil compaction, reducing fertilization of lawns, and by restoring native ecosystems in urban landscapes.

AIE-doped Poly(Ionic Liquid) Photonic Spheres for the Discrimination of Psychoactive Substances.

Drugs of abuse has drawn intense attention due to increasing concerns to public health and safety. The construction of a sensing platform with the capability to identify them remains a big challenge because of the limitations of synthetic complexity, sensing scope and receptor extendibility. Here a kind of poly(ionic liquid) (PIL) photonic crystal spheres doped with aggregation-induced emission (AIE) luminogens was developed. As diverse noncovalent interactions involve in PIL moieties, the single sphere shows different binding affinity to a broad range of psychoactive substances. Furthermore, the dual-channel signals arising from photonic crystal structures and sensitive AIE-luminogens provide high-dimensional information for discriminative detection of targets, even for molecules with slight structural differences. More importantly, such single sphere sensing platform could be flexibly customized through ion-exchange, showing great extendibility to fabricate high-efficiency/high-throughput sensing arrays without tedious synthesis.

Targeted changes in blood lipids improves fibrosis in renal allografts.

BACKGROUND: Chronic interstitial fibrosis is the primary barrier against the long-term survival of transplanted kidneys. Extending the lifespan of allografts is vital for ensuring the long-term health of patients undergoing kidney transplants. However, few targets and their clinical applications have been identified. Moreover, whether dyslipidemia facilitates fibrosis in renal allograft remains unclear. METHODS: Blood samples were collected from patients who underwent kidney transplantation. Correlation analyses were conducted between the Banff score and body mass index, and serum levels of triacylglycerol, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. A rat model of renal transplantation was treated with the lipid-lowering drug, fenofibrate, and kidney fibrosis levels were determined by histochemical staining. Targeted metabolomic detection was conducted in blood samples from patients who underwent kidney transplantation and were divided into fibrotic and non-fibrotic groups. Rats undergoing renal transplantation were fed either an n-3 or n-6 polyunsaturated fatty acid (PUFA)-enriched diet. Immunohistochemical and Masson's trichrome staining were used to determine the degree of fibrosis. RESULTS: Hyperlipidemia was associated with fibrosis development. Treatment with fenofibrate contributed to improve fibrosis in a rat model of renal transplantation. Moreover, n-3 PUFAs from fibrotic group showed significant downregulation compared to patients without fibrotic renal allografts, and n-3 PUFAs-enriched diet contributed to delayed fibrosis in a rat model of renal transplantation. CONCLUSIONS: This study suggests that hyperlipidemia facilitates fibrosis of renal allografts. Importantly, a new therapeutic approach was provided that may delay chronic interstitial fibrosis in transplanted kidneys by augmenting the n-3 PUFA content in the diet.

Advances of Research on Dual-Frequency Solid-State Lasers for Synthetic-Wave Absolute-Distance Interferometry.

Frequency-difference-stabilized dual-frequency solid-state lasers with tunable and large frequency difference have become an ideal light source for the high-accuracy absolute-distance interferometric system due to their stable multistage synthetic wavelengths. In this work, the advances in research on oscillation principles and key technologies of the different kinds of dual-frequency solid-state lasers are reviewed, including birefringent dual-frequency solid-state lasers, biaxial and two-cavity dual-frequency solid-state lasers. The system composition, operating principle, and some main experimental results are briefly introduced. Several typical frequency-difference stabilizing systems for dual-frequency solid-state lasers are introduced and analyzed. The main development trends of research on dual-frequency solid-state lasers are predicted.

Loss of plasma membrane lipid asymmetry can induce ordered domain (raft) formation.

In some cases, lipids in one leaflet of an asymmetric artificial lipid vesicle suppress the formation of ordered lipid domains (rafts) in the opposing leaflet. Whether this occurs in natural membranes is unknown. Here, we investigated this issue using plasma membrane vesicles (PMVs) from rat leukemia RBL-2H3 cells. Membrane domain formation and order was assessed by fluorescence resonance energy transfer and fluorescence anisotropy. We found that ordered domains in PMVs prepared from cells by N-ethyl maleimide (NEM) treatment formed up to ∼37°C, whereas ordered domains in symmetric vesicles formed from the extracted PMV lipids were stable up to 55°C, indicating the stability of ordered domains was substantially decreased in intact PMVs. This behavior paralleled lesser ordered domain stability in artificial asymmetric lipid vesicles relative to the corresponding symmetric vesicles, suggesting intact PMVs exhibit some degree of lipid asymmetry. This was supported by phosphatidylserine mislocalization on PMV outer leaflets as judged by annexin binding, which indicated NEM-induced PMVs are much more asymmetric than PMVs formed by dithiothreitol/paraformaldehyde treatment. Destroying asymmetry by reconstitution of PMVs using detergent dilution also showed stabilization of domain formation, even though membrane proteins remained associated with reconstituted vesicles. Similar domain stabilization was observed in artificial asymmetric lipid vesicles after destroying asymmetry via detergent reconstitution. Proteinase K digestion of proteins had little effect on domain stability in NEM PMVs. We conclude that loss of PMV lipid asymmetry can induce ordered domain formation. The dynamic control of lipid asymmetry in cells may regulate domain formation in plasma membranes.

Cholesterol and sphingomyelin are critical for Fcγ receptor-mediated phagocytosis of Cryptococcus neoformans by macrophages.

Cryptococcus neoformans is a fungal pathogen that causes life-threatening meningoencephalitis in lymphopenic patients. Pulmonary macrophages comprise the first line of host defense upon inhalation of fungal spores by aiding in clearance but can also potentially serve as a niche for their dissemination. Given that macrophages play a key role in the outcome of a cryptococcal infection, it is crucial to understand factors that mediate phagocytosis of C. neoformans. Since lipid rafts (high-order plasma membrane domains enriched in cholesterol and sphingomyelin [SM]) have been implicated in facilitating phagocytosis, we evaluated whether these ordered domains govern macrophages' ability to phagocytose C. neoformans. We found that cholesterol or SM depletion resulted in significantly deficient immunoglobulin G (IgG)-mediated phagocytosis of fungus. Moreover, repletion of macrophage cells with a raft-promoting sterol (7-dehydrocholesterol) rescued this phagocytic deficiency, whereas a raft-inhibiting sterol (coprostanol) significantly decreased IgG-mediated phagocytosis of C. neoformans. Using a photoswitchable SM (AzoSM), we observed that the raft-promoting conformation (trans-AzoSM) resulted in efficient phagocytosis, whereas the raft-inhibiting conformation (cis-AzoSM) significantly but reversibly blunted phagocytosis. We observed that the effect on phagocytosis may be facilitated by Fcγ receptor (FcγR) function, whereby IgG immune complexes crosslink to FcγRIII, resulting in tyrosine phosphorylation of FcR γ-subunit (FcRγ), an important accessory protein in the FcγR signaling cascade. Correspondingly, cholesterol or SM depletion resulted in decreased FcRγ phosphorylation. Repletion with 7-dehydrocholesterol restored phosphorylation, whereas repletion with coprostanol showed FcRγ phosphorylation comparable to unstimulated cells. Together, these data suggest that lipid rafts are critical for facilitating FcγRIII-mediated phagocytosis of C. neoformans.

Rational Approach to Plasmonic Dimers with Controlled Gap Distance, Symmetry, and Capability of Precisely Hosting Guest Molecules in Hotspot Regions.

Plasmonic dimers not only provide a unique platform for studying fundamental plasmonic behavior and effects but also are functional materials for numerous applications. The efficient creation of well-defined dimers with flexible control of structure parameters and thus tunable optical property is the prerequisite for fully exploiting the potential of this nanostructure. Herein, based on a polymer-assisted self-assembly approach in conjugation with molecular cage chemistry, a strategy was demonstrated for constructing cage-bridged plasmonic dimers with controlled sizes, compositions, shape, symmetry, and interparticle gap separation in a modular and high-yield manner. With a high degree of freedom and controllability, this strategy allows facilely accessing various symmetrical/asymmetrical dimers with sub-5 nm gap distance and tailored optical properties. Importantly, as the linkage of the two constituent elements, the molecular cages embedded in the junction endow the assembled dimers with the ability to precisely and reversibly host rich guest molecules in hotspot regions, offering great potential for creating various plasmon-mediated applications.

Arrested Coalescence of Ionic Liquid Droplets: A Facile Strategy for Spatially Organized Multicompartment Assemblies.

Multicompartment assemblies attract much attention for their wide applications. However, the fabrication of multicompartment assemblies usually requires elaborately designed building blocks and careful controlling. The emergence of droplet networks has provided a facile way to construct multiple droplet architectures, which can further be converted to multicompartment assemblies. Herein, the bind motif-free building blocks are presented, which consist of the hydrophobic Tf2 N- -based ionic liquid (IL) dissolving LiTf2 N salt, that can conjugate via arrested coalescence in confined-space templates to form IL droplet networks. Subsequent ultraviolent polymerization generates robust free-standing multicompartment assemblies. The conjugation of building blocks relies not on the peripheral bind motif but on the interfacial instability-induced arrested coalescence, avoiding tedious surface modification and assembly process. By tuning structures of templates and building blocks, multicompartment assemblies with 0D, 1D, 2D, and 3D structures are prepared in a facile and high-throughput way. Importantly, the bottom-up construction enables modular control over the compositions and spatial positions of individual building blocks. Combining with the excellent solvency of ILs, this system can serve as a general platform towards versatile multicompartment architectures. As demonstrations, by tailoring the chambers the multicompartment assemblies can spatiotemporally sense and report the chemical cues and perform various modes of motion.

Dynamical trajectory of glucocorticoids tapering and discontinuation in patients with rheumatoid arthritis commencing glucocorticoids with csDMARDs: a real-world data from 2009 to 2020.

OBJECTIVE: To unravel the dynamical trajectory and features of glucocorticoids (GC) tapering and discontinuation in patients with rheumatoid arthritis (RA) commencing GC with concomitant conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). METHODS: We used data from longitudinal real-world Treat-to-TARget in RA cohort. Patients with RA who started GC and contaminant csDMARDs therapy were included. The changes in GC dose and disease activity were evaluated. GC discontinuation rate was analysed using Kaplan-Meier analysis. The relapse profile within 6 months after GC discontinuation was also analysed. RESULTS: A total of 207 patients with RA were included. During a median follow-up of 38.6 months, 124 patients discontinued GC. The median prednisolone dose of 10 (5-10) mg/day at initiation was reduced by 50% in the first 6 months and then more slowly, to zero by 48 months eventually. The cumulative probabilities of GC discontinuation were 9.7%, 26.6%, 48.0% and 58.6% at month 6, years 1, 2 and 3, with calculated median time to GC cessation of 27 months. In 110 DMARD-naïve patients, the corresponding cumulative probabilities of GC discontinuation were, respectively, 12.7%, 30.0%, 50.9% and 60.6%, with calculated median time to GC cessation of 24 months. Of the 124 patients who discontinued GC, adding other csDMARDs or concomitant csDMARDs increment was documented in 28.2% of them. Approximately half of 124 patients were in clinical remission at GC discontinuation. Within 6 months after GC withdrawal, 79.1% (91/115) of patients maintained relapse free. CONCLUSIONS: In patients with RA commencing GC besides csDMARDs, GC is feasibly discontinued with favourable control of disease activity in real-life setting, mostly without short-term flare. But the withdrawal time is far from reaching the recommended time frame, indicating the gap between real-world practice and current guidelines.

Nanodomains can persist at physiologic temperature in plasma membrane vesicles and be modulated by altering cell lipids.

The formation and properties of liquid-ordered (Lo) lipid domains (rafts) in the plasma membrane are still poorly understood. This limits our ability to manipulate ordered lipid domain-dependent biological functions. Giant plasma membrane vesicles (GPMVs) undergo large-scale phase separations into coexisting Lo and liquid-disordered lipid domains. However, large-scale phase separation in GPMVs detected by light microscopy is observed only at low temperatures. Comparing Förster resonance energy transfer-detected versus light microscopy-detected domain formation, we found that nanodomains, domains of nanometer size, persist at temperatures up to 20°C higher than large-scale phases, up to physiologic temperature. The persistence of nanodomains at higher temperatures is consistent with previously reported theoretical calculations. To investigate the sensitivity of nanodomains to lipid composition, GPMVs were prepared from mammalian cells in which sterol, phospholipid, or sphingolipid composition in the plasma membrane outer leaflet had been altered by cyclodextrin-catalyzed lipid exchange. Lipid substitutions that stabilize or destabilize ordered domain formation in artificial lipid vesicles had a similar effect on the thermal stability of nanodomains and large-scale phase separation in GPMVs, with nanodomains persisting at higher temperatures than large-scale phases for a wide range of lipid compositions. This indicates that it is likely that plasma membrane nanodomains can form under physiologic conditions more readily than large-scale phase separation. We also conclude that membrane lipid substitutions carried out in intact cells are able to modulate the propensity of plasma membranes to form ordered domains. This implies lipid substitutions can be used to alter biological processes dependent upon ordered domains.

Multifunctional Integrated Compartment Systems for Incompatible Cascade Reactions Based on Onion-Like Photonic Spheres.

One of the central aims of synthetic biology and metabolic engineering is to mimic the integrality of eukaryotic cells to construct a multifunctional compartment system to perform multistep incompatible cascade reactions in a one-pot, controlled, and selective fashion. The key challenge is how to address the coexistence of antagonistic reagents and to incorporate these functionalities into an integrated system in a smart and efficient way. A novel strategy called "iterative etching-grafting" is proposed here based on monodispersed photonic spheres (PSs) prepared by microfluidics, which constructs a universal platform for incompatible cascade reactions. As a proof of concept, we spatiotemporally regulated the degree of etching of PSs, then grafted precursory groups of acid and base onto PSs, and incorporated a photocleavage method, which were capable of compartmentalizing the acid and base inside PSs. Utilizing the band-gap offsets of PSs could track the progress of cascade reactions in situ, and grafting various charged polymers on the surface of the pores by surface-initiated atom transfer radical polymerization (SI-ATRP) achieved the selectivity of the substrates, which flexibly constructed a multifunctional and integrated acid-base photonic multicompartment system (PMCS). The created PMCS shows excellent catalytic performance, convenient monitoring, and efficient substrate selectivity in the deacetalization-Knoevenagel cascade reaction. Furthermore, two types of electrophile/nucleophile PMCSs have also been accessibly constructed, demonstrating the facile generation of other incompatible systems with the versatility as well as the advancement and extensibility of the developed strategy.

Creation of Nonspherical Microparticles through Osmosis-Driven Arrested Coalescence of Microfluidic Emulsions.

Droplet-based microfluidics enable the production of emulsions and microparticles with spherical shapes, but the high-throughput fabrication of nonspherical emulsions and microparticles still remains challenging because interfacial tension plays a dominant role during preparation. Herein, ionic liquids (ILs) containing salts, which possess sufficient osmotic pressure to realize water transport and phase separation, are introduced as inner cores of oil-in-oil-in-water double emulsions and it is shown that nonspherical emulsions can be constructed by osmosis-driven arrested coalescence of inner cores. Subsequently, ultraviolet polymerization of the nonspherical emulsions leads to nonspherical microparticles. By tailoring the number, composition, and size of inner cores as well as coalescence time, a variety of nonspherical shapes such as dumbbell, rod, spindle, snowman, tumbler, three-pointed star, triangle, and scalene triangle are created. Importantly, benefitting from excellent solvency of ILs, this system can serve as a general platform to produce nonspherical microparticles made from different materials. Moreover, by controlling the osmotic pressure, programmed coalescence of inner cores in double emulsions is realizable, which indicates the potential to build microreactors. Thus, a simple and high-throughput strategy to create nonspherical microparticles with arrested coalescence shapes is developed for the first time and can be further used to construct novel materials and microreactors.

A meta-analysis of biologic therapies on risk of new or recurrent cancer in patients with rheumatoid arthritis and a prior malignancy.

OBJECTIVES: To explore the risk of new and recurrent cancer in adult RA patients with prior malignancy and subsequently exposed to biologic therapies. METHODS: Separate searches were performed of PubMed, EMBASE and Cochrane Library and conference proceedings for observational studies reporting cancer incidence or recurrence in patients with RA and prior malignancy treated with biologics and conventional synthetic DMARDs (csDMARDs). Mantel-Haenszel fixed-effects method was conducted to calculate relative risk and 95% CI. RESULTS: A total of 12 studies involving 13 598 patients and 32 473 patient-years of follow-up were included (10, 3 and 1 studies for TNF inhibitors [TNFi], rituximab and anakinra, respectively). The crude incidence of new and recurrent cancer per 1000 patient-years were 34.4 for TNFi, 32.3 for rituximab, 32.3 for anakinra and 31.8 for csDMARDs. In the quantitative meta-analysis, biologics were not associated with an increased risk of new or recurrent cancer compared with csDMARDs in patients with RA and prior cancer (TNFi: relative risk = 0.95, 95% CI = 0.83, 1.09; rituximab: relative risk = 0.89, 95% CI = 0.52, 1.53). Secondary analyses of stratification of cancer types, the interval between initiation of TNFi and prior cancer diagnosis, and duration of TNFi exposure, found similar results. CONCLUSION: Compared with csDMARDs, there is no increased risk of developing cancer overall or some specific subtypes in RA patients with a prior cancer receiving biologics. More investigations are warranted to explore the risk of cancer development in individual cancer as well as to determine optimal time to initiate biologic therapy after the diagnosis of cancer or completion of cancer treatment.

Ultrabroadband and coherent mid-infrared supercontinuum generation in Te-based chalcogenide tapered fiber with all-normal dispersion.

We demonstrated an ultrabroadband supercontinuum (SC) generation with high coherence property in all-normal-dispersion (ANDi) Te-based chalcogenide tapered fiber. The fibers made of Ge20As20Se15Te45 core and Ge20As20Se20Te40 cladding glasses were fabricated via isolated stacked extrusion. The waist diameter and length can be accurately controlled by a homemade tapering platform. When the core diameter of the waist was ≤14 µm, the fiber showed an ANDi characteristic in the wavelength range of 1.7-14 µm. A coherent SC generation covered 1.7-12.7 µm was generated in a 7-cm-long tapered fiber, pumped at 5.5 µm. To the best of our knowledge, this is the first SC experimental demonstration in Te-based step-index tapered fiber and the broadest SC generation in chalcogenide tapered fiber when pumped in the normal dispersion regime so far.

Efficient replacement of plasma membrane outer leaflet phospholipids and sphingolipids in cells with exogenous lipids.

Our understanding of membranes and membrane lipid function has lagged far behind that of nucleic acids and proteins, largely because it is difficult to manipulate cellular membrane lipid composition. To help solve this problem, we show that methyl-α-cyclodextrin (MαCD)-catalyzed lipid exchange can be used to maximally replace the sphingolipids and phospholipids in the outer leaflet of the plasma membrane of living mammalian cells with exogenous lipids, including unnatural lipids. In addition, lipid exchange experiments revealed that 70-80% of cell sphingomyelin resided in the plasma membrane outer leaflet; the asymmetry of metabolically active cells was similar to that previously defined for erythrocytes, as judged by outer leaflet lipid composition; and plasma membrane outer leaflet phosphatidylcholine had a significantly lower level of unsaturation than phosphatidylcholine in the remainder of the cell. The data also provided a rough estimate for the total cellular lipids residing in the plasma membrane (about half). In addition to such lipidomics applications, the exchange method should have wide potential for investigations of lipid function and modification of cellular behavior by modification of lipids.