Increased occurrences of consecutive La Niña events under global warming.

Most El Niño events occur sporadically and peak in a single winter1-3, whereas La Niña tends to develop after an El Niño and last for two years or longer4-7. Relative to single-year La Niña, consecutive La Niña features meridionally broader easterly winds and hence a slower heat recharge of the equatorial Pacific6,7, enabling the cold anomalies to persist, exerting prolonged impacts on global climate, ecosystems and agriculture8-13. Future changes to multi-year-long La Niña events remain unknown. Here, using climate models under future greenhouse-gas forcings14, we find an increased frequency of consecutive La Niña ranging from 19 ± 11% in a low-emission scenario to 33 ± 13% in a high-emission scenario, supported by an inter-model consensus stronger in higher-emission scenarios. Under greenhouse warming, a mean-state warming maximum in the subtropical northeastern Pacific enhances the regional thermodynamic response to perturbations, generating anomalous easterlies that are further northward than in the twentieth century in response to El Niño warm anomalies. The sensitivity of the northward-broadened anomaly pattern is further increased by a warming maximum in the equatorial eastern Pacific. The slower heat recharge associated with the northward-broadened easterly anomalies facilitates the cold anomalies of the first-year La Niña to persist into a second-year La Niña. Thus, climate extremes as seen during historical consecutive La Niña episodes probably occur more frequently in the twenty-first century.

Minimizing higher-order aggregation maximizes iron mobilization by small molecules.

The natural product hinokitiol mobilizes iron across lipid bilayers at low concentrations and restores hemoglobinization in iron transporter protein-deficient systems. But hinokitiol fails to similarly mobilize iron at higher concentrations, limiting its uses in chemical biology and medicine. Here we show that at higher concentrations, hinokitiol3:Fe(III) complexes form large, higher-order aggregates, leading to loss of transmembrane iron mobilization. Guided by this understanding and systematic structure-function studies enabled by modular synthesis, we identified FeM-1269, which minimally aggregates and dose-dependently mobilizes iron across lipid bilayers even at very high concentrations. In contrast to hinokitiol, FeM-1269 is also well-tolerated in animals at high doses for extended periods of time. In a mouse model of anemia of inflammation, FeM-1269 increases serum iron, transferrin saturation, hemoglobin and hematocrit. This rationally developed iron-mobilizing small molecule has enhanced potential as a molecular prosthetic for understanding and potentially treating iron transporter deficiencies.

Publisher Correction: Butterfly effect and a self-modulating El Niño response to global warming.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Butterfly effect and a self-modulating El Niño response to global warming.

El Niño and La Niña, collectively referred to as the El Niño-Southern Oscillation (ENSO), are not only highly consequential1-6 but also strongly nonlinear7-14. For example, the maximum warm anomalies of El Niño, which occur in the equatorial eastern Pacific Ocean, are larger than the maximum cold anomalies of La Niña, which are centred in the equatorial central Pacific Ocean7-9. The associated atmospheric nonlinear thermal damping cools the equatorial Pacific during El Niño but warms it during La Niña15,16. Under greenhouse warming, climate models project an increase in the frequency of strong El Niño and La Niña events, but the change differs vastly across models17, which is partially attributed to internal variability18-23. Here we show that like a butterfly effect24, an infinitesimal random perturbation to identical initial conditions induces vastly different initial ENSO variability, which systematically affects its response to greenhouse warming a century later. In experiments with higher initial variability, a greater cumulative oceanic heat loss from ENSO thermal damping reduces stratification of the upper equatorial Pacific Ocean, leading to a smaller increase in ENSO variability under subsquent greenhouse warming. This self-modulating mechanism operates in two large ensembles generated using two different models, each commencing from identical initial conditions but with a butterfly perturbation24,25; it also operates in a large ensemble generated with another model commencing from different initial conditions25,26 and across climate models participating in the Coupled Model Intercomparison Project27,28. Thus, if the greenhouse-warming-induced increase in ENSO variability29 is initially suppressed by internal variability, future ENSO variability is likely to be enhanced, and vice versa. This self-modulation linking ENSO variability across time presents a different perspective for understanding the dynamics of ENSO variability on multiple timescales in a changing climate.

Antibacterial mechanism and structure-activity relationships of Bombyx mori cecropin A.

Bombyx mori cecropin A (Bmcecropin A) has antibacterial, antiviral, anti-filamentous fungal and tumour cell inhibition activities and is considered a potential succedaneum for antibiotics. We clarified the antibacterial mechanism and structure-activity relationships and then directed the structure-activity optimization of Bmcecropin A. Firstly, we found Bmcecropin A shows a strong binding force and permeability to cell membranes like a detergent; Bmcecropin A could competitively bind to the cell membrane with the cell membrane-specific dye DiI, then damaged the membrane for the access of DiI into the cytoplasm and leading to the leakage of electrolyte and proteins. Secondly, we found Bmcopropin A could also bind to and degrade DNA; furthermore, DNA library polymerase chain reaction (PCR) results indicated that Bmcecropin A inhibited DNA replication by non-specific binding. In addition, we have identified C-terminus amidation and serine-lysine- glycine (SLG) amino acids of Bmcecropin A played critical roles in the membrane damage and DNA degradation. Based on the above results, we designed a mutant of Bmcecropin A (E9 to H, D17 to K, K33 to A), which showed higher antibacterial activity, thermostability and pH stability than ampicillin but no haemolytic activity. Finally, we speculated that Bmcecropin A damaged the cell membrane through a carpet model and drew the schematic diagram of its antibacterial mechanism, based on the antibacterial mechanism and the three-dimensional configuration. These findings yield insights into the mechanism of antimicrobial peptide-pathogen interaction and beneficial for the development of new antibiotics.

Study on the epoxidation of chain olefins using biquaternary ammonium phosphotungstic acid phase transfer catalysts under no-solvent condition.

In this study, we have developed a novel catalyst synthesized by phosphotungstic acid and a gemini quaternary ammonium cation salt. This quaternary ammonium salt not only reduces the interfacial tension between olefins and hydrogen peroxide but also forms a notably stable structure with phosphotungstic acid. Dodecene was successfully epoxidized to epoxy dodecane with a selectivity of 82.9 %. The impact of initial conditions was systematically investigated such as molar ratio, temperature, reaction time, and catalyst dosage on the catalytic performance. Characterization of the catalyst morphology was performed by SEM, TEM and SAXS. Raman spectra, FT-IR and XPS spectra were employed to perform the catalyst transformation during the epoxidation reaction. This catalytic mechanism study could provide the industrial application in the epoxidation of long-chain olefins.

Effect of Different Ethylene Oxide Addition Numbers on the Performance of Polyoxyethylene Tallow Amine as a Pesticide Emulsifier.

Surfactant reduces the surface tension of liquids, resulting in improved emulsion stability, and there is great interest in pesticide additives. Ethoxylate is often used as a pesticide emulsifier. However, the degree of ethoxylation and the existence of dioxane byproducts can significantly affect the performance of emulsifiers. Here, a series of polyoxyethylene tallow amines with the addition of different numbers of ethylene oxide (EO) were synthesized and characterized. Their physical and chemical performances were measured. The ability of POEA as a surfactant to reduce water surface tension and the surface adsorption of molecules were assessed based on the static and dynamic surface tensions. The results show that the surfactant molecules preferentially form a saturated adsorption layer in solution, and the mixed-diffusion-kinetics mechanism dominates the adsorption process. With the increase of the EO addition number, the emulsifying property of POEA increases, while the wetting property gradually decreases and the contact angle increases. These results can provide a basis for the selection of pesticide additives. At the same time, the mechanism of removing dioxane by ethoxylate is described, and a simple and low-consumption method is put forward to reduce the dioxane content. It provides a new idea for the removal of dioxane.

Risk Factors Analysis of Severe Liver Injury Induced by Statins.

The aim of this study is to report the risk factors of severe statin induced liver injury (SILI). From the database of Shandong ADR Monitoring Center and Outpatients and inpatients in our hospital, SILI cases reported from 2013 to 2021 were extracted and screened. The diagnostic criteria of SILI, the inclusion and exclusion criteria of severe and general SILI were established separately. After the SILI cases were selected and confirmed, the socio-demographic and clinical characteristics were collected. Single factor chi-square test and multi-factor unconditional logistic regression analysis were used to analyze the influencing factors of severe SILI. From 1391 reported cases, 1211 met SILI diagnostic criteria, of which 157 were severe SILI and 964 were general SILI. Univariate analysis showed that age, drug combination, statin category were the influencing factors of severe SILI (p<0.1). Multivariate logistic analysis showed that drug combination and statin category were the influencing factors of severe SILI (p<0.05). Atorvastatin caused the most serious SILI, and its risk is 1.77 times higher than rosuvastatin. The serious SILI risk of drug combination was 2.08 times higher than statin alone. The patient with these factors should be monitored intensively during clinical treatment, to ensure their medication safety.

Atomic resolution imaging using a novel, compact and stiff scanning tunnelling microscope in cryogen-free superconducting magnet.

We present the design and performance of a novel scanning tunnelling microscope (STM) operating in a cryogen-free superconducting magnet. Our home-built STM head is compact (51.5 mm long and 20 mm in diameter) and has a single arm that provides complete openness in the scanning area between the tip and sample. The STM head consists of two piezoelectric tubes (PTs), a piezoelectric scanning tube (PST) mounted on a well-polished zirconia shaft, and a large PT housed in a sapphire tube called the motor tube. The main body of the STM head is made of tantalum. In this design, we fixed the sapphire tube to the frame with screws so that the tube's position can be changed quickly. To analyse the stiffness of the STM head unit, we identified the lowest eigenfrequencies with 3 and 4 kHz in the bending modes, 8 kHz in a torsional mode, and 9 kHz in a longitudinal mode by finite element analysis, and also measured the low drift rates in the X-Y plane and in the Z direction. The high performance of the home-built STM was demonstrated by images of the hexagonal graphite lattice at 300 K and in a sweeping magnetic field from 0 T to 9 T. Our results confirm the high stability, vibration resistance, insensitivity to high magnetic fields and the application potential of our newly developed STM for the investigation of low-frequency systems with high static support stiffness in physics, chemistry, material and biological sciences.

Highly sensitive curvature fiber sensor based on an enhanced core diameter mismatch.

In this study, a curvature fiber sensor based on an enhanced core diameter mismatch is experimentally proposed and theoretically investigated. The structure is fabricated by splicing two types of step multimode and coreless fibers to excite the high-order cladding modes to improve the curvature sensitivity. Experimental results show that the highest curvature sensitivities of the structure reach -114.74 nm/m-1 in the Dip 1272 nm, -91.08 nm/m-1 in Dip 1408 nm, and -61.10 nm/m-1 in Dip 1644 nm in the measuring range of 0-0.49778 m-1. Meanwhile, the sensor's temperature and strain responses were also tested, which shows little influence on the curvature measurement. Additionally, the proposed fiber sensor exhibits features of easy fabrication, simple structure, and high mechanical strength. This study proposes a device for curvature measurement with potential use in material mechanics and optical fiber sensor design.

Highly-sensitive temperature sensor based on photopolymerized-waveguide embedded Mach-Zehnder interferometer.

Biology, medicine, and chemistry all rely heavily on highly sensitive optical fiber temperature sensors. To the best of our knowledge, this research introduces a unique design framework for high-performance fiber temperature sensors that helps eliminate the all-fiber interferometers' sensitivity bottleneck. A section of photopolymerized waveguide is embedded in a typical Mach-Zehnder interferomenter framework with multimode fiber-single mode fiber-multimode fiber (MSM) structure. The thermal-optical coefficient (TOC) of the photopolymerized waveguide core, which is created via the fiber-end lithography technique, differs dramatically from that of the resin cladding. Due to the considerable TOC difference, the phase difference between the interfering beams significantly increases as the temperature changes. The fundamental variables affecting temperature sensitivity are conceptually explored and experimentally verified. The suggested device achieves a typical temperature sensitivity of 1.15 nm/ ∘C in the range of 30-100 ∘C, which is about 10 times as high as that of the all-fiber MSM sensors. The suggested designing framework offers a fresh thought for creating high-performing fiber optic temperature sensors.

Point-coated long-period fiber grating for temperature measurement.

In this paper, a temperature sensor based on a point-coated long-period fiber grating (PC-LPFG) is proposed and investigated. This structure is fabricated using a thermal filling method. The point-coating approach effectively increases the coupling efficiency between the sensing unit and the surrounding medium. The polymethyl methacrylate (PMMA), with high thermal optical coefficient (TOC) and thermal expansion coefficient (TEC), improves the temperature sensitivity of the PC-LPFG. Experimental results show that the temperature sensitivities of this sensor are 2.948 nm/°C and 6.717 nm/°C in the temperature ranges of 80.4-91°C and 91-97°C, respectively. The hot point-coating method of the PC-LPFG provides a new, to the best of our knowledge, approach to combining optic fiber sensors with high polymer materials.

Lab-on-fiber: laser-induced micro-cavity for a relative humidity measurement.

The lab-on-fiber design philosophy is the foundation for creating high-performance integrated fiber sensors. Hence, this Letter proposes an ultra-compact Fabry-Perot interferometer (FPI) based on a laser-induced micro-cavity (LIMC-FPI) on a fiber end for measuring relative humidity. To our knowledge, this novel approach, named the fiber-end photopolymerization (FEP) technique, is applied to create a micro-cavity. Specifically, a pair of humidity-sensitive polymer pillars and a resin end cap obtained by FEP are integrated to generate the cavity. As the ambient humidity changes, the pillars lengthen or shorten, resulting in the spectral evolution of the LIMC-FPI. A typical humidity sensitivity of 0.18 nm/%RH is obtained experimentally. For monitoring the human breathing process, the LIMC-FPI is responsive in the breathing frequency range of 0.2 to 0.5 Hz, allowing a response and recovery time of less than 0.388 s and 1.171 s, respectively. This work introduces a fresh and cost-effective approach for developing lab-on-fiber concept-based sensors.

Exoskeleton type long-period fiber grating for cross-talk-resistance single-parameter measurement.

This paper proposes a new, to the best of our knowledge, design framework of long-period fiber grating (LPFG) sensors resistant to multi-parameter cross talk. A section of hollow quartz capillary (HQC), which acts as an exoskeleton, is periodically merged with a single-mode fiber (SMF) by the arc-discharge method. The mechanical stress in the SMF is released while the thermal stress is enhanced after a high-temperature fusion process. Under the influence of the elastic-optical effect, the refractive index of the core is periodically modulated along the axial direction to form an exoskeleton long-period fiber grating (Es-LPFG). The unique exoskeleton structure not only induces mode coupling but also enables the proposed device to resist cross talk among the strain, ambient refractive index, and vector bending. The temperature is able to be measured independently with a sensitivity of 74 pm/ ∘C. The novel Es-LPFG is promising in single-parameter sensing, mode-locked lasers, and frequency-locked gain flattening.

Causality assessment of circulating Vitamin D level on venous thromboembolism: A Mendelian randomization study.

BACKGROUND AND AIMS: The associations of vitamin D level with venous thromboembolism (VTE) reported in observational studies, whereas these causal associations were uncertain in European population. Therefore, we used Mendelian randomization (MR) method to explore the causal associations between 25-hydroxyvitamin D (25(OH)D) concentrations and the risk of VTE and its subtypes [including deep vein thrombosis (DVT) and pulmonary embolism (PE)]. METHODS AND RESULTS: We used three kinds of genetic instruments to proxy the exposure of 25(OH)D, including genetic variants significantly associated with 25(OH)D, expression quantitative trait loci of 25(OH)D target genes, and genetic variants within or nearby 25(OH)D target genes. MR analyses did not provide any evidence for the associations of 25(OH)D levels with VTE and its subtypes (p > 0.05). The summary-data-based MR (SMR) analyses indicated that elevated expression of VDR was associated with decreased risk of VTE (OR = 0.81; 95% CI, 0.65-0.998; p = 0.047) and PE (OR = 0.67; 95% CI, 0.50-0.91; p = 0.011), and expression of AMDHD1 was associated with PE (OR = 0.93; 95% CI, 0.88-0.99; p = 0.027). MR analysis provided a significant causal effect of 25(OH)D level mediated by gene AMDHD1 on PE risk (OR = 0.09; 95% CI, 0.01-0.60; p = 0.012). CONCLUSION: Our MR analysis did not support causal association of 25(OH)D level with the risk of VTE and its subtypes. In addition, the expression of VDR and AMDHD1 involved in vitamin D metabolism showed a strong association with VTE or PE and might represent targets for these conditions.

Multi-parameter sensor with high sensitivity based on a long-period fiber grating prepared by a polarization-maintaining fiber.

We propose what we believe to be a novel long-period fiber grating (LPFG) based on a polarization-maintaining fiber (PMF) and single-mode fiber. Due to the principal axis of stress, the resonance peak is strongly dependent on the polarization state of the input light. Under different polarization states, the response of the resonance peak to the change of the external environment is different. A single resonance peak can measure several physical quantities without wavelength overlap using polarization multiplexing. The experimental results show that the PMF-LPFG realizes a high sensitivity torsion and bending measurement under different polarization states (-3.27 nm/rad*m and -13.38 nm/m) and can also measure the ambient temperature (84.10 pm/°C). The PMF-LPFG unit has the advantages of small size, high sensitivity, and multi-parameter measurement. The design scheme of the sensor provides a new idea for a multi-parameter sensor.

High-sensitivity strain sensor based on a helical-core long-period fiber grating.

A highly sensitive strain sensor based on a helical-core long-period fiber grating (HC-LPFG) is proposed and experimentally investigated. The helical core is fabricated in the common single-mode fiber by using a high-frequency CO2 laser and hydrogen-oxygen flame. This helical shape core of the structure experienced the highly centralized refractive index modulation, which enhances the strain sensitivity and shortens the length of the sensing area to 2 mm. Experimental results indicate that the maximum strain sensitivity of the HC-LPFG reaches -97 pm/µÉ› within the measuring range of 0-400 µÉ›.

Super-compact shearography based on a single diffractive optical element with 3-in-1 phase mask.

This Letter communicates a new, to the best of our knowledge, designing framework of shearography. The three elementary functional parts of quantitative shearography, namely imaging, shearing, and phase shifting, are integrated into a single diffractive optical element (DOE), named a 3-in-1 phase mask. The idea breaks through the conventional designing routine of shearography, and converts it from the combination of individual optical elements to the spatial manipulation of phase. The slicing, splicing, and alternating strategy is proposed to generate the 3-in-1 phase mask from a given number of sequenced Fresnel lenses and a modified echelle grating. The operating component is merely a DOE, which renders the optics naturally coaxial. The delivered shearography system enjoys a super-compact configuration, a high level of robustness and stability, and the potential for implementing outside optics laboratories. Crucial system parameters, e.g., shear amount, shear direction, working distance, can be readily shifted on call by re-making the 3-in-1 phase mask. The future of the present idea is in its shape and seems promising with lithography, micromachining, and metasurfaces.

Causal associations between COVID-19 and atrial fibrillation: A bidirectional Mendelian randomization study.

BACKGROUND AND AIMS: Observational studies showed that coronavirus disease (2019) (COVID-19) attacks universally and its most menacing progression uniquely endangers the elderly with cardiovascular disease (CVD). The causal association between COVID-19 infection or its severity and susceptibility of atrial fibrillation (AF) remains unknown. METHODS AND RESULTS: The bidirectional causal relationship between COVID-19 (including COVID-19, hospitalized COVID-19 compared with not hospitalized COVID-19, hospitalized COVID-19 compared with the general population, and severe COVID-19) and AF are determined by using two-sample Mendelian randomization (MR) analysis. Genetically predicted severe COVID-19 was not significantly associated with the risk of AF [odds ratio (OR), 1.037; 95% confidence interval (CI), 1.005-1.071; P = 0.023, q = 0.115]. In addition, genetically predicted AF was also not causally associated with severe COVID-19 (OR, 0.993; 95% CI, 0.888-1.111; P = 0.905, q = 0.905). There was no evidence to support the association between genetically determined COVID-19 and the risk of AF (OR, 1.111; 95% CI, 0.971-1.272; P = 0.127, q = 0.318), and vice versa (OR, 1.016; 95% CI, 0.976-1.058; P = 0.430, q = 0.851). Besides, no significant association was observed for hospitalized COVID-19 with AF. MR-Egger analysis indicated no evidence of directional pleiotropy. CONCLUSION: Overall, this MR study provides no clear evidence that COVID-19 is causally associated with the risk of AF.