Combined strategies with PARP inhibitors for the treatment of BRCA wide type cancer.

Genomic instability stands out as a pivotal hallmark of cancer, and PARP inhibitors (PARPi) emerging as a groundbreaking class of targeted therapy drugs meticulously crafted to inhibit the repair of DNA single-strand breaks(SSB) in tumor cells. Currently, PARPi have been approved for the treatment of ovarian cancer, pancreatic cancer, breast cancer, and prostate cancer characterized by homologous recombination(HR) repair deficiencies due to mutations in BRCA1/2 or other DNA repair associated genes and acquiring the designation of breakthrough therapy. Nonetheless, PARPi exhibit limited efficacy in the majority of HR-proficient BRCA1/2 wild-type cancers. At present, the synergistic approach of combining PARPi with agents that induce HR defects, or with chemotherapy and radiotherapy to induce substantial DNA damage, significantly enhances the efficacy of PARPi in BRCA wild-type or HR-proficient patients, supporting extension the use of PARPi in HR proficient patients. Therefore, we have summarized the effects and mechanisms of the combined use of drugs with PARPi, including the combination of PARPi with HR defect-inducing drugs such as ATRi, CHKi, HR indirectly inducing drugs like VEGFRi, CDKi, immune checkpoint inhibitors and drugs instigating DNA damage such as chemotherapy or radiotherapy. In addition, this review discusses several ongoing clinical trials aimed at analyzing the clinical application potential of these combined treatment strategies.

Requirements for and Barriers to Rehabilitation Services for Children With Disabilities in Middle- and High-Income Countries: Scoping Review.

BACKGROUND: The rehabilitation of children with disabilities has received considerable attention from the United Nations. However, the state of rehabilitation services for children with disabilities worldwide remains far from optimistic, even in economically affluent middle- and high-income countries. OBJECTIVE: This scoping review aimed to identify the rehabilitation needs of children with disabilities and their barriers to rehabilitation services in middle- and high-income countries. METHODS: A systematic search was conducted using MEDLINE and Web of Science for papers published from January 2013 to December 2023. Studies were included if they were peer-reviewed, full-text articles related to children with disabilities, reporting on their access to rehabilitation services, and conducted in countries classified by the World Bank 2023 as middle- and high-income economies. Exclusion criteria included duplicates, unavailable full texts, and studies without distinct outcomes. A total of 27 studies were selected following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, focusing on children, their families, or service providers. RESULTS: The suitability, availability, and affordability of rehabilitation services were identified as the major needs and barriers for children with disabilities in middle- and high-income countries. This included communication barriers, a need for more personnel and facilities, and the stagnation and inadequacy of economic subsidies. CONCLUSIONS: Middle- and high-income countries have relatively well-established rehabilitation infrastructure and support systems. They are nevertheless insufficient for meeting the needs of children with disabilities. More attention should be paid to these issues to improve the well-being of children with disabilities. The data provided by this review can help raise awareness of rehabilitation needs and barriers at the policy level.

Deep-learning-assisted sidewall profiling white light interferometry system for accurately measuring 3D profiles and surface roughness on the groove sidewalls of precision components.

The accurate measurement of surface three-dimensional (3D) profile and roughness on the groove sidewalls of components is of great significance to diverse fields such as precision manufacturing, machining processes, energy transportation, medical equipment, and semiconductor industry. However, conventional optical measurement methods struggle to measure surface profiles on the sidewall of a small groove. Here, we present a deep-learning-assisted sidewall profiling white light interferometry system, which consists of a microprism-based interferometer, an optical path compensation device, and a convolutional neural network (CNN), for the accurate measurement of surface 3D profile and roughness on the sidewall of a small groove. We have demonstrated that the sidewall profiling white light interferometry system can achieve a measurement accuracy of 2.64 nm for the 3D profile on a groove sidewall. Moreover, we have demonstrated that the CNN-based single-image super-resolution (SISR) technique could improve the measurement accuracy of surface roughness by over 30%. Our system can be utilized in cases where the width of the groove is only 1 mm and beyond, limited only by the size of the microprism and the working distance of the objective used in our system.

Rational construction of CQDs-based targeted multifunctional nanoplatform for synergistic chemo-photothermal tumor therapy.

Photothermal therapy combined with chemotherapy has shown great promise in the treatment of cancer. In this synergistic system, a safe, stable, and efficient photothermal agent is desired. Herein, an effective photothermal agent, carbon quantum dots (CQDs), was initially synthesized and then rationally constructed a folic acid (FA)-targeted photothermal multifunctional nanoplatform by encapsulating CQDs and the anticancer drug doxorubicin (DOX) in the liposomes. Indocyanine green (ICG), a near infrared (NIR) photothermal agent, approved by the U.S. Food and Drug Administration, was embedded in the bilayer membrane to further enhance the photothermal effects and facilitate the rapid cleavage of liposomes for drug release. Triggered by the NIR laser, this engineered photothermal multifunctional nanoplatform, not only exhibited an excellent performance with the photothermal conversion efficiency of up to 47.14%, but also achieved controlled release of the payloads. In vitro, and in vivo experiments demonstrated that the photothermal multifunctional nanoplatform had excellent biocompatibility, enhanced tumor-specific targeting, stimuli-responsive drug release, effective cancer cell killing and tumor suppression through multi-modal synergistic therapy. The successful construction of this NIR light-triggered targeted photothermal multifunctional nanoplatform will provide a promising strategy for the design and development of synergistic chemo-photothermal combination therapy and improve the therapeutic efficacy of cancer treatment.

Reusable CS-Ca@PEI/CuMnO2 Hydrogel Beads for Peroxymonosulfate-Activated Degradation of Congo Red.

Metal oxides can activate peroxymonosulfate (PMS) for the catalytic degradation of organic dyes. However, achieving high catalytic efficiency, structural stability, ease of recovery, and recyclability remains challenging for both research and practical applications. To address these requirements, a bimetallic oxide, CuMnO2, was synthesized using a simple hydrothermal approach and was encapsulated to create hydrogel beads, CS-Ca@PEI/CuMnO2. Subsequently, CS-Ca@PEI/CuMnO2 was used to activate PMS and establish a solid-liquid heterogeneous oxidation system (CS-Ca@PEI/CuMnO2/PMS) for the degradation of Congo red (CR). The effects of various parameters such as different systems, catalyst dosages, initial pH values, PMS concentrations, temperatures, and anion types on the catalytic degradation properties of CS-Ca@PEI/CuMnO2 for CR were systematically evaluated. The results indicated that CS-Ca@PEI/CuMnO2 has exceptional degradation capacity, achieving 91.0% degradation of CR at pH 7. After three degradation cycles, the catalyst maintained an 86.9% degradation efficiency compared to its original performance, highlighting its robust structural stability. The presence of reactive radicals, specifically 1O2 and •O2-, were confirmed through quenching experiments, X-ray photoelectron spectroscopy (XPS), and electron paramagnetic resonance spectroscopy (EPR). Liquid chromatography-tandem mass spectrometry (LC-MS) revealed ten proposed intermediates in the catalytic degradation process. Due to its exceptional catalytic performance, structural durability, recyclability, and ease of retrieval, the catalyst shows great potential for effectively removing organic pollutants from industrial wastewater.

Metal-Loaded Synthetic Melanin via Oxidative Polymerization of Neurotransmitter Norepinephrine Exhibiting High Photothermal Conversion.

Polydopamine (PDA)-derived melanin-like materials exhibit significant photothermal conversion owing to their broad-spectrum light absorption. However, their low near-infrared (NIR) absorption and inadequate hydrophilicity compromise their utilization of solar energy. Herein, we developed metal-loaded poly(norepinephrine) nanoparticles (PNE NPs) by predoping metal ions (Fe3+, Mn3+, Co2+, Ca2+, Ga3+, and Mg2+) with norepinephrine, a neuron-derived biomimetic molecule, to address the limitations of PDA. The chelation between catechol and metal ions induces a ligand-to-metal charge transfer (LMCT) through the formation of donor-acceptor pairs, modulating the light absorption behavior and reducing the band gap. Under 1 sun illumination, the Fe-loaded PNE coated wood evaporator achieved a high seawater evaporation rate and efficiency of 1.75 kg m-2 h-1 and 92.4%, respectively, owing to the superior hydrophilicity and photothermal performance of PNE. Therefore, this study offers a comprehensive exploration of the role of metal ions in enhancing the photothermal properties of synthetic melanins.

Broadband frequency comb generation through cascaded quadratic nonlinearity in thin-film lithium niobate microresonators.

Broadband frequency comb generation through cascaded quadratic nonlinearity remains experimentally untapped in free-space cavities with bulk χ(2) materials mainly due to the high threshold power and restricted ability of dispersion engineering. Thin-film lithium niobate (LN) is a good platform for nonlinear optics due to the tight mode confinement in a nano-dimensional waveguide, the ease of dispersion engineering, large quadratic nonlinearities, and flexible phase matching via periodic poling. Here we demonstrate broadband frequency comb generation through dispersion engineering in a thin-film LN microresonator. Bandwidths of 150 nm (80 nm) and 25 nm (12 nm) for center wavelengths at 1560 and 780 nm are achieved, respectively, in a cavity-enhanced second-harmonic generation (doubly resonant optical parametric oscillator). Our demonstration paves the way for pure quadratic soliton generation, which is a great complement to dissipative Kerr soliton frequency combs for extended interesting nonlinear applications.

Association of healthy lifestyle with life expectancy free of five major disabilities in Chinese older adults.

Background: Whether and to what extent multiple healthy lifestyles affect the longevity of people with disabilities, including those in basic activities of daily living, mobility, vision, hearing and cognition, is crucial to policymakers. We aimed to determine the impact of combined lifestyles on life expectancy (LE) lived with and without five disabilities. Methods: We recruited participants (n = 15 121 from the China Longitudinal Healthy Longevity Survey between 2008 and 2018. Healthy lifestyle levels were estimated from six factors: smoking, drinking, physical exercise, diet, cognitive activity, and sleep, which we categorised as favourable and unfavourable using the latent class growth mixture model throughout the follow-up period. We used Multi-state Markov models to assess the different disability stages of LE. Results: Of the total LE at age 65, older adults with a favourable lifestyle spent 59.60% (disability-free LE (DFLE) = 10.24 years) without five disabilities in combination, whereas those with unfavourable lifestyle spent 56.74% (DFLE = 7.28 years). Furthermore, the percentage of DFLE was 64.98 (7.71 years) and 68.38 (9.91 years) in males with unfavourable and favourable lifestyle levels, respectively, and 47.92 (6.62 years) and 55.12 (10.30 years) for females. Compared to older adults with low socioeconomic status (SES) and unfavourable lifestyle level, those with lower SES and favourable lifestyle level had more 3.77 years of DFLE, those with higher SES and unfavourable lifestyle level had more 1.94 years, as well as those with higher SES and favourable lifestyle level had more 5.10 years at age 65. Corresponding associations were found separately for each of the five individual disabilities. Conclusions: A favourable lifestyle level was associated with longer total LE along with a higher proportion of DFLE and may contribute to narrowing socioeconomic health inequalities. Policymakers should develop lifestyle interventions and scale up rehabilitation services in primary care, thereby delaying disabilities to later ages, especially in low- and middle-income countries.

Melanin-Inspired Composite Materials: From Nanoarchitectonics to Applications.

Synthetic melanin is a mimic of natural melanin analogue with intriguing properties such as metal-ion chelation, redox activity, adhesion, and broadband absorption. Melanin-inspired composite materials are formulated by assembly of melanin with other types of inorganic and organic components to target, combine, and build up the functionality, far beyond their natural capabilities. Developing efficient and universal methodologies to prepare melanin-based composite materials with unique functionality is vital for their further applications. In this review, we summarize three types of synthetic approaches, predoping, surface engineering, and physical blending, to access various melanin-inspired composite materials with distinctive structure and properties. The applications of melanin-inspired composite materials in free radical scavenging, bioimaging, antifouling, and catalytic applications are also reviewed. This review also concludes current challenges that must be addressed and research opportunities in future studies.

Exploring sustainable food packaging: Nanocellulose composite films with enhanced mechanical strength, antibacterial performance, and biodegradability.

Food packaging films play a vital role in preserving and protecting food. However, due to their non-biodegradability, conventional packaging materials have led to significant environmental pollution. To overcome this hurdle, we have developed safe, innovative, sustainable and biodegradable packaging materials that can effectively extend the shelf life of food. In this study, two types of cellulose materials cellulose nanofibers (CNF) and carboxymethyl cellulose (CMC) with complementary roles were combined to prepare nanocellulose composite films with high transparency (90.3 %) of a certain thickness (30 ± 0.019 µm) by solution casting method, and their mechanical properties were further optimized by the addition of plasticizer-glycerol (Gly) and cross-linking agent-glutaraldehyde (GA), so as to maintain the strong tensile strength (≈112.60 MPa) and better malleability (4.12 %). In addition, we loaded the natural active agent tea polyphenols (TPs) with different concentrations to study the inhibition effect on E.coli and S.aureus and to simulate food packaging. Finally, we also found that the synthesized nanocellulose composite films can also achieve rapid degradation in a short time through soil burial, water flushing and immersion. The excellent performance demonstrated in this study provides reference value for further replacing petroleum-based materials with biomass materials in the field of food packaging.

Synthesis, characterization, and antibacterial activity of chitosan-chelated silver nanoparticles.

Bacterial infections pose a significant threat to human health and safety, necessitating the urgent resolution of the problem through the development and implementation of highly effective antibacterial agents. However, the emergence of multidrug-resistant bacteria has diminished the satisfactory effectiveness of antibacterial treatments. To overcome this obstacle, we developed effective antibacterial agents by chemical reduction for inhibiting bacterial proliferation and inducing membrane damage. Specifically, four different types of chitosan/Ag nanoparticle (CS-AgNPs-i) (i-1, 2, 3, 4) complexes were synthesized by varying the quantity of chitosan added during the synthesis process. We found that the amount of CS does not affect the morphology and size of CS-AgNPs-i, which remained at approximately 20 nm and all CS-AgNPs were mostly spherical. The zeta potential measurements indicated that the surface of CS-AgNPs carries a positive charge. Notably, elevating the chitosan concentration led to a more pronounced antibacterial impact, particularly evident in its interaction with the peptidoglycan layer on the bacterial surface. Our experimental results undeniably establish the potent antibacterial efficacy of CS-AgNPs against both Escherichia coli and Staphylococcus aureus. Employing live/dead bacterial staining, we reveal the marked capability of CS-AgNPs to effectively hinder bacterial proliferation. Furthermore, our experimental investigations revealed that CS-AgNPs possess broad-spectrum antimicrobial activity. The results of in vitro cytotoxicity experiments substantiated the high biocompatibility of CS-AgNPs with elevated chitosan loading. The study provides valuable insights into the development of nano-antibacterial agents that exhibit significant potential as a substitute to replace traditional antibiotics for medical applications.

pH-Responsive Sorafenib/Iron-Co-Loaded Mesoporous Polydopamine Nanoparticles for Synergistic Ferroptosis and Photothermal Therapy.

Ferroptosis has attracted significant attention as a new mechanism of cell death. Sorafenib (SRF) is widely considered a prototypical ferroptosis-inducing drug, particularly for liver cancer treatment. However, the low solubility and hydrophobic nature of SRF, along with the absence of synergistic therapeutic strategies, still limit its application in cancer treatment. Herein, we report a dual therapeutic method incorporating photothermal therapy and ferroptosis by using Fe-doped mesoporous polydopamine nanoparticles (Fe-mPDA@SRF-TPP) as a carrier for loading SRF and targeting triphenylphosphine (TPP). SRF molecules are efficiently encapsulated within the polydopamine nanospheres with a high loading ratio (80%) attributed to the porosity of Fe-mPDA, and the inherent biocompatibility and hydrophilicity of Fe-mPDA@SRF-TPP facilitate the transport of SRF to the target cancer cells. Under the external stimuli of acidic environment (pH 5.0), glutathione (GSH), and laser irradiation, Fe-mPDA@SRF-TPP shows sustained release of SRF and Fe ions with the ratio of 72 and 50% within 48 h. Fe-mPDA@SRF-TPP nanoparticles induce intracellular GSH depletion, inhibit glutathione peroxidase 4 (GPX4) activity, and generate hydroxyl radicals, all of which are essential components of the therapeutic ferroptosis process for killing MDA-MB-231 cancer cells. Additionally, the excellent near-infrared (NIR) light absorption of Fe-mPDA@SRF-TPP nanoparticles demonstrates their capability for photothermal therapy and further enhances the therapeutic efficiency. Therefore, this nanosystem provides a multifunctional therapeutic platform that overcomes the therapeutic limitations associated with standalone ferroptosis and enhances the therapeutic efficacy of SRF for breast cancer.

Metformin-Loaded Chitosan Hydrogels Suppress Bladder Tumor Growth in an Orthotopic Mouse Model via Intravesical Administration.

Our previous study found that the intravesical perfusion of metformin has excellent inhibitory effects against bladder cancer (BC). However, this administration route allows the drug to be diluted and excreted in urine. Therefore, increasing the adhesion of metformin to the bladder mucosal layer may prolong the retention time and increase the pharmacological activity. It is well known that chitosan (Cs) has a strong adhesion to the bladder mucosal layer. Thus, this study established a novel formulation of metformin to enhance its antitumor activity by extending its retention time. In this research, we prepared Cs freeze-dried powder and investigated the effect of metformin-loaded chitosan hydrogels (MLCH) in vitro and in vivo. The results showed that MLCH had a strong inhibitory effect against proliferation and colony formation in vitro. The reduction in BC weight and the expression of tumor biomarkers in orthotopic mice showed the robust antitumor activity of MLCH via intravesical administration in vivo. The non-toxic profile of MLCH was observed as well, using histological examinations. Mechanistically, MLCH showed stronger functional activation of the AMPKα/mTOR signaling pathway compared with metformin alone. These findings aim to make this novel formulation an efficient candidate for managing BC via intravesical administration.

Analysis of Shear Model for Steel-Fiber-Reinforced High-Strength Concrete Corbels with Welded-Anchorage Longitudinal Reinforcement.

According to the shear capacity test results of six steel-fiber-reinforced high-strength concrete (SFHSC) corbels with welded-anchorage longitudinal reinforcement under concentrated load, the effects of shear span ratio and steel fiber volume fraction on the failure mode, cracking load and ultimate load of corbel specimens were analyzed. On the basis of experimental research, the shear transfer mechanism of corbel structure was discussed. Then, a modified softened strut-and-tie model (MSSTM), composed of the diagonal and horizontal mechanisms, was proposed, for steel-fiber-reinforced high-strength concrete corbels. The contributions of concrete, steel fiber and horizontal stirrups to the shear bearing capacity of the corbels were clarified. A calculation method for the shear bearing capacity of steel-fiber-reinforced high-strength concrete corbels was established and was simplified on this basis. The calculation results of the model were compared with the test values and calculation results of the GB50010-2010 code, the ACI318-19 code, the EN 1992-1-1 code and the CSA A23.3-19 code. The results showed that the concrete corbel with small shear span ratio mainly has two typical failure modes: shear failure and diagonal compression failure. With the increase in shear span ratio, the shear capacity of corbels decreases. Steel fiber can improve the ductility of a reinforced concrete corbel, but has little effect on the failure mode of the diagonal section. The calculated values of the national codes were lower than the experimental values, and the results were conservative. The theoretical calculation values of the shear capacity calculation model of the corbels were close to the experimental results. In addition, the model has a clear mechanical concept considering the tensile properties of steel-fiber-reinforced high-strength concrete and the influence of horizontal stirrups, which can reasonably reflect the shear transfer mechanism of corbels.

pH-Activated Ce-Doped Molybdenum Oxide Nanoclusters for Tumor Microenvironment Responsive Photothermal and Chemodynamic Therapy.

Molybdenum-based nanomaterials have shown promise for anticancer treatment due to their strong photothermal and redox-activated capabilities. Herein, we have fabricated cerium-doped MoOx (Ce-MoOv) with tunable Mo/Ce molar ratios by a one-pot method and investigated their effect on chemodynamic therapy (CDT) and photothermal therapy (PTT). It is found that Ce-MoOv can self-assemble into nanoclusters in acidic conditions and the increasing Ce amount will generate oxygen vacancy defects and induce the valence change of Mo6+/Mo5+ and Ce4+/Ce3+, which leads to strong near-infrared absorption with high photothermal conversion efficiency of 71.31 and 49.86% for 808 and 1064 nm. Other than photothermal conversion, the materials demonstrate pH-/glutathione (GSH)-activated photoacoustic (PA) imaging capability in vitro. In addition, Ce-MoOv acts as a CDT reagent capable of converting endogenous H2O2 to two types of reactive oxygen species (•OH, 1O2) while depleting GSH. Ce-MoOv demonstrates an excellent therapeutic effect against HCT116 cells and effectively reduces the intracellular GSH level and significantly increases the number of reactive radicals under 1064 nm laser irradiation as compared with the no-laser group in vitro. This work provides a new paradigm using lanthanide-doped polymetallic oxides for pH-/GSH-responsive photothermal/chemodynamic therapy with PA imaging ability.

Adjacent Copper Single Atoms Promote C-C Coupling in Electrochemical CO2 Reduction for the Efficient Conversion of Ethanol.

The electrochemical CO2 reduction reaction (CO2RR) using renewable electricity is one of the most promising strategies for reaching the goal of carbon neutrality. Multicarbonous (C2+) products have broad applications, and ethanol is a valuable chemical and fuel. Many Cu-based catalysts have been reported to be efficient for the electrocatalytic CO2RR to C2+ products, but they generally offer limited selectivity and current density toward ethanol. Herein, we proposed a silica-mediated hydrogen-bonded organic framework (HOF)-templated approach to preparing ultrahigh-density Cu single-atom catalysts (SACs) on thin-walled N-doped carbon nanotubes (TWN). The content of Cu in the catalysts prepared by this method could be up to 13.35 wt %. It was found that the catalysts showed outstanding performance for the electrochemical CO2RR to ethanol, and the Faradaic efficiency (FE) of ethanol increased with the increase in Cu-N3 site density. The FE of ethanol over the catalysts with 13.35 wt % Cu could reach ∼81.9% with a partial current density of 35.6 mA cm-2 using an H-type cell, which is the best result for electrochemical CO2RR to ethanol to date. In addition, the catalyst could be stably used for more than 25 h. Experimental and density functional theory (DFT) studies revealed that the adjacent Cu-N3 active sites (one Cu atom coordinates with three N) were the active sites for the reaction, and their high density was crucial for the high FE of ethanol because the adjacent Cu-N3 sites with a short distance could promote the C-C coupling synergistically.

[Chemical composition analysis and value evaluation of stems and leaves of Astragalus membranaceus var. mongholicus].

This study aimed to provide data support for resource utilization of the stems and leaves of Astragalus membranaceus var. mongholicus(SLAM) by analyzing and evaluating the chemical constituents. The crude protein, crude fiber, and soluble saccharide of SLAM were analyzed by Kjeldahl method, filtration method, and UV-Vis spectrophotometry, respectively. The nucleosides, amino acids, flavonoids, and saponins of SLAM were analyzed by ultraperformance liquid chromatography-triple quadrupole mass spectrometry(UPLC-TQ-MS). Combined with principal component analysis(PCA), the quality difference of resource components of SLAM was comprehensively evaluated. The results showed that the average content of crude protein, crude fiber, total polysaccharide, and redu-cing sugar in SLAM was 5.11%, 30.33%, 11.03 mg·g~(-1), and 31.90 mg·g~(-1), respectively. Six nucleosides, 15 amino acids, 22 flavonoids, and one saponin were detected, with an average content of 1.49 mg·g~(-1), 6.00 mg·g~(-1), 1.86 mg·g~(-1), and 35.67 µg·g~(-1), respectively. The content of various types of chemical components in SLAM differed greatly in different harvesting periods and growing years. The results of PCA showed that the quality of SLAM produced in Ningxia was superior. The results can provide references for the utilization of SLAM.

Synthesized spatiotemporal mode-locking and photonic flywheel in multimode mesoresonators.

Dissipative Kerr soliton (DKS) frequency combs-also known as microcombs-have arguably created a new field in cavity nonlinear photonics, with a strong cross-fertilization between theoretical, experimental, and technological research. Spatiotemporal mode-locking (STML) not only adds new degrees of freedom to ultrafast laser technology, but also provides new insights for implementing analogue computers and heuristic optimizers with photonics. Here, we combine the principles of DKS and STML to demonstrate the STML DKS by developing an unexplored ultrahigh-quality-factor Fabry-Pérot (FP) mesoresonator based on graded index multimode fiber (GRIN-MMF). Complementing the two-step pumping scheme with a cavity stress tuning method, we can selectively excite either the eigenmode DKS or the STML DKS. Furthermore, we demonstrate an ultralow noise microcomb that enhances the photonic flywheel performance in both the fundamental comb linewidth and DKS timing jitter. The demonstrated fundamental comb linewidth of 400 mHz and DKS timing jitter of 500 attosecond (averaging times up to 25 µs) represent improvements of 25× and 2.5×, respectively, from the state-of-the-art. Our results show the potential of GRIN-MMF FP mesoresonators as an ideal testbed for high-dimensional nonlinear cavity dynamics and photonic flywheel with ultrahigh coherence and ultralow timing jitter.

Dissipative soliton generation and real-time dynamics in microresonator-filtered fiber lasers.

Optical frequency combs in microresonators (microcombs) have a wide range of applications in science and technology, due to its compact size and access to considerably larger comb spacing. Despite recent successes, the problems of self-starting, high mode efficiency as well as high output power have not been fully addressed for conventional soliton microcombs. Recent demonstration of laser cavity soliton microcombs by nesting a microresonator into a fiber cavity, shows great potential to solve the problems. Here we study the dissipative soliton generation and interaction dynamics in a microresonator-filtered fiber laser in both theory and experiment. We bring theoretical insight into the mode-locking principle, discuss the parameters effect on soliton properties, and provide experimental guidelines for broadband soliton generation. We predict chirped bright dissipative soliton with flat-top spectral envelope in microresonators with normal dispersion, which is fundamentally forbidden for the externally driven case. Furthermore, we experimentally achieve soliton microcombs with large bandwidth of ~10 nm and high mode efficiency of 90.7%. Finally, by taking advantage of an ultrahigh-speed time magnifier, we study the real-time soliton formation and interaction dynamics and experimentally observe soliton Newton's cradle. Our study will benefit the design of the novel, high-efficiency and self-starting microcombs for real-world applications.

Temperature Change between Neighboring Days Contributes to Years of Life Lost per Death from Respiratory Disease: A Multicounty Analysis in Central China.

BACKGROUND: Many epidemiological studies have recently assessed respiratory mortality attributable to ambient temperatures. However, the associations between temperature change between neighboring days and years of life lost are insufficiently studied. Therefore, we assessed the attributable risk of temperature change between neighboring days on life loss due to respiratory disease. METHODS: We obtained daily mortality and weather data and calculated crude rates of years of life lost for 70 counties in Hunan Province, Central China, from 2013 to 2017. A time-series design with distributed lag nonlinear model and multivariate meta-regression was used to pool the relationships between temperature change between neighboring days and rates of years of life lost. Then, we calculated the temperature change between neighboring days related to average life loss per death from respiratory disease. RESULTS: The total respiratory disease death was 173,252 during the study period. The association between temperature change and years of life lost rates showed a w-shape. The life loss per death attributable to temperature change between neighboring days was 2.29 (95% CI: 0.46-4.11) years, out of which 1.16 (95% CI: 0.31-2.01) years were attributable to moderately high-temperature change between neighboring days, and 0.99 (95% CI: 0.19-1.79) years were attributable to moderately low-temperature change between neighboring days. The temperature change between neighboring days related to life loss per respiratory disease death for females (2.58 years, 95% CI: 0.22-4.93) and the younger group (2.97 years, 95% CI: -1.51-7.44) was higher than that for males (2.21 years, 95% CI: 0.26-4.16) and the elderly group (1.96 years, 95% CI: 0.85-3.08). An average of 1.79 (95% CI: 0.18-3.41) life loss per respiratory disease death was related to non-optimal ambient temperature. CONCLUSIONS: The results indicated that more attention should be given to temperature change, and more public health policies should be implemented to protect public health.