Bound-Extended Mode Transition in Type-II Synthetic Photonic Weyl Heterostructures.

Photonic structures with Weyl points (WPs), including type I and type II, promise nontrivial surface modes and intriguing light manipulations for their three-dimensional topological bands. While previous studies mainly focus on exploring WPs in a uniform Weyl structure, here we establish Weyl heterostructures (i.e., a nonuniform Weyl lattice) with different rotational orientations in the synthetic dimension by nanostructured photonic waveguides. In this work, we unveil a transition between bound and extended modes on the interface of type-II Weyl heterostructures by tuning their rotational phases, despite the reversed topological order across the interface. This mode transition is also manifested from the total transmission to total reflection at the interface. All of these unconventional effects are attributed to the tilted dispersion of type-II Weyl band structure that can lead to mismatched bands and gaps across the interface. As a comparison, the type-I Weyl heterostructures lack the phase transition due to the untilted band structure. This work establishes a flexible scheme of artificial Weyl heterostructures that opens a new avenue toward high-dimensional topological effects and significantly enhances our capabilities in on-chip light manipulations.

Perfect Excitation of Topological States by Supersymmetric Waveguides.

Topological photonic states provide intriguing strategies for robust light manipulations, however, it remains challenging to perfectly excite these topological eigenstates due to their complicated mode profiles. In this work, we propose to realize the exact eigenmode of the topological edge states by supersymmetric (SUSY) structures. By adiabatically transforming the SUSY partner to its main topological structure, the edge modes can be perfectly excited with simple single-site input. We experimentally verify our strategy in integrated silicon waveguides in telecommunication wavelength, showing a broad working bandwidth. Moreover, a shortcut-to-adiabaticity strategy is further applied to speed up the adiabatic pump process by inverse-design approaches, thus enabling fast mode evolutions and leading to reduced device size. Our method is universal and beneficial to the topology-based or complex eigenmodes systems, ranging from photonics and microwaves to cold atoms and acoustics.

Functional structural domain synthesis of anti-pancreatic carcinoma pectin-like polysaccharide RN1.

The great structural and functional diversity supports polysaccharides as favorable candidates for new drug development. Previously we reported that a drug candidate pectin-like natural polysaccharide, RN1 might target galectin-3 (Gal-3) to impede pancreatic cancer cell growth in vivo. However, the quality control of polysaccharide-based drug research faces great challenges due to the heterogeneity. A potential solution is to synthesize structurally identified subfragments of this polysaccharide as alternatives. In this work, we took RN1 as an example, and synthesized five subfragments derived from the putative repeating units of RN1. Among them, pentasaccharide 4 showed an approximative binding affinity to Gal-3 in vitro, as well as an antiproliferative activity against pancreatic BxPC-3 cells comparable to that of RN1. Further, we scaled up pentasaccharide 4 to gram-scale in an efficient synthetic route with a 6.9 % yield from D-galactose. Importantly, pentasaccharide 4 significantly suppressed the growth of pancreatic tumor in vivo. Based on the mechanism complementarity of galactin-3 inhibitor and docetaxel, the combination administration of pentasaccharide 4 and docetaxel afforded better result. The result suggested pentasaccharide 4 was one of the functional structural domains of polysaccharide RN1 and might be a leading compound for anti-pancreatic cancer new drug development.

Src is a target molecule of mannose against pancreatic cancer cells growth in vitro & in vivo.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant cancer with limited treatment options. Mannose, a common monosaccharide taken up by cells through the same transporters as glucose, has been shown to induce growth retardation and enhance cell death in response to chemotherapy in several cancers, including PDAC. However, the molecular targets and mechanisms underlying mannose's action against PDAC are not well understood. In this study, we used an integrative approach of network pharmacology, bioinformatics analysis, and experimental verification to investigate the pharmacological targets and mechanisms of mannose against PDAC. Our results showed that the protein Src is a key target of mannose in PDAC. Additionally, computational analysis revealed that mannose is a highly soluble compound that meets Lipinski's rule of five and that the expression of its target molecules is correlated with survival rates and prognosis in PDAC patients. Finally, we validated our findings through in vitro and in vivo experiments. In conclusion, our study provides evidence that mannose plays a critical role in inhibiting PDAC growth by targeting Src, suggesting that it may be a promising therapeutic candidate for PDAC.

Left Bundle Branch Pacing for Heart Failure and Left Bundle Branch Block Patients With Mildly Reduced and Preserved Left Ventricular Ejection Fraction.

BACKGROUND: Left bundle branch block (LBBB) may induce or aggravate heart failure (HF). Few data are available on patients with HF and LBBB with mildly reduced ejection fraction (HFmrEF; left ventricular ejection fraction [LVEF] 40%-50%) and those with preserved EF (HFpEF. LVEF ≥ 50%). We aimed to assess the long-term outcomes of left bundle branch pacing (LBBP) on cardiac function and remodelling in patients with LBBB and symptomatic HFmrEF and HFpEF. METHODS: Nonischemic cardiomyopathy (NICM) patients with HFmrEF and HFpEF (LVEF from 40% to 60% as defined with the use of echocardiography) with LBBB who successfully underwent LBBP (n = 50) were prospectively included from 4 centres. Patient characteristics and echocardiographic and lead parameters were recorded at implantation and during follow-ups of 1, 3, 6, and 12 months. RESULTS: All patients completed 1-year follow up. The LVEF was significantly improved from 46.5 ± 5.2% at baseline to 60.0 ± 6.1% (n = 50; P < 0.001) after 1-year follow up. Higher ΔLVEF and super-response rate were observed in the HFmrEF group (n = 30) than in the HFpEF group (n = 20). CONCLUSIONS: LBBP improved symptoms and reversed remodelling in patients with LBBB and symptomatic HF at 1-year follow-up. Improvement occurred even in HFpEF patients, and the resynchronisation effect was better in HFmrEF group.

Study on Gas Adsorption-Desorption and Diffusion Behaviour in Coal Pores Modified by Nano Fracturing Fluid.

Nanoparticles are added to clean fracturing fluids to formulate nanoparticle-modified clean fracturing fluids, compared with ordinary clean fracturing fluid, it has the advantages of good temperature resistance, low loss of filtration, and so forth, and has good application prospects in coal-bed methane. However, the current research on nanoparticle-modified clean fracturing fluids is mostly focused on the study of their rheological properties. The mechanism of nano-fracking fluid influence on methane adsorption-desorption characteristics is not clear. Therefore, this study chooses Jiulishan anthracite coal (high-rank coal), Pingdingshan coal (medium-rank coal), and Geng village mine long bituminous coal (low-rank coal) of the three rank coal samples. Using indoor experiments and molecular simulation methods, a study on the influence of methane adsorption and desorption capacity and diffusion ability of coal samples provides a modified fracturing fluid formulation of 0.8% CATB + 0.2% NaSal + 1% KCl + SiO2. The experimental results show that nanofracturing fluid-treated coal samples compared to clean fracturing fluid treated coal samples, both methane adsorption and desorption capacities, were increased to some extent. Construction of methane adsorption systems with different apertures and calculation of isosteric heat of adsorption, indicating that the interaction force between methane and coal molecules is smaller after nanofracturing fluid treatment, which facilitated methane desorption. A simulation study of methane diffusion in coal samples treated with two systems of fracturing fluids at different aperture was carried out using molecular dynamics methods, indicating that nanoparticle-modified clean fracturing fluids can reduce the damage of clean fracturing fluids to the desorption-diffusion ability of coal reservoirs. Comparison of 6 MPa as the most suitable pressure for nanofracturing fluids to function provides a basis for the future development of nanofracturing fluids and their popularization.

Change in glomalin-related soil protein along latitudinal gradient encompassing subtropical and temperate blue carbon zones.

Glomalin-related soil protein (GRSP), an abundant and eco-friendly bioproduct associated with arbuscular mycorrhizal fungi (AMF), contributes significantly to the soil particle aggregation and carbon sequestration. Although much research has been conducted on the storage of GRSP at different spatio-temporal scales in terrestrial ecosystems. However, the deposition of GRSP in large-scale coastal environments has not been revealed, which hinders an in-depth understanding of GRSP storage patterns and environmental controls, and this knowledge gap has become one of the key uncertainties in understanding the ecological functions of GRSP as blue carbon components in coastal environments. Therefore, we conducted large-scale experiments (spanning subtropical and warm temperate climate zones, coastlines over 2500 km) to test the relative contributions of environmental drivers that shape unique GRSP storage. In salt marshes of China, we found that the abundance of GRSP ranges from 0.29 mg g-1 to 1.10 mg g-1, and its concentration decreases with increasing latitude (R2 = 0.30, p < 0.01). The GRSP-C/SOC of salt marshes ranged from 4 % to 43 % and increased with the increase in latitude (R2 = 0.13, p < 0.05). The carbon contribution of GRSP does not follow the trend of increasing abundance, but is limited by the total amount of background organic carbon. In salt marsh wetlands, precipitation, clay content and pH are the main factors influencing GRSP storage. GRSP is positively correlated with precipitation (R2 = 0.42, p < 0.01) and clay content (R2 = 0.59, p < 0.01), but negatively correlated with pH (R2 = 0.48, p < 0.01). The relative contributions of the main factors to the GRSP differed across climatic zones. Soil properties, such as clay content and pH, explained 19.8 % of the GRSP in subtropical salt marshes (20°N < 34°N), however, in warm temperate salt marshes (34°N < 40°N), precipitation explained 18.9 % of the GRSP variation. Our study provides insight into the distribution and function of GRSP in coastal environments.

Social determinants of cognitive outcomes in survivors of pediatric brain tumors treated with conformal radiation therapy.

BACKGROUND: Social determinants of health including parental occupation, household income, and neighborhood environment are predictors of cognitive outcomes among healthy and ill children; however, few pediatric oncology studies have investigated this relationship. This study utilized the Economic Hardship Index (EHI) to measure neighborhood-level social and economic conditions to predict cognitive outcomes among children treated for brain tumors (BT) with conformal radiation therapy (RT). METHODS: Two hundred and forty-one children treated on a prospective, longitudinal, phase II trial of conformal photon RT (54-59.4 Gy) for ependymoma, low-grade glioma, or craniopharyngioma (52% female, 79% white, age at RT = 7.76 ±â€…4.98 years) completed serial cognitive assessments (intelligence quotient [IQ], reading, math, and adaptive functioning) for ten years. Six US census tract-level EHI scores were calculated for an overall EHI score: unemployment, dependency, education, income, crowded housing, and poverty. Established socioeconomic status (SES) measures from the extant literature were also derived. RESULTS: Correlations and non-parametric tests revealed EHI variables share modest variance with other SES measures. Income, unemployment, and poverty overlapped most with individual SES measures. Linear mixed models, accounting for sex, age at RT, and tumor location, revealed EHI variables predicted all cognitive variables at baseline and change in IQ and math over time, with EHI overall and poverty most consistent predictors. Higher economic hardship was associated with lower cognitive scores. CONCLUSIONS: Neighborhood-level measures of socioeconomic conditions can help inform understanding of long-term cognitive and academic outcomes in survivors of pediatric BT. Future investigation of poverty's driving forces and the impact of economic hardship on children with other catastrophic diseases is needed.

Tyrosine kinase inhibitors-associated interstitial lung disease used in non-small cell lung cancer: a pharmacovigilance analysis based on the FDA adverse event reporting system database.

BACKGROUND: Interstitial lung disease (ILD) was a relatively common cause of drug-induced mortality. However, the safety profile of the whole TKIs induced ILD was largely unknown. RESEARCH DESIGN AND METHODS: The reported cases of ILD associated with TKIs were downloaded from the FDA adverse event reporting system (FAERS) database between 1 January 2004 and 30 April 2022 to detect ILD signals by disproportionality analysis. Furthermore, the fatality rate and time to onset (TTO) of various TKIs were also calculated. RESULTS: The median age of total 2999 reported cases was 67. The largest reported cases came from osimertinib (n = 736, 24.5%). However, gefitinib had the highest ROR of 12.47 (11.4, 13.64) and IC of 3.53 (3.23, 3.86), means the strongest association with ILD. Trametinib, vemurafenib, larotectinib, selpercatinib, and cabozantinib did not show ILD signal. The median age of dead cases was 72 (Q1:62, Q3:83), and 53.02% (n = 579) were female and 41.11% (n = 449) were male. MET group showed the highest fatality rate of 55.17% with the shortest median TTO of 21 days (Q1: 8.5, Q3: 35.5). CONCLUSIONS: TKIs were significantly associated with ILD. More attention should be paid to female, older, MET group with shorter TTO, as their prognosis might be worse.

Proton therapy and limited surgery for paediatric and adolescent patients with craniopharyngioma (RT2CR): a single-arm, phase 2 study.

BACKGROUND: Compared with photon therapy, proton therapy reduces exposure of normal brain tissue in patients with craniopharyngioma, which might reduce cognitive deficits associated with radiotherapy. Because there are known physical differences between the two methods of radiotherapy, we aimed to estimate progression-free survival and overall survival distributions for paediatric and adolescent patients with craniopharyngioma treated with limited surgery and proton therapy, while monitoring for excessive CNS toxicity. METHODS: In this single-arm, phase 2 study, patients with craniopharyngioma at St Jude Children's Research Hospital (Memphis TN, USA) and University of Florida Health Proton Therapy Institute (Jacksonville, FL, USA) were recruited. Patients were eligible if they were aged 0-21 years at the time of enrolment and had not been treated with previous radiotherapeutic or intracystic therapies. Eligible patients were treated using passively scattered proton beams, 54 Gy (relative biological effect), and a 0·5 cm clinical target volume margin. Surgical treatment was individualised before proton therapy and included no surgery, single procedures with catheter and Ommaya reservoir placement through a burr hole or craniotomy, endoscopic resection, trans-sphenoidal resection, craniotomy, or multiple procedure types. After completing treatment, patients were evaluated clinically and by neuroimaging for tumour progression and evidence of necrosis, vasculopathy, permanent neurological deficits, vision loss, and endocrinopathy. Neurocognitive tests were administered at baseline and once a year for 5 years. Outcomes were compared with a historical cohort treated with surgery and photon therapy. The coprimary endpoints were progression-free survival and overall survival. Progression was defined as an increase in tumour dimensions on successive imaging evaluations more than 2 years after treatment. Survival and safety were also assessed in all patients who received photon therapy and limited surgery. This study is registered with ClinicalTrials.gov, NCT01419067. FINDINGS: Between Aug 22, 2011, and Jan 19, 2016, 94 patients were enrolled and treated with surgery and proton therapy, of whom 49 (52%) were female, 45 (48%) were male, 62 (66%) were White, 16 (17%) were Black, two (2%) were Asian, and 14 (15%) were other races, and median age was 9·39 years (IQR 6·39-13·38) at the time of radiotherapy. As of data cutoff (Feb 2, 2022), median follow-up was 7·52 years (IQR 6·28-8·53) for patients who did not have progression and 7·62 years (IQR 6·48-8·54) for the full cohort of 94 patients. 3-year progression-free survival was 96·8% (95% CI 90·4-99·0; p=0·89), with progression occurring in three of 94 patients. No deaths occurred at 3 years, such that overall survival was 100%. At 5 years, necrosis had occurred in two (2%) of 94 patients, severe vasculopathy in four (4%), and permanent neurological conditions in three (3%); decline in vision from normal to abnormal occurred in four (7%) of 54 patients with normal vision at baseline. The most common grade 3-4 adverse events were headache (six [6%] of 94 patients), seizure (five [5%]), and vascular disorders (six [6%]). No deaths occurred as of data cutoff. INTERPRETATION: Proton therapy did not improve survival outcomes in paediatric and adolescent patients with craniopharyngioma compared with a historical cohort, and severe complication rates were similar. However, cognitive outcomes with proton therapy were improved over photon therapy. Children and adolescents treated for craniopharyngioma using limited surgery and post-operative proton therapy have a high rate of tumour control and low rate of severe complications. The outcomes achieved with this treatment represent a new benchmark to which other regimens can be compared. FUNDING: American Lebanese Syrian Associated Charities, American Cancer Society, the US National Cancer Institute, and Research to Prevent Blindness.

Observation of Weyl Interface States in Non-Hermitian Synthetic Photonic Systems.

Weyl medium has triggered remarkable interest owing to its nontrivial topological edge states in 3D photonic band structures that were mainly revealed as surface modes yet. It is undoubted that the connection of two different Weyl media will give rise to more fruitful physics at their interface, while they face extreme difficulty in high-dimensional lattice matching. Here, we successfully demonstrate the non-Hermitian Weyl interface physics in complex synthetic parameter space, which is implemented in a loss-controlled silicon waveguide array. By establishing non-Hermitian Hamiltonian in the parameter space, new Weyl interfaces with distinct topological origins are predicted and experimentally observed in silicon waveguides. Significantly, our Letter exploits the non-Hermitian parameter to create the synthetic dimension by manipulating the non-Hermitian order, which successfully circumvents the difficulty in lattice matching for high-dimensional interfaces. The revealed rich topological Weyl interface states and their phase transitions in silicon waveguide platform further imply potentials in chip-scale photonics integrations.

Hypogonadism After Treatment for Medulloblastoma: Results From the SJMB03 Trial of Risk-Adapted Radiation Therapy.

PURPOSE: Our purpose was to estimate the cumulative incidence (CI) of hypogonadism in a cohort of pediatric patients treated for medulloblastoma with surgery, risk-adapted craniospinal irradiation, and dose-intensive chemotherapy. METHODS AND MATERIALS: Children and adolescents (n = 156) treated between 2003 and 2013 were evaluated for evidence of hypogonadism and infertility. Clinical information and mean radiation dose to the hypothalamus and gonads and cumulative doses of chemotherapy agents were recorded to estimate CI of hypogonadism and infertility with competing risks. RESULTS: The 5-year CI of hypogonadism was 71.25% (±6.76%) for women and 6.48% (±3.16%) for men (P < .0001) and 50.00% (±9.70%) for puberty age and 28.99% (±5.05%) for prepuberty age at treatment (P = .0068). The 5-year CI by gonadal radiation dose exposure (GRDE) was 61.11% (±12.13%) for high (>2 Gy), 61.18% (±12.92%) for intermediate (1-2 Gy), and 21.97% (±4.76%) for low (<1 Gy) (P < .0001). Sex, puberty status, GRDE, interval from treatment to puberty, and vincristine dose were associated with hypogonadism. Hypogonadism in female sex was highly correlated with GRDE, and dose to hypothalamus was significant when included in multivariable models or when used in models restricted to patients treated after the age of puberty. CI of infertility at 10 years was 55.36% (±14.07%) for women and 23.53% (±10.64%) for men (P = .0389) in a sample of 33 patients. CONCLUSIONS: In the setting of intensive chemotherapy, low-dose gonadal radiation exposure has a significant effect on gonadal function. Women and those achieving age of puberty at time of radiation therapy have a higher risk of hypogonadism. GRDE > 2 Gy was associated with hypogonadism for all groups and >1 Gy in prepubertal patients. Hypothalamus dose was significant when included in multivariable models that included postpubertal patients and those with lower GRDE.

Endocrinopathy After Treatment for Medulloblastoma: Results From the SJMB03 Trial of Risk-Adapted Radiation Therapy.

PURPOSE: The objective of this study was to estimate the cumulative incidence of endocrinopathy in pediatric patients treated for medulloblastoma with surgery, risk-adapted photon craniospinal irradiation, and dose-intensive chemotherapy. METHODS AND MATERIALS: Children and adolescents (n = 156) treated between 2003 and 2013 were evaluated for evidence of endocrinopathy. Clinical information and mean radiation dose to hypothalamus and thyroid were calculated and used to estimate cumulative incidence of growth hormone deficiency, hypothyroidism, adrenal insufficiency, hypogonadism, and precocious puberty. RESULTS: The 5-year cumulative incidences were estimated for growth hormone deficiency, 68.9% (60.9%, 75.6%); hypothyroidism, 48.4% (95% confidence interval (CI), 40.2%-56.1%); adrenal insufficiency, 13.0% (95% CI, 8.3%-18.9%); hypogonadism, 33.9% (95% CI, 25.2%-42.7%); and precocious puberty, 2.0% (95% CI, 0.6%-5.4%). Growth hormone deficiency was associated with increased hypothalamus dose (hazard ratio [HR], 1.035; 95% CI, 1.010-1.061; P = .0055) in average-risk patients and cerebrospinal fluid shunt (HR, 2.532; 95% CI, 1.325-4.838; P = .0049) in high-risk patients. In average-risk patients, hypothyroidism was associated with younger age (HR, 0.902; 95% CI, 0.842-0.973; P = .0070), hypothalamus dose (HR, 1.039; 95% CI, 1.004-1.075; P = .0273), and thyroid dose (HR, 1.070; 95% CI, 1.008-1.136; P = .0263). In high-risk patients, hypothyroidism was associated with increased hypothalamus dose (HR, 1.068; 95% CI, 0.995-1.147; P = .0671) and thyroid dose (HR, 1.050; 95% CI, 1.000-1.104; P = .0515). Adrenal insufficiency was associated with increased hypothalamus dose (HR, 1.112; 95% CI, 1.058-1.170; P < .0001). Growth hormone deficiency incidence was higher when comparing patients treated with cerebrospinal fluid shunt versus those not having a shunt/extraventricular drain placed during initial surgery (HR, 1.712; 95% CI, 1.109-2.643). CONCLUSIONS: Incidence and time to onset of clinically significant endocrinopathy after photon craniospinal irradiation for pediatric medulloblastoma is influenced by radiation dose to target organs and patient age at time of treatment. Advanced radiation therapy methods and dose-reduction strategies are needed to reduce the incidence of endocrinopathy.

Pediatric Craniopharyngioma: The Effect of Visual Deficits and Hormone Deficiencies on Long-Term Cognitive Outcomes After Conformal Photon Radiation Therapy.

PURPOSE: Pediatric patients with craniopharyngioma risk cognitive deficits when treated with radiation therapy. We investigated cognitive outcomes after conformal photon radiation therapy (CRT) and the effect of visual deficits and hormone deficiencies. METHODS AND MATERIALS: One hundred one pediatric patients were enrolled on a single institutional protocol beginning in 1998 (n = 76) or followed a similar nonprotocol treatment plan (n = 25). CRT (54 Gy) was administered using a 1.0- or 0.5-cm clinical target volume margin. Median age at CRT was 9.50 years (range, 3.20-17.63 years). Patients were followed for 10 years with assessment of hearing, vision, hormone deficiencies, and cognitive performance. RESULTS: Intellectual functioning (intelligence quotient) was significantly lower in children treated at a younger age and those who received higher doses to temporal lobes and hippocampi. Black race (-17.77 points, P = .002) and cerebrospinal fluid shunting (-11.52 points, P = .0068) were associated with lower baseline intelligence quotient. Reading scores were lower over time in models incorporating age, shunt, and dose to specific brain structures. Patients treated for growth hormone deficiency within 12 months of CRT had better intelligence and attention outcomes. Among patients with normal baseline vision, the 10-year cumulative incidence of change in visual acuity was 4.00% ± 2.82% and in visual field 10.42% ± 4.48%. Reading scores decreased after treatment (0.7873 points/y, P = .0451) in those with impaired baseline vision. CONCLUSIONS: Cognitive outcomes are selectively affected by dose to brain subvolumes, comorbidities of visual deficits, and treatment of endocrinopathy in pediatric craniopharyngioma. Improved treatment selection, normal tissue sparing methods of irradiation, and posttreatment management of endocrinopathy should be considered.

Spatio-temporal delivery of both intra- and extracellular toll-like receptor agonists for enhancing antigen-specific immune responses.

For cancer immunotherapy, triggering toll-like receptors (TLRs) in dendritic cells (DCs) can potentiate antigen-based immune responses. Nevertheless, to generate robust and long-lived immune responses, a well-designed nanovaccine should consider different locations of TLRs on DCs and co-deliver both antigens and TLR agonist combinations to synergistically induce optimal antitumor immunity. Herein, we fabricated lipid-polymer hybrid nanoparticles (LPNPs) to spatio-temporally deliver model antigen ovalbumin (OVA) on the surface of the lipid layer, TLR4 agonist monophosphoryl lipid A (MPLA) within the lipid layer, and TLR7 agonist imiquimod (IMQ) in the polymer core to synergistically activate DCs by both extra- and intra-cellular TLRs for enhancing adaptive immune responses. LPNPs-based nanovaccines exhibited a narrow size distribution at the mean diameter of 133.23 nm and zeta potential of -2.36 mV, showed a high OVA loading (around 70.83 µg/mg) and IMQ encapsulation efficiency (88.04%). Our data revealed that LPNPs-based nanovaccines showed great biocompatibility to immune cells and an excellent ability to enhance antigen internalization, thereby promoting DCs maturation and cytokines production. Compared to Free OVA, OVA-LPNPs promoted antigen uptake, lysosome escape, depot effect and migration to secondary lymphatic organs. In vivo immunization showed that IMQ-MPLA-OVA-LPNPs with dual agonists induced more powerful cellular and humoral immune responses. Moreover, prophylactic vaccination by IMQ-MPLA-OVA-LPNPs effectively suppressed tumor growth and increased survival efficacy. Hence, the nanovaccines we fabricated can effectively co-deliver antigens and different TLR agonists and realize coordinated stimulation of DCs in a spatio-temporal manner for enhanced immune responses, which provides a promising strategy for cancer immunotherapy.

Anomalous π modes by Floquet engineering in optical lattices with long-range coupling.

Photonic Floquet topological insulators provide a powerful tool to manipulate the optical fields, which have been extensively studied with only nearest-neighbor coupling. Here, we demonstrate that nontrivial Floquet topological phase and photonic π modes are brought from long-range coupling in a one-dimensional periodically driven optical lattice. Interestingly, the long-range coupling is found to give rise to new Floquet π modes that do not exist in the traditional Floquet lattices. We interpret the underlying physics by analyzing the replica bands, which shows quasienergies band crossing and reopening of new nontrivial π gaps due to the long-range coupling. Our results provide a new route in manipulating optical topological modes by Floquet engineering with long-range coupling.

Atrial-His bundle pacing in fulminant myocarditis with ventricular arrhythmia: a case report.

BACKGROUND: Fulminant myocarditis is a clinical syndrome associated with threatening dysrhythmia which temporary pacemaker can be used for life-saving support. As a method of physiological pacing, His bundle pacing (HBP) maintain better cardiac synchronization than traditional right ventricular (RV) pacing. CASE PRESENTATION: It's a severe case of fulminant myocarditis in a 41-year-old patient who presented for recurrent arrhythmias with hemodynamic instability. Temporary His bundle pacing combined with optimal medical therapy and extracorporeal membrane oxygenators (ECMO) supported him through his critical period of hospitalization. CONCLUSIONS: During 1-year follow up, the cardiac function recovery was obvious without any pacing related complications. Echocardiography showed better atrioventricular and intra-ventricular synchronization during HBP in DDD mode. This is the first reported case of temporary His-purkinje conduction system pacing used for severe fulminant myocarditis.

Left Bundle Branch Pacing Postatrioventricular Junction Ablation for Atrial Fibrillation: Propensity Score Matching With His Bundle Pacing.

BACKGROUND: Left bundle branch pacing (LBBP) has emerged as a promising pacing modality to preserve physiological left ventricular activation; however, prospective data evaluating its long-term safety and efficacy in pacemaker-dependent patients following atrioventricular junction (AVJ) ablation are lacking. This study aimed to examine the feasibility, safety, and efficacy of LBBP in patients with atrial fibrillation and heart failure (HF) after AVJ ablation and compare LBBP with His bundle pacing (HBP) through a propensity score (PS) matching analysis. METHODS: We prospectively enrolled patients with atrial fibrillation and HF referred for AVJ ablation and LBBP between July 2017 and December 2019. The control group was patients selected from HBP implants performed from 2012 to 2019 using PS matching with a 1:1 ratio. RESULTS: A total of 99 patients were enrolled in the study. The LBBP implant success rate was 100%. Left ventricular ejection fraction improved from baseline 30.3±4.9 to 1-year 47.3±14.5 in HF patients with reduced ejection fraction and from baseline 56.3±12.1 to 1-year 62.3±9.1 in HF patients with preserved ejection fraction (both P<0.001), and left ventricular ejection fraction in both groups remained stable for up to 3 years of follow-up. A threshold increase >2 V at 0.5 ms occurred in only one patient. Of 176 (81.9%) of 215 patients who received permanent HBP post-AVJ ablation, 86 were matched to the LBBP group by 1:1 PS (propensity score matched His bundle pacing, N=86; propensity score matched left bundle branch pacing, N=86). No significant differences in echocardiographic or clinical outcomes were observed between the 2 groups (P>0.05), whereas lower thresholds, greater sensed R-wave amplitudes, and fewer complications were observed in the propensity score matched left bundle branch pacing group (P<0.05). CONCLUSIONS: LBBP is feasible, safe, and effective in patients with atrial fibrillation and HF post-AVJ ablation and has similar clinical benefits, a higher implant success rate, better pacing parameters, and fewer complications compared with HBP.

Dispersionless Coupling among Optical Waveguides by Artificial Gauge Field.

Coupling among closely packed waveguides is a common optical phenomenon, and plays an important role in optical routing and integration. Unfortunately, this coupling property is usually sensitive to the working wavelength and structure features that hinder the broadband and robust functions. Here, we report a new strategy utilizing an artificial gauge field (AGF) to engineer the coupling dispersion and realize a dispersionless coupling among waveguides with periodically bending modulation. The AGF-induced dispersionless coupling is experimentally verified in a silicon waveguide platform, which already has well-established broadband and robust routing functions (directional coupling and splitting), suggesting potential applications in integrated photonics. As examples, we further demonstrate a three-level-cascaded AGF waveguide network to route broadband light to desired ports with an overwhelming advantage over the conventional ones in comparison. Our method provides a new route of coupling dispersion control by AGF and benefits applications that fundamentally rely on waveguide coupling.