Symmetry‐protected quasi‐bound states in the continuum (BIC) controlled by metasurfaces with broken in‐plane symmetry are widely exploited to achieve highly surface‐sensitive and spectrally sharp ...resonances for nanophotonic biosensors. Through the engineering of silicon‐based asymmetric nanobar pairs, a quasi‐BIC mode is excited showing a dominant toroidal dipole (TD) and electric quadrupole (EQ) resonant feature in the near‐infrared and performs ultrahigh sensitivity in the refractometric monitoring of local environment changes. Contrary to the typical electric and magnetic Mie‐type resonances of dielectric resonators with the enhanced field mostly inside the resonator volume, the TD‐EQ quasi‐BIC mode is found to exhibit strong and tightly confined optical fields at the surface of tilted nanobar pairs, and its refractive‐index (RI) sensitivity can be dramatically increased for nanopillars with larger aspect‐ratio. The measured (simulated) sensitivity and figure of merit for nanobar pairs with a height of 450 nm reach 608 nm/RIU and 46 (612 nm/RIU and 85), respectively. Such ultrahigh sensitive all‐dielectric platform can be fabricated through complementary metal‐oxide‐semiconductor compatible process and is promising for on‐chip integration and sensor miniaturization to a wide range of diagnostic applications.
Quasi‐bound states in the continuum modes in periodic amorphous silicon tilted nanobar pairs are found to exhibit a dominant toroidal dipole and electric quadrupole resonant property. Such higher‐order resonant mode exhibits intriguing near‐field distributions accompanied by a strong electric field tightly confined at the surface of nanobar width and results in ultrahigh refractive index sensitivity for high aspect‐ratio nanopillars.
Chronic granulomatous disease (CGD) is a primary immunodeficiency of phagocyte function due to defective NADPH oxidase (phox). Compared with the common types of
CYBB/
gp91
phox
,
NCF1
/p47
phox
, and
...CYBA
/p22
phox
deficiency,
NCF4
/p40
phox
deficiency is a mild and atypical form of CGD without invasive bacterial or fungal infections. It can be diagnosed using serum-opsonized
E.coli
as a stimulus in dihydrorhodamine (DHR) assay. Patients with
CYBC1
/Eros deficiency, a new and rare form of CGD, present as loss of respiratory burst and gp91
phox
expression in phagocytes. Neutrophils from patients with CGD are deficient in neutrophil extracellular traps (NETosis), autophagy, and apoptosis. The hyper-activation of NF-ĸB and inflammasome in CGD phagocytes also lead to long-lasting production of pro-inflammatory cytokines and inflammatory manifestations, such as granuloma formation and inflammatory bowel disease-like colitis. Patients with CGD and X-linked female carriers also have a higher incidence of autoimmune diseases. The implementation of antimicrobial, anti-fungal, and interferon-γ prophylaxis has greatly improved overall survival. Residual NADPH oxidase activity is significantly associated with disease severity and the chance of survival of the patient. New therapeutic approaches using immunomodulators for CGD-related inflammatory manifestations are under investigation, including pioglitazone, tamoxifen, and rapamycin. Hematopoietic stem cell transplantation (HSCT) is the curative treatment. Outcomes of HSCT have improved substantially over the last decade with overall survival more than 84–90%, but there are debates about designing optimal conditioning protocols using myeloablative or reduced-intensity regimens. The gene therapy for X-linked CGD using hematopoietic stem and progenitor cells transduced ex vivo by lentiviral vector encoding the human gp91phox gene demonstrated persistence of adequate oxidase-positive neutrophils in a small number of patients. Gene therapy using genome-editing technology such as CRISPR/Cas9 nucleases is a promising approach for patients with CGD in the future.
Disruption of the blood-brain barrier (BBB) is critical to initiation and perpetuation of disease in multiple sclerosis (MS). We report an interaction between oligodendroglia and vasculature in MS ...that distinguishes human white matter injury from normal rodent demyelinating injury. We find perivascular clustering of oligodendrocyte precursor cells (OPCs) in certain active MS lesions, representing an inability to properly detach from vessels following perivascular migration. Perivascular OPCs can themselves disrupt the BBB, interfering with astrocyte endfeet and endothelial tight junction integrity, resulting in altered vascular permeability and an associated CNS inflammation. Aberrant Wnt tone in OPCs mediates their dysfunctional vascular detachment and also leads to OPC secretion of Wif1, which interferes with Wnt ligand function on endothelial tight junction integrity. Evidence for this defective oligodendroglial-vascular interaction in MS suggests that aberrant OPC perivascular migration not only impairs their lesion recruitment but can also act as a disease perpetuator via disruption of the BBB.
Augmentation cystoplasty (AC) is an effective surgical procedure for patients with neurogenic bladder whenever conservative treatments have failed. The present study aimed to determine the risks of ...metabolic complications, malignancy, long-term outcomes and histopathologic changes of native bladder and the augmented intestine after AC in children with neurogenic bladder. Pediatric patients < 18 years who underwent AC between 2000 and 2020 were enrolled. Early postoperative complications, long-term outcomes and histopathologic changes in mucosal biopsies of native bladder and the augmented intestine after AC were reviewed. Twenty-two patients with a mean age of 7.6 ± 4.4 years were included. The ileum was used in 19 patients and the sigmoid colon in 3 patients. The length of hospital stay was 14.8 ± 6.8 days. Post-operatively, the urinary continence rate improved from 22.7 to 81.8% (p < 0.001). Hydronephrosis resolved in 17 of 19 patients. Vesicoureteral reflux resolved in 16 (64.0%) of the refluxing ureter units and was downgraded in 7 (28.0%). Grades of hydronephrosis and reflux significantly improved following AC (p < 0.001). The estimated glomerular filtration rate also significantly increased (p = 0.012). Formation of urinary tract stones was the most frequent late complication (in 8 patients, 36.4%). Life-threatening spontaneous bladder perforation occurred in 1 patient. After a mean follow-up of 13.4 ± 5.9 years, there were no cases of mortality, new-onset symptomatic metabolic acidosis, or changes in serum electrolytes. Of the 17 patients who were followed for > 10 years, no cases of malignancy or metaplastic changes were identified in the native bladder or augmented bowel epithelium. AC is a safe and effective procedure with low surgical and metabolic complication rates. In addition, AC provides a satisfactory continence rate and long-term protection of renal function, increases functional capacity, and regresses reflux and hydronephrosis. Individualized surveillance is recommended for the early identification of urolithiasis and metabolic disturbances.
Integrated‐resonant units (IRUs), incorporated with multiple resonators into one building block or one resonator with multiple modes, show a great capacity for achieving controllable smooth and ...linear phase dispersion as well as amplitude manipulation over a continuous and broad bandwidth. Based on an IRU library designed in the wavelength range of 400 to 667 nm, three achromatic deflectors showing constant steering angles of 9.5°, 19°, and 28°, respectively, are numerically validated. Achromatic metalenses with various numerical aperture (NA) values are further experimentally demonstrated, displaying an unvaried focal length throughout the bandwidth of 420–650 nm (≈50% bandwidth to the central wavelength). The focusing efficiency of the achromatic metalens with NA = 0.124 achieves 26.31%, 19.71%, and 20.37%, respectively, at wavelengths of 420, 550, and 650 nm. In addition, a multi‐nanorod IRU design is numerically optimized to achieve above 50% conversion efficiency from visible to near‐infrared (400–1400 nm). Such IRU design is then employed to construct a versatile polarization convertor, generating six different polarization states simultaneously upon one linear‐polarized illumination. The IRU approach with broadband control of amplitude and phase response provides an unprecedented platform in realizing multifunctional full‐color metadevices.
Integrated‐resonant units (IRUs), regarded as a building block consisting of multiple resonances, provide a great capacity for controlling phase dispersion as well as amplitude manipulation over a continuous and broad bandwidth. Here, by incorporating IRUs into metasurfaces, broadband and high efficiency achromatic beam deflectors, achromatic metalenses, and versatile polarization convertors are demonstrated.
Unveiled as a unique feature of polymer ferroelectric crystals, oriented coalescence within monolayers of poly(vinylidenefluoride‐co‐trifluoroethylene)(PVDF‐TrFE) ferroelectric crystals has been ...found regulable upon monolayer roughness, which is accompanied by the adjustment of piezoelectric responses, and thus phase polarity. Simply with the deposition of poly(3‐hexylthiophene (P3HT)‐wrapped molybdenum disulfide (MoS2) sheets, piezoelectric responses of polymer ferroelectric crystals are surprisingly enhanced further. Also dependent on the degrees of phase polarity, the binding energy of P3HT excitons declines to a level comparable to that of inorganic excitons, together with the alteration of work functions. These results suggest mutual polarization between ferroelectric lamellar crystals and originally nonpolar P3HT‐wrapped MoS2 sheets as a result of dipole‐induced dipole phase interactions. As the Fermi levels and driving forces of interfacial electron transition are also adjustable upon involved phase interactions, P3HT‐wrapped MoS2 sheets can photocatalyze hydrogen evolution with an average production rate reaching 4.474 mmol g−1 h−1, which is 1.6 times higher than the results without the aid of phase interactions. Accordingly, amplifying phase interactions has been elucidated feasible, and able to serve as a promising approach to generally promote photocatalytic reactions.
Angiotensin receptor blockers (ARBs) and β blockers are widely used in the treatment of Marfan syndrome to try to reduce the rate of progressive aortic root enlargement characteristic of this ...condition, but their separate and joint effects are uncertain. We aimed to determine these effects in a collaborative individual patient data meta-analysis of randomised trials of these treatments.
In this meta-analysis, we identified relevant trials of patients with Marfan syndrome by systematically searching MEDLINE, Embase, and CENTRAL from database inception to Nov 2, 2021. Trials were eligible if they involved a randomised comparison of an ARB versus control or an ARB versus β blocker. We used individual patient data from patients with no prior aortic surgery to estimate the effects of: ARB versus control (placebo or open control); ARB versus β blocker; and indirectly, β blocker versus control. The primary endpoint was the annual rate of change of body surface area-adjusted aortic root dimension Z score, measured at the sinuses of Valsalva.
We identified ten potentially eligible trials including 1836 patients from our search, from which seven trials and 1442 patients were eligible for inclusion in our main analyses. Four trials involving 676 eligible participants compared ARB with control. During a median follow-up of 3 years, allocation to ARB approximately halved the annual rate of change in the aortic root Z score (mean annual increase 0·07 SE 0·02 ARB vs 0·13 SE 0·02 control; absolute difference –0·07 95% CI –0·12 to –0·01; p=0·012). Prespecified secondary subgroup analyses showed that the effects of ARB were particularly large in those with pathogenic variants in fibrillin-1, compared with those without such variants (heterogeneity p=0·0050), and there was no evidence to suggest that the effect of ARB varied with β-blocker use (heterogeneity p=0·54). Three trials involving 766 eligible participants compared ARBs with β blockers. During a median follow-up of 3 years, the annual change in the aortic root Z score was similar in the two groups (annual increase –0·08 SE 0·03 in ARB groups vs –0·11 SE 0·02 in β-blocker groups; absolute difference 0·03 95% CI –0·05 to 0·10; p=0·48). Thus, indirectly, the difference in the annual change in the aortic root Z score between β blockers and control was –0·09 (95% CI –0·18 to 0·00; p=0·042).
In people with Marfan syndrome and no previous aortic surgery, ARBs reduced the rate of increase of the aortic root Z score by about one half, including among those taking a β blocker. The effects of β blockers were similar to those of ARBs. Assuming additivity, combination therapy with both ARBs and β blockers from the time of diagnosis would provide even greater reductions in the rate of aortic enlargement than either treatment alone, which, if maintained over a number of years, would be expected to lead to a delay in the need for aortic surgery.
Marfan Foundation, the Oxford British Heart Foundation Centre for Research Excellence, and the UK Medical Research Council.
The ambrosia beetle morphologically identified as Euwallacea fornicatus consists of several cryptic species that exhibit large differences in the DNA sequences of several nuclear and mitochondrial ...gene regions.
Based on these differences, we suggest that there are at least three different species each with distinct phylogeography.
Members of this cryptic species complex have invaded many areas outside their native range and cause substantial damage to both agriculture (avocado in particular) and other tree species.
Three of these cryptic species have invaded the USA: two species in California and a third species in both Florida and Hawaii.
Identification of their native range allows directed search for their natural enemies that may be used in biological control of these tree pests.
The rapid increase and spread of Gram‐negative bacteria resistant to many or all existing treatments threaten a return to the preantibiotic era. The presence of bacterial polysaccharides that impede ...the penetration of many antimicrobials and protect them from the innate immune system contributes to resistance and pathogenicity. No currently approved antibiotics target the polysaccharide regions of microbes. Here, describe monolaurin‐based niosomes, the first lipid nanoparticles that can eliminate bacterial polysaccharides from hypervirulent Klebsiella pneumoniae, are described. Their combination with polymyxin B shows no cytotoxicity in vitro and is highly effective in combating K. pneumoniae infection in vivo. Comprehensive mechanistic studies have revealed that antimicrobial activity proceeds via a multimodal mechanism. Initially, lipid nanoparticles disrupt polysaccharides, then outer and inner membranes are destabilized and destroyed by polymyxin B, resulting in synergistic cell lysis. This novel lipidic nanoparticle system shows tremendous promise as a highly effective antimicrobial treatment targeting multidrug‐resistant Gram‐negative pathogens.
The first reported instance of a lipid nanoparticle that efficiently targets the polysaccharide regions of Gram‐negative bacteria is described. In conjunction with polymyxin B, the lipid nanoparticle synergistically eradicates polysaccharides via multimodal mechanisms. This promising innovation holds immense potential in countering the escalating challenge of antibiotic resistance in Gram‐negative bacteria.
Acrylamide (ACR) is present in high-temperature-processed high-carbohydrate foods, cigarette smoke, and industrial pollution. Chronic exposure to ACR may induce neurotoxicity from reactive oxygen ...species (ROS); however, the mechanisms underlying ACR-induced neurotoxicity remain unclear. We studied 28-day subacute ACR toxicity by repeatedly feeding ACR (0, 15, or 30 mg/kg) to rats. We conducted RNA sequencing and Western blot analyses to identify differences in mRNA expression in the blood and in protein expression in the brain tissues, respectively, of the rats. AQP4 transient transfection was performed to identify potential associations with protein regulation. The rats treated with 30 mg/kg ACR exhibited hind-limb muscle weakness. Matrix metalloproteinase (MMP9) expression was higher in the ACR-treated group than in the control group. ACR induced MMP-9 and AQP4 protein expression in the brain tissues of the rats, which subsequently presented with neurotoxicity. In the in vitro study, Neuro-2a cells were transiently transfected with AQP4, which inhibited MMP-9 and TNF receptor-associated factor 6 (TRAF6) expression, and inhibited ACR induced expression of TRAF6, IκBα, and nuclear factor κB (NFκB). Using a combination of in vivo and in vitro experiments, this study revealed that depressive symptoms associated with ACR-induced neurotoxicity are associated with downregulation of AQP4 and induction of the TRAF6 pathway.
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