Immunogenic Cell Death-related Signature Evaluates the Tumor Microenvironment and Predicts the Prognosis in Diffuse Large B-Cell Lymphoma.

Current literatures suggest a growing body of evidence highlighting the pivotal role of Immunogenic Cell Death (ICD) in multiple tumor types. Nevertheless, the potential and mechanisms of ICD in diffuse large B-cell lymphoma (DLBCL) remain inadequately studied. To address this gap, our current study aims to examine the impact of ICD on DLBCL and identify a corresponding gene signature in DLBC. Using the expression profiles of ICD-associated genes, the gene expression omnibus (GEO) samples were segregated into ICD-high and ICD-low subtypes utilizing non-negative matrix factorization clustering. Next, univariate and LASSO Cox regression analyses were employed to establish the ICD-related gene signature. Subsequently, the CIBERSORT tool, ssGSEA, and ESTIMATE algorithm were utilized to examine the association between the signature and tumor immune microenvironment of DLBC. Finally, the oncoPredict algorithm was implemented to evaluate the drug sensitivity prediction of DLBCL patients. These findings suggest that the immune microenvironment of the ICD-high group with a poor prognosis was significantly suppressed. An 8-gene ICD-related signature was identified and validated to prognosticate and evaluate the tumor immune microenvironment in DLBCL. Similarly, the high-risk group exhibited a worse prognosis compared to the low-risk group, and the immune function was considerably suppressed. Moreover, the results of oncoPredict algorithm indicated that patients in the high-risk group exhibited higher sensitivity to Cisplatin, Cytarabine, Epirubicin, Oxaliplatin, and Vincristine with low IC50. In conclusion, the present study provides novel insights into the role of ICD in DLBCL by identifying a new biomarker for the disease and may have implications for the development of immune-targeted therapies for the tumor.

Macroscopic laser pulling based on the Knudsen force in rarefied gas.

Optical pulling is an attractive concept due to the counterintuitive feature, the profound mechanism underneath and promising applications. In recent ten years, optical pulling of micro-nano objects have been fully demonstrated. However, optical pulling of a macroscopic object is challenging. Herein, laser pulling of a macroscopic object is presented in rarefied gas. The pulling force is originated from the Kundsen force when a gauss laser beam irradiates a macroscopic structure composed of the absorptive bulk cross-linked graphene material and a SiO2 layer. A torsional pendulum device qualitatively presents the laser pulling phenomenon. A gravity pendulum device was used to further measure the pulling force that is more than three orders of magnitudes larger than the radiation pressure. This work expands the scope of optical pulling from microscale to macroscale and provides an effective technique approach for macroscopic optical manipulations.

Massive laser pulling of graphene nanosheets in water.

Light manipulation of graphene-based materials attracts much attentions. As a new light manipulation concept, optical pulling develops rapidly in the past decade. However, optical pulling of graphene in liquid is rarely reported. In this work, laser pulling of graphene nanosheets (GN) in pure water by using common gauss beams is presented. This phenomenon holds for multiple incident laser wavelengths including 405 nm, 488 nm, 532 nm and 650 nm. A particle image velocimetry software PIVlab is adopted to analyze the velocity field information of GN. The laser pulling velocity of the GN is approximately ∼ 0.5 mm/s corresponding to ∼ 103 body length/s, which increases with an increase of the incident laser energy. This work presents a contactless mothed to massively pull microscale graphene materials in simple liquid, which supplies a potential manipulation technique for micro-nanofluidic devices and also provides a platform to investigate laser-graphene interaction in a simple liquid phase medium.

Characterizations for the photothermal effect of Rhodamine 6G using white-light interferometry and windowed Fourier transform.

Photothermal phenomenon is one of the natural responses in light-matter interactions in which the energy of the incident light is converted into heat, resulting in a temperature increase in the illuminated material. This effect has a direct influence on the refractive index of the material such that its change of spectral dependency with temperature can be exploited for different applications. However, it is also important to separate/identify the thermal effect from the optical/electronic resonance effect to expand potential applications of light-matter interactions. In this work, we demonstrate the use of a white-light interferometry approach combined with a windowed Fourier transform method and a consistency-checking peak-fitting method to obtain the refractive index of an Rh6G-ethanol dye solution with a sensitivity of about ∼10-6 (RIU) for the visible range. Moreover, we also perform both static and dynamic measurements to study the photothermal effect of the Rh6G solution under external excitation. Importantly, we separate the optical and thermal effects due to the external excitation and obtain very good agreement with the experimental results by modeling the relative refractive index of the Rh6G solution with an expression consisting of spectrally a Fano-like resonance term and a linear dependent thermal term. We find that the response due to the optical effect is about ∼0.2 × 10-3 of that due to the thermal effect in the low-light regime. Our approach to separating the optical and thermal effects could shed light on other fields for potential applications through precision measurements of the transmission phase or refractive index.

Cost-effectiveness analysis of adding durvalumab to chemotherapy as first-line treatment for advanced biliary tract cancer based on the TOPAZ-1 trial.

BACKGROUND: Durvalumab plus gemcitabine and cisplatin has a significant clinical benefit for advanced biliary tract cancer (BTC). However, the high price of durvalumab warrants an exploration of the economics. OBJECTIVE: To investigate the cost-effectiveness of adding durvalumab to gemcitabine and cisplatin compared with gemcitabine and cisplatin in first-line therapy of advanced BTC from the perspective of the Chinese healthcare system. METHODS: According to the TOPAZ-1 trial, a three-state Markov model was built by the TreeAge Pro 2022 software. The total costs and quality-adjusted life years (QALYs) were estimated, and the incremental cost-effectiveness ratio (ICER) was used as the evaluation index. The triple 2021 Chinese per capita gross domestic product (GDP) of $37,663.26/QALY was used as the willingness-to-pay (WTP) threshold. Outputs were analyzed for two scenarios with and without a durvalumab drug charity assistance policy. In the scenario analysis, the base-case model was run multiple times with different prices of durvalumab to determine the effect on the ICER. Moreover, the robustness of the model was tested through sensitivity analyses. RESULTS: Compared with chemotherapy alone, durvalumab plus chemotherapy resulted in an additional 0.12 QALY and an incremental cost of $18,555.19, the ICER was $159,644.70/QALY under the situation of charity assistance, and the ICER was $696,571.11/QALY without charity assistance, both exceeding the WTP threshold in China. The scenario analysis demonstrated that when the price of durvalumab fell by more than 94.2% to less than $0.33/mg, durvalumab plus chemotherapy will be more economical compared with chemotherapy alone under the situation of no charity assistance. One-way sensitivity analyses suggested that the cost of durvalumab had the greatest influence on the ICERs, and the probabilistic sensitivity analyses demonstrated that durvalumab plus chemotherapy was impossible to be cost-effective at the WTP threshold whether the charity assistance was available or not. CONCLUSIONS: Adding durvalumab to gemcitabine and cisplatin was not cost-effective for advanced BTC regardless of receiving and not receiving charitable assistance.

Internal nanocavity based high-resolution and stable structural colours fabricated by laser printing.

Bioinspired structural colors are attracting increasing attention in photonics, display, labeling and so forth. High-resolution and stable coloration is significant but is challenging to be fabricated in a facile and low-cost way. Herein, multilayer architecture containing an internal nanocavity as the structural color unit is obtained conveniently by direct nanosecond laser printing in atmosphere condition. Arbitrary colorful patterns with submicron accuracy can be realized only by a single step. And such structural colors induced by inner structures in the interlayer are antipollutive, antioxidative and easy to clean.

Hyaluronic Acid-Functionalized Hollow Mesoporous Silica Nanoparticles as pH-Sensitive Nanocarriers for Cancer Chemo-Photodynamic Therapy.

Hollow mesoporous silica nanoparticles (HMSNs) served as nanocarriers for transporting doxorubicin hydrochloride (DOX) and indocyanine green (ICG) and were incorporated into a pH-sensitive targeted drug delivery system (DDS). Boronate ester bonds were employed to link HMSNs and dopamine-modified hyaluronic acid (DA-HA), which acted as both the "gatekeeper" and targeting agents (HMSNs-B-HA). Well-dispersed HMSNs-B-HA with a diameter of about 170 nm was successfully constructed. The conclusion was drawn from the in vitro drug release experiment that ICG and DOX (ID) co-loaded nanoparticles (ID@HMSNs-B-HA) with high drug loading efficiency could sustain drug release under acidic conditions. More importantly, in vitro cell experiments perfectly showed that ID@HMSNs-B-HA could well inhibit murine mammary carcinoma (4T1) cells via chemotherapy combined with photodynamic therapy and accurately target 4 T1 cells. In summary, all test results sufficiently demonstrated that the prepared ID@HMSNs-B-HA was a promising nano-DDS for cancer photodynamic combined with chemotherapy.

Circular Phase-Dichroism of Chiral Metasurface Using Birefringent Interference.

Circular phase-dichroism (CPD) has been suggested for the characterization of chiral metasurfaces in supplementing the conventional circular dichroism (CD). Conventional CD probes the bulk properties while the CPD, reported recently in 2D chiral metasurfaces using an air-gap Fabry-Perot setup, is based on the surface properties. Here we propose and demonstrate a robust birefringent interference approach to obtain the CPD by replacing the air-gap with a uniaxial birefringent material in which interference is realized by the difference in the refractive indexes for the ordinary and extraordinary components of the material. We measure the transmission phases of metasurfaces fabricated on birefringent sapphire substrates and obtain clear CPDs for chiral metasurfaces but vanishing for achiral metasurfaces. Importantly, our approach can be applied to metasurfaces fabricated on nonbirefringent substrates by add-on birefringent materials. We confirm our results by a Jones matrix method using data obtained from full-wave simulations, and good agreements with experiments are obtained.

Quantitative measurement and mechanism analysis of the high-efficiency laser propulsion of a graphene sponge.

Laser propulsion of a graphene sponge shows tremendous potential in propellant-free flight, photoresponsive actuators and micro opto-electro mechanical systems. However, the mechanism is still in dispute and the propulsion force hasn't been accurately measured, seriously hindering its development. This work develops a quantitative method to measure the propulsion force. It is found that the characteristics of the force agree qualitatively with the Knudsen force due to laser-induced thermal nonequilibrium in rarefied gas, which might be another possible mechanism of laser propulsion of a graphene sponge. Also, this kind of laser propulsion is highly efficient, stable and sustainable.

Exceptional point-based plasmonic metasurfaces for vortex beam generation.

An exceptional point occurring in a tailor-made lossy optical system has been recently found to alter optical properties in counter-intuitive ways. In the context of tunable plasmonic devices, exceptional points can be useful as a driving mechanism to enhance tunability. Here, we experimentally demonstrate how a plasmonic exceptional point can be incorporated in metasurface Q-plates to have the generated vortex beam tuned through a change of structural parameter. We have observed an orbital rotation in the far-field by 45 degrees in crossing the exceptional point. We expect a new generation of tunable plasmonic devices in polarization control, beam structuring and holograms, which can take advantage of the huge sensitivity from exceptional points.

Effects of hypogonadism on brain development during adolescence in girls with Turner syndrome.

Gonadal steroids play an important role in brain development, particularly during puberty. Girls with Turner syndrome (TS), a genetic disorder characterized by the absence of all or part of the second X chromosome, mostly present a loss of ovarian function and estrogen deficiency, as well as neuroanatomical abnormalities. However, few studies have attempted to isolate the indirect effects of hormones from the direct genetic effects of X chromosome insufficiency. Brain structural (i.e., gray matter [GM] morphology and white matter [WM] connectivity) and functional phenotypes (i.e., resting-state functional measures) were investigated in 23 adolescent girls with TS using multimodal MRI to assess the role of hypogonadism in brain development in TS. Specifically, all girls with TS were divided into a hormonally subnormal group and an abnormal subgroup according to their serum follicle-stimulating hormone (FSH) levels, with the karyotypes approximately matched between the two groups. Statistical analyses revealed significant effects of the "group-by-age" interaction on GM volume around the left medial orbitofrontal cortex and WM diffusion parameters around the bilateral corticospinal tract, anterior thalamic radiation, left superior longitudinal fasciculus, and cingulum bundle, but no significant "group-by-age" or group differences were observed in resting-state functional measures. Based on these findings, estrogen deficiency has a nontrivial impact on the development of the brain structure during adolescence in girls with TS. Our present study provides novel insights into the mechanism by which hypogonadism influences brain development during adolescence in girls with TS, and highlights the important role of estrogen replacement therapy in treating TS.

Characterization of thermal bump due to surface plasmon resonance.

Surface plasmon resonance (SPR) has found wide applications in sensing down to molecular level due to its extreme sensitivity to change of dielectric properties. An unavoidable effect in SPR is surface deformation (thermal bump) due to local heating by incident laser light used in SPR. In addition, changes in the reflection phase from the metal film used in SPR could also contribute to the SPR signal, and thus proper handling of the SPR signal is very important in order to broaden the potential applications of SPR. Here we report a simple Fabry Perot (FP) interference technique for measuring, simultaneously, the thermal bump height as well as the reflection phase shift of gold film used in SPR. We find that the shift of the FP signal is dominated by the effect of the thermal bump while it is small for the effect of the reflection phase shift due to change of dielectric property of the metal. To support our experimental results, we have also performed model simulation for the SPR system and obtain good agreement with the experiment. As both amplitude and phase can be measured, our method could lead to better characterization of SPR and can also be applied to the study of active metasurfaces under external excitation.

Characterization of free-standing 1D photonic crystals using an effective medium approach.

Photonic crystals (PCs) are usually fabricated on bulk substrates which break the symmetry of the PC system for incidence from either side of the PCs. Here we report the fabrication of a free-standing 1D layered dielectric PC by using a two-beam holographic interference method. The free-standing PC exhibits distinct photonic bandgaps as well as Fabry-Perot oscillations in the photonic bands. Furthermore, we show that the PC can be modeled by an effective medium approach and obtain the reflection phase for the photonic bands of the PC. We have also performed full-wave simulations for the PC and obtained very good agreement with the experiment. The free-standing PC enables a better comparison between experiment and simulation, and importantly, it is flexible enabling new applications for PCs.

The Effects of the X Chromosome on Intrinsic Functional Connectivity in the Human Brain: Evidence from Turner Syndrome Patients.

Turner syndrome (TS), a disorder caused by the congenital absence of one of the 2 X chromosomes in female humans, provides a valuable human "knockout model" for studying the functions of the X chromosome. At present, it remains unknown whether and how the loss of the X chromosome influences intrinsic functional connectivity (FC), a fundamental phenotype of the human brain. To address this, we performed resting-state functional magnetic resonance imaging and specific cognitive assessments on 22 TS patients and 17 age-matched control girls. A novel data-driven approach was applied to identify the disrupted patterns of intrinsic FC in TS. The TS girls exhibited significantly reduced whole-brain FC strength within the bilateral postcentral gyrus/intraparietal sulcus, angular gyrus, and cuneus and the right cerebellum. Furthermore, a specific functional subnetwork was identified in which the intrinsic FC between nodes was mostly reduced in TS patients. Particularly, this subnetwork is composed of 3 functional modules, and the disruption of intrinsic FC within one of these modules was associated with the deficits of TS patients in math-related cognition. Taken together, these findings provide novel insight into how the X chromosome affects the human brain and cognition, and emphasize an important role of X-linked genes in intrinsic neural coupling.

Correction of numerical aperture effect on reflection phase measurement using a thick-gap Fabry-Perot etalon.

We propose a method for the measurement of the reflection phase using a thick-gap Fabry-Perot (FP) etalon interferometry technique with correction for the numerical aperture effect of the optical setup. The setup is first calibrated using a known sample by comparing the reflectance from a two-beam interference model for the FP etalon with experimental data. We then apply the correction to a sample of interest and obtain the reflection phase of the sample. Our method can be used to measure the reflection phase of a small sample and could lead to practical applications in optical characterization of metamaterials. Moreover, the principle of our approach could be generalized to other systems in the correction of numerical aperture effect due to microscopic objectives.

Identification of candidate genes involved in wax deposition in Poa pratensis by RNA-seq.

BACKGROUND: The cuticular wax plays important roles in plant resistance to various biotic and abiotic stresses. Understanding the synthesis and secretion of cuticular waxes is necessary in utilizing cuticular waxes to improve crop productivity and plant ecological adaptation. Due to the lack of genomic resources, little genetic research on cuticular wax deposition has been focused on Poa pratensis, a perennial forage and turf grass species that is widely distributed under various habitats. In this study, we performed de novo transcriptome sequencing to explore differentially expressed genes between the leaf non-elongation zone (NEZm) and the emerged blade zone (EBZ) and to identify genes related to cuticular wax deposition. RESULTS: A total of 77,707,414 high quality reads were obtained from llumina HiSeq 2500 platform, which were then assembled into 106,766 unigenes. Among them, 6019 unigenes showed significant differences in expression between NEZm and EBZ. In our assembled sequences, 3087 SSRs molecular markers were discovered. All the unigenes were searched against the NR, Swissprot, GO, COG, and KEGG databases using BLAST program for functional annotation. From 3156 unigenes with more expression in NEZm compared to EBZ, a number of unigenes involved in very long chain fatty acids (VLCFAs) and cuticular wax biosynthesis, transportation and regulation were identified. Several unigenes related to defense response and epidermal patterning were also found. Twelve putative genes involved in VLCFAs and cuticular wax biosynthesis were further analyzed for their expressions using qRT-PCR. CONCLUSIONS: The transcriptome of P. pratensis leaf was deep sequenced, de novo assembled and annotated, and the candidate genes potentially involved in VLCFAs and cuticular wax biosynthesis, secretion and regulation in P. pratensis were identified. This provides fundamental genetic resources in improving plant adaptation to abiotic and biotic stresses.

The Effects of X Chromosome Loss on Neuroanatomical and Cognitive Phenotypes During Adolescence: a Multi-modal Structural MRI and Diffusion Tensor Imaging Study.

The absence of all or part of one X chromosome in female humans causes Turner's syndrome (TS), providing a unique "knockout model" to investigate the role of the X chromosome in neuroanatomy and cognition. Previous studies have demonstrated TS-associated brain differences; however, it remains largely unknown 1) how the brain structures are affected by the type of X chromosome loss and 2) how X chromosome loss influences the brain-cognition relationship. Here, we addressed these by investigating gray matter morphology and white matter connectivity using a multimodal MRI dataset from 34 adolescent TS patients (13 mosaic and 21 nonmosaic) and 21 controls. Intriguingly, the 2 TS groups exhibited significant differences in surface area in the right angular gyrus and in white matter integrity of the left tapetum of corpus callosum; these data support a link between these brain phenotypes and the type of X chromosome loss in TS. We further showed that the X chromosome modulates specific brain-cognition relationships: thickness and surface area in multiple cortical regions are positively correlated with working-memory performance in controls but negatively in TS. These findings provide novel insights into the X chromosome effect on neuroanatomical and cognitive phenotypes and highlight the role of genetic factors in brain-cognition relationships.

Measurement of reflection phase using thick-gap Fabry-Perot etalon.

We report measurement of the reflection phase of a dielectric (glass)/titanium (Ti) surface in the visible wavelength using a thick-gap Fabry-Perot (FP) interferometry technique. Using a two-beam interference model for the reflection peaks and troughs of the FP etalon, we obtain the air-gap spacing of the etalon and, more importantly, the reflection phase of the etalon substrate. We find systematic dependence of the as-measured reflection phase on the air-gap spacing due to the numerical aperture effect of the measuring objective. However, the relative reflection phase of Ti with respect to glass is independent of the air-gap spacing. As a demonstration of our approach in the optical characterization of small metamaterial samples, we also measure the reflection phase of a micron-sized 2D Au sawtooth nanoarray. The experiment is in good agreement with the model simulation.

[Application Progress of Holographic Lithgraphy in Fabrication of Micro-Nano Photonic Structures].

Micro-nano photonic structures are developing vigorously based on the progress of photonics, semiconductor physics and microfabrication technology. A series of results are achieved in structure characterization, theory, and fabrication of them. Most high quality photonic structures are man-made ones; however, there are still some challenges in fabricating artificial large-area and high-quality photon materials. With the advantages of photonic structure processing technology, holographic lithography, a low-cost, time-saving and high-efficiency microfabrication method, performs superior application potentials in making metamaterials as well as photonic crystal templates. In this article, we introduced the principles of holographic lithography and described the applications in fabricating various micro-nano photonic structures, such as three dimensional face-center-cubic, wood-pile, diamond-like photonic crystals, as well as quasi-crystalline structure, chiral metamaterials and periodic defect-mode structures. Moreover, the applications of some structures in solar cell and optical fiber sensing are discussed. The success of fabricating micro-nano photonic structures by holographic lithography would pave the way for more applications of these structures in wide fields.

Exonuclease I aided enzyme-linked aptamer assay for small-molecule detection.

A novel enzyme-linked aptamer assay (ELAA) with the aid of Exonuclease I (Exo I) for colorimetric detection of small molecules was developed. The fluorescein isothiocyanate (FITC)-labeled aptamer was integrated into a double-stranded DNA (dsDNA). In the presence of target, the binding of aptamer with target protected the aptamer from Exo I degradation, which resulted in the FITC tag remaining on the aptamer. Then, the anti-FITC-HRP conjugate was used to produce an optically observable signal. By monitoring the color change, we were able to detect two model molecules, ATP and L-argininamide, with high selectivity and high sensitivity even in the serum matrix. It is expected to be a simple and general ELAA method with wide applicability.