Ovarian cancer mutational processes drive site-specific immune evasion.

High-grade serous ovarian cancer (HGSOC) is an archetypal cancer of genomic instability1-4 patterned by distinct mutational processes5,6, tumour heterogeneity7-9 and intraperitoneal spread7,8,10. Immunotherapies have had limited efficacy in HGSOC11-13, highlighting an unmet need to assess how mutational processes and the anatomical sites of tumour foci determine the immunological states of the tumour microenvironment. Here we carried out an integrative analysis of whole-genome sequencing, single-cell RNA sequencing, digital histopathology and multiplexed immunofluorescence of 160 tumour sites from 42 treatment-naive patients with HGSOC. Homologous recombination-deficient HRD-Dup (BRCA1 mutant-like) and HRD-Del (BRCA2 mutant-like) tumours harboured inflammatory signalling and ongoing immunoediting, reflected in loss of HLA diversity and tumour infiltration with highly differentiated dysfunctional CD8+ T cells. By contrast, foldback-inversion-bearing tumours exhibited elevated immunosuppressive TGFß signalling and immune exclusion, with predominantly naive/stem-like and memory T cells. Phenotypic state associations were specific to anatomical sites, highlighting compositional, topological and functional differences between adnexal tumours and distal peritoneal foci. Our findings implicate anatomical sites and mutational processes as determinants of evolutionary phenotypic divergence and immune resistance mechanisms in HGSOC. Our study provides a multi-omic cellular phenotype data substrate from which to develop and interpret future personalized immunotherapeutic approaches and early detection research.

Single-cell genomic variation induced by mutational processes in cancer.

How cell-to-cell copy number alterations that underpin genomic instability1 in human cancers drive genomic and phenotypic variation, and consequently the evolution of cancer2, remains understudied. Here, by applying scaled single-cell whole-genome sequencing3 to wild-type, TP53-deficient and TP53-deficient;BRCA1-deficient or TP53-deficient;BRCA2-deficient mammary epithelial cells (13,818 genomes), and to primary triple-negative breast cancer (TNBC) and high-grade serous ovarian cancer (HGSC) cells (22,057 genomes), we identify three distinct 'foreground' mutational patterns that are defined by cell-to-cell structural variation. Cell- and clone-specific high-level amplifications, parallel haplotype-specific copy number alterations and copy number segment length variation (serrate structural variations) had measurable phenotypic and evolutionary consequences. In TNBC and HGSC, clone-specific high-level amplifications in known oncogenes were highly prevalent in tumours bearing fold-back inversions, relative to tumours with homologous recombination deficiency, and were associated with increased clone-to-clone phenotypic variation. Parallel haplotype-specific alterations were also commonly observed, leading to phylogenetic evolutionary diversity and clone-specific mono-allelic expression. Serrate variants were increased in tumours with fold-back inversions and were highly correlated with increased genomic diversity of cellular populations. Together, our findings show that cell-to-cell structural variation contributes to the origins of phenotypic and evolutionary diversity in TNBC and HGSC, and provide insight into the genomic and mutational states of individual cancer cells.

Cardiac computed tomography angiography for assessment of endothelial insufficiency of left atrial appendage disc-like occluder.

INTRODUCTION: This study was performed to explore the diagnostic value of cardiac computed tomography angiography (CCTA) for endothelial insufficiency (EIS) of a left atrial appendage (LAA) disc-like occluder. METHODS: Fifty-nine patients with nonvalvular atrial fibrillation who underwent placement of an LAA disc-like occluder (LAmbre; Lifetech Scientific) in our hospital were retrospectively analyzed. Patients who were found to have contrast agent entering the LAA at the 3-month postoperative CCTA examination underwent Hounsfield unit (HU) measurement of the LAA and construction of a three-dimensional (3D) model of the device for preliminary discernment between peri-device leakage (PDL) and EIS. These patients were then further examined by transesophageal echocardiography (TEE) to check for concordance with the computed tomography (CT) findings. According to the CT and TEE results, all patients were divided into the PDL group, total endothelialization group, and EIS group. The endothelial conditions and other implantation-related results were also tracked at the 6-month follow-up. RESULTS: All 59 patients underwent successful implantation of the LAmbre LAA closure device with no severe adverse events during the procedure. Thirty-five patients were found to have contrast agent entering the LAA at the 3-month postoperative CCTA follow-up. Based on the CT HU measurement and the 3D construction analysis results, these 35 patients were divided into the PDL group (19 patients) and the EIS group (16 patients). In the PDL group, the contrast agent infiltrated from the shoulder along the periphery of the occluder on two-dimensional (2D) CT images, and the 3D model showed a gap between the LAA and the device cover. However, the CCTA images of the other 16 patients in the EIS group showed that the contrast agent in the occluder on the 2D CTA images and 3D construction model confirmed the absence of a gap between the LAA and the device cover. TEE confirmed all of the CT results. The 6-month follow-up results showed that 14 of 19 patients in the EIS group achieved total endothelialization, whereas this number in the PDL group was only five of 19 patients. CONCLUSION: CCTA can replace TEE for examination of the endothelialization status, and patients with EIS have a higher chance of endothelialization than patients with PDL.

Effects of Laughter Therapy on Improving Negative Emotions Associated with Cancer: A Systematic Review and Meta-Analysis.

INTRODUCTION: With aging and growth of the population, the risk of cancer incidence and mortality is rapidly increasing. However, psychosocial treatment has been seriously neglected in many healthcare settings. Laughter therapy is a therapeutic program to improve emotional wellbeing and health which has been applied as a complementary treatment. We aim to explore effects of laughter therapy for patients with cancer on their negative emotions such as depression, anxiety, stress, pain, and fatigue. METHODS: We searched the Cochrane Library, Embase, PubMed, Scopus, Web of Science, WANFANG data, Weipu (VIP), Chinese National Knowledge Infrastructure (CNKI) and independently rated the risk of bias in every article using the Cochrane Collaboration's Risk of Bias Assessment Tool. Review Manager and STATA software were used to pool the individually included studies. RESULTS: Seven studies were found eligible to be included in the present review. Overall, study quality was relatively high. Our findings suggest that laughter therapy might have a positive effect on improving emotional response in cancer patients. Arguably, laughter therapy, whether humor or laughter, has a positive effect on anxiety, stress, pain feeling, fatigue, and depression in cancer patients. CONCLUSIONS: Laughter therapy is a convenient, multi-modality, flexible-duration therapy to improve negative emotions in cancer patients, regardless of their gender, age, and type of cancer.

Balancing agricultural production and environmental sustainability: Based on Economic Analysis From North China Plain.

The escalating trend of greenhouse gas emissions presents a dual threat to both food security and the exacerbation of global warming. Addressing this pressing issue demands concerted efforts on local and global scales to champion sustainable food production and foster environmental benefits. In 2015, a pivotal field experiment was conducted in the North China Plain, aiming to delineate the intricate balance between agricultural productivity and environmental stewardship. This study comprised eight meticulously designed treatments, incorporating two key components: the evaluation of economic and environmental parameters encompassing carbon footprint, energy consumption, and the carbon sustainability index. Notably, while the carbon sustainability index exhibited improvement, it also revealed a 9.4% increase in emissions compared to the baseline, underscoring the nuanced trade-offs involved. The findings underscored the efficacy of no-tillage (NT) practices coupled with soybean-based crop rotation, mitigating yield reduction compared to conventional tillage (RT). However, the optimal yield was observed in the RT-MW treatment, amalgamating conventional tillage with minimum tillage practices. Moreover, despite the higher cost associated with soybeans relative to milled wheat, their cultivation yielded a notable increase in net income. These compelling results advocate for the adoption of conservation agriculture as a means to optimize the delicate equilibrium between environmental preservation and economic prosperity. Furthermore, the study underscores the imperative for further research endeavors aimed at devising highly productive agricultural systems that seamlessly integrate environmental sustainability with economic viability, echoing the crucial insights gleaned from analogous contexts.

Stent-to-vessel diameter ratio is associated with in-stent stenosis after flow-diversion treatment of intracranial aneurysms.

BACKGROUND AND PURPOSE: Flow-diversion treatment for intracranial aneurysms has been associated with the development of in-stent stenosis (ISS) for unclear reasons. We assess whether the size of the stent relative to that of the vessel (the stent-to-vessel diameter ratio, or SVR) may be predictive of the development of ISS after treatment with flow diverters. METHODS: We retrospectively reviewed patients with unruptured intracranial aneurysms who underwent flow-diversion treatment using either the Pipeline or Tubridge embolization device from September 2018 to September 2022. The relationship between SVR and ISS was analyzed. Multiple logistic regression models were used to determine the significant predictors. RESULTS: A total of 458 patients with 481 aneurysms were included. In a mean angiographic follow-up of 10.73 ± 3.97 months, ISS was detected in 68 cases (14.1 %). After adjusting for candidate variables, a higher distal SVR (DSVR) was associated with an increased risk of ISS (adjusted odds ratio [aOR] = 3.420, 95 % confidence interval [CI] = 1.182 - 9.889, p = 0.023). We conducted a subgroup analysis of the two different flow diverters to assess the effects of their individual characteristics. Our results showed a significant association between the DSVR and the incidence of ISS in both the Pipeline (aOR = 4.033, 95 % CI = 1.156-14.072, p = 0.029) and Tubridge groups (aOR = 11.981, 95 % CI=1.005-142.774, p = 0.049). CONCLUSION: A higher DSVR was associated with an increased risk of ISS. This may help neurointerventionalists select an appropriate stent size when conducting flow-diversion treatment for intracranial aneurysms.

Disparities and mechanisms of carbon and nitrogen conversion during food waste composting with different bulking agents.

The low C/N ratio, high moisture content, and low porosity of food waste require the addition of bulking agents for adjustment during the composting process. However, the effect and mechanism of different bulking agents on the reduction of carbon and nitrogen losses are unclear. Therefore, this study conducted experiments to evaluate and clarify the differences in carbon and nitrogen transformation between sawdust, rice husk and wheat bran in food waste composting. The results showed that the addition of bulking agents promoted the conversion of carbon and nitrogen into total organic carbon (TOC) and total organic nitrogen (TON) rather than CO2 and NH3. The carbon and nitrogen losses were reduced by 16.00-25.71% and 11.56-29.54%, respectively. Notably, the Sawdust group exhibited the highest carbon retention, whereas the Wheat_bran group demonstrated superior nitrogen retention. The succession of bacterial communities showed that sawdust enhanced the cellulolysis and xylanolysis functions while wheat bran promoted nitrogen fixation. Correlation analysis was further employed to speculate on potential interactions among carbon and nitrogen components. The incorporation of sawdust and rice husk improved humification partly due to the addition of lignocellulose and the accumulation of total dissolved nitrogen (DTN) in the substrate, respectively. In the process of ammonia assimilation, the addition of wheat bran promoted the accumulation of dissolved organic carbon (DOC), contributing to the synthesis of TON to a degree. These findings offer cost-effective strategies for conserving carbon and nitrogen from loss in food waste composting by selecting suitable bulking agents, ultimately producing high-quality fertilizer.

Uncovering the involvement of DoDELLA1-interacting proteins in development by characterizing the DoDELLA gene family in Dendrobium officinale.

BACKGROUND: Gibberellins (GAs) are widely involved in plant growth and development. DELLA proteins are key regulators of plant development and a negative regulatory factor of GA. Dendrobium officinale is a valuable traditional Chinese medicine, but little is known about D. officinale DELLA proteins. Assessing the function of D. officinale DELLA proteins would provide an understanding of their roles in this orchid's development. RESULTS: In this study, the D. officinale DELLA gene family was identified. The function of DoDELLA1 was analyzed in detail. qRT-PCR analysis showed that the expression levels of all DoDELLA genes were significantly up-regulated in multiple shoots and GA3-treated leaves. DoDELLA1 and DoDELLA3 were significantly up-regulated in response to salt stress but were significantly down-regulated under drought stress. DoDELLA1 was localized in the nucleus. A strong interaction was observed between DoDELLA1 and DoMYB39 or DoMYB308, but a weak interaction with DoWAT1. CONCLUSIONS: In D. officinale, a developmental regulatory network involves a close link between DELLA and other key proteins in this orchid's life cycle. DELLA plays a crucial role in D. officinale development.

Fabrication of a flexible stretchable hydrogel-based antenna using a femtosecond laser for miniaturization.

We demonstrated a new method of fabricating a stretchable antenna by injecting liquid metal (LM) into a femtosecond-laser-ablated embedded hydrogel microchannel, and realized miniaturization of a stretchable dipole antenna based on hydrogel substrate. Firstly, symmetrical microchannels with two equal and linear branches were formed by a femtosecond laser in the middle of a hydrogel substrate, and then were filled with LM by use of a syringe needle. Using this method, a stretchable LM-dipole antenna with each dimension of 24 mm × 0.6 mm × 0.2 mm separated by a 2-mm gap, was formed in the middle of a 70 mm × 12 mm × 7 mm hydrogel slab. Since the polyacrylamide (PAAm) hydrogel contained ∼ 95 wt % deionized water with a high permittivity of 79 in the 0.5 GHz - 1.5 GHz range, the hydrogel used to prepare the flexible antenna can be considered as distilled water boxes. Experiments and simulations showed that a 5-cm-long LM-dipole embedded in hydrogel resonated at approximately 927.5 MHz with an S11 value of about - 12.6 dB and omnidirectional radiation direction. Benefiting from the high permittivity of the hydrogel, the dipole length was downsized by about half compared with conventional polymer substrates at the same resonant frequency. By varying the applied strain from 0 to 48%, the resonant frequency of the hydrogel/LM dipole antenna can be tuned from 770.3 MHz to 927.0 MHz. This method provides a simple and scalable technique for the design and preparation of LM-pattern microstructures in hydrogels, and has potential applications in hydrogel-based soft electronic device.

FSS-inspired transmitarray for dynamic beamforming and gain control.

In this paper, we propose a concept of combining the methodology of phase coding modulation with frequency selective surface (FSS) inspired transmitarray (TA) to achieve the ability of dynamical beamforming and gain control in microwave regime. The TA element composed of five-layer stacked bandpass FSS units separated by small air gaps. Each FSS unit comprises a metallic octagon slot with a pair of varactor diodes loaded along the polarization direction. The elaborately designed feeding network makes it possible to modulate the transmission phase of each element. Different phase coding sequences are performed through changing the bias voltage configurations, then the radiation far field of the proposed TA can be tailored in real time. Dynamic beamforming and gain control under different encoding arrangements are exhibited to demonstrate the physical mechanism of electromagnetic (EM) manipulation with this method. The proposed strategy is verified by numerical simulations and experiment. This work adds new function for TA and can reshape its application prospect, such as reconfigurable beam emitter for multilink data transmission, long range point-to-point (PTP) wireless links and radio frequency energy harvesting.

Adsorption-reduction coupling mechanism and reductive species during efficient florfenicol removal by modified biochar supported sulfidized nanoscale zerovalent iron.

Sulfidized nanoscale zerovalent iron (S-nZVI) was a promising material for degrading halogenated contaminants, but the easy aggregation limits its application for in-situ groundwater remediation. Hence, S-nZVI was decorated onto modified biochar (mBC) to obtain better dispersity and reactivity with florfenicol (FF), a widely used antibiotic. Uniform dispersion of S-nZVI particles were achieved on the mBC with plentiful oxygen-containing functional groups and negative surface charge. Thus, the removal rate of FF by S-nZVI@mBC was 2.5 and 3.1 times higher than that by S-nZVI and S-nZVI@BC, respectively. Adsorption and dechlorination of FF showed synergistic effect under appropriate mBC addition (e.g., C/Fe mass ratio = 1:3, 1:1), probably due to the enrichment of FF facilitates its reduction. In contrast, the contact between FF and S-nZVI could be hindered under more mBC addition, significantly decrease the reduction rate of FF and the reduction capacity of per unit Fe0. In addition, sulfur dose altered the surface species of surface Fe and S, and removal rates of FF correlated well with surface reductive species, i.e., FeS (r = 0.90, p < 0.05) and Fe0 (r = 0.98, p < 0.01). These mechanistic insights indicate the importance of rational design for biochar supported S-nZVI, which can lead to more efficient FF degradation.

Abnormal histidine metabolism promotes macrophage lipid accumulation under Ox-LDL condition.

Distinct macrophage populations exert highly heterogeneity and perform various functions, among which, a crucial function of lipid metabolism is highlighted. However, the role of histidine metabolism disorder in macrophage lipid metabolism remains elusive. Addressed this question, we sorted and cultured the bone marrow-derived macrophages (BMDMs) of histidine decarboxylase (Hdc) knockout (Hdc-/-) mice with an in vitro oxidized low-density lipoprotein (ox-LDL) model, and detected the intracellular lipids by Oil Red O staining as well as lipid probe staining. Astemizole, a canonical and long-acting histamine H1 receptor (H1R) antagonist, was applied to elucidate the impact of antagonizing the H1R-dependent signaling pathway on macrophage lipid metabolism. Subsequently, the differential expressed genes were screened and analyzed in the bone marrow-derived CD11b+ immature myeloid cells of Hdc-/- and Hdc+/+ mice with a high fat diet by the microarray study. The expression levels of cholesterol metabolism-related genes were examined by qRT-PCR to explore underlying mechanisms. Lastly, we used a high-sensitivity histidine probe to detect the intracellular histidine in the BMDMs after oxidative stress. The results revealed that histidine metabolism disorder and histamine deficiency aggravated lipid accumulation in the ox-LDL-treated BMDMs. The expression level of H1R gene in the BMDMs was down-regulated after ox-LDL stimulation. The disruption of the H1R-dependent signaling pathway by astemizole further exacerbated ox-LDL-induced lipid deposition in the BMDMs partly by up-regulating scavenger receptor class A (SR-A) for lipid intake, down-regulating neutral cholesteryl ester hydrolase (nCEH) for cholesterol esterification and down-regulating ATP-binding cassette transporters A1 (ABCA1) and ABCG1 for reverse cholesterol transport. The intracellular histidine increased under ox-LDL condition, which was further increased by Hdc knockout. Collectively, these results partially reveal the relationship between histidine metabolism and lipid metabolism in the BMDMs and offer a novel strategy for lipid metabolism disorder-associated diseases.

GdClean: removal of Gadolinium contamination in mass cytometry data.

MOTIVATION: Mass cytometry (Cytometry by Time-Of-Flight, CyTOF) is a single-cell technology that is able to quantify multiplex biomarker expressions and is commonly used in basic life science and translational research. However, the widely used Gadolinium (Gd)-based contrast agents (GBCAs) in magnetic resonance imaging (MRI) scanning in clinical practice can lead to signal contamination on the Gd channels in the CyTOF analysis. This Gd contamination greatly affects the characterization of the real signal from Gd-isotope-conjugated antibodies, severely impairing the CyTOF data quality and ruining downstream single-cell data interpretation. RESULTS: We first in-depth characterized the signals of Gd isotopes from a control sample that was not stained with Gd-labeled antibodies but was contaminated by Gd isotopes from GBCAs, and revealed the collinear intensity relationship across Gd contamination signals. We also found that the intensity ratios of detected Gd contamination signals to the reference Gd signal were highly correlated with the natural abundance ratios of corresponding Gd isotopes. We then developed a computational method named by GdClean to remove the Gd contamination signal at the single-cell level in the CyTOF data. We further demonstrated that the GdClean effectively cleaned up the Gd contamination signal while preserving the real Gd-labeled antibodies signal in Gd channels. All of these shed lights on the promising applications of the GdClean method in preprocessing CyTOF datasets for revealing the true single-cell information. AVAILABILITY AND IMPLEMENTATION: The R package GdClean is available on GitHub at https://github.com/JunweiLiu0208/GdClean. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

RasI/R Quorum Sensing System Controls the Virulence of Ralstonia solanacearum Strain EP1.

Quorum sensing (QS) is a widely conserved bacterial regulatory mechanism that relies on production and perception of autoinducing chemical signals to coordinate diverse cooperative activities, such as virulence, exoenzyme secretion, and biofilm formation. In Ralstonia solanacearum, a phytopathogen causing severe bacterial wilt diseases in many plant species, previous studies identified the PhcBSR QS system, which plays a key role in regulation of its physiology and virulence. In this study, we found that R. solanacearum strain EP1 contains the genes encoding uncharacterized LuxI/LuxR (LuxI/R) QS homologues (RasI/RasR [designated RasI/R here]). To determine the roles of the RasI/R system in strain EP1, we constructed a specific reporter for the signals catalyzed by RasI. Chromatography separation and structural analysis showed that RasI synthesized primarily N-(3-hydroxydodecanoyl)-homoserine lactone (3-OH-C12-HSL). In addition, we showed that the transcriptional expression of rasI is regulated by RasR in response to 3-OH-C12-HSL. Phenotype analysis unveiled that the RasI/R system plays a critical role in modulation of cellulase production, motility, biofilm formation, oxidative stress response, and virulence of R. solanacearum EP1. We then further characterized this system by determining the RasI/R regulon using transcriptome sequencing (RNA-seq) analysis, which showed that this newly identified QS system regulates the transcriptional expression of over 154 genes associated with bacterial physiology and pathogenic properties. Taken together, the findings from this study present an essential new QS system in regulation of R. solanacearum physiology and virulence and provide new insight into the complicated regulatory mechanisms and networks in this important plant pathogen. IMPORTANCE Quorum sensing (QS) is a key regulator of virulence factors in many plant-pathogenic bacteria. Previous studies unveiled two QS systems (i.e., PhcBSR and SolI/R) in several R. solanacearum strains. The PhcBSR QS system is known for its key roles in regulation of bacterial virulence, and the LuxI/LuxR (SolI/R) QS system appears dispensable for pathogenicity in a number of R. solanacearum strains. In this study, a new functional QS system (i.e., RasI/R) was identified and characterized in R. solanacearum strain EP1 isolated from infected eggplants. Phenotype analyses showed that the RasI/R system plays an important role in regulation of a range of biological activities associated with bacterial virulence. This QS system produces and responds to the QS signal 3-OH-C12-HSL and hence regulates critical bacterial abilities in survival and infection. To date, multiple QS signaling circuits in R. solanacearum strains are still not well understood. Our findings from this study provide new insight into the complicated QS regulatory networks that govern the physiology and virulence of R. solanacearum and present a valid target and clues for the control and prevention of bacterial wilt diseases.

Dynamic radiation steering with transmission-type coding metasurface.

In this paper, we integrate continuous transmission amplitude modulation and phase coding into a metasurface, and dynamic transmitted electromagnetic field manipulation is realized in microwave regime. The active metasurface is obtained by placing a PIN diodes loaded amplitude modulation metasurface on a binary phase coding metasurface whose coding matrix is optimized by genetic algorithm. Changing the bias voltage applied on the diodes, the transmission amplitude of the phase coding units covered by amplitude modulation units can be tuned continuously while other coding units are not affected, leading to the fact that the transmitted field pattern of the metasurface varies from strongly directional transmission to diffusion-like radiation. By this means, two degrees of freedom of dynamic amplitude modulation and predesigned phase coding are achieved to control the electromagnetic waves. Additionally, a bias network is designed to ensure the polarization-stability of the metasurface. The proposed concept is predicted by analytical model, and verified by numerical simulations and experiment. This design with low profile and diverse functionalities can yield potential applications ranging from radio frequency energy harvesting to wireless communication systems.

Molecular dynamics study of Cr doping on the crystal structure and surficial/interfacial properties of 2H-MoS2.

Molecular doping has proved to be an efficient technique to improve the properties of pristine materials. A better understanding of it is quite necessary. For the first time, the force field parameters of the transition metal chromium (Cr) doped in 2H-MoS2 in molecular dynamics (MD) were developed. Compared with the DFT calculation results, the error in the stable-state lattice parameters is less than 1%. The optimized force field parameters were used for the MD simulation of different amounts of Cr substitution doping in 2H-MoS2. This study found that the Cr doping at different sites will have a significant impact on the stability of the bulk 2H-MoS2. With increasing doping amount, the water contact angle increases from 69.2° ± 2° to 78.5° ± 0.4°, and the hydrophobic performance is obviously improved. Finally, we also found that the adsorption energy of Cr-MoS2 decreased with increasing Cr doping content, indicating that bulk MoS2 is easier to separate to form single- or fewer-layer 2H-MoS2 in the case of higher doping content. Comparison between the simulated adsorption energies of typical solvents on the 2H-MoS2 surface shows that methanol (CH3OH) and water (H2O) can separate bulk 2H-MoS2, which matched with the experimental results. By using high-precision force field parameters, molecular dynamics were performed to study the surface/interface characteristics of Cr-doped 2H-MoS2, and provided an effective and detailed description for future experimental design.

Metal-Chelatable Porphyrinic Frameworks for Single-Cell Multiplexing with Mass Cytometry.

Single-cell multiplexing is key to exploration of the heterogeneous cell populations in biological systems. Although the state-of-the-art mass cytometry (CyTOF) possesses high resolution and multiple dimensions, the lack of suitable marker materials prohibits fully exploiting the available CyTOF detection channels. Here we report a new design strategy for CyTOF markers using functionalized mesoporous porphyrinic frameworks (MPFs) as scaffolds for chelating metals that have been unachievable by conventional approaches. We developed surface modification for stably dispersing the MPF nanoparticles (<40 nm) during the metalation and antibody conjugation processes. Our markers exhibit higher sensitivity and comparable specificity compared with a polymer-based commercial benchmark. Compatibility with commercial markers during co-staining was also confirmed. Furthermore, our markers show promising performance for immunophenotyping and potential implementation in CyTOF systems.

A Randomized Phase II Trial of Adjuvant Hepatic Arterial Infusion and Systemic Therapy With or Without Panitumumab After Hepatic Resection of KRAS Wild-type Colorectal Cancer.

OBJECTIVE/BACKGROUND: The purpose was to determine whether adding Pmab versus no Pmab to an adjuvant regimen of hepatic arterial infusion (HAI) of floxuridine (FUDR) plus systemic (SYS) leucovorin, fluorouracil, and irinotecan (FOLFIRI) improves 15-month recurrence-free survival for patients with RAS wild-type colorectal cancer. Secondary endpoints included overall survival, toxicity, and influence of predictive biomarkers. METHODS: This phase II trial randomized patients with KRAS wild-type resected colorectal liver metastases to adjuvant HAI FUDR + SYS FOLFIRI +/- Pmab (NCT01312857). Patients were stratified by clinical risk score and previous chemotherapy. Based on an exact binomial design, if one arm had ≥24 patients alive and disease-free at 15 months that regimen was considered promising for further investigation. RESULTS: Seventy-five patients were randomized. Patient characteristics and toxicity were not different in the 2 arms, except for rash in +Pmab arm. Grade 3/4 elevation in bilirubin or alkaline phosphatase did not differ in the 2 arms. Twenty-five (69%; 95% CI, 53-82) patients in the Pmab arm versus 18 (47%; 95% CI, 32-63) patients in the arm without Pmab were alive and recurrence-free at 15 months. Only the Pmab arm met the decision rule, while the other arm did not. After median follow-up of 56.6 months, 3-year recurrence-free survival was 57% (95% CI, 43-76) and 42% (95% CI, 29-61), and 3-year overall survival was 97% (95% CI, 90-99) and 91% (95% CI, 83-99), +/- Pmab, respectively. CONCLUSIONS: The addition of Pmab to HAI FUDR + SYS FOLFIRI showed promising activity without increased biliary toxicity and should be further investigated in a larger trial.

Metamaterial-inspired optically transparent active dual-band frequency selective surface with independent wideband tunability.

This paper presents an optically transparent active bandstop frequency selective surface (FSS) with wideband tunability of two resonance frequencies using the concept of miniaturized element FSS (MEFSS). The proposed design consists of metallic square loop arrays on a new optically transparent substrate as the top layer, a glass interlayer, and periodic patterns of cross dipoles on the substrate as the bottom layer. Two kinds of resonant elements loaded with varactors and the designed bias networks achieve two independent tunable stopbands. The proposed FSS has two large tuning ranges, one is from 1.20 GHz to 2.63 GHz and another is from 2.0 GHz to 5.9 GHz (75% and 99% with respect to the center frequency, respectively). The wideband dual-tuning mechanism is theoretically analyzed and demonstrated by deriving its equivalent circuit (EC) model. The experiment results exhibit reasonable agreement with the numerical simulation responses. This proposed design, with low profile, angular stability, polarization insensitivity, optical transparency, and wideband dual-tunability can play an important role in manipulating electromagnetic wave propagation for manifold applications.

Efficacy of web-based self-management interventions for depressive symptoms: a meta-analysis of randomized controlled trials.

BACKGROUND: The incidence of depression is increasing worldwide. Depression can lead to poor physical health and even suicide. However, in high-income countries, only about 50% of the people with depression receive appropriate therapy, and the detection rate of depression in low- and middle-income countries is relatively lower. Web-based self-management enables remote treatment and solves the problem of insufficient psychological treatment resources. Many past studies have evaluated the effectiveness of web-based self-management of depression, but there has been no synthesis of evidence. Therefore, this study conducted a meta-analysis of the effectiveness of web-based self-management for depressive symptoms. METHOD: Six electronic databases (Cochrane Central Register of Controlled Trials, PubMed, Web of Science, Embase, CINAHL, and PsycINFO) were searched in September 2020. All literature referring to the effects of web-based self-management on depression were shortlisted by performing the medical subject headings (MeSH) search combined with a text word search. RESULTS: A total of 18 eligible randomized controlled trials were identified, and the results from 3055 participants were consolidated. The web-based self-management group exhibited a greater reduction in depressive symptoms than the control group (g = - 0.46; 95% CI: 0.62,0.30), and there was no evidence of publication bias. Subgroup analysis revealed that patients with moderate-to-severe depression benefited from web-based self-management interventions. In terms of interventions, those based on cognitive behavioral therapy (CBT) were highly effective. We noted that the longer the intervention time, the better was the improvement in the status of depression. Furthermore, it was established that participants who communicated with therapists and showed greater adherence to the intervention experienced significant improvement in their symptoms. The results of the intervention group were better than those of the waiting-list, treatment-as-usual, and online psychoeducation groups. CONCLUSIONS: Web-based self-management is a promising therapy for depression. Future research should aim to refine these aspects of the intervention to achieve a beneficial impact.