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Nearly 350 IgG-based therapeutics are approved for clinical use or are under development for many diseases lacking adequate treatment options. These include molecularly engineered biologicals comprising the IgG Fc-domain fused to various effector molecules (so-called Fc-fusion proteins) that confer the advantages of IgG, including binding to the neonatal Fc receptor (FcRn) to facilitate in vivo stability, and the therapeutic benefit of the specific effector functions. Advances in IgG structure-function relationships and an understanding of FcRn biology have provided therapeutic opportunities for previously unapproachable diseases. This article discusses approved Fc-fusion therapeutics, novel Fc-fusion proteins and FcRn-dependent delivery approaches in development, and how engineering of the FcRn-Fc interaction can generate longer-lasting and more effective therapeutics. [ABSTRACT FROM AUTHOR]

This paper focuses on modelling and experimental investigation of cobalt - rich crust cutting by deep sea mining vehicle in low confining pressure. The prediction accuracy of brittle material theoretical models was evaluated by the experimental cutting force obtained from the cobalt - rich crust cutting test. The results show that in 15 MPa confining pressure, the peak cutting force predicted by Evans model is closer to the experimental value when the compressive strength of cobalt - rich crust is less (Take cobalt - rich crust 1 strength as the standard). When the compressive strength of cobalt - rich crust exceeds cobalt - rich crust 1 and the cutting depth is larger, the predicted value of Roxborough model is more accurate. It is underestimated to the cutting forces acting on soft cobalt - rich crusts, semi-hard cobalt - rich crusts, hard cobalt - rich crusts and very hard cobalt - rich crusts by Evans model, which are about 85%, 76%, 91% and 74% respectively. The calibration factor is introduced to modify the peak cutting force estimated by Evans model. Finally, the modified cobalt - rich crust cutting mechanical model in ocean environment is obtained. • Modelling and experimental investigation of mining on cobalt - rich crust cutting in low confining pressure. • The cobalt-rich crust cutting model in ocean environment is first proposed creatively. • Research on the cobalt-rich crust cutting under different cobalt-rich crust strength conditions is original. [ABSTRACT FROM AUTHOR]

In order to improve the walking stability of a biped robot in multiple scenarios and reduce the complexity of the Central Pattern Generator (CPG) model, a new CPG walking controller based on multivariate linear mapping was proposed. At first, in order to establish a dynamics model, the lower limb mechanical structure of the biped robot was designed. According to the Lagrange and angular momentum conservation method, the hybrid dynamic model of the biped robot was established. The initial value of the robot's passive walking was found by means of Poincaré mapping and cell mapping methods. Then, a multivariate linear mapping model was established to form a new lightweight CPG model based on a Hopf oscillator. According to the parameter distribution of the new CPG model, a preliminary parameter-tuning idea was proposed. At last, the joint simulation of MATLAB and V-REP shows that the biped robot based on the new CPG control has a stable periodic gait in flat and uphill scenes. The proposed method could improve the stability and versatility of bipedal walking in various environments and can provide general CPG generation and a tuning method reference for robotics scholars. [ABSTRACT FROM AUTHOR]

The neonatal Fc receptor (FcRn), also known as the Brambell receptor and encoded by Fcgrt, is a MHC class I like molecule that functions to protect IgG and albumin from catabolism, mediates transport of IgG across epithelial cells, and is involved in antigen presentation by professional antigen presenting cells. Its function is evident in early life in the transport of IgG from mother to fetus and neonate for passive immunity and later in the development of adaptive immunity and other functions throughout life. The unique ability of this receptor to prolong the half-life of IgG and albumin has guided engineering of novel therapeutics. Here, we aim to summarize the basic understanding of FcRn biology, its functions in various organs, and the therapeutic design of antibody- and albumin-based therapeutics in light of their interactions with FcRn.

Background & Aims Development of celiac disease is believed to involve the transglutaminase-dependent response of CD4+ T cells toward deamidated gluten peptides in the intestinal mucosa of individuals with specific HLA-DQ haplotypes. We investigated the antigen presentation process during this mucosal immune response. Methods We generated monoclonal antibodies (mAbs) specific for the peptide–MHC (pMHC) complex of HLA-DQ2.5 and the immunodominant gluten epitope DQ2.5-glia-α1a using phage display. We used these mAbs to assess gluten peptide presentation and phenotypes of presenting cells by flow cytometry and enzyme-linked immune absorbent spot (ELISPOT) in freshly prepared single-cell suspensions from intestinal biopsies from 40 patients with celiac disease (35 untreated and 5 on a gluten-free diet) as well as 18 subjects with confirmed noninflamed gut mucosa (controls, 12 presumed healthy, 5 undergoing pancreatoduodenectomy, and 1 with potential celiac disease). Results Using the mAbs, we detected MHC complexes on cells from intestinal biopsies from patients with celiac disease who consume gluten, but not from patients on gluten-free diets. We found B cells and plasma cells to be the most abundant cells that present DQ2.5-glia-α1a in the inflamed mucosa. We identified a subset of plasma cells that expresses B-cell receptors (BCR) specific for gluten peptides or the autoantigen transglutaminase 2 (TG2). Expression of MHC class II (MHCII) was not restricted to these specific plasma cells in patients with celiac disease but was observed in an average 30% of gut plasma cells from patients and controls. Conclusions A population of plasma cells from intestinal biopsies of patients with celiac disease express MHCII; this is the most abundant cell type presenting the immunodominant gluten peptide DQ2.5-glia-α1a in the tissues from these patients. These results indicate that plasma cells in the gut can function as antigen-presenting cells and might promote and maintain intestinal inflammation in patients with celiac disease or other inflammatory disorders. Graphical abstract [ABSTRACT FROM AUTHOR]

Background & Aims Celiac disease is characterized by HLA-DQ2/8-restricted responses of CD4+ T cells to cereal gluten proteins. A diagnosis of celiac disease based on serologic and histologic evidence requires patients to be on gluten-containing diets. The growing number of individuals adhering to a gluten-free diet (GFD) without exclusion of celiac disease complicates its detection. HLA-DQ–gluten tetramers can be used to detect gluten-specific T cells in blood of patients with celiac disease, even if they are on a GFD. We investigated whether an HLA-DQ–gluten tetramer-based assay accurately identifies patients with celiac disease. Methods We produced HLA-DQ–gluten tetramers and added them to peripheral blood mononuclear cells isolated from 143 HLA-DQ2.5 + subjects (62 subjects with celiac disease on a GFD, 19 subjects without celiac disease on a GFD [due to self-reported gluten sensitivity], 10 subjects with celiac disease on a gluten-containing diet, and 52 presumed healthy individuals [controls]). T cells that bound HLA-DQ–gluten tetramers were quantified by flow cytometry. Laboratory tests and flow cytometry gating analyses were performed by researchers blinded to sample type, except for samples from subjects with celiac disease on a gluten-containing diet. Test precision analyses were performed using samples from 10 subjects. Results For the HLA-DQ–gluten tetramer-based assay, we combined flow-cytometry variables in a multiple regression model that identified individuals with celiac disease on a GFD with an area under the receiver operating characteristic curve value of 0.96 (95% confidence interval [CI] 0.89–1.00) vs subjects without celiac disease on a GFD. The assay detected individuals with celiac disease on a gluten-containing diet vs controls with an area under the receiver operating characteristic curve value of 0.95 (95% CI 0.90–1.00). Optimized cutoff values identified subjects with celiac disease on a GFD with 97% sensitivity (95% CI 0.92–1.00) and 95% specificity (95% CI 0.84–1.00) vs subjects without celiac disease on a GFD. The values identified subjects with celiac disease on a gluten-containing diet with 100% sensitivity (95% CI 1.00–1.00]) and 90% specificity (95% CI 0.83–0.98) vs controls. In an analysis of 4 controls with positive results from the HLA-DQ–gluten tetramer test, 2 had unrecognized celiac disease and the remaining 2 had T cells that proliferated in response to gluten antigen in vitro. Conclusions An HLA-DQ–gluten tetramer-based assays that detects gluten-reactive T cells identifies patients with and without celiac disease with a high level of accuracy, regardless of whether the individuals are on a GFD. This test would allow individuals with suspected celiac disease to avoid gluten challenge and duodenal biopsy, but requires validation in a larger study. Clinicaltrials.gov no: NCT02442219 . [ABSTRACT FROM AUTHOR]

Celiac disease is caused by an abnormal intestinal T cell response to cereal gluten proteins. The disease has a strong human leukocyte antigen (HLA) association, and CD4+ T cells recognizing gluten epitopes presented by disease-associated HLA-DQ allotypes are considered to be drivers of the disease. This paper provides an update of the currently known HLA-DQ restricted gluten T cell epitopes with their names and sequences. [ABSTRACT FROM AUTHOR]

Entomological sampling and storage conditions often prioritise efficiency, practicality and conservation of morphological characteristics, and may therefore be suboptimal for DNA preservation. This practice can impact downstream molecular applications, such as the generation of high-throughput genomic libraries, which often requires substantial DNA input amounts. Here, we use a practical Tn5 transposase tagmentation-based library preparation method optimised for 96-well plates and low yield DNA extracts from insect legs that were stored under sub-optimal conditions for DNA preservation. The samples were kept in field vehicles for extended periods of time, before long-term storage in ethanol in the freezer, or dry at room temperature. By reducing DNA input to 6ng, more samples with sub-optimal DNA yields could be processed. We matched this low DNA input with a 6-fold dilution of a commercially available tagmentation enzyme, significantly reducing library preparation costs. Costs and workload were further suppressed by direct post-amplification pooling of individual libraries. We generated medium coverage (>3-fold) genomes for 88 out of 90 specimens, with an average of approximately 10-fold coverage. While samples stored in ethanol yielded significantly less DNA compared to those which were stored dry, these samples had superior sequencing statistics, with longer sequencing reads and higher rates of endogenous DNA. Furthermore, we find that the efficiency of tagmentation-based library preparation can be improved by a thorough post-amplification bead clean-up which selects against both short and large DNA fragments. By opening opportunities for the use of sub-optimally preserved, low yield DNA extracts, we broaden the scope of whole genome studies of insect specimens. We therefore expect these results and this protocol to be valuable for a range of applications in the field of entomology. [ABSTRACT FROM AUTHOR]

• Infrared optical properties optimization of various Si lattice structures are investigated. • Close-to-atomic method(IBF and CMP) is imported to regulate various lattice layers on Si surface. • Removal of amorphous layer above the low-density layer improve the reflectivity notable. • Low-density(about 1 nm) layer and transition layer(about 1 nm) are conducive for optimize the infrared optical properties(reflectivity and photo-thermal absorption). A fundamental challenge in optimizing the infrared optical properties of monocrystalline Si(1 0 0) reflectors is achieving high infrared reflection and low photo-thermal absorption. These requirements have been traditionally satisfied by removing various surface defects to obtain a perfect lattice structure. To supersede the traditional logic of "non-defect surfaces," a surface lattice structure scheme, "Si lattice layer regulation," is proposed. This paper presents a close-to-atomic-scale method for regulating multilayer Si lattices. First, a "multilayer lattice" (disordered, low-density, and transition layers) is introduced by ion beam figuring as a regulation base. Subsequently, the infrared optical properties are improved by reducing the disordered layer above the low-density layer using chemical–mechanical polishing. An experimental comparison proves that the scheme is effective: the reflectivity of the new surface developed in this study increases by 10 % (from 900 to 1500 nm (testing band)), and the photo-thermal absorption of the surface is controlled at 0.116 ppm. Therefore, the optical properties of monocrystalline Si can be optimized by regulating the thickness of the Si atomic layers with different densities. A lattice layer based on the field of materials science (e.g., material band gap and electronic property regulation) is introduced to an optical field with high infrared optical properties on Si surfaces. This allows the optical processing to enter an emerging "close-to-atomic-scale" manufacturing dimension. This work also opens up advanced prospects in the fields of high-energy optics and X-rays and directs research on atomic structure regulation toward a completely new area of optics. [ABSTRACT FROM AUTHOR]

A set of in situ measurement equipment of large aperture strong light element based on the principle of laser scattering is established. The size and distribution of defects (damage points) can be judged by the laser scattering signal. The maximum scanning range is 700 mm*1000 mm. The type and size of defects are directly obtained by scanning the quartz sample with a diameter of 100 mm. The types of defects are pitting and scratches, and the width of the scratches and the diameter of the pitting are mostly in the range of 0–10μm. The processing time could reach 31.06s. The device can realize the on‐line in situ measurement of large aperture optical elements, and has the advantages of fast response speed and high measurement accuracy. [ABSTRACT FROM AUTHOR]

Atlantic Cod (Gadus morhua) has lost the major histocompatibility complex class II presentation pathway. We recently identified CD8-positive T cells, B cells, and plasma cells in cod, but further characterisation of lymphocyte subsets is needed to elucidate immune adaptations triggered by the absence of CD4-positive T lymphocytes. Here, we use single-cell RNA sequencing to examine the lymphocyte heterogeneity in Atlantic cod spleen. We describe five T cell subsets and eight B cell subsets and propose a B cell trajectory of differentiation. Notably, we identify a subpopulation of T cells that are CD8-negative. Most of the CD8-negative T lymphocytes highly express the homologue of monocyte chemotactic protein 1b, and another subset of CD8-negative T lymphocytes express the homologue of the scavenger receptor m130. Uncovering the multiple lymphocyte cell sub-clusters reveals the different immune states present within the B and T cell populations, building a foundation for further work. Single-cell sequencing of naïve and vaccinated Atlantic Cod uncovers multiple B and T lymphocyte subsets including a subset of T lymphocytes expressing neither CD4 or CD8 and reveals different immune states present within B and T cell populations. [ABSTRACT FROM AUTHOR]

Due to rapid advancements in fields of modern optics and opto-electronics, the need for the production of super-smooth surfaces on single crystal silicon has become increasingly pressing. Although previous research has elucidated the mechanism of material removal and defect evolution in chemical mechanical polishing, brittle characteristic of the vulnerable silicon material makes it rather challenging to catch up with the extreme requirements of high performance and highly efficient manufacture. Nevertheless the critical polishing pressure for scratch free super-smooth surface in pragmatic machining remains undiscovered, which greatly hinders improvement in related fields. Consequently, this paper presents a series of analyses and experiments focused on the material removal process at the micro scale. A micron-sized SiO2 ball tip is utilized to simulate the scratching on surface of a single crystal silicon substrate. Experimental results reveal that appropriate pH conditions and a maximal contact pressure of 0.97 GPa (at a scratching speed of 2 µm/s) between the particle and substrate are crucial for achieving a super-smooth surface. Based on these findings, a defect-free chemical mechanical polishing method is proposed, which involves controlling contact pressure for practical fabrication. Further verification using the KDOSP 650γ machining system and ion beam figuring has demonstrated that a defect-free surface with a roughness of 0.209 nm RMS (Root Mean Square) can be achieved at an average removal rate of 316 nm/min. These insights provide new understandings in the fabrication of super-smooth surfaces on single crystal silicon, offering significant benefits for enhancing the performance of brittle single crystal silicon-based devices and the corresponding machining capabilities. [ABSTRACT FROM AUTHOR]

• Finite element level - set (FELS) method was used to simulate the CO 2 laser irradiating process of fused silica optics. • High - resolution morphology detection et al. were conducted to investigate the secondary laser damage characteristics of fused silica optics. • The material migration and re deposition in CO 2 repairing process was verified to be factors that induced laser damage. Fused silica optics, as key components in high - power laser systems, are prone to be damaged under short - pulse ultraviolet (UV) laser irradiation. CO 2 laser is usually used to repair the laser damage and extend the service life of optics. However, the anti - laser damage characteristics of repaired substrates sometimes can't meet the expectation. To facilitate better application of CO 2 laser repairing method, this work studied the CO 2 laser irradiating mechanism of fused silica in detail and investigated the damage characteristics of repaired optical surface through experiments. Firstly, finite element level - set (FELS) method is adopted to simulate CO 2 laser irradiating process. The simulation showed that CO 2 laser irradiation would cause molten material migration, vapor material deposition and affect the formation of residual stress. Various tests of morphology, residual stress, and photo - thermal absorption were conducted to study the changes of laser damage characteristics of repaired craters. The experimental results presented that molten materials migration and vapor materials re deposition occurred in CO 2 laser irradiation, which would promote the formation of residual stress, cause stronger laser absorption, or even induce laser damage. Through the experiment, accuracy of simulation was verified further. In this work, the CO 2 laser repairing mechanism of fused silica and laser damage characteristics of repaired optics are clarified through FELS simulation and experiments. Relative results can provide a certain technical support for the performance improvement of repaired fused silica optics. [ABSTRACT FROM AUTHOR]

T-cell receptor (TCR) sequencing has enabled the development of innovative diagnostic tests for cancers, autoimmune diseases and other applications. However, the rarity of many T-cell clonotypes presents a detection challenge, which may lead to misdiagnosis if diagnostically relevant TCRs remain undetected. To address this issue, we developed TCRpower, a novel computational pipeline for quantifying the statistical detection power of TCR sequencing methods. TCRpower calculates the probability of detecting a TCR sequence as a function of several key parameters: in-vivo TCR frequency, T-cell sample count, read sequencing depth and read cutoff. To calibrate TCRpower, we selected unique TCRs of 45 T-cell clones (TCCs) as spike-in TCRs. We sequenced the spike-in TCRs from TCCs, together with TCRs from peripheral blood, using a 5′ RACE protocol. The 45 spike-in TCRs covered a wide range of sample frequencies, ranging from 5 per 100 to 1 per 1 million. The resulting spike-in TCR read counts and ground truth frequencies allowed us to calibrate TCRpower. In our TCR sequencing data, we observed a consistent linear relationship between sample and sequencing read frequencies. We were also able to reliably detect spike-in TCRs with frequencies as low as one per million. By implementing an optimized read cutoff, we eliminated most of the falsely detected sequences in our data (TCR α-chain 99.0% and TCR β-chain 92.4%), thereby improving diagnostic specificity. TCRpower is publicly available and can be used to optimize future TCR sequencing experiments, and thereby enable reliable detection of disease-relevant TCRs for diagnostic applications. [ABSTRACT FROM AUTHOR]

Celiac disease is an auto-immune disease in which an immune response to dietary gluten leads to inflammation and subsequent atrophy of small intestinal villi, causing severe bowel discomfort and malabsorption of nutrients. The major instigating factor for the immune response in celiac disease is the activation of gluten-specific CD4+ T cells expressing T cell receptors that recognize gluten peptides presented in the context of HLA-DQ2 and DQ8. Here we provide an in-depth characterization of 28 gluten-specific T cell clones. We assess their transcriptional and epigenetic response to T cell receptor stimulation and link this to genetic factors associated with celiac disease. Gluten-specific T cells have a distinct transcriptional profile that mostly resembles that of Th1 cells but also express cytokines characteristic of other types of T-helper cells. This transcriptional response appears not to be regulated by changes in chromatin state, but rather by early upregulation of transcription factors and non-coding RNAs that likely orchestrate the subsequent activation of genes that play a role in immune pathways. Finally, integration of chromatin and transcription factor binding profiles suggest that genes activated by T cell receptor stimulation of gluten‑specific T cells may be impacted by genetic variation at several genetic loci associated with celiac disease. [ABSTRACT FROM AUTHOR]

• A PSD (Power Spectral Density) analysis method based on the contour of removal function was proposed for AMRF technique. • A new polishing path called "non-equal-interval parallel raster path" customized for AMRF technique was proposed and applied to control mid-spatial-frequency ripple error. • Simulation and actual experiment verified the effects of analysis method and polishing path. With the continuous development of high-power laser systems, laser optics gradually changed towards large-aperture, high-quality. To adapt to the fabrication of large-aperture laser optics, a new-type array magnetorheological finishing (AMRF) technique was developed and had made initial progress. However, AMRF technique would introduce more obvious ripple structures (such as 1 mm−1 of spatial frequency) compared to original MRF technique while adopting conventional raster path, and the ripple structures might affect laser beam transmission. For the further application of AMRF technique, the formation mechanism of ripple structures was studied, and a method based on the contour of removal function was proposed to analyze the changes of spatial frequency and evaluate the effect of different polishing paths. According to the analysis method, non-equal-interval parallel raster path was chosen and applied into AMRF process, along with maintaining efficiency while controlling ripple structures. In general, this work could provide a valuable support for the AMRF process of large-aperture laser optics and had a certain significance for the high-power laser system. [ABSTRACT FROM AUTHOR]

Aquaculture is the fastest-growing food sector worldwide but faces sustainability challenges that need to be addressed in many ways, including genetic enhancement. Atlantic cod has re-emerged as an aquaculture species and tools for genetic manipulation are needed. Thus, we compared five formats of CRISPR to determine which was most efficient to generate knock outs in Atlantic cod. Cas9 protein was presented in preformed ribonucleoprotein (RNP) complexes with single guide or with duplex guide RNAs or an mRNA encoding Cas9 was used with the same two formats of guide RNAs. Cas12a was tested as RNP complexes with single guide RNAs. We found Cas9 mRNA with single guide RNA to be the most efficient format to knock out both alleles of the slc45a2 gene, which resulted in an albino-like phenotype in up to 75% of surviving larvae. DNA analysis of individual larvae revealed mosaic genotypes with variable indel mutations. The mortality of injected eggs was high, resulting in low overall efficiency. Nevertheless, this study lays the foundation for further genetic and functional research using the CRISPR/Cas9 genome editing system in Atlantic cod. • The Atlantic cod slc45a2 gene was genetically modified using the CRISPR-Cas9/Cas12a genome-editing system. • Insertions and deletions in the slc45a2 gene in Atlantic cod resulted in albino-like larvae. • Coinjection of Cas9 mRNA and gRNA was more efficient for genome editing than injection of preformed Cas9 or Cas12a RNPs. [ABSTRACT FROM AUTHOR]

Little is known about the repertoire dynamics and persistence of pathogenic T cells in HLA-associated disorders. In celiac disease, a disorder with a strong association with certain HLA-DQ allotypes, presumed pathogenic T cells can be visualized and isolated with HLA-DQ:gluten tetramers, thereby enabling further characterization. Single and bulk populations of HLA-DQ:gluten tetramer-sorted CD4+ T cells were analyzed by high-throughput DNA sequencing of rearranged TCR-α and -β genes. Blood and gut biopsy samples from 21 celiac disease patients, taken at various stages of disease and in intervals of weeks to decades apart, were examined. Persistence of the same clonotypes was seen in both compartments over decades, with up to 53% overlap between samples obtained 16 to 28 years apart. Further, we observed that the recall response following oral gluten challenge was dominated by preexisting CD4+ T cell clonotypes. Public features were frequent among gluten-specific T cells, as 10% of TCR-α, TCR-β, or paired TCR-αβ amino acid sequences of total 1813 TCRs generated from 17 patients were observed in 2 or more patients. In established celiac disease, the T cell clonotypes that recognize gluten are persistent for decades, making up fixed repertoires that prevalently exhibit public features. These T cells represent an attractive therapeutic target. [ABSTRACT FROM AUTHOR]

• The development of new-type arrayed MRF equipment was conducted through theoretical analysis, simulation and experiment. • High removal efficiency of 2.03 × 107 μm3/min and stability better than 5 % were achieved. • Actual experiment verified the effects of arrayed MRF equipment. Along with the continuous development of optical systems, the fabrication of optics gradually moved towards large aperture and high quality. To meet the requirements of optical systems, advanced technologies represented by magnetorheological finishing (MRF) were applied in the processing of optics. According to the background of high-efficiency processing, this work focused on the design of arrayed magnetorheological equipment, including magnetic field theoretical analysis, magnetic field simulation, equipment construction, removal function preparation and stability test. Through the study, arrayed MR (magnetorheological) equipment was preliminarily built and the removal function was prepared. The volume removal rate of arrayed removal function was 2.03 μm3/min after detection, which was 1.35 times of electromagnetic equipment under the same process parameters, and the stability of the removal function was better than 5 %. The results of two-dimensional removal experiment also verified that arrayed MR equipment could significantly improve materials removal efficiency. Based on the experimental results in this work, it is believed that arrayed MR equipment have certain advantages in the improvement of processing efficiency and surface quality, and it could meet the requirement of optical processing at the present stage. The relevant design theories and methods could provide reference to the follow-up research. [ABSTRACT FROM AUTHOR]

An individual's T cell repertoire is skewed towards some specificities as a result of past antigen exposure and subsequent clonal expansion. Identifying T cell receptor signatures associated with a disease is challenging due to the overall complexity of antigens and polymorphic HLA allotypes. In celiac disease, the antigen epitopes are well characterised and the specific HLA-DQ2-restricted T-cell repertoire associated with the disease has been explored in depth. By investigating T cell receptor repertoires of unsorted lamina propria T cells from 15 individuals, we provide the first proof-of-concept study showing that it could be possible to infer disease state by matching against a priori known disease-associated T cell receptor sequences. [ABSTRACT FROM AUTHOR]

Background: Cancer imposes significant psychological distress on both patients and caregivers. Dyadic interventions are designed to concurrently address the health problems of both, yet there remains limited evidence as to which specific dyadic interventions yield the most effective outcomes for both partners., Objectives: To systematically synthesize and evaluate the comparative efficacy of various dyadic interventions on a wide range of outcomes within cancer patient-caregiver dyads., Methods: Searches of eight electronic databases from inception to July 2, 2023, were performed. Data extraction and quality assessment were independently conducted by two reviewers utilizing the Cochrane risk of bias tool and the Jadad score. Stata 17.0 was used for network meta-analysis, with the Surface Under the Cumulative Ranking (SUCRA) curve employed to rank interventions based on efficacy for each outcome. Effect sizes were reported using standardized mean difference (SMD) with a 95 % confidence interval (CI), and publication bias was assessed via Egger's test. The study protocol was registered in PROSPERO under CRD42023467172., Result: A total of 37 studies, spanning 8 countries, were included. According to SUCRA rankings, WeChat couple-based psychosocial support and the eHealth symptom and complication management program were identified as the most effective interventions for improving quality of life in both patients and caregivers (SUCRA = 82.1 %, SMD = 7.30, 95 % CI: 1.02, 13.58; SUCRA = 86.6 %, SMD =1.17, 95 % CI: 0.04, 2.31, respectively). Emotionally focused therapy was ranked as the most effective intervention for enhancing dyadic adjustment (SUCRA = 100 %, SMD = 1.63, 95 % CI: 0.91, 2.36; SUCRA = 99.9 %, SMD = 2.04, 95 % CI: 1.26, 2.82, respectively). Couple-based intimacy enhancement and telephone-based dyadic psychosocial interventions were deemed most effective interventions in alleviating anxiety (SUCRA = 88.2 %, SMD = -0.83, 95 % CI: -1.65, -0.00; SUCRA = 95.6 %, SMD = -1.08, 95 % CI: -1.76, -0.41, respectively), while telephone-based dyadic psychosocial intervention and coping skills training were the most efficacious interventions for reducing depression in both partners (SUCRA = 95.2 %, SMD = -0.89, 95 % CI: -1.55, -0.23; SUCRA = 99.8 %, SMD = -2.31, 95 % CI: -3.27, -1.35, respectively). Additionally, caregiver educational program was ranked highest for reducing caregivers burden (SUCRA = 95.6 %, SMD = -1.20, 95 % CI: -1.55, -0.23)., Conclusion: The highest-ranked dyadic interventions identified in this analysis offer valuable insights for clinical practice, providing strategies to enhance the quality of life, strengthen dyadic relationships, and alleviate anxiety, depression, and caregiver burden. Nevertheless, further robust randomized controlled trials are necessary to confirm these findings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The high-efficiency preparation of large-area microstructures of optical materials and precision graphic etching technology is one of the most important application directions in the atomic and near-atomic-scale manufacturing industry. Traditional focused ion beam (FIB) and reactive ion etching (RIE) methods have limitations in precision and efficiency, hindering their application in automated mass production. The pulsed ion beam (PIB) method addresses these issues by enhancing ion beam deflection to achieve high-resolution material removal on a macro scale, which can reach the equivalent removal resolution of 6.4 × 10 -4 nm. Experiments were conducted on a quartz sample (10 × 10 × 1 mm) with a specific pattern mask using the custom PIB processing device. The surface morphology, etching depth, and roughness were measured post-process. The results demonstrated that precise control over cumulative sputtering time yielded well-defined patterns with expected average etching depths and surface roughness. This confirms the PIB technique's potential for precise atomic depth image transfer and its suitability for industrial automation, offering a significant advancement in microfabrication technology.

Background: The Atlantic cod is a prolific species in the Atlantic, despite its inconsistent specific antibody response. It presents a peculiar case within vertebrate immunology due to its distinct immune system, characterized by the absence of MHCII antigen presentation pathway, required for T cell-dependent antibody responses. Thorough characterisation of immunoglobulin loci and analysis of the antibody repertoire is necessary to further our understanding of the Atlantic cod's immune response on a molecular level., Results: A comprehensive search of the cod genome (gadmor3.0) identified the complete set of IgH genes organized into three sequential translocons on chromosome 2, while IgL genes were located on chromosomes 2 and 5. The Atlantic cod displayed a moderate germline V gene diversity, comprising four V gene families for both IgH and IgL, each with distinct chromosomal locations and organizational structures. 5'RACE sequencing revealed a diverse range of heavy chain CDR3 sequences and relatively limited CDR3 diversity in light chains. The analysis highlighted a differential impact of V-gene germline CDR3 length on receptor CDR3 length between heavy and light chains, underlining different recombination processes., Conclusions: This study reveals that the Atlantic cod, despite its inconsistent antibody response, maintains a level of immunoglobulin diversity comparable to other fish species. The findings suggest that the extensive recent duplications of kappa light chain genes do not result in increased repertoire diversity. This research provides a comprehensive view of the Atlantic cod's immunoglobulin gene organization and repertoire, necessary for future studies of antibody responses at the molecular level., (© 2024. The Author(s).)

Background & Aims: The treatment of celiac disease (CeD) with gluten-free diet (GFD) normalizes gut inflammation and disease-specific antibodies. CeD patients have HLA-restricted, gluten-specific T cells persisting in the blood and gut even after decades of GFD, which are reactivated and disease driving upon gluten exposure. Our aim was to examine the transition of activated gluten-specific T cells into a pool of persisting memory T cells concurrent with normalization of clinically relevant biomarkers during the first year of treatment., Methods: We followed 17 CeD patients during their initial GFD year, leading to disease remission. We assessed activation and frequency of gluten-specific CD4 + blood and gut T cells with HLA-DQ2.5:gluten tetramers and flow cytometry, disease-specific serology, histology, and symptom scores. We assessed gluten-specific blood T cells within the first 3 weeks of GFD in 6 patients and serology in an additional 9 patients., Results: Gluten-specific CD4 + T cells peaked in blood at day 14 while up-regulating Bcl-2 and down-regulating Ki-67 and then decreased in frequency within 10 weeks of GFD. CD38, ICOS, HLA-DR, and Ki-67 decreased in gluten-specific cells within 3 days. PD-1, CD39, and OX40 expression persisted even after 12 months. IgA-transglutaminase 2 decreased significantly within 4 weeks., Conclusions: GFD induces rapid changes in the phenotype and number of gluten-specific CD4 + blood T cells, including a peak of nonproliferating, nonapoptotic cells at day 14. Subsequent alterations in T-cell phenotype associate with the quiescent but chronic nature of treated CeD. The rapid changes affecting gluten-specific T cells and disease-specific antibodies offer opportunities for clinical trials aiming at developing nondietary treatments for patients with newly diagnosed CeD., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)