Effect of the p-Estrogen Receptor at Serine on Its Function and Breast Growth.

BACKGROUND: Estrogen receptor (ER) signaling plays an important role in the development and functional differentiation of the breast and participates in the process of breast cancer. Activated ER can affect various aspects of the cell's behavior, including proliferation, via modulating the expression of many downstream target genes. Phosphorylation is one of the activation pathways of ER. However, the relationship between estrogen receptor phosphorylation sites and breast development and carcinogenesis is not clear. METHODS: Using Crisper-Cas9 gene editing technology, we constructed ER S309A mutant mice. Using carmine staining of the mammary gland of mice at different developmental stages, we examined the breast development of ER S309A mice. Using hematoxylin-eosin (HE) staining of vaginal smears of mice at the same time for 5 consecutive days, we measured the vaginal epithelial keratinocytes. RESULTS: We established ER S309A mutant mice and observed breast defects in ER S309A mice. In addition, we observed decreased reproductive ability, and estrous cycle disorder in ER S309A mice. The number of vaginal epithelial keratino-cytes in the estrous cycle of ER S309A mice was decreased. CONCLUSION: These results suggest that the phosphorylation site of ER at Serine 309 is important for ER function and breast development.

Enhanced Nonradiative Charge Recombination in Microfiber-Based Bismuthene.

After the first report of a graphene-based passive mode-locking ultrafast fiber laser, two-dimensional materials as efficient saturable absorbers offer a new horizon in ultrafast fiber laser. However, the interactions on atomic scale between these two-dimensional materials and fiber and the fiber effect on the carrier dynamics have not been realized. To figure out the exact role of fiber and the carrier dynamics affected by the fiber substrate related to ultrafast photonics, bismuthene, a newly reported 2D quantum material used in a passive mode-locking fiber laser, deposited on α-quartz has been investigated. We surprisingly found that the α-quartz substrate can strongly accelerate the nonradiative electron-hole recombination of bismuthene in theory, and the transient absorption spectra of bismuthene on normal glass and α-quartz further verify the substrate effect on carrier dynamics of bismuthene. The discovery provides new thinking about substrate effect to regulate the performance of ultrafast mode-locking fiber lasers as well as ultrafast photonics.

Nerve growth factor promote osteogenic differentiation of dental pulp stem cells through MEK/ERK signalling pathways.

Nerve growth factor (NGF) and its receptor, tropomyosin receptor kinase A (TrkA), are known to play important roles in the immune and nervous system. However, the effects of NGF on the osteogenic differentiation of dental pulp stem cells (DPSCs) remain unclear. This study aimed to investigate the role of NGF on the osteogenic differentiation of DPSCs in vitro and the underlying mechanisms. DPSCs were cultured in osteogenic differentiation medium containing NGF (50 ng/mL) for 7 days. Then osteogenic-related genes and protein markers were analysed using qRT-PCR and Western blot, respectively. Furthermore, addition of NGF inhibitor and small interfering RNA (siRNA) transfection experiments were used to elucidate the molecular signalling pathway responsible for the process. NGF increased osteogenic differentiation of DPSCs significantly compared with DPSCs cultured in an osteogenic-inducing medium. The NGF inhibitor Ro 08-2750 (10 µM) and siRNA-mediated gene silencing of NGF receptor, TrkA and ERK signalling pathways inhibitor U0126 (10 µM) suppressed osteogenic-related genes and protein markers on DPSCs. Furthermore, our data revealed that NGF-upregulated osteogenic differentiation of DPSCs may be associated with the activation of MEK/ERK signalling pathways via TrkA. Collectively, NGF was capable of promoting osteogenic differentiation of DPSCs through MEK/ERK signalling pathways, which may enhance the DPSCs-mediated bone tissue regeneration.

Rational Synthesis of Functionalized Covalent Organic Frameworks via Four-Component Reaction.

The construction of function-oriented covalent organic frameworks (COFs) remains a challenge as it requires simultaneous consideration of diversified structures, robust linkage, and tailorable functionalities. Herein, we report the rational synthesis of functionalized COFs via a four-component reaction strategy. Through the four-component Debus-Radziszewski reaction, 11 N-substituted imidazole-based COFs with diversified structures were facilely constructed from readily available building blocks. By forming the N-substituted imidazole linkage, these synthesized COFs displayed ultrastability toward strong acids and base. Moreover, the four components reaction allows the rational synthesis of COFs with tailorable functionalities. As an example, the phosphonate-functionalized COF (LZU-530) was rationally constructed for the efficient adsorption of uranium(VI). The uranium(VI) uptake of LZU-530 reaches up to 95 mg·g-1 in 2 M HNO3, which is the highest uptake of the existing organic porous materials under such harsh conditions. Our results highlight the use of multicomponent reaction for the rational synthesis of robust and functionalized COFs toward targeted applications.

High-quality pan-genome of Escherichia coli generated by excluding confounding and highly similar strains reveals an association between unique gene clusters and genomic islands.

The pan-genome analysis of bacteria provides detailed insight into the diversity and evolution of a bacterial population. However, the genomes involved in the pan-genome analysis should be checked carefully, as the inclusion of confounding strains would have unfavorable effects on the identification of core genes, and the highly similar strains could bias the results of the pan-genome state (open versus closed). In this study, we found that the inclusion of highly similar strains also affects the results of unique genes in pan-genome analysis, which leads to a significant underestimation of the number of unique genes in the pan-genome. Therefore, these strains should be excluded from pan-genome analysis at the early stage of data processing. Currently, tens of thousands of genomes have been sequenced for Escherichia coli, which provides an unprecedented opportunity as well as a challenge for pan-genome analysis of this classical model organism. Using the proposed strategies, a high-quality E. coli pan-genome was obtained, and the unique genes was extracted and analyzed, revealing an association between the unique gene clusters and genomic islands from a pan-genome perspective, which may facilitate the identification of genomic islands.

Mapping-based design method for high-quality integral projection system.

A general method for designing an integral projection system is proposed, including optical design and digital preprocessing based on the mapping within the projection system. The per-pixel mapping between the sub-images and the integral projection image is generated by incorporating an integral projection imaging model as well as the ray data of all sub-channels. By tracing rays for sparsely sampled field points of the central sub-channel and constructing the mapping between the central sub-channel and other sub-channels, the efficient acquisition of ray data for all sub-channels is achieved. The sub-image preprocessing pipeline is presented to effectively address issues such as overlapping misalignment, optical aberrations, inhomogeneous illumination, and their collective contribution. An integral projection optical system with a field of view (FOV) of 80°, an F-number of 2, and uniform image performance is given as a design example. The ray tracing simulation results and quantitative analysis demonstrate that the proposed system yields distortion-free, uniformly illuminated, and high-quality integral projection images.

Next-generation sequencing analysis of the molecular spectrum of thalassemia in Southern Jiangxi, China.

BACKGROUND: Thalassemia is an extremely prevalent monogenic inherited blood disorder in southern China. It is important to comprehensively understand the molecular spectrum of thalassemia in an area with such a high prevalence of thalassemia before taking appropriate actions for the prevention and treatment of this disorder. Herein, we explored the clinical feasibility of using next-generation sequencing (NGS) for large-scale population screening to illustrate the prevalence and spectrum of thalassemia in Southern Jiangxi. METHODS: Blood samples collected from 136,312 residents of reproductive age in Southern Jiangxi were characterized for thalassemia by NGS. A retrospective analysis was then conducted on blood samples determined to be positive for thalassemia. RESULTS: In total, 19,827 (14.545%) subjects were diagnosed as thalassemia carriers, and the thalassemia prevalence rate significantly varied by geographical region (p < 0.001). A total of 40 α-thalassemia genotypes including 21 rare genotypes were identified, with -@-SEA/αα being the most prevalent genotype. 42 ß-thalassemia genotypes including 27 rare genotypes were identified, with the most common mutation IVS II-654 C > T accounting for 35.257% of these ß-thalassemia genotypes. Furthermore, 74 genotypes were identified among 608 individuals with combined α- and ß-thalassemia. Notably, most individuals with rare thalassemia mutations had mildly abnormal hematologic parameters including microcytic hypochromia. CONCLUSIONS: Our findings demonstrate the great heterogeneity and diverse spectrum of thalassemia in Southern Jiangxi, emphasizing the importance and necessity of persistent prevention and control of thalassemia in this region. Additionally, our findings further suggest that NGS can effectively identify rare mutations and reduce the misdiagnosis rate of thalassemia.

Influence of HIV/AIDS knowledge on HIV testing behavior among young students (14-27 years) with a history of sexual activity: chain mediation analysis of social discrimination, self-efficacy, and sexual behavior characteristics.

This study used a self-administered questionnaire to investigate the relationship between HIV/AIDS knowledge, social discrimination, HIV self-efficacy, sexual behavioral characteristics and HIV testing behavior among young students with a history of sexual activity in Chongqing. Propensity score matching was used to construct a control group with similar demographic characteristics to the HIV testing group, only without HIV testing behaviors. Structural equation modeling was used to conduct chain-mediated effect analysis. The HIV testing rate among young students with a history of sexual behavior was 17.16%. Young students with HIV testing behavior had higher levels of HIV/AIDS knowledge, lower social discrimination, better self-efficacy, and no difference in sexual behavior characteristic scores between the two groups (P = 0.062). The mediated effect values of social discrimination and self-efficacy were 0.022 and 0.063, respectively, while their chain mediated effect value was 0.007. There was no mediated effect of sexual behavior characteristics. The level of young students' HIV/AIDS knowledge does not directly influence their HIV testing behavior but plays a complete chain mediating effect on HIV testing behavior through social discrimination and self-efficacy. HIV testing behavior should be promoted through the perspectives of enhancing HIV/AIDS knowledge level, reducing social discrimination, and improving self-efficacy.

Cytoplasmic SIRT1 promotes paclitaxel resistance in ovarian carcinoma through increased formation and survival of polyploid giant cancer cells.

Therapeutic resistance is a notable cause of death in patients with ovarian carcinoma. Polyploid giant cancer cells (PGCCs), commonly arising in tumor tissues following chemotherapy, have recently been considered to contribute to drug resistance. As a type III deacetylase, Sirtuin1 (SIRT1) plays essential roles in the cell cycle, cellular senescence, and drug resistance. Accumulating evidence has suggested that alteration in its subcellular localization via nucleocytoplasmic shuttling is a critical process influencing the functions of SIRT1. However, the roles of SIRT1 subcellular localization in PGCC formation and subsequent senescence escape remain unclear. In this study, we compared the differences in the polyploid cell population and senescence state of PGCCs following paclitaxel treatment between tumor cells overexpressing wild-type SIRT1 (WT SIRT1) and those expressing nuclear localization sequence (NLS)-mutated SIRT1 (SIRT1NLSmt ). We investigated the involvement of cytoplasmic SIRT1 in biological processes and signaling pathways, including the cell cycle and cellular senescence, in ovarian carcinoma cells' response to paclitaxel treatment. We found that the SIRT1NLSmt tumor cell population contained more polyploid cells and fewer senescent PGCCs than the SIRT1-overexpressing tumor cell population. Comparative proteomic analyses using co-immunoprecipitation (Co-IP) combined with liquid chromatography-mass spectrometry (LC-MS)/MS showed the differences in the differentially expressed proteins related to PGCC formation, cell growth, and death, including CDK1 and CDK2, between SIRT1NLSmt and SIRT1 cells or PGCCs. Our results suggested that ovarian carcinoma cells utilize polyploidy formation as a survival mechanism during exposure to paclitaxel-based treatment via the effect of cytoplasmic SIRT1 on PGCC formation and survival, thereby boosting paclitaxel resistance. © 2023 The Pathological Society of Great Britain and Ireland.

Spatiotemporal dynamics and influencing factors of human brucellosis in Mainland China from 2005-2021.

BACKGROUND: Brucellosis poses a significant public health concern. This study explores the spatial and temporal dynamic evolution of human brucellosis in China and analyses the spatial heterogeneity of the influencing factors related to the incidence of human brucellosis at the provincial level. METHODS: The Join-point model, centre of gravity migration model and spatial autocorrelation analysis were employed to evaluate potential changes in the spatial and temporal distribution of human brucellosis in mainland China from 2005 to 2021. Ordinary Least Squares (OLS), Geographically Weighted Regression (GWR), and Multi-scale Geographically Weighted Regression (MGWR) models were constructed to analyze the spatial and temporal correlation between the incidence rate of human brucellosis and meteorological and social factors. RESULTS: From 2005 to 2021, human brucellosis in China showed a consistent upward trend. The incidence rate rose more rapidly in South, Central, and Southwest China, leading to a shift in the center of gravity from the North to the Southwest, as illustrated in the migration trajectory diagram. Strong spatial aggregation was observed. The MGWR model outperformed others. Spatio-temporal plots indicated that lower mean annual temperatures and increased beef, mutton, and milk production significantly correlated with higher brucellosis incidence. Cities like Guangxi and Guangdong were more affected by low temperatures, while Xinjiang and Tibet were influenced more by beef and milk production. Inner Mongolia and Heilongjiang were more affected by mutton production. Importantly, an increase in regional GDP and health expenditure exerted a notable protective effect against human brucellosis incidence. CONCLUSIONS: Human brucellosis remains a pervasive challenge. Meteorological and social factors significantly influence its incidence in a spatiotemporally specific manner. Tailored prevention strategies should be region-specific, providing valuable insights for effective brucellosis control measures.

Cognitive benefits of folic acid, docosahexaenoic acid and a combination of both nutrients in mild cognitive impairment; possible alterations though mitochondrial function and DNA damage.

INTRODUCTION: It is uncertain whether folic acid (FA) combined with docosahexaenoic acid (DHA) could improve cognitive performance. This study evaluated the effects of a 12-month FA and DHA supplementation, in combination or alone, on cognitive function, DNA oxidative damage, and mitochondrial function in participants with mild cognitive impairment (MCI). METHODS: This randomized, double-blind, placebo-controlled trial recruited MCI participants aged 60 years and older. Two hundred and eighty participants were randomly divided in equal proportion into four groups: FA+DHA (FA 800µg/d + DHA 800mg/d), FA (800µg/d), DHA (800mg/d), and placebo groups daily orally for 12 months. The primary outcome was cognitive function evaluated by the Wechsler Adult Intelligence Scale-Revised (WAIS-RC). Cognitive tests and blood mechanism-related biomarkers were determined at baseline and 12 months. RESULTS: During the 12-month follow, scores of full intelligence quotient (FIQ) (ßDHA: 1.302, 95%CI: 0.615, 1.990, p < 0.001; ßFA: 1.992, 95%CI: 1.304, 2.679, p < 0.001; ßFA+DHA: 2.777, 95%CI: 2.090, 3.465, p < 0.001), verbal intelligence quotient, and some subtests of the WAIS-RC were significantly improved in FA+DHA and single intervention groups compared to the placebo group. Moreover, the FA and DHA intervention combination was superior to either intervention alone (p < 0.001). Meanwhile, FA, DHA and their combined use significantly decreased 8-OHdG level and increased mitochondrial DNA copy number compared to the placebo (p < 0.05). CONCLUSIONS: Supplementation of FA and DHA, alone or combined, for 12 months can improve cognitive function in MCI participants, possibly through mitigating DNA oxidative damage and enhancing mitochondrial function. Combined supplementation may provide more cognitive benefit than supplementation alone. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000034351. Registered 3 July 2020 - Retrospectively registered, https://www.chictr.org.cn/showproj.html?proj=53345.

The Potential of Berberine to Target Telocytes in Rabbit Heart.

A brand-new class of interstitial cells, called telocytes, has been detected in the heart. Telocytes can connect and transmit signals to almost all cardiomyocytes; this is highly interrelated with the occurrence and development of heart diseases. Modern studies have shown that berberine has a therapeutic effect on cardiovascular health. However, berberine's mechanism of action on the cardiovascular system through cardiac telocytes is unclear. Interestingly, 5 µm of berberine remarkably decreased the concentration of intracellular calcium and membrane depolarization in cultured telocytes, upregulated the expression of CX43 and ß-catenin, and downregulated the expressions of TRPV4 and TRPV1. Here, telocytes were identified in the vascular adventitia and intima, endocardium, myocardium, adventitia, and heart valves. Moreover, telocytes were broadly dispersed around cardiac vessels and interacted directly through gap junctions and indirectly through extracellular vesicles. Together, cardiac telocytes interact with berberine and then deliver drug information to the heart. Telocytes may be an essential cellular target for drug therapy of the cardiovascular system.

Association of thyroid hormone sensitivity index with stroke in patients with coronary artery disease.

BACKGROUND AND AIMS: Thyroid hormones (THs) will affect the occurrence and prognosis of stroke, and the research on THs sensitivity index and stroke in patients with coronary heart disease (CHD) is scarce. The goal of this study is to look into the relationship between central and peripheral THs sensitivity index and stroke in patients with CHD. METHODS: Between January 1, 2014, and September 30, 2020, 30,160 patients with CHD were enrolled in this study. By computing the thyroid feedback quantile index (TFQI), thyroid stimulating hormone index (TSHI), and thyrotropin thyroxine resistance index (TT4RI), the central sensitivity indexes to THs was assessed, and the ratio of serum free triiodothyronine (FT3) to serum free thyroxine (FT4) was used to assess peripheral THs sensitivity. The relationship between central and peripheral THs sensitivity index and stroke was investigated using logistic regression, especially in different types of stroke, ages, sexes, and blood glucose levels. RESULTS: Stroke risk is positive associated with TSHI, TFQI, and PTFQI. In subgroup analysis, the OR values of these relationships are higher in people younger than 65 years old, male, and diagnosed with diabetes. In addition, stroke risk was negatively associated with FT3/FT4, and the OR values of these relationships were lower in people older than 65 years, female, and diagnosed with prediabetes. CONCLUSIONS: This study demonstrates that the increase in the central THs sensitivity index and the decrease in the peripheral THs sensitivity index are associated with a higher risk of stroke in CHD patients, and provides new ideas for the assessment of stroke in patients with CHD.

Molecular transformation of dissolved organic matter in manganese ore-mediated constructed wetlands for fresh leachate treatment.

The organic matter (OM) and nitrogen in Fresh leachate (FL) from waste compression sites pose environmental and health risks. Even though the constructed wetland (CW) can efficiently remove these pollutants, the molecular-level transformations of dissolved OM (DOM) in FL remain uncertain. This study reports the molecular dynamics of DOM and nitrogen removal during FL treatment in CWs. Two lab-scale vertical-flow CW systems were employed: one using only sand as substrates (act as a control, CW-C) and the other employing an equal mixture of manganese ore powder and sand (experimental, CW-M). Over 488 days of operation, CW-M exhibited significantly higher removal rates for chemical oxygen demand (COD), ammonia nitrogen (NH4+-N), and dissolved organic matter (represented by dissolved organic carbon, DOC) at 98.2 ± 2.5%, 99.2 ± 1.4%, and 97.9 ± 1.9%, respectively, in contrast to CW-C (92.8 ± 6.8%, 77.1 ± 28.1%, and 74.7 ± 9.5%). The three-dimensional fluorescence excitation-emission matrix (3D-EEM) and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) analyses unveiled that the influent DOM was predominantly composed of readily biodegradable protein-like substances with high carbon content and low unsaturation. Throughout treatment, it led to the degradation of low O/C and high H/C compounds, resulting in the formation of DOM with higher unsaturation and aromaticity, resembling humic-like substances. CW-M showcased a distinct DOM composition, characterized by lower carbon content yet higher unsaturation and aromaticity than CW-C. The study also identified the presence of Gammaproteobacteria, reported as Mn-oxidizing bacteria with significantly higher abundance in the upper and middle layers of CW-M, facilitating manganese cycling and improving DOM removal. Key pathways contributing to DOM removal encompassed adsorption, catalytic oxidation by manganese oxides, and microbial degradation. This study offers novel insights into DOM transformation and removal from FL during CW treatment, which will facilitate better design and enhanced performance.

Examining the normality assumption of a design-comparable effect size in single-case designs.

What Works Clearinghouse (WWC, 2022) recommends a design-comparable effect size (D-CES; i.e., gAB) to gauge an intervention in single-case experimental design (SCED) studies, or to synthesize findings in meta-analysis. So far, no research has examined gAB's performance under non-normal distributions. This study expanded Pustejovsky et al. (2014) to investigate the impact of data distributions, number of cases (m), number of measurements (N), within-case reliability or intra-class correlation (ρ), ratio of variance components (λ), and autocorrelation (ϕ) on gAB in multiple-baseline (MB) design. The performance of gAB was assessed by relative bias (RB), relative bias of variance (RBV), MSE, and coverage rate of 95% CIs (CR). Findings revealed that gAB was unbiased even under non-normal distributions. gAB's variance was generally overestimated, and its 95% CI was over-covered, especially when distributions were normal or nearly normal combined with small m and N. Large imprecision of gAB occurred when m was small and ρ was large. According to the ANOVA results, data distributions contributed to approximately 49% of variance in RB and 25% of variance in both RBV and CR. m and ρ each contributed to 34% of variance in MSE. We recommend gAB for MB studies and meta-analysis with N ≥ 16 and when either (1) data distributions are normal or nearly normal, m = 6, and ρ = 0.6 or 0.8, or (2) data distributions are mildly or moderately non-normal, m ≥ 4, and ρ = 0.2, 0.4, or 0.6. The paper concludes with a discussion of gAB's applicability and design-comparability, and sound reporting practices of ES indices.

Seconds-Scale Response Sensor for In Situ Oceanic Carbon Dioxide Detection.

Research on the transient variation processes of oceanic dissolved CO2 makes significant sense because of the complexity and dynamics of the marine environment. Yet, it is inherently challenging due to the limitation of the response performance of in situ sensors. Here, we report a novel system solution capable of providing high-performance detection with a seconds-scale response, sub-ppmv level precision, and 3000 m rated depth. Through the proposed strategy, we break the limitation of the membrane on the response performance of the sensor and improve it by 2 orders of magnitude to the τ100 of 3.5 s (τ90 = 2.7 s). By taking water temperature and CO2 concentration as the tracer, we succeed in portraying the water mixing process and reveal the microstructure of the concentration variation profile. By enabling in situ detection at an unprecedented response speed, this instrument can provide new insights and prospects into the research on the carbon cycle in deep-sea unstable regions, such as hydrothermal vents and cold seeps.

Single-cell transcriptome analysis profiles cellular and molecular alterations in submandibular gland and blood in IgG4-related disease.

OBJECTIVES: The aim of this study is to profile the transcriptional landscapes of affected tissues and peripheral blood mononuclear cells (PBMCs) at the single-cell level in IgG4-related disease (IgG4-RD). Identifying the cell populations and crosstalk between immune cells and non-immune cells will assist us in understanding the aetiology of IgG4-RD. METHODS: We performed single-cell RNA sequencing analysis on submandibular glands (SMGs) and PBMCs from patients with IgG4-RD and matched controls. Additionally, bulk RNA sequencing of PBMCs was used to construct the immune repertoire. Furthermore, multiplex immunofluorescence staining was performed to validate the transcriptomic results. RESULTS: We identified three novel subsets of tissue-resident immune cells in the SMGs of patients with IgG4-RD. TOP2A_B cells and TOP2A_T cells had stemness signatures, and trajectory analysis showed that TOP2A_B cells may differentiate into IgG4+plasma cells and that TOP2A_T cells may differentiate into T follicular helper (Tfh) cells. ICOS_PD-1_B cells with Tfh-like characteristics appeared to be an intermediate state in the differentiation from B cells to IgG4+plasma cells. The cellular communication patterns within immune cells and between immune cells and non-immune cells were altered in IgG4-RD compared with controls. Consistently, infection-related pathways were shared in B cells and T cells from SMGs and PBMCs. Furthermore, immune clonotype analysis of PBMC samples showed the complementary determining region 3 amino acid CQQSYSTPYTF was expanded in patients with IgG4-RD. CONCLUSION: Our data revealed the cellular and molecular changes at the single-cell resolution of IgG4-RD and provide valuable insights into the aetiology and novel therapeutic targets of the autoimmune disease.

Real-world efficacy of belimumab in systemic lupus erythematosus: a prospective cohort from a single center in China.

OBJECTIVES: To explore the efficacy and safety of belimumab among Chinese patients with systemic lupus erythematosus (SLE) in a real-world setting. METHODS: A prospective cohort study was performed, and SLE patients taking belimumab on a background of standard-of-care (SoC) treatment were consecutively enrolled from June 2021 to December 2022. Based on baseline characteristics, patients were divided into three groups: the newly diagnosed group, the relapsed group and the refractory group. Patients in the newly diagnosed group were newly diagnosed with SLE within 4 weeks of starting belimumab. Patients in the relapse group experienced a severe flare. Refractory patients were patients with unsatisfactory glucocorticoid taper and/or disease activity control. Clinical data were collected, and disease assessments were conducted regularly. Newly diagnosed patients with SoC alone and healthy controls (HCs) were also enrolled. RESULTS: A total of 123 SLE patients were included in the analysis, with a median follow-up period of 12 months (range 3-18 months). Thirty-three out of 123 patients were newly diagnosed, 32 had relapsed disease, and 58 had refractory disease. The SRI-4 response was achieved with good tolerance by 55.77% of patients at 3 months, 56.63% at 6 months, 63.24% at 9 months, 63.64% at 12 months, and 57.14% at 18 months. Serological parameters (anti-dsDNA and C3/C4), SLEDAI-2K and daily prednisone intake were improved overall and in each group. Among the 3 groups, the newly diagnosed group had the highest SRI-4 rate as well as the greatest improvement in serological parameters and SLEDAI-2K. Compared with newly diagnosed patients with SoC alone, the cumulative prednisone intake of newly diagnosed patients taking belimumab was significantly decreased. CONCLUSION: Our data supported the efficacy of belimumab in Chinese SLE patients in a real-life setting. Our study also provided new evidence showing remarkable achievement of the SRI-4 response during belimumab treatment in newly diagnosed SLE patients.

Design of compact off-axis freeform imaging systems based on optical-digital joint optimization.

Using a freeform optical surface can effectively reduce the imaging system weight and volume while maintaining good performance and advanced system specifications. But it is still very difficult for traditional freeform surface design when ultra-small system volume or ultra-few elements are required. Considering the images generated by the system can be recovered by digital image processing, in this paper, we proposed a design method of compact and simplified off-axis freeform imaging systems using optical-digital joint design process, which fully integrates the design of a geometric freeform system and the image recovery neural network. This design method works for off-axis nonsymmetric system structure and multiple freeform surfaces with complicated surface expression. The overall design framework, ray tracing, image simulation and recovery, and loss function establishment are demonstrated. We use two design examples to show the feasibility and effect of the framework. One is a freeform three-mirror system with a much smaller volume than a traditional freeform three-mirror reference design. The other is a freeform two-mirror system whose element number is reduced compared with the three-mirror system. Ultra-compact and/or simplified freeform system structure as well as good output recovered images can be realized.

Design and fabrication method of holographic waveguide near-eye display with 2D eye box expansion.

Augmented reality near-eye display (AR-NED) technology has attracted enormous interests for its widespread potential applications. In this paper, two-dimensional (2D) holographic waveguide integrated simulation design and analysis, holographic optical elements (HOEs) exposure fabrication, prototype performance evaluation and imaging analysis are completed. In the system design, a 2D holographic waveguide AR-NED integrated with a miniature projection optical system is presented to achieve a larger 2D eye box expansion (EBE). A design method for controlling the luminance uniformity of 2D-EPE holographic waveguide by dividing the two thicknesses of HOEs is proposed, which is easy to fabricate. The optical principle and design method of the HOE-based 2D-EBE holographic waveguide are described in detail. In the system fabrication, laser exposure fabrication method of eliminating stray light for HOEs is proposed, and a prototype system is fabricated and demonstrated. The properties of the fabricated HOEs and the prototype are analyzed in detail. The experimental results verified that the 2D-EBE holographic waveguide has a diagonal field of view (FOV) of 45°, an ultra-thin thickness of 1 mm, and an eye box of 16 mm × 13 mm at an eye relief (ERF) of 18 mm, the MTF values of different FOVs at different 2D-EPE positions can be better than 0.2 at 20 lp/mm, and the whole luminance uniformity is 58%.