Development and evaluation of a human CD47/HER2 bispecific antibody for Trastuzumab-resistant breast cancer immunotherapy.

The treatment for trastuzumab-resistant breast cancer (BC) remains a challenge in clinical settings. It was known that CD47 is preferentially upregulated in HER2+ BC cells, which is correlated with drug resistance to trastuzumab. Here, we developed a novel anti-CD47/HER2 bispecific antibody (BsAb) against trastuzumab-resistant BC, named IMM2902. IMM2902 demonstrated high binding affinity, blocking activity, antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and internalization degradation effects against both trastuzumab-sensitive and trastuzumab-resistant BC cells in vitro. The in vivo experimental data indicated that IMM2902 was more effective than their respective controls in inhibiting tumor growth in a trastuzumab-sensitive BT474 mouse model, a trastuzumab-resistant HCC1954 mouse model, two trastuzumab-resistant patient-derived xenograft (PDX) mouse models and a cord blood (CB)-humanized HCC1954 mouse model. Through spatial transcriptome assays, multiplex immunofluorescence (mIFC) and in vitro assays, our findings provided evidence that IMM2902 effectively stimulates macrophages to generate C-X-C motif chemokine ligand (CXCL) 9 and CXCL10, thereby facilitating the recruitment of T cells and NK cells to the tumor site. Moreover, IMM2902 demonstrated a high safety profile regarding anemia and non-specific cytokines release. Collectively, our results highlighted a novel therapeutic approach for the treatment of HER2+ BCs and this approach exhibits significant anti-tumor efficacy without causing off-target toxicity in trastuzumab-resistant BC cells.

Multiple small-dose infusions of G-CSF-mobilized haploidentical lymphocytes after autologous haematopoietic stem cell transplantation for acute myeloid leukaemia.

This retrospective study analysed 106 acute myeloid leukaemia (AML) patients undergoing autologous haematopoietic stem cell transplantation (ASCT) to assess the impact of multiple small-dose infusions of granulocyte-colony-stimulating factor (G-CSF)-mobilized haploidentical lymphocytes as post-ASCT maintenance therapy. Among them, 50 patients received lymphocyte maintenance therapy, 21 received alternative maintenance therapy, and 35 received no maintenance therapy. Patients receiving lymphocyte maintenance therapy demonstrated significantly higher overall survival (OS) and disease-free survival (DFS) compared to those without maintenance therapy, with 4-year OS and DFS rates notably elevated. While there were no significant differences in recurrence rates among the three groups, lymphocyte maintenance therapy showcased particular benefits for intermediate-risk AML patients, yielding significantly higher OS and DFS rates and lower relapse rates compared to alternative maintenance therapy and no maintenance therapy. The study suggests that multiple small-dose infusions of G-CSF-mobilized haploidentical lymphocytes may offer promising outcomes for AML patients after ASCT, particularly for those classified as intermediate-risk. These findings underscore the potential efficacy of lymphocyte maintenance therapy in reducing disease relapse and improving long-term prognosis in this patient population.

Genome-wide characterization of DNA methyltransferase family genes implies GhDMT6 improving tolerance of salt and drought on cotton.

BACKGROUND: DNA methylation is an important epigenetic mode of genomic DNA modification and plays a vital role in maintaining epigenetic content and regulating gene expression. Cytosine-5 DNA methyltransferase (C5-MTase) are the key enzymes in the process of DNA methylation. However, there is no systematic analysis of the C5-MTase in cotton so far, and the function of DNMT2 genes has not been studied. METHODS: In this study, the whole genome of cotton C5-MTase coding genes was identified and analyzed using a bioinformatics method based on information from the cotton genome, and the function of GhDMT6 was further validated by VIGS experiments and subcellular localization analysis. RESULTS: 33 C5-MTases were identified from three cotton genomes, and were divided into four subfamilies by systematic evolutionary analysis. After the protein domain alignment of C5-MTases in cotton, 6 highly conserved motifs were found in the C-terminus of 33 proteins involved in methylation modification, which indicated that C5-MTases had a basic catalytic methylation function. These proteins were divided into four classes based on the N-terminal difference, of which DNMT2 lacks the N-terminal regulatory domain. The expression of C5-MTases in different parts of cotton was different under different stress treatments, which indicated the functional diversity of cotton C5-MTase gene family. Among the C5-MTases, the GhDMT6 had a obvious up-regulated expression. After silencing GhDMT6 with VIGS, the phenotype of cotton seedlings under different stress treatments showed a significant difference. Compared with cotton seedlings that did not silence GhDMT6, cotton seedlings silencing GhDMT6 showed significant stress resistance. CONCLUSION: The results show that C5-MTases plays an important role in cotton stress response, which is beneficial to further explore the function of DNMT2 subfamily genes.

FLOURY ENDOSPERM24, a heat shock protein 101 (HSP101), is required for starch biosynthesis and endosperm development in rice.

Endosperm is the main storage organ in cereal grain and determines grain yield and quality. The molecular mechanisms of heat shock proteins in regulating starch biosynthesis and endosperm development remain obscure. Here, we report a rice floury endosperm mutant flo24 that develops abnormal starch grains in the central starchy endosperm cells. Map-based cloning and complementation test showed that FLO24 encodes a heat shock protein HSP101, which is localized in plastids. The mutated protein FLO24T296I dramatically lost its ability to hydrolyze ATP and to rescue the thermotolerance defects of the yeast hsp104 mutant. The flo24 mutant develops more severe floury endosperm when grown under high-temperature conditions than normal conditions. And the FLO24 protein was dramatically induced at high temperature. FLO24 physically interacts with several key enzymes required for starch biosynthesis, including AGPL1, AGPL3 and PHO1. Combined biochemical and genetic evidence suggests that FLO24 acts cooperatively with HSP70cp-2 to regulate starch biosynthesis and endosperm development in rice. Our results reveal that FLO24 acts as an important regulator of endosperm development, which might function in maintaining the activities of enzymes involved in starch biosynthesis in rice.

A deleterious Sar1c variant in rice inhibits export of seed storage proteins from the endoplasmic reticulum.

KEY MESSAGE: We identified a dosage-dependent dominant negative form of Sar1c, which confirms the essential role of COPII system in mediating ER export of storage proteins in rice endosperm. Higher plants accumlate large amounts of seed storage proteins (SSPs). However, mechanisms underlying SSP trafficking are largely unknown, especially the ER-Golgi anterograde process. Here, we showed that a rice glutelin precursor accumulation13 (gpa13) mutant exhibited floury endosperm and overaccumulated glutelin precursors, which phenocopied the reported RNAi-Sar1abc line. Molecular cloning revealed that the gpa13 allele encodes a mutated Sar1c (mSar1c) with a deletion of two conserved amino acids Pro134 and Try135. Knockdown or knockout of Sar1c alone caused no obvious phenotype, while overexpression of mSar1c resulted in seedling lethality similar to the gpa13 mutant. Transient expression experiment in tobacco combined with subcellular fractionation experiment in gpa13 demonstrated that the expression of mSar1c affects the subcellular distribution of all Sar1 isoforms and Sec23c. In addition, mSar1c failed to interact with COPII component Sec23. Conversely, mSar1c competed with Sar1a/b/d to interact with guanine nucleotide exchange factor Sec12. Together, we identified a dosage-dependent dominant negative form of Sar1c, which confirms the essential role of COPII system in mediating ER export of storage proteins in rice endosperm.

Reduced-dose post-transplant cyclophosphamide plus low-dose post-transplant anti-thymocyte globulin as graft-versus-host disease prophylaxis with fludarabine-busulfan-cytarabine conditioning in haploidentical peripheral blood stem cell transplantation: A multicentre, randomized controlled clinical trial.

Anti-thymocyte globulin (ATG) or post-transplant cyclophosphamide (PTCy)-based regimens are widely used for graft-versus-host disease (GVHD) prophylaxis in haploidentical haematopoietic stem cell transplantation (haplo-HSCT). To improve the effectiveness of GVHD prophylaxis in haploidentical peripheral blood stem cell transplantation (haplo-PBSCT), we conducted a multicentre, randomized clinical trial to determine the efficacy of reduced-dose PTCy (40 mg/kg/d on days 3 and 4) combined with low-dose post-transplant ATG (2.5 mg/kg on day 8)-based GVHD prophylaxis (reduced-dose PTCy/ATG) with fludarabine-busulfan-cytarabine (FBA) conditioning for patients with haematological malignancies. From 2018 to 2022, 122 patients from four institutions were randomly assigned 1:1 to either a reduced-dose PTCy/ATG or a standard-dose ATG group ('Beijing Protocol', ATG: 10 mg/kg). All patients achieved myeloid engraftment. Cumulative incidences of grade II-IV (11.5% vs 39.3%, p = 0.001) and grade III-IV (6.6% vs 24.6%, p = 0.014) acute GVHD at day 100 were significantly reduced in the reduced-dose PTCy/ATG group. Furthermore, two-year overall survival, disease-free survival and GVHD-free/relapse-free survival were significantly improved in the reduced-dose PTCy/ATG group (75.4% vs 54.1%, p = 0.021; 72.7% vs 55.0%, p = 0.044; 61.3% vs 42.3%, p = 0.022 respectively). Our results demonstrate that the addition of low-dose ATG to reduced-dose PTCy with FBA conditioning is a promising strategy in haplo-PBSCT.

GPA5 Encodes a Rab5a Effector Required for Post-Golgi Trafficking of Rice Storage Proteins.

Dense vesicles (DVs) are vesicular carriers, unique to plants, that mediate post-Golgi trafficking of storage proteins to protein storage vacuoles (PSVs) in seeds. However, the molecular mechanisms regulating the directional targeting of DVs to PSVs remain elusive. Here, we show that the rice (Oryza sativa) glutelin precursor accumulation5 (gpa5) mutant is defective in directional targeting of DVs to PSVs, resulting in discharge of its cargo proteins into the extracellular space. Molecular cloning revealed that GPA5 encodes a plant-unique phox-homology domain-containing protein homologous to Arabidopsis (Arabidopsis thaliana) ENDOSOMAL RAB EFFECTOR WITH PX-DOMAIN. We show that GPA5 is a membrane-associated protein capable of forming homodimers and that it is specifically localized to DVs in developing endosperm. Colocalization, biochemical, and genetic evidence demonstrates that GPA5 acts in concert with Rab5a and VPS9a to regulate DV-mediated post-Golgi trafficking to PSVs. Furthermore, we demonstrated that GPA5 physically interacts with a class C core vacuole/endosome tethering complex and a seed plant-specific VAMP727-containing R-soluble N-ethylmaleimide sensitive factor attachment protein receptor complex. Collectively, our results suggest that GPA5 functions as a plant-specific effector of Rab5a required for mediating tethering and membrane fusion of DVs with PSVs in rice endosperm.

Advances in the study of CD47-based bispecific antibody in cancer immunotherapy.

Tumour therapy has entered the era of immunotherapy. Monoclonal antibodies (mAb), immune checkpoint inhibitors, chimeric antigen receptor T-cell (CAR-T), cytokine-induced killer (CIK), tumour-infiltrating lymphocytes (TILs) and other cellular immunotherapies have become the focus of current research. The CD47/SIRPα target is becoming another popular tumour immunotherapy target following the PDCD1/CD247(PD1/PD-L1) checkpoint inhibitor. In recent years, a large number of CD47/SIRPα mAbs, fusion proteins, and CD47/SIRPα-based bispecific antibodies (BsAbs) are undergoing preclinical and clinical trials and have good curative effects in the treatment of haematological tumours and solid tumours. They bring new vitality and hope for the treatment of patients with advanced tumours. This review summarizes the research progress of CD47/SIRPα-based BsAbs with different targets for tumour treatment. There are 12 and 9 BsAbs in clinical trials and pre-clinical research, respectively. We report on the mechanism of 15 BsAb molecules with different target and analyse the efficacy and safety of preclinical and clinical trials, discuss the issues that may be faced in the development of CD47-based BsAbs, and dual-target molecules, and summarize their development prospects. This review provides a reference for the safety and effectiveness of BsAbs in clinical application and in the future development of antibodies.

Post-Golgi trafficking of rice storage proteins requires the small GTPase Rab7 activation complex MON1-CCZ1.

Protein storage vacuoles (PSVs) are unique organelles that accumulate storage proteins in plant seeds. Although morphological evidence points to the existence of multiple PSV-trafficking pathways for storage protein targeting, the molecular mechanisms that regulate these processes remain mostly unknown. Here, we report the functional characterization of the rice (Oryza sativa) glutelin precursor accumulation7 (gpa7) mutant, which over-accumulates 57-kDa glutelin precursors in dry seeds. Cytological and immunocytochemistry studies revealed that the gpa7 mutant exhibits abnormal accumulation of storage prevacuolar compartment-like structures, accompanied by the partial mistargeting of glutelins to the extracellular space. The gpa7 mutant was altered in the CCZ1 locus, which encodes the rice homolog of Arabidopsis (Arabidopsis thaliana) CALCIUM CAFFEINE ZINC SENSITIVITY1a (CCZ1a) and CCZ1b. Biochemical evidence showed that rice CCZ1 interacts with MONENSIN SENSITIVITY1 (MON1) and that these proteins function together as the Rat brain 5 (Rab5) effector and the Rab7 guanine nucleotide exchange factor (GEF). Notably, loss of CCZ1 function promoted the endosomal localization of vacuolar protein sorting-associated protein 9 (VPS9), which is the GEF for Rab5 in plants. Together, our results indicate that the MON1-CCZ1 complex is involved in post-Golgi trafficking of rice storage protein through a Rab5- and Rab7-dependent pathway.

The protein 4.1R downregulates VEGFA in M2 macrophages to inhibit colon cancer metastasis.

M2 macrophages are crucial components of the tumour microenvironment and have been shown to be closely related to tumour progression. Co-culture with 4.1R-/- M2 macrophages enhances the malignancy of colon cancer (CC), but the mechanism remains unclear. Here, we report that protein 4.1R knockout reduced the phagocytosis of M2 macrophages (M-CSF/IL-4-treated bone marrow cells) and promoted MC38 colon cancer cell proliferation, migration, invasion, tumour formation and epithelial-mesenchymal transition (EMT), which are regulated by M2 macrophages. Further mechanistic dissection revealed that the 4.1R knockout upregulated vascular endothelial growth factor A (VEGFA) secreted by M2 macrophages and promoted colon cancer progression by activating the PI3K/AKT signalling pathway. In summary, our present study identified that 4.1R downregulates VEGFA secretion in M2 macrophages and delays the malignant potential of colon cancer by inhibiting the PI3K/AKT signalling pathway.

Research progress on exosomes derived from mesenchymal stem cells in hematological malignancies.

Mesenchymal stem cells (MSCs) are a subset of multifunctional stem cells with self-renewal and multidirectional differentiation properties that play a pivotal role in tumor progression. MSCs are reported to exert biological functions by secreting specialized vesicles, known as exosomes, with tumor cells. Exosomes participate in material and information exchange between cells and are crucial in multiple physiological and pathological processes. This study provides a comprehensive overview of the roles, mechanisms of action and sources of MSC exosomes in hematological malignancies, and different tumor types.

Genome-wide identification and expression analysis of PUB genes in cotton.

BACKGROUND: The U-box gene encodes a ubiquitin ligase that contain U-box domain. The plant U-box gene (PUB) plays an important role in the response to stresses, but few reports about PUBs in cotton were available. Therefore research on PUBs is of great importance and a necessity when studying the mechanisms of stress- tolerance in cotton. RESULTS: In this study, we identified 93, 96, 185 and 208 PUBs from four sequenced cotton species G. raimondii (D5), G. arboreum (A2), G. hirsutum (AD1) and G. barbadense (AD2), respectively. Prediction analysis of subcellular localization showed that the PUBs in cotton were widely localized in cells, but primarily in the nucleus. The PUBs in cotton were classified into six subfamilies (A-F) on the basis of phylogenetic analysis, which was testified by the analysis of conserved motifs and exon-intron structures. Chromosomal localization analysis showed that cotton PUBs were unevenly anchored on all chromosomes, varying from 1 to 14 per chromosome. Through multiple sequence alignment analysis, 3 tandem duplications and 28 segmental duplications in cotton genome D5, 2 tandem duplications and 25 segmental duplications in A2, and 143 homologous gene pairs in A2 and D5 were found; however no tandem duplications in A2 or D5 were found. Additionally, 105, 14 and 17 homologous gene pairs were found in the intra-subgenome of At and Dt, At sub-genome and Dt sub-genome of G. hirsutum, respectively. Functional analysis of GhPUB85A and GhPUB45D showed that these genes positively responded to abiotic stresses, but the expression patterns were different. In addition, although the expression levels of these two homologous genes were similar, their contributions were different when responding to stresses, specifically showing different responses to abiotic stresses and functional differences between the two subgenomes of G. hirsutum. CONCLUSIONS: This study reported the genome-wide identification, structure, evolution and expression analysis of PUBs in cotton, and the results showed that the PUBs were highly conserved throughout the evolutionary history of cotton. All PUB genes were involved in the response to abiotic stresses (including salt, drought, hot and cold) to varying degrees.

Resequencing of cv CRI-12 family reveals haplotype block inheritance and recombination of agronomically important genes in artificial selection.

Although efforts have been taken to exploit diversity for yield and quality improvements, limited progress on using beneficial alleles in domesticated and undomesticated cotton varieties is limited. Given the complexity and limited amount of genomic information since the completion of four cotton genomes, characterizing significant variations and haplotype block inheritance under artificial selection has been challenging. Here we sequenced Gossypium hirsutum L. cv CRI-12 (the cotton variety with the largest acreage in China), its parental cultivars, and progeny cultivars, which were bred by the different institutes in China. In total, 3.3 million SNPs were identified and 118, 126 and 176 genes were remarkably correlated with Verticillium wilt, salinity and drought tolerance in CRI-12, respectively. Transcriptome-wide analyses of gene expression, and functional annotations, have provided support for the identification of genes tied to these tolerances. We totally discovered 58 116 haplotype blocks, among which 23 752 may be inherited and 1029 may be recombined under artificial selection. This survey of genetic diversity identified loci that may have been subject to artificial selection and documented the haplotype block inheritance and recombination, shedding light on the genetic mechanism of artificial selection and guiding breeding efforts for the genetic improvement of cotton.

Retrospective analysis of the efficacy and influencing factors of autologous hematopoietic stem cell transplantation for multiple myeloma.

This study aims to review the clinical efficacy and factors affecting the treatment of multiple myeloma (MM) by autologous hematopoietic stem cell transplantation (ASCT). The clinical data of 47 patients with MM from the Department of Hematology of Henan Cancer Hospital from September 2010 to July 2018 were retrospectively analyzed. At pre-transplantation of autologous cells, 25.5% were in complete remission (CR), 14.9% were in very good partial remission (VGPR) and 59.6% were in partial remission (PR). Among these cases, one case had PR after three recurrences. At post-transplantation, 51% were in CR, including two cases who received double transplantations, 27.7% were in VGPR, and 21.3% were in PR. The median follow-up time was 27.6 months (4-96 months). The 3-year progression free survival (PFS) and overall survival (OS) were 47.9% and 79.6%, respectively. The Analysis of variance (ANOVA) results revealed that factors that affected OS were international staging system (ISS) stage (P = 0.002), CR and VGPR post-transplantation (P = 0.002), while factors that affected PFS were ISS stage (P = 0.005), pre-transplant induction therapy (P = 0.032), and disease risk stratification (P = 0.017). The curative effects for PFS were CR and VGPR pre-transplantation (P = 0.013) and post-transplantation (P = 0.011). The Cox multivariate regression analysis revealed that ISS stage and CR and VGPR post-transplantation were independent prognostic factors of OS. At post-transplantation, CR and VGPR, ISS stage, and pre-transplant induction therapy were independent prognostic factors for PFS. In conclusion, ASCT can improve the clinical efficacy and survival rate of MM patients. ISS stage, CR and VGPR post-transplantation are independent prognostic factors of OS and PFS, while pre-transplant induction therapy is an independent prognostic factor for PFS.

WD40-REPEAT 5a functions in drought stress tolerance by regulating nitric oxide accumulation in Arabidopsis.

Nitric oxide (NO) generation by NO synthase (NOS) in guard cells plays a vital role in stomatal closure for adaptive plant response to drought stress. However, the mechanism underlying the regulation of NOS activity in plants is unclear. Here, by screening yeast deletion mutants with decreased NO accumulation and NOS-like activity when subjected to H2 O2 stress, we identified TUP1 as a novel regulator of NOS-like activity in yeast. Arabidopsis WD40-REPEAT 5a (WDR5a), a homolog of yeast TUP1, complemented H2 O2 -induced NO accumulation of a yeast mutant Δtup1, suggesting the conserved role of WDR5a in regulating NO accumulation and NOS-like activity. This note was further confirmed by using an Arabidopsis RNAi line wdr5a-1 and two T-DNA insertion mutants of WDR5a with reduced WDR5a expression, in which both H2 O2 -induced NO accumulation and stomatal closure were repressed. This was because H2 O2 -induced NOS-like activity was inhibited in the mutants compared with that of the wild type. Furthermore, these wdr5a mutants were more sensitive to drought stress as they had reduced stomatal closure and decreased expression of drought-related genes. Together, our results revealed that WDR5a functions as a novel factor to modulate NOS-like activity for changes of NO accumulation and stomatal closure in drought stress tolerance.

CATALASE2 functions for seedling postgerminative growth by scavenging H2 O2 and stimulating ACX2/3 activity in Arabidopsis.

Increased fatty acid ß-oxidation is essential for early postgerminative growth in seedlings, but high levels of H2 O2 produced by ß-oxidation can induce oxidative stress. Whether and how catalase (CAT) functions in fine-tuning H2 O2 homeostasis during seedling growth remain unclear. Here, we report that CAT2 functions in early seedling growth. Compared to the wild type, the cat2-1 mutant, with elevated H2 O2 levels, exhibited reduced root elongation on sucrose (Suc)-free medium, mimicking soils without exogenous sugar supply. Treatment with the H2 O2 scavenger potassium iodide rescued the mutant phenotype of cat2-1. In contrast to the wild type, the cat2-1 mutant was insensitive to the CAT inhibitor 3-amino-1,2,4-triazole in terms of root elongation when grown on Suc-free medium, suggesting that CAT2 modulates early seedling growth by altering H2 O2 accumulation. Furthermore, like cat2-1, the acyl-CoA oxidase (ACX) double mutant acx2-1 acx3-6 showed repressed root elongation, suggesting that CAT2 functions in early seedling growth by regulating ACX activity, as this activity was inhibited in cat2-1. Indeed, decreased ACX activity and short root of cat2-1 seedlings grown on Suc-free medium were rescued by overexpressing ACX3. Together, these findings suggest that CAT2 functions in early seedling growth by scavenging H2 O2 and stimulating ACX2/3 activity.

Hydrogen peroxide sulfenylates and inhibits the photorespiratory enzyme PGLP1 to modulate plant thermotolerance.

Climate change is resulting in more frequent and rapidly changing temperatures at both extremes that severely affect the growth and production of plants, particularly crops. Oxidative stress caused by high temperatures is one of the most damaging factors for plants. However, the role of hydrogen peroxide (H2O2) in modulating plant thermotolerance is largely unknown, and the regulation of photorespiration essential for C3 species remains to be fully clarified. Here, we report that heat stress promotes H2O2 accumulation in chloroplasts and that H2O2 stimulates sulfenylation of the chloroplast-localized photorespiratory enzyme 2-phosphoglycolate phosphatase 1 (PGLP1) at cysteine 86, inhibiting its activity and promoting the accumulation of the toxic metabolite 2-phosphoglycolate. We also demonstrate that PGLP1 has a positive function in plant thermotolerance, as PGLP1 antisense lines have greater heat sensitivity and PGLP1-overexpressing plants have higher heat-stress tolerance than the wild type. Together, our results demonstrate that heat-induced H2O2 in chloroplasts sulfenylates and inhibits PGLP1 to modulate plant thermotolerance. Furthermore, targeting CATALASE2 to chloroplasts can largely prevent the heat-induced overaccumulation of H2O2 and the sulfenylation of PGLP1, thus conferring thermotolerance without a plant growth penalty. These findings reveal that heat-induced H2O2 in chloroplasts is important for heat-caused plant damage.

Rashba Metamaterials and Metasurfaces with Zero Reflectivity and Effect of Surface States in Ultrathin Metal Films.

Metals, renowned for their high reflectivity, find extensive use in various technological applications, from mirrors to optical coatings in radars, telescopes, and mobile communications. However, their potential in antireflective coatings has remained largely untapped. In this study, we demonstrate that by applying an ultrathin metallic film onto an oxide layer, we can achieve a flawless optical surface with zero reflectivity. This phenomenon has been successfully observed across various metals, including Sn, Ag, Au, Pt, Bi, and Nb, showcasing its broad applicability. The underlying principle lies in the emergence of surface states, where the Rashba effect is strong, which give rise to the formation of Rashba metamaterial and metasurface (RMM) structures. Remarkably, these RMMs can be fine-tuned to act as high-resolution Veselago lenses. To illustrate, we achieved zero reflectivity with an RMM consisting of a 1 nm thick Sn metal film on a 1 nm Ge buffer, situated on a 60 nm Al2O3/Si substrate. Similar results were observed for other metals (Pt, Au, Ag, and Nb) and semimetals (Bi) by adjusting the film thickness to 2, 3, 5, 10, and 6 nm, respectively. The revelation of RMMs with zero reflectivity (R = 0) has tremendous potential to revolutionize optical device technologies, covering renewable energy, optoelectronics, and the telecommunications industry.

Effect of T1 Slope on Disappearance of Cervical Lordosis after Posterior Cervical Double-Door Laminoplasty Based on Medical Informatics.

Cervical sagittal balance plays a pivotal role in spine surgeries as it has a significant impact on the clinical outcomes in cervical spine surgery. Image processing techniques have significantly improved the accuracy and precision of cervical surgical techniques. This study aims to investigate the effects of T1 slope (T1s) on the disappearance of cervical lordosis after posterior cervical double-door laminoplasty using medical informatics and radiographic measures. To do so, we determined and measured the loss of T1s and cervical lordosis during the postoperative follow-up period in patients with double-door posterior cervical laminoplasty. Patients (n = 40) who underwent posterior cervical double-door laminoplasty participated in this study. For all patients, the difference between the preoperative T1s (angle between the upper edge of T1 and the horizontal line) and preoperative and postoperative cervical lordosis (Cobb method) was estimated, and the linear relationship between the two was statistically analyzed to observe the influence of preoperative T1s on postoperative cervical lordosis disappearance. The average preoperative T1s was 23.54°, and the average preoperative cervical lordosis angle was 8.50°. After 1-20 months of follow-up (mean = 9.53 months), the average postoperative cervical lordosis was 8.50°, and the average loss of cervical lordosis was 0.22°. Twenty cases had different degrees of lordosis angle loss after the operation, with an average loss of 9.31°. All patients were divided into groups A and B, according to a mean value of T1s = 23.54°, of which T1S > 23.54° was group A and T1s < 23.54 was group B. Cervical lordosis was quantified by the C2-C7 Cobb angle. The Cobb angle difference of cervical lordosis was measured before and after the operation, and its correlation with preoperative T1s was assessed. The preoperative Cobb angle and cervical curvature changes in the two groups were statistically compared, and the difference between the two groups was statistically significant (p < 0.05). The group with a T1s > 23.54° had greater loss of preoperative Cobb angle and cervical curvature. In group A, the mean preoperative cervical disability index (NDI) was 32.4 ± 3.4, and the mean postoperative NDI score was 16.5 ± 2.1. The mean preoperative VAS scores of neck pain and neck pain were 5.41 ± 1.1 and 5.55 ± 0.3, respectively, and the improvement in neck pain was -0.2%. The mean preoperative NDI in group B was 30.1 ± 2.9, and the mean postoperative NDI score was 11.5 ± 3.1. The mean VAS score for preoperative neck pain was 5.11 ± 1.2, that for postoperative neck pain was 4.18 ± 0.7, and that for neck pain improved by 18%. There was a significant difference between the two groups (p < 0.05). The disappearance of cervical lordosis after posterior cervical double-door laminoplasty is an important cause of postoperative cervical spine pain. The T1s is meaningful for predicting the loss of postoperative curvature in patients undergoing posterior cervical double-door laminoplasty. This is especially true for patients with good preoperative cervical curvature without ankylosis and kyphosis but with a wide T1s.