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.

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.

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.

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.

Selection of hematopoietic stem cell transplantation for T-cell lymphoblastic lymphoma.

Background: Hematopoietic stem cell transplantation (HSCT) is an important treatment for T-cell lymphoblastic lymphoma/leukemia (T-LBL). To compare the efficacy and influencing factors of autologous hematopoietic stem cell transplantation (auto-HSCT) with those of allogeneic hematopoietic stem cell transplantation (allo-HSCT) from different donors for the treatment of T-cell lymphoblastic lymphoma/leukemia (T-LBL) and provide a basis for selection of appropriate transplant methods and donors. Methods: To provide evidence of appropriate transplant methods for these patients, we retrospectively summarized the clinical characteristics of 75 T-LBL patients receiving HSCT at Henan Cancer Hospital between March 2012 and October 2021. Overall survival (OS), progression-free survival (PFS), cumulative incidence of relapse (CIR), non-relapse mortality (NRM), and related factors affecting efficacy were analyzed. Results: The 3-year CIR (39.9% vs 31.1%, P=0.745), 3-year PFS (60.1% vs 49.6%, P=0.434), and 3-year OS (62.8% vs 53.0%, P=0.450) were not significantly different between the auto-HSCT and allo-HSCT groups. However, the 3-year NRM was significantly higher in the allo-HSCT group (0% vs 27.2%, P=0.033). Multivariate analysis showed that the first complete remission (CR1) after HSCT was an independent influencing factor of higher OS (HR=2.498, P=0.029) and PFS (HR=2.576, P=0.016). The absence of mediastinal invasion in patients receiving HSCT was an independent influencing factor of better PFS (HR=2.977, P=0.029) and lower CIR (HR=4.040, P=0.027). With respect to the impact of donor source, the NRM in the unrelated donor (URD) and haploid donor (HPD) groups was significantly higher than that in the auto-HSCT group (P=0.021 and P=0.003, respectively), while there was no significant difference between matched sibling donors (MSD) and auto-HSCT. Compared with the MSD-HSCT group, the auto-HSCT group showed an increasing trend in 3-year CIR (39.9 ± 11.1% vs 32.6 ± 11.2%, P=0.697) and a lower trend in 3-year OS (62.8 ± 11.4% vs 64.4 ± 12.2%, P=0.929). Conclusions: HSCT is an effective consolidation treatment option for patients with T-LBL without mediastinal invasion and with CR1 before transplantation. For CR1 patients, auto-HSCT and MSD-HSCT are effective modalities for improving survival. In non-CR1 patients without an MSD, matched unrelated donors and haploidentical donor transplantations are the best treatment options to reduce relapse and improve prognosis.

Identification of potential resistance mechanisms and therapeutic targets for the relapse of BCMA CAR-T therapy in relapsed/refractory multiple myeloma through single-cell sequencing.

BACKGROUND: BCMA CAR-T is highly effective for relapsed/refractory multiple myeloma(R/R-MM) and significantly improves the survival of patients. However, the short remission time and high relapse rate of MM patients treated with BCMA CAR-T remain bottlenecks that limit long-term survival. The immune microenvironment of the bone marrow (BM) in R/R-MM may be responsible for this. The present study aims to present an in-depth analysis of resistant mechanisms and to explore potential novel therapeutic targets for relapse of BCMA CAR-T treatment via single-cell RNA sequencing (scRNA-seq) of BM plasma cells and immune cells. METHODS: This study used 10X Genomic scRNA-seq to identify cell populations in R/R-MM CD45+ BM cells before BCMA CAR-T treatment and relapse after BCMA CAR-T treatment. Cell Ranger pipeline and CellChat were used to perform detailed analysis. RESULTS: We compared the heterogeneity of CD45+ BM cells before BCMA CAR-T treatment and relapse after BCMA CAR-T treatment. We found that the proportion of monocytes/macrophages increased, while the percentage of T cells decreased at relapse after BCMA CAR-T treatment. We then reclustered and analyzed the alterations in plasma cells, T cells, NK cells, DCs, neutrophils, and monocytes/macrophages in the BM microenvironment before BCMA CAR-T treatment and relapse after BCMA CAR-T treatment. We show here that the percentage of BCMA positive plasma cells increased at relapse after BCMA CAR-T cell therapy. Other targets such as CD38, CD24, SLAMF7, CD138, and GPRC5D were also found to be expressed in plasma cells of the R/R-MM patient at relapse after BCMA CAR-T cell therapy. Furthermore, exhausted T cells, TIGIT+NK cells, interferon-responsive DCs, and interferon-responsive neutrophils, increased in the R/R-MM patient at relapse after BCMA CAR-T cell treatment. Significantly, the proportion of IL1ßhi Mφ, S100A9hi Mφ, interferon-responsive Mφ, CD16hi Mφ, MARCO hi Mφ, and S100A11hi Mφ significantly increased in the R/R-MM patient at relapse after BCMA CAR-T cell therapy. Cell-cell communication analysis indicated that monocytes/macrophages, especially the MIF and APRIL signaling pathway are key players in R/R-MM patient at relapse after BCMA CAR-T cell therapy. CONCLUSION: Taken together, our data extend the understanding of intrinsic and extrinsic relapse of BCMA CAR-T treatment in R/R-MM patient and the potential mechanisms involved in the alterations of antigens and the induced immunosuppressive microenvironment, which may provide a basis for the optimization of BCMA CAR-T strategies. Further studies should be performed to confirm these findings.

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.

Effects of antibacterial peptide-producing Bacillus subtilis, gallic acid, and cellulase on fermentation quality and bacterial community of whole-plant corn silage.

In the current study, we assessed the effects of antibacterial peptide-producing Bacillus subtilis (BS), gallic acid (GA) and cellulase (CL) on the fermentation quality and bacterial community of various varieties of whole-plant corn silage. Three different varieties of whole-plant corn (Yuqing386, Enxiai298, and Nonghe35) were treated with 0.02% BS (fresh material basis), 0.2% GA (fresh material basis) and 0.02% CL (fresh material basis), after which 45 days of anaerobic fermentation were conducted. With the exception of its low dry matter content, the results showed that Yuqing386's crude protein, water-soluble carbohydrate, and lactic acid contents were significantly higher than those of the other two corn varieties. However, its acid detergent fiber and cellulose contents were significantly lower than those of the other two corn varieties. Among the three corn variety silages, Yuqing386 had the highest relative abundance of Lactobacillus at the genus level and the biggest relative abundance of Firmicutes at the phylum level. In addition, the three additives markedly enhanced the quantity of dry matter and crude protein as compared to the control group. The application of GA considerably decreased the level of neutral detergent fiber while significantly increasing the content of lactic acid and water-soluble carbohydrates. Even though all additives enhanced the structure of the bacterial community following silage, the GA group experienced the greatest enhancement. On a phylum and genus level, the GA group contains the highest relative abundance of Firmicutes and Lactobacillus, respectively. Overall, of the three corn varieties, Yuqing386 provides the best silage qualities. GA has the biggest impact among the additions employed in this experiment to enhance the nutritional preservation and fermentation quality of whole-plant corn silage.

Comparing the application of mNGS after combined pneumonia in hematologic patients receiving hematopoietic stem cell transplantation and chemotherapy: A retrospective analysis.

Rapid and accurate pathogen identification is essential for timely and effective treatment of pneumonia. Here, we describe the use of metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage (BALF) fluid to identify pathogens in patients with hematologic comorbid respiratory symptoms in a retrospective study with 84 patients. In the transplantation group, 8 cases (19.5%) and 47 cases (97.9%) were positive for BALF by conventional method detection and mNGS detection, respectively, and 6 cases (14.0%) and 41 cases (91.1%) in chemotherapy group, respectively. The detection rate of mNGS in both groups was significantly higher than that of conventional detection methods (all P<0.05). Pseudomonas aeruginosa and Streptococcus pneumoniae were the most common bacterial infections in the transplantation and chemotherapy groups, respectively. Aspergillus was the most common fungal infection in both groups. Human betaherpesvirus 5 (HHV-5), torque teno virus and human betaherpesvirus 7 (HHV-7) were the most common pathogen species in both groups. The most common type of infection in patients in the transplantation and chemotherapy groups was the mixed infection of bacteria-virus. Most patients in the transplantation group had mixed infections based on multiple viruses, with 42 cases of viral infections in the transplantation group and 30 cases of viral infections in the chemotherapy group, which were significantly higher in the transplantation group than in the chemotherapy group (χ2 = 5.766, P=0.016). and the mixed infection of virus-virus in the transplantation group was significantly higher than that in the chemotherapy group (27.1% vs 4.4%, P=0.003). The proportion of death due to pulmonary infection was significantly higher in the transplantation group than in the chemotherapy group (76.9% vs 16.7%, χ2 = 9.077, P=0.003). This study demonstrated the value of mNGS of BALF in improving the diagnosis and prognosis of hematologic comorbid pneumonia, helping patients to obtain timely and effective treatment, and giving guidance on the overall treatment plan for patients, with particular benefit for patients with hematologic chemotherapy comorbid pneumonia.

A plastid-targeted heat shock cognate 70-kDa protein confers osmotic stress tolerance by enhancing ROS scavenging capability.

Osmotic stress severely affects plant growth and development, resulting in massive loss of crop quality and quantity worldwide. The 70-kDa heat shock proteins (HSP70s) are highly conserved molecular chaperones that play essential roles in cellular processes including abiotic stress responses. However, whether and how plastid-targeted heat shock cognate 70 kDa protein (cpHSC70-1) participates in plant osmotic stress response remain elusive. Here, we report that the expression of cpHSC70-1 is significantly induced upon osmotic stress treatment. Phenotypic analyses reveal that the plants with cpHSC70-1 deficiency are sensitive to osmotic stress and the plants overexpressing cpHSC70-1 exhibit enhanced tolerance to osmotic stress. Consistently, the expression of the stress-responsive genes is lower in cphsc70-1 mutant but higher in 35S:: cpHSC70-1 lines than that in wild-type plants when challenged with osmotic stress. Further, the cphsc70-1 plants have less APX and SOD activity, and thus more ROS accumulation than the wild type when treated with mannitol, but the opposite is observed in the overexpression lines. Overall, our data reveal that cpHSC70-1 is induced and functions positively in plant response to osmotic stress by promoting the expression of the stress-responsive genes and reducing ROS accumulation.

Photon Drag Currents and Terahertz Generation in α-Sn/Ge Quantum Wells.

We have fabricated α-Sn/Ge quantum well heterostructures by sandwiching nano-films of α-Sn between Ge nanolayers. The samples were grown via e-beam deposition and characterized by Raman spectroscopy, atomic force microscopy, temperature dependence of electrical resistivity and THz time-resolved spectroscopy. We have established the presence of α-Sn phase in the polycrystalline layers together with a high electron mobility µ = 2500 ± 100 cm2 V-1 s-1. Here, the temperature behavior of the resistivity in a magnetic field is distinct from the semiconducting films and three-dimensional Dirac semimetals, which is consistent with the presence of linear two-dimensional electronic dispersion arising from the mutually inverted band structure at the α-Sn/Ge interface. As a result, the α-Sn/Ge interfaces of the quantum wells have topologically non-trivial electronic states. From THz time-resolved spectroscopy, we have discovered unusual photocurrent and THz radiation generation. The mechanisms for this process are significantly different from ambipolar diffusion currents that are responsible for THz generation in semiconducting thin films, e.g., Ge. Moreover, the THz generation in α-Sn/Ge quantum wells is almost an order of magnitude greater than that found in Ge. The substantial strength of the THz radiation emission and its polarization dependence may be explained by the photon drag current. The large amplitude of this current is a clear signature of the formation of conducting channels with high electron mobility, which are topologically protected.

Effects of alfalfa saponins on the production performance, serum biochemical factors, and immune factors in Small-Tailed Han sheep.

This study aimed to determine the potential effects of alfalfa saponins on the production performance, serum biochemical factors, and immune factors in sheep. Twenty Small-Tailed Han sheep were equally and randomly divided into Groups 1-4, fed with diets containing 0, 5, 10, and 20 g alfalfa saponins per kg, respectively, for 40 consecutive days. During the treatments, the body weight change was recorded for each sheep. Before, during, and after the treatments of alfalfa saponins, serum was collected from each group to compare the levels of biochemical and immune factors. All sheep were killed after the treatments, and the longissimus dorsi muscle was collected to compare the meat quality. The results validated the effects of alfalfa saponins on the growth performance and meat quality in Small-Tailed Han sheep, and the supplementation level of 10 g/kg was the best. Alfalfa saponins also had effects on the levels of biochemical factors in serum. However, both dose- and time-dependent effects were observed. After a shorter feeding period (14 days), the concentrations of cholesterol (CHOL) and low-density lipoprotein (LDL) in Groups 2, 3, and 4 were all lower than those in the control group; however, when alfalfa saponins were continuously fed, this effect was not apparent or even gone. Supplying alfalfa saponins increased serum concentrations of IgA, IgG, IgE, IgM, IL-1, IFN-α, and IFN-ß. And this effect was distinctly observed in Groups 3 and 4. Based on the current results, the alfalfa saponins concentration of 10 g/kg (for 14 consecutive days) could be suggested as the optimum ratio for good health conditions of Small-Tailed Han sheep.

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.

Coordination of plant growth and abiotic stress responses by tryptophan synthase ß subunit 1 through modulation of tryptophan and ABA homeostasis in Arabidopsis.

To adapt to changing environments, plants have evolved elaborate regulatory mechanisms balancing their growth with stress responses. It is currently unclear whether and how the tryptophan (Trp), the growth-related hormone auxin, and the stress hormone abscisic acid (ABA) are coordinated in this trade-off. Here, we show that tryptophan synthase ß subunit 1 (TSB1) is involved in the coordination of Trp and ABA, thereby affecting plant growth and abiotic stress responses. Plants experiencing high salinity or drought display reduced TSB1 expression, resulting in decreased Trp and auxin accumulation and thus reduced growth. In comparison with the wild type, amiR-TSB1 lines and TSB1 mutants exhibited repressed growth under non-stress conditions but had enhanced ABA accumulation and stress tolerance when subjected to salt or drought stress. Furthermore, we found that TSB1 interacts with and inhibits ß-glucosidase 1 (BG1), which hydrolyses glucose-conjugated ABA into active ABA. Mutation of BG1 in the amiR-TSB1 lines compromised their increased ABA accumulation and enhanced stress tolerance. Moreover, stress-induced H2O2 disrupted the interaction between TSB1 and BG1 by sulfenylating cysteine-308 of TSB1, relieving the TSB1-mediated inhibition of BG1 activity. Taken together, we revealed that TSB1 serves as a key coordinator of plant growth and stress responses by balancing Trp and ABA homeostasis.

Metagenomic Next Generation Sequencing in the Detection of Pathogens in Cerebrospinal Fluid of Patients After Alternative Donor Transplantation: A Feasibility Analysis.

Central nervous system (CNS) complications can occur in 9%-15% of patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The clinical manifestations of the CNS complications are non-specific, with most of them being disturbances of consciousness, convulsions, headaches, fever, and epilepsy, making it difficult to infer the cause of the complications based on clinical manifestations. We retrospectively analyzed the sensitivity and feasibility of metagenomic next generation sequencing (mNGS) in the diagnosis of CNS infections after allo-HSCT. Lumbar punctures were performed on 20 patients with CNS symptoms after receiving alternative donor HSCT(AD-HSCT) at the Affiliated Cancer Hospital of Zhengzhou University from February 2019 to December 2020, and their cerebrospinal fluid (CSF) was collected. The mNGS technique was used to detect pathogens in the CSF. Routine CSF testing, biochemical analyses, G experiments, GM experiments, ink staining, acid-fast staining, and bacterial cultures were carried out, and quantitative PCR (qPCR) tests were used to detect cytomegalovirus (CMV), Epstein-Barr virus (EBV), BK polyomavirus (BKPyV), and human alphaherpesvirus (HHV). A total of 29 tests were performed with 21 of them being positive. Of the five negative patients, three were diagnosed with a posterior reversible encephalopathy syndrome, one as having transplantation-associated thrombotic microangiopathy, and one with transient seizure caused by hypertension. Fifteen patients tested positive, of which four had single infections and eleven had mixed infections. Five cases of fungal infections, six cases of bacterial infections, and 13 cases of viral infections were detected. Among the 13 cases of viral infections, ten cases were CMV(HHV-5); three were BKPyV; two were Torque teno virus (TTV); Two were HHV-1,two were EBV(HHV4), and one each of HpyV5 and HHV-6B. Thirteen patients tested positive for virus while the qPCR detection method of 6 identical specimens were below the minimum detection limit(<1×103 U/ml). The mNGS technique is highly sensitive, and it can be used to diagnose CNS infections after allo-HSCT.

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.