Proteomics Identifies Circulating TIMP-1 as a Prognostic Biomarker for Diffuse Large B-Cell Lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease, although disease stratification using in-depth plasma proteomics has not been performed to date. By measuring more than 1000 proteins in the plasma of 147 DLBCL patients using data-independent acquisition mass spectrometry and antibody array, DLBCL patients were classified into four proteomic subtypes (PS-I-IV). Patients with the PS-IV subtype and worst prognosis had increased levels of proteins involved in inflammation, including a high expression of metalloproteinase inhibitor-1 (TIMP-1) that was associated with poor survival across two validation cohorts (n = 180). Notably, the combination of TIMP-1 with the international prognostic index (IPI) identified 64.00% to 88.24% of relapsed and 65.00% to 80.49% of deceased patients in the discovery and two validation cohorts, which represents a 24.00% to 41.67% and 20.00% to 31.70% improvement compared to the IPI score alone, respectively. Taken together, we demonstrate that DLBCL heterogeneity is reflected in the plasma proteome and that TIMP-1, together with the IPI, could improve the prognostic stratification of patients.

Identification of novel prognostic autoantibodies in diffuse large B-cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone via a high-throughput antigen microarray.

BACKGROUND: R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) is a standard first-line treatment for diffuse large B-cell lymphoma (DLBCL). However, 20%-40% of patients survive less than 5 years. Novel prognostic biomarkers remain in demand. METHODS: Baseline plasma autoantibodies (AAbs) were assessed in 336 DLBCLs. In the discovery phase (n = 20), a high-density antigen microarray (∼21,000 proteins) was used to expound AAb profiles. In the verification phase (n = 181), with a DLBCL-focused microarray, comparative results based on event-free survival at 24 months (EFS24) and lasso Cox regression models of progression-free survival (PFS) and overall survival (OS) were integrated to identify potential biomarkers. They were further validated by enzyme-linked immunosorbent assay in validation phase 1 (n = 135) and a dynamic cohort (n = 12). In validation phase 2, a two-AAb-based risk score was established. They were further validated in an immunohistochemistry cohort (n = 55) and four independent Gene Expression Omnibus datasets (n = 1598). RESULTS: Four AAbs (CREB1, N4BP1, UBAP2, and DEAF1) were identified that showed associations with EFS24 status (p < .05) and superior PFS and OS (p < .05). A novel risk score model based on CREB1 and N4BP1 AAbs was developed to predict PFS with areas under the curve of 0.72, 0.71, 0.76, and 0.82 at 1, 3, 5, and 7 years, respectively, in DLBCL treated with R-CHOP independent of the International Prognostic Index (IPI) and provided significant additional recurrence risk discrimination (p < .05) for the IPI. CREB1 and N4BP1 proteins and messenger RNAs were also associated with better PFS and OS (p < .05). CONCLUSIONS: This study identified a novel prognostic panel of CREB1, N4BP1, DEAF1, and UBAP2 AAbs that is independent of the IPI in DLBCL.

Filter-Free UV Photodetectors Based on Unipolar Barrier Van der Waals α-In2Se3/h-BN Heterostructures.

Visible-blind ultraviolet (UV) light detection has a wide application range in scenes like space environment monitoring and medical imaging. To realize miniaturized UV detectors with high performance and high integration ability, new device structures without bulky light filters need to be developed based on advanced mechanisms. Here the unipolar barrier van der Waals heterostructure (UB-vdWH) photodetector is reported that realizes filter-free visible-blind UV detection with good stability, robustness, selectivity, and high detection performance. The UB-vdWH shows a responsivity of 2452 A W-1, a photo on-off ratio of 2.94 × 105 and a detectivity of 1.26 × 1015 Jones as a UV detector, owing to the intentionally designed barrier height that suppresses dark current and photoresponse to visible light during the transport process. The good performance remains intact during 104 test cycles or even under high temperatures, which proves the stability, and robustness of the UB-vdWH, thus shows the huge potential for a wider application range.

Generation of selenium-rich wheat mutants and exploration of responsive genes for selenium accumulation.

KEY MESSAGE: Salt tolerance, selenium accumulation and expression of the responsive genes were analyzed in the wheat high selenium mutants. Selenium is an essential trace element for the human body, and its deficiency can lead to various diseases such as Keshan disease and large bone disease. Wheat, being a major staple crop, plays a crucial role in providing dietary selenium supplementation to combat this deficiency. Despite progress in understanding the molecular regulation of selenium accumulation in certain crops, the molecular mechanisms governing selenium accumulation-related gene expression in wheat plants remain poorly understood. In this study, three mutant wheat lines with elevated selenium content were identified. Under the treatment of Na2SeO3 or NaCl, the selenium-rich wheat mutants exhibited decreased sensitivity to both selenium and NaCl compared to the wild type. Additionally, there was an increase in the activities of SOD and POD, while the content of MDA decreased. Through qRT-PCR analysis, the expression of selenium-related genes was affected, revealing that some of these genes not only regulate the response of wheat to salt stress, but also play a role in the process of selenium accumulation. The transcriptome results revealed that the important genes encoding glutathione S-transferases, peroxidases, superoxide dismutases, and UDP-glucosyltransferases may function in the regulation of salt tolerance and selenium accumulation in wheat. These findings significantly contribute to the current understanding of the molecular regulation of selenium accumulation in wheat crops, while also offering novel germplasm resources for cultivating selenium-rich and salt-tolerant wheat lines.

A Three-Dimensional Neuromorphic Photosensor Array for Nonvolatile In-Sensor Computing.

In-sensor computing hardware based on emerging reconfigurable photosensors can effectively reduce redundant data and decrease power consumption, which can greatly promote the evolution of machine vision. However, because of the complex device structures and low integration abilities, the common architectures mainly lie in two dimensions, resulting in low time and area efficiencies. Here we propose a three-dimensional (3D) neuromorphic photosensor array for parallel in-sensor image processing. It is constructed on a vertical Graphite/CuInP2S6/Graphite photosensor unit, where the directional Cu+ ion migrations after voltage pulse programming enable a reconfigurable photovoltaic effect and an in-sensor computing capability. With a memristor-like device structure, van der Waals interfaces, and a high uniformity with a low crosstalk problem, a 10 × 10 array is fabricated for intelligent image recognition. Furthermore, using a vertically stacked 3D 3 × 3 × 3 array, we demonstrate an in-sensor convolution strategy with high time and area efficiencies.

[A multicenter study of neonatal stroke in Shenzhen, China]. / 深圳市新生儿脑卒中多中心现况调查.

OBJECTIVES: To investigate the incidence rate, clinical characteristics, and prognosis of neonatal stroke in Shenzhen, China. METHODS: Led by Shenzhen Children's Hospital, the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022. The incidence, clinical characteristics, treatment, and prognosis of neonatal stroke in Shenzhen were analyzed. RESULTS: The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137, 1/6 060, and 1/7 704, respectively. Ischemic stroke accounted for 75% (27/36); boys accounted for 64% (23/36). Among the 36 neonates, 31 (86%) had disease onset within 3 days after birth, and 19 (53%) had convulsion as the initial presentation. Cerebral MRI showed that 22 neonates (61%) had left cerebral infarction and 13 (36%) had basal ganglia infarction. Magnetic resonance angiography was performed for 12 neonates, among whom 9 (75%) had involvement of the middle cerebral artery. Electroencephalography was performed for 29 neonates, with sharp waves in 21 neonates (72%) and seizures in 10 neonates (34%). Symptomatic/supportive treatment varied across different hospitals. Neonatal Behavioral Neurological Assessment was performed for 12 neonates (33%, 12/36), with a mean score of (32±4) points. The prognosis of 27 neonates was followed up to around 12 months of age, with 44% (12/27) of the neonates having a good prognosis. CONCLUSIONS: Ischemic stroke is the main type of neonatal stroke, often with convulsions as the initial presentation, involvement of the middle cerebral artery, sharp waves on electroencephalography, and a relatively low neurodevelopment score. Symptomatic/supportive treatment is the main treatment method, and some neonates tend to have a poor prognosis.

Identification of novel serological autoantibodies in Chinese prostate cancer patients using high-throughput protein arrays.

Autoantibody (AAb) has a prominent role in prostate cancer (PCa), with few studies profiling the AAb landscape in Chinese patients. Therefore, the AAb landscape in Chinese patients was characterized using protein arrays. First, in the discovery phase, Huprot arrays outlined autoimmune profiles against ~ 21,888 proteins from 57 samples. In the verification phase, the PCa-focused arrays detected 25 AAbs selected from the discovery phase within 178 samples. Then, PCa was detected using a backpropagation artificial neural network (BPANN) model. In the validation phase, an enzyme-linked immunosorbent assay (ELISA) was used to validate four AAb biomarkers from 196 samples. Huprot arrays profiled distinct PCa, benign prostate diseases (BPD), and health AAb landscapes. PCa-focused array depicted that IFIT5 and CPOX AAbs could distinguish PCa from health with an area under curve (AUC) of 0.71 and 0.70, respectively. PAH and FCER2 AAbs had AUCs of 0.86 and 0.88 in discriminating PCa from BPD. Particularly, PAH AAb detected patients in the prostate-specific antigen (PSA) gray zone with an AUC of 0.86. Meanwhile, the BPANN model of 4-AAb (IFIT5, PAH, FCER2, CPOX) panel attained AUC of 0.83 among the two cohorts for detecting patients with gray-zone PSA. In the validation cohort, the IFIT5 AAb was upregulated in PCa compared to health (p < 0.001). Compared with BPD, PAH and FCER2 AAbs were significantly elevated in PCa (p = 0.012 and 0.039). We have demonstrated the first extensive profiling of autoantibodies in Chinese PCa patients, identifying novel diagnostic AAb biomarkers, especially for identification of gray-zone-PSA patients.

High-Speed Optoelectronic Nonvolatile Memory Based on van der Waals Heterostructures.

High-performance optoelectronic nonvolatile memory is promising candidate for next-generation information memory devices. Here, a floating-gate memory is constructed based on van der Waals heterostructure, which exhibits a large storage window ratio (≈75.5%) and an extremely high on/off ratio (107 ), as well as an ultrafast electrical writing/erasing speed (40 ns). The enhanced performance enables as-fabricated devices to present excellent multilevel data storage, robust retention, and endurance performance. Moreover, stable optical erasing operations can be achieved by illuminating the device with a laser pulse, showcasing outstanding optoelectronic storage performance (optical erasing speed ≈ 2.3 ms). The nonvolatile and high-speed characteristics of these devices hold significant potential for the integration of high-performance nonvolatile memory.

Comparison of efficacy and safety between PD-1 inhibitors and PD-L1 inhibitors plus platinum-etoposide as first-line treatment for extensive-stage small-cell lung cancer: a multicenter, real-world analysis.

BACKGROUND: Immunotherapy in combination with platinum-etoposide (EP) chemotherapy has been approved as a first-line treatment for extensive-stage small cell lung cancer (ES-SCLC). However, real-world (RW) data regarding the use of immune checkpoint inhibitors (ICIs) in ES-SCLC are lacking. We aimed to assess the differences between programmed death protein 1 (PD-1) inhibitors and programmed death ligand 1 (PD-L1) inhibitors, both in conjunction with EP chemotherapy, as first-line treatment for ES SCLC. METHODS: We conducted a real-world, multicenter, retrospective cohort, controlled study to compare the prognosis, efficacy, and safety of PD-1 and PD-L1 inhibitors in ES-SCLC patients when used along with chemotherapy. Each patient received up to six cycles of etoposide, carboplatin, or cisplatin combined with ICI drugs, including PD-1 and PD-L1 inhibitors. The primary endpoints were investigator-assessed progression-free survival (PFS) and overall survival (OS). The secondary endpoints were the investigator-assessed objective response rate (ORR) and disease control rate (DCR) according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). RESULTS: Between January 2017 and December 2021, 194 patients with ES-SCLC from three clinical centers in a PLA general hospital were included in our study, including 93 patients in the PD-1 group and 101 patients in the PD-L1 group. At the time of data cutoff, progression-free survival in the PD-1 group (median PFS, 6.8 months; 95% CI, 5.3-8.1) was similar to that in the PD-L1 group (median PFS, 6.4 months; 95% CI, 5.5-7.5); the stratified hazard ratio for PFS was 1.12 (95% CI, 0.83-1.53; P = 0.452). The median OS was similar in the PD-1 and PD-L1 groups (15.8 m vs. 17.7 m, P = 0.566); the hazard ratio was 0.90 (95% CI, 0.62-1.30, P = 0.566). The two groups had comparable investigator-assessed confirmed objective response rates (ORR) (76.3% vs. 76.2%). Adverse effect (AE)-related discontinuation occurred in 4 (4.3%) patients in the PD-1 group and 2 (2.0%) patients in the PD-L1 group. Deaths due to AEs of any cause occurred in 2 (2.2%) patients in the PD-1 inhibitor group and 1 (1.0%) patient in the PD-L1 inhibitor group. CONCLUSIONS: Our research revealed that there were no significant differences in efficacy or prognosis between PD-1 inhibitor + EP chemotherapy and PD-L1 inhibitor + EP chemotherapy. The two groups seemed to have comparable safety profiles, but the number of discontinuation or death events was too small to draw a firm conclusion.

Linear Peptide-Based PET Tracers for Imaging PD-L1 in Tumors.

Programmed cell death receptor 1 (PD-1) and its ligand PD-L1 are particularly interesting immune checkpoint proteins for human cancer treatment. Positron emission tomography (PET) imaging allows for the dynamic monitoring of PD-L1 status during tumor progression, thus informing patients' response index. Herein, we report the synthesis of two linear peptide-based radiotracers, [64Cu]/[68Ga]HKP2201 and [64Cu]/[68Ga]HKP2202, and validate their utility for PD-L1 visualization in preclinical models. The precursor peptide HKP2201 was derived from a linear peptide ligand, CLP002, which was previously identified by phage display and showed nanomolar affinity toward PD-L1. Appropriate modification of CLP002 via PEGylation and DOTA conjugation yielded HKP2201. The dimerization of HKP2201 generated HKP2202. The 64Cu and 68Ga radiolabeling of both precursors was studied and optimized. PD-L1 expression in mouse melanoma cell line B16F10, mouse colon cancer cell line MC38, and their allografts were assayed by immunofluorescence and immunohistochemistry staining. Cellular uptake and binding assays were conducted in both cell lines. PET imaging and ex vivo biodistribution studies were employed in tumor mouse models bearing B16F10 and MC38 allografts. [64Cu]/[68Ga]HKP2201 and [64Cu]/[68Ga]HKP2202 were obtained with satisfactory radiocharacteristics. They all showed lower liver accumulation compared to [64Cu]/[68Ga]WL12. B16F10 and MC38 cells and their tumor allografts sections were verified to express PD-L1. These tracers demonstrated a concentration-dependent cell affinity and a comparable half-maximal effect concentration (EC50) with radiolabeled WL12. Competitive binding and blocking studies demonstrated the specific target of these tracers to PD-L1. PET imaging and ex vivo biodistribution studies revealed notable tumor uptake in tumor-bearing mice and rapid clearance from blood and major organs. Importantly, [64Cu]/[68Ga]HKP2202 showed higher tumor uptake compared to [64Cu]/[68Ga]HKP2201. Of note, [64Cu] labeled tracers showed longer retention in tumors than [68Ga] labeled traces, indicating advantages in the long-term tracking of PD-L1 dynamics. In comparison, [68Ga]HKP2201 and [68Ga]HKP2202 showed lower liver accumulation, enabling its great potential in the fast detection of both primary and metastatic tumors, including hepatic carcinoma. [64Cu]/[68Ga]HKP2201 and [64Cu]/[68Ga]HKP2202 are promising PET tracers for visualizing PD-L1 status. Notably, their combination would cooperate in rapid diagnosis and subsequent treatment guidance. Future assessment of the radiotracers in patients is needed to fully evaluate their clinical value.

Symptoms of depression and anxiety in Chinese adolescents: heterogeneity and associations with executive function.

BACKGROUND: Depression and anxiety are common symptoms associated with significant morbidity in adolescents. Few studies have explored the relationship between latent profiles of adolescent depression-anxiety symptoms and executive function (EF), which is also a major pediatric public health concern. METHODS: The sample included 1,306 participants who were recruited from two schools in Ningxia. The Depression Self-Rating Scale for Children (DSRSC) and the Screen for Child Anxiety Related Emotional Disorders (SCARED) were used to assess the level of depression-anxiety symptoms in adolescents, and their executive function state was assessed using the Behavior Rating Inventory of Executive Function-Self-Report version (BRIEF-SR). Latent profile analysis (LPA) was carried out using Mplus 7.0 to explore the most likely number of profiles based on the subscales of DSRSC and SCARED. The relationship between adolescents' executive function and depression-anxiety symptoms were analyzed by multivariable logistic regression, and the odds ratio were used to test the impact of this relationship. RESULTS: The LPA results show that the three-profile model was the best-fitting model for adolescent depression and anxiety symptoms. The proportions of Profile-1 ("Healthy Group"), Profile-2 ("Anxiety Disorder Group"), and Profile-3 ("Depression-Anxiety Disorder Group") were 61.4%, 23.9%, and 14.7%, respectively. Additional analyses using multivariable logistic regression suggested that poor shifting capacity and emotional control were significantly more likely to be classified into the depression and/or anxiety groups, and worse working memory, task completion, and better inhibition were significantly more likely to be classified into the anxiety group. CONCLUSIONS: The findings contribute to our understanding of the heterogeneity of adolescents' depression-anxiety symptoms and highlight the important role of executive function in influencing mental health outcomes. These findings will guide the improvement and delivery of interventions for the treatment of anxiety and depression in adolescents, mitigating functional impairments in patients and reducing disease risk.

Relationship between chronotypes and aggression in adolescents: a cross-sectional study.

BACKGROUND: This study aimed to investigate the relationship between chronotypes and aggression in adolescents. METHODS: A cross-sectional study was conducted on 755 primary and secondary school students aged 11-16 years in rural areas of Ningxia Province, China. The Chinese version of the Buss-Perry Aggression Questionnaire (AQ-CV) and the Chinese version Morningness-Eveningness Questionnaire (MEQ-CV) were used to assess the aggressive behavior and chronotypes of the study subjects. The Kruskal-Wallis test was then used to compare the differences in aggression among adolescents with different chronotypes, and Spearman correlation analysis to determine the relationship between chronotypes and aggression. Further linear regression analysis was used to investigate the effects of chronotype, personality traits, family environment, and class environment on adolescent aggression. RESULTS: There were significant differences in chronotypes between different age groups and different sexes. Spearman correlation analysis showed that the MEQ-CV total score was negatively correlated with the AQ-CV total score (r = -0.263) and score of each AQ-CV subscale. In Model 1, chronotypes were negatively associated with aggression when controlling for age and sex, and evening-type adolescents might be more likely to exhibit aggressive behavior (b = -0.513, 95% CI: [-0.712, -0.315], P < 0.001); in Model 2, the negative association remained after controlling for family and class environment on the basis of Model 1 (b = -0.404, 95% CI: [-0.601, -0.208], P < 0.001); and in Model 3, the negative association still existed after controlling for personality traits on the basis of Model 2 (b = -0.383, 95% CI: [-0.577, -0.190], P < 0.001). CONCLUSION: Compared to morning-type adolescents, evening-type adolescents were more likely to exhibit aggressive behavior. Given social expectations for MT adolescents, adolescents should be actively guided to develop a good circadian rhythm that may be more conducive to their physical and mental development.

Lowering Contact Resistances of Two-Dimensional Semiconductors by Memristive Forming.

Two-dimensional semiconductors have great potential for beyond-silicon electronics. However, because of the lack of controllable doping methods, Fermi level pinning, and van der Waals (vdW) gaps at the metal-semiconductor interfaces, these devices exhibit high electrical contact resistances, restricting their practical applications. Here, we report a general contact-resistance-lowering strategy by constructing vertical metal-semiconductor-metal memristor structures at the contact regions and setting them into a nonvolatile low-resistance state through a memristive forming process. Through this, we reduce the contact resistances of MoS2 field-effect transistors (FETs) by at least one order of magnitude and improve the on-state current densities of MoTe2 FETs by about two orders of magnitude. We also demonstrate that this strategy is applicable to other two-dimensional semiconductors, including MoSe2, WS2, and WSe2, and a variety of contact metals, including Au, Cu, Ni, and Pd. The good stability and universality indicate the great potential for technological applications.

Ameliorating Effects of Vitamin K2 on Dextran Sulfate Sodium-Induced Ulcerative Colitis in Mice.

Ulcerative colitis (UC) is a chronic recurrent inflammatory illness of the gastrointestinal system. The purpose of this study was to explore the alleviating effect of vitamin K2 (VK2) on UC, as well as its mechanism. C57BL/6J mice were given 3% DSS for seven days to establish UC, and they then received VK2 (15, 30, or 60 mg/kg·bw) and 5-aminosalicylic acid (100 mg/kg·bw) for two weeks. We recorded the clinical signs, body weights, colon lengths, and histological changes during the experiment. We detected the inflammatory factor expressions using enzyme-linked immunosorbent assay (ELISA) kits, and we detected the tight junction proteins using Western blotting. We analyzed the intestinal microbiota alterations and short-chain fatty acids (SCFAs) using 16S rRNA sequencing and targeted metabolomics. According to the results, VK2 restored the colon lengths, improved the colonic histopathology, reduced the levels of proinflammatory cytokines (such as IL-1ß, TNF-α, and IL-6), and boosted the level of the immunosuppressive cytokine IL-10 in the colon tissues of the colitis mice. Moreover, VK2 promoted the expression of mucin and tight junction proteins (such as occludin and zonula occludens-1) in order to preserve the intestinal mucosal barrier function and prevent UC in mice. Additionally, after the VK2 intervention, the SCFAs and SCFA-producing genera, such as Eubacterium_ruminantium_group and Faecalibaculum, were elevated in the colon. In conclusion, VK2 alleviated the DSS-induced colitis in the mice, perhaps by boosting the dominant intestinal microflora, such as Faecalibaculum, by reducing intestinal microflora dysbiosis, and by modulating the expression of SCFAs, inflammatory factors, and intestinal barrier proteins.

Anti-PD1/PDL1 IgG subclass distribution in ten cancer types and anti-PD1 IgG4 as biomarker for the long time survival in NSCLC with anti-PD1 therapy.

BACKGROUND: Antibodies targeting programmed cell death-1(PD1) and its ligand (PDL1) have revolutionized cancer therapy. However, little is known about the preexisted anti-PD1/PDL1 autoantibodies (AAbs) distribution in multiple cancer types, nor is their potential biomarker role for anti-PD1 therapy. METHOD: Plasma anti-PD1/PDL1 AAb IgG and subclasses (IgG1-4) were detected by enzyme-linked immune sorbent assay (ELISA) in 190 cancer patients, covering 10 cancer types (lung, breast, esophageal, colorectal, liver, prostatic, cervical, ovarian, gastric cancers and lymphoma), the comprehensive correlation of AAbs with multiple clinical parameters was analyzed. We further tested these AAbs in 76 non-small cell lung cancer (NSCLC) samples receiving anti-PD1 therapy, the association of AAbs level with survival was analyzed and validated in an independent cohort (n = 32). RESULTS: Anti-PD1/PDL1 AAb IgG were globally detected in 10 types of cancer patients. IgG1 and IgG2 were the major subtypes for anti-PD1/PDL1 AAbs. Correlation analysis revealed a distinct landscape between various cancer types. The random forest model indicated that IgG4 subtype was mostly associated with cancer. In discovery cohort of 76 NSCLC patients, high anti-PD1 IgG4 was associated with a reduced overall survival (OS, p = 0.019), not progression-free survival (PFS, p = 0.088). The negative association of anti-PD1 IgG4 with OS was validated in 32 NSCLC patients (p = 0.032). CONCLUSION: This study reports for the first time the distribution of preexisted anti-PD1/PDL1 AAb IgG and subclasses across 10 cancer types. Moreover, the anti-PD1 AAb IgG4 subclass was identified to associate with OS, which may serve as a potential biomarker for anti-PD1 therapeutic survival benefit in NSCLC patients.

Vertical Barrier Heterostructures for Reliable, Robust, and High-Performance Ultraviolet Detection.

Photodetectors based on low-dimensional materials usually suffer from serious optical power-dependent photoresponse and low reliability, particularly in the ultraviolet regime. The barrier photodetector is an effective and reliable strategy where the barrier layer can block the low-energy charge carriers while allowing for a flow of the high-energy photocarriers. Here, vertical barrier heterostructure photodetectors (VBHPs), consisting of a graphene bottom electrode, a MoS2 light absorber, and an h-BN energy barrier, for reliable, robust, and high-performance ultraviolet detection are reported. The asymmetric barrier distribution in the conduction/valence band at the MoS2 /h-BN interface results in an ultralow noise current of 1.69 × 10-15 A Hz-1/2 at room temperature, stable photo on/off states exceeding 104 cycles at 300 K and 400 K, a light power-independent high responsivity of 416.2 mA W-1 at 360 nm, a high photo on-off ratio of 1.2 × 105 at 360 nm, high measured detectivities (3.2 × 1010 Jones at 266 nm and 9.9 × 1010 Jones at 360 nm), and wide linear dynamic ranges. The VBHPs show a high potential for new-type reliable ultraviolet detection.

Genome and systems biology of Melilotus albus provides insights into coumarins biosynthesis.

Melilotus species are used as green manure and rotation crops worldwide and contain abundant pharmacologically active coumarins. However, there is a paucity of information on its genome and coumarin production and function. Here, we reported a chromosome-scale assembly of Melilotus albus genome with 1.04 Gb in eight chromosomes, containing 71.42% repetitive elements. Long terminal repeat retrotransposon bursts coincided with declining of population sizes during the Quaternary glaciation. Resequencing of 94 accessions enabled insights into genetic diversity, population structure, and introgression. Melilotus officinalis had relatively larger genetic diversity than that of M. albus. The introgression existed between M. officinalis group and M. albus group, and gene flows was from M. albus to M. officinalis. Selection sweep analysis identified candidate genes associated with flower colour and coumarin biosynthesis. Combining genomics, BSA, transcriptomics, metabolomics, and biochemistry, we identified a ß-glucosidase (BGLU) gene cluster contributing to coumarin biosynthesis. MaBGLU1 function was verified by overexpression in M. albus, heterologous expression in Escherichia coli, and substrate feeding, revealing its role in scopoletin (coumarin derivative) production and showing that nonsynonymous variation drives BGLU enzyme activity divergence in Melilotus. Our work will accelerate the understanding of biologically active coumarins and their biosynthetic pathways, and contribute to genomics-enabled Melilotus breeding.

A New Proportionate Filtered-x RLS Algorithm for Active Noise Control System.

The filtered-x recursive least square (FxRLS) algorithm is widely used in the active noise control system and has achieved great success in some complex de-noising environments, such as the cabin in vehicles and aircraft. However, its performance is sensitive to some user-defined parameters such as the forgetting factor and initial gain. Once these parameters are not selected properly, the de-noising effect of FxRLS will deteriorate. Moreover, the tracking performance of FxRLS for mutation is still restricted to a certain extent. To solve the above problems, this paper proposes a new proportional FxRLS (PFxRLS) algorithm. The forgetting factor and initial gain sensitivity are successfully reduced without introducing new turning parameters. The de-noising level and tracking performance have also been improved. Moreover, the momentum technique is introduced in PFxRLS to further improve its robustness and de-noising level. To ensure stability, its convergence condition is also discussed in this paper. The effectiveness of the proposed algorithms is illustrated by simulations and experiments with different user-defined parameters and time-varying noise environments.

The genome of Cleistogenes songorica provides a blueprint for functional dissection of dimorphic flower differentiation and drought adaptability.

Cleistogenes songorica (2n = 4x = 40) is a desert grass with a unique dimorphic flowering mechanism and an ability to survive extreme drought. Little is known about the genetics underlying drought tolerance and its reproductive adaptability. Here, we sequenced and assembled a high-quality chromosome-level C. songorica genome (contig N50 = 21.28 Mb). Complete assemblies of all telomeres, and of ten chromosomes were derived. C. songorica underwent a recent tetraploidization (~19 million years ago) and four major chromosomal rearrangements. Expanded genes were significantly enriched in fatty acid elongation, phenylpropanoid biosynthesis, starch and sucrose metabolism, and circadian rhythm pathways. By comparative transcriptomic analysis we found that conserved drought tolerance related genes were expanded. Transcription of CsMYB genes was associated with differential development of chasmogamous and cleistogamous flowers, as well as drought tolerance. Furthermore, we found that regulation modules encompassing miRNA, transcription factors and target genes are involved in dimorphic flower development, validated by overexpression of CsAP2_9 and its targeted miR172 in rice. Our findings enable further understanding of the mechanisms of drought tolerance and flowering in C. songorica, and provide new insights into the adaptability of native grass species in evolution, along with potential resources for trait improvement in agronomically important species.

The predictive value of systemic immune inflammation index for postoperative survival of gallbladder carcinoma patients.

BACKGROUND: Growing evidence indicates that systemic immune inflammation index (SII) can predict the prognosis of various solid tumors. The objective of this study aimed to investigate the efficacy of SII in predicting the prognosis of gallbladder carcinoma (GBC) patients after radical surgery. METHODS: A consecutive series of 93 patients with GBC who underwent radical resection were enrolled in the retrospective study. The cutoff value for the SII was calculated using the time-dependent receiver operating characteristic (ROC) curve analysis by overall survival (OS) prediction. The associations between the SII and the clinicopathologic characteristics were analyzed using Pearson's χ2 test and Fisher's exact test. Survival curves were calculated using the Kaplan-Meier method. Univariate analysis was performed to evaluate the prognostic relevance of preoperative parameters. The multivariate Cox regression proportional hazard model was used to assess variables significant on univariate analysis. RESULTS: The Kaplan-Meier survival analysis and the multivariate analysis of patients with GBC who received radical resection showed SII independently predicted OS. The univariate analysis showed that the TNM stage, SII, CA19-9, ALP, prealbumin, NLR, MLR, lymph node metastasis, and histopathological type were all associated with overall survival. In time-dependent ROC analysis, the area of the SII-CA19-9 under the ROC curve (AUC) was higher than that of the preoperative SII or CA19-9 levels for the prediction of OS. CONCLUSION: Our results demonstrate that high SII was a predictor of poor long-term outcomes among patients with GBC undergoing curative surgery. SII-CA19-9 classification may be more effective in predicting the postoperative prognosis of GBC patients.