The role of Ca2+ signalling and InsP3R in the pathogenesis of intrahepatic cholestasis of pregnancy.

BACKGROUND: In order to contribute new insights for future prevention and treatment of intrahepatic cholestasis of pregnancy (ICP), and to promote positive pregnancy outcomes, we evaluated serum Ca2+ levels and inositol 1,4,5-trisphosphate receptor (InsP3R) expression in the liver tissue of a rat ICP model. METHODS: After establishing the model by injection of oestradiol benzoate and progesterone into pregnant rats, animals were divided into normal control (n = 5) and ICP model groups (n = 5). The expression of InsP3R protein in the liver, and serum levels of Ca2+, glycocholic acid and bile acid were detected. RESULTS: InsP3R mRNA and protein were significantly lower in the ICP model group compared to the normal group, as determined by qPCR and immunohistochemistry, respectively. Serum enzyme-linked immunosorbent assay results revealed significantly higher levels of glycocholic acid and bile acid in the ICP model group compared to the normal group, while Ca2+ levels were significantly lower. The levers of Ca2+ were significantly and negatively correlated with the levels of glycocholic acid. The observed decrease in Ca2+ was associated with an increase in total bile acids, but there was no significant correlation. CONCLUSIONS: Our results revealed that the expression of InsP3R and serum Ca2+ levels was significantly decreased in the liver tissue of ICP model rats. Additionally, Ca2+ levels were found to be negatively correlated with the level of glycocholic acid.

This study investigated the relationship between serum Ca²⁺ levels, inositol 1,4,5-trisphosphate receptor (InsP3R) expression and intrahepatic cholestasis of pregnancy (ICP) in a rat model. The results indicated a significant decrease in InsP3R expression and Ca²⁺ in the disease group compared to the control group, alongside elevated levels of glycocholic acid and bile acid. The levels of Ca²⁺ exhibited a negative correlation with the levels of glycocholic acid. These findings indicated that the decrease of InsP3R expression and Ca²⁺ levels may be related to the pathogenesis of ICP. The study provides further insight into the treatment of this disease.

Coexistence of a novel chromosomal integrative and mobilizable element Tn7548 with two blaKPC-2-carrying plasmids in a multidrug-resistant Aeromonas hydrophila strain K522 from China.

OBJECTIVES: Herein, we detected one multidrug-resistant Aeromonas hydrophila strain K522 co-carrying two blaKPC-2 genes together with a novel chromosomal integrative and mobilizable element (IME) Tn7548 from China. To reveal the genetic characteristics of the novel reservoir of blaKPC-2 and IME in Aeromonas, a detailed genomic characterization of K522 was performed, and a phylogenetic analysis of Tn7412-related IMEs was carried out. METHODS: Carbapenemases were detected by using the immunocolloidal gold technique and antimicrobial susceptibility was tested by using VITEK 2. The whole-genome sequences of K522 were analysed using phylogenetics, detailed dissection, and comparison. RESULTS: Strain K522 carried a Tn7412-related chromosomal IME Tn7548 and three resistance plasmids pK522-A-KPC, pK522-B-KPC, and pK522-MOX. A phylogenetic tree of 82 Tn7412-related IMEs was constructed, and five families of IMEs were divided. These IMEs shared four key backbone genes: int, repC, and hipAB, and carried various profiles of antimicrobial resistance genes (ARGs). pK522-A-KPC and pK522-B-KPC carried blaKPC-2 and belonged to IncG and unclassified type plasmid, respectively. The blaKPC-2 regions of these two plasmids were the truncated version derived from Tn6296, resulting in the carbapenem resistance of K522. CONCLUSION: We first reported A. hydrophila harbouring a novel Tn7412-related IME Tn7548 together with two blaKPC-2 carrying plasmids and a MDR plasmid. Three of these four mobile genetic elements (MGEs) discovered in A. hydrophila K522 were novel. The emergence of novel MGEs carrying ARGs indicated the rapid evolution of the resistance gene vectors in A. hydrophila under selection pressure and would contribute to the further dissemination of various ARGs in Aeromonas.

Jointly constrained group sparse connectivity representation improves early diagnosis of Alzheimer's disease on routinely acquired T1-weighted imaging-based brain network.

Background: Radiomics-based morphological brain networks (radMBN) constructed from routinely acquired structural MRI (sMRI) data have gained attention in Alzheimer's disease (AD). However, the radMBN suffers from limited characterization of AD because sMRI only characterizes anatomical changes and is not a direct measure of neuronal pathology or brain activity. Purpose: To establish a group sparse representation of the radMBN under a joint constraint of group-level white matter fiber connectivity and individual-level sMRI regional similarity (JCGS-radMBN). Methods: Two publicly available datasets were adopted, including 120 subjects from ADNI with both T1-weighted image (T1WI) and diffusion MRI (dMRI) for JCGS-radMBN construction, 818 subjects from ADNI and 200 subjects solely with T1WI from AIBL for validation in early AD diagnosis. Specifically, the JCGS-radMBN was conducted by jointly estimating non-zero connections among subjects, with the regularization term constrained by group-level white matter fiber connectivity and individual-level sMRI regional similarity. Then, a triplet graph convolutional network was adopted for early AD diagnosis. The discriminative brain connections were identified using a two-sample t-test, and the neurobiological interpretation was validated by correlating the discriminative brain connections with cognitive scores. Results: The JCGS-radMBN exhibited superior classification performance over five brain network construction methods. For the typical NC vs. AD classification, the JCGS-radMBN increased by 1-30% in accuracy over the alternatives on ADNI and AIBL. The discriminative brain connections exhibited a strong connectivity to hippocampus, parahippocampal gyrus, and basal ganglia, and had significant correlation with MMSE scores. Conclusion: The proposed JCGS-radMBN facilitated the AD characterization of brain network established on routinely acquired imaging modality of sMRI. Supplementary Information: The online version of this article (10.1007/s13755-023-00269-0) contains supplementary material, which is available to authorized users.

Association of immune cell traits with Parkinson's disease: a Mendelian randomization study.

Background: Immunity and neuroinflammation play crucial roles in the pathogenesis of Parkinson's disease (PD). Nonetheless, prior investigations into the correlation between immune inflammation and PD have produced varying results. Identifying specific immune cell phenotypes that are truly associated with PD is challenging, and the causal relationship between immune cells and PD remains elusive. Methods: This study conducted a comprehensive two-sample Mendelian randomization (MR) analysis, employing five distinct analytical approaches, to clarify the causal connection between immune cell characteristics and the risk of PD. Utilizing GWAS data, we investigated the causal relationship between 731 immune cell traits and PD. These immune cell phenotypes encompass absolute cell (AC) counts, median fluorescence intensity (MFI), and relative cell (RC) counts for B cells, cDCs, mature stage T cells, monocytes, myeloid cells, TBNK (T cells, B cells, and natural killer cells), and Tregs, as well as the logistic parameter (MP) for cDCs and TBNK. Results: The inverse variance weighted (IVW) analysis indicated that Myeloid DCs (p = 0.004), HVEM expression on CD45RA- CD4+ T cells (p = 0.007), CD62L- CD86+ Myeloid DCs (p = 0.015), and HLA DR expression on monocytes (p = 0.019) were associated with a reduced risk of PD. CD14+ CD16+ monocytes (p = 0.005), HLA DR+ NK cells within CD3- lymphocytes (p = 0.023), and CD28 expression on activated & secreting Tregs (p = 0.032) were associated with an increased risk of PD. Conclusion: This study establishes a causal link between immune cell phenotype and the pathogenesis of PD, identifying several specific immune cell characteristics associated with PD. This could inspire researchers to delve into the pathogenesis of PD at the cellular subtype level, and aid in the identification of potential pharmacological protein targets for PD.

Investigating the shared genetic architecture between frailty and insomnia.

Background: The epidemiological association between frailty and insomnia is well established, yet the presence of a common genetic etiology is still uncertain. Further exploration is needed to ascertain the causal relationship between frailty and insomnia. Methods: Utilizing data obtained from genome-wide association studies (GWAS) summaries, we utilized the linkage disequilibrium score regression (LDSC) to determine the genetic correlation existing between frailty and insomnia. The determination of causality was achieved through the application of two-sample Mendelian randomization. We investigated the enrichment of single nucleotide polymorphism (SNP) at various tissue types utilizing stratified LD score regression (S-LDSC) and multimarker analysis of genome annotation (MAGMA). Common risk SNPs were identified using Multi-Trait Analysis of GWAS (MTAG) and Cross-Phenotype Association (CPASSOC). We further investigated the expression profiles of risk genes in tissues using Summary-data-based Mendelian randomization(SMR) based on pooled data, to explore potential functional genes. Results: Our findings indicated a significant genetic correlation between frailty and insomnia, highlighting SNPs sharing risk (rs34290943, rs10865954), with a pronounced correlation in the localized genomic region 3p21.31. Partitioned genetic analysis revealed 24 functional elements significantly associated with both frailty and insomnia. Furthermore, mendelian randomization revealed a causal connection between frailty and insomnia. The genetic correlation between frailty and insomnia showed enrichment in 11 brain regions (S-LDSC) and 9 brain regions (MAGMA), where four functional genes (RMB6, MST1R, RF123, and FAM212A) were identified. Conclusion: This study suggests the existence of a genetic correlation and common risk genes between frailty and insomnia, contributing to a deeper comprehension of their pathogenesis and assists in identifying potential therapeutic targets.

Cross2SynNet: cross-device-cross-modal synthesis of routine brain MRI sequences from CT with brain lesion.

OBJECTIVES: CT and MR are often needed to determine the location and extent of brain lesions collectively to improve diagnosis. However, patients with acute brain diseases cannot complete the MRI examination within a short time. The aim of the study is to devise a cross-device and cross-modal medical image synthesis (MIS) method Cross2SynNet for synthesizing routine brain MRI sequences of T1WI, T2WI, FLAIR, and DWI from CT with stroke and brain tumors. MATERIALS AND METHODS: For the retrospective study, the participants covered four different diseases of cerebral ischemic stroke (CIS-cohort), cerebral hemorrhage (CH-cohort), meningioma (M-cohort), glioma (G-cohort). The MIS model Cross2SynNet was established on the basic architecture of conditional generative adversarial network (CGAN), of which, the fully convolutional Transformer (FCT) module was adopted into generator to capture the short- and long-range dependencies between healthy and pathological tissues, and the edge loss function was to minimize the difference in gradient magnitude between synthetic image and ground truth. Three metrics of mean square error (MSE), peak signal-to-noise ratio (PSNR), and structure similarity index measure (SSIM) were used for evaluation. RESULTS: A total of 230 participants (mean patient age, 59.77 years ± 13.63 [standard deviation]; 163 men [71%] and 67 women [29%]) were included, including CIS-cohort (95 participants between Dec 2019 and Feb 2022), CH-cohort (69 participants between Jan 2020 and Dec 2021), M-cohort (40 participants between Sep 2018 and Dec 2021), and G-cohort (26 participants between Sep 2019 and Dec 2021). The Cross2SynNet achieved averaged values of MSE = 0.008, PSNR = 21.728, and SSIM = 0.758 when synthesizing MRIs from CT, outperforming the CycleGAN, pix2pix, RegGAN, Pix2PixHD, and ResViT. The Cross2SynNet could synthesize the brain lesion on pseudo DWI even if the CT image did not exhibit clear signal in the acute ischemic stroke patients. CONCLUSIONS: Cross2SynNet could achieve routine brain MRI synthesis of T1WI, T2WI, FLAIR, and DWI from CT with promising performance given the brain lesion of stroke and brain tumor.

Characterization of Cancer Cell Mechanics by Measuring Active Deformation Behavior.

Active deformation behavior reflects cell structural dynamics adapting to varying environmental constraints during malignancy progression. In most cases, cell mechanics is characterized by modeling using static equilibrium systems, which fails to comprehend cell deformation behavior leading to inaccuracies in distinguishing cancer cells from normal cells. Here, a method is introduced to measure the active deformation behavior of cancer cells using atomic force microscopy (AFM) and the newly developed deformation behavior cytometry (DBC). During the measurement, cells are deformed and allows a long timescale relaxation (≈5 s). Two parameters are derived to represent deformation behavior: apparent Poisson's ratio for adherent cells, which is measured with AFM and refers to the ratio of the lateral strain to the longitudinal strain of the cell, and shape recovery for suspended cells, which is measured with DBC. Active deformation behavior defines cancer cell mechanics better than traditional mechanical parameters (e.g., stiffness, diffusion, and viscosity). Additionally, aquaporins are essential for promoting the deformation behavior, while the actin cytoskeleton acts as a downstream effector. Therefore, the potential application of the cancer cell active deformation behavior as a biomechanical marker or therapeutic target in cancer treatment should be evaluated.

Extraction of brain function pattern with visual-capture-task fMRI using dynamic time-window method in ADHD children.

Attention deficit/Hyperactivity disorder (ADHD) has a great impact on children's development. This paper uses a novel adaptive brain state extraction algorithm to construct a dynamic time-window brain network, which captures the brain function pattern characteristics of ADHD children with higher temporal resolution. The test data were acquired by functional magnetic resonance imaging (fMRI) obtained from 23 children with ADHD during the visual-capture-task [age: (8.27 ± 2.77)]. A spatial standard deviation method is used after the initial data processing, to extract the brain activity pattern state; An improved clustering algorithm is constructed to verify the changes made to the dynamic time-window brain network model. There can be seen clear differences between each state within 0.05 s after the test. The results show that our improved new framework can effectively obtain the characteristics of dynamic brain functional connection strength changes during the task. In addition, the new algorithm is able to capture the dynamic changes of the brain network, with an 80 % improvement compared to traditional methods for the average modularity value Q. This work demonstrates a novel approach to find out the pattern changes between dynamic brain function connections, which can be of great significance for the adjuvant treatment of children with ADHD.

Analysis of the correlation between immune cell characteristics and insomnia: a Mendelian randomization study.

Insomnia, recognized as a prevalent sleep disorder, has garnered extensive attention within the realm of public health. Recent studies indicate a close interaction between the immune system and sleep; however, the specific mechanism remains not yet fully understood. Based on the publicly available Genome-Wide Association Study (GWAS) data, we used two-sample Mendelian randomization (MR) analyses to investigate the associations between 731 immune cell traits and insomnia risk. Five MR analysis methods and a comprehensive sensitivity analysis were used to evaluate the reliability of the results. In this study, we identified that 14 immune characteristics among four immune profiles [median fluorescence intensity (MFI), relative cell count (RC), absolute cell count (AC), and morphological parameters (MP)] demonstrated a significant causal association with insomnia. Specifically, eight immune cell characteristics were associated with an increased risk of insomnia, including CD11c+ monocyte% (P < 0.001), CD11c+ HLA DR++ monocyte% (P = 0.004), CD86+ plasmoid dendritic cell (DC) AC (P < 0.001), CD33br HLA DR+ CD14dim AC (P < 0.001), CD8dim AC (P = 0.002), CCR2 on CD14+ CD16- monocyte (P < 0.001), CD39 on monocyte (P < 0.001), and SSC-A on myeloid DC (P < 0.001). Six immune cell characteristics demonstrated protective effects against insomnia, including PB/PC %B cell (P < 0.001), CM CD4+% CD4+ (P < 0.001), T-cell AC (P < 0.001), BAFF-R on IgD- CD38br (P < 0.001), CD16-CD56 on HLA DR+ NK cells (P < 0.001), and CD14 on CD33br HLA DR+ CD14dim (P < 0.001). Our study established the correlation between immune cell characteristics and insomnia, offering a novel theoretical foundation for the concept of sleep-immune cross talk.NEW & NOTEWORTHY This study investigated the association between 731 immune cell characteristics and insomnia using Mendelian randomization, revealing that 14 immune cell characteristics across four groups of immune traits (MFI, RC, AC, and MP) have a significant and causal association with insomnia risk. Our results contribute to the understanding of the sleep-immune cross talk doctrine and offer a new theoretical basis for immune modulation in treating insomnia.

Designing a Compact Dual-Band, Dual-Polarized Antenna for Biotelemetry Communications Using the Characteristic Mode Method.

A compact dual-band, dual-polarized, implantable antenna was designed using the characteristic mode method for operation in the wireless medical telemetry service (WMTS) band (1.4 GHz) and the industrial, scientific, and medical (ISM) band (2.45 GHz). By utilizing slotting techniques and materials with high dielectric constants, the antenna volume was minimized to 47.4 mm3, and circular polarization was gained in the WMTS band by using the characteristic mode method. A three-layer physical model of human tissues was constructed in a simulation, and a biogel and minced pork were used in the measurements. The measured peak gains are -20.85 dBi (1.4 GHz) and -22.15 dBi (2.45 GHz). The measured effective axis ratio bandwidth in the WMTS band is 170 MHz (1.33-1.50 GHz, 12.0%), and the impedance bandwidth in the ISM band is 390 MHz (2.21-2.60 GHz, 16.2%). At 1.4 GHz and 2.45 GHz, the largest 1 g average SAR values are 376 W/Kg and 318 W/Kg, which comply with IEEE C95.1-1999. Moreover, when the communication chain affinity exceeds 20 dB for 1.4 GHz and 2.4 GHz, the transceiver range reaches 8.2 m and 9.7 m. This antenna can be used for implantable wireless telemetry systems.

Androgen signaling stabilizes genomes to counteract senescence by promoting XRCC4 transcription.

Aging is accompanied by a decreased DNA repair capacity, which might contribute to age-associated functional decline in multiple tissues. Disruption in hormone signaling, associated with reproductive organ dysfunction, is an early event of age-related tissue degeneration, but whether it impacts DNA repair in nonreproductive organs remains elusive. Using skin fibroblasts derived from healthy donors with a broad age range, we show here that the downregulation of expression of XRCC4, a factor involved in nonhomologous end-joining (NHEJ) repair, which is the dominant pathway to repair somatic double-strand breaks, is mediated through transcriptional mechanisms. We show that the androgen receptor (AR), whose expression is also reduced during aging, directly binds to and enhances the activity of the XRCC4 promoter, facilitating XRCC4 transcription and thus stabilizing the genome. We also demonstrate that dihydrotestosterone (DHT), a powerful AR agonist, restores XRCC4 expression and stabilizes the genome in different models of cellular aging. Moreover, DHT treatment reverses senescence-associated phenotypes, opening a potential avenue to aging interventions in the future.

Audio-induced medial prefrontal cortical dynamics enhances coadaptive learning in brain-machine interfaces.

Objectives. Coadaptive brain-machine interfaces (BMIs) allow subjects and external devices to adapt to each other during the closed-loop control, which provides a promising solution for paralyzed individuals. Previous studies have focused on either improving sensory feedback to facilitate subject learning or developing adaptive algorithms to maintain stable decoder performance. In this work, we aim to design an efficient coadaptive BMI framework which not only facilitates the learning of subjects on new tasks with designed sensory feedback, but also improves decoders' learning ability by extracting sensory feedback-induced evaluation information.Approach. We designed dynamic audio feedback during the trial according to the subjects' performance when they were trained to learn a new behavioral task. We compared the learning performance of two groups of Sprague Dawley rats, one with and the other without the designed audio feedback to show whether this audio feedback could facilitate the subjects' learning. Compared with the traditional closed-loop in BMI systems, an additional closed-loop involving medial prefrontal cortex (mPFC) activity was introduced into the coadaptive framework. The neural dynamics of audio-induced mPFC activity was analyzed to investigate whether a significant neural response could be triggered. This audio-induced response was then translated into reward expectation information to guide the learning of decoders on a new task. The multiday decoding performance of the decoders with and without audio-induced reward expectation was compared to investigate whether the extracted information could accelerate decoders to learn a new task.Main results. The behavior performance comparison showed that the average days for rats to achieve 80% well-trained behavioral performance was improved by 26.4% after introducing the designed audio feedback sequence. The analysis of neural dynamics showed that a significant neural response of mPFC activity could be elicited by the audio feedback and the visualization of audio-induced neural patterns was emerged and accompanied by the behavioral improvement of subjects. The multiday decoding performance comparison showed that the decoder taking the reward expectation information could achieve faster task learning by 33.8% on average across subjects.Significance. This study demonstrates that the designed audio feedback could improve the learning of subjects and the mPFC activity induced by audio feedback can be utilized to improve the decoder's learning efficiency on new tasks. The coadaptive framework involving mPFC dynamics in the closed-loop interaction can advance the BMIs into a more adaptive and efficient system with learning ability on new tasks.

First Report of Bacterial Leaf Spot on Muskmelon Caused by Pseudomonas syringae pv. syringae in China.

Muskmelon (Cucumis melo L.) is one of the most widely cultivated and economically important fruit crops in the world. In January 2023, muskmelon leaves of cultivar 'Sheng Gu' were observed with irregularly shaped spots in four nurseries in Wanxiang Village, Pudong District of Shanghai, China. Initial symptoms were irregular soaking on the leaves, which progressed to rotting and necrotic spots. The disease incidence of melon seedlings in different nurseries ranged from 10 to 25%. To isolate and identify the causal agent, the small pieces of lesion tissues (5×5 mm) from symptomatic leaves were sterilized in 75% ethanol for 30 s and rinsed three times with sterile water. Following that, tissues were crushed with sterile glass rod in a sterile 2.0 mL centrifuge tube containing 100 µl of sterile water. The suspension was serially diluted before being spread on Luria-Bertani (LB) medium. After 48 h of incubation at 28°C, the cream-colored bacterial colonies from the 10-4 dilution were tiny and purified by streaking on new LB plates. To confirm the species identity of the bacterial isolates, genomic DNA was extracted from four independent representative colonies from different diseased plants, and several conserved genes were amplified and sequenced, including the 16S rRNA gene with primers 27F/1492R, gyrB gene with primers gyrBFor2/gyrBRev2, and rpoD gene with primers rpoDFor2/rpoDRev2 (Lelliot et al. 1966; Murillo et al. 2011). The results showed that the four colonies were identical. Using BLAST analysis in GenBank, the 16S rDNA (accession no. OQ659765, 1,402 bp), the gyrB (accession no. OQ708618, 911 bp), and rpoD sequences (accession no. OQ708619, 798 bp) showed 99.86-100% homology with 99-100% coveage as the corresponding gene sequences in the P. syringae pv. syringae strain HS191 (accession no. CP006256.1). The bacterial isolate was designated as P. syringae pv. syringae strain PDTG. Phylogenetic tree analysis of 16S rDNA, gyrB and rpoD genes further verified that the bacteria isolate was in close proximity to P. syringae pv. syringae. Additionally, all four isolates were detected in PCR with P. syringae pv. syringae specific primers, PsyF/ PsyR (Borschinger et al. 2016; Guilbaud et al. 2016). Ten two weeks old healthy 'Sheng Gu' muskmelon seedlings were inoculated by spraying with a bacterial suspension of 108 CFU/ml, and ten additional healthy plants treated with sterilized water served as the control. The inoculated plants were maintained at 25°C and 75% relative humidity for 7 days in artificial climate room. Water-soaked rot, similar as those seen in the nurseries, appeared on leaves 7 days after inoculation (dai), while the leaves of control plants remained healthy. The bacteria were re-isolated from rot of inoculated leaves and confirmed as the original pathogen by PCR with the PsyF/ PsyR primers and the 16S rRNA gene sequences. To our knowledge, this is the first report of P. syringae pv. syringae causing bacterial leaf spot on muskmelon in China, and this report expands the host range of P. syringae pv. syringae.

Population genomics and pathotypic evaluation of the bacterial leaf blight pathogen of rice reveals rapid evolutionary dynamics of a plant pathogen.

The Xanthomonas oryzae pv. oryzae (Xoo) is a bacterial pathogen causing bacterial blight disease in rice, resulting in significant yield reductions of up to 50% in rice production. Despite its serious threat to food production globally, knowledge of its population structure and virulence evolution is relatively limited. In this study, we employed whole-genome sequencing to explore the diversity and evolution of Xoo in the main rice-growing areas of China over the past 30 years. Using phylogenomic analysis, we revealed six lineages. CX-1 and CX-2 primarily contained Xoo isolates from South China, while CX-3 represented Xoo isolates from North China. Xoo isolates belonging to CX-5 and CX-6 were the most prevalent across all studied areas, persisting as dominant lineages for several decades. Recent sporadic disease outbreaks were primarily caused by Xoo isolates derived from the two major lineages, CX-5 and CX-6, although Xoo isolates from other lineages also contributed to these outbreaks. The lineage and sub-lineage distributions of Xoo isolates were strongly correlated with their geographical origin, which was found to be mainly determined by the planting of the two major rice subspecies, indica and japonica. Moreover, large-scale virulence testing was conducted to evaluate the diversity of pathogenicity for Xoo. We found rapid virulence evolution against rice, and its determinant factors included the genetic background of Xoo, rice resistance genes, and planting environment of rice. This study provides an excellent model for understanding the evolution and dynamics of plant pathogens in the context of their interactions with their hosts, which are shaped by a combination of geographical conditions and farming practices. The findings of this study may have important implications for the development of effective strategies for disease management and crop protection in rice production systems.

Enhancing pharmacokinetic and pharmacodynamic properties of recombinant therapeutic proteins by manipulation of sialic acid content.

The circulatory half-life of recombinant therapeutic proteins is an important pharmacokinetic attribute because it determines the dosing frequency of these drugs, translating directly to treatment cost. Thus, recombinant therapeutic glycoproteins such as monoclonal antibodies have been chemically modified by various means to enhance their circulatory half-life. One approach is to manipulate the N-glycan composition of these agents. Among the many glycan constituents, sialic acid (specifically, N-acetylneuraminic acid) plays a critical role in extending circulatory half-life by masking the terminal galactose that would otherwise be recognised by the hepatic asialoglycoprotein receptor (ASGPR), resulting in clearance of the biotherapeutic from the circulation. This review aims to provide an illustrative overview of various strategies to enhance the pharmacokinetic/pharmacodynamic properties of recombinant therapeutic proteins through manipulation of their sialic acid content.

Farrerol directly activates the deubiqutinase UCHL3 to promote DNA repair and reprogramming when mediated by somatic cell nuclear transfer.

Farrerol, a natural flavanone, promotes homologous recombination (HR) repair to improve genome-editing efficiency, but the specific protein that farrerol directly targets to regulate HR repair and the underlying molecular mechanisms have not been determined. Here, we find that the deubiquitinase UCHL3 is the direct target of farrerol. Mechanistically, farrerol enhanced the deubiquitinase activity of UCHL3 to promote RAD51 deubiquitination, thereby improving HR repair. Importantly, we find that embryos of somatic cell nuclear transfer (SCNT) exhibited defective HR repair, increased genomic instability and aneuploidy, and that the farrerol treatment post nuclear transfer enhances HR repair, restores transcriptional and epigenetic network, and promotes SCNT embryo development. Ablating UCHL3 significantly attenuates farrerol-mediated stimulation in HR and SCNT embryo development. In summary, we identify farrerol as an activator of the deubiquitinase UCHL3, highlighted the importance of HR and epigenetic changes in SCNT reprogramming and provide a feasible method to promote SCNT efficiency.

Occurrence of Tomato Leaf Curl New Delhi Virus in Cucurbit Plants in China.

In August 2022, melon (Cucumis melo), cucumber (Cucumis sativus) and luffa (Luffa aegyptiaca) plants showed virus-like symptoms characteristic of geminiviruses (yellowish green, mosaic patterns and severe curling of leaves, short internodes, and stunting) in 10 greenhouses in Fengxian district and 20 greenhoues in Jiading district of Shanghai, China. Fifty symptomatic leaf samples were randomly collected: 28 from melon, 17 from cucumber, and 5 from luffa. To investigate the etiology of the observed disease, total DNA and RNA was extracted via a DNA extraction kit (Tiangen, Not: DP350) and TRIzol reagent (Sigma-Aldrich, Not: T9424), respectively. Healthy melon plants grown in a growth chamber served as negative control. The DNA and RNA samples were screened for the presence of geminiviruses, Cucurbit chlorotic yellow virus (CCYV), Melon yellow spot virus (MYSV), Cucumber mosaic virus (CMV), Zucchini yellow mosaic virus (ZYMV) and Cucumber green mottle mosaic virus (CGMMV) through PCR or RT‒PCR with geminiviruses (Deng et al. 1994), CCYV, MYSV, CMV, ZYMV and CGMMV (Zeng et al. 2011, 2019) primers. The PCR results showed that 28 melon leaves and 17 cucumber leaves were positive for geminivirus and CCYV, respectively, 5 luffa samples were infected with only geminivirus, and virus was not detected from the healthy plants. These results indicate that these two viruses are widely distributed throughout cucurbit crops in Shanghai, China. All the geminiviruses sequences (approximately 510 bp) were quite similar to each other and were most similar (99.4%) to the Tomato leaf curl New Delhi virus (ToLCNDV) sequence (GenBank Accession No. OP356207) (Li et al. 2022). To confirm the presence of geminiviruses, the segments of DNA-A and DNA-B were amplified by PCR with 4 ToLCNDV-specific primer sets (Mizutani et al. 2011) and sequenced from 10 samples (4 melon, 4 cucumber and 2 luffa). Both DNA-A and DNA-B of the ToLCNDV sequences and features were deposited in GenBank under the accession numbers OQ190939-OQ190948 (DNA-A, 2739 nt) and OQ190949-OQ190958 (DNA-B, 2693 nt). BLASTn analysis of Shanghai isolates of ToLCNDV (DNA-A and DNA-B) showed that the sequences shared nucleotide identities ranged from 99.3% to 100% among them and with values of more than 99.4% nucleotide identity with ToLCNDV isolates from tomato in China (OP356207 and OP356208) (Li et al. 2022). To confirm the virus infection, we have successfully constructed an infectious clone for 0823-1 isolate in the binary plasmid and inoculated melon with and without an infectious clone. The melon plants inoculated with ToLCNDV 15 dpi showed the high accumulation of the virus and displayed symptoms similar to viruses in greenhouse. Based on the complete sequences, results of the molecular phylogenetic analysis (Fig. 2) and infectious clone, these geminiviruses were identified as ToLCNDV. ToLCNDV has been reported to occur and spread by the whitefly (Bemisia tabaci) in many Asian countries (Sohrab et al. 2003; Sohrab et al. 2011; Aamir et al. 2020) and Europe (Juárez et al. 2014; Ruiz et al. 2015; Luigi et al. 2019). Large populations of whiteflies were also present in all our surveyed areas. However, to our knowledge, this is the first report of the occurrence of ToLCNDV in cucurbit plants in China. The presence of ToLCNDV and CCYV can cause severe losses in crop yields or even crop failure. In addition to TYLCV, ToLCNDV is another major geminivirus-induced disease threatening cucurbit and other vegetable production in China.

A Novel Dual-Polarized Magnetoelectric Dipole Antenna and Its Array for LTE and 5G Sub-6 GHz Base Station Applications.

This study presents a novel dual-polarized magnetoelectric dipole antenna and its array with director and rectangular parasitic metal patches for LTE and 5G sub-6 GHz base station applications. This antenna is composed of L-shaped magnetic dipoles, planar electric dipoles, rectangular director, rectangular parasitic metal patches, and η-shaped feed probes. The gain and bandwidth were enhanced by using the director and parasitic metal patches. The measured impedance bandwidth of the antenna was 82.8% (1.62-3.91 GHz, VSWR < 1.5), and its gain was 10 ± 0.5 dBi. The profile of the antenna unit, operated at 1.7 GHz, was only 42 mm (0.227λ0, where λ0 represents the free space wavelength corresponding to the lowest resonance frequency point). Subsequently, four antenna units were arranged in a line array with 0.6λ0 spacing. Both the antenna and its array were fabricated and measured. The measurement results show that the array has good radiation characteristics, such as broad bandwidth covering 1.65-3.97 GHz (VSWR < 1.5), high gain (its gain was great than 15.2 dBi), and high radiation efficiency (>90%). Its HPBWs were 63° ± 4° and 15° ± 2° for H- and E-planes, respectively. The design can cover TD-LTE and 5G sub-6 GHz NR n78 frequency bands very well, meaning that this is a good candidate antenna for base station applications.

Resistance Profiles of Botrytis cinerea to Fluxapyroxad from Strawberry Fields in Shanghai, China.

Fluxapyroxad, a type of succinate dehydrogenase inhibitor fungicide, has been used to control the growth of gray mold on strawberry for more than 5 years in China. Selection for resistance to the causal agent Botrytis cinerea became a threat to the efficacy of fluxapyroxad. In total, 160 B. cinerea isolates collected from Shanghai during 2020 and 2021 were tested for their resistance to fluxapyroxad using mycelial growth inhibition. The results indicated that the curve of baseline sensitivity was unimodal, with an approximately normal distribution and a mean effective concentration of the fungicide that inhibited growth by 50% (EC50) of 0.18 ± 0.01 µg/ml. In total, 27.78 and 48.57% of isolates were resistant to fluxapyroxad in 2020 and 2021, respectively, where the lowest EC50 value of mycelial growth inhibition was 0.03 µg/ml and the highest value was 51.3 µg/ml. Resistance mechanism analysis showed that the succinate dehydrogenase subunit B (SdhB) N230I mutation could lead to resistance and P225F mutation could lead to higher resistance. These data suggest that the resistance frequency of B. cinerea isolates to fluxapyroxad increased in 2021 compared with 2020, which requires appropriate fungicide rotation strategies to be implemented in order to control gray mold on strawberry in the future.

Responses of key root traits in the genus Oryza to soil flooding mimicked by stagnant, deoxygenated nutrient solution.

Excess water can induce flooding stress resulting in yield loss, even in wetland crops such as rice (Oryza). However, traits from species of wild Oryza have already been used to improve tolerance to abiotic stress in cultivated rice. This study aimed to establish root responses to sudden soil flooding among eight wild relatives of rice with different habitat preferences benchmarked against three genotypes of O. sativa. Plants were raised hydroponically, mimicking drained or flooded soils, to assess the plasticity of adventitious roots. Traits included were apparent permeance (PA) to O2 of the outer part of the roots, radial water loss, tissue porosity, apoplastic barriers in the exodermis, and root anatomical traits. These were analysed using a plasticity index and hierarchical clustering based on principal component analysis. For example, O. brachyantha, a wetland species, possessed very low tissue porosity compared with other wetland species, whereas dryland species O. latifolia and O. granulata exhibited significantly lower plasticity compared with wetland species and clustered in their own group. Most species clustered according to growing conditions based on PA, radial water loss, root porosity, and key anatomical traits, indicating strong anatomical and physiological responses to sudden soil flooding.