The mechanism and therapeutic potential of lncRNA MIR497HG/miR-16-5p axis in breast cancer.

BACKGROUND: Breast cancer has become a major public health problem in the current society, and its incidence rate ranks the first among Chinese female malignant tumors. This paper once again confirmed the efficacy of lncRNA in tumor regulation by introducing the mechanism of the diagnosis of breast cancer by the MIR497HG/miR-16-5p axis. METHODS: The abnormal expression of MIR497HG in breast cancer was determined by RT-qPCR method, and the correlation between MIR497HG expression and clinicopathological characteristics of breast cancer patients was analyzed via Chi-square test. To understand the diagnostic potential of MIR497HG in breast cancer by drawing the receiver operating characteristic curve (ROC). The overexpressed MIR497HG (pcDNA3.1-MIR497HG) was designed and constructed to explore the regulation of elevated MIR497HG on biological function of BT549 and Hs 578T cells through Transwell assays. Additionally, the luciferase gene reporter assay and Pearson analysis evaluated the targeting relationship of MIR497HG to miR-16-5p. RESULTS: MIR497HG was decreased in breast cancer and had high diagnostic function, while elevated MIR497HG inhibited the migration and invasion of BT549 and Hs 578T cells. In terms of functional mechanism, miR-16-5p was the target of MIR497HG, and MIR497HG reversely regulated the miR-16-5p. miR-16-5p mimic reversed the effects of upregulated MIR497HG on cell biological function. CONCLUSIONS: In general, MIR497HG was decreased in breast cancer, and the MIR497HG/miR-16-5p axis regulated breast cancer tumorigenesis, providing effective insights for the diagnosis of patients.

Control of the differentiation of regulatory T cells and T(H)17 cells by the DNA-binding inhibitor Id3.

The molecular mechanisms that direct transcription of the gene encoding the transcription factor Foxp3 in CD4(+) T cells remain ill-defined. We show here that deletion of the DNA-binding inhibitor Id3 resulted in the defective generation of Foxp3(+) regulatory T cells (T(reg) cells). We identify two transforming growth factor-ß1 (TGF-ß1)-dependent mechanisms that were vital for activation of Foxp3 transcription and were defective in Id3(-/-) CD4(+) T cells. Enhanced binding of the transcription factor E2A to the Foxp3 promoter promoted Foxp3 transcription. Id3 was required for relief of inhibition by the transcription factor GATA-3 at the Foxp3 promoter. Furthermore, Id3(-/-) T cells showed greater differentiation into the T(H)17 subset of helper T cells in vitro and in a mouse asthma model. Therefore, a network of factors acts in a TGF-ß-dependent manner to control Foxp3 expression and inhibit the development of T(H)17 cells.

HIV envelope-CXCR4 signaling activates cofilin to overcome cortical actin restriction in resting CD4 T cells.

Binding of the HIV envelope to the chemokine coreceptors triggers membrane fusion and signal transduction. The fusion process has been well characterized, yet the role of coreceptor signaling remains elusive. Here, we describe a critical function of the chemokine coreceptor signaling in facilitating HIV infection of resting CD4 T cells. We find that static cortical actin in resting T cells represents a restriction and that HIV utilizes the Galphai-dependent signaling from the chemokine coreceptor CXCR4 to activate a cellular actin-depolymerizing factor, cofilin, to overcome this restriction. HIV envelope-mediated cofilin activation and actin dynamics are important for a postentry process that leads to viral nuclear localization. Inhibition of HIV-mediated actin rearrangement markedly diminishes viral latent infection of resting T cells. Conversely, induction of active cofilin greatly facilitates it. These findings shed light on viral exploitation of cellular machinery in resting T cells, where chemokine receptor signaling becomes obligatory.

First Report of Peanut Black Pod Rot Caused by Berkeleyomyces rouxiae in China.

Peanut (Arachis hypogaea L.) is an important oilseed and cash crop cultivated in over 100 countries worldwide. The major producers are China, India and USA (Ding et al. 2022). In September 2022, peanut pods exhibiting black necrotic symptoms on the shell surface were observed in Puyang, Henan Province, China. These black spots often merged to form larger necrotic spots on the shell. Disease incidence was 100% in susceptible varieties. Symptomatic shell pieces were surface sterilized with 75% ethanol for 3 min, rinsed three times with sterile water, and then transferred onto PDA medium supplemented with 25 µg/ml chloramphenicol (Long et al. 2022). Isolation frequency of a fungus with similar-appearing colonies from symptomatic pods was 81.7%. A pure culture of a representative isolate, PYHB, was obtained through single-sporing and maintained on PDA plates at 25℃ in darkness. The colony initially appeared white but turned black within 2 days. The isolate produced dark brown, unicellular chlamydospores, which were arranged in club-shaped chains consisting of two to seven cells. The size of the unicellular chlamydospores varied from 3.34 to 15.27 µm (average:6.81, n = 100) in length and 8.30 to 15.51 µm (average:11.29, n = 100) in width. The endoconidia were hyaline and cylindrical, measuring 7.91-22.94 × 1.69-4.81 µm (average: 12.16 × 3.13, n = 100). Based on morphological characteristics, the isolate was tentatively identified as a Berkeleyomyces sp. (Nel et al. 2018; Long et al. 2022). The ITS region of r-DNA, the ribosomal large subunit (LSU), the minichromosome maintenance complex component 7 (MCM7), and the 60S ribosomal protein RPL10 (60S) genes were amplified using ITS1/ITS4, LR0R/LR5, rouxMCM7-F/rouxMCM7-R and roux60s-F/roux60s-R primers, respectively (White et al. 1990; Vilgalys and Hester 1990; Nakane and Usami 2020). The sequences were deposited in GenBank (ITS: OR053803; LSU: OR053818; MCM7: OR058549; 60S: OR060656). Through BLASTn analysis of the NCBI GenBank database, the generated ITS and LSU sequences showed 100% identity to Berkeleyomyces rouxiae (GenBank MF952418.1 and MF948662.1, respectively) and B. basicola (GenBank MT221585.1 and MH868639.1, respectively). Importantly, the MCM7 and 60S sequences were 100% identical to B. rouxiae (GenBank MF967114.1 and MF967077.1, respectively). Phylogenetic analysis combining ITS, LSU, MCM7, and 60S sequences showed that the isolate PYHB clustered with B. rouxiae. To evaluate pathogenicity, surface-sterilized healthy peanut pods (n = 90) were immersed in a 1×106 spore/ml conidial suspension obtained from isolate PYHB for 5 min and placed in Petri dishes containing moistened cotton at 25°C for 10 days. Pods (n = 90) inoculated with sterile water served as controls. Inoculated pods displayed black necrosis 10 days after inoculation (dai), whereas no symptoms were observed on the control pods at 21 dai. The reisolated pathogen was shown to be identical to the original inoculum through morphological and phylogenetic analysis. Black root rot is a fungal disease caused by Berkeleyomyces spp. (syn. Thielaviopsis spp.) and affects various crops and ornamentals, such as cotton, tobacco, carrot, holly, and pansy (Rahnama et al. 2022). The causal agents B. rouxiae and B. basicola have similar morphological characteristics but can be differentiated through molecular characterization (Nel et al. 2018). To our knowledge, this is the first report of black pod rot in peanut caused by B. rouxiae in China. The finding from this study will contribute to the development of monitoring and management strategies to combat this destructive disease in peanut cultivation.

Genetic, Phenotypic, and Pathogenic Variation Among Athelia rolfsii, the Causal Agent of Peanut Stem Rot in China.

Peanut stem rot caused by Athelia rolfsii is a serious soilborne disease worldwide and is becoming increasingly important in China. A total of 293 A. rolfsii isolates were collected from four representative peanut producing provinces in northern, central, and southern China. These isolates were assigned to 45 mycelial compatibility groups (MCGs) through pairing testing. The MCG diversity among isolates was greater in the southern sampled provinces compared with the northern provinces. A high level of genetic variability was found among the isolates from Guangdong Province in southern China. Variations were found in mycelial growth rate and sclerotial number, size, and dry weight of isolates sampled from places in different latitudes. Size and dry weight of sclerotia were positively correlated with latitude (P < 0.01), but the number of sclerotia was negatively correlated with latitude (P < 0.01). All tester isolates were pathogenic on peanut but varied in disease index. Inter-simple sequence repeat analysis and unweighted pair-group method with arithmetic average clustering resulted in three distinct clusters that were associated with the geographical location of the collection sites and sclerotial traits but were not associated with virulence of these isolates. These findings imply that genetic diversity, morphological traits, and virulence among A. rolfsii isolates varied in diverse geographical regions in China, and genetic diversity and sclerotial traits might be affected by latitude.

Analysis of endometrial thickness patterns and pregnancy outcomes considering 12,991 fresh IVF cycles.

BACKGROUND: Different endometrial patterns have an important effect on the relationship between endometrial thickness (EMT) and clinical pregnancy rate. There is a significant difference in age, selection of cycle protocols, and clinical pregnancy rates among four groups with diverse endometrial patterns. METHODS: This retrospective study aimed to assess the association between EMT on human chorionic gonadotropin (HCG) administration day and the clinical outcome of fresh in vitro fertilization (IVF). The 5th, 50th, and 95th percentiles for EMT were determined as 8, 11, and 14 mm, respectively. Patients were sub-divided into four groups based on their EMT in different endometrial patterns (Group 1: < 8 mm; Group 2: ≥ 8 and ≤ 11 mm; Group 3: > 11 and ≤ 14 mm; Group 4: > 14 mm). We divided patients into three groups based on their endometrial pattern and evaluated the correlation between EMT and clinical pregnancy rate. RESULTS: We found a positive correlation between pregnancy rates and EMT in all endometrial patterns. Multiple logistic regression analysis proved age, duration of infertility, cycle protocols, number of embryos transferred, progesterone on HCG day, endometrial patterns, and EMT have significant effects on clinical pregnancy rates. Meanwhile, there was a significant difference in age, selection of cycle protocols, and clinical pregnancy rates among four groups with diverse endometrial patterns. CONCLUSIONS: Different endometrial patterns have an important effect on the relationship between EMT and clinical pregnancy rate.

Genome-wide transcriptome profiling provides overwintering mechanism of Agropyron mongolicum.

BACKGROUND: The mechanism of winter survival for perennials involves multiple levels of gene regulation, especially cold resistance. Agropyron mongolicum is one important perennial grass species, but there is little information regarding its overwintering mechanism. We performed a comprehensive transcriptomics study to evaluate global gene expression profiles regarding the winter survival of Agropyron mongolicum. A genome-wide gene expression analysis involving four different periods was identified. Twenty-eight coexpression modules with distinct patterns were performed for transcriptome profiling. Furthermore, differentially expressed genes (DEGs) and their functional characterization were defined using a genome database such as NT, NR, COG, and KEGG. RESULT: A total of 79.6% of the unigenes were characterized to be involved in 136 metabolic pathways. In addition, the expression level of ABA receptor genes, regulation of transcription factors, and a coexpression network analysis were conducted using transcriptome data. We found that ABA receptors regulated downstream gene expression by activating bZIP and NAC transcription factors to improve cold resistance and winter survival. CONCLUSION: This study provides comprehensive transcriptome data for the characterization of overwintering-related gene expression profiles in A. mongolicum. Genomics resources can help provide a better understanding of the overwintering mechanism for perennial gramineae species. By analyzing genome-wide expression patterns for the four key stages of tiller bud development, the functional characteristics of the DEGs were identified that participated in various metabolic pathways and have been shown to be strongly associated with cold tolerance. These results can be further exploited to determine the mechanism of overwintering in perennial gramineae species.

HIV-1 triggers WAVE2 phosphorylation in primary CD4 T cells and macrophages, mediating Arp2/3-dependent nuclear migration.

The human immunodeficiency virus type 1 (HIV-1) initiates receptor signaling and early actin dynamics during viral entry. This process is required for viral infection of primary targets such as resting CD4 T cells. WAVE2 is a component of a multiprotein complex linking receptor signaling to dynamic remodeling of the actin cytoskeleton. WAVE2 directly activates Arp2/3, leading to actin nucleation and filament branching. Although several bacterial and viral pathogens target Arp2/3 for intracellular mobility, it remains unknown whether HIV-1 actively modulates the Arp2/3 complex through virus-mediated receptor signal transduction. Here we report that HIV-1 triggers WAVE2 phosphorylation at serine 351 through gp120 binding to the chemokine coreceptor CXCR4 or CCR5 during entry. This phosphorylation event involves both Gαi-dependent and -independent pathways, and is conserved both in X4 and R5 viral infection of resting CD4 T cells and primary macrophages. We further demonstrate that inhibition of WAVE2-mediated Arp2/3 activity through stable shRNA knockdown of Arp3 dramatically diminished HIV-1 infection of CD4 T cells, preventing viral nuclear migration. Inhibition of Arp2/3 through a specific inhibitor, CK548, also drastically inhibited HIV-1 nuclear migration and infection of CD4 T cells. Our results suggest that Arp2/3 and the upstream regulator, WAVE2, are essential co-factors hijacked by HIV for intracellular migration, and may serve as novel targets to prevent HIV transmission.

Expression of vitamin D receptor as a potential prognostic factor and therapeutic target in pancreatic cancer.

AIMS: Vitamin D insufficiency and deficiency are common among patients with pancreatic carcinoma, but epidemiological studies have shown inconsistent results for vitamin D intake/circulation level and pancreatic cancer risk. The study aims were to investigate the effects of vitamin D on patient survival, and the proliferation or survival of pancreatic cancer cell lines. METHODS AND RESULTS: The present study examined the local expression of vitamin D receptor (VDR) in pancreatic normal and tumour tissues from a cohort of 61 patients, and analysed the potential correlation between VDR and pathological characteristics, including disease prognosis. Among 61 pairs of normal and tumour specimens, VDR was detected in all normal tissues, and was abundantly expressed in 62.5% (15/24) of tumour tissues with high differentiation, but had a significantly lower or undetectable expression level in 75.7% (28/37) of tissues with moderate or low differentiation (P = 0.004). Moreover, high VDR expression was detected in 63.6% (14/22) of small tumours (≤25 mm) and in only 25.6% (10/39) of large tumours (>25 mm) (P = 0.06). Kaplan-Meier analysis showed that a low level of VDR expression in tumour tissues was associated with a poor prognosis (P = 0.037). CONCLUSIONS: VDR expression could be a potential prognostic factor for patients with pancreatic adenocarcinoma, and its effects should be examined in a prospective study. Vitamin D analogues may provide a therapeutic choice for patients with high VDR expression in tumours but a low vitamin D level in the circulation.

[Expression and clinical significance of Tspan 1 and Integrin α6 in human pancreatic ductal adenocarcinoma].

OBJECTIVE: To explore the clinicopathological significance and relationship of Tspan 1 and Integrin α6 expression in pancreatic ductal adenocarcinoma (PDAC) tissue and pancreatic cancer cell lines. METHODS: Immunohistochemistry was used to detect the expression of Tspan 1 and Integrin α6 in 95 paraffin-embedded PDAC specimens and 55 adjacent non-cancerous pancreatic tissues which were collected from May 2004 to January 2013.Western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detected the protein and mRNA expression in 16 paired fresh PDAC specimens of the pancreas and adjacent non-cancerous pancreatic tissues and 6 different pancreatic cancer cell lines.χ(2) test, Spearman-rank correlation analysis, Kaplan-Meier method and multivariate Cox regression analysis were used to analyze the data. RESULTS: Tspan 1 and Integrin α6 were significantly over-expressed in PDAC than in adjacent non-cancerous pancreatic tissues (χ(2) = 7.429, P < 0.05; χ(2) = 15.1, P < 0.01). Lymph node metastasis, TNM stage and post-operation recurrence were positively correlated with the expression of Tspan 1 (χ(2) = 6.688, P < 0.01; χ(2) = 13.055, P < 0.01; χ(2) = 6.116, P < 0.05) . TNM stage was positively correlated with the expression of Integrin α6 (χ(2) = 8.896, P < 0.05) . Tspan 1 was correlated with Integrin α6 (r = 0.223, P < 0.05) . The expressions of Tspan 1 and Integrin α6 were negatively correlated with survival time (χ(2) = 5.263, P < 0.05;χ(2) = 10.124, P < 0.01) . Multivariate analysis revealed that Tspan 1 and Integrin α6 expressions were independent prognostic factors in PDAC patients (χ(2) = 6.152, P < 0.05; χ(2) = 9.479, P < 0.01). Western blot (t = 2.278, P < 0.05; t = 3.153, P < 0.05) and qRT-PCR (t = 2.439, P < 0.05; t = 3.258, P < 0.05) showed that Tspan 1 and Integrin α6 expressions were higher in PDAC tissues than in adjacent non-cancerous pancreatic. Tspan 1 and Integrin α6 were expressed in all six pancreatic cancer cell lines.In SW1990 which derived from metastasis PDAC, Tspan 1 and Integrin α6 expressions were higher than the cell lines from primary tumor. CONCLUSION: Tspan 1 and Integrin α6 expression can up-regulate the invasion and metastasis of PDAC and may be used to predict the prognosis of PDAC.

Factors influencing further vertebral height loss following percutaneous vertebroplasty in osteoporotic vertebral compression fractures: A 1-year follow-up study.

BACKGROUND: Osteoporotic vertebral compression fractures (OVCFs) contribute to back pain and functional limitations in older individuals, with percutaneous vertebroplasty (PVP) emerging as a minimally invasive treatment. However, further height loss post-PVP prompts investigation into contributing factors. AIM: To investigate the factors associated with further height loss following PVP with cement augmentation in OVCF patients. METHODS: A total of 200 OVCF patients who underwent successful PVP between January 2021 and December 2022 were included in this study. "Further height loss" during 1 year of follow-up in OVCF patients with bone edema was defined as a vertical height loss of ≥ 4 mm. The study population was divided into two groups for analysis: The "No Further Height Loss group (n = 179)" and the "Further Height Loss group (n = 21)." RESULTS: In comparing two distinct groups of patients, significant differences existed in bone mineral density (BMD), vertebral compression degree, prevalence of intravertebral cleft (IVF), type of bone cement used, and cement distribution patterns. Results from binary univariate regression analysis revealed that lower BMD, the presence of IVF, cleft distribution of bone cement, and higher vertebral compression degree were all significantly associated with further height loss. Notably, the use of mineralized collagen modified-poly(methyl methacrylate) bone cement was associated with a significant reduction in the risk of further height loss. In multivariate regression analysis, lower BMD and the presence of IVF remained significantly associated with further height loss. CONCLUSION: Further height loss following PVP in OVCF patients is influenced by a complex interplay of factors, especially lower BMD and the presence of IVF. These findings underscore the importance of assessing and managing these factors when addressing height loss following PVP in OVCF patients.

Characterization of Two Novel Single-Stranded RNA Viruses from Agroathelia rolfsii, the Causal Agent of Peanut Stem Rot.

Peanut stem rot is a soil-borne disease caused by Agroathelia rolfsii. It occurs widely and seriously affects the peanut yield in most peanut-producing areas. The mycoviruses that induce the hypovirulence of some plant pathogenic fungi are potential resources for the biological control of fungal diseases in plants. Thus far, few mycoviruses have been found in A. rolfsii. In this study, two mitoviruses, namely, Agroathelia rolfsii mitovirus 1 (ArMV1) and Agroathelia rolfsii mitovirus 2 (ArMV2), were identified from the weakly virulent A. rolfsii strain GP3-1, and they were also found in other A. rolfsii isolates. High amounts of ArMV1 and ArMV2in the mycelium could reduce the virulence of A. rolfsii strains. This is the first report on the existence of mitoviruses in A. rolfsii. The results of this study may provide insights into the classification and evolution of mitoviruses in A. rolfsii and enable the exploration of the use of mycoviruses as biocontrol agents for the control of peanut stem rot.

A dichotomy in cortical actin and chemotactic actin activity between human memory and naive T cells contributes to their differential susceptibility to HIV-1 infection.

Human memory and naive CD4 T cells can mainly be identified by the reciprocal expression of the CD45RO or CD45RA isoforms. In HIV-1 infection, blood CD45RO memory CD4 T cells are preferentially infected and serve as a major viral reservoir. The molecular mechanism dictating this differential susceptibility to HIV-1 remains largely obscure. Here, we report that the different susceptibility of memory and naive T cells to HIV is not determined by restriction factors such as Apobec3G or BST2. However, we observed a phenotypic distinction between human CD45RO and CD45RA resting CD4 T cells in their cortical actin density and actin dynamics. CD45RO CD4 T cells possess a higher cortical actin density and can be distinguished as CD45RO(+)Actin(high). In contrast, CD45RA T cells are phenotypically CD45RA(+)Actin(low). In addition, the cortical actin in CD45RO memory CD4 T cells is more dynamic and can respond to low dosages of chemotactic induction by SDF-1, whereas that of naive cells cannot, despite a similar level of the chemokine receptor CXCR4 present on both cells. We further demonstrate that this difference in the cortical actin contributes to their differential susceptibility to HIV-1; resting memory but not naive T cells are highly responsive to HIV-mediated actin dynamics that promote higher levels of viral entry and early DNA synthesis in resting memory CD4 T cells. Furthermore, transient induction of actin dynamics in resting naive T cells rescues HIV latent infection following CD3/CD28 stimulation. These results suggest a key role of chemotactic actin activity in facilitating HIV-1 latent infection of these T cell subsets.

Genistein interferes with SDF-1- and HIV-mediated actin dynamics and inhibits HIV infection of resting CD4 T cells.

BACKGROUND: Binding of HIV to the chemokine coreceptor CXCR4 mediates viral fusion and signal transduction that promotes actin dynamics critical for HIV infection of blood resting CD4 T cells. It has been suggested that this gp120-mediated actin activity resembles the chemotactic actin dynamics mediated by chemokines such as SDF-1. To determine whether inhibiting SDF-1-mediated chemotactic activity can also inhibit HIV infection, we screened several inhibitors known to reduce SDF-1-mediated chemotaxis of T cells. RESULTS: We found that a tyrosine kinase inhibitor, genistein, inhibited both SDF-1-mediated chemotaxis and HIV infection of resting CD4 T cells. Genistein was also found to interfere with SDF-1- and HIV-mediated actin dynamics in CD4 T cells. This reduction in actin activity correlates with genistein-mediated inhibition of viral DNA accumulation in resting CD4 T cells. In addition, we also tested two other tyrosine kinase inhibitors, sunitinib and AG1478. Sunitinib, but not AG1478, inhibited HIV infection of resting CD4 T cells. We further tested the safety of genistein in 3 Chinese rhesus macaques (Macaca mulatta), and each animal was given a monotherapy of genistein at 10 mg/kg orally for 12 weeks. No adverse drug effects were observed in these animals. CONCLUSIONS: Our results suggest that novel therapeutic strategies can be developed based on targeting cellular proteins involved in HIV-dependent signaling. This approach can interfere with HIV-mediated actin dynamics and inhibit HIV infection.

Clinical Value of Mixed Reality-Assisted Puncture Navigation for Percutaneous Nephrolithotripsy.

OBJECTIVE: To evaluate the clinical value of mixed reality-assisted puncture navigation (MRAPN) in percutaneous nephrolithotripsy (PCNL). METHODS: Two hundred patients undergoing PCN were enrolled, all of whom had kidney stones to be subjected to lithotripsy by PCNL and grouped according to surgical procedure into the MRAPN (n = 100) and non-mixed reality-assisted puncture (non-MRAPN) (n = 100) groups. CT data in DICOM format for all patients in the MRAPN group were imported into 3D reconstruction and mixed reality (MR) post-processing workstations, and holographic 3D visualization modelling. Comparing parameters such as the operative time (OT), puncture time (PT), number of attempts, and estimated blood loss (EBL), a Likert scale was used to assess the clinical value of MRAPN. The Cohen κ coefficient (k) was employed to evaluate consistency among assessors; safety was assessed. RESULTS: There were no significant differences in patient demographic indicators or preoperative general information between the MRAPN and non-MRAPN groups (P > .05). The clinical value of MRAPN was higher for subjective scores regarding surgical planning, intraoperative navigation, didactic guidance and physician-patient communication (all P < .001). The PT was significantly shorter in the MRAPN group (P < .001), with a shorter overall OT and lower EBL (P < .001). There were no significant differences in the overall comparison, length of hospital stay, or preoperative or postoperative creatinine (all P > .05). CONCLUSION: MRAPN can safely and effectively improve the success of PCN, reduce complications, and decrease the PT, OT, and EBL.

Dissection of the Genetic Basis of Resistance to Stem Rot in Cultivated Peanuts (Arachis hypogaea L.) through Genome-Wide Association Study.

Peanut (Arachis hypogaea) is an important oilseed and cash crop worldwide, contributing an important source of edible oil and protein for human nutrition. However, the incidence of stem rot disease caused by Athelia rolfsii poses a major challenge to peanut cultivation, resulting in significant yield losses. In this study, a panel of 202 peanut accessions was evaluated for their resistance to stem rot by inoculating plants in the field with A. rolfsii-infested oat grains in three environments. The mean disease index value of each environment for accessions in subsp. fasitigiate and subsp. hypogaea showed no significant difference. Accessions from southern China displayed the lowest disease index value compared to those from other ecological regions. We used whole-genome resequencing to analyze the genotypes of the accessions and to identify significant SNPs associated with stem rot resistance through genome-wide association study (GWAS). A total of 121 significant SNPs associated with stem rot resistance in peanut were identified, with phenotypic variation explained (PVE) ranging from 12.23% to 15.51%. A total of 27 candidate genes within 100 kb upstream and downstream of 23 significant SNPs were annotated, which have functions related to recognition, signal transduction, and defense response. These significant SNPs and candidate genes provide valuable information for further validation and molecular breeding to improve stem rot resistance in peanut.

LIM kinase 1 modulates cortical actin and CXCR4 cycling and is activated by HIV-1 to initiate viral infection.

Almost all viral pathogens utilize a cytoskeleton for their entry and intracellular transport. In HIV-1 infection, binding of the virus to blood resting CD4 T cells initiates a temporal course of cortical actin polymerization and depolymerization, a process mimicking the chemotactic response initiated from chemokine receptors. The actin depolymerization has been suggested to promote viral intracellular migration through cofilin-mediated actin treadmilling. However, the role of the virus-mediated actin polymerization in HIV infection is unknown, and the signaling molecules involved remain unidentified. Here we describe a pathogenic mechanism for triggering early actin polymerization through HIV-1 envelope-mediated transient activation of the LIM domain kinase (LIMK), a protein that phosphorylates cofilin. We demonstrate that HIV-mediated LIMK activation is through gp120-triggered transient activation of the Rack-PAK-LIMK pathway, and that knockdown of LIMK through siRNA decreases filamentous actin, increases CXCR4 trafficking, and diminishes viral DNA synthesis. These results suggest that HIV-mediated early actin polymerization may directly regulate the CXCR4 receptor during viral entry and is involved in viral DNA synthesis. Furthermore, we also demonstrate that in resting CD4 T cells, actin polymerization can be triggered through transient treatment with a pharmacological agent, okadaic acid, that activates LIMK and promotes HIV latent infection of resting CD4 T cells. Taken together, our results suggest that HIV hijacks LIMK to control the cortical actin dynamics for the initiation of viral infection of CD4 T cells.

Spinoculation triggers dynamic actin and cofilin activity that facilitates HIV-1 infection of transformed and resting CD4 T cells.

Centrifugal inoculation, or spinoculation, is widely used in virology research to enhance viral infection. However, the mechanism remained obscure. Using HIV-1 infection of human T cells as a model, we demonstrate that spinoculation triggers dynamic actin and cofilin activity, probably resulting from cellular responses to centrifugal stress. This actin activity also leads to the upregulation of the HIV-1 receptor and coreceptor, CD4 and CXCR4, enhancing viral binding and entry. We also demonstrate that an actin inhibitor, jasplakinolide, diminishes spin-mediated enhancement. In addition, small interfering RNA (siRNA) knockdown of LIMK1, a cofilin kinase, decreases the enhancement. These results suggest that spin-mediated enhancement cannot be explained simply by a virus-concentrating effect; rather, it is coupled with spin-induced cytoskeletal dynamics that promote receptor mobilization, viral entry, and postentry processes. Our results highlight the importance of cofilin and a dynamic cytoskeleton for the initiation of viral infection. Our results also indicate that caution needs to be taken in data interpretation when cells are spinoculated; some of the spin-induced cellular permissiveness may be beyond the natural capacity of an infecting virus.

Effects of microtubule modulators on HIV-1 infection of transformed and resting CD4 T cells.

Previous studies have observed fluorescently labeled HIV particles tracking along microtubule networks for nuclear localization. To provide direct evidence for the involvement of microtubules in early steps of HIV infection of human CD4 T cells, we used multiple microtubule modulators such as paclitaxel (originally called taxol; 1 µM), vinblastine (1 and 10 µM), colchicine (10 and 100 µM), and nocodazole (10 and 100 µM) to disturb microtubule networks in transformed and resting CD4 T cells. Although these drugs disrupted microtubule integrity, almost no inhibition of HIV-1 infection was observed. Our results do not appear to support an essential role for microtubules in the initiation of HIV infection of CD4 T cells.

Multi-responsive and conductive bilayer hydrogel and its application in flexible devices.

Multi-stimuli-responsive hydrogels are intelligent materials that present advantages for application in soft devices compared with conventional machines. In this paper, we prepared a bilayer hydrogel consisting of a poly(2-(dimethylamino)ethyl methacrylate) layer and a poly(N-isopropylacrylamide) layer. The hydrogel responded to temperature, pH, NaCl, and ethanol by undergoing bending deformation. At 40 °C, it only took 23 s for the hydrogel to bend nearly 300°. Carbon black was also introduced into the hydrogel network to render it conductive. Based on its multi-stimuli-responsive properties and conductivity, the hydrogel was used to construct a 4-arm gripper, thermistor, and finger movement monitor. The time required to grip and release an object was 141 s. The resistance changed with temperature, which affected the brightness of an LED. Finger motions were monitored, and the bending angle could be distinguished.