Pseudorabies virus hijacks the Rab6 protein to promote viral assembly and egress.

Pseudorabies virus (PRV) is recognized as the aetiological agent responsible for Aujeszky's disease, or pseudorabies, in swine populations. Rab6, a member of the small GTPase family, is implicated in various membrane trafficking processes, particularly exocytosis regulation. Its involvement in PRV infection, however, has not been documented previously. In our study, we observed a significant increase in the Rab6 mRNA and protein levels in both PK-15 porcine kidney epithelial cells and porcine alveolar macrophages, as well as in the lungs and spleens of mice infected with PRV. The overexpression of wild-type Rab6 and its GTP-bound mutant facilitated PRV proliferation, whereas the GDP-bound mutant form of Rab6 had no effect on viral propagation. These findings indicated that the GTPase activity of Rab6 was crucial for the successful spread of PRV. Further investigations revealed that the reduction in Rab6 levels through knockdown significantly hampered PRV proliferation and disrupted virus assembly and egress. At the molecular level, Rab6 was found to interact with the PRV glycoproteins gB and gE, both of which are essential for viral assembly and egress. Our results collectively suggest that PRV exploits Rab6 to expedite its assembly and egress and identify Rab6 as a promising novel target for therapeutic treatment for PRV infection.

Pseudorabies virus upregulates low-density lipoprotein receptors to facilitate viral entry.

Pseudorabies virus (PRV) is the causative agent of Aujeszky's disease in pigs. The low-density lipoprotein receptor (LDLR) is a transcriptional target of the sterol-regulatory element-binding proteins (SREBPs) and participates in the uptake of LDL-derived cholesterol. However, the involvement of LDLR in PRV infection has not been well characterized. We observed an increased expression level of LDLR mRNA in PRV-infected 3D4/21, PK-15, HeLa, RAW264.7, and L929 cells. The LDLR protein level was also upregulated by PRV infection in PK-15 cells and in murine lung and brain. The treatment of cells with the SREBP inhibitor, fatostatin, or with SREBP2-specific small interfering RNA prevented the PRV-induced upregulation of LDLR expression as well as viral protein expression and progeny virus production. This suggested that PRV activated SREBPs to induce LDLR expression. Furthermore, interference in LDLR expression affected PRV proliferation, while LDLR overexpression promoted it. This indicated that LDLR was involved in PRV infection. The study also demonstrated that LDLR participated in PRV invasions. The overexpression of LDLR or inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9), which binds to LDLR and targets it for lysosomal degradation, significantly enhanced PRV attachment and entry. Mechanistically, LDLR interacted with PRV on the plasma membrane, and pretreatment of cells with LDLR antibodies was able to neutralize viral entry. An in vivo study indicated that the treatment of mice with the PCSK9 inhibitor SBC-115076 promoted PRV proliferation. The data from the study indicate that PRV hijacks LDLR for viral entry through the activation of SREBPs.IMPORTANCEPseudorabies virus (PRV) is a herpesvirus that primarily manifests as fever, pruritus, and encephalomyelitis in various domestic and wild animals. Owing to its lifelong latent infection characteristics, PRV outbreaks have led to significant financial setbacks in the global pig industry. There is evidence that PRV variant strains can infect humans, thereby crossing the species barrier. Therefore, gaining deeper insights into PRV pathogenesis and developing updated strategies to contain its spread are critical. This study posits that the low-density lipoprotein receptor (LDLR) could be a co-receptor for PRV infection. Hence, strategies targeting LDLR may provide a promising avenue for the development of effective PRV vaccines and therapeutic interventions.

Characterization and discrimination of flavor volatiles of different colored wheat grains after cooking based on GC-IMS and chemometrics.

Changes in flavor volatiles of three colored wheat grains (black, green, and yellow) after cooking were detected via gas chromatography-ion migration spectrometry (GC-IMS) to explore corresponding volatile flavor traits. A total of 52 volatile chemicals were spotted among these cooked wheat grains, including 30 aldehydes (accounting for 73.86-83.78%), 11 ketones (9.53-16.98%), 3 alcohols (0.88-1.21%), 4 furans (4.82-7.44%), 2 esters (0.28-0.42%), and 2 pyrazines (0.18-0.32%). Aldehydes, ketones, and furans were the main volatile compounds in three different cooked wheat. For black-colored wheat, the relative contents of benzene acetaldehyde, benzaldehyde, 2-methyl butanal, and 3-methyl butanal were much higher (p < 0.05). For green-colored wheat, the relative contents of nonanal, 2-pentyl furan, (E)-hept-2-enal, 2-butanone, and acetone were significantly higher (p < 0.05). For yellow-colored wheat, the relative amounts of heptanal, hexanal, and pentanal were much higher (p < 0.05). The overall volatile substances of the three cooked wheat grains might be classified by GC-IMS data coupled with principal component analysis and heatmap clustering analysis. A reliable forecast set was established through orthogonal partial least squares-discriminant analysis (OPLS-DA), and 22 differential volatile compounds were screened out based on variable importance in projection (VIP) being higher than 1.0, as flavor markers for distinguishing the three cooked wheat grains. These results suggest that GC-IMS could be used for characterizing the flavor volatiles of different colored wheat, and the findings could contribute certain information for understand the aroma traits in different colored cooked wheat and related products in the future.

Uncovering the differences in flavor volatiles of different colored foxtail millets based on gas chromatography-ion migration spectrometry and chemometrics.

The differences of volatile organic compounds in commercially available foxtail millets with different colors (black, green, white and yellow) were assayed through gas chromatography-ion migration spectrometry (GC-IMS) to explore their volatile flavor characteristics. Fifty-five volatile components were found in various colored foxtail millets, including 25 kinds of aldehydes (accounting for 39.19-48.69%), 10 ketones (25.36-32.37%), 15 alcohols (20.19-24.11%), 2 ethers (2.29-2.45%), 2 furans (1.49-2.95%) and 1 ester (0.27-0.39%). Aldehydes, alcohols and ketones were the chief volatiles in different colored foxtail millet, followed by furans, esters and ethers. These identified volatile flavor components in various colored foxtail millets obtained by GC-IMS could be well distinguished by principal components and cluster analysis. Meanwhile, a stable prediction model was fitted via partial least squares-discriminant analysis (PLS-DA), in which 17 kinds of differentially volatile components were screened out based on variable importance in projection (VIP>1). These findings might provide certain information for understanding the flavor traits of colored foxtail millets in future.

Oral nifedipine may be a preferential option for treating acute severe hypertension during pregnancy: a meta-analysis.

AIM: To compare oral nifedipine and intravenous labetalol in the treatment of acute severe hypertension in pregnancy (SHP). METHODS: The primary outcomes were the required time to achieve target blood pressure (RTATBP), systolic blood pressure (SBP) and diastolic BP (DBP) after treatment, secondary outcomes were the number of doses (NoD) and adverse events (AEs). RESULTS: There was no difference between oral nifedipine and intravenous labetalol in SBP, DBP, and AE. However, oral nifedipine provided less RTATBP and NoD. CONCLUSION: Oral nifedipine was associated with less RTATBP and NoD and otherwise did not differ from intravenous labetalol.

Combined effects of microplastics and cadmium on the soil-plant system: Phytotoxicity, Cd accumulation and microbial activity.

Microplastics (MPs), an emerging pollutant of concern, widely cooccurred with heavy metals in soil, however, little is known about the combined effects of the interactions of MPs and cadmium (Cd) on the soil-plant system. In this study, the combined effects of several types of MPs and soil Cd contamination on Brassica juncea growth, Cd uptake, and soil microbial carbon metabolism were investigated in a 50-day pot experiment. Aged polyethylene (PE), aged polypropylene (PP), biodegradable polybutylene adipate terephthalate (PBAT) and polylactic acid (PLA) displayed moderate phytotoxicity, with reductions in leaf chlorophyll content and shoot biomass. Compared with the control treatment without MPs or B. juncea, B. juncea growth significantly increased the soil pH by 0.3 pH units, and the growth of B. juncea in the presence of biodegradable PBAT or PLA MPs increased the soil pH by an additional 0.4 or 0.6 pH units, respectively. The presence of PBAT or PLA MPs greatly reduced soil diethylenetriamine pentaacetic acid (DTPA)-extractable Cd concentrations and plant Cd accumulation. The Cd bioconcentration factor was higher in roots than shoots in all treatments except the treatment containing PBAT MPs. The average well color development (AWCD), an indicator of metabolic activity, was highest in the treatment with B. juncea alone and was reduced by both biodegradable and conventional MPs. The microbial utilization efficiency of esters and alcohols was enhanced in the treatment with PBAT MPs, whereas carboxylic acids were preferentially utilized in the treatment with PLA MPs. These findings indicate that co-exposure to MPs and Cd may alter soil microenvironmental characteristics such as soil pH, leading to changes in Cd bioavailability, plant growth and Cd accumulation, and the microbial community's capacity to metabolize carbon. These effects of MPs in soil warrant further exploration.

Characterization of volatile organic compounds of different pigmented rice after puffing based on gas chromatography-ion migration spectrometry and chemometrics.

The distinctness in volatile profiles of pigmented rice with various colors (black, green, purple, red, and yellow) after puffing were assayed through gas chromatography-ion migration spectrometry (GC-IMS) to explore their odor characteristics. Fifty-two volatile components were found in those puffed rice, including 27 kinds of aldehydes (accounting for 59.69-64.37 %), 9 ketones (25.55-29.73 %), 5 alcohols (2.45-5.29 %), 4 pyrazines (1.38-2.36 %), 3 ethers (0.81-1.27 %), 2 furans (0.95-1.39 %), 1 pyridine (1.0-1,16 %), and 1 pyrrole (0.59-0.71 %). Aldehydes and ketones were the two chief volatiles in different pigmented puffed rice. These identified volatile flavor components in various pigmented puffed rice obtained by GC-IMS might be well differentiated by principal component and cluster interpretation. Meanwhile, a stable prediction model was fitted via orthogonal partial least squares-discriminant analysis, and 19 differentially volatile components were screened out based on variable importance projection (VIP) above 1. These findings could add certain information for understanding the flavor profiles of pigmented puffed rice and related products.

Primary malignant melanoma of the cervix: A comprehensive analysis of case reports in the Chinese population.

PURPOSE: Malignant melanoma is a tumor generated from the basal melanocytes of human epidermis. Primary malignant melanoma of the cervix (PMMC) is derived from cervical melanocytes. It is an uncommon disease, mostly occurring in perimenopausal women. PMMC has a bad prognosis and lacks a defined protocol or treatment standards. The aim of this study was to analyze the impact of different surgical procedures and different adjuvant treatment modalities on their prognosis and to find risk factors for their prognosis by integrating published case report data based on the Chinese population. METHODS AND RESULTS: This study included 165 patients with PMMC in the Chinese population. We used the Kaplan-Meier method to build the survival curve, and the log-rank test to examine the variations among the subgroups. Prognostic factors were examined utilizing the Cox proportional hazards regression model. We found that patients who underwent radical hysterectomy-based surgery, those who underwent lymphadenectomy, and those who underwent other treatments in addition to surgery had significantly better survival rates. The overall analysis, showed that age, and FIGO Stage II, III, and IV, increased the risk of death. Moreover, radical hysterectomy (RH), total hysterectomy (TAH), lymphadenectomy, and adjuvant therapy were correlated with a decreased mortality risk. CONCLUSION: After summarizing the current data, we recommend radical hysterectomy, and lymphadenectomy treatment for patients with PMMC. For patients who had already undergone surgery, other treatment options had a positive effect on prognosis. For patients who had already undergone surgery, other treatment options had a positive effect on prognosis; therefore patient-specific treatment options need to be further discussed.

[Research Progress of Pleckstrin Homology Like Domain Family A Member 1 in Tumor].

Pleckstrin homology like domain family A member 1(PHLDA1) is also known as T-cell death-associated gene 51 (TDAG51).Studies have demonstrated that the abnormal expression of PHLDA1 is closely associated with the formation,development,and metastasis of tumors.We summarized the latest research advances in the structure and biological properties of PHLDA1,as well as the roles of PHLDA1 in multiple malignanttumors such as breast cancer,cancer,liver gastric cancer,liver cancer,melanoma,and osteosarcoma,aiming to comprehensively reveal the significance of PHLDA1 in the clinical diagnosis of tumors.

A lipophilic chitosan-modified self-nanoemulsifying system influencing cellular membrane metabolism enhances antibacterial and anti-biofilm efficacy for multi-drug resistant Pseudomonas aeruginosa wound infection.

Wound infections, especially infections with multidrug-resistant bacteria, are a serious public health issue worldwide. In addition, the accumulation microbial biofilm of multidrug-resistant Pseudomonas aeruginosa increases the risk and physically obstruct its healing activity at the wound site. Therefore, the development of an eminent agent to control wound infection is urgently needed. Here, we report a novel chitosan (a natural biological macromolecule)-modified self-nanoemulsifying system (CSN) with lipophilic chlorhexidine acetate (CAA, a poorly water-soluble agent) that was designed and prepared using low-energy emulsification methods. We found that CSN displays better antibacterial efficacy, which occurs more quickly than its aqueous solution, in destroying the structure of the bacterial cell membrane and promoting the leakage of nucleic acids, proteins, K+, and Mg2+ from Pseudomonas aeruginosa cells. Importantly, CSN also accelerates skin wound healing after Pseudomonas aeruginosa infection by inhibiting biofilm formation and eradicating mature biofilms. Moreover, the proteomic results suggested that CSN altered membrane permeability and cellular membrane metabolism, allowing more drug molecules to enter the cytosol. Based on these results, this lipophilic self-nanoemulsifying system may be applied in the treatment of skin wounds caused by multidrug-resistant bacteria, especially Pseudomonas aeruginosa.

Retraction Notice to: Overexpression of MicroRNA-340-5p Inhibits Pulmonary Arterial Hypertension Induced by APE by Downregulating IL-1ß and IL-6.

[This retracts the article DOI: 10.1016/j.omtn.2020.05.022.].

A case report of delayed treatment of acute exertional osteofascial compartment syndrome in the anterior compartment of the calf.

RATIONALE: Acute exertional osteofascial compartment syndrome (OCS) is a rare cause of lower-leg pain and is often associated with delayed diagnosis, which can lead to irreversible muscle and nerve damage. PATIENT CONCERNS: A 23-year-old man presented with acute-onset anterior calf pain and ankle dorsiflexion after hiking. DIAGNOSIS: The patient's pain was initially diagnosed as muscle strain at a county hospital, but was eventually diagnosed as OCS at our hospital 8 days after the injury. This case presents several challenges in the diagnosis and treatment phases. INTERVENTIONS: Three surgeries were performed in total. On the day after admission (9 days after injury), fasciotomy was performed, followed by vacuum sealing drainage (VSD). Six days after the first surgery, necrotic muscle debridement was performed and VSD was reperformed. Ten days after the second surgery, the covering foam material was removed and the incision was sutured. OUTCOMES: Satisfactory postoperative results were achieved. The erythrocyte sedimentation rate, C-reactive protein level, and white blood cell count were within normal ranges. The skin healed well, and nerve damage and muscle strength improved significantly 3 months after surgery. LESSONS: OCS in the absence of trauma or fracture is rare, but treatment delays can have devastating consequences. Acute nontraumatic OCS requires prompt diagnosis and surgical intervention to prevent adverse outcomes. VSD is an effective surgical treatment for this disease.

[An evaluation method for physical properties of medicinal film and its application in screening film formulation of Trillium tschonoskii total saponins].

At present, the evaluation methods for pharmaceutical properties of Chinese medicinal films have many problems, such as poor objectivity for the indexes and no quantitative and standardized evaluation methods. This study established a new method using three important physical property parameters, i.e., flow index, weight loss rate, and elongation rate, which were closely related to the pharmaceutical properties of films. On this basis, the above parameters were taken as indicators to optimize the film formulation of Trillium tschonoskii total saponins and verify the feasibility and suitability of the established method and parameters in formulation optimization. A self-made flow distance detection device and a viscometer were used to measure and characterize the fluidity, where the flow index refers to the ratio of the flow distance per unit time to the viscosity. The weight loss rate was measured by the 3 M transpore~(TM) surgical tape. The film-forming property was characterized by the weight loss rate of the sample within a certain period of time. An electronic tension machine was employed to measure the elongation rate after drying, which was used to characterize the ductility of the film. The results showed that the established method for the determination of flow index, weight loss rate, and elongation rate was stable and reliable. The optimal film formulation of T. tschonoskii total saponins could be obtained by optimization with those indicators. As demonstrated, the above evaluation indicators(flow index, weight loss rate, and elongation rate) can guide the optimization and design of formulation, and the new evaluation method constructed based on this shows a good application prospect in formulation optimization and formulation quality evaluation of medicinal films.

Ionic liquid-based liposome for selective SERS detection.

An ionic liquid (IL)-based liposome was utilized as a substrate to construct a SERS platform. The isotropy of the IL outer surface together with its ion-exchange property led to the array-like growth of Au nanoparticles (NPs), generating hot-spots and resulting in anionic probes being present on the hot-spot regions. The simultaneous strategy of enrichment and localization endowed the platform with ability to detect trace amounts of anionic probes.

Dynamic Behavior Analysis and Stability Control of Tethered Satellite Formation Deployment.

In recent years, Tethered Space Systems (TSSs) have received significant attention in aerospace research as a result of their significant advantages: dexterousness, long life cycles and fuel-less engines. However, configurational conversion processes of tethered satellite formation systems in a complex space environment are essentially unstable. Due to their structural peculiarities and the special environment in outer space, TSS vibrations are easily produced. These types of vibrations are extremely harmful to spacecraft. Hence, the nonlinear dynamic behavior of systems based on a simplified rigid-rod tether model is analyzed in this paper. Two stability control laws for tether release rate and tether tension are proposed in order to control tether length variation. In addition, periodic stability of time-varying control systems after deployment is analyzed by using Floquet theory, and small parameter domains of systems in asymptotically stable states are obtained. Numerical simulations show that proposed tether tension controls can suppress in-plane and out-of-plane librations of rigid tethered satellites, while spacecraft and tether stability control goals can be achieved. Most importantly, this paper provides tether release rate and tether tension control laws for suppressing wide-ranging TSS vibrations that are valuable for improving TSS attitude control accuracy and performance, specifically for TSSs that are operating in low-eccentricity orbits.

Downregulation of interleukin-6 and C-reactive protein underlies a novel inhibitory role of microRNA-136-5p in acute lower extremity deep vein thrombosis.

Deep vein thrombosis (DVT) comprises a critical and common health condition with high incidence, mortality, and long-term adverse sequelae. Several differentially expressed microRNAs (miRNAs) have emerged as promising prognostic markers in DVT. The present study intended to explore the functional relevance of miR-136-5p in acute lower extremity DVT (LEDVT). Rat models of acute LEDVT were established and miR-136-5p expression was altered by agomir or antagomir to assess its effects. In addition, in vitro gain- and loss-experiments, prior to exposure to CoCl2, were performed to investigate effects of miR-136-5p on human umbilical vein endothelial cell (HUVEC) apoptosis and levels of interleukin-6 (IL-6) and C-reactive protein (CRP). miR-136-5p was downregulated, whereas IL-6 and CRP were elevated in acute LEDVT patients. Notably, miR-136-5p was confirmed to target both IL-6 and CRP. Overexpression of miR-136-5p led to reduced length, weight, and ratio of weight to length of the venous thrombus. Furthermore, overexpressed miR-136-5p downregulated the expression of IL-6 and CRP, consequently inhibiting HUVEC apoptosis. Conjointly, our data indicate that the overexpression of miR-136-5p has the potential to bind to the 3'-UTR in the mRNAs for IL-6 and CRP and mitigate acute LEDVT, which provides a basis for new therapeutic targets in acute LEDVT treatment.

Overexpression of MicroRNA-340-5p Inhibits Pulmonary Arterial Hypertension Induced by APE by Downregulating IL-1ß and IL-6.

Pulmonary arterial hypertension (PAH) is a fatal cardiovascular disease that could eventually result in right ventricular failure. Recently, the roles of microRNAs (miRNAs) in PAH have been highlighted. The present study aims to investigate the effects of miRNA (miR)-340-5p on PAH induced by acute pulmonary embolism (APE) and the underlying mechanisms. miR-340-5p was lowly expressed, whereas interleukin 1ß (IL-1ß) and IL-6 were highly expressed in plasma of APE-PAH patients as compared to normal human plasma. Subsequently, IL-1ß and IL-6 were confirmed to be two target genes of miR-340-5p using a dual-luciferase reporter gene assay. By conducting overexpression and rescue experiments, overexpression of miR-340-5p was evidenced to inhibit proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) and inflammation via reducing IL-1ß and IL-6 levels. Meanwhile, miR-340-5p led to the blocked nuclear factor κB (NF-κB) pathway with reduced NF-κB p65, matrix metalloproteinase 2 (MMP2), and MMP9 expression in PASMCs. Finally, the ameliorative effect of miR-340-5p on pathological lesions was further verified in rat models of APE-PAH. Altogether, overexpressed miR-340-5p inhibited the inflammatory response, proliferation, and migration of PASMCs by downregulating IL-1ß and IL-6, thereby suppressing the progression of APE-PAH. miR-340-5p therefore holds promise as an anti-inflammatory therapeutic target.