Cross-kingdom RNA interference mediated by insect salivary microRNAs may suppress plant immunity.

Communication between insects and plants relies on the exchange of bioactive molecules that traverse the species interface. Although proteinic effectors have been extensively studied, our knowledge of other molecules involved in this process remains limited. In this study, we investigate the role of salivary microRNAs (miRNAs) from the rice planthopper Nilaparvata lugens in suppressing plant immunity. A total of three miRNAs were confirmed to be secreted into host plants during insect feeding. Notably, the sequence-conserved miR-7-5P is specifically expressed in the salivary glands of N. lugens and is secreted into saliva, distinguishing it significantly from homologues found in other insects. Silencing miR-7-5P negatively affects N. lugens feeding on rice plants, but not on artificial diets. The impaired feeding performance of miR-7-5P-silenced insects can be rescued by transgenic plants overexpressing miR-7-5P. Through target prediction and experimental testing, we demonstrate that miR-7-5P targets multiple plant genes, including the immune-associated bZIP transcription factor 43 (OsbZIP43). Infestation of rice plants by miR-7-5P-silenced insects leads to the increased expression of OsbZIP43, while the presence of miR-7-5P counteracts this upregulation effect. Furthermore, overexpressing OsbZIP43 confers plant resistance against insects which can be subverted by miR-7-5P. Our findings suggest a mechanism by which herbivorous insects have evolved salivary miRNAs to suppress plant immunity, expanding our understanding of cross-kingdom RNA interference between interacting organisms.

A Novel Classification System of Renal Hilar Tumors for Surgical Guidance: Technique, Outcome, and Safety.

BACKGROUND: This study was designed to develop an innovative classification and guidance system for renal hilar tumors and to assess the safety and effectiveness of robot-assisted partial nephrectomy (RAPN) for managing such tumors. METHODS: A total of 179 patients undergoing RAPN for renal hilar tumors were retrospectively reviewed. A novel classification system with surgical techniques was introduced and the perioperative features, tumor characteristics, and the efficacy and safety of RAPN were compared within subgroups. RESULTS: We classified the tumors according to our novel system as follows: 131 Type I, 35 Type II, and 13 Type III. However, Type III had higher median R.E.N.A.L., PADUA, and ROADS scores compared with the others (all p < 0.001), indicating increased operative complexity and higher estimated blood loss [180.00 (115.00-215.00) ml]. Operative outcomes revealed significant disparities between Type III and the others, with longer operative times [165.00 (145.00-200.50) min], warm ischemia times [24.00 (21.50-30.50) min], tumor resection times [13.00 (12.00-15.50) min], and incision closure times [22.00 (20.00-23.50) min] (all p < 0.005). Postoperative outcomes also showed significant differences, with longer durations of drain removal (77.08 ± 18.16 h) and hospitalization for Type III [5.00 (5.00-6.00) d] (all p < 0.05). Additionally, Type I had a larger tumor diameter than the others (p = 0.009) and pT stage differed significantly between the subtypes (p = 0.020). CONCLUSIONS: The novel renal hilar tumor classification system is capable of differentiating the surgical difficulty of RAPN and further offers personalized surgical steps tailored to each specific classification. It provides a meaningful tool for clinical practice.

Complete genome sequence of a novel robigovirus infecting Mentha arvensis.

The complete genomic sequence of a novel robigovirus, provisionally named "Mentha arvensis robigovirus 1" (MARV1), was determined by combining next-generation sequencing (NGS), reverse transcription polymerase chain reaction (RT-PCR), and rapid amplification of cDNA ends (RACE) PCR. The complete genomic sequence of this new virus is 7617 nucleotides in length, excluding the 3' poly(A) tail. The MARV1 genome encodes a putative replicase, "triple gene block" proteins, and a coat protein. Phylogenetic analysis demonstrated that MARV1 is a member of the genus Robigovirus, with closest relationships to African oil palm ringspot virus (AOPRV). Furthermore, MARV1-derived small interfering RNAs (siRNAs) showed typical patterns of plant-virus-derived siRNAs produced by the host antiviral RNA interference pathway. This is the first report of a plant virus of the genus Robigovirus in M. arvensis.

Complete genome sequence and genetic characterization of a novel segmented RNA virus infecting Nilaparvata lugens.

The brown planthopper (BPH), Nilaparvata lugens, is a significant agricultural pest capable of long-distance migration and transmission of viruses that cause severe disease in rice. In this study, we identified a novel segmented RNA virus in a BPH, and this virus exhibited a close relationship to members of a recently discovered virus lineage known as "quenyaviruses" within the viral kingdom Orthornavirae. This newly identified virus was named "Nilaparvata lugens quenyavirus 1" (NLQV1). NLQV1 consists of five positive-sense, single-stranded RNAs, with each segment containing a single open reading frame (ORF). The genomic characteristics and phylogenetic analysis support the classification of NLQV1 as a novel quenyavirus. Notably, all of the genome segments of NLRV contained the 5'-terminal sequence AUCUG. The characteristic virus-derived small interfering RNA (vsiRNA) profile of NLQV1 suggests that the antiviral RNAi pathway of the host BPH was activated in response to virus infection. These findings represent the first documented report of quenyaviruses in planthoppers, contributing to our understanding of quenyaviruses and expanding our knowledge of insect-specific viruses in planthoppers.

Single-dose methamphetamine administration impairs ORM retrieval in mice via excessive DA-mediated inhibition of PrLGlu activity.

Methamphetamine (METH), an abused psychostimulant, impairs cognition through prolonged or even single-dose exposure, but animal experiments have shown contradictory effects on memory deficits. In this study we investigated the effects and underlying mechanisms of single-dose METH administration on the retrieval of object recognition memory (ORM) in mice. We showed that single-dose METH administration (2 mg/kg, i.p.) significantly impaired ORM retrieval in mice. Fiber photometry recording in METH-treated mice revealed that the activity of prelimbic cortex glutamatergic neurons (PrLGlu) was significantly reduced during ORM retrieval. Chemogenetic activation of PrLGlu or glutamatergic projections from ventral CA1 to PrL (vCA1Glu-PrL) rescued ORM retrieval impairment. Fiber photometry recording revealed that dopamine (DA) levels in PrL of METH-treated mice were significantly increased, and micro-infusion of the D2 receptor (D2R) antagonist sulpiride (0.25 µg/side) into PrL rescued ORM retrieval impairment. Whole-cell recordings in brain slices containing the PrL revealed that PrLGlu intrinsic excitability and basal glutamatergic synaptic transmission were significantly reduced in METH-treated mice, and the decrease in intrinsic excitability was reversed by micro-infusion of Sulpiride into PrL in METH-treated mice. Thus, the impaired ORM retrieval caused by single-dose METH administration may be attributed to reduced PrLGlu activity, possibly due to excessive DA activity on D2R. Selective activation of PrLGlu or vCA1Glu-PrL may serve as a potential therapeutic strategy for METH-induced cognitive dysfunction.

Pharmacological modulation of T cell immunity results in long-term remission of autoimmune arthritis.

Chronic inflammatory diseases like rheumatoid arthritis are characterized by a deficit in fully functional regulatory T cells. DNA-methylation inhibitors have previously been shown to promote regulatory T cell responses and, in the present study, we evaluated their potential to ameliorate chronic and acute animal models of rheumatoid arthritis. Of the drugs tested, decitabine was the most effective, producing a sustained therapeutic effect that was dependent on indoleamine 2,3-dioxygenase (IDO) and was associated with expansion of induced regulatory T cells, particularly at the site of disease activity. Treatment with decitabine also caused apoptosis of Th1 and Th17 cells in active arthritis in a highly selective manner. The molecular basis for this selectivity was shown to be ENT1, a nucleoside transporter, which facilitates intracellular entry of the drug and is up-regulated on effector T cells during active arthritis. It was further shown that short-term treatment with decitabine resulted in the generation of a population of regulatory T cells that were able to suppress arthritis upon adoptive transfer. In summary, a therapeutic approach using an approved drug is described that treats active inflammatory disease effectively and generates robust regulatory T cells with the IDO-dependent capacity to maintain remission.

Anti-Hyperlipidemic Components of the Leaves of Synsepalum dulcificum (Miracle Fruit).

Synsepalum dulcificum (Miracle fruit) is a tropical plant in West and Central Africa, which has been historically used for treating diarrhea in humans and animals. Pharmacological research has shown that the leaves of the plant possess anti-hyperlipidemia activity. However, its anti-hyperlipidemic components have not been reported. In this study, the leaves of S. dulcificum were extracted using 95% ethanol and the extract was fractionated using different polar solvents. The anti-hyperlipidemia activity of the extract and fractions were evaluated using the zebrafish model. The results showed that the ethyl acetate (EA) fraction displayed the best anti-hyperlipidemic effect. A comparison of the high-performance liquid chromatography equipped with diode array detector (HPLC-DAD) profiles of the ethanol extract and different fractions at 350 nm indicated that a peak at 37.4 min has the highest intensity in the EA part, relatively. Then the chemical constituents of the extract and the active fraction were extensively identified using UPLC-Q-Exactive-Orbitrap-MS/MS, showing the main peak was quercitrin and other components in the EA part mainly included quercitrin analogs. Furthermore, the quercitrin was isolated from the plant and its contents in the extract and fractions were determined using high-performance liquid chromatography with ultraviolet detector (HPLC-UV) method. The quantitative results showed that the content of quercitrin in the EA fraction was 10.04% (w/w). Further pharmacological study indicated that quercitrin also possessed potent anti-hyperlipidemia activity (improvement rates of liver fat and total cholesterol were 75.6% and 92.5% at 40 µg/mL, respectively). Besides, quercitrin showed little toxicity to zebrafish embryos.

Three-dimensional on-chip mode converter.

The implementation of transverse mode, polarization, frequency, and other degrees of freedom (d.o.f.s) of photons is an important way to improve the capability of photonic circuits. Here, a three-dimensional (3D) linear polarized (LP) LP11 mode converter was designed and fabricated using a femtosecond laser direct writing (FsLDW) technique. The converter included multi-mode waveguides, symmetric Y splitters, and phase delaying waveguides, which were constructed as different numbers and arrangements of circular cross section waveguides. Finally, the modes (LP11a and LP11b) were generated on-chip with a relatively low insertion loss (IL). The mode converter lays a foundation for on-chip high-order mode generation and conversion between different modes, and will play a significant role in mode coding and decoding of 3D photonic circuits.

Underlying mechanisms and molecular targets of genistein in the management of type 2 diabetes mellitus and related complications.

Diabetes mellitus (DM) is a chronic metabolic disease caused by a complex interaction of genetic and environmental factors and is characterized by persistent hyperglycemia. Long-term hyperglycemia can cause macrovascular and microvascular damage, and compromise the heart, brain, kidney, peripheral nerves, eyes and other organs, leading to serious complications. Genistein, a phytoestrogen derived from soybean, is known for its various biological activities and therapeutic properties. Recent studies found that genistein not only has hypoglycemic activity but can also decrease insulin resistance. In addition, genistein has particular activity in the prevention and treatment of diabetic complications, such as nephropathy, cardiovascular disease, osteoarthrosis, encephalopathy and retinopathy. Therefore, the purpose of this review is to summarize the latest medical research and progress of genistein in DM and related complications and highlights its potential molecular mechanisms and therapeutic targets. Meanwhile, evidence is provided for the development and application of genistein as a potential drug or functional food in the prevention and treatment of diabetes and its related complications.

Hyposterolactone A, a 3α-Hydroxy Steroidal Lactone from the Deep-Sea-Derived Fungus Hypocrea sp. ZEN14.

Chemical investigation of the deep-sea-derived fungus Hypocrea sp. ZEN14 afforded a new 3α-hydroxy steroidal lactone, hyposterolactone A (1) and 25 known secondary metabolites (2-26). The structure of the new compound was established by detailed spectroscopic analysis, electronic circular dichroism (ECD) calculation as well as a J-based configuration analysis. Compound 10 showed potent cytotoxicity against Huh7 and Jurkat cells with IC50 values of 1.4 µM and 6.7 µM, respectively.

Ellagic acid alleviates TNBS-induced intestinal barrier dysfunction by regulating mucin secretion and maintaining tight junction integrity in rats.

In the present study, the mechanism of ellagic acid (EA) in alleviated ulcerative colitis (UC) was investigated. Twenty-four SD rats were randomly distributed into three treatment groups: (1) control group, (2) UC group, and (3) UC + EA group. Samples were collected for analysis after a 15-day trial period. We found that EA mitigated the colitis symptoms in TNBS-treated rats. Besides, EA decreased the expression of cytokines by inhibiting NF-κB signalling. TNBS-induced reduction in tight junction proteins was restored by EA supplementation via regulating RhoA/ROCK/MLC signalling. Further, persistent colonic inflammation destroyed the activity of goblet cells by inhibiting the expression of KLF4 and TFF3. EA also enhanced the expression of MUC2, AGR2, ST6GAL1 and B3GNT6. In summary, our findings demonstrated that dietary supplementation with EA ameliorated TNBS-induced colitis by maintaining intestinal barrier function, which proves its potential role as a therapeutic agent in the attenuation of UC.

Preliminary Study on Rapid and Simultaneous Detection of Viable Escherichia coli O157:H7, Staphylococcus aureus, and Salmonella by PMA-mPCR in Food.

Escherichia coli O157:H7, Staphylococcus aureus, and Salmonella are major foodborne pathogens that are widespread in nature and responsible for several outbreaks of food safety accidents. Thus, a rapid and practical technique (PMA-mPCR) was developed for the simultaneous detection of viable E. coli O157:H7, S. aureus, and Salmonella in pure culture and in a food matrix. To eliminate false positive results, propidium monoazide (PMA) was applied to selectively suppress the DNA amplification of dead cells. The results showed the optimum concentration of PMA is 5.0 µg/mL. The detection limit of this assay by mPCR was 103 CFU/mL in the culture broth, and by PMA-mPCR was 104 CFU/mL both in pure culture and a food matrix (milk and ground beef). In addition, the detection of mixed viable and dead cells was also explored in this study. The detection sensitivity ratio of viable and dead counts was less than 1:10. Therefore, the PMA-mPCR assay proposed here might provide an efficient detection tool for the simultaneous detection of viable E. coli O157:H7, S. aureus, and Salmonella and also have great potential for the detection and concentration assessment of VBNC cells.

Head-to-head comparisons of enhanced CT, 68Ga-PSMA-11 PET/CT and 18F-FDG PET/CT in identifying adverse pathology of clear-cell renal cell carcinoma: a prospective study.

OBJECTIVES: Accurate preoperative prediction of adverse pathology is crucial for treatment planning of renal cell carcinoma (RCC). Previous studies have emphasized the potential of prostate-specific membrane antigen positron emission tomography / computed tomography (PSMA PET/CT) in differentiating between benign and malignant localized renal tumors. However, there is a scarcity of case reports elucidating the identification of aggressive pathological features using PET/CT. Our study was designed to prospectively compare the diagnostic value of enhanced CT, 68Ga-PSMA-11 and 18F-fluorodeoxyglucose (18F-FDG) PET/CT in clear-cell renal cell carcinoma (ccRCC) with necrosis or sarcomatoid or rhabdoid differentiation. MATERIALS AND METHODS: A prospective case series of patients with a newly diagnosed renal mass who underwent enhanced CT, 68Ga-PSMA-11 and 18F-FDG PET/CT within 30 days prior to nephrectomy was included. Complete preoperative and postoperative clinicopathological data were recorded. Patients who received neoadjuvant targeted therapy, declined enhanced CT or PET/CT scanning, refused surgical treatment or had non-ccRCC pathological indications were excluded. Radiological parameters were compared within subgroups of pathological characteristics. Bonferroni corrections were used to adjust for multiple testing and statistical significance was set at a p-value less than 0.017. RESULTS: Seventy-two patients were available for the final analysis. Enhanced CT demonstrated poor performance in identifying necrosis, sarcomatoid or rhabdoid differentiation and adverse pathology (all P > 0.05). The maximum standardized uptake value (SUVmax) of 68Ga-PSMA-11 PET/CT was more effective than 18F-FDG PET/CT in identifying tumor necrosis and adverse pathology, with an area under the curve (AUC) of 0.85 (cutoff value=25.26, p<0.001; Delong test z=2.709, p=0.007) for tumor necrosis and AUC of 0.90 (cutoff value=25.26, p<0.001; Delong test z=3.433, p<0.001) for adverse pathology. However, no significant statistical difference was found between 68Ga-PSMA-11 and 18F-FDG PET/CT in predicting sarcomatoid or rhabdoid feature (AUC of 0.91 vs.0.75, Delong test z=1.998, p=0.046). Subgroup analyses based on age, sex, tumor location, maximal diameter, stage and WHO/ISUP grade demonstrated that 68Ga-PSMA-11 PET/CT SUVmax had a significant predictive value for adverse pathology. Enhanced CT value and SUVmax demonstrated strong reliability [intraclass correlation coefficient (ICC) > 0.80], indicating a robust correlation. CONCLUSIONS: 68Ga-PSMA-11 PET/CT demonstrates distinct advantages in identifying aggressive pathological features of primary ccRCC when compared to enhanced CT and 18F-FDG PET/CT. Further research and assessment are warranted to fully establish the clinical utility of 68Ga-PSMA-11 PET/CT in ccRCC.

Generation, mechanisms, kinetics, and effects of gaseous chlorine dioxide in food preservation.

Food preservation is a critical issue in ensuring food safety and quality. Growing concern around industrial pollution of food and demand for environmentally sustainable food has led to increased interest in developing effective and eco-friendly preservation techniques. Gaseous ClO2 has gained attention for its strong oxidizing properties, high efficacy in microorganism inactivation, and potential for preserving the attributes and nutritional quality of fresh food while avoiding the formation of toxic byproducts or unacceptable levels of residues. However, the widespread use of gaseous ClO2 in the food industry is limited by several challenges. These include large-scale generation, high cost and environmental considerations, a lack of understanding of its mechanism of action, and the need for mathematical models to predict inactivation kinetics. This review aims to provide an overview of the up-to-date research and application of gaseous ClO2 . It covers preparation methods, preservation mechanisms, and kinetic models that predict the sterilizing efficacy of gaseous ClO2 under different conditions. The impacts of gaseous ClO2 on the quality attributes of fresh produce and low-moisture foods, such as seeds, sprouts, and spices, are also summarized. Overall, gaseous ClO2 is a promising preservation approach, and future studies are needed to address the challenges in large-scale generation and environmental considerations and to develop standardized protocols and databases for safe and effective use in the food industry.

Entry Inhibitors of Hepatitis C Virus.

Hepatitis C virus (HCV) infection affects approximately 1% of the world's population and is a major cause of chronic liver diseases. Although antiviral therapy consisting of direct-acting antivirals (DAAs) can cure the majority of HCV patients, it is still limited by viral resistances, drug-drug interactions, and high costs. Moreover, the role of DAAs in the prevention of occurrences of graft reinfection in HCV patients who receive liver transplantations is still under comprehensive clinical investigation, bringing the risk of recipient reinfection. HCV entry is composed of initial non-specific attachment and binding, post-binding interactions with essential host factors, internalization, and virion-cell membrane fusion to release viral RNA to cytosol. Thus, a number of novel and promising targets from either virion or cellular factors of these processes become optimal interfering elements for antiviral therapy, eliminating viral infection at the very beginning. Therefore, entry inhibitors can be supplemented into the future treatment regimens to optimize and widen the prevention and therapeutics of HCV infection. This chapter introduces the basic HCV entry processes and summarizes molecular mechanisms and research status of the current antiviral agents targeting HCV entry in preclinical and clinical study.

Anti-HIV Compounds from the Deep-Sea-Derived Fungus Chaetomium globosum.

Chemical investigation on the deep-sea-derived fungus Chaetomium globosum led to the isolation of nine compounds. By extensive analyses of the 1D and 2D NMR as well as HR-ESI-MS spectra, their structures were elucidated as xylariol A (1), 1,3-dihydro-4,5,6-trihydroxy-7-methylisobenzofuran (2), epicoccone B (3), epicoccolide B (4), chaetoglobosin G (5), chaetoglobosin Fex (6), cochliodone A (7), cochliodone B (8), and chaetoviridin A (9), assorting as four phenolics (1-4), two cytochalosans (5-6), and three azaplilones (7-9). Compounds 1-3 were firstly reported from C. globosum. Under the concentrations of 20 µg/mL, 1, 2, and 3 exhibited potent in vitro anti-HIV activity with the inhibition rates of 70 %, 75 %, and 88 %, respectively.

Lipid Droplets and Their Participation in Zika Virus Infection.

Lipid droplets (LDs) are highly conserved and dynamic intracellular organelles. Their functions are not limited to serving as neutral lipid reservoirs; they also participate in non-energy storage functions, such as cell lipid metabolism, protection from cell stresses, maintaining protein homeostasis, and regulating nuclear function. During a Zika virus (ZIKV) infection, the viruses hijack the LDs to provide energy and lipid sources for viral replication. The co-localization of ZIKV capsid (C) protein with LDs supports its role as a virus replication platform and a key compartment for promoting the generation of progeny virus particles. However, in view of the multiple functions of LDs, their role in ZIKV infection needs further elucidation. Here, we review the basic mechanism of LD biogenesis and biological functions and discuss how ZIKV infection utilizes these effects of LDs to facilitate virus replication, along with the future application strategy of developing new antiviral drugs based on the interaction of ZIKV with LDs.

Effect of Helicobacter Pylori on Plasma Metabolic Phenotype in Patients With Gastric Cancer.

BACKGROUND: Although Helicobacter pylori (Hp) as high risk factor for gastric cancer have been investigated from human trial, present data is inadequate to explain the effect of Hp on the changes of metabolic phenotype of gastric cancer in different stages. PURPOSE: Herein, plasma of human superficial gastritis (Hp negative and positive), early gastric cancer and advanced gastric cancer analyzed by UPLC-HDMS metabolomics can not only reveal metabolic phenotype changes in patients with gastric cancer of different degrees (30 Hp negative, 30 Hp positive, 20 early gastric cancer patients, and 10 advanced gastric cancer patients), but also auxiliarily diagnose gastric cancer. RESULTS: Combined with multivariate statistical analysis, the results represented biomarkers different from Hp negative, Hp positive, and the alterations of metabolic phenotype of gastric cancer patients. Forty-three metabolites are involved in amino acid metabolism, and lipid and fatty acid metabolism pathways in the process of cancer occurrence, especially 2 biomarkers glycerophosphocholine and neopterin, were screened in this study. Neopterin was consistently increased with gastric cancer progression and glycerophosphocholine tended to consistently decrease from Hp negative to advanced gastric cancer. CONCLUSION: This method could be used for the development of rapid targeted methods for biomarker identification and a potential diagnosis of gastric cancer.

Solitumergosterol A, a unique 6/6/6/6/5 steroid from the deep-sea-derived Penicillium solitum MCCC 3A00215.

A unique C30 steroid, solitumergosterol A (1), was isolated from the deep-sea-derived fungus Penicillium solitum MCCC 3A00215. The planar structure and relative configuration of 1 were established mainly on the basis of extensive analysis of its 1D and 2D NMR as well as HRESIMS data, while its absolute configuration was clarified by comparison of the experimental and theoretical ECD spectra. Noteworthily, 1 is a Diels-Alder adduct of a heterogeneous steroid bearing a 6/6/6/6/5 pentacyclic carbon skeleton. Solitumergosterol A (1) exhibited weak in vitro anti-tumor activity against MB231 cells by a RXRα-dependent mechanism.

Anti-Food Allergic Compounds from Penicillium griseofulvum MCCC 3A00225, a Deep-Sea-Derived Fungus.

Ten new (1-10) and 26 known (11-36) compounds were isolated from Penicillium griseofulvum MCCC 3A00225, a deep sea-derived fungus. The structures of the new compounds were determined by detailed analysis of the NMR and HRESIMS spectroscopic data. The absolute configurations were established by X-ray crystallography, Marfey's method, and the ICD method. All isolates were tested for in vitro anti-food allergic bioactivities in immunoglobulin (Ig) E-mediated rat basophilic leukemia (RBL)-2H3 cells. Compound 13 significantly decreased the degranulation release with an IC50 value of 60.3 µM, compared to that of 91.6 µM of the positive control, loratadine.