P2 Levels Research Articles

The effects of Lactobacillus delbrueckii and Lactobacillus rhamnosus on cytokines and their related molecules: An ex vivo study on patients with systemic lupus erythematosus.

This study aimed to assess the ex vivo impact of Lactobacillus delbrueckii (L. delbrueckii) and Lactobacillus rhamnosus (L. rhamnosus) on inflammatory and anti-inflammatory cytokines as well as their related molecules on the peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematosus (SLE) patients. This study was conducted with 20 newly diagnosed SLE patients (18 females, 2 males; mean age: 33.3±12.4 years; range, 18 to 68 years) between September 2017 and September 2018. Extracted PBMCs from each patient were divided into 4 cell groups in our study. Three cell groups act as treatment groups receiving L. rhamnosus (107 CFU/mL), L. delbrueckii (105 CFU/mL) or a mixture of both, and one group act as our untreated control group in the absence of any probiotic agents. All cell groups were cultured in RPMI 1460 medium for 48 h. Then, total RNA was extracted, and cDNA was synthesized. The gene expression levels of forkhead box P3 (FOXP3), transforming growth factor beta (TGF-β), interleukin (IL)-6, IL-10, and IL-2 were evaluated by a quantitative real-time polymerase chain reaction. The results revealed that expression levels of FOXP3, TGF-β, IL-10, and IL-2 increased and the level of IL-6 decreased in probiotics-receiving groups compared to the control group. Lactobacillus delbrueckii and L. rhamnosus enhanced the expression of regulatory T cell-related molecules such as FOXP3 and IL-2 and also increased the expression of IL-10. These probiotics also reduced the expression of IL-6 as proinflammatory cytokines in the PBMCs of SLE patients. The results of the present study show that these probiotics could be effective in regulating the balance of cytokine gene expression ex vivo , and due to their beneficial effects, they can be an intriguing option in the production of new complement drugs for SLE.

The expanding roles of PI4P and PI(4,5)P2 at the plasma membrane: Role of phosphatidylinositol transfer proteins

Phosphoinositides are phosphorylated derivatives of phosphatidylinositol, a phospholipid that is synthesised at the endoplasmic reticulum. The plasma membrane contains the enzymes to phosphorylate phosphatidylinositol and is therefore rich in the phosphorylated derivatives, PI4P and PI(4,5)P2. PI(4,5)P2 is a substrate for phospholipase C and during cell signaling, PI(4,5)P2 levels are reduced. Here I discuss a family of proteins, phosphatidylinositol transfer proteins (PITPs) that can restore PI(4,5)P2 levels.

Mycorrhizae utilization in palm oil nurseries to reduce inorganic fertilizer dose

Fertilization in palm oil nurseries is an invaluable tending activity to obtain healthy and robust seedlings. This research aims is to identify the dose percentage level of the inorganic fertilizer which can be reduced by applying mycorrhizae in oil palm nurseries. The research design used a non-factorial completely randomized design, as the treatment factor was the dose of fertilizer in oil palm nurseries. There are 5 levels of treatment, namely P0 (100% of the standard dose + 50 g mycorrhizae), P1 (75% of the standard dose + 50 g mycorrhizae), P2 (50% of the standard dose + 50 g mycorrhizae), P3 (25% of the standard dose + 50 g mycorrhizae), and P4 (0 inorganic fertilizer + 50 g Mycorrhizae). Each treatment was arranged in four replications. The data were analyzed using ANOVA, if F-count > F-table then it is continued with Duncan Multiple Range Test. The observation variables included plant height, number of leaves and stem diameter, root length, canopy dry weight, roots dry weight, and P uptake. The results showed that there were significant differences in plant height, number of leaves, stem diameter, roots dry weight, canopy dry weight and P uptake in leaves as well as, while the observations of root length showed no significant difference. The application of 50 grams of mycorrhizae with a 50-75% standard dose of fertilization resulted in optimal seedling growth. Mycorrhizae utilization can reduce the application of inorganic fertilizers up to 25-50%.

Multimodal action of KRP203 on phosphoinositide kinases in vitro and in cells

Increased phosphoinositide signaling is commonly associated with cancers. While “one-drug one-target” has been a major drug discovery strategy for cancer therapy, a “one-drug multi-targets” approach for phosphoinositide enzymes has the potential to offer a new therapeutic approach. In this study, we sought a new way to target phosphoinositides metabolism. Using a high-throughput phosphatidylinositol 5-phosphate 4-kinase-alpha (PI5P4Kα) assay, we have identified that the immunosuppressor KRP203/Mocravimod induces a significant perturbation in phosphoinositide metabolism in U87MG glioblastoma cells. Despite high sequence similarity of PI5P4K and PI4K isozymes, in vitro kinase assays showed that KRP203 activates some (e.g., PI5P4Kα, PI4KIIβ) while inhibiting other phosphoinositide kinases (e.g., PI5P4Kβ, γ, PI4KIIα, class I PI3K-p110α, δ, γ). Furthermore, KRP203 enhances PI3P5K/PIKFYVE's substrate selectivity for phosphatidylinositol (PI) while preserving its selectivity for PI(3)P. At cellular levels, 3 h of KRP203 treatment induces a prominent increase of PI(3)P and moderate increase of PI(5)P, PI(3,5)P2, and PI(3,4,5)P3 levels in U87MG cells. Collectively, the finding of multimodal activity of KRP203 towards multi-phosphoinositide kinases may open a novel basis to modulate cellular processes, potentially leading to more effective treatments for diseases associated with phosphoinositide signaling pathways.

Chitosan biomaterial enhances the effect of OECs on the inhibition of sciatic nerve injury-induced neuropathic pain

Neuropathic pain is a common symptom experienced by most clinical diseases at different levels, and its treatment has always been a clinical difficulty. Therefore, it is particularly important to explore new and effective treatment methods. The role of olfactory ensheathing cells (OECs) in nerve injury and pain is recognized by different studies. Our previous study found that transplantation of OECs alleviated hyperalgesia in rats. However, single-cell transplantation lacks medium adhesion and support, and exerts limited analgesic effect. Therefore, on the basis of the previous study, this study investigated the effect of pain relief by co-transplanting OECs with chitosan (CS) (a biological tissue engineering material, as OECs were transplanted into the host medium) to the injured sciatic nerve. The results showed that the pain threshold of sciatic nerve injury of rats was significantly reduced, and the expression level of P2×4 receptor in the spinal cord was significantly increased. While olfactory ensheathing cells combined with chitosan (OECs+CS) transplantation could significantly relieve pain, and the analgesic effect was stronger than that of OECs transplantation alone. OECs+CS transplantation promoted the formation of sciatic nerve remyelination, improved the changes of demyelination, and promoted the repair of sciatic nerve injury more significantly. In addition, the effect of OECs+CS to down-regulate the expression of P2×4 receptor was significantly stronger than that of OECs transplantation, and exerted a better analgesic effect. These data reveal that OECs+CS have a better analgesic effect in relieving neuropathic pain induced by sciatic nerve injury, and provide a new therapeutic strategy for pain treatment.

A novel homeostatic mechanism tunes PI(4,5)P2-dependent signaling at the plasma membrane.

The lipid molecule phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] controls all aspects of plasma membrane (PM) function in animal cells, from its selective permeability to the attachment of the cytoskeleton. Although disruption of PI(4,5)P2 is associated with a wide range of diseases, it remains unclear how cells sense and maintain PI(4,5)P2 levels to support various cell functions. Here, we show that the PIP4K family of enzymes, which synthesize PI(4,5)P2 via a minor pathway, also function as sensors of tonic PI(4,5)P2 levels. PIP4Ks are recruited to the PM by elevated PI(4,5)P2 levels, where they inhibit the major PI(4,5)P2-synthesizing PIP5Ks. Perturbation of this simple homeostatic mechanism reveals differential sensitivity of PI(4,5)P2-dependent signaling to elevated PI(4,5)P2 levels. These findings reveal that a subset of PI(4,5)P2-driven functions might drive disease associated with disrupted PI(4,5)P2 homeostasis.

Purinergic receptor P2 × 7 activates NOX2/JNK signaling to participate in granulosa cell inflammation and apoptosis in polycystic ovary syndrome.

Increasing evidence shows that polycystic ovary syndrome (PCOS) is often accompanied by an inflammatory response, hence, appropriately managing granulosa cell inflammation is critical to regaining ovarian function in PCOS. In this study, the differential levels of purinergic receptor P2 × 7 between the control and PCOS samples in the dataset GSE34526 were assessed, then PCOS mouse models were established. Following evaluating the fluctuations in hormone levels, inflammatory cytokines, and P2 × 7, mice received treatment with the P2 × 7 antagonist A740003. Its effects on hormones, inflammation, apoptosis, and NOX2 signaling in mice were examined. Afterward, primary mouse granulosa cells were isolated, and the mediating role of NOX2 signaling in the P2 × 7 regulatory pathway was confirmed by transfection of NOX2 overexpression plasmids. The results demonstrated that P2 × 7 was significantly elevated in the PCOS samples in the dataset. Compared with the control group, PCOS mice had significant differences in the follicle-stimulating hormone, luteinizing hormone, testosterone, anti-Müllerian hormone, inflammatory factors, and P2 × 7. Treatment with A740003 partially restored these parameter levels, including NOX2 signaling. Based on in vitro experiments on primary mouse granulosa cells, the above findings were re-verified, and the overexpression of NOX2 could reverse the regulatory function of P2 × 7. The present study highlights that P2 × 7 level increases in PCOS, and inhibition of P2 × 7 can reduce disease symptoms. It is involved in inflammation and apoptosis in granulosa cells through NOX2/JNK signaling.

Yin Yang 1 impacts upon preeclampsia by regulating Treg/TH17 cells and PI3K/AKT pathway

Preeclampsia (PE) is a common obstetric syndrome with an unclear etiology and pathogenesis. The study here aimed to investigate the role of Yin Yang 1 (YY1) in PE, and to reveal any YY1-regulated mechanisms in PE. Peripheral blood, placenta, and endometrial tissues of PE patients, healthy volunteers, and patients who had undergone an elective Cesarean section and had a scarred uterus (control group) were collected for analyses. Rat PE models were established by lipopolysaccharide induction. Subsets of these rats were then made to over-express YY1. At 18 d after the PE was established, urine, blood, and placental tissues from all rats were collected. Levels of regulatory-T (Treg) and helper T-type 17 (TH17) cells in both human and rat blood were measured by flow cytometry. ELISA kits were used to evaluate blood levels of inflammatory factors (i.e. IL-6, IL-10, and IL-17) as well. RT-qPCR and Western blot assays were performed to quantify levels of forkhead box P3 (Foxp3), retinoic acid-related orphan receptor C (RORc), and YY1 in the human and rat placenta and endometrial tissues. Expressions of PI3K/AKT pathway-related proteins were also evaluated by Western blots. The results indicated that the PE patients, relative to levels in control group and the healthy control subjects, had decreased circulating levels of Treg cells/increased TH17 cells; tissues from these patients also had relatively-decreased FoxP3 mRNA and protein expressions and elevated RORc mRNA and protein expressions. YY1 was expressed only at low levels in the PE patient placenta and endometrial tissues. In rats, PE rats treated with over-expressed YY1 had (relative to in PE rats without over-induced YY1) increased circulating levels of Treg cells/decreased TH17 cells; tissues from these rats had elevated FoxP3 mRNA and protein expressions and reduced mRNA and protein RORc expressions, as well as indications of alleviated inflammation. In the rat placenta samples, YY1 was also determined to activate the PI3K/AKT pathway. In summary, YY1 regulates the balance among Treg/TH17 cells and so affect the PE process in part through activation of the PI3K/AKT pathway.

The lipid transfer proteins Nir2 and Nir3 sustain phosphoinositide signaling and actin dynamics during phagocytosis.

Changes in membrane phosphoinositides and local Ca2+ elevations at sites of particle capture coordinate the dynamic remodeling of the actin cytoskeleton during phagocytosis. Here, we show that the phosphatidylinositol (PI) transfer proteins PITPNM1 (Nir2) and PITPNM2 (Nir3) maintain phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] homeostasis at phagocytic cups, thereby promoting actin contractility and the sealing of phagosomes. Nir3 and to a lesser extent Nir2 accumulated on endoplasmic reticulum (ER) cisternae juxtaposed to phagocytic cups when expressed in phagocytic COS-7 cells. CRISPR-Cas9 editing of Nir2 and Nir3 genes decreased plasma membrane PI(4,5)P2 levels, store-operated Ca2+ entry (SOCE) and receptor-mediated phagocytosis, stalling particle capture at the cup stage. Re-expression of either Nir2 or Nir3 restored phagocytosis, but not SOCE, proportionally to the PM PI(4,5)P2 levels. Phagosomes forming in Nir2 and Nir3 (Nir2/3) double-knockout cells had decreased overall PI(4,5)P2 levels but normal periphagosomal Ca2+ signals. Nir2/3 depletion reduced the density of contractile actin rings at sites of particle capture, causing repetitive low-intensity contractile events indicative of abortive phagosome closure. We conclude that Nir proteins maintain phosphoinositide homeostasis at phagocytic cups, thereby sustaining the signals that initiate the remodeling of the actin cytoskeleton during phagocytosis.

Quantitative super-resolution microscopy reveals the differences in the nanoscale distribution of nuclear phosphatidylinositol 4,5-bisphosphate in human healthy skin and skin warts.

Introduction: Imaging of human clinical formalin-fixed paraffin-embedded (FFPE) tissue sections provides insights into healthy and diseased states and therefore represents a valuable resource for basic research, as well as for diagnostic and clinical purposes. However, conventional light microscopy does not allow to observe the molecular details of tissue and cell architecture due to the diffraction limit of light. Super-resolution microscopy overcomes this limitation and provides access to the nanoscale details of tissue and cell organization. Methods: Here, we used quantitative multicolor stimulated emission depletion (STED) nanoscopy to study the nanoscale distribution of the nuclear phosphatidylinositol 4,5-bisphosphate (nPI(4,5)P2) with respect to the nuclear speckles (NS) marker SON. Results: Increased nPI(4,5)P2 signals were previously linked to human papillomavirus (HPV)-mediated carcinogenesis, while NS-associated PI(4,5)P2 represents the largest pool of nPI(4,5)P2 visualized by staining and microscopy. The implementation of multicolor STED nanoscopy in human clinical FFPE skin and wart sections allowed us to provide here the quantitative evidence for higher levels of NS-associated PI(4,5)P2 in HPV-induced warts compared to control skin. Discussion: These data expand the previous reports of HPV-induced increase of nPI(4,5)P2 levels and reveal for the first time the functional, tissue-specific localization of nPI(4,5)P2 within NS in clinically relevant samples. Moreover, our approach is widely applicable to other human clinical FFPE tissues as an informative addition to the classical histochemistry.

Uji In Vivo Elaeocarpus sphaericus Schum terhadap Kadar Gula Darah dan Struktur Jaringan Testis, Pankreas, dan Ginjal

Genitri plant (Elaeocarpus sphaericus Schum) has a complex chemical compound that has the potential to lower blood sugar levels. The purpose of this study was to analyze in vivo blood sugar levels and changes in tissue structure of the pancreas, testes seminiferous tubules, and sucrose-induced kidneys. The study used an experimental approach, 24 male Mus musculus mice were grouped into 4 treatment groups. Negative control (P0), positive control giving sucrose at a dose of 1.125 mg/g (P1); Sucrose induction treatment was at a dose of 1.125 mg/g and Gintri seed simplicia was at a dose of 1.300 mg/g (P2). Experimental animals before being induced by sucrose were fasted for 2 hours. Sucrose induction was carried out for 5 days, the experimental animals were given food and drink ad libitum. Checking blood sugar levels every 4 hours through the tail vein. Blood sugar levels of experimental animals P2 and P3 were 126 mg/ each followed by administration of a solution of genitri seeds and fruit for 36 days, every 6 days data was collected on blood sugar levels. On the 37th day, dislocation, surgery and organ harvesting of the testes, pancreas and kidneys were carried out, and preparation of HE staining tissue was made. Data analysis using One Way Anova. The results showed that sucrose induction reduced the diameter of the islets of Langerhans, increased the diameter of the seminiferous tubules of the testes, and reduced the diameter of the glomerulus of the kidney. Giving genitri seeds and fruit lowers blood sugar levels, affects the tissue structure of the pancreas, testes, and glomerulus. The F value of the diameter of the pancreatic islets of Langerhans 16,662; testicular seminiferous tubule diameter 13,433; Glomerular diameter 28,958.

Sfxn5 Regulation of Actin Polymerization for Neutrophil Spreading Depends on a Citrate-Cholesterol-PI(4,5)P2 Pathway.

Cell spreading is an initial and critical step in neutrophil adhesion and migration, leading to neutrophil recruitment to inflammatory tissues. Sideroflexin (Sfxn) family proteins are metabolite transporters located in the mitochondrial membrane. Recombinant SFXN5 protein is a citrate transporter invitro; however, whether Sfxn5 regulates any cellular behavior or function remains unknown. In this study, we found that small interfering RNA transfection or morpholino injection achieving Sfxn5 deficiency in neutrophils significantly decreased neutrophil recruitment in mice and zebrafish, respectively. Sfxn5 deficiency impaired neutrophil spreading and spreading-associated cellular phenotypes, such as cell adhesion, chemotaxis, and ROS production. Actin polymerization is critical for neutrophil spreading, and we found that actin polymerization in spreading neutrophils was partially inhibited by Sfxn5 deficiency. Mechanistically, we observed that the levels of cytosolic citrate and its downstream metabolic products, acetyl-CoA and cholesterol, were decreased in Sfxn5-deficient neutrophils. The levels of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), a mediator for the regulation of actin polymerization by cholesterol, were reduced in the plasma membrane of Sfxn5-deficient neutrophils. Exogenous supplementation with citrate or cholesterol partially reversed the reduction in PI(4,5)P2 levels, defective neutrophil actin polymerization, and cell spreading. Altogether, we demonstrated that Sfxn5 maintains cytosolic citrate levels and ensures the synthesis of sufficient cholesterol to promote actin polymerization in a PI(4,5)P2-dependent manner during neutrophil spreading, which is essential for the eventual inflammatory recruitment of neutrophils. Our study revealed the importance of Sfxn5 in neutrophil spreading and migration, thus identifying, to our knowledge, for the first time, the physiological cellular functions of the Sfxn5 gene.

Early clinical observation of supra-hemodiafiltration with endogenous reinfusion in the treatment of uremic pruritus.

To evaluate the clinical efficacy of supra-hemodiafiltration with endogenous reinfusion (Supra-HFR) for pruritus in uremic maintenance hemodialysis (HD) patients and explore the possible mechanism. This study prospectively included 60 patients with uremia who underwent maintenance hemodialysis and developed pruritus. Patients were randomly divided into a study group (30 cases) and a control group (30 cases). Patients in the study group underwent dialysis once a week with Supra-HFR and twice a week with HD. The group received HD dialysis 3 times a week. Visual analog scales (VAS) scores, 5-D itch scale scores, and 12-Item Pruritus Severity Scale (12-PSS) were used to evaluate the itching degree of patients. Quality of life was assessed using KDTA and SF-36 scores. Blood levels of hypersensitive C-reactive protein, calcium ion (Ca2+), phosphorus ion (P3+ ), free parathyroid hormone (iPTH), and β2-microglobulin (β2-MG) were compared between the two groups before treatment and at follow-up 24 weeks after treatment. Before treatment, there was no significant difference in VAS, 5-D itch scale, and 12-PSS score between the study group and the control group (all p > 0.05). After 24 weeks of treatment, the VAS score of the study group (2.82 ± 0.91) was significantly lower than that of the control group (7.47 ± 1.32, p < 0.001), the 5-D itch scale score of the study group (9.47 ± 2.34) was significantly lower than that of the control group (18.53 ± 4.02, p < 0.001), the 12-PSS score of the study group (11.20 ± 1.81) was significantly lower than that of the control group (16.47 ± 2.09, p < 0.001). KDTA of the study group (64.17 ± 8.07 vs. 47.83 ± 13.46, p < 0.001) and SF-36 scores (65.37 ± 6.28 vs. 55.90 ± 14.28, p = 0.002) were significantly higher than that in the control group. The levels of hs-CRP, P3+ , iPTH, and β2-MG in the study group after treatment were lower than those before treatment, and lower than those in the control group after treatment (all p < 0.05). The Supra-HFR can effectively reduce the itching symptoms of uremia patients and improve their quality of life.

Analysis of the Utilization of Agricultural Waste Fermentation in Increasing Shallot Production

Shallot farming increasing production plays a crucial role in providing fertilizer, but inorganic fertilizers are costly and rare, so that they can cause failure in shallot cultivation. The solution to the fertilizer problem can be utilizing agricultural waste in organic fertilizer. Raw materials from agricultural waste can be processed into solid and liquid organic fertilizers. The benefits of organic fertilizers increase soil fertility while also being able to change or improve soil structure and microbes. The research objective was to determine the utilization of agricultural waste in increasing shallot production. The farm waste consists of egg shells, rice husks, tofu dregs, rice washing water, goat manure, vegetable waste, banana cobs, chicken blood, pineapple skins, and empty palm fruit bunches, which are fermented into organic fertilizer. This study is new to utilizing ten types of organic waste to increase macronutrients. Research activities will be carried out in April 2022. The variables measured are plant height (cm), number of tillers (tubers), dry tuber production (g), and conversion of shallot bulb production per hectare (kg) using an analysis tool factorial randomized block design consisting of two factors, namely the first-factor solid organic fertilizer (P) with levels P0=0 kg/plot, P1=1.5 kg/plot, P2=2.5 kg/plot, and P3=3.5 kg/plot. Then the second factor is liquid organic fertilizer (C) with the treatment level C0=0 ml/liter water/plot, C1=250 ml/liter water/plot, C2=500 ml/liter water/plot, C3=750 ml/liter water/ plot. The research variables were plant height (cm), number of tillers (tubers), dry tuber production (g), and shallot production conversion per hectare (kg). The results showed a significant effect on solid fertilizers at the P3 level compared to the P2, P1, and P0 levels. In contrast, the liquid fertilizer treatment at the C3 level significantly affected the C2, C1, and C0 levels.

Bifidobacterium longum Administration Diminishes Parasitemia and Inflammation During Plasmodium berghei Infection in Mice.

During Plasmodium berghei (P. berghei) infection, infected erythrocytes are sequestered in gut tissues through microvascular circulation, leading to dysbiosis. This study aimed to investigate the effect of Lactobacillus casei (L. casei) and Bifidobacterium longum (B. longum) administration on the parasitemia level, gut microbiota composition, expression of cluster of differentiation 103 (CD103) in intestinal dendritic and T regulatory cells (T reg), plasma interferon gamma (IFN-γ) and tumor necrosis factor (TNF-α) levels in P. berghei infected mice. P. berghei was inoculated intraperitoneally. Infected mice were randomly divided into 5 groups and treated with either L. casei, B. longum, or the combination of both for 5 days before up to 6 days post-infection (p.i). The control group was treated with phosphate-buffered saline (PBS), while uninfected mice were used as negative control. Levels of CD103 and forkhead box P3 (FoxP3) expression were measured by direct immunofluorescense, while plasma IFN-γ and TNF-α level were determined using enzyme-linked immunosorbent assay (ELISA). All treated groups showed an increase in parasitemia from day 2 to day 6 p.i, which was significant at day 2 p.i (p = 0.001), with the group receiving B. longum displaying the lowest degree of parasitemia. Significant reduction in plasma IFN-γ and TNF-α levels was observed in the group receiving B. longum (p = 0.022 and p = 0.026, respectively). The CD103 and FoxP3 expression was highest in the group receiving B. longum (p = 0.01 and p = 0.02, respectively). B. longum showed the best protective effect against Plasmodium infection by reducing the degree of parasitemia and modulating the gut immunity. This provides a basis for further research involving probiotic supplementation in immunity modulation of infectious diseases.

Effect of Nitrogen and Phosphorus levels on growth and yield of direct-seeded rice (Oryza sativa L.) under Nagaland conditions

A field experiment was conducted entitled “Effect of nitrogen and phosphorus levels on growth and yield of direct seeded rice (Oryza sativa L.) under Nagaland condition” during the kharif period i.e., June-October 2018, in the experimental research farm of the School of Agricultural Sciences and Rural Development, Nagaland University. Nine treatments comprising three levels of N (0, 50, 100 kg N ha-1) and three levels of P (0, 40, 80 kg P2O5 ha-1) were used. The study revealed that N2 (100 kg N ha-1), P1 (40 kg P2O5 ha-1) and interaction treatment T8 (100 kg N: 40 kg P2O5) had performed significantly better as compared to other levels and combination treatments in terms of growth and yield in rice crop. Application of N and P levels significantly increased plant height (cm), number of tillers, crop growth rate (g g-1 day-1) and relative growth rate (g g-1 day-1). The highest grain yields (3687.96, 3687.96, 4442.42 kg ha-1) were recorded with N2, P1 and T8. Maximum straw yield was recorded with treatment levels of N2 (7394.96 kg ha-1), P2 (6531.29 kg ha-1) and T8 (8284.06 kg ha-1). The HI (%) was recorded highest with N2 (33.42%), interaction treatment T8 (35.59%) while P levels did not give any significant results.

Combined effect of nitrogen and phosphorous fertiliser on nitrogen absorption and utilisation in rice

The objectives of this study were to investigate the nitrogen (N) and phosphorus (P) balance fertilization strategy in paddy fields, and to evaluate the effects on N uptake and utilization in rice. In 2017-2018, the experiment was conducted using Deyou4727 hybrid rice with four different P fertilizer levels (0, 30, 60, and 90 kg/ha), marked as P0, P1, P2, P3 in turn, and four different N levels (0, 90, 150, and 270 kg/ha), similarly marked as N0, N1, N2, N3 in turn. The results showed that in the N-insufficient (N0, N1) environments, the P1 treatment increased N uptake and promoted transfer to the grain. However, high-P (P3) application increased the dry matter accumulation than other P levels, but limited the production and translocation of dry matter to some extent. In N-sufficient (N2, N3) environments, P2 level increased crop yield and N use efficiency by 11.35% and 37.01%. Unlike P2, none-P (P0) and high-P levels decreased rice dry matter translocation and transport capacity, which further affected N uptake and utilization in N-sufficient environments. Overall, the combination of the N application rate of 90 kg/ha and P application rate of 30 kg/ha, N application rate of 150, 270 kg/ha, and P application rate of 60 kg/ha had a high yield; strong nutrient accumulation and transfer ability. It was more inclined to balance N and P, which was beneficial to plant N absorption and utilization.

A new elasmothere genus and species from the middle Miocene of Tongxin, Ningxia, China, and its phylogenetic relationship

The elasmotheres were well diversified and widespread throughout the Neogene in Eurasia and East Africa. Here we report a new elasmothere genus and species, Tongxinotherium latirhinum gen. et sp. nov., from the Zhang’enbao Formation (middle Miocene) of Tongxin, Ningxia, China. The new genus is characterized by a broad and thick nasal bone, the ‘U’-shaped nasal notch located at the level of P3, the anterior margin of the orbit situated at the level of M2, subhypsodont teeth covered and filled by plentiful cement, slightly developed enamel foldings, expanded protocone with anterior and posterior constrictions, the middle valley and posterior valley closed on the premolars, protoloph separated from the ectoloph on P2, and buccal and lingual cingula present on premolars, but absent on molars. A phylogenetic analysis reveals that Tongxinotherium latirhinum gen. et sp. nov. is more derived than the early elasmotheres, and more primitive than Iranotherium and Ningxiatherium, bridging a morphological and stratigraphical gap between them. The discovery of new material improves the morphological characteristics of the early elasmotheres’ horns and increases the diversity of the middle Miocene elasmotheres. http://zoobank.org/urn:lsid:zoobank.org:pub:7DF2F57F-38DD-4FBF-B3DF-57AADD510131

Potential Role of TRPM8 in Cold-Induced Hypertension and Its Clinical Implications.

Seasonal variation in blood pressure that is higher in winter and lower in summer has been attributed to several factors that include changes in the activity of autonomic nervous system, vasopressin and expression of endothelial nitric oxide synthase (eNOS). Transient receptor potential melastatin 8 (TRPM8), a non-selective Ca2+-permeable cationic channel, serves as a molecular transducer to sense cold by the somatosensory system. TRPM8 is sensitive to protein kinase C (PKC) and phosphatidyl inositol-4,5-biphosphate [PI(4,5)P2] suggesting that TRPM8 is stimulated by phospholipase C (PLC)-coupled receptors. Activated PLC inhibits TRPM8 by reducing cellular PI(4,5)P2 levels and by activating PKC via diacyl glycerol. Bradykinin and prostaglandin E2 (PGE2), which are pro-inflammatory molecules, reduce the responses to cold, suggesting that phospholipase A2 (PLA2), which releases polyunsaturated fatty acids (PUFAs), the precursors of various eicosanoids, from the cell membrane lipid pool can modulate the function of TRPM8. TRPM8 functions as a nociceptor and modulates immune response. These and other studies indicate that cold-induced activation of transient receptor potential melastatin 8 (TRPM8) plays a role in the pathobiology of hypertension, preeclampsia and in the regulation of inflammation and immunity.

WITHDRAWN: Interleukin-35 dampens T helper 22 phenotype shift in CD4+CD25+CD127dim/- regulatory T cells in primary biliary cholangitis

The phenotype shift in regulatory T cells (Tregs) contributes to immunopathogenesis of autoimmune diseases. The current study was aimed to investigate the regulatory function of interleukin-35 (IL-35) to T helper 22 (Th22) cell phenotype shift in Tregs in primary biliary cholangitis (PBC). Fifty-five PBC patients and twenty-four controls were enrolled. CD4+CD25+CD127dim/- Tregs and Th22 cells were investigated by flow cytometry. Forkhead box P3 (FoxP3) and aryl hydrocarbon receptor (AhR) mRNA levels were assessed by real-time polymerase chain reaction. Plasma IL-10 and IL-22 levels were measured by ELISA. Purified Tregs were stimulated with exogenous IL-35, and were co-cultured with autologous CD4+CD25- T cells. Cellular proliferation and cytokine production was measured. Purified Tregs were also cultured into Th22 condition in the presence or absence of exogenous IL-35, and Th22 phenotype were assessed. PBC patients had lower levels of Treg percentage, FoxP3 mRNA, and plasma IL-10, while had higher levels of Th22 proportion, AhR mRNA, and plasma IL-22. Tregs from PBC patients showed reduced immunosuppressive activity, which presented as increased cellular proliferation, interferon-γ production and decreased IL-35/IL-10 secretion in co-culture system. Tregs shifted into Th22 phenotype in PBC patients with elevated CCR4, CCR6, and CCR10 expression as well as increased IL-22 production. IL-35 not only enhanced inhibitory function of Tregs but also suppressed phenotype shift of Tregs into Th22 phenotype in PBC patients. This process was accompanied by elevation of IL-10 and transforming growth factor-β1 secretion by Tregs from PBC patients. The present data suggested that reduced IL-35 might be insufficient to maintain Tregs function and phenotype shift from Tregs into Th22 phenotype in PBC patients.