Salt Compartmentation and Antioxidant Defense in Roots and Leaves of Two Non-Salt Secretor Mangroves under Salt Stress

The effects of increasing NaCl (100–400 mM) on cellular salt distribution, antioxidant enzymes, and the relevance to reactive oxygen species (ROS) homeostasis were investigated in 1-year-old seedlings of two non-salt secretor mangroves, Kandelia obovata and Bruguiera gymnorhiza. K. obovata accumulated less Na+ and Cl− in root cells and leaf compartments under 400 mM NaCl compared to B. gymnorhiza. However, B. gymnorhiza leaves are notable for preferential accumulation of salt ions in epidermal vacuoles relative to mesophyll vacuoles. Both mangroves upregulated antioxidant enzymes in ASC-GSH cycle to scavenge the salt-elicited ROS in roots and leaves but with different patterns. K. obovata rapidly initiated antioxidant defense to reduce ROS at an early stage of salt stress, whereas B. gymnorhiza maintained a high capacity to detoxify ROS at high saline. Collectively, our results suggest that salinized plants of the two mangroves maintained ROS homeostasis through (i) ROS scavenging by antioxidant enzymes and (ii) limiting ROS production by protective salt compartmentation. In the latter case, an efficient salt exclusion is favorable for K. obovata to reduce the formation of ROS in roots and leaves, while the effective vacuolar salt compartmentation benefited B. gymnorhiza leaves to avoid excessive ROS production in a longer term of increasing salinity

T-Helper Cell Cytokine Expression Profiling in Rheumatoid Arthritis Patients by Flow Cytometric Bead Array Analysis

Background: Rheumatoid arthritis (RA) is the most common chronic autoimmune disease affecting multiple joints. A chronic imbalance in cytokine production by T-helper (Th) cells is likely a key factor in RA development. Our objective was to profile the serum cytokine expression from three key Th cell types (Th1, Th2, and Th17) in RA patients in order to correlate the resulting cytokine expression profiles with RA activity. Material and Methods: From a population of RA patients (n = 71) and healthy controls (n = 18), the serum concentrations of seven cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ, and TNF-α) were analyzed by flow cytometric bead array (CBA). Results: The serum concentrations of all seven cytokines were significantly higher in RA patients than in healthy controls. Interestingly, the serum concentration profiles varied with the 28-joint Disease Activity Score (DAS28), a measure of RA activity derived from joint indices (tender joints and swollen joints count) and the erythrocyte sedimentation rate. In the high RA activity group (DAS28 > 5.1), all seven cytokines were significantly elevated. In the moderate RA activity group (DAS28 between 3.2 and 5.1), only IL-2, IL-6, IL-10, and IL-17A were significantly increased. In the low RA activity group (DAS28 ≤ 3.2), only IL-2, IL-4, and TNF-α were significantly elevated. Conclusions: The Th cell-derived cytokine expression profile significantly changes across varying levels of RA activity. Th1/Th17 cell-derived TNF-α and Th2 cell-derived IL-4 appear to play more important roles in the early stages of RA, while all seven cytokines derived from Th1, Th2, and Th17 cells (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ, and TNF-α) are overtly involved in the advanced stages of RA

One Adapter for All Programming Languages? Adapter Tuning for Code Search and Summarization

As pre-trained models automate many code intelligence tasks, a widely used paradigm is to fine-tune a model on the task dataset for each programming language. A recent study reported that multilingual fine-tuning benefits a range of tasks and models. However, we find that multilingual fine-tuning leads to performance degradation on recent models UniXcoder and CodeT5. To alleviate the potentially catastrophic forgetting issue in multilingual models, we fix all pre-trained model parameters, insert the parameter-efficient structure adapter, and fine-tune it. Updating only 0.6\% of the overall parameters compared to full-model fine-tuning for each programming language, adapter tuning yields consistent improvements on code search and summarization tasks, achieving state-of-the-art results. In addition, we experimentally show its effectiveness in cross-lingual and low-resource scenarios. Multilingual fine-tuning with 200 samples per programming language approaches the results fine-tuned with the entire dataset on code summarization. Our experiments on three probing tasks show that adapter tuning significantly outperforms full-model fine-tuning and effectively overcomes catastrophic forgetting.Comment: Accepted to the 45th International Conference on Software Engineering (ICSE 2023

Effect of Metformin on Lactate Metabolism in Normal Hepatocytes under High Glucose Stress in Vitro

Objective To study the effect of metformin on lactate metabolism in hepatocytes in vitro under high glucose stress. In vitro LO2 cells, liver cells were randomly divided into blank control group, 25 tendency/L glucose solution, 27 tendency/L glucose solution,29 tendency/L glucose solution, 31 tendency/L glucose solution, 33 tendency/L glucose solution,35 tendency/L glucose solution treatment group, the optimal concentration of 31 tendency after L, use 30 tendency for L metformin solution, and then divided into blank control group, the optimal concentration of glucose solution, normal liver cells + metformin solution normal liver cells. The optimal concentration of glucose solution normal liver cells + metformin solution respectively in the 12 h, 24 h,48 h on cell count plate to calculate the number of liver cells, and using lactic acid determination kit the optimal concentration of glucose solution + normal liver cells and normal liver cells + the optimal concentration of glucose solution + metformin solution respectively in the 12 h, 24 h, 48 h of cell cultures of lactic acid value. There was no significant change in the lactic acid concentration but significant increase in the number of surviving hepatocytes in the highglycemic control group compared with that in the high-glycemic control group without metformin. Metformin has no significant effect on lactic acid metabolism of hepatocytes under high glucose stress in vitro, and has a protective effect on hepatocytes under high glucose stress. Based on this,it is preliminarily believed that metformin is not the direct factor leading to diabetic lactic acidosis

Hydrogen Sulfide Mediates K+ and Na+ Homeostasis in the Roots of Salt-Resistant and Salt-Sensitive Poplar Species Subjected to NaCl Stress

Non-invasive micro-test techniques (NMT) were used to analyze NaCl-altered flux profiles of K+, Na+, and H+ in roots and effects of NaHS (a H2S donor) on root ion fluxes in two contrasting poplar species, Populus euphratica (salt-resistant) and Populus popularis (salt-sensitive). Both poplar species displayed a net K+ efflux after exposure to salt shock (100 mM NaCl), as well as after short-term (24 h), and long-term (LT) (5 days) saline treatment (50 mM NaCl, referred to as salt stress). NaHS (50 μM) restricted NaCl-induced K+ efflux in roots irrespective of the duration of salt exposure, but K+ efflux was not pronounced in data collected from the LT salt stress treatment of P. euphratica. The NaCl-induced K+ efflux was inhibited by a K+ channel blocker, tetraethylammonium chloride (TEA) in P. popularis root samples, but K+ loss increased with a specific inhibitor of plasma membrane (PM) H+-ATPase, sodium orthovanadate, in both poplar species under LT salt stress and NaHS treatment. This indicates that NaCl-induced K+ loss was through depolarization-activated K+ channels. NaHS caused increased Na+ efflux and a corresponding increase in H+ influx for poplar roots subjected to both the short- and LT salt stress. The NaHS-enhanced H+ influx was not significant in P. euphratica samples subjected to short term salt stress. Both sodium orthovanadate and amiloride (a Na+/H+ antiporter inhibitor) effectively inhibited the NaHS-augmented Na+ efflux, indicating that the H2S-enhanced Na+ efflux was due to active Na+ exclusion across the PM. We therefore conclude that the beneficial effects of H2S probably arise from upward regulation of the Na+/H+ antiport system (H+ pumps and Na+/H+ antiporters), which promote exchange of Na+ with H+ across the PM and simultaneously restricted the channel-mediated K+ loss that activated by membrane depolarization

Intracellular β\u3csub\u3e1\u3c/sub\u3e-Adrenergic Receptors and Organic Cation Transporter 3 Mediate Phospholamban Phosphorylation to Enhance Cardiac Contractility

Rationale: β1ARs (β1-adrenoceptors) exist at intracellular membranes and OCT3 (organic cation transporter 3) mediates norepinephrine entry into cardiomyocytes. However, the functional role of intracellular β1AR in cardiac contractility remains to be elucidated. Objective: Test localization and function of intracellular β1AR on cardiac contractility. Methods and Results: Membrane fractionation, super-resolution imaging, proximity ligation, coimmunoprecipitation, and single-molecule pull-down demonstrated a pool of β1ARs in mouse hearts that were associated with sarco/endoplasmic reticulum Ca2+-ATPase at the sarcoplasmic reticulum (SR). Local PKA (protein kinase A) activation was measured using a PKA biosensor targeted at either the plasma membrane (PM) or SR. Compared with wild-type, myocytes lacking OCT3 (OCT3-KO [OCT3 knockout]) responded identically to the membrane-permeant βAR agonist isoproterenol in PKA activation at both PM and SR. The same was true at the PM for membrane-impermeant norepinephrine, but the SR response to norepinephrine was suppressed in OCT3-KO myocytes. This differential effect was recapitulated in phosphorylation of the SR-pump regulator phospholamban. Similarly, OCT3-KO selectively suppressed calcium transients and contraction responses to norepinephrine but not isoproterenol. Furthermore, sotalol, a membrane-impermeant βAR-blocker, suppressed isoproterenol-induced PKA activation at the PM but permitted PKA activation at the SR, phospholamban phosphorylation, and contractility. Moreover, pretreatment with sotalol in OCT3-KO myocytes prevented norepinephrine-induced PKA activation at both PM and the SR and contractility. Conclusions: Functional β1ARs exists at the SR and is critical for PKA-mediated phosphorylation of phospholamban and cardiac contractility upon catecholamine stimulation. Activation of these intracellular β1ARs requires catecholamine transport via OCT3

Association between systemic lupus erythematosus and inflammatory bowel disease in European and East Asian populations: a two-sample Mendelian randomization study

BackgroundPrevious studies have shown a coexistence phenomenon between systemic lupus erythematosus (SLE) and inflammatory bowel disease (IBD), but the causal relationship between them is still unclear. Therefore, we conducted a two-sample Mendelian randomization (MR) analysis using publicly available summary statistics data to evaluate whether there was a causal relationship between the two diseases.MethodsSummary statistics for SLE and IBD were downloaded from the Open Genome-Wide Association Study and the International Inflammatory Bowel Disease Genetics Consortium. European and East Asian populations were included in this MR work. We adopted a series of methods to select instrumental variables that are closely related to SLE and IBD. To make the conclusion more reliable, we applied a variety of different analysis methods, among which the inverse variance–weighted (IVW) method was the main method. In addition, heterogeneity, pleiotropy, and sensitivity were assessed to make the conclusions more convincing.ResultsIn the European population, a negative causal relationship was observed between SLE and overall IBD (OR = 0.94; 95% CI = 0.90, 0.98; P < 0.004) and ulcerative colitis (UC) (OR = 0.93; 95% CI = 0.88, 0.98; P = 0.006). After removing outliers with Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO), the results remained consistent with IVW. However, there was no causal relationship between SLE and Crohn’s disease. In the East Asian population, no causal relationship was found between SLE and IBD.ConclusionOur results found that genetic susceptibility to SLE was associated with lower overall IBD risk and UC risk in European populations. In contrast, no association between SLE and IBD was found in East Asian populations. This work might enrich the previous research results, and it may provide some references for research in the future