Effects of acute hypoxia and reoxygenation on histological structure, antioxidant response, and apoptosis in razor clam Sinonovacula constricta.

Hypoxia is one of the major environmental problems limiting the healthy development of intensive aquaculture. Marine benthic shellfish are encountering heightened problems related to hypoxic stress as a result of ongoing human activities and aquaculture operations. Razor clam Sinonovacula constricta, a commercially valuable shellfish, has not yet been reported in studies on physiological changes caused by hypoxia and reoxygenation. To understand the negative effects of hypoxia and reoxygenation on the clams, we set up two low-oxygen concentration groups (DO 2.0 mg/L and DO 0.5 mg/L) and assessed multiple aspects of oxidative damage to their hepatopancreas and gills. After the hypoxic stress, the two tissues of the razor clam suffered varying degrees of damage, including cell degeneration and disruption of mitochondrial cristae. After reoxygenation, the 2.0 mg/L group recovered substantially, but the clams in the 0.5 mg/L group still unrecovered. The activities of antioxidant enzymes (MDA, T-AOC, SOD, GPX, and CAT) in clams were considerably altered by acute hypoxia and reoxygenation. Briefly, there was a growing and then declining trend in MDA, T-AOC, and SOD activities in the hepatopancreas, whereas GPX and CAT activities showed the converse trend. In the hepatopancreas and gills, the level of anti-apoptotic gene Bcl-2 transcripts gradually decreased with the duration of hypoxia and increased following reoxygenation. However, changes in the transcript level of the pro-apoptotic gene Bax were in contrast to that of Bcl-2. The TUNEL assay revealed that hypoxia caused apoptosis. Furthermore, at DO 0.5 mg/L, the degree of apoptosis was more significant than at DO 2.0 mg/L, and hepatopancreatic apoptosis was more severe than gill apoptosis. Collectively, our findings imply that hypoxia induces oxidative stress, histological damage, and apoptosis in razor clams in a concentration-dependent and tissue-specific manner. These consequences serve as a reminder that prolonged recovery periods may be required for razor clams to fully recover from oxidative damage resulting from hypoxia-reoxygenation episodes.

Genome-wide meta-analysis identifies susceptibility loci for autoimmune hepatitis type 1.

BACKGROUND AND AIMS: Autoimmune hepatitis (AIH) is a rare and chronic autoimmune liver disease. While genetic factors are believed to play a crucial role in the etiopathogenesis of AIH, our understanding of these genetic risk factors is still limited. In this study, we aimed to identify susceptibility loci to further understand the pathogenesis of this disease. APPROACH AND RESULTS: We conducted a case-control association study of 1,622 Chinese patients with AIH type 1 and 10,466 population controls from two independent cohorts. A meta-analysis was performed to ascertain variants associated with AIH type 1. A single-nucleotide polymorphism within the human leukocyte antigen (HLA) region showed the strongest association with AIH (rs6932730: OR = 2.32; p = 9.21 × 10-73 ). The meta-analysis also identified two non-HLA loci significantly associated with AIH: CD28/CTLA4/ICOS on 2q33.3 (rs72929257: OR = 1.31; p = 2.92 × 10-9 ) and SYNPR on 3p14.2 (rs6809477: OR = 1.25; p = 5.48 × 10-9 ). In silico annotation, reporter gene assays, and CRISPR activation experiments identified a distal enhancer at 2q33.3 that regulated expression of CTLA4. In addition, variants near STAT1/STAT4 (rs11889341: OR = 1.24; p = 1.34 × 10-7 ), LINC00392 (rs9564997: OR = 0.81; p = 2.53 × 10-7 ), IRF8 (rs11117432: OR = 0.72; p = 6.10 × 10-6 ), and LILRA4/LILRA5 (rs11084330: OR = 0.65; p = 5.19 × 10-6 ) had suggestive association signals with AIH. CONCLUSIONS: Our study identifies two novel loci (CD28/CTLA4/ICOS and SYNPR) exceeding genome-wide significance and suggests four loci as potential risk factors. These findings highlight the importance of costimulatory signaling and neuro-immune interaction in the pathogenesis of AIH.

Experiences of breast cancer survivors with exercise rehabilitation: qualitative systematic review and meta-synthesis.

PURPOSE: This study aimed to synthesize and evaluate the available qualitative literature on posttreatment participation in exercise rehabilitation among breast cancer survivors. METHODS: This systematic review followed the Joanna Briggs Institute (JBI) meta-aggregation approach guided by ENTREQ, graded according to the ConQual approach, and evaluated using the JBI Qualitative Assessment and Review Instrument (JBI-QARI). We searched qualitative or mixed methods studies related to the experiences of exercise rehabilitation among breast cancer survivors conducted until April 13, 2023, in nine English and Chinese databases. The selected studies were reviewed independently, and the data were collaboratively synthesized into core themes. RESULTS: A total of 24 studies were included, and 88 findings resulted in five synthesis findings: (a) benefits of participating in exercise rehabilitation, (b) facilitators of participation in exercise rehabilitation, (c) obstacle factors for participating in exercise rehabilitation, (d) evaluation of the exercise program, and (e) recommendations. CONCLUSION: Breast cancer survivors need exercise to recover physically and mentally and to transition from cancer treatment to a normal life. The factors affecting exercise participation in breast cancer survivors are complex. Breast cancer survivors require timely and continuous effective exercise intervention forms, including online, offline, instrumental, and emotional support from others, especially healthcare providers and family members. Moreover, multidisciplinary collaboration is required to develop more effective and convenient exercise interventions.

Low Prealbumin Levels Were Associated with Increased Frequency of Hepatic Encephalopathy in Hepatitis B Virus (HBV)-Related Decompensated Cirrhosis.

BACKGROUND The role of nutritional parameter prealbumin in predicting the incidence of hepatic encephalopathy (HE) remains unclear. This study was designed to assess the diagnostic performance of prealbumin in predicting the incidence of HE in hepatitis B virus (HBV)-related decompensated liver cirrhosis patients. MATERIAL AND METHODS A retrospective cohort of 262 patients with HBV-related decompensated liver cirrhosis was involved in this study. Prealbumin, albumin, and other indicators were collected at admission, and independent factors were identified by logistic regression analysis. The Mann-Whitney U test and receiver operating characteristic (ROC) curves were used to compare the groups and indicators. RESULTS A total of 262 patients were enrolled in the study, including 197 men and 65 women. In patients with HBV-related decompensated liver cirrhosis accompanied by HE, the model for end-stage liver disease (MELD) scores, and prothrombin time (PT) and international normalized ratio (INR) values were significantly increased, while prealbumin and albumin levels were significantly decreased. Multivariate analysis showed that only serum prealbumin level (P=0.014) was independently related to the incidence of HE. Moreover, prealbumin level was negatively correlated with MELD (r=-0.63, P<0.001) and Child-Turcotte-Pugh (r=-0.35, P<0.001) scores. ROC curves were performed, and prealbumin showed the highest area under the ROC curve (0.781) compared with MELD and Child-Turcotte-Pugh scores. CONCLUSIONS Low prealbumin levels were associated with increased frequency of hepatic encephalopathy in HBV-related decompensated cirrhosis, which showed better performance than traditional models.

RIS-Aided Proactive Mobile Network Downlink Interference Suppression: A Deep Reinforcement Learning Approach.

A proactive mobile network (PMN) is a novel architecture enabling extremely low-latency communication. This architecture employs an open-loop transmission mode that prohibits all real-time control feedback processes and employs virtual cell technology to allocate resources non-exclusively to users. However, such a design also results in significant potential user interference and worsens the communication's reliability. In this paper, we propose introducing multi-reconfigurable intelligent surface (RIS) technology into the downlink process of the PMN to increase the network's capacity against interference. Since the PMN environment is complex and time varying and accurate channel state information cannot be acquired in real time, it is challenging to manage RISs to service the PMN effectively. We begin by formulating an optimization problem for RIS phase shifts and reflection coefficients. Furthermore, motivated by recent developments in deep reinforcement learning (DRL), we propose an asynchronous advantage actor-critic (A3C)-based method for solving the problem by appropriately designing the action space, state space, and reward function. Simulation results indicate that deploying RISs within a region can significantly facilitate interference suppression. The proposed A3C-based scheme can achieve a higher capacity than baseline schemes and approach the upper limit as the number of RISs increases.

Metal-Organic Framework Supported Copper Photoredox Catalysts for Iminyl Radical-Mediated Reactions.

Visible-light copper photocatalysis has recently emerged as a viable technology for building sustainable synthetic processes. To broaden the applications of phosphine-ligated copper(I) complexes, we describe herein an effective metal-organic framework (MOF)-supported copper(I) photocatalyst for multiple iminyl radical-mediated reactions. Due to site isolation, the heterogenized copper photosensitizer has a significantly higher catalytic activity than its homogeneous counterpart. Using a hydroxamic acid linker to immobilize copper species on MOF supports affords the heterogeneous catalysts with high recyclability. The post-synthetic modification sequence on MOF surfaces allows for the preparation of previously unavailable monomeric copper species. Our findings highlight the potential of using MOF-based heterogeneous catalytic systems to address fundamental challenges in the development of synthetic methodologies and mechanistic investigations of transition-metal photoredox catalysis.

Phosphine-Triggered Structural Defects in Au44 Homologues Boost Electrocatalytic CO2 Reduction.

The systematic induction of structural defects at the atomic level is crucial to metal nanocluster research because it endows cluster-based catalysts with highly reactive centers and allows for a comprehensive investigation of viable reaction pathways. Herein, by substituting neutral phosphine ligands for surface anionic thiolate ligands, we establish that one or two Au3 triangular units can be successfully introduced into the double-stranded helical kernel of Au44 (TBBT)28 , where TBBT=4-tert-butylbenzenethiolate, resulting in the formation of two atomically precise defective Au44 nanoclusters. Along with the regular face-centered-cubic (fcc) nanocluster, the first series of mixed-ligand cluster homologues is identified, with a unified formula of Au44 (PPh3 )n (TBBT)28-2n (n=0-2). The Au44 (PPh3 )(TBBT)26 nanocluster having major structural defects at the bottom of the fcc lattice demonstrates superior electrocatalytic performance in the CO2 reduction to CO. Density functional theory calculations indicate that the active site near the defects significantly lowers the free energy for the *COOH formation, the rate-determining step in the whole catalytic process.

Graph convolutional networks for computational drug development and discovery.

Despite the fact that deep learning has achieved remarkable success in various domains over the past decade, its application in molecular informatics and drug discovery is still limited. Recent advances in adapting deep architectures to structured data have opened a new paradigm for pharmaceutical research. In this survey, we provide a systematic review on the emerging field of graph convolutional networks and their applications in drug discovery and molecular informatics. Typically we are interested in why and how graph convolution networks can help in drug-related tasks. We elaborate the existing applications through four perspectives: molecular property and activity prediction, interaction prediction, synthesis prediction and de novo drug design. We briefly introduce the theoretical foundations behind graph convolutional networks and illustrate various architectures based on different formulations. Then we summarize the representative applications in drug-related problems. We also discuss the current challenges and future possibilities of applying graph convolutional networks to drug discovery.

A Reconfigurable Visual-Inertial Odometry Accelerated Core with High Area and Energy Efficiency for Autonomous Mobile Robots.

With the wide application of autonomous mobile robots (AMRs), the visual inertial odometer (VIO) system that realizes the positioning function through the integration of a camera and inertial measurement unit (IMU) has developed rapidly, but it is still limited by the high complexity of the algorithm, the long development cycle of the dedicated accelerator, and the low power supply capacity of AMRs. This work designs a reconfigurable accelerated core that supports different VIO algorithms and has high area and energy efficiency, precision, and speed processing characteristics. Experimental results show that the loss of accuracy of the proposed accelerator is negligible on the most authoritative dataset. The on-chip memory usage of 70 KB is at least 10× smaller than the state-of-the-art works. Thus, the FPGA implementation's hardware-resource consumption, power dissipation, and synthesis in the 28 nm CMOS outperform the previous works with the same platform.

Hyperoside Reduces Rotenone-induced Neuronal Injury by Suppressing Autophagy.

Hyperoside has a variety of pharmacological activities, including anti-liver injury, anti-depression, anti-inflammatory, and anti-cancer activities. However, the effect of hyperoside on Parkinson's disease (PD) is still unclear. Therefore, we tried to study the therapeutic effect and mechanism of hyperoside on PD in vivo and in vitro models. Rotenone was used to induce PD rat model and SH-SY5Y cell injury model, and hyperoside was used for intervention. Immunohistochemistry, animal behavior assays, TUNEL and Western blot were constructed to observe the protective effect and related mechanisms of hyperoside in vivo. Cell counting kit-8 (CCK-8), flow cytometry, Rh123 staining and Western blot were used for in vitro assays. Rapamycin (RAP) pretreatment was used in rescue experiments to verify the relationship between hyperoside and autophagy in rotenone-induced SH-SY5Y cells. Hyperoside promoted the number of tyrosine hydroxylase (TH)-positive cells, improved the behavioral defects of rats, and inhibited cell apoptosis in vivo. Different concentrations of hyperoside had no significant effect on SH-SY5Y cell viability, but dramatically reversed the rotenone-induced decrease in cell viability, increased apoptosis and loss of cell mitochondrial membrane potential in vitro. Additionally, hyperoside reversed the regulation of rotenone on the Beclin1, LC3II, Bax, cleaved caspase 3, Cyc and Bcl-2 expressions in rat SNpc tissues and SH-SY5Y cells, while promoted the regulation of rotenone on the P62 and α-synuclcin. Furthermore, RAP reversed the effect of hyperoside on rotenone-induced SH-SY5Y cells. Hyperoside may play a neuroprotective effect in rotenone-induced PD rat model and SH-SY5Y cell model by affecting autophagy.

Antibiofilm Activity of Lactobacillus plantarum 12 Exopolysaccharides against Shigella flexneri.

In developing countries, Shigella flexneri is the most common enteric pathogen causing bacillary dysentery. Biofilm formation by S. flexneri can cause the emergence of antibiotic-resistant strains, which poses serious threats to food safety and human health. In this study, the effects of Lactobacillus plantarum 12 exopolysaccharides (L-EPSs) and S. flexneri exopolysaccharides (S-EPSs) on S. flexneri CMCC51574 biofilm formation were investigated. The results showed that L-EPS could decrease polysaccharide production in the extracellular polymeric matrix of S. flexneri and inhibit biofilm formation by S. flexneri L-EPS could decrease the minimum biofilm elimination concentration (MBEC) of antibiotics against S. flexneri biofilm and inhibit S. flexneri adhesion to and invasion into HT-29 cell monolayers, which might be ascribed to S. flexneri biofilm disturbance by L-EPS. In contrast, S-EPS exhibited the opposite effects compared to L-EPS. The monosaccharide composition analysis showed that L-EPS was composed of mannose, glucuronic acid, galactosamine, glucose, galactose, and xylose, with the molar ratio of 32.26:0.99:1.79:5.63:0.05:4.07, while S-EPS was composed of mannose, glucuronic acid, galactosamine, glucose, and galactose, with the molar ratio of 25.43:2.28:7.13:5.35. L-EPS was separated into the neutral polysaccharide L-EPS 1-1 and the acidic polysaccharide L-EPS 2-1 by ion-exchange chromatography and gel chromatography. L-EPS 2-1 exerted higher antibiofilm activity than L-EPS 1-1. The antibiofilm activity of L-EPS might be associated with its structure.IMPORTANCES. flexneri is a widespread foodborne pathogen causing food contamination and responsible for food poisoning outbreaks related to various foods in developing countries. Not only has biofilm formation by S. flexneri been difficult to eliminate, but it has also increased the drug resistance of the strain. In the present study, it was demonstrated that L-EPSs secreted by Lactobacillus plantrum 12 could inhibit S. flexneri biofilm formation on, adhesion to, and invasion into HT-29 cells. Also, L-EPSs could decrease the minimum biofilm elimination concentration (MBEC) of the antibiotics used against S. flexneri biofilm. Therefore, L-EPSs were shown to be bioactive macromolecules with the potential ability to act against S. flexneri infections.

Physiological function analysis of Lactobacillus plantarum Y44 based on genotypic and phenotypic characteristics.

In our previous studies, Lactobacillus plantarum Y44 showed antioxidant activity and favorable gastric and intestinal transit tolerance. In the current study, we investigated the physiological function of L. plantarum Y44 based on an analysis of its genotype and phenotype. The complete genome of L. plantarum Y44 contained a single circular chromosome of 3,255,555 bp, with a GC content of 44.6%, and a single circular plasmid of 51,167 bp, with a GC content of 38.8%. The L. plantarum Y44 genome contained 3,293 genes including 3,112 protein coding sequences, 16 rRNAs, 66 tRNAs, 4 small (s)RNAs, and 95 pseudo genes. Lactobacillus plantarum Y44 could metabolize 24 different carbohydrate sources. Nineteen complete phosphoenolpyruvate-dependent sugar phosphotransferase system complex genes and intact Embden-Meyerhof-Parnas pathway and hexose monophosphate pathway enzyme genes, as well as abundant carbohydrate active enzyme genes, were identified in the L. plantarum Y44 genome. We also identified genes related to the biosynthesis of exopolysaccharide and surface proteins. Surface proteins played an important role in the L. plantarum Y44 adhesion to HT-29 cell monolayers, as evidenced by the removal of cell surface proteins leading to decreased adhesion capacity. The L. plantarum Y44 genome contained genes encoding chaperones, intracellular proteases, and 2-component systems, which were associated with the general stress response. Genes encoding bile salt hydrolase, F0F1-ATPase, Na+/H+-antiporter, H+/Cl- exchange transporter, cyclopropane-fatty acyl-phospholipid synthase, and alkaline shock protein were identified in the L. plantarum Y44 genome, which might explain the strain's favorable gastric and intestinal transit tolerance. Some genes associated with encoding the NADH system, glutathione system, and thioredoxin system were predicted via in silico analysis and might account for the strain's ability to scavenge reactive oxygen species. Lactobacillus plantarum Y44 was susceptive to 7 antibiotics and did not produce biogenic amines, likely due to the absence of acquired antibiotic resistance genes and amino acid decarboxylase genes. The phenotype profile of L. plantarum Y44 was associated with its genetic characteristics, indicating that strains with certain physiological functions can be screened by analyzing their phenotypic and genotypic characteristics. Lactobacillus plantarum Y44 has the potential to be used as a starter culture in fermented dairy products.

Assembly of Metal-Organic Frameworks of SiF62- in Situ Formed from Borosilicate Glass.

The SiF62- anions are in situ formed in the reactions of MF2 (M = Cu2+, Zn2+, Ni2+, and Co2+) salts and nitrogen-containing ligands in borosilicate glass tubes under solvothermal conditions and then used to further construct a family of metal-organic frameworks (MOFs). This in situ reaction demonstrates a new and facile strategy for the fabrication of MOFs based on SiF62-.

[Crystal structure and crystal form stability of trelagliptin succinate].

In order to investigate trelagliptin succinate's stability in solution, recrystallization and suspension methods in polar solvent (mainly in water and 95% alcohol) were used to study the crystal form transformation of trelagliptin succinate. Single crystal X-ray diffraction, powder X-ray diffraction and thermalgravimetric analysis, and differential scanning calorimetry were used to characterize the structure of the solid state form before and after transformation. The results showed that trelagliptin succinate can easily convert to trelagliptin hemi-succinate mediated by solvent, especially by polar solvent, namely trelagliptin hemi-succinate is more stable than trelagliptin succinate in solution.

Increased phosphorylation of ezrin is associated with the migration and invasion of fibroblast-like synoviocytes from patients with rheumatoid arthritis.

OBJECTIVE: Increasing evidence indicates that the cytoskeletal protein ezrin may play a critical role in cell motility. This study aims to investigate the role of ezrin in regulating the migration and invasion of fibroblast-like synoviocytes (FLSs) from patients with RA. METHODS: Synovial tissues were obtained from 12 patients with RA and 6 with OA, and then FLSs were separated from synovial tissues. The expression of ezrin and phosphorylated ezrin (p-ezrin) was examined by Western blotting or IF staining. A specific inhibitor of ezrin phosphorylation and small interference RNA-mediated ezrin knockdown were used to inhibit the phosphorylation of ezrin. Migration and invasion of FLSs in vitro were measured by the Boyden chamber assay. RESULTS: Increased expression of p-ezrin protein was found in synovial tissue and FLSs in patients with RA compared with patients with OA. Stimulation with TNF-α and IL-1ß increased ezrin phosphorylation in RA FLSs. Inhibition of p-ezrin protein by a specific inhibitor of phosphorylation of ezrin and small interfering RNA-mediated knockdown reduced in vitro migration and invasion, as well as actin stress fibre formation in RA FLS. Furthermore, rho kinase and p38 mitogen-activated protein kinase (MAPK) signal pathways were involved in the phosphorylation of ezrin and invasion of RA FLSs. CONCLUSION: Increased expression of p-ezrin may contribute to aberrant aggressive behaviours of RA FLSs, which are mediated by rho kinase and the p38 MAPK pathway. This suggests a novel strategy targeting phosphorylation of ezrin to prevent synovial invasiveness and joint destruction in RA.

Exopolysaccharide secreted by Lactiplantibacillus plantarum Y12 showed inhibitory effect on the pathogenicity of Shigella flexneri in vitro and in vivo.

Shigella flexneri is a prevalent foodborne and waterborne pathogen that threatens human health. Our previous research indicated that the Lactiplantibacillus plantarum Y12 exopolysaccharide (L-EPS) potentially inhibited the pathogenicity of S. flexneri. The in vitro results of this study demonstrated that L-EPS effectively mitigated the symptoms induced by S. flexneri in HT-29 cells, including inhibited gene expression levels of IL-1ß, IL-6, IL-8, TNF-α, TLR 2/4, and NOD1/2; decreased apoptosis ratio; and alleviated damage degree of intestinal barrier function (Zona occludens 1, Occludin, and Claudin-1). The in vivo results demonstrated that S. flexneri treated with L-EPS elicited mild adverse physiological manifestations, an inflammatory response, and tissue damage. The infection of S. flexneri caused significant alterations in the abundance of phylum (Firmicutes, Bacteroidota, Actinobacteriota, and Proteobacteria), family (Lachnospiraceae, Muribaculaceae, Rikenellaceae, Prevotellaceaea, Ruminococcaceae, and Lactobaillaceae), and genus (Escherichia Shigella and Lachnospirillaceae NK4A136 group) within the cecal microbiota. These changes were accompanied by perturbations in taurine and hypotaurine metabolism, tricarboxylic acid (TCA) cycle activity, arginine biosynthesis, and histidine metabolic pathways. However, intervention with L-EPS attenuated the dysbiosis of cecal microbiota and metabolic disturbances. In summary, our research suggested a potential application of L-EPS as a functional food additive for mitigating S. flexneri infection.

Oral Administration of Fermented Milk from Co-Starter Containing Lactobacillus plantarum Y44 Shows an Ameliorating Effect on Hypertension in Spontaneously Hypertensive Rats.

Fermented dairy foods such as yogurt exhibit some beneficial effects on consumers, including relieving the symptoms of hypertension. This study aims to obtain fermented dairy products from a co-starter that have a great flavor and the auxiliary function of reducing blood pressure after longtime consumption. Commercial starter cultures composed of Lactobacillus delbrueckii subsp. bulgaricus CICC 6047 and Streptococcus thermophilus CICC 6038 were combined with Lactobacillus plantarum strains Y44, Y12, and Y16, respectively, as a combined starter culture to ferment the mixed milk of skim milk and soybean milk. The fermented milk produced using the combined starter culture mixed with L. plantarum Y44 showed an angiotensin-converting-enzyme (ACE) inhibitory activity (53.56 ± 0.69%). Some peptides that regulate blood pressure were released in the fermented milk, such as AMKPWIQPK, GPVRGPFPII, LNVPGEIVE, NIPPLTQTPV, and YQEPVL. In spontaneously hypertensive rat (SHR) oral-administration experiments compared with the gavage unfermented milk group, the gavage feeding of SHRs with the fermented milk produced using the combined starter culture mixed with L. plantarum Y44 significantly reduced the blood pressure of the SHRs after long-term intragastric administration, shown with the systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreasing by 23.67 ± 2.49 mmHg and 15.22 ± 2.62 mmHg, respectively. Moreover, the abundance of short-chain fatty acids (SCFA), bacterial diversity in the gut microbiota, and SCFA levels including acetic acid, propionic acid, and butyric acid in the feces of the SHRs were increased via oral administration of the fermented milk produced using the combined starter culture containing L. plantarum Y44. Furthermore, the ACE-angiotensin II (Ang II)-angiotensin type 1 (AT 1) axis was downregulated, the angiotensin-converting-enzyme 2 (ACE 2)-angiotensin(1-7) (Ang1-7)-Mas receptor axis of the SHRs was upregulated, and then the RAS signal was rebalanced. The fermented milk obtained from the combined starter culture shows the potential to be a functional food with antihypertension properties.

Lactiplantibacillus plantarum DLPT4 Protects Against Cyclophosphamide-Induced Immunosuppression in Mice by Regulating Immune Response and Intestinal Flora.

In this study, the strain Lactiplantibacillus plantarum DLPT4 was investigated for the immunostimulatory activity in cyclophosphamide (CTX)-induced immunosuppressed BALB/c mice. L. plantarum DLPT4 was administered to BALB/c mice by oral gavage for 30 days, and CTX was injected intraperitoneally from the 25th to the 27th days. Intraperitoneal injection of CTX caused damage to the thymic cortex and intestines, and the immune dysfunction of the BALB/c mice. L. plantarum DLPT4 oral administration exerted immunoregulating effects evidenced by increasing serum immunoglobulin (IgA, IgG, and IgM) levels and reducing the genes expression of pro-inflammatory factors (IL-6, IL-1ß, and TNF-α) of the CTX-induced immunosuppressed mice. The results of the metagenome-sequencing analysis showed that oral administration of L. plantarum DLPT4 could regulate the intestinal microbial community of the immunosuppressed mice by changing the ratio of Lactiplantibacillus and Bifidobacterium. Meanwhile, the abundance of carbohydrate enzyme (CAZyme), immune diseases metabolic pathways, and AP-1/MAPK signaling pathways were enriched in the mice administrated with L. plantarum DLPT4. In conclusion, oral administration of L. plantarum DLPT4 ameliorated symptoms of CTX-induced immunosuppressed mice by regulating gut microbiota, influencing the abundance of carbohydrate esterase in the intestinal flora, and enhancing immune metabolic activity. L. plantarum DLPT4 could be a potential probiotic to regulate the immune response.

Cloning and characterization of heat shock transcription factor 1 and its functional role for Hsp70 production in the sea slug Onchidium reevesii.

To investigate the regulatory role of heat shock transcription factor 1 of sea slug Onchidium reevesii (OrHSF1) on Hsp70 expression in the sea slug under stress , the OrHSF1 gene was cloned and bioinformatics analysis was performed, then the gene and protein expressions by RNA interference (RNAi) mediated knockdown of OrHSF1 expression were measured to clarify the regulatory relationship between OrHSF1 and Hsp70 under low-frequency noise (LFN) stress. Our study was the first to clone a 1572 bp sequence of the OrHSF1 gene, with the sequence coding for amino acids (CDS) being 729 bp, encoding 243 amino acids. O. reevesii shared a close evolutionary relationship with mollusks such as the Aplysia californica. OrHSF1 gene is widely expressed in different tissues of sea slugs, with the highest expression in the intestine and the lowest in the reproductive glands. Furthermore, we used RNA interference (RNAi) as a tool to silence the OrHSF1 gene in the central nervous system (CNS) and the results indicated that gene silencing was occurring systematically in the CNS and the suppression of OrHSF1 expression by RNAi-mediated gene silencing altered the expression of Hsp70; besides, the expression trends of OrHSF1 gene and Hsp70 were consistent in the 3 and 5-day RNAi experiment. Moreover, in sea slugs injected with siHSF1 and exposed to LFN, the mRNA expression and protein expression of Hsp70 in the CNS were significantly decreased compared to the low-frequency noise group (P < 0.05). This study demonstrated that OrHSF1 regulates Hsp70 expression in marine mollusks under low-frequency noise, and HSF1-Hsp70 axis plays a key role in stress response.

Deciphering roles of protein post-translational modifications in IgA nephropathy progression and potential therapy.

Immunoglobulin A nephropathy (IgAN), one type of glomerulonephritis, displays the accumulation of glycosylated IgA in the mesangium. Studies have demonstrated that both genetics and epigenetics play a pivotal role in the occurrence and progression of IgAN. Post-translational modification (PTM) has been revealed to critically participate in IgAN development and progression because PTM dysregulation results in impaired degradation of proteins that regulate IgAN pathogenesis. A growing number of studies identify that PTMs, including sialylation, o-glycosylation, galactosylation, phosphorylation, ubiquitination and deubiquitination, modulate the initiation and progression of IgAN. Hence, in this review, we discuss the functions and mechanisms of PTMs in regulation of IgAN. Moreover, we outline numerous compounds that govern PTMs and attenuate IgAN progression. Targeting PTMs might be a useful strategy to ameliorate IgAN.