Average grain size evaluation using scattering-induced attenuation of coda waves.

Grain size is one of the key microstructural factors affecting the mechanical properties of polycrystalline metal materials. In this study, a novel method for grain size evaluation using ultrasonic coda waves is proposed. Different from conventional bulk wave methods that require a point-by-point scanning of the structure, the proposed method allows for a rapid evaluation of the average grain size of the whole part from a single inspection location using one-pass testing data. A piecewise energy attenuation function dealing with different attenuation mechanisms is proposed to obtain the effective attenuation coefficient of coda waves. A power-law model is constructed to correlate the effective attenuation coefficient with the average grain size. Ultrasonic testing on nickel-based superalloy plate specimens with different average grain sizes is performed for model calibration and method verification. The applicability and robustness of the proposed method are further validated using a realistic turbine disk specimen with an irregular shape and non-uniform grain sizes. Results show that the proposed method yields a reliable and accurate estimation of the average grain size with a maximum relative error less than 20 %.

Residual networks without pooling layers improve the accuracy of genomic predictions.

KEY MESSAGE: Residual neural network genomic selection is the first GS algorithm to reach 35 layers, and its prediction accuracy surpasses previous algorithms. With the decrease in DNA sequencing costs and the development of deep learning, phenotype prediction accuracy by genomic selection (GS) continues to improve. Residual networks, a widely validated deep learning technique, are introduced to deep learning for GS. Since each locus has a different weighted impact on the phenotype, strided convolutions are more suitable for GS problems than pooling layers. Through the above technological innovations, we propose a GS deep learning algorithm, residual neural network for genomic selection (ResGS). ResGS is the first neural network to reach 35 layers in GS. In 15 cases from four public data, the prediction accuracy of ResGS is higher than that of ridge-regression best linear unbiased prediction, support vector regression, random forest, gradient boosting regressor, and deep neural network genomic prediction in most cases. ResGS performs well in dealing with gene-environment interaction. Phenotypes from other environments are imported into ResGS along with genetic data. The prediction results are much better than just providing genetic data as input, which demonstrates the effectiveness of GS multi-modal learning. Standard deviation is recommended as an auxiliary GS evaluation metric, which could improve the distribution of predicted results. Deep learning for GS, such as ResGS, is becoming more accurate in phenotype prediction.

Distributional Characteristics Analysis of Allergens in Patients with Allergic Rhinitis in Southern Fujian Province, China.

Background: Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal mucosa. However, few studies focus on the distributional characteristics of allergens in AR patients in Southern Fujian Province, China. Methods: A skin prick test (SPT) was performed and eight common allergens including Dermatophagoides farinae (Df), Dermatophagoides pteronyssinus (Dpt), weeds, animal dander, molds, cockroaches, and mangoes were chosen. Results: The positive reactions rate to the allergens was 65.79% in 6689 patients in Southern Fujian Province. Positive reactions to Df and Dpt had a negative association with age, whereas positive reactions to cockroach and weed had a positive association with age. A linear trend analysis demonstrated a significant positive relationship between positive reactions to various allergens from 2016 to 2019. Positive reactions to Df and Dpt were both correlated with the season. Positive reactions to Df, Dpt, cockroach and weed were related to disease duration and positive reactions to cockroach were correlated with city residence. Multivariate analysis revealed that male positive reactions gradually decreased with age (≤ 60), in contrast to female (≤ 60) positive reactions. Statistical difference was observed between the genders with regard to AR incidence from 2016 to 2019. The positive rate of skin tests was highest in summer in men, whereas in women it was lowest in summer. The gender composition ratios of positive cases in Xiamen, Zhangzhou, and Quanzhou cities differed significantly. The proportion of patients with positive reactions to the allergens in the three cities decreased with age. The highest proportions of patients with positive reactions all occurred during summer in the three cities. Furthermore, there were statistically significant differences in the age composition ratios across the seasons. Conclusion: This study analyzed the distributional characteristics of AR allergens in Southern Fujian Province, China. These findings will inform specific immunotherapy for AR patients.

Deciphering microglial activation and neuronal apoptosis post­traumatic brain injury: The role of TYROBP in inflammation regulation networks.

Traumatic Brain Injury (TBI) represents a significant public health challenge. Recovery from brain injury necessitates the collaborative efforts of various resident neural cells, predominantly microglia. The present study analyzed rat and mouse RNA expression micro­arrays, high­throughput RNA sequencing and single­cell sequencing data sourced from public databases. To construct an inflammation regulation network around TYRO protein tyrosine kinase­binding protein (TYROBP), to evaluate the role of TYROBP in cell death after TBI. These findings indicate that following TBI, neurons predominantly communicate with one another through the CXC chemokine ligand (CXCL) and CC chemokine ligand (CCL) signaling pathways, employing a paracrine mechanism to activate microglia. These activated microglia intensify the pathological progression of brain injury by releasing factors such as tumor necrosis factor α (TNF­α), vascular endothelial growth factor and transforming growth factor ß via the NF­κB pathway. Cells co­culture experiments demonstrated that neurons, impaired by mechanical injury, interact with microglia through non­contact mechanisms. Activated microglia secrete cytokines, including TNF­α, CXCL­8 and CCL2, which trigger an inflammatory response and facilitate neuronal apoptosis. TYROBP gene knockout in microglia was demonstrated to reduce this interaction and reduce neuronal cell apoptosis rates.

Enhancement and modulation of valley polarization in Janus CrSSe with internal and external electric fields.

The valley polarization, induced by the magnetic proximity effect, in monolayer transition metal dichalcogenides (TMDCs), has attracted significant attention due to the intriguing fundamental physics. However, the enhancement and modulation of valley polarization for real device applications is still a challenge. Here, using first-principles calculations we investigate the valley polarization properties of monolayer TMDCs CrS2 and CrSe2 and how to enhance the valley polarization by constructing Janus CrSSe (with an internal electric field) and modulate the polarization in CrSSe by applying external electric fields. Janus CrSSe exhibits inversion symmetry breaking, internal electric field, spin-orbit coupling, and compelling spin-valley coupling. A magnetic substrate of the MnO2 monolayer can induce a modest magnetic moment in CrSe2, CrSe2, and CrSSe. Notably, the Janus structure with an internal electric field has a much larger valley p compared with its non-Janus counterparts. Moreover, the strength of valley polarization can be further modulated by applying external electric fields. These findings suggest that Janus materials hold promise for designing and developing advanced valleytronic devices.

Study on the Bonding Performance of BFRP Bars with Seawater Sand Concrete.

A total of 66 sets of pullout specimens were prepared to investigate the bonding properties of basalt fiber-reinforced polymer reinforcement (hereinafter referred to as BFRP) with seawater sand concrete (hereinafter referred to as SSC). The volume dosages of mono-doped glass fibers and mono-doped polypropylene fibers were 0.1%, 0.2%, and 0.3%; the total volume dosage was set to be constant at 0.3%; and the doping ratios of the hybrid fibers were 1:2, 1:1, and 2:1. The effect on the bonding performance of BFRP reinforcement with SSC was studied on the condition of the diameter D of the BFRP reinforcement being 12 mm; the bond length of SSC being 3D, 5D, and 7D; and the surface characteristics of the reinforcement being sandblasted and threaded. The research showed that due to internal cracks in the matrix, salt crystals in the pores, chloride salts with high brittleness and expansion, as well as sulfate corrosion products such as "Frederick salts" in SSC, the concrete became brittle, resulting in more brittle splitting failures during the pullout test. Doped fibers can increase the ductility effect of concrete, but the bonding effect between the threaded fiber reinforcement and the SSC was not as good as that of the sandblasting group. When the bond length was 5D, the bonding effect between the BFRP reinforcement and SSC was the best, and the bonding performance of the experimental group with doped fibers was better than that of the threaded group. Finally, by combining the ascending segment of the Malvar model with the descending segment of the improved BPE model, a constitutive relationship model suitable for the bond-slip curve between BFRP reinforcement and SSC was fitted, which laid a theoretical foundation for future research on SSC.

Human umbilical cord-derived mesenchymal stromal cells improve myocardial fibrosis and restore miRNA-133a expression in diabetic cardiomyopathy.

BACKGROUND: Diabetic cardiomyopathy (DCM) is a serious health-threatening complication of diabetes mellitus characterized by myocardial fibrosis and abnormal cardiac function. Human umbilical cord mesenchymal stromal cells (hUC-MSCs) are a potential therapeutic tool for DCM and myocardial fibrosis via mechanisms such as the regulation of microRNA (miRNA) expression and inflammation. It remains unclear, however, whether hUC-MSC therapy has beneficial effects on cardiac function following different durations of diabetes and which mechanistic aspects of DCM are modulated by hUC-MSC administration at different stages of its development. This study aimed to investigate the therapeutic effects of intravenous administration of hUC-MSCs on DCM following different durations of hyperglycemia in an experimental male model of diabetes and to determine the effects on expression of candidate miRNAs, target mRNA and inflammatory mediators. METHODS: A male mouse model of diabetes was induced by multiple low-dose streptozotocin injections. The effects on severity of DCM of intravenous injections of hUC-MSCs and saline two weeks previously were compared at 10 and 18 weeks after diabetes induction. At both time-points, biochemical assays, echocardiography, histopathology, polymerase chain reaction (PCR), immunohistochemistry and enzyme-linked immunosorbent assays (ELISA) were used to analyze blood glucose, body weight, cardiac structure and function, degree of myocardial fibrosis and expression of fibrosis-related mRNA, miRNA and inflammatory mediators. RESULTS: Saline-treated diabetic male mice had impaired cardiac function and increased cardiac fibrosis after 10 and 18 weeks of diabetes. At both time-points, cardiac dysfunction and fibrosis were improved in hUC-MSC-treated mice. Pro-fibrotic indicators (α-SMA, collagen I, collagen III, Smad3, Smad4) were reduced and anti-fibrotic mediators (FGF-1, miRNA-133a) were increased in hearts of diabetic animals receiving hUC-MSCs compared to saline. Increased blood levels of pro-inflammatory cytokines (IL-6, TNF, IL-1ß) and increased cardiac expression of IL-6 were also observed in saline-treated mice and were reduced by hUC-MSCs at both time-points, but to a lesser degree at 18 weeks. CONCLUSION: Intravenous injection of hUC-MSCs ameliorated key functional and structural features of DCM in male mice with diabetes of shorter and longer duration. Mechanistically, these effects were associated with restoration of intra-myocardial expression of miRNA-133a and its target mRNA COL1AI as well as suppression of systemic and localized inflammatory mediators.

Study on the Damage of Fiber-Reinforced Seawater Sea Sand Concrete by Freezing and Thawing of Seawater.

The use of seawater and sea sand as replacements for fresh water and river sand in the preparation of seawater and sea sand concrete can effectively address issues such as high transportation costs, extended construction periods, and resource wastage. Nevertheless, in northern coastal areas, the problem of concrete durability in the complex and changing marine environment is more prominent. Research on the durability of seawater sea sand concrete is beneficial to the widening of its application range. To investigate the impact of glass fiber (GF) and polyvinyl alcohol fiber (PVA) with different blending methods on the seawater freeze-thaw resistance of seawater sea sand concrete (SSC), corresponding specimens were prepared, and seawater freeze-thaw cycling tests were conducted. By adopting the slow-freezing method and combining macro-structure and micro-morphology, the damage mechanism and the deterioration law of fiber-reinforced SSC under seawater freezing and thawing were investigated. The results indicate that, macroscopically, the incorporation of GF and PVA can effectively mitigate the damage to the matrix and reduce the effects of external erosive substances on the rate of strength loss, the rate of mass loss, and the relative dynamic elastic modulus. After 75 cycles, the SSC with a total volume doping of 0.3% and a blending ratio of 1:1 showed a 41.23% and 27.55% reduction in mass loss and strength loss, respectively, and a 29.9% improvement in relative dynamic elastic modulus compared with the basic group. Microscopic analysis reveals that the combined effect of freezing and expansion forces, the expansive substances generated by seawater intrusion into the interior of the matrix, and salt crystallization all weaken the bond between aggregate and mortar, leading to accelerated deterioration of the concrete. The incorporation of fibers enables the matrix to become denser and improves its crack-resistant properties, resulting in a better durability than that of the basic group. The damage prediction model established by the NSGM(1,N) model of gray system theory exhibits high accuracy and is suitable for long-term prediction, accurately predicting the damage of seawater sea sand concrete under seawater freeze-thaw coupling.

Genome-Wide Identification and Transcriptome Analysis of the Hsp70 Gene Family in Monodonta labio Reveals Its Role in Response to Nanoplastics Stress.

For marine invertebrates, the disruption of organismal physiology and behavior by nanoplastics (NPs) has been extensively reported. Heat shock proteins (Hsps) are important for redundant protein breakdown, environmental changes, and intracellular protein transport. An exhaustive identification of Hsp70 genes and an experiment where different concentrations of NPs were stressed were performed to study how Hsp70 genes respond to NPs stress in Monodonta labio. Our results identified 15 members of Hsp70 within the genome of M. labio and provided insights into their responses to different concentrations of acute NP stress. Phylogenetic analyses revealed extensive amplification of the Hsp70 genes from the Hsc70 subfamily, with gene duplication events. As a result of NP stress, five of fifteen genes showed significant upregulation or downregulation. Three Hsp70 genes were highly expressed at an NP concentration of 0.1 mg/L, and no genes were downregulated. At 10 mg/L, they showed significant upregulation of two genes and significant downregulation of two genes. At 1 mg/L treatment, three genes were significantly downregulated, and no genes were significantly upregulated. Moreover, a purifying selection was revealed using a selection test conducted on duplicate gene pairs, indicating functional redundancy. This work is the first thorough examination of the Hsp70s in Archaeogastropoda. The findings improve knowledge of Hsp70s in molluscan adaptation to NP stress and intertidal living and offer essential data for the biological study of M. labio.

Effects of Bifidobacterium animalis subsp. lactis IU100 on Immunomodulation and Gut Microbiota in Immunosuppressed Mice.

Probiotics are live microorganisms with immunomodulatory effects in a strain-specific and dose-dependent manner. Bifidobacterium animalis subsp. lactis IU100 is a new probiotic strain isolated from healthy adults. This study aimed to evaluate the effects of IU100 on cyclophosphamide (CTX)-induced immunosuppression in mice. The results showed that IU100 significantly ameliorated CTX-induced decreases in body weight and immune organ indices. The promoted delayed-type hypersensitivity, serum hemolysins and immunoglobulin (IgA, IgG and IgM) levels after IU100 treatment indicated its enhancing role in cellular and humoral immunity. In addition, oral administration of IU100 increased serum cytokine (IL-1ß, IL-2, IL-4, IL-6, IFN-γ, TNF-α) levels dose-dependently, which are associated with CTX-induced shifts in the Th1/Th2 balance. The probiotic IU100 also modulated the composition of gut microbiota by reducing the Firmicutes/Bacteroidetes ratio; increasing beneficial Muribaculaceae and the Lachnospiraceae NK4A136 group; and inhibiting harmful Clostridium sensu stricto 1, Faecalibaculum and Staphylococcus at the genus level. The above genera were found to be correlated with serum cytokines and antibody levels. These findings suggest that IU100 effectively enhances the immune function of immunosuppressed mice, induced by CTX, by regulating gut microbiota.

Time-Series Field Phenotyping of Soybean Growth Analysis by Combining Multimodal Deep Learning and Dynamic Modeling.

The rate of soybean canopy establishment largely determines photoperiodic sensitivity, subsequently influencing yield potential. However, assessing the rate of soybean canopy development in large-scale field breeding trials is both laborious and time-consuming. High-throughput phenotyping methods based on unmanned aerial vehicle (UAV) systems can be used to monitor and quantitatively describe the development of soybean canopies for different genotypes. In this study, high-resolution and time-series raw data from field soybean populations were collected using UAVs. The RGB (red, green, and blue) and infrared images are used as inputs to construct the multimodal image segmentation model-the RGB & Infrared Feature Fusion Segmentation Network (RIFSeg-Net). Subsequently, the segment anything model was employed to extract complete individual leaves from the segmentation results obtained from RIFSeg-Net. These leaf aspect ratios facilitated the accurate categorization of soybean populations into 2 distinct varieties: oval leaf type variety and lanceolate leaf type variety. Finally, dynamic modeling was conducted to identify 5 phenotypic traits associated with the canopy development rate that differed substantially among the classified soybean varieties. The results showed that the developed multimodal image segmentation model RIFSeg-Net for extracting soybean canopy cover from UAV images outperformed traditional deep learning image segmentation networks (precision = 0.94, recall = 0.93, F1-score = 0.93). The proposed method has high practical value in the field of germplasm resource identification. This approach could lead to the use of a practical tool for further genotypic differentiation analysis and the selection of target genes.

Amelioration of diabetic nephropathy in mice by a single intravenous injection of human mesenchymal stromal cells at early and later disease stages is associated with restoration of autophagy.

BACKGROUND AND AIMS: Mesenchymal stromal cells (MSCs) a potentially effective disease-modulating therapy for diabetic nephropathy (DN) but their clinical translation has been hampered by incomplete understanding of the optimal timing of administration and in vivo mechanisms of action. This study aimed to elucidate the reno-protective potency and associated mechanisms of single intravenous injections of human umbilical cord-derived MSCs (hUC-MSCs) following shorter and longer durations of diabetes. METHODS: A streptozotocin (STZ)-induced model of diabetes and DN was established in C57BL/6 mice. In groups of diabetic animals, human (h)UC-MSCs or vehicle were injected intravenously at 8 or 16 weeks after STZ along with vehicle-injected non-diabetic animals. Diabetes-related kidney abnormalities was analyzed 2 weeks later by urine and serum biochemical assays, histology, transmission electron microscopy and immunohistochemistry. Serum concentrations of pro-inflammatory and pro-fibrotic cytokines were quantified by ELISA. The expression of autophagy-related proteins within the renal cortices was investigated by immunoblotting. Bio-distribution of hUC-MSCs in kidney and other organs was evaluated in diabetic mice by injection of fluorescent-labelled cells. RESULTS: Compared to non-diabetic controls, diabetic mice had increases in urine albumin creatinine ratio (uACR), mesangial matrix deposition, podocyte foot process effacement, glomerular basement membrane thickening and interstitial fibrosis as well as reduced podocyte numbers at both 10 and 18 weeks after STZ. Early (8 weeks) hUC-MSC injection was associated with reduced uACR and improvements in multiple glomerular and renal interstitial abnormalities as well as reduced serum IL-6, TNF-α, and TGF-ß1 compared to vehicle-injected animals. Later (16 weeks) hUC-MSC injection also resulted in reduction of diabetes-associated renal abnormalities and serum TGF-ß1 but not of serum IL-6 and TNF-α. At both time-points, the kidneys of vehicle-injected diabetic mice had higher ratio of p-mTOR to mTOR, increased abundance of p62, lower abundance of ULK1 and Atg12, and reduced ratio of LC3B to LC3A compared to non-diabetic animals, consistent with diabetes-associated suppression of autophagy. These changes were largely reversed in the kidneys of hUC-MSC-injected mice. In contrast, neither early nor later hUC-MSC injection had effects on blood glucose and body weight of diabetic animals. Small numbers of CM-Dil-labeled hUC-MSCs remained detectable in kidneys, lungs and liver of diabetic mice at 14 days after intravenous injection. CONCLUSIONS: Single intravenous injections of hUC-MSCs ameliorated glomerular abnormalities and interstitial fibrosis in a mouse model of STZ-induced diabetes without affecting hyperglycemia, whether administered at relatively short or longer duration of diabetes. At both time-points, the reno-protective effects of hUC-MSCs were associated with reduced circulating TGF-ß1 and restoration of intra-renal autophagy.

Combined transplantation of hiPSC-NSC and hMSC ameliorated neuroinflammation and promoted neuroregeneration in acute spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) is a serious clinical condition that has pathological changes such as increased neuroinflammation and nerve tissue damage, which eventually manifests as fibrosis of the injured segment and the development of a spinal cord cavity leading to loss of function. Cell-based therapy, such as mesenchymal stem cells (MSCs) and neural stem cells (NSCs) are promising treatment strategies for spinal cord injury via immunological regulation and neural replacement respectively. However, therapeutic efficacy is rare reported on combined transplantation of MSC and NSC in acute mice spinal cord injury even the potential reinforcement might be foreseen. Therefore, this study was conducted to investigate the safety and efficacy of co-transplanting of MSC and NSC sheets into an SCI mice model on the locomotor function and pathological changes of injured spinal cord. METHODS: To evaluate the therapeutic effects of combination cells, acute SCI mice model were established and combined transplantation of hiPSC-NSCs and hMSCs into the lesion site immediately after the injury. Basso mouse scale was used to perform the open-field tests of hind limb motor function at days post-operation (dpo) 1, 3, 5, and 7 after SCI and every week after surgery. Spinal cord and serum samples were collected at dpo 7, 14, and 28 to detect inflammatory and neurotrophic factors. Hematoxylin-eosin (H&E) staining, masson staining and transmission electron microscopy were used to evaluate the morphological changes, fibrosis area and ultrastructure of the spinal cord. RESULT: M&N transplantation reduced fibrosis formation and the inflammation level while promoting the secretion of nerve growth factor and brain-derived neurotrophic factor. We observed significant reduction in damaged tissue and cavity area, with dramatic improvement in the M&N group. Compared with the Con group, the M&N group exhibited significantly improved behaviors, particularly limb coordination. CONCLUSION: Combined transplantation of hiPSC-NSC and hMSC could significantly ameliorate neuroinflammation, promote neuroregeneration, and decrease spinal fibrosis degree in safe and effective pattern, which would be indicated as a novel potential cell treatment option.

Effect of lite touch on the anxiety of low-risk pregnant women in the latent phase of childbirth: a randomized controlled trial.

Introduction: Women with perinatal anxiety have reduced coping capacity during labor, which affects labor progress and increases the likelihood of a cesarean section. Several non-pharmacological interventions for anxiety during childbirth are available. This study used the "lite touch" method, a non-pharmacological intervention based on physiological responses and obstetric clinical experience in women. We aimed to evaluate whether lite touch could relieve perinatal anxiety and investigate the effect of light skin stroking on the maternal hormones, catecholamine, and cortisol. Methods: This randomized clinical trial involved women with low-risk singleton pregnancies at full term or near term. Eligible pregnant women who were latent and did not undergo epidural anesthesia were randomized into two groups. Participants in the intervention group underwent routine prenatal care, including lite touch, whereas the control group underwent routine prenatal care alone. Demographic data were collected through a questionnaire. Labor anxiety was assessed using the State Anxiety Inventory, and saliva was collected before and after the intervention. Changes in saliva cortisol and catecholamine levels were analyzed using a double-antibody sandwich enzyme-linked immunosorbent assay. Results: In total, 83 participants were included, with 43 and 40 in the intervention and control groups, respectively. In the intervention group, pre-intervention anxiety scores were significantly lower (p < 0.01) than post-intervention anxiety scores, whereas the control group showed no difference in anxiety scores before and after intervention (p > 0.05). Cortisol and catecholamine levels in saliva were significantly lower in the intervention group than in the control group after the intervention (p < 0.01). Discussion: Lite touch can reduce the latent anxiety state of low-risk pregnant women, thereby maintaining in vivo stability and facilitating labor. Clinical trial registration: https://www.chictr.org.cn/aboutEN.html, ChiCTR2300070905, Retrospectively Registered Date: April 26, 2023.

Effect of Lacticaseibacillus paracasei K56 with galactooligosaccharide synbiotics on obese individuals: an in vitro fermentation model.

BACKGROUND: The use of synbiotics is emerging as a promising intervention strategy for regulating the gut microbiota and for preventing or reducing obesity, in comparison with the use of probiotics or prebiotics alone. A previous in vivo study revealed that Lacticaseibacillus paracasei K56 (L. paracasei K56) could alleviate obesity induced in high-fat-diet mice; however, the effect of the synbiotic combination of L. paracasei K56 and prebiotics in obese individuals has not been explored fully. RESULTS: The effect of prebiotics on the proliferation of L. paracasei K56 was determined by spectrophotometry. The results showed that polydextrose (PG), xylooligosaccharide (XOS), and galactooligosaccharide (GOS) had a greater potential to be used as substrates for L. paracasei K56 than three other prebiotics (melitose, stachyose, and mannan-oligosaccharide). An in vitro fermentation model based on the feces of ten obese female volunteers was then established. The results revealed that K56_GOS showed a significant increase in GOS degradation rate and short-chain fatty acid (SCFA) content, and a decrease in gas levels, compared with PG, XOS, GOS, K56_PG, and K56_XOS. Changes in these microbial biomarkers, including a significant increase in Bacteroidota, Bifidobacterium, Lactobacillus, Faecalibacterium, and Blautia and a decrease in the Firmicutes/Bacteroidota ratio and Escherichia-Shigella in the K56_GOS group, were associated with increased SCFA content and decreased gas levels. CONCLUSION: This study demonstrates the effect of the synbiotic combination of L. paracasei K56 and GOS on obese individuals and indicates its potential therapeutic role in obesity treatment. © 2024 Society of Chemical Industry.

Antioxidant Minerals Modified the Association between Iron and Type 2 Diabetes in a Chinese Population.

Inconsistent findings exist regarding the relationship between heme iron intake and type 2 diabetes (T2D) among Western and Eastern populations. Easterners tend to consume a plant-based diet which is abundant in antioxidant minerals. To examine the hypothesis that antioxidant mineral may modify the relationship between iron and T2D, we performed a case-control study by measuring the serum mineral levels in 2198 Chinese subjects. A total of 2113 T2D patients and 2458 controls were invited; 502 T2D patients and 1696 controls were finally analyzed. In the total population, high serum iron showed a positive association with T2D odds (odds ratio [OR] = 1.27 [1.04, 1.55]); high magnesium (OR = 0.18 [0.14, 0.22]), copper (OR = 0.27 [0.21, 0.33]), zinc (OR = 0.37 [0.30, 0.46]), chromium (OR = 0.61 [0.50, 0.74]), or selenium concentrations (OR = 0.39 [0.31, 0.48]) were inversely associated with T2D odds. In contrast, in individuals with higher magnesium (>2673.2 µg/dL), zinc (>136.7 µg/dL), copper (>132.1 µg/dL), chromium (>14.0 µg/dL), or selenium concentrations (>16.8 µg/dL), serum iron displayed no association with T2D (p > 0.05). Serum copper and magnesium were significant modifiers of the association between iron and T2D in individuals with different physiological status (p < 0.05). Our findings support the idea that consuming a diet rich in antioxidant minerals is an effective approach for preventing T2D.

Pseudidiomarina fusca sp. nov., Isolated from the Surface Seawater of the Western Pacific Ocean.

The Gram-negative marine bacterium GXY010T, which has been isolated from the surface seawater of the western Pacific Ocean, is aerobic, non-motile and non-flagellated. Strain GXY010T exhibits growth across a temperature range of 10-42 °C (optimal at 37 °C), pH tolerance from 7.0 to 11.0 (optimal at 7.5) and a NaCl concentration ranging from 1.0 to 15.0% (w/v, optimal at 5.0%). Ubiquinone-8 (Q-8) was the predominant isoprenoid quinone in strain GXY010T. The dominant fatty acids (>10%) of strain GXY010T were iso-C15:0 (14.65%), summed feature 9 (iso-C17:1ω9c and/or 10-methyl C16:0) (12.41%), iso-C17:0 (10.85%) and summed feature 3 (C16:1ω7c and/or C16:1ω6c) (10.41%). Phosphatidylethanolamine (PE), phosphatidylglycerol (PG), diphosphatidylglycerol (DPG), unidentifiable glycolipid (GL) and four non-identifiable aminolipids (AL1-AL4) were the predominant polar lipids of strain GXY010T. The genomic DNA G+C content was identified as a result of 48.0% for strain GXY010T. The strain GXY010T genome consisted of 2,766,857 bp, with 2664 Open Reading Frames (ORFs), including 2586 Coding sequences (CDSs) and 78 RNAs. Strain GXY010T showed Average Nucleotide Identity (ANI) values of 73.4% and 70.6% and DNA-DNA hybridization (DDH) values of 19.2% and 14.5% with reference species Pseudidiomarina tainanensis MCCC 1A02633T (=PIN1T) and Pseudidiomarina taiwanensis MCCC 1A00163T (=PIT1T). From the results of the polyphasic analysis, a newly named species, Pseudidiomarina fusca sp. nov. within the genus Pseudidiomarina, was proposed. The type strain of Pseudidiomarina fusca is GXY010T (=JCM 35760T = MCCC M28199T = KCTC 92693T).

Add-on sirolimus for the treatment of mild or moderate systemic lupus erythematosus via T lymphocyte subsets balance.

OBJECTIVE: The efficacy of sirolimus in treating severe or refractory systemic lupus erythematosus (SLE) has been confirmed by small-scale clinical trials. However, few studies focused on mild or moderate SLE. Therefore, in this study we elucidated clinical efficacy of add-on sirolimus in patients with mild or moderate SLE. METHODS: Data of 17 consecutive patients with SLE were retrospectively collected. SLE Disease Activity Index-2000 (SLEDAI-2K), clinical manifestation, laboratory data and peripheral T lymphocyte subsets with cytokines were collected before and 6 months after sirolimus add-on treatment. T cell subsets were detected by flow cytometry and cytokines were determined by multiplex bead-based flow fluorescent immunoassay simultaneously. Twenty healthy controls matched with age and sex were also included in our study. RESULTS: (1) The numbers of peripheral blood lymphocytes, T cells, T helper (Th) cells, regulatory T (Treg) cells, Th1 cells, Th2 cells and Treg/Th17 ratios in patients with SLE were significantly lower, while the numbers of Th17 cells were evidently higher than those of healthy control (p<0.05). (2) After 6 months of sirolimus add-on treatment, urinary protein, pancytopenia, immunological indicators and SLEDAI-2K in patients with SLE were distinctively improved compared with those before sirolimus treatment (p<0.05). (3) The numbers of peripheral blood lymphocytes, T cells, Th cells, Treg cells, Th2 cells and the ratios of Treg/Th17 in patients with SLE after treatment were clearly higher than those before (p<0.05). (4) The levels of plasma interleukin (IL)-5, IL-6 and IL-10 in patients with SLE decreased notably, conversely the IL-4 levels increased remarkably compared with pretreatment (p<0.05). CONCLUSIONS: (1) Patients with SLE presented imbalanced T cell subsets, especially the decreased ratio of Treg/Th17. (2) Sirolimus add-on treatment ameliorated clinical involvement, serological abnormalities and disease activity without adverse reactions in patients with SLE. (3) The multi-target therapy facilitates the enhanced numbers of Treg cells, Treg/Th17 imbalance and anti-inflammatory cytokines, simultaneously, reducing inflammatory cytokines.

Bifidobacterium animalis subsp. lactis A6 attenuates hippocampal damage and memory impairments in an ADHD rat model.

Attention deficit hyperactivity disorder (ADHD) is commonly accompanied by learning and memory deficits. This study aimed to demonstrate the effects of probiotic Bifidobacterium animalis subsp. lactis A6 (BAA6) on behaviour and memory function in spontaneously hypertensive rats (SHRs). The results showed that BAA6 treatment ameliorated spatial working memory deficits and inhibited hippocampal neuron loss in SHRs. The levels of neurotransmitters such as acetylcholine, dopamine, and norepinephrine, and the brain derived neurotrophic factor increased and that of glutamate decreased in the brain tissue of SHRs after BAA6 administration. Moreover, BAA6 reduced the levels of pro-inflammatory cytokines TNF-α and IL-1ß, and increased the levels of anti-inflammatory IL-10 and antioxidant glutathione in SHRs. 16S rRNA high-throughput sequencing showed that BAA6 treatment changed the gut microbiota composition. BAA6 promoted beneficial Lactobacillus, Romboutsia, Blautia, and Turicibacter, and decreased the enrichment of bacterial genera such as Dietzia, Sporosarcina, Brevibacterium, NK4A214_group, Atopostipes, and Facklamia negatively associated with neurotransmitter release and anti-inflammatory effects in SHRs. Together, these results suggested that BAA6 improved memory function by ameliorating hippocampal damage, abnormal neurotransmitter release and cerebral inflammation by reshaping the gut microbiota in SHRs. This study provides a scientific basis for the development and application of BAA6 as a promising dietary intervention to reduce the risk of ADHD.

Mic19 depletion impairs endoplasmic reticulum-mitochondrial contacts and mitochondrial lipid metabolism and triggers liver disease.

Endoplasmic reticulum (ER)-mitochondria contacts are critical for the regulation of lipid transport, synthesis, and metabolism. However, the molecular mechanism and physiological function of endoplasmic reticulum-mitochondrial contacts remain unclear. Here, we show that Mic19, a key subunit of MICOS (mitochondrial contact site and cristae organizing system) complex, regulates ER-mitochondria contacts by the EMC2-SLC25A46-Mic19 axis. Mic19 liver specific knockout (LKO) leads to the reduction of ER-mitochondrial contacts, mitochondrial lipid metabolism disorder, disorganization of mitochondrial cristae and mitochondrial unfolded protein stress response in mouse hepatocytes, impairing liver mitochondrial fatty acid ß-oxidation and lipid metabolism, which may spontaneously trigger nonalcoholic steatohepatitis (NASH) and liver fibrosis in mice. Whereas, the re-expression of Mic19 in Mic19 LKO hepatocytes blocks the development of liver disease in mice. In addition, Mic19 overexpression suppresses MCD-induced fatty liver disease. Thus, our findings uncover the EMC2-SLC25A46-Mic19 axis as a pathway regulating ER-mitochondria contacts, and reveal that impairment of ER-mitochondria contacts may be a mechanism associated with the development of NASH and liver fibrosis.