Lithium carbonate revitalizes tumor-reactive CD8+ T cells by shunting lactic acid into mitochondria.

The steady flow of lactic acid (LA) from tumor cells to the extracellular space via the monocarboxylate transporter symport system suppresses antitumor T cell immunity. However, LA is a natural energy metabolite that can be oxidized in the mitochondria and could potentially stimulate T cells. Here we show that the lactate-lowering mood stabilizer lithium carbonate (LC) can inhibit LA-mediated CD8+ T cell immunosuppression. Cytoplasmic LA increased the pumping of protons into lysosomes. LC interfered with vacuolar ATPase to block lysosomal acidification and rescue lysosomal diacylglycerol-PKCθ signaling to facilitate monocarboxylate transporter 1 localization to mitochondrial membranes, thus transporting LA into the mitochondria as an energy source for CD8+ T cells. These findings indicate that targeting LA metabolism using LC could support cancer immunotherapy.

Hypoxia in tomato (Solanum lycopersicum) fruit during ripening: Biophysical elucidation by a 3D reaction-diffusion model.

Respiration provides energy, substrates, and precursors to support physiological changes of the fruit during climacteric ripening. A key substrate of respiration is oxygen that needs to be supplied to the fruit in a passive way by gas transfer from the environment. Oxygen gradients may develop within the fruit due to its bulky size and the dense fruit tissues, potentially creating hypoxia that may have a role in the spatial development of ripening. This study presents a 3D reaction-diffusion model using tomato (Solanum lycopersicum) fruit as a test subject, combining the multiscale fruit geometry generated from magnetic resonance imaging and microcomputed tomography with varying respiration kinetics and contrasting boundary resistances obtained through independent experiments. The model predicted low oxygen levels in locular tissue under atmospheric conditions, and the oxygen level was markedly lower upon scar occlusion, aligning with microsensor profiling results. The locular region was in a hypoxic state, leading to its low aerobic respiration with high CO2 accumulation by fermentative respiration, while the rest of the tissues remained well oxygenated. The model further revealed that the hypoxia is caused by a combination of diffusion resistances and respiration rates of the tissue. Collectively, this study reveals the existence of the respiratory gas gradients and its biophysical causes during tomato fruit ripening, providing richer information for future studies on localized endogenous ethylene biosynthesis and fruit ripening.

Responses of key root traits in the genus Oryza to soil flooding mimicked by stagnant, deoxygenated nutrient solution.

Excess water can induce flooding stress resulting in yield loss, even in wetland crops such as rice (Oryza). However, traits from species of wild Oryza have already been used to improve tolerance to abiotic stress in cultivated rice. This study aimed to establish root responses to sudden soil flooding among eight wild relatives of rice with different habitat preferences benchmarked against three genotypes of O. sativa. Plants were raised hydroponically, mimicking drained or flooded soils, to assess the plasticity of adventitious roots. Traits included were apparent permeance (PA) to O2 of the outer part of the roots, radial water loss, tissue porosity, apoplastic barriers in the exodermis, and root anatomical traits. These were analysed using a plasticity index and hierarchical clustering based on principal component analysis. For example, O. brachyantha, a wetland species, possessed very low tissue porosity compared with other wetland species, whereas dryland species O. latifolia and O. granulata exhibited significantly lower plasticity compared with wetland species and clustered in their own group. Most species clustered according to growing conditions based on PA, radial water loss, root porosity, and key anatomical traits, indicating strong anatomical and physiological responses to sudden soil flooding.

scSSA: A clustering method for single cell RNA-seq data based on semi-supervised autoencoder.

BACKGROUND: Single cell sequencing is a technology for high-throughput sequencing analysis of genome, transcriptome and epigenome at the single cell level. It can improve the shortcomings of traditional methods, reveal the gene structure and gene expression state of a single cell, and reflect the heterogeneity between cells. Among them, the clustering analysis of single-cell RNA data is a very important step, but the clustering of single-cell RNA data is faced with two difficulties, dropout events and dimension curse. At present, many methods are only driven by data, and do not make full use of the existing biological information. RESULTS: In this work, we propose scSSA, a clustering model based on semi-supervised autoencoder, fast independent component analysis (FastICA) and Gaussian mixture clustering. Firstly, the semi-supervised autoencoder imputes and denoises the scRNA-seq data, and then get the low-dimensional latent representation. Secondly, the low-dimensional representation is reduced the dimension and clustered by FastICA and Gaussian mixture model respectively. Finally, scSSA is compared with Seurat, CIDR and other methods on 10 public scRNA-seq datasets. CONCLUSION: The results show that scSSA has superior performance in cell clustering on 10 public datasets. In conclusion, scSSA can accurately identify the cell types and is generally applicable to all kinds of single cell datasets. scSSA has great application potential in the field of scRNA-seq data analysis. Details in the code have been uploaded to the website https://github.com/houtongshuai123/scSSA/.

Neddylation modification of the U3 snoRNA-binding protein RRP9 by Smurf1 promotes tumorigenesis.

Neddylation is a posttranslational modification that attaches ubiquitin-like protein Nedd8 to protein targets via Nedd8-specific E1-E2-E3 enzymes and modulates many important biological processes. Nedd8 attaches to a lysine residue of a substrate, not for degradation, but for modulation of substrate activity. We previously identified the HECT-type ubiquitin ligase Smurf1, which controls diverse cellular processes, is activated by Nedd8 through covalent neddylation. Smurf1 functions as a thioester bond-type Nedd8 ligase to catalyze its own neddylation. Numerous ubiquitination substrates of Smurf1 have been identified, but the neddylation substrates of Smurf1 remain unknown. Here, we show that Smurf1 interacts with RRP9, a core component of the U3 snoRNP complex, which is involved in pre-rRNA processing. Our in vivo and in vitro neddylation modification assays show that RRP9 is conjugated with Nedd8. RRP9 neddylation is catalyzed by Smurf1 and removed by the NEDP1 deneddylase. We identified Lys221 as a major neddylation site on RRP9. Deficiency of RRP9 neddylation inhibits pre-rRNA processing and leads to downregulation of ribosomal biogenesis. Consequently, functional studies suggest that ectopic expression of RRP9 promotes tumor cell proliferation, colony formation, and cell migration, whereas unneddylated RRP9, K221R mutant has no such effect. Furthermore, in human colorectal cancer, elevated expression of RRP9 and Smurf1 correlates with cancer progression. These results reveal that Smurf1 plays a multifaceted role in pre-rRNA processing by catalyzing RRP9 neddylation and shed new light on the oncogenic role of RRP9.

On-line status monitoring and surrounding environment perception of an underwater cable based on the phase-locked Φ-OTDR sensing system.

A newly designed phase-locked (PL) Φ-OTDR system was proposed and instrumented. Field tests of water impact, anchor damage towing and tide diagnosing were carried out in a natural freshwater lake as well as the East China Sea. Personnel movement trajectory monitoring and ship flow monitoring were carried out by a buried cable along the floodplain of the Yangtze River. It proved that the proposed system can monitor the real-time status and sense the surrounding environment of existing underwater communication cables, which could be helpful for the maintenance of the cable itself as well as underwater information collection.

Case series on the Charcot neuroarthropathy in hands after cervical central cord syndrome.

BACKGROUND: Charcot neuroarthropathy (CNA) of the upper extremity occurs most frequently in shoulders. However, CNA in the hands is uncommon and seldom be reported. The onset of CNA is usually insidious. If this process continues undetected, it can result in joint deformity, ulceration and/or superinfection, loss of function, and amputation or even death. In this article, we are going to present three cases of CNA in the hands of individuals with cervical spinal cord injury (SCI) with central cord syndrome. CASE PRESENTATION: Three male individuals with cervical spinal stenosis contracted tetraplegia (American Spinal Injury Association Impairment Scale Grade D, D, and B) due to spinal cord contusion after a trauma and developed hand swelling without pain 2 to 3 months after their SCI. X-ray showed degenerative joint changes in the hands. CNA was considered due to the patient's history of cervical SCI, loss of motor function and sensation, symptoms of painless swelling, physical examination, and X-ray findings. The self-care sub scores of Spinal Cord Independence Measure III improved slightly only during rehabilitation and follow-up due to poor hand function. CONCLUSIONS: CNA may develop after a central or peripheral neurological disorder. Nearly every joint of the body can be affected and the lower limbs are the most frequently involved. However, CNA of the hand is rare. We present three patients with CNA in the hands after cervical SCI and review the features and early differential diagnosis of CNA. Currently there is no specific treatment available. Therefore, early identification of CNA and adequate protection to the affected joints seem important.

Paenibacillus apii sp. nov., a novel nifH gene-harbouring species isolated from the rhizospheres of vegetable plants grown in different regions of northern China.

Two nifH gene-harbouring bacterial strains were isolated from rhizospheres of different vegetable plants grown in different regions of northern PR China. The two strains possessed almost identical 16S rRNA gene sequences. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between the two strains were 99.21 and 93.6% respectively, suggesting they belong to one species. Based on 16S rRNA gene phylogeny, the two strains were clustered together with Paenibacillus rhizophilus 7197T, Paenibacillus sabinae T27T and Paenibacillus forsythiae T98T, but on a separate branch. Novelty of the species was confirmed by ANI and dDDH comparisons between the type strain 7124T and its closest relatives, since the obtained values were considerably below the proposed thresholds for the species delineation. The genome size of strain 7124T was 5.40 Mb, comprising 5050 predicted genes with a DNA G+C content of 52.3 mol%. The polar lipids contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and three unidentified lipids. The major cellular fatty acids were anteiso-C15  :  0 (52.9%) and C16  :  0 (23.4 %). Menaquinone-7 was reported as the major respiratory quinone. The diamino acid in the cell-wall peptidoglycan was found to be meso-diaminopimelic acid. Based on phylogenetic, genomic, chemotaxonomic and phenotypic data, the two isolates are considered to represent a novel species of the genus Paenibacillus, for which the name Paenibacillus apii sp. nov. is proposed, with 7124T (=DSM 103172T=CGMCC 1.15689T) as type strain.

Rhizobium rhizophilum sp. nov., an indole acetic acid-producing bacterium isolated from rape (Brassica napus L.) rhizosphere soil.

A novel Gram-stain-negative, aerobic, rod-shaped and indole acetic acid-producing strain, designated 7209-2T, was isolated from rhizosphere of rape (Brassica napus L.) grown in the Yakeshi City, Inner Mongolia, PR China. The 16S rRNA gene sequence analysis indicated that strain 7209-2T belongs to the genus Rhizobium and is closely related to Rhizobium rosettiformans W3T, Rhizobium ipomoeae shin9-1T and Rhizobium wuzhouense W44T with sequence similarities of 98.2, 98.1 and 97.9 %, respectively. Phylogenetic analysis based on concatenated housekeeping recA and atpD gene sequences showed that strain 7209-2T formed a group together with R. wuzhouense W44T and R. rosettiformans W3T, with sequences similarities of 92.6 and 91.1 %, respectively. The genome size of strain 7209-2T was 5.25 Mb, comprising 5027 predicted genes with a DNA G+C content of 61.2 mol%. The average nucleotide identity and digital DNA-DNA hybridization comparisons among 7209-2T and reference strains for the most closely related species showed values below the accepted threshold for species discrimination. The major fatty acids of strain 7209-2T were summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c) and summed feature 2 (C12 : 0 aldehyde and/or unknown 10.953) . The major polar lipids were found to consist of phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine and an unidentified aminophospholipid. The predominant ubiquinone was identified as quinone 10. Based on all the above results, strain 7209-2T represents a novel species of the genus Rhizobium, for which the name Rhizobium rhizophilum sp. nov. is proposed with 7209-2T (=CGMCC 1.15691T=DSM 103161T) as the type strain.

Mesorhizobium rhizophilum sp. nov., a 1-aminocyclopropane-1-carboxylate deaminase producing bacterium isolated from rhizosphere of maize in Northeast China.

A novel 1-aminocyclopropane-1-carboxylate deaminase producing bacterium, Gram- stain-negative, aerobic, motile, rod-shaped strain designated YM1C-6-2T was isolated from rhizosphere of maize grown in Northeast China. The 16S rRNA gene sequence analysis indicated that strain YM1C-6-2T belongs to the genus Mesorhizobium and is closely related to Mesorhizobium alhagi CCNWXJ12-2T and M. camelthorni CCNWXJ40-4T with sequence similarities of 98.4% and 97.9%, respectively. Multilocus sequence analysis of other housekeeping genes revealed that the new isolates YM1C-6-2T forms a phylogenetically group with some species in the genus Mesorhizobium. The genome size of strain YM1C-6-2T was 5.51 Mb, comprising 5378 predicted genes with a DNA G+C content of 64.5%. The average nucleotide identity and digital DNA-DNA hybridization comparisons between YM1C-6-2T and the most related type strains showed values below the accepted threshold for species discrimination. The major fatty acids of strain YM1C-6-2T were C19:0 cyclo ω8c (47.5%), summed feature 8 (C18:1ω7c and/or C18:1ω6c) (19.5%) and C16:0 (15.1%), which differed from the closely related reference strains in their relative abundance. The major polar lipids consist of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine and an unidentified aminophospholipid. The predominant ubiquinone was identified as Quinone 10. Phenotypic and biochemical analysis results indicated that strain YM1C-6-2T can be distinguished from closely related type strains. Based on the above results, strain YM1C-6-2T represents a novel species of the genus Mesorhizobium, for which the name Mesorhizobium rhizophilum sp. nov. is proposed with YM1C-6-2T (= CGMCC 1.15487T = DSM 101712T) as the type strain.

Paenibacillus rhizophilus sp. nov., a nitrogen-fixing bacterium isolated from the rhizosphere of wheat (Triticum aestivum L.).

A novel Gram-stain-variable, endospore-forming, motile, rod-shaped, facultative aerobic bacterium, designated 7197T, was isolated from rhizosphere soil of wheat (Triticum aestivum L.) collected from Yakeshi County, Inner Mongolia, PR China. This isolate was found to have the highest 16S rRNA gene sequence similarity to Paenibacillussabinae T27T (98.0 %), followed by Paenibacillussophorae S27T (97.9 %) and Paenibacillusforsythiae T98T (97.7 %). To ascertain the genomic relatedness of this strain to its phylogenetic neighbours, its genome sequence was determined. The average nucleotide identity values of genome sequences between the novel isolate and the type strains of related species P. sabinae T27T, P. sophorae S27T and P. forsythiae T98T were 87.9 %, 85.8 and 83.9 %, respectively. The polar lipids contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, four unidentified aminophospholipids and one unidentified aminolipid. The major cellular fatty acids were anteiso-C15 : 0 (56.3 %), C16 : 0 (15.7 %) and iso-C15 : 0 (14.1 %).The genome size of strain 7197T was 5.21 Mb, comprising 4879 predicted genes with a DNA G+C content of 51.9 mol%. Menaquinone-7 was reported as the major respiratory quinone. The diamino acid in the cell-wall peptidoglycan was found to be meso-diaminopimelic acid. Based on phylogenetic, genomic, chemotaxonomic and phenotypic characteristics, strain 7197T was classified as a novel species within the genus Paenibacillus, for which the name Paenibacillus rhizophilus sp. nov. is proposed. The type strain of Paenibacillus rhizophilus is 7197T (=DSM 103168T=CGMCC 1.15699T).

[Research advances in nutritional assessment methods in children with chronic liver diseases].

Malnutrition is commonly seen in children with chronic liver diseases, and there are interactions between them. Chronic liver diseases can cause malnutrition and this can affect the prognosis of children with chronic liver diseases. Due to the complexity of nutritional assessment in children with chronic liver diseases, there are still no unified standards for the diagnosis of malnutrition. Early identification of malnutrition and related intervention helps to improve the prognosis of children with chronic liver diseases. This article reviews the features of nutrition in children with chronic liver diseases and related nutritional assessment methods.

Genetic variants in renalase and blood pressure responses to dietary salt and potassium interventions: a family-based association study.

BACKGROUND/AIMS: Renalase (gene name RNLS), a recently discovered enzyme with monoamine oxidase activity, is implicated in the degradation of catecholamines. Recent studies indicate that common variations in the gene with RNLS are associated with hypertension. The aim of this study was to examine the association between genetic variants in RNLS and blood pressure (BP) responses to strict dietary interventions of salt and potassium intake. METHODS: A total of 334 subjects from 124 families were selected and sequentially maintained on a low-salt diet for 7 days (3.0 g/day, NaCl), then a high-salt diet for 7 days (18.0 g/day, NaCl), high-salt diet with potassium supplementation for another 7 days (4.5 g/day, KCl). RESULTS: SNPs rs919115 and rs792205 of the RNLS gene were significantly associated with diastolic BP (DBP) and mean arterial pressure (MAP) responses to high-salt intervention. In addition, rs12356177 was significantly associated with systolic BP (SBP) and DBP responses to low-salt diet, and SBP, DBP or MAP during the high-salt intervention. Unfortunately, no associations for the 7 RNLS SNPs with BP response to high-salt diet with potassium supplementation reached nominal statistical significance. CONCLUSIONS: This family-based study indicates that genetic variants in the RNLS gene are significantly associated with BP responses to dietary salt intake.

High-salt intake suppressed microRNA-133a expression in Dahl SS rat myocardium.

Salt-sensitive individuals show earlier and more serious cardiac damage than nonsalt-sensitive ones. Some studies have suggested that microRNA-133a could reduce cardiac hypertrophy and myocardial fibrosis. The current study aims to investigate the different functions of high-salt intake on salt-sensitive (SS) rats and Sprague-Dawley (SD) rats and the involvement of microRNA-133a in these roles. After high-salt intervention, the left ventricular mass (LVW) and left ventricular mass index (LVMI) of the salt-sensitive high salt (SHS) group were obviously higher than those of the salt-sensitive low salt (SLS) group. However, the difference between the Sprague-Dawley high salt (DHS) group and the Sprague-Dawley low salt (DLS) group was not significant. Compared with SLS group, collagen I and connective tissue growth factor (CTGF) in the heart of SHS group were significantly higher, whereas no statistical difference was observed between the DHS group and the DLS group. Compared with low-salt diet, microRNA-133a in the heart of both strains were significantly decreased, but that in the SHS group decreased more significantly. These results suggest that high salt intervention could down-regulate the expression of myocardial microRNA-133a, which may be one of the mechanisms involved in myocardial fibrosis in salt-sensitive hypertension.

Optimizing the Strength and Toughness of V/Mo-Modified 0.22C-5.24Mn Steel by Short-Time Partial Austenitization Process.

In order to obtain the good match between yield strength and low-temperature toughness, the short-time partial austenitization (SPA) process was employed for V/Mo-bearing 0.22C-5.24Mn steel. The initial microstructure after intercritical tempering was dual-phase ferrite and reversed austenite (RA), while the final microstructure consisted of ferrite, RA, and secondary martensite (SM) after being subjected to the SPA process. (V, Mo)C with disclike morphology mainly precipitated during intercritical tempering, and the aspect ratio of particles decreased, leading to the appearance of near-spherical morphology. After being subjected to SPA process, the resultant multiphase hierarchical microstructure (three layers: outer layer of ferrite, interlayer of SM, and inner layer of RA) enabled a high yield strength of 1097 MPa, a total elongation of 14%, and an impressive impact energy of 33.3 J at -20 °C. The strengthening contribution of (V, Mo)C precipitation was estimated to be about 108 MPa.

The characteristics of the gut microbiota in patients with pulmonary tuberculosis: A systematic review.

Increasing evidence has indicated dysbiosis of the gut microbiota in patients with pulmonary tuberculosis (PTB). However, the change in the intestinal microbiota varies between different studies. This systematic review was conducted to investigate the characteristics of the gut microbiota in PTB patients. The MBASE, MEDLINE, Web of Science, and Cochrane Library electronic databases were systematically searched, and the quality of the retrieved studies was evaluated using the Newcastle-Ottawa scale. A total of 12 studies were finally included in the systematic review. Compared with healthy controls, the index reflecting α-diversity including the richness and/or diversity index decreased in 6 studies, while ß-diversity presented significant differences in PTB patients in 10 studies. Although the specific gut microbiota alterations were inconsistent, short-chain fatty acid-producing bacteria (including Lachnospiraceae, Ruminococcus, Blautia, Dorea, and Faecalibacterium), bacteria associated with an inflammatory state (e.g., Prevotellaceae and Prevotella), and beneficial bacteria (e.g., Bifidobacteriaceae and Bifidobacterium) were commonly noted. Our systematic review identifies key evidence for gut microbiota alterations in PTB patients, in comparison with healthy controls; however, no consistent conclusion could be drawn, due to the inconsistent results and heterogeneous methodologies of the enrolled studies. Therefore, more well-designed research with standard methodologies and large sample sizes is required.

Synergetic impact of high-entropy microdoping modification in Na3V2(PO4)3.

High entropy polyanionic Na3V1.9(Ca,Mg,Cr,Ti,Mn)0.1(PO4)3 was synthesized, which activated a reversible redox reaction of V4+/V5+ and reached a remarkable capacity of 116 mA h g-1 at 1C and maintained 90% capacity retention after 1000 cycles at 10C. Structure evolution and sodium storage mechanisms were revealed by an in situ XRD method, which disclosed the high-entropy effect of material design. Together with the full battery tests, these findings promote the wide applications of high-entropy polyanionic cathodes in SIBs.

Possible contributions of fibrogenesis to recurrent miscarriages - A transcriptome analysis.

Recurrent miscarriages (RM) generally refer to two or more consecutive pregnancy losses. The risk of miscarriages grows with its frequency of occurrences, so as the future obstetric complications or longer-term health problems for patients. Most previous researches sought to discover the etiology of RM by making comparisons between patients with RM and fertile women. Our study collected decidua tissues from patients with RM and single miscarriage (SM) for transcriptome sequencing analysis and aimed at identifying vital factors contributing to additional miscarriages after previous miscarriage. Between the RM and SM group, a total of 122 differentially expressed genes (DEGs) were detected and pathways associated with cell adhesion and ECM remodeling were particularly enriched in the RM group, which indicated abnormally activated fibrogenesis process. Particularly, the enhancement of ITGB6, EGFLAM and COL3A1 in the RM group were validated by RT-qPCR. Our study discovered that fibrogenesis, which might be caused by intrauterine manipulation, could lead to recurrent miscarriages after a previous miscarriage. Therefore, we encourage higher attention to thorough prevention and prompt remedies towards fibrotic disorders related diseases.

SIRT3 regulates cardiolipin biosynthesis in pressure overload-induced cardiac remodeling by PPARγ-mediated mechanism.

Cardiac remodeling is the primary pathological feature of chronic heart failure (HF). Exploring the characteristics of cardiac remodeling in the very early stages of HF and identifying targets for intervention are essential for discovering novel mechanisms and therapeutic strategies. Silent mating type information regulation 2 homolog 3 (SIRT3), as a major mitochondrial nicotinamide adenine dinucleotide (NAD)-dependent deacetylase, is required for mitochondrial metabolism. However, whether SIRT3 plays a role in cardiac remodeling by regulating the biosynthesis of mitochondrial cardiolipin (CL) is unknown. In this study, we induced pressure overload in wild-type (WT) and SIRT3 knockout (SIRT3-/-) mice via transverse aortic constriction (TAC). Compared with WT mouse hearts, the hearts of SIRT3-/- mice exhibited more-pronounced cardiac remodeling and fibrosis, greater reactive oxygen species (ROS) production, decreased mitochondrial-membrane potential (ΔΨm), and abnormal mitochondrial morphology after TAC. Furthermore, SIRT3 deletion aggravated TAC-induced decrease in total CL content, which might be associated with the downregulation of the CL synthesis related enzymes cardiolipin synthase 1 (CRLS1) and phospholipid-lysophospholipid transacylase (TAFAZZIN). In our in vitro experiments, SIRT3 overexpression prevented angiotensin II (AngII)- induced aberrant mitochondrial function, CL biosynthesis disorder, and peroxisome proliferator-activated receptor gamma (PPARγ) downregulation in cardiomyocytes; meanwhile, SIRT3 knockdown exacerbated these effects. Moreover, the addition of GW9662, a PPARγ antagonist, partially counteracted the beneficial effects of SIRT3 overexpression. In conclusion, SIRT3 regulated PPARγ-mediated CL biosynthesis, maintained the structure and function of mitochondria, and thereby protected the myocardium against cardiac remodeling.