Phased Telomere-to-Telomere Reference Genome and Pangenome Reveal an Expansion of Resistance Genes during Apple Domestication.

The cultivated apple (Malus domestica Borkh.) is a cross-pollinated perennial fruit tree of great economic importance. Previous versions of apple reference genomes were unphased, fragmented, and lacked comprehensive insights into the highly heterozygous genome, which impeded genetic studies and breeding programs in apple. In this study, we assembled a haplotype-resolved telomere-to-telomere reference genome for the diploid apple cultivar Golden Delicious. Subsequently, we constructed a pangenome based on twelve assemblies from wild and cultivated apples to investigate different types of resistance gene analogs (RGAs). Our results revealed the dynamics of the gene gain and loss events during apple domestication. Compared with cultivated species, more gene families in wild species were significantly enriched in oxidative phosphorylation, pentose metabolic process, responses to salt, and abscisic acid biosynthesis process. Interestingly, our analyses demonstrated a higher prevalence of RGAs in cultivated apples than their wild relatives, partially attributed to segmental and tandem duplication events in certain RGAs classes. Other types of structural variations, mainly deletions and insertions, have affected the presence and absence of TIR-NB-ARC-LRR (TNL), NB-ARC-LRR (NL), and CC-NB-ARC-LRR (CNL) genes. Additionally, hybridization/introgression from wild species has also contributed to the expansion of resistance genes in domesticated apples. Our haplotype-resolved T2T genome and pangenome provide important resources for genetic studies of apples, emphasizing the need to study the evolutionary mechanisms of resistance genes in apple breeding programs.

Pyruvate kinase M2 sustains cardiac mitochondrial quality surveillance in septic cardiomyopathy by regulating prohibitin 2 abundance via S91 phosphorylation.

The endogenous mitochondrial quality control (MQC) system serves to protect mitochondria against cellular stressors. Although mitochondrial dysfunction contributes to cardiac damage during many pathological conditions, the regulatory signals influencing MQC disruption during septic cardiomyopathy (SC) remain unclear. This study aimed to investigate the involvement of pyruvate kinase M2 (PKM2) and prohibitin 2 (PHB2) interaction followed by MQC impairment in the pathogenesis of SC. We utilized LPS-induced SC models in PKM2 transgenic (PKM2TG) mice, PHB2S91D-knockin mice, and PKM2-overexpressing HL-1 cardiomyocytes. After LPS-induced SC, cardiac PKM2 expression was significantly downregulated in wild-type mice, whereas PKM2 overexpression in vivo sustained heart function, suppressed myocardial inflammation, and attenuated cardiomyocyte death. PKM2 overexpression relieved sepsis-related mitochondrial damage via MQC normalization, evidenced by balanced mitochondrial fission/fusion, activated mitophagy, restored mitochondrial biogenesis, and inhibited mitochondrial unfolded protein response. Docking simulations, co-IP, and domain deletion mutant protein transfection experiments showed that PKM2 phosphorylates PHB2 at Ser91, preventing LPS-mediated PHB2 degradation. Additionally, the A domain of PKM2 and the PHB domain of PHB2 are required for PKM2-PHB2 binding and PHB2 phosphorylation. After LPS exposure, expression of a phosphorylation-defective PHB2S91A mutant negated the protective effects of PKM2 overexpression. Moreover, knockin mice expressing a phosphorylation-mimetic PHB2S91D mutant showed improved heart function, reduced inflammation, and preserved mitochondrial function following sepsis induction. Abundant PKM2 expression is a prerequisite to sustain PKM2-PHB2 interaction which is a key element for preservation of PHB2 phosphorylation and MQC, presenting novel interventive targets for the treatment of septic cardiomyopathy.

Temporal differentiation in the adaptation of functional bacteria to low-temperature stress in partial denitrification and anammox system.

Despite reliable nitrite supply through partial denitrification, the adaptation of denitrifying bacteria to low temperatures remains elusive in partial denitrification and anammox (PDA) systems. Here, temporal differentiations of the structure, activity, and relevant cold-adaptation mechanism of functional bacteria were investigated in a lab-scale PDA bioreactor at decreased temperature. Although distinct denitrifying bacteria dominated after low-temperature stress, both short- and long-term stresses exerted differential selectivity towards the species with close phylogenetic distance. Species Azonexus sp.149 showed high superiority over Azonexus sp.384 under short-term stress, and long-term stress improved the adaptation of Aquabacterium sp.93 instead of Aquabacterium sp.184. The elevated transcription of nitrite reductase genes suggested that several denitrifying bacteria (e.g., Azonexus sp.149) could compete with anammox bacteria for nitrite. Species Rivicola pingtungensis and Azonexus sp.149 could adapt through various adaptation pathways, such as the two-component system, cold shock protein (CSP), membrane alternation, and electron transport chain. By contrast, species Zoogloea sp.273 and Aquabacterium sp.93 mainly depended on the CSP and oxidative stress response. This study largely deepens our understanding of the performance deterioration in PDA systems during cold shock and provides several references for efficient adaptation to seasonal temperature fluctuation.

Clinical study of multifactorial diagnosis in prostate biopsy.

PURPOSE: To study the feasibility of using an artificial intelligence (AI) algorithm for the diagnosis of clinically significant prostate cancer (csPCa) on multiparametric MRI (mpMRI) in combination with conventional clinical information. METHODS: A retrospective study cohort with 505 patients was collected, with complete information on age (≤60, 60-80, and >80 years), PSA (≤4, 4-10, and >10 ng/dL), and pathology results. The patients with ISUP group >2 were classified as csPCa, and the patients with ISUP = 1 or no evidence of prostate cancer were classified as non-csPCa. The diagnosis of mpMRI was made by experienced radiologists following the prostate imaging reporting and data system (PIRADS ≤ 2, PIRADS = 3, and PIRADS > 3). The mpMRI images were processed by a homemade AI algorithm, and the AI results were obtained as positive or negative for csPCa. Two logistic regression models were fitted, with pathological findings as the dependent variable, that is, a conventional model and an AI model. The conventional model used age, PSA, and PIRADS as the independent variables. The AI model took the AI result and the abovementioned clinical information as the independent variables. The predicted probability of the patients from the conventional model and the AI model were used to test the prediction efficacy of the models. The DeLong test was performed to compare differences in the area under the receiver operating characteristic (ROC) area under the curve (AUC) between the conventional model and the AI model. RESULTS: In total, 505 patients were included in the study; 280 were diagnosed with csPCa, and 225 were non-csPCa. The median age was 72.0 (67.0, 76.0) years, with a median PSA value of 13.0 (7.46, 27.5) ng/dL. Statically significant differences were found in age, PSA, PIRADS score and AI results between the csPCa and non-csPCa groups (all p < 0.001). In the multivariable regression models, all the variables were independently associated with csPCa. The conventional model (R2 = 0.361) and the AI model (R2 = 0.474) were compared with analysis of variance (ANOVA) and showed statistically significant differences (χ2 = 63.695, p < 0.001). The AUC of the ROC curve for the conventional model was 0.782 (95% confidence interval [CI]: 0.742-0.823), which was less than the AUC of the AI model with statistical significance (0.849 [95% CI: 0.815-0.883], p < 0.001). CONCLUSION: In combination with routine clinical information, such as age, PSA, and PIRADS category, adding information from the AI algorithm based on mpMRI could improve the diagnosis of csPCa.

Circular RNAs: Biogenesis, Biological Functions, and Roles in Myocardial Infarction.

Non-coding RNAs have been excavated as important cardiac function modulators and linked to heart diseases. Significant advances have been obtained in illuminating the effects of microRNAs and long non-coding RNAs. Nevertheless, the characteristics of circular RNAs are rarely mined. Circular RNAs (circRNAs) are widely believed to participate in cardiac pathologic processes, especially in myocardial infarction. In this review, we round up the biogenesis of circRNAs, briefly describe their biological functions, and summarize the latest literature on multifarious circRNAs related to new therapies and biomarkers for myocardial infarction.

Screening high-risk population of persistent postpartum hypertension in women with preeclampsia using latent class cluster analysis.

BACKGROUND: A significant proportion of women with preeclampsia (PE) exhibit persistent postpartum hypertension (PHTN) at 3 months postpartum associated with cardiovascular morbidity. This study aimed to screen patients with PE to identify the high-risk population with persistent PHTN. METHODS: This retrospective cohort study enrolled 1,000 PE patients with complete parturient and postpartum blood pressure (BP) profiles at 3 months postpartum. The enrolled patients exhibited new-onset hypertension after 20 weeks of pregnancy, while those with PE superimposed upon chronic hypertension were excluded. Latent class cluster analysis (LCCA), a method of unsupervised learning in machine learning, was performed to ascertain maternal exposure clusters from eight variables and 35 subordinate risk factors. Logistic regression was applied to calculate odds ratios (OR) indicating the association between clusters and PHTN. RESULTS: The 1,000 participants were classified into three exposure clusters (subpopulations with similar characteristics) according to persistent PHTN development: high-risk cluster (31.2%), medium-risk cluster (36.8%), and low-risk cluster (32.0%). Among the 1,000 PE patients, a total of 134 (13.4%) were diagnosed with persistent PHTN, while the percentages of persistent PHTN were24.68%, 10.05%, and 6.25% in the high-, medium-, and low-risk clusters, respectively. Persistent PHTN in the high-risk cluster was nearly five times higher (OR, 4.915; 95% confidence interval (CI), 2.92-8.27) and three times (OR, 2.931; 95% CI, 1.91-4.49) than in the low- and medium-risk clusters, respectively. Persistent PHTN did not differ between the medium- and low-risk clusters. Subjects in the high-risk cluster were older and showed higher BP, poorer prenatal organ function, more adverse pregnancy events, and greater medication requirement than the other two groups. CONCLUSION: Patients with PE can be classified into high-, medium-, and low-risk clusters according to persistent PHTN severity; each cluster has cognizable clinical features. This study's findings stress the importance of controlling persistent PHTN to prevent future cardiovascular disease.

Cloning, expression, and characteristic analysis of the novel ß-galactosidase from silkworm, Bombyx mori.

ß-Galactosidase is a critical exoglycosidase involved in the hydrolysis of lactose, the modification and degradation of glycoprotein in vivo. In this study, the ß-galactosidase gene of silkworm (BmGal), whose cDNA comprises 11 exons and contains an intact ORF of 1,821 bp, was cloned. The protein sequence of BmGal showed high similarity with other known insect ß-galactosidases. No activity of the BmGal expressed in Escherichia coli or Pichia pastoris was detected while it was successfully expressed with high enzyme activity in baculovirus expression system in silkworm, and the electrophoresis result revealed that the BmGal showed activity in oligomer mode. Enzyme activity assay showed that its optimum pH was 8.4 and its optimum temperature was 40 °C. What is more, we found that iron ions can stimulate the activity of the enzyme while cobalt, nickel, or lead ions can inhibit its activity significantly. Besides, the temporal-spatial transcription pattern of the BmGal mRNA level was analyzed, which showed that BmGal was transcribed at the highest level in the fifth larval instar but relatively low level in the pupal and adult stage, and the highest transcriptional level of BmGal was found in testis among all the tissues concerned.

Association of Plasma Pro-Brain-Derived Neurotrophic Factor (proBDNF)/Mature Brain-Derived Neurotrophic Factor (mBDNF) Levels with BDNF Gene Val66Met Polymorphism in Alcohol Dependence.

BACKGROUND In a previous study, we reported that pro-brain-derived neurotrophic factor (proBDNF) was involved in the pathology of alcohol dependence, and the single-nucleotide polymorphism (SNP) Val66Met was located at the prodomain of the brain-derived neurotrophic factor gene (BDNF). This polymorphism has been reported to affect intracellular trafficking and activity-dependent secretion of BDNF. Our present research investigated the relationships between the BDNF Val66Met polymorphism and the plasma levels of proBDNF and mature brain-derived neurotrophic factor (mBDNF) in patients with alcohol dependence. MATERIAL AND METHODS The BDNF gene Val66Met polymorphism was genotyped in 59 alcohol-dependent patients and 37 age- and sex-matched controls, and the plasma levels of proBDNF and mBDNF were assessed by enzyme-linked immunosorbent assay in all participants. RESULTS No association was found between the BDNF gene Val66Met polymorphism and alcohol dependence (P>0.05). In comparison with the control group, the level of plasma proBDNF in the alcohol-dependence group was notably increased (Z=-2.228, P=0.026), while the level of mBDNF was remarkedly decreased (Z=-2.014, P=0.044). In the alcohol-dependence group, significant associations were not found between the Val66Met polymorphisms and proBDNF and mBDNF plasma levels (P>0.05). The plasma level of proBDNF was positively correlated with the average daily alcohol consumption in the last month (r=0.344, P=0.008) and drinking history (r=0.317, P=0.014), while the plasma level of mBDNF had negative effects (r=-0.361, P=0.005, with the average daily alcohol consumption; r=-0.427, P=0.001, with drinking history). CONCLUSIONS The BDNF gene Val66Met polymorphism does not appear to affect the secretion of proBDNF and mBDNF in Chinese patients with alcohol dependence. Furthermore, this study reconfirmed that the plasma levels of proBDNF and mBDNF were correlated with the average daily alcohol consumption in the last month and with drinking history.

A label-free electrochemical aptasensor for the analysis of the potassium ion.

Herein, a simple and novel electrochemical method for the detection of potassium ions (K(+)) was developed. In the presence of potassium ions, the potassium ions aptamer will form a G-quadruplex complex. Thus, further addition of hemin in the presence of potassium ions will lead to the formation of a recombined G-quadruplex. Then the electroactive label, hemin, will give an electrochemical response. The linear range of the method covered a large variation of K(+) concentration from 0.1 nM to 0.1 µ M and the detection limit of 0.1 nM was obtained. Moreover, this assay was able to detect K(+) with high selectivity and had great potential applications.

Distinct microbial characteristics of the robust single-stage coupling system during the conversion from anammox-denitritation to anammox-denitratation patterns.

Simultaneous anammox-denitrification is effectively operated in two types, i.e., the anammox-denitritation (SAD pattern) and the anammox-denitratation (PDA pattern). The nitrate derived from inevitable nitrite oxidization likely determines the practical operational pattern of the coupling system, while little information is available regarding the microbial characteristics during the pattern conversion. Here, the single-stage bioreactor coupling anammox with denitrification was operated under conditions with a changed ratio of influent nitrite and nitrate. Results showed that the bioreactor exhibited a robust performance during the conversion from SAD to PDA patterns, corresponding with the total nitrogen removal efficiency ranging from 89.5% to 92.4%. Distinct community structures were observed in two patterns, while functional bacteria including the genera Denitratisoma, Thauera, Candidatus Brocadia, and Ca. Jettenia steadily co-existed. Meanwhile, the high transcription of hydrazine synthase genes demonstrated a stable anammox process, while the up-regulated transcription of nitrite and nitrous oxide reductase genes indicated that the complete denitrification process was enhanced for total nitrogen removal during the PDA pattern. Ecologically, stochastic processes dominantly governed the community assembly in two patterns. The PDA pattern improved the interconnectivity of communities, especially for the cooperative behaviors between dominant denitrifying bacteria and low-abundant species. These findings deepen our understanding of the microbial mechanism underlying the different patterns of the coupling system and potentially expand its engineering application.

Synaptotagmin-7 mediates cardiac hypertrophy by targeting autophagy.

Sustained cardiac hypertrophy damages the heart and weakens cardiac function, often leading to heart failure and even death. Pathological cardiac hypertrophy has become a central therapeutic target for many heart diseases including heart failure. However, the underlying mechanisms of cardiac hypertrophy, especially the involvement of autophagy program, are still ill-understood. Synaptotagmin-7 (Syt7), a multifunctional and high-affinity calcium sensor, plays a pivotal role in asynchronous neurotransmitter release, synaptic facilitation, and vesicle pool regulation during synaptic transmission. However, little is known about whether Syt7 is expressed in the myocardium and involved in the pathogenesis of heart diseases. Here we showed that Syt7 was significantly upregulated in Ang II-treated hearts and cardiomyocytes. Homozygous syt7 knockout (syt7-/-) mice exhibited significantly attenuated cardiac hypertrophy and fibrosis and improved cardiac function. We further found that Syt7 exerted a pro-hypertrophic effect by suppressing the autophagy process. In exploring the upstream mechanisms, microRNA (miR)-93 was identified to participate in the regulation of Syt7 expression. miR-93 protected hearts against Ang II-induced hypertrophy through targeting Syt7-autophagy pathway. In summary, our data reveal a new cardiac hypertrophy regulator and a novel hypertrophy regulating model composed of miR-93, Syt7 and autophagy program. These molecules may serve as potential therapeutic targets in the treatment of cardiac hypertrophy and heart failure.

Transcriptome-Based Weighted Gene Co-Expression Network Analysis Reveals the Photosynthesis Pathway and Hub Genes Involved in Promoting Tiller Growth under Repeated Drought-Rewatering Cycles in Perennial Ryegrass.

Drought stress, which often occurs repeatedly across the world, can cause multiple and long-term effects on plant growth. However, the repeated drought-rewatering effects on plant growth remain uncertain. This study was conducted to determine the effects of drought-rewatering cycles on aboveground growth and explore the underlying mechanisms. Perennial ryegrass plants were subjected to three watering regimes: well-watered control (W), two cycles of drought-rewatering (D2R), and one cycle of drought-rewatering (D1R). The results indicated that the D2R treatment increased the tiller number by 40.9% and accumulated 28.3% more aboveground biomass compared with W; whereas the D1R treatment reduced the tiller number by 23.9% and biomass by 42.2% compared to the W treatment. A time-course transcriptome analysis was performed using crown tissues obtained from plants under D2R and W treatments at 14, 17, 30, and 33 days (d). A total number of 2272 differentially expressed genes (DEGs) were identified. In addition, an in-depth weighted gene co-expression network analysis (WGCNA) was carried out to investigate the relationship between RNA-seq data and tiller number. The results indicated that DEGs were enriched in photosynthesis-related pathways and were further supported by chlorophyll content measurements. Moreover, tiller-development-related hub genes were identified in the D2R treatment, including F-box/LRR-repeat MAX2 homolog (D3), homeobox-leucine zipper protein HOX12-like (HOX12), and putative laccase-17 (LAC17). The consistency of RNA-seq and qRT-PCR data were validated by high Pearson's correlation coefficients ranging from 0.899 to 0.998. This study can provide a new irrigation management strategy that might increase plant biomass with less water consumption. In addition, candidate photosynthesis and hub genes in regulating tiller growth may provide new insights for drought-resistant breeding.

Recent trends in extraction, purification, structural characterization, and biological activities evaluation of Perilla frutescens (L.) Britton polysaccharide.

Perilla frutescens (L.) Britton is an annual herb plant of the Perilla genus in the Labiatae family, which is commonly utilized as an edible and medicinal resource. Polysaccharides are among the major components and essential bioactive compounds of P. frutescens, which exhibit a multitude of biological activities, including antioxidant, antitumor, anti-fatigue, immunoregulation, hepatoprotective, anti-inflammatory, and lipid-lowering effects. As a natural carbohydrate, P. frutescens polysaccharide has the potential to be utilized in the development of drugs and functional materials. In this paper, we provide an overview of progress made on the extraction, purification, structural characterization, and bioactivity of polysaccharides from different parts of P. frutescens. The challenges and opportunities for research are discussed, along with the potential development prospects and future areas of focus in the study of P. frutescens polysaccharides.

A review of the extraction and purification methods, biological activities, and applications of active compounds in Acanthopanax senticosus.

Acanthopanax senticosus (AS) is a geo-authentic crude medicinal plant that grows in China, Korea, Russia, and Japan. AS contains bioactive compounds such as eleutherosides, polysaccharides, and flavonoids. It is also a key traditional herb in the Red List of Chinese Species. AS is mainly distributed in Northeast China, specifically in Heilongjiang, Jilin, and Liaoning provinces. Its active compounds contribute to significant biological activities, including neuroprotective, antioxidant, anti-fatigue, and antitumor effects. However, the extraction methods of active compounds are complex, the extraction efficiency is poor, and the structure-activity relationship is unclear. This study focused on the nutrients in AS, including protein, carbohydrates, and lipids. Particularly, the active ingredients (eleutherosides, polysaccharides, and flavonoids) in AS and their extraction and purification methods were analyzed and summarized. The biological activities of extracts have been reviewed, and the mechanisms of anti-oxidation, antitumor, anti-inflammation, and other activities are introduced in detail. The applications of AS in various domains, such as health foods, medicines, and animal dietary supplements, are then reported. Compared with other extraction methods, ultrasonic or microwave extraction improves efficiency, yet they can damage structures. Challenges arise in the recovery of solvents and in achieving extraction efficiency when using green solvents, such as deep eutectic solvents. Improvements can be made by combining extraction methods and controlling conditions (power, temperature, and time). Bioactive molecules and related activities are exposited clearly. The applications of AS have not been widely popularized, and the corresponding functions require further development.

Biochemical characterization, structure-guided mutagenesis, and application of a recombinant D-allulose 3-epimerase from Christensenellaceae bacterium for the biocatalytic production of D-allulose.

D-Allulose has become a promising alternative sweetener due to its unique properties of low caloric content, moderate sweetness, and physiological effects. D-Allulose 3-epimerase (DAEase) is a promising enzyme for D-Allulose production. However, the low catalytic efficiency limited its large-scale industrial applications. To obtain a more effective biocatalyst, a putative DAEase from Christensenellaceae bacterium (CbDAE) was identified and characterized. The recombinant CbDAE exhibited optimum activity at pH 7.5°C and 55°C, retaining more than 60% relative activity from 40°C to 70°C, and the catalytic activity could be significantly increased by Co2+ supplementation. These enzymatic properties of purified CbDAE were compared with other DAEases. CbDAE was also found to possess desirable thermal stability at 55°C with a half-life of 12.4 h. CbDAE performed the highest relative activity towards D-allulose and strong affinity for D-fructose but relatively low catalytic efficiency towards D-fructose. Based on the structure-guided design, the best double-mutation variant G36N/W112E was obtained which reached up to 4.21-fold enhancement of catalytic activity compared with wild-type (WT) CbDAE. The catalytic production of G36N/W112E with 500 g/L D-fructose was at a medium to a higher level among the DAEases in 3.5 h, reducing 40% catalytic reaction time compared to the WT CbDAE. In addition, the G36N/W112E variant was also applied in honey and apple juice for D-allulose conversion. Our research offers an extra biocatalyst for D-allulose production, and the comprehensive report of this enzyme makes it potentially interesting for industrial applications and will aid the development of industrial biocatalysts for D-allulose.

A Chinese soil conservation dataset preventing soil water erosion from 1992 to 2019.

Soil conservation service (SC) is defined as the ability of terrestrial ecosystems to control soil erosion and protect soil function. A long-term and high-resolution estimation of SC is urgent for ecological assessment and land management on a large scale. Here, a 300-m resolution Chinese soil conservation dataset (CSCD) from 1992 to 2019, for the first time, is established based on the Revised Universal Soil Loss Equation (RUSLE) model. The RUSLE modelling was conducted based on five key parameters, including the rainfall erosivity (interpolation of daily rainfall), land cover management (provincial data), conservation practices (weighted by terrain and crop types), topography (30 m), and soil properties (250 m). The dataset agrees with previous measurements in all basins (R2 > 0.5) and other regional simulations. Compared with current studies, the dataset has long-term, large-scale, and relatively high-resolution characteristics. This dataset will serve as a base to open out the mechanism of SC variations in China and could help assess the ecological effects of land management policies.

Carbon neutral contribution and regional differences of clean energy based on life cycle assessment.

Developing clean energy is an important strategy to achieve global carbon neutrality. In the entire life cycle industrial chain of clean energy systems, fossil energy was directly or indirectly consumed during the processes from raw material production to waste disposal stages. The energy consumed by clean energy construction differed across regions, resulting in various carbon neutrality contributions of clean energy in different regions. We used bibliometrics to sort out the energy consumption of clean energy construction in different regions, including photovoltaic power generation, wind power, hydropower, and other clean energy sources. By combining the loss of land to decrease carbon pool during the operation of clean energy, we analyzed the current research hotspots, development status and trends, and difference in carbon emissions, and summarized the carbon neutral contributions of different regions. The intensity of clean energy carbon emission in China was significantly lower than global mean value. The average intensity of carbon emission in China in the four fields of onshore wind power, offshore wind power, hydropower, and photovoltaic power was 28.8%, 18.2%, 10.1%, and 16.7% lower than global average, respectively. For further research on carbon neutrality of clean energy, it is important to establish a unified life cycle assessment system, put forward construction strategies according to geographical differences, carry out ecological benefit evaluation for clean energy, and establish a clean energy transmission network system.

Transcriptomic study of Suaeda salsa in response to salt and drought stress.

Drought and salinity are the main factors limiting agricultural production. Improving crop resistance to relieve land stress is a major challenge in agriculture. The salt-tolerant species Suaeda salsa is a typical indicator of saline soil. It has a strong drought tolerance and can be used as a model plant to study salt and drought tolerance in plants. In this study, transcriptome sequencing and bioinformatic analysis were performed to study gene expression changes in S. salsa under salt and drought stresses, and to screen out differentially expressed genes. The genetic changes were most abundant in cellular processes, metabolic processes, ion binding, signalling, post-translational modifications, protein conversion, and molecular chaperones, suggesting that the above methods may play a significant role in the response of S. salsa to external salt and drought stress. Enrichment analysis showed that carbohydrate metabolic processes, oxidoreductase activity, transmembrane transport, kinase activity, cellular protein modification processes, and ion-binding pathways are involved in the stress response of S. salsa .

TMBIM6 prevents VDAC1 multimerization and improves mitochondrial quality control to reduce sepsis-related myocardial injury.

BACKGROUND: The regulatory mechanisms involved in mitochondrial quality control (MQC) dysfunction during septic cardiomyopathy (SCM) remain incompletely characterized. Transmembrane BAX inhibitor motif containing 6 (TMBIM6) is an endoplasmic reticulum protein with Ca2+ leak activity that modulates cellular responses to various cellular stressors. METHODS: In this study, we evaluated the role of TMBIM6 in SCM using cardiomyocyte-specific TMBIM6 knockout (TMBIM6CKO) and TMBIM6 transgenic (TMBIM6TG) mice. RESULTS: Myocardial TMBIM6 transcription and expression were significantly downregulated in wild-type mice upon LPS exposure, along with characteristic alterations in myocardial systolic/diastolic function, cardiac inflammation, and cardiomyocyte death. Notably, these alterations were further exacerbated in LPS-treated TMBIM6CKO mice, and largely absent in TMBIM6TG mice. In LPS-treated primary cardiomyocytes, TMBIM6 deficiency further impaired mitochondrial respiration and ATP production, while defective MQC was suggested by enhanced mitochondrial fission, impaired mitophagy, and disrupted mitochondrial biogenesis. Structural protein analysis, Co-IP, mutant TMBIM6 plasmid transfection, and molecular docking assays subsequently indicated that TMBIM6 exerts cardioprotection against LPS-induced sepsis by interacting with and preventing the oligomerization of voltage-dependent anion channel-1 (VDAC1), the major route of mitochondrial Ca2+ uptake. CONCLUSION: We conclude that the TMBIM6-VDAC1 interaction prevents VDAC1 oligomerization and thus sustains mitochondrial Ca2+ homeostasis as well as MQC, contributing to improved myocardial function in SCM.

Screening and characterization of a novel antifreeze peptide from silver carp muscle hydrolysate.

This study aimed to screen and characterize antifreeze peptides from silver carp muscle hydrolysate (SCMH). The SCMH was initially fractionated by ultrafiltration, and the resultant SCMH-IV (<10 kDa) showing 90 % of yeast survival rate was subsequently separated into four fractions using ion-exchange chromatography. The fraction with the best antifreeze activity was further analyzed by liquid chromatography-tandem mass spectrometry. A total of 514 peptides were identified, of which a novel antifreeze peptide (Sc-AFP, KAADSFNHKAFFAKVG) with a thermal hysteresis activity of 0.87 ℃ was selected. The parvalbumin-derived Sc-AFP showed an alanine-rich, α-helical and amphipathic character. Based on molecular dynamics simulations, the Sc-AFP could interact with 48 water molecules via hydrogen bonds, and could be adsorbed onto the ice surface through a total of 21 hydrogen bonds mainly linked to the lysine residues. This could account for its antifreeze properties via preventing the formation and growth of ice crystals.