Region-Controlled Framework Interface Mediated Anion Exchange Chemical Transformation to Designed Metal Phosphosulfide Heteronanostructures.

Postsynthetic chemical transformation provides a powerful platform for creating heteronanostructures (HNs) with well-defined materials and interfaces that generate synergy or enhancement. However, it remains a synthetic bottleneck for the precise construction of HNs with increased degrees of complexity and more elaborate functions in a predictable manner. Herein, we define a general transformative protocol for metal phosphosulfide HNs based on tunable hexagonal Cu1.81S frameworks with corner-, edge- and face-controlled growth of Co2P domains. The region-controlled Cu1.81S-Co2P framework interfaces can serve as "kinetic barriers" in mediating the direction and rate between P and S anion exchange reactions, thus leading to a family of morphology and phase designed Cu3P1-xSx-Co2P HNs with hollow (branched, dotted and crown), porous and core-shell architectures. This study reveals the internal transformation mechanism between metal sulfide and phosphide nanocrystals, and opens up a new way for the rational synthesis of metastable HNs that are otherwise inaccessible.

Phase Transformation from Amorphous RuSx to Ru-RuS2 Hybrid Nanostructure for Efficient Water Splitting in Alkaline Media.

Ruthenium (Ru)-based materials, as a class of efficient hydrogen evolution reaction (HER) catalysts, play an important role in hydrogen generation by electrolysis of water in an alkaline solution for clean hydrogen energy. Hybrid nanostructure (HN) materials, which include two or more components with distinct functionality, show better performance than their individual materials, since HN materials can potentially integrate their advantages and overcome the weaknesses. However, it remains a challenge to construct Ru-based HN materials with desired crystal phases for enhanced HER performances. Herein, a series of new Ru-based HN materials (t-Ru-RuS2, S-Ru-RuS2, and T-Ru-RuS2) through phase engineering of nanomaterials (PEN) and chemical transformation are designed to achieve highly efficient HER properties. Owing to the plentiful formation of heterojunctions and amorphous/crystalline interfaces, the t-Ru-RuS2 HN delivers the most outstanding overpotential of 16 mV and owns a small Tafel slope of 29 mV dec-1 at a current density of 10 mA cm-2, which exceeds commercial Pt/C catalysts (34 mV, 38 mV dec-1). This work shows a new insight for HN and provides alternative opportunities in designing advanced electrocatalysts with low cost for HER in the hydrogen economy.

Characterization of highly polymorphic microsatellite markers for the chinese monal (Lophophorus lhuysii, Galliformes) using Illumina MiSeq sequencing.

BACKGROUND: The Chinese monal (Lophophorus lhuysii, Galliformes) is a vulnerable and endemic bird from southwestern China. To better protect this species and increase its population size, genetic markers are urgently needed for investigation and conservation of both wild and captive populations. METHODS AND RESULTS: By using next-generation sequencing, we developed and characterized markers for seven microsatellite loci of the Chinese monal. PCR examination and statistical analysis indicated that these microsatellites exhibited moderate to high levels of polymorphism, with the expected heterozygosity and polymorphic information content ranging from 0.578 to 0.858 and from 0.540 to 0.841, respectively. Cross-species genome comparison further suggests that these microsatellites are a feature of certain galliform species rather than being specific to the Chinese monal. CONCLUSION: A combination of the seven highly polymorphic loci may provide a fundamental genetic toolkit to assess genetic backgrounds and will contribute to design conservation plan, breeding management and other possible studies of the Chinese monal and other evolutionarily related species in the future.

Differences of the anti-oxidative capability, GPX3, and Cu/ZnSOD expression in Hu sheep testis with different size at six-month-old.

This study aimed to investigate the differences in the anti-oxidant capabilities and related gene expressions of six-month-old Hu sheep with different testis sizes. A total of 201 Hu ram lambs were fed up to 6 months in the same environment. Based on their testis weight and sperm count, 18 individuals were selected and divided into large (n = 9) and small (n = 9) groups, with an average testis weight of 158.67 g ± 5.21 g and 44.58 g ± 4.14 g, respectively. The total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), and malondialdehyde (MDA) concentration in testis tissue were tested. The localization of antioxidant-related genes, GPX3 and Cu/ZnSOD in testis were detected by immunohistochemistry. The GPX3, Cu/ZnSOD expression, and relative mitochondrial DNA (mtDNA) copy number were detected by quantitative real-time PCR. Compared with the small group, the T-AOC (2.69 ± 0.47 vs. 1.16 ± 0.22 U/mgprot) and T-SOD (22.35 ± 2.59 vs. 9.92 ± 1.62 U/mgprot) in the large group were significantly higher, whereas the MDA (0.72 ± 0.13 vs. 1.34 ± 0.17 nM/mgprot) and relative mtDNA copy number in the large group was significantly lower (p < .05). Immunohistochemistry results indicated that the GPX3 and Cu/ZnSOD were expressed in Leydig cells and seminiferous tubule. The expressions of GPX3 and Cu/ZnSOD mRNA in the large group were significantly higher than those in the small group (p < .05). In conclusion, Cu/ZnSOD and GPX3 widely expressed in the Leydig cells and seminiferous tubule, high expression of Cu/ZnSOD and GPX3 in a large group has a higher potential in addressing oxidative stress and contribute to spermatogenesis.

Variants of ADPGK gene and its effect on the male reproductive organ parameters and sperm count in Hu sheep.

ADP-dependent glucokinase (ADPGK) plays an important role instead of hexokinase in regulating energy metabolism via the Embden-Meyerhof-Parnas Pathway. And energy provided via glycolysis promotes testis development and spermatogenesis. In this study, 466 Hu sheep were screened for mutations in the ADPGK gene to examine the association of the ADPGK gene polymorphisms with the testis traits and spermatogenesis. The NC_056060.1: g.31295 C > T SNP was found in the 3'-UTR region, resulting in two genotypes CC and TC type with genotypic frequencies of 0.66 and 0.34, respectively. This mutation was significantly associated with testis weight, testis long circumference, testis short girth, epididymis weight, and sperm concentration (p < 0.05). Moreover, TC genotype individuals had an increased tendency in the expression of the ADPGK gene and had significant reproductive performance advantages compared with CC genotype individuals in the study. And compared with the small testes (<50 g), the ADPGK gene expression of big testes (>160 g) increased significantly. This indicates an association between the ADPGK gene and reproductive organ parameters and sperm count in selected Hu sheep breed, and this SNP may serve as an effective DNA molecular marker for marker-assisted selection in Hu sheep breeding programs.

α-Linolenic acid induced TM4 Sertoli cells proliferation and enhanced total antioxidant capacity.

The present study was undertaken to elucidate the direct ALA effects on mice TM4 Sertoli cells proliferation in vitro. Our results showed that TM4 cells viability was significantly stimulated by ALA (p < 0.05). The 50 µM ALA increased the concentration of total antioxidant capacity, induced the mitochondrial membrane hyperpolarized, and markedly decreased the number of apoptosis cells (p < 0.05). ALA also up-regulated G2/Mitotic-specific cyclin-B1 gene and apoptosis suppressive gene Bcl2 expression (p < 0.05). In conclusion, those results indicated that ALA could increase TM4 Sertoli cells antioxidant capacity, induced the mitochondrial membrane hyperpolarized, inhibited cells apoptosis and stimulated TM4 Sertoli cells proliferation in vitro.

Apolipoprotein A-IV Has Bi-Functional Actions in Alcoholic Hepatitis by Regulating Hepatocyte Injury and Immune Cell Infiltration.

Alcohol abuse can lead to alcoholic hepatitis (AH), a worldwide public health issue with high morbidity and mortality. Here, we identified apolipoprotein A-IV (APOA4) as a biomarker and potential therapeutic target for AH. APOA4 expression was detected by Gene Expression Omnibus (GEO) databases, Immunohistochemistry, and qRT-PCR in AH. Bioinformatics Methods (protein-protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and Gene Set Enrichment Analysis (GSEA) were used to show down-stream gene and pathways of APOA4 in AH. AML-12 cells were used to evaluate the biological function of APOA4 using an ELISA kit (AST, ALT, and IL-1ß) and flow cytometry (ROS activity). Both in vivo and in vitro, APOA4 expression was significantly elevated in the AH model induced by alcohol (ETOH). AML-12 cell damage was specifically repaired by APOA4 deficiency, while AST, ALT, and IL-1ß activity that was increased by ETOH (200 µmol, 12 h) were suppressed. APOA4 inhibition increased intracellular ROS induced by ETOH, which was detected by flow cytometry. Functional and PPI network analyses showed Fcgamma receptor (FCGR) and platelet activation signaling were potential downstream pathways. We identified CIDEC as a downstream gene of APOA4. The CIDEC AUC values for the ROC curves were 0.861. At the same time, APOA4 silencing downregulated the expression of CIDEC, whereas the knockdown of CIDEC did not influence the expression of APOA4 in AML-12 cells. Collectively, APOA4 regulates CIDEC expression and immune cell infiltration and may hold great potential as a biomarker and therapeutic target for AH.

Genome-Wide Identification, Characterization and Expression Analysis of Soybean CHYR Gene Family.

The CHYR (CHY ZINC-FINGER AND RING FINGER PROTEIN) proteins have been functionally characterized in iron regulation and stress response in Arabidopsis, rice and Populus. However, their roles in soybean have not yet been systematically investigated. Here, in this study, 16 GmCHYR genes with conserved Zinc_ribbon, CHY zinc finger and Ring finger domains were obtained and divided into three groups. Moreover, additional 2-3 hemerythrin domains could be found in the N terminus of Group III. Phylogenetic and homology analysis of CHYRs in green plants indicated that three groups might originate from different ancestors. Expectedly, GmCHYR genes shared similar conserved domains/motifs distribution within the same group. Gene expression analysis uncovered their special expression patterns in different soybean tissues/organs and under various abiotic stresses. Group I and II members were mainly involved in salt and alkaline stresses. The expression of Group III members was induced/repressed by dehydration, salt and alkaline stresses, indicating their diverse roles in response to abiotic stress. In conclusion, our work will benefit for further revealing the biological roles of GmCHYRs.

Dexmedetomidine Promotes SH-SY5Y Cell Resistance Against Impairment of Iron Overload by Inhibiting NF-κB Pathways.

Iron overload is a common pathophysiological state underlying many diseases that has a detrimental influence on cells. The protective effects of Dexmedetomidine (Dex), a high selective alpha-2-adrenoceptor agonist, have been revealed through many experimental models, whereas no study reports its effects on an iron overload model. To elucidate these effects, we used FeCl2 with or without Dex to treat SH-SY5Y cells for 24 h and then detected indicators of oxidative stress, inflammation and apoptosis and investigated possible mechanisms further. After treatment with FeCl2 for 24 h, cell viability decreased in a dose dependent manner, and Dex promoted cell survival in FeCl2 incubation, also in a dose-dependent manner. Compared with the FeCl2 group, 20 µM Dex significantly attenuated ROS accumulation, reduced pro-inflammatory cytokine expression, and inhibited apoptosis. Furthermore, 20 µM concentration of Dex remarkably downregulated the expression of pro-apoptotic protein and activation of caspase 3 while increasing anti-apoptotic protein expression. Additionally, Dex also effectively suppressed the expression of NF-κB and its activation. In conclusion, Dex exerted anti-oxidative stress, anti-inflammation, and anti-apoptosis effects on FeCl2-treated SH-SY5Y cells, possibly by inhibiting NF-κB signaling pathway.

Gallic acid caused cultured mice TM4 Sertoli cells apoptosis and necrosis.

OBJECTIVE: The study was designed to determine the cytotoxic effect of gallic acid (GA), obtained by the hydrolysis of tannins, on mice TM4 Sertoli cells apoptosis. METHODS: In the present study, non-tumorigenic mice TM4 Sertoli cells were treated with different concentrations of GA for 24 h. After treatment, cell viability was evaluated using WST-1, mitochondrial dysfunction, cells apoptosis and necrosis was detected using JC-1, Hoechst 33342 and propidium iodide staining. The expression levels of Cyclin B1, proliferating cell nuclear antigen (PCNA), Bcl-2-associated X protein (BAX), and Caspase-3 were also detected by quantitative real-time polymerase chain reaction and Western-blotting. RESULTS: The results showed that 20 to 400 µM GA inhibited viability of TM4 Sertoli cells in a dose-dependent manner. Treatment with 400 µM GA significantly inhibited PCNA and Cyclin B1 expression, however up-regulated BAX and Caspase-3 expression, caused mitochondrial membrane depolarization, activated Caspase-3, and induced DNA damage, thus, markedly increased the numbers of dead cells. CONCLUSION: Our findings showed that GA could disrupt mitochondrial function and caused TM4 cells to undergo apoptosis and necrosis.

[Stored autologous blood transfusion does not increase recurrence of prostate cancer after radical prostatectomy: A preliminary study].

OBJECTIVE: To analyze the association of stored autologous blood transfusion (SABT) with tumor recurrence in PCa patients after radical prostatectomy and explore the application of SABT in this surgical procedure. METHODS: Forty-five PCa patients underwent radical prostatectomy in our hospital in recent five years, of whom, 20 received SABT (group A) and the other 25 allogeneic blood transfusion (group B) intraoperatively. After surgery, we followed up the patients regularly for 3－66 months by examination of the levels of total PSA (tPSA) and free PSA (fPSA), digital rectal examination (DRE), and MRI to observe the biochemical recurrence of the tumor. We compared the data obtained between the two groups of patients. RESULTS: In group A, 8 cases were in stages T1a－T1b and 12 in stages T2a－T2c, and in group B, 14 cases were in stages T1a－T1b and 11 in stages T2a－T2c. The volume of transfused blood was 800 ml in group A and 400－1 200 ml in group B. No statistically significant differences were observed between the two groups in the operation time, intraoperative blood loss or postoperative Gleason scores (P > 0.05), nor in the tPSA level or the results of DRE and MRI at 12, 24, 36, 48 and over 48 months (P > 0.05). CONCLUSIONS: SABT is safe for PCa patients undergoing radical prostatectomy and does not increase the tumor recurrence rate after surgery.

4-Methylcatechol-induced cell damage in TM4 Sertoli cells.

4-Methylcatechol (4-MC) is one of the metabolites of quercetin, which is a potential drug for neuroprotection and tumorigenesis inhibition. This study was performed to investigate the cytotoxic effect of 4-MC in mouse TM4 Sertoli cells. TM4 Sertoli cell viability was significantly inhibited by 4-MC in a time- and dose-dependent manner. The number of apoptotic and dead cells was significantly increased after 4-MC treatment. Caspase 3 activity increased by prolonged exposure of TM4 Sertoli cells to 200 µM 4-MC. The 4-MC significantly upregulated the mRNA level of Bax gene and considerably downregulated the Bcl-2 gene expression in a concentration-dependent manner. Results showed that 4-MC could induce TM4 Sertoli cell apoptosis, and the cytotoxic effect of 4-MC on TM4 Sertoli cells may be associated with upregulated Bax gene expression, which induced caspase cascade activation.

Molecular characterization of SPATA6 and association of its SNPs with testicular size in sheep.

The testis is an important organ for maintaining fertility in males, and testis size is positively correlated with ejaculate volume, sperm motility, thus fertility. Spermatogenesis-associated 6 (SPATA6) is an evolutionarily conserved testis-specific gene reported in many species. However, the effect of SPATA6 expression levels on testicular development and the effect of single nucleotide polymorphisms (SNPs) on testis and epididymis phenotype in sheep have not been studied. The purpose of the research was to investigate the expression profile of SPATA6 and its effect on testicular development and to confirm the effect of SNPs on the testis and epididymis phenotype. In this study, we detected a 1245bp coding sequence (CDS) of SPATA6 and encoded 414 amino acids. The expression levels of SPATA6 were significantly higher in the testis than in other tissues and gradually increased with testis development. Moreover, the expression level in the large testis was significantly higher than that in the small testis at six months. A total of 11 SNPs were detected in the coding region of SPATA6 by cDNA-pooling sequencing and improved multiplex ligation detection reaction (iMLDR) methods. Correlation analysis showed that SNP2 (c. 3631C > G) significantly affected left epididymis weight (LEW) and right epididymis weight (REW), and SNP10 (c. 937 A > G) significantly affected REW. And the combined genotype of SNP1 (c. 4245 G > A) and SNP2 significantly affected REW. The current study concluded that SPATA6 plays an important role in testicular development and the SNPs significantly associated with the epididymis phenotype can provide molecular markers for the early selection of high-fertility Hu sheep.

Extreme precipitation accelerates nitrate leaching in the intensive agricultural region with thick unsaturated zones.

Nitrate accumulation in the soil profile in the intensive agricultural region has been widely concerned in the world. However, the changes in nitrate accumulation characteristics caused by climate change, such as extremely high precipitation, are not well quantified, particularly for the regions with thick unsaturated zones. Here, we resampled the soil profiles taken in normal year (2020) after extreme precipitation year (2021) (>800 cm) in three regions in the southern Loess Plateau (LP) with three different water managements including rainfed orchards (n = 10), well-irrigated orchards (n = 4) and canal-irrigated orchards (n = 8). The accumulation amounts, peak depths, and accumulation depths of nitrate soil profiles of the different regions of two years were compared. The results showed that average nitrate accumulation in normal year at the rainfed region (800-cm depth), well-irrigated region (800-cm depth) and canal-irrigated region (1400-cm depth) were 5995 kg N ha-1, 9765 kg N ha-1, and 19,608 kg N ha-1, respectively. Compared with 2020, extreme precipitation in 2021 led to 56-91% reductions (2060-3702 kg N ha-1) in nitrate accumulation in 0-200 cm soil layer, and average nitrate leaching into the aquifer was >1390 kg N ha-1 in the canal-irrigated region. Average migration depths of nitrate peak in rainfed, well-irrigated and canal-irrigated regions were 92 cm, 115 cm, and 188 cm, respectively; as for nitrate accumulation depths, they were 10 cm, 80 cm and 108 cm, respectively. Vertically, the dried soil layer and paleosol layer (high clay content) in the canal-irrigated region significantly hindered nitrate deep migration caused by the extreme precipitation. The result highlights that extreme precipitation significantly accelerated nitrate leaching in the deep soil profiles, and future vulnerability and risk assessment studies must account for the impacts of extreme precipitation on nitrate leaching.

Transcriptomic analysis of the HPG axis-related tissues reveals potential candidate genes and regulatory pathways associated with testicular size in Hu sheep.

Testicular size is an excellent proxy for selecting high-fertility rams. The hypothalamus-pituitary-gonadal (HPG) axis plays an important role in regulating reproductive capacity in vertebrates, while key genes and regulatory pathways within the HPG axis associated with testicular size remain largely unknown in sheep. This study comprehensively compared the transcriptomic profiles in the hypothalamus, pituitary and testis of rams after sexual maturity between the large-testis group (LTG, testicular weight = 454.29 ± 54.24 g) and the small-testis group (STG, testicular weight = 77.29 ± 10.76 g). In total, 914, 795 and 10518 differentially expressed genes (DEGs) were identified in the hypothalamus, pituitary and testis between LTG and STG, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that these DEGs were mainly involved in the biological processes of reproduction, biological regulation, and development process. Notably, the neuroactive ligand-receptor interaction and cAMP signaling pathways, commonly enriched by the DEGs in the hypothalamus and pituitary between two groups, were considered as two key signal pathways regulating testicular development through the HPGs axis. Weighted gene co-expression network analysis (WGCNA) identified two modules that were significantly associated with testicular size, and 97 key genes were selected with high module membership (MM) and gene significance (GS) in these two modules. Finally, a protein-protein interaction (PPI) network was constructed, and ten genes with the highest degree were represented as hub genes, including FOS, NPY, SST, F2, AGT, NTS, OXT, EDN1, VIP and TAC1. Taken together, these results provide new insights into the molecular mechanism underlying the HPG axis regulating testicular size of Hu sheep.

Effect of Codonopsis pilosula polysaccharide on the quality of sheep semen preservation at 4°C.

OBJECTIVE: This study aimed to investigate the effect of Codonopsis pilosula polysaccharide (CPP) on the motility, mitochondrial integrity, acrosome integrity rate, and antioxidant ability of sheep sperm after preservation at 4°C. METHODS: Semen from healthy adult rams were collected and divided into four groups with separate addition of 0, 200, 400, and 1,000 mg/L CPP. Sperm motility was analyzed using the Computer-Assisted Semen Analysis software after preservation at 4°C for 24, 72, 120, and 168 h. Sperm acrosome integrity rate was analyzed by Giemsa staining at 24, 72, and 120 h, and mitochondrial membrane integrity was analyzed by Mito-Tracker Red CMXRos. The total antioxidant capacity (T-AOC) and malondialdehyde (MDA) content of spermatozoa were measured after 120 h of preservation. RESULTS: The sperm viability and forward-moving sperm under 200 mg/L CPP were significantly higher than that in the control group at 72 h (61.28%±3.89% vs 52.83%± 0.70%, 51.53%±4.06% vs 42.84%±1.14%), and 168 h (47.21%±0.85% vs 41.43%±0.37%, 38.68%±0.87% vs 31.68%±0.89%). The percentage of fast-moving sperm (15.03%±1.10% vs 11.39%±1.03%) and slow-moving sperm (23.63%±0.76% vs 20.29%±1.11%) in the 200 mg/L group was significantly higher than control group at 168 h. The mitochondrial membrane integrity of the sperm in the group with 200 mg/L CPP was significantly higher than those in the control group after storage at 4°C for 120 h (74.76%±2.54% vs 65.67% ±4.51%, p<0.05). The acrosome integrity rate in the group with 200 mg/L (87.66%±1.26%) and 400 mg/L (84.00%±2.95%) was significantly higher than those in the control group (80.65%±0.16%) after storage for 24 h (p<0.05). CPP also increased T-AOC and decreased the MDA concentration after preservation at 4°C (p<0.05). CONCLUSION: Adding CPP could improve the T-AOC of sperm, inhibit lipid peroxidation, and facilitate semen preservation.

Localization and expression of phospholipase A2 and polyunsaturated fatty acid profile in the testis tissues of Hu sheep.

The fatty acid content and the localization and expression of phospholipase A2 (PLA2) in the testis of Hu sheep were investigated. A total of 18 six-month-old Hu sheep were divided into small group (S, with left testis weight < 50 g), medium group (M, with left testis weight among 90-110 g), and large group (L, with left testis weight >160 g), which had six individuals each. The expression of PLA2 in testicular tissues of different sizes was analyzed by immunohistochemistry, RT-qPCR, and Western blot. The fatty acid profile was detected by gas chromatography. Immunohistochemical labeling determined that PLA2 protein was expressed in the Leydig and Sertoli cells of testis, and the immunohistochemical average optional density in the S group was significantly greater than the L group (P < 0.05). RT-qPCR and Western blot analysis showed that PLA2 in the S group was greater than that in the L group (P < 0.05). Docosahexaenoic acid, ω-3 polyunsaturated fatty acid (PUFA), and total PUFA content in the testis of the L group were significantly less than those of the S and M groups (P < 0.01). This study showed that PLA2 content in the S group was greater than that in the L group.

The m7G Methyltransferase Mettl1 Drives Cardiac Hypertrophy by Regulating SRSF9-Mediated Splicing of NFATc4.

Cardiac hypertrophy is a key factor driving heart failure (HF), yet its pathogenesis remains incompletely elucidated. Mettl1-catalyzed RNA N7-methylguanosine (m7G) modification has been implicated in ischemic cardiac injury and fibrosis. This study aims to elucidate the role of Mettl1 and the mechanism underlying non-ischemic cardiac hypertrophy and HF. It is found that Mettl1 is upregulated in human failing hearts and hypertrophic murine hearts following transverse aortic constriction (TAC) and Angiotensin II (Ang II) infusion. YY1 acts as a transcriptional factor for Mettl1 during cardiac hypertrophy. Mettl1 knockout alleviates cardiac hypertrophy and dysfunction upon pressure overload from TAC or Ang II stimulation. Conversely, cardiac-specific overexpression of Mettl1 results in cardiac remodeling. Mechanically, Mettl1 increases SRSF9 expression by inducing m7G modification of SRSF9 mRNA, facilitating alternative splicing and stabilization of NFATc4, thereby promoting cardiac hypertrophy. Moreover, the knockdown of SRSF9 protects against TAC- or Mettl1-induced cardiac hypertrophic phenotypes in vivo and in vitro. The study identifies Mettl1 as a crucial regulator of cardiac hypertrophy, providing a novel therapeutic target for HF.

The positive feedback loop of the NAT10/Mybbp1a/p53 axis promotes cardiomyocyte ferroptosis to exacerbate cardiac I/R injury.

Ferroptosis is a nonapoptotic form of regulated cell death that has been reported to play a central role in cardiac ischemia‒reperfusion (I/R) injury. N-acetyltransferase 10 (NAT10) contributes to cardiomyocyte apoptosis by functioning as an RNA ac4c acetyltransferase, but its role in cardiomyocyte ferroptosis during I/R injury has not been determined. This study aimed to elucidate the role of NAT10 in cardiac ferroptosis as well as the underlying mechanism. The mRNA and protein levels of NAT10 were increased in mouse hearts after I/R and in cardiomyocytes that were exposed to hypoxia/reoxygenation. P53 acted as an endogenous activator of NAT10 during I/R in a transcription-dependent manner. Cardiac overexpression of NAT10 caused cardiomyocyte ferroptosis to exacerbate I/R injury, while cardiomyocyte-specific knockout of NAT10 or pharmacological inhibition of NAT10 with Remodelin had the opposite effects. The inhibition of cardiomyocyte ferroptosis by Fer-1 exerted superior cardioprotective effects against the NAT10-induced exacerbation of post-I/R cardiac damage than the inhibition of apoptosis by emricasan. Mechanistically, NAT10 induced the ac4C modification of Mybbp1a, increasing its stability, which in turn activated p53 and subsequently repressed the transcription of the anti-ferroptotic gene SLC7A11. Moreover, knockdown of Mybbp1a partially abolished the detrimental effects of NAT10 overexpression on cardiomyocyte ferroptosis and cardiac I/R injury. Collectively, our study revealed that p53 and NAT10 interdependently cooperate to form a positive feedback loop that promotes cardiomyocyte ferroptosis to exacerbate cardiac I/R injury, suggesting that targeting the NAT10/Mybbp1a/p53 axis may be a novel approach for treating cardiac I/R.

Effect of corn straw or corncobs in total mixed ration during peri-puberty on testis development in Hu lambs.

Corn straw and corncobs contain large amounts of crude fibers and are widely used in mutton sheep husbandry in northwest China. The aim of this study was to determine whether feeding with corn straw or corncobs affects lamb testis development. A total of 50 healthy Hu lamb at two-month-old (average body weight of 22.3 ± 0.1 kg) were randomly and equally divided into two groups, and the lambs were equally allocated to five pens in each group. The corn straw group (CS) received a diet containing 20% corn straw, whereas the corncobs group (CC) received a diet containing 20% corncobs. After a 77-day feeding trial, the lambs, except the heaviest and lightest in each pen, were humanely slaughtered and investigated. Results revealed no differences in body weight (40.38 ± 0.45 kg vs. 39.08 ± 0.52 kg) between the CS and CC groups. Feeding diet containing corn straw significantly (P < 0.05) increased testis weight (243.24 ± 18.78 g vs. 167.00 ± 15.20 g), testis index (0.60 ± 0.05 vs. 0.43 ± 0.04), testis volume (247.08 ± 19.99 mL vs. 162.31 ± 14.15 mL), diameter of seminiferous tubule (213.90 ± 4.91 µm vs. 173.11 ± 5.93 µm), and the number of sperm in the epididymis (49.91 ± 13.53 × 108/g vs. 19.34 ± 6.79 × 108/g) compared with those in the CC group. The RNA sequencing results showed 286 differentially expressed genes, and 116 upregulated and 170 downregulated genes were found in the CS group compared with the CC group. The genes affecting immune functions and fertility were screened out. Corn straw decreased the mtDNA relative copy number in the testis (P < 0.05). These results suggest that compared with corncobs, feeding corn straw in the early reproductive development stage of lambs increased the testis weight, diameter of seminiferous tubule and the number of cauda sperm.