Regulating NCOA4-Mediated Ferritinophagy for Therapeutic Intervention in Cerebral Ischemia-Reperfusion Injury.

Ischemic stroke presents a global health challenge, necessitating an in-depth comprehension of its pathophysiology and therapeutic strategies. While reperfusion therapy salvages brain tissue, it also triggers detrimental cerebral ischemia-reperfusion injury (CIRI). In our investigation, we observed the activation of nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy in an oxygen-glucose deprivation/reoxygenation (OGD/R) model using HT22 cells (P < 0.05). This activation contributed to oxidative stress (P < 0.05), enhanced autophagy (P < 0.05) and cell death (P < 0.05) during CIRI. Silencing NCOA4 effectively mitigated OGD/R-induced damage (P < 0.05). These findings suggested that targeting NCOA4-mediated ferritinophagy held promise for preventing and treating CIRI. Subsequently, we substantiated the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway effectively regulated the NCOA4-mediated ferritinophagy, by applying the cGAS inhibitor RU.521 and performing NCOA4 overexpression (P < 0.05). Suppressing the cGAS-STING pathway efficiently curtailed ferritinophagy (P < 0.05), oxidative stress (P < 0.05), and cell damage (P < 0.05) of CIRI, while NCOA4 overexpression could alleviate this effect (P < 0.05). Finally, we elucidated the specific molecular mechanism underlying the protective effect of the iron chelator deferoxamine (DFO) on CIRI. Our findings revealed that DFO alleviated hypoxia-reoxygenation injury in HT22 cells through inhibiting NCOA4-mediated ferritinophagy and reducing ferrous ion levels (P < 0.05). However, the protective effects of DFO were counteracted by cGAS overexpression (P < 0.05). In summary, our results indicated that the activation of the cGAS-STING pathway intensified cerebral damage during CIRI by inducing NCOA4-mediated ferritinophagy. Administering the iron chelator DFO effectively attenuated NCOA4-induced ferritinophagy, thereby alleviating CIRI. Nevertheless, the role of the cGAS-STING pathway in CIRI regulation likely involves intricate mechanisms, necessitating further validation in subsequent investigations.

GhVIM28, a negative regulator identified from VIM family genes, positively responds to salt stress in cotton.

The VIM (belonged to E3 ubiquitin ligase) gene family is crucial for plant growth, development, and stress responses, yet their role in salt stress remains unclear. We analyzed phylogenetic relationships, chromosomal localization, conserved motifs, gene structure, cis-acting elements, and gene expression patterns of the VIM gene family in four cotton varieties. Our findings reveal 29, 29, 17, and 14 members in Gossypium hirsutum (G.hirsutum), Gossypium barbadense (G.barbadense), Gossypium arboreum (G.arboreum), and Gossypium raimondii (G. raimondii), respectively, indicating the maturity and evolution of this gene family. motifs among GhVIMs genes were observed, along with the presence of stress-responsive, hormone-responsive, and growth-related elements in their promoter regions. Gene expression analysis showed varying patterns and tissue specificity of GhVIMs genes under abiotic stress. Silencing GhVIM28 via virus-induced gene silencing revealed its role as a salt-tolerant negative regulator. This work reveals a mechanism by which the VIM gene family in response to salt stress in cotton, identifying a potential negative regulator, GhVIM28, which could be targeted for enhancing salt tolerance in cotton. The objective of this study was to explore the evolutionary relationship of the VIM gene family and its potential function in salt stress tolerance, and provide important genetic resources for salt tolerance breeding of cotton.

Molecular Identification and Survey of Trichomonad Species in Pigs in Shanxi Province, North China.

Several trichomonad species have already been identified in pigs, and their pathogenic potential may not be ruled out. To date, however, no information is available regarding the prevalence of trichomonads in pigs in Shanxi Province, North China. In the present study, a total of 362 fecal samples collected from pigs in three representative counties (Qi, Jishan, and Shanyin) in this province were examined for Tetratrichomonas buttreyi, Tritrichomonas foetus, and Pentatrichomonas hominis using a nested polymerase chain reaction (PCR) with primers targeting the small subunit ribosomal RNA (SSU rRNA) gene. The overall prevalence of T. buttreyi was 49.72%, and region and age were found to be significantly associated with T. buttreyi infection, respectively. Only one pig fecal sample from Qi County was found to be positive for T. foetus, and all samples were negative for P. hominis. Molecular evolutionary analysis revealed that some T. buttreyi isolates showed complete genetic identity with those reported previously, and some T. buttreyi isolates and one T. foetus isolate showed minor allelic variations compared with those reported previously. This is the report of the molecular epidemiology of T. foetus and T. buttreyi in pigs in Shanxi Province, North China. These findings not only enrich the knowledge on the distribution of these trichomonad species in pigs in China but also provide baseline information for planning future research and control strategies.

The action mechanism by which C1q/tumor necrosis factor-related protein-6 alleviates cerebral ischemia/reperfusion injury in diabetic mice.

JOURNAL/nrgr/04.03/01300535-202409000-00034/figure1/v/2024-01-16T170235Z/r/image-tiff Studies have shown that C1q/tumor necrosis factor-related protein-6 (CTRP6) can alleviate renal ischemia/reperfusion injury in mice. However, its role in the brain remains poorly understood. To investigate the role of CTRP6 in cerebral ischemia/reperfusion injury associated with diabetes mellitus, a diabetes mellitus mouse model of cerebral ischemia/reperfusion injury was established by occlusion of the middle cerebral artery. To overexpress CTRP6 in the brain, an adeno-associated virus carrying CTRP6 was injected into the lateral ventricle. The result was that oxygen injury and inflammation in brain tissue were clearly attenuated, and the number of neurons was greatly reduced. In vitro experiments showed that CTRP6 knockout exacerbated oxidative damage, inflammatory reaction, and apoptosis in cerebral cortical neurons in high glucose hypoxia-simulated diabetic cerebral ischemia/reperfusion injury. CTRP6 overexpression enhanced the sirtuin-1 signaling pathway in diabetic brains after ischemia/reperfusion injury. To investigate the mechanism underlying these effects, we examined mice with depletion of brain tissue-specific sirtuin-1. CTRP6-like protection was achieved by activating the sirtuin-1 signaling pathway. Taken together, these results indicate that CTRP6 likely attenuates cerebral ischemia/reperfusion injury through activation of the sirtuin-1 signaling pathway.

Research Note: Preliminary functional analysis of EGF-like domains of Eimeria tenella microneme protein 7 identified in sporozoites and merozoites.

Eimeria tenella, an obligate intracellular apicomplexan parasite, is the major causative agent of chicken coccidiosis. Some epidermal growth factor (EGF)-like domain-containing proteins of other members of apicomplexan parasites have been reported to contribute to parasite survival. To date, however, EGF-like domain-containing proteins of E. tenella are not well studied. In this study, a gene fragment that encodes 4 EGF-like domains of E. tenella microneme protein 7 (EGF-EtMIC7) was amplified and expressed using an Escherichia coli expression system. Following generation of polyclonal antibodies that recognize recombinant EGF-EtMIC7 (rEGF-EtMIC7), the expression of EtMIC7 in sporozoites and merozoites was examined. Moreover, its roles in cellular regulation were investigated. The native EtMIC7 in E. tenella sporozoites and merozoites was detected by using Western blot and indirect immunofluorescence assays. rEGF-EtMIC7 could activate Akt, whereas blockade of EGF receptor (EGFR) failed to induce Akt phosphorylation. Compared with the control group, LMH cells treated with rEGF-EtMIC7 showed increased cell proliferation and expressed higher levels of B cell leukemia/lymphoma 2 (BCL-2). These findings contribute to the better understanding of parasite-host interactions at the molecular level during E. tenella infection.

Prevalence and genotype/subtype distribution of Enterocytozoon bieneusi and Blastocystis in donkeys in Shanxi Province, north China.

Enterocytozoon bieneusi and Blastocystis may cause diarrhea in humans and various animals. However, little information is available regarding the prevalence and genetic diversity of E. bieneusi and Blastocystis in donkeys. To fill this gap, we molecularly assessed E. bieneusi and Blastocystis in fecal samples from donkeys (n = 815) in Shanxi Province, north China. The overall prevalence of E. bieneusi and Blastocystis in donkeys was 8.1% and 0.2%, respectively. Region and age were risk factors associated with E. bieneusi infection in donkeys. Three internal transcribed spacer (ITS) genotypes of E. bieneusi were identified in the current study, including two previously described genotypes (D and Henan-IV) and one novel genotype (named SXD1). Of which, genotype D was found to be the most prevalent. Phylogenetic analysis demonstrated that the three genotypes belonged to group 1, implying a potential of zoonotic transmission. Multilocus sequence typing showed that 19, 15, 13, and 22 types were identified at the loci MS1, MS3, MS4, and MS7, respectively, forming six multilocus genotypes (MLGs) distributed in the genotype D. One Blastocystis subtype (ST33) was identified, which has previously been reported only in horses. This is the first molecular-based description of E. bieneusi and Blastocystis infections in donkeys in Shanxi Province, north China, contributing to a better understanding of transmission dynamics and molecular epidemiological characteristics of the two intestinal protozoa.

Anti-aging Factor GRSF1 Attenuates Cerebral Ischemia-Reperfusion Injury in Mice by Inhibiting GPX4-Mediated Ferroptosis.

Abnormal accumulation of senescent cells in tissues has been shown to facilitate the onset and progression of various diseases. As an important protein involving in the regulation of cellular senescence process, researches suggested GRSF1 as a potential senolytic target to improve multiple physiological and pathological processes. However, the underlying mechanism of cellular senescence on cerebral ischemia-reperfusion injury (CIRI) has not been revealed. Here, we investigated the effect of GRSF1 on CIRI and delved into its specific mechanisms. In the present study, we established a mouse model of cerebral ischemia-reperfusion (CIR) and observed low expression of anti-aging factor GRSF1, along with greatly increased levels of senescence-related markers p16 and p21 and senescence-associated secretory phenotype TNF-α. Furthermore, we found that the expression of GPX4 was elevated parallel to GRSF1 in CIR mice with overexpression of GRSF1, oxidative stress, and iron metabolism-related proteins were inhibited. Functionally, overexpressing GRSF1 significantly ameliorated infarct volume and neurological function scores and suppressed apoptosis in CIR mice, while administration of GPX4 inhibitors reversed these beneficial phenotypes. Taken together, our results indicate cellular senescence as an important pathological mechanism to exacerbate cerebral injury during CIRI, while GRSF1 could inhibit oxidative stress-mediated ferroptosis through upregulating GPX4 to attenuate reperfusion injury, which makes senolytic treatment, especially GRSF1, a promising therapeutic target for CIRI.

Prevalence and Multilocus Genotyping of Giardia duodenalis in Donkeys in Shanxi Province, North China.

Giardia duodenalis is a ubiquitous flagellated protozoan, causing significant economic losses to animal husbandry and posing threats to public health. China ranks the world's sixth largest major producer of donkeys, rearing approximately 2.6 million donkeys in 2019, but limited investigation of G. duodenalis prevalence has been conducted in the past, and it is yet to be known whether donkeys in Shanxi Province are infected with G. duodenalis. In the present study, a total of 815 fecal samples collected from donkeys in representative regions of Shanxi Province, North China, were examined for G. duodenalis using nested PCR. Then, the assemblages and multilocus genotypes (MLGs) were examined based on three established loci: namely, ß-giardin (bg), triosephosphate isomerase (tpi), and glutamate dehydrogenase (gdh). The overall prevalence of G. duodenalis in donkeys in Shanxi Province was 16.81% (137/815). The region was identified as the main risk factor for the observed difference in G. duodenalis prevalence in donkeys among the three study areas (χ2 = 21.611, p < 0.001). Assemblages A, E, and B were identified, with the latter as the predominant assemblage. Three MLGs (MLG-novel-1 to 3) were formed based on sequence variation among the three loci. The present study reveals the presence of G. duodenalis in donkeys in Shanxi Province, North China, for the first time, which not only enriches the data on the distribution of G. duodenalis in donkeys in China but also provides useful baseline data for planning control strategies against G. duodenalis infection in the sampled areas.

Neuronal-specific TNFAIP1 ablation attenuates postoperative cognitive dysfunction via targeting SNAP25 for K48-linked ubiquitination.

BACKGROUND: Synaptosomal-associated protein 25 (SNAP25) exerts protective effects against postoperative cognitive dysfunction (POCD) by promoting PTEN-induced kinase 1 (PINK1)/Parkin-mediated mitophagy and repressing caspase-3/gasdermin E (GSDME)-mediated pyroptosis. However, the regulatory mechanisms of SNAP25 protein remain unclear. METHODS: We employed recombinant adeno-associated virus 9 (AAV9)-hSyn to knockdown tumor necrosis factor α-induced protein 1 (TNFAIP1) or SNAP25 and investigate the role of TNFAIP1 in POCD. Cognitive performance, hippocampal injury, mitophagy, and pyroptosis were assessed. Co-immunoprecipitation (co-IP) and ubiquitination assays were conducted to elucidate the mechanisms by which TNFAIP1 stabilizes SNAP25. RESULTS: Our results demonstrated that the ubiquitin ligase TNFAIP1 was upregulated in the hippocampus of mice following isoflurane (Iso) anesthesia and laparotomy. The N-terminal region (residues 1-96) of TNFAIP1 formed a conjugate with SNAP25, leading to lysine (K) 48-linked polyubiquitination of SNAP25 at K69. Silencing TNFAIP1 enhanced SH-SY5Y cell viability and conferred antioxidant, pro-mitophagy, and anti-pyroptosis properties in response to Iso and lipopolysaccharide (LPS) challenges. Conversely, TNFAIP1 overexpression reduced HT22 cell viability, increased reactive oxygen species (ROS) accumulation, impaired PINK1/Parkin-dependent mitophagy, and induced caspase-3/GSDME-dependent pyroptosis by suppressing SNAP25 expression. Neuron-specific knockdown of TNFAIP1 ameliorated POCD, restored mitophagy, and reduced pyroptosis, which was reversed by SNAP25 depletion. CONCLUSIONS: In summary, our findings demonstrated that inhibiting TNFAIP1-mediated degradation of SNAP25 might be a promising therapeutic approach for mitigating postoperative cognitive decline. Video Abstract.

Alternative polyadenylation regulates acetyl-CoA carboxylase function in peanut.

BACKGROUND: Polyadenylation is a crucial process that terminates mRNA molecules at their 3'-ends. It has been observed that alternative polyadenylation (APA) can generate multiple transcripts from a single gene locus, each with different polyadenylation sites (PASs). This leads to the formation of several 3' untranslated regions (UTRs) that vary in length and composition. APA has a significant impact on approximately 60-70% of eukaryotic genes and has far-reaching implications for cell proliferation, differentiation, and tumorigenesis. RESULTS: In this study, we conducted long-read, single-molecule sequencing of mRNA from peanut seeds. Our findings revealed that over half of all peanut genes possess over two PASs, with older developing seeds containing more PASs. This suggesting that the PAS exhibits high tissue specificity and plays a crucial role in peanut seed maturation. For the peanut acetyl-CoA carboxylase A1 (AhACCA1) gene, we discovered four 3' UTRs referred to UTR1-4. RT-PCR analysis showed that UTR1-containing transcripts are predominantly expressed in roots, leaves, and early developing seeds. Transcripts containing UTR2/3 accumulated mainly in roots, flowers, and seeds, while those carrying UTR4 were constitutively expressed. In Nicotiana benthamiana leaves, we transiently expressed all four UTRs, revealing that each UTR impacted protein abundance but not subcellular location. For functional validation, we introduced each UTR into yeast cells and found UTR2 enhanced AhACCA1 expression compared to a yeast transcription terminator, whereas UTR3 did not. Furthermore, we determined ACC gene structures in seven plant species and identified 51 PASs for 15 ACC genes across four plant species, confirming that APA of the ACC gene family is universal phenomenon in plants. CONCLUSION: Our data demonstrate that APA is widespread in peanut seeds and plays vital roles in peanut seed maturation. We have identified four 3' UTRs for AhACCA1 gene, each showing distinct tissue-specific expression patterns. Through subcellular location experiment and yeast transformation test, we have determined that UTR2 has a stronger impact on gene expression regulation compared to the other three UTRs.

Prevalence and Genetic Characterization of Blastocystis in Sheep and Pigs in Shanxi Province, North China: From a Public Health Perspective.

Blastocystis is a common zoonotic intestinal protozoan and causes a series of gastrointestinal symptoms in humans and animals via the fecal-oral route, causing economic losses and posing public health problems. At present, the prevalence and genetic structure of Blastocystis in sheep and pigs in Shanxi province remains unknown. Thus, the present study collected 492 sheep fecal samples and 362 pig fecal samples from three representative counties in northern, central and southern Shanxi province for the detection of Blastocystis based on its SSU rRNA gene. The results showed that the overall prevalence of Blastocystis in the examined sheep and pigs were 16.26% and 14.09%, respectively. Sequences analyses showed that four known subtypes (ST5, ST10, ST14 and ST30) in sheep and two subtypes (ST1 and ST5) in pigs were detected in this study, with ST5 being the predominate subtype among the study areas. Phylogenetic analysis showed that the same subtypes were clustered into the same branch. This study reveals that sheep and pigs in Shanxi province are hosts for multiple Blastocystis subtypes, including the zoonotic subtypes (ST1 and ST5), posing a risk to public health. Baseline epidemiological data are provided that help in improving our understanding of the role of zoonotic subtypes in Blastocystis transmission.

Molecular Identification and Genotyping of Cryptosporidium spp. and Blastocystis sp. in Cattle in Representative Areas of Shanxi Province, North China.

Both Cryptosporidium spp. and Blastocystis sp. are common intestinal protozoa, which can cause zoonotic diseases and economic losses to livestock industry. To evaluate the prevalence and genetic population structure of Cryptosporidium spp. and Blastocystis sp. in beef and dairy cattle in Shanxi Province, north China, a total of 795 fecal samples were collected from beef and dairy cattle in three representative counties in Shanxi Province, and these fecal samples were examined using molecular approaches based on 18S small-subunit ribosomal RNA (SSU rRNA) of Cryptosporidium spp. and Blastocystis sp., respectively. Among 795 cattle fecal samples, 23 were detected as Cryptosporidium-positive and 103 were detected as Blastocystis-positive, and the overall prevalence of Cryptosporidium spp. and Blastocystis sp. in cattle in Shanxi Province was 2.9% and 13.0%, respectively. For Cryptosporidium spp., DNA sequence analysis indicated that all 23 positive samples were identified as C. andersoni. Furthermore, five known subtypes (ST1, ST10, ST14, ST21 and ST26) and three unknown subtypes of Blastocystis sp. were detected among 103 positive samples using DNA sequence analysis. This study reported the occurrence and prevalence of Cryptosporidium spp. and Blastocystis sp. in cattle in Shanxi Province for the first time, which extends the geographical distribution of these two zoonotic parasites and provides baseline data for the prevention and control of these two important zoonotic parasites in cattle in Shanxi Province.

Seroprevalence of Toxoplasma gondii infection in sheep and cattle in Shanxi Province, North China.

Toxoplasmosis is a worldwide zoonotic disease caused by infection with the intracellular protozoan parasite Toxoplasma gondii, posing significant economic losses to the livestock industry. As a major livestock province, little is known of the prevalence of T. gondii infection in sheep and cattle in Shanxi Province, North China. In this study, a total of 1962 blood samples from cattle (n = 978) and sheep (n = 984), collected from 11 administrative cities in Shanxi Province, were examined for antibodies against T. gondii by using the indirect enzyme linked immunosorbent assay (ELISA) kits commercially available. The results showed that antibodies to T. gondii were detected in 306 of the 978 cattle serum samples (31.29%, 95% CI 28.38-34.19), ranging from 12.64% to 60.00% among the different cities. The overall seroprevalence of T. gondii in sheep was 17.78% (175/984, 95% CI 15.40-20.17), ranging from 2.22% to 41.11% among the different administrative cities. The T. gondii seroprevalence was associated with the management mode and geographical location. This is the first report of T. gondii seroprevalence in cattle and sheep in Shanxi Province, North China, which provides baseline data to plan future control strategies for T. gondii infection in this province.

SNAP25 ameliorates postoperative cognitive dysfunction by facilitating PINK1-dependent mitophagy and impeding caspase-3/GSDME-dependent pyroptosis.

Insufficient PTEN-induced kinase 1 (PINK1)-mediated mitophagy and activation of caspase-3/gasdermin E (GSDME)-dependent pyroptosis constitute the potential etiology of postoperative cognitive dysfunction (POCD), a severe neurological complication characterized by learning and memory deficits. Synaptosomal-Associated Protein 25 (SNAP25), a well-defined presynaptic protein that mediates the fusion between synaptic vesicles and plasma membrane, is crucial in autophagy and the trafficking of extracellular proteins to the mitochondria. We investigated whether SNAP25 regulates POCD via mitophagy and pyroptosis. SNAP25 downregulation was observed in the hippocampi of rats undergoing isoflurane anesthesia and laparotomy. SNAP25 silencing restrained PINK1-mediated mitophagy and promoted reactive oxygen species (ROS) production and caspase-3/GSDME-dependent pyroptosis in isoflurane (Iso) + lipopolysaccharide (LPS)-primed SH-SY5Y cells. SNAP25 depletion also destabilized PINK1 on the outer membrane of the mitochondria and blocked Parkin translocation to the mitochondria. In contrast, SNAP25 overexpression alleviated POCD and Iso + LPS-induced defective mitophagy and pyroptosis, which was reversed by PINK1 knockdown. These findings suggest that SNAP25 exerts neuroprotective effects against POCD by boosting PINK1-dependent mitophagy and hindering caspase-3/GSDME-dependent pyroptosis, providing a novel option for the management of POCD.

Inhibition of PINK1-Mediated Mitophagy Contributes to Postoperative Cognitive Dysfunction through Activation of Caspase-3/GSDME-Dependent Pyroptosis.

PTEN-induced kinase 1 (PINK1)-mediated mitophagy and caspase-1/gasdermin D canonical pyroptosis pathways have been implicated in the pathogenesis of postoperative cognitive dysfunction (POCD). However, gasdermin E (GSDME), another recently identified executioner of pyroptosis that can be specifically cleaved by caspase-3, is highly expressed in the brain and neurons. This study aimed to ascertain whether PINK1-dependent mitophagy governs postoperative cognitive capacity through caspase-3/GSDME. Twelve month old male Sprague-Dawley rats underwent exploratory laparotomy under isoflurane anesthesia. Lipopolysaccharide (LPS)-primed SH-SY5Y cells were used to mimic postsurgical neuroinflammation. For the interventional study, rats were administered with adeno-associated virus serotype 9 (AAV9)-mediated silencing of Pink1 and/or caspase-3 inhibitor Ac-DEVD-CHO (Ac-DC). SH-SY5Y cells were treated with siPINK1 and/or Ac-DC. Cognitive performance was assessed using the Morris water maze test. The mitophagy- and pyroptosis-related parameters were determined in the hippocampus and SH-SY5Y cells. Anesthesia/surgery and LPS caused defective PINK1-mediated mitophagy and activation of caspase-3/GSDME-dependent pyroptosis. AAV-9 mediated Pink1 overexpression mitigated cognitive impairment and caspase-3/GSDME-dependent pyroptosis. Conversely, inhibition of PINK1 aggravates POCD and overactivates neuronal pyroptosis. These abnormalities were rescued by Ac-DC treatment. Collectively, PINK1-mediated mitophagy regulates anesthesia and surgery-induced cognitive impairment by negatively affecting the caspase-3/GSDME pyroptosis pathway, which provides a promising therapeutic target for POCD.

Super resolution imaging reconstruction reveals that gold standard methods may not correctly conclude neural/brain functional recovery.

The status of cerebral perfusion and its restoration level play a vital role in the prognosis and clinical decision making of many neurosurgical diseases. As such, gold standard methods including CT, MR and ICP monitoring, which can indicate and measure cerebral perfusion and restoration, have been widely adopted to evaluate whether or not a patient has recovered from neurofunctional disabilities. This robust combination of methods, however, is confronted with a growing number of contradictions in recent years due to its inability to measure the status of cerebral reperfusion in microvasculature level, even though this has been shown to determine neurofunctional restoration as well or even better. To this date, nevertheless, we have very limited imaging methods that could evaluate human cerebral microperfusion both safely and accurately under most neurosurgical conditions. We herein report a new method of acquiring a patient's cerebral microperfusion status noninvasively which could display the precise distribution of microvasculature in deep cerebral regions with a resolution of ∼30 µm, using everyday bed-side ultrasonography combined with a computerized super-resolution reconstruction algorithm. Using this imaging modality, we found that a patient's cerebral microperfusion might not be improved by some routine administrations even though the gold standard method had yielded the opposite conclusions. Our imaging modality retains the safe, portable feature of ordinary ultrasonography while possesses the extraordinary super-resolution nature, which enables an efficient, precise diagnosis of cerebral perfusion. Most importantly, the super resolution nature of this method may also facilitate early-stage evaluation of a patient's neurofunctional restoration level and avoid overoptimistic conclusions from conventional angiography or ICP monitoring.

Seroprevalence and Risk Factors of Chlamydia Infection in Cattle in Shanxi Province, North China.

The information on Chlamydia infection in cattle is limited in Shanxi Province, north China. This study aimed to investigate the seroprevalence and risk factors of Chlamydia and Chlamydia abortus infection in cattle in Shanxi Province. In November 2020, a large-scale investigation of Chlamydia seroprevalence was conducted on 981 cattle serum samples collected from 40 cattle farms in 11 cities of Shanxi Province. The seroprevalence of Chlamydia and C. abortus was examined by indirect hemagglutination assay (IHA) and enzyme-linked immunosorbent assay (ELISA), respectively. The seroprevalence of Chlamydia and C. abortus was 52.29% (513/981) and 2.96% (29/981), respectively, in cattle in Shanxi Province. Location was identified as a risk factor for Chlamydia and C. abortus infection (p < 0.05). Under different management patterns, the seroprevalence of Chlamydia and C. abortus in large-scale animal farming companies was higher than that in household animal farms and animal farming cooperatives, and only the seroprevalence of Chlamydia was significantly different in different management patterns (p < 0.01). The results showed that there was higher seroprevalence of Chlamydia in cattle in Shanxi Province, while C. abortus was not the dominant species. This study provided baseline information on Chlamydia infection in cattle in Shanxi Province, which constitutes valuable data for monitoring livestock health and preventing potential zoonoses.

Altered miRNA Expression Profiles in the Serum of Beagle Dogs Experimentally Infected with Toxocara canis.

Toxocara canis is a neglected roundworm, which can cause debilitating disease in dogs and humans worldwide. Serum is an excellent material for monitoring the occurrence of many diseases. However, no information is available on the expression of microRNAs (miRNAs) in the serum of dogs infected with T. canis. In this study, RNA-seq analysis was performed to identify the serum miRNA profiles in Beagle dogs infected with T. canis at different stages of infection. A total of 3, 25 and 25 differently expressed miRNAs (DEmiRNAs) were identified in dog serum at 24 h post-infection (hpi), 10 days post-infection (dpi) and 36 dpi, respectively, such as cfa-let-7g, cfa-miR-16, cfa-miR-92b, cfa-miR-93, cfa-miR-122, cfa-miR-485 and cfa-miR-451. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that these miRNAs could regulate the pathways related to parasitic infectious diseases and immune system, such as amoebiasis, toxoplasmosis, platelet activation, IL-17 signaling pathway and chemokine signaling pathway. These results provide a foundation to explore the underlying regulatory role of miRNAs in definitive hosts after T. canis infection.

cGAS-STING pathway aggravates early cerebral ischemia-reperfusion injury in mice by activating NCOA4-mediated ferritinophagy.

Stroke patients are often complicated by cerebral ischemia-reperfusion injury (CIRI) after the restoration of cerebral perfusion, and how to prevent CIRI at an early stage has received close attention. The imbalance of iron metabolism is one of the essential factors in the aggravation of CIRI, and NCOA4-mediated ferritinophagy, as a critical pathway to regulate iron metabolism, is expected to be an effective intervention target. We established a mouse model of cerebral ischemia-reperfusion (CIR) with NCOA4 silencing. We found that activation of NCOA4-mediated ferritinophagy atthe early stage of CIR mediated the onset of oxidative stress and contributed to autophagy and apoptosis, and eventually resulted in increased brain injury. This suggests that NCOA4-mediated ferritinophagy plays a vital role in early CIR and can be an effective target to prevent and treat CIRI. We next explored the upstream regulatory targets of NCOA4-mediated ferritinophagy. The previous evidence for the cGAS-STING pathway's importance during CIR and its strong relationship with autophagy attracted our attention. To investigate whether the cGAS-STING pathway regulates NCOA4-mediated ferritinophagy, we further administered a cGAS inhibitor to mice with CIR and overexpressed NCOA4. Along with the inhibition of the cGAS-STING pathway, ferritinophagy, oxidative stress, autophagy, and apoptosis were inhibited, and CIRI was ameliorated, which was attenuated by NCOA4 overexpression. In conclusion, our results suggest that activation of the cGAS-STING pathway exacerbates CIRI at the early stage of CIR, which may be achieved by mediating NCOA4-mediated ferritinophagy.

Testosterone and soluble ST2 as mortality predictive biomarkers in male patients with sepsis-induced cardiomyopathy.

Sepsis-induced cardiomyopathy (SIC) is characterized by high mortality and poor outcomes. This study aimed to explore the relationship between testosterone and soluble ST2 (sST2) and all-cause mortality in patients with SIC. Clinical data from SIC patients at Renmin Hospital of Wuhan University from January 2021 and March 2023 were reviewed. Serum testosterone and sST2 were measured at admission. Kaplan-Meier analysis and receiver operative characteristic curve (ROC) were used to estimate the predictive values of testosterone and sST2 on 28 days and 90 days mortality of SIC. A total of 327 male subjects with SIC were enrolled in this study. During the 28 days and 90 days follow-up, 87 (26.6%) and 103 deaths (31.5%) occurred, respectively. Kaplan-Meier analysis showed significantly higher 28 days and 90 days survival in patients with higher testosterone and decreased sST2 levels (p < 0.001). Testosterone, sST2, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were significantly associated with 28 days and 90 days mortality (p < 0.05). Partial correlation analysis showed strong positive correlation between testosterone and left ventricular ejection fraction (LVEF) (p < 0.001), and negative correlation between testosterone and sST2 (p < 0.001), high-sensitivity troponin I (hs-TnI) levels (p < 0.001) and smoke history (p < 0.01). The concentrations of sST2 were positively related with E/e' ratio (p < 0.001), and negatively correlated with TAPSE (p < 0.001). The combination of testosterone and sST2 enhanced the prediction of both 28 days [area under the ROC curve (AUC), 0.805] and 90 days mortality (AUC, 0.833). Early serum testosterone and sST2 levels could predict mortality of SIC independently and jointly. Further research is needed to determine the utility of biochemical markers in identifying high-risk patients with SIC.