Loss of function of OsL1 gene cause early flowering in rice under short-day conditions.

Heading date is one of the important agronomic traits that affects rice yield. In this study, we cloned a new rice B3 family gene, OsL1, which regulates rice heading date. Importantly, osl1-1 and osl1-2, two different types of mutants of OsL1 were created using the gene editing technology CRISPR/Cas9 system and exhibited 4 days earlier heading date than that of the wild type under short-day conditions. Subsequently, the plants overexpressing OsL1, OE-OsL1, showed a 2-day later heading date than the wild type in Changsha and a 5-day later heading date in Lingshui, but there was no significant difference in other yield traits. Moreover, the results of subcellular localization study indicated that OsL1 protein was located in the nucleus and the expression pattern analysis showed that OsL1 gene was expressed in rice roots, stems, leaves, and panicles, and the expression level was higher at the root and weak green panicle. In addition, the OsL1 gene was mainly expressed at night time under short-light conditions. The transcriptomic analysis indicated that OsL1 might be involved in the Hd1-Hd3a pathway function. Together, our results revealed that the cloning and functional analysis of OsL1 can provide new strategy for molecular design breeding of rice with suitable fertility period. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01444-1.

miR-425-5p Regulates Proliferation of Bovine Mammary Epithelial Cells by Targeting TOB2.

In recent years, rising temperatures have caused heat stress (HS), which has had a significant impact on livestock production and growth, presenting considerable challenges to the agricultural industry. Research has shown that miR-425-5p regulates cellular proliferation in organisms. However, the specific role of miR-425-5p in bovine mammary epithelial cells (BMECs) remains to be determined. The aim of this study was to investigate the potential of miR-425-5p in alleviating the HS-induced proliferation stagnation in BMECs. The results showed that the expression of miR-425-5p significantly decreased when BMEC were exposed to HS. However, the overexpression of miR-425-5p effectively alleviated the inhibitory effect of HS on BMEC proliferation. Furthermore, RNA sequencing analysis revealed 753 differentially expressed genes (DEGs), comprising 361 upregulated and 392 downregulated genes. Some of these genes were associated with proliferation and thermogenesis through enrichment analyses. Further experimentation revealed that TOB2, which acts as a target gene of miR-425-5p, is involved in the regulatory mechanism of BMEC proliferation. In summary, this study suggests that miR-425-5p can promote the proliferation of BMECs by regulating TOB2. The miR-425-5p/TOB2 axis may represent a potential pathway through which miR-425-5p ameliorates the proliferation stagnation of BMECs induced by HS.

Lateralized response of skull bone marrow via osteopontin signaling in mice after ischemia reperfusion.

Skull bone marrow is thought to be an immune tissue closely associated with the central nervous system (CNS). Recent studies have focused on the role of skull bone marrow in central nervous system disorders. In this study, we performed single-cell RNA sequencing on ipsilateral and contralateral skull bone marrow cells after experimental stroke and then performed flow cytometry and analysis of cytokine expression. Skull marrow showed lateralization in response to stroke. Lateralization is demonstrated primarily by the proliferation and differentiation of myeloid and lymphoid lineage cells in the skull bone marrow adjacent to the ischemic region, with an increased proportion of neutrophils compared to monocytes. Analysis of chemokines in the skull revealed marked differences in chemotactic signals between the ipsilateral and contralateral skull, whereas sympathetic signals innervating the skull did not affect cranial bone marrow lateralization. Osteopontin (OPN) is involved in region-specific activation of the skull marrow that promotes inflammation in the meninges, and inhibition of OPN expression improves neurological function.

Model Parameter Estimation As Features to Predict the Duration of Epileptic Seizures From Onset.

The durations of epileptic seizures are linked to severity and risk for patients. It is unclear if the spatiotemporal evolution of a seizure has any relationship with its duration. Understanding such mechanisms may help reveal treatments for reducing the duration of a seizure. Here, we present a novel method to predict whether a seizure is going to be short or long at its onset using features that can be interpreted in the parameter space of a brain model. The parameters of a Jansen-Rit neural mass model were tracked given intracranial electroencephalography (iEEG) signals, and were processed as time series features using MINIROCKET. By analysing 2954 seizures from 10 patients, patient-specific classifiers were built to predict if a seizure would be short or long given 7 s of iEEG at seizure onset. The method achieved an area under the receiver operating characteristic curve (AUC) greater than 0.6 for five of 10 patients. The behaviour in the parameter space has shown different mechanisms are associated with short/long seizures.Clinical relevance-This shows that it is possible to classify whether a seizure will be short or long based on its early characteristics. Timely interventions and treatments can be applied if the duration of the seizures can be predicted.

lncRNA MSTRG4710 Promotes the Proliferation and Differentiation of Preadipocytes through miR-29b-3p/IGF1 Axis.

Obesity, a major global health issue, is increasingly associated with the integral role of long non-coding RNA (lncRNA) in adipogenesis. Recently, we found that lncRNA-MSTRG4710 was highly expressed in the liver of rabbits fed a high-fat diet, but whether it is involved in lipid metabolism remains unclear. A series of experiments involving CCK-8, EDU, qPCR, and Oil Red O staining demonstrated that the overexpression of MSTRG4710 stimulated the proliferation and differentiation of preadipocytes while its knockdown inhibited these processes. Bioinformatics analysis showed that miR-29b-3p was a potential target gene of MSTRG4710, and IGF1 was a downstream target gene of miR-29b-3p. Luciferase reporter gene analysis and qPCR analysis confirmed that miR-29b-3p was a potential target gene of MSTRG4710, and miR-29b-3p directly targeted the 3'UTR of IGF1. The overexpression of miR-29b-3p was observed to regulate IGF1 protein and mRNA levels negatively. Additionally, a total of 414 known differentially expressed genes between the miR-29b-3p mimic, miR-29b-3p negative control (NC), siMSTRG4710, and siMSTRG4710-NC group were screened via transcriptome sequencing technology. The GO- and KEGG-enriched pathways were found to be related to lipid metabolism. The study also established that miR-29b-3p targets IGF1 to inhibit preadipocyte proliferation and differentiation. Notably, IGF1 knockdown significantly reduced preadipocyte proliferation and differentiation. Furthermore, co-transfection of pcDNA3.1(+)-MSTRG4710 and mimics into rabbit preadipocytes revealed that the mimics reversed the promotional effect of pcDNA3.1(+)-MSTRG4710. In conclusion, these results uncover that MSTRG4710 positively regulated cell proliferation and adipogenesis by the miR-29b-3p/IGF1 axis. Our findings might provide a new target for studying adipogenesis in rabbit preadipocytes and obesity.

Ly6C-high monocytes alleviate brain injury in experimental subarachnoid hemorrhage in mice.

BACKGROUND: Subarachnoid hemorrhage (SAH) is an uncommon type of potentially fatal stroke. The pathophysiological mechanisms of brain injury remain unclear, which hinders the development of drugs for SAH. We aimed to investigate the pathophysiological mechanisms of SAH and to elucidate the cellular and molecular biological response to SAH-induced injury. METHODS: A cross-species (human and mouse) multiomics approach combining high-throughput data and bioinformatic analysis was used to explore the key pathophysiological processes and cells involved in SAH-induced brain injury. Patient data were collected from the hospital (n = 712). SAH was established in adult male mice via endovascular perforation, and flow cytometry, a bone marrow chimera model, qPCR, and microglial depletion experiments were conducted to explore the origin and chemotaxis mechanism of the immune cells. To investigate cell effects on SAH prognosis, murine neurological function was evaluated based on a modified Garcia score, pole test, and rotarod test. RESULTS: The bioinformatics analysis confirmed that inflammatory and immune responses were the key pathophysiological processes after SAH. Significant increases in the monocyte levels were observed in both the mouse brains and the peripheral blood of patients after SAH. Ly6C-high monocytes originated in the bone marrow, and the skull bone marrow contribute a higher proportion of these monocytes than neutrophils. The mRNA level of Ccl2 was significantly upregulated after SAH and was greater in CD11b-positive than CD11b-negative cells. Microglial depletion, microglial inhibition, and CCL2 blockade reduced the numbers of Ly6C-high monocytes after SAH. With CCR2 antagonization, the neurological function of the mice exhibited a slow recovery. Three days post-SAH, the monocyte-derived dendritic cell (moDC) population had a higher proportion of TNF-α-positive cells and a lower proportion of IL-10-positive cells than the macrophage population. The ratio of moDCs to macrophages was higher on day 3 than on day 5 post-SAH. CONCLUSIONS: Inflammatory and immune responses are significantly involved in SAH-induced brain injury. Ly6C-high monocytes derived from the bone marrow, including the skull bone marrow, infiltrated into mouse brains via CCL2 secreted from microglia. Moreover, Ly6C-high monocytes alleviated neurological dysfunction after SAH.

Paraneoplastic anti-GAD65 extralimbic encephalitis presented with epilepsy: A case report.

RATIONALE: Autoimmunity targeting glutamic acid decarboxylase 65 (GAD65) is associated with type 1 diabetes mellitus as well as various neurological diseases. In the central nervous system, GAD65 autoimmunity usually presents with limbic encephalitis, whereas extralimbic encephalitis (ELE) has only been reported in a few cases. Moreover, anti-GAD65 ELE in the paraneoplastic context has not yet been reported. PATIENT CONCERNS: A 60-year-old man presented with intermittent cough and sputum for 10 years, with no other diseases. The patient presented with recurrent seizures that were resistant to antiepileptic drugs (AEDs). Chest computed tomography and pathological results confirmed the diagnosis of small cell lung cancer. Paraneoplastic testing found a high level of GAD65 antibodies in his serum, and cerebrospinal fluid analysis revealed lymphocytic pleocytosis, indicating autoimmune encephalitis. Brain magnetic resonance imaging showed multifocal T2 fluid-attenuated inversion recovery hyperintensities in the extralimbic areas including the subcortex and deep white matter of the bilateral frontal lobe, parietal lobe, and insula lobes. DIAGNOSES: Finally, a diagnosis of anti-GAD65 autoimmune ELE with a paraneoplastic etiology from the small cell lung cancer was suspected. INTERVENTIONS: The patient refused any tumor-suppressive treatment or immunotherapy for potential side effects and only received AEDs levetiracetam, sodium valproate, and diazepam. OUTCOMES: The epilepsy of the patient was resistant to AEDs, and the patient died a week after discharge due to disease progression. LESSONS: Anti-GAD65 autoimmune encephalitis can be extralimbic, can present with isolated epilepsy, and extralimbic anti-GAD65 encephalitis can occur with an underlying malignancy.

A Preliminary Study of the Potential Molecular Mechanisms of Individual Growth and Rumen Development in Calves with Different Feeding Patterns.

At present, it is common to feed calves with "Concentrate", "Concentrate + hay" and TMR "Total Mixed Rations" feeding patterns in China, which achieved well feeding efficiency, but the three feeding patterns molecular regulation mechanism in actual production is still unclear. The study aimed to explore the most suitable feeding pattern for Chinese Holstein calves to improve the rumen fermentation function and growth performance of calves. In this regard, the interactions between rumen microorganisms and host metabolism were investigated. The rumen volume and weight of calves in the GF group were significantly higher than those in the GFF and TMR groups (p < 0.05), and the rumen pH of calves in the GF group was 6.47~6.79. Metagenomics analysis revealed that the rumen microbiome of GF and GFF calves had higher relative abundances of Methanobrevibacter, Methanosphaera, and Methanolacinia (p < 0.05). Prevotella multisaccharivorax was significantly more abundant in the rumen of GF calves (p < 0.05), indicating that GF group calves had a stronger ability to ferment sugars. Notably, in the pyruvate metabolic pathway, phosphoenolpyruvate carboxylase was significantly up-regulated in GF calves compared with the TMR group, and pyruvate-phosphate dikinase was significantly down-regulated. Metabolomic results showed that Ursodeoxycholic acid was significantly up-regulated in GF calves, and most of the differential metabolites were enriched in Bile secretion pathways. The association analysis study found that the microorganisms of Prevotella and Ruminococcaceae might cooperate with the host, which was helpful for the digestion and absorption of lipids and made the calves have better growth. The three feeding modes had similar effects, but the 'GF' feeding pattern was more beneficial to the individual growth and ruminal development regarding ruminal morphology, contents physiology and microorganisms. Furthermore, the synergistic effect of rumen microorganisms and the host could more effectively hydrolyze lipid substances and promote the absorption of lipids, which was of great significance to the growth of calves.

Src inhibition rescues FUNDC1-mediated neuronal mitophagy in ischaemic stroke.

BACKGROUND: Ischaemic stroke triggers neuronal mitophagy, while the involvement of mitophagy receptors in ischaemia/reperfusion (I/R) injury-induced neuronal mitophagy remain not fully elucidated. Here, we aimed to investigate the involvement of mitophagy receptor FUN14 domain-containing 1 (FUNDC1) and its modulation in neuronal mitophagy induced by I/R injury. METHODS: Wild-type and FUNDC1 knockout mice were generated to establish models of neuronal I/R injury, including transient middle cerebral artery occlusion (tMCAO) in vivo and oxygen glucose deprivation/reperfusion in vitro. Stroke outcomes of mice with two genotypes were assessed. Neuronal mitophagy was analysed both in vivo and in vitro. Activities of FUNDC1 and its regulator Src were evaluated. The impact of Src on FUNDC1-mediated mitophagy was assessed through administration of Src antagonist PP1. RESULTS: To our surprise, FUNDC1 knockout mice subjected to tMCAO showed stroke outcomes comparable to those of their wild-type littermates. Although neuronal mitophagy could be activated by I/R injury, FUNDC1 deletion did not disrupt neuronal mitophagy. Transient activation of FUNDC1, represented by dephosphorylation of Tyr18, was detected in the early stages (within 3 hours) of neuronal I/R injury; however, phosphorylated Tyr18 reappeared and even surpassed baseline levels in later stages (after 6 hours), accompanied by a decrease in FUNDC1-light chain 3 interactions. Spontaneous inactivation of FUNDC1 was associated with Src activation, represented by phosphorylation of Tyr416, which changed in parallel with the level of phosphorylated FUNDC1 (Tyr18) during neuronal I/R injury. Finally, FUNDC1-mediated mitophagy in neurons under I/R conditions can be rescued by pharmacological inhibition of Src. CONCLUSIONS: FUNDC1 is inactivated by Src during the later stage (after 6 hours) of neuronal I/R injury, and rescue of FUNDC1-mediated mitophagy may serve as a potential therapeutic strategy for treating ischaemic stroke.

Risk of Death from Alzheimer's Disease Associated with Brain Tumor, Glioma, and Glioblastoma.

BACKGROUND: No study has compared the risk of Alzheimer's disease (AD) in patients with brain tumors, gliomas, or glioblastomas with the risk in patients with other tumors. OBJECTIVE: To determine whether, compared with other tumors, brain tumors, gliomas, and glioblastomas increase the risk of AD. METHODS: This study identified a case group of 24,441 patients from the Surveillance, Epidemiology, and End Results (SEER) database who were diagnosed with only one primary tumor at age > 20 years in 1975-2019 and died from AD at age > 65 years as case group. The control group comprised 122,205 subjects from the SEER database who died from causes other than AD but otherwise had the same conditions as those in the case group. RESULTS: There was a significantly lower prevalence of glioma (0.074% versus 0.14%, p = 0.007) and glioblastoma (0.0082% versus 0.074%, p = 0.001) in patients who died from AD than in those who died from other causes, while brain tumors were not significantly associated with AD death (p = 0.227). When adjusted for factors including age at death, sex, race, tumor behavior, radiation therapy and tumor-directed surgery, glioblastoma was related to a significantly lower AD risk than other tumors (odds ratio: 0.19, 95% CI: 0.05-0.77). Additionally, patients who were older, female, American Indian/Alaska Native, had a benign tumor, radiation therapy and tumor-directed surgery had a significantly higher risk of dying from AD. CONCLUSION: Gliomas and glioblastomas were associated with a significantly lower risk of death from AD than other tumors.

The effects of differential feeding on ileum development, digestive ability and health status of newborn calves.

Pre-weaning is the most important period for the growth and development of calves. Intestinal morphology, microbial community and immunity are initially constructed at this stage, and even have a lifelong impact on calves. Early feeding patterns have a significant impact on gastrointestinal development and microbial communities. This study mainly analyzed the effects of three feeding methods on the gastrointestinal development of calves, and provided a theoretical basis for further improving the feeding mode of calves. it is very important to develop a suitable feeding mode. In this study, we selected nine newborn healthy Holstein bull calves were randomly selected and divided into three groups (n = 3), which were fed with starter + hay + milk (SH group), starter + milk (SF group), total mixed ration + milk (TMR group). After 80 days of feeding Feeding to 80 days of age after, the ileum contents and blood samples were collected, and the differences were compared and analyzed by metagenomic analysis and serum metabolomics analysis. Results show that compared with the other two groups, the intestinal epithelium of the SH group was more complete and the goblet cells developed better. The feeding method of SH group was more conducive to the development of calves, with higher daily gain and no pathological inflammatory reaction. The intestinal microbial community was more conducive to digestion and absorption, and the immunity was stronger. These findings are helpful for us to explore better calf feeding patterns. In the next step, we will set up more biological replicates to study the deep-seated reasons for the differences in the development of pre-weaning calves. At the same time, the new discoveries of neuro microbiology broaden our horizons and are the focus of our future attention.

Vaginal Microbiome Dynamics of Cows in Different Parities.

At present, there is still room for research on the relationship between the vaginal microbiome and the reproductive health of dairy cows. In this study, high-throughput 16S rRNA sequencing technology was used to explore the differences of bacterial communities of dairy cows of different births, gain a deeper understanding of cow reproductive physiology, and maintain cow health. With the increase in parity, the number of vaginal flora decreased from 3511 to 469, but the number of species increased significantly, and Chao1 increased from 1226.41 ± 345.40 to 1467.76 ± 269.76. There was a significant difference in the number of vaginal microbiome functions between uncounted cows and calving cows. There was no significant difference in microbial diversity in calves. The relative abundance variation of vaginal microbiota in high-parity cows is less than that in low-parity cows. The amino acid metabolism of calves increased, the endocrine function of high-parity cows was enhanced, and the function of the vaginal microbiome increased after the first delivery, which gradually decreased with the increase in parity. This study also found that Methanobacteria and Caviibacter may be involved in amino acid metabolism and endocrine function, and they may play a key role in cow reproduction. This study provides an important theoretical basis for studying changes in vaginal microorganisms in dairy cows, improves the understanding of reproductive health and production performance, and provides a scientific basis for improving the reproductive management of dairy cows.

miR-383-5p Regulates Preadipocyte Proliferation and Differentiation by Targeting RAD51AP1.

Obesity has become a major health problem worldwide, and increasing evidence supports the importance of microRNAs (miRNAs) in its pathogenesis. Recently, we found that miR-383-5p_1 is highly expressed in the perirenal fat of high-fat-fed rabbits, but it is not yet known whether miR-383-5p is involved in lipid metabolism. Here, we used transcriptome sequencing technology to screen 1642 known differentially expressed genes between miR-383-5p mimic groups and miR-383-5p negative control groups. Gene Ontology Resource (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were enriched in the pathway related to lipid metabolism, and glycine biosynthesis, the NOD receptor signal pathway and nonalcoholic fatty liver were significantly enriched. Afterwards, our research results indicated that miR-383-5p can promote the proliferation and differentiation of rabbit preadipocytes, and there is a direct targeting relationship with RAD51AP1. Mechanistically, miR-383-5p directly interacts with the lipid metabolism and participates in adipogenesis and lipid accumulation by targeting RAD51AP1. In conclusion, our data highlight a physiological role for miRNA in lipid metabolism and suggest the miR-383-5p/RAD51AP1 axis may represent a potential mechanism for controlling lipid accumulation in obesity.

Development of microRNA-based therapeutics for central nervous system diseases.

MicroRNA (miRNA)-mediated gene silencing is a method of RNA interference in which a miRNA binds to messenger RNA sequences and regulates target gene expression. MiRNA-based therapeutics have shown promise in treating a variety of central nervous system diseases, as verified by results from diverse preclinical model organisms. Over the last decade, several miRNA-based therapeutics have entered clinical trials for various kinds of diseases, such as tumors, infections, and inherited diseases. However, such clinical trials for central nervous system diseases are scarce, and many central nervous system diseases, including hemorrhagic stroke, ischemic stroke, traumatic brain injury, intractable epilepsy, and Alzheimer's disease, lack effective treatment. Considering its effectiveness for central nervous system diseases in preclinical experiments, microRNA-based intervention may serve as a promising treatment for these kinds of diseases. This paper reviews basic principles and recent progress of miRNA-based therapeutics and summarizes general procedures to develop such therapeutics for treating central nervous system diseases. Then, the current obstacles in drug development are discussed. This review also provides a new perspective on possible solutions to these obstacles in the future.

Glossopharyngeal Neuralgia Characterized by Otalgia: A Retrospective Study.

Glossopharyngeal neuralgia (GPN) is an uncommon facial pain syndrome and is characterized by paroxysms of excruciating pain in the distributions of the auricular and pharyngeal branches of cranial nerves IX and X. Glossopharyngeal neuralgia characterized by otalgia alone is rare. Herein, the authors analyzed 2 patients with GPN with otalgia as the main clinical manifestation. The clinical features and prognosis of this rare group of patients with GPN were discussed. They both presented with paroxysmal pain in the external auditory meatus and preoperative magnetic resonance imaging suggested the vertebral artery were closely related to the glossopharyngeal nerves. In both patients, compression of the glossopharyngeal nerve was confirmed during microvascular decompression, and the symptoms were relieved immediately after surgery. At 11 to 15 months follow-up, there was no recurrence of pain. A variety of reasons can cause otalgia. The possibility of GPN is a clinical concern in patients with otalgia as the main complaint. The authors think the involvement of the glossopharyngeal nerve fibers in the tympanic plexus via Jacobson nerve may provide an important anatomic basis for GPN with predominant otalgia. Surface anesthesia test of the pharynx and preoperative magnetic resonance imaging is helpful for diagnosis. Microvascular decompression is effective in the treatment of GPN with predominant otalgia.

High expression of miR-30c-5p in satellite cells of high-fat diet-induced obese rabbits inhibited satellite cell proliferation and promoted differentiation.

It was revealed in our previous study that the expression of miR-30c-5p in the skeletal muscle of rabbits fed high-fat diet was highly expressed. In the present study, we further investigated the function of miR-30c-5p in proliferation and differentiation of skeletal muscle satellite cell (SMSC). The results obtained in the present study showed that the skeletal muscle fibers of the rabbits fed the standard normal diet (SND) were orderly, regular, and uniform after HE staining, however, the muscle fibers of the rabbits fed the high-fat diet (HFD) were generally atrophied, some were arranged disorderly, the intercellular space was enlarged, the nucleus was increased, and the morphology and position were abnormal. Compared with the SND group, it was observed that the weekly weight gain and fat percentage were relatively higher, and also the levels of the serum biochemical indexes such as glucose, cholesterol, and triglyceride increased significantly in the rabbits fed with HFD. In addition, the results after the transfection of miR-30c-5p mimic, mimic NC (negative control), miR-30c-5p inhibitor, and inhibitor NC into the SMSCs showed that the cell counting kit-8 (CCK-8) proliferation experiment suggested that the number of cells in the over expression group was significantly lower than that in the mimic NC group at 48, 72, 96 h of cell proliferation. At 48, 72, 120 h, the number of cells in the inhibitor group was significantly higher than that in the mimic NC group. The number of EdU positive cells decreased significantly in the over expression group compared with the mimic NC group, however, it increased significantly in the inhibitor group compared with the inhibitor NC group. Moreover, compared with the mimic NC group, the myotube area increased significantly in the miR-30c-5p mimic group, whereas it decreased significantly in the miR-30c-5p inhibitor group as compared with the inhibitor NC group. In addition, we found that trinucleotide repeat containing adaptor 6A (TNRC6A) was successfully validated as a target gene for miR-30c-5p. The expression of TNRC6A in the miR-30c-5p mimic group was significantly lower than that in the mimic NC group. It was further observed that the expression of TNRC6A increased significantly in the miR-30c-5p inhibitor group as compared to that in the inhibitor NC group. Taken together, the results obtained in this study showed that miR-30c-5p promotes the differentiation as well as inhibits the proliferation of rabbit skeletal muscle satellite cells, and TNRC6A is a target gene of miR-30c-5p.

Integration of Non-Coding RNA and mRNA Profiles Reveals the Mechanisms of Rumen Development Induced by Different Types of Diet in Calves.

Selecting suitable feed types and understanding the gastrointestinal digestive mechanism are helpful for the growth and health of calves in intensive dairy farming. However, the effects on rumen development of changing the molecular genetic basis and the regulatory mechanism by using different feed types are still unclear. Nine 7-day-old Holstein bull calves were randomly divided into GF (concentrate), GFF (alfalfa: oat grass = 3:2) and TMR (concentrate: alfalfa grass: oat grass: water = 0.30:0.12:0.08:0.50) diet experiment groups. Rumen tissue and serum samples were collected for physiological and transcriptomic analysis after 80 days. The results showed that serum α-amylase content and ceruloplasmin activity were significantly higher in the TMR group, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis ncRNAs and mRNAs were significantly enriched in the pathways of rumen epithelial development and stimulated rumen cell growth, including the Hippo signaling pathway, Wnt signaling pathway, thyroid hormone signaling pathway, ECM-receptor interaction and the absorption of protein and fat. The circRNAs/lncRNA-miRNAs-mRNA networks constructed, including novel_circ_0002471, novel_circ_0012104, TCONS_00946152, TCONS_00960915, bta-miR-11975, bta-miR-2890, PADI3 and CLEC6A, participated in metabolic pathways of lipid, immune system, oxidative stress and muscle development. In conclusion, the TMR diet could improve rumen digestive enzyme activities, stimulate rumen nutrient absorption and stimulate the DEGs related to energy homeostasis and microenvironment balance, and is thus better than the GF and GFF diets for promoting rumen growth and development.

NHC-Activations on α-, ß-, γ-, and Beyond.

Over the recent decades, due to the special electronic characteristics and diverse reactivities, N-heterocyclic carbene (NHC) has received significant interest in organocatalyzed reactions. The formation of Breslow intermediates by NHC can convert into acyl anion equivalent, enolates, homoenolate, acyl azolium, and vinyl enolate etc., and the cycloaddition reactions of these species has attracted lots of attention. In this review, we focus on the summry of the development of NHC-activation of carbonyl carbon (or imine carbon) in situ, α-, ß-, γ-, and beyond, and the cycloaddition reaction of these species.

Chiral NHC-Catalyzed [4+2] Cycloadditions: Highly Diastereo/Enantioselective Access to Spiro[cyclohex-4-ene-1,3'-indoles] and DFT Calculations.

A highly efficient NHC-catalyzed cycloaddition of (E)-alkenylisatins and γ-chloroenals with a broad substrate scope has been developed to provide spiro[cyclohex-4-ene-1,3'-indole] in good yields (up to 99 % yield) with excellent diastereo- and enantioselectivities (up to >20 : 1 d.r., >99 % ee) under mild conditions without the use of metal and additives. Based on computational investigations, the role of the NHC on the diastereo- and enantioselectivity is discussed.

MicroRNAs modulate neuroinflammation after intracerebral hemorrhage: Prospects for new therapy.

Intracerebral hemorrhage (ICH) is the most common subtype of hemorrhagic stroke. After ICH, blood components extravasate from vessels into the brain, activating immune cells and causing them to release a series of inflammatory mediators. Immune cells, together with inflammatory mediators, lead to neuroinflammation in the perihematomal region and the whole brain, and neuroinflammation is closely related to secondary brain injury as well as functional recovery of the brain. Despite recent progress in understanding the pathophysiology of ICH, there is still no effective treatment for this disease. MicroRNAs (miRNAs) are non-coding RNAs 17-25 nucleotides in length that are generated naturally in the human body. They bind complementarily to messenger RNAs and suppress translation, thus regulating gene expression at the post-transcriptional level. They have been found to regulate the pathophysiological process of ICH, particularly the neuroinflammatory cascade. Multiple preclinical studies have shown that manipulating the expression and activity of miRNAs can modulate immune cell activities, influence neuroinflammatory responses, and ultimately affect neurological functions after ICH. This implicates the potentially crucial roles of miRNAs in post-ICH neuroinflammation and indicates the possibility of applying miRNA-based therapeutics for this disease. Thus, this review aims to address the pathophysiological roles and molecular underpinnings of miRNAs in the regulation of neuroinflammation after ICH. With a more sophisticated understanding of ICH and miRNAs, it is possible to translate these findings into new pharmacological therapies for ICH.