Pharmacokinetics of tilmicosin in plasma, urine and feces after a single intragastric administration in donkey (Equus asinus).

Tilmicosin, a macrolide antibiotic, has the potential to treat bacterial infections in donkeys. However, the pharmacokinetics of tilmicosin in donkeys have not been reported. The aim of this study was to investigate the pharmacokinetics of tilmicosin in donkey plasma, urine, and feces after a single intragastric administration to determine the suitability of tilmicosin for donkeys. A total of 5 healthy male donkeys with similar body weights were selected. The donkeys were administered a single dose of 10 mg · kg-1 body weight (BW) tilmicosin by gavage. The concentrations of tilmicosin in plasma, urine, and feces were determined. The results showed that after a single intragastric administration of 10 mg · kg-1 body weight, tilmicosin in donkey plasma reached a maximum concentration of 11.23 ± 5.37 mg · L-1 at 0.80 ± 0.10 h, with a half-life of 14.49 ± 7.13 h, a mean residence time of 28.05 ± 3.05 h, a Cl/F of 0.48 ± 0.18 L · kg-1 · h-1, and a Vd/F of 9.28 ± 2.63 Lkg-1. The percentage of tilmicosin excreted through the urine of donkeys is 2.47%, and the percentage excreted through the feces is 66.43%. Our study provides data to inform the use of tilmicosin in donkeys.

Climate warming promotes collateral antibiotic resistance development in cyanobacteria.

Both cyanobacterial blooms and antibiotic resistance have aggravated worldwide and posed a great threat to public health in recent years. As a significant source and reservoir of water environmental resistome, cyanobacteria exhibit confusing discrepancy between their reduced susceptibility and their chronic exposure to antibiotic mixtures at sub-inhibitory concentrations. How the increasing temperature affects the adaptive evolution of cyanobacteria-associated antibiotic resistance in response to low-level antibiotic combinations under climate change remains unclear. Here we profiled the antibiotic interaction and collateral susceptibility networks among 33 commonly detected antibiotics in 600 cyanobacterial strains isolated from 50 sites across four eutrophicated lakes in China. Cyanobacteria-associated antibiotic resistance level was found positively correlated to antibiotic heterogeneity across all sites. Among 528 antibiotic combinations, antagonism was observed for 62 % interactions and highly conserved within cyanobacterial species. Collateral resistance was detected in 78.5 % of pairwise antibiotic interaction, leading to a widened or shifted upwards mutant selection window for increased opportunity of acquiring second-step mutations. We quantified the interactive promoting effect of collateral resistance and increasing temperature on the evolution of both phenotypic and genotypic cyanobacteria-associated resistance under chronic exposure to environmental level of antibiotic combinations. With temperature increasing from 16 °C to 36 °C, the evolvability index and genotypic resistance level increased by 1.25 - 2.5 folds and 3 - 295 folds in the collateral-resistance-informed lineages, respectively. Emergence of resistance mutation pioneered by tolerance, which was jointly driven by mutation rate and persister fraction, was found to be accelerated by increased temperature and antibiotic switching rate. Our findings provided mechanic insights into the boosting effect of climate warming on the emergence and development of cyanobacteria-associated resistance against collateral antibiotic phenotypes.

Can botulinum toxin injection alleviate the pain of bruxism? A Bayesian network analysis and a single-arm analysis.

Background/purpose: There is inconsistent evidence regarding whether the botulinum toxin A (BTA) injection can relieve pain caused by bruxism. This study aimed to estimate the efficiency of BTA injection in relieving pain caused by bruxism at different follow-up periods. Materials and methods: Five electronic databases were searched from 2005 to 2022 using search terms related to botulinum toxin and bruxism. Only controlled clinical trials were included. Two investigators reviewed each article and discussed any disagreements until a consensus was reached. Pain outcomes as evaluated by the visual analogue scale (VAS) were subjected to single-arm and Bayesian network meta-analyses. Pooling data were measured by a random-effects model. Results: Eleven studies with a total of 365 bruxism patients were included. According to the single-arm analyses of the pooled data, the reduction in bruxism-related pain after BTA injection measured 4.06 points (95% CI = 3.37 to 4.75) on the VAS, and the pain relief was significant in the first 6 months after treatment (P < 0.01). According to the Bayesian analysis, BTA also resulted in significantly greater pain relief than oral splinting (mean difference (MD), -1.5; 95% credible interval (CrI) = -2.7 to -0.19) or saline injection (MD, -3.3; 95% CrI = -6.2 to -0.32). Conclusion: BTA significantly relieves the pain of bruxism for 6 months after injection, and its therapeutic efficacy was higher than that of oral splinting. Nevertheless, further long-term follow-up randomized controlled trials comparing BTA with other management or drugs are warranted.

Prognostic factors of palatal adenoid cystic carcinoma: A single-center analysis of 85 cases.

Objective: The purpose of this retrospective study was to describe the clinicopathological characteristics of primary adenoid cystic carcinoma (ACC) of the palate and to identify the factors affecting prognosis. Methods: The medical records of 85 patients with primary ACC of the palate treated with surgery, with or without adjuvant radiotherapy/chemotherapy, from 2009 to 2019 were reviewed. The relationship of different clinical parameters with locoregional recurrence (LR), distant metastasis (DM), and overall survival (OS) were analyzed. Results: Median follow-up time was 44.6 months. LR and DM rates were 24.7% and 25.9%, respectively, and the 5-year OS and disease-free survival (DFS) rates were 85.9% and 55.1%, respectively. Multivariate analysis showed that positive margins were independently associated with the risk of LR (p < .001). Positive margins (p = .001) and high histological grade (p = .031) were significantly associated with shorter OS. Conclusion: Positive surgical margins are a strong adverse prognostic factor affecting LR and OS in patients with ACC; apart from that, high histopathological grade is an independent predictor of poor OS. Level of Evidence: Level 3 (Prognosis - Cohort study).

Alleviative Effect of Rutin on Zearalenone-Induced Reproductive Toxicity in Male Mice by Preventing Spermatogenic Cell Apoptosis and Modulating Gene Expression in the Hypothalamic-Pituitary-Gonadal Axis.

Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin found in many agricultural products and can cause reproductive disorders, mainly affecting spermatogenesis in male animals. Rutin (RUT) is a natural flavonoid compound recognized for its significant antioxidant, anti-inflammatory and estrogenic properties. The present study aimed to determine the protective role of RUT against ZEN-induced reproductive toxicity in male mice. Twenty-four adult Kunming male mice were divided into four groups: control, RUT (500 mg/kg RUT), ZEN (10 mg/kg ZEN), ZEN + RUT (500 mg/kg RUT + 10 mg/kg ZEN), with six replicates per treatment. The results indicated that RUT mitigated ZEN-induced disruption in spermatogenic cell arrangement, decreased spermatozoa count, and increased sperm mortality in the testes. RUT significantly restored ZEN-induced reduction in T, FSH, LH, and E2 serum levels. Moreover, RUT mitigated ZEN-induced apoptosis by increasing the mRNA expression level of bcl-2, decreasing the mRNA expression level of kiss1-r, and decreasing the protein expression level of caspase 8 in reproductive tissues. These findings indicate the protective role of RUT against ZEN-induced reproductive toxicity in male mice by regulating gonadotropin and testosterone secretions to maintain normal spermatogenesis via the HPG axis, which may provide a new application direction for RUT as a therapeutic agent to mitigate ZEN-induced reproductive toxicity.

FD-Net: Feature Distillation Network for Oral Squamous Cell Carcinoma Lymph Node Segmentation in Hyperspectral Imagery.

Oral squamous cell carcinoma (OSCC) has the characteristics of early regional lymph node metastasis. OSCC patients often have poor prognoses and low survival rates due to cervical lymph metastases. Therefore, it is necessary to rely on a reasonable screening method to quickly judge the cervical lymph metastastic condition of OSCC patients and develop appropriate treatment plans. In this study, the widely used pathological sections with hematoxylin-eosin (H&E) staining are taken as the target, and combined with the advantages of hyperspectral imaging technology, a novel diagnostic method for identifying OSCC lymph node metastases is proposed. The method consists of a learning stage and a decision-making stage, focusing on cancer and non-cancer nuclei, gradually completing the lesions' segmentation from coarse to fine, and achieving high accuracy. In the learning stage, the proposed feature distillation-Net (FD-Net) network is developed to segment the cancerous and non-cancerous nuclei. In the decision-making stage, the segmentation results are post-processed, and the lesions are effectively distinguished based on the prior. Experimental results demonstrate that the proposed FD-Net is very competitive in the OSCC hyperspectral medical image segmentation task. The proposed FD-Net method performs best on the seven segmentation evaluation indicators: MIoU, OA, AA, SE, CSI, GDR, and DICE. Among these seven evaluation indicators, the proposed FD-Net method is 1.75%, 1.27%, 0.35%, 1.9%, 0.88%, 4.45%, and 1.98% higher than the DeepLab V3 method, which ranks second in performance, respectively. In addition, the proposed diagnosis method of OSCC lymph node metastasis can effectively assist pathologists in disease screening and reduce the workload of pathologists.

Genomic alterations in oral multiple primary cancers.

Oral squamous cell carcinoma (OSCC) is the predominant type of oral cancer, while some patients may develop oral multiple primary cancers (MPCs) with unclear etiology. This study aimed to investigate the clinicopathological characteristics and genomic alterations of oral MPCs. Clinicopathological data from patients with oral single primary carcinoma (SPC, n = 202) and oral MPCs (n = 34) were collected and compared. Copy number alteration (CNA) analysis was conducted to identify chromosomal-instability differences among oral MPCs, recurrent OSCC cases, and OSCC patients with lymph node metastasis. Whole-exome sequencing was employed to identify potential unique gene mutations in oral MPCs patients. Additionally, CNA and phylogenetic tree analyses were used to gain preliminary insights into the molecular characteristics of different primary tumors within individual patients. Our findings revealed that, in contrast to oral SPC, females predominated the oral MPCs (70.59%), while smoking and alcohol use were not frequent in MPCs. Moreover, long-term survival outcomes were poorer in oral MPCs. From a CNA perspective, no significant differences were observed between oral MPCs patients and those with recurrence and lymph node metastasis. In addition to commonly mutated genes such as CASP8, TP53 and MUC16, in oral MPCs we also detected relatively rare mutations, such as HS3ST6 and RFPL4A. Furthermore, this study also demonstrated that most MPCs patients exhibited similarities in certain genomic regions within individuals, and distinct differences of the similarity degree were observed between synchronous and metachronous oral MPCs.

Digital pathology-based artificial intelligence models for differential diagnosis and prognosis of sporadic odontogenic keratocysts.

Odontogenic keratocyst (OKC) is a common jaw cyst with a high recurrence rate. OKC combined with basal cell carcinoma as well as skeletal and other developmental abnormalities is thought to be associated with Gorlin syndrome. Moreover, OKC needs to be differentiated from orthokeratinized odontogenic cyst and other jaw cysts. Because of the different prognosis, differential diagnosis of several cysts can contribute to clinical management. We collected 519 cases, comprising a total of 2 157 hematoxylin and eosin-stained images, to develop digital pathology-based artificial intelligence (AI) models for the diagnosis and prognosis of OKC. The Inception_v3 neural network was utilized to train and test models developed from patch-level images. Finally, whole slide image-level AI models were developed by integrating deep learning-generated pathology features with several machine learning algorithms. The AI models showed great performance in the diagnosis (AUC = 0.935, 95% CI: 0.898-0.973) and prognosis (AUC = 0.840, 95%CI: 0.751-0.930) of OKC. The advantages of multiple slides model for integrating of histopathological information are demonstrated through a comparison with the single slide model. Furthermore, the study investigates the correlation between AI features generated by deep learning and pathological findings, highlighting the interpretative potential of AI models in the pathology. Here, we have developed the robust diagnostic and prognostic models for OKC. The AI model that is based on digital pathology shows promise potential for applications in odontogenic diseases of the jaw.

Does a hydropower reservoir cascade really harm downstream nutrient regimes.

River damming is believed to largely intercept nutrients, particularly retain more phosphorus (P) than nitrogen (N), and thus harm primary productivity, fishery catches, and food security downstream, which seriously constrain global hydropower development and poverty relief in undeveloped regions and can drive geo-political disputes between nations along trans-boundary rivers. In this study, we investigated whether reservoirs can instead improve nutrient regimes downstream. We measured different species of N and P as well as microbial functions in water and sediment of cascade reservoirs in the upper Mekong River over 5 years and modelled the influx and outflux of N and P species in each reservoir. Despite partially retaining total N and total P, reservoirs increased the downstream flux of ammonium and soluble reactive phosphorus (SRP). The increase in ammonium and SRP between outflux and influx showed positive linear relationships with the hydraulic residence time of the cascade reservoirs; and the ratio of SRP to dissolved inorganic nitrogen increased along the reservoir cascade. The lentic environment of reservoirs stimulated algae-mediated conversion of nitrate into ammonium in surface water; the hypoxic condition and the priming effect of algae-induced organic matter enhanced release of ammonium from sediment; the synergy of microbial phosphorylation, reductive condition and sediment geochemical properties increased release of SRP. This study is the first to provide solid evidence that hydropower reservoirs improve downstream nutrient bioavailability and N-P balance through a process of retention-transformation-transport, which may benefit primary productivity. These findings could advance our understanding of the eco-environmental impacts of river damming.

Paternal p,p'-DDE exposure and pre-pubertal high-fat diet increases the susceptibility to fertility impairment and sperm Igf2 DMR2 hypo-methylation in male offspring.

The hypothesis of paternal origins of health and disease (POHaD) indicates that paternal exposure to adverse environment could alter the epigenetic modification in germ line, increasing the disease susceptibility in offspring or even in subsequent generations. p,p'-Dichlorodiphenyldichloroethylene (p,p'-DDE) is an anti-androgenic chemical and male reproductive toxicant. Gestational p,p'-DDE exposure could impair reproductive development and fertility in male offspring. However, the effect of paternal p,p'-DDE exposure on fertility in male offspring remains uncovered. From postnatal day (PND) 35 to 119, male rats (F0) were given 10 mg/body weight (b.w.) p,p'-DDE or corn oil by gavage. Male rats were then mated with the control females to generate male offspring. On PND35, the male offspring were divided into 4 groups according whether to be given the high-fat diet (HF): corn oil treatment with control diet (C-C), p,p'-DDE treatment with control diet (DDE-C), corn oil treatment with high-fat diet (C-HF) or p,p'-DDE treatment with high-fat diet (DDE-HF) for 35 days. Our results indicated that paternal p,p'-DDE exposure did not affect the male fertility of male offspring directly, but decreased sperm quality and induced testicular apoptosis after the high-fat diet treatment. Further analysis demonstrated that paternal exposure to p,p'-DDE and pre-pubertal high-fat diet decreased sperm Igf2 DMR2 methylation and gene expression in male offspring. Hence, paternal exposure to p,p'-DDE and pre-pubertal high-fat diet increases the susceptibility to male fertility impairment and sperm Igf2 DMR2 hypo-methylation in male offspring, posing a significant implication in the disease etiology.

Using low-protein diet in egg production for win-win of productivity and environmental benefits should be prudent: Evidence from pilot test.

A shortage of feed protein resources restricts poultry productivity. Key strategies to alleviate this problem include improvements to the structure of the gut microbiota by the appropriate intake of high-quality protein, improvements to the comprehensive protein utilization rate, and reducing the consumption of protein raw materials. In addition, damage to the environment caused by nitrogen emissions needs to be reduced. The aim of the study was to evaluate the effects of dietary protein levels on laying performance, host metabolism, ovarian health, nitrogen emissions, and the gut microbial structure and function of laying hens. In total, 360 hens at the age of 38 weeks were randomly allotted four treatments. Each of the groups consisted of nine replicates, with 10 birds per replicate, used for 12 weeks of study. Dietary protein levels of the four groups were 13.85 %, 14.41 %, 15.63 %, and 16.30 %. Results revealed that, compared with the 13.85 % crude protein (CP) group, the 15.63 % CP group experienced significantly enhanced final body weight, average daily gain, egg production, and egg mass. Compared with the 16.30 % CP group, the other groups' serum concentrations of immunoglobulin G (IgG) and immunoglobulin M (IgM) were significantly reduced. Compared with the 16.30 % CP group, the 13.85 % and 15.63 % groups had increased CP utilization rates but reduced nitrogen emission rate, and daily per egg and per kilogram egg nitrogen emissions rose with increased dietary protein levels. Compared to the 13.85 % and 14.41 % CP groups, the 16.30 % CP group exhibited a significant increase in the expression of genes related to amino acids and carbohydrate metabolic pathways. According to the linear discriminant analysis effect size diagram, the predominant bacteria in the 15.63 % CP group (e.g., Subdoligranulum, and Ruminococcaceae_UCG-013) were significantly related to CP utilization. The results of this study emphasize that production performance is significantly reduced when protein levels are too low, whereas too high protein levels lead to gut microbiota imbalance and a reduction in the utilization efficiency of nutrients. Therefore, on the premise of ensuring the health of hens, the structure of the gut microbiota can be improved by appropriately reducing protein levels, which helps to balance the relationships among host health, productivity, resources, and the environment.

Rapid and signal crowdedness-robust in situ sequencing through hybrid block coding.

Spatial transcriptomics technology has revolutionized our understanding of cell types and tissue organization, opening possibilities for researchers to explore transcript distributions at subcellular levels. However, existing methods have limitations in resolution, sensitivity, or speed. To overcome these challenges, we introduce SPRINTseq (Spatially Resolved and signal-diluted Next-generation Targeted sequencing), an innovative in situ sequencing strategy that combines hybrid block coding and molecular dilution strategies. Our method enables fast and sensitive high-resolution data acquisition, as demonstrated by recovering over 142 million transcripts using a 108-gene panel from 453,843 cells from four mouse brain coronal slices in less than 2 d. Using this advanced technology, we uncover the cellular and subcellular molecular architecture of Alzheimer's disease, providing additional information into abnormal cellular behaviors and their subcellular mRNA distribution. This improved spatial transcriptomics technology holds great promise for exploring complex biological processes and disease mechanisms.

Architectural and cytological features of epithelial dysplasia associated with transformation risk.

OBJECTIVES: This study explored associations between histological features of dysplasia and malignant transformation, as well as genomic copy number alterations. MATERIALS AND METHODS: Overall, 201 samples were collected from patients of oral leukoplakia. The associations of dysplastic features with malignant transformation and copy number alterations were investigated by Cox proportional hazards regression analysis and the Mann-Whitney U-test. RESULTS: Eight individual histological features, such as irregular epithelial stratification (p = 0.001), mitoses high in epithelium (p = 0.033), extension of changes along minor gland ducts (p < 0.001), etc., were associated with greater risk of malignant transformation. A model including histological features and age showed good performance for predicting malignant transformation (area under receiver operating characteristic curve: 0.806). Irregular epithelial stratification (p = 0.007), abnormal nuclear shape (p = 0.005), abnormal cell size (p = 0.004), etc. were associated with greater genomic instability. CONCLUSIONS: A Cox proportional hazards model using eight histological features and patient age reliably predicted the malignant potential of oral epithelial dysplasia. Identification of these histological features closely related to malignant transformation may aid the management of oral potentially malignant disorders and early detection of oral squamous cell carcinoma.

Neoadjuvant tislelizumab combined with chemotherapy in locally advanced oral or oropharyngeal squamous cell carcinoma: a real-world retrospective study.

Objectives: The treatment of locally advanced oral or oropharyngeal squamous cell carcinoma (LAOOPSCC) is surgery and radiotherapy or chemoradiotherapy but with unsatisfactory survival rate. Neoadjuvant programmed death-1 (PD-1) therapy are being used in several clinical trials. Therefore, in this retrospective study we aimed to determine the feasibility of neoadjuvant tislelizumab plus chemotherapy followed by surgery for LAOOPSCC. Materials and methods: The clinical data of 33 patients with LAOOPSCC who received neoadjuvant PD-1 inhibitors and chemotherapy between April 2021 and October 2022 were retrospectively analyzed. Patients with stage III-IV LAOOPSCC received tislelizumab, albumin-bound paclitaxel, and cisplatin every 3 weeks (Q3W) for two cycles, followed by surgery and adjuvant radiotherapy or concurrent chemoradiotherapy. A median follow-up period was 20 months. Results: The objective response rate (ORR) was 66.7%, with the major pathological response (MPR) rate at 54.5%, and the pathological complete response (pCR) rate was 33.3%. Sixteen patients underwent limited surgeries, and 15 patients were remitted from undergoing mandibulectomy and 9 patients were remitted from undergoing near total glossectomy or total glossectomy. A significant difference in the overall survival (OS) and disease-free survival (DFS) was observed in patients who achieved major pathological response (MPR) than who did not. The most common adverse events in neoadjuvant therapy were alopecia, decreased appetite or anorexia, leukopenia, and fatigue. Conclusion: Neoadjuvant PD-1 inhibitors combined with chemotherapy are feasible and safe, with a high pathological response and possible organ preservation in oral or oropharyngeal squamous cell carcinoma. However, further studies with a larger cohort of patients and longer follow-up period is required to strengthen our findings and evaluate the survival benefits of the treatment.

Head and neck carcinoma in children: A clinicopathological study of 42 cases.

Background/purpose: Cancer is an important part of the global burden of childhood diseases. Head and neck carcinoma in children is rare and related research is limited. This study aimed to investigate the clinicopathological features of childhood head and neck carcinoma. Materials and methods: Forty-two cases of childhood head and neck carcinoma treated in our institution were reviewed and analyzed. Results: Median age overall was 11 years. Twenty-three patients (54.8%) were male and 19 (45.2%) were female. Parotid gland location was most common (54.8%). Mucoepidermoid carcinoma and squamous cell carcinoma were the most common histological types (57.1% and 11.9%, respectively). Two patients had a history of bone marrow transplantation and two had a history of odontogenic keratocyst. The recurrence rate after treatment was 8.6%. Conclusion: Early diagnosis and treatment and close follow-up of childhood head and neck carcinoma are warranted to prevent recurrence and improve clinical outcome.

Responses of soil nutrients and rhizosphere microbial communities of a medicinal plant Pinelliaternata to vermicompost.

Vermicomposting is an important strategy for restoring soil function and fertility. However, information on the effects of vermicompost application in intensive Pinellia ternata planting systems has rarely been reported. Here, we focus on the effects of different vermicompost levels and chemical fertilizer (CF) strategies on soil chemical properties, soil enzymes, and soil rhizosphere microbial communities (bacteria and fungi) in a field experiment. Compared to no added fertilizers (CK), vermicompost was more effective than the CF treatment in increasing P. ternata yield. We found that the 5 t ha-1 vermicompost treatment (VC2) significantly increased the tuber yield by 44.43% and 6.55% compared to the CK and CF treatment, respectively, and water-soluble exudates by 6.56% and 9.63% (P < 0.05). The vermicompost and CF treatments significantly increased the total phosphorus (TP), urease (Ure), and soil catalase (Cat) contents (P < 0.05). Compared to the vermicompost and CK treatments, the CF treatment significantly decreased soil organic carbon (SOC), C/N ratio, and soil acid phosphatase (Pac) (P < 0.05). Redundancy analysis (RDA) showed that Ure and total potassium (TK) were the major drivers in the bacterial community, whereas TP, total nitrogen (TN), Pac, and TK were the major drivers in the fungal community. We also found a positive correlation between soil enzyme activities, including between Ure and bacterial genera (Clostridium, Pseudoclavibacter, Stella, Hyphomicrobium, Mesorhizobium, and Adlercreutzia). In summary, vermicompost application promotes P. ternata soil microecosystems and improves soil fertility, soil enzyme activities, and rhizosphere microbial structure and function. Vermicomposting is a novel and promising approach to sustainable ecological cultivation of Chinese herbs via the promotion of soil properties and beneficial organisms.

Biomarkers of malignant transformation in oral leukoplakia: from bench to bedside. / å£è ”ç™½æ–‘ç™Œå˜ç”Ÿç‰©æ ‡å¿—ç‰©ï¼š ä»ŽåŸºç¡€ç§‘ç ”åˆ°ä¸´åºŠåº”ç”¨.

Oral leukoplakia is a common precursor lesion of oral squamous cell carcinoma, which indicates a high potential of malignancy. The malignant transformation of oral leukoplakia seriously affects patient survival and quality of life; however, it is difficult to identify oral leukoplakia patients who will develop carcinoma because no biomarker exists to predict malignant transformation for effective clinical management. As a major problem in the field of head and neck pathologies, it is imperative to identify biomarkers of malignant transformation in oral leukoplakia. In this review, we discuss the potential biomarkers of malignant transformation reported in the literature and explore the translational probabilities from bench to bedside. Although no single biomarker has yet been applied in the clinical setting, profiling for genomic instability might be a promising adjunct.

[Effects of Governor Vessel electroacupuncture on chloridion homeostasis in the cortex of rats with limb spasm after cerebral ischemia-reperfusion].

OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of Governor Vessel on chloridion (Cl-) homeostasis and the expression of γ-aminobutyric acid (GABA) and Na+-K+-Cl- cotransporter 1 (NKCC1) in the cerebral cortex of cerebral ischemia-reperfusion injury (CIRI) model rats, so as to explore its mechanism underl-ying alleviating limb spasm after stroke. METHODS: Forty-five male SD rats were randomly divided into normal, sham-operation, model, EA and baclofen groups, with 9 rats in each group. The CIRI model was established by occlusion of the middle cerebral artery and reperfusion. EA(100 Hz) was applied to "Dazhui" (GV14), "Jizhong"(GV6) and "Houhui" for 30 min. Rats of the baclofen group received gavage of baclofen solution (0.4 mg/kg, 1 mL/100 g), once daily for 7 consecutive days. Neurological deficit score was assessed according to Zea Longa's method. The muscular tone of quadriceps femoris of the limb was evaluated by modified Ashworth scale and electrophysiological recor-ding methods, separately. TTC staining was used to detect cerebral infarction volume, and the brain water content of rats in each group was determined by wet and dry weight method. The contents of Cl- and GABA in the cerebral cortex were detected by colorimetric method, and the expression levels of NKCC1 mRNA and protein in the cerebral cortex were detected by quantitative real-time PCR and Western blot, separately. RESULTS: No significant differences were found between the normal and sham-operation groups in all the indexes. Compared with the normal and sham-operation groups, the neurological deficit score, modified Ashworth muscle tone score, brain water content, cerebral infarct volu-me percent, Cl- content and expression levels of NKCC1 mRNA and protein were all evidently increased (P<0.01), and muscle tone of electrophyiological electromyogram (EMG) signal and GABA content were strikingly decreased (P<0.01) in the model group. Compared with the model group, both EA and baclofen groups had an obvious increase in EMG signal displayed muscle tone, and GABA content (P<0.05, P<0.01), and a marked decrease in the neurological deficit score, modified Ashworth score, brain water content, cerebral infarct percent, Cl- content and expression levels of NKCC1 mRNA and protein (P<0.05, P<0.01). CONCLUSION: EA stimulation of acupoints of the Governor Vessel can improve the degree of limb spasm and reduce the degree of cerebral edema and infarction in rats with stroke, which may be related to its functions in protecting Cl- homeostasis, up-regulating GABA concentration, and down-regulating the expression of NKCC1 protein and mRNA in the cerebral cortex.

FSHR-mTOR-HIF1 signaling alleviates mouse follicles from AMPK-induced atresia.

The majority of activated ovarian follicles undergo atresia during reproductive life in mammals, and only a small number of follicles are ovulated. Though hormone treatment has been widely used to promote folliculogenesis, the molecular mechanism behind follicle selection and atresia remains under debate due to inconsistency among investigation models. Using a high-throughput molecular pathology strategy, we depicted a transcriptional atlas of mouse follicular granulosa cells (GCs) under physiological condition and obtained molecular signatures in healthy and atresia GCs during development. Functional results revealed hypoxia-inducible factor 1 (HIF1) as a major effector downstream of follicle-stimulating hormone (FSH), and HIF1 activation is essential for follicle growth. Energy shortage leads to prevalent AMP-activated protein kinase (AMPK) activation and drives follicular atresia. FSHR-mTOR-HIF1 signaling helps follicles escape from the atresia fate, while energy stress persists. Our work provides a comprehensive understanding of the molecular network behind follicle selection and atresia under physiological condition.