Factors influencing traumatic brain injuries in maxillofacial fractures: A 12-year retrospective analysis of 2841 patients.

BACKGROUND/AIM: Results of studies investigating the association between traumatic brain injury (TBI) and maxillofacial fractures (MFs) have varied considerably. The present study aimed to evaluate the correlation between TBIs and MFs, as well as the impact of age, sex, trauma mechanism, and season on TBIs. MATERIALS AND METHODS: This 12-year retrospective study of 2841 patients used univariate and multivariate logistic regression to assess the association between MFs and other factors impacting TBIs. RESULTS: Among 2841 patients, 1978 TBIs occurred in 829 (29.2%), with intracranial injuries (n = 828) is the most common. Of 829 patients with TBIs, 688 were male and 141 were female, corresponding to a male-to-female ratio of 4.9:1.0. The most common age group was 40-49 years (24.6%). Vehicles (including motor vehicles and electric vehicles) accidents were the primary causes of injuries. Multivariate regression analyses revealed an increased risk for TBIs among males (odds ratio [OR] 0.632, p < 0.001). Patients >40 years of age were at higher risk for TBIs, especially those ≥70 years (OR 3.966, p = 0.001). Vehicle accidents were a high-risk factor for TBIs (OR 6.894, p < 0.001), and winter was the most prevalent season for such injuries (OR 1.559, p = 0.002). Risk for TBI increased by 136.4% in combined midfacial and mandibular fractures (p = 0.016) and by 101.6% in multiple midfacial fractures (p = 0.045). TBIs were less common in single mandibular fractures, notably in single-angle fractures, with a risk of only 0.204-fold. CONCLUSION: TBIs in MFs were significantly correlated with sex, age, aetiology, season and fracture location. Maxillofacial surgeons and emergency physicians must be aware of the possible association between TBIs and MFs to assess and manage this complicated relationship in a timely manner.

The CBL-CIPK network is involved in the physiological crosstalk between plant growth and stress adaptation.

Plants have evolved to deal with different stresses during plant growth, relying on complex interactions or crosstalk between multiple signalling pathways in plant cells. In this sophisticated regulatory network, Ca2+ transients in the cytosol ([Ca2+ ]cyt ) act as major physiological signals to initiate appropriate responses. The CALCINEURIN B-LIKE PROTEIN (CBL)-CBL-INTERACTING PROTEIN KINASE (CIPK) network relays physiological signals characterised by [Ca2+ ]cyt transients during plant development and in response to environmental changes. Many studies are aimed at elucidating the role of the CBL-CIPK network in plant growth and stress responses. This review discusses the involvement of the CBL-CIPK pathways in two levels of crosstalk between plant development and stress adaptation: direct crosstalk through interaction with regulatory proteins, and indirect crosstalk through adaptation of correlated physiological processes that affect both plant development and stress responses. This review thus provides novel insights into the physiological roles of the CBL-CIPK network in plant growth and stress adaptation.

Subchronic toxicity study of ferric oxide nanoparticles through intragastric administration: A 94-d, repeated dose study in Sprague Dawley rats.

In this study, the toxicity of ferric oxide nanoparticles (Fe2O3 NPs) administered through gavage to Sprague Dawley (SD) rats for 94 d, consecutively and the recovery after Fe2O3 NPs withdrawal for 30 d were evaluated. The vehicle control group, low-, medium-, and high-dose groups were administered with the vehicle (0.5% sodium carboxymethyl cellulose [CMC-Na]), 125, 250, and 500 mg/kg of Fe2O3 NPs, respectively, administered every morning for 94 d. There was no significant difference in the body weight, food intake, hematological, blood biochemical, and urine indices of SD rats in each administration group and the control group (P > 0.05). There was no significant difference in organ weight, organ indices, and the coefficient of the visceral brain between the SD rats in the different dosage groups and the SD rats in the vehicle control group (P > 0.05). Histopathological observations showed that there was no correlation between the pathological lesions of the organs observed in this study and the dose of Fe2O3 NPs (P > 0.05). The no-observed-adverse-effect level (NOAEL) dose of Fe2O3 NPs was initially determined to be 500 mg/kg administered to SD rats through oral gavage for 94 d, consecutively, followed by recovery after Fe2O3 NPs withdrawal for 30 d.

Evaluation of subchronic toxicity of the compound of diphenhydramine hydrochloride and caffeine after 28 days of repeated oral administration in Sprague-Dawley rats and beagle dogs.

This study was designed to evaluate the subchronic toxicity of the compound of diphenhydramine hydrochloride (DH) and caffeine in Sprague-Dawley (SD) rats and beagle dogs. A total of 180 SD rats (15/sex/group) were randomly divided into the compound low-, medium- and high-dose groups (51, 102, 204 mg/kg), DH group (60 mg/kg), caffeine group (144 mg/kg) and the vehicle control group. Sixty beagle dogs (5/sex/group) were randomly divided into the compound low-, medium- and high-dose groups (male: 14.20, 28.30, 56.60 mg/kg, female: 5.66, 14.20, 28.30 mg/kg), DH group (male: 16.60 mg/kg, female: 8.30 mg/kg), caffeine group (male: 40.00 mg/kg, female: 20.00 mg/kg) and the vehicle control group. Rats and dogs were given continuous oral administration for 28 days following a 28-day recovery period. The adverse effects of the compound on rats and beagle dogs mainly included anorexia and liver function impairment. Most adverse effects induced by administration were reversible. Under the experimental conditions, the no-observed-adverse-effect level (NOAEL) of the compound of DH and caffeine was 51 mg/kg/day for SD rats and 28.30 mg/kg/day (male) and 5.66 mg/kg/day (female) for beagle dogs.

Epidemiology of maxillofacial fractures in northwest China: an 11-year retrospective study of 2240 patients.

BACKGROUND: The aim of this study was to determine the epidemiological pattern of maxillofacial fractures in northwestern China by retrospectively analysing the demographics, aetiologies, concomitant injuries, fracture sites, and management. METHODS: A 10-year retrospective analysis of 2240 patients with maxillofacial fractures admitted to the General Hospital of Ningxia Medical University was conducted. The extracted data included sex, age, aetiology, fracture site, concomitant injuries, time of treatment, therapeutic approaches and complications. Statistical analyses were performed, including descriptive analysis and the chi-square test. Logistic regression was used to determine the impact factors of maxillofacial fractures and concomitant injuries. P values < 0.05 were considered statistically significant. RESULTS: The age of the included patients ranged from 1 to 85 years, and the mean age was 35.88 ± 15.69 years. The male-to-female ratio was 3.9:1. The most frequent aetiology of maxillofacial fractures was road traffic accidents (RTAs) (56.3%), and the most common fracture sites were the anterior wall of the maxillary sinus, arcus zygomaticus and mandibular body. A total of 1147 patients (51.2%) were affected by concomitant injuries, with craniocerebral injury being the most common. Logistic regression analyses revealed increased risks of mid-facial fractures in elderly individuals (odds ratio (OR) = 1.029, P < 0.001) and females (OR = 0.719, P = 0.005). Younger patients had a higher risk of mandibular fractures (OR = 0.973, P < 0.001). RTAs increased the risk for mid-facial fractures and high falls increased the risk for mandibular fractures. CONCLUSIONS: The maxillofacial fracture pattern is correlated with sex, age and aetiology. Patients were mainly young and middle-aged males, and the main cause of injury was RTAs, mostly causing compound fractures. Medical staff must be systematically educated to comprehensively examine patients with injuries resulting from RTAs. The management of patients with fractures requires thorough consideration of the patient's age, aetiology, fracture site, and concomitant injuries.

Metabolic syndrome and its components are associated with thyroid volume in adolescents.

OBJECTIVE: To explore the association between metabolic syndrome (MetS) and its component and thyroid volume in Chinese adolescents, and to compare the detection rate of MetS under the three different diagnostic criteria. METHODS: A total of 1097 school students (610 males and 487 females, ages 12-15 years) were enrolled. All the participants underwent physical examination, biochemical test, and thyroid gland ultrasonography. The thyroid volume of normal, overweight and obese group was compared. We also analyzed the association between the number of MetS components and thyroid volume. Linear and multiple linear regression were applied to explore the association between metabolic parameters and thyroid volume. RESULTS: The thyroid volume of the males in overweight (t = 3.784, P < 0.001) and obese group (t = 5.068, P < 0.001) was significantly larger than that in normal group; the thyroid volume of the females in overweight group (t = 4.627,P < 0.001) was significantly larger than that of normal group. As the number of MetS components increased, the thyroid volume also increased significantly (F = 10.64, P < 0.01). Height, weight, body mass index (BMI), waist circumference, hip circumference, systolic blood pressure, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), uric acid and triglyceride were all positively associated with thyroid volume in the adolescents (P all < 0.001). Meanwhile, there was a negative association between high-density lipoprotein cholesterol (HDL-C) and thyroid volume (P < 0.001). According to multiple linear regression, waist circumference (ß = 0.029, 95 %CI: 0.015 ~ 0.042; P < 0.01) and waist height ratio (ß = 3.317, 95 %CI: 1.661 ~ 4.973; P < 0.01) were predict factors of thyroid volume. No statistical difference was found in the detection rates of metabolic syndrome under the three diagnostic criteria. CONCLUSIONS: Overweight, obesity and metabolic syndrome was associated with adolescent thyroid volume. Central obesity may be an independent risk factor for thyroid enlargement in adolescents.

Formulation and Characterization of Novel Dry Suspension and Dry Emulsion of 20(S)-Protopanaxadiol.

To improve the absorption of poorly water-soluble 20(S)-protopanaxadiol (20(S)-PPD), novel 20(S)-PPD-loaded redispersible dry suspension and dry emulsion were developed in this study. 20(S)-PPD dry suspension (PPD-DS) was prepared by enabling drug fully dispersed with suspending agent Avicel CL611 and solubilizer Poloxamer 188. 20(S)-PPD dry emulsion (PPD-DE) was prepared by employing oleic acid as oil phase, Cremophor RH-40 as surfactant, and n-butyl alcohol as co-surfactant. Both PPD-DS and PPD-DE were evaluated for their physicochemical characterization after being dispersed in distilled water. The in vivo pharmacokinetics was evaluated by UPLC-MS/MS. The droplet size of PPD-DS and PPD-DE was in the scope of 1446-1653 nm and 652.8-784.5 nm. The sedimentation volume ratios of PPD-DS and PPD-DE were both at value of 1. The zeta potential of PPD-DS and PPD-DE were from - 53.7 to - 70.4 mV and - 27.5 to - 34.5 mV, respectively, which indicated stable systems. PPD-DS and PPD-DE both achieved dramatically enhanced aqueous solubility and higher perfusion of 20(S)-PPD in rats' intestine. Although statistically, no oral bioavailability enhancements of 20(S)-PPD were achieved in PPD-DE and PPD-DS, there were some improvements in the pharmacokinetic behaviors. Especially, PPD-DS could be a promising drug delivery carrier for 20(S)-PPD with the advantages of long-term stability, dosing flexibility, and the convenience of administering to infants and to those who have difficulty swallowing tablets or capsules.

Exogenous melatonin enhances salt stress tolerance in maize seedlings by improving antioxidant and photosynthetic capacity.

Melatonin (N-acetyl-5-methoxytryptamine) is an important biological hormone in many abiotic stress responses and developmental processes. In this study, the protective roles of melatonin were investigated by measuring the antioxidant defense system and photosynthetic characteristics in maize under salt stress. The results indicated that NaCl treatment led to the decrease in plant growth, chlorophyll contents and photochemical activity of photosystem II (PSII). However, the levels of reactive oxygen species increased significantly under salt stress. Meanwhile, we found that application of exogenous melatonin alleviated reactive oxygen species burst and protected the photosynthetic activity in maize seedlings under salt stress through the activation of antioxidant enzymes. In addition, 100 µM melatonin-treated plants showed high photosynthetic efficiency and salinity. Immunoblotting analysis of PSII proteins showed that melatonin application alleviated the decline of 34 kDa PSII reaction center protein (D1) and the increase of PSII subunit S protein. Taken together, our study promotes more comprehensive understanding in the protective effects of exogenous melatonin in maize under salt stress, and it may be involved in activation of antioxidant enzymes and regulation of PSII proteins.

Purification, characterization, and gene cloning of a new cold-adapted ß-galactosidase from Erwinia sp. E602 isolated in northeast China.

ß-Galactosidases are widely used in industry for elimination of lactose from milk products. A new ß-galactosidase was obtained from bacterial strain Erwinia sp. E602, newly isolated in northeast China. The enzyme was purified with the methods of ammonium sulfate fractionation, ion exchange, and gel filtration chromatography for further study of the enzymatic characteristics. The purified enzyme had a molecular weight of near 110 kDa. The optimum reaction temperature and pH of this enzyme was determined to be 40°C and 7.0, respectively, indicating that this enzyme was a mesophilic neutral ß-galactosidase. Furthermore, the enzyme retained near 10% of the activity at 0°C, which also suggested its cold-adapted property. Kinetics of the ß-galactosidase was studied, and the Km (Michaelis constant) and Vmax (maximum enzymatic reaction rate) of this enzyme were 0.21 mmol/L and 263.16 µmol/mg per minute, respectively. The effects of metal ions on the enzymatic activity and the lactose hydrolysis efficiency in milk, as well as its trans-glycosylation activity, were studied in this work. The ß-galactosidase coding gene was cloned to be a 3-kb length fragment, which shared at most 81% of identity with the published sequences in NCBI Blast database (https://blast.ncbi.nlm.nih.gov). Results in this work suggested it is a new ß-galactosidase and it has potential to be used in dairy and food processing.

The Arabidopsis Calcium-Dependent Protein Kinases (CDPKs) and Their Roles in Plant Growth Regulation and Abiotic Stress Responses.

As a ubiquitous secondary messenger in plant signaling systems, calcium ions (Ca2+) play essential roles in plant growth and development. Within the cellular signaling network, the accurate decoding of diverse Ca2+ signal is a fundamental molecular event. Calcium-dependent protein kinases (CDPKs), identified commonly in plants, are a kind of vital regulatory protein deciphering calcium signals triggered by various developmental and environmental stimuli. This review chiefly introduces Ca2+ distribution in plant cells, the classification of Arabidopsis thaliana CDPKs (AtCDPKs), the identification of the Ca2+-AtCDPK signal transduction mechanism and AtCDPKs' functions involved in plant growth regulation and abiotic stress responses. The review presents a comprehensive overview of AtCDPKs and may contribute to the research of CDPKs in other plants.

Biodegradation of lignin and nicotine with white rot fungi for the delignification and detoxification of tobacco stalk.

BACKGROUND: Tobacco stalk is one kind of abundant crop residues in China. The high lignification of tobacco stalk increases its reusing cost and the existing of nicotine will cause serious pollution. The biodegradation of lignocellulosic biomass has been demonstrated to be an environmental and economical approach for the utilization of plant stalk. Meanwhile, many nicotine-degrading microorganisms were found in nature. However, microorganisms which could degraded both nicotine and lignin haven't been reported. Therefore, it's imperative to find some suitable microorganisms to break down lignin and simultaneously remove nicotine in tobacco stalk. RESULTS: The nicotine in tobacco stalk could be degraded effectively by Trametes versicolor, Trametes hirsute and Phanerochaete chrysosporium. The nicotine content in tobacco stalk was lowered to below 500 mg/kg (a safe concentration to environment) after 10 days of fermentation with Phanerochaete chrysosporium and Trametes versicolor, and 15 days with Trametes hirsute. The degradation rate of lignin in the fermented tobacco stalk was 37.70, 51.56 and 53.75% with Trametes versicolor, Trametes hirsute and Phanerochaete chrysosporium, respectively. Meanwhile, 24.28% hemicellulose was degraded by Phanerochaete chrysosporium and 28.19% cellulose was removed by Trametes hirsute. Through the enzyme activity analysis, the main and highest ligninolytic enzymes produced by Phanerochaete chrysosporium, Trametes hirsute and Trametes versicolor were lignin peroxidase (88.62 U · L-1), manganese peroxidase (100.95 U · L-1) and laccase (745.65 U · L-1). Meanwhile, relatively high and stable cellulase activity was also detected during the fermentation with Phanerochaete chrysosporium, and the highest endoglucanase, exoglucanase and filter paper enzyme activities were 0.38 U · mL-1, 0.45 U · mL-1 and 0.35U · mL-1, respectively. Moreover, the products in the fermentation of tobacco stalk with P. chrysosporium were identified with GC-MS, besides the chemicals produced in the degradation of lignin and nicotine, some small molecular valuable chemicals and fatty acid were also detected. CONCLUSIONS: Our study developed a new method for the degradation and detoxification of tobacco stalk by fermentation with white rot fungi Phanerochaete chrysosporium and Trametes hirsute. The different oxidative enzymes and chemical products detected during the degradation indicated a possible pathway for the utilization of tobacco stalk.

Fatal disease associated with Swine Hepatitis E virus and Porcine circovirus 2 co-infection in four weaned pigs in China.

BACKGROUND: In recent decades, Porcine circovirus 2 (PCV2) infection has been recognized as the causative agent of postweaning multisystemic wasting syndrome, and has become a threat to the swine industry. Hepatitis E virus (HEV) is another high prevalent pathogen in swine in many regions of the world. PCV2 and HEV are both highly prevalent in pig farms in China. CASE PRESENTATION: In this study, we characterized the HEV and PCV2 co-infection in 2-3 month-old piglets, based on pathogen identification and the pathological changes observed, in Hebei Province, China. The pathological changes were severe, and general hyperemia, hemorrhage, inflammatory cell infiltration, and necrosis were evident in the tissues of dead swine. PCR was used to identify the pathogen and we tested for eight viruses (HEV, Porcine reproductive and respiratory syndrome virus, PCV2, Classical swine fever virus, Porcine epidemic diarrhea virus, Transmissible gastroenteritis coronavirus, Porcine parvovirus and Pseudorabies virus) that are prevalent in Chinese pig farms. The livers, kidneys, spleens, and other organs of the necropsied swine were positive for HEV and/or PCV2. Immunohistochemical staining showed HEV- and PCV2-antigen-positive signals in the livers, kidneys, lungs, lymph nodes, and intestine. CONCLUSION: HEV and PCV2 co-infection in piglets was detected in four out of seven dead pigs from two pig farms in Hebei, China, producing severe pathological changes. The natural co-infection of HEV and PCV2 in pigs in China has rarely been reported. We speculate that co-infection with PCV2 and HEV may bring some negative effect on pig production and recommend that more attention should be paid to this phenomenon.

[Isolation of microorganisms producing enzyme capable of degrading tobacco straw and nicotine].

OBJECTIVE: The aim of this study was to screen tobacco straw and nicotine degrading microorganism. METHODS: The bacterium was isolated from tobacco field soil using medium containing tobacco straw as the sole carbon and nitrogen source. We identified the bacterium through morphological and physiological characterization combined with the result of 16S rRNA gene sequence and data analysis. We also studied the lignocelluloses degradation and enzyme activities related to the degradation of lignin and cellulose in liquid state fermentation of tobacco stalk. RESULTS: The bacterium was identified as Bacillus megaterium and we had demonstrated that it has a good ability to degrade lignin in tobacco straw when fermented in liquid state. It showed the highest laccase production of 418. 52 U/L while the highest lignin peroxides and manganese peroxides activity was 19. 71 U/L and 64. 71 U/L. On the other hand, we also found that nicotine in tobacco stem was totally degraded 20 d after inoculation. CONCLUSION: to the isolated Bacillus megaterium is capable of degrading tobacco straw partially and nicotine totally.

The Contribution of Microorganisms to the Quality and Flavor Formation of Chinese Traditional Fermented Meat and Fish Products.

Guizhou sour meat and sour fish, Chaoshan fish sauce, Sichuan sausage and bacon, Cantonese sausage, Jinhua ham, and Xinjiang air-dried beef are eight representatives of Chinese traditional fermented meat and fish products (FMFPs), which are favored by Chinese consumers due to their high nutritional value and quality. The quality of the spontaneously fermented Chinese traditional FMFP is closely correlated with microorganisms. Moreover, the dominant microorganisms are significantly different due to regional differences. The effects of microorganisms on the texture, color, flavor, nutrition, functional properties, and safety of Chinese traditional FMFPs have not been not fully described. Additionally, metabolic pathways for flavor formation of Chinese traditional FMFPs have not well been summarized. This article describes the seven characteristic Chinese traditional FMFPs and correlated dominant microorganisms in different regions of China. The effects of microorganisms on the texture, color, and flavor of Chinese traditional FMFPs are discussed. Furthermore, the metabolic pathways of microbial regulation of flavor formation in Chinese traditional FMFPs are proposed. This work provides a theoretical basis for improvement of Chinese traditional FMFPs by inoculating functional microorganisms isolated from Chinese traditional fermented foods.

Combined treatment for a rare malignant glomus tumor of the esophagus with pulmonary and liver metastases: a case report and review of literature.

Background: Glomus tumors are typically benign soft tissue tumors that occur at the extremities; malignant and viscerally occurring cases are extremely rare. Case presentation: We report a 49-year old male patient with a malignant esophageal glomus tumor that was complicated by lung and liver metastases. Genetic test results guided the patient's individualized treatment. Consequently, treatment with Anlotinib combined with Tislelizumab achieved significant clinical benefits. Conclusion: Our case report demonstrates that immunotherapy combined with anti-angiogenic therapy in patients with malignant esophageal glomus tumors can achieve significant efficacy and suggests the potential value of next-generation sequencing (NGS) detection in guiding personalized treatments in patients with malignant esophageal glomus tumors.

Automated detection and classification of mandibular fractures on multislice spiral computed tomography using modified convolutional neural networks.

OBJECTIVE: To evaluate the performance of convolutional neural networks (CNNs) for the automated detection and classification of mandibular fractures on multislice spiral computed tomography (MSCT). STUDY DESIGN: MSCT data from 361 patients with mandibular fractures were retrospectively collected. Two experienced maxillofacial surgeons annotated the images as ground truth. Fractures were detected utilizing the following models: YOLOv3, YOLOv4, Faster R-CNN, CenterNet, and YOLOv5-TRS. Fracture sites were classified by the following models: AlexNet, GoogLeNet, ResNet50, original DenseNet-121, and modified DenseNet-121. The performance was evaluated for accuracy, sensitivity, specificity, and area under the curve (AUC). AUC values were compared using the Z-test and P values <.05 were considered to be statistically significant. RESULTS: Of all of the detection models, YOLOv5-TRS obtained the greatest mean accuracy (96.68%). Among all of the fracture subregions, body fractures were the most reliably detected (with accuracies of 88.59%-99.01%). For classification models, the AUCs for body fractures were higher than those of condyle and angle fractures, and they were all above 0.75, with the highest AUC at 0.903. Modified DenseNet-121 had the best overall classification performance with a mean AUC of 0.814. CONCLUSIONS: The modified CNN-based models demonstrated high reliability for the diagnosis of mandibular fractures on MSCT.

Complete response to disitamab vedotin in HER2-low metastatic endometrial carcinoma: a case report and review of the literature.

Endometrial cancer (EC) is one of the most common gynecologic malignancies with increasing morbidity. The prognosis for patients diagnosed with early-stage EC remains favorable; however, for patients with recurrent or metastatic EC, the prognosis is poor and treatment options, until recently, are limited. Antibody drug conjugates (ADCs) represent innovative strategies in cancer treatment; however, there are less investigations regarding their efficacy in EC. This report describes an EC case with low human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) expression score (IHC 2+) that experienced recurrent metastasis in the abdominal and peritoneal following post-surgical chemotherapy and radiotherapy. Subsequently, the commencement of HER2-targeted ADC, disitamab vedotin (RC48; 2.5 mg/kg), administered intravenously every two weeks, was initiated. The tumor lesions shrunk markedly after three cycles of treatment and disappeared by the completion of ten cycles of therapy. The patient is still in remission at present. The current findings imply the potential efficacy of HER2-targeted ADCs for patients with HER2-low metastatic EC.

Emergent surgical retrieval of a left atrial appendage occluder migrated into the left ventricular outflow tract with secondary massive mitral regurgitation: A case report and literature review.

Thrombotic complications of atrial fibrillation continue to pose a significant challenge in clinical practice today. Left atrial appendage occlusion (LAAO) has emerged as a promising alternative to oral anticoagulation for high-risk patients with atrial fibrillation. However, despite the potential benefits, there is still the possibility of life-threatening complications such as device dislocation. In this case study, we present a patient who experienced severe hemodynamic disturbances due to the embolization of LAAO device into the left ventricular outflow tract, resulting in a torn mitral valve and secondary massive mitral regurgitation, just 3 hours after the procedure. As a result, emergent surgical intervention was required to remove the device and repair the mitral valve. We also conducted a review of previous studies on the retrieval of dislodged left atrial appendage occluders through surgical procedures. It is crucial to maintain vigilance, foster interdisciplinary collaboration, and respond promptly to ensure the safety and efficacy of LAAO procedures.

Discovery of a terpene synthase synthesizing a nearly non-flexible eunicellane reveals the basis of flexibility.

Eunicellane diterpenoids, containing a typical 6,10-bicycle, are bioactive compounds widely present in marine corals, but rarely found in bacteria and plants. The intrinsic macrocycle exhibits innate structural flexibility resulting in dynamic conformational changes. However, the mechanisms controlling flexibility remain unknown. The discovery of a terpene synthase, MicA, that is responsible for the biosynthesis of a nearly non-flexible eunicellane skeleton, enable us to propose a feasible theory about the flexibility in eunicellane structures. Parallel studies of all eunicellane synthases in nature discovered to date, including 2Z-geranylgeranyl diphosphate incubations and density functional theory-based Boltzmann population computations, reveale that a trans-fused bicycle with a 2Z-configuration alkene restricts conformational flexibility resulting in a nearly non-flexible eunicellane skeleton. The catalytic route and the enzymatic mechanism of MicA are also elucidated by labeling experiments, density functional theory calculations, structural analysis of the artificial intelligence-based MicA model, and mutational studies.

A Two-Generation Reproductive Toxicity Study of Cerium Nitrate in Sprague-Dawley Rats.

A two-generation reproductive toxicity study was performed to evaluate the effects of cerium nitrate on the development of the parent, offspring, and third generation of Sprague-Dawley (SD) rats. A total of 240 SD rats (30 rats/sex/group) were randomly divided into four dosage groups according to body weight: 0 mg/kg, 30 mg/kg, 90 mg/kg, and 270 mg/kg. The rats were administered different dosages of cerium nitrate by oral gavage. There were no observed changes related to cerium nitrate in body weight, food consumption, sperm survival rate, motility, mating rate, conception rate, abortion rate, uterine plus fetal weight, uterine weight, corpus luteum number, implantation rate, live fetus number (rate), stillbirth number (rate), absorbed fetus number (rate), appearance, visceral, and skeletal in rats of each generation dosage group. In addition, the pathological findings showed no significant lesions associated with cerium nitrate toxicity in all tissues and organs, including reproductive organs. In conclusion, the present study showed that long-term oral gavage of cerium nitrate at 30 mg/kg, 90 mg/kg, and 270 mg/kg had no significant effect on reproduction and the developmental ability of their offspring in rats. The no-observed-adverse-effect level (NOAEL) of cerium nitrate in SD rats was higher than 270 mg/kg.