Mechanisms of immune regulation by the placenta: Role of type I interferon and interferon-stimulated genes signaling during pregnancy.

Pregnancy is a unique condition where the maternal immune system is continuously adapting in response to the stages of fetal development and signals from the environment. The placenta is a key mediator of the fetal/maternal interaction by providing signals that regulate the function of the maternal immune system as well as provides protective mechanisms to prevent the exposure of the fetus to dangerous signals. Bacterial and/or viral infection during pregnancy induce a unique immunological response by the placenta, and type I interferon is one of the crucial signaling pathways in the trophoblast cells. Basal expression of type I interferon-ß and downstream ISGs harbors physiological functions to maintain the homeostasis of pregnancy, more importantly, provides the placenta with the adequate awareness to respond to infections. The disruption of type I interferon signaling in the placenta will lead to pregnancy complications and can compromise fetal development. In this review, we focus the important role of placenta-derived type I interferon and its downstream ISGs in the regulation of maternal immune homeostasis and protection against viral infection. These studies are helping us to better understand placental immunological functions and provide a new perspective for developing better approaches to protect mother and fetus during infections.

Twist1-IRF9 Interaction Is Necessary for IFN-Stimulated Gene Anti-Zika Viral Infection.

An efficient immune defense against pathogens requires sufficient basal sensing mechanisms that can deliver prompt responses. Type I IFNs are protective against acute viral infections and respond to viral and bacterial infections, but their efficacy depends on constitutive basal activity that promotes the expression of downstream genes known as IFN-stimulated genes (ISGs). Type I IFNs and ISGs are constitutively produced at low quantities and yet exert profound effects essential for numerous physiological processes beyond antiviral and antimicrobial defense, including immunomodulation, cell cycle regulation, cell survival, and cell differentiation. Although the canonical response pathway for type I IFNs has been extensively characterized, less is known regarding the transcriptional regulation of constitutive ISG expression. Zika virus (ZIKV) infection is a major risk for human pregnancy complications and fetal development and depends on an appropriate IFN-ß response. However, it is poorly understood how ZIKV, despite an IFN-ß response, causes miscarriages. We have uncovered a mechanism for this function specifically in the context of the early antiviral response. Our results demonstrate that IFN regulatory factor (IRF9) is critical in the early response to ZIKV infection in human trophoblast. This function is contingent on IRF9 binding to Twist1. In this signaling cascade, Twist1 was not only a required partner that promotes IRF9 binding to the IFN-stimulated response element but also an upstream regulator that controls basal levels of IRF9. The absence of Twist1 renders human trophoblast cells susceptible to ZIKV infection.

Association between PRKG1 gene and gene-environment interactions with pediatric asthma.

OBJECTIVE: To investigate the relationship between single nucleotide polymorphisms (SNPs) of cGMP-dependent protein kinase I (PRKG1) gene and gene-environment interactions with bronchial asthma in children. METHODS: 109 asthma patients and 158 healthy controls from the General Hospital of Northern Theater Command were enrolled, based case-control study. The iMLDR® multiple SNP typing technique was applied to detect the genotypes of rs7903366, rs7081864, rs7070958 and rs7897633 in PRKG1 gene. The percentage of eosinophils (EOS%) in peripheral blood and serum immunoglobulin E (IgE) in the case group were also measured. Gene-environment interactions were examined using the generalized multi-factor dimensionality reduction (GMDR) method. RESULTS: There were polymorphisms in four SNPs of PRKG1 gene in the case and control groups. The genotype and allele frequencies distribution of rs7897633 demonstrated statistical significance (p < 0.05). There were no statistically significant differences in EOS% and IgE among genotypes at the four SNPs of PRKG1 gene (p > 0.05). The haplotypes CAGA and TGAC presented significant association with asthma risk (p < 0.05). The four-factor model indicated a potential gene-environment interaction in rs7897633, allergen exposure, residence, and environmental tobacco smoke (ETS) exposure (p < 0.05). CONCLUSIONS: The rs7897633 in PRKG1 gene was associated with susceptibility to childhood asthma, and C allele is a protective factor. The haplotype CAGA had a protective effect against asthma risk and TGAC was linked to the high risk of developing asthma. Moreover, the interaction of rs7897633, allergen exposure, residence, and ETS exposure conferred susceptibility to childhood asthma.

Incidence and risk factors of post-operative delirium in glioma patients: A prospective cohort study in general wards.

AIMS: Glioma patients are at high risk for postoperative delirium (POD), yet studies focusing on this population in general neurosurgical ward settings are limited. This paper investigates the incidence of POD and related risk factors in glioma patients hospitalized in general wards. DESIGN: Prospective observational study. METHODS: This prospective study included 133 adult glioma patients hospitalized in the general neurosurgery ward. In addition to collecting routine perioperative general clinical data, patients' psychological status was assessed preoperatively using the Hospital Anxiety and Depression Scale (HADS). POD was assessed within 3 days postoperatively using the Confusion of Consciousness Assessment method, twice daily. The incidence of POD was calculated, and risk factors were identified using logistic regression analysis. RESULTS: The incidence of POD in glioma patients admitted to the general ward was 31.6% (40/133). Multivariate regression revealed advanced age (age > 50 years), frontal lobe tumour, presence of preoperative anxiety or depression, retention of a luminal drain, postoperative pain, indwelling catheter these six factors were independent risk factors for the development of delirium in patients after surgery. CONCLUSION: In general ward settings, supratentorial glioma patients exhibit a high risk of POD. Critical risk factors include preoperative psychological conditions, as well as postoperative pain, drainage and catheterization. Rigorous preoperative evaluations, effective pain management strategies and the integration of humanistic care principles are essential in mitigating the risk of POD for glioma patients. RELEVANCE TO CLINICAL PRACTICE: In general ward settings, this study reveals the high occurrence of POD in glioma patients and identifies preoperative psychological states, age, tumour location and several postoperative factors as significant risk factors for POD, which provides a framework for targeted interventions. By integrating these insights into clinical practice, healthcare teams can better identify glioma patients at risk for POD and implement preventive measures, thereby enhancing recovery and overall care quality for glioma patients in general neurosurgical wards. REPORTING METHOD: This study adheres to the STROBE guidelines, ensuring a transparent and comprehensive reporting of the observational research methodology and results. PATIENT OR PUBLIC CONTRIBUTION: Patients involvement was limited to the provision of data through their participation in the study's assessments and the collection of clinical information. The study did not involve a direct patient or public contribution in the design, conduct, analysis, or interpretation of the data, nor in the preparation of the manuscript.

Placenta-derived interferon-stimulated gene 20 controls ZIKA virus infection.

Zika virus is a positive-sense single-stranded RNA virus, which can be transmitted across the placenta and has adverse effects on fetal development during pregnancy. The severity of these complications highlights the importance of prevention and treatment. However, no vaccines or drugs are currently available. In this study, we characterize the IFNß-mediated anti-viral response in trophoblast cells in order to identify critical components that are necessary for the successful control of viral replication and determine whether components of the IFN-induced response can be used as a replacement therapy for ZIKA virus infection during pregnancy. We identify and characterize interferon-stimulated gene 20 (ISG20) as playing a central role in controlling Zika virus infection in trophoblast cells and successfully establish a recombinant ISG20-Fc protein that effectively decreases viral titers in vitro and in vivo by maintaining its exonuclease activity and displaying potential immune modulatory functions. Recombinant ISG20-Fc has thus the potential to be further developed as an anti-viral treatment against ZIKA viral infection in high-risk populations, particularly in pregnant women.

How I do it: a purely endoscopic endonasal approach for anterior clinoidal meningioma.

BACKGROUND: Surgery for anterior clinoid meningiomas (ACMs) remains challenging due to their tight adhesion to vital neurovascular and has been traditionally performed through a transcranial approach. METHOD: We present the key steps of the endoscopic endonasal approach (EEA) for ACMs with a video illustration and figures. The relevant surgical anatomy is described along with the indications and limitations of this approach. CONCLUSION: The EEA offers a good treatment option for selected ACMs. It allows for the removal of involved hyperostotic bone and dural attachments, early identification and control of the neurovascular structure, and avoidance of brain retraction.

[Research status of Bovis Calculus and relevant Chinese patent medicines based on bibliometric analysis].

With scarce resources, natural Bovis Calculus is expensive and hard to meet clinical demand. At the moment, four kinds of Bovis Calculus are available on the market: the natural product, in vitro cultured product, synthesized product, and the product formed in cow after manual intervention. In this study, papers on the four kinds of Bovis Calculus products and relevant Chinese patent medicines were searched from Web of Science, PubMed, and China National Knowledge Infrastructure(CNKI). CiteSpace, citexs AI, and CNKI were employed for bibliometric analysis and knowledge map analysis. On this basis, the status, trend, and focuses of research on Bovis Calculus and relevant Chinese patent medicines were summarized. The results suggested overall slow development in the research on Bovis Calculus and relevant Chinese patent medicines with three typical growth stages. It is consistent with the development of Bovis Calculus substitutes and the national policy for the development of traditional Chinese medicine. At the moment, the research on Bovis Calculus and relevant Chinese patent medicines has been on the rise. In recent years, there has been an explosion of research on them, particularly the quality control of Bovis Calculus and the Chinese patent medicines, the pharmacological efficacy of Chinese patent medicines, such as Angong Niuhuang Pills, and the comparison of the quality of various Bovis Calculus products. However, there is a paucity of research on the pharmacological efficacy and the mechanism of Bovis Calculus. This medicinal and the relevant Chinese patent medicines have been studied from diverse perspectives and China becomes outstanding in this research field. However, it is still necessary to reveal the chemical composition, pharmacological efficacy, and mechanism through multi-dimensional deep research.

Phloem Companion Cell-Specific Transcriptomic and Epigenomic Analyses Identify MRF1, a Regulator of Flowering.

The phloem plays essential roles in the source-to-sink relationship and in long-distance communication, and thereby coordinates growth and development throughout the plant. Here we employed isolation of nuclei tagged in specific cell types coupled with low-input, high-throughput sequencing approaches to analyze the changes of the chromatin modifications H3K4me3 and H3K27me3 and their correlation with gene expression in the phloem companion cells (PCCs) of Arabidopsis(Arabidopsis thaliana) shoots in response to changes in photoperiod. We observed a positive correlation between changes in expression and H3K4me3 levels of genes that are involved in essential PCC functions, including regulation of metabolism, circadian rhythm, development, and epigenetic modifications. By contrast, changes in H3K27me3 signal appeared to contribute little to gene expression changes. These genomic data illustrate the complex gene-regulatory networks that integrate plant developmental and physiological processes in the PCCs. Emphasizing the importance of cell-specific analyses, we identified a previously uncharacterized MORN-motif repeat protein, MORN-MOTIF REPEAT PROTEIN REGULATING FLOWERING1 (MRF1), that was strongly up-regulated in the PCCs in response to inductive photoperiod. The mrf1 mutation delayed flowering, whereas MRF1 overexpression had the opposite effect, indicating that MRF1 acts as a floral promoter.

MgI2-Catalyzed Nucleophilic Ring-Opening Reactions of Donor-Acceptor Cyclopropanes with Indoline-2-thiones.

MgI2-catalyzed nucleophilic ring-opening reactions of donor-acceptor cyclopropanes with indoline-2-thiones as easy-to-handle sulfur nucleophiles were investigated. A series of functionalized γ-indolylthio butyric acid derivatives were synthesized in good to excellent yields under mild reaction conditions. Furthermore, the thioether functionalized ring-opening products could be transformed to sulfone and methionine analogues.

Correlation analysis of physical fitness and its impact on falls in 2130 community- dwelling older adults: a retrospective cross-sectional study.

BACKGROUND: As the community-dwelling population ages in Taiwan, concerns regarding long-term care have grown more urgent. Physical fitness plays a key role in enabling community-dwelling older adults to independently complete daily tasks and avoid falling accidents. However, the effect of physical fitness on falls and other fitness-related factors remains poorly understood. METHODS: In this retrospective cross-sectional study, 2130 community-dwelling older adults were recruited from a rural region of Taiwan. Each of these participants completed a demographics interview and frailty questionnaire and reported their history of falls. We evaluated each participant's height and body weight measurements, calf circumference, bone mass density, and results on the grip strength, single-leg standing, chair sit-and-reach, 8-ft up-and-go, 30-second chair stand, 2-minute step, 30-second arm curl, 6-m walk, and back scratch tests to determine their overall physical fitness, which consisted of their body composition, muscular strength and endurance, flexibility, and cardiopulmonary fitness. RESULTS: The prevalence of falls in the preceding year among the older adults surveyed was 20.8%, and the resultant hospitalization rate was 10.9%. The older adults who were more physically active in the past week, had regular exercise habits, lived with family, and had no history of hospitalization due to falls, exhibited greater performance on the physical fitness tests. Three time fallers exhibited lower levels of overall physical fitness than did those who had not fallen. The nonfallers outperformed the fallers in grip strength (participants who had not fallen and those who had fallen once, twice, or three times in the preceding year: 24.66 ± 0.19 vs. 23.66 ± 0.35 vs. 20.62 ± 0.71 vs. 22.20 ± 0.90 kg) and single-leg standing duration (19.38 ± 0.39 vs. 16.33 ± 0.78 vs. 13.95 ± 1.67 vs. 12.34 ± 1.82 seconds). CONCLUSIONS: Exercise habits, living status, hospitalization due to falls, and amount of exercise were all associated with physical fitness in community-dwelling older adults. The results of all of the assessments indicated that the participants who had fallen three times exhibited lower levels of physical fitness than did those who had not fallen in the previous year. Physical measurements, including grip strength and single-leg standing duration, are associated with an individual's risk of falling, which indicates that they should be considered in the development of geriatric physical fitness and fall-prevention programs.

Association of histological subtype with risk of recurrence in craniopharyngioma patients: a systematic review and meta-analysis.

It is controversial whether there is a different risk of recurrence between two histological subtypes in craniopharyngioma (CP) patients. Some reported that adamantinomatous craniopharyngioma (ACP) had a higher risk of recurrence than papillary craniopharyngioma (PCP), but others reported that there is no significant difference between them. So, we conducted this systematic review and meta-analysis to determine the association between the histological subtype of CP and the rate of recurrence. A comprehensive literature search was undertaken in PubMed, EMBASE, and Web of Science for all English articles published up to November 2020. Recurrence data stratified by ACP and PCP were extracted from studies meeting inclusion criteria. A pooled analysis of the association between the histological subtype of craniopharyngioma and rates of recurrence was performed. Thirteen articles containing 974 patients were included. When stratified by two pathological subtypes, the total recurrence rate of ACP was 26.0% and PCP was 14.1%, which showed ACP associated with a higher risk of tumor recurrence than PCP (odds ratio [OR] = 2.12, 95% confidence interval [CI] = 1.36, 3.30, P = 0.00). This is the first meta-analysis focusing on histological subtypes of CP. PCP associates with a lower risk of recurrence than ACP, indicating that ACP could act as one of recurrence risk factors for CP patients. Nevertheless, large sample size and well-designed multicenter studies in which the other clinical variables are controlled to determine the histological subtype of CP as an independent recurrence risk factor are needed.

Use of Retroauricular Flaps to Reconstruct Defects of the Helical Rim and Adjuvant Intralesional Corticosteroids after Resection of Large Keloids.

BACKGROUND: The optimal treatment for large helical rim keloids remains unclear. AIMS: The authors evaluated patient outcomes when retro auricular flaps were used to reconstruct helical rim defects and adjuvant intralesional corticosteroids were prescribed after resection of large keloids. MATERIALS AND METHODS: The authors evaluated 7 females with 12 large keloids of the helical rim (5 patients had lesions in both ears). All patients were aged 18 to 33 years. The authors used retro auricular flaps to reconstruct the helical rim defects and prescribed adjuvant intralesional corticosteroids after resection. The lesion area ranged from 2.5 × 2.0 to 3.5 × 3.5 cm2. The flap size ranged from 2.5 × 3.0 to 3.5 × 4.5 cm2. The flaps and wound bases received 3 steroid injections at approximately 1, 2, and 3 months postoperatively. RESULTS: No flap necrosis or complications were noted. The postoperative esthetic results were satisfactory in 8 patients and excellent in 4. All patients were followed up for 14 to 28 months (median, 20.6 months). No recurrence was noted, although 3 patients exhibited mild scarring of the wound flap base. CONCLUSIONS: A retro auricular flap is safe and effective for reconstructing helical rim defects; adjuvant intralesional corticosteroids prevent scarring of the flap wound base after resection of large keloids.

Reconstruction of Large Acquired Palatal Defects Using Facial-Submental Artery Island Flap.

OBJECTIVE: To evaluate the feasibility and clinical effect of facial-submental artery island flap (FSAIF) in the repair of palatal defects, and to provide reference for the clinical application of submental artery island flap. METHODS: Nine patients with palatal defects, the range of nasal palatal perforation defects were 3 cm × 4cm to 3 cm × 6 cm (median 3 cm × 5.4 cm), were repaired by FSAIF, and the sizes of FSAIF were 4 cm × 9cm to 4 cm × 12 cm (median 4 cm × 10.4 cm,). Postoperative clinical efficacy was evaluated, including infection and necrosis of mucosal flap and postoperative palatal fistula perforation. Patients were followed up to evaluate their chewing, swallowing, speech function, and satisfaction of appearance. RESULTS: All patients were successfully repaired with FSAIF. Followed up 13∼35 months, there was no palatal fistula perforation in all patients. The speech, agitation, and swallowing function were not affected and the patients were satisfied with the appearance. CONCLUSION: FSAIF is a safe and reliable method for palatal defect repair.

[DNA methylation diversity analysis of Lycium barbarum samples from different cultivation areas based on MSAP].

Obvious epigenetic differentiation occurred on Lycium barbarum in different cultivation areas in China. To investigate the difference and change rule of DNA methylation level and pattern of L. barbarum from different cultivation areas in China, the present study employed fluorescence-assisted methylation-sensitive amplified polymorphism(MSAP) to analyze the methylation level and polymorphism of 53 genomic DNA samples from Yinchuan Plain in Ningxia, Bayannur city in Inner Mongolia, Jingyuan county and Yumen city in Gansu, Delingha city in Qinghai, and Jinghe county in Xinjiang. The MSAP technical system suitable for the methylation analysis of L. barbarum genomic DNA was established and ten pairs of selective primers were selected. Among amplified 5'-CCGG-3' methylated sites, there were 35.85% full-methylated sites and 39.88% hemi-methylated sites, showing a high degree of epigenetic differentiation. Stoichiometric analysis showed that the ecological environment was the main factor affecting the epigenetic characteristics of L. barbarum, followed by cultivated varieties. Precipitation, air temperature, and soil pH were the main ecological factors affecting DNA methylation in different areas. This study provided a theoretical basis for the analysis of the epigenetic mechanism of L. barbarum to adapt to the diffe-rent ecological environments and research ideas for the introduction, cultivation, and germplasm traceability of L. barbarum.

Discovery of novel VEGFR-2 inhibitors embedding 6,7-dimethoxyquinazoline and diarylamide fragments.

VEGF/VEGFR-2 signaling plays a critical part in tumor angiogenesis. Inhibition of this pathway has been considered as a promising approach for cancer treatment. In this work, a series of 6,7-dimethoxy-4-anilinoquinazoline derivatives bearing diarylamide moiety were designed, synthesized and evaluated as potent inhibitors of VEGFR-2 kinase. Their in vitro antiproliferation activities against two human cancer cell lines Hep-G2 and MCF-7 have also been determined. Among them, compound 14b exhibited the most potent inhibitory activity against VEGFR-2 with IC50 value of 0.016 ± 0.002 µM and it showed the most potent antiproliferative effect against Hep-G2 and MCF-7 with IC50 values at low-micromolar range. Molecular docking studies revealed that these compounds represented by the most potent compound 14b could bind well to the ATP-binding site of VEGFR-2, which suggested that compound 14b could be a potential anticancer agent targeting VEGFR-2.

Fugitive Emissions of Volatile Organic Compounds from a Tailings Pond in the Oil Sands Region of Alberta.

Tailings ponds in the oil sands (OS) region in Alberta, Canada, have been associated with fugitive emissions of volatile organic compounds (VOCs) and other pollutants to the atmosphere. However, the contribution of tailings ponds to the total fugitive emissions of VOCs from OS operations remains uncertain. To address this knowledge gap, a field study was conducted in the summer of 2017 at Suncor's Pond 2/3 to estimate emissions of a suite of pollutants including 68 VOCs using a combination of micrometeorological methods and measurements from a flux tower. The results indicate that in 2017, Pond 2/3 was an emission source of 3322 ± 727 tons of VOCs including alkanes, aromatics, and oxygenated and sulfur-containing organics. While the total VOC emissions were approximately a factor of 2 higher than those reported by Suncor, the individual VOC species emissions varied by up to a factor of 12. A chemical mass balance (CMB) receptor model was used to estimate the contribution of the tailings pond to VOC pollution events in a nearby First Nations and Metis community in Fort McKay. CMB results indicate that Suncor Pond 2/3 contributed up to 57% to the total mass of VOCs measured at Fort McKay, reinforcing the importance of accurate VOC emission estimation methods for tailings ponds.

Increased nuclear translation of YAP might act as a potential therapeutic target for NF1-related plexiform neurofibroma.

Plexiform neurofibroma (pNF) in the head and neck is a characteristic feature in patients with neurofibromatosis type 1 (NF1) and is associated with significant disfigurement and psychological distress. Yes-associated protein (YAP), the key molecule involved in the Hippo pathway, is a vital transductor that regulates the proliferation and remyelinating of Schwann cells. The functional status of YAP and its feasibility as a potential target are still unknown in pNF. A total of 17 pNF tumor tissue specimens from the head and neck were collected at the Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. Histologically, diagnosis of the Schwann cell region in pNF was achieved with hematoxylin-eosin staining, positive reactions for S100, SOX10, ERK and p-ERK, and low identification of Ki67 and SMA. Compared with normal nerve tissue, obviously increased nuclear YAP was detected in the Schwann cell region of pNF, with a mean nuclear staining rate of 67.11%. Based on the shNF1 Schwann cell model (the RSC96 cell line), with upregulated expression of RAS, ERK and p-ERK, p-YAP (Ser127) and p-YAP (Ser397) were significantly decreased and total YAP and nuclear YAP were increased. According to a confocal assay, the interference of shNF1 substantially promoted YAP nuclear translocation. Compared with control Schwann cells, the YAP inhibitor CA3 might have a more sensitive effect (IC50: NC=0.96±0.04, shNF1=0.71±0.02, P<0.05) on the shNF1 Schwann cell model than the classic MEK1/2 inhibitor selumetinib (IC50: NC=14.36±0.95, shNF1=24.83±0.98, P>0.05). For in vivo inhibition, the CA3 group and the selumetinib group displayed a similar inhibition effect with no significant difference. Increased nuclear translation and the functional state of YAP implies that the YAP-Hippo pathway might play an important role in the formation and remyelination of pNF. Compared with selumetinib, the YAP inhibitor can exhibit a similar but more sensitive effect on NF1-/- Schwann cells. These observations imply that YAP as a novel or adjuvant therapy target in the treatment of pNF.

Single-stage endoscopic endonasal approach for the complete removal of trigeminal schwannomas occupying both the middle and posterior fossae.

To introduce a purely endoscopic endonasal trans-Meckel's cave approach or a transclival approach for trigeminal schwannomas (TSs) involving both the middle and posterior fossae. This retrospective study reviewed the medical records and intraoperative videos of 8 patients with TSs occupying both the middle and posterior fossae who underwent an endoscopic endonasal approach (EEA) between January 2017 and October 2019. All 8 patients received total resection under a single-stage EEA. Six patients underwent endoscopic endonasal resection via a purely trans-Meckel's cave approach, and 2 patients underwent endoscopic endonasal resection via a trans-Meckel's cave approach combined with a transclival approach. There was no surgical-related hemorrhage or mortality and no cerebrospinal fluid leakage. All headache symptoms completely improved postoperatively (n = 3 patients). All cranial nerve (CN) symptoms (CN IX and CN VI) improved postoperatively. The most common preoperative symptom was facial numbness (n = 5 patients); 2 of these 5 patients showed a partial improvement, 1 patient experienced worsening, and 2 patients remained unchanged at the last follow-up. Four patients developed postoperative complications, including CN VI palsy (n = 2), dry eye (n = 2), mastication weakness (n = 1), and facial numbness (n = 2). All complications except for dry eye were relieved at the last follow-up, but the patients with dry eye did not develop corneal keratopathy. The endoscopic endonasal trans-Meckel's cave and transclival approaches provide adequate exposure and improve the rate of total resection for TSs occupying both the middle and posterior fossae with minimal invasion. It may be possible to use these approaches as a safe alternative to conventional surgical approaches.

Pituitary adenoma with posterior area invasion of cavernous sinus: surgical anatomy, approach, and outcomes.

We found a series of Knosp grade 3A-4 pituitary adenomas in the posterior areas of the cavernous sinus (CS), a triangular-like structure on axial MRI. In this study, we dissected the surrounding neurovascular structure, discussed the surgical approach, and analyzed outcomes for patients with this invasion into this area. Eight embalmed adult cadaveric specimens were prepared for this study to demonstrate in detail the surgical anatomy related to this triangular-like structure. We used the "two points and one line" method to determine the surgical approach, and 35 cases with this area invasion were retrospectively reviewed. According to the endoscopic and microsurgical anatomy, the triangular-like structure appearing on the axial MRI is correlated with a square-based pyramid structure in the CS, and the upper surface is the posterior portion of the oculomotor triangle. A total of 37 posterior areas of the CS were involved in 35 patients. The accuracy of the "two points and one line" method in predicting the surgical approach is 86.5% (32/37). All three patients with Knosp 3A underwent gross total resection (GTR). Twenty (62.5%) patients with Knosp 4 underwent GTR, 9 (28.1%) patients underwent subtotal resection, and 3 (9.4%) patients underwent partial resection. Preoperative symptoms were alleviated to varying degrees, and no worsening occurred. Postoperative complications included two (5.7%) cases of cerebrospinal fluid leakage, one (2.9%) case of meningitis, two (5.7%) cases of permanent diabetes insipidus, and three (8.6%) cases of transient cranial nerve palsy. The "two points and one line" method is of great value in predicting the surgical approach of pituitary adenomas with CS invasion. The anatomic description of this particular square-based pyramid structure in the CS refines the understanding of pituitary adenomas with CS invasion.

Design, synthesis, herbicidal activity and CoMFA of aryl-formyl piperidinone HPPD inhibitors.

Isoxazole, nicotinic acid and benzoic acid are important components in many natural products and useful synthons to build macrostructures having valuable biological activities. In continuation of our effort to discover 4-hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) inhibitors and search for active fragments from natural products, a series of substituted aryl-formyl piperidinone derivatives with natural product fragments was rationally designed, synthesized and tested for their herbicidal activity. Compound I-9 was considered the most effective candidate with an IC50 value of 0.260 µM. The molecular docking results showed that the triketone group of compound I-9 forms a bidentate complex with a metal ion, and the benzene ring interacted with Phe424 and Phe381 via π-π stacking, which was similar to the mechanisms of mesotrione. The present work indicates that compound I-9 may serve as a potential lead compound for further development of green HPPD inhibitors.