Senaparib as first-line maintenance therapy in advanced ovarian cancer: a randomized phase 3 trial.

Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors as maintenance therapy after first-line chemotherapy have improved progression-free survival in women with advanced ovarian cancer; however, not all PARP inhibitors can provide benefit for a biomarker-unselected population. Senaparib is a PARP inhibitor that demonstrated antitumor activity in patients with solid tumors, including ovarian cancer, in phase 1 studies. The multicenter, double-blind, phase 3 trial FLAMES randomized (2:1) 404 females with advanced ovarian cancer (International Federation of Gynecology and Obstetrics stage III-IV) and response to first-line platinum-based chemotherapy to senaparib 100 mg (n = 271) or placebo (n = 133) orally once daily for up to 2 years. The primary endpoint was progression-free survival assessed by blinded independent central review. At the prespecified interim analysis, the median progression-free survival was not reached with senaparib and was 13.6 months with placebo (hazard ratio 0.43, 95% confidence interval 0.32-0.58; P < 0.0001). The benefit with senaparib over placebo was consistent in the subgroups defined by BRCA1 and BRCA2 mutation or homologous recombination status. Grade ≥3 treatment-emergent adverse events occurred in 179 (66%) and 27 (20%) patients, respectively. Senaparib significantly improved progression-free survival versus placebo in patients with advanced ovarian cancer after response to first-line platinum-based chemotherapy, irrespective of BRCA1 and BRCA2 mutation status and with consistent benefits observed between homologous recombination subgroups, and was well tolerated. These results support senaparib as a maintenance treatment for patients with advanced ovarian cancer after a response to first-line chemotherapy. ClinicalTrials.gov identifier: NCT04169997 .

"Cloth-to-Clothes-Like" Fabrication of Soft Actuators.

Inspired by adaptive natural organisms and living matter, soft actuators appeal to a variety of innovative applications such as soft grippers, artificial muscles, wearable electronics, and biomedical devices. However, their fabrication is typically limited in laboratories or a few enterprises since specific instruments, strong stimuli, or specialized operation skills are inevitably involved. Here a straightforward "cloth-to-clothes-like" method to prepare soft actuators with a low threshold by combining the hysteretic behavior of liquid crystal elastomers (LCEs) with the exchange reaction of dynamic covalent bonds, is proposed. Due to the hysteretic behavior, the LCEs (resemble "cloth") effectively retain predefined shapes after stretching and releasing for extended periods. Subsequently, the samples naturally become soft actuators (resemble "clothes") via the exchange reaction at ambient temperatures. As a post-synthesis method, this strategy effectively separates the production of LCEs and soft actuators. LCEs can be mass-produced in bulk by factories or producers and stored as prepared, much like rolls of cloth. When required, these LCEs can be customized into soft actuators as needed. This strategy provides a robust, flexible, and scalable solution to engineer soft actuators, holding great promise for mass production and universal applications.

Analysis of vertical differentiation of vegetation in Taishan World Heritage site based on cloud model.

While the forests on Mount Taishan are predominantly man-made, there is a notable vertical variation in vegetation. This study employs the method of cloud model, quantifying uncertainty (fuzziness and randomness) of things. Utilizing digital elevation model (DEM) and vegetation distribution data, we constructed elevation cloud models for Mount Taishan's deciduous broad-leaved, temperate coniferous, and mixed coniferous-broadleaved forests. Using three numerical features of the cloud model-Expectation (EX), Entropy (EN), and Hyper-entropy (HE)-we quantitatively analyzed the macro regularity and local heterogeneity of Mount Taishan's forests vertical distribution from the perspective of uncertainty theory. The results indicate: (1) The EX of the core zone elevation of deciduous broad-leaved forest is 716.65 m, temperate coniferous forest is 1053.51 m, and mixed coniferous-broadleaved forest is 1384.09 m. The variation range of the core zone distribution height is smaller in the mixed coniferous-broadleaved forest (EN: 53.74 m) compared to deciduous broad-leaved forest (EN: 99.63 m) and temperate coniferous forest (EN: 121.70 m). (2) The fuzziness and randomness of the distribution height of the lower extension zones of deciduous broad-leaved forest and temperate coniferous forest (EN: 75.15 m, 184.56 m; HE: 24.09 m, 63.54 m) are greater than those of the upper extension zones (EN: 44.75 m, 42.49 m; HE: 14.48 m, 13.23 m). (3) The distribution fuzziness and randomness within temperate coniferous forests exceed those of deciduous broad-leaved forests. Within the core zones, the uncertainty regarding the vertical distribution of vegetation across different aspects remains consistent, which retains the characteristic of man-made forests. However, in transition areas, there is significant disparity, reflecting the adaptive relationship between vegetation and its environment to some extent. In the upper and lower extension zones of deciduous broad-leaved forests, the EX values for the vertical distribution height of mixed coniferous and broad-leaved forests differ significantly from those of deciduous broad-leaved forests (the difference is 22.82-39.15 m), yet closely resemble those of temperate coniferous forests (the difference is 4.79-7.94 m). This suggests a trend wherein deciduous broad-leaved tree species exhibit a proclivity to encroach upon coniferous forest habitats. The elevation cloud model of vertical vegetation zones provides a novel perspective and method for the detailed analysis of Mount Taishan's vegetation vertical differentiation.

piR-1919609 Is an Ideal Potential Target for Reversing Platinum Resistance in Ovarian Cancer.

PURPOSE: PIWI-interacting RNAs (piRNAs) are a type of noncoding small RNA that can interact with PIWI-like RNA-mediated gene silencing (PIWIL) proteins to affect biological processes such as transposon silencing through epigenetic effects. Recent studies have found that piRNAs are widely dysregulated in tumors and associated with tumor progression and a poor prognosis. Therefore, this study aimed to investigate the effect of piR-1919609 on the proliferation, apoptosis, and drug resistance of ovarian cancer cells. METHODS: In this study, we used small RNA sequencing to screen and identify differentially expressed piRNAs in primary ovarian cancer, recurrent ovarian cancer, and normal ovaries. A large-scale verification study was performed to verify the expression of piR-1919609 in different types of ovarian tissue, including ovarian cancer tissue and normal ovaries, by RT-PCR and to analyze its association with the clinical prognosis of ovarian cancer. The expression of PIWILs in ovarian cancer was verified by RT-PCR, Western blotting and immunofluorescence. The effects of piR-1919609 on ovarian cancer cell proliferation, apoptosis and drug resistance were studied through in vitro and in vivo models. RESULTS: (1) piR-1919609 was highly expressed in platinum-resistant ovarian cancer tissues (p < 0.05), and this upregulation was significantly associated with a poor prognosis and a shorter recurrence time in ovarian cancer patients (p < 0.05). (2) PIWIL2 was strongly expressed in ovarian cancer tissues (p < 0.05). It was expressed both in the cytoplasm and nucleus of ovarian cancer cells. (3) Overexpression of piR-1919609 promoted ovarian cancer cell proliferation, inhibited apoptosis, and promoted tumor growth in nude mice. (4) Inhibition of piR-1919609 effectively reversed ovarian cancer drug resistance. CONCLUSION: In summary, we showed that piR-1919609 is involved in the regulation of drug resistance in ovarian cancer cells and might be an ideal potential target for reversing platinum resistance in ovarian cancer.

Identification of PDZD11 as a Potential Biomarker Associated with Immune Infiltration for Diagnosis and Prognosis in Epithelial Ovarian Cancer.

Purpose: Evidence has indicated that PDZD11 is involved in regulating adherens junction. However, the distinct effect of its aberrant expression on epithelial ovarian cancer (EOC) awaits clarification. Methods: In this study, public databases (Gene Expression Omnibus, The Cancer Genome Atlas, and The Genotype-Tissue Expression), online analysis tools (Kaplan-Meier plotter and TIMER), and data analysis methods (Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and the CIBERSORT algorithm) were fully utilized to analyze the differential expression, diagnostic efficiency, prognostic significance, potential function, and correlation with immune infiltration of PDZD11. The differential expression of PDZD11 was tested by immunohistochemistry in EOC tissues (78 cases) and control tissues (37 cases). Results: Our results indicate that PDZD11 was remarkably overexpressed in EOC, which was associated with advanced cancer stages, no lymphatic metastasis status, and poor prognosis. Moreover, PDZD11 played a role in cell adhesion, cell proliferation, and immune responses. Also, PDZD11 was significantly related to the abundances of infiltrating immune cells in EOC, including neutrophils, macrophages, dendritic cells, CD8+ T cells, and CD4+ T cells, and its expression was positively co-expressed with well-known immune checkpoints, including TIGIT, TIM3, LAG3, CTLA4, and PD-1. Conclusion: These results suggest that PDZD11 could be a potential diagnostic and prognostic biomarker associated with immune infiltration in EOC, and our findings might help elucidate the function of PDZD11 in carcinogenesis.

Auditory brainstem implants for hearing rehabilitation in NF2-schwannomatosis: A systematic review and single-arm meta-analysis.

BACKGROUND: NF2-schwannomatosis (NF2) is an autosomal dominant disorder prone to hearing loss. Auditory brainstem implants (ABIs) offer a promising solution for hearing rehabilitation in NF2. OBJECTIVE: To synthesize existing literature on ABI implantation in NF2, focusing on audiological outcomes and ABI-related complications. METHODS: The systematic review followed PRISMA guidelines and was registered in the PROSPERO database (CRD42022362155). Relevant studies were identified by searching PubMed, EMBASE, CENTRAL, CMB, and CNKI from inception to August 2023. Data on environmental sound discrimination, open-set discrimination, closed-set discrimination, and ABI-related complications were extracted and subjected to meta-analysis. Publication bias was evaluated using funnel plots and Egger's test. RESULTS: Thirty-three studies were included. The pooled estimate was 58% (95% CI 49-66%) for environmental sound discrimination and 55% (95% CI 40-69%) for closed-set discrimination. Regarding open-set discrimination, the pooled estimates were 30% (95% CI 19-42%) for sound only, 46% (95% CI 37-54%) for lip-reading only, and 63% (95% CI 55-70%) for sound plus lip-reading. The pooled occurrence of ABI-related complications was 33% (95% CI 15-52%). CONCLUSION: This meta-analysis underscores the effectiveness and safety of ABIs in NF2, providing valuable insights for evidence-based decision-making and hearing rehabilitation strategies.

Visual outcomes and optimal timing for repeat surgery in cases of postoperative hematoma following transsphenoidal surgery for pituitary neuroendocrine tumors: A retrospective cohort study.

OBJECTIVE: To investigate the visual outcomes and optimal timing for repeat surgery in cases of postoperative hematoma following transsphenoidal surgery for pituitary neuroendocrine tumors (PitNETs). METHODS: A retrospective study was conducted on 28 patients who developed evident postoperative hematoma out of a total of 9,010 patients. The hematomas were classified into three types based on their CT appearance. Type 1a - mild high density with no tension, Type 1b - thin-layer high density; Type 2a - solid high density with large empty cavities, Type 2b - solid high density with small empty cavities; Type 3 -solid high density with no cavity showing high tension. Patient data were collected for analysis. RESULTS: The study cohort comprised 10 female and 18 male patients, with a mean age of 51.5±11.9 years. Most patients presented with large adenomas (median diameter 36mm). Postoperative visual sight improved in 12 patients, remained stable in 11 patients, and worsened in 5 patients. Notably, no patients experienced worsened visual sight beyond twenty-four hours after the operation. Among the five patients with visual deterioration, four had CT type 3 hematoma (4/6, 66.7%), and one had CT type 2b hematoma (1/9, 11.1%). Patients in the type 3 CT group were significantly more prone to experience visual deterioration compared to those in the type 2 group (odds ratio [OR] 2.154 [95% CI 1.858-611.014], P=.027). Four patients underwent repeat surgery after visual deterioration, resulting in visual improvement following a prolonged recovery period. Postoperative hematoma had limited impact on pituitary dysfunction and hyponatremia. CONCLUSION: Our study reveals a significant association between postoperative hematoma CT types and visual deterioration. For patients with stable visual sight and type 1 or 2a hematoma, conservative strategies may be considered. Conversely, type 2b and 3 patients are at higher risk of visual deterioration, especially within the first 24 hours after the operation. Consequently, early reoperation before vision worsens may be a prudent approach to reduce risks and improve visual outcomes, particularly in type 3 patients.

Deep learning algorithm-based multimodal MRI radiomics and pathomics data improve prediction of bone metastases in primary prostate cancer.

PURPOSE: Bone metastasis is a significant contributor to morbidity and mortality in advanced prostate cancer, and early diagnosis is challenging due to its insidious onset. The use of machine learning to obtain prognostic information from pathological images has been highlighted. However, there is a limited understanding of the potential of early prediction of bone metastasis through the feature combination method from various sources. This study presents a method of integrating multimodal data to enhance the feasibility of early diagnosis of bone metastasis in prostate cancer. METHODS AND MATERIALS: Overall, 211 patients diagnosed with prostate cancer (PCa) at Gansu Provincial Hospital between January 2017 and February 2023 were included in this study. The patients were randomized (8:2) into a training group (n = 169) and a validation group (n = 42). The region of interest (ROI) were segmented from the three magnetic resonance imaging (MRI) sequences (T2WI, DWI, and ADC), and pathological features were extracted from tissue sections (hematoxylin and eosin [H&E] staining, 10 × 20). A deep learning (DL) model using ResNet 50 was employed to extract deep transfer learning (DTL) features. The least absolute shrinkage and selection operator (LASSO) regression method was utilized for feature selection, feature construction, and reducing feature dimensions. Different machine learning classifiers were used to build predictive models. The performance of the models was evaluated using receiver operating characteristic curves. The net clinical benefit was assessed using decision curve analysis (DCA). The goodness of fit was evaluated using calibration curves. A joint model nomogram was eventually developed by combining clinically independent risk factors. RESULTS: The best prediction models based on DTL and pathomics features showed area under the curve (AUC) values of 0.89 (95% confidence interval [CI], 0.799-0.989) and 0.85 (95% CI, 0.714-0.989), respectively. The AUC for the best prediction model based on radiomics features and combining radiomics features, DTL features, and pathomics features were 0.86 (95% CI, 0.735-0.979) and 0.93 (95% CI, 0.854-1.000), respectively. Based on DCA and calibration curves, the model demonstrated good net clinical benefit and fit. CONCLUSION: Multimodal radiomics and pathomics serve as valuable predictors of the risk of bone metastases in patients with primary PCa.

H2O2-triggered controllable carbon monoxide delivery for photothermally augmented gas therapy.

Carbon monoxide (CO) gas therapy has shown great potential as a very promising approach in the ongoing fight against tumors. However, delivering unstable CO to the tumor site and safely releasing it for maximum efficacy still have unsatisfactory outcomes. In this study, we've developed nanotheranostics (IN-DPPCO NPs) based on conjugated polymer IN-DPP and carbon monoxide (CO) carrier polymer mPEG(CO) for photothermal augmented gas therapy. The IN-DPPCO NPs can release CO with the hydrogen peroxide (H2O2) overexpressed in the tumor microenvironment. Meanwhile, IN-DPPCO NPs exhibit strong absorption in the near-infrared window, showing a high photothermal conversion efficiency of up to 41.5% under 808 nm laser irradiation. In vitro and in vivo experiments demonstrate that these nanotheranostics exhibit good biocompatibility. Furthermore, the synergistic CO/photothermal therapy shows enhanced therapeutic efficacy compared to gas therapy alone. This work highlights the great promise of conjugated polymer nanoparticles as versatile nanocarriers for spatiotemporally controlled and on-demand delivery of gaseous messengers to achieve precision cancer theranostics.

Pituitary neuroendocrine tumor: A neuropsychological comparison with intra-axial tumor.

OBJECTIVE: Despite pituitary neuroendocrine tumor (PitNET) being extra-axial tumors without direct damage to brain tissue, patients with PitNET exhibit neuropsychological impairments. However, it remains unclear whether there are neuropsychological differences between PitNET and intra-axial tumors that directly destroy the brain parenchyma. This prospective study aims to clarify this distinction to inform decision-making for intracranial tumors of diverse origins. METHODS: A total of 146 patients with PitNET, 74 patients with glioma representing intra-axial tumors, and 52 age-, sex-, and education-matched healthy controls were recruited. All patients received standard treatment and postoperative rehabilitation. Clinical data were meticulously collected, and neuropsychological tests were administered to all participants both before and 3 months after surgery. RESULTS: Both PitNET and glioma patients experience the dual burden of cognitive and affective deficits. However, the feature of these deficits differs substantially. In PitNET patients, the deficits are relatively mild and focal, whereas in glioma patients, they are severe and extensive. Specifically, PitNET patients exhibit deficits in memory, anxiety, and negative affect. In contrast, glioma patients display deficits in executive function, attention, anxiety, positive/negative affect, and empathy. Notably, except for persistent memory deficits, the majority of neuropsychological scores declines in PitNET patients are restorable and can reach improvement within a short period after standard surgical therapy and perioperative management. Conversely, glioma patients not only fail to show improvements but also demonstrate worsening in terms of general cognition and memory postoperatively. INTERPRETATION: As an extra-axial tumor, PitNET may exhibit distinctive cognitive and affective functioning compared to intra-axial tumors, highlighting the need for specific treatment approaches for PitNET patients.

A novel lysosomal targeted near-infrared probe for ratio detection of carbon monoxide in cells and in vivo.

Carbon monoxide (CO) as an endogenous gas signaling molecule possesses important physiological functions and is of great significance in the treatment of various diseases. Real-time tracking of CO in living organisms has become a research hotspot in recent years. This article presents a lysosomal targeted near-infrared ratio fluorescence probe (TBM-CO) for selective detection of CO based on the dicyanoisophorone skeleton and morpholine fragment. The probe TBM-CO with weak ICT effect can be transformed to precursor TBM-NH2 with strong ICT effect by the traditional Tsuji-Trost reaction procession in the presence of Pd2+ ions. The mechanism was proved by DFT calculation or the MS and HPLC results respectively. In the near-infrared region an obvious ratio fluorescence intensity change (F686 / F616) is observed in vitro spectral experiments. The concentration titration experiments indicate that there is a good liner relationship between the ratio fluorescence intensity and the concentration in the range of 0 to 50 µM (R2 = 0.996) and the detection limit is calculated as 0.38 µM. The cell fluorescence imaging and co-localization experiments further demonstrate that TBM-CO is able to detect the exogenous and endogenous CO in lysosomal subcellular organelle. Finally, it was used to detect the changes of CO concentration in living mice successfully. In short, a probe with three advantages of near-infrared emission, ratiometric fluorescence and organelle targeting was reported and used to detect CO successfully in cells and in living mice.

Clinical and Pathological Features of Pit1/SF1 Multilineage Pituitary Neuroendocrine Tumor.

BACKGROUND AND OBJECTIVES: Lineage-based classification has critical clinical implications in pituitary neuroendocrine tumor (PitNET). As the most prevalent subtype of multilineage PitNET, PitNET originating from both pituitary-specific positive transcription factor 1 (Pit1) and steroidogenic factor-1 (SF1) lineages (Pit1/SF1-adenoma) is expected to exhibit rich and varied clinical behaviors. A comprehensive understanding of the clinical and pathological characteristics of Pit1/SF1-adenoma will provide mechanistic insight and influence the prognosis and treatment of PitNET. METHODS: A retrospective study was conducted by reviewing 57 cases of Pit1/SF1-adenoma between 2018 and 2022. We also included 88 cases of PitNET arising from Pit1 cell lineage (Pit1-adenoma) and 70 cases of PitNET arising from SF1 cell lineage (SF1-adenoma) as controls. Comprehensive data, including demographic, symptom, endocrinal, radiological, surgical, pathological, and prognostic information, were systematically collected. All specimens were immunostained for pituitary transcription factors (PTFs) and pituitary hormones. RESULTS: The detection rate was 8.0% for Pit1/SF1-adenoma within PitNET surgical specimens. Pit1/SF1-adenoma displayed a male predominance, with the mean diagnosis age falling between Pit1-adenoma and SF1-adenoma. The endocrine activity of Pit1/SF1-adenoma was lower than Pit1-adenoma but higher than SF1-adenoma. Pit1/SF1-adenoma had a higher incidence of cavernous sinus invasion (56.1%) than both Pit1-adenoma (38.6%, P = .039) and SF1-adenoma (27.1%, P = .001). Furthermore, Pit1/SF1-adenoma showed more postoperative complications than Pit1-adenoma (29.8% vs 8.0%, P = .001). Nonfunctional Pit1/SF1-adenoma had a higher radiological tumor recurrence rate than nonfunctional SF1-adenoma (34.8% vs 10.9%, P = .021). Notably, the immunostaining pattern was diverse in Pit1/SF1-adenoma, with various combinations of staining intensity for PTFs and 15 combinations for 6 pituitary hormones. Intriguingly, various PTFs combinations had no different impact on the outcome of Pit1/SF1-adenoma. CONCLUSION: Pit1/SF1-adenoma represents a unique pathological subtype of PitNET, characterized by distinctive clinical behaviors. Identifying Pit1/SF1-adenoma can facilitate more precise management of PitNET by the practical use of Pit1/SF1 immunostaining.

Betaine alleviates cognitive impairment induced by homocysteine through attenuating NLRP3-mediated microglial pyroptosis in an m6A-YTHDF2-dependent manner.

Dementia, with homocysteine (Hcy) as an important risk factor, is a severe public health problem in the aging society. Betaine serves as a methyl donor and plays an important role in reducing Hcy. However, the effects and mechanisms of betaine on Hcy-induced cognitive impairment remain unclear. Firstly, SD rats were injected with Hcy (400 µg/kg) through vena caudalis, and betaine (2.5 % w/v) was supplemented via drinking water for 14 days. Betaine supplementation could attenuate Hcy-induced cognitive impairment in the Y maze and novel object recognition tests by repairing brain injury. Meanwhile, microglial activation was observed to be inhibited by betaine supplementation using immunofluorescence and sholl analysis. Secondly, HMC3 cells were treated with betaine, which was found to decrease the ROS level, ameliorate cell membrane rupture, reduce the release of LDH, IL-18 and IL-1ß, and attenuate the damage of microglia to neurons. Mechanistically, betaine alleviates cognitive impairment by inhibiting microglial pyroptosis via reducing the expressions of NLRP3, ASC, pro-caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, IL-18 and IL-1ß. Betaine treatment can increase SAM/SAH ratio, confirming its enhancement on methylation capacity. Furthermore, betaine treatment was found to enhance N6-methyladenosine (m6A) modification of NLRP3 mRNA, and reduced the NLRP3 mRNA stability through increasing the expression of the m6A reader YTH N6-methyladenosine RNA binding protein 2 (YTHDF2). Finally, silencing YTHDF2 could reverse the inhibitory effect of betaine on pyroptosis. Our data demonstrated that betaine attenuated Hcy-induced cognitive impairment by suppressing microglia pyroptosis via inhibiting the NLRP3/caspase-1/GSDMD pathway in an m6A-YTHDF2-dependent manner.

[Corrigendum] Long non­coding RNA HR1 participates in the expression of SREBP­1c through phosphorylation of the PDK1/AKT/FoxO1 pathway.

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that the data panel for the "Huh7+BSA" experiment shown in Fig. 1D on p. 2852, showing the relative size of lipid droplets as determined in morphological studies using oil red O staining, had also appeared previously in the following article published by the same research group [Li D, Cheng M, Niu Y, Chi X, Liu X, Fan J, Fan H, Chang Y and Yang W: Identification of a novel human long non-coding RNA that regulates hepatic lipid metabolism by inhibiting SREBP-1c. Int J Biol Sci 13: 349-357, 2017]. Upon examining their original data, the authors have realized that this data panel was inadvertently selected incorrectly in Fig. 1, and the revised version of Fig. 1, containing the correct data panel for Fig. 1D, is shown on the next page. Note that this error did not significantly affect the results or the conclusions reported in this paper. All the authors agree to the publication of this Corrigendum, and are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to correct this error. Moreover, the authors apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 18: 2850-2856, 2018; DOI: 10.3892/mmr.2018.9278].

Identification of HSPD1 as a novel invasive biomarker associated with mitophagy in pituitary adenomas.

BACKGROUND: The crucial role of mitophagy in tumor progression has been recognized. Therefore, our study aimed to investigate the potential correlation between pituitary adenoma invasiveness and the mitophagy processes. METHODS: In this study, we used transcriptomics of postoperative tissue from 32 patients and quantitative proteomics of 19 patients to screen for mitophagy-related invasion genes in pituitary adenomas. The invasive predictive value of target genes was analyzed by Lasso regression model, CytoHubba plugin and expression validation. Co-expression correlation analysis was used to identify paired proteins for target genes, and a predictive model for pituitary adenoma invasiveness was constructed by target genes and paired proteins and assessed using ROC analysis, calibration curves and DCA. GO function, pathway (GSEA or GSVA) and immune cell analysis (ssGSEA or CIBERSORT) were further utilized to explore the action mechanism of target gene. Finally, immunohistochemistry and cell function experiments were used to detect the differential expression and key roles of the target genes in pituitary adenomas. RESULTS: Finally, Heat shock protein family D member 1 (HSPD1) was identified as a target gene. The quality of a predictive model for pituitary adenoma invasiveness consisting of HSPD1 and its paired protein expression profiles was satisfactory. Moreover, the expression of HSPD1 was significantly lower in invasive pituitary adenomas than in non-invasive pituitary adenomas. Downregulation of HSPD1 may be significantly related to invasion process, mitochondria-related pathway and immune cell regulation in pituitary adenomas. CONCLUSION: The downregulation of HSPD1 may serve as a predictive indicator for identifying invasive pituitary adenomas.

In silico and in vitro analyses of a novel FoxO1 agonist reducing Aß levels via downregulation of BACE1.

AIMS: FoxO1 is an important target in the treatment of Alzheimer's disease (AD). However, FoxO1-specific agonists and their effects on AD have not yet been reported. This study aimed to identify small molecules that upregulate the activity of FoxO1 to attenuate the symptoms of AD. METHODS: FoxO1 agonists were identified by in silico screening and molecular dynamics simulation. Western blotting and reverse transcription-quantitative polymerase chain reaction assays were used to assess protein and gene expression levels of P21, BIM, and PPARγ downstream of FoxO1 in SH-SY5Y cells, respectively. Western blotting and enzyme-linked immunoassays were performed to explore the effect of FoxO1 agonists on APP metabolism. RESULTS: N-(3-methylisothiazol-5-yl)-2-(2-oxobenzo[d]oxazol-3(2H)-yl) acetamide (compound D) had the highest affinity for FoxO1. Compound D activated FoxO1 and regulated the expression of its downstream target genes, P21, BIM, and PPARγ. In SH-SY5Y cells treated with compound D, BACE1 expression levels were downregulated, and the levels of Aß1-40 and Aß1-42 were also reduced. CONCLUSIONS: We present a novel small-molecule FoxO1 agonist with good anti-AD effects. This study highlights a promising strategy for new drug discovery for AD.

Internal carotid artery injury during endoscopic transsphenoidal pituitary surgery: risk factors, management.

BACKGROUND: Transsphenoidal surgeons should try to avoid internal carotid artery (ICA) injury but also be prepared to manage it. We analyzed our experience with ICA injury during endoscopic transsphenoidal pituitary surgery and present associated risk factors and a management protocol. METHODS: We retrospectively reviewed and analyzed the medical records of 1596 patients who underwent endoscopic transsphenoidal surgery for pituitary tumor resection in our institution from January 2009 to October 2022. RESULTS: Six patients experienced an ICA injury. All received timely and effective hemostasis with immediate direct tamponade followed by endovascular treatment. No serious postoperative complications occurred. CONCLUSIONS: We proposed a treatment plan for ICA injuries encountered during endoscopic transsphenoidal surgery and described our hemostasis process, methods of endovascular treatment, and means of postoperative follow-up in detail.

Diagnostic and Monitoring Value of ß-2 Transferrin and Transferrin for Intracranial Infection After Neurosurgery.

BACKGROUND AND OBJECTIVES: After neurosurgery, intracranial infection is a common complication with high rates of clinical impairment and death. Traditional diagnostic approaches are time-consuming. Early and correct diagnosis improves infection control, treatment success, and survival. Novel markers are used to diagnose and classify post-neurosurgical meningitis (PNM) to overcome the difficulties of diagnosing postoperative intracranial infections and avoid the drawbacks of existing diagnostic measures. The objective was to investigate the diagnostic value of ß-2 transferrin (ß-2TF) and transferrin (TF) in the cerebrospinal fluid (CSF) for the identification of intracranial infection after neurosurgery. METHODS: Owing to their symptoms and laboratory results, 168 patients with suspected intracranial infection after neurosurgery were divided into 3 groups: post-neurosurgical bacterial meningitis (PNBM; n = 61), post-neurosurgical aseptic meningitis (PNAM; n = 45), and non-PNM (n = 62). We measured lactate (LA), ß-2TF, and TF levels in the CSF. RESULTS: CSF LA levels were significantly higher in the PNM, PNBM, and PNAM groups compared with the non-PNM group ( P < .05). The CSF ß-2TF level in PNM, PNBM, and PNAM were statistically higher than those in non-PNMs ( P < .05). CSF TF levels in the PNBM group were statistically higher than those in the PNAM and non-PNM groups ( P < .05). The PNBM and non-PNM receiver operating curve (ROC) analysis indicates that the cutoff values for the combination (LA, ß-2TF, TF) was 0.349, and the area under the curve (AUC) was 0.945 ( P < .0001), with 92.86% sensitivity and 92.98% specificity. The PNAM and non-PNM ROC analysis indicates that the cutoff values for the combination (LA, ß-2TF, TF) was 0.346, and the AUC was 0.962 ( P < .0001), with 89.29% sensitivity and 90.24% specificity. The PNM and non-PNM ROC analysis indicates that the cutoff values for the combination (LA, ß-2TF, TF) was 0.609, and the AUC was 0.941 ( P < .0001), with 96.36% sensitivity and 82.83% specificity. A Glasgow Coma Scale score ≤8, LA, ß-2TF/TF ratio, length of hospital stay, intensive care unit admission, poor surgical wound, and craniotomy were associated with poor outcomes ( P < .05). LA and ß-2TF were independent risk factors for intracranial infection. CONCLUSION: Postoperative cerebral infections can be identified using CSF ß-2TF as a particular marker protein. CSF TF helps distinguish PNBM from PNAM. Combining CSF LA with them improves diagnostic speed, sensitivity, and accuracy. LA and ß-2TF were independent risk factors for cerebral infection.

Betaine attenuates age-related suppression in autophagy via Mettl21c/p97/VCP axis to delay muscle loss.

Age-related impairment of autophagy accelerates muscle loss and lead to sarcopenia. Betaine can delay muscle loss as a dietary methyl donor via increasing S-adenosyl-L-methionine (SAM, a crucial metabolite for autophagy regulation) in methionion cycle. However, whether betaine can regulate autophagy level to attenuate degeneration in aging muscle remains unclear. Herein, male C57BL/6J young mice (YOU, 2-month-old), old mice (OLD, 15-month-old), and 2%-betaine-treated old mice (BET, 15-month-old) were employed and raised for 12 weeks. All mice underwent body composition examination and grip strength test before being sacrificed. Betaine alleviated age-related decline in muscle mass and strength. Meanwhile, betaine preserved the expression autophagy markers (Atg5, Atg7, LC3-II, and Beclin1) both at transcriptional and translational level during the aging process. RNA-sequencing results generated from mice gastrocnemius muscle found Mettl21c, a SAM-dependent autophagy-regulating methyltransferase, was significantly higher expressed in BET and YOU group. Results were further validated by qPCR and western bloting. In vitro, C2C12 cells with or without Mettl21c RNA interference were treated different concentration of betaine (0 mM, 10 mM) under methionine-starved condition. Compared with control group, betaine upregulated autophagy markers expression and autophagy flux. By increasing the SAM level, betaine facilitated trimethylation of p97 (Mettl21c downstream effector) into valosin-containing protein (VCP). Increased VCP promoted autophagic turnover of cellular components, ATP production, and cell differentiation. Knock-down of Metthl21c dismissed improvements mentioned above. Collectively, betaine could enhance aged skeletal muscle autophagy level via Mettl21c/p97/VCP axis to delay muscle loss.

Performance analysis of a two-level polling control system based on LSTM and attention mechanism for wireless sensor networks.

A continuous-time exhaustive-limited (K = 2) two-level polling control system is proposed to address the needs of increasing network scale, service volume and network performance prediction in the Internet of Things (IoT) and the Long Short-Term Memory (LSTM) network and an attention mechanism is used for its predictive analysis. First, the central site uses the exhaustive service policy and the common site uses the Limited K = 2 service policy to establish a continuous-time exhaustive-limited (K = 2) two-level polling control system. Second, the exact expressions for the average queue length, average delay and cycle period are derived using probability generating functions and Markov chains and the MATLAB simulation experiment. Finally, the LSTM neural network and an attention mechanism model is constructed for prediction. The experimental results show that the theoretical and simulated values basically match, verifying the rationality of the theoretical analysis. Not only does it differentiate priorities to ensure that the central site receives a quality service and to ensure fairness to the common site, but it also improves performance by 7.3 and 12.2%, respectively, compared with the one-level exhaustive service and the one-level limited K = 2 service; compared with the two-level gated- exhaustive service model, the central site length and delay of this model are smaller than the length and delay of the gated- exhaustive service, indicating a higher priority for this model. Compared with the exhaustive-limited K = 1 two-level model, it increases the number of information packets sent at once and has better latency performance, providing a stable and reliable guarantee for wireless network services with high latency requirements. Following on from this, a fast evaluation method is proposed: Neural network prediction, which can accurately predict system performance as the system size increases and simplify calculations.