Challenges with computing scalar and ad-hoc implicatures in Mandarin-speaking 4-8-year-old autistic children.

INTRODUCTION: Mixed findings have been reported about the computation of scalar or/and ad-hoc implicatures in primarily school-age autistic verbal children and adolescents: while some studies reported their struggles with both implicatures, others observed their strengths in computing scalar implicatures. This study extends the previous investigation by testing the derivation of scalar (including both number and quantifier) and ad-hoc implicatures of a younger group of Mandarin-speaking autistic 4-8-year-olds; moreover, we assess the biological, linguistic, and cognitive factors affecting children's implicature acquisition. METHODS: The participants included 22 4-8-year-old autistic verbal children (mean age = 67.64 months) and 19 typically developing (TD) children who did not significantly differ in age, receptive vocabulary, and non-verbal IQ. Both groups completed a computer-based Truth Value Judgment task, assessing their knowledge of scalar (involving the number 'three' and the quantifier 'some') and ad-hoc implicatures. We also examined whether their implicature computation was linked to age, receptive vocabulary, non-verbal IQ, and Theory of Mind (ToM). RESULTS: Compared with the TD controls, autistic children derived significantly fewer scalar and ad-hoc implicatures. Specifically, TD children successfully computed number and ad-hoc implicatures, contrasting to the bimodal distribution of their pragmatic vs. logical responses to quantifier implicatures. Though autistic children performed better with number implicatures slightly above the chance level, they had difficulties in computing quantifier and ad-hoc implicatures. Further, autistic children's knowledge of the number and ad-hoc implicatures was linked to their ToM skills. CONCLUSIONS: These findings underscore the overall delayed implicature knowledge of young autistic children, and their low sensitivity to the implicatures is related to the core ToM deficits. Furthermore, our data confirm the coherent pattern of the earlier acquisition of number over quantifier implicatures and illuminate the distinct mechanisms underlying the computation of scalar vs. ad-hoc implicatures.

Phase separation of SPIN1 through its IDR facilitates histone methylation readout and tumorigenesis.

Spindlin1 (SPIN1) is a unique multivalent histone modification reader that plays a role in ribosomal RNA transcription, chromosome segregation, and tumorigenesis. However, the function of the extended N-terminal region of SPIN1 has remained unclear. Here, we discovered that SPIN1 can form phase-separated and liquid-like condensates both in vitro and in vivo through its N-terminal intrinsically disordered region (IDR). The phase separation of SPIN1 recruits the histone methyltransferase MLL1 to the same condensates and enriches the H3K4 methylation marks. This process also facilitates the binding of SPIN1 to H3K4me3 and activates tumorigenesis-related genes. Moreover, SPIN1-IDR enhances the genome-wide chromatin binding of SPIN1 and facilitates its localization to genes associated with the MAPK signaling pathway. These findings provide new insights into the biological function of the IDR in regulating SPIN1 activity and reveal a previously unrecognized role of SPIN1-IDR in histone methylation readout. Our study uncovers the crucial role of appropriate biophysical properties of SPIN1 in facilitating gene expression and links phase separation to tumorigenesis, which provides a new perspective for understanding the function of SPIN1.

Dietary flavonoids modulate the gut microbiota: A new perspective on improving autism spectrum disorder through the gut-brain axis.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with an unknown etiology. It is associated with various factors and causes great inconvenience to the patient's life. The gut-brain axis (GBA), which serves as a bidirectional information channel for exchanging information between the gut microbiota and the brain, is vital in studying many neurodegenerative diseases. Dietary flavonoids provide anti-inflammatory and antioxidant benefits, as well as regulating the structure and function of the gut microbiota. The occurrence and development of ASD are associated with dysbiosis of the gut microbiota. Modulation of gut microbiota can effectively improve the severity of ASD. This paper reviews the links between gut microbiota, flavonoids, and ASD, focusing on the mechanism of dietary flavonoids in regulating ASD through the GBA.

Transcription factor CmHSFA4-CmMYBS3 complex enhances salt tolerance in chrysanthemum by repressing CmMYB121 expression.

Excessive soil salinity not only hampers plant growth and development but can also lead to plant death. Previously, we found that heat shock factor A4 (CmHSFA4) enhances the tolerance of chrysanthemum (Chrysanthemum morifolium) to salt. However, the underlying molecular mechanism remains unclear. In this study, we identified a candidate MYB transcription factor, CmMYB121, which responded to salt stress. We observed that the CmMYB121 transcription is suppressed by CmHSFA4. Moreover, overexpression of CmMYB121 exacerbated chrysanthemum sensitivity to salt stress. CmHSFA4 directly bound to the promoter of CmMYB121 at the heat shock element (HSE). Protein-protein interaction assays identified an interaction between CmHSFA4 and CmMYBS3, a transcriptional repressor, and recruited the corepressor TOPLESS (CmTPL) to inhibit CmMYB121 transcription by impairing the H3 and H4 histone acetylation levels of CmMYB121. Our study demonstrated that a CmHSFA4-CmMYBS3-CmTPL complex modulates CmMYB121 expression, consequently regulating the tolerance of chrysanthemum to salt. The findings shed light on the responses of plants to salt stress.

Genetic structural analysis of different breeds and geographical groups of Fenneropenaeus chinensis reveals population diversity.

Fenneropenaeus chinensis is a commercially important shrimp species cultured in China. This study investigated eight F. chinensis populations in China, including four geographical populations, three commercial breeds, and one wild population captured from the Yellow Sea. Population stratification analysis revealed that the Hebei geographical population and commercial breeding "Huanghai No. 4" were relatively independent and stable, reflecting a relatively closed breeding environment, whereas gene introgression was present between other populations. Selective signature analysis detected artificial selection for vision, growth, and disease resistance in the Hebei population. Neuronal development-related genes were detected to be under selection in the Changyi and Rizhao populations. Fertility of the Rizhao population was also investigated. Additionally, genes in the glycosaminoglycan biosynthesis-chondroitin sulfate/dermatan sulfate pathway were involved in the high pH tolerance of the "Huanghai No. 4" population. This study provided support for the genetic mechanism of parsing economic traits and the development of molecular breeding technologies.

Genomic characterization and outbreak investigations of methicillin-resistant Staphylococcus aureus in a county-level hospital in China.

Methicillin-resistant Staphylococcus aureus (MRSA) is a common pathogen contributing to healthcare-associated infections, which can result in multiple sites infections. The epidemiological characteristics of MRSA exhibit variability among distinct regions and healthcare facilities. The aim of this study was to investigate the molecular epidemiology and nosocomial outbreak characteristics of MRSA in a county-level hospital in China. A total of 130 non-repetitive MRSA strains were collected from December 2020 to November 2021. Whole-genome sequencing (WGS) was performed to identify antimicrobial resistance and virulence factors. Phylogenetic analysis was conducted to ascertain genetic diversity and phylogenetic relationships. Independent transmission scenarios were determined by the phylogeny derived from single nucleotide polymorphisms (SNPs) within the core genome. All the MRSA isolates were collected from the intensive care unit (30.00%, 39/130), the department of otorhinolaryngology (10.00%, 13/130) and the department of burn unit (9.23%, 12/130). The clinical samples mainly included phlegm (53.85%, 70/130), purulent fluid (24.62%, 32/130), and secretions (8.46%, 11/130). The resistance rates to erythromycin, clindamycin and ciprofloxacin were 75.38, 40.00, and 39.23%, respectively. All the isolates belonged to 11 clonal complexes (CCs), with the major prevalent types were CC5, CC59, and CC398, accounting for 30.00% (39/130), 29.23% (38/130), and 16.92% (22/130), respectively. Twenty sequence types (STs) were identified, and ST59 (25.38%, 33/130) was the dominant lineage, followed by ST5 (23.84%, 31/130) and ST398 (16.92%, 22/130). Three different SCCmec types were investigated, most of isolates were type IV (33.85%, 44/130), followed by type II (27.69%, 36/130) and type III (0.77%, 1/130). The common clonal structures included CC5-ST5-t2460-SCCmec IIa, CC59-ST59-t437-SCCmec IV and CC398-ST398-t034-SCCmec (-), with rates of 16.92% (22/130), 14.62% (19/130), and 13.84% (18/130), respectively. Only 12 panton-valentine leucocidin (PVL) positive strains were identified. Two independent clonal outbreaks were detected, one consisting of 22 PVL-negative strains belongs to CC5-ST5-t2460-SCCmec IIa and the other consisting of 8 PVL-negative strains belongs to CC5-ST5-t311-SCCmec IIa. Overall, our study indicated that the CC5 lineage emerged as the predominant epidemic clone of MRSA, responsible for nosocomial outbreaks and transmission within a county-level hospital in China, highlighting the necessity to strengthen infection control measures for MRSA in such healthcare facilities.

Rational Design of PARP1/c-Met Dual Inhibitors for Overcoming PARP1 Inhibitor Resistance Induced by c-Met Overexpression.

The emergence of resistance to PARP1 inhibitors poses a current therapeutic challenge, necessitating the development of novel strategies to overcome this obstacle. The present study describes the design and synthesis of a series of small molecules that target both PARP1 and c-Met. Among them, compound 16 is identified as a highly potent dual inhibitor, exhibiting excellent inhibitory activities against PARP1 (IC50 = 3.3 nM) and c-Met (IC50 = 32.2 nM), as well as demonstrating good antiproliferative effects on HR-proficient cancer cell lines and those resistant to PARP1 inhibitors. Importantly, compound 16 demonstrates superior antitumor potency compared to the PARP1 inhibitor Olaparib and the c-Met inhibitor Crizotinib, either alone or in combination, in MDA-MB-231 and HCT116OR xenograft models. These findings highlight the potential of PARP1/c-Met dual inhibitors for expanding the indications of PARP1 inhibitors and overcoming tumor cells' resistance to them.

Vestibular-evoked myogenic potential abnormalities in Parkinson's disease with freezing of gait.

BACKGROUND: Vestibular dysfunction is closely associated with the pathophysiology of Parkinson's disease (PD) accompanied by freezing of gait (FOG); however, evidence supporting this clinical association is lacking. Vestibular-evoked myogenic potentials (VEMPs) have been widely acknowledged as a crucial electrophysiological parameter in the clinical evaluation of vestibular function. OBJECTIVE: The present study investigated the possible correlation of FOG occurrence with VEMP observations in patients diagnosed with PD. METHODS: Altogether, 95 idiopathic PD patients were recruited into the present cross-sectional study. All patients underwent motor and non-motor assessments using serial scales. In addition, the electrophysiological vestibular evaluation was conducted, which included cervical (cVEMP) and ocular VEMP (oVEMP) assessments. Furthermore, the correlations of bilateral c/oVEMP absence with clinical phenotypes, especially FOG, among the PD patients were analyzed. RESULTS: Among the 95 patients with PD, 44 (46.3%) had bilateral oVEMP absence and 23 (24.2%) had bilateral cVEMP absence, respectively. The proportions of patients with bilateral oVEMP absence (77.8% vs 30.9%, p = 0.004) and bilateral cVEMP absence (44.4% vs 19.5%, p = 0.035) were higher in the patient group exhibiting FOG than in the group without FOG. Following the adjustment of confounding variables, bilateral oVEMP absence (OR = 8.544, p = 0.007), rather than bilateral cVEMP absence, was shown to independently predict FOG occurrence in patients with PD. CONCLUSION: The close correlation between bilateral oVEMP absence and FOG in PD patients sheds new light on the possible role of central vestibular/upper brainstem dysfunction in FOG development in patients with PD.

Establishment of cluster of differentiation 20 immobilized cell membrane chromatography for the screening of active antitumor components in traditional Chinese medicine.

Non-Hodgkin lymphoma (NHL) is a heterogeneous group of malignant tumors occurring in B or T lymphocytes, and no small molecule-positive drugs to treat NHL have been marketed. Cluster of differentiation 20 (CD20) is an important molecule regulating signaling for the life and differentiation of B lymphocytes and possesses the characteristics of a drug target for treating NHL. 2-Methoxyestradiol induces apoptosis in lymphoma Raji cells and CD20 protein is highly expressed by Raji lymphoma cells. Therefore, in this study, a CD20-SNAP-tag/CMC model was developed to validate the interaction of 2-methoxyestradiol with CD20. 2-Methoxyestradiol was used as a small molecule control compound, and the system was validated for good applicability. The cell membrane chromatography model was combined with high-performance liquid chromatography ion trap time-of-flight mass spectroscopy (HPLC-IT-TOF-MS) in a two-dimensional system to successfully identify, analyze, and characterize the potential active compounds of Schisandra chinensis (Turcz.) Baill. extract and Lysionotus pauciflorus Maxim. extract, including Schisandrin A, Schizandrol A, Schizandrol B, Schisantherin B, and Nevadensin, which can act on CD20 receptors. The five potential active compounds were analyzed by non-linear chromatography. The thermodynamic and kinetic parameters of their interaction with CD20 were also analyzed, and the mode of interaction was simulated by molecular docking. Their inhibitory effects on lymphoma cell growth were assessed using a Cell Counting Kit-8 (CCK-8). Nevadensin and Schizandrin A were able to induce apoptosis in Raji cells within a certain concentration range. In conclusion, the present experiments provide some bases for improving NHL treatment and developing small molecule lead compounds targeting CD20 with low toxicity and high specificity.

The distinct development of stimulus and response serial dependence.

Serial dependence (SD) is a phenomenon wherein current perceptions are biased by the previous stimulus and response. This helps to attenuate perceptual noise and variability in sensory input and facilitates stable ongoing perceptions of the environment. However, little is known about the developmental trajectory of SD. This study investigates how the stimulus and response biases of the SD effect develop across three age groups. Conventional analyses, in which previous stimulus and response biases were assessed separately, revealed significant changes in the biases over time. Previous stimulus bias shifted from repulsion to attraction, while previous response bias evolved from attraction to greater attraction. However, there was a strong correlation between stimulus and response orientations. Therefore, a generalized linear mixed-effects (GLME) analysis that simultaneously considered both previous stimulus and response, outperformed separate analyses. This revealed that previous stimulus and response resulted in two distinct biases with different developmental trajectories. The repulsion bias of previous stimulus remained relatively stable across all age groups, whereas the attraction bias of previous response was significantly stronger in adults than in children and adolescents. These findings demonstrate that the repulsion bias towards preceding stimuli is established early in the developing brain (at least by around 10 years old), while the attraction bias towards responses is not fully developed until adulthood. Our findings provide new insights into the development of the SD phenomenon and how humans integrate two opposing mechanisms into their perceptual responses to external input during development.

Morning blood pressure surge and intracranial atherosclerotic plaque characteristics: a high-resolution magnetic resonance vessel wall imaging study.

OBJECTIVE: To investigate the relationship between morning blood pressure surge (MBPS) and intracranial atherosclerotic plaque burden and vulnerability. METHODS: A total of 267 ischaemic stroke patients were retrospectively analysed. Sleep-trough and prewaking MBPS were calculated from ambulatory blood pressure monitoring (ABPM). Plaque characteristics, including intraplaque haemorrhage (IPH), maximum wall thickness (max WT), and stenosis degree, were obtained from high-resolution MR vessel wall imaging (HR-vwMRI). Linear and logistic regression were used to detect the association. RESULTS: Subjects with the top tertile of sleep-trough MBPS (≥15.1 mmHg) had a lower prevalence (9.1% vs. 19.6%, P = .029) of severe stenosis (≥70%) than others. Subjects within the top tertile of prewaking MBPS (≥7.6 mmHg) had a lower percentage of IPH (27.3% vs. 40.4%, P = .035) than others. After adjusting for stroke risk factors (age, sex, diabetes, hyperlipidaemia, hyperhomocysteinaemia, smoking, and family stroke history) and 24-h mean systolic blood pressure, 10 mmHg sleep-trough MBPS increment was associated with 0.07mm max WT reduction, and the top tertile MBPS group was associated with a lower chance of severe stenosis (odd ratio = 0.407, 95% CI, 0.175-0.950). Additionally, an increased prewaking MBPS is associated with a lower incidence of IPH, with OR = 0.531 (95% CI, 0.296-0.952). Subgroup analysis demonstrated that the positive findings could only be seen in non-diabetic subjects. CONCLUSION: Increment of MBPS is negatively associated with intracranial atherosclerotic plaque burden and vulnerability, and this relationship remains significant in the non-diabetic subgroup. ADVANCES IN KNOWLEDGE: This study provided evidence that MBPS was associated with the intracranial atherosclerotic plaque burden and vulnerability on HR-vwMRI.

Atrophy patterns in hippocampus and amygdala subregions of depressed patients with Parkinson's disease.

We aimed to explore the subregional atrophy patterns of the amygdala and hippocampus in Parkinson's disease (PD) with depression and their correlation with the severity of the depressive symptom. MRI scans were obtained for 34 depressed PD patients (DPD), 22 nondepressed PD patients (NDPD), and 28 healthy controls (HC). Amygdala and hippocampal subregions were automatically segmented, and the intergroup volume difference was compared. The relationships between the volumes of the subregions and depression severity were investigated. Logistic analysis and Receiver operator characteristic curve were used to find independent predictors of DPD. Compared with the HC group, atrophy of the bilateral lateral nucleus, left accessory basal nucleus, right cortical nucleus, right central nucleus, and right medial nucleus subregions of the amygdala were visible in the DPD group, while the right lateral nucleus subregion of the amygdala was smaller in the DPD group than in the NDPD group. The DPD group showed significant atrophy in the left molecular layer, left GC-DG, left CA3, and left CA4 subregions compared with the HC group for hippocampal subregion volumes. Also, the right lateral nuclei volume and disease duration were independent predictors of DPD. To sum up, DPD patients showed atrophy in multiple amygdala subregions and left asymmetric hippocampal subregions. The decreased amygdala and hippocampal subregion volumes were correlated with the severity of depressive symptoms. The volume of right lateral nuclei and disease duration could be used as a biomarker to detect DPD.

White matter microstructure alterations in type 2 diabetes mellitus and its correlation with cerebral small vessel disease and cognitive performance.

Microstructural abnormalities of white matter fiber tracts are considered as one of the etiology of diabetes-induced neurological disorders. We explored the cerebral white matter microstructure alteration accurately, and to analyze its correlation between cerebral small vessel disease (CSVD) burden and cognitive performance in type 2 diabetes mellitus (T2DM). The clinical-laboratory data, cognitive scores [including mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA), California verbal learning test (CVLT), and symbol digit modalities test (SDMT)], CSVD burden scores of the T2DM group (n = 34) and healthy control (HC) group (n = 21) were collected prospectively. Automatic fiber quantification (AFQ) was applied to generate bundle profiles along primary white matter fiber tracts. Diffusion tensor images (DTI) metrics and 100 nodes of white matter fiber tracts between groups were compared. Multiple regression analysis was used to analyze the relationship between DTI metrics and cognitive scores and CSVD burden scores. For fiber-wise and node-wise, DTI metrics in some commissural and association fibers were increased in T2DM. Some white matter fiber tracts DTI metrics were independent predictors of cognitive scores and CSVD burden scores. White matter fiber tracts damage in patients with T2DM may be characterized in specific location, especially commissural and association fibers. Aberrational specific white matter fiber tracts are associated with visuospatial function and CSVD burden.

KIT-SNAP-tag/cell membrane chromatography model coupled with liquid chromatography-mass spectrometry for anti-GIST compound screening from Evodia rutaecarpa.

Gastrointestinal mesenchymal tumors, as the most common mesenchymal tumors in the gastrointestinal tract, are adjuvantly treated with multi-targeted tyrosine kinase inhibitors, such as imatinib and sunitinib, but there are problems of drug resistance and complex methods of monitoring therapeutic agents. The pathogenesis of this disease is related to mutations in tyrosine kinase (KIT) or platelet-derived growth factor receptor α, an important target for drug therapy. In recent years, the screening of relevant tyrosine kinase inhibitors from traditional Chinese medicine has become a hotspot in antitumor drug research. In the current study, the KIT-SNAP-tag cell membrane chromatography (KIT-SNAP-tag/CMC) column was prepared with satisfying specificity, selectivity, and reproducibility by chemically bonding high KIT expression cell membranes to the silica gel surface using the SNAP-tag technology. The KIT-SNAP-tag/CMC-HPLC-MS two-dimensional coupling system was investigated using the positive drug imatinib, and the results showed that the system was a reliable model for screening potential antitumor compounds from complex systems. This system screened and identified three potential active compounds of evodiamine (EVO), rutaecarpin (RUT), and dehydroevodiamine (DEVO), which possibly target the KIT receptor, from the alcoholic extract of the traditional Chinese medicine Evodia rutaecarpa. Then, the KD values of the interaction of EVO, RUT, and DEVO with KIT receptors measured using nonlinear chromatography were 7.75 (±4.93) × 10-6, 1.42 (±0.71) × 10-6, and 2.34 (±1.86) × 10-6 mol/L, respectively. In addition, the methyl thiazolyl tetrazolium assay validated the active effects of EVO and RUT in inhibiting the proliferation of high KIT-expressing cells in the ranges of 0.1-10 µmol/L and 0.1-50 µmol/L, respectively. In conclusion, the KIT-SNAP-tag/CMC could be a reliable model for screening antitumor components from complex systems.

Zinc oxide nanoparticles induce acute lung injury via oxidative stress-mediated mitochondrial damage and NLRP3 inflammasome activation: In vitro and in vivo studies.

The widespread application of zinc oxide nanoparticles (ZnO-NPs) brings convenience to our lives while also renders threats to public health and ecological environment. The lung has been recognized as a primary target of ZnO-NPs, however, the detrimental effects and mechanism of ZnO-NPs on the respiratory system have not been thoroughly characterized so far. To investigate the effect of ZnO-NPs on acute lung injury (ALI), Sprague Dawley rats were intratracheally instilled with ZnO-NPs suspension at doses of 1, 2, and 4 mg/kg/day for 3 consecutive days. Our study revealed that ZnO-NPs induced ALI in rats characterized by increased airway resistance, excessive inflammatory response and lung histological damage. In addition, we identified several molecular biomarkers related to the potential mechanism of ZnO-NP-induced ALI, including oxidative stress, mitochondrial damage, and NLRP3 inflammasome activation. The results of in vitro experiments showed that the viability of A549 cells decreased with the increase in ZnO-NPs concentration. Meanwhile, it was also found that ZnO-NP treatment induced the production of ROS, the decrease in mitochondrial membrane potential and activation of NLRP3 inflammasome in A549 cells. Furthermore, to explore the underlying molecular mechanisms of ZnO-NP-induced ALI, N-acetyl-L-cysteine (a ROS scavenger), Cyclosporin A (an inhibitor for mitochondrial depolarization) and Glibenclamide (an inhibitor for NLRP3 inflammasome activity) were used to pre-treat A549 cells before ZnO-NPs stimulation in the in vitro experiments, respectively. The results from this study suggested that ZnO-NP-induced ROS production triggered the accumulation of damaged mitochondria and assembly of NLRP3 inflammatory complex, leading to maturation and release of IL-1ß. Moreover, ZnO-NP-induced NLRP3 inflammasome activation was partly mediated by mitochondrial damage. Taken together, our study suggested that ZnO-NPs induced ALI through oxidative stress-mediated mitochondrial damage and NLRP3 inflammasome activation and provided insight into the mechanisms of ZnO-NPs-induced ALI.

Application of SNAP-tag-EGFR cell membrane chromatography model in screening antitumor active components of Silybum marianum (L.) Gaertn.

The SNAP-tag-epidermal growth factor receptor (SNAP-tag-EGFR) cell membrane chromatography (CMC) model is a powerful tool for investigating ligand-receptor interactions and screening active ingredients in traditional Chinese medicine. Most tyrosine kinase inhibitors (TKIs) target epidermal growth factor receptors. However, TKIs associated with significant side effects and drug resistance must be addressed immediately. Therefore, there is an urgent need to develop new TKIs with high efficiency and low toxicity. Because of its low toxicity and side effects, traditional Chinese medicine has been widely employed to treat various diseases, including cancer. Hence, this study aimed to use the SNAP-tag-EGFR/CMC-high-performance liquid chromatography-mass spectrometry (HPLC-MS) two-dimensional system model as the research tool to screen and identify potential EGFR antagonists from the Chinese medicine Silybum marianum (L.) Gaertn. The applicability of the system was verified using the positive control drug osimertinib. Four potential EGFR antagonists were screened from the Chinese medicine Silybum marianum (L.) Gaertn.. They were identified as silydianin, silychristin, silybin, and isosilybin. Additionally, their pharmacological activity was preliminarily verified using a CCK-8 assay. The kinetic parameters of the four active ingredients interacting with EGFR and their binding modes with EGFR were analyzed using nonlinear chromatography (NLC) and molecular docking. This study identified silydianin, silychristin, silybin, and isosilybin from Silybum marianum (L.) Gaertn. and verified their potential antitumor effects on EGFR.

Analysis and experiment of a pneumatic-hydraulic composite support system for in-situ mirror processing and testing.

To address the deformation issues caused by the self-gravity and machining stresses in the process of large-aperture mirror fabrication, this paper proposes an in-situ switchable pneumatic-hydraulic hybrid supporting system that enables the seamless transition between machining and testing. By facilitating in-situ switching, this system not only reduces the machining time of large-aperture mirrors, thereby enhancing production efficiency, but also mitigates the risks associated with traditional switching methods that may result in mirror damage due to human error. Three typical working conditions of the hybrid supporting system, namely hydraulic machining support, air-floating testing support, and three-point rigid support, are investigated in terms of mirror loading through a finite element simulation. Additionally, an experimental platform is constructed to validate the proposed system. The experimental results affirm the feasibility of the designed pneumatic-hydraulic hybrid supporting system. This system will serve as a technological support to advance the rapid development of large-aperture space telescope manufacturing techniques.

Total thyroidectomy versus less-than-total thyroidectomy for papillary thyroid carcinoma of isthmus: a systematic review and meta-analysis.

Background: Papillary thyroid carcinoma of isthmus (PTCI) has a more aggressive nature, a higher rate of lymph node metastasis and tumor recurrence. Clinicians have different preferences for the surgical approach to PTCI, but there are no definitive guidelines. The purpose of this article is to compare the oncologic outcomes and complications of total thyroidectomy and less-than-total thyroidectomy for PTCI using meta-analysis. Methods: We searched PubMed, Embase, Cochrane Library, and Web of Science databases for articles that met the inclusion criteria, with an unlimited start date and an end date of February 19, 2023. Exclusion criteria were applied to filter out articles for further analysis. Ultimately, seven articles were used for analysis, all of which were retrospective studies. The MINORS scale was adopted to evaluate the quality of the included literature, and Review Manager 5.4 was used for data analysis. Results: A total of 814 patients were included in the seven articles, including 401 in the less-than-total thyroidectomy group (trial group) and 413 in the total thyroidectomy group (control group). The results of the meta-analysis showed that there was no significant difference in the tumor recurrence rate between the two groups after total thyroidectomy or less-than-thyroidectomy for PTCI (odds ratio, 1.51; 95% confidence interval: 0.49, 4.65; P=0.47), and there was no statistical difference in the incidence of all postoperative complications between the two groups. Conclusions: There may be some limitations in this analysis, such as publication bias and the fact that the included articles were all retrospective studies with a certain degree of heterogeneity. PTCI patients with early staging and no significant lymph node metastases may be able to choose a more conservative surgical approach, which is less-than-total thyroidectomy. Patients with relatively late staging and significant preoperative lymph node metastases or extra thyroidal extension may opt for total thyroidectomy plus lymph node dissection in the central region and, if necessary, lymph node dissection in the lateral cervical region.