Self-assembled soft alloy with Frank-Kasper phases beyond metals.

Soft building blocks, such as micelles, cells or soap bubbles, tend to adopt near-spherical geometry when densely packed together. As a result, their packing structures do not extend beyond those discovered in metallic glasses, quasicrystals and crystals. Here we report the emergence of two Frank-Kasper phases from the self-assembly of five-fold symmetric molecular pentagons. The µ phase, an important intermediate in superalloys, is indexed in soft matter, whereas the ϕ phase exhibits a structure distinct from known Frank-Kasper phases in metallic systems. We find a broad size and shape distribution of self-assembled mesoatoms formed by molecular pentagons while approaching equilibrium that contribute to the unique packing structures. This work provides insight into the manipulation of soft building blocks that deviate from the typical spherical geometry and opens avenues for the fabrication of 'soft alloy' structures that were previously unattainable in metal alloys.

A CT-based deep learning radiomics nomogram outperforms the existing prognostic models for outcome prediction in clear cell renal cell carcinoma: a multicenter study.

OBJECTIVES: To develop and validate a CT-based deep learning radiomics nomogram (DLRN) for outcome prediction in clear cell renal cell carcinoma (ccRCC), and its performance was compared with the Stage, Size, Grade, and Necrosis (SSIGN) score, the University of California, Los Angeles, Integrated Staging System (UISS), the Memorial Sloan-Kettering Cancer Center (MSKCC), and the International Metastatic Renal Cell Database Consortium (IMDC). METHODS: A multicenter of 799 localized (training/ test cohort, 558/241) and 45 metastatic ccRCC patients were studied. A DLRN was developed for predicting recurrence-free survival (RFS) in localized ccRCC patients, and another DLRN was developed for predicting overall survival (OS) in metastatic ccRCC patients. The performance of the two DLRNs was compared with that of the SSIGN, UISS, MSKCC, and IMDC. Model performance was assessed with Kaplan-Meier curves, time-dependent area under the curve (time-AUC), Harrell's concordance index (C-index), and decision curve analysis (DCA). RESULTS: In the test cohort, the DLRN achieved higher time-AUCs (0.921, 0.911, and 0.900 for 1, 3, and 5 years, respectively), C-index (0.883), and net benefit than SSIGN and UISS in predicting RFS for localized ccRCC patients. The DLRN provided higher time-AUCs (0.594, 0.649, and 0.754 for 1, 3, and 5 years, respectively) than MSKCC and IMDC in predicting OS for metastatic ccRCC patients. CONCLUSIONS: The DLRN can accurately predict outcomes and outperformed the existing prognostic models in ccRCC patients. CLINICAL RELEVANCE STATEMENT: This deep learning radiomics nomogram may facilitate individualized treatment, surveillance, and adjuvant trial design for patients with clear cell renal cell carcinoma. KEY POINTS: • SSIGN, UISS, MSKCC, and IMDC may be insufficient for outcome prediction in ccRCC patients. • Radiomics and deep learning allow for the characterization of tumor heterogeneity. • The CT-based deep learning radiomics nomogram outperforms the existing prognostic models in ccRCC outcome prediction.

Association of intracranial atherosclerosis with cerebral small vessel disease in a community-based population.

BACKGROUND AND PURPOSE: The purpose of this study was to explore the relationship between intracranial atherosclerosis and cerebral small vessel disease (CSVD). METHODS: Community-dwelling residents of Lishui, China in the PRECISE (Polyvascular Evaluation for Cognitive Impairment and Vascular Events) study were involved. Intracranial atherosclerosis was grouped by the severity of intracranial artery plaques with stenosis and burden. Four imaging markers including lacunes, white matter hyperintensity (WMH), cerebral microbleeds (CMBs), and perivascular spaces (PVS) as well as the CSVD burden scores were assessed. Logistic regression or ordinal logistic regression models with odds ratio (OR) or common OR (cOR) were used to estimate the relationship between intracranial atherosclerosis and CSVD markers and burdens. RESULTS: The mean age was 61.20 ± 6.68 years, and 1424 (46.52%) were men among 3061 participants included at baseline. Intracranial atherosclerotic burden was associated with the severity of the lacunes (OR = 4.18, 95% confidence interval [CI] = 1.83-9.58), modified WMH burden (cOR = 1.94, 95% CI = 1.01-3.71), presence of CMBs (OR = 2.28, 95% CI = 1.05-4.94), and CMB burden (OR = 2.23, 95% CI = 1.03-4.80). However, it was not associated with the WMH burden and PVS. Intracranial atherosclerotic burden was associated with CSVD burden (Wardlaw: cOR = 2.73, 95% CI = 1.48-5.05; Rothwell: cOR = 2.70, 95% CI = 1.47-4.95). The association between intracranial atherosclerosis and CSVD was obvious in participants with both anterior and posterior circulation artery stenosis. CONCLUSIONS: Based on a Chinese community population, there may be an association between intracranial atherosclerosis and CSVD, but its mechanism in relation to vascular risk factors still needs to be clarified.

Automatic cerebral computed tomography venographic imaging based on the prior knowledge of cerebral blood circulation.

BACKGROUND AND PURPOSE: Current clinical computed tomography venographic (cCTV) images present limited cerebral venous profiles. Therefore, this study aimed to develop an automatic cerebral CTV imaging technique using computed tomographic perfusion (CTP) images in a cohort of patients with stroke. MATERIALS AND METHODS: We retrospectively evaluated 10 (intracerebral hemorrhage) and 2 (acute ischemic stroke) patients who underwent institutional CTP imaging. CTV images were processed with the proposed CTV (pCTV) technique, and pCTV and cCTV images were then independently evaluated by two experienced neuroradiologists blinded to all clinical information using a novel scoring method that considered overall image quality, venous visibility, and arterial mis-segmentation. Venous visibility was separately evaluated for the dural sinus, superficial vein, and deep vein. Then, statistical analysis was performed to determine whether the pCTV technique was superior to the cCTV technique. RESULTS: In total, 14 sets of pCTV images were generated and compared with cCTV images. The overall image quality and venous visibility scores of pCTV images were significantly higher than those of cCTV images (all values of p<0.05), especially for the dural sinus (median [25th, 75th percentiles], 14.00 [13.63, 15.50] vs. 7.50 [7.00, 10.88]), and superficial vein (9.00 [8.88, 10.00] vs. 3.25 [1.63, 8.25]), while the difference in arterial mis-segmentation was not statistically significant (p= 0.164). CONCLUSIONS: This study proposed an automatic cerebral CTV imaging technique to eliminate residual bone and soft tissues, minimize the impact of the cerebral arterial system, and present a relatively comprehensive cerebral venous system, which would help physicians assess cerebral venous outflow profiles after stroke and seek imaging markers associated with clinical outcomes.

The radiomics-based tumor heterogeneity adds incremental value to the existing prognostic models for predicting outcome in localized clear cell renal cell carcinoma: a multicenter study.

PURPOSE: Tumor heterogeneity, which is associated with poor outcomes, has not been exhibited in the University of California, Los Angeles, Integrated Staging System (UISS), and the Stage, Size, Grade and Necrosis (SSIGN) scores. Radiomics allows an in-depth characterization of heterogeneity across the tumor, but its incremental value to the existing prognostic models for clear cell renal cell carcinoma (ccRCC) outcome is unknown. The purpose of this study was to evaluate the association between the radiomics-based tumor heterogeneity and postoperative risk of recurrence in localized ccRCC, and to assess its incremental value to UISS and SSIGN. METHODS: A multicenter 866 ccRCC patients derived from 12 Chinese hospitals were studied. The endpoint was recurrence-free survival (RFS). A CT-based radiomics signature (RS) was developed and assessed in the whole cohort and in the subgroups stratified by UISS and SSIGN. Two combined nomograms, the R-UISS (combining RS and UISS) and R-SSIGN (combining RS and SSIGN), were developed. The incremental value of RS to UISS and SSIGN in RFS prediction was evaluated. R statistical software was used for statistics. RESULTS: Patients with low radiomics scores were 4.44 times more likely to experience recurrence than those with high radiomics scores (P<0.001). Stratified analysis suggested the association is significant among low- and intermediate-risk patients identified by UISS and SSIGN. The R-UISS and R-SSIGN showed better predictive capability than UISS and SSIGN did with higher C-indices (R-UISS vs. UISS, 0.74 vs. 0.64; R-SSIGN vs. SSIGN, 0.78 vs. 0.76) and higher clinical net benefit. CONCLUSIONS: The radiomics-based tumor heterogeneity can predict outcome and add incremental value to the existing prognostic models in localized ccRCC patients. Incorporating radiomics-based tumor heterogeneity in ccRCC prognostic models may provide the opportunity to better surveillance and adjuvant clinical trial design.

Aspirin platelet reactivity on platelet function and clinical outcome in minor stroke or transient ischemic attack.

OBJECTIVE: Whether aspirin platelet reactivity affects platelet function and clinical outcomes with different antiplatelet therapies in patients with mild stroke or transient ischemic attack (TIA) remains unclear. We conducted a subgroup analysis of the PRINCE trial. MATERIALS AND METHODS: Patients with mild stroke or TIA were randomized into aspirin+ticagrelor, or aspirin+clopidogrel groups; aspirin reaction units (ARU) were measured at the baseline and after 7 ± 2 days to assess response to treatment. High on-treatment platelet reactivity (HPR) was defined as ≥550 ARU (poor response to aspirin). The platelet functions of ticagrelor and clopidogrel were measured using the VerifyNow P2Y12 assay for P2Y12 reaction units (PRU); HPR to P2Y12 was defined as >208 PRU (poor response to P2Y12). Clinical outcomes included stroke and clinical vascular and bleeding events after 90 days. RESULTS: Among 628 enrolled patients, 69 (11%) were poor aspirin responders. After 7 ± 2 days, the proportion of poor P2Y12 responders for ticagrelor versus clopidogrel significantly reduced in poor (2.6% versus 27.4%) and good (14.3% versus 29.4%) aspirin responders. There were significant interactions between treatment groups, and between treatment groups and aspirin platelet reactivity for poor P2Y12 responders (P = 0.01). After 90 ± 7 days, there were no significant interactions between treatment groups and aspirin platelet reactivity for new stroke risk (good aspirin responders: 5.5% versus 8.8%, hazard ratio [HR]: 0.61; 95% confidence interval [CI], 0.32 to 1.16; P = 0.13; poor aspirin responders: 8.6% versus 8.8%, HR: 0.97, 95% CI: 0.20-4.81; P = 0.97; P for interaction = 0.60). Major bleeding was less frequent in poor than good aspirin responders (ticagrelor/aspirin: 0.4%/0%; clopidogrel/aspirin: 1.4%/0%). CONCLUSIONS: In patients with minor stroke or TIA, clopidogrel, and particularly ticagrelor, decreased platelet function in poor versus good aspirin responders. The poor platelet reactivity of aspirin could not sufficiently reduce the risk of recurrent stroke with ticagrelor or clopidogrel; however, HPR (poor aspirin response) may have a protective effect on clinically relevant major bleeding.

Unimolecular Nanoparticles toward More Precise Regulations of Self-Assembled Superlattices in Soft Matter.

The hierarchical self-assembly process opens up great potential for the construction of nanostructural superlattices. Precise regulation of self-assembled superlattices, however, remains a challenge. Even when the primary molecules are precise, the supramolecular motifs (or secondary building blocks) can vary dramatically. In the present work, we propose the concept of unimolecular nanoparticles (UMNPs). The UMNPs act as the supramolecular motif and directly pack into the superlattices. A highly branched giant molecule is presented. We systematically explore its conformations and the superlattice of this giant molecule. Moreover, intriguing complex phases are discovered when blending this UMNP with other conventional giant molecules. These binary mixtures provide direct evidence to support our previously proposed self-sorting process in the self-assembly of "soft alloys". The concept of UMNPs offers a unique approach toward more precise regulation of self-assembled superlattices in soft matter.

Soft Alloys Constructed with Distinct Mesoatoms via Self-Sorting Assembly of Giant Shape Amphiphiles.

The packing structures of spherical motifs affect the properties of resultant condensed materials such as in metal alloys. Inspired by the classic metallurgy, developing complex alloy-like packing phases in soft matter (also called "soft alloys") is promising for the next-generation superlattice engineering. Nevertheless, the formation of many alloy-like phases in single-component soft matter is usually thermodynamically unfavourable and technically challenging. Here, we utilize a novel self-sorting assembly approach to tackle this challenge in binary blends of soft matter. Two types of giant shape amphiphiles self-sort to form their discrete spherical motifs, which further simultaneously pack into alloy-like phases. Three unconventional spherical packing phases have been observed in these binary systems, including MgZn2 , NaZn13 , and CaCu5 phases. It's the first time that the CaCu5 phase is experimentally observed in soft matter. This work demonstrates a general approach to constructing unconventional spherical packing phases and other complex superlattices in soft matter.

Superlattice Engineering with Chemically Precise Molecular Building Blocks.

Correlating nanoscale building blocks with mesoscale superlattices, mimicking metal alloys, a rational engineering strategy becomes critical to generate designed periodicity with emergent properties. For molecule-based superlattices, nevertheless, nonrigid molecular features and multistep self-assembly make the molecule-to-superlattice correlation less straightforward. In addition, single component systems possess intrinsically limited volume asymmetry of self-assembled spherical motifs (also known as "mesoatoms"), further hampering novel superlattices' emergence. In the current work, we demonstrate that properly designed molecular systems could generate a spectrum of unconventional superlattices. Four categories of giant molecules are presented. We systematically explore the lattice-forming principles in unary and binary systems, unveiling how molecular stoichiometry, topology, and size differences impact the mesoatoms and further toward their superlattices. The presence of novel superlattices helps to correlate with Frank-Kasper phases previously discovered in soft matter. We envision the present work offers new insights about how complex superlattices could be rationally fabricated by scalable-preparation and easy-to-process materials.

Temporal persistence of residual fetal cell-free DNA from a deceased cotwin after selective fetal reduction in dichorionic diamniotic twin pregnancies.

OBJECTIVES: To determine the temporal persistence of the residual cell-free DNA (cfDNA) of the deceased cotwin in maternal circulation after selective fetal reduction and evaluate its long persistence in noninvasive prenatal testing (NIPT). METHODS: Dichorionic diamniotic twins (N = 5) undergoing selective fetal reduction because of a trisomy were recruited. After informed consent, maternal blood was collected immediately before reduction and periodically after reduction until birth. The plasma cfDNA of each sample was sequenced and analyzed for fetal aneuploidy and fetal fractions. RESULTS: In all pregnancies, the fetal fraction of the cfDNA of the deceased fetus increased to peak at 7-9 weeks after fetal reduction, and subsequently decreased gradually to almost undetectable during the late third trimester. The NIPT T-scores persistently reflected the detection of fetal trisomy up to 16 (median 9.5) weeks after fetal reduction. CONCLUSIONS: Residual cfDNA from the deceased cotwin after selective reduction at 14-17 gestational weeks led to the persistent generation of false-positive NIPT results for up to 16 weeks postdemise. Thus, providing NIPT for pregnancies with a cotwin demise in early second trimester is prone to misleading results and not recommended.

Geometry-Directed Self-Assembly of Polymeric Molecular Frameworks.

Despite the significant advances in creating assembled structures from polymers, engineering the assembly of polymeric materials into framework structures remains an outstanding challenge. In this work, we present a facile strategy to construct polymeric molecular frameworks through the assembly of T-shape polymer-rod-sphere amphiphiles in the bulk state. Various frameworks are yielded as a result of delicate interplays among three components of the T-shape amphiphiles. The internal structure of frameworks was revealed by combining experimental investigations and computational simulations. The frameworks display good solution-processability, thermal stability, and uniform pore-forming capability, which endow the resultant frameworks with great potential in scalable fabrications.

Clinical Application of Cell-Free DNA Sequencing-Based Noninvasive Prenatal Testing for Trisomies 21, 18, 13 and Sex Chromosome Aneuploidy in a Mixed-Risk Population in Iran.

PURPOSE: To report the clinical experience and performance of plasma cell-free DNA sequencing-based noninvasive -prenatal testing (NIPT) as a screening method in detecting trisomy 21, 18, 13 (T21/T18/T13) as well as sex chromosome aneuploidy (SCA) in a mixed-risk population in Iran. METHODS: In a 2-year period between January 1, 2015, and December 31, 2016, over 150 medical centers in Iran offered NIPT as clinical screening tests for fetal T21, T18, T13 and SCA. All NIPT positive cases were recommended to undergo invasive prenatal diagnosis. RESULTS: 11,414 maternal blood samples were received for NIPT, for which 11,223 samples obtained NIPT results. Among 11,213 cases with confirmatory results, 94 T21, 39 T18, 8 T13, 15 XO, 6 XXX, 3 XYY, 5 XXY and 11,042 euploid cases were detected. The overall sensitivity of NIPT was 98.90, 100.00, 100.00, 90.91, 100.00, 100.00 and 100.00%, and specificities were 99.96, 99.97, 99.99, 99.96, 99.98, 100.00 and 99.99% for detecting T21, T18, T13, XO, XXX, XYY and XXY, respectively. CONCLUSION: With a stringent protocol, our prospective large-scale multicentric nationwide study demonstrated that NIPT showed excellent performance as screening test for the detection of fetal T21, T18, T13 and SCA in mixed-risk pregnancies in Iran.

An AGAMOUS MADS-box protein, SlMBP3, regulates the speed of placenta liquefaction and controls seed formation in tomato.

AGAMOUS (AG) MADS-box transcription factors have been shown to play crucial roles in floral organ and fruit development in angiosperms. Here, we isolated a tomato (Solanum lycopersicum) AG MADS-box gene SlMBP3 and found that it is preferentially expressed in flowers and during early fruit developmental stages in the wild-type (WT), and in the Nr (never ripe) and rin (ripening inhibitor) mutants. Its transcripts are notably accumulated in the pistils; transcripts abundance decrease during seed and placental development, increasing again during flower development. SlMBP3-RNAi tomato plants displayed fleshy placenta without locular gel and extremely malformed seeds with no seed coat, while SlMBP3-overexpressing plants exhibited advanced liquefaction of the placenta and larger seeds. Enzymatic activities related to cell wall modification, and the contents of cell wall components and pigments were dramatically altered in the placentas of SlMBP3-RNAi compared with the WT. Alterations in these physiological features were also observed in the placentas of SlMBP3-overexpressing plants. The lignin content of mature seeds in SlMBP3-RNAi lines was markedly lower than that in the WT. RNA-seq and qRT-PCR analyses revealed that genes involved in seed development and the biosynthesis of enzymes related to cell wall modification, namely gibberellin, indole-3-acetic acid, and abscisic acid were down-regulated in the SlMBP3-RNAi lines. Taking together, our results demonstrate that SlMBP3 is involved in the regulation of placenta and seed development in tomato.

Efficacy and safety of mirvetuximab soravtansine in recurrent ovarian cancer with FRa positive expression: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of mirvetuximab soravtansine in treating recurrent ovarian cancer with folate receptor alpha (FRa) expression. METHODS: A comprehensive search was conducted on online databases, including PubMed, Cochrane Library, and EMBASE, to identify relevant literature about the efficacy and safety of mirvetuximab soravtansine in recurrent ovarian cancer with FRa-positive expression. The keywords were the following: recurrent ovarian cancer, mirvetuximab soravtansine, FRa, and antibody-drug conjugate. Furthermore, studies that satisfied the necessary qualifications were carefully evaluated for further meta-analysis. RESULTS: This meta-analysis involved the examination of seven trials with a total of 631 patients. According to the pooled data, the objective response rate (ORR) was 36% (95%CI: 27%-45%). Similarly, the disease control rate (DCR) was 88% (95% CI: 84-91%). Furthermore, the median progression-free survival (PFS) was determined to be 6.1 months (95% CI: 4.27-7.47). The overall response rate and PFS for platinum-resistant ovarian cancer were found to be 29% (95% CI: 25-32%) and 6.26 months (95% CI: 4.67-7.85), respectively. The most often observed adverse events (AEs) in patients with recurrent ovarian cancer (OC) receiving mirvetuximab soravtansine were blurred vision (all grades: 45%, Grade III: 2%), nausea (all grades: 42%, Grade III: 1%), and diarrhea (all grades: 42%, Grade III: 2%). These AEs were specifically associated with the safety profile of mirvetuximab soravtansine in this patient population. CONCLUSION: The efficacy of mirvetuximab soravtansine in treating recurrent ovarian cancer with FRa-positive expression is satisfactory, and the safety is tolerable.

Tirofiban combined with Aspirin in the Treatment of Acute Penetrating Artery Territory Infarction (STRATEGY): protocol for a multicentre, randomised controlled trial.

BACKGROUND: Perforating artery territorial infarction (PAI) caused by branch atheromatous disease (BAD) is prone to recurrence and early progression without an effective and well-documented antiplatelet treatment regimen. Tirofiban, an adjunctive antiplatelet agent, has shown great potential to treat acute ischaemic stroke. However, whether the combination of tirofiban and aspirin can improve the prognosis of PAI remains unclear. AIM: To explore an effective and safe antiplatelet regimen for reducing the risk of recurrence and early neurological deterioration (END) in PAI caused by BAD by comparing the tirofiban and aspirin combination with placebo and aspirin combination. METHODS: Tirofiban combined with Aspirin in the Treatment of Acute Penetrating Artery Territory Infarction (STRATEGY) trial is an ongoing multicentre, randomised, placebo-controlled trial in China. Eligible patients shall be randomly assigned to receive standard aspirin with tirofiban or placebo on the first day and standard aspirin from days 2 to 90. The primary endpoint is a new stroke or END within 90 days. The primary safety endpoint is severe or moderate bleeding within 90 days. DISCUSSION: The STRATEGY trial will assess whether tirofiban combined with aspirin is effective and safe in preventing recurrence and END in patients with PAI. TRIAL REGISTRATION NUMBER: NCT05310968.

MOF-Enhanced Aluminosilicate Ceramic Membranes Using Non-Firing Processes for Pesticide Filtration and Phytochrome Removal.

Aluminosilicates, abundant and crucial in both natural environments and industry, often involve uncontrollable chemical components when derived from minerals, making further chemical purification and reaction more complicated. This study utilizes pure alumina and fumed silica powders as more controllable sources, enhancing aluminosilicate reactivity through room temperature (non-firing) processing and providing a robust framework that resists mechanical stress and high temperature. By embedding iron-based metal-organic frameworks (Fe-MOF/non-firing aluminosilicate membranes) within the above matrix, these ceramic membranes not only preserve their mechanical robustness but also gain significant chemical functionality, enhancing their capacity to removing phytochromes from the vegetables. Sodium hydroxide and sodium silicate were selected as activators to successfully prepare high-strength, non-firing aluminosilicate membranes. These membranes demonstrated a flexural strength of 8.7 MPa under wet-culture conditions with a molar ratio of Al2O3:SiO2:NaOH:Na2SiO3 at 1:1:0.49:0.16. The chlorophyll adsorption of spinach conducted on these membranes showed a removal rate exceeding 90% at room temperature and pH = 9, highlighting its potential for the selective adsorption of chlorophyll. This study underscores the potential of MOF-enhanced aluminosilicate ceramic membranes in environmental applications, particularly for agricultural pollution control.

Polysomnography and Neuropsychological Analysis of Patients With Post-Traumatic Stress Disorder Two Years After the COVID-19 Pandemic in Wuhan.

OBJECTIVE: We used polysomnography (PSG) monitoring and neuropsychological scales to explore the characteristics of coronavirus disease-2019 (COVID-19) patients diagnosed with post-traumatic stress disorder (PTSD) in Wuhan, two years after the onset of the COVID-19 pandemic. METHODS: A total of 42 patients in the Sleep Medicine Center were diagnosed with insomnia between December 2021 and May 2022; they were divided into the PTSD group (patients with PTSD diagnosed with insomnia after COVID-19 infection) and the non-PTSD group (patients with insomnia without PTSD). A healthy control group was simultaneously included. RESULTS: The PTSD group was more significant than the non-PTSD group in partial manifestations of sleep disorders, neuropsychological clinical symptoms, and partial PSG data. Patients with different COVID-19 subtypes showed significant differences in the course of disease, sleep disorders, neuropsychological clinical symptoms, relevant scale scores, and PSG data analysis. CONCLUSION: The emotional anxiety and depression of COVID-19 patients diagnosed with PTSD two years after the COVID-19 pandemic in Wuhan are more significant, and will not be self-alleviated with the passage of time. It is necessary to continue to pay attention to the PTSD symptoms and sleep psychology of COVID-19 infected patients, and take appropriate measures. Patients with severe and critical COVID-19 have more severe sleep and mental disorders, and there is a significant correlation between the duration of the disease and the severity of mental and mental disorders and sleep disorders after recovery.

Pulsed Low-Intensity Focused Ultrasound (LIFU) Activation of Ovarian Follicles.

Objective: A biological system's internal morphological structure or function can be changed as a result of the mechanical effect of focused ultrasound. Pulsed low-intensity focused ultrasound (LIFU) has mechanical effects that might induce follicle development with less damage to ovarian tissue. The potential development of LIFU as a non-invasive method for the treatment of female infertility is being considered, and this study sought to explore and confirm that LIFU can activate ovarian follicles. Results: We found a 50% increase in ovarian weight and in the number of mature follicles on the ultrasound-stimulated side with pulsed LIFU and intraperitoneal injection of 10 IU PMSG in 10-day-old rats. After ultrasound stimulation, the PCOS-like rats had a decrease in androgen levels, restoration of regular estrous cycle and increase in the number of mature follicles and corpora lutea, and the ratio of M1 and M2 type macrophages was altered in antral follicles of PCOS-like rats, consequently promoting further development and maturation of antral follicles. Conclusion: LIFU treatment could trigger actin changes in ovarian cells, which might disrupt the Hippo signal pathway to promote follicle formation, and the mechanical impact on the ovaries of PCOS-like rats improved antral follicle development.

Mucins and mucinous ovarian carcinoma: Development, differential diagnosis, and treatment.

Mucinous ovarian carcinoma (MOC) is a rare histological type of epithelial ovarian cancer. It has poor response to conventional platinum-based chemotherapy regimens and PARPi-based maintenance treatment, resulting in short survival and poor prognosis in advanced-disease patients. MOC is characterized by mucus that is mainly composed of mucin in the cystic cavity. Our review discusses in detail the role of mucins in MOC. Mucins are correlated with MOC development. Furthermore, they are valuable in the differential diagnosis of primary and secondary ovarian mucinous tumors. Some types of mucins have been studied in the context of chemoresistance and targeted therapy for ovarian cancer. This review may provide a new direction for the diagnosis and treatment of advanced MOC.

Using the PEAR1 Polymorphisms Rs12041331 and Rs2768759 as Potential Predictive Markers of 90-Day Bleeding Events in the Context of Minor Strokes and Transient Ischemic Attack.

In this study, we explored the relationship between the platelet endothelial aggregation receptor 1 (PEAR1) polymorphisms, platelet reactivity, and clinical outcomes in patients with minor stroke or transient ischemic attack (TIA). Randomized controlled trial subgroups were assessed, wherein patients received dual antiplatelet therapy for at least 21 days. Platelet reactivity was measured at different time intervals. Genotypes were categorized as wild-type, mutant heterozygous, and mutant homozygous. Clinical outcomes were evaluated after 90 days. The rs12041331 polymorphism predominantly influenced adenosine diphosphate channel platelet activity, with the AA genotype displaying significantly lower residual platelet activity to the P2Y12 response unit (p < 0.01). This effect was more evident after 7 days of dual antiplatelet treatment (p = 0.016). Mutant A allele carriers had decreased rates of recurrent stroke and complex endpoint events but were more prone to bleeding (p = 0.015). The rs2768759 polymorphism majorly impacted arachidonic acid (AA) channel platelet activity, which was particularly noticeable in the C allele carriers. Our regression analysis demonstrated that rs12041331 AA + GA and rs2768759 CA predicted 90-day post-stroke bleeding. In conclusion, the PEAR1 polymorphisms rs12041331 and rs2768759 interfere with platelet aggregation and the performance of antiplatelet drugs. These genetic variations may contribute to bleeding events associated with minor stroke and TIA.