Epithelial cells derived exosomal miR-203a-3p facilitates stromal inflammation of type IIIA chronic prostatitis/chronic pelvic pain syndrome by targeting DUSP5 and increasing MCP-1 generation.

Increased proinflammatory cytokines and infiltration of inflammatory cells in the stroma are important pathological features of type IIIA chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS-A), and the interaction between stromal cells and other cells in the inflammatory microenvironment is closely related to the inflammatory process of CP/CPPS-A. However, the interaction between stromal and epithelial cells remains unclear. In this study, inflammatory prostate epithelial cells (PECs) released miR-203a-3p-rich exosomes and facilitated prostate stromal cells (PSCs) inflammation by upregulating MCP-1 expression. Mechanistically, DUSP5 was identified as a novel target gene of miR-203a-3p and regulated PSCs inflammation through the ERK1/2/MCP-1 signaling pathway. Meanwhile, the effect of exosomes derived from prostatic fluids of CP/CPPS-A patients was consistent with that of exosomes derived from inflammatory PECs. Importantly, we demonstrated that miR-203a-3p antagomirs-loaded exosomes derived from PECs targeted the prostate and alleviated prostatitis by inhibiting the DUSP5-ERK1/2 pathway. Collectively, our findings provide new insights into underlying the interaction between PECs and PSCs in CP/CPPS-A, providing a promising therapeutic strategy for CP/CPPS-A.

Exploring the effects of Hippo signaling pathway on rumen epithelial proliferation.

BACKGROUND: The current understanding to the mechanism of rumen development is limited. We hypothesized that the Hippo signaling pathway controlled the proliferation of rumen epithelium (RE) during postnatal development. In the present study, we firstly tested the changes of the Hippo signaling pathway in the RE during an early growing period from d5 to d25, and then we expanded the time range to the whole preweaning period (d10-38) and one week post weaning (d45). An in vitro experiment was also carried out to verify the function of Hippo signaling pathway during RE cell proliferation. RESULTS: In the RE of lambs from d5 to d25, the expression of baculoviral IAP repeat containing (BIRC3/5) was increased, while the expressions of large tumor suppressor kinase 2 (LATS2), TEA domain transcription factor 3 (TEAD3), axin 1 (AXIN1), and MYC proto-oncogene (MYC) were decreased with rumen growth. From d10 to d38, the RE expressions of BIRC3/5 were increased, while the expressions of LATS2 and MYC were decreased, which were similar with the changes in RE from d5 to d25. From d38 to d45, different changes were observed, with the expressions of LATS1/2, MOB kinase activator 1B (MOB1B), and TEAD1 increased, while the expressions of MST1 and BIRC5 decreased. Correlation analysis showed that during the preweaning period, the RE expressions of BIRC3/5 were positively correlated with rumen development variables, while LAST2 was negatively correlated with rumen development variables. The in vitro experiment validated the changes of LATS2 and BIRC3/5 in the proliferating RE cells, which supported their roles in RE proliferation during preweaning period. CONCLUSIONS: Our results suggest that the LATS2-YAP1-BIRC3/5 axis participates in the RE cell proliferation and promotes rumen growth during the preweaning period.

Facile Prepared MOF-OH-PAN Nanofiber for Separation Co(II) from Waste Batteries.

Recovering cobalt from waste batteries is crucial for resource recycling and environmental protection. Here, MOF-OH, a Zr-based MOF, was synthesized and merged into a polyacrylonitrile (PAN) matrix to create MOF-OH-PAN nanofibers (NFs). These NFs showed a high cobalt ion adsorption capacity of 33.1 mg/g, retaining over 90% of the capacity after six cycles. The adsorption mechanism involves Co(II) surface diffusion followed by strong bonding with functional groups. This technology enables efficient cobalt recovery from waste batteries, supporting reuse and reducing resource depletion and environmental pollution. The study provides insights into waste battery resource management, highlighting environmental and economic benefits and contributing to green resource recovery and circular economy initiatives.

Can Robotic Arm-assisted Total Knee Arthroplasty Remain Cost-effective in Volume-based Procurement System in China? A Markov Model-based Study.

OBJECTIVE: The volume based procurement (VBP) program in China was initiated in 2022. The cost-effectiveness of robotic arm assisted total knee arthroplasty is yet uncertain after the initiation of the program. The objective of the study was to investigate the cost-effectiveness of robotic arm-assisted total knee arthroplasty and the influence of the VBP program to its cost-effectiveness in China. METHODS: The study was a Markov model-based cost-effectiveness study. Cases of primary total knee arthroplasty from January 2019 to December 2021 were included retrospectively. A Markov model was developed to simulate patients with advanced knee osteoarthritis. Manual and robotic arm-assisted total knee arthroplasties were compared for cost-effectiveness before and after the engagement of the VBP program in China. Probability and sensitivity analysis were conducted. RESULTS: Robotic arm-assisted total knee arthroplasty showed better recovery and lower revision rates before and after initiation of the VBP program. Robotic arm-based TKA was superior to manual total knee arthroplasty, with an increased effectiveness of 0.26 (16.87 vs 16.61) before and 0.52 (16.96 vs 16.43) after the application of Volume-based procurement, respectively. The procedure is more cost-effective in the new procurement system (17.13 vs 16.89). Costs of manual or robotic arm-assisted TKA were the most sensitive parameters in our model. CONCLUSION: Based on previous and current medical charging systems in China, robotic arm-assisted total knee arthroplasty is a more cost-effective procedure compared to traditional manual total knee arthroplasty. As the volume-based procurement VBP program shows, the procedure can be more cost-effective.

Bioprinted biomimetic hydrogel matrices guiding stem cell aggregates for enhanced chondrogenesis and cartilage regeneration.

Articular cartilage tissue has limited self-repair capabilities, with damage frequently progressing to irreversible degeneration. Engineered tissues constructed through bioprinting and embedded with stem cell aggregates offer promising therapeutic alternatives. Aggregates of bone marrow mesenchymal stromal cells (BMSCs) demonstrate enhanced and more rapid chondrogenic differentiation than isolated cells, thus facilitating cartilage repair. However, it remains a key challenge to precisely control biochemical microenvironments to regulate cellular adhesion and cohesion within bioprinted matrices simultaneously. Herein, this work reports a bioprintable hydrogel matrix with high cellular adhesion and aggregation properties for cartilage repair. The hydrogel comprises an enhanced cell-adhesive gelatin methacrylate and a cell-cohesive chitosan methacrylate (CHMA), both of which are subjected to photo-initiated crosslinking. By precisely adjusting the CHMA content, the mechanical stability and biochemical cues of the hydrogels are finely tuned to promote cellular aggregation, chondrogenic differentiation and cartilage repair implantation. Multi-layer constructs encapsulated with BMSCs, with high cell viability reaching 91.1%, are bioprinted and photo-crosslinked to support chondrogenic differentiation for 21 days. BMSCs rapidly form aggregates and display efficient chondrogenic differentiation both on the hydrogels and within bioprinted constructs, as evidenced by the upregulated expression of Sox9, Aggrecan and Collagen 2a1 genes, along with high protein levels. Transplantation of these BMSC-laden bioprinted hydrogels into cartilaginous defects demonstrates effective hyaline cartilage repair. Overall, this cell-responsive hydrogel scaffold holds immense promise for applications in cartilage tissue engineering.

Targeting AQP9 enhanced the anti-TNF therapy response in Crohn's disease by inhibiting LPA-hippo pathway.

Although anti-TNF antibodies are extensively used to treat Crohn's disease (CD), a significant proportion of patients, up to 40%, exhibit an inadequate response to this therapy. Our objective was to identify potential targets that could improve the effectiveness of anti-TNF therapy in CD. Through the integration and analysis of transcriptomic data from various CD databases, we found that the expression of AQP9 was significantly increased in anti-TNF therapy-resistant specimens. The response to anti-TNF therapy in the CD mouse model was significantly enhanced by specifically inhibiting AQP9. Further experiments found that the blockade of AQP9, which is dominantly expressed in macrophages, decreased inflamed macrophage functions and cytokine expression. Mechanistic studies revealed that AQP9 transported glycerol into macrophages, where it was metabolized to LPA, which was further metabolized to LPA, resulting in the activation of the LPAR2 receptor and downstream hippo pathway, finally promoting the expression of cytokines, especially IL23 and IL1ß⊡ Taken together, the expansion of AQP9+ macrophages is associated with resistance to anti-TNF therapy in Crohn's disease. These findings indicated that AQP9 could be a potential target for enhancing anti-TNF therapy in Crohn's disease.

Dietary supplements: clinical cholesterol-lowering efficacy and potential mechanisms of action.

This review aims to analyse the efficacy of dietary supplements in reducing plasma cholesterol levels. Focusing on evidence from meta-analyses of randomised controlled clinical trials, with an emphasis on potential mechanisms of action as supported by human, animal, and cell studies. Certain dietary supplements including phytosterols, berberine, viscous soluble dietary fibres, garlic supplements, soy protein, specific probiotic strains, and certain polyphenol extracts could significantly reduce plasma total and low-density lipoprotein (LDL) cholesterol levels by 3-25% in hypercholesterolemic patients depending on the type of supplement. They tended to be more effective in reducing plasma LDL cholesterol level in hypercholesterolemic individuals than in normocholesterolemic individuals. These supplements worked by various mechanisms, such as enhancing the excretion of bile acids, inhibiting the absorption of cholesterol in the intestines, increasing the expression of hepatic LDL receptors, suppressing the activity of enzymes involved in cholesterol synthesis, and activating the adenosine monophosphate-activated protein kinase signalling pathway.

Experimental investigation of confinement effect in single molecule amplification via real-time digital PCR on a multivolume droplet array SlipChip.

BACKGROUND: Digital polymerase chain reaction (digital PCR) is an important quantitative nucleic acid analysis method in both life science research and clinical diagnostics. One important hypothesis is that by physically constraining a single nucleic acid molecule in a small volume, the relative concentration can be increased therefore further improving the analysis performance, and this is commonly defined as the confinement effect in digital PCR. However, experimental investigation of this confinement effect can be challenging since it requires a microfluidic device that can generate partitions of different volumes and an instrument that can monitor the kinetics of amplification. (96). RESULTS: Here, we developed a real-time digital PCR system with a multivolume droplet array SlipChip (Muda-SlipChip) that can generate droplet of 125 nL, 25 nL, 5 nL, and 1 nL by a simple "load-slip" operation. In the digital region, by reducing the volume, the relative concentration is increased, the amplification kinetic can be accelerated, and the time to reach the fluorescence threshold, or Cq value, can be reduced. When the copy number per well is much higher than one, the relative concentration is independent of the partition volume, thus the amplification kinetics are similar in different volume partitions. This system is not limited to studying the kinetics of digital nucleic acid amplification, it can also extend the dynamic range of the digital nucleic acid analysis by additional three orders of magnitude by combining a digital and an analog quantification algorithm. (140). SIGNIFICANCE: In this study, we experimentally investigated for the first time the confinement effect in the community of digital PCR via a new real-time digital PCR system with a multivolume droplet array SlipChip (Muda-SlipChip). And a wider dynamic range of quantification methods compared to conventional digital PCR was validated by this system. This system provides emerging opportunities for life science research and clinical diagnostics. (63).

Effects of building envelope features on airflow and pollutant dispersion within a symmetric street canyon.

Building envelope features (BEFs) have attracted more and more attention as they have a significant impact on flow structure and pollutant dispersion within street canyons. This paper conducted CFD numerical models validated by wind-tunnel experiments, to explore the effects of the BEFs on characteristics of the airflow and pollutant distribution inside a symmetric street canyon under perpendicular incoming flow. Three different BEFs (balconies, overhangs, and wing walls) and their locations and continuity/discontinuity structures were considered. For each canyon with various BEFs, the air exchange rate (ACH), airflow patterns, and pollutant distributions were evaluated and compared in detail. The results show that compared to the regular canyon, the BEFs will reduce the ACH of the canyon, but increase the disturbances (the proportion of ACH') inside the canyon. The BEFs on the leeward wall have the least influence on the in-canyon airflow and pollutant distributions, followed by that on the windward wall. Then when the BEFs are on both walls, the ventilation capacity of the canyon is weakened greatly, and the pollutant concentration in the ground center is increased significantly, especially near the windward side. Moreover, the discontinuity BEFs will weaken the effect of the continuity BEFs on the in-canyon flow and dispersion, specifically, the discontinuity BEFs reduced the region of high pollutant concentration distributions. These findings can help optimize the BEFs design to enhance ventilation and mitigate traffic pollution.

Small extracellular vesicles from young plasma reverse age-related functional declines by improving mitochondrial energy metabolism.

Recent investigations into heterochronic parabiosis have unveiled robust rejuvenating effects of young blood on aged tissues. However, the specific rejuvenating mechanisms remain incompletely elucidated. Here we demonstrate that small extracellular vesicles (sEVs) from the plasma of young mice counteract pre-existing aging at molecular, mitochondrial, cellular and physiological levels. Intravenous injection of young sEVs into aged mice extends their lifespan, mitigates senescent phenotypes and ameliorates age-associated functional declines in multiple tissues. Quantitative proteomic analyses identified substantial alterations in the proteomes of aged tissues after young sEV treatment, and these changes are closely associated with metabolic processes. Mechanistic investigations reveal that young sEVs stimulate PGC-1α expression in vitro and in vivo through their miRNA cargoes, thereby improving mitochondrial functions and mitigating mitochondrial deficits in aged tissues. Overall, this study demonstrates that young sEVs reverse degenerative changes and age-related dysfunction, at least in part, by stimulating PGC-1α expression and enhancing mitochondrial energy metabolism.

Analysis of the Cadmium Removal Mechanism of Human Gut Bacteria Enterococcus faecalis Strain ATCC19433 from a Genomic Perspective.

Cadmium (Cd) is one of the most well-known toxic metals capable of entering the human body via the food chain, leading to serious health problems. Human gut microbes play a pivotal role in controlling Cd bioavailability and toxicity within the human gastrointestinal tract, primarily due to their capacity for Cd adsorption and metabolism. In this work, a Cd-resistant bacterial strain, Enterococcus faecalis strain ATCC19433 was isolated from human gut microbiota. Cd binding assays and comprehensive characterization analyses were performed, revealing the ability of strain ATCC19433 to remove Cd from the solution. Cd adsorption primarily occurred on the bacterial cell walls, which was ascribed to the exciting of functional groups on the bacterial surfaces, containing alkyl, amide II, and phosphate groups; meanwhile, Cd could enter cells, probably through transport channels or via diffusion. These results indicated that Cd removal by the strain was predominantly dependent on biosorption and bioaccumulation. Whole-genome sequencing analyses further suggested the probable mechanisms of biosorption and bioaccumulation, including Cd transport by transporter proteins, active efflux of Cd by cadmium efflux pumps, and mitigating oxidative stress-induced cell damage by DNA repair proteases. This study evaluated the Cd removal capability and mechanism of Enterococcus faecalis strain ATCC19433 while annotating the genetic functions related to Cd removal, which may facilitate the development of potential human gut strains for the removal of Cd.

Super-enhancer mediated upregulation of MYEOV suppresses ferroptosis in lung adenocarcinoma.

Super-enhancers (SEs) exerted a crucial role in regulating the transcription of oncogenes across various malignancies while the roles of SEs driven genes and the core regulatory elements remain elusive in LUAD. In this study, cancer-specific-SE-genes of lung adenocarcinoma (LUAD) were profiled through H3K27ac ChIP-seq data of cancer cell lines and normal lung tissues, which enriched in in biological processes and pathways integral to the pathophysiology of LUAD. Based on this study, LUAD cells were susceptible to SEs inhibitors, with a reduction of cell proliferation as well as an elevation of apoptosis upon JQ1 or THZ1 intervention. Moreover, the integration of SEs landscapes, CRISPRi, ChIP-PCR, Hi-C data analysis and dual-luciferase reporter assays revealed that myeloma overexpressed gene (MYEOV) was aberrantly overexpressed in LUAD via transcriptional activation by the core SE elements. Functionally, the knockdown of MYEOV undermined cell proliferation in vitro and tumor growth in vivo. In addition, the knockdown of MYEOV generated a prominent ferroptotic phenotype, characterized by elevation of intracellular ferrous iron, reactive oxygen species and lipid peroxidation, together with alteration in marker proteins (SLC7A11, GPX4, FTH1, and ACSL4). Instead, the overexpression of MYEOV accelerated cell proliferation and abrogated ferroptosis. Clinically, the overexpression of MYEOV was observed in LUAD tissues indicating a poor prognosis in patients with LUAD. Mechanistically, SMPD1-induced autophagic degradation of GPX4 assumed a crucial role in the process of ferroptosis triggered by MYEOV knockdown. Serving as an oncogene repressing ferroptosis, promoting proliferation as well as shortening survival in LUAD, SEs-mediated activation of MYEOV might distinguish as a promising therapeutic target.

Accuracy of MRI-Based Radiomics in Diagnosis of Placenta Accreta Spectrum: A PRISMA Systematic Review and Meta-Analysis.

BACKGROUND Placenta accreta syndrome (PAS) can lead to severe obstetric bleeding, and can be life-threatening. This study aimed to assess the precision of radiomics features derived from magnetic resonance imaging (MRI) for diagnosing PAS. MATERIAL AND METHODS A comprehensive search was conducted in the databases PubMed, Embase, Web of Science, and the Cochrane library from inception to October 2023. We included diagnostic accuracy studies utilizing radiomics-MRI in PAS patients, with histopathology serving as the reference standard. The overall diagnostic odds ratio (DOR), sensitivity, specificity, and area under the curve (AUC) were computed to gauge the diagnostic accuracy of MRI-based radiomic features in PAS patients. Quality assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies 2. Statistical analyses were carried out using Stata 14.2, MetaDiSc 1.4, and Review Manager 5.3 software. RESULTS Seven studies involving 672 patients were incorporated. The aggregated DOR, sensitivity, specificity, and AUC for radiomics in detecting PAS were 78% (confidence interval32, 191), 87% (76%, 93%), 92% (89%, 94%), and 0.93 (0.91-0.95), respectively. The meta-analysis revealed notable heterogeneity among the included studies, with no evidence of a threshold effect. Subgroup analysis demonstrated that, in comparison to manual segmentation and validation groups with ≤100 cases and internal validation datasets, automated segmentation, validation groups with >100 cases, and external validation datasets exhibited superior diagnostic performance . CONCLUSIONS Our findings indicate that MRI-based radiomic features perform well in assessing the diagnostic risk of PAS during prenatal diagnosis. This noninvasive and convenient tool may prove valuable in facilitating the identification of PAS.

Efficient Cr(VI) removal by pyrite/porous biochar: Critical role of potassium salt and sulphur.

The excessive accumulation of hexavalent chromium (Cr(VI)) in the environment poses a risk to environment and human health. In the present study, a potassium bicarbonate-modified pyrite/porous biochar composite (PKBC) was prepared in a one-step process and applied for the efficient removal of Cr(VI) in wastewater. The results showed that PKBC can significantly remove Cr(VI) within 4 h over a wide range of pH (2-11). Meanwhile, the PKBC demonstrated remarkable resistance towards interference from complex ions. The addition of potassium bicarbonate increased the pore structure of the material and promoted the release of Fe2+. The reduction of Cr(VI) in aqueous solution was primarily attributed to the Fe(II)/Fe(III) redox cycle. The sulphur species achieved Fe(II)/Fe(III) cycle through electron transfer with iron, thus ensuring the continuous reduction capacity of PKBC. Besides, the removal rate was also maintained at more than 85% in the actual water samples treatment process. This work provides a new way to remove hexavalent chromium from wastewater and demonstrates the potential critical role of potassium bicarbonate and sulphur.

[Clinical study of constructing nomogram model based on multi-dimensional clinical indicators to predict prognosis of knee osteoarthritis].

OBJECTIVE: To analyze the factors affecting the prognosis of patients with knee osteoarthritis, and to construct a nomogram prediction model in conjunction with multi-dimensional clinical indicators. METHODS: The clinical data of 234 patients with knee osteoarthritis who were treated in our hospital from January 2015 to June 2021 were retrospectively analyzed, including 126 males and 108 females；age more than 60 years old for 135 cases, age less than 60 years old for 99 cases. Lysholm knee function score was used to evaluate the prognosis of the patients, and the patients were divided into good prognosis group for 155 patients and poor prognosis group for 79 patients according to the prognosis. The clinical data of the subjects in the experimental cohort were analyzed by single factor and multiple factors. The patients were divided into experimental cohort and verification cohort, the results of the multiple factor analysis were visualized to obtain a nomogram prediction model, the receiver operating characteristic curve（ROC）, calibration curve and decision curve were used to evaluate the model's discrimination, accuracy and clinical benefit rate. RESULTS: The results of multivariate analysis showed that smoking, pre-treatment K-L grades of Ⅲ to Ⅳ, and high levels of interleukin 6 （IL-6） and matrix metallo proteinase-3 （MMP-3） were risk factors for the prognosis of patients with knee osteoarthritis. ROC test results showed that the area under the curve of the nomogram model in the experimental cohort and validation cohort was 0.806[95%CI（0.742, 0.866）] and 0.786[（95%CI（0.678, 0.893）], respectively. The results of the calibration curve showed that the Brier values of the experimental cohort and verification cohort were 0.151 points and 0.134 points, respectively. When the threshold probability value in the decision curve was set to 31%, the clinical benefit rates of the experimental cohort and validation cohort were 51% and 56%, respectively. CONCLUSION: The prognostic model of patients with knee osteoarthritis constructed based on multi-dimensional clinical data has both theoretical and practical significance, and can provide a reference for taking targeted measures to improve the prognosis of patients.

Comprehensive whole-genome resequencing unveils genetic diversity and selective signatures of the Xiangdong black goat.

Xiangdong black goats, indigenous to Hunan Province, China, exhibit remarkable adaptation to challenging environments and possess distinct black coat coloration alongside exceptional meat quality attributes. Despite their significance, comprehensive genomic investigations of this breed have been notably lacking. This study involved a comprehensive examination of population structure, genomic diversity, and regions of selection in Xiangdong black goats utilizing whole-genome sequencing data from 20 samples of this breed and 139 published samples from six other Chinese goat breeds. Our genomic analysis revealed a total of 19,133,125 biallelic single nucleotide polymorphisms (SNPs) within the Xiangdong black goat genome, primarily located in intergenic and intronic regions. Population structure analysis indicated that, compared with Jintang, Guizhou and Chengdu goats, Xiangdong black goats exhibit a reduced level of genetic differentiation but exhibit relatively greater divergence from Jining goats. An examination of genetic diversity within Xiangdong black goats revealed a moderate level of diversity, minimal inbreeding, and a substantial effective population size, which are more reflective of random mating patterns than other Chinese goat breeds. Additionally, we applied four distinct selective sweep methods, namely, the composite likelihood ratio (CLR), fixation index (F ST), θ π ratio and cross-population extended haplotype homozygosity (XP-EHH), to identify genomic regions under positive selection and genes associated with fundamental biological processes. The most prominent candidate genes identified in this study are involved in crucial aspects of goat life, including reproduction (CCSER1, PDGFRB, IFT88, LRP1B, STAG1, and SDCCAG8), immunity (DOCK8, IL1R1, and IL7), lactation and milk production (SPP1, TLL1, and ERBB4), hair growth (CHRM2, SDC1, ITCH, and FGF12), and thermoregulation (PDE10A). In summary, our research contributes valuable insights into the genomic characteristics of the Xiangdong black goat, underscoring its importance and utility in future breeding programs and conservation initiatives within the field of animal breeding and genetics.

A sonographic endometrial thickness <7 mm in women undergoing in vitro fertilization increases the risk of placenta accreta spectrum.

BACKGROUND: The prevalence of placenta accreta spectrum, a potentially life-threatening condition, has exhibited a significant global rise in recent decades. Effective screening methods and early identification strategies for placenta accreta spectrum could enable early treatment and improved outcomes. Endometrial thickness plays a crucial role in successful embryo implantation and favorable pregnancy outcomes. Extensive research has been conducted on the impact of endometrial thickness on assisted reproductive technology cycles, specifically in terms of pregnancy rates, live birth rates, and pregnancy loss rates. However, limited knowledge exists regarding the influence of endometrial thickness on placenta accreta spectrum. OBJECTIVE: This study aimed to evaluate the association between preimplantation endometrial thickness and the occurrence of placenta accreta spectrum in women undergoing assisted reproductive technology cycles. STUDY DESIGN: A total of 4637 women who had not undergone previous cesarean delivery and who conceived by in vitro fertilization or intracytoplasmic sperm injection-embryo transfer treatment and subsequently delivered at the Third Affiliated Hospital of Guangzhou Medical University between January 2008 and December 2020 were included in this study. To explore the relationship between endometrial thickness and placenta accreta spectrum, we used smooth curve fitting, threshold effect, and saturation effect analysis. Multivariate logistic regression analysis was performed to evaluate the independent association between endometrial thickness and placenta accreta spectrum while adjusting for potential confounding factors. Propensity score matching was performed to reduce the influence of bias and unmeasured confounders. Furthermore, we used causal mediation effect analysis to investigate the mediating role of endometrial thickness in the relationship between gravidity and ovarian stimulation protocol and the occurrence of placenta accreta spectrum. RESULTS: Among the 4637 women included in this study, pregnancies with placenta accreta spectrum (159; 3.4%) had significantly thinner endometrial thickness (non-placenta accreta spectrum, 10.08±2.04 mm vs placenta accreta spectrum, 8.88±2.21 mm; P<.001) during the last ultrasound before embryo transfer. By using smooth curve fitting, it was found that changes in endometrial thickness had a significant effect on the incidence of placenta accreta spectrum up to a thickness of 10.9 mm, beyond which the effect plateaued. Then, the endometrial thickness was divided into the following 4 groups: ≤7, >7 to ≤10.9, >10.9 to ≤13, and >13 mm. The absolute rates of placenta accreta spectrum in each group were 11.91%, 3.73%, 1.35%, and 2.54%, respectively. Compared with women with an endometrial thickness from 10.9 to 13 mm, the odds of placenta accreta spectrum increased from an adjusted odds ratio of 2.27 (95% confidence interval, 1.33-3.86) for endometrial thickness from 7 to 10.9 mm to an adjusted odds ratio of 7.15 (95% confidence interval, 3.73-13.71) for endometrial thickness <7 mm after adjusting for potential confounding factors. Placenta previa remained as an independent risk factor for placenta accreta spectrum (adjusted odds ratio, 11.80; 95% confidence interval, 7.65-18.19). Moreover, endometrial thickness <7 mm was still an independent risk factor for placenta accreta spectrum (adjusted odds ratio, 3.91; 95% confidence interval, 1.57-9.73) in the matched cohort after PSM. Causal mediation analysis revealed that approximately 63.9% of the total effect of gravidity and 18.6% of the total effect of ovarian stimulation protocol on placenta accreta spectrum were mediated by endometrial thickness. CONCLUSION: The findings of our study indicate that thin endometrial thickness is an independent risk factor for placenta accreta spectrum in women without previous cesarean delivery undergoing assisted reproductive technology treatment. The clinical significance of this risk factor is slightly lower than that of placenta previa. Furthermore, our results demonstrate that endometrial thickness plays a significant mediating role in the relationship between gravidity or ovarian stimulation protocol and placenta accreta spectrum.

Humidity-Induced Self-Oscillating and Self-Healing Hypercrosslinked Metal-Organic Polyhedra Membranes.

Designing autonomously oscillating materials is highly desirable for emerging smart material fields but challenging. Herein, a type of hypercrosslinked metal-organic polyhedra (HCMOPs) membranes formed by covalent crosslinking of boronic acid-modified Zr-based MOPs with polyvinyl alcohol (PVA) are rationally designed. In these membranes, MOPs serve as high-connectivity nodes and provide dynamic borate bonds with PVA in hypercrosslinked networks, which can be broken/formed reversibly upon the stimulus of water vapor. The humidity response characteristic of HCMOPs promotes their self-oscillating and self-healing properties. HCMOP membranes can realize a self-oscillating property above the water surface even after loading a cargo that is 1.5 times the weight of the membrane due to the fast adsorption and desorption kinetics. Finally, the HCMOP actuator can realize energy conversion from mechanical energy into electricity when coupled with a piezoelectric membrane. This work not only paves a new avenue to construct MOP-polymer hybrid materials but also expands the application scopes of MOPs for smart actuation devices.

High-Fidelity Sensitive Tracing Circulating Tumor Cell Telomerase Activity.

Dynamic tracing of intracellular telomerase activity plays a crucial role in cancer cell recognition and correspondingly in earlier cancer diagnosis and personalized precision therapy. However, due to the complexity of the required reaction system and insufficient loading of reaction components into cells, achieving a high-fidelity determination of telomerase activity is still a challenge. Herein, an Aptamer-Liposome mediated Telomerase activated poly-Molecular beacon Arborescent Nanoassembly(ALTMAN) approach was described for direct high-fidelity visualization of telomerase activity. Briefly, intracellular telomerase activates molecular beacons, causing their hairpin structures to unfold and produce fluorescent signals. Furthermore, multiple molecular beacons can self-assemble, forming arborescent nanostructures and leading to exponential amplification of fluorescent signals. Integrating the enzyme-free isothermal signal amplification successfully increased the sensitivity and reduced interference by leveraging the skillful design of the molecular beacon and the extension of the telomerase-activated TTAGGG repeat sequence. The proposed approach enabled ultrasensitive visualization of activated telomerase exclusively with a prominent detection limit of 2 cells·µL-1 and realized real-time imaging of telomerase activity in living cancer cells including blood samples from breast cancer patients and urine samples from bladder cancer patients. This approach opens an avenue for establishing a telomerase activity determination and in situ monitoring technique that can facilitate both telomerase fundamental biological studies and cancer diagnostics.

Near-Field Terahertz Morphological Reconstruction Nanoscopy for Subsurface Imaging of Protein Layers.

Protein layers formed on solid surfaces have important applications in various fields. High-resolution characterization of the morphological structures of protein forms in the process of developing protein layers has significant implications for the control of the layer's quality as well as for the evaluation of the layer's performance. However, it remains challenging to precisely characterize all possible morphological structures of protein in various forms, including individuals, networks, and layers involved in the formation of protein layers with currently available methods. Here, we report a terahertz (THz) morphological reconstruction nanoscopy (THz-MRN), which can reveal the nanoscale three-dimensional structural information on a protein sample from its THz near-field image by exploiting an extended finite dipole model for a thin sample. THz-MRN allows for both surface imaging and subsurface imaging with a vertical resolution of ∼0.5 nm, enabling the characterization of various forms of proteins at the single-molecule level. We demonstrate the imaging and morphological reconstruction of single immunoglobulin G (IgG) molecules, their networks, a monolayer, and a heterogeneous double layer comprising an IgG monolayer and a horseradish peroxidase-conjugated anti-IgG layer. The established THz-MRN presents a useful approach for the label-free and nondestructive study of the formation of protein layers.