The AAA-ATPase Yta4/ATAD1 interacts with the mitochondrial divisome to inhibit mitochondrial fission.

Mitochondria are in a constant balance of fusion and fission. Excessive fission or deficient fusion leads to mitochondrial fragmentation, causing mitochondrial dysfunction and physiological disorders. How the cell prevents excessive fission of mitochondria is not well understood. Here, we report that the fission yeast AAA-ATPase Yta4, which is the homolog of budding yeast Msp1 responsible for clearing mistargeted tail-anchored (TA) proteins on mitochondria, plays a critical role in preventing excessive mitochondrial fission. The absence of Yta4 leads to mild mitochondrial fragmentation in a Dnm1-dependent manner but severe mitochondrial fragmentation upon induction of mitochondrial depolarization. Overexpression of Yta4 delocalizes the receptor proteins of Dnm1, i.e., Fis1 (a TA protein) and Mdv1 (the bridging protein between Fis1 and Dnm1), from mitochondria and reduces the localization of Dnm1 to mitochondria. The effect of Yta4 overexpression on Fis1 and Mdv1, but not Dnm1, depends on the ATPase and translocase activities of Yta4. Moreover, Yta4 interacts with Dnm1, Mdv1, and Fis1. In addition, Yta4 competes with Dnm1 for binding Mdv1 and decreases the affinity of Dnm1 for GTP and inhibits Dnm1 assembly in vitro. These findings suggest a model, in which Yta4 inhibits mitochondrial fission by inhibiting the function of the mitochondrial divisome composed of Fis1, Mdv1, and Dnm1. Therefore, the present work reveals an uncharacterized molecular mechanism underlying the inhibition of mitochondrial fission.

Oocytes orchestrate protein prenylation for mitochondrial function through selective inactivation of cholesterol biosynthesis in murine species.

Emerging research and clinical evidence suggest that the metabolic activity of oocytes may play a pivotal role in reproductive anomalies. However, the intrinsic mechanisms governing oocyte development regulated by metabolic enzymes remain largely unknown. Our investigation demonstrates that geranylgeranyl diphosphate synthase1 (Ggps1), the crucial enzyme in the mevalonate pathway responsible for synthesizing isoprenoid metabolite geranylgeranyl pyrophosphate from farnesyl pyrophosphate, is essential for oocyte maturation in mice. Our findings reveal that the deletion of Ggps1 that prevents protein prenylation in fully grown oocytes leads to subfertility and offspring metabolic defects without affecting follicle development. Oocytes that lack Ggps1 exhibit disrupted mitochondrial homeostasis and the mitochondrial defects arising from oocytes are inherited by the fetal offspring. Mechanistically, the excessive farnesylation of mitochondrial ribosome protein, Dap3, and decreased levels of small G proteins mediate the mitochondrial dysfunction induced by Ggps1 deficiency. Additionally, a significant reduction in Ggps1 levels in oocytes is accompanied by offspring defects when females are exposed to a high-cholesterol diet. Collectively, this study establishes that mevalonate pathway-protein prenylation is vital for mitochondrial function in oocyte maturation and provides evidence that the disrupted protein prenylation resulting from an imbalance between farnesyl pyrophosphate and geranylgeranyl pyrophosphate is the major mechanism underlying impairment of oocyte quality induced by high cholesterol.

A Piezoelectric Nanogenerator-Driven Dual-Mode Platform for Visualization and Impedance Sensing.

Traditional visual biosensing platforms rely on color to display detection results, which can be influenced by individual visual abilities, equipment, parameters, and lighting conditions during photo capture. This limitation significantly impedes the advancement of next-generation portable electrochemical biosensors. Therefore, we propose a visual biosensing device that utilizes distance as an indicator, enabling the facile determination of the length of discoloration, which is inversely proportional to the concentration of the target analyte. The separation of the Signal Generation (SG) and Signal Output (SO) regions effectively mitigates potential interference from the sample color. Additionally, the SG region can be disassembled to facilitate electrochemical impedance spectroscopy (EIS) detection in laboratory settings, enabling dual-mode detection. Meanwhile, the utilization of piezoelectric nanogenerators (PENG) empowers the entire point-of-care testing (POCT) sensing device, effectively addressing the issue of a limited battery life. The biosensing device exhibited a satisfactory linear range (EIS mode, 5 pg/L to 5 mg/L; visual mode, 0.5 ng/L to 5 mg/L) and a low limit of detection (EIS mode, 2.3 pg/L; visual mode, 0.14 ng/L) with S/N = 3 for ochratoxin A (OTA) under optimized conditions. The self-powered and cost-effective dual-mode biosensing platform developed for OTA detection offers clear and easily interpretable results, demonstrating a high accuracy in laboratory settings.

Programmable DNA Templates for Silver Nanoclusters Synthesis To Develop On-Demand FRET Aptasensor.

DNA-templated silver nanoclusters (AgNCs-DNA) can be synthesized via a one-pot method bypassing the tedious process of biomolecular labeling. Appending an aptamer to DNA templates results in dual-functionalized DNA strands that can be utilized for synthesizing aptamer-modified AgNCs, thereby enabling the development of label-free fluorescence aptasensors. However, a major challenge lies in the necessity to redesign the dual-functionalized DNA strand for each specific target, thus increasing the complexity and hindering widespread application of these aptasensors. To overcome this challenge, we designed six DNA strands (DNA1-DNA6) that incorporate the templates for AgNCs synthesis and A4-linker for further aptamer coupling. Among all the synthesized AgNCs-DNA samples, it was found that both AgNCs-DNA1 and AgNCs-DNA2 stood out for their excellent long-term stability. After capturing the T4-linker that connected with aptamer1 specific for aflatoxin B1 (AFB1), however, we found that only AgNCs-DNA1/aptamer1 maintained excellent long-term stability. This finding highlighted the potential of AgNCs-DNA1 as a versatile label-free fluorescence probe for the development of on-demand fluorescence aptasensors. To emphasize its benefits in aptasensing applications, we utilized AgNCs-DNA1/aptamer1 as the fluorescence probe and MoS2 nanosheets as the quencher to develop a FRET aptasensor for AFB1 detection. This aptasensor demonstrated remarkable sensitivity, enabling the detection of AFB1 within a wide concentration range of 0.03-120 ng/mL, with a limit of detection as low as 3.6 pg/mL (S/N = 3). The versatility of the aptasensor has been validated through the recognition of diverse targets, employing aptamer2 specific for ochratoxin A and aptamer3 specific for zearalenone, thereby showcasing its extensive applicability for on-demand detection. The universal applicability of this aptasensor holds great promise for future applications in diverse fields including food safety, environmental monitoring, and clinical diagnosis.

Tailoring Charge Flow in Carbon-Defective Cu-MOF with Pd Nanoparticles: A Boost for Visible Light Organic Photoelectrochemical Transistor in Bioanalysis.

The photoactive material was of significant importance in organic photoelectrochemical transistor (OPECT) bioanalysis as it influences the photoinduced voltage and the µC* product, resulting in a varying sensor sensitivity. The utilization of metal-organic frameworks (MOFs) as photoactive materials in OPECT analysis is promising, yet it remains a grand challenge due to the inherently narrow light absorption range and high electron-hole recombination rate. Herein, Pd NPs were encapsulated as electron acceptors into the Cu-MOF using a double-solvent method, followed by pyrolysis at the proper temperature. After pyrolysis, Cu-MOF transformed into a carbon defect-rich composite of CuO and Cu2O while retaining its high porosity and structural morphology. The resulting carbon defect-rich pyrolysis Cu-MOF (p-Cu-MOF) served as an active support, facilitating the separation of electrons and holes. The photoelectrons trigger the electron transfer of adjacent active metal components and the formation of a Schottky junction between Pd and the MOFs. This effect induces the electron donation from the MOFs. Moreover, Pd/pyrolysis Cu-MOF exhibits significantly higher visible light absorption, better water stability, and higher electrical conductivity compared to Cu-MOF and Pd/Cu-MOF. An OPECT sensor was fabricated by utilizing Pd/p-Cu-MOF as the photoactive material and poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) as the channel material on an integrated laser-etched FTO. The aptamer was used as the recognition element, enabling sensitive and efficient detection of residual isocarbophos.

Noble Metal Nanoparticle-Based Photothermal Therapy: Development and Application in Effective Cancer Therapy.

Photothermal therapy (PTT) is a promising cancer therapy modality with significant advantages such as precise targeting, convenient drug delivery, better efficacy, and minimal adverse effects. Photothermal therapy effectively absorbs the photothermal transducers in the near-infrared region (NIR), which induces the photothermal effect to work. Although PTT has a better role in tumor therapy, it also suffers from low photothermal conversion efficiency, biosafety, and incomplete tumor elimination. Therefore, the use of nanomaterials themselves as photosensitizers, the targeted modification of nanomaterials to improve targeting efficiency, or the combined use of nanomaterials with other therapies can improve the therapeutic effects and reduce side effects. Notably, noble metal nanomaterials have attracted much attention in PTT because they have strong surface plasmon resonance and an effective absorbance light at specific near-infrared wavelengths. Therefore, they can be used as excellent photosensitizers to mediate photothermal conversion and improve its efficiency. This paper provides a comprehensive review of the key role played by noble metal nanomaterials in tumor photothermal therapy. It also describes the major challenges encountered during the implementation of photothermal therapy.

An In-Situ-Tag-Generation Proximity Labeling Technology for Recording Cellular Interactions.

Obtaining information about cellular interactions is fundamental to the elucidation of physiological and pathological processes. Proximity labeling technologies have been widely used to report cellular interactions in situ; however, the reliance on addition of tag molecules typically restricts their application to regions where tags can readily diffuse, while the application in, for example, solid tissues, is susceptible. Here, we propose an "in-situ-tag-generation mechanism" and develop the GalTag technology based on galactose oxidase (GAO) for recording cellular interactions within three-dimensional biological solid regions. GAO mounted on bait cells can in situ generate bio-orthogonal aldehyde tags as interaction reporters on prey cells. Using GalTag, we monitored the dynamics of cellular interactions and assessed the targeting ability of engineered cells. In particular, we recorded, for the first time, the footprints of Bacillus Calmette-Guérin (BCG) invasion into the bladder tissue of living mice, providing a valuable perspective to elucidate the anti-tumor mechanism of BCG.

Target-Induced Photocurrent-Polarity-Switching PEC Sensing Platform Based on In Situ Generation of Oxygen Vacancy-Modulated Energy Band Structures.

The polarity of the photocurrent can be modulated by tunable bipolar photoelectrochemical (PEC) behavior, which is anticipated to address the issues of high background signal caused by traditional unidirectional increasing/decreasing response and false-positive/false-negative problems. Here, a new approach is suggested for the first time, which employs a target-induced enzyme-catalyzed reaction and in situ oxygen vacancy (OV) generation to achieve heterojunction photocurrent switching for highly sensitive detection of alkaline phosphatase (ALP). Among them, the ALP can catalyze the decomposition of ascorbic acid phosphate to produce ascorbic acid, which not only acts as an electron donor to change the redox environment but also acts as a reducing agent to introduce OVs into BiOBr semiconductors in cooperation with illumination. The introduction of vacancies can effectively modulate the energy band structure of BiOBr, while with the change of redox conditions, the transfer path of photogenerated carriers is changed, thus realizing the switching of photocurrents, which leads to its use in the construction of a negative-background anti-interference PEC sensing platform, achieving a wide linear range from 0.005 to 500 U·L-1 with a low detection limit of 0.0017 U·L-1. In conclusion, the photocurrent switching operation of this system is jointly regulated by chemistry, optics, and carrier motion, which provides a new idea for the construction of a PEC sensing platform based on photocurrent polarity switching.

Decreased LONP1 expression contributes to DNA damage and meiotic defects in oocytes.

Meiotic defects in oocytes are the primary reason for decreased female fertility with advanced maternal age. In this study, we revealed that decreased expression of ATP-dependent Lon peptidase 1 (LONP1) in aged oocytes and oocyte-specific depletion of LONP1 disrupt oocyte meiotic progression accompanying with mitochondrial dysfunction. In addition, LONP1 downregulation increased oocyte DNA damage. Moreover, we demonstrated that splicing factor proline and glutamine rich directly interacts with LONP1 and mediate the effect of LONP1 depletion on meiotic progression in oocytes. In summary, our data suggest that decreased expression of LONP1 is involved in advanced maternal age-related meiosis defects and that LONP1 represents a new therapeutic target to improve aged oocyte quality.

Decreased HAT1 expression in granulosa cells disturbs oocyte meiosis during mouse ovarian aging.

BACKGROUND: With advanced maternal age, abnormalities during oocyte meiosis increase significantly. Aneuploidy is an important reason for the reduction in the quality of aged oocytes. However, the molecular mechanism of aneuploidy in aged oocytes is far from understood. Histone acetyltransferase 1 (HAT1) has been reported to be essential for mammalian development and genome stability, and involved in multiple organ aging. Whether HAT1 is involved in ovarian aging and the detailed mechanisms remain to be elucidated. METHODS: The level of HAT1 in aged mice ovaries was detected by immunohistochemical and immunoblotting. To explore the function of HAT1 in the process of mouse oocyte maturation, we used Anacardic Acid (AA) and small interfering RNAs (siRNA) to culture cumulus-oocyte complexes (COCs) from ICR female mice in vitro and gathered statistics of germinal vesicle breakdown (GVBD), the first polar body extrusion (PBE), meiotic defects, aneuploidy, 2-cell embryos formation, and blastocyst formation rate. Moreover, the human granulosa cell (GC)-like line KGN cells were used to investigate the mechanisms of HAT1 in this progress. RESULTS: HAT1 was highly expressed in ovarian granulosa cells (GCs) from young mice and the expression of HAT1 was significantly decreased in aged GCs. AA and siRNAs mediated inhibition of HAT1 in GCs decreased the PBE rate, and increased meiotic defects and aneuploidy in oocytes. Further studies showed that HAT1 could acetylate Forkhead box transcription factor O1 (FoxO1), leading to the translocation of FoxO1 into the nucleus. Resultantly, the translocation of acetylated FoxO1 increased the expression of amphiregulin (AREG) in GCs, which plays a significant role in oocyte meiosis. CONCLUSION: The present study suggests that decreased expression of HAT1 in GCs is a potential reason corresponding to oocyte age-related meiotic defects and provides a potential therapeutic target for clinical intervention to reduce aneuploid oocytes.

Adsorption Recycling and High-Value Reutilization of Heavy-Metal Ions from Wastewater: As a High-Performance Anode Lithium Battery.

The dazzling adsorbent products make people overlook the harm of heavy metals adsorbed on them. Hazardous waste adsorbents cause secondary pollution. In this study, waste lignocellulose was dissolved by alkaline urea solvent and high-intensity ultrasound, then cross-linked by epichlorohydrin to make hydrogel, which was utilized to adsorb toxic heavy-metal wastewater. In situ deposition and high-temperature carbonization turn the gel that has absorbed heavy metals into carbon aerogel-loaded metal oxide energy storage materials that may be employed as anodes in lithium-ion batteries with excellent electrochemical performance. The best reversible capacity was 435.86 mAh g-1 after 100 cycles at 0.2C, indicating that the hazardous solid waste generated by the removal of heavy metals using biomass-based adsorbent has potential lithium battery applications. Thus, we provide a fresh perspective on the efficient recycling of heavy metals as well as an environmentally friendly, high-value conservation strategy for lowering the danger of heavy-metal hazardous wastes.

Coordination Construction of the Dual Superoxide Dismutase Catalytic Center Nanozyme: Synergistic Contribution of the Site, Structure, and Electron Transfer Pathway.

Superoxide dismutase (SOD) mimics are limited by a single active center, and their performance is difficult to achieve the activity level of natural SOD. Herein, we exhibit the coordination construction of different SOD active centers (Cu and Mn) and structural regulation of framework carbonization in MOFs. The obtained catalytic activity and excellent biocompatibility are comparable to Cu/Zn-SOD. The improvement of catalytic performance was attributed to the bimetallic sites' synergistic catalysis (enhancing the substrate affinity and accelerating the reaction process) on the one hand and the contribution of framework carbonization on the other hand, which not only regulate the relative position and valence of metal nodes but improve the spatial adaptability of the reaction and reduce the reaction barrier, and the increased conductivity of the framework accelerates the electron transfer process in the reaction. The excellent biocompatibility results from the fixing effect of the carbonized framework on the metal nodes. Mn/Cu-C-N2 was encapsulated in a chitosan film as an antioxidant compared with a pure chitosan film; the anthocyanin content of blueberries increased 2 times after being stored at room temperature for 7 days, and the content was 83% of the fresh blueberries, providing exciting potential for biological applications limited by the performance of SOD nanozymes.

Ce/Zr-MOF with Dual Cycle Synergistic Catalysis Pathway Enabling Enhanced Peroxidase-like Performance for Wearable Hydrogel Patch Visualization Sensing Platform.

Engineering the activity of enzyme-like catalysts should be a top priority to make them superior substitutes for natural enzymes. Herein, a Ce/Zr bimetal-organic framework (Ce/Zr-MOF) was designed and synthesized by a one-pot hydrothermal method, which has enhanced performance in mimicking peroxidase (POD) than its single-metal counterparts. To further comprehend the mechanism of activity enhancement, the role of the bimetallic synergistic catalysis process in H2O2 decomposition and reactive oxygen species formation was elucidated, and the possible dual cycle synergistic catalysis pathway of bimetallic catalysis is proposed for the first time. The enhanced POD-like activity mainly depends on the introduction of Ce, which improved the conductivity and electron-transfer capability of Ce/Zr-MOF and promoted the generation of •OH. Integrated with a hydrogel substrate, a wearable all-solid-state H2O2 sensor for early diagnosis of plant health was produced. The detection limit can be as low as 3.3 µM, which is lower than that of some instrument-based colorimetric methods and has great potential in the development of visualized sensing applications. The concept of dual cycle synergistic catalysis pathway we proposed not only deepens the comprehension regarding sensing and catalytic mechanisms but also provides novel perspectives into the design of enzyme-like catalysts for extensive usage.

Potential drug-drug interactions in outpatients with depression of a psychiatry department.

Objective: This study aims to explore the prevalence and associated risk factors for potential drug-drug interactions (pDDIs) in prescriptions among outpatients with depression, and report the widespread relevant drug interactions. Methods: The cross-sectional retrospective study was conducted on outpatients in a psychiatric hospital. We included prescriptions of outpatients with a principal diagnosis of depression from April 1st to June 30th in 2021. The patients were ≥ 18 years old and treated with two or more drugs including at least one psychotropic drug. pDDIs were detected and identified mainly using Medscape's drug interactions checker. Gender, the number of concomitant drugs, age and diagnosis were analysed as potential risk factors for the occurrence of pDDIs by logistic regression. Results: A total of 13,617 prescriptions were included in the present analysis, and 4222 prescriptions (31.0%) were at risk of 8557 pDDIs. The risk of pDDIs in patients who were prescribed 4-6 drugs (OR: 3.49, 95% CI: 3.11-3.91, p < 0.001) or 7 or more drugs simultaneously (OR: 7.86, 95% CI: 1.58-39.04, p < 0.05) increased compared with patients prescribed 2-3 drugs. Patients with recurrent depressive disorders (OR: 1.18, 95% CI: 1.02-1.36, p < 0.05) had an increased risk of pDDIs compared with patients with depressive episodes. In terms of severity of pDDIs identified by Medscape's drug interactions checker, 0.7%, 16.4%, 77.5% and 5.4% of pDDIs were classified as contraindicated, serious, monitor closely and minor, respectively. The most common pDDI was escitalopram + quetiapine (374 prescriptions), which was classified as serious and monitor closely due to different mechanisms of interaction. Increased central nervous system (CNS)-depressant effect was the most frequent potential clinical adverse outcome of the identified pDDIs. Conclusions: pDDIs in outpatients with depression were prevalent in this retrospective study. The number of concomitant drugs and severity of the disease were important risk factors for pDDIs. The pDDIs of the category monitor closely were the most common, and the CNS-depressant effect was the most frequent potential clinical adverse outcome.

Human Endometrium-Derived Adventitial Cell Spheroid-Loaded Antimicrobial Microneedles for Uterine Regeneration.

Asherman's syndrome (AS) occurs as a consequence of severe damage to the endometrial basalis, usually leading to menstrual abnormalities, infertility, and recurrent miscarriage in women. Currently, human endometrium-derived adventitial cells (En-ADVs) are considered ideal seed cells with high pluripotency for regenerative medicine. However, critical issues such as noninvasive repair of tissues, targeting of native stem cells, and continuous action in the injured sites are not well resolved. Herein, En-ADV spheroid-loaded hierarchical microneedles (MN/En-ADV) for in situ intrauterine repair are developed. The flexible microneedles are fabricated with gelatin methacryloyl and lactoferrin, imparting the characteristics of rapid degradation and antimicrobial activity. Benefiting from an array of microwells on microneedles, En-ADVs can rapidly form 3D cell spheroids, which display higher potential for cell proliferation, differentiation, and migration than dissociated cells. With the application of MN/En-ADV, the repaired uteri show well-defined myometrial regeneration, angiogenesis, and an increase of endometrial receptivity in a rat AS model. Notably, embryos are able to implant in the reconstructed sites and remain viable, indicating that this system promotes the restoration of both normal morphology and reproductive function in the injured uterus. It is anticipated that multifunctional MN/En-ADV can be an ideal candidate for versatile in situ tissue regeneration.

Bone-forming perivascular cells: Cellular heterogeneity and use for tissue repair.

Mesenchymal progenitor cells are broadly distributed across perivascular niches-an observation conserved between species. One common histologic zone with a high frequency of mesenchymal progenitor cells within mammalian tissues is the tunica adventitia, the outer layer of blood vessel walls populated by cells with a fibroblastic morphology. The diversity and functions of (re)generative cells present in this outermost perivascular niche are under intense investigation; we have reviewed herein our current knowledge of adventitial cell potential with a somewhat narrow focus on bone formation. Antigens of interest to functionally segregate adventicytes are discussed, including CD10, CD107a, aldehyde dehydrogenase isoforms, and CD140a, among others. Purified adventicytes (such as CD10+ , CD107alow , and CD140a+ cells) have stronger osteogenic potential and promote bone formation in vivo. Recent bone tissue engineering applications of adventitial cells are also presented. A better understanding of perivascular progenitor cell subsets may represent a beneficial advance for future efforts in tissue repair and bioengineering.

The recurrent factors of idiopathic vocal process granulomas after cold steel excision.

OBJECTIVE: To identify the factors predicting postoperative recurrence after cold steel excision for the market trader with idiopathic vocal process granulomas (VPGs). MATERIAL AND METHODS: The market traders with idiopathic VPGs who do not respond to medical treatment were treated by cold steel excision. The factors considered likely to affect the recurrence were evaluated by univariate and multivariate logistic regression. RESULTS: The total of 80 idiopathic VPGs underwent the cold steel excision. All postoperative 6 months, the complete remission rate was 37.5% (30 VPGs) and 50 recurrences developed (62.5%). The recurrence rate was not significantly associated with sex (P = 0.119), side (P = 0.468), VPG size (P = 0.726), LPR (P = 0.293), diabetes mellitus (P = 0.5611), cerebrovascular disease (P = 0.129), or chronic pulmonary disease (P = 0.190). Multivariate logistic regression showed that only vocalization frequency (P = 0.006) and smoking and alcohol consumption (P = 0.001) were independent predictors of recurrence. There was no significant correlation between age and recurrence (P = 0.59). However, recurrence was more common in those aged 51-60 years than those aged ≥61 years (P = 0.019). Of the recurrent 49 VPGs treated conservatively via behavioural modification and oral deanxit, the granulomas disappeared spontaneously in 38 (77.6%) within 6-10 months and in 11 (22.4%) within 2-3 years. CONCLUSIONS: The market traders with VPG would be a high recurrence rate after cold steel excision, the frequency of voice use and smoking and alcohol consumption were significant independent predictors of recurrence. Antidepressant medications and behavioural modification could effectively improve the outcome of VPG.

Extended middle meatal antrostomy via antidromic extended medial wall for the treatment of fungal maxillary sinusitis.

OBJECTIVE: The objective of this study was to compare the long-term results of extended middle meatal antrostomy (MMA) and MMA combined with inferior meatal antrostomy (IMA, combined approach) for the treatment of fungal maxillary sinusitis (FMS). METHODS AND MATERIALS: A retrospective analysis including 90 patients with non-invasive FMS was treated with endoscopic extended MMA via antidromic extended medial wall (extended MMA group), or with both MMA and IMA (combined approach group). The recurrence rate, operation time, and complications were evaluated at postoperative 12 and 36 months. RESULTS: Of the 90 patients, 52 patients were in the extended MMA group and 38 patients in the combined approach group. CT revealed the thin medial wall or bone defect in 63.33% (57/90) patients. The mean operation time in the extended MMA group was significantly shorter than that of combined approach group (42.5 ± 6.5 vs 57.4 ± 4.9, P < 0.01). At postoperative 12 months postoperatively, the recurrence rate was 3.85% (2/52) in the extended MMA group and 0.0% (0/38) in the combined approach group, the difference wasn't significant (X2 = 0.618, P > 0.05). The recurrence rate wasn't increased during the follow-up period over time in both groups.13.5% (7/52) patients complained of cheek numbness in the extended MMA group, 60.5% (23/38) patients complained of cheek numbness and epiphora in 5.3% (2/38) patients in the combined approach group, the difference was significant (X2 test, P < 0.01). However, no major complications were observed in both groups. In addition, IMA closure was observed in 4 (10.5%) in the combined approach group at 12 months postoperatively and in 9 (23.6%) at 36 months postoperatively. CONCLUSIONS: Extended MMA via antidromic extended medial wall may effectively prevent the recurrence and reduce the complications of FMS, IMA wasn't necessary for the treatment of FMS in most cases.

Attenuated monoamine oxidase a impairs endometrial receptivity in women with adenomyosis via downregulation of FOXO1†.

The establishment of endometrial receptivity is a prerequisite for successful pregnancy. Women with adenomyosis possess a lower chance of clinical pregnancy after assisted reproductive technology, which is partially due to impaired endometrial receptivity. The establishment of endometrial receptivity requires the participation of multiple processes, and proper endometrial epithelial cell (EEC) proliferation is indispensable. Monoamine oxidase A (MAOA) is a key molecule that regulates neurotransmitter metabolism in the nervous system. In the present study, we demonstrated a novel role for MAOA in the establishment of endometrial receptivity in women with adenomyosis and in an adenomyotic mouse model. Attenuated MAOA impairs endometrial receptivity by promoting inappropriate proliferation of EECs via the downregulation of FOXO1 during the window of implantation. These results revealed that MAOA plays a vital role in endometrial receptivity in female reproduction.

A high level of KLF12 causes folic acid-resistant neural tube defects by activating the Shh signaling pathway in mice†.

Although adequate periconceptional folic acid (FA) supplementation has reduced the occurrence of pregnancies affected by neural tube defects (NTDs), the mechanisms underlying FA-resistant NTDs are poorly understood, and thus NTDs still remain a global public health concern. A high level of Krüppel-like factor 12 (KLF12) exerts deleterious effects on heath in most cases, but evidence for its roles in development has not been published. We observed KLF12-overexpressing mice showed disturbed neural tube development. KLF12-overexpressing fetuses died in utero at approximately 10.5 days post-coitus, with 100% presenting cranial NTDs. Neither FA nor formate promoted normal neural tube closure in mutant fetuses. The RNA-seq results showed that a high level of KLF12 caused NTDs in mice via overactivating the sonic hedgehog (Shh) signaling pathway, leading to the upregulation of patched 1, GLI-Krüppel family member GLI1, hedgehog-interacting protein, etc., whereas FA metabolism-related enzymes did not express differently. PF-5274857, an antagonist of the Shh signaling pathway, significantly promoted dorsolateral hinge point formation and partially rescued the NTDs. The regulatory hierarchy between a high level of KLF12 and FA-resistant NTDs might provide new insights into the diagnosis and treatment of unexplained NTDs in the future.