Immune micro-environment analysis and drug screening for ovarian endometriosis.

BACKGROUND: Patients of ovary endometriosis have an abnormal immune micro-environment, leading to endometrial tissue that from retrograde menstruation evade immune surveillance and subsequently develop into ectopic lesions. OBJECTIVE: This study aims to elucidate the crucial immune cells and molecular pathways that are associated with an aberrant immune micro-environment of endometriosis. METHOD: In this study, we identified differentially expressed genes between ovarian ectopic endometrial tissue (OVE) and eutopic endometrial tissue from patients with endometriosis (PE) and non-endometriosis patients (CON) by analyzing the mRNA sequencing data. Additionally, we used WGCNA(Weighted Gene Co-expression Network Analysis) to screen for key genes related to immune cell infiltration and compared the sub-types of infiltrating immune cells using CIBERSORT(cell-type identification by estimating relative subsets of RNA transcript). Subsequently, we conducted a single-cell analysis on the identified key genes. Furthermore, we analyzed potential drugs suitable for ovarian endometriosis treatment using pRRophertic. RESULTS: Seven key genes associated with immune cell infiltration were screened out. The expression of these genes in OVE was significantly lower than that in PE and CON. These key genes were mainly enriched in the NK cell-mediated cytotoxicity pathway, especially for CD16 + CD56dim NK. Moreover, NK cells infiltration in ovarian endometriosis was significantly reduced compared with PE and CON, while M2 macrophage shown the opposite. Results of the single-cell analysis showed that the expression of the seven key genes in NK cells and monocyte-macrophages in OVE was significantly lower than that in PE or CON. Additionally, we identified potential drugs suitable for ovarian endometriosis treatment. CONCLUSION: The decreased infiltration of NK cells and increased infiltration of M2 macrophages contribute to the evasion of immune surveillance against endometrial tissue, promoting the progression of OVE. Therefore, potential strategies for the treatment of OVE include increasing NK cell activation and decreasing M2 macrophage polarization.

Identification of a pathogenic SMCHD1 variant in a Chinese patient with bosma arhinia microphthalmia syndrome: a case report.

BACKGROUND: Bosma arhinia microphthalmia syndrome (BAMS; MIM603457) is a rare genetic disorder, predominantly autosomal dominant. It is a multi-system developmental disorder characterized by severe hypoplasia of the nose and eyes, and reproductive system defects. BAMS is extremely rare in the world and no cases have been reported in Chinese population so far. Pathogenic variants in the SMCHD1 gene (MIM614982) cause BAMS, while the underlying molecular mechanisms requires further investigation. CASE PRESENTATION: In this study, a Chinese girl who has suffered from congenital absence of nose and microphthalmia was enrolled and subsequently submitted to a comprehensive clinical and genetic evaluation. Whole-exome sequencing (WES) was employed to identify the genetic entity of thisgirl. A heterozygous pathogenic variant, NM_015295, c.1025G > C; p. (Trp342Ser) of SMCHD1 was identified. By performing very detailed physical and genetic examinations, the patient was diagnosed as BAMS. CONCLUSION: This report is the first description of a variant in SMCHD1 in a Chinese patient affected with BAMS.Our study not only furnished valuable genetic data for counseling of BAMS, but also confirmed the diagnosis of BAMS, which may help the management and prognosis for this patient.

Identification of a novel MYO1D variant associated with laterality defects, congenital heart diseases, and sperm defects in humans.

The establishment of left-right asymmetry is a fundamental process in animal development. Interference with this process leads to a range of disorders collectively known as laterality defects, which manifest as abnormal arrangements of visceral organs. Among patients with laterality defects, congenital heart diseases (CHD) are prevalent. Through multiple model organisms, extant research has established that myosin-Id (MYO1D) deficiency causes laterality defects. This study investigated over a hundred cases and identified a novel biallelic variant of MYO1D (NM_015194: c.1531G>A; p.D511N) in a consanguineous family with complex CHD and laterality defects. Further examination of the proband revealed asthenoteratozoospermia and shortened sperm. Afterward, the effects of the D511N variant and another known MYO1D variant (NM_015194: c.2293C>T; p.P765S) were assessed. The assessment showed that both enhance the interaction with ß-actin and SPAG6. Overall, this study revealed the genetic heterogeneity of this rare disease and found that MYO1D variants are correlated with laterality defects and CHD in humans. Furthermore, this research established a connection between sperm defects and MYO1D variants. It offers guidance for exploring infertility and reproductive health concerns. The findings provide a critical basis for advancing personalized medicine and genetic counseling.

Gasdermin E promotes translocation of p65 and c-jun into nucleus in keratinocytes for progression of psoriatic skin inflammation.

Gasdermin E (GSDME) has recently been identified as a critical executioner to mediate pyroptosis. While epidermal keratinocytes can initiate GSDME-mediated pyroptosis, the role of keratinocyte GSDME in psoriatic dermatitis remains poorly characterized. Through analysis of GEO datasets, we found elevated GSDME levels in psoriatic lesional skin. Additionally, GSDME levels correlated with both psoriasis severity and response to biologics treatments. Single-cell RNA sequencing (scRNA-seq) from a GEO dataset revealed GSDME upregulation in keratinocytes of psoriasis patients. In the imiquimod (IMQ)-induced psoriasis-like dermatitis mouse model, both full-length and cleaved forms of caspase-3 and GSDME were elevated in the epidermis. Abnormal proliferation and differentiation of keratinocytes and dermatitis were attenuated in Gsdme-/- mice and keratinocyte-specific Gsdme conditional knockout mice after IMQ stimulation. Exposure of keratinocytes to mixed cytokines (M5), mimicking psoriatic conditions, led to GSDME cleavage. Moreover, the interaction between GSDME-FL and p65 or c-jun was significantly increased after M5 stimulation. GSDME knockdown inhibited nuclear translocation of p65 and c-jun and decreased upregulation of psoriatic inflammatory mediators such as IL1ß, CCL20, CXCL1, CXCL8, S100A8, and S100A9 in M5-challenged keratinocytes. In conclusion, GSDME in keratinocytes contributes to the pathogenesis and progression of psoriasis, potentially in a pyroptosis-independent manner by interacting and promoting translocation of p65 and c-jun. These findings suggest that keratinocyte GSDME could serve as a potential therapeutic target for psoriasis treatment.

hnRNPA2B1 represses the disassembly of arsenite-induced stress granules and is essential for male fertility.

Although the composition and assembly of stress granules (SGs) are well understood, the molecular mechanisms underlying SG disassembly remain unclear. Here, we identify that heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) is associated with SGs and that its absence specifically enhances the disassembly of arsenite-induced SGs depending on the ubiquitination-proteasome system but not the autophagy pathway. hnRNPA2B1 interacts with many core SG proteins, including G3BP1, G3BP2, USP10, and Caprin-1; USP10 can deubiquitinate G3BP1; and hnRNPA2B1 depletion attenuates the G3BP1-USP10/Caprin-1 interaction but elevates the G3BP1 ubiquitination level under arsenite treatment. Moreover, the disease-causing mutation FUSR521C also disassembles faster from SGs in HNRNPA2B1 mutant cells. Furthermore, knockout of hnRNPA2B1 in mice leads to Sertoli cell-only syndrome (SCOS), causing complete male infertility. Consistent with this, arsenite-induced SGs disassemble faster in Hnrnpa2b1 knockout (KO) mouse Sertoli cells as well. These findings reveal the essential roles of hnRNPA2B1 in regulating SG disassembly and male mouse fertility.

METTL14 affects UVB-induced human dermal fibroblasts photoaging via miR-100-3p biogenesis in an m6A-dependent manner.

Exposure to ultraviolet radiation can lead to skin photoaging, which increases the risk of skin tumors. This study aims to investigate how microRNA m6A modification contributes to skin photoaging. This study found that skin fibroblasts exposed to a single UVB dose of 30 mJ/cm2 exhibited characteristics of photoaging. The m6A level of total RNA decreased in photoaged cells with a down-regulated level of METTL14, and overexpression of METTL14 displayed a photoprotective function. Moreover, miR-100-3p was a downstream target of METTL14. And METTL14 could affect pri-miR-100 processing to mature miR-100-3p in an m6A-dependent manner via DGCR8. Furthermore, miR-100-3p targeted at 3' end untranslated region of ERRFI1 mRNA with an inhibitory effect on translation. Additionally, photoprotective effects of overexpression of METTL14 were reversed by miR-100-3p inhibitor or overexpression of ERRFI1. In UVB-induced photoaging of human skin fibroblasts, METTL14-dependent m6A can regulate miR-100-3p maturation via DGCR8 and affect skin fibroblasts photoaging through miR-100-3p/ERRFI1 axis.

Integration of hydrothermal liquefaction of Cyanophyta and supercritical water oxidation of its aqueous phase products: Biocrude production and nutrient removal.

Cyanophyta has the potential to produce biocrude via hydrothermal liquefaction (HTL). However, aqueous phase products (APs), as by-products of HTL, pose a risk of eutrophication for the high levels of carbon, nitrogen, and phosphorus. Supercritical water oxidation (SCWO) can efficiently convert organics into small molecules, offering a technique for the harmless treatment of APs. Effects of holding time, pressure, and moisture content on the biocrude yields from isothermal HTL (300 °C) and fast HTL (salt bath temperature of 500 °C) were comprehensively investigated. Biocrude properties were characterized by elemental analysis, FT-IR and GC-MS. Subsequently, the APs obtained under the conditions producing the highest biocrude yield were subjected to SCWO at 550 °C with different oxidation coefficients (n) from 0 to 2. Removal rates of chemical oxygen demand (COD), ammonia nitrogen (NH3-N), and total phosphorus (TP) were further explored. The results show that the highest biocrude yields from isothermal HTL and fast HTL were 24.2 wt% (300 °C, 1800 s, 25 MPa, and 80 wt% moisture content) and 21.9 wt% (500 °C, 40 s, 25 MPa, and 80 wt% moisture content), respectively. The biocrude primarily consisted of N-containing heterocyclic compounds, amides, and acids. SCWO effectively degraded the COD and TP in APs, while the NH3-N required further degradation. At n = 2, the highest removal rates of COD, NH3-N and TP were 98.5 %, 22.6 % and 89.1 %, respectively.

Association between single nucleotide polymorphisms, TGF-ß1 promoter methylation, and polycystic ovary syndrome.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is a common endocrine and metabolic disease in women. Hyperandrogenaemia (HA) and insulin resistance (IR) are the basic pathophysiological characteristics of PCOS. The aetiology of PCOS has not been fully identified and is generally believed to be related to the combined effects of genetic, metabolic, internal, and external factors. Current studies have not screened for PCOS susceptibility genes in a large population. Here, we aimed to study the effect of TGF-ß1 methylation on the clinical PCOS phenotype. METHODS: In this study, three generations of family members with PCOS with IR as the main characteristic were selected as research subjects. Through whole exome sequencing and bioinformatic analysis, TGF-ß1 was screened as the PCOS susceptibility gene in this family. The epigenetic DNA methylation level of TGF-ß1 in peripheral blood was detected by heavy sulfite sequencing in patients with PCOS clinically characterised by IR, and the correlation between the DNA methylation level of the TGF-ß1 gene and IR was analysed. We explored whether the degree of methylation of this gene affects IR and whether it participates in the occurrence and development of PCOS. RESULTS: The results of this study suggest that the hypomethylation of the CpG4 and CpG7 sites in the TGF-ß1 gene promoter may be involved in the pathogenesis of PCOS IR by affecting the expression of the TGF-ß1 gene. CONCLUSIONS: This study provides new insights into the aetiology and pathogenesis of PCOS.

Vitamin B12 is associated negatively with anemia in older Chinese adults with a low dietary diversity level: evidence from the Healthy Ageing and Biomarkers Cohort Study (HABCS).

OBJECTIVE: The associations between plasma vitamin B12 level and anemia under different dietary patterns in elderly Chinese people are poorly understood. We aimed to examine the associations between plasma vitamin B12 levels and anemia under different dietary patterns in adults aged 65 years and older in nine longevity areas in China. METHODS: A total of 2405 older adults completed a food frequency questionnaire at the same time as a face-to-face interview. The dietary diversity score (DDS) was assessed based on the food frequency questionnaire, with the low DDS group referring to participants with a DDS score ≤ 4 points. Vitamin B12 levels were divided into two groups of high (>295 pg/mL) and low (≤ 295 pg/mL) with the median used as the cut-off point. Sub-analyses were also performed on older adults divided into tertiles of vitamin B12 levels: low (< 277 pg/mL), medium (277-375 pg/mL) and high (> 375 pg/mL) to study the association of these levels with anemia. RESULTS: Six hundred ninety-five (28.89%) of these people were diagnosed with anemia and had a mean age of 89.3 years. Higher vitamin B12 levels were associated with a decreased risk of anemia (multi-adjusted OR, 0.59, [95% CI, 0.45 ~ 0.77] P < 0.001) in older adults with a low DDS, whereas no significant association between vitamin B12 levels and anemia was found in older adults with a high DDS in a full-model after adjustment for various confounding factors (multi-adjusted OR, 0.88, [95% CI, 0.65 ~ 1.19], P = 0.41). CONCLUSION: The relationship between vitamin B12 levels and the prevalence of anemia was significant only when the level of dietary diversity in the older adults was relatively low. The dietary structure of the population should be taken into consideration in combination in order to effectively improve anemia status by supplementing vitamin B12.

Dopamine in the prefrontal cortex plays multiple roles in the executive function of patients with Parkinson's disease.

Parkinson's disease can affect not only motor functions but also cognitive abilities, leading to cognitive impairment. One common issue in Parkinson's disease with cognitive dysfunction is the difficulty in executive functioning. Executive functions help us plan, organize, and control our actions based on our goals. The brain area responsible for executive functions is called the prefrontal cortex. It acts as the command center for the brain, especially when it comes to regulating executive functions. The role of the prefrontal cortex in cognitive processes is influenced by a chemical messenger called dopamine. However, little is known about how dopamine affects the cognitive functions of patients with Parkinson's disease. In this article, the authors review the latest research on this topic. They start by looking at how the dopaminergic system, is altered in Parkinson's disease with executive dysfunction. Then, they explore how these changes in dopamine impact the synaptic structure, electrical activity, and connection components of the prefrontal cortex. The authors also summarize the relationship between Parkinson's disease and dopamine-related cognitive issues. This information may offer valuable insights and directions for further research and improvement in the clinical treatment of cognitive impairment in Parkinson's disease.

Temporal segmentation of EEG based on functional connectivity network structure.

In the study of brain functional connectivity networks, it is assumed that a network is built from a data window in which activity is stationary. However, brain activity is non-stationary over sufficiently large time periods. Addressing the analysis electroencephalograph (EEG) data, we propose a data segmentation method based on functional connectivity network structure. The goal of segmentation is to ensure that within a window of analysis, there is similar network structure. We designed an intuitive and flexible graph distance measure to quantify the difference in network structure between two analysis windows. This measure is modular: a variety of node importance indices can be plugged into it. We use a reference window versus sliding window comparison approach to detect changes, as indicated by outliers in the distribution of graph distance values. Performance of our segmentation method was tested in simulated EEG data and real EEG data from a drone piloting experiment (using correlation or phase-locking value as the functional connectivity strength metric). We compared our method under various node importance measures and against matrix-based dissimilarity metrics that use singular value decomposition on the connectivity matrix. The results show the graph distance approach worked better than matrix-based approaches; graph distance based on partial node centrality was most sensitive to network structural changes, especially when connectivity matrix values change little. The proposed method provides EEG data segmentation tailored for detecting changes in terms of functional connectivity networks. Our study provides a new perspective on EEG segmentation, one that is based on functional connectivity network structure differences.

[Liver targeting of compound liposomes mediated by glycyrrhetinic acid derivative receptor and its effect on hepatic stellate cells].

The 3-succinate-30-stearyl glycyrrhetinic acid(18-GA-Suc) was inserted into glycyrrhetinic acid(GA)-tanshinone Ⅱ_A(TSN)-salvianolic acid B(Sal B) liposome(GTS-lip) to prepare liver targeting compound liposome(Suc-GTS-lip) mediated by GA receptors. Next, pharmacokinetics and tissue distribution of Suc-GTS-lip and GTS-lip were compared by UPLC, and in vivo imaging tracking of Suc-GTS-lip was conducted. The authors investigated the effect of Suc-GTS-lip on the proliferation inhibition of hepatic stellate cells(HSC) and explored their molecular mechanism of improving liver fibrosis. Pharmacokinetic results showed that the AUC_(Sal B) decreased from(636.06±27.73) µg·h·mL~(-1) to(550.39±12.34) µg·h·mL~(-1), and the AUC_(TSN) decreased from(1.08±0.72) µg·h·mL~(-1) to(0.65±0.04) µg·h·mL~(-1), but the AUC_(GA) increased from(43.64±3.10) µg·h·mL~(-1) to(96.21±3.75) µg·h·mL~(-1). The results of tissue distribution showed that the AUC_(Sal B) and C_(max) of Sal B in the liver of the Suc-GTS-lip group were 10.21 and 4.44 times those of the GTS-lip group, respectively. The liver targeting efficiency of Sal B, TSN, and GA in the Suc-GTS-lip group was 40.66%, 3.06%, and 22.08%, respectively. In vivo imaging studies showed that the modified liposomes tended to accumulate in the liver. MTT results showed that Suc-GTS-lip could significantly inhibit the proliferation of HSC, and RT-PCR results showed that the expression of MMP-1 was significantly increased in all groups, but that of TIMP-1 and TIMP-2 was significantly decreased. The mRNA expressions of collagen-I and collagen-Ⅲ were significantly decreased in all groups. The experimental results showed that Suc-GTS-lip had liver targeting, and it could inhibit the proliferation of HSC and induce their apoptosis, which provided the experimental basis for the targeted treatment of liver fibrosis by Suc-GTS-lip.

Ultra-high static magnetic fields cause immunosuppression through disrupting B-cell peripheral differentiation and negatively regulating BCR signaling.

To increase the imaging resolution and detection capability, the field strength of static magnetic fields (SMFs) in magnetic resonance imaging (MRI) has significantly increased in the past few decades. However, research on the side effects of high magnetic field is still very inadequate and the effects of SMF above 1 T (Tesla) on B cells have never been reported. Here, we show that 33.0 T ultra-high SMF exposure causes immunosuppression and disrupts B cell differentiation and signaling. 33.0 T SMF treatment resulted in disturbance of B cell peripheral differentiation and antibody secretion and reduced the expression of IgM on B cell membrane, and these might be intensity dependent. In addition, mice exposed to 33.0 T SMF showed inhibition on early activation of B cells, including B cell spreading, B cell receptor clustering and signalosome recruitment, and depression of both positive and negative molecules in the proximal BCR signaling, as well as impaired actin reorganization. Sequencing and gene enrichment analysis showed that SMF stimulation also affects splenic B cells' transcriptome and metabolic pathways. Therefore, in the clinical application of MRI, we should consider the influence of SMF on the immune system and choose the optimal intensity for treatment.

Four-Dimensional Micro/Nanorobots via Laser Photochemical Synthesis towards the Molecular Scale.

Miniaturized four-dimensional (4D) micro/nanorobots denote a forerunning technique associated with interdisciplinary applications, such as in embeddable labs-on-chip, metamaterials, tissue engineering, cell manipulation, and tiny robotics. With emerging smart interactive materials, static micro/nanoscale architectures have upgraded to the fourth dimension, evincing time-dependent shape/property mutation. Molecular-level 4D robotics promises complex sensing, self-adaption, transformation, and responsiveness to stimuli for highly valued functionalities. To precisely control 4D behaviors, current-laser-induced photochemical additive manufacturing, such as digital light projection, stereolithography, and two-photon polymerization, is pursuing high-freeform shape-reconfigurable capacities and high-resolution spatiotemporal programming strategies, which challenge multi-field sciences while offering new opportunities. Herein, this review summarizes the recent development of micro/nano 4D laser photochemical manufacturing, incorporating active materials and shape-programming strategies to provide an envisioning of these miniaturized 4D micro/nanorobots. A comparison with other chemical/physical fabricated micro/nanorobots further explains the advantages and potential usage of laser-synthesized micro/nanorobots.

Construction of α-Halogenated Boronic Esters via Visible Light-Induced C-H Bromination.

α-Halogenated boronic esters are versatile building blocks that can be diversified into a wide variety of polyfunctionalized molecules. However, their synthetic potential has been hampered by limited preparation methods. Herein, we report a visible light-induced C-H bromination reaction of readily available benzyl boronic esters. This method features high yields, mild conditions, simple operation, and good functional group tolerance. The analogous chlorides and iodides can be accessed via Finkelstein reaction. Synthesis of halogenated geminal diborons has also been demonstrated.

Gasdermin D-mediated keratinocyte pyroptosis as a key step in psoriasis pathogenesis.

Gasdermin D (GSDMD)-mediated pyroptosis has a significant pro-inflammation characteristic due to dramatic secretion of pro-inflammatory substances. However, its role remains unclear in psoriasis as one chronic inflammatory skin disorder with high prevalence. We found that N-terminal GSDMD (N-GSDMD) was aberrantly expressed in epidermis of skin lesion in psoriasis patients and imiquimod-induced psoriasis-like dermatitis (IIPLD) mice. In epidermis of IIPLD mice and M5 (simulating psoriatic inflammatory challenge)-treated keratinocytes cultured in vitro, cleavage products of caspase-1, GSDMD and IL-1ß were increased. M5-stimulated keratinocyte presented typical pyroptosis morphology accompanied with PI-staining. Gsdmd-/- keratinocytes could not present pyroptosis morphology while stimulated with M5. Electroporation of recombinant N-GSDMD could make the pyroptosis morphology reappear. In Gsdmd-/- mice or keratinocyte-specific Gsdmd conditional knockout mice, we observed the alleviation of psoriatic inflammation and epidermal aberrant expression of Ki-67 and differentiation markers (loricrin and keratin 5) after imiquimod stimulation. Transplanting skin tissue from control mice to Gsdmd-/- mice can evoke the response to imiquimod stimulation in the background of Gsdmd-/- mice (not limited in transplanting area). In M5-stimulated keratinocytes, disulfiram or GSDMD siRNA transfection can inhibit pyroptosis and eliminate disproportionate increases of Ki-67 and PI. We further validated that topically application of disulfiram (pyroptosis inhibitor) also alleviated IIPLD in mice. These findings indicate a novel mechanism that GSDMD-mediated keratinocyte pyroptosis facilitates hyperproliferation and aberrant differentiation induced by immune microenvironment in psoriatic skin inflammation, which contributes to pathogenesis of psoriasis. Our study provides an innovative insight that targeting pyroptosis can be considered as a therapeutic strategy against psoriasis.

Exploring EEG characteristics of multi-level mental stress based on human-machine system.

Objective.The understanding of cognitive states is important for the development of human-machine systems (HMSs), and one of the fundamental but challenging issues is the understanding and assessment of the operator's mental stress state in real task scenarios.Approach.In this paper, a virtual unmanned vehicle (UAV) driving task with multi-challenge-level was created to explore the operator's mental stress, and the human brain activity during the task was tracked in real time via electroencephalography (EEG). A mental stress analysis dataset for the virtual UAV task was then developed and used to explore the neural activation patterns associated with mental stress activity. Finally, a multiple attention-based convolutional neural network (MACN) was constructed for automatic stress assessment using the extracted stress-sensitive neural activation features.Main Results.The statistical results of EEG power spectral density (PSD) showed that frontal theta-PSD decreased with increasing task difficulty, and central beta-PSD increased with increasing task difficulty, indicating that neural patterns showed different trends under different levels of mental stress. The performance of the proposed MACN was evaluated based on the dimensional model, and results showed that average three-class classification accuracies of 89.49%/89.88% were respectively achieved for arousal/valence.Significance.The results of this paper suggest that objective assessment of mental stress in a HMS based on a virtual UAV scenario is feasible, and the proposed method provides a promising solution for cognitive computing and applications in human-machine tasks.

GSDMA3 deficiency reprograms cellular metabolism and modulates BCR signaling in murine B cells.

Metabolism plays a crucial role in B cell differentiation and function. GSDMA3 is related to mitochondrial metabolism and is involved in immune responses. Here, we used Gsdma3 KO mice to examine the effect of GSDMA3 on B cells. The results demonstrated that GSDMA3 deficiency reprogrammed B cell metabolism, evidenced by upregulating PI3K-Akt-mTOR signaling, along with elevated ROS reproduction and reduced maximal oxygen consumption rate in mitochondria. Moreover, the BCR signaling in the KO B cells was impaired. The reduced BCR signaling was associated with decreased BCR clustering, caused by inhibited activation of WASP. However, GSDMA3 deficiency had no effects on B cell development and functions in humoral immunity, which might be associated with the compensation of upregulated GSDMA2 expression and the fine balance between PI3K signaling and BCR signals interaction. Our observations reveal a previously unknown influence of GSDMA3 on B cells under physiological and immunized states.

A Systematic Review and Meta-Analysis of Interventions to Promote Adjuvant Endocrine Therapy Adherence Among Breast Cancer Survivors.

PURPOSE: Adjuvant endocrine therapy (AET) adherence among breast cancer survivors is often suboptimal, leading to higher cancer recurrence and mortality. Intervention studies to promote AET adherence have burgeoned, more than doubling in number since this literature was last reviewed. The current aim is to provide an up-to-date systematic review and meta-analysis of interventions to enhance AET adherence and to identify strengths and limitations of existing interventions to inform future research and clinical care. METHODS: Systematic searches were conducted in three electronic databases. Studies were included in the systematic review if they examined an intervention for promoting AET adherence among breast cancer survivors. Studies were further included in the meta-analyses if they examined a measure of AET adherence (defined as compliance or persistence beyond initiation) and reported (or provided upon request) sufficient information to calculate an effect size. RESULTS: Of 5,045 unique records, 33 unique studies representing 375,951 women met inclusion criteria for the systematic review. Interventions that educated patients about how to manage side effects generally failed to improve AET adherence, whereas policy changes that lowered AET costs consistently improved adherence. Medication reminders, communication, and psychological/coping strategies showed varied efficacy. Of the 33 studies that met the inclusion criteria for the systematic review, 25 studies representing 367,873 women met inclusion criteria for the meta-analysis. The meta-analysis showed statistically significant effects of the adherence interventions overall relative to study-specified control conditions (number of studies [k] = 25; odds ratio, 1.412; 95% CI, 1.183 to 1.682; P = .0001). Subgroup analyses showed that there were no statistically significant differences in effect sizes by study design (randomized controlled trial v other), publication year, directionality of the intervention (unidirectional v bidirectional contact), or intervention type. CONCLUSION: To our knowledge, this is the first known meta-analysis to demonstrate a significant effect for interventions to promote AET adherence. The systematic review revealed that lowering medication costs and a subgroup of psychosocial and reminder interventions showed the most promise, informing future research, policy, and clinical directions.

Effect of longitudinal-bending elliptical ultrasonic vibration assistance on electrosurgical cutting and hemostasis.

Electrosurgical devices are widely used for tissue cutting and hemostasis in minimally invasive surgery (MIS) for their high precision and low trauma. However, tissue adhesion and the resulting thermal injury can cause infection and impede the wound-healing process. This paper proposes a longitudinal-bending elliptical ultrasonic vibration-assisted (EUV-A) electrosurgical cutting system that incorporates an ultrasonic vibration in the direction of the cut by introducing an elliptical motion of the surgical tip. Compared with a solely longitudinal ultrasonic vibration-assisted (UV-A) electrosurgical device, the EUV-A electrode contacts the tissue intermittently, thus allowing for a cooler cut and preventing tissue accumulation. The experimental results reveal that the EUV-A electrode demonstrates better performance than the UV-A electrode for both anti-adhesion and thermal injury through in vitro experiments in porcine samples. The tissue removal mechanism of EUV-A electrosurgical cutting is modeled to investigate its anti-adhesion effect. In addition, lower adhesion, lower temperature, and faster cutting are demonstrated through in vivo experiments in rabbit samples. Results show that the EUV-A electrode causes lower thermal injury, indicative of faster postoperative healing. Finally, efficacy of the hemostatic effect of the EUV-A electrode is demonstrated in vivo for vessels up to 3.5 mm (equivalent to that of electrocautery). The study reveals that the EUV-A electrosurgical cutting system can achieve safe tissue incision and hemostasis.