SLC25A17 inhibits autophagy to promote triple-negative breast cancer tumorigenesis by ROS-mediated JAK2/STAT3 signaling pathway.

BACKGROUND: SLC25A17, a peroxisomal solute carrier, has been implicated in various physiological and pathological processes. However, its precise roles and underlying mechanisms in triple-negative breast cancer (TNBC) remain incompletely understood. METHODS: The expression and survival data of breast cancer were derived from TCGA and GEO databases. A variety of in vitro assays were conducted, including proliferation, apoptosis, cell cycle, migration, and invasion. Reactive oxygen species (ROS) were measured by immunofluorescence microscopy and flow cytometry. The levels of autophagy were assessed by mRFP-GFP-LC3 confocal microscopy scanning, western blotting, and electron microscopy. RESULTS: SLC25A17 was highly expressed in breast cancer tissues, which was found to be associated with unfavorable prognosis. Functional assays demonstrated that SLC25A17 knockdown suppressed proliferation, epithelial-mesenchymal transition (EMT), migration, and invasion. Moreover, it prompted apoptosis and autophagy. On the other hand, SLC25A17 knockdown promoted autophagy through triggering ROS accumulation, which was counteracted by N-acetyl-l-cysteine (NAC). Furthermore, the pro-apoptotic effect of SLC25A17 knockdown was reversed when treated with autophagy inhibitor 3-MA in TNBC cells, suggesting that SLC25A17 knockdown-induced autophagic cell death. Mechanistically, SLC25A17 performed its function through regulation JAK2/STAT3 signaling in TNBC. In a nude mice xenograft study, SLC25A17 knockdown markedly decreased breast tumor growth and metastasis. CONCLUSION: SLC25A17 up-regulation may be a critical factor driving TNBC progression by modulating ROS production and autophagy. Consequently, targeting SLC25A17 could be an effective therapeutic strategy against TNBC.

Total duration of spontaneous blastocyst collapse during the expansion stage is an independent predictor of euploidy and live birth rates.

RESEARCH QUESTION: Is the total duration of spontaneous blastocyst collapse to re-expansion before biopsy related to ploidy and live birth rates after single euploid blastocyst transfer? DESIGN: This was a retrospective cohort study of 600 preimplantation genetic testing cycles for aneuploidy (PGT-A) cycles, involving 2203 biopsied blastocysts, at a large reproductive medicine centre. Features of spontaneous blastocyst collapse from full to expanded stage, before biopsy, were observed using an embryoscope viewer for embryos cultured in a time-lapse incubator. In total, 568 cycles of frozen blastocyst transfers, either single euploid or mosaic, were performed. Correlations between collapse features and PGT-A outcomes were evaluated, as well as live birth rate, following euploid embryo transfer. RESULTS: Blastocysts with lower morphological quality or delayed development had significantly higher rates of collapse, multiple collapses, and a longer duration of collapse to re-expansion. After controlling for confounders, such as oocyte age, morphological quality of blastocyst, and day of biopsy, multivariate logistic regression revealed that the total duration of collapse to re-expansion was an independent predictor of lower euploidy rate; the multivariate OR was 0.85 (95% CI 0.77-0.95; P = 0.00). Furthermore, even with euploid embryo transfer, the probability of a live birth decreased as the total duration of collapse to re-expansion increased; the multivariate OR was 0.79 (95% CI 0.64-0.98; P = 0.033). CONCLUSION: The total duration of blastocyst collapse to re-expansion could be used as a predictor of lower euploidy and live birth rate. When developing blastocyst algorithms for pregnancy prediction, the duration of spontaneous blastocyst collapse should be included as a significant variable.

Series of Viologen-Based Metal-Organic Polyhedra with Photo/Electrochromic Behavior for Inkless Printing and UV Detection.

The fabrication of molecular crystalline materials with fast, multistimuli-responsive behavior and the construction of the corresponding structure-activity relationship are of extraordinary significance for the development of smart materials. In this context, three multistimuli-responsive functional metal-organic polyhedra (MOP), {[Dy2(bcbp)3(NO3)1.5(H2O)7]·Cl4.2·(NO3)0.3·H2O}n (1), {[Dy2(bcbp)4(H2O)8]Cl6}n (2), and {[Eu2(bcbp)4(H2O)10]Cl6·H2O}n (3; bcbp = 1,1'-bis(4-carboxyphenyl)-4,4'-bipyridinium), were successfully prepared and characterized. All of the compounds exhibit rapid and reversible photochromic and electrochromic dual-responsive behaviors. Furthermore, benefiting from the well-defined crystal structure and different responsive behaviors, the photoinduced electron transfer (PIET) process and structure-activity relationship were explored. In addition, considering the excellent photochromic performance, function filter paper and smart organic glass were successfully prepared and used for ink-free printing and UV light detection.

Observations on the Therapeutic Efficacy of Biomimetic Physiotherapy Combined with Manipulation Therapy in Managing Myofascial Pelvic Pain Syndrome in Women.

Objective: This study aims to investigate the clinical efficacy of biomimetic physiotherapy combined with manipulation therapy in the management of female myofascial pelvic pain syndrome (MPPS). Methods: A total of 120 patients diagnosed with MPPS at our hospital from June 2018 to June 2021 were included. All patients had a history of sexual activity, met the diagnostic criteria for female chronic pelvic pain, and exhibited pelvic floor muscle and myofascial trigger points in gynecological examinations. Based on treatment methods, patients were categorized into a control group (n=64, treated with biomimetic physiotherapy) and an experimental group (n=56, treated with biomimetic physiotherapy plus manipulation therapy). Pre- and post-treatment assessments in both groups included pelvic floor muscle surface electromyogram, Visual Analogue Scale (VAS) score, pelvic floor muscle tenderness score, and pelvic floor muscle strength. Results: After treatment, in the control group, the mean values of pre-resting potential and post-resting potential declined significantly, from (9.58±2.22) to (4.06±0.77) and from (8.18±1.78) to (3.56±0.61), respectively. In the experimental group, these values decreased from (9.61±2.77) to (3.15±0.58), and from (8.16±1.78) to (2.79±0.59). The VAS score exhibited a noteworthy decrease from (6.18±1.00) to (3.15±0.56) in the control group and from (6.20±1.13) to (2.04±0.68) in the experimental group. The pelvic floor muscle tenderness score decreased from (8.14±0.86) to (3.78±0.77) in the control group and from (7.91±1.03) to (1.93±0.80) in the experimental group. Furthermore, the percentage of patients whose pelvic floor muscle strength increased from

Kinase Inhibitors and Kinase-Targeted Cancer Therapies: Recent Advances and Future Perspectives.

Over 120 small-molecule kinase inhibitors (SMKIs) have been approved worldwide for treating various diseases, with nearly 70 FDA approvals specifically for cancer treatment, focusing on targets like the epidermal growth factor receptor (EGFR) family. Kinase-targeted strategies encompass monoclonal antibodies and their derivatives, such as nanobodies and peptides, along with innovative approaches like the use of kinase degraders and protein kinase interaction inhibitors, which have recently demonstrated clinical progress and potential in overcoming resistance. Nevertheless, kinase-targeted strategies encounter significant hurdles, including drug resistance, which greatly impacts the clinical benefits for cancer patients, as well as concerning toxicity when combined with immunotherapy, which restricts the full utilization of current treatment modalities. Despite these challenges, the development of kinase inhibitors remains highly promising. The extensively studied tyrosine kinase family has 70% of its targets in various stages of development, while 30% of the kinase family remains inadequately explored. Computational technologies play a vital role in accelerating the development of novel kinase inhibitors and repurposing existing drugs. Recent FDA-approved SMKIs underscore the importance of blood-brain barrier permeability for long-term patient benefits. This review provides a comprehensive summary of recent FDA-approved SMKIs based on their mechanisms of action and targets. We summarize the latest developments in potential new targets and explore emerging kinase inhibition strategies from a clinical perspective. Lastly, we outline current obstacles and future prospects in kinase inhibition.

The Key Role of Plant Hormone Signaling Transduction and Flavonoid Biosynthesis Pathways in the Response of Chinese Pine (Pinus tabuliformis) to Feeding Stimulation by Pine Caterpillar (Dendrolimus tabulaeformis).

In nature, plants have developed a series of resistance mechanisms to face various external stresses. As understanding of the molecular mechanisms underlying plant resistance continues to deepen, exploring endogenous resistance in plants has become a hot topic in this field. Despite the multitude of studies on plant-induced resistance, how plants respond to stress under natural conditions remains relatively unclear. To address this gap, we investigated Chinese pine (Pinus tabuliformis) using pine caterpillar (Dendrolimus tabulaeformis) under natural conditions. Healthy Chinese pine trees, approximately 10 years old, were selected for studying induced resistance in Huangtuliangzi Forestry, Pingquan City, Chengde City, Hebei Province, China. Pine needles were collected at 2 h and 8 h after feeding stimulation (FS) via 10 pine caterpillars and leaf clipping control (LCC), to simulate mechanical damage caused by insect chewing for the quantification of plant hormones and transcriptome and metabolome assays. The results show that the different modes of treatments significantly influence the contents of JA and SA in time following treatment. Three types of differentially accumulated metabolites (DAMs) were found to be involved in the initial response, namely phenolic acids, lipids, and flavonoids. Weighted gene co-expression network analysis indicated that 722 differentially expressed genes (DEGs) are positively related to feeding stimulation and the specific enriched pathways are plant hormone signal transduction and flavonoid biosynthesis, among others. Two TIFY transcription factors (PtTIFY54 and PtTIFY22) and a MYB transcription factor (PtMYB26) were found to be involved in the interaction between plant hormones, mainly in the context of JA signal transduction and flavonoid biosynthesis. The results of this study provide an insight into how JA activates, serving as a reference for understanding the molecular mechanisms of resistance formation in conifers responding to mandibulate insects.

Effects of Oxygen Therapy on Patients with a Chronic Wound: A Systematic Review and Meta-analysis.

OBJECTIVE: To synthesize the effects of oxygen-based therapy on patients with a chronic wound. DATA SOURCES: The authors searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials for relevant randomized controlled trials from database inception. Investigators measured risk of bias using the Cochrane Collaboration's Risk of Bias tool. STUDY SELECTION: The included randomized controlled trials focused on the effects (short- or long-term wound healing, amputation rate, percentage of reduction in ulcer size, and poststudy transcutaneous oxygen measurement [TcPO2]) of oxygen-based therapy (including hyperbaric oxygen therapy, topical oxygen therapy, and continuous diffusion of oxygen) on patients with a chronic wound. DATA EXTRACTION: Researchers extracted information regarding participant characteristics and primary and secondary outcomes from the included studies. DATA SYNTHESIS: Pooled effects of 31 included studies showed that patients treated with oxygen had better short-term wound healing (risk ratio [RR], 1.544; 95% CI, 1.199 to 1.987), a higher percentage reduction in the ulcer area (standardized mean difference [SMD], 0.999; 95% CI, 0.439 to 1. 599), lower amputation rates (RR, 0.529; 95% CI, 0.325 to 0.862), shorter wound healing time (SMD, -0.705; 95% CI, -0.908 to -0.501), and higher poststudy TcPO2 (SMD, 2.128; 95% CI, 0.978 to 3.278) than those in the control group. For long-term wound healing, there was no statistically significant difference (RR, 1.227; 95% CI, 0.976 to 1.542). CONCLUSIONS: Oxygen-based therapy improves short-term parameters of wound healing in patients with chronic wounds.

A national survey of iodine nutrition in children aged 3-6 years in China and its relationship with children's physical growth.

Iodine, an essential trace element for the human body, plays a pivotal role in sustaining health. Malnutrition has emerged as a pressing public health concern, posing a significant threat to human well-being. Iodine deficiency poses a substantial threat to the development of children, potentially leading to neurological developmental disorders and mental retardation. Conversely, excessive iodine intake can result in structural and functional abnormalities in the thyroid gland. In this study, we selected children aged 3-6 years through a stratified cluster sampling approach in six regions across China to explore the correlation between iodine nutrition and their physical growth. A total of 5920 preschool children participated in this study, with a median urinary iodine concentration (UIC) of 177.33 [107.06, 269.92] µg/L. Among these children, 250 (4.2%) exhibited stunting, 180 (3.0%) were underweight, 198 (3.3%) experienced wasting, 787 (3.3%) were overweight and 414 (7.0%) were classified as obese. The multivariate linear regression revealed that UIC exhibited a positive correlation with body mass index z-Score (BMIZ) in overweight children (ß = 0.038; 95% CI: 0.001, 0.075). In normally growing children, the associations between UIC and height-for-age z-score, weight-for-age z-score and BMIZ displayed nonlinear patterns. Our findings suggest that iodine nutrition is adequate for Chinese children aged 3-6 years. Furthermore, iodine nutrition is intricately linked to the growth and development of these children. Consequently, it is imperative to implement decisive measures to prevent both iodine deficiency and excess.

Effect of fly ash and curing temperature on the properties of magnesium phosphate repair mortar.

This article is aimed at discussing the combined effect of mineral admixture and servicing temperature, especially in cold environment, on the properties of magnesium phosphate repair mortar (MPM). The influence mechanism of fly ash content on the microstructure and performance of MPM were firstly investigated, and then the evolution rules in properties of fly ash modified MPM cured at - 20 °C, 0 °C, 20 °C and 40 °C were further revealed. The results show that the incorporation of fly ash has no significant effect on the setting time and fluidity of MPM. When MPM is modified with 10 wt% and 15 wt% fly ash, its mechanical properties, adhesive strength, water resistance, and volume stability are effectively improved. Fly ash reduces the crystallinity and continuity of struvite enriched in hardened MPM, and its particles are embedded among struvite and unreacted MgO. The compressive strength of MPM-10 cured for various ages increases with the elevating of curing temperature, while the flexural strength, interfacial bonding strength, strength retention and linear shrinkage exhibits the opposite laws. When cured at 0 °C and - 20 °C, MPM-10 still has good early strength, water resistance and interfacial bonding properties, which indicates that MPM-10 provides with an ability of emergency repair of cracked components served in cold environments.

Interaction of prenatal maternal selenium and manganese levels on child neurodevelopmental trajectories-the Shanghai birth cohort study.

OBJECTIVE: The fetal brain is particularly plastic, and may be concurrently affected by chemical exposure and malnutritional factors. Selenium is essential for the developing brain, and excess manganese exposure may exert neurotoxic effects. However, few epidemiological studies have evaluated the interaction of manganese and selenium assessed in different prenatal stages on postnatal neurodevelopmental trajectories. METHODS: This study contained 1024 mother-child pairs in the Shanghai-birth-cohort study from 2013 to 2016 recruited since early/before pregnancy with complete data on manganese and selenium levels in different prenatal stages and infant neurodevelopmental trajectories. Whole blood manganese and selenium in early pregnancy and around birth were measured by inductively-coupled-plasma-mass-spectrometry (ICP-MS), children's cognitive development was evaluated at 6, 12, and 24 months of age using Age & Stage-Questionnaire (ASQ)-3 and Bayley-III. Multiple linear regression was used to investigate the interaction of prenatal selenium and manganese on neurodevelopmental trajectories. RESULTS: The prenatal manganese and selenium levels were 1.82 ± 0.98 µg/dL and 13.53 ± 2.70 µg/dL for maternal blood in early pregnancy, and 5.06 ± 1.67 µg/dL and 11.81 ± 3.35 µg/dL for umbilical cord blood, respectively. Higher prenatal Se levels were associated with better neurocognitive performances or the consistently-high-level trajectory (P < 0.05), with more significant associations observed in early pregnancy than around birth. However, such positive relationships became non-significant or even adverse in high (vs. low) manganese status, and the effect differences between low and high manganese were more significant in early pregnancy. CONCLUSIONS: Prenatal Selenium was positively associated with child neurodevelopment, but prenatal high manganese may mitigate such favorable effects. The effects were mainly observed in earlier prenatal stage.

Progress and Innovative Combination Therapies in Trop-2-Targeted ADCs.

Precise targeting has become the main direction of anti-cancer drug development. Trophoblast cell surface antigen 2 (Trop-2) is highly expressed in different solid tumors but rarely in normal tissues, rendering it an attractive target. Trop-2-targeted antibody-drug conjugates (ADCs) have displayed promising efficacy in treating diverse solid tumors, especially breast cancer and urothelial carcinoma. However, their clinical application is still limited by insufficient efficacy, excessive toxicity, and the lack of biological markers related to effectiveness. This review summarizes the clinical trials and combination therapy strategies for Trop-2-targeted ADCs, discusses the current challenges, and provides new insights for future advancements.

Collision-attachment simulation of membrane fouling by oppositely and similarly charged colloids.

The fouling propensity of oppositely charged colloids (OCC) and similarly charged colloids (SCC) on reverse osmosis (RO) and nanofiltration (NF) membranes are systematically investigated using a developed collision-attachment approach. The probability of successful colloidal attachment (i.e., attachment efficiency) is modelled by Boltzmann energy distribution, which captures the critical roles of colloid-colloid/membrane interaction and permeate drag. Our simulations highlight the important effects of ionic strength Is, colloidal size dp and initial flux J0 on combined fouling. In a moderate condition (e.g., Is =10 mM, dp=50 nm and J0= 100 L/m2h), OCC mixtures shows more severe fouling compared to the respective single foulant owing to electrostatic neutralization. In contrast, the flux loss of SCC species falls between those of the two single foulants but more closely resembles that of the single low-charged colloids due to its weak electrostatic repulsion. Increased ionic strength Is leads to less severe fouling for OCC but more severe fouling for SCC, as a result of the suppressed electrostatic attraction/repulsion. At a high Is (e.g., 3-5 M), all the single and mixed systems show the identical pseudo-stable flux Js. Small colloidal size leads to the drag-controlled condition, where severe fouling occurs for both single and mixed foulants. On the contrary, better flux stability appears at greater dp for both individual and mixed species, thanks to the increasingly dominated role of energy barrier and thus lowered attachment efficiency. Furthermore, higher J0 above limiting flux exerts greater permeate drag, leading to elevated attachment efficiency, and thus more flux losses for both OCC and SCC. Our modelling gains deep insights into the role of energy barrier, permeate drag, and attachment efficiency in governing combined fouling, which provides crucial guidelines for fouling reduction in practical engineering.

Carboxymethyl chitosan modification of cobalt-zinc bimetallic MOF for tetracycline hydrochloride removal: Exploration of the enhancement mechanism of the process.

This study synthesized a carboxymethyl chitosan-modified bimetallic Co/Zn-ZIF (CZ@CMC) with strong hydrophilicity and adsorption performance via the one-pot method. Tetracycline hydrochloride (TCH) was used as the model contaminant to evaluate the adsorption and peroxymonosulfate (PMS) activation properties of CZ@CMC. Mechanism showed that the adsorption behavior occurred through pore filling, electrostatic attraction, surface complexation, hydrogen bonding, and π-π stacking. In addition, a CZ@CMC/PMS system was constructed, which had excellent catalytic performance. The hydrophilicity and selective adsorption properties of CMC conferred a greatly accelerated CZ@CMC in catalyzing the PMS process with kobs of 0.095 min-1, in which OH, 1O2, SO4-, O2-, and Co(III) were the main ROS which quenching tests, EPR, and chemical probe experiments verified. In addition, the degradation pathways of TCH were obtained utilizing DFT and HPLC-MS and analyzed to show that the system possessed a good detoxification capacity. This work is expected to provide a green, efficient, and stable strategy to enhance the adsorption properties of catalytic materials and subsequently their co-catalytic properties.

[Association analysis between mixed exposure to phenols and semen quality].

Phenols such as bisphenols, parabens, and triclosan are common environmental endocrine disruptors. Previous epidemiological studies have suggested that phenols may affect semen quality, but the results were inconsistent. In addition, most existing studies have been limited to the effects of a single chemical compound, ignoring the health effects of mixed exposure to multiple chemicals. Thus, we aimed to explore the associations between individual and mixed exposure to phenols and various semen quality parameters. In this study, a rapid and sensitive method was used to determine 18 phenolic compounds in urine samples of 799 volunteers who donated sperm samples to the Shanghai Human Sperm Bank. A spot urine sample was collected from each subject on the day of their clinic visit and stored at -20 ℃ until testing. Urine samples (200 µL) were extracted and added with 20 µL of an internal standard and 50 µL of ß-glucuronidase solution. The mixtures were then incubated for 12 h at 37 ℃. After hydrolysis, the samples were extracted twice using ethyl acetate (500 µL). The concentrations of the 18 phenolic compounds were measured using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Semen quality parameters were analyzed using a computer-aided semen analyzer. Multiple linear regressions were used to detect the associations between individual phenol exposure and semen quality parameters. In addition, weighted quantile sum (WQS) models were used to explore the associations between mixed-phenol exposure and semen quality parameters. After adjusting for potential covariates, the results of multiple linear regressions showed that exposure to ethyl paraben (EtP) was significantly negatively associated with sperm concentration and total sperm count (P<0.05). In addition, exposure to mixed phenols was significantly associated with decreased sperm concentration; methyl paraben (MeP) and EtP were identified as the main contributors to this decrease. Thus, phenol exposure may be associated with decreased semen quality in young males, particularly with respect to sperm concentration and total sperm count.