Metformin-induced changes of the gut microbiota in patients with type 2 diabetes mellitus: results from a prospective cohort study.

BACKGROUND: The influence of the microbiota on hypoglycemic agents is becoming more apparent. The effects of metformin, a primary anti-diabetes drug, on gut microbiota are still not fully understood. RESEARCH DESIGN AND METHODS: This prospective cohort study aims to investigate the longitudinal effects of metformin on the gut microbiota of 25 treatment-naïve diabetes patients, each receiving a daily dose of 1500 mg. Microbiota compositions were analyzed at baseline, and at 1, 3, and 6 months of medication using 16S rRNA gene sequencing. RESULTS: Prior to the 3-month period of metformin treatment, significant improvements were noted in body mass index (BMI) and glycemic-related parameters, such as fasting blood glucose (FPG) and hemoglobin A1c (HbA1c), alongside homeostasis model assessment indices of insulin resistance (HOMA-IR). At the 3-month mark of medication, a significant reduction in the α-diversity of the gut microbiota was noted, while ß-diversity exhibited no marked variances throughout the treatment duration. The Firmicutes to Bacteroidetes ratio. markedly decreased. Metformin treatment consistently increased Escherichia-Shigella and decreased Romboutsia, while Pseudomonas decreased at 3 months. Fuzzy c-means clustering identified three longitudinal trajectory clusters for microbial fluctuations: (i) genera temporarily changing, (ii) genera continuing to decrease (Bacteroides), and (iii) genera continuing to increase(Lachnospiraceae ND3007 group, [Eubacterium] xylanophilum group, Romboutsia, Faecalibacterium and Ruminococcaceae UCG-014). The correlation matrix revealed associations between specific fecal taxa and metformin-related clinical parameters HbA1c, FPG, Uric Acid (UA), high-density lipoproteincholesterol (HDL-C), alanine aminotransferase (ALT), hypersensitive C-reactive protein (hs-CRP), triglyceride (TG) (P < 0.05). Metacyc database showed that metformin significantly altered 17 functional pathways. Amino acid metabolism pathways such as isoleucine biosynthesis predominated in the post-treatment group. CONCLUSIONS: Metformin's role in glucose metabolism regulation may primarily involve specific alterations in certain gut microbial species rather than an overall increase in microbial species diversity. This may suggest gut microbiota targets in future studies on metabolic abnormalities caused by metformin.

Mitochondrial Protein TAMM41 Modulates Depressive-like Behaviors.

Several lines of evidence have highlighted the crucial role of mitochondria-based therapy in depression. However, there are still less mitochondrial targets for the depression treatment. TAM41 mitochondrial translocator assembly and maintenance homolog (TAMM41) is a mitochondrial inner membrane protein for maintaining mitochondrial function, which is tightly related to many brain diseases including Alzheimer's diseases and epilepsy. Here, we investigated whether TAMM41 would be a potential target to treat depression. We found that the expression of TAMM41 was markedly lower in corticosterone-induced depression, lipopolysaccharide-induced depression, and depressed patients. Meanwhile, loss of TAMM41 resulted in increased immobility in the forced swim test (FST), tail suspension test (TST), and center time in open field test (OFT), suggesting depressive-like behaviors in mice. Moreover, genetic overexpression of TAMM41 obviously exerted antidepressant-like activities. Mechanistically, proteomics revealed that pacsin1 might be the underlying target of TAMM41. Further data supported that TAMM41 regulated the expression of pacsin1, and its antidepressant-like effect at least partially was attributed to pacsin1. In addition, exosomes containing TAMM41 was sufficient to exhibit antidepressant-like effect, suggesting an alternative strategy to exert the effect of TAMM41. Taken together, the present study demonstrates the antidepressant-like effect of TAMM41 and sheds light on its molecular mechanism. These finding provide new insights into a therapeutic strategy targeting mitochondria in the development of novel antidepressants.

Clinical outcomes of frozen-thawed embryo transfer in natural cycles with luteinized unruptured follicles.

OBJECTIVE: To assess the effect of luteinized unruptured follicles (LUF) on frozen-thawed embryo transfer cycles performed in natural cycles (FET-NC). METHODS: Retrospective cohort study, held in a university hospital with 3415 cycles for frozen-thawed embryo transfer, performed between June 2019 and September 2022. Using propensity score matching, 242 patients with a diagnosis of LUF (LUF group) were matched with 484 ovulated patients (ovulation group). Stratified by the type of embryo transferred, the LUF group included 168 blastocyst transfer patients (blastocyst group) and 74 cleavage-stage embryo transfer patients (cleavage-embryo group). The ovulation group included 324 patients with blastocyst transfer (blastocyst group) and 160 patients with transferred cleavage-stage embryos. Clinical pregnancy rate was retrospectively analyzed between the LUF and ovulation groups, as well as between each subgroup. RESULTS: After using propensity score matching, the general characteristics of the LUF and ovulation groups were similar. The implantation and clinical pregnancy rates in the LUF group were not significantly different from those in the ovulation group (44.98 % vs. 45.29 %, p = 0.93; 53.72 % vs. 52.48 %, p = 0.75). The implantation and pregnancy rates of transferred cleavage-stage embryos in the LUF group were also not significantly different from those in the ovulation group (32.39 % vs. 36.40 %, p = 0.42; 47.30 % vs. 47.50 %, p = 0.98). The implantation and pregnancy rates of transferred blastocysts in the LUF group were also not significantly different from those in the ovulation group (53.11 % vs. 52.03 %, p = 0.82; 56.55 % vs. 54.94 %, p = 0.73). There was also no significant difference in the miscarriage rate between the groups. CONCLUSION: In the natural cycle, LUF does not affect the clinical pregnancy outcomes of FET. If adequate luteal support is given, the clinical pregnancy outcomes were similar between the LUF group and ovulation group.

Optimization of parameters for a fringe projection measurement system by use of an improved differential evolution method.

Fringe projection 3D measurement is widely used for object surface reconstruction. While improving measurement accuracy is a crucial task. Measurement accuracy is profoundly affected by various optical structural parameters. However, the current practice of system construction lacks theoretical guidelines and often relies on the experience of the operator, inevitably leading to unpredictable error. This paper investigates a theoretical optimization model and proposes an automatic optimization method for qualitatively determining the multiple optimal optical structural parameters in fringe projection measurement system. The aim is to enhance measurement accuracy conducting a rational comprehensive optimal structural parameters design prior to the system construction. Firstly, the mathematical model of the measurement system is established based on the principle of optical triangulation, and the phase sensitivity criterion is defined as the optimization norm. Within the full measurement range, the optimization merit function is formulated by combing three positions: the center position, the left and right boundary of the CCD. The imaging effectiveness criteria and sensor geometric dimensions are taken into account as the constraint boundaries. Subsequently, a combined improved differential evolution and Levy flight optimization algorithm is applied to search for the optimal parameters. The optimal structural parameters of the system were designed based on the optimization process. Experimental results validated the improvement in measurement accuracy achieved by the optimized structural parameters.

Fully dispersed cobalt diatomic site with significantly improved Fenton-like catalysis performance for organic pollutant degradation.

A novel strategy for better catalytic performance in terms of precisely tuning the metal atom number of active centers is gradually getting attention. In this paper, the Co atom pair sites on N-doped porous carbon was engineered. The binuclear Co2 site structure was identified by aberration-corrected scanning transmission electron microscopy and X-ray absorption spectroscopy. As expected, the Co2NC display an outstanding Fenton-like catalysis activity in tetracycline degradation with turnover frequency exceeding 0.91 min-1 that is approximately 4 times higher than the conventional CoN4 site. The EPR tests indicated that the ROS strength stimulated by the binuclear site was much stronger than that of single site. Theoretical density functional theory calculations reveal that the optimized adsorption configuration is the O1 of peroxymonosulfate (PMS) interacting with two Co atoms, leading to stronger interaction effect and electron transfer for PMS comparing to single atom sites.

f25, a novel synthetic quinoline derivative, inhibits tongue cancer cell invasion and survival by the PPAR pathway in vitro and vivo.

Tongue cancer has a very high incidence in China, and there is a need to develop new anti-tumour drugs against it. We synthesised 31 novel quinoline derivatives to test their anti-tumour activity. A compound referred to as "f25" was identified through screening for its high in vitro toxicity against an oral squamous carcinoma cell line (CAL-27). f25 exhibited significant cytotoxicity against CAL-27 cells (IC50 = 7.70 ± 0.58 µΜ). f25 also inhibited the migration and invasion of CAL-27 cells to a level comparable with that of the chemotherapy agent cisplatin. Moreover, f25 promoted the apoptosis of CAL-27 cells. Transcriptome sequencing and western blotting showed that the mechanism of action of f25 against CAL-27 cells involved the peroxisome proliferator-activated receptor (PPAR) signalling pathway. Specifically, f25 could bind to PPAR-α, PPAR-ß, and PPAR-γ and increase their expression. In vivo experiments showed that treatment with f25 led to a reduction in tumour volume in nude mice without significant toxicity. Overall, this study highlights the potential of quinoline compounds (particularly f25) for the design and synthesis of anti-tumour drugs. It also underscores the importance of the PPAR signalling pathway as a target for potential cancer therapies.

Research on Genotype Markers for Plant Height and Assisted Breeding of Key Sorghum Resources in China.

Dwarfing and the selection of optimal plant types constitute the primary focus of sorghum breeding. However, the lack of clarity regarding the gene types associated with plant height genes Dw1-Dw4 in the primary breeding materials has led to increased plant heights in improved offspring of the same plant height type, resulting in unsatisfactory morphological traits. This study aimed to elucidate the gene types related to plant height in breeding materials, validate the regulatory mechanisms, and establish a material improvement system. The goal was to achieve molecular-marker-assisted dwarf breeding through the detection of plant height genes and the test cross verification of main Chinese sorghum materials. Using 38 main male sterile lines and 57 main restorer lines of grain sorghum as materials, three plant height genes were detected and classified. Ninety-five F1 generation hybrids of these materials, along with typical materials, were measured at the wax maturity stage. Test cross results demonstrated that the variation in dw1-dw3 genes in the breeding materials significantly influenced the plant height of hybrid offspring. The main male sterile lines in Chinese sorghum predominantly exhibited the "three-dwarf" type of Kafir and its improved lines, characterized by the genotype (Dw1-Dw2-dw3-dw4). On the other hand, restorer lines mainly showcased the improved "two-dwarf" (Dw1-Dw2-dw3-dw4) genotype of the Kaoliang/Caudatum subspecies, along with the "three-dwarf" type of some Kafir and its improved lines. The test materials predominantly contained dw3 genes, with relatively fewer dw1 genes in the restorer lines. The primary restorer materials lacked the dw2 gene, and dw2 significantly influenced plant type. The increased plant height in improved offspring of the same plant height type material was attributed to differences in gene types. Therefore, the enhancement of plant height in breeding materials should prioritize the use of different methods in conjunction with Dw1 and Dw2 classification.

Metagenomics next-generation sequencing (mNGS) reveals emerging infection induced by Klebsiella pneumoniaeniae.

OBJECTIVES: The increasing emergence of hypervirulent Klebsiella pneumoniae (hv-Kp) and carbapenem-resistant K. pneumoniae (CR-Kp) is a serious and substantial public health problem. The use of the last resort antimicrobials, tigecycline and polymyxin to combat infections is complicated by the expanding repertoire of newly-identified CR-hvKp. The transmission and co-occurrence of the corresponding antimicrobial resistance and virulence determinants are largely unknown. The aim of this study was to investigate the dissemination and dynamics of CR-Kp and its antibiotic resistance in a hospitalised patient. METHODS: Metagenomic next-generation sequencing (mNGS) was conducted for different specimens collected from an elderly male hospitalised patient. CR-Kp strains were examined using antibiotic susceptibility and string testing. Antimicrobial and virulence genes were annotated using whole-genome sequencing (WGS). RESULTS: A clinical case of a patient infected with a variety of CR-Kp isolates was reported. The co-occurrence of KPC-2 and NDM-1 in the patient was revealed. The CR-Kp isolates, such as BALF2, and Sputum T1 and T3, were classified into ST11 and ST147, respectively. The genetic signature (iuc operon) of hypervirulence was identified in strain T1, although string testing indicated its intermediate virulence. CONCLUSIONS: In this study, multiple infections of CR-Kp isolates were revealed by mNGS, and their dissemination was attributed to plasmid variations, mgrB inactivation and integrative conjugative elements (ICEs). Furthermore, the finding indicated one likely convergence to form CR-hvKp, different from acquisition of carbapenem-resistance determinants in hvKp. A combination of mNGS and WGS is beneficial for clinical diagnosis and anti-infection therapy, and facilitates a better understanding of genetic variants conferring antimicrobial and virulence properties.

1-Methylcyclopropene Alleviates Postharvest Chilling Injury of Snap Beans by Enhancing Antioxidant Defense System.

Research background: Chilling injury is a major disorder affecting the quality of tropical and subtropical vegetables during low temperature storage. Snap bean (Phaseolus vulgaris L.) is sensitive to chilling injury. The main purpose of the present study is to investigate the alleviating effects of 1-methylcyclopropene (1-MCP) on chilling injury of snap bean. In addition, the related mechanisms were also detected from the perspective of the changes of antioxidant defense system. Experimental approach: Snap beans were exposed to different volume fractions of 1-MCP. After 24 h of treatment, snap beans were stored at 4 °C for up to 14 days. Chilling injury index, electrolyte leakage, titratable acidity and total soluble solids were determined. Contents of chlorophyll, ascorbic acid and malondialdehyde were assessed. The total antioxidant capacity, Fe(II) ion chelating capacity, scavenging capacities on free radicals and activities of antioxidant enzymes were detected. Total phenol content and activities of related metabolic enzymes were also determined. Results and conclusions: 1-MCP treatment reduced chilling injury index, electrolyte leakage rate and malondialdehyde content of snap beans. The amounts of total soluble solids, titratable acid, ascorbic acid and total chlorophyll in 1-MCP-treated snap beans were significantly higher than those of control. The snap beans treated with 1-MCP showed stronger total antioxidant capacity and metal chelating activity. The 1-MCP treatment enhanced scavenging effects of snap beans on superoxide, hydroxyl and 1,1-diphenyl-2-trinitrophenylhydrazine radicals. The activities of peroxidase, ascorbate peroxidase, superoxide dismutase and catalase in 1-MCP-treated group were higher than of control. The treatment also enhanced the accumulation of phenolic compounds in snap beans by regulating the activities of phenol-metabolizing enzymes such as shikimate dehydrogenase, phenylalanine ammonia lyase enzyme, cinnamic acid 4-hydroxylase and polyphenol oxidase. In conclusion, with the mechanism that involves the activation of enzymatic and non-enzymatic antioxidant systems, 1-MCP has the ability to avoid chilling injury of snap bean. Novelty and scientific contribution: This study gives insights into whether 1-MCP can regulate postharvest cold resistance in vegetables by enhancing the enzymatic antioxidant system and inducing the accumulation of non-enzymatic antioxidants. Considering the results, 1-MCP treatment could be an effective method to alleviate postharvest chilling injury of snap beans during low temperature storage.

The impact of global warming on the signature virulence gene, thermolabile hemolysin, of Vibrio parahaemolyticus.

IMPORTANCE: In this study, Vibrio parahaemolyticus strains were collected from a large number of aquatic products globally and found that temperature has an impact on the virulence of these bacteria. As global temperatures rise, mutations in a gene marker called thermolabile hemolysin (tlh) also increase. This suggests that environmental isolates adapt to the warming environment and become more pathogenic. The findings can help in developing tools to analyze and monitor these bacteria as well as assess any link between climate change and vibrio-associated diseases, which could be used for forecasting outbreaks associated with them.

Upregulated RPA2 in endometrial tissues of repeated implantation failure patients impairs the endometrial decidualization.

PURPOSE: To investigate the expression and underlying mechanism of RPA2 in endometrium of patients with repeated implantation failure (RIF). METHODS: In this study, we retrieved the expression profiles from GEO databases and filtered the differentially expressed genes between RIF and the fertile control group. Ultimately, RPA2 was confirmed as a target gene. RPA2 expression in endometrial tissues of RIF patients, the control group, and different phases was detected by RT-qPCR, immunohistochemistry, and Western blotting. The role of RPA2 in endometrial decidualization was performed by in vitro decidualization inducing by 8-Br-cAMP and MPA. Furthermore, RT-qPCR was used to detect changes in the decidual biomarkers after transfection of RPA2 overexpression vector in human endometrium stromal cell (HESC). RESULTS: RPA2 was significantly upregulated in the mid-secretory endometrium of patients with RIF. As a proliferation-related gene, RPA2 was obviously higher expressed at proliferative phase during the normal menstrual cycles. Moreover, the downregulation of RPA2 was discovered during decidualization of HESC. Furthermore, RPA2 overexpression impaired decidualization by inhibiting the expression of prolactin (PRL) and insulin-like growth factor-binding protein 1 (IGFBP1). CONCLUSIONS: Our finding indicated that aberrant upregulation of RPA2 attenuated decidualization of HESC in RIF women and provided new potential therapeutic targets.

Decoupled learning for brain image registration.

Image registration is one of the important parts in medical image processing and intelligent analysis. The accuracy of image registration will greatly affect the subsequent image processing and analysis. This paper focuses on the problem of brain image registration based on deep learning, and proposes the unsupervised deep learning methods based on model decoupling and regularization learning. Specifically, we first decompose the highly ill-conditioned inverse problem of brain image registration into two simpler sub-problems, to reduce the model complexity. Further, two light neural networks are constructed to approximate the solution of the two sub-problems and the training strategy of alternating iteration is used to solve the problem. The performance of algorithms utilizing model decoupling is evaluated through experiments conducted on brain MRI images from the LPBA40 dataset. The obtained experimental results demonstrate the superiority of the proposed algorithm over conventional learning methods in the context of brain image registration tasks.

Cancer-associated fibroblasts: tumor defenders in radiation therapy.

Cancer-associated fibroblasts (CAFs) are an important component of the tumor microenvironment that are involved in multiple aspects of cancer progression and considered contributors to tumor immune escape. CAFs exhibit a unique radiation resistance phenotype, and can survive clinical radiation doses; however, ionizing radiation can induce changes in their secretions and influence tumor progression by acting on tumor and immune cells. In this review, we describe current knowledge of the effects of radiation therapies on CAFs, as well as summarizing understanding of crosstalk among CAFs, tumor cells, and immune cells. We highlight the important role of CAFs in radiotherapy resistance, and discuss current and future radiotherapy strategies for targeting CAFs.

Proprioceptive Acuity Assessment in Multiple Directions Across Multiple Joints in the Upper Limb.

Proprioception is essential for precise movement as it helps the body transmit important data about its surroundings to the central nervous system for maintaining body posture and position. This study aimed to investigate the effect of direction and joint angle on upper limb proprioception. Thirty individuals (all males) completed a position reproduction activity in 13 directions and three joint angles. It was discovered that upper limb proprioception is dependent on joint angle, direction, and range of motion. The position reproduction error was found to be dependent on the direction, which had a significantly lower accuracy in the direction with a larger range of motion. In addition, upper limb repositioning errors increased at greater limb elevation angles. Our findings also showed that the joint angle did not significantly affect the absolute error of elbow flexion. With an increase in the elbow flexion, the increase of the gravitational moment of the upper arm and hand coupled with the increase of the muscle arm of the biceps brachii possibly causes slight changes in muscle length perceived by spindles or muscular force perceived by Golgi tendon organs.

A health-promoting role of exclusive breastfeeding on infants through restoring delivery mode-induced gut microbiota perturbations.

The establishment of human gut microbiota in early life is closely associated with both short- and long-term infant health. Delivery mode and feeding pattern are two important determinants of infant gut microbiota. In this longitudinal cohort study, we examined the interplay between the delivery mode and feeding pattern on the dynamics of infant gut microbiota from 6 weeks to 6 months post-delivery in 139 infants. We also assessed the relationship between infant respiratory infection susceptibility and gut microbial changes associated with delivery mode and feeding pattern. At 6 weeks postpartum, the composition and structure of gut microbiota of cesarean section-delivered (CSD) infants differed from those of vaginally delivered (VD) infants, with decreased Bacteroides and Escherichia-Shigella and increased Klebsiella, Veillonella, and Enterococcus. At 6 months postpartum, these delivery mode-induced microbial shifts were restored by exclusive breastfeeding, resulting in similar gut microbial profiles between VD and CSD infants who were exclusively breastfed (P = 0.57) and more variable gut microbial profiles between VD and CSD infants who were mixed fed (P < 0.001). We identified that the VD-associated genera were enriched in healthy infants, while the CSD-associated genera were enriched in infants who suffered from respiratory infections. Our findings indicate that exclusive breastfeeding may play a health-promoting role by reducing infant respiratory infection susceptibility through the restoration of gut microbiota perturbations caused by cesarean section.

Identification of Key Genes Regulating Sorghum Mesocotyl Elongation through Transcriptome Analysis.

Sorghum with longer mesocotyls is beneficialfor improving its deep tolerance, which is important for the seedling rates. Here, we perform transcriptome analysis between four different sorghum lines, with the aim of identifying the key genes regulating sorghum mesocotyl elongation. According to the mesocotyl length (ML) data, we constructed four comparison groups for the transcriptome analysis and detected 2705 common DEGs. GO and KEGG enrichment analysis showed that the most common category of DEGs were involved in cell wall, microtubule, cell cycle, phytohormone, and energy metabolism-related pathways. In the cell wall biological processes, the expression of SbEXPA9-1, SbEXPA9-2, SbXTH25, SbXTH8-1, and SbXTH27 are increased in the sorghum lines with long ML. In the plant hormone signaling pathway, five auxin-responsive genes and eight cytokinin/zeatin/abscisic acid/salicylic acid-related genes showed a higher expression level in the long ML sorghum lines. In addition, five ERF genes showed a higher expression level in the sorghum lines with long ML, whereas two ERF genes showed a lower expression level in these lines. Furthermore, the expression levels of these genes were further analyzed using real-time PCR (RT-qPCR), which showed similar results. This work identified the candidate gene regulating ML, which may provide additional evidence to understand the regulatory molecular mechanisms of sorghum mesocotyl elongation.

Simultaneous nitrogen removal via heterotrophic nitrification and aerobic denitrification by a novel Lysinibacillus fusiformis B301.

Simultaneous nitrogen removal via heterotrophic nitrification and aerobic denitrification (HN-AD) has received widespread attention in biological treatment of wastewater. This study reported a novel Lysinibacillus fusiformis B301 strain, which effectively removed nitrogenous pollutants via HN-AD in one aerobic reactor with no nitrite accumulated. It exhibited the optimal nitrogen removal efficiency under 30°C, citrate as the carbon source and C/N ratio of 15. The maximum nitrogen removal rates were up to 2.11 mgNH4 + -N/(L·h), 1.62 mgNO3 - -N/(L·h), and 1.41 mgNO2 - -N/(L·h), respectively, when ammonium, nitrate, and nitrite were employed as the only nitrogen source under aerobic conditions. Ammonium nitrogen was preferentially consumed via HN-AD in the coexistence of three nitrogen species, and the removal efficiencies of total nitrogen were up to 94.26%. Nitrogen balance analysis suggested that 83.25% of ammonium was converted to gaseous nitrogen. The HD-AD pathway catalyzed by L. fusiformis B301 followed NH 4 + → N H 2 OH → NO 2 - → NO 3 - → NO 2 - → N 2 , supported by the results of key denitrifying enzymatic activities. PRACTITIONER POINTS: The novel Lysinibacillus fusiformis B301 exhibited the outstanding HN-AD ability. The novel Lysinibacillus fusiformis B301 simultaneously removed multiple nitrogen species. No nitrite accumulated during the HN-AD process. Five key denitrifying enzymes were involved in the HN-AD process. Ammonium nitrogen (83.25%) was converted to gaseous nitrogen by the novel strain.

PCGEM1 promotes cell proliferation and migration in endometriosis by targeting miR-124-3p-mediated ANTXR2 expression.

BACKGROUND: Endometriosis, a common gynaecological disease in women, affects 10% of women of childbearing age. Among infertile women, this proportion is as high as 30-50%. Despite the high prevalence of endometriosis, the pathogenesis of endometriosis is still unclear. METHODS: In the present study, bioinformatics analysis and molecular and animal experiments were employed to explore the functions of PCGEM1 in the pathogenesis of endometriosis. We established an endometriosis rat model and isolated endometrial stromal cells (ESCs) and primary normal ESCs (NESCs). Bioinformatics analysis was adopted to study the roles of PCGEM1 in promoting the pathogenesis of endometriosis. Luciferase reporter assays and RNA pull-down assays were carried out to study the mechanism by which PCGEM1 regulates ANTXR2. RESULTS: Our results indicated that PCGEM1 promoted the motility and proliferation of ectopic endometrial cells, and the underlying mechanism was due to the direct binding of PCGEM1 to miR-124-3p to modulate ANTXR2 expression. CONCLUSION: PCGEM1 can influence endometrial stromal cell proliferation and motility and may be a novel therapeutic target for endometriosis.

Dual-Functional Nanoplatform Based on Bimetallic Metal-Organic Frameworks for Synergistic Starvation and Chemodynamic Therapy.

Tumor microenvironment (TME)-responsive chemodynamic therapy (CDT) mediated by nanozymes has been extensively studied in oral squamous cell carcinoma. However, the low catalytic efficiency due to insufficient H2O2 in the TME is still a major challenge for its clinical translation. Herein, we present an antitumor nanoplatform based on a Mn-Co organometallic framework material (MnCoMOF), which shows peroxidase-like (POD-like) activity, loaded with glucose oxidase (GOx@MnCoMOF), demonstrating the ability of H2O2 self-supply and H2O2 conversion to toxic hydroxyl radicals. The encapsulated GOx efficiently catalyzes glucose into gluconic acid and H2O2 at the tumor site, which can cut off the energy supply to inhibit tumor growth and produce a large amount of H2O2 and acid to compensate for their lack in the tumor microenvironment. The POD-like activity of MnCoMOF can convert H2O2 into hydroxyl radicals and eliminate tumor cells. The nanoplatform exhibits enhanced tumor cell cytotoxicity in a high-glucose medium compared with a low-glucose medium, illustrating sufficient generation of H2O2 from glucose by GOx. The in vivo results indicate that GOx@MnCoMOF has excellent antitumor efficacy and can remodel the immune-suppressive tumor microenvironment. In conclusion, the GOx@MnCoMOF nanoplatform possesses dual enzymatic activities, i.e., POD-like and glucose oxidase, to achieve improved tumor-suppressive efficiency through synergistic starvation and chemodynamic therapy, thus providing a new strategy for the clinical treatment of oral cancer.

Stable Phase Equilibria of the Quaternary Water-Salt System Li+, Rb+, Mg2+//SO4 2--H2O at T = 273.2 K.

The phase equilibria for the quaternary system Li+, Rb+, Mg2+//SO4 2- - H2O at 273.2 K were studied by the isothermal dissolution equilibrium method. Based on the measured data, the space diagram, stable phase diagram, water content diagram, and the diagram of density vs composition are plotted. The stable phase diagram in the system consists of four quaternary invariant points, nine univariate curves, and six crystallization zones. For the invariant points, E1 and E4 belong to the commensurate type, and E2 and E3 belong to the incommensurate type. The order of the crystallization area is Rb2SO4·MgSO4·6H2O > 3Li2SO4·Rb2SO4·2H2O > Li2SO4·Rb2SO4 > MgSO4·7H2O > Li2SO4·H2O > Rb2SO4. The density of the equilibrium liquid changed regularly with the content of Rb2SO4 in the solution. By comparing the stable phase diagram of the partial ternary subsystems at T = 273.2 K and T = 298.2 K, it is found that the crystallization regions of Rb2SO4 increases with the decrease in temperature, which indicates that cooling is conducive to the crystallization of Rb2SO4. By comparing the stable phase diagram of the system at T = 273.2 K and T = 308.2 K, it was found that the system was composed of four invariant points, nine univariate curves, and six crystal regions. The double salt 3Li2SO4·Rb2SO4·2H2O is converted to 3Li2SO4·Rb2SO4. The crystallization region of single salt MgSO4·7H2O, Rb2SO4 and double salt Li2SO4·Rb2SO4 decreased obviously.