Fighting ferroptosis: Protective effects of dexmedetomidine on vital organ injuries.

Vital organ injury is one of the leading causes of global mortality and socio-economic burdens. Current treatments have limited efficacy, and new strategies are needed. Dexmedetomidine (DEX) is a highly selective α2-adrenergic receptor that protects multiple organs by reducing inflammation and preventing cell death. However, its exact mechanism is not yet fully understood. Understanding the underlying molecular mechanisms of its protective effects is crucial as it could provide a basis for designing highly targeted and more effective drugs. Ferroptosis is the primary mode of cell death during organ injury, and recent studies have shown that DEX can protect vital organs from this process. This review provides a detailed analysis of preclinical in vitro and in vivo studies and gains a better understanding of how DEX protects against vital organ injuries by inhibiting ferroptosis. Our findings suggest that DEX can potentially protect vital organs mainly by regulating iron metabolism and the antioxidant defense system. This is the first review that summarizes all evidence of ferroptosis's role in DEX's protective effects against vital organ injuries. Our work aims to provide new insights into organ therapy with DEX and accelerate its translation from the laboratory to clinical settings.

Identifying distinct markers in two Sorghum varieties for baijiu fermentation using untargeted metabolomics and molecular network approaches.

The quality of strong-flavor Baijiu, a prominent Chinese liquor, is intricately tied to the choice of sorghum variety used in fermentation. However, a significant gap remains in our understanding of how glutinous and non-glutinous sorghum varieties comprehensively impact Baijiu flavor formation through fermentation metabolites. This study employed untargeted metabolomics combined with feature-based molecular networking (FBMN) to explore the unique metabolic characteristics of these two sorghum varieties during fermentation. FBMN analysis revealed 267 metabolites within both types of fermented sorghum (Zaopei) in the cellar. Further multidimensional statistical analyses highlighted sphingolipids, 2,5-diketopiperazines, and methionine derivatives as critical markers for quality control. These findings represent a significant advancement in our understanding and provide valuable insights for regulating the quality of Baijiu flavors.

Comprehensive evaluation of global health cities development levels.

Introduction: How to scientifically assess the health status of cities and effectively assist in formulating policies and planning for health city development remains a profound challenge in building a global "health community." Methods: This study employs the Building Research Establishment's International Healthy Cities Index (BRE HCI), encompassing ten environmental categories and fifty-eight indicators, to guide and support the scientific development of healthy cities. The entropy weight-TOPSIS method and the rank sum ratio (RSR) method were applied to comprehensively rank and categorize the health development levels of fifteen global cities. Furthermore, through cluster analysis, this research identifies universal and unique indicators that influence the development of healthy cities. Results: The results indicate that: (1) Within the scope of 58 evaluation indicators, the precedence in weight allocation is accorded to the kilometres of bicycle paths and lanes per 100,000 population (0.068), succeeded by m2 of public indoor recreation space per capita (0.047), and kilometres of bicycle paths and lanes per 100,000 population (0.042). (2) Among the ten environmental categories, the top three in terms of weight ranking are transport (0.239), leisure and recreation (0.172), and resilience (0.125). Significant disparities exist between different cities and environmental categories, with the issue of uneven health development within cities being particularly prominent. (3) The study categorizes the development levels of healthy cities into three tiers based on composite scores: it classifies Singapore, Shanghai, and Amsterdam at an excellent level; places Dubai and Johannesburg at a comparatively poor level; and situates the remaining ten cities at a moderate level. (4) The analysis identifies 53 international common indicators and 5 characteristic indicators from the 58 indicators based on the significance of the clustering analysis (p < 0.05). Discussion: The study proposes four strategic recommendations based on these findings: establishing a comprehensive policy assurance system, refining urban spatial planning, expanding avenues for multi-party participation, and augmenting distinctive health indicators. These measures aim to narrow the developmental disparities between cities and contribute to healthy global cities' balanced and sustainable growth. However, due to existing limitations in sample selection, research methodology application, and the control of potential confounding variables, further in-depth studies are required in the future.

FAM134B deletion exacerbates apoptosis and epithelial-to-mesenchymal transition in rat lungs exposed to hyperoxia.

Oxygen therapy is widely used in clinical practice; however, prolonged hyperoxia exposure may result in hyperoxic acute lung injury (HALI). In this study, we investigated the role of FAM134B in hyperoxia-induced apoptosis, cell proliferation, and epithelial-to-mesenchymal transition (EMT) using RLE-6TN cells and rat lungs. We also studied the effect of CeO2-NPs on RLE-6TN cells and lungs following hyperoxia exposure. FAM134B was inhibited in RLE-6TN cells and rat lungs following hyperoxia exposure. Overexpressing FAM134B promoted cell proliferation, and reduced EMT and apoptosis following hyperoxia exposure. FAM134B activation increased ER-phagy, decreased apoptosis, improved lung structure damage, and decreased collagen fiber deposition to limit lung injury. These effects could be reversed by PI3K/AKT pathway inhibitor LY294002. Additionally, CeO2-NPs protected RLE-6TN cells and lung damage following hyperoxia exposure by ameliorating impaired ER-phagy. Therefore, FAM134B restoration is a potential therapeutic target for the HALI. Moreover, CeO2-NPs can be used for the treatment of HALI.

Nur77 improves ovarian function in reproductive aging mice by activating mitophagy and inhibiting apoptosis.

Reproductive aging not only affects the fertility and physical and mental health of women but also accelerates the aging process of other organs. There is an urgent need newfor novel mechanisms, targets, and drugs to break the vicious cycle of mitochondrial dysfunction, redox imbalance, and germ cell apoptosis associated with ovarian aging. Autophagy, recognized as a longevity mechanism, has recently become a focal point in anti-aging research. Although mitophagy is a type of autophagy, its role and regulatory mechanisms in ovarian aging, particularly in age-related ovarian function decline, remain unclear. Nerve growth factor inducible gene B (Nur77) is an early response gene that can be stimulated by oxidative stress, DNA damage, metabolism, and inflammation. Recent evidence recommends that decreased expression of Nur77 is associated with age-related myocardial fibrosis, renal dysfunction, and Parkinson's disease; however, its association with ovarian aging has not been studied yet. We herein identified Nur77 as a regulator of germ cell senescence, apoptosis, and mitophagy and found that overexpression of Nur77 can activate mitophagy, improve oxidative stress, reduce apoptosis, and ultimately enhance ovarian reserve in aged mice ovaries. Furthermore, we discovered an association between Nur77 and the AKT pathway through String and molecular docking analyses. Experimental confirmation revealed that the AKT/mTOR signaling pathway is involved in the regulation of Nur77 in ovarian function. In conclusion, our results suggest Nur77 as a promising target for preventing and treating ovarian function decline related to reproductive aging.

Spatiotemporal analysis of microstructure, sensory attributes, and full-spectrum metabolomes reveals the relationship between bitterness and nootkatone in Alpinia oxyphylla miquel fruit peel and seeds.

The Alpinia oxyphylla fruit (AOF) is a popular condiment and traditional Chinese medicine in Asia, known for its neuroprotective compound nootkatone. However, there has not been a comprehensive study of its flavor or the relationship between sensory and bioactive compounds. To address this issue, we examined AOF's microstructure, flavor, and metabolomic profiles during fruit maturation. The key markers used to distinguish samples included fruit expansion, testa pigmentation, aril liquefaction, oil cell expansion, peel spiciness, aril sweetness, and seed bitterness. A full-spectrum metabolomic analysis, combining a nontargeted metabolomics approach for volatile compounds and a widely targeted metabolomics approach for nonvolatile compounds, identified 1,448 metabolites, including 1,410 differentially accumulated metabolites (DAMs). Notably, 31 DAMs, including nootkatone, were associated with spicy peel, sweet aril, and bitter seeds. Correlational analysis indicated that bitterness intensity is an easy-to-use biomarker for nootkatone content in seeds. KEGG enrichment analysis linked peel spiciness to phenylpropanoid and capsaicin biosynthesis, seed bitterness to terpenoid (especially nootkatone) biosynthesis, and aril sweetness to starch and sucrose metabolism. This investigation advances the understanding of AOF's complex flavor chemistry and underlying bioactive principle, encapsulating the essence of the adage: "no bitterness, no intelligence" within the realm of phytochemistry.

Association of the incidence of postherpetic neuralgia with early treatment intervention of herpes zoster and patient baseline characteristics: A systematic review and meta-analysis of cohort studies.

OBJECTIVES: To conduct a meta-analysis of the association between postherpetic neuralgia (PHN), baseline characteristics of patients with herpes zoster (HZ), and early interventions. METHODS: Literature searches were conducted in seven databases, in June 2021 and updated in June 2022. Two investigators independently conducted literature screening and data extraction, and the studies were evaluated according to the Newcastle-Ottawa scale. RESULTS: A total of 53 cohort studies were included. The meta-analyses identified skin lesions, timing of initial treatment (≥3 days), and comorbidities as potential risk factors for PHN. In contrast, female sex (odds ratio [OR] = 1.13, 95% confidence interval [CI]: 0.99-1.29), cervical herpes (OR = 0.80, 95% CI: 0.21-2.99), lumbar herpes (OR = 1.29, 95% CI: 0.61-2.74), and immunosuppressive therapy (OR = 1.96, 95% CI: 0.22-17.12), were not significantly associated with PHN. In addition, glucocorticoid use (OR = 0.61, 95% CI: 0.22-1.70) may be a protective factor for the development of PHN; however, the difference was not statistically significant. CONCLUSION: A series of baseline characteristics were identified among populations at high risk of developing PHN from HZ. Additionally, the timing of initial treatment is associated with PHN occurrence. The preventive effect of glucocorticoids warrants further validation.

Changes in symptom burden and quality of life among women with uterine fibroids receiving relugolix combination therapy: a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of findings from two research studies (known as clinical trials). The studies looked at how well a medicine called relugolix combination therapy worked in women with heavy menstrual bleeding (heavy bleeding during a period) with uterine fibroids (noncancerous or benign growths in the uterus). In this analysis of the studies, researchers looked at how patients self-reported their uterine fibroid symptoms before and after taking relugolix combination therapy. Researchers also looked at how patients self-reported the impact of uterine fibroids on their health-related quality of life before and after taking relugolix combination therapy. WHAT WERE THE RESULTS?: Women took either relugolix combination therapy or placebo (a pill that contains no medicine) by mouth once daily for 24 weeks. Women completed the Uterine Fibroid Symptom and Quality of Life questionnaire (where "quality of life" refers to the women's health-related quality of life related to uterine fibroids) before, during, and after treatment. The questionnaire let researchers see if the women felt that relugolix combination therapy decreased the burden of uterine fibroid symptoms and improved the women's health-related quality of life related to uterine fibroids. More women said that they felt less distress due to their uterine fibroid symptoms and that their health-related quality of life related to uterine fibroids was better after taking relugolix combination therapy compared with women who took placebo. WHAT DO THE RESULTS MEAN?: Relugolix combination therapy may lessen distress associated with uterine fibroid symptoms and improve health-related quality of life related to uterine fibroids.

A Study on the Preparation of a Vulcanizing Mixture and Its Application in Natural Rubber Latex.

The traditional preparation process of natural rubber latex requires tedious treatment of a variety of rubber additives. In this paper, a new process of wet mixed grinding was used to prepare a reinforced vulcanization mixture and a rapid vulcanization effect. The effect of different amounts of vulcanization mixtures on the mechanical properties of natural latex film was studied, and the pre-vulcanization process of latex and the vulcanization process of film were optimized. The results showed that with the increase in the amount of vulcanization mixture, the tensile strength increased from 5.96 MPa to 29.28 MPa, and the tear strength increased from 7.59 kN/m to 52.81 kN/m. When the vulcanization temperature of the latex film is heated from 80 °C to 100 °C, the vulcanization time is shortened by 5~6 times. The new vulcanization mixture prepared in this work has the characteristics of simple production and fast vulcanization speed, which provides a new solution for the development of the latex product industry.

Effects of Total Intravenous Anesthesia on Circadian Rhythms in Patients Undergoing Cardiac Transcatheter Closure.

Objective To evaluate the effects of total intravenous anesthesia on the circadian rhythms in the patients undergoing cardiac transcatheter closure. Methods Thirty patients undergoing cardiac transcatheter closure under elective intravenous anesthesia were included in this study.Paired t-tests were performed to compare the mRNA levels of the genes encoding circadian locomotor output cycles kaput(CLOCK),brain and muscle ARNT-1 like protein-1(BMAL1),cryptochrome 1(CRY1),and period circadian clock 2(PER2),the Munich Chronotype Questionnaire(MCTQ)score,and the Pittsburgh Sleep Quality Index(PSQI)score before and after anesthesia.Multiple stepwise regression analysis was performed to screen the factors influencing sleep chronotype and PSQI total score one week after surgery. Results The postoperative mRNA level of CLOCK was higher [1.38±1.23 vs.1.90±1.47;MD(95%CI):0.52(0.20-0.84),t=3.327,P=0.002] and the postoperative mRNA levels of CRY1 [1.56±1.50 vs.1.13±0.98;MD(95%CI):-0.43(-0.81--0.05),t=-2.319,P=0.028] and PER2 [0.82±0.63 vs.0.50±0.31;MD(95%CI):-0.33(-0.53--0.12),t=-3.202,P=0.003] were lower than the preoperative levels.One week after surgery,the patients presented advanced sleep chronotype [3∶03±0∶59 vs.2∶42±0∶37;MD(95%CI):-21(-40--1),t=-2.172,P=0.038],shortened sleep latency [(67±64)min vs.(37±21)min;MD(95%CI):-30.33(-55.28--5.39),t=-2.487,P=0.019],lengthened sleep duration [(436±83)min vs.(499±83)min;MD(95%CI):62.80(26.93-98.67),t=3.581,P=0.001],increased sleep efficiency [(87.59±10.35)% vs.(92.98±4.27)%;MD(95%CI):5.39(1.21-9.58),t=2.636,P=0.013],decreased sleep quality score [1.13±0.78 vs.0.80±0.71;MD(95%CI):-0.33(-0.62--0.05),t=-2.408,P=0.023],and declined PSQI total score [6.60±3.17 vs.4.03±2.58;MD(95%CI):-2.57(-3.87--1.27),t=-4.039,P<0.001].Body mass index(BMI)(B=-227.460,SE=95.475,t=-2.382,P=0.025),anesthesia duration(B=-47.079,SE=18.506,t=-2.544,P=0.017),and mRNA level of PER2(B=2815.804,SE=1080.183,t=2.607,P=0.015)collectively influenced the sleep chronotype,and the amount of anesthesia medicine(B=0.067,SE=0.028,t=2.385,P=0.024)independently influenced the PSQI one week after surgery. Conclusions Total intravenous anesthesia can improve sleep habits by advancing sleep chronotype.BMI,anesthesia duration,and mRNA level of PER2 collectively influence sleep chronotype one week after surgery.The amount of anesthesia medicine independently influences the PSQI total score one week after surgery.

Extend the benchmarking indel set by manual review using the individual cell line sequencing data from the Sequencing Quality Control 2 (SEQC2) project.

Accurate indel calling plays an important role in precision medicine. A benchmarking indel set is essential for thoroughly evaluating the indel calling performance of bioinformatics pipelines. A reference sample with a set of known-positive variants was developed in the FDA-led Sequencing Quality Control Phase 2 (SEQC2) project, but the known indels in the known-positive set were limited. This project sought to provide an enriched set of known indels that would be more translationally relevant by focusing on additional cancer related regions. A thorough manual review process completed by 42 reviewers, two advisors, and a judging panel of three researchers significantly enriched the known indel set by an additional 516 indels. The extended benchmarking indel set has a large range of variant allele frequencies (VAFs), with 87% of them having a VAF below 20% in reference Sample A. The reference Sample A and the indel set can be used for comprehensive benchmarking of indel calling across a wider range of VAF values in the lower range. Indel length was also variable, but the majority were under 10 base pairs (bps). Most of the indels were within coding regions, with the remainder in the gene regulatory regions. Although high confidence can be derived from the robust study design and meticulous human review, this extensive indel set has not undergone orthogonal validation. The extended benchmarking indel set, along with the indels in the previously published known-positive set, was the truth set used to benchmark indel calling pipelines in a community challenge hosted on the precisionFDA platform. This benchmarking indel set and reference samples can be utilized for a comprehensive evaluation of indel calling pipelines. Additionally, the insights and solutions obtained during the manual review process can aid in improving the performance of these pipelines.

A putative triradial macrofossil from the Ediacaran Jiangchuan Biota.

The late Ediacaran Jiangchuan biota, from the Dengying Formation in eastern Yunnan, is well-known for its diverse macroalgal fossils, opening a window onto eukaryotic-dominated ecosystems from the late Neoproterozoic of South China. Although multiple lines of evidence suggest that metazoans had already evolved by the late Ediacaran, animal fossils have not yet been formally described from this locality. Here, we report a putative disc-shaped macrofossil from the Jiangchuan biota, Lobodiscus tribrachialis gen. et sp. nov. This specimen shows the triradial symmetry characteristic of trilobozoans, a group of Ediacaran macrofossils previously documented in Australia and Russia. Lobodiscus could record the youngest known occurrence of trilobozoans, strengthening taxonomic and ecological continuities between the Ediacaran "White Sea" and "Nama" assemblages. Our findings may expand the known paleogeographical distribution of trilobozoans and provide data for Ediacaran biostratigraphic correlations across the Yangtze block and globally, helping to track the diversification of early metazoan-grade organisms.

Simultaneous detection of norepinephrine and 5-hydroxytryptophan using poly-alizarin/multi-walled carbon nanotubes-graphene modified carbon fiber microelectrode array sensor.

Multi-walled carbon nanotubes, graphene and alizarin polymer composites coated carbon fiber microelectrode array sensor (p-AZ/MWCNT-GR/CFMEA) was constructed and used for the simultaneous detection of norepinephrine (NE) and 5-hydroxytryptophan (5-HT). The morphology and structural characteristics of sensor are characterized using scanning electron microscopy, energy dispersive spectroscopy and X-ray diffraction. Its electrochemical behavior has been studied with cyclic voltammetry and electrochemical impedance spectroscopy. The sensor exhibits excellent electrochemical activity for the oxidation of NE and 5-HT, two well separated oxidation peaks with the peak potential difference of 220 mV are observed on the cyclic voltammogram. NE and 5-HT both show two electrons and two protons electrochemical reaction on the p-AZ/MWCNT-GR/CFMEA. Under the optimized experiment conditions, the linear ranges of the sensor for NE and 5-HT are 0. 08- 8 µM and 0. 1-20 µM with detection limits of 4. 22 nM and 14. 2 nM (S/N = 3), respectively. In addition, the microsensor array show good reproducibility, stability and selectivity for the determination of NE and 5-HT. Finally, the p-AZ/MWCNT-GR/CFMEA is applied to the simultaneous detection of NE and 5-HT in human serum samples and macrophages.

Degradation of Ciprofloxacin in Water by Magnetic-Graphene-Oxide-Activated Peroxymonosulfate.

Antibiotics are extensively applied in the pharmaceutical industry, while posing a tremendous hazard to the ecosystem and human health. In this study, the degradation performance of ciprofloxacin (CIP), one of the typical contaminants of antibiotics, in an oxidation system of peroxymonosulfate (PMS) activated by magnetic graphene oxide (MGO) was investigated. The effects of the MGO dosage, PMS concentration and pH on the degradation of CIP were evaluated, and under the optimal treatment conditions, the CIP degradation rate was up to 96.5% with a TOC removal rate of 63.4%. A kinetic model of pseudo-secondary adsorption indicated that it involves an adsorption process with progressively intensified chemical reactions. Furthermore, the MGO exhibited excellent recyclability and stability, maintaining strong catalytic activity after three regenerative cycles, with a CIP removal rate of 87.0%. EPR and LC-MS experiments suggested that •OH and SO4-• generated in the MGO/PMS system served as the main reactants contributing to the decomposition of the CIP, whereby the CIP molecule was effectively destroyed to produce other organic intermediates. Results of this study indicate that organic pollutants in the aqueous environment can be effectively removed in the MGO/PMS system, in which MGO has excellent catalytic activity and stabilization for being recycled to avoid secondary pollution, with definite research value and application prospects in the field of water treatment.

[Inhibitory Effects and Mechanisms of Three Benzodiazepines on Helicobacter pylori].

Objective To explore the inhibitory effects and mechanisms of benzodiazepines on Helicobacter pylori (Hp).Methods The Hp international standard strain ATCC43504 was treated with benzodiazepines diazepam,midazolam,and remimazolam,respectively.The treatments with amoxicillin and clarithromycin were taken as the positive controls,and that with water for injection as the negative control.The inhibition zone of each drug was measured by the disk diffusion method.The minimum inhibitory concentration(MIC)and minimum bactericidal concentration(MBC)of each drug against Hp were determined.Hp suspension was configured and treated with diazepam and midazolam,respectively.The bacterial suspension without drug added was used as the control group.The concentration of K+ in each bacterial suspension was measured by an automatic biochemical analyzer before drug intervention(T0)and 1(T1),2(T2),3(T3),4(T4),5(T5),6(T6),and 7 h(T7)after intervention.Hp urease was extracted and treated with 1/2 MIC diazepam,1 MIC diazepam,2 MIC diazepam,1/2 MIC midazolam,1 MIC midazolam,2 MIC midazolam,1 mg/ml acetohydroxamic acid,and water for injection,respectively.The time required for the rise from pH 6.8 to pH 7.7 in each group was determined by the phenol red coloring method.Results The inhibition zones of diazepam,midazolam,remimazolam,amoxicillin,clarithromycin,and water for injection against Hp were 52.3,42.7,6.0,72.3,60.8,and 6.0 mm,respectively.Diazepam and midazolam showed the MIC of 12.5 µg/ml and 25.0 µg/ml and the MBC of 25 µg/ml and 50 µg/ml,respectively,to Hp.The concentrations of K+ in the diazepam,midazolam,and control groups increased during T1-T7 compared with those at T0(all P<0.01).The concentration of K+ in diazepam and midazolam groups during T1-T4 was higher than that in the control group(all P<0.01).The time of inhibiting urease activity in the 1/2 MIC diazepam,1 MIC diazepam,2 MIC diazepam,1/2 MIC midazolam,1 MIC midazolam,and 2 MIC midazolam groups was(39.86±5.11),(36.52±6.65),(38.58±4.83),(39.25±6.19),(36.36±4.61),and(35.81±6.18)min,respectively,which were shorter than that in the acetohydroxamic acid group(all P<0.01)and had no significance differences from that in the water for injection group(all P>0.05).Conclusion Diazepam and midazolam exerted inhibitory effects on Hp,which may be related to the cleavage of Hp cells rather than inhibiting urease.

Enhanced Carrier Dynamics of CsPbBr3 Nanocrystals Enabled by Short-Ligand Ethanedithiol for Efficient Photoelectrocatalytic Photoanodes.

Photoelectrochemical (PEC) water splitting is a potential solution for a low-carbon society and clean energy storage due to its ability to produce hydrogen and oxygen. However, the slow oxidation half-reaction of the process has limited its overall efficacy, necessitating the development of an efficient photoanode. Colloidal CsPbBr3 nanocrystals (NCs) have been identified as promising candidates due to their high light absorption and valence band position. However, the presence of the electrical insulator, long-chain oleate molecules, on the surface of the CsPbBr3 NCs has hindered efficient charge carrier separation and transport. To solve this problem, short-chain 1,2-ethanedithiol (EDT) ligands were used to replace the oleate ligands on the surface of the CsPbBr3 NCs through a solid-state ligand exchange method. This resulted in a reduction of the nanocrystal spacing and a cross-linking reaction, which improved the photogenerated carrier separation and transport while still passivating the dangling bonds on the CsPbBr3 NC surface. Ultimately, this led to a remarkable photocurrent density of 3.34 mA cm-2 (1.23 VRHE), which was 5.2 times higher than that of the pristine oleate-CsPbBr3 NC (0.64 mA cm-2)-based device. This work presents an efficient way of developing inorganic lead halide perovskite colloidal nanocrystal-based photoanodes through surface ligand engineering.

Pan­cancer analysis identified ARHGAP23 as a potential biomarker for pancreatic adenocarcinoma.

Rho GTPASE-activating protein 23 (ARHGAP23) is known to activate RHO-GTPase and has an important role in the infiltration and metastasis of tumors. Although previous studies suggested its involvement in certain human cancers, its role in pan-cancer remains unclear. In the present study, the expression, prognosis and potential functions of ARHGAP23 in pan-cancer were evaluated through various public databases such as Human Protein Atlas, Tumor IMmune Estimation Resource, Gene Set Co-Expression Analysis, Gene Expression Profiling Interactive Analysis, cBio Cancer Genomics Portal, Tumor-Immune System Interactions Database (TISIDB) and others. Through these data combined with a variety of biological information analysis methods, the potential role of ARHGAP23 as a carcinogenic gene was explored in the present study. The present analysis revealed that ARHGAP23 expressed abnormalities in >10 tumors, which was associated with differences in prognosis. Furthermore, the findings of the present study indicated that ARHGAP23 is associated with DNA methylation and multiple immune cell infiltrations in these tumors. ARHGAP23 expression was related to clinical prognosis, DNA methylation and immune infiltration. These findings support the potential of ARHGAP23 as a prognostic biomarker and a molecular target for cancer treatment.

A Plain Language Summary to learn about relugolix combination therapy for the treatment of pain associated with endometriosis.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of research studies (known as clinical trials) called SPIRIT 1 and SPIRIT 2. The SPIRIT 1 and SPIRIT 2 studies compared how well a medicine called relugolix combination therapy worked in relieving pain in women with moderate to severe endometriosis compared to a placebo, a pill with no active medication. Endometriosis occurs when tissue similar to what normally lines the uterus grows in other places, such as the ovaries, fallopian tubes, and bowels. WHAT WERE THE RESULTS?: Researchers looked at 1261 adult women with moderate to severe endometriosis. Randomly, 420 (33%) of these women were assigned to relugolix combination therapy, 420 (33%) were assigned to delayed relugolix combination therapy (relugolix alone first and then relugolix combination therapy for the remainder of the study), and 421 (33%) were assigned to placebo. The SPIRIT 1 and SPIRIT 2 studies showed that more women taking relugolix combination therapy (75% from SPIRIT 1 and 75% from SPIRIT 2) for 24 weeks had both less pelvic or groin pain during menstrual periods from endometriosis and no need for more pain medicines than women who took placebo (27% from SPIRIT 1 and 30% from SPIRIT 2). The SPIRIT 1 and SPIRIT 2 studies also showed that more women taking relugolix combination therapy (59% from SPIRIT 1 and 66% from SPIRIT 2) for 24 weeks had both less pelvic or groin pain between menstrual periods from endometriosis and no need for more pain medicines than women who took placebo (40% from SPIRIT 1 and 43% from SPIRIT 2). Women taking relugolix combination therapy had less pelvic or groin pain during and between menstrual periods within 4 weeks of starting the medicine. The most common side effects were headaches, the common cold, and hot flushes or feeling hot among women taking relugolix combination therapy, delayed relugolix combination therapy, and placebo. Relugolix combination therapy was considered safe for those with no major medical problems. Women taking relugolix combination therapy had little to no loss of bone mineral density (a way of knowing how strong bones are) after 24 weeks of treatment. WHAT DO THE RESULTS OF THESE STUDIES TELL US?: Women with moderate to severe endometriosis taking relugolix combination therapy had much less pain from endometriosis than women taking placebo. Clinical Trial Registration: NCT03204318 (SPIRIT-1); NCT03204331 (SPIRIT-2) (ClinicalTrials.gov).