Search

Background: Although selpercatinib has shown clinical benefits for rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC), its cost-effectiveness requires further evaluation., Aim: This study aimed to evaluate the cost-effectiveness of selpercatinib versus chemotherapy and pembrolizumab in the first-line treatment of RET fusion-positive NSCLC from the perspective of the United States (US) payer., Method: A partitioned survival model was developed based on data from the LIBRETTO-431 trial. Cost and utility values for the health state were obtained from database data or published literature. The measured outcomes included quality-adjusted life-years (QALYs) and the incremental cost-effectiveness ratio (ICER). One-way sensitivity analysis and probabilistic sensitivity analyses (PSA) were conducted to assess the uncertainty of the model., Results: Selpercatinib increased QALYs in patients with RET fusion-positive NSCLC by 0.90 compared to chemotherapy plus pembrolizumab, with an additional cost of $542,517.45, resulting in an ICER of $603,286.49/QALY, which exceeded the willingness-to-pay (WTP) threshold ($150,000) in the US. One-way sensitivity analysis suggested that the utility of progressed disease, the utility of progression-free survival, the price of selpercatinib, the discount, the price of pemetrexed, and the price of pembrolizumab had the greatest influence on the cost- effectiveness analysis process. In the PSA, 99.9% of the scatter points were distributed above the US WTP threshold of $150,000., Conclusion: From the perspective of the US payer, selpercatinib is not cost-effective compared to chemotherapy and pembrolizumab for first-line treatment in patients with RET fusion-positive NSCLC., Competing Interests: Conflicts of interest All of the authors have indicated that they have no conflicts of interest with regard to the content of the article. This manuscript is original and has not been previously published, nor has it been simultaneously submitted to any other journal., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Psychologists in faculty affairs/faculty development (FAFD) roles can contribute to faculty vitality in academic health centers (AHCs) and mitigate barriers to advancement and retention. We describe a novel psychologist-led consultation service within an Office for Faculty Success (OFS) to support faculty across their career trajectories. We used 5 years of consultation data including faculty demographics, presenting concerns, and post-consultation evaluation data on consultation satisfaction and perceived benefits to examine trends and demographic group differences in consultation frequency, presenting concerns, and perceived benefits. From 2018 to 2023, 434 individuals presented for 683 consultations. Promotion in rank was the most frequent presenting concern. Women and racially/ethically minoritized faculty were found to present more frequently for repeat consultations, for concerns related to careers negotiation and advancement, and for intersectionality issues specific to gender and/or racial minority identities. From years one to five, there was a 93% increase in number of annual consultations performed and users were highly satisfied with the service (3.86/4). The consultation service is a unique, highly acceptable addition to interventions focused on career satisfaction and retention for AHC faculty, especially for women, early career, and minoritized faculty, and can serve as a model for other institutions., Competing Interests: Declarations Conflict of interest Lara M. Stepleman, Taylor M. Coleman, Jack Brady, Hanah Yi, Lisa Leggio, Danielle Zimmerman and William V. McCall have no conflicts of interest to declare that are relevant to the content of this article. Ethics Approval This study was approved as an exempt study by the Institutional Review Board at Augusta University. Consent for Publication Not applicable. Human and Animal Rights This study was approved as an exempt study by the Institutional Review Board at Augusta University., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Although amivantamab has shown clinical benefits for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) exon 20 insertions, its cost-effectiveness requires further investigation., Aim: To evaluate the cost-effectiveness of amivantamab plus chemotherapy for the treatment of NSCLC patients with EGFR exon 20 insertions from the United States payer perspective., Method: A partitioned survival model was developed based on the data from the PAPILLON trial. Costs were derived from the pricing files of Medicare and Medicaid Services and published literature, and utility values were derived from previous studies. A 3% annual discount rate was applied to both costs and outcomes. The primary outcome was the incremental cost-effectiveness ratio (ICER). One-way sensitivity analysis, probabilistic sensitivity analysis and scenario analysis, were conducted to test the model stability., Results: Amivantamab plus chemotherapy yielded an additional 1.12 quality-adjusted life years (QALYs) while increasing costs by $483,769.50 relative to the chemotherapy regimen, leading to an ICER of $432,401.16/QALY. The combination of amivantamab with chemotherapy was not cost effective at a threshold of $150,000/QALY. In the scenario analysis, the results showed that the ICERs were $263,680.69/QALY and $418,416.35/QALY when different utility values and 10-year time horizons were adopted, respectively. For PSA, the probability that amivantamab plus chemotherapy would be cost-effective was 0% if the willingness-to-pay (WTP) threshold was $150,000/QALY., Conclusion: Amivantamab plus chemotherapy is unlikely to be a cost-effective option for NSCLC patients with EGFR exon 20 insertions. Reducing the cost of amivantamab may produce favorable economic outcomes., Competing Interests: Conflicts of interest All of the authors have indicated that they have no conflicts of interest with regard to the content of the article. This manuscript is original and has not been previously published, nor has it been simultaneously submitted to any other journal., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

There is a chronic inflammation in PCOS patients, which is correlated with the pathogenesis of PCOS. IL-18 and IL-18BP are related with some inflammatory diseases, while less explored in PCOS. Whether IL-18BP could be a potential drug of PCOS remains unknown.IL-18 and testosterone levels were evaluated in serum of 10 non-PCOS control patients and 20 PCOS patients. Female C57/BL6 mice were gavaged with letrozole to induce PCOS mouse model and IL-18 level was evaluated in the serum of PCOS mouse model, and IL-18 is intraperitoneally injected in female mice, IL-18BP is intraperitoneally injected in the PCOS mice models. Then the body weights, estrous cycles, reproductive hormones and morphology of ovaries were analyzed. The level of ovarian chronic inflammation, fibrosis and endoplasmic reticulum (ER) stress are evaluated.IL-18 levels are increased in the serum of PCOS patients and PCOS mice models respectively. The serum DHEAS, iWAT weight and adipocyte size were increased in IL-18 group compared to the control group (P < 0.05). In the PCOS mouse model treated with IL-18BP, the body weight and serum LH/FSH ratio was decreased compared to the PCOS group (P < 0.05). The expression levels of inflammatory factors and fibrosis-related genes, the expression level of endoplasmic reticulum stress-related genes, and the ROS positive area of ovarian tissue was decreased (P < 0.05).IL-18 is involved in inducing PCOS phenotypes, while IL-18BP relieves PCOS phenotypes by alleviating ovarian chronic inflammation, fibrosis and ER stress in PCOS mice., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Introduction: Orthodox Jewish women face unique social, cultural, and religious factors that may influence uptake of BRCA1/2 genetic testing. We examined the impact of a web-based decision aid (DA) on BRCA1/2 genetic testing intention/completion among Orthodox Jewish women. We conducted a single-arm pilot study among 50 Orthodox Jewish women who were given access to a web-based DA entitled RealRisks and administered serial surveys at baseline and 1 and 6 months after exposure to the DA. Descriptive statistics were conducted for baseline characteristics and study measures. Comparisons were made to assess changes in study measures over time. Fifty Orthodox Jewish women enrolled in the study with a mean age of 43.9 years (standard deviation [SD] 14.6), 70% Modern Orthodox, 2% with personal history of breast cancer, and 68% and 16% with a family history of breast or ovarian cancer, respectively. At baseline, 27 (54%) participants intended to complete genetic testing. Forty-three participants (86%) completed RealRisks and the 1-month survey and 38 (76%) completed the 6-month survey. There was a significant improvement in BRCA1/2 genetic testing knowledge and decrease in decisional conflict after exposure to the DA. At 1 month, only 20 (46.5%) completed or intended to complete genetic testing (p = 0.473 compared to baseline). While the DA improved genetic testing knowledge and reduced decisional conflict, genetic testing intention/completion did not increase over time. Future interventions should directly address barriers to BRCA1/2 genetic testing uptake and include input from leaders in the Orthodox Jewish community., Gov Id: NCT03624088 (8/7/18)., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Osteoarthritis (OA), a prevalent chronic disease among the elderly, presents a complex pathogenesis and currently lacks effective treatment. Traditional observational studies are time-consuming, labor-intensive, susceptible to confounding factors, and cannot establish causal relationships. Mendelian randomization (MR) analysis, leveraging genetic variation to assess causal associations between exposures and outcomes, offers a cost-effective and efficient alternative. Over the past decade, large-scale genome-wide association studies have identified numerous genetic variants linked to OA risk factors, facilitating MR study design. In this review, we systematically identified 52 MR studies meeting specific criteria and evaluated their quality, exploring the impact of lifestyle, nutrition, comorbidities, circulating metabolites, plasma proteins, and other health factors on OA risk. We discuss the results and potential mechanisms of MR findings, addressing conflicting evidence based on existing literature and our prior research. With the ongoing expansion of genome-wide association data, we anticipate MR's role in future OA studies to broaden, particularly in drug development research using targeted MR approaches. We thus aim for this paper to offer valuable insights for researchers and clinicians in related fields., (© 2024. The Author(s).)

Background: Cervical cancer is a prevalent malignancy and an important health concern worldwide. Recent research has highlighted the potential impact of metabolic factors, such as hyperlipidemia and diabetes, on cancer progression, increased mortality, and patient outcomes. However, insufficient data have been reported regarding their relationship with cervical cancer. This study aimed to investigate the relationships between metabolic disorders, including dyslipidemia, dysglycemia, and metabolic syndrome, and survival in patients with cervical cancer., Methods: We retrospectively analyzed demographic information, clinical characteristics, and metabolic health indicators of patients with cervical cancer. Patients were categorized into groups based on specific metabolic conditions: high triglyceride, high low-density lipoprotein, high cholesterol, and diabetes groups. Additionally, the presence of metabolic syndrome and other metabolic comorbidities was recorded. The log-rank test was used to compare survival rates between different patient groups and identify associated risk factors. Survival curves generated via the Cox proportional hazards model were used to evaluate the associations between metabolic parameters and survival., Results: The Cox proportional hazards model was used to analyze data from 840 patients with cervical cancer between 28 and 72 years old who underwent surgery. The hazard ratio (HR) of mortality was 1.804 (95% CI 1.394-2.333, p < 0.001) in the high-density lipoprotein group, 0.758 (95% CI 0.558 to 1.030, p < 0.001) in the high-triglyceride group, 1.794 (95% CI 1.304-2.470, p < 0.001) in the high low-density lipoprotein group, and 0.011 (95% CI 0.005-0.025, p < 0.001) in the diabetes group. These factors were significantly associated with reduced survival in patients with cervical cancer, and these associations persisted after adjusting for age, cancer stage, treatment type, and the presence of metabolic syndrome or other comorbidities., Conclusion: This study highlights the importance of metabolic health and the significance of controlling metabolic disorders, including hyperlipidemia, diabetes, and metabolic syndrome, to improve survival outcomes in patients with cervical cancer. Future research should explore the impact of managing multiple metabolic conditions on the prognosis of these patients., (© 2024. The Author(s).)

Purpose: Major pathological response (MPR) has become a surrogate endpoint for overall survival (OS) in non-small cell lung cancer (NSCLC) after neoadjuvant therapy, however, the prognostic histologic features and optimal N descriptor after neoadjuvant therapy are poorly defined., Methods: We retrospectively analyzed data from 368 NSCLC patients who underwent surgery after neoadjuvant chemotherapy (NAC) from January 2010 to December 2020. The percentage of residual viable tumors in the primary tumor, lymph nodes (LN), and inflammation components within the tumor stroma were comprehensively reviewed. The primary endpoint was OS., Results: Of the 368 enrolled patients, 12.0% (44/368) achieved MPR in the primary tumor, which was associated with significantly better OS (HR, 0.36 0.17-0.77, p = 0.008) and DFS (HR = 0.59, 0.36-0.92, p = 0.038). In patients who did not have an MPR, we identified an immune-activated phenotype in primary tumors, characterized by intense tumor-infiltrating lymphocyte or multinucleated giant cell infiltration, that was associated with similar OS and DFS as patients who had MPR. Neoadjuvant pathologic grade (NPG), consisting of MPR and immune-activated phenotype, identified 30.7% (113/368) patients that derived significant OS (HR 0.28, 0.17-0.46, p < 0.001) and DFS (HR 0.44, 0.31-0.61, p < 0.001) benefit from NAC. Moreover, the combination of NPG and the number of positive LN stations (nS) in the multivariate analysis had a higher C-index (0.711 vs. 0.663, p < 0.001) than the ypTNM Stage when examining OS., Conclusion: NPG integrated with nS can provide a simple, practical, and robust approach that may allow for better stratification of patients when evaluating neoadjuvant chemotherapy in clinical practice., (© 2024. Springer Nature Switzerland AG.)

Purpose: Previous studies assessed different components of telemedicine management pathway for OSA instead of the whole pathway. This randomized, controlled, and non-inferiority trial aimed to assess whether telemedicine management is clinically inferior to in-person care in China., Methods: Adults suspected of OSA were randomized to telemedicine (web-based questionnaires, self-administered home sleep apnea test [HSAT], automatically adjusting positive airway pressure [APAP], and video-conference visits) or in-person management (paper questionnaires, in-person HSAT set-up, APAP, and face-to-face visits). Participants with an apnea-hypopnea index (AHI) ≥ 15 events/hour received APAP for 3 months. The non-inferiority analysis was based on the change in Functional Outcomes of Sleep Questionnaire (FOSQ) score and APAP adherence. Cost-effectiveness analysis was performed., Results: In the modified intent-to-treat analysis set (n = 111 telemedicine, 111 in-person), FOSQ scores improved 1.73 (95% confidence interval [CI], 1.31-2.14) points with telemedicine and 2.05 (1.64-2.46) points with in-person care. The lower bound of the one-sided 95% non-inferiority CI for the difference in change between groups of - 0.812 was larger than the non-inferiority threshold of - 1. APAP adherence at 3 months was 243.3 (223.1-263.5) minutes/night for telemedicine and 241.6 (221.3-261.8) minutes/night for in-person care. The lower bound of the one-sided 95% non-inferiority CI of - 22.2 min/night was higher than the non-inferiority delta of - 45 min/night. Telemedicine had lower total costs than in-person management (CNY 1482.7 ± 377.2 vs. 1912.6 ± 681.3; p < 0.0001), driven by patient costs, but no significant difference in QALYs., Conclusions: Functional outcomes and adherence were not clinically inferior in patients managed by a comprehensive telemedicine approach compared to those receiving in-person care in China., Clinical Trial Registration: https://www.chictr.org.cn , Registration number ChiCTR2000030546. Retrospectively registered on March 06, 2020., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: TRPV1 is a nonselective Ca 2+ channel protein that is widely expressed and plays an important role during the occurrence and development of many cancers. Activation of TRPV1 channels can affect tumour progression by regulating proliferation, apoptosis and migration. Some studies have also shown that activating TRPV1 can affect tumour progression by modulating tumour immunity. However, the effects of TRPV1 on the development of non-small cell lung cancer (NSCLC) have not been explored clearly., Method: The Cancer Genome Atlas (TCGA) database and spatial transcriptomics datasets from 10 × Genomics were used to analyze TRPV1 expression in various tumour tissues. Cell proliferation and apoptosis were examined by cell counting kit 8 (CCK8), colony formation, and flow cytometry. Immunohistochemistry, qPCR, and western blotting were used to determine the mRNA and protein expression levels of TRPV1 and other related molecules. Tumour xenografts in BALB/C and C57BL/6J mice were used to determine the effects of TRPV1 on NSCLC development in vivo. Neurotransmitter content was examined by LC-MS/MS, ELISA and Immunohistochemistry. Immune cell infiltration was assessed by flow cytometry., Results: In this study, we found that TRPV1 expression was significantly upregulated in NSCLC and that patients with high TRPV1 expression had a poor prognosis. TRPV1 knockdown can significantly inhibit NSCLC proliferation and induce cell apoptosis through Ca 2+ -IGF1R signaling. In addition, TRPV1 knockdown resulted in increased infiltration of CD4 + T cells, CD8 + T cells, GZMB + CD8 + T cells and DCs and decreased infiltration of immunosuppressive MDSCs in NSCLC. In addition, TRPV1 knockout effectively decreased the expression of M2 macrophage markers CD163 and increased the expression of M1-associated, costimulatory markers CD86. Knockdown or knockout of TRPV1 significantly inhibit tumour growth and promoted an antitumour immune response through supressing γ-aminobutyric acid (GABA) secretion in NSCLC., Conclusion: Our study suggests that TRPV1 acts as a tumour promoter in NSCLC, mediating pro-proliferative and anti-apoptotic effects on NSCLC through IGF1R signaling and regulating GABA release to affect the tumour immune response., (© 2023. Springer Nature Switzerland AG.)

Pre-eclampsia (PE) is thought to be related to placental dysfunction, particularly poor extravillous trophoblast (EVT) invasion and migration abilities. However, the pathogenic mechanism is not fully understood. This article describes the impact of the cyclic adenosine monophosphate(cAMP) signaling pathway on EVT behavior, focusing on EVT proliferation, invasion, and migration. Here, we used the HTR8/SV-neo cell line to study human EVT function in vitro. HTR8/SV-neo cells were treated with different concentrations of forskolin (cAMP pathway-specific agonist) to alter intracellular cAMP levels, and dimethyl sulfoxide (DMSO) was used as the control. First, a cAMP assay was performed to measure the cAMP concentration in HTR8/SV-neo cells treated with different forskolin concentrations, and cell proliferation was assessed by constructing cell growth curves and assessing colony formation. Cell invasion and migration were observed by Transwell experiments, and intracellular epithelial-mesenchymal transition (EMT) marker expression was evaluated by quantitative real-time polymerase chain reaction (qPCR) and Western blotting (WB). According to our research, the intracellular cAMP levels in HTR8/SV-neo cells were increased in a dose-dependent manner, and HTR8/SV-neo cell proliferation, invasion and migration were significantly enhanced. The expression of EMT and angiogenesis markers was upregulated. Additionally, with the increase in intracellular cAMP levels, the phosphorylation of intracellular mitogen-activated protein kinase (MAPK) signaling pathway components was significantly increased. These results suggested that the cAMP signaling pathway promoted the phosphorylation of MAPK signaling components, thus enhancing EVT functions, including proliferation, invasion, and migration, and to a certain extent, providing a novel direction for the treatment of PE patients., (© 2023. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Copper ionophore NSC319726 has attracted researchers' attention in treating diseases, particularly cancers. However, its potential effects on male reproduction during medication are unclear. This study aimed to determine whether NSC319726 exposure affected the male reproductive system. The reproductive toxicity of NSC319726 was evaluated in male mice following a continuous exposure period of 5 weeks. The result showed that NSC319726 exposure caused testis index reduction, spermatogenesis dysfunction, and architectural damage in the testis and epididymis. The exposure interfered with spermatogonia proliferation, meiosis initiation, sperm count, and sperm morphology. The exposure also disturbed androgen synthesis and blood testis barrier integrity. NSC319726 treatment could elevate the copper ions in the testis to induce cuproptosis in the testis. Copper chelator rescued the elevated copper ions in the testis and partly restored the spermatogenesis dysfunction caused by NSC319726. NSC319726 treatment also decreased the level of retinol dehydrogenase 10 (RDH10), thereby inhibiting the conversion of retinol to retinoic acid, causing the inability to initiate meiosis. Retinoic acid treatment could rescue the meiotic initiation and spermatogenesis while not affecting the intracellular copper ion levels. The study provided an insight into the bio-safety of NSC319726. Retinoic acid could be a potential therapy for spermatogenesis impairment in patients undergoing treatment with NSC319726., (© 2024. The Author(s).)

Polypeptide N-Acetylgalactosaminyltransferase (GALNTs) are critical enzymes that initiate mucin type-O glycosylation, and are closely associated with the occurrence and development of multiple cancers. However, the significance of GALNT2 in clear cell renal cell carcinoma (ccRCC) progression remains largely undetermined. Based on public multi-omics analysis, GALNT2 was strongly elevated in ccRCC versus adjoining nontumor tissues, and it displayed a relationship with poor overall survival (OS) of ccRCC patients. In addition, GALNT2 over-expression accelerated proliferation of renal cancer cell (RCC) lines. In contrast, GALNT2 knockdown using shRNAs suppressed cell proliferation, and this was rescued by LATS2 knockdown. Similarly, GALNT2 deficiency enhanced p-LATS2/LATS2 expression. LATS2 is activated by phosphorylation (p-LATS2) and, in turn, phosphorylate the downstream substrate protein YAP. Phosphorylated YAP (p-YAP) stimulated its degradation and cytoplasmic retention, as it was unable to translocate to the nucleus. This resulted in reduced cell proliferation. Subsequently, we explored the upstream miRNAs of GALNT2. Using dual luciferase reporter assay, we revealed that miR-139-5p interacted with the 3' UTR of GALNT2. Low miR-139-5p expression was associated with worse ccRCC patient outcome. Based on our experiments, miR-139-5p overexpression inhibited RCC proliferation, and this phenotype was rescued by GALNT2 overexpression. Given these evidences, the miR-139-5p-GALNT2-LATS2 axis is critical for RCC proliferation, and it is an excellent candidate for a new therapeutic target in ccRCC., (© 2024. The Author(s).)

Objective: The present study investigated the predictive diseases progression value of preoperative fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with local advanced cervical cancer (LACC)., Methods: In total, 267 patients [median age 58 (range: 27-85) years old] with LACC underwent 18 F-FDG PET/CT prior to any treatment. The maximum standardized uptake values (SUV max ), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary lesion and metastatic lymph nodes were measured on PET/CT and correlated with clinicopathological features and progression-free survival (PFS)., Results: The median follow-up was 36.52 (range: 3.09-61.29) months. During the observation period, 80 (30.0%) patients exhibited disease progression. Univariate analysis showed that FIGO stage, concurrent chemoradiotherapy (CRT), serum level of carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC-Ag), primary tumor MTV (pMTV) and TLG (pTLG), lymph nodes SUV max (nSUV max ) and TLG (nTLG), and total metabolic activity (sMTV, sTLG) were associated with PFS. nSUV max  ≥ 5.29, CEA ≥ 7.11 ng/ml and deficiency of concurrent CRT were independent risk factor for PFS (p = 0.006, p = 0.008, p = 0.014). The 3-year PFS for patients with high nSUV max were 42.2% compared to 56.3% for low nSUV max values., Conclusion: Pretreatment cervical and lymph nodes metabolic parameters were associated with PFS in patients with LACC., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Bladder cancer, predominantly affecting men, is a prevalent malignancy of the urinary system. Although platinum-based chemotherapy has demonstrated certain enhancements in overall survival when compared to surgery alone, the efficacy of treatments is impeded by the unfavorable side effects of conventional chemotherapy medications. Nonetheless, immunotherapy exhibits potential in the treatment of bladder cancer., Methods: To create an immune-associated prognostic signature for bladder cancer, bioinformatics analyses were performed utilizing The Cancer Genome Atlas (TCGA) database in this study. By identifying differential gene expressions between the high-risk and low-risk groups, a potential therapeutic drug was predicted using the Connectivity Map database. Subsequently, the impact of this drug on the growth of T24 cells was validated through MTT assay and 3D cell culture techniques., Results: The signature included 1 immune-associated LncRNA (NR2F1-AS1) and 16 immune-associated mRNAs (DEFB133, RBP7, PDGFRA, CGB3, PDGFD, SCG2, ADCYAP1R1, OPRL1, PGR, PSMD1, TANK, PRDX1, ADIPOR2, S100A8, AHNAK, EGFR). Based on the assessment of risk scores, the patients were classified into cohorts of low-risk and high-risk individuals. The cohort with low risk demonstrated a considerably higher likelihood of survival in comparison to the group with high risk. Furthermore, variations in immune infiltration were noted among the two categories. Cephaeline, a possible medication, was discovered by analyzing variations in gene expression. It exhibited promise in suppressing the viability and growth of T24 bladder cancer cells., Conclusion: The novel predictive pattern allows for efficient categorization of patients with bladder cancer, enabling focused and rigorous treatment for those expected to have a worse prognosis. The discovery of a possible curative medication establishes a basis for forthcoming immunotherapy trials in bladder cancer., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: Mice can develop arterial damage and even atherosclerosis under intermittent hypoxia (IH); however, the specific mechanism of arterial damage induced by IH remains unclear. Hence, this research aimed to illustrate the underlying mechanism linking IH to arterial injury., Materials and Methods: The differential gene expression of the thoracic aorta under normoxia or IH mice was analyzed utilizing RNA sequencing. Furthermore, GO, KEGG pathway, and CIBERSORT analyses were carried out. For verification of the expression of candidate genes affected by IH, quantitative RT-qPCR (qRT-PCR) was conducted. Immunohistochemical (IHC) staining revealed immune cell infiltration in the thoracic aorta., Results: The thickness of the intima-media of the mouse aorta was increased, and the fiber structure was disordered under IH. Transcriptomics analysis showed that in the aorta, 1137 upregulated genes and 707 downregulated genes were affected by IH, significantly related to the activation of the immune system and cell adhesion. Furthermore, B cell infiltration around the aorta was observed under IH., Conclusions: IH might lead to structural changes in the aorta by activating the immune response and enhancing cell adhesion., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

To be able to formulate any plausible strategies for sustainability, it is critical to establish a clear understanding of the international metals trade system complexity and the consequences in emergent embodied carbon emissions (ECE). For this purpose, we proposed a two-layer framework based on the multi-regional input-output model for calculating ECE: the intermediate production and final consumption trade layers. The proposed framework model combines the construction of a clustering index system and conducting cluster analysis from both the regional and sectoral dimensions. It is shown that developed regions transfer carbon emissions to developing regions via metals trading. This happens especially in the intermediate production stage at a level of 1.35 times higher than the final consumption stage. Furthermore, the metal sector suffers the most from carbon transfers from manufacturing, with the most carbon emissions transferred to mining. Moreover, considering environmental and technological factors to cluster regions and sectors into four and three clusters. China and Russia are in a cluster under greater pressure to reduce emissions as compared to other nations. Also, the construction and manufacturing form a cluster that their reduction of carbon emissions will effectively reduce the ECE of the metal sector. As a result, policy implications for reducing carbon emissions are investigated for each cluster in the international trade of metals contributing to the ultimate goal of global sustainable development., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Key Message: A novel strong fertility restorer gene Rf12 for C-type cytoplasmic male sterility of maize was finely mapped on chromosome 2. Its best candidate gene Zm00001d007531 is predicted to encode a p-type PPR protein. The lack of strong restorer gene of maize CMS-C greatly limits its application in hybrid seed production. Therefore, the cloning of maize CMS-C novel strong restorer genes is necessary. In this study, a strong restorer line ZH91 for maize CMS-C was found, and the novel restorer gene named Rf12 in ZH91 had been mapped in a 146 kb physical interval on maize chromosome 2. Using the third-generation high-throughput sequencing (ONT), the whole genome sequence of ZH91 was got, and with integrating the annotation information of the reference genome B73&#95;RefGen&#95;v4 and B73&#95;RefGen&#95;v5, four candidate genes were predicted in ZH91 within the mapping region. Then using gene cloning, stranded specific RNA sequencing, qRT-PCR analysis and subcellular localization, Zm00001d007531 was identified as the most likely candidate gene of Rf12. Zm00001d007531 encodes a p-type PPR protein with 19 PPR motifs and targets mitochondria and chloroplast. Stranded specific RNA sequencing and qRT-PCR results both show that the expression of Zm00001d007531 between anthers of near-isogenic lines C478 Rf12Rf12 and C478 rf12rf12 was significantly difference in pollen mother cell stage. And the result of sequence alignment for Zm00001d007531 gene in 60 materials showed that there are twelve SNPs in CDS region of Zm00001d007531 were tightly linked to the fertility. The finding of a novel strong restorer germplasm resource ZH91 for maize CMS-C can greatly promote the application of maize CMS-C line in maize hybrid seeds production, and the identification of candidate gene Zm00001d007531 can accelerate the backcrossing process of maize CMS-C strong restorer gene Rf12 to some extent., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Intestinal microecology was closely related to immune regulation, but the related mechanism was still unclear. This study aimed to reveal how microorganisms improved immune response via casepase-3 and Bak of FAS/CD95 pathway. Bifidobacterium animalis F1-7 inhibited the melanoma B16-F10 cells in vitro effectively; had a potent anticancer effect of lung cancer mice; effectively improved the spleen immune index and CD3 + (75.8%) and CD8 + (19.8%) expression level; strengthened the phagocytosis of macrophages; inhibited the overexpression of inflammatory factors IL-6 (319.10 ± 2.46 pg/mL), IL-8 (383.05 ± 9.87 pg/mL), and TNF-α (2003.40 ± 11.42 pg/mL); and promoted the expression of anti-inflammatory factor IL-10 (406.00 ± 3.59 pg/mL). This process was achieved by promoting caspase-8/3 and BH3-interacting domain death agonist (Bid), Bak genes, and protein expression. This study confirmed the B. animalis F1-7 could act as an effective activator to regulate immune response by promoting the expression of caspase-8/3, Bid and Bak genes, and proteins and by activating the FAS/CD95 pathway. Our study provided a data support for the application of potentially beneficial microorganisms of B. animalis F1-7 as an effective activator to improve immunity., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Groundwater chemical composition can be changed due to long-term coal mining activities, but it was unclear how it was induced in Taiyuan Formation limestone (TFL) regarding the lack of relevant quantitative studies. The aim of this research is to improve understanding of the chemical composition changes in groundwater of L 4 limestone in the coal mining area based on the available hydrochemical and hydrodynamical reports and studies during the period 1978-2020. The systematical analysis of the groundwater composition and field allows to make the hydrogeological characterization with the relatively independent blocks by the factor groups "Planar division & Vertical zonation" and "High water pressure, Poor recharge & Little water inflow," which determines different hydrochemical types and high TDS concentration. The long-term groundwater drainage has caused the eastern and southern limestone aquifer to demonstrate a wide range of depression cones and depletion of groundwater resources, the majority areas were dewatered, and the karstification process changed significantly. An analysis of chemical compositions changes due to extensive permanent drainage of L 4 limestone water revealed the decrease in the TDS concentration. The solubility of calcite, dolomite, and gypsum changed, which resulted in the decreasing tendency of Ca 2+  + Mg 2+ ions. Evaporation and concentration were found to be the main factors determining the L 4 limestone water composition, whereas ion exchange was the primary factor for rock-water interaction. These findings are helpful for mine enterprises to take necessary measures for preventing and controlling the groundwater quality degradation from the extensive coalmine drainage., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Precise selection of patients who could benefit from immune checkpoint inhibitors (ICIs) is an important challenge for immunotherapy in lung cancer. POTEE (POTE Ankyrin Domain Family Member E) is a member of one primate-specific gene family which have been identified as cancer-related antigens and potential target for immunotherapy of cancer. Here, we investigated the correlation between POTEE mutation and the clinical outcome of ICIs treatment in non-small cell lung cancer (NSCLC). We merged three NSCLC cohorts (n = 165) to assess predictive value of POTEE mutation of immunotherapy efficacy in NSCLC. The prognostic analysis and the potential molecular mechanism exploration were conducted based on the data from The Cancer Genome Atlas (TCGA) database. In the merged cohort, patients with POTEE-mutation (POTEE-Mut) had a significantly higher objective response rate (ORR) (100% vs 27.7%; P < 0.001) and longer progression-free survival (PFS) (P = 0.001; HR 0.08; 95% CI 0.01 - 0.54) compared to patients with POTEE wild-type (POTEE-WT) in NSCLC. Also, patients with POTEE-Mut showed higher ORR (100% vs 27.2%; P < 0.001) and longer PFS (P = 0.001; HR 0.07; 95% CI 0.01 - 0.52) in lung adenocarcinoma (LUAD). POTEE mutation was significantly associated with higher tumor mutational burden (TMB) and higher neoantigen load (NAL), but not with PD-L1 expression in LUAD. Gene set enrichment analyses (GSEA) analysis revealed prominent enrichment of signatures related to DNA repair in POTEE-Mut group (P < 0.001) in LUAD. Our results indicate that POTEE mutation could serve as a potential predictive biomarker for ICIs in LUAD. However, prospective cohort studies are still needed for further validation., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Galactosidases are industrially important enzymes that hydrolyze galactosidic bonds in carbohydrates. Identifying new galactosidases with distinct functional characteristics is of paramount importance. In this study, we report the finding of a novel β-galactosidase PoβGal35A from the fungus Penicillium oxalicum. PoβGal35A belongs to the glycoside hydrolase family 35 (GH35), functions optimally at 70 °C and pH 5.0, and exhibits a specific high activity (191 ± 6.2 U/mg) towards pNPβgal. Ca 2+ , Fe 3+ and Ba 2+ ions enhance the activity of the enzyme, whereas Cu 2+ and Hg 2+ significantly reduce it. This enzyme releases galactose from β-1,3-galactan, β-1,4-galactan, β-1,6-galactan, as well as arabinogalactan from larchwood (LWAG). In addition, PoβGal35A acts synergistically with arabinosidase to degrade LWAG. These results suggest that PoβGal35A is a high activity exo-β-1,3/4/6-galactanase that can be used to establish glycan blocks in glycoconjugates, and thus provides a new tool for biotechnological applications., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Rapid and precise estimation of glycosylated serum protein (GSP) of human serum is of great importance for the treatment and diagnosis of diabetes mellitus. In this study, we propose a novel method for estimation of GSP level based on the combination of deep learning and time domain nuclear magnetic resonance (TD-NMR) transverse relaxation signal of human serum. Specifically, a principal component analysis (PCA)-enhanced one-dimensional convolutional neural network (1D-CNN) is proposed to analyze the TD-NMR transverse relaxation signal of human serum. The proposed algorithm is proved by accurate estimation of GSP level for the collected serum samples. Furthermore, the proposed algorithm is compared with 1D-CNN without PCA, long short-term memory network (LSTM) and some conventional machine learning algorithms. The results indicate that PCA-enhanced 1D-CNN (PC-1D-CNN) has the minimum error. This study proves that proposed method is feasible and superior to estimate GSP level of human serum using TD-NMR transverse relaxation signals., (© 2023. The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.)

Over the last decades, advanced oxidation processes (AOPs) have been widely used in surface and ground water pollution control. The heterogeneous electro-Fenton (EF) process has gained much attention due to its properties of high catalytic performance, no generation of iron sludge, and good recyclability of catalyst. As of October 2022, the cited papers and publications of EF are around 1.3 × 10 -5 and 3.4 × 10 -3 in web of science. Among the AOP techniques, the contaminant removal efficiencies by EF process are above 90% in most studies. Current reviews mainly focused on the mechanism of EF and few reviews comprehensively summarized heterogeneous catalysts and their applications in wastewater treatment. Thus, this review focuses on the current studies covering the period 2012-2022, and applications of heterogeneous catalysts in EF process. Two kinds of typical heterogeneous EF systems (the addition of solid catalysts and the functionalized cathode catalysts) and their applications for organic contaminants degradation in water are reviewed. In detail, solid catalysts, including iron minerals, iron oxide-based composites, and iron-free catalysts, are systematically described. Different functionalized cathode materials, containing Fe-based cathodes, carbonaceous-based cathodes, and heteroatom-doped cathodes, are also reviewed. Finally, emphasis and outlook are made on the future prospects and challenges of heterogeneous EF catalyst for wastewater treatments., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Oxidative damage is important in calcium oxalate (CaOx) stone development but occurs via multiple pathways. Studies have shown that klotho plays an essential role in ameliorating oxidative damage. This study aims to explore the role of klotho in CaOx stones and whether the underlying mechanism is related to the regulation of Keap1-Nrf2-ARE signaling., Methods: The levels of GSH, SOD, CAT, MDA, and ROS were examined by ELISA. The klotho, Bcl-2, caspase-3, Keap1, Nrf2, HO-1, and NQO1 mRNA levels were measured by qRT‒PCR, and their protein levels were detected by Western blotting. Renal tissue apoptosis was examined by TUNEL staining, and crystal cell adherence and apoptosis in HKC cells were assessed based on the Ca 2+ concentrations and by flow cytometry. The renal pathological changes and the adhesion of CaOx crystals in the kidneys were examined by hematoxylin-eosin and von Kossa staining, respectively., Results: We constructed a CaOx kidney stone model in vitro. By regulating the klotho gene, klotho overexpression inhibited the CaOx-induced promotion of crystal cell adherence and apoptosis in HKC cells, and these effects were reversed by klotho knockdown. Moreover, our in vivo assay demonstrated that klotho overexpression alleviated glyoxylate administration-induced renal oxidative damage, renal apoptosis, and crystal deposition in the kidneys of mice, and these effects were also associated with activation of the Keap1-Nrf2-ARE pathway., Conclusion: Klotho protein inhibits the oxidative stress response of HKC cells through the Keap1-Nrf2-ARE signaling pathway, reduces the apoptosis of and adhesion of CaOx crystals to HKC cells, and decreases the occurrence of CaOx kidney stones., Clinical Trial Registration: 20220304., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

With the awakening of environmental awareness, the importance of air quality to human health and the proper functioning of social mechanisms is becoming increasingly prominent. The low cost and high efficiency of catalytic technique makes it a natural choice for achieving deep air purification. Stainless steel alloys have demonstrated their full potential for application in a variety of catalytic fields. The diversity of 3D networks or fibrous structures increases the turbulence within the heterogeneous catalysis, balance the temperature distribution in the reaction bed and, in combination with a highly thermally conductive skeleton, avoid agglomeration and deactivation of the active components; corrosion resistance and thermal stability are adapted to highly endothermic/exothermic or corrosive reaction environments; oxide layers formed by bulk transition metals activated by thermal treatment or etching can significantly alter the physico-chemical properties between the substrate and active species, further improving the stability of stainless steel catalysts; suitable electronic conductivity can be applied to the electrothermal catalysis, which is expected to provide guidance for the reduction of intermittent emission exhausts and the storage of renewable energy. The current applications of stainless steel as catalyst or support in the air purification have covered soot particle capture and combustion, catalytic oxidation of VOCs, SCR, and air sterilization. This paper summarizes several preparation methods and presents the relationships between the preparation process and the activity, and reviews its application and the current status of research in atmospheric environmental management, proposing the advantages and challenges of the stainless steel-based catalysts., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Gold (Au) nanoparticles supported on certain platforms display highly efficient activity on nitroaromatics reduction. In this study, steam-activated carbon black (SCB) was used as a platform to fabricate Au/SCB composites via a green and simple method for 4-nitrophenol (4-NP) reduction. The obtained Au/SCB composites exhibit efficient catalytic performance in reduction of 4-NP (rate constant k app  = 2.1925 min -1 ). The effects of SCB activated under different steam temperature, Au loading amount, pH, and reaction temperature and NaBH 4 concentration were studied. The structural advantages of SCB as a platform were analyzed by various characterizations. Especially, the result of N 2 adsorption-desorption method showed that steam activating process could bring higher surface area (from 185.9689 to 249.0053 m 2 /g), larger pore volume (from 0.073268 to 0.165246 cm 3 /g), and more micropore for SCB when compared with initial CB, demonstrating the suitable of SCB for Au NP anchoring, thus promoting the catalytic activity. This work contributes to the fabrication of other supported metal nanoparticle catalysts for preparing different functional nanocomposites for different applications., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The purpose of this study was to investigate and compare the abilities of 1 H nuclear magnetic resonance (NMR) transverse relaxation constant time (T 2 ) and longitudinal relaxation constant time (T 1 ) to screen people at the risk of diabetes and metabolic syndrome. Human blood samples were collected for NMR detection and biochemical examinations. Bivariate correlations, categorical analyses were performed to explore the relationship between NMR relaxation time and metabolic biomarkers. Results show that NMR relaxation time of human serum correlated well with some biomarkers associated with diabetes and metabolic syndrome. Statistically significant differences in NMR relaxation time between subjects with normal and poor metabolic health were observed. NMR relaxation time, especially T 2 , can be used to screen people at risk of diabetes and metabolic syndrome., (© 2022. The Author(s), under exclusive licence to The Japan Society for Analytical Chemistry.)

Objective: To explore the main risk factors for non-positional obstructive sleep apnea (NPOSA)., Methods: A total of 560 patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) were divided into non-positional obstructive sleep apnea (NPOSA) and positional obstructive sleep apnea (POSA) groups. All patients were assessed by the Friedman staging system and anthropometry before overnight polysomnography. Blood tests were performed to determine the fasting blood glucose level and lipid profile. Forward logistic regression analysis was performed to evaluate the effects of all parameters on positional dependency., Results: The study sample consisted of 318 NPOSA patients and 242 POSA patients (88% and 85% were men, respectively). The mean apnea-hypopnea index (AHI) was 57.0 events/h in the NPOSA group, compared with 25.7 events/h in the POSA group. The POSA group had a significantly smaller neck circumference (NC), waist circumference (WC), hip circumference (HC), lower body mass index (BMI), AHI, fasting blood glucose, and apolipoprotein-B (apoB) levels than did the NPOSA group (all, P < 0.01). The minimal nocturnal oxyhemoglobin saturation (minSpO 2 ) and apoB/apoA ratio were higher in the POSA group than in the NPOSA group (both, P < 0.001). The AHI, minSpO 2 , WC, and fasting blood glucose level were included in the logistic regression models., Conclusion: The AHI, WC, minSpO 2 , and fasting blood glucose level are the main independent risk factors for NPOSA., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

MCM-48 molecular sieve with a large specific area (1470.87 m 2 /g) was hydrothermally synthesized for VOCs elimination by the adsorption method. The dynamic adsorption behaviors of toluene on this material were evaluated via breakthrough curves under both dry and wet conditions. A high toluene adsorption capacity of 171.13 mg/g was observed under dry conditions; however, in the presence of water vapor (20% RH), the adsorption capacity greatly decreased to 58.88 mg/g due to the competitive occupation of adsorption sites between water molecules and toluene molecules. To improve the affinity to toluene, functionalized MCM-48 materials were obtained by the co-condensation method and grafting method, respectively. It was found that co-M48(1:5)-100/48 sample by co-condensation method presents the highest dynamic adsorption capacity at both dry condition (194.62 mg/g) and 20% RH (122.42 mg/g), which has a significant advantage in the same type of adsorbent. This could be ascribed to the conjugated π-electrons effect between aromatic rings of phenyl groups uniformly distributed in MCM-48 skeleton and toluene molecules, which was qualitatively confirmed by FTIR. Moreover, cycle tests confirmed that this adsorbent possesses superior stability. The Yoon-Nelson model was successfully employed to describe the dynamic adsorption behavior of toluene over the organofunctionalized MCM-48 adsorbents, and the adsorption force of toluene was explained. Finally, a diagram describing the effect of different functionalization methods on the hydrophobicity and organophilicity of MCM-48 was given for a better understanding., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Targeted therapy has gradually become the first-line clinical tumor therapy due to its high specificity and low rate of side effects. TOPK (T-LAK cell-originated protein kinase), a MAP kinase, is highly expressed in various tumor tissues, while it is rarely expressed in normal tissues, with the exceptions of testicular germ cells and some fetal tissues. It can promote cancer cell proliferation and migration and is also related to drug resistance. Therefore, TOPK is considered a good therapeutic target. Moreover, a number of studies have shown that targeting TOPK can inhibit the proliferation of cancer cells and promote their apoptosis. Here, we discussed the biological functions of TOPK in cancer and summarized its tumor-related signaling network and known TOPK inhibitors. Finally, the role of TOPK in targeted cancer therapy was concluded, and future research directions for TOPK were assessed., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have a higher risk of obstructive sleep apnea (OSA). However, the relationship between CRSwNP and OSA remains unclear. The aim of this research study was to evaluate the association of multiple single nucleotide polymorphism (SNP) variations in CRSwNP with sleep- and breath-related parameters in men with OSA., Methods: We included eight CRSwNP SNPs in 2320 participants after strict screening. For each participant, the genetic risk score (GRS) was calculated based on the cumulative effect of multiple genetic variants of CRSwNP. A bivariate correlation analysis was used to assess the relationship between CRSwNP genetic polymorphisms and polysomnography parameters in men with OSA. Logistic regression analyses were used to assess the relationship between the risk of OSA and CRSwNP genetic polymorphisms., Results: In moderate OSA, rs28383314 was related to the oxygen desaturation index, and rs4807532 was positively associated with the microarousal index (r = 0.09, P = 0.03 and r = 0.11, P = 0.01, respectively). The CRSwNP GRS was positively correlated with the oxygen desaturation index and cumulative time percentage with SpO 2 < 90% in moderate OSA (r = 0.13, P < 0.001 and r = 0.1, P = 0.01, respectively). There was no association between the CRSwNP GRS and the risk of OSA (OR = 1.007; 95% CI, 0.973-1.042; P = 0.702)., Conclusion: In men with moderate OSA, single CRSwNP genetic variations correlated with sleep-related parameters, and the cumulative effects of CRSwNP genetic variations were associated with the hypoxic index. CRSwNP may be a predisposing condition for sleep disorders in men with moderate OSA., (© 2021. The Author(s).)

In this research, one-step synthesis of redox co-precipitation method (using sodium lauryl sulfate, KMnO 4 , and metal precursor) was well applicable in universally preparing low-dimensional Me-MnOx nanosheet catalysts with different metal doping (Me=Co, Ni, or Sn). NH 3 -SCR activity was explored to the relationship with structure morphology and physio-chemical properties via the characterization techniques of SEM, XRD, XPS, H 2 -TPR, and NH 3 -TPD. It was found that Ni-MnOx has a relatively poor activity at low-down temperature but was improved as the reaction temperature rising. Co-MnOx presented a relatively stable catalytic activity of which the NOx conversion rate can be maintained 80~90% in a wide temperature window of 100-250 °C with relatively better N 2 selectivity. Compared with Co- or Ni-modified MnOx, Sn-MnOx catalyst has an excellent low-temperature catalytic activity (93% NOx conversion at 100 °C) that was maintained > 80% before 200 °C but with poor selectivity to N 2 . Due to its nanosheet-structured solid solution structure, Sn-MnOx promoted the interaction between MnOx and SnO 2 with the increased contents of adsorbed oxygen and also the numbers of surface Lewis acid sites, which integrally promoted the NH 3 -SCR reaction at low temperature and also contributed to an acceptable resistances to water and sulfur. High content of adsorbed oxygen was beneficial to improve the catalytic activity at lower temperatures, while the electron cycle interaction of different metal valence ions will play a more important role with the increase of reaction temperature., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study examined the association between perceived discrimination and healthcare avoidance and delay (HAD) among transgender adults in South Korea (hereafter Korea). We conducted a nationwide cross-sectional survey of 244 Korean transgender adults in 2017. Discrimination within the last 12 months was categorized into four groups based on the reason(s) of discrimination experienced: (1) 'never experienced' discrimination, (2) 'only due to transgender identity,' (3) 'due to reason(s) other than transgender identity,' and (4) 'due to both transgender identity and other reason(s).' Korean transgender adults who experienced discrimination 'only due to transgender identity' and 'due to both transgender identity and other reason(s)' reported 1.91-times (95% CI 1.02-3.55) and 1.96-times (95% CI 1.32-2.92) higher prevalence of past 12-month HAD, respectively, than those who had no such experiences. Our findings suggest that institutional efforts are needed to protect transgender people from discrimination, which can contribute to improved access to healthcare among transgender populations in Korea., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study aimed to investigate the expression and function of interferon regulatory factor-1 (IRF-1) in non-small cell lung cancer (NSCLC). IRF-1 expression and its prognostic value were investigated through bioinformatic analysis. The protein expression levels of IRF-1, cleaved caspase 3, and LC3-I/II were analyzed by western blotting. A lentiviral vector was used to overexpress or knockdown IRF-1 in vitro. Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) were analyzed by JC-1 and DCFH-DA staining, respectively. ATP, SOD, MDA, cell viability, LDH release, and caspase 3 activity were evaluated using commercial kits. Compared to the levels in normal tissues, IRF-1 expression was significantly lower in lung cancer tissues and was a prognostic factor for NSCLC. Cisplatin treatment-induced IRF-1 activation, ROS production, ATP depletion, SOD consumption, and MDA accumulation in A549 lung cancer cells. IRF-1 overexpression promoted mitochondrial depolarization, oxidative stress, and apoptotic cell death and inhibited autophagy in A549 cells, and these effects could be reversed by IRF-1 knockdown. These data suggest that IRF-1 regulates apoptosis, autophagy and oxidative stress, which might be served as a potential target for increasing chemotherapy sensitivity of lung cancer., (© 2022. The Author(s).)

The water environment plays an essential role in the mangrove wetland ecosystem. Predicting water quality will help us better protect water resources from pollution, allowing the mangrove ecosystem to perform its normal ecological role. New approaches to solve such nonlinear problems need further research since the complexity of water quality data and they are easily affected by the noise. In this paper, we propose a water quality prediction model named CNN-LSTM with Attention (CLA) to predict the water quality variables. We conduct a case study on the water quality dataset of Beilun Estuary to predict pH and NH 3 -N. Linear interpolation and wavelet techniques are used for missing data filling and data denoising, respectively. The hybrid model CNN-LSTM is highly capable of resolving nonlinear time series prediction problems, and the attention mechanism captures longer time dependence. The experimental results show that our model outperforms other ones, and can predict with different time lags in a stable manner., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Key Message: A novel genic male-sterile mutant ms40 was obtained from EMS treated RP125. The key candidate gene ZmbHLH51 located on chromosome 4 was identified by map-based cloning. This study further enriched the male sterile gene resources for both production applications and theoretical studies of abortion mechanisms. Maize male-sterile mutant 40 (ms40) was obtained from the progeny of the ethyl methanesulfonate (EMS) treated inbred line RP125. Genetic analysis indicated that the sterility was controlled by a single recessive nuclear gene. Cytological observation of anthers revealed that the cuticles of ms40 anthers were abnormal, and no Ubisch bodies were observed on the inner surface of ms40 anthers through scanning electron microscopy(SEM). Moreover, its tapetum exhibited delayed degradation and then blocked the formation of normal microspores. Using map-based cloning strategy, the ms40 locus was found to locate in a 282-kb interval on chromosome 4, and five annotated genes were predicted within this region. PCR-based sequencing detected a single non-synonymous SNP (G > A) that changed glycine (G) to arginine (A) in the seventh exon of Zm00001d053895, while no sequence difference between ms40 and RP125 was found for the other four genes. Zm00001d053895 encodes the bHLH transcription factor ZmbHLH51 which is localized in the nucleus. Phylogenetic analysis showed that ZmbHLH51 had the highest homology with Sb04g001650, a tapetum degeneration retardation (TDR) bHLH transcription factor in Sorghum bicolor. Co-expression analysis revealed a total of 1192 genes co-expressed with ZmbHLH51 in maize, 647 of which were anther-specific genes. qRT-PCR results suggested the expression levels of some known genes related to anther development were affected in ms40. In summary, these findings revealed the abortion characteristics of ms40 anthers and lay a foundation for further studies on the mechanisms of male fertility., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Recent years have witnessed a booming interest in grid-scale electrochemical energy storage, where much attention has been paid to the aqueous zinc ion batteries (AZIBs). Among various cathode materials for AZIBs, manganese oxides have risen to prominence due to their high energy density and low cost. However, sluggish reaction kinetics and poor cycling stability dictate against their practical application. Herein, we demonstrate the combined use of defect engineering and interfacial optimization that can simultaneously promote rate capability and cycling stability of MnO 2 cathodes. β-MnO 2 with abundant oxygen vacancies (V O ) and graphene oxide (GO) wrapping is synthesized, in which V O in the bulk accelerate the charge/discharge kinetics while GO on the surfaces inhibits the Mn dissolution. This electrode shows a sustained reversible capacity of ~ 129.6 mAh g -1 even after 2000 cycles at a current rate of 4C, outperforming the state-of-the-art MnO 2 -based cathodes. The superior performance can be rationalized by the direct interaction between surface V O and the GO coating layer, as well as the regulation of structural evolution of β-MnO 2 during cycling. The combinatorial design scheme in this work offers a practical pathway for obtaining high-rate and long-life cathodes for AZIBs., (© 2021. The Author(s).)

Flexible, compact, lightweight and sustainable power sources are indispensable for modern wearable and personal electronics and small-unmanned aerial vehicles (UAVs). Hierarchical honeycomb has the unique merits of compact mesostructures, excellent energy absorption properties and considerable weight to strength ratios. Herein, a honeycomb-inspired triboelectric nanogenerator (h-TENG) is proposed for biomechanical and UAV morphing wing energy harvesting based on contact triboelectrification wavy surface of cellular honeycomb structure. The wavy surface comprises a multilayered thin film structure (combining polyethylene terephthalate, silver nanowires and fluorinated ethylene propylene) fabricated through high-temperature thermoplastic molding and wafer-level bonding process. With superior synchronization of large amounts of energy generation units with honeycomb cells, the manufactured h-TENG prototype produces the maximum instantaneous open-circuit voltage, short-circuit current and output power of 1207 V, 68.5 μA and 12.4 mW, respectively, corresponding to a remarkable peak power density of 0.275 mW cm -3 (or 2.48 mW g -1 ) under hand pressing excitations. Attributed to the excellent elastic property of self-rebounding honeycomb structure, the flexible and transparent h-TENG can be easily pressed, bent and integrated into shoes for real-time insole plantar pressure mapping. The lightweight and compact h-TENG is further installed into a morphing wing of small UAVs for efficiently converting the flapping energy of ailerons into electricity for the first time. This research demonstrates this new conceptualizing single h-TENG device's versatility and viability for broad-range real-world application scenarios.

Purpose: To evaluate whether a predictive model based on nocturnal minimal oxygen saturation (SpO 2 ) alone can accurately detect the presence of obstructive sleep apnea (OSA) in a population with suspected OSA., Methods: A total of 4297 participants with suspected OSA were enrolled in this study, and laboratory-based polysomnography (PSG) tests were performed at sea level in all subjects. Nocturnal minimal SpO 2 was obtained automatically as part of the PSG test. Stratified sampling was used to divide the participants' data into the training set (75%) and the test set (25%). An OSA detection model based on minimal SpO 2 alone was created using the training set data and its performance was evaluated using the independent test set data ("hold-out" evaluation). Gender-specific models, and models based on minimal SpO 2 in combination with other predictive factors (age, body mass index, waist-to-hip ratio, snoring grade, Epworth Sleepiness Scale score, and comorbidities), were also created and compared in terms of OSA detection performance., Results: The prevalence of OSA was 85.6% in our study population. The models including multiple predictors, and the gender-specific models, failed to outperform the model based solely on minimal SpO 2 , which showed good predictive performance (C statistic, 0.922) having an overall accuracy rate of 0.86, sensitivity of 0.87, specificity of 0.84, positive predictive value of 0.97, and positive likelihood ratio of 5.34. In addition, the model based on minimal SpO 2 alone could also accurately predict the presence of moderate-to-severe OSA and severe OSA, with C statistics of 0.914 and 0.900, respectively., Conclusions: A predictive model based on nocturnal minimal SpO 2 alone may be an alternative option to detect the presence of OSA in a high-risk population when standard diagnostic tests are unavailable.

Background: The beneficial effects of weight reduction on obstructive sleep apnea (OSA) are highly variable. Whether or not the variability is associated with the effects of age and sex remains unclear. This study examined this issue with large cross-sectional data., Method: Anthropometric measurements, polysomnographic variables, biochemical indicators, and medical history were collected for each participant. Multivariable linear regression with interaction terms was used to estimate the modification effect of age on the associations between OSA severity (assessed by apnea-hypopnea index, AHI) with obesity indices (body mass index, BMI; neck circumference, NC; waist circumference, WC; waist-to-hip ratio, WHR) in a sex-specific manner, and vice versa. To facilitate interpretation of the results, participants were further classified into six subpopulations according to both sex and age, and population-specific beta-coefficients were calculated and compared., Results: A total of 5756 adults (4600 men) with suspected OSA were included in the study. BMI, NC, WC, and WHR were all positively correlated with AHI after adjusting for potential confounders in all populations. In men, these associations were much stronger and more significant in younger than older individuals (P for interaction < 0.001). For example, a 10% increase in BMI was independently associated with a 32% increase in AHI for men < 40 years old, whereas the corresponding increases were 21% and 17% for men 40-60 and > 60 years old, respectively. By contrast, no modification effect of age was observed in women (P for interaction > 0.05). A 10% increase in BMI was associated with 26%, 27%, and 24% increases in AHI for women < 40, 40-60, and > 60 years old, respectively., Conclusions: Age modifies the associations between obesity indices and OSA severity in a sex-specific manner. These findings may broaden the understanding of age- and sex-related heterogeneities in the pathogenic role of obesity in OSA, and may be beneficial for individualized risk evaluation and treatment management for patients with OSA.

In this study, a novel magnetic cassava stalk composite (M-EMCS) was prepared through modification with ethylenediamine tetraacetic anhydride (EDTAD) and loading of Fe 3 O 4 . The surface morphology, molecular structure, and magnetic characteristics of the composite were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), vibrating-sample magnetometer (VSM), and X-ray diffraction (XRD). It was shown that EDTAD and Fe 3 O 4 were successfully modified and loaded in cassava straw (CS), respectively. The capacity of M-EMCS to absorb heavy metals under different influencing factors was tested by atomic absorption spectroscopy. The adsorption processes of both Pb 2+ and Zn 2+ were suitably described by second-order kinetic models and Langmuir models, indicating monolayer chemisorption. M-EMCS had high adsorption rates and adsorption capacities for these two metal ions. The adsorption of Pb 2+ and Zn 2+ reached a plateau after 10 min, and the adsorption capacity of Pb 2+ (163.93 mg/g) was higher than that of Zn 2+ (84.74 mg/g). Thermodynamic analysis showed that the adsorption of two metals by M-EMCS was spontaneous, endothermic, and irreversible. XPS analysis showed that M-EMCS mainly removes Pb 2+ and Zn 2+ through ion exchange, chelation, and redox. Graphical abstract.

Nitric oxides (NO x , which mainly include more than 90% NO) are one of the major air pollutants leading to a series of environmental problems, such as acid rain, haze, photochemical smog, etc. The selective catalytic oxidation of NO to NO 2 (NO-SCO) is regarded as a key process for the development of selective catalytic reduction of NO x by ammonia (via fast selective catalytic reduction reaction) and also the simultaneous removal of multipollutant (pre-oxidation and post-absorption). Until now, scholars have developed various types of NO-SCO catalysts, dividing the main groups into noble metals (Pt, Pd, Ru, etc.), metal oxides (Mn-, Co-, Cr-, Ce-based, etc.), perovskite-type oxides (LaMnO 3 , LaCoO 3 , LaCeCoO 3 , etc.), carbon materials (activated carbon, carbon fiber, carbon nanotube, graphene, etc.), and zeolites (ion-exchanged ZSM-5, CHA, SAPO, MCM-41, etc.) in this review. This paper summarizes the recent progress of the above typical catalysts and mostly analyzes the catalytic performance for NO oxidation in terms of the H 2 O and/or SO 2 resistances and also the influencing factors, and their reaction mechanisms are described in detail. Finally, this review points out the key problems and possible solutions of the current researches and presents the application prospects and future development directions of NO-SCO technology using the above typical catalysts.

Purpose: The purposes of this study were to evaluate the ability of visceral adiposity variables [the lipid accumulation product (LAP), the visceral adiposity index (VAI), and the triglyceride-glucose index (TyG)] in predicting obstructive sleep apnea hypopnea syndrome (OSAHS) and to determine the effect of sex on the prediction., Methods: A total of 5539 subjects admitted to the sleep center for suspected OSAHS were consecutively recruited from 2007 to 2016. Anthropometric measurements, biological indicators, Epworth sleepiness scale score, and polysomnographic variables were collected. Prediction models for diagnosing OSAHS were established in the test group by logistic regression and verified in the validation group by receiver operating characteristic (ROC) curves., Results: A total of 4703 patients were included in total. LAP and TyG were of moderate diagnostic accuracy for OSAHS, with the diagnostic efficiency differing between men and women. A prediction model was developed that combined visceral adiposity indicators with waist circumstance and the lowest SpO 2 . The sensitivity of those indicators were both 84% in men and women, respectively, and their specificity were both 90%. In addition, the model was confirmed in the validation group with a sensitivity and specificity of 83% and 85% in men and 85% and 84% in women., Conclusions: LAP and TyG were of moderate efficiency in screening for OSAHS. The prediction model provides a simple and practical screening tool for OSAHS.