Assessment of stress levels and reproductive condition in giant pandas: insights from hair, faecal and saliva samples.

Concerted conservation efforts have brought the giant panda (Ailuropoda melanoleuca) back from the brink of extinction, but pandas continue to face anthropogenic threats in the wild and breeding success in captivity remains low. Because stress can have detrimental impacts on reproduction, monitoring stress- and sex-steroid levels would help assess the effectiveness of conservation mitigation measures in panda populations as well as monitor the welfare and reproductive health of captive animals. In this proof-of-concept study, we used faecal sex steroid and cortisol concentrations (n = 867 samples collected from five males and five females at Beijing Zoo every 4 days over the course of 12 months) as a reference to investigate if testosterone, estradiol, progesterone and cortisol can be meaningfully measured in panda hair (n = 10) using radio-immuno-assays. Additionally, we calculated the ratio of testosterone to cortisol (T:C ratio) for each male, which can provide a biomarker of stress and physical performance. Our findings revealed distinct monthly variations in faecal sex-steroid and cortisol concentrations, reflecting reproductive seasonality and visitor-related stress among individual pandas. Notably, the oldest male had a significantly lower T:C ratio than other males. Our results confirm that the level of sex steroids and cortisol can be assayed by panda hair, and the hair cortisol concentrations correlate significantly with that in faeces with one month lag behind (r = 0.68, P = 0.03). However, the concentrations of hormones detected in saliva are lower than those in faeces by two orders of magnitude, making it difficult to ensure accuracy. By assessing the applicability of hair, faecal and salivary sampling, we can infer their utility in monitoring the reproductive status and acute and chronic stress levels of giant pandas, thereby providing a means to gauge the success of ongoing habitat restoration efforts and to discuss the feasibility of sample collection from wild populations.

The association between dietary patterns before pregnancy and gestational diabetes mellitus: a matched case-control study in China.

BACKGROUND AND OBJECTIVES: We aimed to explore the relationship between dietary patterns and gestational diabetes mellitus (GDM) during pre-pregnancy six months using principal component analysis (PCA) and the geometric framework for nutrition (GFN). METHODS AND STUDY DESIGN: We conducted a case-control study that included 210 GDM pregnant women and 210 controls. The dietary intake of all participants was assessed by a validated semi-quantitative food frequency questionnaire (FFQ). Major dietary patterns were extracted by PCA. A conditional logistic regression model was used to determine whether specific dietary patterns are associated with the risk of GDM. Meanwhile, the relationship between dietary patterns and GDM was visualized using GFN. RESULTS: Four major dietary patterns were identified: "protein-rich pattern," "plant-based pattern," "oil-pickles-desserts pattern," and "cereals-nuts pattern." After adjustment for confounders, the "plant-based pattern" was associated with decreased risk of GDM (Q4 vs. Q1: OR = 0.01, 95% CI: 0.00-0.08), whereas no significant association was found in other dietary patterns. Moreover, there was no dietary intake of ice cream cones and deep-fried dough sticks for the population, which would produce fewer patients with GDM. Deep-fried dough sticks had statistically significant differences in the case and control groups (p < 0.001), while ice cream cones had the opposite result. CONCLUSIONS: The "plant-based pattern" may reduce the risk of GDM. Besides, although the "cereals-nuts pattern" had no association with GDM risk, avoiding the intake of deep-fried dough sticks could decrease GDM risk.

The cuproptosis-related signature predicts the prognosis and immune microenvironments of primary diffuse gliomas: a comprehensive analysis.

BACKGROUND: Evidence has revealed a connection between cuproptosis and the inhibition of tumor angiogenesis. While the efficacy of a model based on cuproptosis-related genes (CRGs) in predicting the prognosis of peripheral organ tumors has been demonstrated, the impact of CRGs on the prognosis and the immunological landscape of gliomas remains unexplored. METHODS: We screened CRGs to construct a novel scoring tool and developed a prognostic model for gliomas within the various cohorts. Afterward, a comprehensive exploration of the relationship between the CRG risk signature and the immunological landscape of gliomas was undertaken from multiple perspectives. RESULTS: Five genes (NLRP3, ATP7B, SLC31A1, FDX1, and GCSH) were identified to build a CRG scoring system. The nomogram, based on CRG risk and other signatures, demonstrated a superior predictive performance (AUC of 0.89, 0.92, and 0.93 at 1, 2, and 3 years, respectively) in the training cohort. Furthermore, the CRG score was closely associated with various aspects of the immune landscape in gliomas, including immune cell infiltration, tumor mutations, tumor immune dysfunction and exclusion, immune checkpoints, cytotoxic T lymphocyte and immune exhaustion-related markers, as well as cancer signaling pathway biomarkers and cytokines. CONCLUSION: The CRG risk signature may serve as a robust biomarker for predicting the prognosis and the potential viability of immunotherapy responses. Moreover, the key candidate CRGs might be promising targets to explore the underlying biological background and novel therapeutic interventions in gliomas.

In-situ monitoring of cellular H2O2 within 3D cell clusters using conductive scaffolds.

Accurately monitoring H2O2 concentrations in 3D cell clusters is challenging due to limited diffusion and rapid degradation of H2O2 in the culture medium. Despite the incorporation of three-dimensional cell culture approaches, the detection technology has largely remained as a 2D planar system. In this study, we present a versatile approach of 3D electrochemical sensing utilizing carbon nanotubes as conductive scaffolds for in-situ monitoring of H2O2 in cell clusters. These scaffolds enabled direct contact between H2O2 released from cells and the electrodes, thereby improving sensitivity and ensuring biocompatibility for cell aggregates. The scaffolds exhibited electrocatalytic behavior with a limit of detection of 6.7 nM H2O2. Additionally, the electrochemical responses of cell clusters with the scaffolds exhibited significantly higher current compared to clusters without scaffolds when stimulated with model drugs. This study underscores the potential of conductive scaffolds for real-time monitoring of H2O2 released from cell clusters in 3D microenvironments.

Investigating distinct clinical features and constructing a nomogram model for survival probability in adults with cerebellar high-grade gliomas.

BACKGROUND: The clinical features of cerebellar high-grade gliomas (cHGGs) in adults have not been thoroughly explored. This large-scale, population-based study aimed to comprehensively outline these traits and construct a predictive model. METHODS: Patient records diagnosed with gliomas were collected from various cohorts and analyzed to compare the features of cHGGs and supratentorial HGGs (sHGGs). Cox regression analyses were employed to identify prognostic factors for overall survival and to develop a nomogram for predicting survival probabilities in patients with cHGGs. Multiple machine learning methods were applied to evaluate the efficacy of the predictive model. RESULTS: There were significant differences in prognosis, with SEER-cHGGs showing a median survival of 7.5 months and sHGGs 14.9 months (p < 0.001). Multivariate Cox regression analyses revealed that race, WHO grade, surgical procedures, radiotherapy, and chemotherapy were independent prognostic factors for cHGGs. Based on these factors, a nomogram was developed to predict 1-, 3-, and 5-year survival probabilities, with AUC of 0.860, 0.837, and 0.810, respectively. The model's accuracy was validated by machine learning approaches, demonstrating consistent predictive effectiveness. CONCLUSIONS: Adult cHGGs are distinguished by distinctive clinical features different from those of sHGGs and are associated with an inferior prognosis. Based on these risk factors affecting cHGGs prognosis, the nomogram prediction model serves as a crucial tool for clinical decision-making in patient care.

Nanotechnology as a new strategy for the diagnosis and treatment of gliomas.

Glioma is the most common malignant tumor of the central nervous system (CNS), and is characterized by high aggressiveness and a high recurrence rate. Currently, the main treatments for gliomas include surgical resection, temozolomide chemotherapy and radiotherapy. However, the prognosis of glioma patients after active standardized treatment is still poor, especially for glioblastoma (GBM); the median survival is still only 14.6 months, and the 5-year survival rate is only 4-5%. The current challenges in glioma treatment include difficulty in complete surgical resection, poor blood‒brain barrier (BBB) drug permeability, therapeutic resistance, and difficulty in tumor-specific targeting. In recent years, the rapid development of nanotechnology has provided new directions for diagnosing and treating gliomas. Nanoparticles (NPs) are characterized by excellent surface tunability, precise targeting, excellent biocompatibility, and high safety. In addition, NPs can be used for gene therapy, photodynamic therapy, and antiangiogenic therapy and can be combined with biomaterials for thermotherapy. In recent decades, breakthroughs in diagnosing and treating gliomas have been made with various functional NPs, and NPs are expected to become a new strategy for glioma diagnosis and treatment. In this paper, we review the main obstacles in the treatment of glioma and discuss the potential and challenges of the latest nanotechnology in the diagnosis and treatment of glioma.

Overexpression of AcWRKY31 Increases Sensitivity to Salt and Drought and Improves Tolerance to Mealybugs in Pineapple.

Pineapple is a globally significant tropical fruit, but its cultivation faces numerous challenges due to abiotic and biotic stresses, affecting its quality and quantity. WRKY transcription factors are known regulators of stress responses, however, their specific functions in pineapple are not fully understood. This study investigates the role of AcWRKY31 by overexpressing it in pineapple and Arabidopsis. Transgenic pineapple lines were obtained using Agrobacterium-mediated transformation methods and abiotic and biotic stress treatments. Transgenic AcWRKY31-OE pineapple plants showed an increased sensitivity to salt and drought stress and an increased resistance to biotic stress from pineapple mealybugs compared to that of WT plants. Similar experiments in AcWRKY31-OE, AtWRKY53-OE, and the Arabidopsis Atwrky53 mutant were performed and consistently confirmed these findings. A comparative transcriptomic analysis revealed 5357 upregulated genes in AcWRKY31-OE pineapple, with 30 genes related to disease and pathogen response. Notably, 18 of these genes contained a W-box sequence in their promoter region. A KEGG analysis of RNA-Seq data showed that upregulated DEG genes are mostly involved in translation, protein kinases, peptidases and inhibitors, membrane trafficking, folding, sorting, and degradation, while the downregulated genes are involved in metabolism, protein families, signaling, and cellular processes. RT-qPCR assays of selected genes confirmed the transcriptomic results. In summary, the AcWRKY31 gene is promising for the improvement of stress responses in pineapple, and it could be a valuable tool for plant breeders to develop stress-tolerant crops in the future.

Genome-wide identification and expression analysis of calmodulin and calmodulin-like genes in passion fruit (Passiflora edulis) and their involvement in flower and fruit development.

BACKGROUND: The calmodulin (CaM) and calmodulin-like (CML) proteins play regulatory roles in plant growth and development, responses to biotic and abiotic stresses, and other biological processes. As a popular fruit and ornamental crop, it is important to explore the regulatory mechanism of flower and fruit development of passion fruit. RESULTS: In this study, 32 PeCaM/PeCML genes were identified from passion fruit genome and were divided into 9 groups based on phylogenetic analysis. The structural analysis, including conserved motifs, gene structure and homologous modeling, illustrates that the PeCaM/PeCML in the same subgroup have relative conserved structural features. Collinearity analysis suggested that the expansion of the CaM/CML gene family likely took place mainly by segmental duplication, and the whole genome replication events were closely related with the rapid expansion of the gene group. PeCaM/PeCMLs were potentially required for different floral tissues development. Significantly, PeCML26 had extremely high expression levels during ovule and fruit development compared with other PeCML genes, suggesting that PeCML26 had potential functions involved in the development of passion fruit flowers and fruits. The co-presence of various cis-elements associated with growth and development, hormone responsiveness, and stress responsiveness in the promoter regions of these PeCaM/PeCMLs might contribute to their diverse regulatory roles. Furthermore, PeCaM/PeCMLs were also induced by various abiotic stresses. This work provides a comprehensive understanding of the CaM/CML gene family and valuable clues for future studies on the function and evolution of CaM/CML genes in passion fruit. CONCLUSION: A total of 32 PeCaM/PeCML genes were divided into 9 groups. The PeCaM/PeCML genes showed differential expression patterns in floral tissues at different development stages. It is worth noting that PeCML26, which is highly homologous to AtCaM2, not only interacts with multiple BBR-BPC TFs, but also has high expression levels during ovule and fruit development, suggesting that PeCML26 had potential functions involved in the development of passion fruit flowers and fruits. This research lays the foundation for future investigations and validation of the potential function of PeCaM/PeCML genes in the growth and development of passion fruit.

The impact of telomere length on the risk of idiopathic normal pressure hydrocephalus: a bidirectional Mendelian randomization study.

Idiopathic normal pressure hydrocephalus (iNPH) affects mainly aged populations. The gradual shortening of telomere length (TL) is one of the hallmarks of aging. Whereas the genetic contribution of TL to the iNPH is incompletely understood. We aimed to investigate the causal relationship between TL and iNPH through the Mendelian randomization (MR) analysis. We respectively obtained 186 qualified single nucleotide polymorphisms (SNPs) of TL and 20 eligible SNPs of iNPH for MR analysis. The result of MR analysis showed that genetically predicted longer TL was significantly associated with a reduced odd of iNPH (odds ratio [OR] = 0.634 95% Confidence interval [CI] 0.447-0.899, p = 0.011). The causal association remained consistent in multivariable MR (OR = 0.530 95% CI 0.327-0.860, p = 0.010). However, there was no evidence that the iNPH was causally associated with the TL (OR = 1.000 95% CI 0.996-1.004, p = 0.955). Our study reveals a potential genetic contribution of TL to the etiology of iNPH, that is a genetically predicted increased TL might be associated with a reduced risk of iNPH.

Terpinen-4-ol Improves Lipopolysaccharide-Induced Macrophage Inflammation by Regulating Glutamine Metabolism.

Terpinen-4-ol (T-4-O) is an important component of tea tree oil and has anti-inflammatory effects. Currently, there are very few studies on the mechanisms by which T-4-O improves lipopolysaccharide (LPS)-induced macrophage inflammation. In this study, LPS-stimulated mouse RAW264.7 macrophages were used as a model to analyze the effects of T-4-O on macrophage inflammatory factors and related metabolic pathways in an inflammatory environment. The results showed that T-4-O significantly decreased the expression levels of inflammatory cytokines induced by LPS. Cellular metabolism results showed that T-4-O significantly decreased the ratio of the extracellular acidification rate and oxygen consumption rate. Non-targeted metabolomics results showed that T-4-O mainly affected glutamine and glutamate metabolism and glycine, serine, and threonine metabolic pathways. qPCR results showed that T-4-O increased the transcript levels of GLS and GDH and promoted glutamine catabolism. Western blotting results showed that T-4-O inhibited the mTOR and IκB, thereby decreasing NF-κB activity. The overall results showed that T-4-O inhibited mTOR phosphorylation to promote glutamine metabolism and increased cell oxidative phosphorylation levels, thereby inhibiting the expression of LPS-induced inflammatory cytokines.

AMPK targets PDZD8 to trigger carbon source shift from glucose to glutamine.

The shift of carbon utilization from primarily glucose to other nutrients is a fundamental metabolic adaptation to cope with decreased blood glucose levels and the consequent decline in glucose oxidation. AMP-activated protein kinase (AMPK) plays crucial roles in this metabolic adaptation. However, the underlying mechanism is not fully understood. Here, we show that PDZ domain containing 8 (PDZD8), which we identify as a new substrate of AMPK activated in low glucose, is required for the low glucose-promoted glutaminolysis. AMPK phosphorylates PDZD8 at threonine 527 (T527) and promotes the interaction of PDZD8 with and activation of glutaminase 1 (GLS1), a rate-limiting enzyme of glutaminolysis. In vivo, the AMPK-PDZD8-GLS1 axis is required for the enhancement of glutaminolysis as tested in the skeletal muscle tissues, which occurs earlier than the increase in fatty acid utilization during fasting. The enhanced glutaminolysis is also observed in macrophages in low glucose or under acute lipopolysaccharide (LPS) treatment. Consistent with a requirement of heightened glutaminolysis, the PDZD8-T527A mutation dampens the secretion of pro-inflammatory cytokines in macrophages in mice treated with LPS. Together, we have revealed an AMPK-PDZD8-GLS1 axis that promotes glutaminolysis ahead of increased fatty acid utilization under glucose shortage.

Tumor treating fields for newly diagnosed high-grade glioma based on the criteria of 2021 WHO CNS5: A retrospective analysis of Chinese patients in a single center.

BACKGROUND AND OBJECTIVE: High-grade glioma (HGG) is known to be characterized by a high degree of malignancy and a worse prognosis. The classical treatment is safe resection supplemented by radiotherapy and chemotherapy. Tumor treating fields (TTFields), an emerging physiotherapeutic modality that targets malignant solid tumors using medium-frequency, low-intensity, alternating electric fields to interfere with cell division, have been used for the treatment of new diagnosis of glioblastoma, however, their administration in HGG requires further clinical evidence. The efficacy and safety of TTFields in Chinese patients with HGG were retrospectively evaluated by us in a single center. METHODS: We enrolled and analyzed 52 patients with newly diagnosed HGG undergoing surgery and standard chemoradiotherapy regimens from December 2019 to June 2022, and followed them until June 2023. Based on whether they used TTFields, they were divided into a TTFields group and a non-TTFields group. Progression-free survival (PFS) and overall survival (OS) were compared between the two groups. RESULTS: There were 26 cases in the TTFields group and 26 cases in the non-TTFields group. In the TTFields group, the median PFS was 14.2 months (95% CI: 9.50-18.90), the median OS was 19.7 months (95% CI: 14.95-24.25) , the median interval from surgery to the start of treatment with TTFields was 2.47 months (95% CI: 1.47-4.13), and the median duration of treatment with TTFields was 10.6 months (95% CI: 9.57-11.63). 15 (57.69%) patients experienced an adverse event and no serious adverse event was reported. In the non-TTFields group, the median PFS was 9.57 months (95% CI: 6.23-12.91) and the median OS was 16.07 months (95% CI: 12.90-19.24). There was a statistically significant difference in PFS (p = 0.005) and OS (p = 0.007) between the two groups. CONCLUSIONS: In this retrospective analysis, TTFields were observed to improve newly diagnosed HGG patients' median PFS and OS. Compliance was much higher than reported in clinical trials and safety remained good.

Polyvalent mpox mRNA vaccines elicit robust immune responses and confer potent protection against vaccinia virus.

The 2022 mpox outbreak led the World Health Organization (WHO) to declare it a public health emergency of international concern (PHEIC). There is a need to develop more effective and safer mpox virus (MPXV)-specific vaccines in response to the mpox epidemic. The mRNA vaccine is a promising platform to protect against MPXV infection. In this study, we construct two bivalent MPXV mRNA vaccines, designated LBA (B6R-A29L) and LAM (A35R-M1R), and a quadrivalent mRNA vaccine, LBAAM (B6R-A35R-A29L-M1R). The immunogenicity and protective efficacy of these vaccines alone or in combination were evaluated in a lethal mouse model. All mRNA vaccine candidates could elicit potential antigen-specific humoral and cellular immune responses and provide protection against vaccinia virus (VACV) infection. The protective effect of the combination of two bivalent mRNA vaccines and the quadrivalent vaccine was superior to that of the individual bivalent mRNA vaccine. Our study provides valuable insights for the development of more efficient and safer mRNA vaccines against mpox.

Quantification for photochemical loss of volatile organic compounds upon ozone formation chemistry at an industrial city (Zibo) in North China Plain.

Volatile organic compounds (VOCs) are consumed by photochemical reactions during transport, leading to inaccuracies in estimating the local ozone (O3) formation mechanism and its subsequent strategy for O3 attainment. To comprehensively quantify the deviations in O3 formation mechanism by consumed VOCs (C-VOCs), a 5-month field campaign was conducted in a typical industrial city in Northern China over incorporating a 0-D box model (implemented with MCMv3.3.1). The averaged C-VOCs concentration was 6.8 ppbv during entire period, and Alkenes accounted for 62% dominantly. Without considering C-VOCs, the relative incremental reactivity (RIR) of anthropogenic VOCs (AVOC, overestimated by 68%-75%) and NOx (underestimated by 137%-527%) demonstrated deviations at multiple scenarios, and the RIR deviations for precursors in High-O3-periods (HOP) were lower than Low-O3-periods (LOP). The RIR deviations from individual species involved C-VOCs calculation did not impact the identification for the high-ranking-RIR AVOC species but non-negligible. Monthly comparisons showed that higher C-VOCs concentrations would lead to higher RIR deviations. The daily maximum of net Ox production rate (P(Ox)) and the regional transport Ox (Trans(Ox)) without C-VOCs were underestimated by 56%-194% and 81%-243%, respectively. After considering C-VOCs, the contribution of HO2+NO for Ox gross production (G(Ox)) decreased by 7% (LOP) and 7% (HOP), but OH + NO2 for Ox destruction (D(Ox)) decreased by 16% (LOP) and 23% (HOP), and alkenes + O3 increased for D(Ox) by 12% (LOP) and 22% (HOP). This implies that VOCs-NOx-O3 sensitivity was deviated between with/without C-VOCs, and severe O3 pollution rendered deviations in O3 formation, especially via NOx-driving chemistry. Based on RIR(NOx)/RIR(AVOC) with/without C-VOCs, the sensitivity regime shifted from VOCs-limited (-0.93) to transition (1.38) at LOP, and from VOCs-limited (0.19) to NOx-limited (3.79) at HOP. Our results reflected that the NOx limitation degree was underestimated without constraint C-VOCs, especially HOP, and provided implication to more precise O3 pollution control strategies.

Model Predictive Control With Guaranteed Feasibility of Inequality Path Constraints.

This article concerns nonlinear model predictive control (MPC) with guaranteed feasibility of inequality path constraints (PCs). For MPC with PCs, the existing methods, such as direct multiple shooting, cannot guarantee feasibility of PCs because the PCs are enforced at finitely many time points only. Therefore, this article presents a novel MPC framework that is capable of not only achieving stability control but also guaranteeing feasibility of PCs during the rolling optimization stages of MPC. Under the above MPC framework, an algorithm is first proposed by applying the semi-infinite programming technique to the rolling optimization of MPC. However, it takes heavy computational time to achieve guaranteed feasibility of PCs. Therefore, to guarantee feasibility of PCs meanwhile effectively reducing the computation burden of the closed-loop system, an event-triggered sampling mechanism is constructed in the above path-constrained MPC algorithm. Moreover, sufficient conditions are given for asymptotic convergence of the closed-loop systems. Finally, the effectiveness of the proposed results is illustrated via a cart-damper-spring system.

A Concise Synthesis of (-)-Ambrox.

(-)-Ambrox, a highly prized and commercially significant component of ambergris, finds widespread application in perfumery, cigarettes, cosmetics, and the food industry. Despite considerable attention to this research area over the years, an environmentally friendly and practical method for synthesizing (-)-ambrox has remained elusive. This study presents a succinct and efficient approach to (-)-ambrox synthesis, involving two consecutive alkylations at C-6, followed by an acid-catalyzed cyclization to give bicyclic ketones starting from (R)-carvone. Subsequent reduction, Barton Vinyl Iodide synthesis, alkylation, and an acid-catalyzed cyclization collectively achieved the synthesis of (-)-ambrox with a satisfactory yield of 26.2 %.

An orally administered bacterial membrane protein nanodrug ameliorates doxorubicin cardiotoxicity through alleviating impaired intestinal barrier.

The cardiotoxicity caused by Dox chemotherapy represents a significant limitation to its clinical application and is a major cause of late death in patients undergoing chemotherapy. Currently, there are no effective treatments available. Our analysis of 295 clinical samples from 132 chemotherapy patients and 163 individuals undergoing physical examination revealed a strong positive correlation between intestinal barrier injury and the development of cardiotoxicity in chemotherapy patients. We developed a novel orally available and intestinal targeting protein nanodrug by assembling membrane protein Amuc_1100 (obtained from intestinal bacteria Akkermansia muciniphila), fluorinated polyetherimide, and hyaluronic acid. The protein nanodrug demonstrated favorable stability against hydrolysis compared with free Amuc_1100. The in vivo results demonstrated that the protein nanodrug can alleviate Dox-induced cardiac toxicity by improving gut microbiota, increasing the proportion of short-chain fatty acid-producing bacteria from the Lachnospiraceae family, and further enhancing the levels of butyrate and pentanoic acids, ultimately regulating the homeostasis repair of lymphocytes in the spleen and heart. Therefore, we believe that the integrity of the intestinal barrier plays an important role in the development of chemotherapy-induced cardiotoxicity. Protective interventions targeting the intestinal barrier may hold promise as a general clinical treatment regimen for reducing Dox-induced cardiotoxicity.

Superconductivity of thulium substituted clathrate hexahydrides at moderate pressure.

Due to the BCS theory, hydrogen, the lightest element, would be the prospect of room-temperature superconductor after metallization, but because of the difficulty of the hydrogen metallization, the theory about hydrogen pre-compression was proposed that the hydrogen-rich compounds could be a great option for the high Tc superconductors. The superior properties of TmH6, YbH6 and LuH6 indicated the magnificent potential of heavy rare earth elements for low-pressure stability. Here, we designed XTmH12 (X = Y, Yb, Lu, and La) to obtain higher Tc while maintaining low pressure stability. Most prominently, YbTmH12 can stabilize at a pressure of 60 GPa. Compared with binary TmH6 hydride, its Tc was increased to 48 K. The results provide an effective method for the rational design of moderate pressure stabilized hydride superconductors.

The impact of neurocognitive and psychiatric disorders on the risk of idiopathic normal pressure hydrocephalus: A bidirectional Mendelian randomization study.

BACKGROUND: Neurocognitive and psychiatric disorders have been proved that they can comorbid more often with idiopathic normal pressure hydrocephalus (iNPH) than general population. However, the potential causal association between these disorders and iNPH has not been assessed. Thus, our study aims to investigate the causal relationship between them based on a bidirectional Mendelian randomization (MR) analysis. METHODS: Random effects of the inverse variance weighted (IVW) method were conducted to obtain the causal association among the neurocognitive disorders, psychiatric disorders, and iNPH. Genome-wide association studies (GWAS) of 12 neurocognitive and psychiatric disorders were downloaded via the OpenGWAS database, GWAS Catalog, and Psychiatric Genomics Consortium, whereas GWAS data of iNPH were obtained from the FinnGen consortium round 9 release, with 767 cases and 375,610 controls of European ancestry. We also conducted the sensitivity analysis in these significant causal inferences using weighted median model, Cochrane's Q test, MR-Egger regression, MR Pleiotropy Residual Sum and Outlier detect and the leave-one-out analysis. RESULTS: For most of the neurocognitive and psychiatric disorders, no causal association was established between them and iNPH. We have found that iNPH (odds ratio [OR] = 1.030, 95% confidence interval [CI]: 1.011-1.048, p = .001) is associated with increased risk for schizophrenia, which failed in validation of sensitivity analysis. Notably, genetically predicted Parkinson's disease (PD) is associated with increased risk of iNPH (OR = 1.256, 95% CI: 1.045-1.511, p = .015). CONCLUSION: Our study has revealed the potential causal effect in which PD associated with an increased risk of iNPH. Further study is warranted to investigate the association between PD and iNPH and the potential underlying mechanism.