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The Tibetan Plateau (TP) and the Arctic are the most sensitive regions to global climate change. However, the interdecadal varibility of winter extreme precipitation over the TP and its linkage with Arctic sea ice are still unclear. In this study, the characteristics and mechisnems of the TP extreme precipitation (TPEP) influenced by Arctic sea ice on interdecadal timescale are studied based on the daily precipitation, monthly sea ice concentration and ERA5 reanalysis data from 1980 to 2018. We found that the dominant mode of the TPEP in winter mostly exhibits a uniform spatial variation on the interdecadal timescale, with an opposite weak variation in the southeastern TP, and the Arctic sea ice concentration (SIC) before 2002 are larger than that after 2003. The interdecadal variation of TPEP is affected by two teleconnection wave trains regulated by the Barents and Kara Sea ice. In the light ice years, a remarkable positive geopotential height (HGT) anomaly appears over the Barents‒Kara Sea and a remarkable negative HGT anomaly is located over the Lake Baikal. Two wave trains originating over the Barents‒Kara Sea can be observed. The southern branch forms a wave train through the North Atlantic along the subtropical westerly jet stream, showing a ‘+ − + − +’ pattern of HGT anomalies from Arctic to the TP. Negative HGT anomaly controls the western TP, which creates dynamic and water vapor conditions for the TPEP. The northern branch forms a wave train through the Lake Baikal and the southeast of the TP, showing a ‘+ − +’ HGT anomaly distribution. Positive HGT anomaly controls the southeastern TP, which is not conducive to precipitation in the region. When the SIC in the Barents‒Kara Sea increases, the situation is opposite. The above analysis also reveals the reason for the difference in the east‒west distribution of the TPEP.

Abstract Background Circadian rhythm is crucial to the function of the immune system. Disorders of the circadian rhythm can contribute to inflammatory diseases such as Ulcerative colitis (UC). This Mendelian Randomization (MR) analysis applies genetic tools to represent the aggregated statistical results of exposure to circadian rhythm disorders and UC and its comorbidities, allowing for causal inferences. Methods Summary statistics of protein, DNA methylation and gene expression quantitative trait loci in individuals of European ancestry (pQTL, mQTL, and eQTL, respectively) were used. Genetic variants located within or near 152 circadian clock-related genes and closely related to circadian rhythm disorders were selected as instrumental variables. Causal relationships with UC and its comorbidities were then estimated through employed Summary data-based Mendelian Randomization (SMR) and Inverse-Variance-Weighted MR (IVW-MR). Results Through preliminary SMR analysis, we identified a potential causal relationship between circadian clock-related genes and UC along with its comorbidities, which was further confirmed by IVW-MR analysis. Our study identified strong evidence of positive correlation involving seven overlapping genes (CSNK1E, OPRL1, PIWIL2, RORC, MAX, PPP5C, and AANAT) through MWAS and TWAS in UC, four overlapping genes (OPRL1, CHRNB2, FBXL17, and SIRT1) in UC with PSC, and three overlapping genes (ARNTL, USP7, and KRAS) in UC with arthropathy. Conclusions This SMR study demonstrates the causal effect of circadian rhythm disorders in UC and its comorbidities. Furthermore, our investigation pinpointed candidate genes that could potentially serve as drug targets.

Abstract Nonlinear nanophotonic circuits, renowned for their compact form and integration capabilities, hold potential for advancing high-capacity optical signal processing. However, limited practicality arises from low nonlinear conversion efficiency. Transition metal dichalcogenides (TMDs) could present a promising avenue to address this challenge, given their superior optical nonlinear characteristics and compatibility with diverse device platforms. Nevertheless, this potential remains largely unexplored, with current endeavors predominantly focusing on the demonstration of TMDs’ coherent nonlinear signals via free-space excitation and collection. In this work, we perform direct integration of TMDs onto a plasmonic nanocircuitry. By controlling the polarization angle of the input laser, we show selective routing of second-harmonic generation (SHG) signals from a MoSe2 monolayer within the plasmonic circuit. Routing extinction ratios of 14.86 dB are achieved, demonstrating good coherence preservation in this hybrid nanocircuit. Additionally, our characterization indicates that the integration of TMDs leads to a 13.8-fold SHG enhancement, compared with the pristine nonlinear plasmonic nanocircuitry. These distinct features—efficient SHG generation, coupling, and controllable routing—suggest that our hybrid TMD-plasmonic nanocircuitry could find immediate applications including on-chip optical frequency conversion, selective routing, switching, logic operations, as well as quantum operations.

AbstractPouteria caimito is a commercially valuable tropical fruit tree and has medicinal effects in Brazilian folklore. In this thesis, thirteen compounds were isolated for the first time from the fruit of P. caimito by ethanol extraction and various chromatographic column chromatography methods. The thirteen compounds were identified by NMR, HR-ESI-MS and various physicochemical data to contain nine triterpenoids. The results of activity screening experiments showed that compounds 2, 3 and 5 exhibited anti-inflammatory activity, while most of the triterpenoids exhibited anti-RSV, and anti-HSV activity to varying degrees. Based on these results, the content of compound 5 was determined due to its good pharmacological activity to be 13.3250 mg/kg in the fresh fruit. This study scientifically demonstrated the health benefits of consuming P. caimito fruits and also provided new ideas for further development and utilization of P. caimito. It not only has good potential as an anti-inflammatory or antiviral functional food but also can be considered a natural source of triterpenoids.

Background: Oxaliplatin-associated shock (referred to as shock) is a rare but life-threatening adverse event. Objectives: This pioneering cohort study aimed to quantitatively investigate the association between oxaliplatin use and shock in patients with stage III colorectal cancer (CRC), identify potential independent risk factors for shock, and assess the cycle-to-shock during oxaliplatin treatment. Design: The study utilized a nested case–control (NCC) design to assess the association between oxaliplatin and shock and employed a case-crossover approach to address unmeasured confounders. Methods: All newly diagnosed stage III CRC patients were identified from the CRC Health Database (2012–2016). Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CIs) for oxaliplatin’s link to shock incidence. Results: Among 6932 oxaliplatin recipients, 331 suffered shock. In all, 3309 controls were selected via risk-set sampling for the shock cases. Oxaliplatin use is associated with a doubled risk of shock (adjusted OR: 2.08, 95% CI: 1.23–3.52). Two independent risk factors were male sex (adjusted OR: 1.33, 95% CI: 1.05–1.69) and heart diseases (adjusted OR: 1.65, 95% CI: 1.17–2.32). The case-crossover analysis revealed a more than fourfold risk (OR: 4.4, 95% CI: 1.67–11.62). In total, 22 of 331 shock cases were exposed to oxaliplatin within 2 days of shock onset, with a median cycle-to-shock time at the seventh cycle. Conclusion: Oxaliplatin use significantly increased shock risk in stage III CRC patients. Male sex and heart disease are two independent risk factors.

Myofibrillar proteins (MPs) have a notable impact on the firmness and flexibility of gel-based products. Therefore, enhancing the gelation and emulsification properties of scallop MPs is of paramount significance for producing high-quality scallop surimi products. In this study, we investigated the effects of high-intensity ultrasound on the physicochemical and gelation properties of MPs from bay scallops (Argopecten irradians). The carbonyl content of MPs significantly increased with an increase in ultrasound power (150, 350, and 550 W), indicating ultrasound-induced MP oxidation. Meanwhile, high-intensity ultrasound treatment (550 W) enhanced the emulsifying capacity and the short-term stability of MPs (up to 72.05 m2/g and 153.05 min, respectively). As the ultrasound power increased, the disulfide bond content and surface hydrophobicity of MPs exhibited a notable increase, indicating conformational changes in MPs. Moreover, in the secondary structure of MPs, the α-helix content significantly decreased, whereas the β-sheet content increased, thereby suggesting the ultrasound-induced stretching and flexibility of MP molecules. Sodium-dodecyl sulfate–polyacrylamide gel electrophoresis and scanning electron microscopy analysis further elucidated that high-intensity ultrasound induced MP oxidation, leading to modification of amino acid side chains, intra- and intermolecular cross-linking, and MP aggregation. Consequently, high-intensity ultrasound treatment was found to augment the viscoelasticity, gel strength, and water-holding capacity of MP gels, because ultrasound treatment facilitated the formation of a stable network structure in protein gels. Thus, this study offers theoretical insights into the functional modification of bay scallop MPs and the processing of its surimi products.

This study uses high magnesium nickel slag (HMNS) directly as a raw material, to prepare high-temperature-resistant HMNS silico-aluminophosphate geopolymer (HMNSGP) activated by different types of acid activators including Al(H2PO4)3, H3PO4 and KH2PO4. By using characterization techniques such as XRD, FTIR, SEM-EDS, and MIP, the micro-properties, pore structure, and reaction mechanism of HMNSGP were investigated. The high temperature resistance of HMNSGP was evaluated by comparing compressive experiments before and after high temperature and TG-DSC. The results showed that the best samples were prepared using aluminium dihydrogen phosphate (ADP) at a P/Al molar ratio of 0.6. At room temperature, the main phases geopolymerized of the sample are crystalline products (Newberyite) and amorphous hydrated products (-Si-O-P-O-Si-, -Al-O-P-O-, -Si-O-Al-O-Si- and -P-O-Mg-). At 1200 °C, HMNSGP can still maintain its integrity, and its compressive strength can be increased to 48.4 MPa. The HMNSGP prepared using H3PO4 has the same hydration products as the optimal samples, but the lower amount of gel phase causes spallation at high temperatures. Besides primary phases geopolymerized with ADP as activator, the KH2PO4 sample includes crystalline products (K-struvite). However, this phase decomposes at 207 °C, affecting its high-temperature resistance while a significant volume shrinkage occurs at 1200 °C. In summary, using ADP with a P/Al molar ratio of 0.6 can directly prepare HMNS into an environmentally friendly refractory geopolymer material, the compressive strength shows stable growth after being exposed to 1200 °C. This results suggested that HMNSGP prepared with ADP can be used for structural applications, laying the foundation for future replacement of refractory cement.

BackgroundFollowing COVID-19, reports suggest Long COVID and autoimmune diseases (AIDs) in infected individuals. However, bidirectional causal effects between Long COVID and AIDs, which may help to prevent diseases, have not been fully investigated.MethodsSummary-level data from genome-wide association studies (GWAS) of Long COVID (N = 52615) and AIDs including inflammatory bowel disease (IBD) (N = 377277), Crohn’s disease (CD) (N = 361508), ulcerative colitis (UC) (N = 376564), etc. were employed. Bidirectional causal effects were gauged between AIDs and Long COVID by exploiting Mendelian randomization (MR) and Bayesian model averaging (BMA).ResultsThe evidence of causal effects of IBD (OR = 1.06, 95% CI = 1.00–1.11, p = 3.13E-02), CD (OR = 1.10, 95% CI = 1.01–1.19, p = 2.21E-02) and UC (OR = 1.08, 95% CI = 1.03–1.13, p = 2.35E-03) on Long COVID was found. In MR-BMA, UC was estimated as the highest-ranked causal factor (MIP = 0.488, MACE = 0.035), followed by IBD and CD.ConclusionThis MR study found that IBD, CD and UC had causal effects on Long COVID, which suggests a necessity to screen high-risk populations.

Background: Colon adenocarcinoma (COAD) has increasing incidence and is one of the most common malignant tumors. The mitochondria involved in cell energy metabolism, oxygen free radical generation, and cell apoptosis play important roles in tumorigenesis and progression. The relationship between mitochondrial genes and COAD remains largely unknown. Methods: COAD data including 512 samples were set out from the UCSC Xena database. The nuclear mitochondrial-related genes (NMRGs)-related risk prognostic model and prognostic nomogram were constructed, and NMRGs-related gene mutation and the immune environment were analyzed using bioinformatics methods. Then, a liver metastasis model of colorectal cancer was constructed and protein expression was detected using Western blot assay. Results: A prognostic model for COAD was constructed. Comparing the prognostic model dataset and the validation dataset showed considerable correlation in both risk grouping and prognosis. Based on the risk score (RS) model, the samples of the prognostic dataset were divided into high risk group and low risk group. Moreover, pathologic N and T stage and tumor recurrence in the two risk groups were significantly different. The four prognostic factors, including age and pathologic T stage in the nomogram survival model also showed excellent predictive performance. An optimal combination of nine differentially expressed NMRGs was finally obtained, including LARS2 , PARS2 , ETHE1 , LRPPRC , TMEM70 , AARS2 , ACAD9 , VARS2 , and ATP8A2 . The high-RS group had more inflamed immune features, including T and CD4 + memory cell activation. Besides, mitochondria-associated LRPPRC and LARS2 expression levels were increased in vivo xenograft construction and liver metastases assays. Conclusion: This study established a comprehensive prognostic model for COAD, incorporating nine genes associated with nuclear-mitochondrial functions. This model demonstrates superior predictive performance across four prognostic factors: age, pathological T stage, tumor recurrence, and overall prognosis. It is anticipated to be an effective model for enhancing the prognosis and treatment of COAD.

Intrahepatic cholangiocarcinoma (iCCA) is an aggressive liver malignancy with limited treatment options and a dismal prognosis. The tumor immune microenvironment (TIME) is crucial for iCCA progression, yet its comprehensive characterization remains incomplete. This study utilized mass cytometry by time of flight (CyTOF) to comprehensively analyze immune cell populations in fresh iCCA tumor samples and adjacent peritumor liver tissues. Notably, NK cell percentages significantly decreased in iCCA lesions compared to peritumor liver tissues. Conversely, an enrichment of immunosuppressive CD39+Foxp3+CD4+ regulatory T cells (CD39+T-regs) and exhausted-like CD8+ T cells (with pronounced CD39 and PD-1 expression) within TIME was identified and confirmed by multiplex immunofluorescence staining in an independent patient cohort (n = 140). Crucially, tumor-infiltrating CD39+T-regs and CD39+PD-1+CD8+ T cells emerged as independent prognostic indicators associated with an unfavorable prognosis in iCCA. These findings unveil the intricate immune landscape within iCCA, offering valuable insights for disease management and novel cancer immunotherapies.

Background:Cynanchum paniculatum (Bunge) Kitag. ex H.Hara, a member of the Asclepiadaceae family, has a rich history as a traditional Chinese medicinal plant used to treat digestive disorders. However, its potential anti-cancer effects in pancreatic cancer remain largely unexplored.Aim: This study delves into the intricate anti-pancreatic cancer mechanisms of C. paniculatum (Bunge) Kitag. ex H.Hara aqueous extract (CPAE) by elucidating its role in apoptosis induction and the inhibition of invasion and migration.Methods: A comprehensive set of methodologies was employed to assess CPAE’s impact, including cell viability analyses using MTT and colony formation assays, flow cytometry for cell cycle distribution and apoptosis assessment, scratch-wound and Matrigel invasion assays for migration and invasion capabilities, and immunoblotting to measure the expression levels of key proteins involved in apoptosis and metastasis. Additionally, a murine xenograft model was established to investigate CPAE’s in vivo anti-cancer potential.Results: CPAE exhibited time- and dose-dependent suppression of proliferation and colony formation in pancreatic cancer cells. Notably, CPAE induced apoptosis and G2/M phase arrest, effectively activating the caspase-dependent PARP pathway. At non-cytotoxic doses, CPAE significantly curtailed the metastatic abilities of pancreatic cells, effectively suppressing epithelial-mesenchymal transition (EMT) and downregulating the TGF-β1/Smad2/3 pathway. In vivo experiments underscored CPAE’s ability to inhibit tumor proliferation.Conclusion: This study illuminates the multifaceted anti-proliferative, pro-apoptotic, anti-invasive, and anti-migratory effects of CPAE, both in vitro and in vivo. CPAE emerges as a promising herbal medicine for pancreatic cancer treatment, with its potential mediated through apoptosis induction via the caspase-dependent PARP pathway and MET suppression via the TGF-β1/Smad2/3 signaling pathway at non-cytotoxic doses. These findings advocate for further exploration of CPAE’s therapeutic potential in pancreatic cancer.