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BACKGROUND: Pyroptosis could regulate tumor cell trafficking, invasion, and metastasis, as well as the tumor microenvironment (TME). However, prognostic characteristics of pyroptosis-related genes (PRGs) and their effect on the progression of glioma remain insufficient. METHODS: The genetic, transcriptional, and survival data of patients with glioma used for bioinformatic analysis were obtained from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases. RESULTS: Screening of two different molecular subtypes revealed that PRG variations were associated with characteristics of TME cell infiltration, clinicopathological characteristics, and prognosis of patients with glioma. After Cox regression of differentially expressed genes, a risk score for predicting overall survival (OS) and progression-free survival (PFS) were calculated. Its predictive accuracy in patients with glioma was validated. The high-risk group of PRG signature had a poorer OS than the low-risk group (training cohort, P< 0.001; validation cohort, P< 0.001). A high risk score implies more immune cell infiltration and better immunotherapy response to immune checkpoint blockers. In addition, the differential expression of three pyroptosis-pairs in tumor and normal tissues was identified. Furthermore, the risk score was significantly associated with chemotherapeutic drug sensitivity and cancer stem cell (CSC) index. Subsequently, a highly accurate nomogram was established to facilitate applicability in the preliminary clinical application of risk score. CONCLUSION: Our findings may provide the basis for future research targeting pyroptosis in glioma and evaluation of prognosis and development of more effective immunotherapy strategies.

In this study, the relationship between AO and winter synoptic temperature variability (STV) over the Northern Hemisphere is examined in 34 CMIP5/CMIP6 model outputs. With significant model bias around the North Pacific and North Atlantic, most models fail to capture the correct AO–STV pattern in historical simulations compared to observations. To investigate the bias of AO–STV relationship simulations, AO-related processes for the connection between AO and winter STV are examined in high pattern score (HPS) models and low pattern score (LPS) models, respectively. Furthermore, the bias of AO impact can be traced back to AO pattern simulations. On the one hand, compared to observations, HPS models can overall capture the intensity in the North Pacific and North Atlantic center of AO. On the other hand, LPS models tend to overestimate the North Pacific center and underestimate the North Atlantic center. In addition, similar to historical simulations, a robust AO–STV relationship can still be found over the Northern Hemisphere in future projections based on HPS models. Meanwhile, the uncertainty of the projected AO–STV relationship in the multimodel ensemble is confined mainly to the North Pacific, consistent with the large diversity of intensity over the North Pacific center of AO, which is related to the uncertainty of the relationship between AO and regional mode variability.

Marine heatwaves (MHWs) are extreme climatic events that can have a significant impact on marine ecosystems and their services across the world. We examine the spatiotemporal variation of summer MHWs in the north Indian Ocean (NIO) and find that the whole NIO Basin exhibits a pronounced spatial variability as well as a significant increasing trend in MHW frequency. We show that the NIO has two leading MHW modes linked to two distinct sea surface temperature (SST) patterns during summer. The first MHW mode is associated with basinwide warming, which is preconditioned by a decaying El Niño–Southern Oscillation (ENSO) and sustained throughout the summer by anomalous northeasterlies extending from the anticyclonic circulation of the western North Pacific subtropical high (WNPSH). The combined effect of thermocline warming due to downwelling oceanic planetary waves, decreased wind-induced evaporative cooling, and enhanced insolation cause basinwide summer MHWs. The second MHW mode exhibits a zonal dipole pattern, which has unfavorable cooling conditions in the previous seasons. The second MHW mode is associated with a phase change of ENSO and is greatly influenced by the formation of an interhemispheric pressure difference (IHPD) due to strengthening of the Australian high (AH) and weakening of the WNPSH. The IHPD induces cross-equatorial southerly winds across the eastern Indian Ocean. These winds favor the transformation of basinwide cooling conditions into zonal SST patterns via wind–evaporation–SST and thermocline–SST feedback, causing MHWs with a zonal dipole pattern. These MHW modes have a significant influence on the distribution and intensity of summer precipitation in the NIO.

This study presents a novel mechanism for the generation of extreme El Niño events by analyzing interactions between tropical cyclones (TCs) in the western North Pacific (WNP) in spring [March–May (MAM)] and summer [June–August (JJA)] and sea surface warming in the eastern tropical Pacific. It is suggested that anomalously strong TCs in the WNP in MAM and JJA are essential for the formation of extreme El Niño events. MAM TCs excite considerable westerly wind bursts (WWBs) and facilitate the generation of El Niño events in late spring. The sea surface temperature (SST) in the central-eastern tropical Pacific increases prominently during the following summer, which is due to the warm water carried by downwelling Kelvin waves induced by the anomalous westerlies in the western tropical Pacific associated with the WNP TCs, as well as the lessening cold water upwelling resulting from the deepening thermocline in the eastern tropical Pacific. The developing El Niño in turn contributes to the TC activities over the southeastern quadrant of the WNP in summer, characterized by a stronger intensity, higher frequency, and longer duration. The resulting JJA TC-induced westerlies could further enhance the eastern tropical Pacific warm SST anomalies, and thus an extreme El Niño event tends to appear in the following autumn and winter. These physical processes are verified by several sets of atmosphere–ocean coupled model experiments. Significance Statement Tropical cyclone activity is one of the most destructive phenomena in the world. Extreme El Niño events can also cause devastating climate disasters. Understanding the relationship between these two events can help with disaster forecasting and prevention. This study finds that TC activity in the western North Pacific contributes to the appearance of extreme El Niño events. Abnormally active TC activity in spring can cause strong near-equatorial westerly wind anomalies, eastward transport of warm water from the western tropical Pacific, and a deepening ocean thermocline in the east, resulting in the earlier onset of El Niño events. Influenced by the El Niño event, the TC activity in summer is strengthened, which in turn continues to promote the surface warming of the central-eastern tropical Pacific, eventually resulting in extreme event occurrence.

Streptococcus mutans is one of the major cariogenic pathogens in the oral cavity. The dlt operon is responsible for the process of D-alanylation of lipoteichoic acid and is related to the virulence of S. mutans. The dlt operon contributes to the adhesion, biofilm formation, stress response, interspecies competitiveness and autolysis of S. mutans. In addition, we have summarized the possible regulatory networks of the dlt operon. This review highlights the significant role of the dlt operon in S. mutans and provides new ideas for ecological caries prevention.

O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) is a ubiquitous posttranslational modification occurring in both animals and plants. Thousands of proteins along with their O-GlcNAcylation sites have been identified in various animal systems, yet the O-GlcNAcylated proteomes in plants remain poorly understood. Here, we report a large-scale profiling of protein O-GlcNAcylation in a site-specific manner in rice. We first established the metabolic glycan labeling strategy (MGL) with N-azidoacetylgalactosamine (GalNAz) in rice seedlings, which enabled incorporation of azides as a bioorthogonal handle into O-GlcNAc. By conjugation of the azide-incorporated O-GlcNAc with alkyne-biotin containing a cleavable linker via click chemistry, O-GlcNAcylated proteins were selectively enriched for mass spectrometry (MS) analysis. A total of 1,591 unambiguous O-GlcNAcylation sites distributed on 709 O-GlcNAcylated proteins were identified. Additionally, 102 O-GlcNAcylated proteins were identified with their O-GlcNAcylation sites located within a serine/threonine-enriched peptide, causing ambiguous site assignment. The identified O-GlcNAcylated proteins are involved in multiple biological processes such as transcription, translation and plant hormone signaling. Furthermore, we discovered two O-GlcNAc transferases (OsOGTs) in rice. By expressing OsOGTs in Escherichia coli and Nicotiana benthamiana leaves, we confirmed their OGT enzymatic activities and used them to validate the identified rice O-GlcNAcylated proteins. Our dataset provides a valuable resource for studying O-GlcNAc biology in rice, and the MGL method should facilitate the identification of O-GlcNAcylated proteins in various plants.

Autism spectrum disorder (ASD) is a complex disease with unclear etiology. Studies have shown that ferroptosis is also related to ASD progression, but the specific mechanism is still unclear. Valproic acid (VPA) induced neuronal ferroptosis in vitro. Mechanistic studies showed that both VPA and ferroptosis inducers promoted the expression of DDIT4 in neurons, thereby inhibiting the activation of the PI3K/Akt pathway. DDIT4 increased the accumulation of ROS, MDA and Fe

Formononetin-inhibited IgE-mediated mast cell activation and attenuated IgE/Ag-induced allergic inflammation by suppressing USP5 or USP13 expression and increasing proteasome-mediated FcεRIγ degradation.

High-level ab initio calculations on rate constants and thermochemistry for the reactions of alkyl cyclohexanes + HȮ2 were carried out and the results can be employed in chemical kinetics model development for alkyl cyclohexane combustion.

The addition of ether functional groups to a metallophthalocyanine ring is known to significantly decrease the oxidation potentials of the ring. In this light, the impact of the branching of alkyl-ether groups on the electronic properties was investigated via the synthesis of non-peripheral ([Formula: see text]-substituted n-butyl (1), iso-butyl (2) and sec-butyl (3) 1,4,8,11,15,18,22,25-octabutoxyphthalocyanines, in conjunction with Co and Cu metal centers. From 1 to 3 the first and second ring-based oxidation potentials were decreased by 70 mV and 110 mV respectively both for Cu and Co-containing complexes; the UV-visible Q-band maxima only changed by 4-8 nm, consistent with the destabilization of both the HOMO and LUMO, as confirmed by TD-DFT calculations. The reversibility of both redox couples was improved via branching (3) for the Co complexes. All six complexes were structurally characterized, with varying levels and types of ring distortions. All molecules show 1-D supramolecular stacking, but for n-butoxy 1Co an intermolecular Co-O interaction aligns the molecular stacks, while for sec-butoxy 3Co only [Formula: see text]-[Formula: see text] stacking of the Pc-ring was present. Both 3Co and 3Cu were ring-oxidized at lower potentials than 1Co and 1Cu, and the increased steric bulk from the branched ether chains prevented the overlap of their N8C8 inner rings.

Most of the current research on green energy and the pandemic focuses on how green investments changed after the epidemic and how the pandemic affected the local economy. The correlation between the rate of return on green energy and the number of confirmed cases in China and the rest of the globe is the main topic of this research. The daily cumulative confirmed Covid-19 cases in China and the rest of the world, and daily price of green energy are used as time series variables. They are daily data from the end of January 2020 to the end of July 2022. The study's findings largely show how the price of green energy has changed in relation to the pandemic's progression. A VAR (12) model makes a forecast on how the pandemic, which is expected to become stationary after the tenth period, would affect the price of green energy. The ARMA-GARCH model's findings demonstrate a statistically significant negative correlation between the price of green energy and the number of verified cases. In other words, compared to the pandemic, the price of green energy is lower. The pandemic has had no impact on the rate of return of green energy throughout the specified period, though.

Upadacitinib, an oral selective and reversible Janus kinase (JAK) inhibitor, showed favorable efficacy and safety in patients with moderate-to-severe ulcerative colitis (UC). The objective was to characterize upadacitinib pharmacokinetics in UC patients across Phase 2b and 3 trials and evaluate the relationships between upadacitinib plasma exposures and key efficacy or safety endpoints.Population pharmacokinetics and exposure-response analyses were performed to characterize upadacitinib pharmacokinetics in UC patients and evaluate the relationships between plasma exposures and key efficacy or safety endpoints at the end of 8-week induction and 52-week maintenance periods. Data from 1234 UC patients from Phase 2 and 3 induction trials and 449 UC patients from a Phase 3 maintenance trial were used for these analyses. Additionally, data from patients with rheumatoid arthritis, atopic dermatitis, Crohn's disease, and healthy volunteers were used in the pharmacokinetics analysis. Quartile plots and logistic regression models were used to evaluate the exposure-response relationships across upadacitinib doses of 7.5-45 mg once daily (QD) for induction and 15-30 mg QD for maintenance.Upadacitinib plasma exposures were dose-proportional in UC patients across the evaluated dose range. Upadacitinib pharmacokinetics in UC were consistent between the induction and maintenance periods, and with other patient populations. Upadacitinib plasma exposures associated with the 45 mg QD induction dose maximized efficacy for Week 8 clinical and endoscopic endpoints. Plasma exposures associated with upadacitinib 30 mg maintenance dose provided additional incremental benefit compared to 15 mg QD for Week 52 key clinical and endoscopic endpoints. No trends were observed in the evaluated safety events with increasing plasma exposures at the end of induction or maintenance periods.These analyses supported selection of upadacitinib UC induction and maintenance doses.Data from studies NCT02819635 and NCT03653026 were included in these analyses.

This multi-center study was aimed at retrospectively evaluating the feasibility, safety, clinical outcomes, and surgical learning curve of an optimized procedure for right upper lobectomy (RUL), which is challenging because of the anatomical structures and features of this lobe.This study included 45 RUL cases of robot-assisted thoracoscopy (RATS) in a pilot cohort and 187 RUL cases of video-assisted thoracoscopy (VATS) in three cohorts. A total of 121 and 111 patients underwent traditional and optimized RUL, respectively. The optimized surgical procedure was performed to consecutively transect the superior arterial trunk and bronchus, and finally disconnect the pulmonary vein and posterior ascending artery with interlobar fissures. Clinical and radiological data were reviewed retrospectively.Optimized RUL can be performed successfully by RATS or VATS. The optimized procedure yielded better clinical outcomes than the traditional procedure, including shorter operation times, less blood loss, fewer complications, shorter hospital times, lower costs, and a lower likelihood of postoperative intermedius bronchial kinking. Additionally, for calcified interlobar lymph nodes, the optimized VATS group was less likely to be converted to thoracotomy than the traditional group. The skills required to perform optimized VATS RUL can be gained by surgeons after 12 to 15 cases. The two RUL procedures in the pilot cohort showed similar disease-free survival.The optimized RUL was safe, economical, and feasible, with a short learning curve and satisfactory disease-free survival.

Background: Chronic psychological stress (PS) hinders the treatment of diabetes-associated cognitive decline (DACD). However, the impact of chronic PS on the risk of developing DACD remains unclear. There is growing evidence that gut flora interventions are promising targets for treating stress-related diseases. Objective: We examined whether chronic PS triggers or exacerbates the onset of DACD in rats and aimed to elucidate whether ZiBuPiYin recipe (ZBPYR) prevents and treats chronic PS-aggravated DACD by dynamically maintaining the components of the gut microbiota. Methods: We performed chronic PS (restraint, rotation, and congestion) on ZDF rats to establish a model. Cognitive function was evaluated by behavioral experiments, and activation of the hypothalamic-pituitary-adrenal axis was detected by ELISA. Weekly feces from rats were collected for 16 S RNA sequencing. Results: We found that chronic PS promoted cognitive abnormalities and exacerbated DACD phenotypes. Additionally, chronic PS altered intestinal flora diversity, dynamically elevating the abundance of Alistipes and Coprococcus; enriching Module 1 (Dorea, Blautia, Ruminococcus) and Module 48 (Blautia); and inhibiting Module 20 (Lactobacillus, SMB53), and Module 42 (Akkermansia). ZBPYR significantly alleviated hyperglycemia and cognitive impairment in chronic PS-aggravated DACD rats and dynamically reduced the abundance of Alistipes and Coprococcus; significantly enriched Module 3 (Ruminococcus) and Module 45 (Lactobacillus, Coprococcus, SMB53); and suppressed Module 2 (Lactobacillus), Module 16 (Turicibacter, Trichococcus, Lactobacillus, 02d06, Clostridium), Module 23 (Bifidobacterium), and Module 43 (Clostridium). Conclusion: ZBPYR might prevent and treat chronic PS-aggravated DACD by dynamically regulating Lactobacillus, Alistipes, and Coprococcus.

Leading modes of interannual variability in upper-ocean salinity in the tropical Indian Ocean (TIO) and their connections were studied based on 17 years (2002–18) of oceanic historical and reanalysis data. Empirical orthogonal function (EOF) analysis depicted the dominant roles of the first two leading modes in salinity variability in the TIO over a wide range of interannual time scales. Among the rich oscillations of the leading EOF modes, a coherent near-biennial band was identified with basinwide loading of sea surface salinity anomalies (SSSa) (EOF1) leading/lagging the northeast–southwest dipolar mode of SSSa (EOF2) by around 4 months across the TIO, with southwestward migration of SSSa center. The spatial loadings of the SSSa leading modes in the TIO were strongly shaped by sea surface temperature–related freshwater fluxes and wind-driven regional ocean circulation on a near-biennial time scale. Composite analysis of the mixed layer salinity budget reflected characteristic features of basin-scale ocean–atmosphere coupling, both temporally and regionally during the life cycle of the near-biennial fluctuation in anomalous salinity in the TIO. Consistent with the intrinsic oscillation paradigm in the observed Indian Ocean dipole (IOD) variation, the dynamic and thermodynamic feedbacks associated with switches from the positive to negative IOD modes provided the phase-connection mechanisms for the SSSa leading-mode displacement over the TIO. Significance Statement This study investigates the leading modes of interannual variability in upper-ocean salinity in the tropical Indian Ocean (TIO). The intrinsic oscillation and associated dynamic and thermodynamic feedbacks over the TIO drive the basinwide connections of upper-ocean salinity variability. Our results show that a coherent near-biennial band is identifiable within the leading modes of sea surface salinity anomalies (SSSa), in which the wind-induced horizontal advections and evaporation-minus-precipitation anomalies associated with the switches from positive to negative Indian Ocean dipole modes mainly provide the phase-transition mechanism of SSSa. This research illustrates substantial evidence for the displacement of basin-scale sea surface temperature anomalies modulating the structures of SSSa and inducing the dynamical connections of leading modes of SSSa on the near-biennial time scale.