Hypoxia and ferroptosis.

Ferroptosis is a novel, iron-dependent cell death characterized by the excessive accumulation of ferroptosis lipid peroxides ultimately leading to oxidative damage to the cell membrane. Iron, lipid, amino acid metabolism, and other signaling pathways all control ferroptosis. Numerous bodily tissues experience hypoxia under normal and pathological circumstances. Tissue cells can adjust to these changes by activating the hypoxia-inducible factor (HIF) signaling pathway and other mechanisms in response to the hypoxic environment. In recent years, there has been increasing evidence that hypoxia and ferroptosis are closely linked, and that hypoxia can regulate ferroptosis in specific cells and conditions through different pathways. In this paper, we review the possible positive and negative regulatory mechanisms of ferroptosis by hypoxia-inducible factors, as well as ferroptosis-associated ischemic diseases, with the intention of delivering novel therapeutic avenues for the defense and management of hypoxic illnesses linked to ferroptosis.

Omentin-1 attenuates lipopolysaccharide-induced inflammation and osteogenic differentiation in periodontal ligament stem cells and reduces M1 macrophages polarization through repressing endoplasmic reticulum stress.

Periodontitis is featured as the periodontium's pathologic destruction caused by the host's overwhelmed inflammation. Omentin-1 has been reported to be aberrantly downregulated in patients with periodontitis, but the specific regulation of Omentin-1 during the pathogenesis of periodontitis remains unclear. In this study, human periodontal ligament stem cells (hPDLSCs) were stimulated by lipopolysaccharide (LPS) from Porphyromonas gingivalis to establish an in vitro inflammatory periodontitis model. hPDLSCs were treated with recombinant human Omentin-1 (250, 500 and 750ng/mL) for 3h before LPS stimulation. Results revealed that Omentin-1 significantly inhibited LPS-induced inflammation in hPDLSCs through reducing the production of proinflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß and IL-6) and downregulating the expression of Cox2 and iNOS. Meanwhile, Omentin-1 significantly enhanced alkaline phosphatase (ALP) activity and Alizarin red-stained area, accompanied by increasing expression osteogenic markers BMP2, OCN and Runx2, confirming that Omentin-1 restores osteogenic differentiation in LPS-induced hPDLSCs. In addition, the conditioned medium (CM) from LPS-induced hPDLSCs was harvested to culture macrophages, which resulted in macrophage polarization towards M1, while CM from Omentin-1-treated hPDLSCs reduced M1 macrophages polarization and elevated M2 polarization. Furthermore, Omentin-1 also inhibited LPS-triggered endoplasmic reticulum (ER) stress in hPDLSCs, and additional treatment of the ER stress activator tunicamycin (TM) partially reversed the functions of Omentin-1 on inflammation, osteogenic differentiation and macrophages polarization. In summary, Omentin-1 exerted a protective role against periodontitis through inhibiting inflammation and enhancing osteogenic differentiation of hPDLSCs, providing a novelty treatment option for periodontitis.

Development and validation of novel interpretable survival prediction models based on drug exposures for severe heart failure during vulnerable period.

BACKGROUND: Severe heart failure (HF) has a higher mortality during vulnerable period while targeted predictive tools, especially based on drug exposures, to accurately assess its prognoses remain largely unexplored. Therefore, this study aimed to utilize drug information as the main predictor to develop and validate survival models for severe HF patients during this period. METHODS: We extracted severe HF patients from the MIMIC-IV database (as training and internal validation cohorts) as well as from the MIMIC-III database and local hospital (as external validation cohorts). Three algorithms, including Cox proportional hazards model (CoxPH), random survival forest (RSF), and deep learning survival prediction (DeepSurv), were applied to incorporate the parameters (partial hospitalization information and exposure durations of drugs) for constructing survival prediction models. The model performance was assessed mainly using area under the receiver operator characteristic curve (AUC), brier score (BS), and decision curve analysis (DCA). The model interpretability was determined by the permutation importance and Shapley additive explanations values. RESULTS: A total of 11,590 patients were included in this study. Among the 3 models, the CoxPH model ultimately included 10 variables, while RSF and DeepSurv models incorporated 24 variables, respectively. All of the 3 models achieved respectable performance metrics while the DeepSurv model exhibited the highest AUC values and relatively lower BS among these models. The DCA also verified that the DeepSurv model had the best clinical practicality. CONCLUSIONS: The survival prediction tools established in this study can be applied to severe HF patients during vulnerable period by mainly inputting drug treatment duration, thus contributing to optimal clinical decisions prospectively.

Identification of glycosyltransferases mediating 2-O-arabinopyranosyl and 2-O-galactosyl substitutions of glucuronosyl side chains of xylan.

Xylan is one of the major hemicelluloses in plant cell walls and its xylosyl backbone is often decorated at O-2 with glucuronic acid (GlcA) and/or methylglucuronic acid (MeGlcA) residues. The GlcA/MeGlcA side chains may be further substituted with 2-O-arabinopyranose (Arap) or 2-O-galactopyranose (Gal) residues in some plant species, but the enzymes responsible for these substitutions remain unknown. During our endeavor to investigate the enzymatic activities of Arabidopsis MUR3-clade members of the GT47 glycosyltransferase family, we found that one of them was able to transfer Arap from UDP-Arap onto O-2 of GlcA side chains of xylan, and thus it was named xylan 2-O-arabinopyranosyltransferase 1 (AtXAPT1). The function of AtXAPT1 was verified in planta by its T-DNA knockout mutation showing a loss of the Arap substitution on xylan GlcA side chains. Further biochemical characterization of XAPT close homologs from other plant species demonstrated that while the poplar ones had the same catalytic activity as AtXAPT1, those from Eucalyptus, lemon-scented gum, sea apple, 'Ohi'a lehua, duckweed and purple yam were capable of catalyzing both 2-O-Arap and 2-O-Gal substitutions of xylan GlcA side chains albeit with differential activities. Sequential reactions with XAPTs and glucuronoxylan methyltransferase 3 (GXM3) showed that XAPTs acted poorly on MeGlcA side chains, whereas GXM3 could efficiently methylate arabinosylated or galactosylated GlcA side chains of xylan. Furthermore, molecular docking and site-directed mutagenesis analyses of Eucalyptus XAPT1 revealed critical roles of several amino acid residues at the putative active site in its activity. Together, these findings establish that XAPTs residing in the MUR3 clade of family GT47 are responsible for 2-O-arabinopyranosylation and 2-O-galactosylation of GlcA side chains of xylan.

Nonsurgical Correction of Congenital Auricular Anomalies: Design and Effectiveness of the Ear Splint.

Congenital auricular anomaly is a common problem for newborns. In recent years, the correction technology of ear molding has gradually become the mainstream therapy. Therefore, the purpose of this case report is to describe ear molding devices with low-temperature thermoplastic splints, designed by occupational therapists and called the Ear Splint for Taiwan, and to explore its effectiveness in treating newborns with congenital auricular anomalies. The ear splint is made by an occupational therapist based on the theory of corrective mechanics. The molded splint adjusts the ear to normal shape. Patients who received ear treatments at the Mennonite Christian Hospital in 2020 were enrolled as the subjects. A posttest research design was adopted in this case report to conduct a questionnaire survey among parents. The ear splint is a double C-shaped bracket. In this case report, there were two subjects in total, and two different types of malformed ears. According to the questionnaire survey, the average score of auricle shape improvement effectiveness after interventions were 5 and 4 points (5 excellent; 1 bad). The results of this case report indicate that it is feasible for occupational therapists to use the ear splint to mold the congenital auricular anomalies of newborns. Preliminary evidence shows that ear shapes can be corrected. The ear splint provides an early interventional therapy for newborns with congenital auricular anomalies in Taiwan.

Passive laser power stabilization in a broadband noise spectrum via a second-harmonic generator.

An extremely conspicuous passive power noise stabilization is the first, to the best of our knowledge, discovered in a cavity-enhanced second-harmonic generation (SHG) process. Differing from the SHG as a buffer reservoir, the stronger strength of the nonlinear interaction pushes the power noise suppression level to a higher value and exhibits a broadband noise reduction performance due to the mechanism of dynamic pump suppression in the SHG process. The noise is suppressed to near shot noise limit (SNL) among the kHz to MHz frequency range, accompanied by a maximum noise reduction of 35 dB. A comprehensive demonstration indicates that the nonlinear interaction has no function on the phase noise of fundamental and harmonic waves. A theoretical model is also established that is consistent well with the experimental results. The methodology is beneficial to multiple optical metrology experiments.

Differences and Mechanism of Waxy Corn Starch and Normal Corn Starch in the Preparation of Recrystallized Resistant Starch (RS3).

This study prepared resistant starch (RS) from waxy corn starch and normal corn starch and analyzed the effects of its molecular and microstructural characteristics on RS content. The RS content of waxy corn resistant starch (RS-WCS) was highest at 57.8%, whereas that of normal corn resistant starch (RS-NCS) was 41.46%. The short-chain amylose contents of RS-WCS and RS-NCS were 47.08% and 37.24%, respectively, proportional to their RS content. Additionally, RS content positively correlated with crystallinity, short-range order degree, and degree of polymerization (DP), exceeding 25. Electron microscopic images, before and after enzymolysis, revealed that RS-WCS was hydrolyzed from the surface to the center by pancreatic α-amylase, while RS-NCS underwent simultaneous hydrolysis at the surface and center. These results indicate that the higher RS content in RS-WCS, compared to RS-NCS, is attributable to the synergistic effects of molecular structure and microstructure.

Ganoderma lucidum Polysaccharide Supplementation Significantly Activates T-Cell-Mediated Antitumor Immunity and Enhances Anti-PD-1 Immunotherapy Efficacy in Colorectal Cancer.

Ganoderma lucidum polysaccharide (GLP) is a prebiotic with immunomodulatory effects. However, the therapeutic potential of GLP in tumor immunotherapy has not been fully explored, especially in T cell-mediated antitumor immunity. In this study, we found that GLP significantly inhibited tumor growth and activated antitumor immunity in colorectal cancer (CRC). In the spleens and tumor tissues, the proportion of cytotoxic CD8+T cells and Th1 helper cells increased, while immunosuppressive Tregs decreased. Additionally, microbiota dysbiosis was alleviated by GLP, and short-chain fatty acid production was increased. Meanwhile, GLP decreased the ratio of kynurenine and tryptophan (Kyn/Trp) in the serum, which contributed to antitumor immunity of T cells. More importantly, the combination of GLP and the immune checkpoint inhibitor anti-PD-1 monoclonal antibody further enhanced the efficacy of anti-PD-1 immunotherapy. Thus, GLP as a prebiotic has the potential to be used in tumor immunotherapy.

A rice GT61 glycosyltransferase possesses dual activities mediating 2-O-xylosyl and 2-O-arabinosyl substitutions of xylan.

MAIN CONCLUSION: A member of the rice GT61 clade B is capable of transferring both 2-O-xylosyl and 2-O-arabinosyl residues onto xylan and another member specifically catalyses addition of 2-O-xylosyl residue onto xylan. Grass xylan is substituted predominantly with 3-O-arabinofuranose (Araf) as well as with some minor side chains, such as 2-O-Araf and 2-O-(methyl)glucuronic acid [(Me)GlcA]. 3-O-Arabinosylation of grass xylan has been shown to be catalysed by grass-expanded clade A members of the glycosyltransferase family 61. However, glycosyltransferases mediating 2-O-arabinosylation of grass xylan remain elusive. Here, we performed biochemical studies of two rice GT61 clade B members and found that one of them was capable of transferring both xylosyl (Xyl) and Araf residues from UDP-Xyl and UDP-Araf, respectively, onto xylooligomer acceptors, whereas the other specifically catalysed Xyl transfer onto xylooligomers, indicating that the former is a xylan xylosyl/arabinosyl transferase (named OsXXAT1 herein) and the latter is a xylan xylosyltransferase (named OsXYXT2). Structural analysis of the OsXXAT1- and OsXYXT2-catalysed reaction products revealed that the Xyl and Araf residues were transferred onto O-2 positions of xylooligomers. Furthermore, we demonstrated that OsXXAT1 and OsXYXT2 were able to substitute acetylated xylooligomers, but only OsXXAT1 could xylosylate GlcA-substituted xylooligomers. OsXXAT1 and OsXYXT2 were predicted to adopt a GT-B fold structure and molecular docking revealed candidate amino acid residues at the predicted active site involved in binding of the nucleotide sugar donor and the xylohexaose acceptor substrates. Together, our results establish that OsXXAT1 is a xylan 2-O-xylosyl/2-O-arabinosyl transferase and OsXYXT2 is a xylan 2-O-xylosyltransferase, which expands our knowledge of roles of the GT61 family in grass xylan synthesis.

Asymmetric 1,4-Addition of Diarylphosphine Oxides to α, ß-Unsaturated 2-Acyl Imidazoles.

Here we introduce a metal-free, catalytic and enantioselective strategy from α,ß-unsaturated 2-acyl imidazoles to the chiral phosphorous 2-acyl imidazoles. Interestingly, this methodology was catalyzed by the classical and commercial oxazaborolidine under mild conditions. This strategy features a wide range of substrates scope with good yields and excellent enantioselectivities. The possible mechanism further suggests the key of this reaction through the cleavage of diarylphosphine oxides using Frustrated Lewis Pairs theory.

Broadband and robust Mach-Zehnder interferometer for Rydberg atomic system.

We present a broadband and robust Mach-Zehnder interferometer (MZI) with meter-scale arm length, aiming to acquire the full information of an atomic system. We utilize a pre-loading phase shifter as servo actuator, broadening the servo bandwidth to 108 kHz without sacrificing the size of the piezoelectric transducer (PZT) and mirror. An auxiliary laser at 780 nm, counter-propagating with the probe laser, is employed to achieve arbitrary phase locking of the MZI, boosting a phase accuracy of 0.45 degrees and an Allan deviation of 0.015 degrees, which breaks the current record. By utilizing our robust MZI, the measurement accuracy of atomic system can be theoretically predicted to improve by 2.3 times compared to the most stable MZI in other literatures. In addition, we also demonstrate the sensitivity improvement in imaginary part and real part of the susceptibility in virtue of the completed interferometer, which exhibits tremendous potential in atom-based measurement system.

High expression of SHP2 predicts a promising prognosis in colorectal cancer.

Background: Src homology 2 domain-containing phosphatase 2 (SHP2) is hyper-activated in some solid tumors. Previous findings suggest that the expression of SHP2 in colorectal cancer (CRC) may be associated with prognosis. However, validation with large sample data is lacking. Materials and Methods: Tissue microarrays containing 860 CRCs and 197 mucosal tissues adjacent to the tumors were constructed. Immunohistochemistry was used to evaluate the expression of SHP2. Differences between SHP2 expression and clinicopathological parameters were evaluated. Kaplan-Meier survival curves and log-rank tests were used to analyze the relationships between SHP2 expression and the overall survival of patients. A Cox proportional hazard regression model was used for univariate and multivariate analyses of prognostic factors. Results: SHP2 expression in CRCs tissues was significantly higher than those in adjacent mucosal tissues (P < 0.001). SHP2 expression was related to tumor differentiation, depth of invasion, distant metastasis, vascular tumor thrombus, lymph node metastasis, and TNM classification (P < 0.05). The prognosis of the high-expression group of SHP2 was significantly better than that of the low-expression group (P = 0.008). Univariate analysis showed that the expression of SHP2 was a prognostic factor for CRC (P = 0.008). Multivariate analysis demonstrated that SHP2 remained an independent prognostic factor for CRC (P = 0.033). Conclusion: The expression of SHP2 was significantly higher in CRC tissues than in adjacent normal tissues. High expression of SHP2 was associated with a promising outcome, suggesting that SHP2 may be a favorable prognostic indicator of CRC.

The benefit of omeprazole exposure on all-cause mortality and length of ICU/hospital stay might vary with age in critically ill pediatric patients: A cohort study.

PURPOSE: To investigate the association between proton pump inhibitors (PPIs) administration during hospitalization and mortality and length of stay in critically ill pediatric patients. MATERIALS AND METHODS: This is a retrospective observational cohort study on pediatric ICU patients (0 to 18 years). Propensity score matching (PSM), Kaplan-Meier curves, Cox proportional hazards model and Linear regression model was applied for assessing the effects of PPIs on mortality and other outcomes during hospitalization. RESULTS: A total of 2269 pediatric ICU patients were included, involving 1378 omeprazole (OME) users and 891 non-OME users. The results showed significant association between OME exposure and decreased ICU stay (ß -0.042; 95% CI -0.073--0.011; P = 0.008) but prolonged non-ICU hospital stay (ß 0.121; 95% CI 0.097-0.155; P = 0.040). No statistical significance was observed between OME exposure and reduced mortality, but the OME group had a slightly decreased tendency in 28-day mortality (HR 0.701; 95% CI 0.418-1.176) and in-hospital mortality (HR 0.726; 95% CI 0.419-1.257). Furthermore, subgroup analyses revealed that the decreased tendency of mortality were more obvious in patients less than 1 year old compared with older pediatric patients, although not statistically significant. In addition, we also observed that OME exposure was significantly associated with reduced mortality of general ICU subgroup. CONCLUSIONS: This study provided a sign that PPIs used only in the ICU, rather than throughout hospital stay, might provide more benefit for critically ill pediatric patients. Additionally, younger pediatric patients might gain relatively more benefit than older children when receiving PPIs.

Multicolored inorganic electrochromic materials: status, challenge, and prospects.

Against the backdrop of advocacy for green and low-carbon development, electrochromism has attracted academic and industrial attention as an intelligent and energy-saving applied technology due to its optical switching behavior and its special principles of operation. Inorganic electrochromic materials, represented by transition metal oxides, are considered candidates for the next generation of large-scale electrochromic applied technologies due to their excellent stability. However, the limited color diversity and low color purity of these materials greatly restrict their development. Starting from the multicolor properties of inorganic electrochromic materials, this review systematically elaborates on recent progress in the aspects of the intrinsic multicolor of electrochromic materials, and structural multicolor based on the interaction between light and microstructure. Finally, the challenges and opportunities of inorganic electrochromic technology in the field of multicolor are discussed.

A meta-analysis of associations of IL-10 gene polymorphisms with acute leukemia susceptibility.

BACKGROUND: Recently, increasing evidence has demonstrated that IL-10 single nucleotide polymorphisms (SNPs) are associated with the risk of acute leukemia (AL), but the findings of different articles remain controversial. Thus, we performed a meta-analysis to further investigate the exact roles of IL-10 SNPs in AL susceptibility. METHODS: Six common Chinese and English databases were utilized to retrieve eligible studies. The strength of the association was assessed by calculating odds ratios and 95 % confidence intervals. All analyses were carried out using Review Manager (version 5.3) and STATA (version 15.1). The registered number of this research is CRD42022373362. RESULTS: A total of 6391 participants were enrolled in this research. The results showed that the AG genotype of rs1800896 increased AL risk in the heterozygous codominant model (AG vs. AA, OR = 1.41, 95 % CI = 1.04-1.92, P = 0.03) and overdominant model (AG vs. AA + GG, OR = 1.32, 95 % CI = 1.04-1.70, P = 0.03). In the subgroup analysis, associations between the G allele, GG genotype, AG genotype, AG + GG genotype of rs1800896 and increased AL risk were also observed in the mixed population based on allelic, homozygote codominant, heterozygous codominant, dominant, and overdominant models. Furthermore, an association between the AC genotype of rs1800872 and increased AL risk was observed in the Caucasian population in the overdominant model. However, the rs1800871, rs3024489 and rs3024493 polymorphisms did not affect AL risk. CONCLUSION: IL-10 rs1800896 and rs1800872 affected the susceptibility of AL and therefore may be biomarkers for early screening and risk prediction of AL.

Application of Oxazaborolidine Catalysts (CBS) on Enantioselective 1,4-Addition of Diarylphosphine Oxides to α,ß-Unsaturated Thioesters.

Here, we report the first catalytic enantioselective 1,4-addition of diarylphosphine oxides to α,ß-unsaturated thioesters. Importantly, the most common and commercial oxazaborolidine (CBS) was employed as a catalyst for its new application without being activated by strong protonic acids or Lewis acids and led to the chiral thioesters in excellent yields and enantioselectivities. Furthermore, this method features mild reaction conditions (room temperature and air-insensitive), good substrate tolerance, and easy scalability.

Cell metabolism-based optimization strategy of CAR-T cell function in cancer therapy.

Adoptive cell therapy (ACT) using chimeric antigen receptor (CAR)-modified T cells has revolutionized the field of immune-oncology, showing remarkable efficacy against hematological malignancies. However, its success in solid tumors is limited by factors such as easy recurrence and poor efficacy. The effector function and persistence of CAR-T cells are critical to the success of therapy and are modulated by metabolic and nutrient-sensing mechanisms. Moreover, the immunosuppressive tumor microenvironment (TME), characterized by acidity, hypoxia, nutrient depletion, and metabolite accumulation caused by the high metabolic demands of tumor cells, can lead to T cell "exhaustion" and compromise the efficacy of CAR-T cells. In this review, we outline the metabolic characteristics of T cells at different stages of differentiation and summarize how these metabolic programs may be disrupted in the TME. We also discuss potential metabolic approaches to improve the efficacy and persistence of CAR-T cells, providing a new strategy for the clinical application of CAR-T cell therapy.

The high expression of FOXE1 in colorectal cancer predicts a promising prognosis: a retrospective study.

Purpose Forkhead box (FOX) family proteins regulate transcription and DNA repair and are involved in cell growth, differentiation, embryogenesis, and lifespan. The transcription factor FOXE1 is a member of the FOX family. The relationship between the expression level of FOXE1 and colorectal cancer (CRC) prognosis remains controversial. It is vital to verify the relationship between FOXE1 expression and the prognosis of patients with CRC. Methods We constructed a tissue microarray containing 879 primary colorectal cancer tissues and 203 normal mucosa samples. The tumor and normal mucosa tissues were stained with FOXE1 by immunohistochemistry, and the staining results were divided into two groups: high expression group and low expression group. Chi-square test was performed for the classification variable of the difference between FOXE1 expression levels and clinicopathological parameters. The survival curve was calculated according to the Kaplan-Meier method and the logarithmic rank test. The Cox proportional risk regression model was used for multivariate analysis of prognostic factors in patients with CRC.Results The expression level of FOXE1 in colorectal cancer was higher than that in the normal mucosa adjacent to cancer, although the difference was not significant. However, the expression of FOXE1 was correlated with tumor size, T stage, N stage, M stage, and pTNM stage. Univariate and multivariate analyses suggested that FOXE1 could be used as an independent prognostic factor in patients with CRC. Conclusions FOXE1 may be a potential independent prognostic factor for colorectal cancer patients.