Exploring the efficacy and safety of anti-BCMA chimeric antigen receptor T-cell therapy for multiple myeloma: Systematic review and meta-analysis.

Objective: Multiple myeloma (MM) is a bone marrow cancer that profoundly affects plasma cells involved in the immune response. Myeloma cells alter the average production of cells in the bone marrow. Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy allows genetic modifications of an individual's T-cells to increase the expression of CARs used to identify and attach BCMA proteins to the malignant cells. Our main objective is to perform a systematic review and meta-analysis to explore the efficacy and safety of anti-BCMA CAR T-cell therapy for MM. Material and Methods: We searched five databases, PubMed, CNKI, EMBASE, Cochrane, Web of Science, and CNKI, for studies published on anti-BCMA,CAR-T-cell treatment for MM. Inclusion criteria involved prospective single-arm studies either single or multi-center, in various MM phases and studies that reported anti-BCMA,CAR-T-cell treatment for MM. We excluded non-English publications and conference papers. All statistical analyses were performed in R software and Review Manager 5.4.1. Results: Thirteen articles were included in the analysis. We found that the overall response survival complete response increase was statistically significant. Similarly, the reduction in cytokine release syndrome grades 3 and 4 and neurotoxicity after follow-up was statistically significant. However, the reduction in minimal residual disease negativity (MRDN) was not statistically significant. Conclusion: Using anti-BCMA CAR T-cell therapy in MM was highly efficacious and safe in lowering the adverse outcomes and improving the survival outcomes, complete response, and overall response.

Association between Serum Lactate Dehydrogenase Level and 30-day Mortality in Patients with Intracranial Hemorrhage with Acute Leukemia in the Induction Phase: A Cohort Study.

Objectives This study aimed to identify the association between lactate dehydrogenase (LDH) levels and 30-day mortality in patients with intracranial hemorrhage (ICH) with acute leukemia during the induction phase. Methods This cohort study included patients with acute leukemia with ICH during induction. We evaluated serum LDH levels upon admission. Multivariable Cox regression analyzed the LDH 30-day mortality association. Interaction and stratified analyses based on factors like age, sex, albumin, white blood cell count, hemoglobin level, and platelet count were conducted. Results We selected 91 patients diagnosed with acute leukemia and ICH. The overall 30-day mortality rate was 61.5%, with 56 of the 91 patients succumbing. Among those with LDH levels ≥ 570 U/L, the mortality rate was 74.4% (32 out of 43), which was higher than the 50% mortality rate of the LDH < 570 U/L group (24 out of 48) ( p = 0.017). In our multivariate regression models, the hazard ratios and their corresponding 95% confidence intervals for Log2 and twice the upper limit of normal LDH were 1.27 (1.01, 1.58) and 2.2 (1.05, 4.58), respectively. Interaction analysis revealed no significant interactive effect on the relationship between LDH levels and 30-day mortality. Conclusions Serum LDH level was associated with 30-day mortality, especially in patients with LDH ≥ 570 U/L.

Quantum-Geometry-Induced Anomalous Hall Effect in Nonunitary Superconductors and Application to Sr_{2}RuO_{4}.

The polar Kerr effect and the closely related anomalous charge Hall effect are among the most distinguishing signatures of the superconducting state in Sr_{2}RuO_{4}, as well as in several other compounds. These effects are often thought to be derived from chiral superconducting pairing, and different mechanisms have been invoked for the explanation. However, the intrinsic mechanisms proposed previously often involve unrealistically strong interband Cooper pairing. We show in this Letter that, even without interband pairing, nonunitary superconducting states can support the intrinsic anomalous charge Hall effect, thanks to the quantum geometric properties of the Bloch electrons. The key here is to have a normal-state spin Hall effect, for which a nonzero spin-orbit coupling is essential. A finite charge Hall effect then naturally arises at the onset of a spin-polarized nonunitary superconducting pairing. It depends on both the spin polarization and the normal-state electron Berry curvature, the latter of which is the imaginary part of the quantum geometric tensor of the Bloch states. Applying our results to the weakly paired Sr_{2}RuO_{4} we conclude that, if the reported Kerr effect is of intrinsic origin, the superconducting state is most likely nonunitary and has odd parity. Our theory may be generalized to other superconductors that exhibit the polar Kerr effect.

Hepatocyte mitochondrial DNA mediates macrophage immune response in liver injury induced by trichloroethylene.

We have previously shown that excessive activation of macrophage proinflammatory activity plays a key role in TCE-induced immune liver injury, but the mechanism of polarization is unclear. Recent studies have shown that TLR9 activation plays an important regulatory role in macrophage polarization. In the present study, we demonstrated that elevated levels of oxidative stress in hepatocytes mediate the release of mtDNA into the bloodstream, leading to the activation of TLR9 in macrophages to regulate macrophage polarization. In vivo experiments revealed that pretreatment with SS-31, a mitochondria-targeting antioxidant peptide, reduced the level of oxidative stress in hepatocytes, leading to a decrease in mtDNA release. Importantly, SS-31 pretreatment inhibited TLR9 activation in macrophages, suggesting that hepatocyte mtDNA may activate TLR9 in macrophages. Further studies revealed that pharmacological inhibition of TLR9 by ODN2088 partially blocked macrophage activation, suggesting that the level of macrophage activation is dependent on TLR9 activation. In vitro experiments involving the extraction of mtDNA from TCE-sensitized mice treated with RAW264.7 cells further confirmed that hepatocyte mtDNA can activate TLR9 in mouse peritoneal macrophages, leading to macrophage polarization. In summary, our study comprehensively confirmed that TLR9 activation in macrophages is dependent on mtDNA released by elevated levels of oxidative stress in hepatocytes and that TLR9 activation in macrophages plays a key role in regulating macrophage polarization. These findings reveal the mechanism of macrophage activation in TCE-induced immune liver injury and provide new perspectives and therapeutic targets for the treatment of OMDT-induced immune liver injury.

[Spectral Characteristics and Sources of Dissolved Organic Matter in Inflow Rivers of Baiyangdian Lake Water in Summer Flood Season].

DOM is the largest reservoir of organic carbon in the world, and it plays a crucial role in the biogeochemical cycles of natural water bodies. A river is a transition area connecting source water and receiving water that controls the DOM exchange between them. Therefore, in this study, ultraviolet visible spectroscopy (UV-vis) and three-dimensional fluorescence spectroscopy (EEMs) combined with parallel factor analysis (PARAFAC) were used to analyze the spectral characteristics and sources of dissolved organic matter in the Fuhe River, Xiaobai River, Baigouyin River, and Puhe River of Baiyangdian. The results showed that a245 and a355 in the Fuhe River and Xiaobai River were significantly higher than those in the Baigouyin River and Puhe River. E2/E3 showed that the DOM relative molecular mass of the inflow river water body was Puhe River > Baigouyin River > Fuhe River > Xiaobai River. Three components, tyrosine-like (C1), terrigenous humus (C2), and tryptophan-like (C3), were determined using three-dimensional fluorescence through PARAFAC. There was no difference among the fluorescence components (P>0.05), but there were differences among the C2 and C3 components (P<0.05). The proportion of easily degradable protein-like components (C1+C3) was higher than that of humus-like components (C2). The autogeny index BIX was greater than 1, and the humification index HIX was less than 4, indicating that the autogeny characteristics of the river bodies were obvious, and the humification degree was weak. The FI index was the highest (1.96±0.25), and the HIX index was the lowest (0.46±0.08), and the self-generated source characteristics gradually strengthened along the direction of the river entering the lake, indicating that the water body of the Fuhe River showed higher endogenous and autogenic characteristics. Based on the correlation analysis of fluorescence components and characteristic parameters of DOM, the correlations between the Fuhe River and Xiaobaihe River and between the Baigouyin River and Puhe River bodies were similar. The correlation between fluorescence components of DOM and water quality parameters of each lake was significantly different, and it was strongly correlated with nitrogen and phosphorus in water. According to multiple linear regression analysis, there was no significant difference among C1 components, but there was a significant difference between C2 and C3 components. In summary, the carbon cycle process of Baiyangdian Lake was further understood through the study on the DOM spectral characteristics and sources of the inflow river waters in the summer flood season.

Pharmacokinetics, pharmacodynamics, and safety of frunexian in healthy Chinese volunteer adults: A randomized dose-escalation phase I study.

The purpose of this study was to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of frunexian (formerly known as EP-7041 and HSK36273) injection, a small molecule inhibitor of activated coagulation factor XI (FXIa), in healthy Chinese adult volunteers. This study was a randomized, placebo- and positive-controlled, sequential, ascending-dose (0.3/0.6/1.0/1.5/2.25 mg/kg/h) study of 5-day continuous intravenous infusions of frunexian. Frunexian administration exhibited an acceptable safety profile with no bleeding events. Steady state was rapidly reached with a median time ranging from 1.02 to 1.50 h. The mean half-life ranged from 1.15 to 1.43 h. Frunexian plasma concentration at a steady state and area under the concentration-time curve exhibited dose-proportional increases. The dose-escalation study of frunexian demonstrated its progressively enhanced capacities to prolong activated partial thromboplastin time (aPTT) and inhibit FXIa activity. The correlations between PK and PD biomarkers (aPTT/baseline and FXI clotting activity/baseline) were described by the two Emax models, with the EC50 values of 8940 and 1300 ng/mL, respectively. Frunexian exhibits good safety and PK/PD properties, suggesting it is a promising candidate for anticoagulant drug.

A reference-grade genome of the xerophyte Ammopiptanthus mongolicus sheds light on its evolution history in legumes and drought tolerance mechanisms.

Plants grown under extreme environments represent unique sources for stress-resistant genes and mechanisms. Ammopiptanthus mongolicus (Leguminosae) is a xerophytic legume shrub with evergreen broadleaves native to the semi-arid and desert regions, however, its drought tolerance mechanisms have not been well understood. Here, we report the assembly of a reference-grade genome, its evolutionary history within the legume family, and examination to its drought tolerance mechanisms. The assembled genome size was 843.07 Mb and 98.7% of the assembly was successfully anchored to the nine chromosomes of the plant. 47,611 genes were predicted to be protein-coding and 70.71% of the genome is composed of repetitive sequences dominated by transposable elements, particularly long-terminal-repeat retrotransposons (LTR-RTs). Evolutionary analyses revealed two whole-genome duplication (WGD) events shared by the genus Ammopiptanthus and other legumes at 130 and 58 million years ago (Mya), whereas no species-specific WGD was found within this genus. Further ancestral genome reconstruction indicated that the A. mongolicus genome had fewer rearrangements within the legume family, confirming it is a "relict plant". Transcriptomic analyses revealed that cuticular wax biosynthesis and transport genes were highly expressed under both normal and polyethylene glycol (PEG)-induced dehydration conditions, and significant induction of ethylene biosynthesis and signaling related genes was also observed in leaves experiencing the dehydration stress, indicating that enhanced ethylene response and formation of thick waxy cuticles are two major mechanisms of drought tolerance in A. mongolicus. Consistently, ectopic expression of AmERF2, an ethylene response factor unique for A. mongolicus, resulted in marked increase of drought tolerance in transgenic Arabidopsis thaliana plants, demonstrating the application potential of A. mongolicus genes in crop improvement.

Effect of corneal cross-linking on biomechanical changes following transepithelial photorefractive keratectomy and femtosecond laser-assisted LASIK.

Purpose: To evaluate the change in corneal biomechanics in patients with postoperative ectasia risk when combining two common laser vision correction procedures (tPRK and FS-LASIK) with cross-linking (in tPRK Xtra and FS-LASIK Xtra). Methods: The study included 143 eyes of 143 myopic, astigmatic patients that were divided into non-cross-linked refractive surgery groups (non-Xtra groups, tPRK and FS-LASIK) and cross-linked groups (Xtra groups, tPRK Xtra and FS-LASIK Xtra) according to an ectasia risk scoring system. The eyes were subjected to measurements including the stress-strain index (SSI), the stiffness parameter at first applanation (SP-A1), the integrated inverse radius (IIR), the deformation amplitude at apex (DA), and the ratio of deformation amplitude between apex and 2 mm from apex (DARatio2mm). The measurements were taken preoperatively and at 1, 3, and 6 months postoperatively (pos1m, pos3m, and pos6m). Posterior demarcation line depth from the endothelium (PDLD) and from the ablation surface (DLA) were recorded at pos1m. Results: SP-A1 significantly decreased, while IIR, deformation amplitude, and DARatio2mm increased significantly postoperatively in all four groups (p < 0.01)-all denoting stiffness decreases. In the FS-LASIK group, the changes in IIR, DA, and DARatio2mm were 32.7 ± 15.1%, 12.9 ± 7.1%, and 27.2 ± 12.0% respectively, which were significantly higher (p < 0.05) compared to 20.1 ± 12.8%, 6.4 ± 8.2%, and 19.7 ± 10.4% in the FS-LASIK Xtra group. In the tPRK group, the change in IIR was 27.3 ± 15.5%, significantly larger than 16.9 ± 13.4% in the tPRK Xtra group. The changes of SSI were minimal in the tPRK (-1.5 ± 21.7%, p = 1.000), tPRK Xtra (8.4 ± 17.9%, p = 0.053), and FS-LASIK Xtra (5.6 ± 12.7%, p = 0.634) groups, but was significant in the FS-LASIK group (-12.1 ± 7.9%, p < 0.01). After correcting for baseline biomechanical metrics, preoperative bIOP and the change in central corneal thickness (△CCT) from pre to pos6m, the changes in the IIR in both FS-LASIK and tPRK groups, as well as DA, DARatio2mm and SSI in the FS-LASIK group remained statistically greater than their corresponding Xtra groups (all p < 0.05). Most importantly, after correcting for these covariates, the changes in DARatio2mm in the FS-LASIK Xtra became statistically smaller than in the tPRK Xtra (p = 0.017). Conclusion: The statistical analysis results indicate that tPRK Xtra and FS-LASIK Xtra effectively reduced the biomechanical losses caused by refractive surgery (tPRK and FS-LASIK). The decrease in corneal overall stiffness was greater in FS-LASIK than in tPRK, and the biomechanical enhancement of CXL was also higher following LASIK than after tPRK.

U-shaped association between sleep duration and biological aging: Evidence from the UK Biobank study.

Previous research on sleep and aging largely has failed to illustrate the optimal dose-response curve of this relationship. We aimed to analyze the associations between sleep duration and measures of predicted age. In total, 241,713 participants from the UK Biobank were included. Habitual sleep duration was collected from the baseline questionnaire. Four indicators, homeostatic dysregulation (HD), phenoAge (PA), Klemera-Doubal method (KDM), and allostatic load (AL), were chosen to assess predicted age. Multivariate linear regression models were utilized. The association of sleep duration and predicted age followed a U-shape (All p for nonlinear <0.05). Compared with individuals who sleep for 7 h/day, the multivariable-adjusted beta of ≤5 and ≥9 h/day were 0.05 (95% CI 0.03, 0.07) and 0.03 (95% CI 0.02, 0.05) for HD, 0.08 (95% CI 0.01, 0.14) and 0.36 (95% CI 0.31, 0.41) for PA, and 0.21 (95% CI 0.12, 0.30) and 0.30 (95% CI 0.23, 0.37) for KDM. Significant independent and joint effects of sleep and cystatin C (CysC) and gamma glutamyltransferase (GGT) on predicted age metrics were future found. Similar results were observed when conducting stratification analyses. Short and long sleep duration were associated with accelerated predicted age metrics mediated by CysC and GGT.

Identification and biological characteristics of Enterococcus casseliflavus TN-47 isolated from Monochamus alternatus.

With the widespread use of antibiotics, the incidence of antibiotic resistance in microorganisms has increased. Monochamus alternatus is a trunk borer of pine trees. This study aimed to investigate the in vitro antimicrobial and biological characteristics of Enterococcus casseliflavus TN-47 (PP411196), isolated from the gastrointestinal tract of M. alternatus in Jilin Province, PR China. Among 13 isolates obtained from the insects, five were preliminarily screened for antimicrobial activity. E. casseliflavus TN-47, which exhibited the strongest antimicrobial activity, was identified. E. casseliflavus TN-47 possessed antimicrobial activity against Staphylococcus aureus USA300 and Salmonella enterica serovar Pullorum ATCC 19945. Furthermore, E. casseliflavus TN-47 was sensitive to tetracyclines, penicillins (ampicillin, carbenicillin, and piperacillin), quinolones and nitrofuran antibiotics, and resistant to certain beta-lactam antibiotics (oxacillin, cefradine and cephalexin), macrolide antibiotics, sulfonamides and aminoglycosides. E. casseliflavus TN-47 could tolerate low pH and pepsin-rich conditions in the stomach and grow in the presence of bile acids. E. casseliflavus TN-47 retained its strong auto-aggregating ability and hydrophobicity. This strain did not exhibit any haemolytic activity. These results indicate that E. casseliflavus TN-47 has potential as a probiotic. This study provides a theoretical foundation for the future applications of E. casseliflavus TN-47 and its secondary metabolites in animal nutrition and feed.

Enterococcus casseliflavus regulates amino acid metabolism in edible insect Clanis bilineata tsingtauica: a functional metagenomics study.

Introduction: The soybean hawkmoth, Clanis bilineata tsingtauica, is an edible insect that possesses high nutritional, medicinal and economic value. It has developed into a characteristic agricultural industry in China. Methods: The dominant gut bacterium in diapause larvae of soybean hawkmoths was identified by metagenomics, and the effect of diapause time on gut microbiome composition, diversity and function was investigated. Results: Enterococcus and Enterobacter were measured to be the dominant genera, with Enterococcus casseliflavus and Enterococcus pernyi being the dominant species. Compared to the controls, the relative abundance of E. casseliflavus and E. pernyi on day 14 was lower by 54.51 and 42.45%, respectively. However, the species richness (including the index of Chao and ACE) of gut microbiota increased on day 28 compared to controls. The gene function was mainly focused on carbohydrate and amino acid metabolism. Metabolic pathways annotated for amino acids on day 14 increased by 9.83% compared to controls. It is speculated that diapause soybean hawkmoths may up-regulate amino acid metabolism by reducing E. casseliflavus abundance to maintain their nutritional balance. Additionally, tetracycline, chloromycetin and ampicillin were screened as the top three antibiotics against E. casseliflavus. Discussion: This study not only extends our knowledge of gut microbiome in soybean hawkmoths at the species level, but also provides an initial investigation of gene functionality in interaction with insect hosts.

Comparison of stress hyperglycemia ratio and glycemic gap on acute ICH in-hospital outcomes.

OBJECTIVE: To compare the effect of different indicators on stress-induced hyperglycemia for predicting in-hospital outcomes of acute intracerebral hemorrhage. METHODS: Using data from the Chinese Stroke Center Alliance database, which is a national, multicenter, prospective, and consecutive program. Stress-induced hyperglycemia was described as glycemic gap (GG, defined as fasting blood glucose [FBG] minus estimated average blood glucose) and stress hyperglycemia ratio (SHR, defined as FBG-to-estimated average blood glucose ratio [SHR 1] or FBG-to-HbA1c ratio [SHR 2]). The primary outcome was in-hospital mortality, and the second outcome was hematoma expansion. RESULTS: A total of 71,333 patients with acute intracerebral hemorrhage were included. In multivariate analyses, the highest levels of GG (OR 1.68, 95% CI 1.12-2.51), SHR 1 (OR 1.73, 95% CI 1.15-2.60), and SHR 2 (OR 2.07, 95% CI 1.33-3.23) were associated with in-hospital death (all the p trends <0.01). Only the highest level of SHR 2 (OR 1.24 [1.02-1.51], p trend >0.05) was related to hematoma expansion. No association between GG or SHR 1 and hematoma expansion was observed. The areas under the ROC curve of GG, SHR 1, and SHR 2 for in-hospital mortality were 0.8808 (95% CI 0.8603-0.9014), 0.8796 (95% CI 0.8589-0.9002), and 0.8806 (95% CI 0.8600-0.9012). The areas under the ROC curve of SHR 2 for hematoma expansion were 0.7133 (95% CI 0.6964-0.7302). INTERPRETATION: SHR (FBG-to-HbA1c ratio) was associated with both in-hospital death and hematoma expansion in intracerebral hemorrhage, and might serve as an accessory indicator for the in-hospital prognosis of intracerebral hemorrhage.

Functional Investigation and Two-sample Mendelian Randomization Study of Inguinal Hernia Hub Genes Obtained by Bioinformatics Analysis.

BACKGROUND: Inguinal hernia in adults is a common and frequent disease in surgery, prone to occur in the elderly or in those with a weak abdominal wall. Despite its prevalence, Molecular mechanisms underlying inguinal hernia formation are unclear. OBJECTIVE: This study aims to identify potential gene markers for inguinal hernia and available drugs. METHODS: Pubmed2Ensembl text mining was used to identify genes related to "inguinal hernia" keywords. The GeneCodis system was used to specify GO biological process terms and KEGG pathways defined in the Kyoto Encyclopedia of Genes and Genomes (KEGG). The STRING tool was used to construct protein-protein interaction networks, which were then visualized using Cytoscape.CytoHubba and Molecular Complex Detection were utilized to analyze the module (MCODE). A GO and KEGG analysis of gene modules was conducted using the DAVID platform database. Hub genes are those that are concentrated in prominent modules. The druggene interaction database was also used to identify potential drugs for inguinal hernia patients based on their interactions between the hub genes. Finally, a Mendelian randomization study was conducted based on genome-wide association studies to determine whether hub genes cause inguinal hernias. RESULTS: The identification of 96 genes associated with inguinal hernia was carried out using text mining techniques. It was constructed using PPI networks with 80 nodes and 476 edges, and the sequence of the genes was performed using CytoHubba. MCODE analysis identified three gene modules. Three modules contain 37 genes clustered as hub candidate genes associated with inguinal hernia patients. The PI3K-Akt, MAPK, AGE-RAGE, and HIF-1 pathways were found to be enriched in signaling pathways. Sixteen of the 37 genes were found to be targetable by 30 existing drugs. The relationship between hub genes and inguinal hernia was examined using Mendelian randomization. The research revealed nine genes that may be connected with inguinal hernia, such as POMC, CD40LG, TFRC, VWF, LOX, IGF2, BRCA1, TNF, and HGF in the plasma. By inverse variance weighting, ALB was associated with an increased risk of inguinal hernia with an OR of 1.203 (OR [95%] = 1,04 [1.012 to 1.089], p = 0.008). CONCLUSION: We identified potential hub genes for inguinal hernia, predicted potential drugs for inguinal hernia, and reverse-validated potential genes by Mendelian randomization. This may provide further insights into asymptomatic pre-diagnostic methods and contribute to studies to understand the molecular mechanisms of risk genes associated with inguinal hernia.

Comparison of indocyanine green and blue-stained glue for preoperative localization for pulmonary nodules.

Background: In patients with pulmonary nodules undergoing computed tomography (CT)-guided localization procedures, a range of liquid-based materials have been employed to date in an effort to guide video-assisted thoracoscopic surgery (VATS) procedures to resect target nodules. However, the relative performance of these different liquid-based localization strategies has yet to be systematically evaluated. Accordingly, this study was developed with the aim of examining the relative safety and efficacy of CT-guided indocyanine green (IG) and blue-stained glue (BSG) PN localization. Methods: Consecutive patients with PNs undergoing CT-guided localization prior to VATS from November 2021 - April 2022 were enrolled in this study. Safety and efficacy outcomes were compared between patients in which different localization materials were used. Results: In total, localization procedures were performed with IG for 121 patients (140 PNs), while BSG was used for localization procedures for 113 patients (153 PNs). Both of these materials achieved 100% technical success rates for localization, with no significant differences between groups with respect to the duration of localization (P = 0.074) or visual analog scale scores (P = 0.787). Pneumothorax affected 8 (6.6%) and 8 (7.1%) patients in the respective IG and BSG groups (P = 0.887), while 12 (9.9%) and 10 (8.8%) patients of these patients experienced pulmonary hemorrhage. IG was less expensive than BSG ($17.2 vs. $165). VATS sublobar resection procedure technical success rates were also 100% in both groups, with no instances of conversion to thoracotomy. Conclusions: IG and BSG both offer similarly high levels of clinical safety and efficacy when applied for preoperative CT-guided PN localization, with IG being less expensive than BSG.

STING-dependent trained immunity contributes to host defense against Clostridium perfringens infection via mTOR signaling.

Clostridium perfringens (C. perfringens) infection is recognized as one of the most challenging issues threatening food safety and perplexing agricultural development. To date, the molecular mechanisms of the interactions between C. perfringens and the host remain poorly understood. Here, we show that stimulator of interferon genes (STING)-dependent trained immunity protected against C. perfringens infection through mTOR signaling. Heat-killed Candida albicans (HKCA) training elicited elevated TNF-α and IL-6 production after LPS restimulation in mouse peritoneal macrophages (PM). Although HKCA-trained PM produced decreased levels of TNF-α and IL-6, the importance of trained immunity was demonstrated by the fact that HKCA training resulted in enhanced bacterial phagocytic ability and clearance in vivo and in vitro during C. perfringens infection. Interestingly, HKCA training resulted in the activation of STING signaling. We further demonstrate that STING agonist DMXAA is a strong inducer of trained immunity and conferred host resistance to C. perfringens infection in PM. Importantly, corresponding to higher bacterial burden, reduction in cytokine secretion, phagocytosis, and bacterial killing were shown in the absence of STING after HKCA training. Meanwhile, the high expression levels of AKT/mTOR/HIF1α were indeed accompanied by an activated STING signaling under HKCA or DMXAA training. Moreover, inhibiting mTOR signaling with rapamycin dampened the trained response to LPS and C. perfringens challenge in wild-type (WT) PM after HKCA training. Furthermore, STING­deficient PM presented decreased levels of mTOR signaling-related proteins. Altogether, these results support STING involvement in trained immunity which protects against C. perfringens infection via mTOR signaling.

Higher serum carotenoid concentrations were associated with the lower risk of cancer-related death: Evidence from the National Health and Nutrition Examination Survey.

The study focuses on the association between serum carotenoids and cancer-related death. Using data from the National Health and Nutrition Examination Survey (2001-2006 and 2017-2018), the study encompasses 10,277 participants older than age 20 years, with recorded baseline characteristics and serum carotenoid concentrations (including α-carotene, trans-ß-carotene, cis-ß-carotene, ß-cryptoxanthin, trans-lycopene, and lutein/zeaxanthin). We hypothesized that serum carotenoid concentrations were negatively associated with cancer-related death. The weighted chi-square analyses indicate significant negative correlations between higher serum concentrations of α-carotene, ß-cryptoxanthin, trans-lycopene, and total carotenoids, and the risk of cancer-related deaths. Using weighted Cox regression analysis, this study confirms that α-carotene, ß-cryptoxanthin, trans-lycopene, and total carotenoids, as continuous or categorical variables, are inversely related to cancer mortality (P < .0001). Furthermore, considering competitive risk events, lower concentrations of serum ß-cryptoxanthin (Fine-Gray P = 1.12e-04), trans-lycopene (P = 5.68e-14), and total carotenoids (P = .03) are associated with an increased risk of cancer-related deaths. The research reveals a crucial inverse relationship between serum carotenoid concentrations and cancer-related death.

Dihydroartemisinin is an inhibitor of trained immunity through Akt/mTOR/HIF1α signaling pathway.

Trained immunity is mechanistically defined as the metabolically and epigenetically mediated long-term functional adaptation of the innate immune system, characterized by a heightened response to a secondary stimulation. Given appropriate activation, trained immunity represents an attractive anti-infective therapeutic target. Nevertheless, excessive immune response and subsequent inflammatory cascades may contribute to pathological tissue damage, indicating that the negative impacts of trained immunity appear to be significant. In this study, we show that innate immune responses such as the production of extracellular traps, pro-inflammatory cytokines, and autophagy-related proteins were markedly augmented in trained BMDMs. Furthermore, heat-killed C. albicans priming promotes the activation of the AIM2 inflammasome, and AIM2-/- mice exhibit impaired memory response induced by heat-killed C. albicans. Therefore, we establish that the AIM2 inflammasome is involved in trained immunity and emerges as a promising therapeutic target for potentially deleterious effects. Dihydroartemisinin can inhibit the memory response induced by heat-killed C. albicans through modulation of mTOR signaling and the AIM2 inflammasome. The findings suggest that dihydroartemisinin can reduce the induction of trained immunity by heat-killed C. albicans in C57BL/6 mice. Dihydroartemisinin is one such therapeutic intervention that has the potential to treat of diseases characterized by excessive trained immunity.

Efficient hydrogenation of diethyl malonate to 1,3-propanediol over CuGa/SiO2 bimetallic catalysts.

Cu catalysts with different compositions and different Cu and promoter contents were prepared by precipitation-gel method and studied for the selective hydrogenation of syngas or biomass-based diethyl malonate (DEM) to valuable 1,3-propanediol (1,3-PDO). The Ga-promoted 70Cu6Ga/SiO2 catalyst was found to exhibit the highest catalytic performance, achieving 100% DEM conversion and 76.6% 1,3-PDO selectivity under reaction conditions of 160 °C and 8 MPa H2. The 70Cu6Ga/SiO2 bimetallic catalyst also presented obviously better stability than that of the monometallic 70Cu/SiO2 catalyst in a continuous flow reactor over 180 h time-on stream. Characterization results showed that the incorporation of Ga increased the interaction between Cu and Ga species, hindered the full reduction of Cu2+ species, and thus increased the proportion of Cu+ and the number of Lewis acidic sites on the catalyst surface. The synergistic effect between Cu0 and Cu+ enhanced the adsorption and activation of ester carbonyl groups and their subsequent hydrogenation, eventually contributed to the outstanding performances of the CuGa/SiO2 bimetallic catalysts.

Dynamical Janus-Like Behavior Excited by Passive Cold-Heat Modulation in the Earth-Sun/Universe System: Opportunities and Challenges.

The utilization of solar-thermal energy and universal cold energy has led to many innovative designs that achieve effective temperature regulation in different application scenarios. Numerous studies on passive solar heating and radiation cooling often operate independently (or actively control the conversion) and lack a cohesive framework for deep connections. This work provides a concise overview of the recent breakthroughs in solar heating and radiation cooling by employing a mechanism material in the application model. Furthermore, the utilization of dynamic Janus-like behavior serves as a novel nexus to elucidate the relationship between solar heating and radiation cooling, allowing for the analysis of dynamic conversion strategies across various applications. Additionally, special discussions are provided to address specific requirements in diverse applications, such as optimizing light transmission for clothing or window glass. Finally, the challenges and opportunities associated with the development of solar heating and radiation cooling applications are underscored, which hold immense potential for substantial carbon emission reduction and environmental preservation. This work aims to ignite interest and lay a solid foundation for researchers to conduct in-depth studies on effective and self-adaptive regulation of cooling and heating.