Hyperexpression of tumor necrosis factor receptor 2 inhibits differentiation of myeloid-derived suppressor cells by instigating apolarity during ageing.

During the ageing process, TNF-α can promote the expansion of myeloid-derived suppressor cells (MDSCs). However, it remains unclear which receptor(s) of TNF-α are involved in and how they modulate this process. Here, we report that TNFR2 hyperexpression induced by either TNF-α or IL-6, two proinflammatory factors of senescence-associated secretory phenotype (SASP), causes cellular apolarity and differentiation inhibition in aged MDSCs. Ex vivo overexpression of TNFR2 in young MDSCs inhibited their polarity and differentiation, whereas in vivo depletion of Tnfr2 in aged MDSCs promotes their differentiation. Consequently, the age-dependent increase of TNFR2 versus unaltered TNFR1 expression in aged MDSCs significantly shifts the balance of TNF-α signaling toward the TNFR2-JNK axis, which accounts for JNK-induced impairment of cell polarity and differentiation failure of aged MDSCs. Consistently, inhibiting JNK attenuates apolarity and partially restores the differentiation capacity of aged MDSCs, suggesting that upregulated TNFR2/JNK signaling is a key factor limiting MDSC differentiation during organismal ageing. Therefore, abnormal hyperexpression of TNFR2 represents a general mechanism by which extrinsic SASP signals disrupt intrinsic cell polarity behavior, thereby arresting mature differentiation of MDSCs with ageing, suggesting that TNFR2 could be a potential therapeutic target for intervention of ageing through rejuvenation of aged MDSCs.

Green development level assessment and obstacle analysis of China's coal-resource-based regions.

Coal is the main source of energy in China, however, in the context of carbon neutrality, how coal-resource-based regions can not only undertake the national supply of terminal energy and industrial raw materials, but also achieve regional green development is an important issue. In this paper, first, we constructed a green development indicator system for coal-resource-based regions named the green development indicator system of coal-resource-based regions (GDISCR), which could coordinate the relationship among the economy, energy, and environment when evaluating the green development level. Second, we proposed a new evaluation model named dynamic spatial TOPSIS, which comprehensively considered the spatial differences of research subjects and the differences over time in the evaluation process. Third, we introduced the obstacle analysis model to find the obstacle factors preventing green development of coal-resource-based regions. Finally, we evaluated ten coal-resource-based provinces to evaluate their green growth levels and demonstrate the effectiveness of our methodology. The following were the major conclusions: (1) The average comprehensive evaluation value of the 10 coal-resource-based provinces was 0.3956, based on which the coal-resource-based provinces could be divided into two types, namely, provinces with better or worse green development levels. (2) The obstacles restricting the green development of provinces with coal resources were dynamic, but the importance of an obstacle factor for provinces was relatively fixed. (3) The greatest obstacle to the green development of provinces with coal resources was technological capacity in the economy, with an average obstacle degree of 27.48% in 2022, and they had similar difficulties in energy transition but different difficulties in environmental protection. On the basis of these findings, some feasible recommendations for the environmentally friendly growth of coal-resource-based provinces are discussed.

[Growth response of coniferous trees to climate change in the Qinling Mountains, China]. / ç§¦å²­å±±åœ°é’ˆå¶æ ‘ç§æ ‘æœ¨ç”Ÿé•¿å¯¹æ°”å€™å˜åŒ–çš„å“åº”.

As an important geographical boundary, the subalpine coniferous forests in the Qinling Mountains have critical effects on water conservation, biodiversity conservation and climate regulation at the regional and even larger scale. In recent decades, temperature significantly increased in the Qinling Mountains, with significant spatial heterogeneity. An understanding of the responses of the Qinling coniferous trees to climate change is important for the protection and management of mountain forests under climate change. In this study, we synthesized the relationships between the radial growth of coniferous trees and climate at different altitudes in the western, central, and eas-tern Qinling Mountains. The effects of climate change on coniferous trees were investigated from the aspects of radial growth, NDVI, phenology, and species distribution range. Furthermore, know-ledge gaps in the responses of tree growth to climate change and possible future directions in this field were discussed.

Programmed PPAR-α downregulation induces inflammaging by suppressing fatty acid catabolism in monocytes.

Inflammaging is associated with an increased risk of chronic disease. Monocytes are the principal immune cells for the production of inflammatory cytokines and contribute to inflammaging in the elderly. However, the underlying mechanisms remain largely unknown. Here, we found that monocytes from aged individuals contained high levels of lipid droplets (LDs), and this increase was correlated with impaired fatty acid oxidation. Downregulated peroxisome proliferator-activated receptor (PPAR)-α may be responsible for the pro-inflammatory phenotype of monocytes in aged individuals, as it was positively correlated with LD accumulation and increasing TNF-α concentration. Interestingly, interventions that result in PPAR-α upregulation, such as fenofibrate treatment, TNF-α neutralization, or calorie restriction, reversed the effect of aging on monocytes. Thus the downregulation of PPAR-α and LD levels in monocytes represents a novel biomarker for inflammaging. Furthermore, PPAR-α activation in the elderly may also alleviate long-term inflammaging, preventing the development of life-limiting chronic diseases.

Comparative effectiveness of prolonged exposure and cognitive processing therapy for military service members in an intensive treatment program.

OBJECTIVE: While the comparative efficacy of prolonged exposure (PE) and cognitive processing therapy (CPT) has been examined in outpatient settings, there is a dearth of literature on the relative effectiveness of these interventions when adapted for an intensive treatment format. In an expanded secondary analysis of a previous study, we sought to examine the comparative effectiveness of PE and CPT delivered in the naturalistic setting of an intensive treatment format including maintenance of outcomes through a 6-month follow-up period. METHOD: A sample of 296 veterans with posttraumatic stress disorder (PTSD) received either PE (n = 186) or CPT (n = 90), alongside other trauma-informed interventions, in a 2-week intensive clinical program. Treatment selection was determined collaboratively between patient and therapist. Our primary outcome was self-reported PTSD symptom severity (i.e., PTSD Checklist for DSM-5, PCL-5); secondarily, we examined self-reported depression (i.e., Patient Health Questionnaire) symptom severity outcomes. RESULTS: A mixed-model regression controlling for age and gender revealed a significant effect of time from baseline to endpoint (p < .001), 3-month (p < .001), and 6-month follow-up (p < .001) on PCL-5 scores but no significant effect of treatment or effect of treatment by time interaction (all ps > .05; model: Wald's χ² = 232.38, p < .001). Results were similar for depression outcomes. Attrition at posttreatment was not significantly different between groups: 7.2% for CPT and 6.5% PE (z score = 0.22). CONCLUSIONS: Both PE and CPT are associated with comparable improvements when delivered as part of a 2-week intensive outpatient program. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Co-activation of Akt, Nrf2, and NF-κB signals under UPRER in torpid Myotis ricketti bats for survival.

Bats hibernate to survive stressful conditions. Examination of whole cell and mitochondrial proteomes of the liver of Myotis ricketti revealed that torpid bats had endoplasmic reticulum unfolded protein response (UPRER), global reduction in glycolysis, enhancement of lipolysis, and selective amino acid metabolism. Compared to active bats, torpid bats had higher amounts of phosphorylated serine/threonine kinase (p-Akt) and UPRER markers such as PKR-like endoplasmic reticulum kinase (PERK) and activating transcription factor 4 (ATF4). Torpid bats also had lower amounts of the complex of Kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) (p65)/I-κBα. Cellular redistribution of 78 kDa glucose-regulated protein (GRP78) and reduced binding between PERK and GRP78 were also seen in torpid bats. Evidence of such was not observed in fasted, cold-treated, or normal mice. These data indicated that bats activate Akt, Nrf2, and NF-κB via the PERK-ATF4 regulatory axis against endoplasmic reticulum stresses during hibernation.

Efficient removal of As(III) via simultaneous oxidation and adsorption by magnetic sulfur-doped Fe-Cu-Y trimetal oxide nanoparticles.

A novel magnetic sulfur-doped Fe-Cu-Y trimetal oxide (MST) nanomaterial was successfully synthesized by a chemical coprecipitation method to remove As(III) via simultaneous oxidation and adsorption and then characterized by BET, VSM, FESEM, XPS, and FTIR techniques. The effect of solution initial pH on the adsorption of As(III), and the adsorption kinetics and isotherm were investigated in detail. The results indicated that the MST nanoparticles exhibited an excellent performance for As(III) removal in a pH range of 7-10 and were easily separated from aqueous solution with a magnet. The maximum removal capability for As(III) reached 202.0 mg/g at pH 7.0. The adsorption of As(III) was well fitted by the pseudo-second-order kinetic model and Langmuir isotherm model, respectively. The investigation of mechanism revealed that As(III) could be oxidized to As(V) by O2- and OH free radicals, generated via the dissolved O2 obtaining an electron from Cu(I) on the surface of the adsorbent and Fenton/Fenton-like reaction, respectively. Meanwhile, the produced As(V) was adsorbed onto the surface of the nanoparticles through the electrostatic attraction or diffusion. The adsorbed As(V) further interacted with -OH groups via ion exchange or with Y(III) on the surface of the adsorbent to form a precipitate. Therefore, the MST nanoparticles are promising for the removal of arsenic from water.

Lipid droplet-dependent fatty acid metabolism controls the immune suppressive phenotype of tumor-associated macrophages.

Tumor-associated macrophages (TAMs) promote tumor growth and metastasis by suppressing tumor immune surveillance. Herein, we provide evidence that the immunosuppressive phenotype of TAMs is controlled by long-chain fatty acid metabolism, specifically unsaturated fatty acids, here exemplified by oleate. Consequently, en-route enriched lipid droplets were identified as essential organelles, which represent effective targets for chemical inhibitors to block in vitro polarization of TAMs and tumor growth in vivo. In line, analysis of human tumors revealed that myeloid cells infiltrating colon cancer but not gastric cancer tissue indeed accumulate lipid droplets. Mechanistically, our data indicate that oleate-induced polarization of myeloid cells depends on the mammalian target of the rapamycin pathway. Thus, our findings reveal an alternative therapeutic strategy by targeting the pro-tumoral myeloid cells on a metabolic level.

Synergism of CuS and tartaric acid in the reduction of Cr(VI) under an irradiation of simulated solar light.

The synergism of CuS and tartaric acid (TA) in the reduction of Cr(VI) with an irradiation of simulated solar light was investigated through observing the effects of solution pH, temperature, CuS loading and TA concentration on the removal efficiency of Cr(VI). Approximately 32% and 54% of the initial Cr(VI) (100 µmol/L) were reduced within 180 min by TA and CuS with light, respectively. Under the same condition, however, almost a complete removal of the initial Cr(VI) was achieved within 130 min in the coexistence of CuS and TA. In the case, it is considered that Cr(VI) was rapidly reduced in two main pathways. One is that H2S produced from the dissolution of CuS in weak acidic solution directly reduced Cr(VI) to Cr(III). The other is that Cu(II) released from CuS reacted with TA to form complexes with photochemical activity, producing Cu(I) through ligand-to-metal electron transfer, and then the reduction of Cr(VI) was coupled with a conversion of Cu(I) to Cu(II). Thus, a cycle catalytic system was established for the reduction of Cr(VI). Moreover, it is observed that the reaction could be divided into two stages: the initial chemical reduction of Cr(VI) by H2S and the later photochemical reduction of Cr(VI) by Cu(II)-TA complexes.

Increased vessel perfusion predicts the efficacy of immune checkpoint blockade.

Immune checkpoint blockade (ICB) has demonstrated curative potential in several types of cancer, but only for a small number of patients. Thus, the identification of reliable and noninvasive biomarkers for predicting ICB responsiveness is an urgent unmet need. Here, we show that ICB increased tumor vessel perfusion in treatment-sensitive EO771 and MMTV-PyVT breast tumor as well as CT26 and MCA38 colon tumor models, but not in treatment-resistant MCaP0008 and 4T1 breast tumor models. In the sensitive tumor models, the ability of anti-cytotoxic T lymphocyte-associated protein 4 or anti-programmed cell death 1 therapy to increase vessel perfusion strongly correlated with its antitumor efficacy. Moreover, globally enhanced tumor vessel perfusion could be detected by Doppler ultrasonography before changes in tumor size, which predicted final therapeutic efficacy with more than 90% sensitivity and specificity. Mechanistically, CD8+ T cell depletion, IFN-γ neutralization, or implantation of tumors in IFN-γ receptor knockout mice abrogated the vessel perfusion enhancement and antitumor effects of ICB. These results demonstrated that ICB increased vessel perfusion by promoting CD8+ T cell accumulation and IFN-γ production, indicating that increased vessel perfusion reflects the successful activation of antitumor T cell immunity by ICB. Our findings suggest that vessel perfusion can be used as a novel noninvasive indicator for predicting ICB responsiveness.

S100A4 Protects Myeloid-Derived Suppressor Cells from Intrinsic Apoptosis via TLR4-ERK1/2 Signaling.

Myeloid-derived suppressor cells (MDSCs) often expand during cancer or chronic inflammation and dampen immune responses. However, mechanisms underlying their capacity to escape intrinsic apoptosis in the inflammatory environment are still largely unknown. In this study, we investigated this in mouse tumor models with MDSC accumulation. Spontaneous rejection of tumors implanted into mice deficient for the small Ca2+-binding protein S100A4 (S100A4-/-) was accompanied by low numbers of peripheral MDSCs. This was independent of S100A4 expression on tumor cells. In contrast, MDSCs from S100A4-/- tumor-bearing mice showed a diminished resistance to the induction of intrinsic apoptosis. Further studies demonstrated that S100A4 protects MDSCs from apoptosis through toll-like receptor-4/extracellular signal-regulated kinase-dependent caspase-9 inhibition. The finding that S100A4 is critical for MDSC survival in inflammatory environments might have important implications for the clinical treatment of cancer or inflammation-related diseases.

Insights into the mechanism of persulfate activated by rice straw biochar for the degradation of aniline.

This study investigated the degradation of aniline by persulfate (PS) activated with rice straw biochar (RSBC). The results demonstrate that aniline could be rapidly decomposed by a combination of PS and RSBC. The degradation efficiency of aniline was up to 94.1% within 80 min, and meanwhile 52% of the total organic carbon was removed. In the initial pH range of 3-9, aniline could be efficiently removed. Reactive species resulting in the rapid degradation of aniline were investigated via radical and hole quenching experiments with various scavengers (e.g., methanol, tert-butyl alcohol and EDTA) and electron paramagnetic resonance technique. Based on the analysis and observation made here, it is speculated that the predominant reactive species responsible for the degradation of aniline may be holes instead of SO4- and OH radicals. It is concluded that RSBC could be used as an effective catalyst to activate PS for the degradation of aniline.

Adaptation of peroxisome proliferator-activated receptor alpha to hibernation in bats.

BACKGROUND: Hibernation is a survival mechanism in the winter for some animals. Fat preserved instead of glucose produced is the primary fuel during winter hibernation of mammals. Many genes involved in lipid metabolism are regulated by the peroxisome proliferator-activated receptor alpha (PPARα). The role of PPARα in hibernation of mammals remains largely unknown. Using a multidisciplinary approach, we investigated whether PPARα is adapted to hibernation in bats. RESULTS: Evolutionary analyses revealed that the ω value of Pparα of the ancestral lineage of hibernating bats in both Yinpterochiroptera and Yangochiroptera was lower than that of non-hibernating bats in Yinpterochiroptera, suggesting that a higher selective pressure acts on Pparα in hibernating bats. PPARα expression was found to be increased at both mRNA and protein levels in distantly related bats (Rhinolophus ferrumequinum and Hipposideros armiger in Yinpterochiroptera and Myotis ricketti in Yangochiroptera) during their torpid episodes. Transcription factors such as FOXL1, NFYA, NFYB, SP1, TBP, and ERG were bioinformatically determined to have a higher binding affinity to the potential regulatory regions of Pparα in hibernating than in non-hibernating mammals. Genome-wide bioinformatic analyses of 64 mammalian species showed that PPARα has more potential target genes and higher binding affinity to these genes in hibernating than in non-hibernating mammals. CONCLUSIONS: We conclude that PPARα is adapted to hibernation in bats based on the observations that Pparα has a more stringent functional constraint in the ancestral lineage of hibernating bats and a higher level of expression in hibernating than in non-hibernating bats. We also conclude that PPARα plays a very important role in hibernation as hibernators have more PPARα target genes than non-hibernators, and PPARα in hibernators has a higher binding affinity for its target genes than in non-hibernators.

Prognostic role of C-reactive protein and interleukin-6 in dialysis patients: a systematic review and meta-analysis.

Inflammation may be associated with mortality in dialysis patients. This study aims to summarize the prognostic value of two common inflammatory markers, C-reactive protein (CRP) and interleukin-6 (IL-6) for dialysis outcome. A total of 109 CRP studies and 22 IL-6 studies were identified from PubMed and EMBASE after systematic searching and assessment. The combined hazard ratios (HRs) of CRP and IL-6 for mortality were analyzed. For all-cause mortality (ACM), both CRP and IL-6 could significantly predict the outcome, with the pooled HRs of 1.142 (95%CI: 1.118-1.166) and 1.152 (95%CI: 1.094-1.214) for CRP and IL-6, respectively. For cardiovascular disease mortality (CVDM), the pooled HR of CRP (1.182, 95%CI: 1.134-1.232) was close to that of IL-6 (1.181, 95%CI: 1.068-1.307). Therefore, elevated levels of CRP or IL-6 were significantly associated with higher ACM and higher CVDM in dialysis patients. The predictive value of the inflammatory biomarkers may be useful in clinical practice.

Prognostic role of C-reactive protein in breast cancer: a systematic review and meta-analysis.

BACKGROUND: Recent studies have shown that C-reactive protein (CRP) may be associated with breast cancer. The purpose of this study is to summarize the predictive role of CRP for survival in breast cancer as shown in all available studies worldwide. METHODS: Related studies were identified and evaluated for quality through multiple search strategies. Data were collected from studies comparing overall, cancer-specific, and disease-free survival (OS, CSS, and DFS) in patients with elevated CRP levels and those having lower levels. Studies were pooled, and combined hazard ratios (HRs) of CRP for survival were calculated. RESULTS: A total of 10 studies (n=4,502) were included for this meta-analysis (9 for OS, 3 for CSS, and 3 for DFS). For overall and disease-free survival, the pooled HRs of CRP were significant at 1.62 (95% confidence interval [95% CI], 1.20-2.18) and 1.81 (95% CI, 1.44-2.26), respectively. For cancer-specific survival, the pooled HR in higher CRP expression in breast cancer was 2.08 (95% CI, 1.48-2.94), which could strongly predict poorer survival in breast cancer. CONCLUSIONS: CRP has a critical prognostic value in patients with breast cancer as an inflammation biomarker.

Prognostic role of microRNA-21 in various carcinomas: a systematic review and meta-analysis.

BACKGROUND: Recent studies have shown that microRNAs (miRNA) could play a potential role as diagnostic and prognostic biomarkers of cancers. The aim of this meta-analysis is to summarize the global predicting role of miR-21 for survival in patients with a variety of carcinomas. DESIGN: Eligible studies were identified and assessed for quality through multiple search strategies. Data were collected from studies comparing overall, relapse-free or cancer-specific survival (CSS) in patients with cancer having higher miR-21 expression with those having lower levels. Pooled hazard ratios (HRs) of miR-21 for survival were calculated. RESULTS: A total of 17 studies dealing with various carcinomas were included for this global meta-analysis. For overall survival (OS), the pooled hazard ratio (HR) of higher miR-21 expression in cancerous tissue was 1·69 (95% CI: 1·33-2·16, P < 0·001), which could significantly predict poorer survival in general carcinomas. For relapse-free or CSS, elevated miR-21 was also a significant predictor, with a pooled HR of 1·48 (95% CI: 1·03-2·11, P = 0·033). Importantly, subgroup analysis suggested that higher expression of miR-21 correlated with worse OS in head and neck squamous cell carcinoma (HNSCC) (HR 1·46, 95% CI: 1·13-1·87, P = 0·004) and carcinomas in digestion system (HR 1·56, 95% CI: 1·08-2·26, P = 0·018). CONCLUSIONS: Our findings suggest that miR-21 detection has a prognostic value in patients with cancer, especially in HNSCC and digestion system cancers.

Prognostic role of systemic inflammatory response in renal cell carcinoma: a systematic review and meta-analysis.

PURPOSE: To summarize the global predicting role of systemic inflammatory response for survival in renal cell carcinoma. METHODS: Eligible studies were identified and assessed for quality through multiple search strategies. Data were collected from studies comparing overall, cancer-specific or relapse-free survival in patients with elevated C-reactive protein (CRP), platelet count (PC) and erythrocyte sedimentation rate (ESR) levels with those with lower levels. Studies were pooled, and combined hazard ratios (HRs) of CRP, PC and ESR for survival were calculated, respectively. RESULTS: A total of 47 studies were included for meta-analysis (18 for CRP, 15 for PC and 14 for ESR). For overall survival, the pooled HR of CRP (3.23, 95% CI: 1.77, 5.89) was higher than that of PC (1.96, 95% CI: 1.40, 2.75) and that of ESR (1.86, 95% CI: 1.34, 2.59). These indicators were strong predictors for cancer-specific survival with individual HRs being 3.46 (95% CI, 2.80, 4.27) of CRP, 3.22 (95% CI, 2.25, 4.62) of PC, and 3.85 (95% CI, 3.31, 4.48) of ESR, respectively. All three inflammatory indictors also predicted relapse-free survival (HRs > 2.0). CONCLUSION: The systemic inflammatory response predicted poor survival in patients with renal cell carcinoma.

The impacts of thiazolidinediones on circulating C-reactive protein levels in different diseases: a meta-analysis.

OBJECTIVES: Thiazolidinediones (TZDs), including rosiglitazone and pioglitazone, are widely used as antidiabetic agents. Here we present an updated meta-analysis of the respective effects of rosiglitazone and pioglitazone on the levels of C-reactive protein (CRP), a biomarker and predictor of CAD risks. METHODS AND RESULTS: PubMed and EMBASE were systematically searched using the terms "C-reactive protein" and "rosiglitazone" or "pioglitazone" or "thiazolidinedione". A total of 59 rosiglitazone studies and 36 pioglitazone studies were included for evaluation. These were classified as 2-group studies and 1-group studies according to their study design. Standard mean difference (SMD) of CRP and 95% CI were calculated to evaluate the effect of TZDs on CRP. The overall SMD for rosiglitazone treatment is -0.392 (95% CI, [-0.446, -0.338]) in 2-group studies and -0.424 (95% CI, [-0.501, -0.346]) in 1-group studies. The overall SMD for pioglitazone treatment is -0.577 (95% CI, [-0.732, -0.421]) in 2-group studies and -0.327 (95% CI, [-0.439, -0.216]) in 1-group studies. Moreover, TZDs were found to significantly reduce CRP levels in both diabetes mellitus (DM) and non-DM patients. CONCLUSIONS: Our meta-analysis suggested that both rosiglitazone and pioglitazone significantly decrease serum CRP levels. TZDs presented their CRP-lowering effect in both DM and non-DM patients.