Search

Abstract T lymphopenia, occurring in the early phase of sepsis in response to systemic inflammation, is commonly associated with morbidity and mortality of septic infections. We have previously shown that a sufficient number of T cells is required to constrain Toll-like receptors (TLRs) mediated hyperinflammation. However, the underlying mechanisms remains unsolved. Herein, we unveil that CD4+ T cells engage with MHC II of macrophages to downregulate TLR pro-inflammatory signaling. We show further that the direct contact between CD4 molecule of CD4+ T cells or the ectodomain of CD4 (soluble CD4, sCD4), and MHC II of resident macrophages is necessary and sufficient to prevent TLR4 overactivation in LPS and cecal ligation puncture (CLP) sepsis. sCD4 serum concentrations increase after the onset of LPS sepsis, suggesting its compensatory inhibitive effects on hyperinflammation. sCD4 engagement enables the cytoplasmic domain of MHC II to recruit and activate STING and SHP2, which inhibits IRAK1/Erk and TRAF6/NF-κB activation required for TLR4 inflammation. Furthermore, sCD4 subverts pro-inflammatory plasma membrane anchorage of TLR4 by disruption of MHC II-TLR4 raft domains that promotes MHC II endocytosis. Finally, sCD4/MHCII reversal signaling specifically interferes with TLR4 but not TNFR hyperinflammation, and independent of the inhibitive signaling of CD40 ligand of CD4+ cells on macrophages. Therefore, a sufficient amount of soluble CD4 protein can prevent excessive inflammatory activation of macrophages via alternation of MHC II-TLR signaling complex, that might benefit for a new paradigm of preventive treatment of sepsis.

Soil salinity is one of the main factors limiting agricultural development worldwide and has an adverse effect on plant growth and yield. To date, plant growth-promoting rhizobacteria (PGPR) are considered to be one of the most promising eco-friendly strategies for improving saline soils. The bacterium Bacillus megaterium ZS-3 is an excellent PGPR strain that induces growth promotion as well as biotic stress resistance and tolerance to abiotic stress in a broad range of host plants. In this study, the potential mechanisms of protection against salinity stress by B. megaterium ZS-3 in Arabidopsis thaliana were explored. Regulation by ZS-3 improved growth in A. thaliana under severe saline conditions. The results showed that ZS-3 treatment significantly increased the biomass, chlorophyll content and carotenoid content of A. thaliana. Compared to the control, the leaf area and total fresh weight of plants inoculated with ZS-3 increased by 245% and 271%, respectively; the chlorophyll a, chlorophyll b, and carotenoid contents increased by 335%, 146%, and 372%, respectively, under salt stress. Physiological and biochemical tests showed that ZS-3 regulated the content of osmotic substances in plants under salt stress. Compared to the control, the soluble sugar content of the ZS-3-treated group was significantly increased by 288%, while the proline content was significantly reduced by 41.43%. Quantification of Na+ and K+ contents showed that ZS-3 treatment significantly reduced Na+ accumulation and increased the K+/Na+ ratio in plants. ZS-3 also isolated Na+ in vesicles by upregulating NHX1 and AVP1 expression while limiting Na+ uptake by downregulating HKT1, which protected against Na+ toxicity. Higher levels of peroxidase and catalase activity and reduced glutathione were detected in plants inoculated with ZS-3 compared to those in uninoculated plants. In addition, it was revealed that ZS-3 activates salicylic acid (NPR1 and PR1) and jasmonic acid/ethylene (AOS, LOX2, PDF1.2, and ERF1) signaling pathways to induce systemic tolerance, thereby inducing salt tolerance in plants. In conclusion, the results of this study indicate that ZS-3 has the potential to act as an environmentally friendly salt tolerance inducer that can promote plant growth in salt-stressed environments.

China's energy carbon emissions are projected to peak in 2030 with approximately 110% of its 2020 level under the following conditions: 1) China's gross primary energy consumption is 5 Gtce in 2020 and 6 Gtce in 2030; 2) coal's share of the energy consumption is 61% in 2020 and 55% in 2030; 3) non-fossil energy's share increases from 15% in 2020 to 20% in 2030; 4) through 2030, China's GDP grows at an average annual rate of 6%; 5) the annual energy consumption elasticity coefficient is 0.30 in average; and 6) the annual growth rate of energy consumption steadily reduces to within 1%. China's electricity generating capacity would be 1,990 GW, with 8,600 TW h of power generation output in 2020. Of that output 66% would be from coal, 5% from gas, and 29% from non-fossil energy. By 2030, electricity generating capacity would reach 3,170 GW with 11,900 TW h of power generation output. Of that output, 56% would be from coal, 6% from gas, and 37% from non-fossil energy. From 2020 to 2030, CO2 emissions from electric power would relatively fall by 0.2 Gt due to lower coal consumption, and relatively fall by nearly 0.3 Gt with the installation of more coal-fired cogeneration units. During 2020–2030, the portion of carbon emissions from electric power in China's energy consumption is projected to increase by 3.4 percentage points. Although the carbon emissions from electric power would keep increasing to 118% of the 2020 level in 2030, the electric power industry would continue to play a decisive role in achieving the goal of increase in non-fossil energy use. This study proposes countermeasures and recommendations to control carbon emissions peak, including energy system optimization, green-coal-fired electricity generation, and demand side management.

Background: Spinal metastases are the most common type of metastatic bone tumors. Various therapeutic approaches have been used to treat spinal metastases, but traditional treatments are often limited and ineffective. Minimally invasive interventional technology has been successfully performed in the clinical setting. Objectives: This study is designed to evaluate the curative effect of spinal metastases treated by percutaneous vertebroplasty (PVP) and transcatheter arterial infusion/chemoembolization (TAI/TACE). Patients and Methods: A prospective study was performed for 18 consecutive patients with spinal metastases justified by imaging findings and pathology, including 12 men and 6 women, with the mean age of 64.56 ± 11.07 years (range, 50 -90 years). All patients first underwent PVP and then TAI/TACE. The degree of pain relief was assessed with visual analogue scale (VAS) and WHO standard. The rating of the activity of daily life (ADL) was utilized to evaluate the quality of life. The activities of daily life (ADL) were evaluated with modified Barthel index system. The size of tumor and further bone invasion were evaluated three months after surgery. Results: We achieved a 100% success rate of all interventional operations. The effective rates of pain relief were respectively 94%, 94%, 89%, and 78% for one-day post-op, one-week post-op, one-month post-op, and three-months post-op. VAS for back pain was 7.7 ± 0.8,5.3 ± 0.6,3.4 ± 0.8,2.0 ± 0.6, and 1.5 ± 0.6 for pre-operative, one-day post-op, one-week post-op, one-month post-op, and three-months post-op, respectively. The improvement of VAS was respectively 2.3 ± 0.6, 4.3 ± 0.9,1.4 ± 0.8, and 1.8 ± 0.7. Preoperative and postoperative 3 months Barthel index was 45.3 ± 12.5 and 85.6 ± 14.2, respectively. There were significant difference in pain relief and the ability of daily life between pre-operation and post-operation time points (P < 0.05). There were no severe clinical or radiographic complications after interventions. Conclusion: PVP combined with TAI/TACE is a safe and effective technique for treatment of spinal metastases. PVP is effective for pain relief but has a limited antitumor effect, while TACE kills tumors more thoroughly compared to PVP. The combination of two therapies can make up for the shortcomings of each other and obtain definite effect, which markedly improves the patients' living quality. [ABSTRACT FROM AUTHOR]

Pancreatic neuroendocrine tumors (PNET) are uncommon pancreatic neoplasms, accounting for 1-2% of all pancreatic tumors. However, they have a better prognosis and long-term survival compared to exocrine pancreatic cancer. PNETs can be divided into functional or nonfunctional based upon whether or not they excrete active substances relevant to specific clinical syndromes. Skeletal muscle metastasis is also a rare condition and differentiation between a primary soft tissue sarcoma and metastatic carcinoma is difficult without biopsy. Thus, skeletal muscle metastases from pancreatic neoplasms are exceedingly rare, with only a few cases reported in the literature. We present a 34-year-old man with metastatic pancreatic neuroendocrine carcinoma that was initially thought to be a primary soft tissue tumor. Pathology and immunohistochemistry demonstrated the tumor to be a metastasis from a pancreatic neuroendocrine carcinoma. A brief review of the literature on this subject is also presented. [ABSTRACT FROM AUTHOR]