Salicylic Acid's impact on Sedum alfredii growth and cadmium tolerance: Comparative physiological, transcriptomic, and metabolomic study.

With the acceleration of industrialization, Cd pollution has emerged as a major threat to soil ecosystem health and food safety. Hyperaccumulating plants like Sedum alfredii Hance are considered to be used as part of an effective strategy for the ecological remediation of Cd polluted soils. This study delved deeply into the physiological, transcriptomic, and metabolomic responses of S. alfredii under cadmium (Cd) stress when treated with exogenous salicylic acid (SA). We found that SA notably enhanced the growth of S. alfredii and thereby increased absorption and accumulation of Cd, effectively alleviating the oxidative stress caused by Cd through upregulation of the antioxidant system. Transcriptomic and metabolomic data further unveiled the influence of SA on photosynthesis, antioxidant defensive mechanisms, and metal absorption enrichment pathways. Notably, the interactions between SA and other plant hormones, especially IAA and JA, played a central role in these processes. These findings offer us a comprehensive perspective on understanding how to enhance the growth and heavy metal absorption capabilities of hyperaccumulator plants by regulating plant hormones, providing invaluable strategies for future environmental remediation efforts.

Jasmonic acid's impact on Sedum alfredii growth and cadmium tolerance: A physiological and transcriptomic study.

Soil cadmium (Cd) pollution is escalating, necessitating effective remediation strategies. This study investigated the effects of exogenous jasmonic acid (JA) on Sedum alfredii Hance under Cd stress, aiming to enhance its phytoextraction efficiency. Initially, experiments were conducted to assess the impact of various concentrations of JA added to environments with Cd concentrations of 100, 300, and 500 µmol/L. The results determined that a concentration of 1 µmol/L JA was optimal. This concentration effectively mitigated the level of ROS products by enhancing the activity of antioxidant enzymes. Additionally, JA fostered Cd absorption and accumulation, while markedly improving plant biomass and photosynthetic performance. In further experiments, treatment with 1 µmol/L JA under 300 µmol/L Cd stress was performed and transcriptomic analysis unveiled a series of differentially expressed genes (DEGs) instrumental in the JA-mediated Cd stress response. These DEGs encompass not only pathways of JA biosynthesis and signaling but also genes encoding functions that influence antioxidant systems and photosynthesis, alongside genes pertinent to cell wall synthesis, and metal chelation and transport. This study highlights that JA treatment significantly enhances S. alfredii's Cd tolerance and accumulation, offering a promising strategy for plant remediation and deepening our understanding of plant responses to heavy metal stress.

Malignant hyperthermia: Report on a successful rescue of a case with the highest temperature of 44.2°C.

Malignant hyperthermia (MH) is an inherited skeletal muscle disorder caused primarily by a genetic mutation, usually in the calcium channel gene of the muscle. This mutation can lead to muscle hypersensitivity to volatile anesthetics (such as sevoflurane) and the depolarizing muscle relaxant succinylcholine, resulting in hyperthermia, muscle stiffness, metabolic disturbances, and other severe physiological reactions. This condition may prove fatal unless it is recognized in its early stages and treatment is administered promptly and aggressively. We report a 13-year-old adolescent who underwent laparoscopic appendectomy and developed MH after the use of inhalational anesthetics, manifested by unremitting hyperthermia with a maximum temperature of 44.2°C, muscle rigidity, tachycardia, hypercapnia; and malignant arrhythmias, cardiogenic shock, hyperkalemia, metabolic, and respiratory acidosis. After early and timely recognition, multidisciplinary management and administration of dantrolene, the case was successfully treated. Exome sequencing revealed a point mutation (amino acid change) on the RYR1 gene: c.12700G>C(p.Val4234Leu). Due to the lack of ready-made dantrolene in our hospital, the patient in this case received dantrolene treatment only 6 h after the first observation of high body temperature. We review the development of the disease and summarize the success of treatment and what can be done to improve the chances of saving the patient's life if dantrolene is not available in time.

DOCK8 inhibits the immune function of neutrophils in sepsis by regulating aerobic glycolysis.

INTRODUCTION: This study endeavored to investigate the role of DOCK8 in modulating the immune function triggered by sepsis. METHODS: Expression of DOCK8 in the whole blood of sepsis patients and its enrichment pathways were assayed by bioinformatics. Pearson analysis was used to predict the relationship between glycolytic signaling pathway and its relevance to neutrophil function in sepsis. A sepsis mouse model was then built by performing cecal ligation and puncture treatment on male mice. Neutrophils were isolated, and their purity was tested by flow cytometry. Neutrophils were then stimulated by lipopolysaccharide to build a sepsis cell model. Next, quantitative reverse transcription polymerase chain reaction and CCK-8 were applied to test the expression of DOCK8 and cell viability, western blot to assay the expression of HK-2, PKM2, and LDHA proteins, ELISA to measure the concentrations of TNF-α, IL-1ß, and IL-6, Transwell to detect the chemotaxis of neutrophils and flow cytometry to detect the phagocytic activity of neutrophils. Finally, in different treatment groups, we used Seahorse XF 96 to analyze the extracellular acidification rate (ECAR) of sepsis cells and used enzyme-linked immunosorbent assay to detect the contents of pyruvic acid, lactic acid, and ATP in sepsis cells. RESULTS: DOCK8 was downregulated in sepsis blood and activated neutrophils. Aerobic glycolysis was positively correlated with sepsis. Activated neutrophils promoted the expression of inflammatory factors TNF-α, IL-1ß, and IL-6. Low expression of DOCK8 facilitated the proliferation, chemotaxis, and phagocytic activity of sepsis cells and promoted the expression of inflammatory factors. Bioinformatics analysis revealed that DOCK8 was enriched in the glycolytic signaling pathway. Low expression of DOCK8 induced ECAR, promoted the protein expression of HK-2, PKM2 and LDHA, and favored the increase of pyruvate, lactate, and ATP contents. While 2-DG treatment could restore these effects. CONCLUSION: DOCK8 may inhibit sepsis-induced neutrophil immune function by regulating aerobic glycolysis and causing excessive inflammation, which helps to explore potential therapeutic targets.

The relationship between expression of PD-L1 and HIF-1α in glioma cells under hypoxia.

Hypoxia inducible factor-1α (HIF-1α) up-regulates the expression of programmed death ligand-1 (PD-L1) in some extracranial malignancies. However, whether it could increase PD-L1 expression in intracranial tumor is still unknown. Here, we explored the relationship between HIF-1α and PD-L1 expression in glioma, and investigated their clinical significance. In glioma patients, HIF-1α and PD-L1 were overexpressed in high grade glioma tissues and were significantly associated with poor survival. In glioma cells, PD-L1 expression was induced under hypoxia condition, and the enhanced PD-L1 expression was abrogated by either HIF-1α knock-down or HIF-1α inhibitor treatment. Furthermore, ChIP-qPCR analysis showed the direct binding of HIF-1α to PD-L1 proximal promoter region, providing evidence that HIF-1α up-regulates PD-L1 in glioma. In glioma murine model, the combination treatment with HIF-1α inhibitor and anti-PD-L1 antibody caused a more pronounced suppressive effect on tumor growth compared to either monotherapy. Immunologically, the combination treatment improved both dendritic cell (DC) and CD8+ T cell activation. Overall, our results demonstrated that positive correlation between PD-L1 and HIF-1α in glioma, and provide an alternative strategy, inhibiting HIF-1α, as combination therapies with immunotherapies to advance glioma treatment.

Actin Gamma 1, a new skin cancer pathogenic gene, identified by the biological feature-based classification.

Skin cancer is the most common form of cancer that accounting for at least 40% of cancer cases around the world. This study aimed to identify skin cancer-related biological features and predict skin cancer candidate genes by employing machine learning based on biological features of known skin cancer genes. The known skin cancer-related genes were fetched from database and encoded by the enrichment scores of gene ontology and pathways. The optimal features of the skin cancer related genes were selected with a series of feature selection methods, such as mRMR, IFS, and Random Forest algorithm. Quantitative PCR (Q-PCR) was performed for the predicted genes. Effects on proliferation and metastasis of skin cancer cell line A431 were detected through MTT and transwell assay. The effects on myosin light chain (MLC) phosphorylation of Actin Gamma 1 (ACTG1) were detected by Western blot. A total of 1233 GO terms and 55 KEGG pathway terms were identified as the optimal features for the depiction of skin cancer. According to those terms, 1134 possible skin cancer-related genes were predicted. We further identified 16 new biomarkers in expression and the classification model can predict skin cancer cases with 100% accuracy. Among the 16 genes, ACTG1 had significantly high expression in skin cancer tissue. Our investigation suggested that ACTG1 can regulate the cell proliferation and migration through ROCK signaling pathway.

Computed tomography appearance of inflammatory myofibroblastic tumor in the abdomen: CT features and pathologic correlation.

OBJECTIVE: To evaluate CT findings of abdominal inflammatory myofibroblastic tumor (IMT) and the relationship with morphological character. MATERIALS AND METHODS: CT examinations and pathological findings of ten intra-abdominal IMTs were retrospectively analyzed. The histopathological characteristics of the IMTs were confirmed by two pathologists and two radiologists evaluated CT findings of the lesion, with emphasis on the imaging features compared with the corresponding histopathology. RESULTS: The most common imaging characteristics were presence of heterogeneity, all tumors showed varying degrees of contrast enhancement. Two major different CT patterns were individualized. In type one, the tumor had a distinct boundary without a lobular appearance and displayed hypo-enhanced enhancement after administration of contrast in correlated with the mainly histopathologic findings of spindle cells myxoid and hypocellular fibrous (6/10; 60%). In type two, the lesions exhibited indistinct boundaries or complete capsule, ill-defined growth patterns or low intralesional attenuation with marked heterogeneous or circumferential enhancement, which correlated well with the presence of abundance of micromodule and inflammatory cell infiltration (4/10; 40%). CONCLUSIONS: Two major different contrast enhancement CT patterns were individualized can help to determine the relationships with histopathologic findings, while cannot be reliably differentiated from other solid lesions based solely on the CT appearance, combined with diagnostic biopsy may facilitate to achieve a correct diagnosis and treatment.

Blocking HMGB1 signal pathway protects early radiation-induced lung injury.

It has been reported that HMGB1 participated in various types of lung injury. In this study, we explored whether blocking HMGB1 has a preventive effect on the early radiation-induced lung injury and investigate the mechanism. Mice model of radiation-induced lung injury were accomplished by a single dose irradiation (15 Gy) to the whole thorax. Irradiated mice were treated with HMGB1-neutralizing antibody intraperitoneally dosed 10 µg, 50 µg, 100 µg/mouse respectively and were sacrificed after one week post-irradiation. Lung tissue slices were stained by H&E, and alveolitis was quantified by Szapiel scoring system. The level of cytokines TNF-γ in bronchoalveolar lavage fluid was detected by ELISA method. And p65NF-κB, p50NF-κB protein expression in mice lung tissues was detected by Western blot analysis. The results showed that blocking HMGB1 inhibited the inflammatory response, and thereby decreased the degree of alveolitis of irradiated lung tissue. In addition, HMGB1 antagonist can restrain the expression of type Th2 or Th17 derived inflammatory cytokines TNF-α, IL-6 and IL-17A, promote the expression of Th1 type cytokines INF-γ, and inhibit p65 NF-κB but promote p50 NF-κB activation, which promoted the resolution of the radiation-induced inflammatory response. In conclusion, blocking HMGB1 can reduce the degree of early radiation-induced lung injury, and its mechanism may be related to the promotion of p50NF-κB activation and its downstream molecules expression. Inhibiting HMGB1 may be a new target to deal with early radiation-induced lung injury.

Clinical and pathological analysis of 116 cases of adult adrenal cortical adenoma and literature review.

BACKGROUND: The aim of this study is to investigate origin, gross features, microscopic features, immunohistochemical properties, and differential diagnosis of adrenal cortical adenoma (ACA) in patients ≥20 years old. METHODS: The clinicopathological features of 116 cases of ACA and the immunohistochemical features of 50 cases of ACA were evaluated, and the relevant literature was reviewed. RESULTS: In our cohort, 76.72% (89/116) of the cases were functional, and 27 cases had non-functional, benign adrenal adenomas. ACA presented as an island tumor with an envelope, and the mean tumor size was 3.6 cm (range 1-5 cm), with a mean tumor weight of 9.28 g (range 5-113 g). The shape of the tumor cells was consistent, and mitosis was rarely observed. Forty of the 46 patients with cortisol-secreting ACA had tumors containing granule cells. Primary aldosteronism was observed in 43 cases. Thirty-eight cases had endoscopically visible tumors, with clear cells and lipid-rich cytoplasm arranged in irregular patches or strips. Cortisol-producing ACAs were associated with atrophy of the non-tumorous cortex. Adrenocortical adenomas displayed positive immunohistochemical staining for MELAN-A, Syn (46 of 50 cases of ACA), NSE (44 of 50 cases of ACA), Vim (42 of 50 cases of ACA) and Ki-67 <5% (24 of 50 cases of ACA; the remaining 26 cases were negative for Ki-67). CONCLUSION: Prediction of endocrine syndrome in functional ACA was possible based on its structure and morphologic features, which could prevent an unanticipated postoperative crisis. However, a clinical study is needed to validate these findings.

Prognostic significance of high-risk human papillomavirus and p16(INK4A) in patients with esophageal squamous cell carcinoma.

The prognostic value of the HPV status in ESCC is much controversial, this study aimed to determine the prognostic importance of high-risk HPV and p16 in patients with ESCC. A total of 105 consecutive patients who underwent esophagectomy in 2008 were included in this study. All specimens with ESCC were tested by in situ hybridization for HPV16/18 and immunohistochemistry for p16 expression. Kappa values were calculated using Cohen's kappa test. The 5-year overall survival (OS) and progression-free survival (PFS) were calculated in relation to the two markers and the Cox proportional hazards model was used to determine the hazard ratio (HR) of variables. Thirty-nine (37.1%) of 105 were p16-positive, and HPV was detected in 29 of the 105 patients (27.6%) with ESCC. P16 was detected in 25 of the 29 patients (86.2%) who were HPV-positive, and only 14 of 76 patients (18.4%) who were HPV-negative (P < 0.001). Cohen's kappa coefficient revealed an agreement in two researchers (kappa = 0.61). The 5-year OS rate and PFS rate in the p16-positive group were 64.1% and 58.7%, respectively, and the rates in the p16-negative group were 45.5%, 37.9%, respectively. The difference of survival rate between the two groups remained statistically significant. P16-positive patients had better 5-year rates of OS and PFS than p16-negative group (P = 0.02 and P = 0.007 by the Log-rank test, respectively). Using HPV status as a stratification factor, we found differences in OS and PFS that were consistent with those based on p16 expression. P16 is a very good marker of HPV infection for ESCC. HPV-positive or p16-positive ESCC is a distinct entity with a favorable prognosis compared with HPV-negative or p16-negative ESCC.

Expression of interleukin-17A in lung tissues of irradiated mice and the influence of dexamethasone.

PURPOSE: To investigate the expressions of IL-17A in different phases of radiation-induced lung injury and the effect of dexamethasone. METHODS: The thorax of C57BL/6 mice was irradiated with 15 Gy rays. Mice from dexamethasone-treated group were injected intraperitoneally with dexamethasone (0.42 mg/kg/day) every day for the first month after irradiation. IL-17A in lung tissues was detected by immunohistochemistry. IL-17A, TGF-ß1, and IL-6 in bronchoalveolar lavage fluid were detected by ELISA. Lung inflammation and collagen deposition were observed by H&E and Masson methods. The degree of alveolitis and fibrosis was judged according to scoring. RESULTS: IL-17A expression was appreciable at 1 week, peaked at 4 weeks, and subsequently declined at 8 weeks after irradiation. IL-17A was reduced after dexamethasone application at all the observation periods. Dexamethasone also inhibited expressions of TGF-ß, IL-6, and TNF-α in bronchoalveolar lavage fluid. Moreover, dexamethasone attenuated the severity of lung injury by reducing the infiltration of inflammatory cells and collagen deposition. Terms of survival and the time of death in mice of treatment group were postponed and survival rate was improved. CONCLUSIONS: IL-17A plays an important role in the process of radiation-induced lung injury. And dexamethasone may provide a protective role in lung injury induced by radiation.

Interleukin-17A antagonist attenuates radiation-induced lung injuries in mice.

OBJECTIVE: To investigate the effect of interleukin-17A (IL-17A) antibodies on radiation-induced lung injuries in mice. METHODS: The thorax of 135 mice were divided into Sham (n = 30), radiation control (RC, n = 35), treatment (n = 35, IL-17A-neutralizing antibody, 4 µg/mouse, IV, 4 days per month for 4 months) and placebo group (n = 35) before a single dose irradiation (15 Gy) to the thorax. Inflammation and collagen contents in the lung tissues were examined, and the concentration of IL-17A, TGF-ß1, and IL-6 in bronchoalveolar lavage fluid (BALF) were measured. In another 50 animals, 180-day survival rate following the irradiation and treatment was calculated by Kaplan-Meier method. RESULTS: Sixteen weeks after the irradiation and treatment, there was significant inflammatory cell infiltration and interstitial collagen depositions in the radiation control and placebo groups, whereas these changes were relatively mild in the treatment group. The percentage of grade II and III alveolitis in the treatment group (16%, P < .05) was lower than in the RC (72%) or placebo group (64%). The mean Aschcroft fibrosis scores were 2.8 (treatment group), 5.2 (RC), and 4.8 (placebo group), respectively. The scores of treatment group was lower than that of RC (P < .001) or placebo group (P < .001). The IL-17A, TGF-ß, and IL-6 concentrations in the treatment group were lower than in the RC and placebo group (P < .01) following the irradiation. The 180-day mortality rate in the treatment group was lower than in the RC group 16.7% versus 75.0%, P < .05). CONCLUSION: IL-17A antibody treatment alleviates radiation-induced pneumonitis and subsequent fibrosis, and improvise postirradiation survival.

[Early high-volume hemofiltration treatment in severe sepsis].

OBJECTIVE: To evaluate the effect of early application of high-volume hemofiltration treatment (HVHF) on the levels of lactic acid, pro-inflammatory cytokines and C-reactive protein (CRP) in plasma, as well as APACHE II score in patients suffering from severe sepsis. METHODS: Thirty patients meeting the diagnosis of severe sepsis were enrolled in the trial within 24 hours of insults. The level of lactic acid, interleukin-6 (IL-6) and CRP in plasma were measured before HVHF and at 24, 48 or 72 h following HVHF treatment. RESULT: The plasma levels of lactic acid and IL-6 decreased significantly at 24 h, 48 h, 72 h after HVHF (P <0.05), while, IL-10 did not differ significantly following HVHF (P>0.05), when compared with that before HVHF. CONCLUSION: The early application of HVHF could clear the plasma lactic acid and pro-inflammatory cytokines, and improve the tissue oxygenation in severe sepsis.