TSPO exacerbates acute cerebral ischemia/reperfusion injury by inducing autophagy dysfunction.

Autophagy is considered a double-edged sword, with a role in the regulation of the pathophysiological processes of the central nervous system (CNS) after cerebral ischemia-reperfusion injury (CIRI). The 18-kDa translocator protein (TSPO) is a highly conserved protein, with its expression level in the nervous system closely associated with the regulation of pathophysiological processes. In addition, the ligand of TSPO reduces neuroinflammation in brain diseases, but the potential role of TSPO in CIRI is largely undiscovered. On this basis, we investigated whether TSPO regulates neuroinflammatory response by affecting autophagy in microglia. In our study, increased expression of TSPO was detected in rat brain tissues with transient middle cerebral artery occlusion (tMCAO) and in BV2 microglial cells exposed to oxygen-glucose deprivation or reoxygenation (OGD/R) treatment, respectively. In addition, we confirmed that autophagy was over-activated during CIRI by increased expression of autophagy activation related proteins with Beclin-1 and LC3B, while the expression of p62 was decreased. The degradation process of autophagy was inhibited, while the expression levels of LAMP-1 and Cathepsin-D were significantly reduced. Results of confocal laser microscopy and transmission electron microscopy (TEM) indicated that autophagy flux was disordered. In contrast, inhibition of TSPO prevented autophagy over-activation both in vivo and in vitro. Interestingly, suppression of TSPO alleviated nerve cell damage by reducing reactive oxygen species (ROS) and pro-inflammatory factors, including TNF-α and IL-6 in microglia cells. In summary, these results indicated that TSPO might affect CIRI by mediating autophagy dysfunction and thus might serve as a potential target for ischemic stroke treatment.

Suspended phosphorus sustains algal blooms in a dissolved phosphorus-depleted lake.

The expansion of algal bloom in surface waters is a global problem in the freshwater ecosystem. Differential reactivity of organic phosphorus (Po) compounds from organic debris, suspended particulate matter (SPM), and sediment towards hydrolysis can dictate the extent of supply often limited inorganic P (Pi) for algal growth, thereby controlling the extent of bloom. Here, we combined solution P-31 nuclear magnetic resonance (31P NMR), sequential extraction, enzymatic hydrolysis, and 16S rRNA measurements to characterize speciation and biogeochemical cycling of P in Lake Erhai, China. Lower ratios of diester-P/monoester-P in SPM in January (mean 0.09) and July (0.14) than that in April (0.29) reflected the higher degree of diester-P remineralization in cold and warm months. Both H2O-Pi and Po were significantly higher in SPM (mean 1580 mg ·kg-1 and 1618 mg ·kg-1) than those in sediment (mean 8 mg ·kg-1 and 387 mg ·kg-1). In addition, results from enzymatic hydrolysis experiments demonstrated that 61% Po in SPM and 58% in sediment in the H2O, NaHCO3, and NaOH extracts could be hydrolyzed. These results suggested that H2O-Pi and Po from SPM were the primarily bioavailable P sources for algae. Changes of Pi contents (particularly H2O-Pi) in algae and alkaline phosphatase activity (APA) during the observation periods were likely to be controlled by the strategies of P uptake and utilization of algae. P remobilization/remineralization from SPM likely resulted from algae and bacteria (e.g., Pseudomonas). Collectively, these results provide important insights that SPM P could sustain the algal blooms even if the dissolved P was depleted in the water column.

Preoperative α-blockade versus no blockade for pheochromocytoma-paraganglioma patients undergoing surgery: a systematic review and updated meta-analysis.

BACKGROUND: Surgical resection of pheochromocytomas and paragangliomas (PPGLs) is associated with a significant risk of intraoperative hemodynamic instability and cardiovascular complications. α-blockade remains the routine preoperative medical preparation despite controversies over the lack of evidence. We presented an updated meta-analysis to ulteriorly evaluate the potential efficacy of preoperative α-blockade versus no blockade for PPGL patients undergoing surgery. MATERIALS AND METHODS: Randomized and nonrandomized comparative studies assessing preoperative α-blockade for PPGL surgery in adults were identified through a systematic literature search via MEDLINE, Embase, Web of Science, and CENTRAL up to November 2022. Outcome data of intraoperative hemodynamic parameters and major postoperative events were extracted. Mean difference and risk ratio were synthesized as appropriate for each outcome to determine the cumulative effect size. RESULTS: Fifteen nonrandomized studies involving 3542 patients were finally eligible. Intraoperatively, none of the analyzed hemodynamic parameters differed between patients with or without α-blockade: maximum and minimum systolic blood pressure, hypertensive and hypotensive hemodynamic instability episodes, and peak heart rate, subgroup analysis of normotensive PPGL patients yielded similar results with the overall effects. Postoperatively, α-blockade was associated with prolonged hypotension and vasopressor usage (risk ratio: 4.21, 95% CI: 1.17-15.18, P =0.03). ICU admission, length of stay, overall cardiovascular morbidity, and mortality were similar between the two groups. CONCLUSIONS: Preoperative α-blockade ensured neither more stable intraoperative hemodynamics nor better perioperative outcome over no blockade for PPGL surgery. However, large-volume randomized controlled trials are still warranted to ascertain these findings.

Extensive abundances and characteristics of microplastic pollution in the karst hyporheic zones of urban rivers.

Cities are potential areas for microplastic pollution due to large-scale production and the use of plastic products. The karst ecosystem in southwestern China is fragile, and pollutants are more likely to be transported over long distance, resulting in higher pollution risks. Understanding the abundance and composition of microplastics in karst urban water systems is crucial for microplastic pollution management in a karst region. This study investigates the abundances and characteristics of microplastics typically found in river sediments in 10 cities in karst regions of Southwest China. The results show that the abundance of microplastics in sediments ranged from 800 items·kg-1 to 4400 items·kg-1, with an average of 2273 ± 775 items·kg-1 (n = 30), indicating high abundance. Polyamide (PA) was the most common plastic polymer types in all sediment samples. The abundance of microplastics in the downstream (2527 ± 698 items·kg-1) was higher than that in the midstream (2350 ± 999 items·kg-1) and upstream areas (1943 ± 370 items·kg-1), indicating a gradual accumulation effect in the karst water systems. Microplastic abundance in cities (2119 ± 838 items·kg-1) was lower than in counties (2427 ± 671 items·kg-1). No significant correlation was found between microplastic abundance in rivers of urban areas and the level of regional population and economy, but significantly negatively correlated with the efficiency of urban sewage treatment. The results obtained from this study provided insights into the management of microplastic pollution in urban river of a karst region.

A comprehensive gene expression profile analysis of prostate cancer cells resistant to paclitaxel and the potent target to reverse resistance.

Background: Paclitaxel resistance is the major clinical obstacle in the chemotherapy of prostate cancer (PCa), but the resistant mechanism is less investigated.Purpose: To establish two paclitaxel-resistant PCa cells, provide a comprehensive gene expression profile analysis of resistant cells and the potential target to reverse resistance.Methods: Two Paclitaxel-resistant PCa cells (PC3/PR, LNcap/PR) were established by gradually increasing drug concentration. MTT and transwell assays were performed to detect drug sensitivity, cell proliferation and migration abilities. RNA-Sequencing (RNA-seq) and bioinformatic analyses were performed to identify abnormally expressed genes (AEGs) in resistant cells, and annotate the biological functions of AEGs. The role of the candidate AEG, TLR-4, on the resistant phenotypes was further investigated.Results: The resistance index of resistant cells was 2-3, and they showed a slower proliferation and increased migration ability. 4741 AEGs were screened out (Log2fold change absolute: log2FC(abs) > 1) in the resistant cells, and they were enriched in 2'-5'-oligoadenylate synthetase activity and chemical carcinogenesis. A number of AEGs, CCND2, IGFBP3, FOS, SHH, ZEB2, and members of FGF, FGFR and WNT families were also identified to be involved in cancer- and resistant phenotype-related processes. Finally, TLR-4 was validated significantly increased in resistant cells, and knockdown of TLR-4 increased drug-sensitivity, inhibited the proliferation and migration abilities.Conclusions: The study provided a comprehensive gene expression profile of paclitaxel-resistant PCa cells, and TLR-4 could be a potential target to reverse paclitaxel resistance.

A novel prognostic model based on three clinic-related miRNAs for prostate cancer.

Background: Prostate cancer (PCa) is the second most common malignant tumor in men worldwide. MiRNAs have been reported to play significant roles in prognosis prediction for patients with malignant tumors. Methods: The survival-related miRNAs (sDMIRs) were identified by Cox regression analysis. A risk score model (RSM) was established based on three sDMIRs. The expression levels of sDMIRs in cell lines and clinical samples were detected via quantitative polymerase chain reaction. The correlations between sDMIRs and clinicopathological characteristics of PCa patients were evaluated using the chi-square test and Fisher's exact probability method. Results: Four sDMIRs were remarkably related to the prognosis of PCa patients based on univariate Cox analysis, of which miR-10a-5p, miR-20a-5p, and miR-508-3p were used to establish the RSM. The OS in the low-risk group was better than that in the high-risk group. In the verification of various prostate cell lines and clinical samples from 162 PCa patients, the prominently higher expression of miR-10a-5p and miR-20a-5p and lower expression of miR-508-3p were detected in PCa cell lines and tumor tissues, especially the more advanced T-stage. Besides, the higher expression of miR-20a-5p and miR-10a-5p was significantly correlated to the higher level of PSA, Gleason score, more advanced T-stage, and distant metastasis status. Conclusion: We identify and validate the clinical significance of three sDMIRs and establish a verified RSM to evaluate the prognosis for PCa patients. The findings not only provide a reliable tool for clinical decision-makers to evaluate patients' prognosis but also offer a novel perspective into the field of biomarker identification.

Fuel from within: Can suspended phosphorus maintain algal blooms in Lake Dianchi.

Extensive algal bloom in the surface water is a pressing issue in Lake Dianchi that causes lake restoration to be difficult owing to complex and variable phosphorus (P) sources in the water column. P released from algae, suspended particles (SS), and sediment can provide sustainable P sources for algal blooms. However, little is known regarding the dynamic of P speciation in these substances from different sources. In this study, solution 31P nuclear magnetic resonance (31P NMR) and chemical sequential extraction were employed to identify P speciation in algae, SS, and sediment during different periods. Results showed that dissolved inorganic P (Pi) directly accumulated in algae in the form of orthophosphate (ortho-P) and pyrophosphate (pyro-P). Algae preferentially utilized Pi, followed by organic P (Po) in the water column when the Pi was insufficient during growth and reproduction. The 31P NMR spectra demonstrated that ortho-P, orthophosphate monoesters (mono-P), orthophosphate diesters (diester-P), and pyro-P dominated the P compounds across the samples tested. Increasing remineralization of SS mono-P driven by intense alkaline phosphatase activities was caused by increasing P needs of algae and pressure of P supply in the water column. The higher ratios of diester-P to mono-P in sediment (mean 0.55) than those in algae (mean 0.07) and SS (mean 0.11 in surface water, 0.14 in bottom water) suggested that the degradation and regeneration occurred within these P compounds during or after sedimentation. Pi content in algae during growth and reproduction was controlled by its P absorption and utilization strategies. Results of this study provide insights into the dynamic cycling of P in algae, SS, and sediment, explaining the reason for algal blooms in the surface water with low concentrations of dissolved P.

Dynamics of vaginal microbiome in female beagles at different ages.

Age-related changes in human vaginal microbiota composition have been reported, and such changes might be influenced by humidity, external stimuli, hormone levels, drug to use, and other factors. However, there is no report about the vaginal microbiota composition of female beagles at different ages. To investigate the effects of aging on the vaginal microbiota independent of other effects, we analyzed the vaginal microbiomes of 23 beagles at a wide range of ages from 1 year to 7 years old (except the 3rd year), 1-2 y were categorized into youth stage (YS), 4-5 y were categorized into middle stage (MS), and 6-7 y were categorized into elderly stage (ES) based on age. Samples were collected by scraping the vaginal mucosa of YS (n = 8), MS (n = 5) and ES (n = 10), and analyzed by 16S-rRNA gene high-throughput-sequencing. The diversity of the vaginal microbiome in female beagles was found to continuously change with age. We also found associations between age and specific members and functions of the vaginal microbiome. The metabolism of terpenoids and polyketide and the cell motility are significantly enhanced with age. Our results suggest that the proportion of Tenericutes might be a biomarker which could distinguish between YS and others.

Effect of cascade damming on microplastics transport in rivers: A large-scale investigation in Wujiang River, Southwest China.

Rivers are the important channels for transporting microplastics into the ocean from land. Prosperous dam construction changed the connectivity of rivers, thereby reducing the flux of microplastics to the ocean. However, this process currently lacks verification for the large-scale watersheds. In this study, we investigated the Wujiang River in China to evaluate the interception of cascade dams on microplastics. The results showed that: 1) The midstream exhibits a high abundance of microplastics (606.6-1046.2 items·kg-1) while the upstream and downstream reach exhibits relatively low pollution levels. The small-sized microplastics of 0-0.5 mm are easily migrated into downstream while the large-sized microplastics of 0.5-5 mm tend to deposit. 2) Ten kinds of plastic materials were found, in which polyethylene and polypropylene, originated from the developed tourism and fishery, account for 74.2% in all samples. 3) The earliest microplastics were found in the sediments of 1962. The abundance of microplastics in the sediments in seven reservoirs increased over time, impling the contribution of increasing human activities. 4) Positive correlations between the abundance of microplastics in sediments and local gross domestic product (GDP) (n = 33, R2 = 0.89, p < 0.05) and negative correlations between microplastics abundance and reservoir basin area (n = 33, R2 = 0.42, p < 0.05) revealed that GDP and watershed area are the key factors that control the distribution of microplastics. Our results help to understand the migration of microplastics between terrestrial and marine ecosystems.

Heavy metal pollution caused by cyanide gold leaching: a case study of gold tailings in central China.

It is known that the tailings of gold mines have brought serious heavy metal pollution; however, the heavy metal pollution caused by gold tailings in specific geological environments and extraction processes still must be studied. This study investigated the distribution, speciation, bioaccumulation, and pollution of heavy metals in soils from the Yueliangbao gold tailings area in central China, where gold was extracted by cyanidation. The results show that the concentrations of Cu, Pb, Zn, Mn, Mo, and Cd in the soils of the tailings pond were higher than those in the local background. The concentrations of heavy metals related to mineralization activities, such as Cu, Pb, Zn, and Mo, varied with the distance to the tailings pond center. There was a decreasing trend of tailings pond center > tailings pond entrance > surrounding environment. This study's gold tailings pond differed from those of other regions because of its high content of unextracted Cu remaining in the pond. The proportion of non-residual Cu in the tailing pond soil was much higher than that of residual Cu, indicating it was likely to migrate to the surrounding environment. The pollution assessment indicated that the tailings pond soils were heavily polluted by Cu, and the level of heavy metal pollution in soils was positively correlated with the distance to the tailings pond center. Consequently, this tailings pond may become a source of Cu pollution in the surrounding environment, thus endangering environmental safety and human health. The study of heavy metal concentrations in the dominant plants showed that Chinese brake (Pteris vittata L.), Ramose scouring rush (Equisetum ramosissimum), and Manyflower silvergrass (Miscanthus floridulus) had the potential to be used for the phytostabilization of Cu.

N-Myc-Interacting Protein Negatively Regulates TNF-α-Induced NF-κB Transcriptional Activity by Sequestering NF-κB/p65 in the Cytoplasm.

NF-κB is a major regulator of gene transcription involved in immune, inflammation, apoptosis and stress responses. However, the regulation of NF-κB is not completely understood. Here, we report that the N-Myc and STATs Interactor (NMI), an IFN-inducible protein, is an important negative regulator of NF-κB activity. We found that NMI negatively regulates TNF-α-induced IL-6 and IL-1ß production in HeLa cells. Overexpression of NMI inhibits NF-κB transcriptional activity, in contrast, depletion of NMI by shRNA increases NF-κB transcriptional activity. Mechanistically, NMI associates with NF-κB/p65 and inhibits NF-κB/p65 nuclear translocation and thereby negatively regulates NF-κB/p65 transcriptional activity. Taken together, our results demonstrate that NMI modulates the NF-κB signaling pathway by sequestering NF-κB/p65 in the cytoplasm, resulting in reduced IL-6 and IL-1ß production after TNF-α stimulation. Treatment with IFNα in the presence of NMI leads to increased apoptosis in tumor cells. These findings reveal a novel mechanism by which NMI regulates NF-κB activity.