LncRNA CamK-A Regulates Ca2+-Signaling-Mediated Tumor Microenvironment Remodeling.

Cancer cells entail metabolic adaptation and microenvironmental remodeling to survive and progress. Both calcium (Ca2+) flux and Ca2+-dependent signaling play a crucial role in this process, although the underlying mechanism has yet to be elucidated. Through RNA screening, we identified one long noncoding RNA (lncRNA) named CamK-A (lncRNA for calcium-dependent kinase activation) in tumorigenesis. CamK-A is highly expressed in multiple human cancers and involved in cancer microenvironment remodeling via activation of Ca2+-triggered signaling. Mechanistically, CamK-A activates Ca2+/calmodulin-dependent kinase PNCK, which in turn phosphorylates IκBα and triggers calcium-dependent nuclear factor κB (NF-κB) activation. This regulation results in the tumor microenvironment remodeling, including macrophage recruitment, angiogenesis, and tumor progression. Notably, our human-patient-derived xenograft (PDX) model studies demonstrate that targeting CamK-A robustly impaired cancer development. Clinically, CamK-A expression coordinates with the activation of CaMK-NF-κB axis, and its high expression indicates poor patient survival rate, suggesting its role as a potential biomarker and therapeutic target.

High level of TXNDC9 predicts poor prognosis and contributes to the NF-κB-regulated metastatic potential in gastric cancer.

Gastric cancer (GC) is the most frequent malignant tumor in the digestive system, with high metastasis potential and poor prognosis. This study aimed to investigate the prognostic value and biological function of thioredoxin domain-containing protein 9 (TXNDC9) in GC. The expression of TXNDC9 was analyzed based on The Cancer Genome Atlas (TCGA) database. The prognostic value of TXNDC9 was evaluated by Kaplan-Meier curves and Cox regression analysis. The mRNA and protein expression of TXNDC9 were analyzed using quantitative real-time PCR and western blot analysis. The effects of TXNDC9 on GC cell invasion and EMT were assessed in vitro, and its effects on tumorigenesis were confirmed using animal experiments. The activity of the NF-κB signaling pathway was examined by both in vitro and in vivo experiments. TXNDC9 was highly expressed in GC tissues and cell lines. A high level of TXNDC9 was associated with poor overall survival and served as an independent prognostic biomarker in GC patients. The knockdown of TXNDC9 led to restrained GC cell invasion, microtubule formation, and EMT in vitro, and suppressed tumorigenesis in vivo. In addition, the NF-κB signaling pathway was demonstrated to mediate the functional role of TXNDC9 in GC. In conclusion, this study found that high TXNDC9 predicted poor prognosis in GC, and served as an oncogene by enhancing tumor cell invasion and EMT through the NF-κB signaling pathway.

LncRNA wires up Hippo and Hedgehog signaling to reprogramme glucose metabolism.

The Hippo pathway plays essential roles in organ size control and cancer prevention via restricting its downstream effector, Yes-associated protein (YAP). Previous studies have revealed an oncogenic function of YAP in reprogramming glucose metabolism, while the underlying mechanism remains to be fully clarified. Accumulating evidence suggests long noncoding RNAs (lncRNAs) as attractive therapeutic targets, given their roles in modulating various cancer-related signaling pathways. In this study, we report that lncRNA breast cancer anti-estrogen resistance 4 (BCAR4) is required for YAP-dependent glycolysis. Mechanistically, YAP promotes the expression of BCAR4, which subsequently coordinates the Hedgehog signaling to enhance the transcription of glycolysis activators HK2 and PFKFB3. Therapeutic delivery of locked nucleic acids (LNAs) targeting BCAR4 attenuated YAP-dependent glycolysis and tumor growth. The expression levels of BCAR4 and YAP are positively correlated in tissue samples from breast cancer patients, where high expression of both BCAR4 and YAP is associated with poor patient survival outcome. Taken together, our study not only reveals the mechanism by which YAP reprograms glucose metabolism, but also highlights the therapeutic potential of targeting YAP-BCAR4-glycolysis axis for breast cancer treatment.

Perioperative management of bronchoscopy in a child patient with central core disease: A case report and literature review.

INTRODUCTION: We described the perioperative management of a child patient with central core disease for bronchoscopy with bronchoalveolar lavage. It is safe to avoid triggering agents (volatile anesthetics and succinylcholine) probably in preventing this appearance of malignant hyperthermia (MH). It is important to recognize potential complications and know how to prevent and manage them in patients with this condition. PRESENTATION OF CASE: A 5-year-old boy (weight: 8.8 kg; height: 63 cm) presented to the pediatric department after five days of intermittent fever (highest body temperature is 39.3 °C) and cough, and aggravation 1 day, meanwhile he had phlegm in throat but he couldn't cough out. The child was found to have motor retardation at his one-month-old physical examination, then genetic analysis showed central core disease. Bronchoscopy with bronchoalveolar lavage was performed for better treatment under the premise of symptomatic treatment. DISCUSSION: The patients with central core disease are particularly to develop malignant hyperthermia, so adequate precautions are in place to prevent and treat MH before anesthetic induction. The anesthesiologists need to make adequate preoperative anesthesia management strategies to ensure the safety of the child with central core disease for bronchoscopy with bronchoalveolar lavage. The child was discharged from the hospital one week after anti-inflammatory and anti-asthmatic treatment. CONCLUSION: We summarized the anesthetic precautions and management in patients with central core disease, meanwhile we offered some suggestions about anesthetic focus on bronchoscopy with bronchoalveolar lavage.

Advances in neuroimaging studies of alcohol use disorder (AUD).

Alcohol use disorder (AUD) is a worldwide problem and the most common substance use disorder. Chronic alcohol consumption may have negative effects on the body, the mind, the family, and even society. With the progress of current neuroimaging methods, an increasing number of imaging techniques are being used to objectively detect brain impairment induced by alcoholism and serve a vital role in the diagnosis, prognosis, and treatment assessment of AUD. This article organizes and analyzes the research on alcohol dependence concerning the main noninvasive neuroimaging methods, structural magnetic resonance imaging, functional magnetic resonance imaging, and electroencephalography, as well as the most common noninvasive brain stimulation - transcranial magnetic stimulation, and intersperses the article with joint intra- and intergroup studies, providing an outlook on future research directions.

A phosphatidic acid-binding lncRNA SNHG9 facilitates LATS1 liquid-liquid phase separation to promote oncogenic YAP signaling.

Long noncoding RNAs (lncRNAs) are emerging as a new class of important regulators of signal transduction in tissue homeostasis and cancer development. Liquid-liquid phase separation (LLPS) occurs in a wide range of biological processes, while its role in signal transduction remains largely undeciphered. In this study, we uncovered a lipid-associated lncRNA, small nucleolar RNA host gene 9 (SNHG9) as a tumor-promoting lncRNA driving liquid droplet formation of Large Tumor Suppressor Kinase 1 (LATS1) and inhibiting the Hippo pathway. Mechanistically, SNHG9 and its associated phosphatidic acids (PA) interact with the C-terminal domain of LATS1, promoting LATS1 phase separation and inhibiting LATS1-mediated YAP phosphorylation. Loss of SNHG9 suppresses xenograft breast tumor growth. Clinically, expression of SNHG9 positively correlates with YAP activity and breast cancer progression. Taken together, our results uncover a novel regulatory role of a tumor-promoting lncRNA (i.e., SNHG9) in signal transduction and cancer development by facilitating the LLPS of a signaling kinase (i.e., LATS1).

[Control of Sludge Bulking Caused by Unknown Reason Through FeCl3 Coupled with Biochemical Methods].

Filamentous bulking could commonly influence effluent water quality in sewage treatment plants. Existing technologies are slowly effective, time consuming, and poorly adaptable. For now, enhancing organics substrates (COD) and dissolved oxygen (DO) concentration, adding FeCl3 into the reactor, and maintaining alternant aeration conditions are common methods to control filamentous bulking, but the effects of coupling techniques on the control of bulking are rarely reported. In this study, the filamentous bulking resulting from unintentionally erupted Candidatus Saccharibacteria was controlled by FeCl3 coupled with biochemical methods, which transforming step-feed A/O processes to the SBR process in the emergency by increasing DO to (7.45±0.49) mg·L-1 during aeration, enhancing COD to (332.73±106.06) mg·L-1, and adding FeCl3 into the reactor to set the starting concentration to 120 mg·L-1. As the results showed, FeCl3 coupled with the biochemical method quickly counteracted the bulking sludge mainly composed of Candidatus Saccharibacteria caused by unknown reason, while the Sludge Volume Index dropped from 274 mL·g-1 to 56 mL·g-1 within 14 days. The relative abundance of Candidatus Saccharibacteria decreased from 97.64% to 32.67% at the genus level because FeCl3 coupled with the biochemical method inhibited growth of Candidatus Saccharibacteria. Meanwhile, effluents of both COD and PO43--P met the effluent requirements of the I-A discharge standard in China and removal efficiency of NH4+-N increased from 65.33% to 74.65%. The results showed that FeCl3 coupled with the biochemical method exhibited good performance in the control of bulking caused by unknown reasons.

Subacute Combined Degeneration, Pernicious Anemia and Gastric Neuroendocrine Tumor Occured Simultaneously Caused by Autoimmune Gastritis.

Subacute combined degeneration (SCD) is a relatively rare myelopathy mainly caused by vitamin B12 (VitB12) deficiency. There are many causes contributing to VitB12 deficiency. Autoimmune gastritis might lead to severe VitB12 malabsorption and in its advanced stage pernicious anemia (PA) may occur. Besides, long-term hypergastrinemia arising from achlorhydria in autoimmune gastritis is associated with neuroendocrine tumors (NETs). Patients diagnosed with SCD coexistent with PA and NET are seldomly reported. We describe a 34-year-old woman with an initial complaint of progressive fatigue, weakness and numbness in her limbs and disturbed gait. Physical examination revealed appearance of anemia, ataxia, decrease of superficial and deep sense, and positive Babinski's sign. Laboratory tests disclosed macrocytic anemia, elevated intrinsic factor antibody and spinal MRI showed extensive T2-weighted hyperintensity in the dorsal columns. A gastric polyp was revealed by gastroscopy and histology showed an NET in the background of severe atrophic gastritis. Symptoms of the patient were relieved by a multidisciplinary therapy. In patients with SCD, PA should be suspected and prompt further investigations to elucidate causes and direct treatment.

The role of repetitive transcranial magnetic stimulation (rTMS) in the treatment of cognitive impairment in patients with Alzheimer's disease: A systematic review and meta-analysis.

BACKGROUND: Although repetitive transcranial magnetic stimulation (rTMS) has been considered a potentially effective treatment for cognitive impairment in patients with Alzheimer's disease (AD), previous studies have produced inconsistent results. The objective of this meta-analysis was to evaluate the effects of rTMS on cognitive function in patients with AD. METHODS: PubMed, EMBASE, Web of Science, MEDLINE and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for relevant terms. Abstracts of all papers were carefully reviewed, followed by data extraction, quality assessment, data synthesis and subgroup analyses. RESULT: A total of 12 studies with 231 patients were included, with 8 randomized controlled studies and 4 self-controlled studies. Eleven studies used high frequency rTMS (≥ 5 Hz), but only one study directly compared the difference between low-frequency (1 Hz) and high-frequency (20 Hz). Random-effects analysis revealed that rTMS could significantly improve cognition compared with sham-rTMS (SMD: 0.60, 95% CI: 0.35-0.85, P < .0001). In subgroup analyses, the effect for stimulation at a single target was 0.13 (95% CI: -0.35-0.62) and multiple targets 0.86 (95% CI: 0.18-1.54). Treatment for ≤3 sessions produced an effect of 0.29 (95% CI: -1.04-1.62), whereas treatment for ≥5 sessions produced an effect of 2.77 (95% CI: 2.22-3.32). No differences were found for rTMS combined with medication or cognitive training. CONCLUSIONS: rTMS can significantly improve cognitive ability in patients with mild to moderate AD. Stimulation of multiple sites and long-term treatment are better at improving AD-associated cognitive performance. Furthermore, some novel interventional targets, like precuneus (PC), may be a more effective therapeutic site to improve memory in AD.

The Protective Effects of Fasciotomy on Reperfusion Injury of Skeletal Muscle of Rabbits.

The authors aim to investigate protective effects of fasciotomy against ischemia reperfusion injury of skeletal muscle in rabbit and to compare the treatment effects of prereperfusion + fasciotomy and fasciotomy + postreperfusion against ischemia reperfusion injury of skeletal muscle. 24 healthy male Japanese white rabbits were randomly divided into 3 groups, and 4 hours' ischemia was established in these rabbits through surgery. Six hours' reperfusion was performed in group A; reperfusion + postfasciotomy was performed in group B; and prefasciotomy + reperfusion was performed in group C. Result showed that prefasciotomy and postfasciotomy could protect skeletal muscle against ischemia reperfusion injury, reduced MDA (malondialdehyde) expression, MPO (myeloperoxidase) expression, and apoptosis of muscle in the reperfused areas, increased Bcl-2 expression, and decreased Bax expression. The MDA and MPO levels in group B and group C were significantly lower than those in group A, and MDA and MPO levels in group C were significantly lower than those in group B. Prefasciotomy and postfasciotomy could protect against ischemia reperfusion injury in skeletal muscle. The protective effects of prefasciotomy against ischemia reperfusion injury are better than postfasciotomy.

[Limestone and pyrite-limestone constructed wetlands for treating river water].

Polluted river water was treated with limestone and pyrite-limestone subsurface horizontal constructed wetlands. The aims were to know the performance of two wetlands on removal of common pollutants, especially nitrogen and phosphorus, and analyze the actions of these minerals. The relationship between hydraulic retention time and purification performance of two constructed wetlands was studied. The optimal hydraulic retention time for pollutant removal was about 3 d, The average removal efficiency of COD, TN and TP were 51%, 70% and 95%, respectively. With same influent and hydraulic loading, the average removal efficiency of COD, NH4+ -N, TN and TP were 53.93%, 82.13%, 66%, 50.9%, and 51.66%, 77.43%, 72.06%, 97.35% for limestone and pyrite-limestone constructed wetlands, respectively. There were few differences between limestone and pyrite-limestone wetlands on COD removal, but the nitrogen and phosphorus removal of pyrite-limestone constructed wetland was higher than that of limestone constructed wetland. The phosphorus removal of pyrite-limestone wetland was more efficiency and stable, not affected by temperature.

[Investigation of nitrobenzene removal by iron sulfide (FeS)].

The nitrobenzene removal performance by iron sulfide was investigated in batch experiments. The effects of different factors were studied. The results showed that the removal efficiency of nitrobenzene was 90% as initial nitrobenzene concentration was 0.96 mmol x L(-1), dosage of FeS was 1.2 g and the reaction time was 180 minutes. Initial nitrobenzene concentration, dosage of FeS, temperature and reused times of FeS had a significant influence on the removal efficiency of nitrobenzene. As the initial nitrobenzene concentration was in range of 0.74 to 1.74 mmol x L(-1), the removal efficiency of nitrobenzene decreased by 4.7% with every 0.1 mmol x L(-1) increasing of initial nitrobenzene concentration. As the dosage of FeS was in the range of 0.3 to 1.5 g, the removal efficiency of nitrobenzene increased by 20% with every 0.3 g increasing of FeS. As the dosage of FeS was 1.8 g, the removal efficiency of nitrobenzene was 100%. In the temperature range of 10 to 25 degrees C, the removal efficiency of nitrobenzene increased by 1.6% with 1 degrees C increasing. As the temperature was 30 degrees C, the removal efficiency of nitrobenzene was 100%. The removal efficiency of nitrobenzene decreased as the reused times of FeS increased. Rotational speed hardly had any influence on the removal efficiency of nitrobenzene. As the rotational speed was in the range of 10 to 80 r x min(-1), the removal efficiency of nitrobenzene was around 75%. The nitrobenzene removal performance by iron sulfide was satisfied in the treatment of simulated chemical industrial wastewater, and after 60 min, the removal efficiency of nitrobenzene was 100%.

[Performance of nitrogen and phosphorus removal of sulfur/limestone autotrophic denitrification system].

In order to investigate the performance of nitrogen and phosphorus removal of the sulfur/limestone system from low C/N municipal sewage, a sulfur/limestone packed column reactor fed with synthetic wastewater, and operated in the way of anaerobic biological filter was constructed. The effects of HRT, initial concentration of phosphate, pH and temperature on nitrogen and phosphorus removal were studied. The results showed that with influent of NO3(-) -N 30 mg/L, PO4(3-) -P 15 mg/L, the optimal HRT value was 6 h, and removal rates of TN and phosphorus were 100% and 44.64% respectively. Initial concentration of phosphate and initial pH had a significant influence on nitrogen and phosphorus removal. In order to keep nitrogen removal rate higher than 90%, initial concentration of phosphate should not be below 0.4 mg/L; the optimal pH value was 6.5, and removal rates of TN and phosphorus were 91.51% and 47.68% respectively. Temperature had a positive impact on that system, the nitrogen and phosphorus removal rate decreased with decreasing temperature. The nitrate removal efficiency was high in the temperature range of 18-30 degrees C, and the efficiency of phosphorus removal rate reached about 50%, when the temperature was between 25-30 degrees C. The dephosphorization behavior of sulfur/ limestone system correlated closely with autotrophic denitrification process, and the mechanism of phosphate removal of the SLAD system was mainly due to chemical precipitation. The system had the performance of nitrogen and phosphorus removal from low C/N municipal sewage, the highest phosphorus removal rate could reach 50%.

[Non-nitrification pathway for NH4+ -N removal in pilot-scale drinking water biological processes].

The non-nitrification pathway for NH4+ -N removal in pilot-scale drinking water biological treatment processes and its possible mechanism were investigated through calculating N and DO stoichiometric balance. With more than 2 mg/L NH4+ -N in the influent, for the fluidized bed bioreactor (FBBR), the total of NH4+ -N, NO2(-) -N, NO3(-) -N in the influent was 0.91 mg/L higher than that in the effluent, and for the biofilter, its DO consumption was 2.90 mg/L less than the stoichiometric amount. The results suggested that nitrogen loss occurred in both reactors and a part of NH4+ -N was removed through non-nitrification pathway. Because the utilization of phosphorus and organic matters was independent of nitrogen loss, the assimilation and denitrification could be excluded from the possible mechanisms. Because the very low C/N in the influent and the accumulation of NO2(-) -N in the reactors were similar with the wastewater biological processes, the "autotrophic removal of nitrogen" was regarded as the most probable non-nitrification pathway. In this mechanism, the couple of short-cut nitrification and ANAMMOX (or OLAND) leading to the transformation of NH4+ -N and NO2(-) -N into gaseous N2 was responsible for the nitrogen loss in drinking water biological processes.

[Pilot-scale study on riparian Scirpus yagara Ohw zone improving water quality of river].

In one year polluted water was treated with Scirpus yagara Ohw to investigate its impact on river water quality in pilot scale test, and COD, NH4(+) -N, TP, turbidity and water temperature were tested. The results show that the Scirpus yagara Ohw gives better water quality in summer and autumn than in winter and spring. In summer, the Scirpus yagara Ohw zone removes 44.10% of the COD, 78.66% of the ammonia, 69.44% of the phosphorous, and 99.53% of the turbidity. It also can improve water quality to some extent in winter. The Scirpus yagara Ohw can reduce effluent temperature and effluent temperature difference between evening and morning and then improve water microenvironment locally. Comparisons between the Scirpus yagara Ohw riparian zone and control zone showed that the Scirpus yagara Ohw affects importantly on removing pollutants, improving local microenvironment of water.

[Pilot-scale study on riparian mixed plant zones treating polluted river water].

The polluted river water is treated with pilot-scale riparian zones of no aquatic plant, Vetiveria zizanioides + submerged plants, and weed+ Typha angustifolia L. + Phragmites communis. It is shown that the vegetation water zones are better than the no vegetation water zone and Vetiveria zizanioides + submerged plants zone is the best in improving water quality. The average removals of the Vetiveria zizanioides + submerged plant zone is 43.5% COD, 71.1% ammonia and 69.3% total phosphorus respectively. The dissolved oxygen (DO) and temperature of effluents from the three water zones are also investigated. It shows that DO of effluent from the vegetation zones are more stable than that of effluent from the no vegetation zone, and the temperature of the effluent from the vegetation zones are lower than that from the no vegetation zones. The submerged plants have special role in water quality improvement, and should be studied further.