MicroRNA-989 controls Aedes albopictus pupal-adult transition process by influencing cuticle chitin metabolism in pupae.

BACKGROUND: Aedes albopictus is a vector of numerous devastating arboviruses and places heavy burdens on global public health. Chitin is one of the important components of cuticles and targeting chitin metabolism is a promising strategy for preventing mosquito dispersal and mosquito-borne diseases. Increasing evidence suggests that microRNAs (miRNAs) play crucial roles in various physiological processes of insects. METHODS: A previous analysis suggested that the microRNA miR-989 is potentially involved in chitin metabolism in Ae. albopictus pupae. In the present study, we found that the expression level of miR-989 was significantly overexpressed after injection of agomir. A dual-luciferase assay was used to determine the direct target of miR-989. Survival rate, eclosion rate and malformation rate were statistically analyzed to evaluate the potential effect of miR-989. Hematoxylin-eosin staining and chitin staining were used to evaluate the microstructural changes in the cuticles of Ae. albopictus pupae. RESULTS: Overexpression of miR-989 resulted in a significantly reduced survival rate and eclosion rate of pupae and an elevated malformation rate of adults. The results suggested that miR-989 acted as a regulator of chitin metabolism in Ae. albopictus pupae by affecting the transcript levels of the Ae. albopictus genes encoding chitin synthase 1 (AaCHS1) and chitinase 10 (AaCht10). The altered expression levels of the two chitin metabolism-related enzymes (CHS1 and Cht10, respectively) caused the structural changes in cuticles and further affected the pupal-adult transition process of Ae. albopictus. XM_029863591.1 was proven to be the target gene of miR-989 and displayed similar effects on pupae as miR-989. CONCLUSIONS: The microRNA miR-989 was found to be essential for chitin metabolism in old and new cuticles of Ae. albopictus pupae. The results of the current study suggested that miR-989 could be used as a potential target to control Ae. albopictus.

Differences in the EEG Power Spectrum and Cross-Frequency Coupling Patterns between Young and Elderly Patients during Sevoflurane Anesthesia.

Electroencephalography (EEG) is widely used for monitoring the depth of anesthesia in surgical patients. Distinguishing age-related EEG features under general anesthesia will help to optimize anesthetic depth monitoring during surgery for elderly patients. This retrospective cohort study included 41 patients aged from 18 to 79 years undergoing noncardiac surgery under general anesthesia. We compared the power spectral signatures and phase-amplitude coupling patterns of the young and elderly groups under baseline and surgical anesthetic depth. General anesthesia by sevoflurane significantly increased the spectral power of delta, theta, alpha, and beta bands and strengthened the cross-frequency coupling both in young and elderly patients. However, the variation in EEG power spectral density and the modulation of alpha amplitudes on delta phases was relatively weaker in elderly patients. In conclusion, the EEG under general anesthesia using sevoflurane exhibited similar dynamic features between young and elderly patients, and the weakened alteration of spectral power and cross-frequency coupling patterns could be utilized to precisely quantify the depth of anesthesia in elderly patients.

Molecular identification of the chitinase genes in Aedes albopictus and essential roles of AaCht10 in pupal-adult transition.

BACKGROUND: Aedes albopictus is an increasingly serious threat in public health due to it is vector of multiple arboviruses that cause devastating human diseases, as well as its widening distribution in recent years. Insecticide resistance is a serious problem worldwide that limits the efficacy of chemical control strategies against Ae. albopictus. Chitinase genes have been widely recognized as attractive targets for the development of effective and environmentally safe insect management measures. METHODS: Chitinase genes of Ae. albopictus were identified and characterized on the basis of bioinformatics search of the referenced genome. Gene characterizations and phylogenetic relationships of chitinase genes were investigated, and spatio-temporal expression pattern of each chitinase gene was evaluated using qRT-PCR. RNA interference (RNAi) was used to suppress the expression of AaCht10, and the roles of AaCht10 were verified based on phynotype observations, chitin content analysis and hematoxylin and eosin (H&E) stain of epidermis and midgut. RESULTS: Altogether, 14 chitinase-related genes (12 chitinase genes and 2 IDGFs) encoding 17 proteins were identified. Phylogenetic analysis showed that all these AaChts were classified into seven groups, and most of them were gathered into group IX. Only AaCht5-1, AaCht10 and AaCht18 contained both catalytic and chitin-binding domains. Different AaChts displayed development- and tissue-specific expression profiling. Suppression of the expression of AaCht10 resulted in abnormal molting, increased mortality, decreased chitin content and thinning epicuticle, procuticle and midgut wall of pupa. CONCLUSIONS: Findings of the present study will aid in determining the biological functions of AaChts and also contribute to using AaChts as potential target for mosquito management.

Impact of Different KDIGO Criteria on Clinical Outcomes for Early Identification of Acute Kidney Injury after Non-Cardiac Surgery.

The Kidney Disease Improving Global Outcomes (KDIGO) guidelines are currently used in acute kidney injury (AKI) diagnosis and include both serum creatinine (SCR) and urine output (UO) criteria. Currently, many AKI-related studies have inconsistently defined AKI, which possibly affects the comparison of their results. Therefore, we hypothesized that the different criteria in the KDIGO guidelines vary in measuring the incidence of AKI and its association with clinical outcomes. We retrospectively analyzed that data of patients admitted to the intensive care unit after non-cardiac surgery in 2019. Three different criteria used to define AKI were included: UOmean, mean UO < 0.5 mL/kg/h over time; UOcont, hourly UO < 0.5 mL/kg/h over time; or SCR, KDIGO guidelines SCR criteria. A total of 777 patients were included, and the incidence of UOmean-AKI was 33.1%, the incidence of UOcont-AKI was 7.9%, and the incidence of SCR-AKI was 2.0%. There were differences in the length of ICU stay and hospital stay between AKI and non-AKI patients under different criteria. We found differences in the incidence and clinical outcomes of AKI after non-cardiac surgery when using different KDIGO criteria.

Transcutaneous Electrical Acupoint Stimulation Combined With Auricular Acupressure Reduces Postoperative Delirium Among Elderly Patients Following Major Abdominal Surgery: A Randomized Clinical Trial.

Background: Postoperative delirium is common in elderly patients following major surgery. This study aimed to assess the effect of transcutaneous electrical acupoint stimulation combined with auricular acupressure on the incidence of postoperative delirium among older patients undergoing major abdominal surgery. Methods: In this single-center, randomized controlled clinical trial, 210 patients aged 65 years or older undergoing major abdominal surgery were randomized to receive either intervention treatment (transcutaneous electrical acupoint stimulation started at 30 min before anesthesia until the end of the surgery, followed by intermittent auricular acupressure in the first three postoperative days; n = 105) or standard care (n = 105). The primary outcome was the incidence of delirium at the first seven postoperative days or until hospitalization depended on which came first. Secondary outcomes included delirium severity, opioid consumption, postoperative pain score, sleep quality, length of postoperative hospital stay, and postoperative 30-day complications. Enrollment was from April 2019 to March 2020, with follow-up ending in April 2020. Results: All of the 210 randomized patients [median age, 69.5 years, 142 (67.6%) male] completed the trial. The incidence of postoperative delirium was significantly reduced in patients received intervention treatment (19/105 (18.1%) vs. 8/105 (7.6%), difference, -10.5% [95% CI, -1.5% to -19.4%]; hazard ratio, 0.41 [95% CI, 0.18 to 0.95]; P= 0.023). Patients in the control group had a higher postoperative Memorial Delirium Assessment Scale (4 vs. 3; difference, -1; 95% CI, -1 to 0; P = 0.014) and a greater increase in Pittsburgh Sleep Quality Index score from baseline to postoperative day three (2.5 vs. 2.0; difference, -1; 95% CI, -2 to -1; P < 0.001) than patients in the intervention group. No significant difference was observed as of other secondary outcomes. Conclusion: In elderly patients undergoing major abdominal surgery, transcutaneous electrical acupoint stimulation combined with auricular acupressure reduced the incidence of postoperative in-hospital delirium compared with standard care. A multicenter, randomized clinical trial with a larger sample size is necessary to verify these findings. Clinical Trial Registration: [https://clinicaltrials.gov], identifier [NCT03726073].

Effects of heavy metals on bacterial community surrounding Bijiashan mining area located in northwest China.

Heavy metal (HM) pollution is a severe and common environmental problem in mining area soil. It is imperative to understand the micro ecological characteristics of mining area soil for HM contaminated soil remediation. This study described the effects of HM pollution level and soil physical and chemical parameters on microbial diversity. In this study, high-throughput sequencing technology was used to study the effects of HM pollution on the diversity and composition of the soil microbial community. The soil groups were barren, exhibiting alkaline pH, low total nitrogen (TN), and total potassium (TK) according to soil fertility standard. Compared with the control group, there was severe multiple HM pollution in the other five groups, including lead (Pb), cadmium (Cd), zinc (Zn), and copper (Cu). The dominant phyla accounting for more than 1% of the overall community in all soil groups were Proteobacteria (34.432 ± 7.478%), Actinobacteria (22.947 ± 4.297%), Acidobacteria (10.47 ± 2.439%), Chloroflexi (7.89 ± 2.980%), Planctomycetota (5.993 ± 1.558%), Bacteroidota (4.275 ± 1.980%), Cyanobacteria (3.478 ± 2.196%), Myxococcus (2.888 ± 0.822%), Gemmatimonadota (2.448 ± 0.447%), Firmicutes (1.193 ± 0.634%), Patescibacteria (0.435 ± 0.813%), and Nitrospirota (0.612 ± 0.468%). Proteobacteria and Actinobacteria were predominant at the phylum level, which showed a certain tolerance to HMs. In addition, redundancy analysis (RDA) results showed that Pb, Cu, Zn, and Cd were strongly correlated with each other (P < 0.01). Other nutrient elements (except for TK) were significantly positively correlated with each other. Cu and nutrient element TK had an important impact on bacterial community structure. Therefore, bacteria with the function of HM tolerance and bioremediation in extreme environments should be researched, which provides a foundation for future ecological remediation of contaminated soil by using microbial remediation technology.

Comparison of two vasopressor protocols for preventing hypotension post-spinal anesthesia during cesarean section: a randomized controlled trial.

BACKGROUND: Norepinephrine infusion decreases hypotension after spinal anesthesia during cesarean section. This study aimed to compare the efficacy of norepinephrine infusion and ephedrine bolus against post-spinal hypotension in parturients. METHODS: In this double-blinded, randomized controlled clinical trial, parturients scheduled for elective cesarean section were randomly allocated to receive norepinephrine infusion (0.05 µg·kg-1·min-1) just before spinal anesthesia continuing for 30 min or ephedrine bolus (0.15 mg/kg) just before spinal anesthesia. A rescue bolus (5 µg norepinephrine for the norepinephrine group, and 5 mg ephedrine for the ephedrine group) was administered whenever hypotension occurred. Our primary outcome was the incidence of hypotension within 30 min of spinal anesthesia administration. Secondary outcomes included maternal and neonatal outcomes 30 min after spinal block, and neonatal cerebral oxygenation 10 min after birth. RESULTS: In total, 190 patients were enrolled; of these patients, 177 were included in the final analysis. Fewer patients suffered hypotension in the norepinephrine group than in the ephedrine group (29.5% vs. 44.9%, odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.28-0.95, P = 0.034). Moreover, the tachycardia frequency was lower in the norepinephrine group than in the ephedrine group (OR: 0.22, 95% CI: 0.11-0.44, P < 0.001), and patients suffered less nausea and vomiting (OR: 0.28, 95% CI: 0.11-0.70, P = 0.004). There was no difference in Apgar scores and umbilical arterial blood gas analysis between the two groups. However, neonatal cerebral regional saturations were significantly higher after birth in the norepinephrine group than in the ephedrine group (mean difference: 2.0%, 95% CI: 0.55%-3.45%, P = 0.008). CONCLUSION: In patients undergoing elective cesarean section with spinal anesthesia, norepinephrine infusion compared to ephedrine bolus resulted in less hypotension and tachycardia, and exhibited potential neonatal benefits. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02542748; https://clinicaltrials.gov/ct2/show/record/NCT02542748.

Piperlongumine Alleviates Mouse Colitis and Colitis-Associated Colorectal Cancer.

Colorectal cancer is one of the most common and lethal cancers in the world. An important causative factor of colorectal cancer is ulcerative colitis. In this study, we investigated the therapeutic effects of piperlongumine (PL) on the dextran sulfate sodium (DSS)-induced acute colitis and azoxymethane (AOM)/DSS-induced colorectal cancer mouse models. Our results showed that PL could inhibit the inflammation of DSS-induced mouse colitis and reduce the number of large neoplasms (diameter >2 mm) of AOM/DSS-induced mouse colorectal cancer by downregulation of proinflammatory cytokines cyclooxygenase-2 and interleukin-6 and epithelial-mesenchymal transition-related factors, ß-catenin, and snail expressions, but fail to improve the colitis symptoms and to decrease the incidence of colonic neoplasms and the number of small neoplasms (diameter <2 mm). These data suggested that PL might be an effective agent in treating colitis and colorectal cancer.

Vitamin C: A stem cell promoter in cancer metastasis and immunotherapy.

Vitamin C is an electron donor and is involved in a variety of biochemical reactions in stem cell and cancer stem cell, as well as collagen synthesis and the regulation of hypoxia-inducible factor synthesis, which two affect extracellular matrix remodelling and hence cancer metastasis. Specific doses of vitamin C can stop cancer cell glycolysis and block nitroso synthesis, indicating the potential of vitamin C in cancer treatment. Recent studies preliminary revealed Vitamin C enhance the cancer's immune response to anti PD-L1 therapy through multiple indirect approaches. Herein we reviewed the recent function of vitamin C for further research in sequential aspects of cancer stem cell, extracellular matrix remodeling, cancer metastasis and cancer immunotherapy.

Notoginsenoside R1 activates the Ang2/Tie2 pathway to promote angiogenesis.

BACKGROUND: Therapeutic angiogenesis is a novel strategy for the treatment of ischemic diseases that involves promotion of angiogenesis in ischemic tissues via the use of proangiogenic agents. However, effective proangiogenic drugs that activate the Ang2/Tie2 signaling pathway remain scarce. PURPOSE: We aimed to investigate the proangiogenic activity of notoginsenoside R1 (NR1) isolated from total saponins of Panax notoginseng with regard to activation of the Ang2/Tie2 signaling pathway. METHODS: We examined the proangiogenic effects of NR1 by assessing the effects of NR1 on the proliferation, migration, invasion and tube formation of human umbilical vein endothelial cells (HUVECs). The aortic ring assay and vascular endothelial growth factor receptor inhibitor (VRI)-induced vascular regression in the zebrafish model were used to confirm the proangiogenic effects of NR1 ex vivo and in vivo. Furthermore, the molecular mechanism was investigated by Western blot analysis. RESULTS: We found that NR1 promoted the proliferation, mobility and tube formation of HUVECs in vitro. NR1 also increased the number of sprouting vessels in rat aortic rings and rescued VRI-induced vascular regression in zebrafish. NR1-induced angiogenesis was dependent on Tie2 receptor activation mediated by increased autocrine Ang2 in HUVECs, and inhibition of the Ang2/Tie2 pathway abrogated the proangiogenic effects of NR1. CONCLUSIONS: Our results suggest that NR1 promotes angiogenesis by activating the Ang2/Tie2 signaling pathway. Thus, NR1-induced activation of the Ang2/Tie2 pathway is an effective proangiogenic approach. NR1 may be useful agent for the treatment of ischemic diseases.

PAK5 facilitates the proliferation, invasion and migration in colorectal cancer cells.

Colorectal cancer (CRC) is the third-most common cancer around the world, accounting for approximately 10% of cancer-related mortality. Deeper molecular understanding of colorectal carcinogenesis will provide evidences for identification of early diagnostic indicators and novel therapeutic strategies for CRC treatment. The p21cdc42/rac1 -activated kinase 5 (PAK5) has been reported to be involved in a variety of tumor-promoting behaviors, whereas the underlying mechanisms of PAK5 in CRC progression are still obscure. Our current study revealed an upregulated expression of PAK5 in human CRC tissues as compared with normal adjacent biopsies, which was associated with tumor progression and metastasis. We further unraveled that inhibition of PAK5 was correlated with restrained proliferation, migration, and invasion of CRC cells in vitro and in vivo. Moreover, we showed an indispensable role of PAK5 in interacting with Cdc42 and Integrin ß1, ß3, thus, to facilitate the migration and invasion of CRC cells. Collectively, we pointed out a potential of PAK5 to serve as a novel therapeutic target in restricting CRC proliferation and metastasis. The uncovered mechanisms will deepen the comprehension with regard to the mechanisms of CRC progression, as well as providing new insights for therapeutic intervention in colorectal cancer.

Regulating Cofactor Balance In Vivo with a Synthetic Flavin Analogue.

A novel strategy to regulate cofactor balance in vivo for whole-cell biotransformation using a synthetic flavin analogue is reported. High efficiency, easy operation, and good applicability were observed for this system. Confocal laser scanning microscopy was employed to verify that the synthetic flavin analogue can directly permeate into Escherichia coli cells without modifying the cell membrane. This work provides a promising intracellular redox regulatory approach to construct more efficient cell factories.

Submucosal Tunnel Endoscopic Resection for Esophageal Submucosal Tumors: A Multicenter Study.

BACKGROUND: Submucosal tumors (SMTs) are primarily benign tumors, but some may have a malignant potential. Endoscopic submucosal dissection that has been used for removing esophageal SMTs could cause perforation. Submucosal tunnel endoscopic resection (STER) is an improved and an effective technique for treating esophageal SMTs. AIMS: This study was conducted to evaluate the efficacy and safety of STER for treating esophageal SMTs. METHODS: A retrospective study design was adopted to analyze the baseline characteristics, clinical outcomes, and follow-up data of patients with esophageal SMTs, which originated from the muscularis propria layer and were treated with STER from September 2011 to May 2018. RESULTS: A total of 119 lesions were included from 115 patients who were successfully treated with STER. The mean age of the patients was 49.7 ± 10.7 years. The lesions were primarily located in the middle and lower esophagus. The mean size of the lesions was 19.4 ± 10.0 mm. The mean operation duration was 46.7 ± 25.6 min, and the mean duration of hospitalization was 5.9 ± 2.8 days. The total en bloc resection rate and the complete resection rate were 97.5% and 100%, respectively. Regarding complications, there were 9 (7.8%) cases of perforation, 2 (1.7%) cases of pneumothorax, and 9 (7.8%) cases of subcutaneous emphysema. Histopathological results revealed 113 (95.0%) cases of leiomyoma, 5 (4.2%) cases of gastrointestinal stromal tumors, and 1 (0.8%) case of a granular cell tumor. During the mean 15-month follow-up, there were no cases of recurrence and distant metastasis. CONCLUSIONS: STER is a safe and feasible technique for treating esophageal SMTs originating from the muscularis propria layer.