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Abstract Objective Cognitive dysfunction is a common complication of diabetes after central nervous system involvement. The impact of exercise, as an important non-pharmacological intervention strategy, on cognitive function remains controversial. Thus, we conducted a meta-analysis to assess the impact of exercise on cognitive function of elderly patients with type2 diabetes mellitus (T2DM). Methods We computer searched PubMed, Web of Science, Embase, CINAHL, Cochrane Library, CNKI, Wanfang date, and VIP, and traced back the references included in the literature from 1974 to July 2024. We used RevMan5.4 software for data analysis, and also conducted sensitivity, subgroup, and publication bias analyses. Results Eight eligible studies with a combined total of 747 elderly patients with T2DM were included. Meta-analysis showed that the combined effect size of exercise intervention on cognitive improvement in elderly patients with T2DM was significant [SMD = 0.65, 95% CI (0.48, 0.82), P 6 month intervention [SMD = 0.21, 95% CI (0.45, 0.81), P

Background With the gradual deepening of the comprehensive reform of community health services, the prevention and control of single diseases for the entire population in the community is also constantly being optimized, However, there is still a lack of appropriate evaluation methods in the community to reflect its prevention and control effectiveness evaluation. Objective By analyzing and exploring the cost effect of the existing whole-population prevention and control measures of osteoporosis in Fenglin community, from 2016 to 2022, this paper answers the initial results and possible problems of the whole-population prevention and control of single disease in the community. Methods This study conducted a cost-effectiveness analysis on 4 293 community residents who received osteoporosis prevention and treatment in Fenglin community from 2016 to 2022. Divide the research object into three states based on bone density values: healthy, low bone mass, and osteoporosis, and construct a Markov model to analyze the influencing factors of different state transitions. And based on the predicted values of the Markov model combined with quality adjusted life years (QALY) , the increment of quality adjusted life years (QALY) is calculated. All costs invested in prevention and control work from 2016 to 2022 are counted, and the effectiveness of prevention and control is evaluated by the cost/quality adjusted life year increment ratio. Quality adjusted life years (QALY) are obtained by calculating the health utility value and expected life determined through literature search. Results The total cost of osteoporosis prevention and treatment in Fenglin community was 33 814 102.15 yuan. The total quality-adjusted life years of 4 293 community osteoporosis prevention and treatment population were 77 098.288 9 at the first diagnosis, the average per capita was 17.959, and the standard deviation was 9.34. At the second diagnosis, the total quality-adjusted life years were 79 616.936 1, the mean per capita was 18.546, the standard deviation was 9.342, and the difference between the two diagnoses was 2 518.647 2. The incremental cost-effectiveness ratio (ICER) is 2 132.907 0 yuan /QALY, and the incremental cost-effectiveness ratio (ICER) is less than 1 times (66 965.10 yuan) per capita GDP, indicating that the intervention scheme is fully cost-effective. Conclusion This study combined Markov model and quality-adjusted life years (QALY) to make a preliminary evaluation of the prevention and treatment effect of osteoporosis in Fenglin community. The results showed that the intervention program of osteoporosis prevention and treatment in Fenglin community was worth investing, and provided a certain basis for the accurate prevention and treatment decision of osteoporosis in the future.

The effects of adding dried Lyophyllum decastes (DLR) or dried L. decastes by-products (DBY) on physicochemical properties and nutritional functions of extruded barley flour (BF) were analyzed. Results revealed a notable decrease in the degree of starch gelatinization in the DLR and DBY groups compared to the control group with nothing added. Gastrointestinal digestion simulation using the INFOGEST 2.0 method indicated that the antioxidant capacity of DBY was significantly higher than the BF group and DLR group (P 0.5, P < 0.05). In summary, the incorporation of L. decastes or its by-products effectively enhanced the quality and functional attributes of barley flour products. Notably, DBY exhibited superior antioxidant activity and modulation of the gut microbiota. These findings offer theoretical support for the development of extruded L. decastes-barley products.

Amentoflavone (AME) is a flavonoid compound found in over 120 plants. Its extensive pharmacological activity for treating cardiocerebrovascular diseases and neurological disorders have attracted the attention of researchers in recent years. However, owing to the poor solubility and low bioavailability of AME, it has not been developed as a drug for treating these diseases. This review focuses on two aspects of AME: First, it provides a detailed summary and introduction to AME based on its chemical structure, physicochemical properties, plant sources, extraction and purification methods, administration systems, and pharmacokinetic properties. Second, it summarizes the effects of AME on cardiocerebrovascular diseases and neurological disorders, and its specific pharmacological mechanisms. This review aims to promote the use of AME for treating cardiocerebrovascular diseases and neurological disorders. AME exhibits multiple activities, indicating its potential as a natural drug for treating these diseases. Further studies on its pharmacokinetics and toxicology are required to ensure its safety and efficacy.

Objectives: Triple-negative breast cancer (TNBC) is the deadliest subtype of breast cancer (BC). Tumor-derived extracellular vesicles (EVs) trigger tumor progression by promoting M2 polarization. Some lncRNAs can be encapsulated into EVs for intercellular communication. Herein, we investigated the mechanism of TNBC-derived EV-shuttled lncRNA MALAT1 on macrophage polarization/tumorigenesis. Methods: BC-associated targeted EV-derived lncRNAs were screened. Tumor tissues/tissues adjacent to cancer of TNBC patients, and blood samples of all subjects were collected. MALAT1/POSTN mRNA levels in tumor tissues/tissues adjacent to cancer, and MALAT1 expression in EVs and its correlation with TNBC patient overall survival were assessed by RT-qPCR/Kaplan-Meier survival analysis/log-rank test. TNBC patient M2 infiltration was detected by flow cytometry. MALAT1/POSTN levels in EVs/macrophages were regulated by transfection. Hippo/YAP activation was determined by Western blot. Nude mouse xenograft model was established and metastasis was detected by H&E staining. Results: MALAT1/POSTN were up-regulated and correlated with M2 infiltration/poor prognosis in TNBC patients. TNBC-derived EVs induced M2 polarization. MALAT1 was highly expressed in TNBC-derived EVs and could be transferred to macrophages via EVs to induce M2 polarization. POSTN overexpression diminished the inhibitory effect of MALAT1 knockdown on M2 markers. EVs activated the Hippo/YAP pathway in macrophages. The Hippo/YAP pathway inhibition abrogated the effect of POSTN overexpression on M2 marker expression. TNBC-EV-derived MALAT1 facilitated M2 polarization, and thus promoting occurrence and metastasis of TNBC in vitro and in vivo. Conclusions: TNBC-EV-derived MALAT1 activated the Hippo/YAP axis by up-regulating POSTN, thereby inducing M2 polarization to promote TNBC occurrence and metastasis in vivo.

Common cancer complications include bone cancer pain (BCP), which was not sufficiently alleviated by traditional analgesics. More safe and effective therapy was urgent needed. Metformin relieved osteoarthritis pain, but the analgesia of Metformin in BCP was not well studied. The study aimed to explore the Metformin-mediated analgesic effect and its molecular mechanisms in BCP rats. We demonstrated that Walker 256 cell transplantation into the medullary cavity of the tibia worsened mechanical allodynia in BCP rats, increased the expression of TGFβ1 in the metastatic bone tissue, and raised the expression of TGFβRI and TRPV1 in the L4-6 dorsal root ganglion (DRG) of BCP rats. While, selectively blockade of TGFβRI by SD208 could obviously elevated the paw withdraw threshold (PWT) of BCP rats, together with decreased TRPV1 expression in L4-6 DRG. Notably, continuous Metformin treatment reduced TGFβ1, TGFβRI and TRPV1 expression, and relieved mechanical allodynia of BCP rats in a long-term effect. In conclusion, these results illustrated that Metformin ameliorated bone cancer pain, and the downregulation of TGFβ1-TGFβRI-TRPV1 might be a potential mechanism of Metformin-mediated analgesia in BCP.

Amyotrophic lateral sclerosis (ALS) is one of the most common neurodegenerative diseases, yet effective treatment is lacking. Moreover, the underlying pathomechanisms of ALS remain unclear, with impaired mitophagy function being increasingly recognized as a contributing factor. FUN14 domain-containing protein 1 (FUNDC1) is an autophagy receptor localized to the outer mitochondrial membrane and a mitochondrial membrane protein that mediates mitophagy and therefore considered as important factor in neurodegenerative diseases. However, its specific role in ALS is not yet clear. Therefore, this study aimed to investigate the regulatory role of FUNDC1 in ALS and determine its regulatory mechanisms. ALS transgenic mice were obtained and maintained under standard conditions. Cell lines were generated by stable transfection with hSOD1G93A or control vectors. Mice received intrathecal injections of AAV9 vectors expressing FUNDC1 or EGFP. Motor function was assessed through behavioral tests, and histological and immunostaining analyses were performed. Colocalization analysis was conducted in transfected cells, and protein expression was evaluated via western blotting. We first observed that FUNDC1 was significantly downregulated in the spinal cord tissues of SOD1G93A mice. FUNDC1 overexpression considerably improved locomotor activity and prolonged survival time in SOD1G93A mice. Mechanistically, reduced expression of FUNDC1 resulted in decreased mitophagy, as indicated by decreased recruitment through LC3 in SOD1G93A mice and cellular models. Consequently, this led to increased mitochondrial accumulation and cell apoptosis, exacerbating the ALS phenotype. Furthermore, we identified transcription factor FOXD3 as an essential upstream factor of FUNDC1, resulting in reduced transcription of FUNDC1 in ALS lesions. This study suggests a novel strategy of targeting FUNDC1-mediated mitophagy for developing therapeutic interventions to mitigate disease progression and improve outcomes for ALS patients.

Accurate significant wave height (SWH) forecasting is essential for various marine activities. While traditional numerical and mathematical-statistical methods have made progress, there is still room for improvement. This study introduces a novel transformer-based approach called the 2D-Geoformer to enhance SWH forecasting accuracy. The 2D-Geoformer combines the spatial distribution capturing capabilities of SWH numerical models with the ability of mathematical-statistical methods to identify intrinsic relationships among datasets. Using a comprehensive long time series of SWH numerical hindcast datasets as the numerical forecasting database and ERA5 reanalysis SWH datasets as the observational proxies database, with a focus on a 72-hour forecasting window, the 2D-Geoformer is designed. By training the potential connections between SWH numerical forecasting fields and forecasting errors, we can retrieve SWH forecasting errors for each numerical forecasting case. The corrected forecasting results can be obtained by subtracting the retrieved SWH forecasting errors from the original numerical forecasting fields. During long-term validation periods, this method consistently and effectively corrects numerical forecasting errors for almost every case, resulting in a significant reduction in root mean square error compared to the original numerical forecasting fields. Further analysis reveals that this method is particularly effective for numerical forecasting fields with higher errors compared to those with relatively smaller errors. This integrated approach represents a substantial advancement in SWH forecasting, with the potential to improve the accuracy of operational SWH forecasts. The 2D-Geoformer combines the strengths of numerical models and mathematical-statistical methods, enabling better capture of spatial distributions and intrinsic relationships in the data. The method's effectiveness in correcting numerical forecasting errors, particularly for cases with higher errors, highlights its potential for enhancing SWH forecasting accuracy in operational settings.

Background and purpose: Robotic thyroid surgery has been carried out worldwide since Kang first applied it to the thyroid in 2007. The proportion of axillary approach is increasing rapidly in China due to the continuous verification of safety, radicalness and cosmetic properties of cancer treatment. The advantages and clinical value of Da Vinci Xi robotic unilateral axillary approach in the treatment of unilateral papillary thyroid microcarcinoma (PTMC) was investigated by comparing and analyzing the clinical efficacy in 95 patients undergoing a gasless, unilateral axillary approach Da Vinci Xi robotic thyroid surgery for PTMC and 91 patients undergoing conventional surgery. Methods: The clinical data of 186 cases of unilateral PTMC undergoing thyroidectomy in the Department of Head and Neck Surgery of Shanghai cancer Hospital from March 2020 to November 2021 were retrospectively analyzed, and they were divided into the robotic group (95 cases) and the open group (91 cases) according to the surgical methods. The general clinical data, surgical results, postoperative complications, satisfaction of incision, learning curve and surgical costs were analyzed and compared between the two groups. Results: There was no statistically significant difference between the two groups in gender, age, incidence of Hashimoto’s thyroiditis, tumor diameter, location and number of lesions (P>0.05). However, the operation time was significantly longer in the robotic group [(126.65±34.76) min]than in the open group [(60.99±21.12) min], and after 36 operations, the operation time reached a stable level. The operation cost was significantly higher in the robotic group [(47 940.66±4 404.30) yuan] than in the open group [(15 807.73±2 295.35) yuan]. There was no significant difference in intraoperative hemorrhage [robotic group: (20.48±18.83) mL; open group: (16.15±13.95) mL], the number of removed lymph nodes (robotic group: 2.61±2.77; open group: 2.97±2.20) and the number of positive lymph nodes (robotic group: 1.01±1.61; open group: 0.78±1.36) between the two groups (P>0.05). The incidence of postoperative temporary vocal hoarseness and transient hypocalcemia was lower in the robotic group (1.10%, 2.10%, respectively) than in the open group (2.20%, 3.30%, respectively), however there was no statistically significant difference (P>0.05). The postoperative satisfaction of incision was significantly higher in the robotic group (very satisfied 87.4%, satisfied 11.6%) than in the open group (very satisfied 71.4%, satisfied 26.4%), and the difference was statistically significant (P

Abstract Glioblastoma (GBM) is notorious for malignant neovascularization that contributes to undesirable outcome. However, its mechanisms remain unclear. This study aimed to identify prognostic angiogenesis‐related genes and the potential regulatory mechanisms in GBM. RNA‐sequencing data of 173 GBM patients were obtained from the Cancer Genome Atlas (TCGA) database for screening differentially expressed genes (DEGs), differentially transcription factors (DETFs), and reverse phase protein array (RPPA) chips. Differentially expressed genes from angiogenesis‐related gene set were extracted for univariate Cox regression analysis to identify prognostic differentially expressed angiogenesis‐related genes (PDEARGs). A risk predicting model was constructed based on 9 PDEARGs, namely MARK1, ITGA5, NMD3, HEY1, COL6A1, DKK3, SERPINA5, NRP1, PLK2, ANXA1, SLIT2, and PDPN. Glioblastoma patients were stratified into high‐risk and low‐risk groups according to their risk scores. GSEA and GSVA were applied to explore the possible underlying GBM angiogenesis‐related pathways. CIBERSORT was employed to identify immune infiltrates in GBM. The Pearson's correlation analysis was performed to evaluate the correlations among DETFs, PDEARGs, immune cells/functions, RPPA chips, and pathways. A regulatory network centered by three PDEARGs (ANXA1, COL6A1, and PDPN) was constructed to show the potential regulatory mechanisms. External cohort of 95 GBM patients by immunohistochemistry (IHC) assay demonstrated that ANXA1, COL6A1, and PDPN were significantly upregulated in tumor tissues of high‐risk GBM patients. Single‐cell RNA sequencing also validated malignant cells expressed high levels of the ANXA1, COL6A1, PDPN, and key DETF (WWTR1). Our PDEARG‐based risk prediction model and regulatory network identified prognostic biomarkers and provided valuable insight into future studies on angiogenesis in GBM.

Abstract Background Prophylactic vasopressor infusion can effectively assist with fluid loading to prevent spinal anesthesia-induced hypotension. However, the ideal dose varies widely among individuals. We hypothesized that hypotension-susceptible patients requiring cesarean section (C-section) could be identified using combined ultrasound parameters to enable differentiated prophylactic medical interventions. Methods This prospective observational trial was carried out within a regional center hospital for women and children in Sichuan Province, China. Singleton pregnant women undergoing combined spinal-epidural anesthesia for elective C-sections were eligible. Women with contraindications to spinal anesthesia or medical comorbidities were excluded. Velocity time integral (VTI) and left ventricular end-diastolic area (LVEDA) in the supine and left lateral positions were measured on ultrasound before anesthesia. Stroke volume, cardiac output, and the percentage change (%) in each parameter between two positions were calculated. Vital signs and demographic data were recorded. Spinal anesthesia-induced hypotension was defined as a mean arterial pressure decrease of > 20% from baseline. The area under the receiver operating characteristic curve (AUROC) was used to analyze the associations of ultrasound measurements, vital signs, and demographic characteristics with spinal anesthesia-induced hypotension. This exploratory study did not have a predefined outcome; however, various parameter combinations were compared using the AUROC to determine which combined parameters had better predictive values. Results Patients were divided into the normotension (n = 31) and hypotension groups (n = 57). A combination of heart rate (HR), LVEDAs, and VTI% was significantly better at predicting hypotension than was HR (AUROC 0.827 vs. 0.707, P = 0.020) or LVEDAs (AUROC 0.827 vs. 0.711, P = 0.039) alone, but not significantly better than VTI% alone (AUROC 0.827 vs. 0.766, P = 0.098). Conclusion The combined parameters of HR and LVEDAs with VTI% may predict spinal anesthesia-induced hypotension more precisely than the single parameters. Future research is necessary to determine whether this knowledge improves maternal and neonatal outcomes. Trial registration ChiCTR1900025191.

Abstract Epilepsy is a widespread neurological disorder affecting more than 65 million people, but the mechanisms of epilepsy remains unknown. Abnormal synaptic transmission has a crucial role in the occurrence and development of epilepsy. Here, we found that syntabulin, a neuronal transporter, was mainly localized in neurons, and its expression was increased in epileptic tissues. Knockdown of syntabulin increased susceptibility and severity of epilepsy, whereas overexpression of syntabulin had the opposite effect. Mechanistically, in the epileptic brain tissue, syntabulin mainly translocated syntaxin 1B (STX1B) rather than syntaxin 1A (STX1A) to the presynaptic membrane, which resulted in increased presynaptic transmitter release. Further studies showed that syntabulin had a more significant effect on presynaptic functionality of GABAergic activity over that of excitatory synapses and resulted in an excitation/inhibition (E/I) imbalance, thereby regulating the epileptic phenotype. In addition, we found that the increased expression of syntabulin in epileptic brain tissue was mainly regulated by transcription factor TFAP2A. In summary, syntabulin plays a protective role in epilepsy by maintaining a proper E/I balance in the hippocampus.

Abstract The pathophysiological mechanisms underlying epileptogenesis are poorly understood but are considered to actively involve an imbalance between excitatory and inhibitory synaptic transmission. Excessive activation of autophagy, a cellular pathway that leads to the removal of proteins, is known to aggravate the disease. Toll-like receptor (TLR) 7 is an innate immune receptor that regulates autophagy in infectious and noninfectious diseases. However, the relationship between TLR7, autophagy, and synaptic transmission during epileptogenesis remains unclear. We found that TLR7 was activated in neurons in the early stage of epileptogenesis. TLR7 knockout significantly suppressed seizure susceptibility and neuronal excitability. Furthermore, activation of TLR7 induced autophagy and decreased the expression of kinesin family member 5 A (KIF5A), which influenced interactions with γ-aminobutyric acid type A receptor (GABAAR)-associated protein and GABAARβ2/3, thus producing abnormal GABAAR-mediated postsynaptic transmission. Our results indicated that TLR7 is an important factor in regulating epileptogenesis, suggesting a possible therapeutic target for epilepsy.

Abstract Purpose This paper was mainly conducted to investigate the effect of chronic endometritis (CE) on the clinical outcome of patients with unexplained infertility. Materials and methods 145 patients with unexplained infertility from the Reproductive Center of our hospital from January 2018 to December 2021 were selected as the unexplained infertility group. 42 patients with definite infertility causes were selected as the control group during the same period. Both groups of patients underwent hysteroscopy and immunohistochemical tests for CD38 and CD138. According to the results of hysteroscopy and immunohistochemistry, the incidence of CE between the two groups was analyzed. Patients with CE as CE group accepted oral antibiotic therapy for 14 days. Another 58 patients with unexplained infertility who did not undergo hysteroscopy and immunohistochemical tests for CD38 and CD138 were selected as the unexamined group. Both groups of patients were expected natural pregnancy. Follow-up lasted for 1 year, and the pregnant patients were followed up until delivery.The clinical pregnancy rate, spontaneous abortion rate and baby-carrying home rate of the two groups were compared. Results There were 75 patients with CE in the unexplained infertility group, and the prevalence rate was 51.7% (75/145). Compared with the control group (28.6%), the incidence of CE was significantly higher (P

Background: Bone marrow mesenchymal stem cells (BMMSCs) possess the ability of adipogenic differentiation. Icariin (ICA) is a prenylated flavonol glycoside with diverse pharmacological activities and has been reported to promote osteogenic differentiation of BMMSCs. Nevertheless, the effects of ICA on BMMSC adipogenic differentiation into brown fat cells are still unclear. This study aimed to explore the effects and mechanistic basis of ICA on the differentiation of BMMSCs into brown fat cells. Methods: Oil Red-O staining assay was applied to detect the adipogenic differentiation of BMMSCs after induction. RT-qPCR and Western blot were conducted to detect the expression of lipogenic markers PPARγ and FABP4 as well as the brown fat biomarkers BMP7, PGC-1α, and UCP1 in BMMSCs. Moreover, phosphodiesterase-5A (PDE5A) expression in BMMSCs treated with ICA was measured by RT-qPCR and Western blot. Results: ICA promoted the adipogenic differentiation of BMMSCs and increased the expression levels of lipogenic markers PPARγ and FABP4 and the brown fat biomarkers BMP7, PGC-1α, and UCP1 during the adipogenic differentiation of BMMSCs. Furthermore, PDE5A was identified as a target of ICA, and its expression was reduced by ICA treatment. Moreover, PDE5A inhibition enhanced BMP7, PGC-1α, and UCP1 levels in BMMSCs. Additionally, overexpression of PDE5A notably reversed the effects of ICA in the differentiation of BMMSCs into brown fat cells. Conclusion: ICA induces the differentiation of BMMSCs into brown fat cells via PDE5A inhibition, highlighting the therapeutic value of ICA for treating obesity-related diseases.

Th17 cells produce a range of characteristic Th17 type cytokines and express transcription factors governed by epigenetic regulation to engage the Th17 programme. Here the authors implicate the RNA 5- methylcytosine (m5C) methyltransferase Nsun2 in Th17 cells and the promotion of colitis in a murine model.

Abstract Background The present study aimed to evaluate whether the operating table height affected the success rate and incidences of complications of combined spinal-epidural anesthesia administered by residents during training. Methods One-hundred-and-eighty patients were randomly allocated according to landmarks on the resident’s body: umbilicus (group U), lowest rib margin (R), and xiphoid process (X). The success rates of combined spinal-epidural anesthesia, and the incidences of paresthesia and vessel trauma were recorded. Results There were no differences between the three groups in the success rates of combined spinal-epidural anesthesia, and the incidences of paresthesia and vessel trauma. However, paresthesia during epidural catheter advancement was more common on the left side (66.7%) than the right side (33.3%) (P = 0.03). In group R, the success rate of epidural anesthesia was higher during the residents’ third time (100%) than their first time (50%; P = 0.01). Most residents (83%) preferred the table height at which the needle insertion point was at the level of their lowest rib margin. Conclusions Neither the success nor the complication of combined spinal-epidural anesthesia in lateral decubitus position during residents’ training affected by the operating table height. However, paresthesia was more likely to occur on the left side when a stiff catheter was inserted into the epidural space. It may be better to keep the table height at residents’ lowest rib margin. It was not just preferred by most of residents but also better for their training of performing epidural anesthesia. Trial registration The trial was registered prior to patient enrollment at Chinese Clinical Trial Registry (NCT: ChiCTR1800016078, Principal investigator: Juan Gu, Date of registration: 9 May 2018). Registry URL http://www.chictr.org.cn

Abstract The Nod‐like receptor (NLR) family CARD domain containing 5 (NLRC5) has been reported as an activator of human leukocyte antigen (HLA) class I that is responsible for immune activity in cancer treatment. This work focuses on the role of BMI1 proto‐oncogene (BMI1) in the NLRC5‐HLA class I axis and in immune escape in non‐small cell lung cancer (NSCLC). First, immunoblot analysis and/or reverse transcription‐quantitative polymerase chain reaction were performed, which identified decreased NLRC5 and HLA class I levels in NSCLC tissues and cell lines. NSCLCs were co‐cultured with activated CD8+ T cells. Overexpression of NLRC5 in NSCLC cells elevated the expression of HLA class I and increased the activity of T cells and IL‐2 production, and it reduced the PD‐1/PD‐L1 levels. The ubiquitination and immunoprecipitation assays confirmed that BMI1 bound to NLRC5 to induce is ubiquitination and protein degradation. Downregulation of BMI1 in NSCLC cells elevated NLRC5 and HLA class I levels, and consequently promoted T cell activation and decreased PD‐1/PD‐L1 levels in the co‐culture system. However, overexpression of BMI1 in cells led to inverse trends. In summary, this study demonstrates that BMI1 induces ubiquitination and protein degradation of NLRC5 and suppresses HLA class I expression, which potentially helps immune escape in NSCLC.

Epilepsy is considered to result from an imbalance between excitation and inhibition of the central nervous system. Pathogenic mutations in the methyl-CpG binding domain protein 5 gene (MBD5) are known to cause epilepsy. However, the function and mechanism of MBD5 in epilepsy remain elusive. Here, we found that MBD5 was mainly localized in the pyramidal cells and granular cells of mouse hippocampus, and its expression was increased in the brain tissues of mouse models of epilepsy. Exogenous overexpression of MBD5 inhibited the transcription of the signal transducer and activator of transcription 1 gene (Stat1), resulting in increased expression of N-methyl-d-aspartate receptor (NMDAR) subunit 1 (GluN1), 2A (GluN2A) and 2B (GluN2B), leading to aggravation of the epileptic behaviour phenotype in mice. The epileptic behavioural phenotype was alleviated by overexpression of STAT1 which reduced the expression of NMDARs, and by the NMDAR antagonist memantine. These results indicate that MBD5 accumulation affects seizures through STAT1-mediated inhibition of NMDAR expression in mice. Collectively, our findings suggest that the MBD5-STAT1-NMDAR pathway may be a new pathway that regulates the epileptic behavioural phenotype and may represent a new treatment target.

AIM: To report the outcomes of penetrating canaloplasty for corticosteroid-induced glaucoma in a case series. METHODS: Penetrating canaloplasty is a bleb-independent filtering surgery unifying canaloplasty and trabeculectomy. In this study, the surgery was performed to restore the natural outflow through surgically expanded Schlemm's canal and generated trabeculum ostium. A total of 10 eyes of 8 patients were treated with penetrating canaloplasty for corticosteroid-induced glaucoma. Intraocular pressure (IOP) and the number of glaucoma medications at postoperative 3, 6, 12, 18, 24, 36, and 48mo were documented as primary endpoint. Complications after the surgery were recorded as secondary endpoint. RESULTS: Penetrating canaloplasty was accomplished successfully for all 10 eyes, with a mean follow-up of 20.4±13.0mo (range 6-48mo). The mean preoperative IOP and number of anti-glaucoma medications were 45.1±6.5 mm Hg and 3.3±0.5 respectively. The mean post-operative IOP at 3, 6, 12, 18, 24, 36, and 48mo were 15.8±6.0, 14.7±3.3, 15.3±2.0, 15.6±2.6, 17.5±1.8, 16.5±4.9, and 14.0 mm Hg. The number of anti-glaucoma medications at these time points were all 0. This surgery failed to control the IOP in 1 eye at 1mo after surgery. Hyphaema occurred in 3 eyes on the first day after surgery. Postoperative transient IOP increasing was encountered with in two eyes from 1wk to 1mo after surgery. Choroidal detachment developed in one eye but responded well to conservative treatment. CONCLUSION: Penetrating canaloplasty is effective for corticosteroid-induced glaucoma without serious complications, making it a viable or preferred alternative option.

Highlights Cas9 RNA functions as a miRNA sponge. Let-7 is the dominant regulated miRNA by Cas9 RNA. RNA sequence optimization of Cas9 by synonymous mutation improves its safety.

Azathioprine is clinically used as an immunosuppressant for treating autoimmune diseases. However it has narrow therapeutic indices due to frequent myelosuppression. Polymorphic variants of genes coding for thiopurine S-methyltransferase (TPMT) and nucleoside diphosphate-linked moiety X motif 15 (NUDT15) are critical determinants of AZA intolerance, and the differences in frequencies of the two genetic variants exist among people of different ethnicities. Most reports regarding NUDT15 variant, AZA-induced myelosuppression occurred in patients with inflammatory bowel disease and acute lymphoblastic leukemia. Moreover, detailed clinical characteristics were not frequently reported. Here we present the case of a young Chinese female with the NUDT15 c.415C>T (rs116855232, TT) homozygous variant and wild-type TPMT*2 (rs1800462), TPMT*3B (rs1800460), and TPMT*3C (rs1142345) who received high doses of AZA (2.3 mg/kg/d) for systematic lupus erythematosus and had not been told to undergo routine blood cell counts during AZA ingestion. The patient had suffered from severe AZA-induced myelosuppression and alopecia. Moreover, dynamic changes in blood cell counts and responses to treatment were observed. We also conducted a systematic review of published case reports of patients exclusively with NUDT15 c.415C>T homozygous or heterozygous variants to review the characteristics of dynamic changes in blood cells so as to provide reference information for clinical treatment.

Abstract Background We report a case of fetal heart rate decelerations and relaxation of pelvic muscles and fetal descent using transperineal ultrasound after initiation of epidural labor analgesia. Case presentation A 32-year-old woman, G1P0 with gestational age of 40 weeks, required epidural analgesia when her cervical dilatation was 2 cm. Baseline transperineal ultrasound examination was performed before epidural puncture. The fetal heart rate tracing was normal before the initiation of analgesia. Approximately 10 min after the epidural administration of the loading dose, the patient reported onset of analgesia and the FHR tracing showed variable-decelerations. There was no hypotension or evidence of uterine tachysystole. Transperineal ultrasound was performed again after epidural analgesia took effect. The anteroposterior diameter of the levator hiatus increased from 5.3 to 6.6 cm and angle of progress increased from 116°to 133°. The relaxation of pelvic muscle and rapid descent of fetal head may have contributed to the FHR deceleration. The midwife elevated the fetal head through the vagina with her hand, and the FHR recovered soon thereafter. Conclusions Changes in fetal heart rate after initiation of neuraxial analgesia are unpredictable. In addition to FHR and tocodynametric monitoring, performing TPU may helpful in distinguishing the reasons for FHR change and initiating corresponding corrective measures.

ABSTRACT: The distributed acoustic sensor (DAS) uses a single optical cable as the sensing unit, which can capture the acoustic and vibration signals along the optical cable in real-time. So it is suitable for monitoring downhole production activities in the process of oil and gas development. The authors applied the DAS system in a gas production well in the South China Sea for in situ monitoring of the whole wellbore for the first time and obtained the distributed acoustic signals along the whole wellbore. These signals can clearly distinguish the vertical section, curve section, and horizontal production section. The collected acoustic signal with the frequency of approximately 50 Hz caused by the electric submersible pump exhibit a signal-to-noise ratio higher than 27 dB. By analyzing the acoustic signals in the production section, it can be located the layers with high gas production rates. Once an accurate physical model is built in the future, the gas production profile will be obtained. In addition, the DAS system can track the trajectory of downhole tools in the wellbore to guide the operation. Through the velocity analysis of the typical signals, the type of fluids in the wellbore can be distinguished. The successful application of the system provides a promising whole wellbore acoustic monitoring tool for the production of marine gas hydrate, with a good application prospect.©2022 China Geology Editorial Office.

Recently, mental health has received increasing attention, particularly preoperative anxiety, which constitutes a bad emotional experience for surgical patients. Many experts have studied preoperative anxiety in terms of its related risk factors, interventions, and postoperative effects; however, there has been no systematic analysis of published articles. This paper presents a bibliometric review of documents related to preoperative anxiety published between 2001 and 2021. A detailed data analysis of 1,596 publications was conducted using CiteSpace and VOSviewer. Since the 20th century, the field of preoperative anxiety has gradually developed; research began around 2000 and has made a huge leap forward since 2016. Developed countries, led by the United States, were the first to conduct research, but preoperative anxiety research in developing countries like Turkey and China has gradually increased and led to an irreplaceable contribution. Intervention has remained the main topic of preoperative anxiety research, and measures have developed from premedication to the provision of education and information. Moreover, the use of advanced equipment such as virtual reality has emerged with great popularity. Based on previous research, the application of virtual reality combined with pediatric patients will become a new research direction.

Abstract Our objective in this paper is to study the oscillatory and asymptotic behavior of the solutions of third-order neutral differential equations with damping and distributed deviating arguments. New oscillation criteria are established, which are based on a refinement generalized Riccati transformation. An important tool for this investigation is the integral averaging technique. Moreover, we provide an example to illustrate the main results.

Abstract Background Emergence agitation (EA) after general anesthesia is a common complication in the post-anesthesia care unit (PACU). Once EA occurs, there are still no guidelines established for the treatment in adults. Propofol is excessively used in managing agitated patients in the PACU, but it lacks analgesia and can result in apnea. Intraoperative infusion of dexmedetomidine has been proven to have a preventive effect on EA, but the treatment effect of dexmedetomidine on EA remains unknown. This study aims to compare the effects between dexmedetomidine and propofol on relieving EA in adult patients after general anesthesia in the PACU. Methods In this randomized, superiority, controlled clinical study, a total of 120 adult patients aged 18–65 years of both genders, with American Society of Anesthesiologists (ASA) classification I or II developing EA in the PACU after general anesthesia, will be enrolled. Patients will be randomized at a 1:1 ratio into two groups, receiving either a single dose of dexmedetomidine (0.7μg/kg) or propofol (0.5 mg/kg). The primary outcome is the proportion of patients having a recurrent EA within 15 min after intervention in the PACU. Discussion Previous studies have focused on premedication for preventing EA, while therapeutics for reliving EA have rarely been reported. To our knowledge, this study is the first randomized, superiority, controlled trial to compare a bolus of dexmedetomidine with the current routine care for this indication. Trial registration ClinicalTrials.gov NCT04142840 . Registered on October 26, 2019

Background: Long non-coding RNA (LncRNA) is a prognostic factor for malignancies, and N7-Methylguanosine (m7G) is crucial in the occurrence and progression of tumors. However, it has not been documented how well m7G-related LncRNAs predict the development of breast cancer (BC). This study aims to develop a predictive signature based on long non-coding RNAs (LncRNAs) associated with m7G to predict the prognosis of breast cancer patients.Methods: The Cancer Genome Atlas (TCGA) database provided us with the RNA-seq data and matching clinical information of individuals with breast cancer. To identify the signature of N7-Methylguanosine-Related LncRNAs and create a prognostic model, we employed co-expression network analysis, least absolute shrinkage selection operator (LASSO) regression analysis, univariate Cox regression analysis, and multivariate Cox regression analysis. The signature was assessed using the Kaplan-Meier analysis and Receiver Operating Characteristic (ROC) curve. A nomogram and principal component analysis (PCA) were employed to confirm the predictive signature’s usefulness. Then, we examined the drug sensitivity between the two risk groups and utilized single-sample gene set enrichment analysis (ssGSEA) to investigate the association between predictive factors and the tumor immune microenvironment in high-risk and low-risk groups.Results: Nine m7G-related LncRNAs (LINC01871, AP003469.4, Z68871.1, AC245297.3, EGOT, TFAP2A-AS1, AL136531.1, SEMA3B-AS1, AL606834.2) that are independently associated with the overall survival time (OS) of BC patients make up the signature we developed. For predicting 1-, 3-, and 5-year survival rates, the areas under the ROC curve (AUC) were 0.715, 0.724, and 0.726, respectively. The Kaplan-Meier analysis revealed that the prognosis of BC patients in the high-risk group was worse than that of those in the low-risk group. When compared to clinicopathological variables, multiple regression analysis demonstrated that risk score was a significant independent predictive factor for BC patients. The results of the ssGSEA study revealed a substantial correlation between the predictive traits and the BC patients’ immunological status, low-risk BC patients had more active immune systems, and they responded better to PD1/L1 immunotherapy.Conclusion: The prognostic signature, which is based on m7G-related LncRNAs, can be utilized to inform patients’ customized treatment plans by independently predicting their prognosis and how well they would respond to immunotherapy.

Objective: To investigate the associations of Fc receptor-like 5 (FCRL5) gene polymorphisms and mRNA expression with liver fibrosis in chronic hepatitis B (CHB).Methods: A total of 114 CHB patients with liver fibrosis and 120 CHB patients without liver fibrosis were selected for this study. The gender, age, body mass index (BMI), alanine transaminase (ALT) value, aspartate aminotransferase (AST) value, aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis index based on 4 factors (FIB-4) were recorded. Two polymorphisms of the FCRL5 gene (rs6427384 and rs6692977) were genotyped. The mRNA expression level of FCRL5 in peripheral blood monocytes was determined.Results: ALT, AST, APRI, and FIB-4 in patients with fibrosis were significantly higher than those in non-fibrosis patients. There was statistically significant difference between fibrosis and non-fibrosis groups in the genotype distribution (χ2 = 7.805, p = 0.020) and allele frequencies (χ2 = 13.252, p < 0.001) at FCRL5 rs6692977. When compared with CC genotype, the genotype CT or TT at rs6692977 was significantly associated with a increased risk of liver fibrosis in CHB patients (CT vs. CC: OR = 1.921, 95% CI = 1.093–3.375, p = 0.023; TT vs. CC: OR = 2.598, 95% CI = 1.067–6.324, p = 0.031). The mRNA relative expression levels of FCRL5 in patients with liver fibrosis were significantly higher than those in the non-fibrosis group (t = 13.456, p

Cryptotanshinone (CT), an active component of the traditional Chinese medicine Salvia miltiorrhiza Bunge, exhibits a wide range of biological and pharmacological activities. Although the anticancer activity of CT is well known, the knowledge of its effect on the regulation of cancer cell metabolism is relatively new. The present study investigated the anticancer mechanism of CT in ovarian cancer with a focus on cancer metabolism. CCK8 assays, apoptosis assays, and cell cycle assays were conducted to reveal the growth-suppressive effect of CT on ovarian cancer A2780 cells. To explore the potential underlying mechanisms of CT, the changes in endogenous metabolites in A2780 cells before and after CT intervention were investigated using the gas chromatography–mass spectrometry (GC-MS) approach. A total of 28 important potential biomarkers underwent significant changes, mainly involving aminoacyl-tRNA biosynthesis, energy metabolism, and other pathways. Changes in the ATP and amino acid contents were verified with in vitro and in vivo experiments. Our results indicate that CT may exert an anti-ovarian cancer effect by inhibiting ATP production, promoting the protein catabolic process, and inhibiting protein synthesis, which may lead to cell cycle arrest and apoptosis.

Objective To investigate the role of metabolically normal obesity in non-alcoholic fatty liver disease(NAFLD). Methods From 2011 to 2012, a cross-section survey with 4 757 participants enrolled from four communities in Wenzhou was conducted. Data collection was conducted through questionnaire survey, physical examination, laboratory examination, and multiple logistic regression analysis was used to comprehensively identify the risk factors of NAFLD. Results 1 068 individuals(22.4%) were diagnosed as metabolically healthy obesity. The prevalence of NAFLD was 43.5%. Among the various obesity phenotypes, the proportions ranked from high to low were metabolically unhealthy obese(MUO), metabolically unhealthy nonobese(MUNO), metabolically healthy obese(MHO) and metabolically healthy nonobese(MHNO). Obesity was defined by waist circumference and BMI, the risk of NAFLD in MHO population was 3.38 times(95% CI:2.13-5.37) and 4.69 times(95% CI:3.01-7.16) higher than that of MHNO, respectively. Conclusions MHO is associated with an increased risk of NAFLD in the Chinese population. It is necessary to screen for NAFLD in obese subjects regardless state of metabolic health.

BackgroundLarge fluctuations in blood glucose levels greatly impact the health and life span of elderly individuals. This study describes the characteristics of variability in glycemic indices in centenarians with the aim of emphasizing the importance of glycemic variability in elderly people.MethodsWe recruited individuals from Rugao City, Jiangsu Province, China from April 2020 to May 2021. The study cohort included 60 centenarians and 60 first-generation offspring, as well as 20 randomly selected non-cohabitant control individuals aged 60–80 years. A FreeStyle Libre H (hospital version) continuous glucose monitoring (CGM) device (Abbott Ireland UK) was used to measure glycemic variability. The indices measured included the time in target glucose range (TIR), time below target glucose range (TBR), time above target glucose range (TAR), mean amplitude of glycemic excursions (MAGE), mean of daily differences (MODD), coefficient of variation (CV), standard deviation of blood glucose (SDBG), continuous overlapping net glycemic action (CONGA), glucose management indicator (GMI) and estimated glycated hemoglobin (eHbA1c). Logistic regression was used to analyze the association between glycemic variability and longevity.ResultsMean blood glucose (MBG), eHbA1c, GMI, mean fasting plasma glucose (M-FPG) and CONGA were lower in the centenarian group (p all < 0.05). PPGE-2 was higher in the control group than that measured in the centenarian and first-generation offspring groups (p < 0.05). There were no differences between the groups in MAGE, MODD, MAG, or TIR (p > 0.05). The risk of not achieving longevity increased with each one unit increase in MBG by 126% [2.26 (1.05–4.91)], eHbA1c by 67% [1.67 (1.03–2.72)], GMI by 568% [6.68 (1.11–40.30)], M-FPG by 365% [4.65 (1.57–13.75)], M-PPG1h by 98% [1.98 (1.18–3.31)], CONGA1 by 102% [2.02 (1.01–4.06)], Li by 200% [3.00 (1.04–8.61)], and PPGE-2 by 150% [2.50 (1.39–4.50)]. However, the risk of achieving longevity decreased with each unit increase of LBGI by 53% [0.47 (0.28–0.80)], ADRR by 60% [0.40 (0.18–0.86)], and TBR by 11% [0.89 (0.80–0.98)].ConclusionFluctuation in blood glucose levels in centenarians is relatively small. Maintaining an average blood glucose level and keeping blood glucose fluctuations in the normal range is conducive to longevity.

Abstract Objective Breast cancer (BC) remains a public-health issue on a global scale. Long non-coding RNAs (lncRNAs) play functional roles in BC. This study focuses on effects of NEAT1 on BC cell invasion, migration and chemotherapy resistance via microRNA (miR)-141-3p and KLF12. Methods After extraction and identification of serum extracellular vesicles (EVs), NEAT1 expression in EVs was detected and its association with clinical characteristics of BC patients was analyzed. Besides, the gain-of function was performed to investigate the roles of NEAT1 and miR-141-3p in BC, and levels of NEAT1, miR-141-3p, KLF12 and MDR1 after EV treatment were detected by RT-qPCR and Western blot analysis. Furthermore, the in vitro findings were confirmed via lung metastases in nude mice. Results NEAT1 expression in serum EVs was high and related to lymph node metastasis, progesterone receptor, estrogen receptor and Ki-67 in BC patients. After EV treatment, NEAT1 and KLF12 levels were increased, miR-141-3p expression was decreased, the abilities of proliferation, invasion, migration and in vivo metastasis were enhanced, and the sensitivity of cells to cisplatin, paclitaxel and 5-fluorouracil was decreased. After NEAT1 interference, NEAT1 and KLF12 levels in BC cells treated with EVs were decreased, miR-141-3p expression was increased, cell proliferation, invasion, migration and in vivo metastasis were decreased, and drug resistance sensitivity was increased. NEAT1 can bind to miR-141-3p and upregulates KLF12 expression. Conclusions EVs inhibit the regulation of KLF12 by miR-141-3p by transporting NEAT1 to BC cells, thus promoting BC cell invasion, migration, and chemotherapy resistance.

Wildfires have a significant impact on the atmosphere, terrestrial ecosystems, and society. Real-time monitoring of wildfire locations is crucial in fighting wildfires and reducing human casualties and property damage. Geostationary satellites offer the advantage of high temporal resolution and are gradually being used for real-time fire detection. In this study, we constructed a fire label dataset using the stable VNP14IMG fire product and used the random forest (RF) model for fire detection based on Himawari-8 multiband data. The band calculation features related brightness temperature, spatial features, and auxiliary data as input used in this framework for model training. We also used a recursive feature elimination method to evaluate the impact of these features on model accuracy and to exclude redundant features. The daytime and nighttime RF models (RF-D/RF-N) are separately constructed to analyze their applicability. Finally, we extensively evaluated the model performance by comparing them with the Japan Aerospace Exploration Agency (JAXA) wildfire product. The RF models exhibited higher accuracy, with recall and precision rates of 95.62% and 59%, respectively, and the recall rate for small fires was 19.44% higher than that of the JAXA wildfire product. Adding band calculation features and spatial features, as well as feature selection, effectively reduced the overfitting and improved the model’s generalization ability. The RF-D model had higher fire detection accuracy than the RF-N model. Omission errors and commission errors were mainly concentrated in the adjacent pixels of the fire clusters. In conclusion, our VIIRS fire product and Himawari-8 data-based fire detection model can monitor the fire location in real time and has excellent detection capability for small fires, making it highly significant for fire detection.

Rapid urbanization brings a series of dilemmas to the development of human society. To address urban sustainability, Sustainable Development Goal 11 (SDG 11) is formulated by the United Nations (UN). Quantifying progress and interactions toward SDG 11 indicators is essential to achieving Sustainable Development Goals (SDGs). However, it is limited by a lack of data in many countries, particularly at small scales. To address the gap, this study used systematic methods to calculate the integrated index of SDG 11 at prefecture-level cities with different economic groups in the Yellow River Basin based on Big Earth Data and statistical data, analyzed its spatial aggregation characteristics using spatial statistical analysis methods, and quantified synergies and trade-offs among indicators under SDG 11. We found the following results: (1) except for SDG 11.1.1, the performance of the integrated index and seven indicators improved from 2015 to 2020. (2) In GDP and disposable income groups, the top 10 cities had higher values, whereas the bottom 10 cities experienced greater growth rates in the integrated index. However, the indicators’ values and growth rates varied between the two groups. (3) There were four pairs of indicators with trade-offs that were required to overcome and eight pairs with synergies that were crucial to be reinforced and cross-leveraged in the future within SDG 11 at a 0.05 significance level. Our study identified indicators that urgently paid attention to the urban development of the Yellow River Basin and laid the foundation for local decision-makers to more effectively implement the 2030 Agenda for Sustainable Development (the 2030 Agenda).

Abstract Through considerable effort in research and clinical studies, the immune system has been identified as a participant in the onset and progression of brain injury after ischaemic stroke. Due to the involvement of all types of immune cells, the roles of the immune system in stroke pathology and associated effects are complicated. Past research concentrated on the functions of monocytes and neutrophils in the pathogenesis of ischaemic stroke and tried to demonstrate the mechanisms of tissue injury and protection involving these immune cells. Within the past several years, an increasing number of studies have elucidated the vital functions of T cells in the innate and adaptive immune responses in both the acute and chronic phases of ischaemic stroke. Recently, the phenotypes of T cells with proinflammatory or anti-inflammatory function have been demonstrated in detail. T cells with distinctive phenotypes can also influence cerebral inflammation through various pathways, such as regulating the immune response, interacting with brain-resident immune cells and modulating neurogenesis and angiogenesis during different phases following stroke. In view of the limited treatment options available following stroke other than tissue plasminogen activator therapy, understanding the function of immune responses, especially T cell responses, in the post-stroke recovery period can provide a new therapeutic direction. Here, we discuss the different functions and temporal evolution of T cells with different phenotypes during the acute and chronic phases of ischaemic stroke. We suggest that modulating the balance between the proinflammatory and anti-inflammatory functions of T cells with distinct phenotypes may become a potential therapeutic approach that reduces the mortality and improves the functional outcomes and prognosis of patients suffering from ischaemic stroke.

Background: Both bone marrow mesenchymal stem cell (BM-MSC) and transforming growth factor-β1 (TGF-β1) have a strong anti-inflammatory capacity in stroke. But their relationship has not been well addressed. In this study, we investigated how intravenous BM-MSC transplantation in rats effected the expression of TGF-β1 48 h post cerebral ischemia, and we analyzed the main cells that produce TGF-β1. Methods: We used a distal middle cerebral artery occlusion (dMCAO) model in twenty Sprague–Dawley (SD) rats. The rats were randomly divided into two groups: the ischemic control group and the postischemic BM-MSC transplantation group. One hour after the dMCAO model was established, the rats were injected in the tail vein with either 1 ml saline or 1 × 106 BM-MSCs suspended in 1 ml saline. ELISAs were used to detect TGF-β1 content in the brain infarct core area, striatum and the plasma at 48 h after cerebral infarction. Immunofluorescent staining of brain tissue sections for TGF-β1, Iba-1, CD68 and NeuN was performed to determine the number and the proportion of double stained cells and to detect possible TGF-β1 producing cells in the brain tissue. Results: Forty-eight hours after ischemia, the TGF-β1 content in the infarcted area of the BM-MSC transplantation group (23.94 ± 4.48 pg/ml) was significantly lower than it was in the ischemic control group (34.18 ± 4.32 pg/ml) (F = 13.534, P = 0.006). The TGF-β1 content in the rat plasma in the BM-MSC transplantation group (75.91 ± 12.53 pg/ml) was significantly lower than it was in the ischemic control group (131.18 ± 16.07 pg/ml) (F = 36.779, P = 0.0002), suggesting that after transplantation of BM-MSCs, TGF-β1 levels in the plasma decreased, but there was no significant change in the striatum area. Immunofluorescence staining showed that the total number of nucleated cells (1037.67 ± 222.16 cells/mm2) in the infarcted area after transplantation was significantly higher than that in the ischemic control group (391.67 ± 69.50 cells/mm2) (F = 92.421, P

Abstract. This review attempts to unveil the possible mechanisms underlying how gut lymph affects lung and further gives rise to acute respiratory distress syndrome, as well as potential interventional targets under the condition of ischemia-reperfusion injury. We searched electronic databases including PubMed, MEDLINE, Cochrane Central Register of Controlled Trials, Google Scholar, Web of Science, and Embase to identify relevant literatures published up to December 2019. We enrolled the literatures including the Mesh Terms of “gut lymph or intestinal lymph and acute lung injury or acute respiratory distress syndrome.” Gut is considered to be the origin of systemic inflammation and the engine of multiple organ distress syndrome in the field of critical care medicine, whereas gut lymph plays a pivotal role in initiation of ischemia-reperfusion injury-induced acute respiratory distress syndrome. In fact, in the having been established pathologic model of sepsis leading to multiple organ dysfunction named by Gut Lymph theory, a variety of literatures showed the position and role of changes in gut lymph components in the initiation of systemic inflammatory response, which allows us to screen out potential intervention targets to pave the way for future clinic and basic research.

Abstract We studied the biological activity of pevonedistat, a first‐in‐class NEDD8‐activating enzyme (NAE) inhibitor, in combination with various cytotoxic chemotherapy agents and small molecule inhibitors in lymphoma preclinical models. Pevonedistat induced cell death in activated B‐cell (ABC) diffuse large B‐cell lymphoma (DLBCL) cell lines and to a lesser degree in germinal center B‐cell (GCB) DLBCL cell lines. In pevonedistat sensitive cells, we observed inhibition of NF‐κB activity by p65 co‐localization studies, decreased expression of BCL‐2/Bcl‐XL, and upregulation of BAK levels. Pevonedistat enhanced the activity of cytarabine, cisplatin, doxorubicin, and etoposide in ABC‐, but not in the GCB‐DLBCL cell lines. It also exhibited synergy with ibrutinib, selinexor, venetoclax, and A‐1331852 (a novel BCL‐XL inhibitor). In vivo, the combination of pevonedistat and ibrutinib or pevonedistat and cytarabine prolonged survival in SCID mice xenograft models when compared with monotherapy controls. Our data suggest that targeting the neddylation pathway in DLBCL is a viable therapeutic strategy and support further clinical studies of pevonedistat as a single agent or in combination with chemotherapy or novel targeted agents.

ABSTRACT: The permeability of a natural gas hydrate reservoir is a critical parameter associated with gas hydrate production. Upon producing gas from a hydrate reservoir via depressurization, the permeability of sediments changes in two ways with hydrate dissociation, increasing with more pore space released from hydrate and decreasing due to pore compression by stronger effective stress related to depressurization. In order to study the evolution of sediment permeability during the production process with the depressurization method, an improved pore network model (PNM) method is developed to establish the permeability change model. In this model, permeability change induced by hydrate dissociation is investigated under hydrate occurrence morphology of pore filling and grain coating. The results obtained show that hydrate occurrence in sediment pore is with significant influence on permeability change. Within a reasonable degree of pore compression in field trial, the effect of pore space release on the reservoir permeability is greater than that of pore compression. The permeability of hydrate containing sediments keeps increasing in the course of gas production, no matter with what hydrate occurrence in sediment pore.

Thin films of a chemically stable and electrochemically active cerium(IV)-based metal–organic framework (MOF), Ce-MOF-808, are capable of electrocatalyzing the reduction of dopaquinone (DAQ) generated by the electrochemical pre-oxidation of dopamine (DA) present in 3-(N-morpholino)propanesulfonic acid buffer solutions. As the first study reporting the use of pristine cerium-based MOFs in electrochemical DA detection, the stability of the MOF during electrochemical operations, optimized thin-film loading, and the electrocatalytic mechanism are investigated. By utilizing the cathodic Faradaic responses for the reduction of the electrochemically pre-generated DAQ as a probe to detect DA in the electrolyte, the interference signals from the commonly coexisting ascorbic acid and uric acid can be effectively reduced.

Long-term satellite observations of the water levels of lakes are crucial to our understanding of lake hydrological basin systems. The Ice, Cloud, and Land Elevation satellite (ICESat) and ICESat-2 were employed to monitor the water level of Qinghai Lake in the hydrological basin. The median of absolute deviation (MAD) method was exploited to remove the outliers. The results confirmed that the MAD range of ICESat was from 0.0525 to 0.2470 m, and the range of σ was from 0.0778 to 0.3662 m; the MAD range of ICESat-2 was from 0.0291 to 0.0490 m, and the range of σ was from 0.0431 to 0.0726 m; ICESat-2 was less than that of ICESat. The reference ellipsoid and geoid transfer equations were applied to convert the water level to the World Geodetic System (WGS84) and Earth Gravitational Model 2008 (EGM2008) geoid. The water level, as derived from laser altimeters, was validated by the Xiashe Hydrological Station; with ICESat, the coefficient of association (R) was 0.8419, the root mean square error (RMSE) was 0.1449 m, and the mean absolute error (MAE) was 0.1144 m; with ICESat-2, the R was 0.6917, the RMSE was 0.0531 m, and the MAE was 0.0647 m. The water levels from ICESat-2 are much more accurate than those from ICESat. The two combined laser altimeters showed that the R was 0.9931, the RMSE was 0.1309 m, and the MAE was 0.1035 m. The water level rise was 3.6584 m from 2004 to 2020. The rising rate was 0.2287 m/a. The collaborative use of the ICESat-2 and ICESat satellites made it easier to obtain the lake water levels.

Tuta absoluta, a destructive tomato pest worldwide, has recently invaded China. Neochrysocharis formosa, a host-feeding parasitoid wasp, has thelytokous (TH) and arrhenotokous (AR) strains with sympatric distributions in many regions of China. To clarify the biocontrol potential of the two strains, we evaluated the host-killing behaviors on different instar larvae of T. absoluta and the life history traits of the two strains reared on T. absoluta. Our results showed that both strains can parasitize, feed and directly kill 1st to 3rd instar T. absoluta larvae. In contrast, in 4th instar larvae, both strains only kill larvae by host-stinging. When the 1st instar host was constantly provided, the TH strain showed significantly greater biocontrol potential than the AR strain. The former had higher fecundity (2.10-fold), killed more larval hosts (1.57-fold), survived longer (1.37-fold), and had more offspring (2.07-fold) that successfully emerged. In summary, the TH strain of N. formosa is a better candidate for biological control than the AR strain of T. absoluta. These results will play a pivotal role in building a biological control technology system for the notorious pest T. absoluta. [ABSTRACT FROM AUTHOR]

Background: Rh(D) phenotype in a sample from a 19-year-old female patient showed weak positivity (1+). A follow- up sample was requested to further define the Rh(D) phenotype, her Rh(D) phenotype was tested by using another reagent, Rh(D) phenotype still showed weak reactivity (1+), RhCcEe phenotype was Ccee. Methods: Seven samples from the family members of the proposita were received. The RhDCcEe phenotypes were typed by the micro-column gel card and the unexpected antibodies were assayed by indirect anti-human globulin test (IAT). Genomic DNA was extracted from the blood sample and the novel RHD1058G>C allele was detected through an established sequence-specific primer PCR (PCR-SSP), RHD exons 1 - 10 were sequenced afterward by exon-specific amplification. The distribution of RHD1058G>C allele and RHD weak positive phenotype were investigated in the pedigrees. Results: The unexpected antibodies all were negative in the family members. The novel RHD1058G>C allele was found in the proposita, her father, and grandfather. Five family members were detected serologically with the common Rh(D)-positive phenotypes either as homozygote of RHD/RHD or heterozygote of RHD/RHd. Two family members were detected as weak D phenotypes in accordance with the genotyping results by PCR-SSP, and both of them have a D1058Ce haplotype and a dce haplotype. One member, her father, was tested common Rh(D)-positive with D1058Ce haplotype and a Dce haplotype. Conclusions: These data allow us to describe the characteristics of the weak D phenotype with a novel c.RHD-1058G>C allele, which may be partial D and increase the risk of RHD alloantibody. The novel RHD1058G>C allele was inherited in three generations in a family rather than spontaneous mutation in an individual. [ABSTRACT FROM AUTHOR]

Big Earth data are produced from satellite observations, Internet-of-Things, model simulations, and other sources. The data embed unprecedented insights and spatiotemporal stamps of relevant Earth phenomena for improving our understanding, responding, and addressing challenges of Earth sciences and applications. In the past years, new technologies (such as cloud computing, big data and artificial intelligence) have gained momentum in addressing the challenges of using big Earth data for scientific studies and geospatial applications historically intractable. This paper reviews the big Earth data analytics from several aspects to capture the latest advancements in this fast-growing domain. We first introduce the concepts of big Earth data. The architecture, various functionalities, and supporting modules are then reviewed from a generic methodology aspect. Analytical methods supporting the functionalities are surveyed and analyzed in the context of different tools. The driven questions are exemplified through cutting-edge Earth science researches and applications. A list of challenges and opportunities are proposed for different stakeholders to collaboratively advance big Earth data analytics in the near future.

With inherent ‘S’ characteristics and the one-tunnel-with-two-units arrangement of the pump-turbine, hydraulic transient changes in the successive start-up process are complex, and the optimal control is difficult. This paper aims to study the dynamic characteristics and successive start-up control strategy optimization of two hydraulic couplings pumped storage units (PSUs) under low-head extreme conditions. Firstly, an accurate model of two hydraulic coupling PSUs’ successive start-up is established. Based on this model, the influence of the interval time of successive start-up on the dynamic characteristics of PSUs is carried out. It is shown that the change of the interval time of the successive start-up (ΔT) of the two PSUs has a significant impact on the dynamic response stability of the low-head start-up. If ΔT is more than 40 s, the hydraulic oscillation and speed fluctuation of the PSUs deteriorate. Secondly, with the different controller parameters for the two PSUs, a novel multi-objective optimization scheme with fractional order PID controller (FOPID) is proposed to figure out the best control scheme for the successive start-up. Furthermore, selecting the sum of the rise time (Tr) of the rotating speed of two PSUs and the sum of the integral time absolute error (ITAE) of two PSUs is the objective. Meanwhile, the optimization scheme of PID with different parameters (PIDDP) is used to compare and verify the optimization method proposed in this paper. The results for this extreme condition indicate that FOPID has more significant advantages in optimizing the instability of the successive start-up process, with the better Pareto front, and the optimized scheme has a more stable dynamic transition process of flow, water hammer pressure, and rotational speed.