bluuebunny/crossref_metadata_2025 huggingface dataset:
Promotion of Au nanoparticles on carbon frameworks for alkali-free aerobic oxidation of benzyl alcohol
Authors: Du Zhongtian , Zhang Sen , Yang Sihan , Yang Wenhao , Luo Jingjie , Liang Changhai
Published: January 2023

We synthesized a series of modified Co-ZIF-67 materials with tunable morphology to support fine Au nanoparticles for the alkali-free aerobic oxidation of benzyl alcohol. Structure promotion was performed using Stöber silica as a hard template, which was subsequently removed by NaOH etching before gold immobilization. The texture structure of Au/(Si)C was greatly improved with increasing surface area and volume. CoOx was simultaneously introduced into the carbon shell from the Co-ZIF-67 precursor, which consequently facilitated the specific Au-support interaction via bimetallic synergy. XRD, XPS, and TEM images demonstrated the redispersion of both Au and CoOx as well as the electronic delivery between metals. Analysis of the chemical and surface composition suggested a surface rich in Auδ+ with abundant lattice oxygen contributed by CoOx in the final Au/(Si)C, which improved the transformation rate of benzyl alcohol even in an alkali-free condition. Au/(Si)C with finely dispersed Au particles showed excellent catalytic performance in the alkali-free environment, with 89.3% benzyl conversion and 74.5% benzaldehyde yield under very mild conditions.
Characterization of gut dominant microbiota in obese patients with nonalcoholic fatty liver disease
Authors: Jin Li-ting , Xu Ming-Zhi
Published: January 2023

In obese patients, non-alcoholic fatty liver (NAFLD) is common. However, whether there is a connection between the gut microbiota and the onset of NAFLD in obese people is yet unknown. Using quantitative real-time PCR, the microbiota of feces of the eligible 181 obese individuals was identified to compare the differences in gut microbiota between obesity with NAFLD and simple obesity. According to the findings, the gut dominant microbiota was similar between obesity with NAFLD and simple obesity. Nonetheless, compared to the simple obesity group, the quantity of Faecalibacterium prausnitzii colonies was much lower in the obesity with the NAFLD group. Bacteroides were present in greater than 65% of both groups. Bacteroides, Clostridium leptum, and Clostridium butyricum accounted for more than 80% of the cases in the obesity with NAFLD group, whereas Bacteroides, Clostridium butyricum, and F. prausnitzii accounted for more than 80% of the cases in the simple obesity group. We look for potential contributing variables to obesity-related NAFLD and potential prevention measures for obese people. Based on a multi-factor logistic regression analysis, lymphocytes may be a risk factor for obesity with NAFLD while F. prausnitzii may be a protective factor. Additionally, F. prausnitzii is positively impacted by Bacteroides, Clostridium leptum, Clostridium butyricum, and Eubacterium rectale, yet adversely impacted by Enterobacteriaceae. Notably, lymphocytes and F. prausnitzii may help determine whether obese patients would develop NAFLD.
Proenkephalin A and bioactive adrenomedullin are useful for risk prognostication in cardiac surgery
Authors: Hill Aileen , Bergmann Deborah , Schulte Janin , Zayat Rashad , Marx Gernot , Simon Tim-Philipp , Mossanen Jana , Brücken Anne , Stoppe Christian
Published: January 2023

Introduction

Various clinical scores have been developed to predict organ dysfunction and mortality in patients undergoing cardiac surgery, but outcome prediction may be inaccurate for some patient groups. Proenkephalin A (penKid) and bioactive adrenomedullin (bio-ADM) have emerged as promising biomarkers correlating with shock and organ dysfunction. This imposes the question of whether they can be used as prognostic biomarkers for risk stratification in the perioperative setting of cardiac surgery.

Methods

Patients undergoing cardiac surgery were prospectively enrolled in this observational study. PenKid and bio-ADM plasma levels, as well as markers evaluating inflammation and organ dysfunction, were measured at five perioperative time points from before the induction of anesthesia to up to 48 h postoperatively. Clinical data regarding organ dysfunction and patient outcomes were recorded during the intensive care unit (ICU)-stay with a special focus on acute kidney injury (AKI).

Results

In 136 patients undergoing cardiac surgery, the bio-ADM levels increased and the penKid levels decreased significantly over time. PenKid was associated with chronic kidney disease (CKD), the incidence of AKI, and renal replacement therapy (RRT). Bio-ADM was associated with lactate and the need for vasopressors. PenKid was useful to predict an ICU-length of stay (LOS)>1 day and added prognostic value to the European System for Cardiac Operative Risk Evaluation Score (EuroSCORE) II when measured after the end of cardiopulmonary bypass and 24 h after cardiac surgery. For bio-ADM, the same was true when measured 24 h after surgery. PenKid also added prognostic value to the EuroSCORE II for the combined outcome “ICU length of stay >1 day and in-hospital mortality.”

Conclusion

The combination of preoperative EuroSCORE II and intraoperative measurement of penKid may be more useful to predict a prolonged ICU LOS and increased mortality than EuroSCORE II alone. Bio-ADM correlates with markers of shock. More research is encouraged for early risk stratification and validation of penKid and bio-ADM as a tool involved in clinical decisions, which may enable the early initiation of organ protective strategies.
Novel Insight Into Long-Term Risk of Major Adverse Cardiovascular and Cerebrovascular Events Following Lower Extremity Arteriosclerosis Obliterans
Authors: Sun Ji , Deng Qiang , Wang Jun , Duan Shoupeng , Chen Huaqiang , Zhou Huixin , Zhou Zhen , Yu Fu , Guo Fuding , Liu Chengzhe , Xu Saiting , Song Lingpeng , Wang Yijun , Feng Hui , Yu Lilei
Published: January 2023

Graphical Abstract

Central illustration: lower extremity arteriosclerosis obliterans as a prognostic factor for the occurrence of major cardiovascular and cerebrovascular adverse events.
Identifying encephalopathy in patients admitted to an intensive care unit: Going beyond structured information using natural language processing
Authors: Ariño Helena , Bae Soo Kyung , Chaturvedi Jaya , Wang Tao , Roberts Angus
Published: January 2023

Background

Encephalopathy is a severe co-morbid condition in critically ill patients that includes different clinical constellation of neurological symptoms. However, even for the most recognised form, delirium, this medical condition is rarely recorded in structured fields of electronic health records precluding large and unbiased retrospective studies. We aimed to identify patients with encephalopathy using a machine learning-based approach over clinical notes in electronic health records.

Methods

We used a list of ICD-9 codes and clinical concepts related to encephalopathy to define a cohort of patients from the MIMIC-III dataset. Clinical notes were annotated with MedCAT and vectorized with a bag-of-word approach or word embedding using clinical concepts normalised to standard nomenclatures as features. Machine learning algorithms (support vector machines and random forest) trained with clinical notes from patients who had a diagnosis of encephalopathy (defined by ICD-9 codes) were used to classify patients with clinical concepts related to encephalopathy in their clinical notes but without any ICD-9 relevant code. A random selection of 50 patients were reviewed by a clinical expert for model validation.

Results

Among 46,520 different patients, 7.5% had encephalopathy related ICD-9 codes in all their admissions (group 1, definite encephalopathy), 45% clinical concepts related to encephalopathy only in their clinical notes (group 2, possible encephalopathy) and 38% did not have encephalopathy related concepts neither in structured nor in clinical notes (group 3, non-encephalopathy). Length of stay, mortality rate or number of co-morbid conditions were higher in groups 1 and 2 compared to group 3. The best model to classify patients from group 2 as patients with encephalopathy (SVM using embeddings) had F1 of 85% and predicted 31% patients from group 2 as having encephalopathy with a probability >90%. Validation on new cases found a precision ranging from 92% to 98% depending on the criteria considered.

Conclusions

Natural language processing techniques can leverage relevant clinical information that might help to identify patients with under-recognised clinical disorders such as encephalopathy. In the MIMIC dataset, this approach identifies with high probability thousands of patients that did not have a formal diagnosis in the structured information of the EHR.
Analysis of geothermal fluid chemical characteristics and genetic model—A case study from the urban area of Jingmen China
Authors: Liu Rui , Li Hongmei , Zhao Zhan , Zhang Zeyu
Published: January 2023

Over the years, scholars both at home and abroad have been committed to the research of geothermal fluid chemistry and genetic model, and geochemical and isotopic methods are usually the first choice for evaluation. In this paper, the characteristics of geothermal fluids and their genesis patterns in the Jingmen urban area are analyzed and studied by comprehensive utilization of techniques such as hydrochemistry, trace elements, and isotope analysis. The results show that the water chemical type of surface water and groundwater is Ca-HCO3 type, while the geothermal fluid belongs to the Ca-SO4 type. The recharge source of the geothermal fluid is the infiltration recharge of meteoric precipitation, and the recharge altitude is 395–435 m, and the geothermal fluid is modern water (less than 5–10 years old). The water-rock reaction has not reached equilibrium, and the dissolution is still in progress. The estimated mixing ratio of cold-water ranges from 30%–40%. The thermal reservoirs are mainly calcareous dolomite and dolomite of the Lower Triassic Jialingjiang Formation (T1j). The red sandstone and mudstone of the Upper Cretaceous Paomagang Formation (K2p) distributed in the area are good caprocks of the geothermal field. The geothermal energy in the urban area of Jingmen is a system of lateral “seepage.” Thermal water surges up along the Jingmen fracture and fracture zone, forming a relatively high-temperature center, and a part of its “seeps” laterally into the shallow pore aquifer or pore-fracture aquifer, which mixed with the cold water in it to form medium and low-temperature hot water around the center of the geothermal area.
Lithospheric electrical structure across the Bangong-Nujiang Suture in northern tibet revealed by magnetotelluric
Authors: Yang Zhen , Liang Hongda , Gao Rui , Han Jiangtao , Xin Zhonghua , Kang Jianqiang , Shi Zhuoxuan , Zhang Lu , Qi Rui , Li Huilin
Published: January 2023

Competing hypotheses have been proposed to explain the subduction polarity of the Bangong-Nujiang Tethyan Ocean and the formation of the high-conductivity anomaly beneath the Qiangtang terrane. However, the lithospheric architecture of the northern Tibetan Plateau is still poorly understood due to inhospitable environments and topography. Therefore, in the winter of 2021, a 440 km long, SN-trending broadband magnetotelluric (MT) profile was recorded in northern Tibet to detect its regional lithospheric structure. The nonlinear conjugate gradients algorithm is conducted to invert the individual TM mode data. A reliable 2D electrical model was obtained by ablation processing and analysis of broadband magnetotelluric data to test the lithospheric electrical structure and dynamics between the northern Lhasa and Qiangtang terranes. The inversion results reveal the lithospheric structure at a depth of 100 km in northern Tibet, which synthesizes geological, geochemical and deep seismic reflection evidence and firmly identifies that the trace of the south-dipping conductor mainly resulted from the southward subduction of the Bangong-Nujiang Tethyan Ocean under the Lhasa terrane and the trace of the north-dipping conductor likely due to the northward subduction of the Bangong-Nujiang Tethyan Ocean under the Qiangtang terrane. In addition, the magnetotelluric profile also images a high-conductivity lithospheric-scale anticline beneath the central Qiangtang terrane, which may correspond to the upwelling of postcollisional magmatism triggered by northward subduction of the Bangong-Nujiang Tethyan Ocean under the Qiangtang terrane, aqueous fluid and/or partial melting.
Dysbiosis of gut microbiota and decreased propionic acid associated with metabolic abnormality in Cushing’s syndrome
Authors: Zhang Qin , Hu Wen-mu , Deng Yu-ling , Wan Jin-jing , Wang Yu-jun , Jin Ping
Published: January 2023

Objective

Chronic hypercortisolism leads to a phenotype resembling metabolic syndrome. We aimed to investigate the association between gut microbiota and metabolic abnormalities in endogenous hypercortisolism (Cushing’s syndrome).

Methods

A total of 23 patients with Cushing’s syndrome (18 female and 5 men, aged 47.24 ± 12.99 years) and 30 age-, sex-and BMI-matched healthy controls (18 female and 12 men, aged 45.03 ± 6.69 years) were consecutively recruited. Differences in gut microbiota and plasma short-chain fatty acid (SCFAs) concentrations between the Cushing’s syndrome patients and controls were analyzed by 16S rRNA sequencing and gas chromatography-mass spectrometry (GC-MS).

Results

Compared to the controls, the Simpson and Pielou indices of α diversity were dramatically decreased in Cushing’s syndrome (P < 0.05). The gut microbiota community structure differed significantly between Cushing’s syndrome patients and controls. Compared to controls, the bacterial communities of the Cushing’s syndrome patients were enriched in Proteobacteria and Escherichia-Shigella, and depleted in Firmicutes, including Agathobacter, Blautia, Anaerostipes, Eubacterium_eligens_group, and Lachnospira. Spearman analysis demonstrated that HbA1c, SBP, DBP, and cortisol levels were significantly positively correlated with Proteobacteria and Escherichia-Shigella, whereas negatively correlated with Agathobacter, Blautia, Anaerostipes, Eubacterium_hallii_group, and Lachnospira, etc. Cushing’s syndrome patients also had a lower propionic acid concentration (0.151±0.054 vs. 0.205±0.032 µg/mL, P=0.039) than controls. Furthermore, the level of propionic acid was negatively correlated with systolic pressure and cortisol levels (P<0.05).

Conclusion

Gut microbiota dysbiosis and decreased propionic acid levels were observed in patients with Cushing’s, suggesting that the gut microbiota may be a potential therapeutic intervention target to improve hypercortisolism-related metabolic abnormalities.
Association between serum uric acid levels and atrial fibrillation in different fasting glucose patterns: A case-control study
Authors: Zhong Xia , Jiao Huachen , Zhao Dongsheng , Yang Mengqi , Teng Jing
Published: January 2023

Background

Previous studies have shown both dysglycaemia and hyperuricemia are associated with an increased risk of atrial fibrillation (AF), while the relationship between serum uric acid (SUA) levels and AF in different fasting glucose patterns (FBG) is unclear. Therefore, this study aimed to determine the association between SUA and AF in different FBG patterns.

Methods

A total of 1840 patients in this case-control study were enrolled, including 920 AF patients and 920 controls. Patients were divided into three groups according to the different FBG patterns: normoglycemic, impaired fasting glucose (IFG), and diabetes mellitus (DM). Multivariate logistic regression models were performed to evaluate the relationship between SUA and AF in different FBG patterns. Pearson correlation analysis was used to explore the correlation between SUA and metabolic factors. Receiver operating characteristic (ROC) curve models indicated the diagnostic efficiency of SUA for diagnosing AF.

Results

SUA was independently associated with AF after adjusting for all confounding factors in different FBG patterns(normoglycemic: OR=1.313, 95% CI:1.120-1.539; IFG: OR=1.386, 95% CI:1.011-1.898; DM: OR=1.505, 95% CI:1.150-1.970). Pearson’s correlation analysis suggested that SUA in AF patients was correlated with several different metabolic factors in different FBG patterns (p<0.05). ROC curve analysis showed that SUA in the normoglycemic group combined with CHD and APOB [AUC: 0.906 (95% CI: 0.888-0.923)], in the IFG group combined with CHD and Scr [AUC: 0.863 (95% CI: 0.820-0.907)], in the DM group combined with CHD and SBP [AUC: 0.858 (95% CI: 0.818-0.898)] had the highest AUC for predicting AF.

Conclusion

Findings implied a significant association between SUA and AF in different FBG patterns and provide specific models combined with other factors (CHD, APOB, SCr, SBP), which might contribute to the diagnosis of AF.
Exploring the shared molecular mechanism of microvascular and macrovascular complications in diabetes: Seeking the hub of circulatory system injury
Authors: Yuchen Cao , Hejia Zhao , Fanke Meng , Qixin Deng , Liyang Cai , Xi Guo , Yanxia Chen , Xiongyi Yang , Zhuohang Xie , Guoguo Yi , Min Fu
Published: January 2023

Background

Microvascular complications, such as diabetic retinopathy (DR) and diabetic nephropathy (DN), and macrovascular complications, referring to atherosclerosis (AS), are the main complications of diabetes. Blindness or fatal microvascular diseases are considered to be identified earlier than fatal macrovascular complications. Exploring the intrinsic relationship between microvascular and macrovascular complications and the hub of pathogenesis is of vital importance for prolonging the life span of patients with diabetes and improving the quality of life.

Materials and methods

The expression profiles of GSE28829, GSE30529, GSE146615 and GSE134998 were downloaded from the Gene Expression Omnibus database, which contained 29 atherosclerotic plaque samples, including 16 AS samples and 13 normal controls; 22 renal glomeruli and tubules samples from diabetes nephropathy including 12 DN samples and 10 normal controls; 73 lymphoblastoid cell line samples, including 52 DR samples and 21 normal controls. The microarray datasets were consolidated and DEGs were acquired and further analyzed by bioinformatics techniques including GSEA analysis, GO-KEGG functional clustering by R (version 4.0.5), PPI analysis by Cytoscape (version 3.8.2) and String database, miRNA analysis by Diana database, and hub genes analysis by Metascape database. The drug sensitivity of characteristic DEGs was analyzed.

Result

A total of 3709, 4185 and 8086 DEGs were recognized in AS, DN, DR, respectively, with 1820, 1666, 888 upregulated and 1889, 2519, 7198 downregulated. GO and KEGG pathway analyses of DEGs and GSEA analysis of common differential genes demonstrated that these significant sites focused primarily on inflammation-oxidative stress and immune regulation pathways. PPI networks show the connection and regulation on top-250 significant sites of AS, DN, DR. MiRNA analysis explored the non-coding RNA upstream regulation network and significant pathway in AS, DN, DR. The joint analysis of multiple diseases shows the common influenced pathways of AS, DN, DR and explored the interaction between top-1000 DEGs at the same time.

Conclusion

In the microvascular and macrovascular complications of diabetes, immune-mediated inflammatory response, chronic inflammation caused by endothelial cell activation and oxidative stress are the three links linking atherosclerosis, diabetes retinopathy and diabetes nephropathy together. Our study has clarified the intrinsic relationship and common tissue damage mechanism of microcirculation and circulatory system complications in diabetes, and explored the mechanism center of these two vascular complications. It has far-reaching clinical and social value for reducing the incidence of fatal events and early controlling the progress of disabling and fatal circulatory complications in diabetes.
Pharmacoeconomic analysis (CER) of Dulaglutide and Liraglutide in the treatment of patients with type 2 diabetes
Authors: Su Yu , Zhang Shuo , Wu Zezhen , Liu Weiting , Chen Jingxian , Deng Feiying , Chen Fengwu , Zhu Dan , Hou Kaijian
Published: January 2023

Aim

To evaluate the treatment effect Fand pharmacoeconomic value of Dugaglutide in women with type 2 diabetes.

Methods

Women (n=96) with type 2 diabetes recruited from June 2019 to December 2021 were randomized into two equal groups. The control group was treated with Liraglutide, and the observation group was treated with Dulaglutide, both for 24 weeks. The blood glucose levels, biochemical index, insulin resistance index (HOMA-IR), cost-effect ratio (CER), and drug safety were determined and compared between the two groups.

Results

Blood glucose levels, the biochemical index, and HOMA-IR were lower in both groups after the treatment (P < 0.05), and there was no statistical difference in the blood glucose levels, biochemical index and HOMA-IR between the two groups (P > 0.05). The CER levels did not differ statistically between the two groups (P > 0.05). Both the cost and the incidence of drug side effects during solution injection were lower in the observation group than in the control group after 24 weeks of treatment (P < 0.05).

Conclusion

Both Dulaglutide and Liraglutide can reduce blood glucose levels, improve biochemical index, and HOMA-IR levels in women with type 2 diabetes. Dulaglutide is more cost-effective and safe.

Clinical trial registration

https://www.chictr.org.cn/index.aspx, identifier ChiCTR1900026514.
Estradiol-independent restoration of T-cell function in post-reproductive females
Authors: King Tristin L. , Bryner B. Shaun , Underwood Kaden B. , Walters McKenna R. , Zimmerman Shawn M. , Johnson Nathan K. , Mason Jeffrey B.
Published: January 2023

Aging leads to a general decline in protective immunity. The most common age-associated effects are in seen T-cell mediated immune function. Adult mice whose immune systems show only moderate changes in T-cell subsets tend to live longer than age-matched siblings that display extensive T-cell subset aging. Importantly, at the time of reproductive decline, the increase in disease risks in women significantly outpace those of men. In female mice, there is a significant decline in central and peripheral naïve T-cell subsets at the time of reproductive failure. Available evidence indicates that this naïve T-cell decline is sensitive to ovarian function and can be reversed in post-reproductive females by transplantation of young ovaries. The restoration of naïve T-cell subsets due to ovarian transplantation was impressive compared with post-reproductive control mice, but represented only a partial recovery of what was lost from 6 months of age. Apparently, the influence of ovarian function on immune function may be an indirect effect, likely moderated by other physiological functions. Estradiol is significantly reduced in post-reproductive females, but was not increased in post-reproductive females that received new ovaries, suggesting an estradiol-independent, but ovarian-dependent influence on immune function. Further evidence for an estradiol-independent influence includes the restoration of immune function through the transplantation of young ovaries depleted of follicles and through the injection of isolated ovarian somatic cells into the senescent ovaries of old mice. While the restoration of naïve T-cell populations represents only a small part of the immune system, the ability to reverse this important functional parameter independent of estradiol may hold promise for the improvement of post-reproductive female immune health. Further studies of the non-reproductive influence of the ovary will be needed to elucidate the mechanisms of the relationship between the ovary and health.
Metformin improves polycystic ovary syndrome in mice by inhibiting ovarian ferroptosis
Authors: Peng Qingjie , Chen Xiaojiang , Liang Xiaoxia , Ouyang Jiahui , Wang Qiangqiang , Ren Shuai , Xie Haibo , Wang Chunhong , Sun Yaqun , Wu Xin , Liu Hetao , Hei Changchun , Sun Miao , Chang Qing , Liu Xinrui , Li Guangyong , He Rui
Published: January 2023

Background and objective

PCOS is a common metabolic disorder in women of reproductive age, which pathogenesis is very complex. The role of ferroptosis in PCOS is a novel finding, and the mechanistic studies are not clear. Metformin is a commonly used drug of PCOS but few studies on whether metformin can improve the follicle development and ovarian function in PCOS. We aims to use PCOS mouse model to study the effect of metformin on PCOS based on the ovarian function and explored the regulation of metformin in PCOS mice by intervening in ferroptosis pathway.

Materials and methods

C57 BL/6J female mice aged 4-5 weeks were purchased and gavaged with letrozole (1 mg/kg/day) combined with high-fat diet for 21days to establish PCOS model, and control group was set up. After modeling, the mice were divided into PCOS model group and metformin treatment group (Met) (n=6).The Met group were gavaged metformin (200 mg/kg/day) for 28 days. The body weight, estrous cycle, glucose tolerance test (OGTT)and insulin resistance test (ITT) were monitored. Then, The mice were euthanized to collect serum and ovaries. Elisa was used to detect changes in related serum hormones (E2, LH, FSH, TP). Ovaries used for molecular biology experiments to detect changes in GPX4, SIRT3, AMPK/p-AMPK, and mTOR/p-mTOR by Western blot and qPCR.

Results

Compared with the model group mice, body weight was significantly reduced, and their estrous cycle was restored in Met group. The results of OGTT and ITT showed an improvment of glucose tolerance and insulin resistance. Morphological results showed that after metformin treatment, polycystic lesions in ovaries were reduced, the ovarian function was restored, and the expressions of SIRT3 and GPX4 were elevated. WB results demonstrated that the expressions of p-mTOR and p-AMPK in ovaries were significantly reduced in Model group, but reversed in MET group.

Conclusion

Our study confirmed metformin could not only improve body weight and metabolism disorders, but also improve ovarian dysfunction in PCOS mice.In addition, we explored metformin could regulate ferroptosis to improve PCOS via the SIRT3/AMPK/mTOR pathway. Our study complements the mechanisms by which metformin improves PCOS.
Performance of a dual-hormone closed-loop system versus insulin-only closed-loop system in adolescents with type 1 diabetes. A single-blind, randomized, controlled, crossover trial
Authors: Lindkvist Emilie Bundgaard , Laugesen Christian , Reenberg Asbjørn Thode , Ritschel Tobias Kasper Skov , Svensson Jannet , Jørgensen John Bagterp , Nørgaard Kirsten , Ranjan Ajenthen G.
Published: January 2023

Objective

To assess the efficacy and safety of a dual-hormone (DH [insulin and glucagon]) closed-loop system compared to a single-hormone (SH [insulin only]) closed-loop system in adolescents with type 1 diabetes.

Methods

This was a 26-hour, two-period, randomized, crossover, inpatient study involving 11 adolescents with type 1 diabetes (nine males [82%], mean ± SD age 14.8 ± 1.4 years, diabetes duration 5.7 ± 2.3 years). Except for the treatment configuration of the DiaCon Artificial Pancreas: DH or SH, experimental visits were identical consisting of: an overnight stay (10:00 pm until 7:30 am), several meals/snacks, and a 45-minute bout of moderate intensity continuous exercise. The primary endpoint was percentage of time spent with sensor glucose values below range (TBR [<3.9 mmol/L]) during closed-loop control over the 26-h period (5:00 pm, day 1 to 7:00 pm, day 2).

Results

Overall, there were no differences between DH and SH for the following glycemic outcomes (median [IQR]): TBR 1.6 [0.0, 2.4] vs. 1.28 [0.16, 3.19]%, p=1.00; time in range (TIR [3.9-10.0 mmol/L]) 68.4 [48.7, 76.8] vs. 75.7 [69.8, 87.1]%, p=0.08; and time above range (TAR [>10.0 mmol/L]) 28.1 [18.1, 49.8] vs. 23.3 [12.3, 27.2]%, p=0.10. Mean ( ± SD) glucose was higher during DH than SH (8.7 ( ± 3.2) vs. 8.1 ( ± 3.0) mmol/L, p<0.001) but coefficient of variation was similar (34.8 ( ± 6.8) vs. 37.3 ( ± 8.6)%, p=0.20). The average amount of rescue carbohydrates was similar between DH and SH (6.8 ( ± 12.3) vs. 9.5 ( ± 15.4) grams/participant/visit, p=0.78). Overnight, TIR was higher, TAR was lower during the SH visit compared to DH. During and after exercise (4:30 pm until 7 pm) the SH configuration produced higher TIR, but similar TAR and TBR compared to the DH configuration.

Conclusions

DH and SH performed similarly in adolescents with type 1 diabetes during a 26-hour inpatient monitoring period involving several metabolic challenges including feeding and exercise. However, during the night and around exercise, the SH configuration outperformed DH.
Obesity and endocrine-related cancer: The important role of IGF-1
Authors: Zhong Wentao , Wang Xueqing , Wang Yufei , Sun Guoqian , Zhang Jia , Li Zhuo
Published: January 2023

Obesity is increasingly becoming a global epidemic of concern and is considered a risk factor for several endocrine-related cancers. Moreover, obesity is associated with cancer development and poor prognosis. As a metabolic abnormality, obesity leads to a series of changes in insulin, IGF-1, sex hormones, IGFBPs, and adipokines. Among these factors, IGF-1 plays an important role in obesity-related endocrine cancers. This review describes the role of obesity in endocrine-related cancers, such as prostate cancer, breast cancer and pancreatic cancer, focusing on the mechanism of IGF-1 and the crosstalk with estrogen and adipokines. In addition, this review briefly introduces the current status of IGF-1R inhibitors in clinical practice and shows the prospect of IGF-1R inhibitors in combination with other anticancer drugs.
Muscle regeneration in gilthead sea bream: Implications of endocrine and local regulatory factors and the crosstalk with bone
Authors: Otero-Tarrazón Aitor , Perelló-Amorós Miquel , Jorge-Pedraza Violeta , Moshayedi Fatemeh , Sánchez-Moya Albert , García-Pérez Isabel , Fernández-Borràs Jaume , García de la serrana Daniel , Navarro Isabel , Blasco Josefina , Capilla Encarnación , Gutierrez Joaquin
Published: January 2023

Fish muscle regeneration is still a poorly known process. In the present study, an injury was done into the left anterior epaxial skeletal muscle of seventy 15 g gilthead sea bream (Sparus aurata) juveniles to evaluate at days 0, 1, 2, 4, 8, 16 and 30 post-wound, the expression of several muscle genes. Moreover, transcripts’ expression in the bone (uninjured tissue) was also analyzed. Histology of the muscle showed the presence of dead tissue the first day after injury and how the damaged fibers were removed and replaced by new muscle fibers by day 16 that kept growing up to day 30. Gene expression results showed in muscle an early upregulation of igf-2 and a downregulation of ghr-1 and igf-1. Proteolytic systems expression increased with capn2 and ctsl peaking at 1 and 2 days post-injury, respectively and mafbx at day 8. A pattern of expression that fitted well with active myogenesis progression 16 days after the injury was then observed, with the recovery of igf-1, pax7, cmet, and cav1 expression; and later on, that of cav3 as well. Furthermore, the first days post-injury, the cytokines il-6 and il-15 were also upregulated confirming the tissue inflammation, while tnfα was only upregulated at days 16 and 30 to induce satellite cells recruitment; overall suggesting a possible role for these molecules as myokines. The results of the bone transcripts showed an upregulation first, of bmp2 and ctsk at days 1 and 2, respectively; then, ogn1 and ocn peaked at day 4 in parallel to mstn2 downregulation, and runx2 and ogn2 increased after 8 days of muscle injury, suggesting a possible tissue crosstalk during the regenerative process. Overall, the present model allows studying the sequential involvement of different regulatory molecules during muscle regeneration, as well as the potential relationship between muscle and other tissues such as bone to control musculoskeletal development and growth, pointing out an interesting new line of research in this group of vertebrates.
A dynamic game model for assessing risk of coordinated physical-cyber attacks in an AC/DC hybrid transmission system
Authors: Liu Xuecheng , Shi Libao
Published: January 2023

The widely used intelligent measuring equipment not only makes the operation of AC/DC hybrid transmission system more safe and reliable, but also inevitably brings new problems and challenges such as the threats and hidden dangers of cyber attacks. Given this, how to effectively and comprehensively assess the inherent vulnerabilities of AC/DC hybrid transmission systems under the coordinated physical-cyber attacks is of critical significance. In this paper, a three-stage physical-cyber attack and defense risk assessment framework based on dynamic game theory is proposed. In the framework, the dynamic game process between attacker and defender is carried out for the power grid risk, which is expressed as the product of the attacker’s success probability in attacking the substation and the load loss caused by the attack. Regarding the probability of a successful attack, it depends on the number of funds invested by both attacker and defender sides considering the marginal effect, while the corresponding load loss caused depends on the cyber attack vector and the optimal load shedding scheme. For the solution of the proposed three-stage dynamic game framework, it is converted into a bi-level mathematical programming problem, in which the upper-level problem is solved by using the backward induction method to get the subgame perfect Nash equilibrium, and the lower-level problem is solved by using an improved particle swarm optimization algorithm to get the optimal amount of load shedding. Finally, the case study is performed on a modified IEEE 14-node AC/DC hybrid transmission test system, and the inherent weaknesses of the power grid are identified based on the risk assessment results, verifying the effectiveness of the proposed framework and method.
Simultaneous treatment of phosphorus and fluoride wastewater using acid-modified iron-loaded electrode capacitive deionization: Preparation and performance
Authors: Dai Zhijian , Qin Tian , Bai Chengke , Wu Zhibin , Gao Ya , Qin Pufeng
Published: January 2023

Here, capacitive deionization technology (CDI) using modified activated carbon fiber felt (ACF) electrodes was proposed to provide a new strategy for the challenge of simultaneous phosphorus and fluoride wastewater treatment. The acid-modified iron-loaded ACF (A@Fe-ACF) was obtained by modifying ACF through a two-step impregnation method. After the modification, the oxygen-containing functional groups on ACF increased and provided more adsorption sites. The electron transfer efficiency on the A@Fe-ACF was increased by introducing Fe and synergistically promoted the adsorption of phosphorus and fluorine. Results showed that the removal efficiencies of total phosphorus (TP) and total fluorine (TF) in wastewater reached 89.4% and 85% under optimal conditions (voltage intensity 1.5 V, pH 7, plate spacing 1 cm), while the adsorption mechanism of phosphorus and fluorine was dominated by chemical adsorption. Meanwhile, A@Fe-ACF electrode has good recyclability and stability after five cycles.
Mapping of nighttime light trends and refugee population changes in Ukraine during the Russian–Ukrainian War
Authors: Huang Chaoqing , Hong Song , Niu Xiaoxiao , Wu Qian , Zhong Yanmei , Yang Huan , Zhang Haoran
Published: January 2023

The nighttime lights accurately and coherently depict how humans live. This study uses nighttime light measurements to quantify changes in nighttime lighting and refugee population in Ukraine before and after the war. We combined the Theil–Sen estimator with the M-K test to explore the trends of nighttime light. In addition, we constructed a linear model using nighttime light data and a portion of the UNHCR refugee data. Our results reveal that 1 week after the start of the Russo-Ukrainian War, the nighttime light area and the average nighttime light DN value in Ukraine exhibited a steep decline of about 50 percent. Our findings showed taht refugee population changes calculated through models and nighttime light data were mostly consistent with UNHCR data. We thought that the nighttime light data might be used directly to dynamically estimate changes in the refugee movement throughout the war. Nighttime light changes has significant implications for international humanitarian assistance and post-war reconstruction.
Immunogenic cell death: The cornerstone of oncolytic viro-immunotherapy
Authors: Palanivelu Lalitha , Liu Ching-Hsuan , Lin Liang-Tzung
Published: January 2023

According to the World Health Organization, cancer is one of the leading global health concerns, causing nearly 10 million deaths in 2020. While classical chemotherapeutics produce strong cytotoxicity on cancer cells, they carry limitations of drug resistance and off-target effects and sometimes fail to elicit adequate antitumor protection against tumor relapse. Additionally, most cancer cells have developed various ways to escape immune surveillance. Nevertheless, novel anticancer strategies such as oncolytic viro-immunotherapy can trigger immunogenic cell death (ICD), which can quickly grasp the attention of the host defense machinery, resulting in an ensuing antitumor immune response. Specifically, oncolytic viruses (OVs) can infect and destroy targeted cancer cells and stimulate the immune system by exposing pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) to promote inflammatory reactions, and concomitantly prime and induce antitumor immunity by the release of neoantigens from the damaged cancer cells. Thus, OVs can serve as a novel system to sensitize tumor cells for promising immunotherapies. This review discusses the concept of ICD in cancer, centralizing ICD-associated danger signals and their consequence in antitumor responses and ICD induced by OVs. We also shed light on the potential strategies to enhance the immunogenicity of OVs, including the use of genetically modified OVs and their combination with ICD-enhancing agents, which are helpful as forthcoming anticancer regimens.
Spatiotemporal local and abscopal cell death and immune responses to histotripsy focused ultrasound tumor ablation
Authors: Pepple Ashley L. , Guy Joey L. , McGinnis Reliza , Felsted Amy E. , Song Brian , Hubbard Ryan , Worlikar Tejaswi , Garavaglia Hannah , Dib Joe , Chao Hannah , Boyle Nicoleen , Olszewski Michal , Xu Zhen , Ganguly Anutosh , Cho Clifford S.
Published: January 2023

Introduction

Histotripsy is a novel focused ultrasound tumor ablation modality with potent immunostimulatory effects.

Methods

To measure the spatiotemporal kinetics of local andabscopal responses to histotripsy, C57BL/6 mice bearing bilateral flank B16 melanoma or Hepa1-6 hepatocellular carcinoma tumors were treated with unilateral sham or partial histotripsy. Treated and contralateral untreated (abscopal) tumors were analyzed using multicolor immunofluorescence, digital spatial profiling, RNA sequencing (RNASeq), and flow cytometry.

Results

Unilateral histotripsy triggered abscopal tumor growth inhibition. Within the ablation zone, early high mobility group box protein 1 (HMGB1) release and necroptosis were accompanied by immunogenic cell death transcriptional responses in tumor cells and innate immune activation transcriptional responses in infiltrating myeloid and natural killer (NK) cells. Delayed CD8+ T cell intratumoral infiltration was spatiotemporally aligned with cancer cell features of ferroptosis; this effect was enhanced by CTLA-4 blockade and recapitulated in vitro when tumor-draining lymph node CD8+ T cells were co-cultured with tumor cells. Inoculation with cell-free tumor fractions generated by histotripsy but not radiation or freeze/thaw conferred partial protection from tumor challenge.

Discussion

We propose that histotripsy may evoke local necroptotic immunogenic cell death, priming systemic adaptive immune responses and abscopal ferroptotic cancer cell death.
Tachykinin receptor 3 in the lateral habenula alleviates pain and anxiety comorbidity in mice
Authors: Zhang Wen-Wen , Chen Teng , Li Shi-Yi , Wang Xin-Yue , Liu Wen-Bo , Wang Yu-Quan , Mi Wen-Li , Mao-Ying Qi-Liang , Wang Yan-Qing , Chu Yu-Xia
Published: January 2023

The coexistence of chronic pain and anxiety is a common clinical phenomenon. Here, the role of tachykinin receptor 3 (NK3R) in the lateral habenula (LHb) in trigeminal neuralgia and in pain-associated anxiety was systematically investigated. First, electrophysiological recording showed that bilateral LHb neurons are hyperactive in a mouse model of trigeminal neuralgia made by partial transection of the infraorbital nerve (pT-ION). Chemicogenetic activation of bilateral LHb glutamatergic neurons in naive mice induced orofacial allodynia and anxiety-like behaviors, and pharmacological activation of NK3R in the LHb attenuated allodynia and anxiety-like behaviors induced by pT-ION. Electrophysiological recording showed that pharmacological activation of NK3R suppressed the abnormal excitation of LHb neurons. In parallel, pharmacological inhibition of NK3R induced orofacial allodynia and anxiety-like behavior in naive mice. The electrophysiological recording showed that pharmacological inhibition of NK3R activates LHb neurons. Neurokinin B (NKB) is an endogenous high-affinity ligand of NK3R, which binds NK3R and activates it to perform physiological functions, and further neuron projection tracing showed that the front section of the periaqueductal gray (fPAG) projects NKB-positive nerve fibers to the LHb. Optogenetics combined with electrophysiology recordings characterize the functional connections in this fPAG NKB → LHb pathway. In addition, electrophysiological recording showed that NKB-positive neurons in the fPAG were more active than NKB-negative neurons in pT-ION mice. Finally, inhibition of NKB release from the fPAG reversed the analgesic and anxiolytic effects of LHb Tacr3 overexpression in pT-ION mice, indicating that fPAG NKB → LHb regulates orofacial allodynia and pain-induced anxious behaviors. These findings for NK3R suggest the cellular mechanism behind pT-ION in the LHb and suggest that the fPAG NKB → LHb circuit is involved in pain and anxiety comorbidity. This previously unrecognized pathway might provide a potential approach for relieving the pain and anxiety associated with trigeminal neuralgia by targeting NK3R.
Biomaterials delivery strategies to repair degenerated intervertebral discs by regulating the inflammatory microenvironment
Authors: Xia Yuanliang , Wang Hengyi , Yang Ruohan , Hou Yulin , Li Yuehong , Zhu Jianshu , Fu Changfeng
Published: January 2023

Intervertebral disc degeneration (IVDD) is one of the leading causes of lower back pain. Although IVDD cannot directly cause death, it can cause pain, psychological burdens, and economic burdens to patients. Current conservative treatments for IVDD can relieve pain but cannot reverse the disease. Patients who cannot tolerate pain usually resort to a strategy of surgical resection of the degenerated disc. However, the surgical removal of IVDD can affect the stability of adjacent discs. Furthermore, the probability of the reherniation of the intervertebral disc (IVD) after surgery is as high as 21.2%. Strategies based on tissue engineering to deliver stem cells for the regeneration of nucleus purposes (NP) and annulus fibrosus (AF) have been extensively studied. The developed biomaterials not only locally withstand the pressure of the IVD but also lay the foundation for the survival of stem cells. However, the structure of IVDs does not provide sufficient nutrients for delivered stem cells. The role of immune mechanisms in IVDD has recently become clear. In IVDD, the IVD that was originally in immune privilege prevents the attack of immune cells (mainly effector T cells and macrophages) and aggravates the disease. Immune regulatory and inflammatory factors released by effector T cells, macrophages, and the IVD further aggravate IVDD. Reversing IVDD by regulating the inflammatory microenvironment is a potential approach for the treatment of the disease. However, the biological factors modulating the inflammatory microenvironment easily degrade in vivo. It makes it possible for different biomaterials to modulate the inflammatory microenvironment to repair IVDD. In this review, we have discussed the structures of IVDs and the immune mechanisms underlying IVDD. We have described the immune mechanisms elicited by different biological factors, including tumor necrosis factors, interleukins, transforming growth factors, hypoxia-inducible factors, and reactive oxygen species in IVDs. Finally, we have discussed the biomaterials used to modulate the inflammatory microenvironment to repair IVDD and their development.
Transcription factor TFII-I fine tunes innate properties of B lymphocytes
Authors: Singh Amit , Kaileh Mary , De Supriyo , Mazan-Mamczarz Krystyna , Bayarsaihan Dashzeveg , Sen Ranjan , Roy Ananda L.
Published: January 2023

The ubiquitously expressed transcription factor TFII-I is a multifunctional protein with pleiotropic roles in gene regulation. TFII-I associated polymorphisms are implicated in Sjögren’s syndrome and Lupus in humans and, germline deletion of the Gtf2i gene in mice leads to embryonic lethality. Here we report a unique role for TFII-I in homeostasis of innate properties of B lymphocytes. Loss of Gtf2i in murine B lineage cells leads to an alteration in transcriptome, chromatin landscape and associated transcription factor binding sites, which exhibits myeloid-like features and coincides with enhanced sensitivity to LPS induced gene expression. TFII-I deficient B cells also show increased switching to IgG3, a phenotype associated with inflammation. These results demonstrate a role for TFII-I in maintaining immune homeostasis and provide clues for GTF2I polymorphisms associated with B cell dominated autoimmune diseases in humans.
The microbiota as a modulator of mucosal inflammation and HIV/HPV pathogenesis: From association to causation
Authors: Moreno Elena , Ron Raquel , Serrano-Villar Sergio
Published: January 2023

Although the microbiota has largely been associated with the pathogenesis of viral infections, most studies using omics techniques are correlational and hypothesis-generating. The mechanisms affecting the immune responses to viral infections are still being fully understood. Here we focus on the two most important sexually transmitted persistent viruses, HPV and HIV. Sophisticated omics techniques are boosting our ability to understand microbiota-pathogen-host interactions from a functional perspective by surveying the host and bacterial protein and metabolite production using systems biology approaches. However, while these strategies have allowed describing interaction networks to identify potential novel microbiota-associated biomarkers or therapeutic targets to prevent or treat infectious diseases, the analyses are typically based on highly dimensional datasets —thousands of features in small cohorts of patients—. As a result, we are far from getting to their clinical use. Here we provide a broad overview of how the microbiota influences the immune responses to HIV and HPV disease. Furthermore, we highlight experimental approaches to understand better the microbiota-host-virus interactions that might increase our potential to identify biomarkers and therapeutic agents with clinical applications.