bluuebunny/crossref_metadata_2025 huggingface dataset:
Radiocarbon dating and its applications in Chinese archeology: An overview
Authors: Chen Xianglong
Published: February 2023

Radiocarbon dating is a well-established chronometric technique that has been widely employed in Chinese archeology since the first radiocarbon laboratory started operating in the Institute of Archaeology at the Chinese Academy of Sciences in 1965. In the three decades of studies that followed, achievements were made in radiocarbon dating, especially in measurement techniques, sample preparation, and the establishment of regional chronological frameworks. There is no doubt that Chinese archeology entered a golden age with the assistance of radiocarbon dating techniques at the beginning of the 2000s. It is, however, also true that compared to Western countries, China has reported far fewer radiocarbon dates than expected. This paper presents an overview of the history of the radiocarbon dating technique and its significant applications in Chinese archeology, focusing on the transition from β-decay counting to accelerator mass spectrometry. Some of the breakthroughs in studies of the Upper Paleolithic, early Homo sapiens, neolithization, and the Xia and Shang dynasties are highlighted. We conclude the paper with a brief discussion of future work and research directions that need to be explored.
Identification of groundwater potential zones in the Rabigh-Yanbu area on the western coast of Saudi Arabia using remote sensing (RS) and geographic information system (GIS)
Authors: Alharbi Talal , Abdelrahman Kamal , El-Sorogy Abdelbaset S. , Ibrahim Elkhedr
Published: February 2023

The groundwater potential zones in the Rapigh-Yanbu area, on the west coast of Saudi Arabia, were evaluated using remote sensing and geographic information system data leading to the establishment of major watershed development and management strategies. Many factors, including slope, drainage density, land use, geology, lineament density, elevation, yearly precipitation, and soil type distribution, affect the hydrogeological characteristics of coastal aquifers. The Rabigh-Yanbu coastline groundwater potential zones were located and mapped using these characteristics. The annual precipitation rate is categorized into 2–28 mm, 29–52 mm, 53–76 mm,77–107 mm, and 108–164 mm within the study area. The highest elevation was ordered with the lowest rank of 1, while the lowest elevation was given the highest rank of 5. Slopes of 0°–9° were present in the majority of the study region, while slopes of 9°–63° were present in the northwest. Based on the slope, the research area was separated into five classes; 0-3o; 4-9o; 10–16o; 17–25o; 26–63o. Based on the drainage density map; 0–0.36 km2, 0.37–0.53 km2, 0.54–0.73 km2, 0.74–1.32 km2, 1.33–3.31 km2. The majority of the fractures trended NE–SW and NW–SE. A map of lineament density was made using the line density method. This map makes it obvious that the region was divided into five classes; 0–0.02 km2, 0.03–0.08 km2, 0.09–0.13 km2, 0.14–0.2 km2, and 0.21–0.34 km2. The classification of soil types in the study region into four classes such as clay loam, clay, sandy clay, and loam. Accordingly, the clay soil was ranked 1, while the loam soil was given the highest rank of 4. The Precambrian rocks had low groundwater potential because of their reduced porosity and were ranked 1, while Quaternary deposits had a high porosity and good groundwater potential and were given a high rank of 3. According to the likelihood of groundwater supply, the area is divided into four categories: very good, good, moderate, and poor. The area with very good groundwater potential covered 1,384 km2, while the area with good groundwater potential covered 30,498 km2, according to the findings. The study area had 34,412 km2 of somewhat appropriate land for groundwater development. In contrast, 1,734 km2 of the study area is scarce. The best zones featured the lowest slopes, the least number of lineaments, and the most drainage. The lineaments, which serve as the main conduits for groundwater flow and storage, have significant levels of groundwater recharge capacity in the study area. Managing groundwater according to these identified potential zones will maximize their benefits and increase the groundwater yield. This will help in creating new agricultural, urban, and industrial communities in this strategic area and contribute toward achieving the goals of Saudi Vision 2030.
The preliminary study on cardiac structure and function in Chinese patients with primary hyperparathyroidism
Authors: Chen Rong , Song An , Wang Ou , Jiang Yan , Li Mei , Xia Weibo , Lin Xue , Xing Xiaoping
Published: February 2023

Purpose

Recent evidences show that primary hyperparathyroidism (PHPT) patients have a high prevalence of cardiovascular diseases. However, the reported changes in cardiac status are inconsistent in previous studies. The present work evaluated the cardiac structure and function in PHPT patients by echocardiography.

Methods

PHPT patients and age- and sex-matched healthy controls were enrolled in this case-control study. Biochemical parameters were retrospectively collected from PHPT patients. Cardiac function and structure were assessed in all subjects using echocardiography.

Results

A total of 153 PHPT patients and 51 age- and sex-matched healthy controls were enrolled in this study. The mean serum calcium and parathyroid hormone (PTH) levels in PHPT patients were 2.84 ± 0.28mmol/L and 206.9 (130.0, 447.5) pg/ml, respectively. Left ventricular ejection fraction (LVEF) and early to late mitral annular velocity (E/A) were significantly lower in PHPT patients than in healthy controls (68.2 ± 6.0 vs. 70.7 ± 16.7%, 1.0 ± 0.5 vs. 1.4 ± 0.5, respectively, p both < 0.05). The left ventricular mass index (LVMI) and the relative wall thickness (RWT) were not significantly different between the two groups. However, the difference in LVEF between PHPT patients without hypertension and diabetes and the control groups disappeared. The majority of PHPT patients had normal cardiac geometry; however, a proportion of them exhibited concentric remodeling (normal LVMI, RWT≥0.42). Serum calcium, corrected calcium, ionized calcium and PTH were inversely related to E/A, whereas serum phosphorus and 24-hour urine calcium were positively related to E/A. Furthermore, biochemical parameters were not correlated with LVEF.

Conclusions

These findings demonstrate that PHPT patients exhibit diastolic cardiac dysfunction reflected by decreased E/A, as well as possible cardiac structural abnormalities. The serum calcium, phosphorus, and parathyroid hormone levels may influence cardiac structure and function.
The gut microbial metabolite trimethylamine N-oxide and cardiovascular diseases
Authors: Zhen Jing , Zhou Zhou , He Meng , Han Hai-Xiang , Lv En-Hui , Wen Peng-Bo , Liu Xin , Wang Yan-Ting , Cai Xun-Chao , Tian Jia-Qi , Zhang Meng-Ying , Xiao Lei , Kang Xing-Xing
Published: February 2023

Morbidity and mortality of cardiovascular diseases (CVDs) are exceedingly high worldwide. Researchers have found that the occurrence and development of CVDs are closely related to intestinal microecology. Imbalances in intestinal microecology caused by changes in the composition of the intestinal microbiota will eventually alter intestinal metabolites, thus transforming the host physiological state from healthy mode to pathological mode. Trimethylamine N-oxide (TMAO) is produced from the metabolism of dietary choline and L-carnitine by intestinal microbiota, and many studies have shown that this important product inhibits cholesterol metabolism, induces platelet aggregation and thrombosis, and promotes atherosclerosis. TMAO is directly or indirectly involved in the pathogenesis of CVDs and is an important risk factor affecting the occurrence and even prognosis of CVDs. This review presents the biological and chemical characteristics of TMAO, and the process of TMAO produced by gut microbiota. In particular, the review focuses on summarizing how the increase of gut microbial metabolite TMAO affects CVDs including atherosclerosis, heart failure, hypertension, arrhythmia, coronary artery disease, and other CVD-related diseases. Understanding the mechanism of how increases in TMAO promotes CVDs will potentially facilitate the identification and development of targeted therapy for CVDs.
The impact of oxidative stress-induced mitochondrial dysfunction on diabetic microvascular complications
Authors: Zhang Ziwei , Huang Qingxia , Zhao Daqing , Lian Fengmei , Li Xiangyan , Qi Wenxiu
Published: February 2023

Diabetes mellitus (DM) is a metabolic disease characterized by chronic hyperglycaemia, with absolute insulin deficiency or insulin resistance as the main cause, and causes damage to various target organs including the heart, kidney and neurovascular. In terms of the pathological and physiological mechanisms of DM, oxidative stress is one of the main mechanisms leading to DM and is an important link between DM and its complications. Oxidative stress is a pathological phenomenon resulting from an imbalance between the production of free radicals and the scavenging of antioxidant systems. The main site of reactive oxygen species (ROS) production is the mitochondria, which are also the main organelles damaged. In a chronic high glucose environment, impaired electron transport chain within the mitochondria leads to the production of ROS, prompts increased proton leakage and altered mitochondrial membrane potential (MMP), which in turn releases cytochrome c (cyt-c), leading to apoptosis. This subsequently leads to a vicious cycle of impaired clearance by the body’s antioxidant system, impaired transcription and protein synthesis of mitochondrial DNA (mtDNA), which is responsible for encoding mitochondrial proteins, and impaired DNA repair systems, contributing to mitochondrial dysfunction. This paper reviews the dysfunction of mitochondria in the environment of high glucose induced oxidative stress in the DM model, and looks forward to providing a new treatment plan for oxidative stress based on mitochondrial dysfunction.
Successful eradication of an invasive alien Pallas’s squirrel (Callosciurus erythraeus Pallas 1779) population in the Netherlands with support of the local community
Authors: La Haye Maurice J. J. , Janssen René , Adriaens Tim , Huysentruyt Frank , Voskamp Paul J. , Lammers Wiebe , Dijkstra Vilmar
Published: February 2023

The Pallas’s squirrel (Callosciurus erythraeus) is an invasive alien species in several countries in Europe, but also in Argentina and Japan. The species is a threat to indigenous squirrel species and difficult to eradicate. In 2008 a population of this species was discovered in the south of the Netherlands, close to the Belgian border. The range and number of Pallas’s squirrels in the area was determined using sightings of local citizens, foresters and an extensive inventory with hair tubes and camera traps. The population was successfully eradicated during an eradication campaign with several stages from 2011 till 2015. The population appeared to be larger than expected. In total, 249 individuals were trapped in an area as large as 50 km2. Trapped squirrels were not killed, but sterilized and rehomed in animal parks across Europe. The eradication campaign was successful due to the cooperation and support of the general public, who were informed by flyers, lectures and several appeals in local media and on social media platforms. Both helped in getting support of the general public, but sterilization and rehoming must be properly supervised. The total costs of eradication summed up to at least €330,000. No Pallas’s squirrels were reported after October 2015, however sightings of ‘dark colored’ squirrels from the area are still reported by the general public and verified by an expert of the Dutch Mammal Society until today.
Longitudinal section cell morphology of Chinese fir roots and the relationship between root structure and function
Authors: Li Linxin , Zhang Ting , Lin Jingquan , Lian Xiaoqian , Zou Xianhua , Ma Xiangqing , Wu Pengfei
Published: February 2023

Introduction

The longitudinal section cell morphology of Chinese fir roots was studied to better understand the relationship between root structure and root function.

Materials

In this study, the adjusted microwave paraffin section method and the selected two sample transparency methods were used to process the Chinese fir roots and combined with the laser scanning confocal microscopy (LSCM) technique, the morphology of Chinese fir roots longitudinal section can be clearly observed in a short time. At the same time, the observation effect of the longitudinal section cell morphology of the LSCM image of the thick section of the Chinese fir roots and the ordinary optical imaging of the thin section was analyzed and compared.

Results and Discussion

The results showed that: (1) There were apparent differences in the observation effect of cell morphology in longitudinal sections of Chinese fir roots obtained using various treatment methods. Under LSCM, the section with a thickness of 20 μm generated by the microwave paraffin section technique displayed complete cell morphology and clear structure in the root cap, meristem zone, and elongation zone. The overall imaging effect was good; the thickness was 0.42–1.01, 0.64–1.57, and 0.95–2.71 mm, respectively. The cell arrangement in maturation zone cells was more regular. (2) Compared to the ordinary optical imaging of thin sections, the thick sections of roots made by the microwave paraffin section method shortened the time to obtain high-quality sections to ensure the observation effect. Therefore, adopting the microwave paraffin cutting approach to produce thicker root sections under LSCM allows for rapid observation of the cell morphology in longitudinal sections of Chinese fir roots. The current study provides the efficient operation procedure for the microscopic observation technology of the longitudinal section of Chinese fir roots, which is not only beneficial to reveal the relationship between the root structure and function from the microscopic point of view but also provides a technical reference for the anatomical study of other organs and the observation of the longitudinal section cell morphology of plant roots with similar structural characteristics.
Fusarium verticillioides of maize plant: Potentials of propitious phytomicrobiome as biocontrol agents
Authors: Omotayo Oluwadara Pelumi , Babalola Olubukola Oluranti
Published: February 2023

Disease outbreaks have been recorded due to exposure to Fusarium verticillioides and fumonisin, a mycotoxin produced by this fungus. F. verticillioides is a fungal pathogen of maize that causes infections, such as wilting and rotting, while contact with its fumonisin derivative manifests in the form of mild to severe illnesses in humans and animals. Maize infection by F. verticillioides causes loss or reduction in expected crop yield, thereby influencing households and nations’ economies. While several efforts have been made to control the pathogenic fungus and its occurrence in the environment, it remains a challenge in agriculture, particularly in maize production. Several microorganisms which are plant-associated, especially those associated with the rhizosphere niche have been noted to possess antagonistic effects against F. verticillioides. They can inhibit the pathogen and tackle its debilitating effects on plants. Hence this study reviews the use of rhizosphere-associated biocontrol agents, such as Bacillus spp., Pseudomonas, Enterobacter, and Microbacterium oleivorans which forms part of the phytomicrobiome in other to prevent and control this toxicogenic fungus. These microorganisms were found to not only be effective in controlling its occurrence on maize plants but are environmentally safe and promote crop yield.
Different recovery patterns of CMV-specific and WT1-specific T cells in patients with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation: Impact of CMV infection and leukemia relapse
Authors: Luo Xiao-Hua , Poiret Thomas , Liu Zhenjiang , Meng Qingda , Nagchowdhury Anurupa , Ljungman Per
Published: February 2023

In allogeneic hematopoietic cell transplantation (allo-HSCT), both virus-specific T cells and leukemia-specific T cells need to be reconstituted to protect patients from virus infections and primary disease relapse. Cytomegalovirus (CMV) infection remains an important cause of morbidity and mortality after allo-HSCT. Emerging data indicate that CMV reactivation is associated with reduced risk of leukemia relapse in patients with acute myeloid leukemia (AML) undergoing allo-HSCT. In a cohort of 24 WT1+ AML patients during the first year following HSCT, CMV specific CD8+ T cells (CMV-CTL) reconstituted much faster than WT1-specific CD8+ T cell (WT1-CTL) after allo-SCT. Moreover, CMV-CTL expressed lower levels of exhaustion markers and were more functional as identified by production of IFN-γ/TNF-α and expression of Eomes/T-bet. Interestingly, our patients with CMV reactivation presented higher frequency of CMV-CTL, lower levels of Eomes+T-bet- and higher levels of Eomes+T-bet+ expression in response to WT1 and CMV pp65 antigen during the first year after transplantation as compared to patients without CMV reactivation. Kinetics of CMV-CTL and WT1-CTL after transplantation might be associated with measurable residual disease and later leukemia relapse. Our results support that CMV reactivation, aside from the CMV-CTL reconstitution, could influence WT1-CTL reconstitution after allo-HSCT, thus potentially contributing to the remission/relapse of AML.
A large-scale plasma proteome Mendelian randomization study identifies novel causal plasma proteins related to primary biliary cholangitis
Authors: Yang Hongqun , Chen Lanlan , Liu Yahui
Published: February 2023

Background and aims

Primary biliary cholangitis (PBC) is a progressive chronic autoimmune cholestatic liver disease characterized by the destruction of small intrahepatic bile ducts leading to biliary cirrhosis. Liver biopsy is required in the diagnosis of Antimitochondrial antibody-negative patients. Therefore, novel biomarkers are needed for the non-invasive diagnosis of PBC. To identify novel biomarkers for PBC, we conducted large-scale plasma proteome Mendelian randomization (MR).

Methods

A total of 21,593 protein quantitative trait loci (pQTLs) for 2297 circulating proteins were used and classified into four different groups. MR analyses were conducted in the four groups separately. Furthermore, the results were discovered and replicated in two different cohorts of PBC. Colocalization analysis and enrichment analysis were also conducted.

Results

Three plasma proteins (ficolin-1, CD40 and protein FAM177A1) were identified and replicated as being associated with PBC. All of them showed significant protective effects against PBC. An increase in ficolin-1 (OR=0.890 [0.843-0.941], p=3.50×10-5), CD40 (OR=0.814 [0.741-0.895], p=1.96×10-5) and protein FAM177A1 (OR=0.822 [0.754-0.897], p=9.75×10-6) reduced the incidence of PBC. Ficolin-1 (PP4 = 0.994) and protein FAM177A1 (PP4 = 0.995) colocalized with the expression of the genes FCN1 and FAM177A1 in whole blood, respectively. Furthermore, CD40 (PP4 = 0.977) and protein FAM177A1 (PP4 = 0.897) strongly colocalized with PBC.

Conclusions

We expand the current biomarkers for PBC. In total, three (ficolin-1, CD40, and protein FAM177A1) plasma proteins were identified and replicated as being associated with PBC in MR analysis. All of them showed significant protective effects against PBC. These proteins can be potential biomarkers or drug targets for PBC.
Zika virus induced microcephaly and aberrant hematopoietic cell differentiation modeled in novel neonatal humanized mice
Authors: Schmitt Kimberly , Curlin James Z. , Remling-Mulder Leila , Aboellail Tawfik , Akkina Ramesh
Published: February 2023

Introduction

Immunocompetent and immunocompromised murine models have been instrumental in answering important questions regarding ZIKV pathogenesis and vertical transmission. However, mimicking human congenital zika syndrome (CZS) characteristics in these murine models has been less than optimal and does not address the potential viral effects on the human immune system.

Methods

Here, we utilized neonatal humanized Rag2-/-γc-/- mice to model CZS and evaluate the potential viral effects on the differentiation of human hematopoietic stem cells in vivo. Newborn Rag2-/-γc-/- mice were engrafted with ZIKV-infected hematopoietic stem cells (HSC) and monitored for symptoms and lesions.

Results

Within 13 days, mice displayed outward clinical symptoms that encompassed stunted growth, hunched posture, ruffled fur, and ocular defects. Striking gross pathologies in the brain and visceral organs were noted. Our results also confirmed that ZIKV actively infected human CD34+ hematopoietic stem cells and restricted the development of terminally differentiated B cells. Histologically, there was multifocal mineralization in several different regions of the brain together with ZIKV antigen co-localization. Diffuse necrosis of pyramidal neurons was seen with collapse of the hippocampal formation.

Discussion

Overall, this model recapitulated ZIKV microcephaly and CZS together with viral adverse effects on the human immune cell ontogeny thus providing a unique in vivo model to assess the efficacy of novel therapeutics and immune interventions.
The safety of combining immune checkpoint inhibitors and platinum-based chemotherapy for the treatment of solid tumors: A systematic review and network meta-analysis
Authors: Mei Ting , Wang Ting , Deng Qianyue , Gong Youling
Published: February 2023

Objective

Combination treatment regimens consisting of both immune checkpoint inhibitors (ICI) and chemotherapeutic agents have emerged as the standard of care for a range of cancers. This network meta-analysis (NMA) examined the toxicity profiles and safety rankings of these different ICI-based combination regimens.

Methods

The PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched for all randomized controlled trials (RCTs) published as of March 1, 2022 comparing two or more treatment regimens in which at least one arm was comprised of an ICI + platinum-based chemotherapeutic regimen. Treatment-related adverse events (AEs) of any grade and AEs of grade 3 or higher were the primary endpoints for this analysis, while specific AE types were secondary endpoints. This NMA combined both direct and indirect comparisons when analyzing odds ratios (ORs) and the surface under the cumulative ranking curve (SUCRA) for different ICI-based treatment regimens.

Results

In total, 33 RCTs enrolling 19,012 cancer patients were included in this NMA. Of the analyzed regimens, avelumab + chemotherapy and camrelizumab + chemotherapy were associated with a significantly greater risk of AEs of any grade relative to ipilimumab + chemotherapy, durvalumab + chemotherapy, or pembrolizumab + chemotherapy. No significant differences in the risk of AEs of grade 3 or higher were observed when comparing different ICI regimens. Hepatotoxicity and pyrexia were the most common AEs associated with atezolizumab + chemotherapy treatment. Ipilimumab + chemotherapy was associated with a relatively higher risk of gastrointestinal and skin toxicity. Skin toxicity and hypothyroidism were the major AEs associated with nivolumab + chemotherapy. Fatigue and pneumonia were the most common AEs respectively associated with sugemalimab + chemotherapy and pembrolizumab + chemotherapy regimens.

Conclusions

Of the evaluated regimens, camrelizumab + chemotherapy and avelumab + chemotherapy were associated with significantly higher rates of AEs of any grade, whereas durvalumab and sintilimab were relatively safe PD-L1 and PD-1 inhibitors, respectively, when administered in combination with platinum-based chemotherapy. However, none of the evaluated ICI + chemotherapy regimens exhibited any differences with respect to the incidence of grade 3 or higher AEs, offering guidance that may be of value in routine clinical practice.
Transforming growth factor receptor III (Betaglycan) regulates the generation of pathogenic Th17 cells in EAE
Authors: Duesman Samuel J. , Ortega-Francisco Sandra , Olguin-Alor Roxana , Acevedo-Dominguez Naray A. , Sestero Christine M. , Chellappan Rajeshwari , De Sarno Patrizia , Yusuf Nabiha , Salgado-Lopez Adrian , Segundo-Liberato Marisol , de Oca-Lagunas Selina Montes , Raman Chander , Soldevila Gloria
Published: February 2023

The transforming growth factor receptor III (TβRIII) is commonly recognized as a co-receptor that promotes the binding of TGFβ family ligands to type I and type II receptors. Within the immune system, TβRIII regulates T cell development in the thymus and is differentially expressed through activation; however, its function in mature T cells is unclear. To begin addressing this question, we developed a conditional knock-out mouse with restricted TβRIII deletion in mature T cells, necessary because genomic deletion of TβRIII results in perinatal mortality. We determined that TβRIII null mice developed more severe autoimmune central nervous neuroinflammatory disease after immunization with myelin oligodendrocyte peptide (MOG35-55) than wild-type littermates. The increase in disease severity in TβRIII null mice was associated with expanded numbers of CNS infiltrating IFNγ+ CD4+ T cells and cells that co-express both IFNγ and IL-17 (IFNγ+/IL-17+), but not IL-17 alone expressing CD4 T cells compared to Tgfbr3fl/fl wild-type controls. This led us to speculate that TβRIII may be involved in regulating conversion of encephalitogenic Th17 to Th1. To directly address this, we generated encephalitogenic Th17 and Th1 cells from wild type and TβRIII null mice for passive transfer of EAE into naïve mice. Remarkably, Th17 encephalitogenic T cells from TβRIII null induced EAE of much greater severity and earlier in onset than those from wild-type mice. The severity of EAE induced by encephalitogenic wild-type and Tgfbr3fl/fl.dLcKCre Th1 cells were similar. Moreover, in vitro restimulation of in vivo primed Tgfbr3fl/fl.dLcKCre T cells, under Th17 but not Th1 polarizing conditions, resulted in a significant increase of IFNγ+ T cells. Altogether, our data indicate that TβRIII is a coreceptor that functions as a key checkpoint in controlling the pathogenicity of autoreactive T cells in neuroinflammation probably through regulating plasticity of Th17 T cells into pathogenic Th1 cells. Importantly, this is the first demonstration that TβRIII has an intrinsic role in T cells.
Provenance and paleoenvironmental significance of sediments in the Beipo seamount of the northern South China Sea during the last deglaciation
Authors: Tian Xu , Zhang Xilin , Wang Jinli , Sun Zhilei , Liu Ming , Zhao Jinhuan , Zhang Lin , Fan Dejiang , Xu Fangjian
Published: February 2023

The sedimentary processes of seamount regions are closely related to climate change and ocean evolution. The clay minerals, grain size and 14C ages of core SCS18-1, which was collected from the Beipo seamount in the northern South China Sea (SCS) were analyzed to discuss the provenance and paleoenvironmental conditions during the last deglaciation. The sediments of core SCS18-1 are dominated by clayey silt, which is mainly composed of illite (55.2~62.1%) and chlorite (17.1~22.5%), with subordinate kaolinite (9.5~12.6%) and smectite (7.3~15.1%). The illite chemical index and illite crystallinity indicate strong physical weathering conditions. The results of the end-member modeling algorithm (EMMA) suggest that the sediments of core SCS18-1 consist of three end-members containing EM1 (0.98 μm), EM2 (9.29 μm) and EM3 (44.19 μm), with average contents of 3%, 66% and 31%, respectively. The finest endmember represents fluvial mud, the middle and coarsest endmembers are considered fluvial fine silt and eolian dust, respectively. The mean grain size is mainly controlled by the coarser fraction EM3. Based on the clay minerals, grain size and SEM analysis, we can conclude that since the onset of the last deglaciation (16.1 ka BP), the sediments of core SCS18-1 mainly originate from fluvial input, and eolian material also contributed to the sediments. The clay mineral assemblages of core SCS18-1 are stable and originate mainly from Taiwan. Additionally, the Pearl River appears to be a secondary contributor of clay minerals. Further, the Luzon Islands only account for a small proportion. Major kaolinite and moderate illite and chlorite are thought to originate from the Pearl River, predominant illite and chlorite from Taiwan, and principal smectite from the Luzon Islands. Both the relative content of EM1+ EM2 and the illite chemical index effectively represent the variation of East Asia summer monsoon (EASM) strength. Meanwhile, the relative content of EM3 effectively represents the East Asian winter monsoon (EAWM) change. The material supply of core SCS18-1 is mainly controlled by solar radiation in the Northern Hemisphere.
Effect of pemafibrate on liver enzymes and shear wave velocity in non-alcoholic fatty liver disease patients
Authors: Sugimoto Ryosuke , Iwasa Motoh , Eguchi Akiko , Tamai Yasuyuki , Shigefuku Ryuta , Fujiwara Naoto , Tanaka Hideaki , Kobayashi Yoshinao , Ikoma Jiro , Kaito Masahiko , Nakagawa Hayato
Published: February 2023

Background/Aims

Pemafibrate is a selective peroxisome proliferator-activated receptor α modulator that improves serum alanine aminotransferase (ALT) in dyslipidemia patients. Pemafibrate was reported to reduce ALT in non-alcoholic fatty liver disease (NAFLD) patients, but efficacy was not clearly elucidated due to the small size of previous study populations. Therefore, we explored pemafibrate efficacy in NAFLD patients.

Methods

We retrospectively evaluated pemafibrate efficacy on liver enzymes (n = 132) and liver shear wave velocity (SWV, n = 51) in NAFLD patients who had taken pemafibrate for at least 24 weeks.

Results

Patient ALT levels were decreased from 81.0 IU/L at baseline to 48.0 IU/L at week 24 (P < 0.0001). Serum levels of aspartate aminotransferase (AST), γ-glutamyl transpeptidase (γ-GTP) and triglyceride (TG) were significantly decreased, and high-density lipoprotein cholesterol and platelet count were significantly increased, with no change in body weight being observed. Study participant SWV values decreased from 1.45 m/s at baseline to 1.32 m/s at week 48 (P < 0.001). Older age (P = 0.035) and serum TG levels (P = 0.048) were significantly associated with normalized ALT. Changes in AST, ALT, γ-GTP and body weight were significantly correlated with change in SWV.

Conclusion

Pemafibrate significantly improves liver function, serum TG and liver stiffness in NAFLD patients. Pemafibrate is a promising therapeutic agent for NAFLD and may be a candidate for NAFLD patients with elevated TG.
Diversity, distribution and organic substrates preferences of microbial communities of a low anthropic activity cave in North-Western Romania
Authors: Bogdan Diana Felicia , Baricz Andreea Ionela , Chiciudean Iulia , Bulzu Paul-Adrian , Cristea Adorján , Năstase-Bucur Ruxandra , Levei Erika Andrea , Cadar Oana , Sitar Cristian , Banciu Horia Leonard , Moldovan Oana Teodora
Published: February 2023

Introduction

Karst caves are characterized by relatively constant temperature, lack of light, high humidity, and low nutrients availability. The diversity and functionality of the microorganisms dwelling in caves micro-habitats are yet underexplored. Therefore, in-depth investigations of these ecosystems aid in enlarging our understanding of the microbial interactions and microbially driven biogeochemical cycles. Here, we aimed at evaluating the diversity, abundance, distribution, and organic substrate preferences of microbial communities from Peștera cu Apă din Valea Leșului (Leșu Cave) located in the Apuseni Mountains (North-Western Romania).

Materials and Methods

To achieve this goal, we employed 16S rRNA gene amplicon sequencing and community-level physiological profiling (CLPP) paralleled by the assessment of environmental parameters of cave sediments and water.

Results and Discussion

Pseudomonadota (synonym Proteobacteria) was the most prevalent phylum detected across all samples whereas the abundance detected at order level varied among sites and between water and sediment samples. Despite the general similarity at the phylum-level in Leșu Cave across the sampled area, the results obtained in this study suggest that specific sites drive bacterial community at the order-level, perhaps sustaining the enrichment of unique bacterial populations due to microenvironmental conditions. For most of the dominant orders the distribution pattern showed a positive correlation with C-sources such as putrescine, γ-amino butyric acid, and D-malic acid, while particular cases were positively correlated with polymers (Tween 40, Tween 80 and α-cyclodextrin), carbohydrates (α-D-lactose, i-erythritol, D-mannitol) and most of the carboxylic and ketonic acids. Physicochemical analysis reveals that sediments are geochemically distinct, with increased concentration of Ca, Fe, Al, Mg, Na and K, whereas water showed low nitrate concentration. Our PCA indicated the clustering of different dominant orders with Mg, As, P, Fe, and Cr. This information serves as a starting point for further studies in elucidating the links between the taxonomic and functional diversity of subterranean microbial communities.
Hypertension, sleep quality, depression, and cognitive function in elderly: A cross-sectional study
Authors: Chen Jiajie , Chen Xi , Mao Ruxue , Fu Yu , Chen Qin , Zhang Cuntai , Zheng Kai
Published: February 2023

Background

Hypertension, sleep disorders, and depression are highly prevalent in the elderly population and are all associated with cognitive impairment, but the role that sleep quality and depression play in the association between hypertension and cognitive impairment is unclear. The aim of this study was to investigate whether sleep quality and depression have a mediating role in the association between hypertension and cognitive impairment.

Methods

A cross-sectional study was conducted to collect data from the Tongji Hospital Comprehensive Geriatric Assessment Database. Sleep quality, depression and cognitive function were measured by the Pittsburgh Sleep Quality Index (PSQI), the Geriatric Depression Scale (GDS-15) and the Mini-Mental State Examination (MMSE), respectively. Correlation analysis, regression analysis and Bootstrap analysis were used to examine correlations between key variables and mediating effects of sleep quality and depression. Adjustments for multiple comparisons were performed using Benjamini-Hochberg adjustment for multiple testing.

Results

A total of 827 participants were included, hypertension was present in 68.3% of the sample. After correcting for covariates, hypertensive patients aged 65 years or older had worse cognitive function, poorer-sleep quality and higher levels of depression. Sleep quality was significantly negatively associated with depression and cognitive function, while depression was negatively associated with cognitive function. Mediation analysis revealed that hypertension can affect cognitive function in older adults through a single mediating effect of sleep quality and depression and a chain mediating effect of sleep quality and depression.

Conclusion

This study found that sleep quality and depression can mediate the relationship between hypertension and cognitive function in elderly. Enhanced supervision of sleep quality and depression in elderly patients with hypertension may be beneficial in maintaining cognitive function.
Prediction of STN-DBS for Parkinson’s disease by uric acid-related brain function connectivity: A machine learning study based on resting state function MRI
Authors: Chang Bowen , Xiong Chi , Ni Chen , Chen Peng , Jiang Manli , Mei Jiaming , Niu Chaoshi
Published: February 2023

Introduction

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by dyskinesia and is closely related to oxidative stress. Uric acid (UA) is a natural antioxidant found in the body. Previous studies have shown that UA has played an important role in the development and development of PD and is an important biomarker. Subthalamic nucleus deep brain stimulation (STN-DBS) is a common treatment for PD.

Methods

Based on resting state function MRI (rs-fMRI), the relationship between UA-related brain function connectivity (FC) and STN-DBS outcomes in PD patients was studied. We use UA and DC values from different brain regions to build the FC characteristics and then use the SVR model to predict the outcome of the operation.

Results

The results show that PD patients with UA-related FCs are closely related to STN-DBS efficacy and can be used to predict prognosis. A machine learning model based on UA-related FC was successfully developed for PD patients.

Discussion

The two biomarkers, UA and rs-fMRI, were combined to predict the prognosis of STN-DBS in treating PD. Neurosurgeons are provided with effective tools to screen the best candidate and predict the prognosis of the patient.
Association of blood pressure variability during acute care hospitalization and incident dementia
Authors: Ebinger Joseph E. , Driver Matthew P. , Botting Patrick , Wang Minhao , Cheng Susan , Tan Zaldy S.
Published: February 2023

Background and objectives

Recognized as a potential risk factor for Alzheimer's disease and related dementias (ADRD), blood pressure variability (BPV) could be leveraged to facilitate identification of at-risk individuals at a population level. Granular BPV data are available during acute care hospitalization periods for potentially high-risk patients, but the incident ADRD risk association with BPV measured in this setting is unknown. Our objective was to evaluate the relation of BPV, measured during acute care hospitalization, and incidence of ADRD.

Methods

We retrospectively studied adults, without a prior ADRD diagnosis, who were admitted to a large quaternary care medical center in Southern California between January 1, 2013 and December 31, 2019. For all patients, determined BPV, calculated as variability independent of the mean (VIM), using blood pressure readings obtained as part of routine clinical care. We used multivariable Cox proportional hazards regression to examine the association between BP VIM during hospitalization and the development of incident dementia, determined by new ICD-9/10 coding or the new prescription of dementia medication, occurring at least 2 years after the index hospitalization.

Results

Of 81,892 adults hospitalized without a prior ADRD diagnosis, 2,442 (2.98%) went on to develop ADRD (2.6 to 5.2 years after hospitalization). In multivariable-adjusted Cox models, both systolic (HR 1.05, 95% CI 1.00–1.09) and diastolic (1.06, 1.02–1.10) VIM were associated with incident ADRD. In pre-specified stratified analyses, the VIM associations with incident ADRD were most pronounced in individuals over age 60 years and among those with renal disease or hypertension. Results were similar when repeated to include incident ADRD diagnoses made at least 1 or 3 years after index hospitalization.

Discussion

We found that measurements of BPV from acute care hospitalizations can be used to identify individuals at risk for developing a diagnosis of ADRD within approximately 5 years. Use of the readily accessible BPV measure may allow healthcare systems to risk stratify patients during periods of intense patient-provider interaction and, in turn, facilitate engagement in ADRD screening programs.
On the accuracy of code complexity metrics: A neuroscience-based guideline for improvement
Authors: Hao Gao , Hijazi Haytham , Durães João , Medeiros Júlio , Couceiro Ricardo , Lam Chan Tong , Teixeira César , Castelhano João , Castelo Branco Miguel , Carvalho Paulo , Madeira Henrique
Published: February 2023

Complexity is the key element of software quality. This article investigates the problem of measuring code complexity and discusses the results of a controlled experiment to compare different views and methods to measure code complexity. Participants (27 programmers) were asked to read and (try to) understand a set of programs, while the complexity of such programs is assessed through different methods and perspectives: (a) classic code complexity metrics such as McCabe and Halstead metrics, (b) cognitive complexity metrics based on scored code constructs, (c) cognitive complexity metrics from state-of-the-art tools such as SonarQube, (d) human-centered metrics relying on the direct assessment of programmers’ behavioral features (e.g., reading time, and revisits) using eye tracking, and (e) cognitive load/mental effort assessed using electroencephalography (EEG). The human-centered perspective was complemented by the subjective evaluation of participants on the mental effort required to understand the programs using the NASA Task Load Index (TLX). Additionally, the evaluation of the code complexity is measured at both the program level and, whenever possible, at the very low level of code constructs/code regions, to identify the actual code elements and the code context that may trigger a complexity surge in the programmers’ perception of code comprehension difficulty. The programmers’ cognitive load measured using EEG was used as a reference to evaluate how the different metrics can express the (human) difficulty in comprehending the code. Extensive experimental results show that popular metrics such as V(g) and the complexity metric from SonarSource tools deviate considerably from the programmers’ perception of code complexity and often do not show the expected monotonic behavior. The article summarizes the findings in a set of guidelines to improve existing code complexity metrics, particularly state-of-the-art metrics such as cognitive complexity from SonarSource tools.
Preparation and activity evaluation of angiotensin-I converting enzyme inhibitory peptides from protein hydrolysate of mulberry leaf
Authors: Chen Yu , Zhang Yu , Qi Qianhui , Liang Feng , Wang Nan , Chen Qihe , Li Xue , Sun Suling , Wang Xinquan , Bai Kaiwen , Wang Wei , Jiao Yingchun
Published: February 2023

Angiotensin-I converting enzyme (ACE) inhibitory peptides drew wide attention in the food industry because of their natural reliability, non-toxicity, and safety. However, the characteristics of ACE inhibitory peptides obtained from protein hydrolysate of mulberry leaf prepared by Flavourzyme were still unclear. Based on the single-factor test, the Plackett–Burman test and response surface test were used to determine the key factors affecting the ACE inhibition rate in mulberry leaf protein hydrolysate and the optimum conditions of enzymatic hydrolysis. The results showed that the optimum technical parameters were as follows: the ratio of material to liquid is 1: 25 (w / v, g/mL), the Flavourzyme to substrate ratio was 3,000 U/g, the temperature of enzymatic hydrolysis was 50°C, pH was 6.3, and the time of enzymatic hydrolysis was 2.9 h. The ACE inhibitory peptides in the mulberry leaf protein hydrolysates were purified by ultrafiltration and gel filtration, aiming to obtain the highest active component. The 12 peptide sequences were identified by reverse liquid chromatography-mass spectrometry, and then, they were docked to the crystal structure of human angiotensin-I converting enzyme (1O8A), and the interaction mechanisms of 12 peptide sequences and 1O8A were analyzed. The docking results showed that among the 12 peptide sequences, ERFNVE (792.37 Da), TELVLK (351.72 Da), MELVLK (366.72 Da), and FDDKLD (376.67 Da), all had the lowest docking energy, and inhibition constant. The chemosynthetic ERFNVE (IC50: 2.65 mg/mL), TELVLK (IC50: 0.98 mg/mL), MELVLK (IC50:1.90 mg/mL) and FDDKLD (IC50:0.70 mg/mL) demonstrated high ACE-inhibitory activity with competitive inhibition mode. These results indicated that the ACE-inhibiting peptides from mulberry leaf protein hydrolyzed (FHMP) had the potential activities to inhibit ACE and could be used as functional food or drugs to inhibit ACE. This work provides positive support for mining the biological activity of mulberry leaves in the treatment of hypertension.
Myo-inositol supplementation improves cardiometabolic factors, anthropometric measures, and liver function in obese patients with non-alcoholic fatty liver disease
Authors: Arefhosseini Sara , Roshanravan Neda , Tutunchi Helda , Rostami Somayyeh , Khoshbaten Manuchehr , Ebrahimi-Mameghani Mehrangiz
Published: February 2023

Background

Non-alcoholic fatty liver disease (NAFLD) as the hepatic manifestation of metabolic syndrome is closely associated with type 2 diabetes mellitus. Myo-inositol (MI)—a 6-C sugar alcohol—with insulin-mimetic, anti-diabetic, lipid-lowering, and anti-inflammatory properties has exerted favorable effects on insulin resistance-related disorders and metabolic disease, while recent animal studies revealed its positive effects on liver function. This study aimed to investigate the effects of MI supplementation on cardiometabolic factors, anthropometric measures, and liver function in obese patients with NAFLD.

Methods

This double-blinded placebo-controlled randomized clinical trial was carried out on 48 obese patients with NAFLD who were randomly assigned to either MI (4g/day) or placebo (maltodextrin 4g/day) along with dietary recommendations for 8 weeks. Glycemic indices, lipid profile, liver enzymes anthropometric measures, and blood pressure were evaluated pre- and post-intervention. Dietary intakes were assessed using a 3-day 24 h recall and analyzed by Nutritionist IV software. Insulin resistance was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR), and beta-cell function (HOMA-B) was also estimated.

Results

Anthropometric measures decreased significantly in both groups, while the reduction in weight (p = 0.049) and systolic blood pressure (p = 0.006) in the MI group was significantly greater than in the placebo group after adjusting for baseline values and energy intake. Although energy and macronutrient intakes decreased significantly in both groups, between-group differences were not significant after adjusting for the potential confounders. MI supplementation led to a significant reduction in serum fasting insulin (p = 0.008) and HOMA-IR (p = 0.046). There were significant improvements in lipid profile, liver enzymes, and aspartate aminotransferase/alanine aminotransferase ratio as well as serum ferritin level in the MI group, compared to the placebo group at the endpoint. By MI supplementation for eight weeks, 1 in 3 patients reduced one- grade in the severity of NAFLD.

Conclusion

MI supplementation could significantly improve IR, lipid profile, and liver function in patients with NAFLD. Further clinical trials with larger sample sizes, longer duration, different MI doses, and other inositol derivatives are recommended.