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Introduction: Ginger (Zingiber officinale Roce.) is a widely consumed food item and a prominent traditional Chinese medicinal herb. The intrinsic quality of ginger may differ due to variations in its origin and processing techniques. To evaluate the quality of ginger, a straightforward and efficient discriminatory approach has been devised, utilizing 6-gingerol, 8-gingerol, and 10-gingerol as benchmarks.Methods: In order to categorize ginger samples according to their cultivated origins with different longitude and latitude (Shandong, Anhui, and Yunnan provinces in China) and processing methods (liquid nitrogen pulverization, ultra-micro grinding, and mortar grinding), similarity analysis (SA), hierarchical cluster analysis (HCA), and principal component analysis (PCA) were employed. Furthermore, there was a quantitative determination of the significant marker compounds gingerols, which has considerable impact on maintaining quality control and distinguishing ginger products accurately. Moreover, discrimination analysis (DA) was utilized to further distinguish and classify samples with unknown membership degrees based on the eigenvalues, with the aim of achieving optimal discrimination between groups.Results: The findings obtained from the high-performance liquid chromatography (HPLC) data revealed that the levels of various gingerols present in all samples exhibited significant variations. The study confirmed that the quality of ginger was primarily influenced by its origin and processing method, with the former being the dominant factor. Notably, the sample obtained from Anhui province and subjected to liquid nitrogen pulverization demonstrated the highest content of gingerols.Conclusion: The results obtained from the analysis of SA, HCA, PCA, and DA were consistent and could be employed to evaluate the quality of ginger. As such, the combination of HPLC fingerprints and chemo metric techniques provided a dependable approach for comprehensively assessing the quality and processing of ginger.

Introduction: Ginger (Zingiber officinale Roce.) is a widely consumed food item and a prominent traditional Chinese medicinal herb. The intrinsic quality of ginger may differ due to variations in its origin and processing techniques. To evaluate the quality of ginger, a straightforward and efficient discriminatory approach has been devised, utilizing 6-gingerol, 8-gingerol, and 10-gingerol as benchmarks. Methods: In order to categorize ginger samples according to their cultivated origins with different longitude and latitude (Shandong, Anhui, and Yunnan provinces in China) and processing methods (liquid nitrogen pulverization, ultra-micro grinding, and mortar grinding), similarity analysis (SA), hierarchical cluster analysis (HCA), and principal component analysis (PCA) were employed. Furthermore, there was a quantitative determination of the significant marker compounds gingerols, which has considerable impact on maintaining quality control and distinguishing ginger products accurately. Moreover, discrimination analysis (DA) was utilized to further distinguish and classify samples with unknown membership degrees based on the eigenvalues, with the aim of achieving optimal discrimination between groups. Results: The findings obtained from the high-performance liquid chromatography (HPLC) data revealed that the levels of various gingerols present in all samples exhibited significant variations. The study confirmed that the quality of ginger was primarily influenced by its origin and processing method, with the former being the dominant factor. Notably, the sample obtained from Anhui province and subjected to liquid nitrogen pulverization demonstrated the highest content of gingerols. Conclusion: The results obtained from the analysis of SA, HCA, PCA, and DA were consistent and could be employed to evaluate the quality of ginger. As such, the combination of HPLC fingerprints and chemo metric techniques provided a dependable approach for comprehensively assessing the quality and processing of ginger., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Liu, Zuo, Zhang, Liang, Liu, Yu, Yu and Peng.)

The broken phosphorus (P) cycle has led to widespread eutrophication of freshwaters. Despite reductions in anthropogenic nutrient inputs that have led to improvement in the chemical status of running waters, corresponding improvements in their ecological status are often not observed. We tested a novel combination of complementary statistical modeling approaches, including random‐effect regression trees and compositional and ordinary linear mixed models, to examine the potential reasons for this disparity, using low‐frequency regulatory data available to catchment managers. A benthic Trophic Diatom Index (TDI) was linked to potential stressors, including nutrient concentrations, soluble reactive P (SRP) loads from different sources, land cover, and catchment hydrological characteristics. Modeling suggested that SRP, traditionally considered the bioavailable component, may not be the best indicator of ecological impacts of P, as shown by a stronger and spatially more variable negative relationship between total P (TP) concentrations and TDI. Nitrate‐N (p < 0.001) and TP (p = 0.002) also showed negative relationship with TDI in models where land cover was not included. Land cover had the strongest influence on the ecological response. The positive effect of seminatural land cover (p < 0.001) and negative effect of urban land cover (p = 0.030) may be related to differentiated bioavailability of P fractions in catchments with different characteristics (e.g., P loads from point vs. diffuse sources) as well as resilience factors such as hydro‐morphology and habitat condition, supporting the need for further research into factors affecting this stressor–response relationship in different catchment types. Advanced statistical modeling indicated that to achieve desired ecological status, future catchment‐specific mitigation should target P impacts alongside multiple stressors. Core Ideas: Soluble reactive P (SRP) alone was not the best indicator of diatom response.Total P (TP) association with diatoms was more spatially variable than SRP.Nitrate‐N and TP have a combined negative effect on the ecological response.Seminatural land use had the most important influence on ecological response.We recommend catchment‐specific mitigation of multiple stressors. [ABSTRACT FROM AUTHOR]

The chemical and stable isotopic compositions (δ34SSO4 and δ18OSO4) of Xijiang River water in southwest China, were measured to determine the extent of rock weathering and associated CO2 consumption rates, and to assess the contamination sources of river water. The SO42− concentration in the river water was in the range of 0.05 to 0.96 mmol L−1 (mean value = 0.32 mmol L−1) and was characterized by δ34SSO4 values ranging from −9.1 to 5.1‰ (mean value = −2.1‰) and δ18OSO4 values ranging from −0.4 to 10.8‰ (mean value = 5.0‰). The δ34SSO4 and δ18OSO4 values ranged from high to low from the upper reaches to the lower reaches in all the river water samples. The results indicate that the oxidation of sulfide and anthropogenic inputs are the dominant processes affecting SO42− sources and S cycling of the Xijiang River during high‐discharge conditions, which are controlled by regional hydrological processes that are affected by natural processes and anthropogenic inputs Core Ideas: The dual isotopes (δ34SSO4 and δ18OSO4) of sulfate indicated S sources.The weathering rates of carbonate and silicate were calculated.The relative contributions of various sources are identified. [ABSTRACT FROM AUTHOR]

Point sources such as wastewater treatment plants, terrestrial agriculture, and aquaculture may release antibiotic residues, antibiotic resistant bacteria, and antibiotic resistance genes (ARGs) into aquatic ecosystems. However, there is a lack of quantitative studies attributing environmental ARG abundance to specific sources. The goal of this study was to evaluate the role of freshwater trout farms in the release and dissemination of ARGs into the environment. Sediment samples upstream and downstream from five rainbow trout farms were collected over time in southern Chile. A microfluidic quantitative polymerase chain reaction approach was used to quantify an ARG array covering different mechanisms of resistance, and data were analyzed using principal component analysis (PCA) and linear mixed regression models. Surveys were also conducted to obtain information about management practices, including antibiotic use, at the farms. Florfenicol and oxytetracycline were used at these farms, although at different rates. A total of 93 samples were analyzed. In the PCA, strB, sul1, sul2, qacG, tet(A), tet(B), tet(C), tet(W), and floR grouped together. A statistically significant increase in abundance of qacG, strB, sul1, and several tet genes was found downstream from the farms compared with upstream sites, and retention ponds had the highest ARG abundance at each site. Antibiotic resistance gene levels returned to baseline at an average distance of 132.7 m downstream from the farms. Although results from this study indicate an influence of trout farms on the presence of ARGs in the immediate environment, the extent of their contribution to ARG dissemination is unknown and deserves further investigation. Core Ideas: Point sources contribute to antimicrobial resistance (AMR) in the environment.Antibiotic resistance genes (ARG) were quantified in river sediment samples.Freshwater trout farms in southern Chile increased ARG abundance in the watershed.The extent of the contribution of the trout farms on ARG dissemination is uncertain.Epidemiological methods are needed to attribute environmental AMR to specific point sources. [ABSTRACT FROM AUTHOR]

External morphology has been shown to influence predation and locomotion of decapod larvae and is, therefore, directly related to their ability to survive and disperse. The first goal of this study was to characterize first-stage blue crab zoeal morphology and its variability across larval broods to test whether inter-brood differences in morphology exist. The second was to identify possible correlations between maternal characteristics and zoeal morphology. The offspring of 21 individuals were hatched in the laboratory, photographed, and measured. Zoeae exhibited substantial variability, with all metrics showing significant inter-brood differences. The greatest variability was seen in the zoeal abdomen, rostrum, and dorsal spine length. A principal component analysis showed no distinct clustering of broods, with variation generally driven by larger zoeae. Using observed morphology, models of drag induced by swimming and sinking also showed significant inter-brood differences, with a maximum twofold difference across broods. In contrast to trends in other decapod taxa, maternal characteristics (female carapace width and mass and egg sponge volume and mass) are not significant predictors of zoeal morphology. These results suggest that brood effects are present across a wide range of morphological characteristics and that future experiments involving Callinectes sapidus morphology or its functionality should explicitly account for inter-brood variation. Additionally, inter-brood morphological differences may result in differential predation mortality and locomotory abilities among broods. [ABSTRACT FROM AUTHOR]

Maternal provisioning is particularly important in invertebrates with abbreviated development because large energy reserves must be provided for the developing embryo. In this context, the objective of the present study was to analyze in an aquatic invertebrate with direct development the effect of temperature on female biochemical composition and reserve allocation to maturing ovaries, which determine egg quality. A decapod crustacean, the freshwater shrimp Neocaridina davidi, was used as experimental model. Newly hatched juveniles were exposed to 28 °C or 33 °C. Females showed mature ovaries and spawned at 28 °C (control ovigerous females), but no ovigerous female was found at 33 °C. After a 200-day period, half of the females at 33 °C were transferred to 28 °C, where they rapidly showed mature ovaries and spawned (transferred ovigerous females). Ovigerous females and females that did not spawn at 28 °C (control non-ovigerous females) and at 33 °C (high-temperature non-ovigerous females) were sacrificed to determine their biochemical composition. The number, volume, weight, and biochemical composition of the eggs from transferred and control ovigerous females were also analyzed as indicators of their quality. Female biochemical composition was not influenced by temperature, because control and high-temperature non-ovigerous females had similar lipid, protein, and glycogen contents. However, ovarian maturation and spawning were inhibited at 33 °C, which indicates a negative effect of this temperature on nutrient transfer to the oocytes. This effect was rapidly reversed after females were moved to 28 °C; the eggs from control and transferred ovigerous females were of similar quality, except for a lower protein content in the latter. The present results provide valuable information on reserve allocation to reproduction under thermal stress. [ABSTRACT FROM AUTHOR]

Butenolide is an environmentally friendly antifouling natural product, but its efficiency and mechanism in preventing biofilm formation have not been examined. Furthermore, controlling the release of butenolide from paints into seawater is technically challenging. A coating was developed by mixing butenolide with a biodegradable polymer, poly (e-caprolactone)-based polyurethane, and a one-month in situ anti-biofilm test was conducted in a subtidal area. The constant release of butenolide from the surface suggested that its release was well controlled. Direct observation and confocal microscope investigation indicated that the coating was effective against both biofilm formation and attachment of large fouling organisms. Metatranscriptomic analysis of biofilm samples implied that the coating selectively inhibited the adhesion of microbes from a variety of phyla and targeted particular functional pathways including energy metabolism, drug transport and toxin release. These integrated analyses demonstrated the potential application of this butenolide/polymer coating as an anti-biofilm material. [ABSTRACT FROM AUTHOR]

In the present study, the chemical composition of the essential oils from aerial parts ofCentaurea grinensisReuter (K) collected at Žuta Lova, near Senj (Croatia), and aerial parts (L1) and flowers (L2) ofC. apiculataLedeb. collected near Rebro village, near Breznik town, Znepole Region (Bulgaria), both belonging to subgenusLopholoma(Cass.) Dobrocz, was evaluated by GC and GC-MS. The main components ofKwere 4-vinyl guaiacol (21.5%), hexadecanoic acid (16.2%), acetophenone (12.5%). Caryophyllene oxide (15.8%) together with sphathulenol (14.5%) and humulene epoxide II (9.4%) were recognized as the main constituent of both the aerial part (L1) and flowers (L2) ofC. apiculata. Furthermore, a complete review on the composition of the essential oils of all theCentaureataxa belonging to subgenusLopholomastudied so far has been inserted and cluster analysis (PCA) was carried out. [ABSTRACT FROM PUBLISHER]

The genetic and morphometric population structures of the semiterrestrial crab Armases angustipes from along the Brazilian coast were examined. The influence of the Central South Equatorial Current on larval dispersal of A. angustipes also was evaluated. Six populations were sampled from estuarine areas in São Luis do Maranhão, Maranhão; Natal, Rio Grande do Norte; Maceió, Alagoas; Ilhéus, Bahia; Aracruz, Espírito Santo; and Guaratuba, Paraná. Patterns of genetic differentiation were assessed using DNA sequence data corresponding to parts of the mitochondrial cytochrome c oxidase subunit 1. Geometric morphometric techniques were used to evaluate morphological variation in shape and size of the carapace and right cheliped propodus. Our results revealed low genetic variability and lack of phylogeographic structure; geometricmorphometrics showed statistically significant morphological differentiation and geographic structuring. Our data indicate the absence of possible barriers to gene flow for this mobile species, and no clear correlation of morphological or genetic variation with ocean currents and/or geographic distance. Our results also suggest that historical geological and climatological events and/or possible bottleneck effects influenced the current low genetic variability among the populations of A. angustipes. [ABSTRACT FROM AUTHOR]

The first 2 years of life are a critical window of opportunity for ensuring optimal child growth and development. In Ethiopia, the magnitude of the minimum acceptable diet ranges from 7 to 74⋅6 %. The evidence revealed the variation and unrelated data on the prevalence of minimum acceptable diet. Therefore, the present study aimed to assess the minimum acceptable diet and its associated factors among children aged 6-23 months in Lalibela town administration, northeast Ethiopia. A community-based cross-sectional study was conducted in Lalibela town administration, northeast Ethiopia among 387 mothers/caregivers with children aged 6-23 months from May 1 to 30, 2022. The data were entered by Epidata version 3.1 and analysed by SPSS version 25.0. A multivariable binary logistic regression model was fitted to identify factors associated with minimum acceptable diet. The degrees of association were assessed using an adjusted odds ratio with a 95 % confidence interval and P -value of 0⋅05. The magnitude of minimum acceptable diet in the study area was 16⋅7 % (95 % confidence interval: 12⋅8-20⋅6 %). Sex of child, getting infant and young child feeding counselling at antenatal care, infant feeding practice-related knowledge and childhood illness are the variables that were found to be an independent predictor of minimum acceptable diet. Health facilities should strengthen infant feeding counselling starting from antenatal care visits during pregnancy for the recommended minimum acceptable diet is crucial., (© The Author(s) 2023.)

The cell as a system of many components, governed by the laws of physics and chemistry drives molecular functions having an impact on the spatial organization of these systems and vice versa. Since the relationship between structure and function is an almost universal rule not only in biology, appropriate methods are required to parameterize the relationship between the structure and function of biomolecules and their networks, the mechanisms of the processes in which they are involved, and the mechanisms of regulation of these processes. Single molecule localization microscopy (SMLM), which we focus on here, offers a significant advantage for the quantitative parametrization of molecular organization: it provides matrices of coordinates of fluorescently labeled biomolecules that can be directly subjected to advanced mathematical analytical procedures without the need for laborious and sometimes misleading image processing. Here, we propose mathematical tools for comprehensive quantitative computer data analysis of SMLM point patterns that include Ripley distance frequency analysis, persistent homology analysis, persistent 'imaging', principal component analysis and co-localization analysis. The application of these methods is explained using artificial datasets simulating different, potentially possible and interpretatively important situations. Illustrative analyses of real complex biological SMLM data are presented to emphasize the applicability of the proposed algorithms. This manuscript demonstrated the extraction of features and parameters quantifying the influence of chromatin (re)organization on genome function, offering a novel approach to study chromatin architecture at the nanoscale. However, the ability to adapt the proposed algorithms to analyze essentially any molecular organizations, e.g., membrane receptors or protein trafficking in the cytosol, offers broad flexibility of use., (© 2023 The Authors.)

Alternative splicing (AS) events modulate certain pathways and phenotypic plasticity in cancer. Although previous studies have computationally analyzed splicing events, it is still a challenge to uncover biological functions induced by reliable AS events from tremendous candidates. To provide essential splicing event signatures to assess pathway regulation, we developed a database by collecting two datasets: (i) reported literature and (ii) cancer transcriptome profile. The former includes knowledge-based splicing signatures collected from 63,229 PubMed abstracts using natural language processing, extracted for 202 pathways. The latter is the machine learning-based splicing signatures identified from pan-cancer transcriptome for 16 cancer types and 42 pathways. We established six different learning models to classify pathway activities from splicing profiles as a learning dataset. Top-ranked AS events by learning model feature importance became the signature for each pathway. To validate our learning results, we performed evaluations by (i) performance metrics, (ii) differential AS sets acquired from external datasets, and (iii) our knowledge-based signatures. The area under the receiver operating characteristic values of the learning models did not exhibit any drastic difference. However, random-forest distinctly presented the best performance to compare with the AS sets identified from external datasets and our knowledge-based signatures. Therefore, we used the signatures obtained from the random-forest model. Our database provided the clinical characteristics of the AS signatures, including survival test, molecular subtype, and tumor microenvironment. The regulation by splicing factors was additionally investigated. Our database for developed signatures supported retrieval and visualization system., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Islets transplanted for type-1 diabetes have their viability reduced by warm ischemia, dimethyloxalylglycine (DMOG; hypoxia model), oxidative stress and cytokine injury. This results in frequent transplant failures and the major burden of patients having to undergo multiple rounds of treatment for insulin independence. Presently there is no reliable measure to assess islet preparation viability prior to clinical transplantation. We investigated deep morphological signatures (DMS) for detecting the exposure of islets to viability compromising insults from brightfield images. Accuracies ranged from 98 % to 68 % for; ROS damage, pro-inflammatory cytokines, warm ischemia and DMOG. When islets were disaggregated to single cells to enable higher throughput data collection, good accuracy was still obtained (83-71 %). Encapsulation of islets reduced accuracy for cytokine exposure, but it was still high (78 %). Unsupervised modelling of the DMS for islet preparations transplanted into a syngeneic mouse model was able to predict whether or not they would restore glucose control with 100 % accuracy. Our strategy for constructing DMS' is effective for the assessment of islet pre-transplant viability. If translated into the clinic, standard equipment could be used to prospectively identify non-functional islet preparations unable to contribute to the restoration of glucose control and reduce the burden of unsuccessful treatments., Competing Interests: No conflict of interest., (© 2023 The Authors.)

Mass spectrometry focusing on small endogenous molecules has become an integral part of biomarker discovery in the pursuit of an in-depth understanding of the pathophysiology of various diseases, ultimately enabling the application of personalized medicine. While LC-MS methods allow researchers to gather vast amounts of data from hundreds or thousands of samples, the successful execution of a study as part of clinical research also requires knowledge transfer with clinicians, involvement of data scientists, and interactions with various stakeholders. The initial planning phase of a clinical research project involves specifying the scope and design, and engaging relevant experts from different fields. Enrolling subjects and designing trials rely largely on the overall objective of the study and epidemiological considerations, while proper pre-analytical sample handling has immediate implications on the quality of analytical data. Subsequent LC-MS measurements may be conducted in a targeted, semi-targeted, or non-targeted manner, resulting in datasets of varying size and accuracy. Data processing further enhances the quality of data and is a prerequisite for in-silico analysis. Nowadays, the evaluation of such complex datasets relies on a mix of classical statistics and machine learning applications, in combination with other tools, such as pathway analysis and gene set enrichment. Finally, results must be validated before biomarkers can be used as prognostic or diagnostic decision-making tools. Throughout the study, quality control measures should be employed to enhance the reliability of data and increase confidence in the results. The aim of this graphical review is to provide an overview of the steps to be taken when conducting an LC-MS-based clinical research project to search for small molecule biomarkers., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 THE AUTHORS.)

Background: Dysregulation of long noncoding RNAs (lncRNAs) has been reported to be associated with multiple tumors where they act as tumor suppressors or accelerators. The lncRNA CYTOR was identified as an oncogene involved in many cancers, such as gastric cancer, colorectal cancer, hepatocellular carcinoma, and renal cell carcinoma. However, the role of CYTOR in bladder cancer (BCa) has rarely been reported., Methods: Using cancer datasets from The Cancer Genome Atlas (TCGA) program, we analyzed the association between CYTOR expression and prognostic value, oncogenic pathways, antitumor immunity and immunotherapy response in BCa. The influence of CYTOR on the immune infiltration pattern in the urothelial carcinoma microenvironment was further verified in our dataset. Single-cell analysis revealed the role of CYTOR in the tumor microenvironment (TME) of BCa. Finally, we evaluated the expression of CYTOR in BCa in the Peking University First Hospital (PKU-BCa) dataset and its correlation with the malignant phenotype of BCa in vitro and in vivo ., Results: The results indicated that CYTOR was highly expressed in multiple cancer samples, including BCa, and increased CYTOR expression contributed to poor overall survival (OS). Additionally, elevated CYTOR expression was significantly correlated with clinicopathological features of BCa, such as female sex, advanced TNM stage, high histological grade and non-papillary subtype. Functional characterization revealed that CYTOR may be involved in immune-related pathways and the epithelial mesenchymal transformation (EMT) process. Moreover, CYTOR had a significant association with infiltrating immune cells, including M2 macrophages and regulatory T cells (Tregs). CYTOR facilitates the crosstalk between cancer-associated fibroblasts (CAFs) and macrophages, and mediates M2 polarization of macrophages. Correlation analysis revealed a positive correlation between CYTOR expression and programmed cell death-1 ( PD-1 )/programmed death ligand 1 ( PD-L1 )/expression and other targets for specific immunotherapy in BCa, which are recognized to predict the efficacy of immunotherapy., Conclusions: These results suggest that CYTOR serves as a potential biomarker for predicting survival outcome, TME cell infiltration characteristics and immunotherapy response in BCa., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Short-chain fatty acids (SCFAs) exhibit anticancer activity in cellular and animal models of colon cancer. Acetate, propionate, and butyrate are the three major SCFAs produced from dietary fiber by gut microbiota fermentation and have beneficial effects on human health. Most previous studies on the antitumor mechanisms of SCFAs have focused on specific metabolites or genes involved in antitumor pathways, such as reactive oxygen species (ROS) biosynthesis. In this study, we performed a systematic and unbiased analysis of the effects of acetate, propionate, and butyrate on ROS levels and metabolic and transcriptomic signatures at physiological concentrations in human colorectal adenocarcinoma cells. We observed significantly elevated levels of ROS in the treated cells. Furthermore, significantly regulated signatures were involved in overlapping pathways at metabolic and transcriptomic levels, including ROS response and metabolism, fatty acid transport and metabolism, glucose response and metabolism, mitochondrial transport and respiratory chain complex, one-carbon metabolism, amino acid transport and metabolism, and glutaminolysis, which are directly or indirectly linked to ROS production. Additionally, metabolic and transcriptomic regulation occurred in a SCFAs types-dependent manner, with an increasing degree from acetate to propionate and then to butyrate. This study provides a comprehensive analysis of how SCFAs induce ROS production and modulate metabolic and transcriptomic levels in colon cancer cells, which is vital for understanding the mechanisms of the effects of SCFAs on antitumor activity in colon cancer., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.)

Background & Aims: Although extensive experimental evidence on the process of liver regeneration exists, in humans, validation is largely missing. However, liver regeneration is critically affected by underlying liver disease. Within this project, we aimed to systematically assess early transcriptional changes during liver regeneration in humans and further assess how these processes differ in people with dysfunctional liver regeneration., Methods: Blood samples of 154 patients and intraoperative tissue samples of 46 patients undergoing liver resection were collected and classified with regard to dysfunctional postoperative liver regeneration. Of those, a matched cohort of 21 patients were used for RNA sequencing. Samples were assessed for circulating cytokines, gene expression dynamics, intrahepatic neutrophil accumulation, and spatial transcriptomics., Results: Individuals with dysfunctional liver regeneration demonstrated an aggravated transcriptional inflammatory response with higher intracellular adhesion molecule-1 induction. Increased induction of this critical leukocyte adhesion molecule was associated with increased intrahepatic neutrophil accumulation and activation upon induction of liver regeneration in individuals with dysfunctional liver regeneration. Comparing baseline gene expression profiles in individuals with and without dysfunctional liver regeneration, we found that dual-specificity phosphatase 4 (DUSP4) expression, a known critical regulator of intracellular adhesion molecule-1 expression in endothelial cells, was markedly reduced in patients with dysfunctional liver regeneration. Mimicking clinical risk factors for dysfunctional liver regeneration, we found liver sinusoidal endothelial cells of two liver disease models to have significantly reduced baseline levels of DUSP4., Conclusions: Exploring the landscape of early transcriptional changes of human liver regeneration, we observed that people with dysfunctional regeneration experience overwhelming intrahepatic inflammation. Subclinical liver disease might account for DUSP4 reduction in liver sinusoidal endothelial cells, which ultimately primes the liver for an aggravated inflammatory response., Impact and Implications: Using a unique human biorepository, focused on liver regeneration (LR), we explored the landscape of circulating and tissue-level alterations associated with both functional and dysfunctional LR. In contrast to experimental animal models, people with dysfunctional LR demonstrated an aggravated transcriptional inflammatory response, higher intracellular adhesion molecule-1 (ICAM-1) induction, intrahepatic neutrophil accumulation and activation upon induction of LR. Although inflammatory responses appear rapidly after liver resection, people with dysfunctional LR have exaggerated inflammatory responses that appear to be related to decreased levels of LSEC DUSP4, challenging existing concepts of post-resectional LR., (© 2023 The Author(s).)

The Mollisol region of Northeast China is an important crop production base of China. The soil quality of this region has greatly decreased in recent decades due to unreasonable land management, which in turn has reduced crop yields. The objectives of this study were to investigate the spatial distribution of a soil quality index (SQI) and the relationship between crop yield and soil quality in a catchment of the Chinese Mollisol region. A total of 168 soil samples were collected based on a 200- by 200-m grid and 4 yr of corn (Zea mays L.) yields and 15 soil quality indicators, including physical, chemical, and biological properties, were analyzed. Principal component analysis indicated that the critical indicators for characterizing soil quality were soil organic matter, total N, sucrase activity, NH4 +-N, microbial biomass C, and microbial biomass N. The SQI varied from 0.147 to 0.804 with a mean value of 0.388. The spatial distribution of soil quality and corn yield showed that high values of both soil quality and corn yield were located in the north, and low values were in the south of the catchment. An empirical equation between corn yield and SQI was fitted, and cross-validation results showed that the empirical equations could be used to assess soil quality effects on corn yield with acceptable accuracy in the research area. Hence, to realize agricultural sustainability, effective soil conservation measures, such as no-till, cover crops, and retaining crop residues should be implemented in the study area instead of current cropland management measures. [ABSTRACT FROM AUTHOR]

Head and neck radiotherapy induces important toxicity, and its efficacy and tolerance vary widely across patients. Advancements in radiotherapy delivery techniques, along with the increased quality and frequency of image guidance, offer a unique opportunity to individualize radiotherapy based on imaging biomarkers, with the aim of improving radiation efficacy while reducing its toxicity. Various artificial intelligence models integrating clinical data and radiomics have shown encouraging results for toxicity and cancer control outcomes prediction in head and neck cancer radiotherapy. Clinical implementation of these models could lead to individualized risk-based therapeutic decision making, but the reliability of the current studies is limited. Understanding, validating and expanding these models to larger multi-institutional data sets and testing them in the context of clinical trials is needed to ensure safe clinical implementation. This review summarizes the current state of the art of machine learning models for prediction of head and neck cancer radiotherapy outcomes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

This study investigated the effects of different cooking methods on non-volatile flavor (free amino acids, 5'-nucleotides, and organic acids, etc.) of Coregonus peled meat. The volatile flavor characteristics were also analyzed by electric nose and gas chromatography-ion migration spectrometry (GC-IMS). The results indicated that the content of flavor substances in C. peled meat varied significantly. The electronic tongue results indicated that the richness and umami aftertaste of roasting were significantly greater. The content of sweet free amino acids, 5'-nucleotides, and organic acids was also higher in roasting group. Electronic nose principal component analysis can distinguish C. peled meat cooked (the first two components accounted for 98.50% and 0.97%, respectively). A total of 36 volatile flavor compounds were identified among different groups, including 16 aldehydes, 7 olefine aldehydes, 6 alcohols, 4 ketones, and 3 furans. In general, roasting was recommended and gave more flavor substances in C. peled meat., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

The layer-by-layer application of biopolymeric coatings to mandarin fruits as a postharvest treatment to improve fruit coating efficacy has been reported. A single 1 % (w/v) chitosan application was evaluated, and polyelectrolyte complexes such as 1.5 % (w/v) alginate/chitosan, 1 % (w/v) hydroxypropyl methylcellulose/chitosan, and 0.2 % (w/v) locust bean gum/chitosan were applied to mandarin fruits. The quality of coated mandarin fruits was observed at temperatures: 20 ± 2 °C (up to 10 days) and 5 °C (up to 28 days). Changes in the fruit metabolism were observed by evaluating bioactive compounds (polyphenolic compounds and flavonoids), antioxidant activity, and organic acids during the preservation of mandarin fruits. All of the tested combinations of layer-by-layer coatings significantly impacted the quality of mandarin fruits throughout storage, both at room temperature and cold storage, respectively. The overall best performance was observed for a layer-by-layer hydroxypropyl methylcellulose/chitosan coating in terms of visual aspects, bioactive compounds, antioxidant activity, and organic acids content., Competing Interests: The authors declare no financial interests/personal relationships which may be considered as potential competing interests., (© 2023 The Authors.)

Heart failure is caused by various factors, making the underlying pathogenic mechanisms difficult to identify. Since cardiovascular disease tends to worsen over time, early diagnosis is key for treatment. In addition, understanding the qualitative changes in the heart associated with aging, where information on the direct influences of aging on cardiovascular disease is limited, would also be useful for treatment and diagnosis. To fill these research gaps, the focus of our study was to detect the structural and functional molecular changes associated with the heart over time, with a focus on glycans, which reflect the type and state of cells., Methods: We investigated glycan localization in the cardiac tissue of normal mice and their alterations during aging, using evanescent-field fluorescence-assisted lectin microarray, a technique based on lectin-glycan interaction, and lectin staining., Results: The glycan profiles in the left ventricle showed differences between the luminal side (medial) and wall side (lateral) regions. The medial region was characterized by the presence of sialic acid residues. Moreover, age-related changes in glycan profiles were observed at a younger age in the medial region. The difference in the age-related decrease in the level of α-galactose stained with Griffonia simplicifolia lectin-IB4 in different regions of the left ventricle suggests spatiotemporal changes in the number of microvessels., Conclusions: The glycan profile, which retains diverse glycan structures, is supported by many cell populations, and maintains cardiac function. With further research, glycan localization and changes have the potential to be developed as a marker of the signs of heart failure., Competing Interests: The authors declare no competing or financial interests., (© 2022 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.)

Aging is associated with the loss of facial subcutaneous fat and with increased abdominal subcutaneous fat. Site specific differences in adipocyte phenotype and/or gene expression may play a role in these age-related changes. In this study, we isolated and characterized human facial preadipocytes and investigated distinct metabolic properties such as a differentiation pattern in relation to abdominal preadipocytes. Subcutaneous preadipocytes were isolated from human facial and abdominal skin and cultured in the presence of differentiation factors including rosiglitazone, a known peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist, isobutyl-methyl xanthine (IBMX) and insulin. Differentiation was characterized microscopically and by quantitative real-time PCR. Unexpected superior adipogenic capacity of facial preadipocytes was observed; more facial preadipocytes differentiated in response to rosiglitazone than abdominal preadipocytes and facial preadipocytes retained their ability to differentiate through passage 11 compared with passage 5 for abdominal preadipocytes. Experiments confirmed a reduced lipolysis response in facial versus abdominal adipocytes after exposure to isoproterenol, which was consistent with the reduced β2-adrenergic receptor expression by 60% in the facial cells. The expression of other lipid metabolic gene markers was similar in both facial and abdominal adipocytes with the exception of β3-adrenergic receptor which was only found in abdominal adipose tissue. Gene profiling, by microarray analysis, identified that several HOX genes are robustly reduced in facial adipocytes compared to abdominal adipocytes, suggesting different characteristics between the 2 fat depots. These differences may have implications for development of treatments for facial fat loss during aging. [ABSTRACT FROM AUTHOR]

Targeting SARS-CoV-2 papain-like protease using inhibitors is a suitable approach for inhibition of virus replication and dysregulation of host anti-viral immunity. Engaging all five binding sites far from the catalytic site of PLpro is essential for developing a potent inhibitor. We developed and validated a structure-based pharmacophore model with 9 features of a potent PLpro inhibitor. The pharmacophore model-aided virtual screening of the comprehensive marine natural product database predicted 66 initial hits. This hit library was downsized by filtration through a molecular weight filter of ≤ 500 g/mol. The 50 resultant hits were screened by comparative molecular docking using AutoDock and AutoDock Vina. Comparative molecular docking enables benchmarking docking and relieves the disparities in the search and scoring functions of docking engines. Both docking engines retrieved 3 same compounds at different positions in the top 1 % rank, hence consensus scoring was applied, through which CMNPD28766, aspergillipeptide F emerged as the best PLpro inhibitor. Aspergillipeptide F topped the 50-hit library with a pharmacophore-fit score of 75.916. Favorable binding interactions were predicted between aspergillipeptide F and PLpro similar to the native ligand XR8-24. Aspergillipeptide F was able to engage all the 5 binding sites including the newly discovered BL2 groove, site V. Molecular dynamics for quantification of Cα-atom movements of PLpro after ligand binding indicated that it exhibits highly correlated domain movements contributing to the low free energy of binding and a stable conformation. Thus, aspergillipeptide F is a promising candidate for pharmaceutical and clinical development as a potent SARS-CoV-2 PLpro inhibitor., (© 2022 The Author(s).)

The large amount of data generated during the COVID-19 pandemic requires advanced tools for the long-term prediction of risk factors associated with COVID-19 mortality with higher accuracy. Machine learning (ML) methods directly address this topic and are essential tools to guide public health interventions. Here, we used ML to investigate the importance of demographic and clinical variables on COVID-19 mortality. We also analyzed how comorbidity networks are structured according to age groups. We conducted a retrospective study of COVID-19 mortality with hospitalized patients from Londrina, Parana, Brazil, registered in the database for severe acute respiratory infections (SIVEP-Gripe), from January 2021 to February 2022. We tested four ML models to predict the COVID-19 outcome: Logistic Regression, Support Vector Machine, Random Forest, and XGBoost. We also constructed a comorbidity network to investigate the impact of co-occurring comorbidities on COVID-19 mortality. Our study comprised 8358 hospitalized patients, of whom 2792 (33.40%) died. The XGBoost model achieved excellent performance (ROC-AUC = 0.90). Both permutation method and SHAP values highlighted the importance of age, ventilatory support status, and intensive care unit admission as key features in predicting COVID-19 outcomes. The comorbidity networks for old deceased patients are denser than those for young patients. In addition, the co-occurrence of heart disease and diabetes may be the most important combination to predict COVID-19 mortality, regardless of age and sex. This work presents a valuable combination of machine learning and comorbidity network analysis to predict COVID-19 outcomes. Reliable evidence on this topic is crucial for guiding the post-pandemic response and assisting in COVID-19 care planning and provision., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Published by Elsevier Inc.)

Coordination between legs is necessary to complete bipedal balance task goals. Assessing bilateral homonymous muscle coordination may provide insight into the inherent neuromuscular control of the two legs in achieving equilibrium. This work introduced a method based on a normalized cross-correlation analysis to analyze bilateral homonymous muscle coordination during bipedal balancing on different support surfaces, revealing the temporal similarity in shape (i.e., form) between two electromyographic (EMG) signals (i.e., EMG-EMG correlation). Two levels of EMG-EMG correlation were considered: individual homonymous muscles and groups (patterns) of homonymous muscles relevant to the current task. In order to analyze the patterns of homonymous muscles, a principal component analysis (PCA) was applied to the cross-correlation coefficients to provide insights into functionally specialized groups of homonymous muscles constrained by the nervous system to work cooperatively. This proposed method has advantages that can be applied to several purposes. For example,•Analyzing the EMG-EMG correlation provides essential information about the inherent neuromuscular function in postural control.•At the level of individual homonymous muscles, this method can be applied to assess the neuromuscular performance after injury to the specific muscles.•At the level of multiple homonymous muscles, this method can be used to monitor the cooperative work of several pairs of homonymous muscles in achieving equilibrium., (© 2022 The Author(s).)

Nitrogen modified atmosphere was an effective way to control pest infestation in grains. In this study, the quality changes of rice during nitrogen modified atmosphere packaging storage (N 2 -MAPS) were monitored. An un-targeted metabolomics method was used to detect the rice metabolites and explore the mechanism of N 2 -MAPS for delaying rice deterioration. In this study, two rice species were studied under N 2 -MAPS and conventional storage at 30 °C for 150 days. The quality changes of rice during storage were monitored. The results showed that N 2 -MAPS could retard the increase of fatty acid value and amylose content, and defer the decrease of enzyme activities. And N 2 -MAPS had no significant influence on texture characteristics of rice. The metabolomics results suggested some metabolites and pathways were affected by N 2 -MAPS and revealed that N 2 -MAPS could protect rice cells from oxidative damage, maintain cell integrity and stability by regulating the metabolism to delay the rice deterioration., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background and Purpose: Predicting tumour response would be useful for selecting patients with locally advanced rectal cancer (LARC) for organ preservation strategies. We aimed to develop and validate a prediction model for T downstaging (ypT0-2) in LARC patients after neoadjuvant chemoradiotherapy and to identify those who may benefit from consolidation chemotherapy., Materials and Methods: cT3-4 LARC patients at three tertiary medical centers from January 2012 to January 2019 were retrospectively included, while a prospective cohort was recruited from June 2021 to March 2022. Eight filter (principal component analysis, least absolute shrinkage and selection operator, partial least-squares discriminant analysis, random forest)-classifier (support vector machine, logistic regression) models were established to select radiomic features. A nomogram combining radiomics and significant clinical features was developed and validated by calibration curve and decision curve analysis. Interaction test was conducted to investigate the consolidation chemotherapy benefits., Results: A total of 634 patients were included (426 in training cohort, 174 in testing cohort and 34 in prospective cohort). A radiomic prediction model using partial least-squares discriminant analysis and a support vector machine showed the best performance (AUC: 0.832 [training]; 0.763 [testing]). A nomogram combining radiomics and clinical features showed significantly better prognostic performance (AUC: 0.842 [training]; 0.809 [testing]) than the radiomic model. The model was also tested in the prospective cohort with AUC 0.727. High-probability group (score > 81.82) may have potential benefits from ≥ 4 cycles consolidation chemotherapy (OR: 4.173, 95 % CI: 0.953-18.276, p = 0.058, p interaction  = 0.021)., Conclusion: We identified and validated a model based on multicenter pre-treatment radiomics to predict ypT0-2 in cT3-4 LARC patients, which may facilitate individualised treatment decision-making for organ-preservation strategies and consolidation chemotherapy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

The producing area of Chinese white tea has been expanded to Xinyang and Yunnan from Fuding region. In this study, six sensory tastes and fifty-one chemical components including seventeen phenolic compounds, three purine alkaloids and twenty amino acids were determined in eighteen Bai mudan sub-type of white tea by electronic tongue, high performance liquid chromatography and amino acid analyzer for geographical identification, respectively. Additionally, in vitro antioxidant activities were evaluated by five various assays. Multivariate statistical analyses such as PCA, HCA and PLS-DA, completely divided these white teas into Xinyang, Yunnan and Fuding groups, indicating the feasibility of white tea classification by the production region. Twelve characteristic compounds (VIP > 1.0, P  < 0.05) like gallic acid, theaflavin and L-glutamic acid contributed to the geographical identification. In conclusion, this study explored the chemical, taste and antioxidant capacity differences among three main production regions, and revealed their potential relations in white tea., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Anaemia remains among the most prevalent nutritional problems among children in developing countries. In Ethiopia, more than half of children <5 years of age are anaemic. In the early stages of life, it leads to poor cognitive performance, delay psychomotor development and decreases working capacity in later life. The present study aimed to assess the prevalence and associated factors of anaemia among children aged 6-23 months in the Bale zone. A community-based cross-sectional study was conducted from 1 to 30 June 2021. Multistage stratified sampling and simple random sampling techniques were employed to select 770 samples. An interviewer-administered questionnaire was used to collect data on socio-demographic, child health and feeding practices. Haemoglobin levels were estimated using a portable Hemosmart machine. Children with haemoglobin values below 11 g/dl were considered anaemic. Binary logistic regression analysis was performed to identify factors associated with anaemia. Statistical significance was set at P < 0⋅05. The prevalence of anaemia was 47⋅9 % (95 % CI (44⋅4, 51⋅5)). The multivariate analysis showed that child age (6-11 months) (AOR 1⋅47; 95 % CI (1⋅06, 2⋅03)), household food insecurity (AOR 1⋅44; 95 % CI (1⋅01, 2⋅04)), having diarrhoea and cough in the past 2 weeks (AOR 1⋅70; 95 % CI (1⋅18, 2⋅44)) and (AOR 1⋅97; 95 % CI (1⋅28, 3⋅04), respectively), not consuming the recommended dietary diversity (AOR 2⋅72; 95 % CI (1⋅96, 3⋅77)) and stunting (AOR 1⋅88; 95 % CI (1⋅31, 2⋅70)) were significantly associated with anaemia. Anaemia in children aged 6-23 months was a severe public health problem in the study area. Integrated nutritional interventions combined with iron fortification and supplementation is recommended., (© The Author(s) 2022.)

Green tea processed from albino tea varieties often has umami taste and fresh aroma. This study identified green teas made from two types of albino tea cultivar, one having the white shoots (called Naibai, NB) and the other having the yellow shoots (called Huangjinya, HJY). Taste compounds analyses showed that galloylated catechins were highly concentrated in HJY green teas, whereas non-galloylated catechins and amino acids were more abundant in NB green teas. CsTA (involved in the catabolism of galloylated catechins) showed high expression in HJY tea shoots, resulting in gallic acid as a precursor for β -glucogallin biosynthesis being abundant in HJY. CsPDX2.1 (responsible for theanine hydrolyzation) had a lower expression level in NB than HJY shoots. Fatty acid-derived volatiles (FADVs), glycosidically bound volatiles (GBVs) and carotenoid-derived volatiles (CDVs) were highly concentrated in HJY green teas, whereas amino acids-derived volatiles were highly concentrated in NB green teas., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Background & Aims: Histological assessment of liver biopsies is the gold standard for diagnosis of non-alcoholic steatohepatitis (NASH), the progressive form of non-alcoholic fatty liver disease (NAFLD), despite its well-established limitations. Therefore, non-invasive biomarkers that can offer an integrated view of the liver are needed to improve diagnosis and reduce sampling bias. Hepatic stellate cells (HSCs) are central in the development of hepatic fibrosis, a hallmark of NASH. Secreted HSC-specific proteins may, therefore, reflect disease state in the NASH liver and serve as non-invasive diagnostic biomarkers., Methods: We performed RNA-sequencing on liver biopsies from a histologically characterised cohort of obese patients (n = 30, BMI >35 kg/m 2 ) to identify and evaluate HSC-specific genes encoding secreted proteins. Bioinformatics was used to identify potential biomarkers and their expression at single-cell resolution. We validated our findings using single-molecule fluorescence in situ hybridisation (smFISH) and ELISA to detect mRNA in liver tissue and protein levels in plasma, respectively., Results: Hepatic expression of SPARC-related modular calcium-binding protein 2 ( SMOC2 ) was increased in NASH compared to no-NAFLD ( p.adj <0.001). Single-cell RNA-sequencing data indicated that SMOC2 was primarily expressed by HSCs, which was validated using smFISH. Finally, plasma SMOC2 was elevated in NASH compared to no-NAFLD ( p <0.001), with a predictive accuracy of AUROC 0.88., Conclusions: Increased SMOC2 in plasma appears to reflect HSC activation, a key cellular event associated with NASH progression, and may serve as a non-invasive biomarker of NASH., Impact and Implications: Non-alcoholic fatty liver disease (NAFLD) and its progressive form, non-alcoholic steatohepatitis (NASH), are the most common forms of chronic liver diseases. Currently, liver biopsies are the gold standard for diagnosing NAFLD. Blood-based biomarkers to complement liver biopsies for diagnosis of NAFLD are required. We found that activated hepatic stellate cells, a cell type central to NAFLD pathogenesis, upregulate expression of the secreted protein SPARC-related modular calcium-binding protein 2 (SMOC2). SMOC2 was elevated in blood samples from patients with NASH and may hold promise as a blood-based biomarker for the diagnosis of NAFLD., Competing Interests: All authors declare that they have no conflicts of interest. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2022 The Author(s).)

Although aroma is one of the most essential factors determining the quality of Fu brick tea (FBT), the aroma profiles of FBTs from different manufacturing areas are rarely investigated. The aroma profiles of FBTs manufactured in five typical provinces of China were comprehensively analyzed on the basis of headspace gas chromatography-ion mobility spectrometry (HS-GC-IMS), headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS), sensory evaluation, odor activity value (OAV), and relative odor activity value (ROAV). HS-GC-IMS and HS-SPME-GC-MS identified 63 and 93 volatile organic compounds (VOCs), respectively. Multivariate statistical analysis indicated that the FBTs from different production regions had remarkably varied aromas. HS-SPME-GC-MS revealed that 27 VOCs (OAV >1) contributed to the overall aroma of the samples, of which 15 key differential compounds can effectively distinguish the aroma profiles of different FBTs. FBT from Shaanxi manifested a strong floral and fruity aroma; that from Hunan had a floral, grassy, and pine-woody aroma; that from Guizhou presented a grassy and herbal aroma; that from Guangxi exhibited a sweet, floral, and minty aroma; and that from Zhejiang possessed various fruit flavors and floral fragrance. OAV analysis identified the biomarkers responsible for the variation in the aroma characteristics of diverse FBTs. These biomarkers included linalool, 6-methyl-5-hepten-2-one, α-ionone, hexanal, and ethyl hexanoate. Sensory evaluation demonstrated that the infusion color and aroma of FBT samples from different provinces also greatly varied. Network correlation analysis revealed that Aspergillus and Eurotium were the crucial microorganisms for the metabolism and formation of VOCs. These findings provide new insight into the VOCs and fragrance features of FBTs produced in different regions of China., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Transcriptome level expression data connected to the spatial organization of the cells and molecules would allow a comprehensive understanding of how gene expression is connected to the structure and function in the biological systems. The spatial transcriptomics platforms may soon provide such information. However, the current platforms still lack spatial resolution, capture only a fraction of the transcriptome heterogeneity, or lack the throughput for large scale studies. The strengths and weaknesses in current ST platforms and computational solutions need to be taken into account when planning spatial transcriptomics studies. The basis of the computational ST analysis is the solutions developed for single-cell RNA-sequencing data, with advancements taking into account the spatial connectedness of the transcriptomes. The scRNA-seq tools are modified for spatial transcriptomics or new solutions like deep learning-based joint analysis of expression, spatial, and image data are developed to extract biological information in the spatially resolved transcriptomes. The computational ST analysis can reveal remarkable biological insights into spatial patterns of gene expression, cell signaling, and cell type variations in connection with cell type-specific signaling and organization in complex tissues. This review covers the topics that help choosing the platform and computational solutions for spatial transcriptomics research. We focus on the currently available ST methods and platforms and their strengths and limitations. Of the computational solutions, we provide an overview of the analysis steps and tools used in the ST data analysis. The compatibility with the data types and the tools provided by the current ST analysis frameworks are summarized., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Prediction models for major nutrients of rice were built using near-infrared (NIR) spectral data based on the artificial neural network (ANN). Scientific interpretation of the weight values was proposed and performed to understand the wavenumbers contributing to the prediction of nutrients. NIR spectra were acquired from 110 rice samples. Carbohydrate and moisture contents were predicted with values for the determination coefficient, relative root mean square error, range error ratio, and residual prediction deviation of 0.98, 0.11 %, 44, and 7.3, and 0.97, 0.80 %, 27, and 5.8, respectively. The results agreed well with ones reported in the previous studies and acquired by the conventional partial least squares (PLS)-variable importance in projection method. This study demonstrates that the combination of NIR and ANN is a powerful and accurate tool to monitor nutrients of rice and scientific interpretation of weights can be performed to overcome black box nature of the ANN., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

This study examined the changes in metabolites together with the flavor profiles of germinated Sacha inchi seeds during roasting by using gas chromatography. The results indicated that roasting partially increased the browning index, amino acid levels, total phenolic content, and antioxidant capacity, but slightly decreased the levels of reducing sugars. Oxidized and rancid compounds were significantly decreased at a 180 °C roasting temperature. Pyrazine, furan, and pyrrole were Maillard reaction products that were increased at 180 °C of roasting. Roasting at 145 °C for 45 min after germination for 4 days was determined to be the optimal conditions for roasting germinated Sacha inchi seeds, which reduced the off-flavor and burned taste. The roasted germinated Sacha inchi seed contains higher amino acids than raw seed, which could be used as an alternative source for food products and supplements. In addition, the roasted germinated seeds at 4 days were recommended for food applications., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Supercritical carbon-dioxide (SC-CO 2 ) is a promising two-phase technology for flavor components (volatile oil and alkylamides) extract from Zanthoxylum bungeanum pericarp. However, the gastric protective effect of SC-CO 2 extract from Z. bungeanum (SZB) have not been systematically investigated. In this study, response surface methodology (RSM) was employed to optimize the yield of SZB, and the average yield of 11.07 % were obtained under optimal parameters (30 MPa, 43 °C and time 75 min). Here, limonene, linalool and hydroxy-α-sanshool were identified as the main compounds of SZB by GC-MS and UPLC-Q-Extractive Orbitrap/MS analysis. When the gastric protective effect of SZB (5, 10 and 20 mg/kg, p.o.) were evaluated, significant increase in body weight and organ indexes of rat, and decreased gastric lesion were observed. Furthermore, nineteen serum metabolites were regarded as the potential biomarkers for the gastric protective effect of SZB. Collectively, this study provides a comprehensive perspective into the chemical composition analysis and gastric protective effect of Z. bungeanum SC-CO 2 extract., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors. Published by Elsevier Ltd.)

The aroma of the fermented milk produced by twenty-eight Lactobacillus delbrueckii subsp. bulgaricus strains was evaluated via quantitative descriptive analysis. According to the sensory analysis results, the fermented milks were grouped into milky-type, cheesy-type, fermented-type and miscellaneous-type. The representative samples of cheese-type and fermented-type were analyzed by headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) and flavoromics. A total of 95 volatile compounds were identified and particularly, 12 aroma-active compounds were detected by using gas chromatography-olfactometry-mass spectrometry (GC-O-MS). Among the different aroma types, 2,3-butanedione, δ-decalactone, acetaldehyde, butanoic acid, acetic acid and hexanoic acid were finally screened out as the key aroma-active compounds by quantitative and odor activity value (OAV) analysis combined with aroma recombination, omission and addition experiments. These findings were valuable in developing specific fermented milk products with different aroma profiles., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Background: Low-grade inflammation has been implicated in the pathophysiology of severe mental disorders (SMDs) and a link between immune activation and clinical characteristics is suggested. However, few studies have investigated how patterns across immune markers are related to diagnosis and illness course., Methods: A total of 948 participants with a diagnosis of schizophrenia (SCZ, N = 602) or bipolar (BD, N = 346) spectrum disorder, and 814 healthy controls (HC) were included. Twenty-five immune markers comprising cell adhesion molecules (CAMs), interleukin (IL)-18-system factors, defensins, chemokines and other markers, related to neuroinflammation, blood-brain barrier (BBB) function, inflammasome activation and immune cell orchestration were analyzed. Eight immune principal component (PC) scores were constructed by PC Analysis (PCA) and applied in general linear models with diagnosis and illness course characteristics., Results: Three PC scores were significantly associated with a SCZ and/or BD diagnosis (HC reference), with largest, however small, effect sizes of scores based on CAMs, BBB markers and defensins (p < 0.001, partial η 2  = 0.02-0.03). Number of psychotic episodes per year in SCZ was associated with a PC score based on IL-18 system markers and the potential neuroprotective cytokine A proliferation-inducing ligand (p = 0.006, partial η 2  = 0.071)., Conclusion: Analyses of composite immune markers scores identified specific patterns suggesting CAMs-mediated BBB dysregulation pathways associated with SMDs and interrelated pro-inflammatory and neuronal integrity processes associated with severity of illness course. This suggests a complex pattern of immune pathways involved in SMDs and SCZ illness course., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ole A. Andreassen reports a relationship with HealthLytix that includes: consulting or advisory. Ole A. Andreassen reports a relationship with Lundbeck that includes: speaking and lecture fees. Ole A. Andreassen reports a relationship with Sunovion that includes: speaking and lecture fees., (© 2022 The Author(s).)

Gallic acid (GA) is a natural polyphenolic compound with many health benefits. To assess the potential risk of long-term consumption of GA to gut health, healthy dogs were fed a basal diet supplemented with GA (0%, 0.02%, 0.04%, and 0.08%) for 45 d, and fecal microbiota and metabolomics were evaluated. This study demonstrated that GA supplementation regulated serum lipid metabolism by reducing serum triglyceride, fat digestibility, and Bacteroidetes/Firmicutes ratio. In addition, the relative abundance of Parasutterella was significantly lower, and the SCFAs-producing bacteria were increased along with fecal acetate and total SCFAs contents accumulation in the 0.08% GA group. Metabolomics data further elucidated that 0.08% GA significantly affected carbohydrate metabolism by downregulating succinic acid in fece, thereby alleviating inflammation and oxidative stress. Overall, this study confirmed the beneficial effects of long-term consumption of GA on lipid metabolism and gut health, and the optimal level of GA supplementation was 0.08%., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

KDM6A is the disease causative gene of type 2 Kabuki Syndrome, a rare multisystem disease; it is also a known cancer driver gene, with multiple somatic mutations found in a few cancer types. In this study, we looked at eleven missense variants in lung squamous cell carcinoma, one of the most common lung cancer subtypes, to see how they affect the KDM6A catalytic mechanisms. We found that they influence the interaction with histone H3 and the exposure of the trimethylated Lys27, which is critical for wild-type physiological function to varying degrees, by altering the conformational transition., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Purpose: Endotheliopathy of trauma (EoT), as defined by circulating levels of syndecan-1 ≥ 40 ng/mL, has been reported to be associated with significantly increased transfusion requirements and a doubled 30-day mortality. Increased shedding of the glycocalyx points toward the endothelial cell membrane composition as important for the clinical outcome being the rationale for this study., Results: The plasma metabolome of 95 severely injured trauma patients was investigated by mass spectrometry, and patients with EoT vs. non-EoT were compared by partial least square-discriminant analysis, identifying succinic acid as the top metabolite to differentiate EoT and non-EoT patients (VIP score = 3). EoT and non-EoT patients' metabolic flux profile was inferred by integrating the corresponding plasma metabolome data into a genome-scale metabolic network reconstruction analysis and performing a functional study of the metabolic capabilities of each group. Model predictions showed a decrease in cholesterol metabolism secondary to impaired mevalonate synthesis in EoT compared to non-EoT patients. Intracellular task analysis indicated decreased synthesis of thromboxanA2 and leukotrienes, as well as a lower carnitine palmitoyltransferase I activity in EoT compared to non-EoT patients. Sensitivity analysis also showed a significantly high dependence of eicosanoid-associated metabolic tasks on alpha-linolenic acid as unique to EoT patients., Conclusions: Model-driven analysis of the endothelial cells' metabolism identified potential novel targets as impaired thromboxane A2 and leukotriene synthesis in EoT patients when compared to non-EoT patients. Reduced thromboxane A2 and leukotriene availability in the microvasculature impairs vasoconstriction ability and may thus contribute to shock in EoT patients. These findings are supported by extensive scientific literature; however, further investigations are required on these findings., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

With the advancement of blueberry industrialization, cultivation measures for obtaining high-quality fruits and technologies for obtaining high levels of the main secondary metabolites have become inevitable requirements for further development of the blueberry industry. This study applied different shading treatments and found that the FT1 shading treatment yielded the largest values for the single fruit weight, solid longitudinal diameter and transverse diameter of blueberry fruit as well as the highest solidity-acid ratio and total phenol and vitamin C contents. Moreover, 470 known metabolites were obtained from blueberry fruits. Interestingly, the differentially abundant metabolites related to ABC transporters, pyrimidine metabolism, and purine metabolism pathways were commonly identified from the three comparisons, which indicated that these three metabolic pathways in blueberry fruits are vulnerable to shading treatment. This study provides a theoretical basis for the application of summer shading to improve the quality and antioxidant substances of small berries., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Objective: To obtain complete DNA sequences of adenoviral (AdV) D8 genome from patients with conjunctivitis and determine the relation of sequence variation to clinical outcomes., Design: This study is a post hoc analysis of banked conjunctival swab samples from the BAYnovation Study, a previously conducted, randomized controlled clinical trial for AdV conjunctivitis., Participants: Ninety-six patients with AdV D8-positive conjunctivitis who received placebo treatment in the BAYnovation Study were included in the study., Methods: DNA from conjunctival swabs was purified and subjected to whole-genome viral DNA sequencing. Adenovirus D8 variants were identified and correlated with clinical outcomes, including 2 machine learning methods., Main Outcome Measures: Viral DNA sequence and development of subepithelial infiltrates (SEIs) were the main outcome measures., Results: From initial sequencing of 80 AdV D8-positive samples, full adenoviral genome reconstructions were obtained for 71. A total of 630 single-nucleotide variants were identified, including 156 missense mutations. Sequence clustering revealed 3 previously unappreciated viral clades within the AdV D8 type. The likelihood of SEI development differed significantly between clades, ranging from 83% for Clade 1 to 46% for Clade 3. Genome-wide analysis of viral single-nucleotide polymorphisms failed to identify single-gene determinants of outcome. Two machine learning models were independently trained to predict clinical outcome using polymorphic sequences. Both machine learning models correctly predicted development of SEI outcomes in a newly sequenced validation set of 16 cases ( P = 1.5 × 10 -5 ). Prediction was dependent on ensemble groups of polymorphisms across multiple genes., Conclusions: Adenovirus D8 has ≥ 3 prevalent molecular substrains, which differ in propensity to result in SEIs. Development of SEIs can be accurately predicted from knowledge of full viral sequence. These results suggest that development of SEIs in AdV D8 conjunctivitis is largely attributable to pathologic viral sequence variants within the D8 type and establishes machine learning paradigms as a powerful technique for understanding viral pathogenicity., (© 2022 Published by Elsevier Inc. on behalf of the American Academy of Ophthalmology.)

Abstract: 6,7-Dimethylesculetin (D), geniposide (G) and rhein (R) are the three major active ingredients of Yin-Chen-Hao-Tang (YCHT), a famous Chinese herbal formula, which has been shown to be clinically effective for treating hepatic injury (HI) syndrome. The present study was conducted to investigate the therapeutic and synergistic effects of COC (combination of D, G and R) on HI rats by combining pharmacokinetic with biochemical analysis strategy. Plasma was analyzed by using reversed-phase high performance liquid chromatography (RP-HPLC). Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) models were built to evaluate the therapeutic and synergistic effects of COC at the biochemical level. Here, we report that the COC combination could increase the plasma level, slow elimination rate, exert a more robust therapeutic effect than any one or two of the three individual compounds by hitting multiple targets in a rat model of HI. Overall, this beneficially accounts for the popular view that traditional Chinese medicine (TCM) formula usually takes multi-component to exert their therapeutic effects. We suggest that dissecting the mode of action of clinically effective formula to be capable of producing a sufficient effect at low doses. [Copyright &y& Elsevier]

• By modifying FSCV components, simultaneous fMRI data can be acquired with minimal imaging artifacts. • We detect and quantify evoked dopamine and/or tissue oxygen changes using FSCV during BOLD fMRI. • FSCV-fMRI is used to derive a neurotransmitter-inclusive hemodynamic response function (HRF). • Dopamine-derived HRFs can identify brain regions that encode dopamine release amplitude. The vascular contributions of neurotransmitters to the hemodynamic response are gaining more attention in neuroimaging studies, as many neurotransmitters are vasomodulatory. To date, well-established electrochemical techniques that detect neurotransmission in high magnetic field environments are limited. Here, we propose an experimental setting enabling simultaneous fast-scan cyclic voltammetry (FSCV) and blood oxygenation level-dependent functional magnetic imaging (BOLD fMRI) to measure both local tissue oxygen and dopamine responses, and global BOLD changes, respectively. By using MR-compatible materials and the proposed data acquisition schemes, FSCV detected physiological analyte concentrations with high temporal resolution and spatial specificity inside of a 9.4 T MRI bore. We found that tissue oxygen and BOLD correlate strongly, and brain regions that encode dopamine amplitude differences can be identified via modeling simultaneously acquired dopamine FSCV and BOLD fMRI time-courses. This technique provides complementary neurochemical and hemodynamic information and expands the scope of studying the influence of local neurotransmitter release over the entire brain. [ABSTRACT FROM AUTHOR]