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Background: Pseudomonas juntendi is a newly identified opportunistic pathogen, of which we have limited understanding. P. juntendi strains are often multidrug resistant, which complicates clinical management of infection. Methods: A strain of Pseudomonas juntendi (strain L4326) isolated from feces was characterized by MALDI-TOF-MS and Average Nucleotide Identity BLAST. This strain was further subject to whole-genome sequencing and Maximum Likelihood phylogenetic analysis. The strain was phenotypically characterized by antimicrobial susceptibility testing and conjugation assays. Results: We have isolated the novel P. juntendi strain L4236, which was multidrug resistant, but retained sensitivity to amikacin. L4236 harbored a megaplasmid that encoded blaOXA−1 and a novel blaIMP−1 resistance gene variant. P. juntendi strain L4236 was phylogenetically related to P. juntendi strain SAMN30525517. Conclusion: A rare P. juntendi strain was isolated from human feces in southern China with a megaplasmid coharboring blaIMP−1−like and blaOXA−1. Antimicrobial selection pressures may have driven acquisition of drug-resistance gene mutations and carriage of the megaplasmid. [ABSTRACT FROM AUTHOR]

Nitrogen (N2) fixation in oligotrophic surface waters is the main source of new nitrogen to the ocean1 and has a key role in fuelling the biological carbon pump2. Oceanic N2 fixation has been attributed almost exclusively to cyanobacteria, even though genes encoding nitrogenase, the enzyme that fixes N2 into ammonia, are widespread among marine bacteria and archaea3–5. Little is known about these non-cyanobacterial N2 fixers, and direct proof that they can fix nitrogen in the ocean has so far been lacking. Here we report the discovery of a non-cyanobacterial N2-fixing symbiont, ‘Candidatus Tectiglobus diatomicola’, which provides its diatom host with fixed nitrogen in return for photosynthetic carbon. The N2-fixing symbiont belongs to the order Rhizobiales and its association with a unicellular diatom expands the known hosts for this order beyond the well-known N2-fixing rhizobia–legume symbioses on land6. Our results show that the rhizobia–diatom symbioses can contribute as much fixed nitrogen as can cyanobacterial N2 fixers in the tropical North Atlantic, and that they might be responsible for N2 fixation in the vast regions of the ocean in which cyanobacteria are too rare to account for the measured rates.A symbiosis between a diatom and a newly discovered species of alphaproteobacteria, ‘Candidatus Tectiglobus diatomicola’, can fix nitrogen in the ocean, providing evidence that nitrogen fixers other than cyanobacteria have a key role in the marine environment. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a chronic inflammatory disease characterized by cartilage destruction, synovitis, and osteophyte formation. Disease‐modifying treatments for OA are currently lacking. Because inflammation mediated by an imbalance of M1/M2 macrophages in the synovial cavities contributes to OA progression, regulating the M1 to M2 polarization of macrophages can be a potential therapeutic strategy. Basing on the inherent immune mechanism and pathological environment of OA, an immunoglobulin G‐conjugated bilirubin/JPH203 self‐assembled nanoparticle (IgG/BRJ) is developed, and its therapeutic potential for OA is evaluated. After intra‐articular administration, IgG conjugation facilitates the recognition and engulfment of nanoparticles by the M1 macrophages. The internalized nanoparticles disassemble in response to the increased oxidative stress, and the released bilirubin (BR) and JPH203 scavenge reactive oxygen species (ROS), inhibit the nuclear factor kappa‐B pathway, and suppress the activated mammalian target of rapamycin pathway, result in the repolarization of macrophages and enhance M2/M1 ratios. Suppression of the inflammatory environment by IgG/BRJ promotes cartilage protection and repair in an OA rat model, thereby improving therapeutic outcomes. This strategy of opsonization involving M1 macrophages to engulf carrier‐free BR/JPH203 nanoparticles to suppress inflammation for OA therapy holds great potential for OA intervention and treatment. [ABSTRACT FROM AUTHOR]

Prodrugs have been explored as an alternative to conventional chemotherapy; however, their target specificity remains limited. The tumor microenvironment harbors a range of microorganisms that potentially serve as tumor-targeting vectors for delivering prodrugs. In this study, we harness bacteria-cancer interactions native to the tumor microbiome to achieve high target specificity for prodrug delivery. We identify an oral commensal strain of Lactobacillus plantarum with an intrinsic cancer-binding mechanism and engineer the strain to enable the surface loading of anticancer prodrugs, with nasopharyngeal carcinoma (NPC) as a model cancer. The engineered commensals show specific binding to NPC via OppA-mediated recognition of surface heparan sulfate, and the loaded prodrugs are activated by tumor-associated biosignals to release SN-38, a chemotherapy compound, near NPC. In vitro experiments demonstrate that the prodrug-loaded microbes significantly increase the potency of SN-38 against NPC cell lines, up to 10-fold. In a mouse xenograft model, intravenous injection of the engineered L. plantarum leads to bacterial colonization in NPC tumors and a 67% inhibition in tumor growth, enhancing the efficacy of SN-38 by 54%. The chemotherapeutic efficacy of prodrug is limited by its cancer-targeting ability. Here this group reports an engineered commensal Lactobacillus plantarum strain with anticancer prodrugs loading on the surface for nasopharyngeal carcinoma cell-targeting and growth inhibition. [ABSTRACT FROM AUTHOR]

Here we presented an electrophysiological dataset collected from layer V of the primary motor cortex (M1) and the corresponding behavior dataset from normal and hemi-parkinson rats over 5 consecutive weeks. The electrophysiological dataset was constituted by the raw wideband signal, neuronal spikes, and local field potential (LFP) signal. The open-field test was done and recorded to evaluate the behavior variation of rats among the entire experimental cycle. We conducted technical validation of this dataset through sorting the spike data to form action potential waveforms and analyzing the spectral power of LFP data, then based on these findings a closed-loop DBS protocol was developed by the oscillation activity response of M1 LFP signal. Additionally, this protocol was applied to the hemi-parkinson rat for five consecutive days while simultaneously recording the electrophysiological data. This dataset is currently the only publicly available dataset that includes longitudinal closed-loop DBS recordings, which can be utilized to investigate variations of neuronal activity within the M1 following long-term closed-loop DBS, and explore additional reliable biomarkers. [ABSTRACT FROM AUTHOR]

Simple Summary: Two subspecies of largemouth bass (Micropterus salmoides, LMB) with different thermal tolerance, northern largemouth bass (NLMB) and Florida largemouth bass (FLMB), were subjected to acute and chronic thermal stress at 33 °C. Then, variations of 12 candidate biomarkers between NLMB and FLMB were analyzed. Compared to NLMB, FLMB exhibited a lower plasma cortisol level and a higher expression of hsp90 under acute thermal stress. Additionally, lower expression of hsp70 in FLMB was observed under chronic thermal stress. The differences in plasma cortisol levels and hsp expression represent variations in thermal tolerance between the two subspecies of LMB, providing valuable information for the identification and breeding of LMB varieties with better thermal tolerance in the future. Affected by the continuously rising temperature, thermal stress leads to a delinked growth rate and resistance to stress in cultured largemouth bass (Micropterus salmoides, LMB) in China. Identification of LMB with better thermal resistance will benefit the breeding of new varieties. However, there has been limited reporting on the evaluation to identify LMB with better thermal resistance. LMB consists of the northern LMB (Micropterus salmoides salmoides, NLMB) and the Florida LMB (Micropterus salmoides floridanus, FLMB). Due to their different geographical distributions, it has been suggested that FLMB exhibit better thermal resistance compared to NLMB. In this study, NLMB and FLMB were subjected to thermal stress for 3 h (acute) and 60 d (chronic) at 33 °C, respectively. Subsequently, the variations of 12 candidate biomarkers between NLMB and FLMB were analyzed. Exposure to acute thermal stress significantly increased plasma cortisol, blood glucose, and lactate levels; activities of superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT), glucose kinase (GK), pyruvate kinase (PK), lactate dehydrogenase (LDH), and glucose 6 phosphatase (G6Pase); and the expressions of hsp70 and hsp90 in both NLMB and FLMB (p < 0.05). Compared to NLMB, FLMB exhibited a lower plasma cortisol level and a higher expression of hsp90 under acute thermal stress (p < 0.05). Exposure to chronic thermal stress significantly increased plasma cortisol and blood glucose levels, as well as activities of GK, PK, LDH, and G6Pase, as well as expressions of hsp70 and hsp90 in both NLMB and FLMB (p < 0.05). Additionally, FLMB showed a lower expression of hsp70 compared to NLMB (p < 0.05). In conclusion, our results showed that LMB with lower plasma cortisol level and higher expression of hsp90 under acute thermal stress, as well as lower expression of hsp70 under chronic thermal stress were suggested to have better thermal resistance. Our study provides valuable information for identifying and breeding LMB varieties with better thermal resistance in the future. [ABSTRACT FROM AUTHOR]

Environmental stressors such as drought, salinity, and heavy metals pose significant obstacles to achieving sustainable food security, necessitating the development of universally applicable and cost-effective solutions to ameliorate soil under stress. Biochar, an eco-friendly material to increase crop yield, has been researched for almost two decades and has great potential for global use in enhancing stress resistance. However, there hasn't been comprehensive research on the impact of biochar application on soil properties, and root and crop growth. To optimize and promote biochar application in agriculture under stress, this study integrates over 100 peer-reviewed articles to explain how biochar promotes crop growth by enhancing soil resistance to stress. Biochar's distinctive properties, such as porous structure, alkaline nature, enriched surface functional groups, and nutrient content, are responsible for the following soil environment benefits: improved soil physiochemical properties, increased nutrient cycling, and boosted microbial growth. Moreover, the research emphasizes that the enhanced stress resistance of biochar optimizes nutrient absorption, alleviates soil pollutants, and thereby enhances overall crop productivity. The study discusses the roles and mechanisms of biochar on soil under stress, as well as the challenges linked to the sustainable and economical implementation of biochar in extreme soil conditions. This review aims to provide a theoretical basis for the widespread and cost-effective use of biochar in improving soil under stresses, thereby enhancing soil health and food security. Highlights: Biochar's physicochemical properties help with stress resilience. Biochar's effect on multiple stresses mitigation promotes soil nutrients circulating. Biochar provides virtuous cycles for crop stress resistance and root growth. [ABSTRACT FROM AUTHOR]

Innate immune response is the first line of host defense against pathogenic microorganisms, and its excessive or insufficient activation is detrimental to the organism. Many individual microRNAs (miRNAs) have emerged as crucial post-transcriptional regulators of immune homeostasis in Drosophila melanogaster. However, the synergistical regulation of miRNAs located within a cluster on the Imd-immune pathway remains obscured. In our study, a genetic screening with 52 transgenic UAS-miRNAs was performed to identify ten miRNAs or miRNA clusters, including the miR310~313 cluster, which may function on Imd-dependent immune responses. The miRNA RT-qPCR analysis showed that the expression of miR-310~313 cluster members exhibited an increase at 6–12 h post E. coli infection. Furthermore, the overexpression of the miR-310~313 cluster impaired the Drosophila survival. And the overexpression of miR-310/311/312 reduced Dpt expression, an indication of Imd pathway induced by Gram-negative bacteria. Conversely, the knockdown of miR-310/311/312 led to increases in Dpt expression. The Luciferase reporter expression assays and RT-qPCR analysis confirmed that miR-310~313 cluster members directly co-targeted and inhibited Imd transcription. These findings reveal that the members of the miR-310~313 cluster synergistically inhibit Imd-dependent immune responses by co-targeting the Imd gene in Drosophila. [ABSTRACT FROM AUTHOR]

Background: Retinal detachment (RD) is a vision-threatening disorder of significant severity. Individuals with high myopia (HM) face a 2 to 6 times higher risk of developing RD compared to non-myopes. The timely identification of high myopia-related retinal detachment (HMRD) is crucial for effective treatment and prevention of additional vision impairment. Consequently, our objective was to streamline and validate a machine-learning model based on clinical laboratory omics (clinlabomics) for the early detection of RD in HM patients. Methods: We extracted clinlabomics data from the electronic health records for 24,440 HM and 5607 HMRD between 2015 and 2022. Lasso regression analysis assessed fifty-nine variables, excluding collinear variables (variance inflation factor > 10). Four models based on random forest, gradient boosting machine (GBM), generalized linear model, and Deep Learning Model were trained for HMRD diagnosis and employed for internal validation. An external test of the models was done. Three random data sets were further processed to validate the performance of the diagnostic model. The primary outcomes were the area under the receiver operating characteristic curve (AUC) and the area under the precision-recall curve (AUCPR) to diagnose HMRD. Results: Nine variables were selected by all models. Given the AUC and AUCPR values across the different sets, the GBM model was chosen as the final diagnostic model. The GBM model had an AUC of 0.8550 (95%CI = 0.8322–0.8967) and an AUCPR of 0.5584 (95%CI = 0.5250–0.5879) in the training set. The AUC and AUCPR in the internal validation were 0.8405 (95%CI = 0.8060–0.8966) and 0.5355 (95%CI = 0.4988–0.5732). During the external test evaluation, it reached an AUC of 0.7579 (95%CI = 0.7340–0.7840) and an AUCPR of 0.5587 (95%CI = 0.5345–0.5880). A similar discriminative capacity was observed in the three random data sets. The GBM model was well-calibrated across all the sets. The GBM-RD model was implemented into a web application that provides risk prediction for HM individuals. Conclusion: GBM algorithms based on nine features successfully predicted the diagnosis of RD in patients with HM, which will help ophthalmologists to establish a preliminary diagnosis and to improve diagnostic accuracy in the clinic. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the effectiveness of different biomarkers to identify the levels of protein oxidation in pork patties induced by assorted cooking methods. To achieve this purpose, pork patties prepared from longissimus dorsi were cooked using three methods (frying, steaming, and roasting) at different internal temperatures (60, 70, 80, and 90 °C). Traditional biomarkers including total carbonyl and total thiol and novel biomarkers including α-aminoadipic semialdehyde (AAS) and lysinonorleucine (LNL) were determined. Results demonstrated that total thiol and AAS were the most successful biomarkers in distinguishing the three cooking methods in relation to protein oxidation, with AAS being the most sensitive. Moreover, as indicated by the biomarkers of total thiol and AAS, frying caused the highest level of protein oxidation, while steaming resulted in the lowest level when pork patties were cooked to the internal temperatures of 70 or 80 °C. [ABSTRACT FROM AUTHOR]

Quantitative phase imaging (QPI) provides 3D structural and morphological information for label free living cells. Unfortunately, this quantitative phase information cannot meet doctors' diagnostic requirements of the clinical "gold standard," which displays stained cells' pathological states based on 2D color features. To make QPI results satisfy the clinical "gold standard," the virtual staining method by QPI for label free lymphocytes based on self-supervised iteration Cycle-Consistent Adversarial Networks (CycleGANs) is proposed herein. The 3D phase information of QPI is, therefore, trained and transferred to a kind of 2D "virtual staining" image that is well in agreement with "gold standard" results. To solve the problem that unstained QPI and stained "gold standard" results cannot be obtained for the same label free living cell, the self-supervised iteration for the CycleGAN deep learning algorithm is designed to obtain a trained stained result as the ground truth for error evaluation. The structural similarity index of our virtual staining experimental results for 8756 lymphocytes is 0.86. Lymphocytes' area errors after converting to 2D virtual stained results from 3D phase information are less than 3.59%. The mean error of the nuclear to cytoplasmic ratio is 2.69%, and the color deviation from the "gold standard" is less than 6.67%. [ABSTRACT FROM AUTHOR]

To investigate the regulatory role of the cyp19a1b aromatase gene in the sexual differentiation of largemouth bass (Micropterus salmoides, LMB), we obtained the full-length cDNA sequence of cyp19a1b using rapid amplification of cDNA ends technique. Tissue expression characteristics and feedback with 17-β-estradiol (E2) were determined using quantitative real-time PCR (qRT-PCR), while gonad development was assessed through histological section observations. The cDNA sequence of LMB cyp19a1b was found to be1950 base pairs (bp) in length, including a 5′ untranslated region of 145 bp, a 3′ untranslated region of 278 bp, and an open reading frame encoding a protein consisting of 1527 bp that encoded 508 amino acids. The qRT-PCR results indicated that cyp19a1b abundantly expressed in the brain, followed by the gonads, and its expression in the ovaries was significantly higher than that observed in the testes (P < 0.05). After feeding fish with E2 for 30 days, the expression of cyp19a1b in the pseudo-female gonads (XY-F) was significantly higher than that in males (XY-M) (P < 0.05), whereas expression did not differ significantly between XX-F and XY-F fish (P > 0.05). Although the expression of cyp19a1b in XY-F and XX-F fish was not significantly different after 60 days (P>0.05), both exhibited significantly higher levels than that of XY-M fish (P<0.05). Histological sections analysis showed the presence of oogonia in both XY-F and XX-F fish at 30 days, while spermatogonia were observed in XY-M fish. At 60 days, primary oocytes were abundantly observed in both XY-F and XX-F fish, while a few spermatogonia were visible in XY-M fish. At 90 days, the histological sections' results showed that a large number of oocytes were visible in XY-F and XX-F fish. Additionally, the gonads of XY-M fish contained numerous spermatocytes. These results suggest that cyp19a1b plays a pivotal role in the development of ovaries and nervous system development in LMB. [ABSTRACT FROM AUTHOR]

Background: The genetic improvement in growth and food habit domestication of largemouth bass (Micropterus salmoides) have made breakthroughs in past decades, while the relevant work on disease resistance were rarely carried out. Major histocompatibility complex (MHC) genes, which are well known as their numbers and high polymorphisms, have been used as candidate genes to mine disease-resistant-related molecular markers in many species. Methods and results: In present study, we developed and characterized 40 polymorphic and biallelic InDel markers from the major histocompatibility complex genes of largemouth bass. The minor allele frequency, observed heterozygosity, expected heterozygosity and polymorphic information content of these markers ranged from 0.0556 to 0.5000, 0.1111 to 0.6389, 0.1064 to 0.5070, and 0.0994 to 0.3750, respectively. Three loci deviated significantly from Hardy-Weinberg equilibrium, while linkage disequilibrium existed at none of these loci. Conclusion: These InDel markers might provide references for the further correlation analysis and molecular assisted selection of disease resistance in largemouth bass. [ABSTRACT FROM AUTHOR]

Background: The genetic improvement in growth and food habit domestication of largemouth bass (Micropterus salmoides) have made breakthroughs in past decades, while the relevant work on disease resistance were rarely carried out. Major histocompatibility complex (MHC) genes, which are well known as their numbers and high polymorphisms, have been used as candidate genes to mine disease-resistant-related molecular markers in many species. Methods and results: In present study, we developed and characterized 40 polymorphic and biallelic InDel markers from the major histocompatibility complex genes of largemouth bass. The minor allele frequency, observed heterozygosity, expected heterozygosity and polymorphic information content of these markers ranged from 0.0556 to 0.5000, 0.1111 to 0.6389, 0.1064 to 0.5070, and 0.0994 to 0.3750, respectively. Three loci deviated significantly from Hardy-Weinberg equilibrium, while linkage disequilibrium existed at none of these loci. Conclusion: These InDel markers might provide references for the further correlation analysis and molecular assisted selection of disease resistance in largemouth bass. [ABSTRACT FROM AUTHOR]

Primary sclerosing cholangitis (PSC), a rare chronic cholestatic liver disease, is characterized by intrahepatic or extrahepatic strictures accompanied by biliary fibrosis. So far, there are no effective therapies to slow down the progression of this disease. Farnesoid X receptors (FXRs) are ligand-activated transcription factors involved in the control of bile acid (BA) synthesis and enterohepatic circulation. Therefore, targeting FXRs holds promise as a potential approach for treating PSC. Pediococcus pentosaceus Li05 is a probiotic that was isolated from healthy volunteers and has previously been shown to have an anti-inflammatory effect in DSS-induced colitis. In this study, we established a 3,5-diethoxycarbonyl-1,4-Dihydrocollidine (DDC)-induced cholestasis mouse model and investigated the effects of Pediococcus pentosaceus Li05 on PSC. Our findings revealed that administration of Li05 significantly attenuated liver damage, hepatic inflammation, and fibrosis, as well as bile duct hyperplasia. Li05 activated the hepatic FXR-SHP and ileal FXR-FGF15 signaling pathways to decrease the expression of Cyp7a1. In addition, the Li05-modulated gut microbiota structure especially improved the abundance of 7α-dehydroxylation bacteria like Eubacterium. The intervention of Li05 also improved the intestinal barrier and reduced bacterial endotoxin translocation. Based on these findings, Li05 shows promise for future application as a therapeutic strategy for cholestasis. [ABSTRACT FROM AUTHOR]

Objective: Pulmonary arterial hypertension (PAH) is a severe complication of systemic lupus erythematosus (SLE). However, the genetic signatures of SLE‐associated PAH have not been well studied. We aimed to identify genetic variants implicated in SLE‐associated PAH susceptibility within the major histocompatibility complex (MHC) region and assess the contribution to clinical outcomes. Methods: A total of 172 patients with SLE‐associated PAH confirmed by right heart catheterization, 1,303 patients with SLE without PAH, and 9,906 healthy controls were included. Deep sequencing of the MHC region was performed to identify alleles, single‐nucleotide polymorphisms, and amino acids. We compared patients with SLE‐associated PAH with patients with SLE without PAH and healthy controls. Clinical association study was conducted to explore the contribution to phenotypes. Results: A total of 19,881 genetic variants were identified within the MHC region. HLA‐DQA1*03:02 was identified as a novel genetic variant associated with SLE‐associated PAH in the discovery cohort (P = 5.68 × 10−12) and authenticated in an independent replication cohort (P = 1.30 × 10−9). The strongest associated amino acid position was mapped to HLA‐DQα1 in the region affecting MHC/peptide‐CD4+ T cell receptor affinity and antigen binding. Clinical association study demonstrated that patients with SLE‐associated PAH with HLA‐DQA1*03:02 had significantly lower rates of target role achievement (P = 0.005) and survival (P = 0.04). Conclusion: This study, based on the largest cohort of SLE‐associated PAH, is the first to investigate how MHC region genetic variants contribute to SLE‐associated PAH susceptibility. HLA‐DQA1*03:02 is a novel genetic risk factor and a prognostic factor in SLE‐associated PAH. Patients with SLE with this allele require regular monitoring and careful follow‐up for early diagnosis and interventions for potential PAH. [ABSTRACT FROM AUTHOR]

With the transformation and upgrading of the manufacturing industry and the advent of the industrial revolution, the complexity of part structures and the variety of materials have increased. The demand for cutting tool performance is becoming increasingly diverse, posing numerous challenges to the design and development of tools. By studying natural cutting phenomena, scholars have discovered that biological structures such as teeth and claws possess unique characteristics. The design and development of tools based on the imitation of these biological structures have become a new research direction. To address the high energy consumption and reduce cutting resistance in the cutting process, limpet teeth were prepared, and their geometric features were extracted. The structural features of limpet teeth were applied to the design of tool structures, and five bionic tools were designed and fabricated. Taking cutting force as the performance indicator, the cutting performance of the bionic tools was investigated by comparing them with conventional tools. The analysis of cutting forces found that effortless tool exhibited a significant force-saving effect, with a reduction in cutting force by 16.2%. Through a single-factor experiment, the influence of cutting parameters on the effortless tool was explored. The results showed that limpet bionic cutting tools with appropriate size parameters exhibited a significant force-saving effect, improving tool cutting performance. [ABSTRACT FROM AUTHOR]

The estrogen inhibits colonic smooth muscle contractions, which may lead to constipation. However, the mechanisms of inhibition are poorly understood. Therefore, the present study examined the effect of estrogen on rat colonic smooth muscle contractions and its potential association with the large-conductance Ca2+-activated K+ channels β1 (BKβ1) subunit. Twenty-four female Sprague Dawley rats were randomly assigned to 4 groups. After 2 weeks of intervention, the contraction activity of isolated colonic smooth muscle and the expression of BKβ1 in colonic smooth muscle of rats were detected. Additionally, in order to investigate the effects of estrogen on BKβ1 expression and calcium mobilization, in vitro experiments were conducted using rat and human colonic smooth muscle cells (SMCs). BKβ1 shRNA was used to investigate whether calcium mobilization is affected by BKβ1 in colonic SMCs. To explore the relationship between ERβ and BKβ1, serial deletions, site-directed mutagenesis, a dual-luciferase reporter assay, and chromatin immunoprecipitation assays were employed. In response to E2, colonic smooth muscle strips showed a decrease in tension, while IBTX exposure transiently increased tension. Furthermore, in these muscle tissues, BKβ1 and α-SMA were found to be co-expressed. The E2 group showed significantly higher BKβ1 expression. In cultured colonic SMCs, the expression of BKβ1 was found to increase in the presence of E2 or DPN. E2 treatment reduced Ca2+ concentrations, while BKβ1 shRNA treatment increased Ca2+ concentrations relative to the control. ERβ-initiated BKβ1 expression appears to occur via binding to the BKβ1 promoter. These results indicated that E2 may upregulate BKβ1 expression via ERβ and inhibit colonic smooth muscle contraction through ERβ by directly targeting BKβ1. [ABSTRACT FROM AUTHOR]

The stable isotope technique has been used in tracking nitrogen cycling processes, but the isotopic characteristics are influenced by environmental conditions. To better understand the variability of nitrate isotopes in nature, we investigated the influence of organic carbon sources on isotope fractionation characteristics during microbial denitrification. Denitrifying cultures were inoculated with freshwater samples and enriched with five forms of organic compounds, that is, acetate, citrate, glucose, cellobiose, and leucine. Though the isotope enrichment factors of nitrogen and oxygen (15ε and 18ε) changed with carbon sources, 18ε/15ε always followed a proportionality near 1. Genome‐centred metagenomics revealed the enrichment of a few populations, such as Pseudomonas, Enterobacter, and Atlantibacter, most of which contained both NapA‐ and NarG‐type nitrate reductases. Metatranscriptome showed that both NapA and NarG were expressed but to different extents in the enrichments. Furthermore, isotopic data collected from a deep reservoir was analysed. The results showed δ18O‐ and δ15N‐nitrate did not correlate in the surface water where nitrification was active, but 18ε/15ε followed a proportionality of 1.05 ± 011 in deeper waters (≥ 12 m) where denitrification controlled the nitrate isotope. The independence of 18ε/15ε from carbon sources provides an opportunity to determine heterotrophic denitrification and helps the interpretation of nitrate isotopes in freshwaters. [ABSTRACT FROM AUTHOR]

Acceptance of artificial pelleted diets contributes to increasing the cultured areas and output of carnivorous fish. However, the mechanism of acceptance of artificial pelleted diets remains largely unknown. In this study, the easy acceptance of artificial pelleted diets (EAD) group and the not easy acceptance of artificial pelleted diets (NAD) group of Largemouth bass (Micropterus salmoides) were divided based on the ratios of stomach weight/body weight (SB) after 0.5 h feeding, which was bigger than 18% in the EAD group and ranged from 8 to 12% in the NAD group. Through transcriptome and proteome sequencing, a total of 2463 differentially expressed genes (DEGs) and 230 differentially expressed proteins (DEPs) were identified, respectively. Integrated analyses of transcriptome and proteome data revealed that 152 DEPs were matched with the corresponding DEGs (named co-DEGs-DEPs), and 54 co-DEGs-DEPs were enriched in 16 KEGG pathways, including the metabolic pathways, steroid biosynthesis, fatty acid biosynthesis, etc. Furthermore, 3 terpenoid backbone biosynthesis-related genes (Hmgcr, Hmgcs, and Fdps) in metabolic pathways, 10 steroid biosynthesis-related genes (Fdft1, Sqle, Lss, Cyp51a1, Tm7sf2, Nsdhl, Hsd17b7, Dhcr24, Sc5d, and Dhcr7), and 3 fatty acid biosynthesis-related genes (Acaca, Fasn, and Ascl) were all up-regulated in the EAD group, suggesting that the lipid metabolism pathway and steroid biosynthesis pathway play important roles in early food habit domestication in Largemouth bass. In addition, the detection results of randomly selected 15 DEGs and 15 DEPs indicated that both transcriptome and proteome results in the study were reliable. Our study provides useful information for further research on the mechanisms of food habit domestication in fish. [ABSTRACT FROM AUTHOR]

It has been reported that Akkermansia muciniphila improves host metabolism and reduces inflammation; however, its potential effects on bile acid metabolism and metabolic patterns in metabolic‐associated fatty liver disease (MAFLD) are unknown. In this study, we have analysed C57BL/6 mice under three feeding conditions: (i) a low‐fat diet group (LP), (ii) a high‐fat diet group (HP) and (iii) a high‐fat diet group supplemented with A. muciniphila (HA). The results found that A. muciniphila administration relieved weight gain, hepatic steatosis and liver injury induced by the high‐fat diet. A. muciniphila altered the gut microbiota with a decrease in Alistipes, Lactobacilli, Tyzzerella, Butyricimonas and Blautia, and an enrichment of Ruminiclostridium, Osclibacter, Allobaculum, Anaeroplasma and Rikenella. The gut microbiota changes correlated significantly with bile acids. Meanwhile, A. muciniphila also improved glucose tolerance, gut barriers and adipokines dysbiosis. Akkermansia muciniphila regulated the intestinal FXR‐FGF15 axis and reshaped the construction of bile acids, with reduced secondary bile acids in the caecum and liver, including DCA and LCA. These findings provide new insights into the relationships between probiotics, microflora and metabolic disorders, highlighting the potential role of A. muciniphila in the management of MAFLD. [ABSTRACT FROM AUTHOR]

Sulphur‐driven denitrification is a low‐cost process for the treatment of nitrate‐contaminated water. However, a comprehensive understanding of core populations and microbial interactions of a sulphur‐based denitrifying system is lacking. This study presents results from three replicated denitrifying systems amended with thiosulphate and operated under a low C/N ratio. Amplicon sequencing revealed gradual enrichments of a few abundant denitrifiers. Based on genome‐centred metagenomics and metatranscriptomics, a core set of microbes was identified in the systems, with Pseudomonas 1 and Thauera 2 being the most abundant ones. Although the replicates showed different enrichments, generalized observations were summarized. Most core populations conserved energy from denitrification coupled with sulphur. Pseudomonas 1 and Thauera 2 were able to finish complete denitrification. Surprisingly, they were also able to synthesize almost all amino acids and vitamins. In contrast, less abundant members, including Pseudomonas 2, were relatively auxotrophic and required an exogenous supply of amino acids and vitamins. The high expression of enzymes involved in biosynthesis and transport systems indicated their syntrophic relationships. The genomic findings suggested life strategies and interactions of the core thiosulphate‐based denitrifying microbiome, with implications for nitrate‐polluted water remediation. [ABSTRACT FROM AUTHOR]

Pork fat (PF) is a necessary ingredient in making traditional fish cakes (TFCs), which contains saturated fatty acids with potential health concerns. While linseed oil (LO) containing α‐linolenic acid is a potential nutrient‐enhancing fat substitute. In this study, the effect of pork fat and linseed oil level on gel quality, sensory characteristics, microstructure, and protein conformation of TFCs were characterized. Results showed that the TFCs with 30% pork fat (wt/wt) had the highest gel strength. Additionally, sensory evaluation determined that TFCs with 30% pork fat scored the best by a sensory panel with high gel strength, water‐holding capacity, and fresh and sweet taste. The gel strength, chewiness, and hardness of nutrient‐enriched fish cakes with 20% linseed oil replaced for pork fat were higher than that only with pork fat (wt/wt) without changing in tenderness and elasticity. Visual results showed that the network was uniform at a moderate level of linseed oil addition (20% LO/PF replacement ratio). The results of this study provided technical guidelines for standardizing the TFC manufacture processes, and useful insight for the development of fish cakes with reduced animal fat content for additional health benefits for consumers. [ABSTRACT FROM AUTHOR]

The cross-linked conjugated polymer poly(tetraphenylethene-co-biphenyl) (PTPEBP) nanoparticles were prepared by Suzuki-miniemulsion polymerization. The structure, morphology, and pore characteristics of PTPEBP nanoparticles were characterized by FTIR, NMR, SEM, and nitrogen adsorption and desorption measurements. PTPEBP presents a spherical nanoparticle morphology with a particle size of 56 nm; the specific surface area is 69.1 m2/g, and the distribution of the pore size is centered at about 2.5 nm. Due to the introduction of the tetraphenylethene unit, the fluorescence quantum yield of the PTPEBP nanoparticles reaches 8.14% in aqueous dispersion. Combining the porosity and nanoparticle morphology, the fluorescence sensing detection toward nitroaromatic explosives in the pure aqueous phase has been realized. The Stern–Volmer quenching constant for 2,4,6-trinitrophenol (TNP) detection is 2.50 × 104 M−1, the limit of detection is 1.07 μM, and the limit of quantification is 3.57 μM. Importantly, the detection effect of PTPEBP nanoparticles toward TNP did not change significantly after adding other nitroaromatic compounds, indicating that the anti-interference and selectivity for TNP detection in aqueous media is remarkable. In addition, the spike recovery test demonstrates the potential of PTPEBP nanoparticles for detecting TNP in natural environmental water samples. [ABSTRACT FROM AUTHOR]

As the interest in "natural" and "safe" products grows, the use of natural products instead of synthetic preservatives to combat food spoilage and poisoning caused by microorganisms during processing and storage has become a prioritized option. The present research evaluated the antibacterial activity of the Mentha longifolia L. essential oil (MLEO) against several pathogenic bacteria, and the mechanism of action against methicillin‐resistant Staphylococcus aureus (MRSA). Gas Chromatography Quadrupole Time‐of‐Flight Mass Spectrometry (GC‐Q‐TOF MS) analysis suggested that main components of MLEO were carvone (47.39%) and limonene (12.48%). The oil showed considerable antibacterial activity with MIC values of 0.394–1.576 mg/mL, and could be a promising bactericide. Non‐targeted metabolomics analysis based on GC‐Q‐TOF MS identified 66 different metabolites, and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of these metabolites revealed that MLEO achieves the effects by affecting amino acid metabolism in MRSA. [ABSTRACT FROM AUTHOR]

Simple Summary: The prognosis of patients with primary central nervous system lymphoma (PCNSL) is poor due to the high recurrence rate and lack of consensus on the optimal treatment for refractory or relapsed diseases. Despite having good prognostic scores, such as an MSKCC score or IELSG score, none of them are able to fully explain the clinical outcomes of patients with PCNSL, and they are complicated at the same time. Thus, there is an urgent need to develop simple and readily available parameters that help to stratify the prognosis of patients, especially those at high risk, and provide them with appropriate treatment measures. For the first time, this study identified that pretreatment serum total bilirubin (STB) could predict the prognosis of patients with PCNSL receiving high-dose methotrexate-based combination immunochemotherapy. The results from this study demonstrate that STB is a simple, cost-effective prognostic biomarker that clinicians can apply easily and quickly into routine practice. Primary central nervous system lymphoma (PCNSL) is a predominantly aggressive neoplasm isolated to the central nervous system or vitreoretinal space. Bilirubin is an important biomarker reflecting hepatic function and oxidative stress status that is associated with the occurrence and development of various tumors. However, its prognostic role in PCNSL has yet to be evaluated. Therefore, we conducted a prospective–retrospective study to analyze the predictive value of serum total bilirubin (STB) in PCNSL patients. The association between the pretreatment STB and clinical outcomes in PCNSL was developed in the discovery cohort (retrospective [n = 44] and prospective [n = 45]) and validated in an independent retrospective cohort (n = 69). A generalized additive model, Kaplan–Meier curve, and Cox analysis were applied. In the discovery cohort, the STB showed a linear relationship with overall survival (OS, p = 0.011) and progression-free survival (PFS, p = 0.0476). The median STB level of 12.0 µmol/L was determined as the cutoff value to predict the clinical outcomes with area under the receiver operating characteristic curve (AUROC) values of 0.9205 and 0.8464 for OS and PFS, respectively. The median STB level resulted in similar accuracy for predicting the clinical outcomes in the validation cohort with AUROC values of 0.8857 and 0.8589 for OS and PFS, respectively. In both the discovery and validation cohorts, the Kaplan–Meier survival curve and Cox regression analysis showed that the upper median STB groups showed significantly worse OS than the lower median STB groups. In conclusion, the pretreatment STB could be considered a novel biomarker to predict the clinical outcomes in patients with PCNSL receiving high-dose methotrexate-based combination immunochemotherapy. [ABSTRACT FROM AUTHOR]

Considerable evidence suggests that insulin resistance is closely linked to Parkinson's disease (PD), leading to agents aiming at treating diabetes can be regarded as new neuroprotective strategies in PD, notably glucagon‐like peptide‐1 (GLP‐1). However, the extremely short half‐life of GLP‐1 due to degradation by the ubiquitous proteolytic enzyme limits its clinical application. In this study, we engineered the recombinant integrant probiotic strain Escherichia coli Nissle 1917 (EcN) to create a strain EcN‐GLP‐1 that effectively delivers the heterologous GLP‐1 molecule. Subsequently, we assessed its neuroprotective effects on 1‐methyl‐4‐phenyl‐1, 2, 3, 6‐tetrahydropyridine (MPTP)‐induced PD mice. We demonstrated that EcN‐GLP‐1 treatment could improve motor deficits, increase tyrosine hydroxylase‐positive neurons, suppress microglia and astrocyte activation, reduce brain and colon inflammation, and ameliorate colonic barrier function damaged by MPTP induction. Meanwhile, we confirmed that the oral administration of EcN‐GLP‐1 could restore the disturbance of gut microbiota in the MPTP‐induced PD mice, by reducing the relative abundances of Akkermansia and Oscillospira, and increasing the level of Prevotella in the gut. These results support further development of an engineered probiotic platform in which production of GLP‐1 for gut‐brain disorders, such as PD. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effects of galacto-oligogalactose (GOS) glycosylation on the structural and functional properties of fish gelatin (FG). Results showed that with the increase of glycosylation time, grafting degree and browning increased, and new protein bands with increased molecular weight were observed by SDS-PAGE. Structural analysis showed that glycosylation reduced intrinsic fluorescence intensity and increased surface hydrophobicity of FG. FTIR analysis showed α-helix content decreased while random coil content increased in glycosylated FG. Emulsion activity index and emulsion stability index along with foam activity and foam stability were significantly elevated in GOS-4 and GOS-8, but FG glycosylated longer than 12 h exhibited less pronounced improvement. Glycosylated FG showed lower gel strength than control. The results indicate that moderate glycosylation could be applied to improve interfacial properties of FG. [ABSTRACT FROM AUTHOR]

Red cultural heritage is precious material and spiritual wealth, and is a non renewable cultural heritage with unique characteristics and protection value. In this paper, red cultural heritage in Mentougou District is taken as the research object. Through GIS, the classification and spatial distribution characteristics of the red cultural heritage in Mentougou are analyzed. On this basis, the analytic hierarchy process (AHP) is introduced to conduct quantitative value evaluation, determine evaluation factors and weights, and form a more systematic and scientific evaluation system suitable for Mentougou red cultural heritage. This paper aims to provide technical and methodological references for the evaluation and planning of the protection and utilization of red cultural heritage, and more scientifically protect and inherit red cultural heritage. [ABSTRACT FROM AUTHOR]

This paper concerns an optimization problem with objectives given as the difference of two $ \Phi_c $-convex functions, where a set constraint and a conic constraint are involved. In the framework of $ c $-conjugacy, where $ c $ is a coupling function, we firstly construct the generalized Lagrange and Fenchel dual problems by using the perturbation approach. Then, we obtain complete characterizations of the strong duality for these two dual problems, respectively. As applications, we provide corresponding results for minimization of the difference of two evenly quasiconvex functions. [ABSTRACT FROM AUTHOR]

Aiming at the performance requirements of positioning accuracy and stability of piezoelectric inertial actuators in fields including micro‐operation and biomedical engineering, a piezoelectric inertial actuator with wedge‐shaped friction foot structure using bimorph films is proposed in this paper. The wedge‐shaped friction foot structure can adjust the friction force in different driving stages, which suppresses the backward motion and effectively improves the output performance of the actuator. And the bimorph films are processed by Micro Electromechanical Systems (MEMS) manufacturing process technology. It enables the actuator to move steadily with a small tip mass and facilitates the miniaturization of actuator. The simulation model is constructed based on the dynamic model of actuator and the prototype parameters are optimized from the results of simulation tests. Then a series of output performance experiments are carried out. Experimental results show that the proposed actuator has the advantages of high resolution, stability, and displacement linearity. And the highest resolution of 0.035 µm is achieved. Depending on above results, the cell drug injection simulation experiments are successfully conducted. The success of experiments shows that the prototype has good output performance and great application potential and value in the field of cell manipulation. [ABSTRACT FROM AUTHOR]

Background/aims: Timely detection and treatment of retinal detachment (RD) could effectively save vision and reduce the risk of progressing visual field defects. High myopia (HM) is known to be associated with an increased risk of RD. Evidently, it should be clearly discriminated the individuals with high or low risk of RD in patients with HM. By using multi-parametric analysis, risk assessment, and other techniques, it is crucial to create cutting-edge screening programs that may be utilized to improve population eye health and develop person-specific, cost-effective preventative, and targeted therapeutic measures. Therefore, we propose a novel, routine blood parameters-based prediction model as a screening program to help distinguish who should offer detailed ophthalmic examinations for RD diagnosis, prevent visual field defect progression, and provide personalized, serial monitoring in the context of predictive, preventive, and personalized medicine (PPPM/3 PM). Methods: This population-based study included 20,870 subjects (HM = 19,284, HMRD = 1586) who underwent detailed routine blood tests and ophthalmic evaluations. HMRD cases and HM controls were matched using a nested case-control design. Then, the HMRD cases and HM controls were randomly assigned to the discovery cohort, validation cohort 1, and validation cohort 2 maintaining a 6:2:2 ratio, and other subjects were assigned to the HM validation cohort. Receiver operating characteristic curve analysis was performed to select feature indexes. Feature indexes were integrated into seven algorithm models, and an optimal model was selected based on the highest area under the curve (AUC) and accuracy. Results: Six feature indexes were selected: lymphocyte, basophil, mean platelet volume, platelet distribution width, neutrophil-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio. Among the algorithm models, the algorithm of conditional probability (ACP) showed the best performance achieving an AUC of 0.79, a diagnostic accuracy of 0.72, a sensitivity of 0.71, and a specificity of 0.74 in the discovery cohort. A good performance of the ACP model was also observed in the validation cohort 1 (AUC = 0.81, accuracy = 0.72, sensitivity = 0.71, specificity = 0.73) and validation cohort 2 (AUC = 0.77, accuracy = 0.71, sensitivity = 0.70, specificity = 0.72). In addition, ACP model calibration was found to be good across three cohorts. In the HM validation cohort, the ACP model achieved a diagnostic accuracy of 0.81 for negative classification. Conclusion: We have developed a routine blood parameters-based model with an ACP algorithm that could potentially be applied in the clinic with a PPPM approach for serial monitoring and predicting the occurrence of RD in HM and can facilitate the prevention of HM progression to RD. According to the current study, routine blood measures are essential in patient risk classification, predictive diagnosis, and targeted therapy. Therefore, for high-risk RD persons, novel screening programs and prompt treatment plans are essential to enhance individual outcomes and healthcare offered to the community with HM. [ABSTRACT FROM AUTHOR]

In this article, optimality conditions on (weak) efficient solutions in multiobjective optimization problems are investigated by using the image space analysis. A class of strong separation functions is constructed by oriented distance functions. Simultaneously, a generalized Lagrange function is introduced by the class of strong separation functions. Then, generalized Karush-Kuhn-Tucker (KKT for short) necessary optimality conditions are established without constraint qualifications or regularity conditions. Under the suitable assumptions, Lagrangian-type sufficient optimality conditions are also characterized. Moreover, the difference between strong separation and weak separation methods is explained. [ABSTRACT FROM AUTHOR]

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The least squares support vector machine (LS-SVM) is an effective method to deal with classification and regression problems and has been widely studied and applied in the fields of machine learning and pattern recognition. The learning algorithms of the LS-SVM are usually conjugate gradient (CG) and sequential minimal optimization (SMO) algorithms. Based on this, we propose a conjugate functional gain SMO algorithm and theoretically prove its asymptotic convergence. This algorithm combines the conjugate direction method and the functional gain SMO algorithm with second-order information, which increases the functional gain of the plain SMO algorithm. In addition, we also provide a generalized SMO-type algorithm framework with a simple iterative format and easy implementation for other LS-SVM training algorithms. The numerical results show that the execution time of this algorithm is significantly shorter than that of the other plain SMO-type algorithms and CG-type algorithms. [ABSTRACT FROM AUTHOR]

Bifidobacterium pseudocatenulatum LI09 could prevent D-galactosamine-induced liver injury. Our previous study has preliminarily determined that different intestinal microbiota profiles existed in the LI09-treated rats. Due to the sample size limitation, some subsequent analyses could not be achieved. In the current study, we conducted different experiments and bioinformatic analyses to characterise the distinct intestinal bacterial microbiota profiles in the LI09-treated rats with liver injury (i.e., LI09 group). Partition around medoids clustering analysis determined two intestinal microbiota profiles (i.e., Cluster_1_LI09 and Cluster_2_LI09) in LI09 group. Compared with Cluster_2_LI09, Cluster_1_LI09 group was determined at less dysbiotic microbial status and with lower level of liver injury. The two microbiota profiles were determined with distinct representative amplicon sequence variants (ASVs), among which, ASV1_Akkermansia and ASV3_Bacteroides were most associated with Cluster_1_LI09 and Cluster_2_LI09, respectively. Multiple representative phylotypes in Cluster_1_LI09 negatively correlating with liver function variables were assigned to Parabacteroides, suggesting Parabacteroides could benefit LI09 on modulating the liver function. In addition, ASV310_Lachnospiraceae, ASV501_Muribaculaceae and ASV484_Lachnospiraceae were determined as network gatekeepers in Cluster_1_LI09 network. The relevant results suggest that some intestinal bacteria could assist LI09 in lowering the intestinal microbial dysbiosis in the rats with liver injury, and their clinical application deserves further investigation. [ABSTRACT FROM AUTHOR]

Competing endogenous RNA (ceRNA)‐mediated signaling pathway dysregulation provides great insight into comprehensively understanding the molecular mechanism and combined targeted therapy for glioblastoma. circRNA is characterized by high stability, tissue/developmental stage‐specific expression and abundance in brain and plays significant roles in the initiation and progression of cancer. Our previous published data have demonstrated that RPN2 was significantly upregulated in glioma and promoted tumor progression via the activation of the Wnt/β‐catenin pathway. Furthermore, we proved that miR‐422a regulated the Wnt/β‐catenin signaling pathway by directly targeting RPN2. In this study, based on the glioblastoma microarray profiles, we identified the upstream circTOP2A, which completely bound to miR‐422a and was co‐expressed with the RPN2. circTOP2A was significantly overexpressed in glioma and conferred a poor prognosis. circTOP2A could regulate RPN2 expression by sponging miR‐422a, verified by western blot, dual‐luciferase reporter gene assay, and RNA pull‐down assay. Functional assays including CCK8, transwell and FITC‐annexin V were performed to explore the RPN2‐mediated role of the circTOP2A effect on the glioma malignant phenotype. Additionally, TOP/FOP and immunofluorescence analysis were used to confirm that sh‐circTOP2A could suppress the Wnt/β‐catenin pathway partly through RPN2. Finally, a tumor xenograft model was applied to validate the biological function of circTOP2A in vivo. Taken together, our findings reveal the critical role of circTOP2A in promoting glioma proliferation and invasion via a ceRNA mechanism and provide an exploitable biomarker and therapeutic target for glioma patients. [ABSTRACT FROM AUTHOR]

Objective: Homeobox B2 (HOXB2) is known to be correlated with the development and prognosis of various cancers. However, its role in colon cancer remains unclear. Aims: In this study, we explored the prognostic value of HOXB2 in colon adenocarcinoma (COAD). Methods: A total of 264 colon adenocarcinoma cases were retrospectively enrolled to evaluate HOXB2 expression and clinical significance. Chi-square test was applied to identify relationship between clinical features and HOXB2 expression. The effect of HOXB2 expression and clinical features on the survival of COAD patients was evaluated using Kaplan–Meier and Cox regression analyses. Cellular assays and mice models were conducted to validate the tumor-related role of HOXB2 in COAD. Results: Higher expression of HOXB2 in COAD tissues was significantly associated with tumor size, invasion depth, and lymph node metastasis (all P < 0.05). Univariate and multivariate analyses showed that high expression of HOXB2 was significantly correlated with a poor overall survival. In vitro cellular assays combined with knockdown strategies demonstrated that HOXB2 can promote tumor proliferation and invasion of COAD, which was further confirmed by in vivo xenograft experiments. Conclusions: HOXB2 may be a valuable biomarker and potential therapeutic target for the treatment of COAD. [ABSTRACT FROM AUTHOR]

The current study aims to evaluate the potential roles of taking probiotics postoperatively in attenuating the gastrointestinal complications and disturbed gut microbiota in colorectal cancer (CRC) patients undergoing chemotherapy. One hundred eligible CRC patients who were treated with radical surgery and needed to receive chemotherapy were recruited. Half of them were randomly assigned to the Probio group to take a probiotic combination from post-operation to the end of the first chemotherapeutic course. The other half of patients taking placebo instead were classified as the Placebo group. Gastrointestinal complications such as nausea, acid reflux, abdominal pain, abdominal distention, constipation, and diarrhea were recorded during chemotherapy. Fecal samples were collected preoperatively and after the first cycle of postoperative chemotherapy for 16S rRNA high-throughput sequencing and short-chain fatty acids (SCFAs) analysis. Results showed that probiotics administration could effectively reduce chemotherapy-induced gastrointestinal complications, particularly in diarrhea (p < 0.01). Additionally, chemotherapy also reduced the bacterial diversity indexes of the gut microbiota in CRC patients, which could be significantly increased by taking probiotics. Moreover, this chemotherapy caused significant changes in the composition of the gut microbiota, as indicated by decreased phylum levels of Firmicutes and increased Bacteroidetes, Proteobacteria, and Verrucomicrobia. In particular, several bacterial genera such as Akkermansia and Clostridium were significantly increased, while Prevotella, Lactobacillus, and Roseburia were decreased (p < 0.05). However, probiotic administration could effectively restore these taxa changes both at the phylum and genus levels, and mildly increase the genus levels of Bifidobacterium, Streptococcus, and Blautia. Furthermore, probiotics could also promote the production of SCFAs, particularly increasing acetate, butyrate, and propionate (p < 0.0001). These results support the beneficial effects of the probiotic interventions as novel alternative or complementary strategies in chemoprevention. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the leading cause of dementia in aged population. Oxidative stress and neuroinflammation play important roles in the pathogenesis of AD. Investigation of hub genes for the development of potential therapeutic targets and candidate biomarkers is warranted. The differentially expressed genes (DEGs) in AD were screened in GSE48350 dataset. The differentially expressed oxidative stress genes (DEOSGs) were analyzed by intersection of DEGs and oxidative stress-related genes. The immune-related DEOSGs and hub genes were identified by weighted gene co-expression network analysis (WGCNA) and protein–protein interaction (PPI) analysis, respectively. Enrichment analysis was performed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. The diagnostic value of hub genes was assessed by receiver operating characteristic analysis and validated in GSE1297. The mRNA expression of diagnostic genes was determined by qRT-PCR analysis. Finally, we constructed the drug, transcription factors (TFs), and microRNA network of the diagnostic genes. A total of 1160 DEGs (259 up-regulated and 901 down-regulated) were screened in GSE48350. Among them 111 DEOSGs were identified in AD. Thereafter, we identified significant difference of infiltrated immune cells (effector memory CD8 T cell, activated B cell, memory B cell, natural killer cell, CD56 bright natural killer cell, natural killer T cell, plasmacytoid dendritic cell, and neutrophil) between AD and control samples. 27 gene modules were obtained through WGCNA and turquoise module was the most relevant module. We obtained 66 immune-related DEOSGs by intersecting turquoise module with the DEOSGs and identified 15 hub genes through PPI analysis. Among them, 9 hub genes (CCK, CNR1, GAD1, GAP43, NEFL, NPY, PENK, SST, and TAC1) were identified with good diagnostic values and verified in GSE1297. qRT-PCR analysis revealed the downregulation of SST, NPY, GAP43, CCK, and PENK and upregulation of NEFL in AD. Finally, we identified 76 therapeutic agents, 152 miRNAs targets, and 91 TFs regulatory networks. Our study identified 9 key genes associated with oxidative stress and immune reaction in AD pathogenesis. The findings may help to provide promising candidate biomarkers and therapeutic targets for AD. [ABSTRACT FROM AUTHOR]

The two-stage stochastic variational inequality (TSVI) is a popular modeling paradigm recently with a wide range of applications in stochastic programming, game problems, equilibrium, etc. To numerically solve a TSVI, samples drawn from the true probability distribution are employed to discretely approximate the original problem with continuous probability distribution. However, this key assumption can hardly be fulfilled in practice because the perceived data may usually contain noise. This leads to the so-called statistically robust analysis. This paper considers the statistical robustness of TSVIs. We first give some preliminaries on both TSVIs and statistical robustness, which lay the foundation for the subsequent discussion. Then both qualitative and quantitative statistical robustness of TSVIs are studied. [ABSTRACT FROM AUTHOR]

This paper concentrates on necessary conditions for properly efficient solutions in nonsmooth multiobjective optimization problems. We first present a generalization of Tucker's alternative theorem for conic nonlinear systems, provided that a closedness condition holds. Some sufficient conditions for the validity of such a closedness condition are given. As applications, under the weak Abadie regularity condition, we then establish the primal and the strong Karush/Kuhn–Tucker (dual) necessary optimality conditions for an efficient solution to be locally properly efficient in Borwein's sense. The primal and the dual conditions are formulated as an equivalent pair by means of the Tucker-type alternative results. Finally we give an example to illustrate that Borwein's locally properly efficient solution cannot be reduced to the only efficient one in the main results. [ABSTRACT FROM AUTHOR]