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Abstract Lotus (Nelumbo nucifera Gaertn), a kind of perennial aquatic plant, is widely cultivated and consumed by people in Asian countries. Lotus plumule flavonoids (LPF) have been recognized as a hypoglycemic agent. LPF was optimally obtained using novel ultrasonic-microwave assisted synergistic extraction (UMSE) method by response surface methodology (RSM) on the basis of the results of single-factor experiments. Furthermore, the hypoglycemic activity of LPF was investigated by measuring the body weight, fasting blood glucose (FBG) level, and oral glucose tolerance test (OGTT) and analyzing the physiological indexes in streptozotocin-diabetic mice model. The optimum extraction conditions consisted of microwave power 355 W, ultrasonic power 423 W, extraction time 15 min, solid-liquid ratio 1:40, ultrasound/interval time 1/0, and ethanol concentration 70% with the maximum LPF yield of 2.62%. LPF supplementation significantly decreased the body weight, FBG, OGTT, serum total cholesterol (TC), serum total triglycerides (TG), and insulin levels, indicating the antidiabetic activity of LPF. This research verified that the UMSE technique was highly efficient to extract LPF to the maximum extent and the flavonoids from L. plumule exhibited hypoglycemic activity, which showed broad development and application prospects.

Abstract Purpose Increased tibial tubercle-trochlear groove distance (TT-TG) was proposed as one of the main risk factors for patellofemoral instability (PFI). The increased TT-TG distance indicated externalization of the tibial tubercle with the reference of the trochlear groove. However, in the case of severe trochlear dysplasia, the reference point on the trochlear groove was indistinct, and the accuracy of TT-TG was controversial. The purpose of this study was to evaluate the accuracy of TT-TG and TT-PCL in consideration of the mild and severe trochlear dysplasia. Methods From 2015 to 2020, MRI findings of consecutive knee joints with PFI symptoms diagnosed in our hospital were retrospectively analyzed. All knees with trochlear dysplasia were diagnosed by longitudinal MRI scan and lateral radiograph. The knees were classified according to the four-type classification system described by Dejour et al. Twenty cases of type A (mild trochlear dysplasia); 20 cases of type B, C, and D (severe trochlear dysplasia); and 20 cases of normal type were selected and divided into normal group (normal trochlea), mild group (type A), and severe group (type B, type C, type D). Tibial tubercle-trochlear groove distance (TT-TG), tibial tubercle-posterior cruciate ligament distance (TT-PCL), and the Dejour classification of trochlear dysplasia were assessed by 2 experienced orthopedics. The reliability of TT-TG distance and TT-PCL distance was tested by intraclass correlation coefficients (ICCs). Results Comparing the differences between TT-TG and TT-PCL in the normal, mild, and severe groups, the TT-TG and TT-PCL in the mild and severe groups show different meanings (normal, 8.83 ± 3.62 mm vs. 8.44 ± 4.57 mm, P > 0.05; mild, 17.30 ± 4.81 mm vs. 20.09 ± 5.05 mm, P < 0.05; severe, 10.79 ± 4.24 mm vs. 12.31 ± 5.43 mm, P > 0.05). The Pearson correlation coefficient of TT-TG and TT-PCL measurements of trochlear dysplasia were r = 0.480 (mild group, P = 0.032) and r = 0.585 (severe group, P < 0.001). The intra-observer ICCs of TT-TG were r = 0.814 (mild group) and r = 0.739 (severe group). The inter-observer ICCs of TT-TG were r = 0.810 (mild group) and r = 0.713 (severe group). In the normal knee, the Pearson correlation coefficient of TT-TG and TT-PCL was r = 0.787(P < 0.001), the intra-observer ICC of TT-TG was r = 0.989, and the inter-observer ICC of TT-TG was r = 0.978. Conclusion Compared with the mild trochlear dysplasia, the inter-observer and intra-observer correlations of TT-TG measurements decreased in the group of severe dysplastic trochlea (inter-observer ICC, 0.810 vs. 0.713; intra-observer ICC, 0.814 vs. 0.739). In the present study, the determination of TT-TG and TT-PCL distance are of great significance for patients with low-grade trochlear dysplasia. And TT-PCL, without referring to the abnormal trochlear groove, is an effective indicator to measure the lateralization of tibial tuberosity in patients with severe dysplastic trochlea.

BackgroundLeptomeningeal metastases (LM) have become increasingly common in non-small cell lung cancer (NSCLC) patients who harbor epidermal growth factor receptor (EGFR) mutation treated with EGFR-TKI and are correlated with inferior prognosis. Evidence in prior research demonstrated that EGFR amplification was more likely presented in advanced clinical stages and was associated with worse survival. However, whether EGFR amplification is a prognostic marker in NSCLC–LM is still inconclusive.MethodsThis study enrolled patients diagnosed with NSCLC–LM from June 2019 to September 2021 and who had received previous EGFR-TKI at Guangdong Sanjiu Brain Hospital. Cerebrospinal fluid (CSF) samples were collected and subjected to targeted next-generation sequencing of 168 cancer-related genes. Clinical characteristics and overall survival (OS) were compared in patients with and without EGFR amplification.ResultsThis study enrolled 53 NSCLC–LM patients, all of whom had EGFR mutations. TP53 and EGFR amplifications are the two most frequent mutations in the study cohort, presenting at 72% (38 of 53) and 40% (21 of 53), respectively. The rate of EGFR amplification was much higher at the time of leptomeningeal progression than at initial diagnosis (p < 0.01). Karnoskfy performance status was poorer (p = 0.021), and CSF pressure was higher (p = 0.0067) in patients with EGFR amplification than those without. A multivariable Cox proportional hazard regression model showed that EGFR amplification was an independent prognostic factor for poorer OS (8.3 vs. 15 months; p = 0.017). The median OS was shorter in NSCLC–LM patients with mutated TP53 than those with wild-type TP53, but the difference was not statistically significant (10 vs. 17.3 months, p = 0.184).ConclusionsEGFR gene amplification could be a potential resistance mechanism to EGFR-TKI failure in NSCLC–LM and is associated with inferior clinical outcomes.

Alkaline pH can induce triacylglyceride accumulation in microalgae, however its molecular mechanism remains elusive. Here, we investigated the effect of 2-[N-cyclohexylamino]-ethane-sulfonic acid (CHES) -induced intracellular alkalization on the lipid production in Phaeodactylum tricornutum. Intracellular pH was increased upon CHES treatment, displaying a high BCECF fluorescence ratio. CHES treatment significantly induced lipid accumulation but had no change in cell density and biomass. The expression of genes involved in photoreaction, carbon fixation, glycolysis, pentose phosphate pathway, amino acid catabolism, GS/GOGAT cycle, TCA cycle, triacylglyceride assembly, de novo fatty acid synthesis were up-regulated, while that in amino acid biosynthesis were down-regulated under CHES conditions. Correspondingly, the activity of phosphoribulokinase, carbonic anhydrase, pyruvate dehydrogenase and acetaldehyde dehydrogenase were enhanced by CHES treatment. Chloroplast-specific biological processes were activated by CHES treatment in P. tricornutum, which redirects the flux of carbon into lipid biosynthesis, meanwhile stimulates de novo fatty acid biosynthesis, leading to lipid accumulation under CHES conditions. These indicate an enhancement of intermediate metabolism, resulting in lipid accumulation by CHES.

Cirrhosis is the end stage of chronic liver diseases like chronic hepatitis B. In China, hepatitis B accounts for around 60% of cases of cirrhosis. So far, clinical and laboratory indexes for the early diagnosis of cirrhosis are far from satisfactory. Nevertheless, there haven’t been specific drugs for cirrhosis. Thus, it is quite necessary to uncover more specific factors which play their roles in cirrhosis and figure out the possible therapeutic targets. Among emerging factors taking part in the initiation and progression of cirrhosis, gut microbiota might be a pivot of systemic factors like metabolism and immune and different organs like gut and liver. Discovery of detailed molecular mechanism in gut microbiota and gut liver axis leads to a more promising prospect of developing new drugs intervening in these pathways. Time-based medication regimen has been proofed to be helpful in hormonotherapy, especially in the use of glucocorticoid. Thus, circadian rhythms, though haven’t been strongly linked to hepatitis B and its complications, are still pivotal to various pathophysiological progresses. Gut microbiota as a potential effective factor of circadian rhythms has also received increasing attentions. Here, our work, restricting cirrhosis to the post-hepatitis B one, is aimed to summarize how circadian rhythms and hepatitis B-related cirrhosis can intersect via gut microbiota, and to throw new insights on the development of new and time-based therapies for hepatitis B-related cirrhosis and other cirrhosis.

Fucosylated oligosaccharides have important biological functions as well as an excellent antiviral activity. A novel α 1–2-fucosyltransferase (α 2FT) from Treponema primitia (Tp2FT) was cloned and expressed in Escherichia coli BL21(DE3) and purified as an N-His6-tagged fusion protein (His6-Tp2FT). Mass spectrometry was carried out to identify the products of enzymatic reaction. The Tp2FT exhibited strict acceptor substrate specificity for type 1 structure (Galβ1-3GlcNAc)-containing glycans. It might be a promising emzyme for the chemo-enzymatic synthesis of lacto-N-fucopentaose I (LNFP I), which is one of the important fucosylated oligosaccharides. In this study, different in vitro experiments were used to study the biological activities of LNFP I. It could reduce the concentrations of inflammatory cytokines and effectively inhibit the synthesis of enterovirus 71 proliferation. LNFP I was an inhibitor of enterovirus 71 in the early stages of infection, it can used in infant nutrition and might provide a new drug for hand foot mouth disease.

Globally, aging and diabetes are considered prevalent threats to human health. Chlorella pyrenoidosa polysaccharide (CPP) is a natural active ingredient with multiple health benefits including antioxidant and hypolipidemic activities. In this study, the aging-related diabetic (AD) mice model was established to investigate the underlying hypoglycemic and antioxidant mechanisms of CPP. It improved superoxide dismutase, catalase (CAT), glutathione peroxidase (GSH-px), and malondialdehyde activities in liver and insulin secretion. CAT and GSH-px activity in the brain increased after CPP administration. In addition, through histopathological examinations, it was evident that injuries in the liver, brain, jejunum, and pancreas were restored by CPP. This restoration was likely mediated via the activation of glucagon-like peptide-1 receptor/FOXO-1 (forkhead box O1) pathway concurrent with the inhibition of interleukin-6 receptor/FOXO-1 pathway. Furthermore, metabolomics and correlation analysis revealed that CPP possibly relived AD through changes in insulin levels and declined oxidative stress as regulated by phenylpyruvic acid. These findings suggested that CPP exerted antioxidant and hypoglycemic roles in an AD mice model, thereby providing a sound scientific foundation for further development and utilization of CPP.

Aythya marila is a large diving duck belonging to the family Anatidae. However, the phylogenetic relationship among these Aythya species remains unclear due to the presence of extensive interspecific hybridization events within the Aythya genus. Here, we sequenced and annotated the complete mitochondrial genome of A. marila, which contained 22 tRNAs, 13 protein-coding genes (PCGs), 2 ribosomal RNAs, and 1 D-loop, with a length of 16,617 bp. The sizes of the PCGs ranged from 297 to 1824 bp and were all, except for ND6, located on the heavy chain (H). ATG and TAA were the most common start and termination codons of the 13 PCGs, respectively. The fastest- and slowest-evolving genes were ATP8 and COI, respectively. Codon usage analysis indicated that CUA, AUC, GCC, UUC, CUC, and ACC were the six most frequent codons. The nucleotide diversity values indicated a high level of genetic diversity in A. marila. FST analysis suggested a widespread gene exchange between A. baeri and A. nyroca. Moreover, phylogenetic reconstructions using the mitochondrial genomes of all available Anatidae species showed that, in addition to A. marila, four major clades among the Anatidae (Dendrocygninae, Oxyurinae, Anserinae, and Anatinae) were closely related to A. fuligula. Overall, this study provides valuable information on the evolution of A. marila and new insights into the phylogeny of Anatidae.

Accurate measurement of low-level thoron gas and high-accuracy calibration of thoron measurement devices are essential for assessing and preventing thoron radiological risks. This study aimed to develop a thoron gas measurement technique using an airflow-through scintillation cell for both low-level measurement and high-accuracy calibration. To achieve this, a compartment model was developed to estimate the influence of progeny deposition and accumulation on the wall of the scintillation cell to prevent an overestimation of thoron. A self-developed scintillation cell was utilised to implement and validate this technique. The lower detection limit and measurement uncertainty were then evaluated to assess the feasibility of the technique for low-level measurement and high-accuracy calibration. The results showed that the compartment model effectively addressed the influence of progeny deposition. The measurement technique achieved a lower detection limit below 100 Bq m−3 even with the coexistence of that of 100 Bq m−3 of radon and attained a measurement uncertainty (k = 2) below 10% when the concentration of thoron exceeded 1000 Bq m−3. In summary, this study developed a reliable and practical thoron gas measurement technique using an airflow-through scintillation cell with a consideration of progeny deposition, and is expected to contribute to the assessment and prevention of thoron radiological risk.

In this article, an experimental study on the gate-induced drain leakage (GIDL) current repairing worst hot carrier degradation (HCD) in Si p-FinFETs is investigated with the aid of an ultra-fast measurement (UFM) technique (~30 μs). It is found that increasing GIDL bias from 3 V to 4 V achieves a 114.7% VT recovery ratio from HCD. This over-repair phenomenon of HCD by UFM GIDL is deeply discussed through oxide trap behaviors. When the applied gate-to-drain GIDL bias reaches 4 V, a significant electron trapping and interface trap generation of the fresh device with GIDL repair is observed, which greatly contributes to the approximate 114.7% over-repair VT ratio of the device under worst HCD stress (−2.0 V, 200 s). Based on the TCAD simulation results, the increase in the vertical electric field on the surface of the channel oxide layer is the direct cause of an extraordinary electron trapping effect accompanied by the over-repair phenomenon. Under a high positive electric field, a part of channel electrons is captured by oxide traps in the gate dielectric, leading to further VT recovery. Through the discharge-based multi-pulse (DMP) technique, the energy distribution of oxide traps after GIDL recovery is obtained. It is found that over-repair results in a 34% increment in oxide traps around the conduction energy band (Ec) of silicon, which corresponds to a higher stabilized VT shift under multi-cycle HCD-GIDL tests. The results provide a trap-based understanding of the transistor repairing technique, which could provide guidance for the reliable long-term operation of ICs.

The insulin-like growth factor 2 gene (igf2) is thought to be a key factor that could regulate animal growth. In fish, few researchers have reported on the single nucleotide polymorphisms (SNPs) located in igf2 and their association with growth traits. We screened the SNPs of igf2 from the spotted sea bass (Lateolabrax maculatus) by Sanger sequencing and made an association between these SNPs with growth traits. The full-length complementary (c) DNA of igf2 was 1045 bp, including an open reading frame of 648 bp. The amino acid sequence of Igf2 contained a signal peptide, an IGF domain, and an IGF2_C domain. Multiple sequence alignment showed that the IGF domain and IGF2_C domain were conserved in vertebrates. The genome sequence of igf2 had a length of 6227 bp. Fourteen SNPs (13 in the introns and one in one of the exons) were found in the genome sequence of igf2. Four SNPs located in the intron were significantly associated with growth traits (p < 0.05). These results demonstrated that these SNPs could be candidate molecular markers for breeding programs in L. maculatus.

Background: Scavenger receptor class B (SRB) is a multifunctional protein in animals that participates in physiological processes, including recognition of a wide range of ligands. Astaxanthin is a major carotenoid found in shrimp. However, the molecular mechanism of astaxanthin and SRB protein binding has not been reported. Results: In the present study, a member of the SRB subfamily, named PmSRB, was identified from the transcriptome of black tiger shrimp (Penaeus monodon). The open reading frame of PmSRB was 1557 bp in length and encoded 518 amino acids. The structure of PmSRB included a putative transmembrane structure at the N-terminal region and a CD36 domain. Multiple sequence alignment indicated that the CD36 domain were conserved. Phylogenetic analysis showed four separate branches (SRA, SRB, SRC, and croquemort) in the phylogenetic tree and that PmSRB was clustered with SRB of Eriocheir sinensis. Quantitative real-time polymerase chain reaction showed that the PmSRB gene was widely expressed in all tissues tested, with the highest expression level observed in the lymphoid organ and brain. Subcellular localization analysis revealed that PmSRB-GFP (green fluorescent protein) fusion proteins were predominantly localized in the cell membrane. The recombinant proteins of PmSRB showed binding activities against astaxanthin in vitro. Conclusions: PmSRB was identified and characterized in this study. It is firstly reported that PmSRB may take as an important mediator of astaxanthin uptake in shrimp.How to cite: Fan S, Wang F, Xie Z, et al. Molecular characterization and functional analysis of scavenger receptor class B from black tiger shrimp (Penaeus monodon). Electron J Biotechnol 2021; 51. https://doi.org/10.1016/j.ejbt.2021.03.003

Higher order topological systems add an additional layer of complexity to the bulk boundary correspondence by being able to sustain additional modes such as corner and hinge states. Here, the authors use electrical circuits to realize a two-dimensional quasicrystalline quadrupole topological insulator without discrete translational symmetry and observe localized corner modes.

Abstract Background Cultural differences in affective and cognitive intrinsic motivation could pose challenges for global public health campaigns, which use cognitive or affective goals to evoke desired attitudes and proactive health-promoting actions. This study aimed to identify cross-cultural differences in affective and cognitive intrinsic motivation and discuss the potential value of this information for public health promotion. Methods A cross-sectional survey using cross-culturally validated need for affect (NFA) and need for cognition (NFC) scales was carried out among 1166 Chinese participants, and the results were compared with published data from 980 American participants. Additionally, we assessed a highly prevalent symbolic geriatric health condition, hearing loss, in 500 Chinese community-dwelling seniors. The Chinese NFA scale was developed following the translation-back translation procedure, and the psychometric evaluation was performed by applying confirmatory factor analysis (CFA), exploratory structural equation modeling (ESEM), correlation analysis and multigroup invariance test. MANOVA and Hedge’s g statistic were employed to compare the NFA and NFC levels between individuals from different countries and between Chinese seniors with and without hearing loss. The relation of early hearing intervention intention to NFA and NFC was also explored in the Chinese sample. Results A basic two-factor model of NFA adequately fit the sample data from Chinese and American cultures. The questionnaire demonstrated reasonable invariance of the factor structure and factor loadings across the groups. Those in the primary Chinese sample had lower NFA and NFC than their American peers. This difference held in the senior sample. Moreover, Chinese seniors with hearing loss had even lower NFA and NFC than those without hearing loss. Their early hearing intervention intention was low but was associated with intrinsic motivation. Conclusions The Need for Affect (NFA) construct may be generalized beyond its Western origins. There was a general lack of affective and cognitive intrinsic motivation in Chinese individuals, particularly in seniors with hearing loss, compared with their American peers. These differences point to a potential challenge in framing effective messages for some cultures in the geriatric public health domain. Ideally, recognizing and understanding this challenge will inspire the consideration of novel persuasive strategies for these audiences.

Abstract Ozone is widely used in daily life, but studies have shown that O3 can damage human trachea and lungs, leading to diseases such as asthma, emphysema, and bronchitis. Therefore, it is of great significance to develop a simple and efficient detection method for monitoring O3 in living cells. In this study, 3-(but-3-en-1-yl)-2-(7-(but-3-en-1-yloxy)-2-oxo-2H-chromen-3-yl)benzo[d]thiazol-3-ium (BCT) as a new type of water-soluble fluorescent probe was synthesized by substitution reaction of 4-bromo-1-butene and hydroxycoumarin-benzothiazole derivatives, which can specifically detect ozone in aqueous solution. The interaction of ozone on the probe can be completed within 20 min, the fluorescence intensity is significantly enhanced, and it has the advantages of high sensitivity (detection limit LOD = 43 nM). The influence of pH on the fluorescent performance of BCT shows that the probe with super stability under weak alkali and acidic environment, which provides the necessary conditions for its detection of ozone in physiological system detection. Therefore, BCT is expected to become an effective tool for detecting ozone in cellular organisms.

Abstract Image classification is one of the mainstream tasks of computer vision. However, the most existing methods use labels of the same granularity level for training. This leads to ignoring the hierarchy that may help to differentiate different visual objects better. Embedding hierarchical information into the convolutional neural networks (CNNs) can effectively regulate the semantic space and thus reduce the ambiguity of prediction. To this end, a multi‐task learning framework, named as Hierarchical Bilinear Convolutional Neural Network (HB‐CNN), is developed by seamlessly integrating CNNs with multi‐task learning over the hierarchical visual concept structures. Specifically, the labels with a tree structure are used as the supervision to hierarchically train multiple branch networks. In this way, the model can not only learn additional information (e.g. context information) as the coarse‐level category features, but also focus the learned fine‐level category features on the object properties. To smoothly pass hierarchical conceptual information and encourage feature reuse, a connectivity pattern is proposed to connect features at different levels. Furthermore, a bilinear module is embedded to generalise various orderless texture feature descriptors so that our model can capture more discriminative features. The proposed method is extensively evaluated on the CIFAR‐10, CIFAR‐100, and ‘Orchid’ Plant image sets. The experimental results show the effectiveness and superiority of our method.

Both open-circuit voltage and fill factor of organic solar cells are affected by the metal-organic semiconductor interface. Here, the authors demonstrate that the voltage can continue to rise when the Fermi level is forced up to the semiconductor density-of-states tail.

Abstract Due to their potentials in light‐weight, flexible, and semitransparent devices, organic photovoltaics are of great significance in the field of renewable energy. However, the narrow intrinsic absorption spectrum of organic materials hinders the full utilization of solar energy. To fabricate a highly efficient opaque solar cell, it is greatly necessary to modify the optical properties of the device to improve light absorption. In addition, the growing interest in building‐integrated photovoltaics drives the development of semitransparent devices. The preparation of semitransparent solar cells with excellent performance imposes high requirements on the high efficiency and appropriate visible light transmittance of effective optical management. In this review, the recent research progress of optical management in organic photovoltaics is reviewed, including the design of light‐absorbing materials, the modification of different layers, adding a light‐trapping structure, and changing the light absorption capabilities of specific materials, so as to provide strategies of how to improve the performance of organic photovoltaic devices and present the prospect of the area.

Nontyphoidal Salmonella (NTS) in children remains a growing burden on public health and often causes children to be hospitalized with diarrheic symptoms. In this work, 260 strains of human Salmonella isolated from Jilin, China were characterized by serotypes and antimicrobial resistance using whole genome sequencing (WGS). The most prevalent serotype was Salmonella enteritidis (47.3%), followed by S. I 4,[5],12:i:- (33.1%), and Salmonella Typhimurium (7.3%). Furthermore, the consistency between resistance phenotype and genotype was confirmed. Similarly, strains harbored blaTEM−1B and tetA genes were detected, which verified the level of resistant phenotype in β-lactams and tetracyclines. The presence of a single mutation in parC, gyrA, and qnrS1 genes corresponding to quinolones was also observed. In our work, multilocus sequence typing (MLST) and core genome multilocus sequence typing (cgMLST) were found to have a high resolution to molecular traceability, and the combination of both was conducive to practical application in an actual situation. Taking all of this into account, we suggested that the comprehensive surveillance of Salmonella infection in children should be carried out to monitor antimicrobial-resistant trends from various sources and to alert on outbreaks of foodborne diseases to protect public health.

BackgroundThe disparities of hr-HPV infection among races/ethnicities have not been fully discussed. This study aimed to investigate the difference of hr-HPV infection between Chinese Han and Mongols minority women in Inner Mongolia.MethodsGenotyping and histopathology data of Chinese Han and Mongols minority women in Inner Mongolia from Chinese Multi-Center Screening Trial were used to analyze the hr-HPV prevalence, and type-specific distribution in abnormal pathology results.ResultsThe hr-HPV infection rates of Han women was 15.9% while of Mongols was 21.6% (P < 0.001). The most prevalent genotypes in Han women were ranked as HPV-16,−52,−18/-58,−31/-39, and−59 while in Mongols were−16,−31,−58,−18 and−52. When analyzing the age-specific of hr-HPV infection, two peaks were found at age of 40–44 (20.5%) and 55–59 (23.5%) years in Han women while three peaks were observed at age of 30–34 (22.1%), 45–49 (22.9%), and 55–59 (31.8%) years, respectively, in Mongols. HPV-16 accounting for 62.5 and 53.8% of the CINII+ in Han and Mongols, respectively.ConclusionThe prevalence of hr-HPV was significantly different between the Han and Mongols minority women in Inner Mongolia, races/ethnicities background should be taken into consideration for the refinement of cervical cancer screening strategies and vaccine implementation in China.

Immunomagnetic separation based on Fe3O4 magnetic nanoparticles (MNPs) has been widely performed in sample pretreatment. The oriented conjugation strategy can achieve a better capture effect than the N-(3-dimethylamlnopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) /N-hydroxysuccinimide (NHS) method. However, immunoglobulin yolk (IgY) cannot be oriented through an SPA strategy like immunoglobulin G (IgG). In this article, an oriented conjugation nanoprobe was prepared for the enrichment of bacteria based on pH adjusting. The main factors affecting the enrichment efficiency were studied, such as the pH of the buffer system, the concentration of IgY, the concentration of nanoprobe, and the enrichment time. Under the optimal conditions, the enrichment efficiency toward target bacteria could reach 92.8%. Combined with PCR, the limit of detection (LOD) was found to be 103 CFU/ml, which was lower than the PCR only. In conclusion, we provided a new protocol for the oriented conjugation of IgY and high sensitivity detection with simple pretreatment.

Summary: A 10,000 ton-CO2/y mineralization curing (CMC) process was demonstrated in Jiaozuo city, China by retrofitting a traditional autoclaved curing plant. An industrial concrete formula with synergistic effects of aggregate gradation, early hydration, and alkali excitation was developed using local solid wastes resources. Approximately 90% of the raw materials, including fly ash, furnace blaster slag, steel slag, and carbide slag, came from coal-based industries. An extraordinary phenomenon of high-temperature accumulation from room temperature to 140°C was first observed in an industrial scale because of the rapid and strong exothermic carbonation reaction. A step pressure-equalizing procedure was developed to achieve a rapid carbonation rate, a high CO2 conversion ratio of >98%, and efficient carbonation exotherm recycling. The global warming potential life cycle analysis revealed that compared with autoclaved curing, CMC showed significantly decreased the emission of 182 kg CO2-Eq/m3-product, with direct CO2 sequestration accounting for ∼65% of the reduction.

Liver cancer has a high mortality rate. Chronic inflammation is one of the leading causes of hepatocellular carcinoma. Recent studies suggested high levels of trimethylamine N-oxide (TMAO) may correlate with increased risk of inflammatory-induced liver cancer. However, the mechanisms by which TMAO promotes liver cancer remain elusive. Here, we established a model of inflammatory-induced liver cancer by treating Hepa1-6 cells and Huh7 cells with TNF-α. TMAO synergistically increased the proliferation, migration and invasion of Hepa1-6 cells and Huh7 cells in the presence of TNF-α. We conducted bulk RNA-Seq of the TMAO-treated cell model of inflammatory Hepatocellular carcinoma (HCC) and evaluated the influence of the differentially expressed genes (DEGs) on clinical prognosis using Kaplan-Meier Plotter Database and Gene Expression Profiling Interactive Analysis (GEPIA) database. Univariate and multivariate Cox regression analyses of tumor microenvironment and DEGs were performed using Timer2.0. Upregulation of POSTN, LAYN and HTRA3 and downregulation of AANAT and AFM were positively related to poorer overall survival in human liver cancer. Moreover, higher expression of POSTN and HTRA3 positively correlated with infiltration of neutrophils, which can promote tumor progression. In vitro experiments showed TMAO activates ILK/AKT/mTOR signaling via POSTN, and knocking down POSTN significantly reduced ILK/AKT/mTOR signaling and the tumorigenicity of Hepa1-6 cells and Huh7 cells. Collectively, our results suggest the gut microbial metabolite TMAO and POSTN may represent potential therapeutic targets for liver cancer.

The gastrointestinal (GI) tract plays an essential role in food digestion, absorption, and the mucosal immune system; it is also inhabited by a huge range of microbes. The GI tract is densely innervated by a network of 200–600 million neurons that comprise the enteric nervous system (ENS). This system cooperates with intestinal microbes, the intestinal immune system, and endocrine systems; it forms a complex network that is required to maintain a stable intestinal microenvironment. Understanding how gut microbes influence the ENS and central nervous system (CNS) has been a significant research subject over the past decade. Moreover, accumulating evidence from animal and clinical studies has revealed that gut microbiota play important roles in various neurological diseases. However, the causal relationship between microbial changes and neurological disorders currently remains unproven. This review aims to summarize the possible contributions of GI microbiota to the ENS and CNS. It also provides new insights into furthering our current understanding of neurological disorders.

Frailty is a complicated syndrome that occurs at various ages, with highest incidence in aged populations, suggesting associations between the pathogenesis of frailty and age-related changes. Gut microbiota (GM) diversity and abundance change with age, accompanied by increased levels of trimethylamine oxide (TMAO), a systemic inflammation-inducing GM metabolite. Thus, we hypothesized that TMAO may be involved in the development of frailty. We successfully established and verified a novel model of frailty in adult mice based on a 4-week intraperitoneal injection regime of TMAO followed by LPS challenge. The frailty index significantly increased in TMAO-treated mice after LPS challenge. TMAO also decreased claudin-1 immunofluorescent staining intensity in the jejunum, ileum, and colon, indicating that the destruction of intestinal wall integrity may increase vulnerability to exogenous pathogens and invoke frailty. 16S sequencing showed that TMAO significantly reduced the GM Firmicutes/Bacteroidetes (F/B) ratio, but not α-diversity. Interestingly, after LPS challenge, more genera of bacterial taxa were differently altered in the control mice than in the TMAO-treated mice. We infer that a variety of GM participate in the maintenance of homeostasis, whereas TMAO could blunt the GM and impair the ability to recover from pathogens, which may explain the continuous increase in the frailty index in TMAO-treated mice after LPS challenge. TMAO also significantly increased serum imidazole metabolites, and led to different patterns of change in serum peptide and phenylpropanoid metabolites after LPS stimulation. These changes indicate that glucose metabolism may be one mechanism by which GM inactivation causes frailty. In conclusion, TMAO leads to frailty by destroying intestinal barrier integrity and blunting the GM response.

Enterovirus 71 (EV71) is the main cause of hand, foot and mouth disease that results in high rates of severe diseases in small children. Lacto-N-fucopentaose I (LNFPI) can inhibit pathogen invasion and regulate intestinal flora. However, whether LNFPI inhibits EV71 infection remains unknown. In this study, we examined the effect and mechanism of LNFPI against EV71. LNFPI reduced capsid protein VP1 to block virus adsorption, inhibited cyclin E transcription and promoted CDK2 expression in EV71-induced human rhabdomyosarcoma cells, thereby causing virus-induced S phase arrest and inhibiting death receptor and mitochondria-induced apoptosis. The effects of LNFPI on apoptosis were further confirmed in Caenorhabditis elegans. The correlation analysis revealed that LNFPI inhibited cell apoptosis by reducing the abundance of Sphingomonas, Stenotrophomonas and Achromatic, which are associated with pro-apoptotic genes in C. elegans, and by increasing the abundance of Micromonospora, which is related to apoptotic inhibition. These findings lead to further recommendations for LNFPI supplementation in infant formula, as it could offer antiviral benefits to formula-fed infants.

Carbon and nitrogen play a fundamental role in the production of Monascus pigments. However, their effects on pigment biosynthesis remain undetermined. In this study, we found that Monascus kaoliang produces pigments via liquid fermentation using glycerol and peptone as suitable carbon and nitrogen sources, respectively. Comparative transcriptomic profiling was performed using RNA sequencing. It indicated that the differentially expressed genes (DEGs) of carbon were enriched using amino acids and carbohydrates via the transport and metabolism pathways, respectively. DEGs of nitrogen were enriched only using general functional prediction pathways. These data provide a comprehensive interpretation of the linkage between primary and secondary metabolisms in M. kaoliang. Moreover, they provide insights into the effects of various substances involved in secondary metabolism.

It is known that nutrition and immunity are connected, but the mechanism is not very clear. Endogenous retroviruses (ERV) account for 8 to 10% of the human and mouse genomes and play an important role in some biological processes of animals. Recent studies indicate that the activation of ERV can affect the expression of the immunity- or inflammation-related genes, and the activities of ERV are subjected to regulation of many factors including nutritional factors. Therefore, we hypothesize that nutritional status can affect the expression of the immunity- or inflammation-related genes via ERV. To verify this hypothesis, the nutritional status of animals was altered by fasting or overfeeding, and the expression of intact ERV (ERVK18P, ERVK25P) and immunity- or inflammation-related genes (DDX41, IFIH1, IFNG, IRF7, STAT3) in the liver was determined by quantitative PCR, followed by overexpressing ERVK25P in goose primary hepatocytes and determining the expression of the immunity- or inflammation-related genes. The data showed that compared with the control group (no fasting), the expression of ERV and the immunity- or inflammation-related genes was increased in the liver of the fasted chickens but decreased in the liver of the fasted geese. Moreover, compared with the control group (routinely fed), the expression of ERV and the immunity- or inflammation-related genes was increased in the liver of the overfed geese. In addition, overexpression of ERVK25P in goose primary hepatocytes can induce the expression of the immunity- or inflammation-related genes. In conclusion, these findings suggest that ERV mediate the effects of fasting and overfeeding on the expression of the immunity- or inflammation-related genes, the mediation varied with poultry species, and ERV and the immunity- or inflammation-related genes may be involved in the development of goose fatty liver. This study provides a potential mechanism for the connection between nutrition and immunity.

Abstract Background Whether vastus medialis obliquus atrophy exists in patients with patellofemoral pain syndrome and whether the amount of atrophy differs between the vastus medialis obliquus and vastus lateralis muscles remain unknown. Materials From June 2016 to March 2019, 61 patients with patellofemoral pain syndrome were retrospectively included in the study group, and an age-, sex-, and body mass index-matched cohort of 61 patients with normal knees was randomly selected as the control group. All enrolled subjects had undergone CT scans in the supine position. The cross-sectional areas of the vastus medialis obliquus and the vastus lateralis muscle in the sections 0, 5, 10, 15, and 20 mm above the upper pole of the patella were measured, and the vastus medialis obliquus/vastus lateralis muscle area ratio was evaluated. Results In the study group, the vastus medialis obliquus areas and the vastus lateralis muscle areas in the sections that were 0, 5, 10, 15, and 20 mm above the upper pole of the patella were significantly smaller than the respective areas in the control group (P < 0.05). The vastus medialis obliquus/vastus lateralis muscle area ratio was significantly smaller at the upper pole of the patella (the section 0 mm above the upper pole of the patella) than the corresponding ratio in the control group (P < 0.05). No significant difference was noted between the two groups in the sections 5, 10, 15, and 20 mm above the upper pole of the patella (P > 0.05). Conclusion In patients with patellofemoral pain syndrome, vastus medialis obliquus and vastus lateralis muscle atrophy existed in sections 0–20 mm above the upper pole of the patella, compared with normal controls, and atrophy of the vastus medialis obliquus was more evident than that of the vastus lateralis muscle at the upper pole of the patella. These findings support the rationale for the use of general quadriceps exercise combined with vastus medialis obliquus strengthening exercise as part of the rehabilitation programme for the patients with patellofemoral pain syndrome.

Abstract Background SPG11 mutation-related autosomal recessive hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) is the most common cause in complicated forms of HSP, usually presenting comprehensive mental retardation on early-onset stage preceding spastic paraplegias in childhood. However, there are many instances of sporadic late-onset HSP-TCC cases with a negative family history, and potential mild cognitive deficits in multiple domains may be easily neglected and inaccurately described. Methods In this study, we performed next generation sequencing in four sporadic late-onset patients with HSP-TCC, and combined Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) to evaluate cognition of the patients. Results By evolutionary conservation and structural modeling analysis, we have revealed 4 novel pathogenic SPG11 mutations, and firstly confirmed mild cognitive impairment (MCI) with normal MMSE scores (≥27) and decreased MoCA scores (

Abstract The aim of this study was to explore the effects and mechanisms of 95% ethanol extract of Chlorella pyrenoidosa (CPE95) on lipid metabolism in hyperlipidemic rats. For the sake of chemical composition analysis of CPE95, liquid chromatography–mass spectrometry (LC‐MS) was used for determination. After treatment with CPE95, serum high‐density lipoprotein cholesterol content of the hyperlipidemic rats was increased, while the contents of cholesterol, triglyceride, and low‐density lipoprotein cholesterol were decreased strikingly. Moreover, the result of histopathology analysis showed that the accumulation and fatty deformation of the livers were relieved. Real‐time quantitative PCR and Western blotting were used to determine the expression levels of lipid metabolism‐related genes. The gene expression level of adenosine 5’‐monophosphate‐activated protein kinase was descended, and expressions of sterol regulatory element‐binding protein‐1c, acetyl‐CoA carboxylase, and 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase were all downregulated in the CPE95‐treated rats. It suggested that CPE95 may effectively improve the hyperlipidemia in rats and would be potential for functional food component to reduce blood lipid.

In this article, we present an experimental study on the impact of post-metallization annealing conditions on the negative-bias temperature instability (NBTI) of Si p-channel fin field-effect transistors (p-FinFETs) with atomic layer deposition tungsten (ALD W) as the gate-filling metal. The effects of annealing conditions on the tensile stress of the W film, impurity element concentration in the gate stack, fresh interface quality, threshold voltage shift ( ${\Delta }$ V $_{T}$ ), pre-existing traps ( ${\Delta } {N} _{\mathrm {HT}}$ ), generated traps, and their relative contributions were studied. The time exponents of ${\Delta }$ V $_{T}$ , the impacts of stress bias and temperature on NBTI degradation, and the recovery kinetics of the generated traps were analyzed. For devices with a B2H6-based W-filling metal, a 34% reduction in the fresh interface states, reduced ${\Delta }$ V $_{T}$ , and a 29% improvement in the operation overdrive voltage could be achieved by optimizing the annealing conditions. The NBTI is alleviated mainly because of the reduction in the generated traps, while the energy distribution of ${\Delta } {N} _{\mathrm {HT}}$ is insensitive to the annealing conditions. Furthermore, the relative contribution of the generated bulk insulator traps to the total number of generated traps could be reduced by optimizing the annealing conditions.

A coaxial optical fiber interferometer (COFI) is proposed here for ammonia sensing, which comprises two light-carrying single-mode fibers (SMF) fused to a section of no-core fiber (NCF), thus forming an optical interferometer. The outer surface of the COFI is coated with a layer of polyacrylic acid (PAA)/polyaniline (PAni) film. The refractive index (RI) of the sensitive layer varies when PAA/PAni interacts with ammonia, which leads to the resonance wavelength shift. The surface morphology and structure of the PAA/PAni composites were characterized by using a scanning electron microscope (SEM) and Fourier-transform infrared (FTIR) spectroscopy. When the sensor was exposed to an ammonia atmosphere of different concentrations at room temperature, the sensing performance of the PAA/PAni composite film was superior to that of a sensitive film formed by single-component PAA or PAni. According to the experimental results, the composite film formed by 5 wt% PAA mixed with 2 wt% PAni shows better performance when used for ammonia sensing. A maximum sensitivity of 9.8 pm/ppm was obtained under the ammonia concentration of 50 ppm. In addition, the sensor shows good performance in response time (100 s) and recovery time (180 s) and has good stability and selectivity. The proposed optical fiber ammonia sensor is adapted to monitor leakage in its production, storage, transportation, and application.

Conventional enzyme-based continuous glucose sensors in interstitial fluid usually rely on dissolved oxygen as the electron-transfer mediator to bring electrons from oxidase to electrode while generating hydrogen peroxide. This may lead to several problems. First, the sensor may provide biased detection results owing to fluctuation of oxygen in interstitial fluid. Second, the polymer coatings that regulate the glucose/oxygen ratio can affect the dynamic response of the sensor. Third, the glucose oxidation reaction continuously produces corrosive hydrogen peroxide, which may compromise the long-term stability of the sensor. Here, we introduce an oxygen-independent nonenzymatic glucose sensor based on water splitting-assisted electrocatalysis for continuous glucose monitoring. For the water splitting reaction (i.e., hydrogen evolution reaction), a negative pretreatment potential is applied to produce a localized alkaline condition at the surface of the working electrode for subsequent nonenzymatic electrocatalytic oxidation of glucose. The reaction process does not require the participation of oxygen; therefore, the problems caused by oxygen can be avoided. The nonenzymatic sensor exhibits acceptable sensitivity, reliability, and biocompatibility for continuous glucose monitoring in hypoxic environments, as shown by the in vitro and in vivo measurements. Therefore, we believe that it is a promising technique for continuous glucose monitoring, especially for clinically hypoxic patients.

Grain refinement has been found to be an effective method for simultaneously enhancing strength and toughness. To avoid the sharp coarsening of grains in Cu-Ni-Sn alloys during solution treatment and thereby overcoming the tradeoff between strength and ductility, this work attempted to modify the composition and improve the thermal stability of the fine-grained structure in Cu-Ni-Sn alloys. The grain growth behavior during a solution treatment of the Cu-15Ni-8Sn alloys with/without Si and Ti additions was systematically investigated. The result reveals that compared to the grain size of 146 μm in the based alloy (without trace additions) after solution processing at 1073 K for 2 h, the fine-grained structure with a size below 20 μm is maintained owing to the benefit from Si and Ti addition. It was observed that the addition of Si and Ti offer the inhibition effect on the dissolution of the γ phase and Ni16Si7Ti6 particles after solution treatment. The grain boundary movement is severely hindered by these two aspects: the pinning effect from these particles, and the drag effect induced by additional solute atoms. Based on the analysis of grain growth kinetics, the activation energy of grain growth is increased from 156 kJ/mol to 353 kJ/mol with the addition of Si and Ti.

Diffuse intrinsic pontine glioma (DIPG) is a primary glial glioma that occurs in all age groups but predominates in children and is the main cause of solid tumor-related childhood mortality. Due to its rapid progression, the inability to operate and insensitivity to most chemotherapies, there is a lack of effective treatment methods in clinical practice for DIPG patients. The prognosis of DIPG patients is extremely poor, with a median survival time of no more than 12 months. In recent years, there have been continuous breakthroughs for immunotherapies in various hematological tumors and malignant solid tumors with extremely poor prognoses, which provides new insights into tumors without effective treatment strategies. Meanwhile, with the gradual development of stereotactic biopsy techniques, it is gradually becoming easier and safer to obtain live DIPG tissue, and the understanding of the immune properties of DIPG has also increased. On this basis, a series of immunotherapy studies of DIPG are under way, some of which have shown encouraging results. Herein, we review the current understanding of the immune characteristics of DIPG and critically reveal the limitations of current immune research, as well as the opportunities and challenges for immunological therapies in DIPG, hoping to clarify the development of novel immunotherapies for DIPG treatment.

The emergence and development of high-performance materials have benefited from the revolution in modern manufacturing technology, in which additive manufacturing (AM) is the most representative over the last four decades [...]

Concrete cracks have always been the focus of research because of the serious damage they cause to structures. With the updating of hardware and algorithms, the detection of concrete structure surface cracks based on computer vision has received extensive attention. This paper proposes an improved algorithm based on the open-source model Deeplabv3+ and names it Deeplabv3+ BDF according to the optimization strategy used. Deeplabv3+ BDF first replaces the original backbone Xception with MobileNetv2 and further replaces all standard convolutions with depthwise separable convolutions (DSC) to achieve a light weight. The feature map of a shallow convolution layer is additionally fused to improve the detail segmentation effect. A new strategy is proposed, which is different from the two-stage training. The model training is carried out in the order of transfer learning, coarse-annotation training and fine-annotation training. The comparative test results show that Deeplabv3+ BDF showed good performance in the validation set and achieved the highest mIoU and detection efficiency, reaching real-time and accurate detection.

Background: PAX1 methylation (PAX1m) and HPV viral load (VL) have been reported to detect cervical high-grade squamous intraepithelial lesions (HSIL), but the relationship between them is unclear. This study aimed to evaluate the correlation between HPV VL and PAX1m and its effectiveness in predicting cervical lesions. (2) Methods: A total of 476 women referred to colposcopy for abnormal cervical screening at the Peking University People’s Hospital between November 2020 and November 2021 were enrolled. PAX1m and HPV VL were determined by QMSP and BMRT-HPV reports type-specific VL/10,000 cells, respectively. (3) Results: PAX1m was significantly increased in HSIL, especially in cervical cancer, but there was no significant difference between cervical intraepithelial neoplasms 1(CIN1) and CIN2. However, HPV VL significantly differed between CIN1 and CIN2 but not between CIN3 and cervical cancer. In general, PAX1m positively correlated with all hrHPV VL, mainly in the HPV16/18 VL (p < 0.001), but had no relationship with the other 12 types of hrHPV VL. PAX1m had the highest specificity in diagnosing CIN2+, followed by HPV16/18 VL, which are higher than cytology ≥ASCUS. (4) Conclusions: Hypermethylation of PAX1 is associated with high HPV VL, especially HPV16/18, and both present advantageous specificity in detecting CIN2+.

Abstract Background The solid transport media is a small size card that allows fast, easy DNA extraction from a variety of biological samples. In 2016 we developed a solid media transport card; for that pilot study to control the self-collection we used a pseudo-self-collection technique. The current study expands this prior work using true self-collections and only the POI card, and aims to evaluate the solid media transport card to detect HR-HPV in self-samples compared to liquid transport media. Methods Ten thousand eight hundred eighty-five women between the ages of 30–59 with no screening for 3 years were enrolled. The self-collected sample was first applied to a new solid media transport card (Labeled as SC) then the brush placed in 6 ml ThinPrep liquid (Labeled as SL). Then a physician collected a direct endocervical specimen into ThinPrep liquid (Labeled as DL). Samples were tested with Cobas 4800 and the SeqHPV NGS assay for HR-HPV. Patients positive on any test were recalled for colposcopy and biopsy. Results Ten thousand three hundred thirty-nine participants had complete data. The mean age was 43.9 years. CIN 2+ rates were 1.4% (142/10339). The agreement in HPV detection between the two different self-sample collection media was also good (Cobas HPV kappa = 0.86; SeqHPV kappa = 0.98). Tested with Cobas, the sensitivity of Cobas-SL and Cobas-SC for CIN 2+ was95.07 and 94.37%; and for CIN3+ was 96.30, 96.30% respectively. The specificity of Cobas-SC, and Cobas-SL for CIN2+ was 88.74 and 87.35%; for CIN3 was 88.04and 86.65% respectively. Tested with SeqHPV, the sensitivity for CIN2+ of Seq-SC and Seq-SL was 95.77 and 96.48%; for CIN3+, both the SC and SL specimens had a sensitivity of 100%. The specificity for CIN2+ of Seq-SC and Seq-SL was 89.54 and 89.53%; for CIN3+ was 88.84,88.82% respectively. For both HR-HPV assays, the sensitivities were similar for the two self-sample media (SC vs SL, p = 1.00). Conclusions The solid transport card for collecting vaginal self-samples as accurate as liquid transport media assayed by two different PCR based HR-HPV tests. The solid transport media is a suitable medium for collecting and storing vaginal self-samples.

Composition modification (elemental modification) is found to be an effective method for tuning the bimodal microstructure (equiaxed and column grains) observed in the selective laser melted (SLM) metallic materials, and thereby improving their properties. However, optimization for the powder composition is a tedious task consuming energy, time and resources. One of the non-equilibrium processes, melting spinning (MS), matches the solidification conditions of the SLM process (especially the cooling rate), which offers the possibility of using the MS process as the first step in optimizing the elements/alloy design and development for the SLM process. In this work, SLM and MS processes were employed to fabricate the Cu-Ni-Sn alloy to compare the microstructural features and the resultant properties. The result reveals that the sample fabricated by MS shows a similar supersaturated structure as the SLM counterpart and both these samples exhibit analogous microstructure consisting of fine equiaxed grains, column grains, intragranular and intergranular γ-(CuxNi1-x)3Sn phase. The results confirm the possibility of using the MS process as the first step in the alloy design/development for the SLM process.

Mitochondrial DNA is a useful molecular marker for phylogenetic and evolutionary analysis. In the current study, we determined the complete mitochondrial genome of Eophona personata, the Japanese Grosbeak, and the phylogenetic relationships of E. personata and 16 other species of the family Fringillidae based on the sequences of 12 mitochondrial protein-coding genes. The mitochondrial genome of E. personata consists of 16,771 base pairs, and contains 13 protein-coding genes, 22 transfer RNA (tRNA) genes, 2 ribosomal RNA (rRNA) genes, and one control region. Analysis of the base composition revealed an A+T bias, a positive AT skew and a negative GC skew. The mitochondrial gene order and arrangement in E. personata was similar to the typical avian mitochondrial gene arrangement. Phylogenetic analysis of 17 species of Fringillidae, based on Bayesian inference and Maximum Likelihood (ML) estimation, showed that the genera Coccothraustes and Hesperiphona are closely related to the genus Eophona, and further showed a sister-group relationship of E. personata and E. migratoria.

BackgroundImmune checkpoint inhibitors (ICIs) brought about a major paradigm shift in non-small cell lung cancer (NSCLC) treatment. However, the use of ICIs is related to an unforeseeable pattern of immune-related adverse events (irAEs). Hence, more precise biomarkers are needed to predict the incidence of irAEs to prevent overtreatment of ICIs and decrease occurrences of irAEs. This study was designed to identify capable clinical features and plasma inflammatory factors for predicting irAEs.MethodsA total of 67 patients who received ICI monotherapy or ICI-based combination therapy were retrospectively identified. Clinical characteristics and plasma inflammatory cytokines were collected and analyzed to screen potential biological markers associated with irAEs. The chi-square test, Fisher’s test, and the Mann–Whitney U test were performed for the primary analysis. The optimal cutoff value was determined by a receiver operating characteristic (ROC) curve. Univariate and multivariate logistic regression models were used to identify risk factors of irAEs. Univariate and multivariate Cox proportional hazards were also performed.ResultsOut of 67 patients, 40 (59.7%) experienced irAEs, and 7 (10.4%) experienced severe adverse events (grade ≥ 3). Among these analyzed immune profile biomarkers, only interleukin−10 (IL-10) was related to the risk of irAEs. A high baseline IL−10 plasma level (odds ratio (OR) = 5.318, 95% CI 1.174–24.081, p = 0.030) was found to be a tremendous and independent risk factor for the development of irAEs. Also, for the dynamic analysis, upregulation of IL-10 after one cycle of ICI treatment was positively related to the occurrence of irAEs (OR = 5.712, 95% CI 1.088–29.993, p = 0.039). When pneumonitis, the most common irAEs, was analyzed, only baseline high-expression IL-10 was accompanied with the incidence of pneumonitis (OR = 9.969, 95% CI 1.144–86.843, p = 0.037).ConclusionBaseline and dynamic IL-10 plasma levels are tremendously and independently related to higher risk in the development of irAEs and could be utilized for medical practice to monitor adverse events in patients with ICI treatment.

Diabetes, a chronic physiological dysfunction affecting people of different age groups and severely impairs the harmony of peoples’ normal life worldwide. Despite the availability of insulin preparations and several synthetic oral antidiabetic drugs, there is a crucial need for the discovery and development of novel antidiabetic drugs because of the development of resistance and side effects of those drugs in long-term use. On the contrary, plants or herbal sources are getting popular day by day to the scientists, researchers, and pharmaceutical companies all over the world to search for potential bioactive compound(s) for the discovery and development of targeted novel antidiabetic drugs that may control diabetes with the least unwanted effects of conventional antidiabetic drugs. In this review, we have presented the prospective candidates comprised of either isolated phytochemical(s) and/or extract(s) containing bioactive phytoconstituents which have been reported in several in vitro, in vivo, and clinical studies possessing noteworthy antidiabetic potential. The mode of actions, attributed to antidiabetic activities of the reported phytochemicals and/or plant extracts have also been described to focus on the prospective phytochemicals and phytosources for further studies in the discovery and development of novel antidiabetic therapeutics.

Pancreatitis is the leading cause of hospitalization in gastroenterology, and no medications are available for treating this disease in current clinical practice. FXR plays an anti-inflammatory role in diverse inflammatory diseases, while its function in pancreatitis remains unknown. In this study, we initially observed a marked increase of nuclear FXR in pancreatic tissues of human patients with pancreatitis. Deleting the FXR in pancreatic acinar cells (FXRacinarΔ/Δ) led to more severe pancreatitis in mouse models of caerulein-induced acute and chronic pancreatitis, while the FXR agonist GW4064 significantly attenuated pancreatitis in caerulein or arginine-induced acute pancreatitis and caerulein-induced chronic pancreatitis. FXR deletion impaired the viability and stress responses of pancreatic exocrine organoids (PEOs) in vitro. Utilizing RNA-seq and ChIP-seq of PEOs, we identified Osgin1 as a direct target of FXR in the exocrine pancreas, which was also increasingly expressed in human pancreatitis tissues compared to normal pancreatic tissues. Pancreatic knockdown of Osgin1 by AAV-pan abolished the therapeutic effects of FXR activation on pancreatitis, whereas pancreatic overexpression of Osgin1 effectively alleviated caerulein-induced pancreatitis. Mechanistically, we found that the FXR-OSGIN1 axis stimulated autophagic flux in the pancreatic tissues and cell lines, which was considered as the intrinsic mechanisms through which FXR-OSGIN1 protecting against pancreatitis. Our results highlight the protective role of the FXR-OSGIN1 axis in pancreatitis and provided a new target for the treatment of this disease.

Objective. This study evaluated the distribution of vaginal microbiota dysbiosis and the association with HPV viral load test in high-risk HPV-positive women before and after 50 years old. Methods. For this cross-sectional study, 388 HPV-positive women prior to referral to colposcopy in Peking University Peoples’ Hospital were included and classified as younger than 50 years (n=307) and aged 50 years or older (n=81), midvagina bacterial community composition was characterized by FlashDetect™ MAX vaginal microbe detection kit, and BMRT-HPV reported type-specific viral loads/10,000 cells. Results. The community state type (CST) IV was the most common CST occurring in 148 women (38.1%). The proportion of CST IV in those aged 50 years or older was significantly higher than those younger than 50 years (women) (66.7% vs. 30.6%); the difference was statistically significant (

The successful occupation of the eastern Eurasian Steppe in the Late Pleistocene improved cultural connections between western Eurasia and East Asia. We document multiple waves of lithic technological transmission between the eastern Eurasian Steppe and northern China during 50–11 cal. ka BP. These waves are apparent in the sequential appearance of three techno-complexes in northern China: (1) the Mousterian techno-complex, (2) the blade techno-complex mixed with Mousterian elements, (3) and the microlithized blade techno-complex. These lithic techno-complexes were transmitted under different paleoenvironmental conditions along different pathways through the eastern Eurasian Steppe. The Mousterian techno-complex and the blade techno-complex mixed with Mousterian elements were only dispersed in the north and west peripheries of northern China (50–33 cal. ka BP). We argue that these techno-complexes failed to penetrate into the hinterland of northern China because they were not well suited to local geographical conditions. In contrast, the microlithized blade technology which diffused from the eastern Eurasian Steppe was locally modified into a Microblade techno-complex which was highly suited to local environmental conditions, and proliferated across the hinterland of northern China (28/27-11 cal. ka BP). The subsequent spread of microblade technology over vast regions of Mongolia and Siberia indicates that the Pleistocene inhabitants of northern China not only adopted and modified technologies from their neighbors in the Eurasian Steppe, but these modified variants were subsequently transmitted back into the Eurasian Steppe. These episodes of technological transmission indicate complicated patterns of population dispersal and technological interaction across northern China and the eastern Eurasian Steppe.