Synthetic enhancers including TFREs improve transgene expression in CHO cells.

The human cytomegalovirus major immediate early gene (CMV) promoter is currently the most preferred promoter for recombinant therapeutic proteins (RTPs) production in CHO cells. To enhance the production of RTPs, five synthetic enhancers including multiple transcription factor regulatory elements (TFREs) were evaluated to enhance recombinant protein level in transient and stably transfected CHO cells. Compared with the control, four elements can enhance the report genes expression under both two transfected states. Further, the function of these four enhancers on human serum albumin (HSA) were investigated. We found that the transient expression can increase by up to 1.5 times, and the stably expression can maximum increase by up to 2.14 times. The enhancement of transgene expression was caused by the boost of their corresponding mRNA levels. Transcriptomics analysis was performed and found that transcriptional activation and cell cycle regulation genes were involved. In conclusion, optimization of enhancers in the CMV promoter could increase the production yield of transgene in transfected CHO cells, which has significance for developing high-yield CHO cell expression system.

CPBA-CLIM: An entity-relation extraction model for ontology-based knowledge graph construction in hazardous chemical incident management.

In recent years, hazardous chemical incidents have occurred frequently, resulting in significant human casualties, property damage, and environmental pollution due to human or natural factors. Accurately mining the lessons learned from accumulating incident reports and constructing the knowledge graph for hazardous chemical incident management can assist managers in identifying patterns and analyzing common attributes, thereby preventing the recurrence of similar incidents. This article addresses the challenges of dispersed textual information, specialized vocabulary, and data formats in hazardous chemical incidents. We propose a novel entity-relation extraction model called CPBA-CLIM (content-position-based attention-cross-label intersect matching) to provide an accurate data foundation for constructing the hazardous chemical incident knowledge graph. The content-position-based attention module, based on content-position attention, incorporates contextual semantic information into the combined encoding of bidirectional encoder representations from the transformer's content and position to obtain dynamic word vectors that align with the thematic context of the text. Additionally, the cross-label intersect matching strategy evaluates the rationality of entity-relation interactions in sets containing potential overlaps, reducing the impact of entity-relation overlap on triplet extraction accuracy. Comparative experimental results on public datasets demonstrate the model's outstanding performance in overlapping triplets. Qualitative experiments on a self-constructed dataset integrate our model with ontology construction techniques, successfully establishing a knowledge graph for managing hazardous chemical incidents. This research effectively enhances the degree of automation and efficiency in knowledge graph construction, thus offering support and decision-making foundations for hazardous chemical safety management.

Synergistic promotion of transient transgene expression in CHO cells by PDI/XBP-1s co-transfection and mild hypothermia.

Transient gene expression system is an important tool for rapid production of recombinant proteins in Chinese hamster ovary (CHO) cells. However, their low productivity is the main hurdle to overcome. An effective approach through which to obtain high protein yield involves targeting transcriptional, post-transcriptional events (PTEs), and culture conditions. Here, we investigated the effects of protein disulfide isomerase (PDI) and spliced X-box binding protein 1 (XBP-1s) co-overexpression combined with mild hypothermia on the transient yields of recombinant proteins in CHO cells. The results showed that the gene of interest (GOI) and the PDI/XBP-1s helper vector at a co-transfection ratio of 10:1 could obviously increase transient expression level of recombinant protein in CHO cells. However, PDI/XBP-1s overexpression had no significance effect on the mRNA levels of the recombinant protein, suggesting that it targeted PTEs. Moreover, the increased production was due to the enhancing of cell specific productivity, not related to cell growth, viability, and cell cycle. In addition, combined PDI/XBP-1s co-overexpression and mild hypothermia could further improve Adalimumab expression, compared to the control/37 °C and PDI/XBP-1s/37 °C, the Adalimumab volume yield of PDI/XBP-1s/33 °C increased by 203% and 142%, respectively. Mild hypothermia resulted in 3.52- and 2.33-fold increase in the relative mRNA levels of PDI and XBP-1s, respectively. In conclusion, the combination of PDI/XBP-1s overexpression and culture temperature optimization can achieve higher transient expression of recombinant protein, which provides a synergetic strategy to improve transient production of recombinant protein in CHO cells.

Protective role of curcumin in disease progression from non-alcoholic fatty liver disease to hepatocellular carcinoma: a meta-analysis.

Background: Pathological progression from non-alcoholic fatty liver disease (NAFLD) to liver fibrosis (LF) to hepatocellular carcinoma (HCC) is a common dynamic state in many patients. Curcumin, a dietary supplement derived from the turmeric family, is expected to specifically inhibit the development of this progression. However, there is a lack of convincing evidence. Methods: The studies published until June 2023 were searched in PubMed, Web of Science, Embase, and the Cochrane Library databases. The SYstematic Review Center for Laboratory animal Experimentation (SYRCLE) approach was used to evaluate the certainty of evidence. StataSE (version 15.1) and Origin 2021 software programs were used to analyze the critical indicators. Results: Fifty-two studies involving 792 animals were included, and three disease models were reported. Curcumin demonstrates a significant improvement in key indicators across the stages of NAFLD, liver fibrosis, and HCC. We conducted a detailed analysis of common inflammatory markers IL-1ß, IL-6, and TNF-α, which traverse the entire disease process. The research results reveal that curcumin effectively hinders disease progression at each stage by suppressing inflammation. Curcumin exerted hepatoprotective effects in the dose range from 100 to 400 mg/kg and treatment duration from 4 to 10 weeks. The mechanistic analysis reveals that curcumin primarily exerts its hepatoprotective effects by modulating multiple signaling pathways, including TLR4/NF-κB, Keap1/Nrf2, Bax/Bcl-2/Caspase 3, and TGF-ß/Smad3. Conclusion: In summary, curcumin has shown promising therapeutic effects during the overall progression of NAFLD-LF-HCC. It inhibited the pathological progression by synergistic mechanisms related to multiple pathways, including anti-inflammatory, antioxidant, and apoptosis regulation.

The influence of lifestyle habits on levels of depression among rural middle school students in Northeastern China.

Background: Depression rates among adolescents have risen dramatically over the past decade. Therefore, preventing depression among adolescents is particularly important. Differences in lifestyle habits may play a role in depression. Purpose: This study aimed to explore the influence of living habits on depression levels among rural middle school students in Northeast China and to provide a theoretical basis for developing interventions to reduce depression levels in middle school students. Methods: A total of 296 middle school students aged 13-15 years from Benxi City, Northeast China completed the anthropometric measurements, Physical Activity Scale-3 (PARS-3), and the Self-Rating Depression Scale (SDS). Their average screen time in the most recent week, parents' education level, and monthly family income were collected through a questionnaire. Results: Females had higher depression scores than males (41.0 ± 6.9 vs. 37.9 ± 8.0). Physical activity (ß = -0.38, t = -7.06, P < 0.01), family income (ß = -0.20, t = -4.07, P < 0.01), screen time (ß = 0.16, t = 3.34, P < 0.01), age (ß = 0.15, t = 3.16, P < 0.01), sex (ß = -0.13, t = -2.74, P < 0.01), and sleep quality (ß = -0.08, t = -1.87, P < 0.01) are important factors related to depression levels. Conclusion: The preliminary analysis results showed that among middle school students in rural Northeast China, the depression level of females was significantly higher than that of males. Poor quality sleep, low levels of physical activity, low household income, and long screen time were positively associated with depression. Therefore, strengthening physical activity, improving sleep quality, and reducing screen time are of clinical relevance in preventing and reducing depression.

Effect of valproic acid combined with transplantation of olfactory ensheathing cells modified by neurotrophic 3 gene on nerve protection and repair after traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) often leads to cognitive and neurological dysfunction. Valproic acid (VPA) has a neuroprotective effect in acute central nervous system diseases; the neurotrophin 3 gene (NT-3) can maintain the survival of neurons, and olfactory ensheathing cells (OECs) can promote the growth of nerve axons. This study aimed to evaluate the restorative effect of VPA combined with NT-3 modified OECs (NT-3-OECs) on neurological function after TBI. METHODS: The neurological severity score (NSS) of rats was evaluated on the 1st, 7th, 14th, and 28th day after TBI modeling and corresponding intervention. Hematoxylin-eosin (HE) staining, p75 nerve growth factor receptor (P75), glial fibrillary acidic protein (GFAP), and neurofilament protein (NF)staining, and argyrophilic staining were used to observe the morphology of brain tissue 28 days after modeling. Moreover, TdT-mediated dUTP Nick-End Labeling (TUNEL) was used to detect the apoptosis rate of neurons. The changes in synapses and mitochondria in the injured area were observed by electron microscope. RESULTS: NT-3-OECs transplantation can increase the content of NT-3 in brain tissue, and NT-3-OECs can survive for >28 days. The NSS score of the TBI-VPA-NT-3-OECs group 28 days after cell transplantation was significantly lower than that of the other model treatment groups (P < 0.05). The morphological structure of the brain tissue was more complete, and the neurofilament fibers were neatly arranged, achieving better results than those of the other groups. The apoptosis rate of nerve cells in the TBI-VPA-NT-3-OECs group was significantly lower than in the other treatment groups (P < 0.05). Furthermore, the number of synapses in the combined intervention group was significantly higher than in the other treatment groups, and the mitochondrial structure was more complete. CONCLUSION: NT-3-OECs have good biological function, and VPA combined with NT-3-OECs transplantation can effectively improve the prognosis of TBI rats.

Research progress on the regulation of oxidative stress by phenolics: the role of gut microbiota and Nrf2 signaling pathway.

In recent years, the increase in high-calorie diets and sedentary lifestyles has made obesity a global public health problem. An unbalanced diet promotes the production of proinflammatory cytokines and causes redox imbalance in the body. Phenolics have potent antioxidant activity and cytoprotective ability. They can scavenge free radicals and reactive oxygen species, and enhance the activity of antioxidant enzymes, thus combating the body's oxidative stress. They can also improve the body's inflammatory response, enhance the enzyme activity of lipid metabolism, and reduce the contents of cholesterol and triglyceride. Most phenolics are biotransformed and absorbed into the blood after the action by gut microbiota; these metabolites then undergo phase I and II metabolism and regulate oxidative stress by scavenging free radicals and increasing expression of antioxidant enzymes. Phenolics induce the expression of genes encoding antioxidant enzymes and phase II detoxification enzymes by stimulating Nrf2 to enter the nucleus and bind to the antioxidant response element after uncoupling from Keap1, thereby promoting the production of antioxidant enzymes and phase II detoxification enzymes. The absorption rate of phenolics in the small intestine is extremely low. Most phenolics reach the colon, where they interact with the microbiota and undergo a series of metabolism. Their metabolites will reach the liver via the portal vein and undergo conjugation reactions. Subsequently, the metabolites reach the whole body to exert biological activity by traveling with the systemic circulation. Phenolics can promote the growth of probiotics, reduce the ratio of Firmicutes/Bacteroidetes (F/B), and improve intestinal microecological imbalance. This paper reviews the nutritional value, bioactivity, and antioxidant mechanism of phenolics in the body, aiming to provide a scientific basis for the development and utilization of natural antioxidants and provide a reference for elucidating the mechanism of action of phenolics for regulating oxidative stress in the body. © 2023 Society of Chemical Industry.

More severe initial manifestations and worse short-term functional outcome of intracerebral hemorrhage in the plateau than in the plain.

Intracerebral hemorrhage (ICH) is one of the most devastating forms of stroke. However, studies on ICH at high altitude are insufficient. We aimed to compare the initial manifestations, imaging features and short-term functional outcomes of ICH at different altitudes, and further explore the effect of altitude on the severity and prognosis of ICH. We retrospectively recruited ICH patients from January 2018 to July 2021 from two centers at different altitudes in China. Information regarding to clinical manifestations, neuroimages, and functional outcomes at discharge were collected and analyzed. Association between altitude and initial severity, neuroimages, and short-term prognosis of ICH were also investigated. A total of 724 patients with 400 lowlanders and 324 highlanders were enrolled. Compared with patients from the plain, those at high altitude were characterized by more severe preliminary manifestations (P < 0.0001), larger hematoma volume (P < 0.001) and poorer short-term functional outcome (P < 0.0001). High altitude was independently associated with dependency at discharge (adjusted P = 0.024), in-hospital mortality (adjusted P = 0.049) and gastrointestinal hemorrhage incidence (adjusted P = 0.017). ICH patients from high altitude suffered from more serious initial manifestations and worse short-term functional outcome than lowlanders. Control of blood pressure, oxygen supplementation and inhibition of inflammation may be critical for ICH at high altitude.

Multi-task learning for aspect level semantic classification combining complex aspect target semantic enhancement and adaptive local focus.

Aspect-based sentiment analysis (ABSA) is a fine-grained and diverse task in natural language processing. Existing deep learning models for ABSA face the challenge of balancing the demand for finer granularity in sentiment analysis with the scarcity of training corpora for such granularity. To address this issue, we propose an enhanced BERT-based model for multi-dimensional aspect target semantic learning. Our model leverages BERT's pre-training and fine-tuning mechanisms, enabling it to capture rich semantic feature parameters. In addition, we propose a complex semantic enhancement mechanism for aspect targets to enrich and optimize fine-grained training corpora. Third, we combine the aspect recognition enhancement mechanism with a CRF model to achieve more robust and accurate entity recognition for aspect targets. Furthermore, we propose an adaptive local attention mechanism learning model to focus on sentiment elements around rich aspect target semantics. Finally, to address the varying contributions of each task in the joint training mechanism, we carefully optimize this training approach, allowing for a mutually beneficial training of multiple tasks. Experimental results on four Chinese and five English datasets demonstrate that our proposed mechanisms and methods effectively improve ABSA models, surpassing some of the latest models in multi-task and single-task scenarios.

A cross-modal conditional mechanism based on attention for text-video retrieval.

Current research in cross-modal retrieval has primarily focused on aligning the global features of videos and sentences. However, video conveys a much more comprehensive range of information than text. Thus, text-video matching should focus on the similarities between frames containing critical information and text semantics. This paper proposes a cross-modal conditional feature aggregation model based on the attention mechanism. It includes two innovative modules: (1) A cross-modal attentional feature aggregation module, which uses the semantic text features as conditional projections to extract the most relevant features from the video frames. It aggregates these frame features to form global video features. (2) A global-local similarity calculation module calculates similarities at two granularities (video-sentence and frame-word features) to consider both the topic and detail features in the text-video matching process. Our experiments on the four widely used MSR-VTT, LSMDC, MSVD and DiDeMo datasets demonstrate the effectiveness of our model and its superiority over state-of-the-art methods. The results show that the cross-modal attention aggregation approach can effectively capture the primary semantic information of the video. At the same time, the global-local similarity calculation model can accurately match text and video based on topic and detail features.

An alternative method of Bakri balloon placement for postpartum hemorrhage after vaginal delivery.

OBJECTIVES: We developed a new Bakri balloon tamponade (BBT) placement technique after vaginal delivery, which aimed to be faster without balloon slippage. This study compared the new method with standard placement of BBT in women with postpartum hemorrhage (PPH) after vaginal delivery. MATERIAL AND METHODS: This study was undertaken of women who underwent vaginal delivery at the obstetrics and gynecology departments of the Hospital of Chengdu University of Traditional Chinese Medicine, Sichuan Provincial Hospital for Women and Children, and Si Chuan JINXIN Women and Children Hospital between January 2014 and December 2020. Women who underwent BBT for PPH were grouped according to placement method into the old-BBT group and the new-BBT group. RESULTS: Of 20487 childbirths by vaginal delivery, 512 (2.50%) had PPH, 77 women underwent BBT (old-BBT n = 28, new-BBT n = 49). Background characteristics were similar except prothrombin time (PT, p < 0.01) and activated partial thromboplastin time (APTT, p < 0.004) were lower in the new-BBT group than the old-BBT group. The operation time was shorter in the new-BBT group (p < 0.001) with less bleeding (p < 0.003) and saline injection (p < 0.001). A balloon slippage was less likely (p < 0.008) and postoperative bleeding (p < 0.01), transfusion rate (p < 0.03), transfusion volume (p < 0.002), and hospital stay was lower in the new-BBT group (p < 0.015). Multivariate analysis suggested PT (OR = 0.039, 95% CI: 0.002-0.730, p < 0.030), international normalized ratio (OR = 8.244, 95% CI: 3.807-17.850, p < 0.009), and BBT method (OR = 5.200, 95% CI: 1.745-15.493, p < 0.003), were associated with requiring a blood transfusion. CONCLUSIONS: This method of BBT placement reduced operation time, balloon slippage, bleeding, and hospital stay in women with PPH after vaginal delivery.

CMV/AAT promoter of MAR-based episomal vector enhanced transgene expression in human hepatic cells.

We have previously developed a non-viral episomal vector based on matrix attachment region (MAR) that can facilitate plasmid replication episomally in mammal cells. In this study, we have focused on the development of an alternative tissue specific episomal vector by incorporating into cis-acting elements. We found that AAT promoter demonstrated the highest eGFP expression level in HepG2, Huh-7 and HL-7702 hepatic cells. Furthermore, hCMV enhancer when combined with AAT promoter significantly improved the eGFP expression level in the transfected HepG2 cells. The mean fluorescence intensity of eGFP in hCMV2 group was 1.33 fold, which was higher than that of the control (p < 0.01), followed by the hCMV1 group (1.21 fold). In addition, the percentages of eGFP-expressing cells in hCMV1 and hCMV2 groups were observed to be 49.3% and 57.2%, which were significantly higher than that of the enhancer-devoid control vector (44.3%) (p < 0.05). Moreover, the eGFP protein were up to 3.5 fold and 5.1 fold (p < 0.05), respectively. This observation could be related with the activities of some specific transcription factors (TFs) during the transcriptional process, such as SRF, REL and CREB1. The composite CMV/AAT promoter can be thus used for efficient transgene expression of MAR-based episomal vector in liver cells and as a potential gene transfer tools for the management of liver diseases. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03774-x.

Inhibition of galectin-3 post-infarction impedes progressive fibrosis by regulating inflammatory profibrotic cascades.

AIMS: Acute myocardial infarction (MI) causes inflammation, collagen deposition, and reparative fibrosis in response to myocyte death and, subsequently, a pathological myocardial remodelling process characterized by excessive interstitial fibrosis, driving heart failure (HF). Nonetheless, how or when to limit excessive fibrosis for therapeutic purposes remains uncertain. Galectin-3, a major mediator of organ fibrosis, promotes cardiac fibrosis and remodelling. We performed a preclinical assessment of a protein inhibitor of galectin-3 (its C-terminal domain, Gal-3C) to limit excessive fibrosis resulting from MI and prevent ventricular enlargement and HF. METHODS AND RESULTS: Gal-3C was produced by enzymatic cleavage of full-length galectin-3 or by direct expression of the truncated form in Escherichia coli. Gal-3C was intravenously administered for 7 days in acute MI models of young and aged rats, starting either pre-MI or 4 days post-MI. Echocardiography, haemodynamics, histology, and molecular and cellular analyses were performed to assess post-MI cardiac functionality and pathological fibrotic progression. Gal-3C profoundly benefitted left ventricular ejection fraction, end-systolic and end-diastolic volumes, haemodynamic parameters, infarct scar size, and interstitial fibrosis, with better therapeutic efficacy than losartan and spironolactone monotherapies over the 56-day study. Gal-3C therapy in post-MI aged rats substantially improved pump function and attenuated ventricular dilation, preventing progressive HF. Gal-3C in vitro treatment of M2-polarized macrophage-like cells reduced their M2-phenotypic expression of arginase-1 and interleukin-10. Gal-3C inhibited M2 polarization of cardiac macrophages during reparative response post-MI. Gal-3C impeded progressive fibrosis post-MI by down-regulating galectin-3-mediated profibrotic signalling cascades including a reduction in endogenous arginase-1 and inducible nitric oxide synthase (iNOS). CONCLUSION: Gal-3C treatment improved long-term cardiac function post-MI by reduction in the wound-healing response, and inhibition of inflammatory fibrogenic signalling to avert an augmentation of fibrosis in the periinfarct region. Thus, Gal-3C treatment prevented the infarcted heart from extensive fibrosis that accelerates the development of HF, providing a potential targeted therapy.

Combination of MAR and intron increase transgene expression of episomal vectors in CHO cells.

Previous work has shown that the EF-1α promoter of episomal vectors maintains high-level transgene expression in stably transfected Chinese hamster ovary (CHO) cells. However, the transgene expression levels need to be further increased. Here, we first incorporated matrix attachment regions (MARs), ubiquitous chromatin opening element (UCOE), stabilizing anti repressor elements 40 (STAR 40) elements into episomal vector at different sites and orientations, and systemically assessed their effects on transgene expression in transfected CHO-K1 cells. Results showed that enhanced green fluorescent protein (eGFP) expression levels increased remarkably when MAR X-29 was inserted upstream of the promoter, followed by the insertion of MAR1 downstream of the poly A, and the orientation had no significant effect. Moreover, MAR X-29 combined with human cytomegalovirus intron (hCMVI) yielded the highest transgene expression levels (4.52-fold). Transgene expression levels were not exclusively dependent on transgene copy numbers and were not related to the mRNA expression level. In addition, vector with MAR X-29+hCMVI can induce herpes simplex virus thymidine kinase (HSV-TK) protein expression, and the HSV-TK protein showed a cell-killing effect and an obvious bystander effect on HCT116 cells. In conclusion, the combination of MAR X-29 and hCMV intron can achieve high efficiency transgene expression mediated by episomal vectors in CHO-K1 cells.

Maternal and neonatal outcomes in women with twin pregnancies based on gestational weight gain: An updated systematic review and meta-analysis.

Objective: This updated systematic review and meta-analysis aimed to assess maternal and fetal outcomes of pregnancies based on the Institute of Medicine (IOM) guidelines of gestational weight gain (GWG). Methods: PubMED, SCOPUS, EMBASE and Web of Science were searched up to 30th July 2022. All studies evaluating maternal and/or neonatal outcomes of twin pregnancies based on the IOM guidelines of gestational weight gain were included. Results: Twenty two studies were included. Mothers with twin pregnancies experiencing inadequate GWG showed higher incidence of gestational diabetes with the risk ratio (RR) 1.22 95% CI (0.95,1.57), p=0.0005, i2= 69% and premature rupture of membrane (PROM) with RR 1.14 95% CI (0.99, 1.30), p=0.07; i2=0% that coincided with higher rates of preterm birth, low birth weight, small for gestational age (SGA) and admission to NICU in neonates. Mothers with excessive GWG had higher risk of developing gestational hypertension with RR 1.59 95% CI (1.22, 2.07), p=0.0006, i2=75% and extremely preterm delivery (<32 weeks). Conclusion: Within the limitations of this review, GWG was found to be a predictable risk factor for adverse maternal and neonatal outcomes of twin pregnancies.

Microencapsulation protected Lactobacillus viability and its activity in modulating the intestinal microbiota in newly weaned piglets.

Lactobacilli are sensitive to heat, which limits their application as probiotics in livestock production. Lactobacillus rhamnosus LB1 was previously shown to reduce enterotoxigenic Escherichia coli (ETEC) and Salmonella infections in pigs. To investigate its potential in the application, the bacterium was microencapsulated and examined for its survival from feed pelleting and long-term storage as well as its function in modulating pig intestinal microbiota. The in vitro studies showed that freshly microencapsulated Lactobacillus rhamnosus LB1 had viable counts of 9.03 ± 0.049 log10 colony-forming units/g, of which only 0.06 and 0.87 Log of viable counts were reduced after storage at 4 and 22 °C for 427 d. The viable counts of encapsulated Lactobacillus rhamnosus LB1 were 1.06 and 1.54 Log higher in the pelleted and mash feed, respectively, than the non-encapsulated form stored at 22 °C for 30 d. In the in vivo studies, 80 piglets (weaned at 21 d of age) were allocated to five dietary treatments for a 10-d growth trial. The dietary treatments were the basal diet (CTL) and basal diet combined with either non-encapsulated LB1 (NEP), encapsulated LB1 (EP), bovine colostrum (BC), or a combination of encapsulated LB1 and bovine colostrum (EP-BC). The results demonstrated that weaning depressed feed intake and reduced growth rates in pigs of all the treatments during 21 to 25 d of age; however, the body weight gain was improved during 25 to 31 d of age in all groups with the numerically highest increase in the EP-BC-fed pigs during 21 to 31 d of age. Dietary treatments with EP, particularly in combination with BC, modulated pig intestinal microbiota, including an increase in Lactobacillus relative abundance. These results suggest that microencapsulation can protect Lactobacillus rhamnosus LB1 against cell damage from a high temperature during processing and storage and there are possible complementary effects between EP and BC.

Both in vitro and in vivo studies were conducted to verify if the microencapsulation method reported previously could preserve the viability of Lactobacillus rhamnosus LB1 after feed pelleting and long-term storage, and the probiotic functions of the bacterium either alone or in combination with bovine colostrum (BC) in the weaning transition phase of piglets. The results demonstrated that microencapsulation protected Lactobacillus rhamnosus LB1 against cell damage from a high temperature during processing and storage. Dietary treatments with encapsulated LB1, particularly in combination with BC, modulated pig intestinal microbiota, including an increase in Lactobacillus relative abundance during the weaning transition.

The safety concerns regarding immune checkpoint inhibitors in liver cancer patients rising mainly from CHB.

Aim: To analyze the safety of immune checkpoint inhibitors in primary liver cancer patients and to identify the risk factors for immune-related adverse events (irAEs). Methods: The study enrolled 106 patients with primary liver cancer, including 81 with hepatocellular carcinoma and 25 with intrahepatic cholangiocarcinoma. We analyzed the differences between groups in irAE occurrence, including those with and without targeted drugs and those who received interventional therapy. Results: The incidence of irAEs was 39%, with thyroid function, liver function, and skin events being the most common. There was no correlation among irAE incidence and the liver cancer type, stage, or severity; grade of Child-Pugh score; and Barcelona Clinical Liver Cancer classification. However, being overweight was a significant risk factor for irAEs, correlating with high body mass index. The combination of targeted drugs and/or transcatheter arterial chemoembolization therapy did not increase the incidence of irAEs. Conclusion: Being overweight is a potential risk factor for irAEs in primary liver cancer patients. However, there is no correlation between irAE incidence and the liver cancer type, stage, or severity or a combination of targeted drugs or transarterial chemoembolization therapy.

C-X-C chemokine receptor type 7 antibody enhances neural plasticity after ischemic stroke.

Stromal cell-derived factor-1 and its receptor C-X-C chemokine receptor 4 (CXCR4) have been shown to regulate neural regeneration after stroke. However, whether stromal cell-derived factor-1 receptor CXCR7, which is widely distributed in the developing and adult central nervous system, participates in neural regeneration remains poorly understood. In this study, we established rat models of focal cerebral ischemia by injecting endothelin-1 into the cerebral cortex and striatum. Starting on day 7 after injury, CXCR7-neutralizing antibody was injected into the lateral ventricle using a micro drug delivery system for 6 consecutive days. Our results showed that CXCR7-neutralizing antibody increased the total length and number of sprouting corticospinal tract fibers in rats with cerebral ischemia, increased the expression of vesicular glutamate transporter 1 and growth-related protein 43, markers of the denervated spinal cord synapses, and promoted the differentiation and maturation of oligodendrocyte progenitor cells in the striatum. In addition, CXCR7 antibody increased the expression of CXCR4 in the striatum, increased the protein expression of RAS and ERK1/2 associated with the RAS/ERK signaling pathway, and improved rat motor function. These findings suggest that CXCR7 improved neural functional recovery after ischemic stroke by promoting axonal regeneration, synaptogenesis, and myelin regeneration, which may be achieved by activation of CXCR4 and the RAS/ERK1/2 signaling pathway.

Advances in health-promoting effects of natural polysaccharides: Regulation on Nrf2 antioxidant pathway.

Natural polysaccharides (NPs) possess numerous health-promoting effects, such as liver protection, kidney protection, lung protection, neuroprotection, cardioprotection, gastrointestinal protection, anti-oxidation, anti-diabetic, and anti-aging. Nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant pathway is an important endogenous antioxidant pathway, which plays crucial roles in maintaining human health as its protection against oxidative stress. Accumulating evidence suggested that Nrf2 antioxidant pathway might be one of key regulatory targets for the health-promoting effects of NPs. However, the information concerning regulation of NPs on Nrf2 antioxidant pathway is scattered, and NPs show different regulatory behaviors in their different health-promoting processes. Therefore, in this article, structural features of NPs having regulation on Nrf2 antioxidant pathway are overviewed. Moreover, regulatory effects of NPs on this pathway for health-promoting effects are summarized. Furthermore, structure-activity relationship of NPs for health-promoting effects by regulating the pathway is preliminarily discussed. Otherwise, the prospects on future work for regulation of NPs on this pathway are proposed. This review is beneficial to well-understanding of underlying mechanisms for health-promoting effects of NPs from the view angle of Nrf2 antioxidant pathway, and provides a theoretical basis for the development and utilization of NPs in promoting human health.