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Telomerase has been considered as a biomarker for early diagnosis and prognosis assessment of hepatocellular carcinoma (HCC), while the highly sensitive and specific methods remain challenging. To detect telomerase, a novel surface-enhanced Raman scattering (SERS) biosensor was constructed using the dual DNA-catalyzed amplification strategy composed of strand displacement amplification (SDA) and catalytic hairpin assembly (CHA). This strategy relies on the extension reaction of telomerase primer induced by telomerase, forming long-stranded DNAs with repetitive sequence to catalyze the follow-up SDA event. Subsequently, the SDA products can trigger the CHA reaction between the SERS probes (Au-Ag nanocages (Au-AgNCs) modified with hairpin DNA1 and Raman reporters) and capture substrate (Au@SiO2 array labeled with hairpin DNA2), resulting in the formation of numerous “hot spots” to significantly enhance the SERS signal. Results are promising that the established biosensor presented excellent reproducibility, specificity and sensitivity. Moreover, ELISA was applied as the golden standard to verify the application of the proposed biosensor in real samples and the results confirmed the satisfactory accuracy of our method. Therefore, the proposed SERS biosensor has the potential to be an ideal tool for the early screening of HCC.

IntroductionBamboo is one of the fastest-growing plants on earth, and its young culms are formed by the elongation of internodes. However, the mathematical intricacies of its internode elongation are not well understood.MethodsThis study investigated the internode length growth of Phyllostachys edulis, Phyllostachys iridescens, and Pseudosasa amabilis at ten different culm height developmental stages (G1–G10).Results and discussionThe tempo of internode elongation from the culm base to the tip generally followed a “slow-fast-slow” growth rhythm. The internode length and the serial number relationship showed a right-skewed curve. As the bamboo grows taller, the longest internode moves from the base to the middle of the culm. The relationship between relative internode number (RIN) and relative cumulative internode length (RCIL) displayed a typical S-shaped growth curve. The modified Brière (MBE) sigmoid equation achieved better goodness-of-fit than the logistic, power, and third-order functions in fitting the RIN-RCIL curves with the smallest average root mean square error (RMSE). The elongation rates of internodes varied not only with the growth of culm height, but also with the position of the bamboo culm from base to tip. In addition, as the bamboo grows in height, more internodes gradually contribute to the culm height growth. At G1 development stage, 24.01–38.23% of the internodes contributed 65.27–73.59% of the culm height, whereas at G10 stage, 49.28–61.07% of the internodes contributed 66.70–78.18% of the culm height. Our findings provide new insights into the mathematical characterization of bamboo internode elongation patterns involved in the rapid culm growth.

This study aimed to evaluate the impacts of wild and breeding juvenile rice field eel under conditions of ammonia and heat stress. The growth performance (FBW, WGR, SGR, and FCR) of 360 wild (24.22 ± 0.30 g) and 360 breeding (24.16 ± 0.27 g) strains was significantly hindered by ammonia and heat stress. The inhibitory effects were more obvious when the two stresses were combined. The growth performance and survival rates of the breeding strains outperformed that of the wild strains under identical stress conditions, this was explained by the expression of the growth-related gene (gh). They have increased the enzyme activity (CAT and GSH-Px) and expression of immune-related genes (cat, gpx3, and hsp90α) in response to oxidative stress. However, the results of certain indicator enzymes indicate the presence of oxidative damage in their tissues. The presence of an inflammatory response in the tissues was suggested by the up-regulation of genes associated with pro-inflammatory cytokines (il-1β and il-8) and the down-regulation of genes related to anti-inflammatory cytokines (il-10). Additionally, the presence of tissue damage was shown by the up-regulation of genes connected to apoptosis (cas2, cas8, and cas9) and the down-regulation of genes connected to tight junctions (zo-1). Nevertheless, it is noteworthy that breeding strains exhibited superior adaptability to ammonia and heat stress in comparison to wild strains.

Monopterus albus is one of China’s renowned and superior aquaculture species, with its seedlings mainly sourced from wild capture. One of the bottlenecks in M. albus aquaculture is the high mortality rate and low feeding initiation rate from stocking wild fry to the initiation of feeding. In production, trash fish is commonly used to wean M. albus juveniles onto feeding. In this study, we introduced three other natural feeds, earthworms (EW), yellow mealworms (YMW), and fly maggots (FM), with frozen trash fish (TF) serving as the control group, to evaluate the effects of these four natural feeds on the survival rate, feeding initiation, antioxidant enzymes activity, and body composition of M. albus juveniles under recirculating water aquaculture conditions. The experiment comprised four treatments, each with three replicates. Each replicate consisted of stocking 150 M. albus juveniles weighing 10.02 ± 0.89 g in size, raised for 5 weeks. The survival rate of the YMW group was 73.33%–85.33%, which was significantly higher than that of the other three bait groups (p < 0.05). The four bait groups showed no significant differences in final body weight and specific growth rate (SGR) (p > 0.05). The EW group showed the highest final body weight, with an average SGR of 2.73, whereas the YMW group had an average SGR of 1.87. The average daily feeding amount was significantly higher in EW and YMW groups than in the other two groups (p < 0.05). The percentage of feeding amount to fish weight in the EW group reached 7.3% in the fifth week. After 5 weeks of cultivation, NO2−-N content was significantly higher in the waters of the TF and EW groups than in the waters of the FM and YMW groups (p < 0.05), there was no significant difference in TAN content among the treatment groups (p > 0.05). Liver malondialdehyde content was significantly higher in the TF group than in the other bait groups (p < 0.05). GSH-Px activity was significantly higher in the EW group than in the FM group and YMW group. No significant differences in SOD and CAT activity and T-AOC were observed among the bait groups (p > 0.05). The increase in crude protein content was significantly higher in the TF group than in the FM group, but the increase in crude ash content was significantly lower in the TFgroup. In conclusion, Tenebrio molitor could potentially serve as one of the alternative feeds during the initial stages of M. albus juveniles stocking.

Fish intestinal health under intensive aquaculture mode plays an important role in growth, development, and immune function. The present study was aimed to systematically investigate the differences of intestinal health between wild and cultured Monopterus albus by biochemical parameters, histomorphology, and molecular biology. A total of 15 healthy M. albus per group, with an average body weight of 45 g, were sampled to analyze intestinal health parameters. Compared with wild fish, the cultured M. albus in the foregut had lower trypsin, lipase, SOD, CAT, T-AOC, and GSH-Px activities (P < 0.05) and higher amylase activity and MDA content (P < 0.05). The villus circumference and goblet cells in the cultured group were significantly lower than those in the wild group (P < 0.05). In addition, the cultured fish showed lower relative expression levels of occludin, zo-1, zo-2, claudin-12, claudin-15, mucin5, mucin15, lysozyme, complement 3, il-10, tgf-β1, tgf-β2, and tgf-β3 (P < 0.05) and higher il-1β, il-6, il-8, tnf-a, and ifnγ mRNA expressions than those of wild fish (P < 0.05). In terms of gut microbiota, the cultured group at the phylum level displayed higher percentages of Chlamydiae and Spirochaetes and lower percentages of Firmicutes, Bacteroidetes, Actinobacteria, Cyanobacteria, and Verrucomicrobia compared to the wild group (P < 0.05). At the genus level, higher abundances of Pseudomonadaceae_Pseudomonas and Spironema and lower abundances of Lactococcus and Cetobacterium were observed in the cultured group than in the wild group (P < 0.05). To our knowledge, this is the first investigation of the intestinal health status between wild and cultured M. albus in terms of biochemistry, histology, and molecular biology levels. Overall, the present study showed significant differences in intestinal health between wild and cultured M. albus and the main manifestations that wild M. albus had higher intestinal digestion, antioxidant capacity, and intestinal barrier functions than cultured M. albus. These results would provide theoretical basis for the subsequent upgrading of healthy aquaculture technology and nutrient regulation of intestinal health of cultured M. albus.

BackgroundOsteoporosis (OP) is typically diagnosed by evaluating bone mineral density (BMD), and it frequently results in fractures. Here, we investigated the causal relationships between diet-derived circulating antioxidants and the risk of OP using Mendelian randomization (MR).MethodsPublished studies were used to identify instrumental variables related to absolute levels of circulating antioxidants like lycopene, retinol, ascorbate, and β-carotene, as well as antioxidant metabolites such as ascorbate, retinol, α-tocopherol, and γ-tocopherol. Outcome variables included BMD (in femoral neck, lumbar spine, forearm, heel, total body, total body (age over 60), total body (age 45–60), total body (age 30–45), total body (age 15–30), and total body (age 0–15)), fractures (in arm, spine, leg, heel, and osteoporotic fractures), and OP. Inverse variance weighted or Wald ratio was chosen as the main method for MR analysis based on the number of single nucleotide polymorphisms (SNPs). Furthermore, we performed sensitivity analyses to confirm the reliability of the findings.ResultsWe found a causal relationship between absolute retinol levels and heel BMD (p = 7.6E-05). The results of fixed effects IVW showed a protective effect of absolute retinol levels against heel BMD, with per 0.1 ln-transformed retinol being associated with a 28% increase in heel BMD (OR: 1.28, 95% CI: 1.13–1.44). In addition, a sex-specific effect of the absolute circulating retinol levels on the heel BMD has been observed in men. No other significant causal relationship was found.ConclusionThere is a positive causal relationship between absolute retinol levels and heel BMD. The implications of our results should be taken into account in future studies and in the creation of public health policies and OP prevention tactics.

To investigate the impact of the effect of high temperature stimulation on Monopterus albus larvae after a certain period of time, five experimental groups were established at different temperatures. Then, the M. albus under high temperature stress was fed at 30°C for 70 days. After that, the growth index of the M. albus was counted and analyzed. In terms of growth index, high temperature stress had significant effects on FCR, FBW, WGR, and SGR of M. albus (p < 0.05). The SR increased after being stimulated by temperature (p < 0.1). The study revealed that liver cells of M. albus were harmed by elevated temperatures of 36°C and 38°C. In the experimental group, the activities of digestive enzymes changed in the same trend, reaching the highest point in the 32°C group and then decreasing, and the AMS activity in the 38°C group was significantly different from that in the 30°C group (p < 0.05). The activities of antioxidase in liver reached the highest at 34°C, which was significantly different from those at 30°C (p < 0.05). In addition, the expression levels of TLR1, C3, TNF-α, and other genes increased in the experimental group, reaching the highest point at 34°C, and the expression level of the IL-1β gene reached the highest point at 32°C, which was significantly different from that at 30°C (p < 0.05). However, the expression level of the IRAK3 gene decreased in the experimental group and reached its lowest point at 34°C (p < 0.05). The expression level of the HSP90α gene increased with the highest temperature stimulus and reached its highest point at 38°C (p < 0.05). In the α diversity index of intestinal microorganisms in the experimental group, the observed species, Shannon, and Chao1 indexes in the 34°C group were the highest (p < 0.05), and β diversity analysis revealed that the intestinal microbial community in the experimental group was separated after high temperature stimulation. At the phylum level, the three dominant flora are Proteus, Firmicutes, and Bacteroides. Bacteroides and Macrococcus abundance increased at the genus level, but Vibrio and Aeromonas abundance decreased. To sum up, appropriate high-temperature stress can enhance the immunity and adaptability of M. albus. These results show that the high temperature stimulation of 32°C–34°C is beneficial to the industrial culture of M. albus.

IntroductionThis trial was conducted to compare the effect of diets supplemented with plant essential oil (PEO) and coated plant essential oil (CEO) on growth performance, immunity, antioxidant activity, and fecal microbiota of weaned piglets.MethodsA total of 360 21-day-old weaned piglets were randomly allocated into three groups, namely, CON, PEO, and CEO (basal diets supplemented with 0, 500 mg/kg PEO, and 500 mg/kg CEO, respectively) for a 4-week feeding trial.Results and discussionThe results showed that dietary supplementation with CEO improved the average final weight and average daily gain, decreased the diarrhea rate, increased antioxidant enzyme activities, enhanced immunoglobulin concentrations, and decreased concentrations of pro-inflammatory cytokines in the serum of weaned piglets (p

Background: Patients with Triple-negative breast cancer (TNBC) face a poor prognosis and limited therapeutic options. Current data on eribulin usage to treat TNBC is scarce. Therefore, we sought to compare the feasibility and tolerability of eribulin-based regimens with other chemotherapy regimens in patients with TNBC.Method: This retrospective study was conducted at Fujian Medical University Cancer Hospital and included 159 patients with TNBC enrolled between October 2011 and January 2023. Patients underwent treatment with eribulin-based and other chemotherapy regimens. The study’s primary endpoints were progression-free survival (PFS) and overall survival (OS), while its secondary endpoint was objective response rate (ORR), disease control rate (DCR), and safety. Tumour response was assessed using RECIST V.1.1 criteria.Results: Of the 159 participants in the study, 42 individuals (26.4%) received treatment with eribulin, whereas 117 participants (73.6%) were administered alternative chemotherapy regimens, which included nab-paclitaxel-based therapy (n = 45) and platinum-based therapy (n = 51). The follow-up period for all patients ended on 31 December 2022, and the median follow-up time was 18.3 months (range:0.7–27.5). Following propensity score matching (PSM), eribulin-based treatment resulted in longer median progression-free survival compared to platinum-based (hazard ratio (HR) = 0.41, p = 0.006), nab-paclitaxel-based (hazard ratio = 0.36, p = 0.001) and other chemotherapy (HR = 0.39, p < 0.001). Also, eribulin induced a remarkable prolongation of the median overall survival duration in all three comparative groups. The group receiving eribulin treatment showed significantly reduced incidences of any grade of anaemia, peripheral neuropathy, nausea and vomiting, and hair loss compared to other chemotherapy groups.Conclusion: For the salvage treatment of advanced TNBC, treatment with eribulin produced longer median PFS and OS than other chemotherapy regimens, with a well-tolerated safety profile. Therefore, further investigation of eribulin-based treatment in larger randomized trials for patients with advanced TNBC is warranted.

IntroductionPhysical exercise can improve cognitive function, and the degree of impact on cognitive function is related to exercise modality, intensity, and duration. However, few studies have been conducted on the effects of competitive sports on cognitive function. The 1,500 m freestyle is the longest pool-based swimming event in the Olympic Games. This study explores the effects of 1,500 m freestyle at maximal speed on athletes’ cognitive function and analyzes the potential mechanism of cognitive function reduction in freestyle at maximal speed from the perspective of hemoglobin oxygenation difference (Hbdiff).MethodsA total of 13 male university swimmers were required to take part in a 1,500 m freestyle competition, swimming at maximal speed. The relevant indicators, including cognitive function and freestyle at maximal speed, before and after the competition were tested and analyzed. Cognitive function was assessed using the Schulte grid test (SGT), the trail-making test (TMT), and the digit span test (DST). The neurobiological characteristics of cognitive function, such as the prefrontal cortex (PFC), response time (RT), and accuracy rate (ACC), were tested using functional near-infrared spectroscopy (fNIRS).ResultsA significant decrease in scores for SGT, TMT, and digit span test-backward (DST-B) (p < 0.01). Oxygenated hemoglobin (Oxy-Hb) concentrations in the right frontopolar area (R-FPA) of brain channels 8 (p < 0.01) and 9 (CH8, 9) (p < 0.05), the right dorsolateral prefrontal cortex (R-DLPFC) CH10 (p < 0.05), and the middle dorsolateral prefrontal cortex (M-DLPFC) CH18 (p < 0.01) were significantly altered, and the right area of the brain was activated. The total Oxy-Hb concentrations in the regions of interest (ROIs) of R-FPA, R-DLFPC, and M-DLFPC were changed significantly (p < 0.01).DiscussionThe exhaustive performance of a 1,500 m freestyle event resulted in both physical fatigue and a decline in cognitive function. This decline may be attributed to the activation of specific regions of interest, namely the FPA, DLPFC, and M-DLPFC, within the prefrontal cortex (PFC), as well as alterations in functional connectivity.

Brain abscess originates from a localized cerebritis area of brain parenchyma, remaining a refractory infectious disease in the central nervous system. Causative pathogens can be wide-ranging, including bacteria, fungi, or parasites; thus, precise pathogen identification and individualized antimicrobial therapy determine patients’ outcomes. Here, we report two cases where both patients only presented with limb dysfunction, but without symptoms, signs, or biological evidence of infection. Samples were obtained through brain stereoscopic surgeries and microbial identifications were performed to confirm the infection of Fusobacterium nucleatum. Further appropriate treatments were given, and the patients recovered well. Patient 1 was a 73-year-old male with a 20-day history of left-sided limbs weakness. A brain MRI showed a space-occupying lesion with a heterogeneously ring-enhancement character in the right frontal lobe. This patient underwent puncture biopsy of the lesion with robot-assisted guidance to confirm a brain abscess. Empirical antibiotic therapy was immediately given until the pathogen was identified as Fusobacterium nucleatum; thus, he received specific antibiotic therapy with metronidazole and recovered well after treatment. Patient 2 was a 22-year-old female with heart disease history who complained of right-sided limb weakness for nine days. A brain MRI showed a circular enhanced lesion with a thin capsule wall and surrounding edema in the left frontal lobe. This patient underwent puncture drainage of the lesion with robot-assisted guidance and a brain abscess was confirmed. Empirical antibiotic therapy was given until the pathogen was identified as Fusobacterium nucleatum and then she also received metronidazole treatment. Her symptoms recovered and the lesion disappeared after 1 month. Hence, we reviewed the diagnosis and treatment of cryptogenic brain abscess caused by Fusobacterium nucleatum and highlight that precise neurosurgical interventions and identification of causative pathogens are crucial for the management of brain abscess.

Improving nitrogen use efficiency (NUE) without compromising yield remains a crucial agroecological challenge in theory and practice. Some meta-analyses conducted in recent years investigated the impact of nitrogen (N) fertilizer on crop yield and gaseous emissions, but most are region-specific and focused on N sources and application methods. However, various factors affecting yield and N fertilizer efficiency in wheat crops on a global scale are not extensively studied, thus highlighting the need for a comprehensive meta-analysis. Using 109 peer-reviewed research studies (published between 2000 and 2022) from 156 experimental sites (covering 36.8, 38.6 and 24.6% of coarse, medium, and fine texture soils, respectively), we conducted a global meta-analysis to elucidate suitable N management practices and the key factors influencing N fertilization efficiency in wheat as a function of yield and recovery efficiency and also explained future perspectives for efficient N management in wheat crop. Overall, N fertilization had a significant impact on wheat yield. A curvilinear relationship was found between N rates and grain yield, whereas maximum yield improvement was illustrated at 150-300 kg N ha-1. In addition, N increased yield by 92.18% under direct soil incorporation, 87.55% under combined chemical and organic fertilizers application, and 72.86% under split application. Site-specific covariates (climatic conditions and soil properties) had a pronounced impact on N fertilization efficiency. A significantly higher yield response was observed in regions with MAP > 800 mm, and where MAT remained < 15 °C. Additionally, the highest yield response was observed with initial AN, AP and AK concentrations at < 20, < 10 and 100-150 mg kg-1, respectively, and yield response considerably declined with increasing these threshold values. Nevertheless, regression analysis revealed a declining trend in N recovery efficiency (REN) and the addition of N in already fertile soils may affect plant uptake and RE. Global REN in wheat remained at 49.78% and followed a negative trend with the further increase of N supply and improvement in soil properties. Finally, an advanced N management approach such as “root zone targeted fertilization” is suggested to reduce fertilizer application rate and save time and labor costs while achieving high yield and NUE.

Objective: This paper briefly reviews the structure and function of NLRP3 inflammasomes, signaling pathway, relationship with synovitis in KOA, and intervention of traditional Chinese medicine (TCM) in NLRP3 inflammasomes as a means to improve its therapeutic potential and clinical application.Method: Literatures about NLRP3 inflammasomes and synovitis in KOA were reviewed to analyze and discuss.Result: NLRP3 inflammasome can activate NF-κB mediated signal transduction, which in turn causes the expression of proinflammatory cytokines, initiates the innate immune response, and triggers synovitis in KOA. The TCM monomer/active ingredient, decoction, external ointment, and acupuncture regulating NLRP3 inflammasomes are helpful to alleviate synovitis in KOA.Conclusion: The NLRP3 inflammasome plays a significant role in the pathogenesis of synovitis in KOA, TCM intervention targeting the NLRP3 inflammasome can be a novel approach and therapeutic direction for the treatment of synovitis in KOA.

The variability and heterogeneity of tumor antigens and the tumor-driven development of immunosuppressive mechanisms leading to tumor escape from established immunological surveillance. Here, the tumor cells were genetically modified to achieve an inducible overexpression of the N-terminal domain of gasdermin D (GSDMD-NT) and effectively cause pyroptosis under a strict control. Pyroptotic tumor cells release damage-associated molecular patterns (DAMPs) and inflammatory cytokines to promote the maturation and migration of bone marrow-derived dendritic cells (BMDCs). Furthermore, local tumor delivery, and preventive or therapeutic subcutaneous immunization of the modified cells, followed by the induction of GSDMD-NT expression, significantly stimulated both the systemic and local responses of antitumor immunity, and reprogrammed the tumor microenvironment, leading to the dramatic suppression of tumor growth in mice. This study has explored the application potency of inducing the pyroptosis of tumor cells in the field of tumor immunotherapy, especially for developing a new and promising personalized tumor vaccine.

The Asian swamp eel (Monopterus albus) is one of the most widely distributed freshwater fish in China. In this study, we identified the single nucleotide polymorphisms (SNPs) of M. albus from 19 wild populations in China using restriction-site associated DNA sequencing (RAD-seq), and used SNP markers to investigate the swamp eel the genetic diversity and population genetic structure. A total of 8941794 SNPs were identified. Phylogenetic and principal component analysis suggested that the 19 populations were clustered into four groups: The Jiaoling County (JL) and Poyang Lake (PYH)populations in Group Ⅰ; the Chengdu City (CD), Dali City (YN), Eli Village (EL), Dongting Lake (DTH), Huoqiu County (HQ), and Chaohu Lake (CH) populations in Group Ⅱ; the Puyang City (PY), Chongming Island (CM), Tai Lake (TH), Gaoyou Lake (GYH), Weishan Lake (WSH), Haimen City (HM), Hongze Lake (HZH), Baiyangdian Lake (BYD), Dagushan (DGS), and Pinghu City (PH) populations in group Ⅲ; and the Lingshui County (LS) populations in Group Ⅳ. All 19 populations may have evolved from four ancestors. The genetic diversity was relatively high in CM, GYH, and HM; and low in LS, EL, and JL. The LS, and CM populations had the highest and lowest differentiation from the other populations, respectively. These findings provide new insights for germplasm resources protection and artificial breeding of M. albus.

In China, the first tunnel was built in accordance with the 30-ton heavy-haul railway standard. Based on the change in water and soil pressure obtained from long-term on-site monitoring, the cavity mechanism of the surrounding rock at the bottom of a heavy-haul railway tunnel under rich water conditions was explored in this study. The cavity characteristics and degradation depth of the three types of surrounding rock under different axial loads and hydrodynamic pressures were analyzed through laboratory tests. The structural defects at the bottom of the tunnel and local cracks in the surrounding rock were determined to provide a flow channel for groundwater. The dynamic load of heavy-haul trains causes groundwater to exert high hydrodynamic pressure on the fine cracks. The continuous erosion of the bottom surrounding rock leads to a gradual loss of surrounding rock particles, which would further exacerbate with time. The cohesive soil surrounding rock is noticeably affected by the combined action of heavy-haul load and groundwater in the three types of surrounding rock, and the surrounding rock cavity is characterized by overall hanging. In the simulation experiment, the particle loss of the surrounding rock reached 1,445 g, which is 24.2% higher than that of the pebble soil surrounding rock and 40.8% higher than that of sandy soil surrounding rock. The findings of this study could be helpful for developing methods for defect prediction and treatment of heavy-haul railway tunnels.

In prolonged intense exercise training, the training load of athletes may be reduced once their hemoglobin concentrations ([Hb]s) are decreased dramatically. We previously reported that intermittent hypoxia exposure (IHE) could be used to alleviate the decrease of [Hb] and help to maintain the training load in rats. To further explore the feasibility of applying IHE intervention to athletes during prolonged intense exercise training, 6 trained swimmers were recruited to conduct a 4-week IHE intervention at the intervals after their [Hb] dropped for 10% or more during their training season. IHE intervention lasted 1 h and took place once a day and five times a week. Hematological and hormonal parameters, including [Hb], red blood cells (RBC), hematocrit (Hct), reticulocytes, serum erythropoietin (EPO), testosterone (T) and cortisol (C) were examined. After the IHE intervention was launched, [Hb], RBC and Hct of the subjects were increased progressively with their maximum levels (P < 0.01) showing at the third or fourth week, respectively. An increase in reticulocyte count (P < 0.01) suggests that IHE intervention promotes erythropoiesis to increase [Hb]. Besides, serum level of EPO, the hormone known to stimulate erythropoiesis, was overall higher than that before the IHE intervention, although it was statistically insignificant. Furthermore, the serum level of T, another hormone known to stimulate erythropoiesis, was increased progressively with the maximum level showing at the fourth week. Collectively, this study further confirms that IHE intervention may be used as a new strategy to prevent intense exercise training-induced reductions in [Hb].

Ameliorating graft injury induced by ischemia and hypoxia, expanding the donor pool, and improving graft quality and recipient prognosis are still goals pursued by the transplant community. The preservation of organs during this process from donor to recipient is critical to the prognosis of both the graft and the recipient. At present, static cold storage, which is most widely used in clinical practice, not only reduces cell metabolism and oxygen demand through low temperature but also prevents cell edema and resists apoptosis through the application of traditional preservation solutions, but these do not improve hypoxia and increase oxygenation of the donor organ. In recent years, improving the ischemia and hypoxia of grafts during preservation and repairing the quality of marginal donor organs have been of great concern. Hemoglobin-based oxygen carriers (HBOCs) are “made of” natural hemoglobins that were originally developed as blood substitutes but have been extended to a variety of hypoxic clinical situations due to their ability to release oxygen. Compared with traditional preservation protocols, the addition of HBOCs to traditional preservation protocols provides more oxygen to organs to meet their energy metabolic needs, prolong preservation time, reduce ischemia–reperfusion injury to grafts, improve graft quality, and even increase the number of transplantable donors. The focus of the present study was to review the potential applications of HBOCs in solid organ preservation and provide new approaches to understanding the mechanism of the promising strategies for organ preservation.

PACS1 neurodevelopmental disorder (PACS1-NDD) is a category of rare disorder characterized by intellectual disability, speech delay, dysmorphic facial features, and developmental delay. Other various physical abnormalities of PACS1-NDD might involve all organs and systems. Notably, there were only two unique missense mutations [c.607C > T (p.Arg203Trp) and c.608G > A (p.Arg203Gln)] in PACS1 that had been identified as pathogenic variants for PACS1-NDD or Schuurs-Hoeijmakers syndrome (SHMS). Previous reports suggested that these common missense variants were likely to act through dominant-negative or gain-of-function effects manner. It is still uncertain whether the intragenic deletion or duplication in PACS1 will be disease-causing. By using whole-exome sequencing, we first identified a novel heterozygous multi-exon deletion covering exons 12–24 in PACS1 (NM_018026) in four individuals (two brothers and their father and grandfather) in a three-generation family. The younger brother was referred to our center prenatally and was evaluated before and after the birth. Unlike SHMS, no typical dysmorphic facial features, intellectual problems, and structural brain anomalies were observed among these four individuals. The brothers showed a mild hypermyotonia of their extremities at the age of 3 months old and recovered over time. Mild speech and cognitive delay were also noticed in the two brothers at the age of 13 and 27 months old, respectively. However, their father and grandfather showed normal language and cognitive competence. This study might supplement the spectrum of PACS1-NDD and demonstrates that the loss of function variation in PACS1 displays no contributions to the typical SHMS which is caused by the recurrent c.607C > T (p.Arg203Trp) variant.

Background: Breast cancer (BC) is one of the most frequently diagnosed malignancies among females. As a huge heterogeneity of malignant tumor, it is important to seek reliable molecular biomarkers to carry out the stratification for patients with BC. We surveyed immune- associated lncRNAs that may be used as potential therapeutic targets in BC.Methods: LncRNA expression data and clinical information of BC patients were downloaded from the TCGA database for a comprehensive analysis of candidate genes. A model consisting of immune-related lncRNAs enriched in BC cancerous tissues was established using the univariate Cox regression analysis and the iterative Lasso Cox regression analysis. The prognostic performance of this model was validated in two independent cohorts (GSE21653 and BC-KR), and compared with known prognostic biomarkers. A nomogram that integrated the immune-related lncRNA signature and clinicopathological factors was constructed to accurately assess the prognostic value of this signature. The correlation between the signature and immune cell infiltration in BC was also analyzed.Results: The Kaplan-Meier analysis showed that the OS of Patients in the low-risk group had significantly better survival than those in the high-risk group, Clinical subgroup analysis showed that the predictive ability was independent of clinicopathological factors. Univariate/multivariate Cox regression analysis showed immune lncRNA signature is an important prognostic factor and an independent prognostic marker. In addition, GSEA and GSVA analysis as well as comprehensive analysis of immune cells showed that the signature was significantly correlated with the infiltration of immune cells.Conclusion: We successfully constructed an immune-associated lncRNA signature that can accurately predict BC prognosis.

Acinetobacter baumannii often causes serious nosocomial infections. Because of its serious drug resistance problems, complex drug resistance mechanism, and rapid adaptation to antibiotics, it often shows pan-drug resistance and high fatality rates, which represent great challenges for clinical treatment. Therefore, identifying new ways to overcome antibiotic resistance is particularly important. In this study, mice immunized with A. baumannii outer membrane vesicles (AbOMVs) produced high IgG levels for a long time, and this antiserum significantly increased the small molecule intracellular aggregation rate and concentrations. In vitro experiments demonstrated that the combined used of anti-AbOMV serum and quinolone antibiotics significantly increased the sensitivity of the bacteria to these antibiotics. Mouse sepsis model experiments demonstrated that delivery of these antibodies using both active and passive immunization strategies significantly improved the susceptibility to quinolone antibiotics, improved the survival rate of mice infected with A. baumannii, and reduced the bacterial load in the organs. In a pneumonia model, the combination of serum anti-AbOMVs and levofloxacin improved levofloxacin sensitivity, which significantly reduced the bacterial loads in the lung and spleen compared with those of the antibiotic or antibody alone. This combination also significantly reduced lung inflammatory cell infiltration and inflammatory cytokine aggregation. In this study, the main protein targets that bound to these antibodies were identified. Structural modeling showed that seven of the proteins were porins. Therefore, we speculated that the anti-AbOMV antibodies mainly improved the intracellular aggregation of antibiotics by affecting porins, thus improving susceptibility to quinolone antibiotics. This study provides a method to improve susceptibility to existing antibiotics and a novel idea for the prevention and treatment of pan-drug-resistant A. baumannii.

Objective: lncRNAs are recently thought to play a significant role in cellular homeostasis during pathological process of diseases by competing inhibiting miRNA function. The aim of present study was to assess the function of long non-coding RNA (lncRNA) MEG3 and its functional interaction with microRNA-181b in cerebral ischemic infarct of mice and hypoxia-induced neurons apoptosis. Methods: To address this question, we performed the experiments with in vivo middle cerebral artery occlusion (MCAO) mice model and in vitro oxygen-glucose deprivation (OGD)-cultured neuronal HT22 cell line. Relative expression of MEG3, miR-181b and 12/15-LOX (lipoxygenase) mRNA was determined using quantitative RT-PCR. Western blot was used to evaluate 12/15-LOX protein expression. TUNEL assay was performed to assess cell apoptosis.Results: In both MCAO mice and OGD-cultured HT22 cell, ischemia or hypoxia treatment results in a time-dependent increase in MEG3 and 12/15-LOX expression and decrease in miR-181b expression. Knockdown of MEG3 contributes to attenuation of hypoxia-induced apoptosis of HT22 cell. Also, expression level of MEG3 negatively correlated with miR-181b expression and positively correlated with 12/15-LOX expression. In contrary to MEG3, miR-181b overexpression attenuated hypoxia-induced HT22 cell apoptosis, as well as suppressed hypoxia-induced increase in 12/15-LOX expression. By luciferase reporter assay, we concluded that miR-181b directly binds to 12/15-LOX 3’-UTR, thereby negatively regulates 12/15-LOX expression. Conclusion: Our data suggested that long non-coding RNA MEG3 functions as a competing endogenous RNA for miR-181b to regulate 12/15-LOX expression in middle cerebral artery occlusion-induced ischemic infarct of brain nerve cells.