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Abstract Background Trauma represents a significant global health challenge.The development of an effective scoring tool capable of predicting mortality risk in trauma cases is essential. This study aimed to investigate the combined effects of quick sequential organ failure assessment (qSOFA) and hypothermia (H) along with prothrombin time (PT) in predicting the prognosis of patients with severe trauma. Methods A retrospective cohort study was conducted to analyze data from severe trauma patients in the Trauma Database of the Trauma Center at the Second Affiliated Hospital of Soochow University between January 2017 and December 2021. Patients were categorized into survival and non-survival groups based on clinical outcomes. Baseline and clinical data were compared between the groups, and prognostic factors were explored using logistic regression analysis. Receiver operating characteristic (ROC) curves generated by 10-fold cross-validation using the caret in R programming language were used to assess the predictive efficacy of Injury Severity Score (ISS) and qSOFA + H + PT score for trauma patient mortality. Results A total of 509 severe trauma patients (377 males and 132 females) were included, with a median age of 53 years (range: 42–65 years). The mortality rate was found to be 23.4%. Logistic regression analysis revealed that age, ISS, and qSOFA + H + PT were significant predictors of death in severe trauma patients, with odds ratios of 1.035 (95%CI:1.014–1.057), 1.052 (95%CI:1.017–1.090), and 6.124 (95%CI:3.107–12.072), respectively (P

Abstract Vascular endothelial injury initiates atherosclerosis (AS) progression. N-Acetylneuraminic acid (Neu5Ac) metabolic disorder was found to intensify endothelial mitochondrial damage. And GLS2-associated glutaminolysis disorder contributed to mitochondrial dysfunction. However, mechanisms underlying Neu5Ac-associated mitochondrial dysfunction as well as its association with GLS2 remains unclear. In this study, we constructed GLS2−/−ApoE−/− mice by using HBLV-GLS2 shRNA injection. And methods like immunofluorescence, western blotting, transmission electron microscopy were applied to detect profiles of endothelial injury and AS progression both in vivo and in vitro. We demonstrated that Neu5Ac accumulation increased GLS2 expression and promoted glutaminolysis disorder, which further induced endothelial mitochondrial dysfunction via a pyroptosis-dependent pathway in vivo and in vitro. Mechanically, Neu5Ac interacted with SIRT3 and led to FOXO3a deacetylation and phosphorylation, further facilitated c-Myc antagonism and ultimately increased GLS2 levels. Inhibition of GLS2 could improve mitochondrial function and mitigate pyroptosis process. In addition, blocking Neu5Ac production using neuraminidases (NEUs) inhibitor could rescue endothelial damage and alleviate AS development in ApoE−/− mice. These findings proposed that Neu5Ac induced GLS2-mediated glutaminolysis disorder and then promoted mitochondrial dysfunction in a pyroptosis-dependent pathway. Targeting GLS2 or inhibiting Neu5Ac production could prevent AS progression.

Abstract Background Microcirculation abnormality in septic shock is closely associated with organ dysfunction and mortality rate. It was hypothesized that the arterial blood glucose and interstitial fluid (ISF) glucose difference (GA−I) as a marker for assessing the microcirculation status can effectively evaluate the severity of microcirculation disturbance in patients with septic shock. Methods The present observational study enrolled patients with septic shock admitted to and treated in the intensive care unit (ICU) of a tertiary teaching hospital. The parameters reflecting organ and tissue perfusion, including lactic acid (Lac), skin mottling score, capillary refill time (CRT), venous-to-arterial carbon dioxide difference (Pv-aCO2), urine volume, central venous oxygen saturation (ScvO2) and GA−I of each enrolled patient were recorded at the time of enrollment (H0), H2, H4, H6, and H8. With ICU mortality as the primary outcome measure, the ICU mortality rate at any GA−I interval was analyzed. Results A total of 43 septic shock patients were included, with median sequential organ failure assessment (SOFA) scores of 10.5 (6–16), and median Acute Physiology and Chronic Health Evaluation (APACHAE) II scores of 25.7 (9–40), of whom 18 died during ICU stay. The GA−I levels were negative correlation with CRT (r = 0.369, P

Abstract To improve the speed of mass transfer, a magnetic suspension platform (MSP) is used to transport the display chips. A novel 6‐DOF MSP is proposed in this paper. An improved Halbach array is used to supply the magnetic flux density. Two types of permanent magnets are utilised in the improved Halbach array. The smaller permanent magnet serves to consolidate the magnetic flux density, thereby enhancing the uniformity of the magnetic field. The finite element method is employed to analyse how variations in angle impact both the strength and uniformity of the magnetic flux density. The results show that the magnetisation direction of 45° is the most effective in terms of improving the uniformity and strength of the magnetic density. Finally, a 6‐DOF MSP prototype is manufactured. A magnetic density measurement experiment and a stable suspension experiment for the actuator are conducted. The results indicate an enhancement in the uniformity of the magnetic field within the air gap. Additionally, the maximum suspension positioning accuracy of the actuator is about 750 nm.

Abstract China’s renewable energy innovation is essential for realizing its carbon neutrality targets and the low-carbon transition, but few studies have spatially examined its characteristics and spillover effects. To fill the research gap, this study investigates its distribution and trends from a spatiotemporal dimension and focuses on the spatial effects of the influencing factors to identify those that have a significant impact on renewable energy innovation by using China’s provincial panel data from 2006 to 2019. The results show the following findings. (1) Renewable energy innovation shows distinct spatial differences across China’s provinces such that it is high in the east and south and low in the west and north, which exhibits spatial locking and path-dependence. (2) There is a positive spatial correlation with renewable energy innovation. (3) R&D investment and GDP per capita significantly promote renewable energy innovation, but the former effect is mainly observed in the local area, whereas the latter shows spatial effects. More market-oriented policies should be taken for the improvement of renewable energy innovation and the establishment of regional coordination mechanisms are proposed.

Abstract Background Minimally invasive vascular intervention (MIVI) is a powerful technique for the treatment of cardiovascular diseases, such as abdominal aortic aneurysm (AAA), thoracic aortic aneurysm (TAA) and aortic dissection (AD). Navigation of traditional MIVI surgery mainly relies only on 2D digital subtraction angiography (DSA) images, which is hard to observe the 3D morphology of blood vessels and position the interventional instruments. The multi-mode information fusion navigation system (MIFNS) proposed in this paper combines preoperative CT images and intraoperative DSA images together to increase the visualization information during operations. Results The main functions of MIFNS were evaluated by real clinical data and a vascular model. The registration accuracy of preoperative CTA images and intraoperative DSA images were less than 1 mm. The positioning accuracy of surgical instruments was quantitatively assessed using a vascular model and was also less than 1 mm. Real clinical data used to assess the navigation results of MIFNS on AAA, TAA and AD. Conclusions A comprehensive and effective navigation system was developed to facilitate the operation of surgeon during MIVI. The registration accuracy and positioning accuracy of the proposed navigation system were both less than 1 mm, which met the accuracy requirements of robot assisted MIVI.

Abstract Background Atherosclerosis (AS) is the leading underlying cause of the majority of clinical cardiovascular events. Retention of foamy macrophages in plaques is the main factor initiating and promoting the atherosclerotic process. Our previous work showed that ox-LDL induced macrophage retention in plaques and that the guidance receptor Uncoordinated-5 homolog B (Unc5b) was involved in this process. However, little is known about the role of Unc5b in regulating macrophage accumulation within plaques. Results In the present study, we found that Unc5b controls macrophage migration and thus promotes plaque progression in ApoE−/− mice. The immunofluorescence colocalization assay results first suggested that fucosyltransferase 8 (Fut8) might participate in the exacerbation of atherosclerosis. Animals with Unc5b overexpression showed elevated levels of Fut8 and numbers of macrophages and an increased lesion size and intimal thickness. However, these effects were reversed in ApoE−/− mice with Unc5b knockdown. Furthermore, Raw264.7 macrophages with siRNA-mediated silencing of Unc5b or overexpression of Unc5b were used to confirm the regulatory mechanisms of Unc5b and Fut8 in vitro. In response to ox-LDL exposure, Unc5b and Fut8 were both upregulated, and macrophages showed reduced pseudopod formation and migratory capacities. However, these capacities were restored by blocking Unc5b or Fut8. Furthermore, the IP assay indicated that Fut8 regulated the level of α-1,6 fucosylation of Unc5b, which mainly occurs in the endoplasmic reticulum (ER), and genetic deletion of the main fucosylation sites or Fut8 resulted in hypofucosylation of Unc5b. Moreover, the macrophage migration mediated by Unc5b depended on inactivation of the p-CDC42/p-PAK pathway. Conversely, macrophages with Unc5b overexpression displayed activation of the p-CDC42/p-PAK pathway and decreased migration both in vivo and in vitro. Conclusion These results demonstrated that hypofucosylation of Unc5b regulated by Fut8 is positively associated with the delay of the atherosclerotic process by promoting the migration of foamy macrophages. These findings identify a promising therapeutic target for atherosclerosis.

BackgroundMany Gram-negative bacteria use quorum sensing (QS) signal molecules to monitor their local population density and to coordinate their collective behaviors. The diffusible signal factor (DSF) family represents an intriguing type of QS signal to mediate intraspecies and interspecies communication. Recently, accumulating evidence demonstrates the role of DSF in mediating inter-kingdom communication between DSF-producing bacteria and plants. However, the regulatory mechanism of DSF during the Xanthomonas-plant interactions remain unclear.MethodsPlants were pretreated with different concentration of DSF and subsequent inoculated with pathogen Xanthomonas campestris pv. campestris (Xcc). Pathogenicity, phynotypic analysis, transcriptome combined with metabolome analysis, genetic analysis and gene expression analysis were used to evaluate the priming effects of DSF on plant disease resistance.ResultsWe found that the low concentration of DSF could prime plant immunity against Xcc in both Brassica oleracea and Arabidopsis thaliana. Pretreatment with DSF and subsequent pathogen invasion triggered an augmented burst of ROS by DCFH-DA and DAB staining. CAT application could attenuate the level of ROS induced by DSF. The expression of RBOHD and RBOHF were up-regulated and the activities of antioxidases POD increased after DSF treatment followed by Xcc inoculation. Transcriptome combined with metabolome analysis showed that plant hormone jasmonic acid (JA) signaling involved in DSF-primed resistance to Xcc in Arabidopsis. The expression of JA synthesis genes (AOC2, AOS, LOX2, OPR3 and JAR1), transportor gene (JAT1), regulator genes (JAZ1 and MYC2) and responsive genes (VSP2, PDF1.2 and Thi2.1) were up-regulated significantly by DSF upon Xcc challenge. The primed effects were not observed in JA relevant mutant coi1-1 and jar1-1.ConclusionThese results indicated that DSF-primed resistance against Xcc was dependent on the JA pathway. Our findings advanced the understanding of QS signal-mediated communication and provide a new strategy for the control of black rot in Brassica oleracea.

Ball-shell rotors with non-standard shapes, non-uniform conductive coatings, and eccentric masses machined by conventional processes constrain the improvement of levitation and torque accuracy of magnetically levitated momentum balls. This paper focuses on the machining method of multilayer ball-shell rotors to develop a ball-shell rotor with a standard shape and uniform conductive coating, which can improve the levitation and torque accuracy of magnetically levitated momentum balls. In this paper, a machining method for multi-coated ball-shell rotors is proposed. The machining process combining hemispherical surface and workpiece is adopted, and the whole sphere is assembled by threading, which effectively reduces the machining error. The influence of the cutting depth and feed rate of the tool on the cutting force of the ball shell was analyzed through the cutting force model. The effect of cutting force on the deformation of the ball shell was analyzed by the finite element method. The superiority of the machining method was verified by measuring the dimensions of the ball shell with a coordinate measuring machine. Compared with the traditional machining process and assembly method, the proposed ball-shell rotor machining method effectively improves the dimensional accuracy, reduces the center of mass to center of mass deviation, and ensures the levitation accuracy and output torque accuracy of the magnetically levitated momentum ball. Measurement results show that the diameter values of the pure iron ball shell are between 98.694 and 98.707 mm with a machining error of ±0.007 mm, and the diameter values of the spray-painted ball shell are between 99.490 and 99.510 mm with a machining error of ±0.01 mm. The machining static equilibrium of the pure iron ball shell and the spray-painted ball shell is good by the static equilibrium test method.

Purpose: To screen VSX1 gene sequence variations and describe the clinical features of families with keratoconus (KC) from northwest China.Methods: We screened VSX1 sequence variations and clinical data of 37 families including 37 probands with diagnosed KC from Ningxia Eye Hospital (China). VSX1 was screened by targeted next-generation sequencing (NGS) and verified by Sanger sequencing. In silico analysis including Mutation Taster, MutationAssessor, PROVEAN, MetaLR, FATHMM, M-CAP, FATHMM-XF_coding and DANN was performed to identify the pathogenicity of the sequence variations as well as the conserved amino acid variations of VSX1 was implemented by Clustal X. All subjects were assessed in Pentacam Scheimpflug tomography and corneal biomechanical Corvis ST examinations.Results: Five VSX1 gene variants, were identified in six (16.2%) unrelated families with KC. In silico analysis predicted deleterious effects of the three missense variants (p.G342E, p.G160V, and p.L17V) in the encoded protein. Another previously reported synonymous variation (p.R27R) in the first exon and one heterozygous change in the first intron (c.425-73C>T) were identified in three KC families. Clinical examination of the asymptomatic first-degree parents from these six families who shared the gene with the proband had suspected KC changes in topographic and biomechanical markers. These variants co-segregated with the disease phenotype in all affected individuals but not in unaffected family members or healthy controls, though with variable expressivity.Conclusion: The variant p.G342E of VSX1 is implicated in the pathogenesis of KC, which expands the range of the spectrum of VSX1 mutations with an autosomal dominant inheritance pattern and variable expression in the clinical phenotype. Genetic screening combined with clinical phenotype may help in the genetic counseling of patients with KC and identification of individuals with subclinical KC.

SEP genes are famous for their function in the morphological novelty of bisexual flowers. Although the diverse functions of SEP genes were reported, only the regulatory mechanisms underlying floral organ development have been addressed. In this study, we identified SEP-like genes in Gossypium and found that SEP3 genes were duplicated in diploid cotton varieties. GhSEP4.1 and GhSEP4.2 were abundantly transcribed in the shoot apical meristem (SAM), but only GhSEP4.2 was expressed in the leaf vasculature. The expression pattern of GhSEPs in floral organs was conserved with that of homologs in Arabidopsis, except for GhSEP2 that was preponderantly expressed in ovules and fibers. The overexpression and silencing of each single GhSEP gene suggested their distinct role in promoting flowering via direct binding to GhAP1 and GhLFY genomic regions. The curly leaf and floral defects in overexpression lines with a higher expression of GhSEP genes revealed the concentration-dependent target gene regulation of GhSEP proteins. Moreover, GhSEP proteins were able to dimerize and interact with flowering time regulators. Together, our results suggest the dominant role of GhSEP4.2 in leaves to promote flowering via GhAP1-A04, and differently accumulated GhSEP proteins in the SAM alternately participate in forming the dynamic tetramer complexes to target at the different loci of GhAP1 and GhLFY to maintain reproductive growth. The regulatory roles of cotton SEP genes reveal their conserved and diversified functions.

Curcumin (CUR) is a natural bioactive compound that has attracted attention as a “golden molecule” due to its therapeutic properties against several types of tumors. Nonetheless, the antitumor application of CUR is hampered due to its extremely low aqueous solubility and chemical instability. Herein, a novel type of CUR-loaded polymeric micelles with intracellular K+-responsive controlled-release properties is designed and developed. The polymeric micelles are self-assembled by poly (N-isopropylacrylamide-co-acryloylamidobenzo-15-crown-5-co-N, N-dimethylacrylamide)-b-DSPE (PNDB-b-DSPE) block copolymers, and CUR. CUR is successfully loaded into the micelles with a CUR loading content of 6.26 wt%. The proposed CUR-PNDB-DSPE polymeric micelles exhibit a significant CUR release in simulated intracellular fluid due to the formation of 2 : 1 ‘‘sandwich’’ host–guest complexes of 15-crown-5 and K+, which lead to the hydrophilic outer shell of micelles to collapse and the drug to rapidly migrate out of the micelles. In vitro, the B16F10 cell experiment indicates that CUR-PNDB-DSPE micelles exhibit a high cellular uptake and excellent intracellular drug release in response to the intracellular K+ concentration. Moreover, CUR-PNDB-DSPE micelles show high cytotoxicity to B16F10 cells compared to free CUR and CUR-PEG-DSPE micelles. The polymeric micelles with intracellular K+-responsive controlled release properties proposed in this study provide a new strategy for designing novel targeted drug delivery systems for CUR delivery for cancer treatment.

Gossypium hirsutum is most broadly cultivated in the world due to its broader adaptation to the environment and successful breeding of early maturity varieties. However, how cotton responds to environmental cues to adjust flowering time to achieve reproductive success is largely unknown. SOC1 functions as an essential integrator for the endogenous and exogenous signals to maximize reproduction. Thus we identified six SOC1-like genes in Gossypium that clustered into two groups. GhSOC1-1 contained a large intron and clustered with monocot SOC1s, while GhSOC1-2/3 were close to dicot SOC1s. GhSOC1s expression gradually increased during seedling development suggesting their conserved function in promoting flowering, which was supported by the early flowering phenotype of 35S:GhSOC1-1 Arabidopsis lines and the delayed flowering of cotton silencing lines. Furthermore, GhSOC1-1 responded to short-day and high temperature conditions, while GhSOC1-2 responded to long-day conditions. GhSOC1-3 might function to promote flowering in response to low temperature and cold. Taken together, our results demonstrate that GhSOC1s respond differently to light and temperature and act cooperatively to activate GhLFY expression to promote floral transition and enlighten us in cotton adaptation to environment that is helpful in improvement of cotton maturity.

Neutrophils constitute abundant cellular components in atherosclerotic plaques. Most of the current studies are focused on the roles of granular proteins released by neutrophils in atherosclerosis. Here, we revealed a unique subset of neutrophils which exhibit the characteristics of antigen-presenting cell (APC) (which were called APC-like neutrophils afterwards) in atherosclerosis. The roles of APC-like neutrophils and relevant mechanisms were investigated in hyperlipidemic patients and atherosclerotic mice. Higher percentages of neutrophils and APC-like neutrophils were found in peripheral blood of hyperlipidemic patients than that of healthy donors. Meanwhile, we also identified higher infiltration of neutrophils and APC-like neutrophils in atherosclerotic mice. Ox-LDL induced Phorbol-12-myristate-13-acetate (PMA)-activated neutrophils to acquire the APC-like phenotype. Importantly, upon over-expression of APC-like markers, neutrophils acquired APC functions to promote the proliferation and interferon-γ production of CD3+ T cells via HLA-DR/CD80/CD86. In accordance with what found in vitro, positive correlation between neutrophils and CD3+ T cells was observed in hyperlipidemic patients. In conclusion, our work identifies a proinflammatory neutrophil subset in both hyperlipidemic patients and atherosclerotic mice. This unique phenotype of neutrophils could activate the adaptive immune response to promote atherosclerosis progression. Thus, this neutrophil subset may be a new target for immunotherapy of atherosclerosis.

Tetramethylpyrazine (TMP), a Chinese traditional herbal extraction widely used in treating cardiovascular diseases, could attenuate vascular endothelial injuries, but the underlying mechanism remains incomprehensive. Vascular glycocalyx coating on the endothelium would be damaged and caused endothelial dysfunction in the inflammatory microenvironment, which was the initial factor of morbidity of many vascular diseases, such as atherosclerosis (AS). Here, we thoroughly investigated the molecular mechanism of TMP on vascular endothelial glycocalyx in the LPS-induced inflammatory model both in vitro and in vivo. Results showed that pretreatment with TMP significantly inhibited glycocalyx degradation and monocytes adhesion to the endothelial process. Moreover, TMP pretreatment inhibited the expression of HPSE1 (a major degrading enzyme of endothelial glycocalyx), Toll-like receptor 4 (TLR4), and the translocation of nuclear factor kappa B p65 (NF-κB p65). We were utilized withTLR4 siRNA, NF-κB inhibitor, and HPSE1 overexpression analysis confirmed TMP’s protection on endothelial glycocalyx injury, which further contributed to the monocyte-endothelial adhesion process. It was indicated that TMP might suppress glycocalyx degradation through TLR4/NF-κB/HPSE1 signaling pathway. Taken together, our results enriched the occurrence molecular mechanism of glycocalyx shedding and molecular regulation mechanism of TMP in protecting integrity of the glycocalyx structure during inflammation. As TMP is currently used in clinical applications, it may be considered a novel strategy against atherosclerosis through its ability to protect endothelial glycocalyx.

Atherosclerosis is a chronic inflammatory disease. Interleukin-17-producing CD4+ T cells (Th17 cells) play important roles in the progression of atherosclerosis. However, most of the studies were focused on the advanced stage of atherosclerosis. In the current study, we investigated the roles of Th17 cells, relevant mechanisms in hyperlipidemic patients, and different stages of atherosclerotic mice. Human blood samples were collected, and percentages of Th17 cells, macrophages, and neutrophils were analyzed by flow cytometry. ApoE−/− mice were fed with high-fat diet (HFD) and sacrificed at different time points to evaluate the infiltration of inflammatory cells at different stages of atherosclerosis. Furthermore, essential mechanisms of IL-17A in atherosclerotic inflammatory milieu formation were studied in vivo by intraperitoneal injection with monoclonal anti-murine IL-17 antibody. Our study reveals the higher percentages of Th17 cells, monocytes, and neutrophils in hyperlipidemic patients compared to healthy donors. Meanwhile, we also identify an infiltration of Th17 cells in the early stage of atherosclerosis (4 weeks after HFD), which maintains at high level until late stage of atherosclerosis (20 weeks after HFD). What is more, inflammatory cells including macrophages and neutrophils were also accumulated in atherosclerotic lesions. Neutralization of IL-17 in ApoE−/− mice resulted in less infiltration of macrophages and neutrophils and smaller atherosclerotic lesions. Importantly, in accordance with what is found in the mouse model, positive correlations between Th17 cells and macrophages or neutrophils were observed in hyperlipidemic patients. In conclusion, our clinical and mouse model data together reveal a pro-atherogenic role of Th17 cells through the promotion of inflammation in hyperlipidemic conditions and different stages of atherosclerosis, which further supports the notion that IL-17 may be a therapy target for the treatment of atherosclerosis.

Animals possess an inborn ability to recognize certain odors to avoid predators, seek food, and find mates. Innate odor preference is thought to be genetically hardwired. Here we report that acquisition of innate odor recognition requires spontaneous neural activity and is influenced by sensory experience during early postnatal development. Genetic silencing of mouse olfactory sensory neurons during the critical period has little impact on odor sensitivity, discrimination, and recognition later in life. However, it abolishes innate odor preference and alters the patterns of activation in brain centers. Exposure to innately recognized odors during the critical period abolishes the associated valence in adulthood in an odor-specific manner. The changes are associated with broadened projection of olfactory sensory neurons and expression of axon guidance molecules. Thus, a delicate balance of neural activity is needed during the critical period in establishing innate odor preference and convergent axon input is required to encode innate odor valence.

Abstract Background The chemosensory system plays an important role in orchestrating sexual behaviors in mammals. Pheromones trigger sexually dimorphic behaviors and different mouse strains exhibit differential responses to pheromone stimuli. It has been speculated that differential gene expression in the sensory organs that detect pheromones may underlie sexually-dimorphic and strain-specific responses to pheromone cues. Results We have performed transcriptome analyses of the mouse vomeronasal organ, a sensory organ recognizing pheromones and interspecies cues. We find little evidence of sexual dimorphism in gene expression except for Xist, an essential gene for X-linked gene inactivation. Variations in gene expression are found mainly among strains, with genes from immune response and chemosensory receptor classes dominating the list. Differentially expressed genes are concentrated in genomic hotspots enriched in these families of genes. Some chemosensory receptors show exclusive patterns of expression in different strains. We find high levels of single nucleotide polymorphism in chemosensory receptor pseudogenes, some of which lead to functionalized receptors. Moreover, we identify a number of differentially expressed long noncoding RNA species showing strong correlation or anti-correlation with chemoreceptor genes. Conclusions Our analyses provide little evidence supporting sexually dimorphic gene expression in the vomeronasal organ that may underlie dimorphic pheromone responses. In contrast, we find pronounced variations in the expression of immune response related genes, vomeronasal and G-protein coupled receptor genes among different mouse strains. These findings raised the possibility that diverse strains of mouse perceive pheromone cues differently and behavioral difference among strains in response to pheromone may first arise from differential detection of pheromones. On the other hand, sexually dimorphic responses to pheromones more likely originate from dimorphic neural circuits in the brain than from differential detection. Moreover, noncoding RNA may offer a potential regulatory mechanism controlling the differential expression patterns.

Abstract Deoxyarbutin (DeoxyArbutin, dA), a natural compound widely used in skin lighting, displayed selectively cytotoxicity in vitro. In the study, we found that dA significantly inhibited viability/proliferation of B16F10 melanoma cells, induced tumour cell arrest and apoptosis. Furthermore, dA triggered its pro-apoptosis through damaging the mitochondrial function (membrane potential loss, ATP depletion and ROS overload generation etc.) and activating caspase-9, PARP, caspase-3 and the phosphorylation of p38. Treatment with p38 agonist confirmed the involvement of p38 pathway triggered by dA in B16F10 cells. The in vivo finding also revealed that administration of dA significantly decreased the tumour volume and tumour metastasis in B16F10 xenograft model by inhibiting tumour proliferation and inducing tumour apoptosis. Importantly, the results indicated that dA was specific against tumour cell lines and had no observed systemic toxicity in vivo. Taken together, our study demonstrated that dA could combate tumour in vitro and in vivo by inhibiting the proliferation and metastasis of tumour via a p38-mediated mitochondria associated apoptotic pathway.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency and hemoglobin E (HbE, β26 Glu-Lys) are two common red cell disorders in Southeast Asia. G6PD deficiency produces hemolytic anemia, which can be triggered by certain drugs or infections. HbE is asymptomatic or is manifested as microcytic, minimally hemolytic anemia. The association between G6PD deficiency and HbE is little understood. This study aimed to investigate G6PD deficiency and HbE in a Kachin ethnic group in the China-Myanmar border area. G6PD enzyme activity was measured using a quantitative G6PD assay, G6PD variants genotyped by the SNaPshot assay, and an HbE gene mutation identified by an amplification refractory mutation system and subsequently confirmed by using a reverse dot blot hybridization assay from 100 unrelated individuals in the study area. G6PD enzyme activity ranged from 0.4 to 24.7 U/g Hb, and six males had severe G6PD deficiency (1.2-4.5 U/g Hb). Among the 24 G6PD-deficient subjects, 22 (92%) had the Mahidol 487G>A mutation (12 male hemizygotes, one female homozygote, and nine female heterozygotes), while the G6PD genotypes in two female subjects were unknown. HbE was identified in 39 subjects (20 males and 19 females), including 15 HbEE (seven males and eight females) and 24 HbAE (13 males and 11 females). Twenty-three subjects co-inherited both G6PD deficiency and HbE (22 with HbAE and one with HbEE). Whereas mean Hb levels were not significantly different between the HbA and HbE groups, G6PD-deficient males had significantly lower Hb levels than G6PD-normal males (P < 0.05, t-test). However, it is noteworthy that two G6PD-deficient hemizygous males with HbAE were severely anemic with Hb levels below 50 g/L. This study revealed high prevalence of co-inheritance of G6PD deficiency with HbAE in the Kachin ethnicity, and a potential interaction of the G6PD Mahidol 487G>A and HbAE in males leading to severe anemia. The presence of 6% males with severe G6PD deficiency raised a major concern in the use of primaquine for radical cure of vivax malaria.

The use of self-expanding metallic stents (SEMSs) is the current treatment of choice for malignant gastrointestinal obstructions. However, these stents can promote only drainage and have no antitumor effect. Some studies have reported that drug-eluting SEMSs may have tumor inhibition potential. The aim of this study was to evaluate the efficiency and safety of paclitaxel-eluting SEMSs (PEMSs) in rabbit esophageal cancer models.A PEMS was covered with a paclitaxel-incorporated membrane, in which the concentration of paclitaxel was 10% (wt/vol). The rabbit models were created endoscopically. Then, a PEMS or SEMS was endoscopically inserted into the rabbit esophagus. Two weeks after stent placement, the rabbits were sacrificed, and we evaluated the tumor volume, area of the wall defect, area of the tumor under endoscopic ultrasound (EUS) before and after stent placement, status of the proximal esophageal obstruction, tumor metastasis food-intake and weight loss.A total of 26 rabbits received stent insertion and survived until sacrifice, and migration occurred in 4 cases, 3 in SEMS group and 1 in PEMS group. For the remaining 22 rabbits, at the sacrificed time, the average tumor volume was 7.00±4.30 cm3 in the SEMS group and 0.94±1.51 cm3 in the PEMS group (P

The mammalian vomeronasal organ encodes pheromone information about gender, reproductive status, genetic background and individual differences. It remains unknown how pheromone information interacts to trigger innate behaviors. In this study, we identify vomeronasal receptors responsible for detecting female pheromones. A sub-group of V1re clade members recognizes gender-identifying cues in female urine. Multiple members of the V1rj clade are cognate receptors for urinary estrus signals, as well as for sulfated estrogen (SE) compounds. In both cases, the same cue activates multiple homologous receptors, suggesting redundancy in encoding female pheromone cues. Neither gender-specific cues nor SEs alone are sufficient to promote courtship behavior in male mice, whereas robust courtship behavior can be induced when the two cues are applied together. Thus, integrated action of different female cues is required in pheromone-triggered mating behavior. These results suggest a gating mechanism in the vomeronasal circuit in promoting specific innate behavior.

Olfaction based behavioral experiments are important for the investigation of sensory coding, perception, decision making and memory formation. The predominant experimental paradigms employ forced choice operant assays, which require associative learning and reinforced training. Animal performance in these assays not only reflects odor perception but also the confidence in decision making and memory. In this study, we describe a versatile and automated setup, "Poking-Registered Olfactory Behavior Evaluation System" (PROBES), which can be adapted to perform multiple olfactory assays. In addition to forced choice assays, we employ this system to examine animal's innate ability for odor detection, discrimination and preference without elaborate training procedures. These assays provide quantitative measurements of odor discrimination and robust readouts of odor preference. Using PROBES, we find odor detection thresholds are at lower concentrations in naïve animals than those determined by forced choice assays. PROBES-based automated assays provide an efficient way of analyzing innate odor-triggered behaviors.

Activity plays critical roles in development and maintenance of the olfactory system, which undergoes considerable neurogenesis throughout life. In the mouse olfactory epithelium, each olfactory sensory neuron (OSN) stably expresses a single odorant receptor (OR) type out of a repertoire of ∼1200 and the OSNs with the same OR identity are distributed within one of the few broadly-defined zones. However, it remains elusive whether and how activity modulates such OR expression patterns. Here we addressed this question by investigating OR gene expression via in situ hybridization when sensory experience or neuronal excitability is manipulated. We first examined the expression patterns of fifteen OR genes in mice which underwent neonatal, unilateral naris closure. After four-week occlusion, the cell density in the closed (sensory-deprived) side was significantly lower (for four ORs), similar (for three ORs), or significantly higher (for eight ORs) as compared to that in the open (over-stimulated) side, suggesting that sensory inputs have differential effects on OSNs expressing different OR genes. We next examined the expression patterns of seven OR genes in transgenic mice in which mature OSNs had reduced neuronal excitability. Neuronal silencing led to a significant reduction in the cell density for most OR genes tested and thinner olfactory epithelium with an increased density of apoptotic cells. These results suggest that sensory experience plays important roles in shaping OR gene expression patterns and the neuronal activity is critical for survival of OSNs.

This document presents the findings of a study on risk factors for early death in severe non-brain-injured trauma patients. The study analyzed various indicators, including Glasgow Coma Scale (GCS) score, spinal injury, blood pH, and clotting function, to determine their predictive value for early death. The results showed that lower GCS scores, spinal injury, lower blood pH, and longer activated partial thromboplastin time (APTT) were associated with increased early death. The combination of these indicators had the highest predictive value for early death. However, the study had limitations, such as its retrospective design and small sample size. [Extracted from the article]