Pan-Cancer Analysis of the LOX Family Reveals that LOX Affects Tumor Prognosis by Affecting Immune Infiltration.

The lysyl oxidase (LOX) gene family encodes for a group of copper-dependent enzymes that play a crucial role in the cross-linking of collagen and elastin fibers in the extracellular matrix (ECM). Dysregulation of LOX gene expression has been implicated in various pathological conditions, including cancer. Several studies have shown that the LOX gene family is involved in cancer progression and metastasis. The goal of this article is to conduct a comprehensive analysis of the LOX family's role in pan-cancer multiplexes. We utilized pan-cancer multi-omics sequencing data from TCGA to investigate the relationship between LOX family genes and tumors at four different levels: mutation, copy number variation, methylation, and gene expression. In addition, we also examined the relationship between LOX family genes and tumors at the cell line level using tumor cell line sequencing data from CCLE. Taking into account the impact of LOX family genes on lung cancer, we developed a LOX family lung cancer prognostic model to forecast the disease's prognosis. Our findings revealed that LOXL2 had the highest mutation frequency in tumors, while all four LOX family genes experienced some degree of copy number variation in diverse tumors. We observed that LOX, LOXL1 to LOXL3 were predominantly highly expressed in tumors including LUAD. The expression trends of LOX and LOXL1 to LOXL3 were consistent across tumor cell lines, but differed somewhat from LOXL4. Utilizing 25 LOX family-related genes, we constructed a LOX family prognostic model that performed well in predicting the prognosis of lung cancer. Through pan-cancer analysis, we gain further knowledge of the role of LOX family genes in different tumors, offering a novel pathway for future research into the relationship between LOX family genes and tumors.

Non-volatile and volatile compound changes in blueberry juice inoculated with different lactic acid bacteria strains.

BACKGROUND: Lactic acid bacteria (LABs) are widely present in foods and affect the flavour of fermented cultures. This study investigates the effects of fermentation with Lactobacillus acidophilus JYLA-16 (La), Lactobacillus plantarum JYLP-375 (Lp), and Lactobacillus rhamnosus JYLR-005 (Lr) on the flavour profile of blueberry juice. RESULTS: This study showed that all LABs strains preferentially used glucose rather than fructose as the carbon source during fermentation. Lactic acid was the main fermentation product, reaching 7.76 g L-1 in La-fermented blueberry juice, 5.86 g L-1 in Lp-fermented blueberry juice, and 6.41 g L-1 in Lr-fermented blueberry juice. These strains extensively metabolized quinic acid, whereas oxalic acid metabolism was almost unaffected. Sixty-four volatile compounds were identified using gas chromatography-ion mobility spectrometry (GC-IMS). All fermented blueberry juices exhibited decreased aldehyde levels. Furthermore, fermentation with La was dominated by alcohols, Lp was dominated by esters, and Lr was dominated by ketones. Linear discriminant analysis of the electronic nose and principal component analysis of the GC-IMS data effectively differentiated between unfermented and fermented blueberry juices. CONCLUSION: This study informs LABs selection for producing desirable flavours in fermented blueberry juice and provides a theoretical framework for flavour detection. © 2023 Society of Chemical Industry.

Acute pancreatitis in intraductal papillary mucinous neoplasm: a single-center retrospective cohort study with systematic review and meta-analysis.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) is a cystic tumor of the pancreas arising from abnormal papillary proliferation of ductal epithelial cells, and is a precancerous lesion of pancreatic malignancy. This study aimed to evaluate associations between acute pancreatitis (AP) and histologic subtypes of IPMN. METHODS: In the clinical study, patients with IPMN confirmed by surgical resection specimens at our institute between 2009 and 2021 were eligible for inclusion. Associations and predictive accuracy of AP on the presence of HGD were determined by logistic regressions. In addition, a systematic review and meta-analysis was conducted through literatures upon search in PubMed, Embase, CENTRAL, China National Knowledge Infrastructure (CKNI), and Wanfang database, up to June, 2023. Pooled effects of the associations between AP and HGD and intestinal epithelial subtype subtype, shown as odds ratios (ORs) with 95% confidence intervals (CIs), were calculated using random effects model. RESULTS: The retrospective cohort study included 47 patients (32 males, 15 females) diagnosed with IPMN at our center between 2009 and 2021, including 11 cases with AP (median 62 years) and 36 cases (median 64.5 years) without. Accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of AP in predicting HGD were 78.7%, 57.1%, 82.5%, 36.4%, and 91.7%, respectively. Univariate logistic regression analysis showed that AP group had greater odds of presence of HGD (OR: 6.29,95% CI: 1.14-34.57) than non-AP group. Meta-analysis of five case-control studies in the literature included 930 patients and showed that AP-IPMN patients had higher odds for HGD (OR: 2.13, 95% CI 1.38-3.29) and intestinal epithelial subtype (OR: 5.38, 95% CI: 3.50-8.27) compared to non-AP IPMN. CONCLUSIONS: AP is predictive of malignancy in patients with IPMN.

Non-invasive arterial blood pressure measurement and SpO2 estimation using PPG signal: a deep learning framework.

BACKGROUND: Monitoring blood pressure and peripheral capillary oxygen saturation plays a crucial role in healthcare management for patients with chronic diseases, especially hypertension and vascular disease. However, current blood pressure measurement methods have intrinsic limitations; for instance, arterial blood pressure is measured by inserting a catheter in the artery causing discomfort and infection. METHOD: Photoplethysmogram (PPG) signals can be collected via non-invasive devices, and therefore have stimulated researchers' interest in exploring blood pressure estimation using machine learning and PPG signals as a non-invasive alternative. In this paper, we propose a Transformer-based deep learning architecture that utilizes PPG signals to conduct a personalized estimation of arterial systolic blood pressure, arterial diastolic blood pressure, and oxygen saturation. RESULTS: The proposed method was evaluated with a subset of 1,732 subjects from the publicly available ICU dataset MIMIC III. The mean absolute error is 2.52 ± 2.43 mmHg for systolic blood pressure, 1.37 ± 1.89 mmHg for diastolic blood pressure, and 0.58 ± 0.79% for oxygen saturation, which satisfies the requirements of the Association of Advancement of Medical Instrumentation standard and achieve grades A for the British Hypertension Society standard. CONCLUSIONS: The results indicate that our model meets clinical standards and could potentially boost the accuracy of blood pressure and oxygen saturation measurement to deliver high-quality healthcare.

Factors related to microimplant-assisted rapid palatal expansion in teenagers and young adults: A cone-beam computed tomography study.

INTRODUCTION: For patients with maxillary transverse deficiency, selecting an appropriate therapeutic method is important for the treatment effect and prognosis. Our study aimed to explore factors related to microimplant-assisted rapid palatal expansion (MARPE) in teenagers and young adults using cone-beam computed tomography. METHODS: Twenty-five patients who underwent MARPE were included in this retrospective study from February 2014 to June 2019. Midpalatal suture density (MPSD) ratio, midpalatal suture maturation (MPSM), bone effect, dentoalveolar effect, and dental effect in maxillary first molar were evaluated using cone-beam computed tomography. Spearman correlation analysis was used to analyze the correlation between the MPSD ratio, MPSM, age, and the expansion amount generated by MARPE. RESULTS: Twenty-five patients (mean age, 19.84 ± 3.96 years; range, 15-29 years) with maxillary transverse deficiency were analyzed. Age was negatively correlated with bone expansion, alveolar expansion, and alveolar change (all P <0.05). There was a negative correlation between MPSM and nasal cavity variation, bone expansion, and alveolar change (all P <0.05). The bone expansion was negatively correlated with MPSD ratio 3 (r = -0.417; P <0.05) and MPSD ratio 4 (all P <0.05). CONCLUSIONS: Age, MPSM, and MPSD ratio were significantly related to the MARPE effect. Age, MPSM, and MPSD ratio should be considered when choosing MARPE.

[Clinical features and genetic analysis of two Chinese pedigrees affected with Joubert syndrome].

OBJECTIVE: To explore the clinical characteristics and genetic basis of two Chinese pedigrees affected with Joubert syndrome. METHODS: Clinical data of the two pedigrees was collected. Genomic DNA was extracted from peripheral blood samples and subjected to high-throughput sequencing. Candidate variants were verified by Sanger sequencing. Prenatal diagnosis was carried out for a high-risk fetus from pedigree 2. RESULTS: The proband of pedigree 1 was a fetus at 23+5 weeks gestation, for which both ultrasound and MRI showed "cerebellar vermis malformation" and "molar tooth sign". No apparent abnormality was noted in the fetus after elected abortion. The fetus was found to harbor c.812+3G>T and c.1828G>C compound heterozygous variants of the INPP5E gene, which have been associated with Joubert syndrome type 1. The proband from pedigree 2 had growth retardation, mental deficiency, peculiar facial features, low muscle tone and postaxial polydactyly of right foot. MRI also revealed "cerebellar dysplasia" and "molar tooth sign". The proband was found to harbor c.485C>G and c.1878+1G>A compound heterozygous variants of the ARMC9 gene, which have been associated with Joubert syndrome type 30. Prenatal diagnosis found that the fetus only carried the c.485C>G variant. A healthy infant was born, and no anomalies was found during the follow-up. CONCLUSION: The compound heterozygous variants of the INPP5E and ARMC9 genes probably underlay the disease in the two pedigrees. Above finding has expanded the spectrum of pathogenic variants underlying Joubert syndrome and provided a basis for genetic counseling and prenatal diagnosis.

Incorporating Heterogeneous Features into the Random Subspace Method for Bearing Fault Diagnosis.

In bearing fault diagnosis, machine learning methods have been proven effective on the basis of the heterogeneous features extracted from multiple domains, including deep representation features. However, comparatively little research has been performed on fusing these multi-domain heterogeneous features while dealing with the interrelation and redundant problems to precisely discover the bearing faults. Thus, in the current study, a novel diagnostic method, namely the method of incorporating heterogeneous representative features into the random subspace, or IHF-RS, is proposed for accurate bearing fault diagnosis. Primarily, via signal processing methods, statistical features are extracted, and via the deep stack autoencoder (DSAE), deep representation features are acquired. Next, considering the different levels of predictive power of features, a modified lasso method incorporating the random subspace method is introduced to measure the features and produce better base classifiers. Finally, the majority voting strategy is applied to aggregate the outputs of these various base classifiers to enhance the diagnostic performance of the bearing fault. For the proposed method's validity, two bearing datasets provided by the Case Western Reserve University Bearing Data Center and Paderborn University were utilized for the experiments. The results of the experiment revealed that in bearing fault diagnosis, the proposed method of IHF-RS can be successfully utilized.

Reciprocal Expression of Differentiated Embryonic Chondrocyte Expressed Genes Result in Functional Antagonism in Gastric Cancer.

BACKGROUND: Differentiated embryonic chondrocyte expressed genes (DECs) are critical regulators of cellular proliferation and differentiation. However, DEC1 and DEC2 as family member have opposite or identical roles in tumor, acting as an "accelerator" or a "brake" in progression. AIMS: The possible crosstalk between DEC1 and DEC2 in the gastric cancer (GC). METHODS: The association of DEC1 and DEC2 expression with prognosis was investigated by immunohistochemistry. The expression pattern of DECs in GC cells was examined using the CCLE database. DECs knockdown or overexpression was conducted via lentiviral transfection. The proliferation of GC cells was evaluated by CCK8, EdU, and Colony forming. ChIP and luciferase reporter assays were used to verify interaction between DEC1 and the DEC2 promoter. The combination downstream with DEC1 and DEC2 was predicted by bioinformation, with Western blot providing further verification. RESULTS: We found that reciprocal expression of DEC1 and DEC2 works together to sustain the progression of GC by promoting cell growth. We confirmed this observation in vivo, showing that inhibition DEC1expression could increase DEC2 expression. DEC1 suppresses DEC2 expression by directly binding to the E-box of the DEC2 promoter in GC cells. Furthermore, this regulation of DEC1 on DEC2 enables the further indirect or cooperative activation of additional downstream target genes, MAPK, and STAT3. CONCLUSION: Our data demonstrate that DEC1 and DEC2 interact physically and functionally and identify a novel mode of cross-regulatory interaction between DECs that abrogates their functional activity.

Targeted Next-Generation Sequencing Reveals a Large Novel ß-Thalassemia Deletion that Removes the Entire HBB Gene.

ß-Thalassemia (ß-thal) is one of the most common monogenic recessive inherited diseases worldwide. The mutation spectrum of ß-thal has been increasingly broadened by various genetic testing methods. The discovery and identification of novel and rare pathogenic thalassemia variants enable better disease prevention, especially in high prevalence regions. In this study, a Chinese thalassemia family with an unclear etiology was recruited to the Thalassemia Screening Program. Blood samples collected from them were primarily screened by hematology analysis and clinical routine genetic screening. Subsequently, targeted next-generation sequencing (NGS) and Sanger sequencing were performed to find and identify a novel deletion variant. The deletion, discovered by targeted NGS, was validated through real-time quantitative polymerase chain reaction (qPCR). First, a large novel ß-thal deletion (3488 bp) related to a high Hb F level, NC_000011.9: g.5245533_5249020del (Chongqing deletion) (GRCh37/hg19), was found and identified in the proband and her mother. The deletion removed the entire ß-globin gene and led to absent ß-globin (ß0). We then validated this large novel deletion in the proband and her mother by qPCR. We first discovered and identified a large novel ß-thal deletion related to elevated Hb F level, it helps broaden the spectrum of pathogenic mutants that may cause ß-thal intermedia (ß-TI) or ß-thal major (ß-TM), paving the way for effective thalassemia screening. Next-generation sequencing has the potential of finding rare and novel thalassemia mutants.

Physicians' knowledge, attitude, and prescribing behavior regarding stress ulcer prophylaxis in China: a multi-center study.

BACKGROUND: Perioperative patients are at risk of developing stress ulcers (SU), which can cause clinically important bleeding. Stress ulcer prophylaxis (SUP) is widely applied to the patients in Intensive care unit (ICU) as well as the general ward, so it may lead to overmedication. However, there have been no surveys regarding SUP knowledge or prescribing habits. OBJECTIVE: Our study assessed the knowledge, attitudes, and prescribing behavior of the surgeons toward perioperative patients regarding SUP and determined factors associated with low knowledge and high level of prescribing behaviors. METHODS: We performed a cross-sectional survey using questionnaires, randomly sampling 1266 surgeons on their current SUP practices. RESULTS: Proton pump inhibitors for SUP were used the most (94%); 43% used lansoprazole. Guideline awareness was inconsistent; the most familiar guideline was the National Medical Journal of China, and 46% were unaware of any guidelines. The predictors of low knowledge score regarding SUP in multivariable analysis were the hospital grade (p = 0.000), the type of hospital (p = 0.044), attendance at continuing education programs (p = 0.037), the awareness of clinical practice guidelines (CPGs) for SUP (p = 0.000). Twenty-one percent of physicians were high prescribers. High prescribing behavior was associated with hospital grade(p = 0.000), education level(p = 0.010) and attendance at continuing education programs (p = 0.000). CONCLUSION: We found that most surgeons used SUP, primarily proton pump inhibitors. However, surgeons knew little about the SUP guidelines, which may lead to insufficient SUP knowledge and overmedication. In addition, hospital grade, the type of hospital and attendance at continuing education programs may also affect the low knowledge of SUP. Hospital grade, education level and attendance at continuing education programs may affect high prescribing behavior.

Population stratification enables modeling effects of reopening policies on mortality and hospitalization rates.

OBJECTIVE: Study the impact of local policies on near-future hospitalization and mortality rates. MATERIALS AND METHODS: We introduce a novel risk-stratified SIR-HCD model that introduces new variables to model the dynamics of low-contact (e.g., work from home) and high-contact (e.g., work on-site) subpopulations while sharing parameters to control their respective R0(t) over time. We test our model on data of daily reported hospitalizations and cumulative mortality of COVID-19 in Harris County, Texas, from May 1, 2020, until October 4, 2020, collected from multiple sources (USA FACTS, U.S. Bureau of Labor Statistics, Southeast Texas Regional Advisory Council COVID-19 report, TMC daily news, and Johns Hopkins University county-level mortality reporting). RESULTS: We evaluated our model's forecasting accuracy in Harris County, TX (the most populated county in the Greater Houston area) during Phase-I and Phase-II reopening. Not only does our model outperform other competing models, but it also supports counterfactual analysis to simulate the impact of future policies in a local setting, which is unique among existing approaches. DISCUSSION: Mortality and hospitalization rates are significantly impacted by local quarantine and reopening policies. Existing models do not directly account for the effect of these policies on infection, hospitalization, and death rates in an explicit and explainable manner. Our work is an attempt to improve prediction of these trends by incorporating this information into the model, thus supporting decision-making. CONCLUSION: Our work is a timely effort to attempt to model the dynamics of pandemics under the influence of local policies.

Intramedullary nailing via suprapatellar approach versus locked plating of proximal extra-articular tibial fractures: a randomized control trial.

OBJECTIVE: Currently, nailing through the suprapatellar approach and minimally invasive plating have been generally accepted in the management of displaced proximal tibial fractures. This investigation was aimed at comparing these two treatment methods in terms of their effectiveness and safety. METHODS: We randomized 328 patients into one of two groups: one underwent intramedullary nailing via the suprapatellar approach (IMN group), while the other underwent locking compressive plate (LCP group) placement. The primary outcome was the Iowa Knee Score at 12 months. The clinical history, amount of intra-operative blood loss, rate of fracture healing, and post-operative complications were assessed as secondary outcomes. Participants were assessed at one, two, three, six and 12 months after surgery. RESULTS: Follow-up data for a year were available for 152 and 154 patients in the IMN group and LCP group, respectively. No intergroup difference was detected with regard to the Iowa Knee Scores (91 ± 8.2 in the IMN group and 90 ± 7.3 in the LCP group, respectively (p = 0.26)), at 12 months. Duration of operation (83.5 ± 35.3 min), amount of blood loss (55 ± 43 mL), duration of fluoroscopy (53.7 ± 3.9 s), and cases with difficult reduction (n = 46) in the IMN group did not differ significantly from those in the LCP group (80.1 ± 43.6 min; 65 ± 56 mL; 48 ± 12 s; 32) (p < 0.05). The two groups had similar post-operative complications and rate of fracture union, with the pre-injury activity level being restored in most patients. Removal of the implants was performed in 31.6% and 63.0% of the cases in the IMN and LCP groups, respectively, indicating a significant intergroup difference. CONCLUSION: Both IMN through the suprapatellar approach and minimally invasive LCP were found to yield no significant intergroup difference of clinical outcomes in the treatment of proximal, extra-articular tibial fractures. However, the requirement of implant removal was more relevant to LCP.

Cutaneous Immunoprofiles of Three Spotted Fever Group Rickettsia Cases.

Spotted fever group rickettsia (SFGR) can cause mild to fatal illness. The early interaction between the host and rickettsia in skin is largely unknown, and the pathogenesis of severe rickettsiosis remains an important topic. A surveillance of SFGR infection by PCR of blood and skin biopsy specimens followed by sequencing and immunohistochemical (IHC) detection was performed on patients with a recent tick bite between 2013 and 2016. Humoral and cutaneous immunoprofiles were evaluated in different SFGR cases by serum cytokine and chemokine detection, skin IHC staining, and transcriptome sequencing (RNA-seq). A total of 111 SFGR cases were identified, including 79 "Candidatus Rickettsia tarasevichiae," 22 Rickettsia raoultii, 8 Rickettsia sibirica, and 2 Rickettsia heilongjiangensis cases. The sensitivity to detect SFGR in skin biopsy specimens (9/24, 37.5%) was significantly higher than that in blood samples (105/2,671, 3.9%) (P < 0.05). As early as 1 day after the tick bite, rickettsiae could be detected in the skin. R. sibirica infection was more severe than "Ca Rickettsia" and R. raoultii infections. Increased levels of serum interleukin-18 (IL-18), IP10, and monokine induced by gamma interferon (MIG) and decreased levels of IL-2 were observed in febrile patients infected with R. sibirica compared to those infected with "Ca Rickettsia." RNA-seq and IHC staining could not discriminate between SFGR-infected and uninfected tick bite skin lesions. However, the type I interferon (IFN) response was differently expressed between R. sibirica and R. raoultii infections at the cutaneous interface. It is concluded that skin biopsy specimens were more reliable for the detection of SFGR infection in human patients although the immunoprofile may be complicated by immunomodulators induced by the tick bite.

Cellular analysis of a novel mutation p. Ser287Tyr in TOR1A in late-onset isolated dystonia.

BACKGROUND: Variations in TOR1A were thought to be associated with early-onset isolated dystonia. The variant S287Y (NM_000113.2: c.860C > A, p. Ser287Tyr, rs766483672) was found in our late-onset isolated dystonia patient. This missense variant is adjacent to R288Q (c.863G > A, p. Arg288Gln), which was reported to be associated with isolated dystonia. The potentially pathogenic role of S287Y is not conclusively known. METHODS: Cytological and molecular biological analyses were performed in vitro to determine whether this variant damages the structure and function of the cell. RESULTS: Compared with the SH-SY5Y cells overexpressing wild-type TOR1A, the cells overexpressing the protein with S287Y have an enlarged peri-nuclear space. The same changes in nuclear morphology were also found in the cells overexpressing the pathogenic variants ΔE (NM_000113.2:c.904_906delGAG, p. Glu302del), F205I (NM_000113.2:c.613 T > A, p. Phe205Ile), and R288Q (NM_000113.2:c.863G > A, p. Arg288Gln). Mutated proteins with S287Y presented a higher tendency to form dimers under reducing conditions. The same tendencies were observed in other mutated proteins but not in wild-type torsinA. CONCLUSIONS: TorsinA with S287Y damages the structure of the cell nucleus and may be a novel pathogenic mutation that causes isolated dystonia.

Association between gene polymorphisms of voltage-dependent Ca2+ channels and hypertension in the Dai people of China: a case-control study.

BACKGROUND: Abnormal calcium homeostasis related to the development of hypertension. As the key regulator of intracellular calcium concentration, voltage-dependent calcium channels (VDCCs), the variations in these genes may have important effects on the development of hypertension. Here we evaluate VDCCs variability with respect to hypertension in the Dai ethnic group of China. METHODS: A total of 1034 samples from Dai individuals were collected, of which 495 were used as cases, and 539 were used as controls. Blood pressure was measured using a standard mercury measurement method, three times with a rest for 5 min, and the average was used for analyses. Seventeen single nucleotide polymorphisms (SNPs) in the four protein-coding genes (CACNA1A, CACNA1C, CACNA1S, CACNB2) of VDCCs were identified by multiplex PCR-SNP typing technique. Chi-square tests and regression models were used to analyse the associations of SNPs with hypertension. RESULTS: The results of chi-square tests showed that the allele frequencies of 5 SNPs were significantly different between the case and the control groups (P < 0.05), but the statistical significance was lost after Bonferroni's correction. However, after adjusting for BMI, age, sex and other factors by logistic regression analyses, the results showed that 5 SNPs consistent with chi-square tests (rs2365293, rs17539088, rs16917217, rs61839222 and rs10425859) were still statistically positive. CONCLUSIONS: This finding suggested that the significant association of these SNPs with hypertension may be noteworthy in future studies.

Essential oils as natural preservatives for bakery products: Understanding the mechanisms of action, recent findings, and applications.

Bakery products, as an important part of a healthy diet, are characterized by their limited shelf-life. Microbiological spoilage of these products not only affects the quality characteristics and result in the economic loss but also threatens consumer's health. Incorporation of chemical preservatives, as one of the most conventional preserving techniques, lost its popularity due to the increasing consumer's health awareness. Therefore, the bakery industry is seeking alternatives to harmful antimicrobial agents that can be accepted by health-conscious customers. In this regard, essential oils have been previously used as either a part of product ingredient or a part of the packaging system. Therefore, the antimicrobial aspect of essential oils and their ability in delaying the microbiological spoilage of bakery products have been reviewed. Several types of essential oils, including thyme, cinnamon, oregano, and lemongrass, can inhibit the growth of harmful microorganisms in bakery products, resulting in a product with extended shelf-life and enhanced safety. Research revealed that several bioactive compounds are involved in the antimicrobial activity of essential oils. However, some limitations, such as the possible negative effects of essential oils on sensory parameters, may limit their applications, especially in high concentrations. In this case, they can be used in combination with other preservation techniques such as using appropriate packaging materials. Further research regarding the commercial production of the bakery products formulated with essential oils is required in this area.

Functional Analysis of Sheep POU2F3 Isoforms.

POU domain class 2 transcription factor 3 (POU2F3) plays an important role in keratinocyte proliferation and differentiation. Our previous study identified four sheep POU2F3 transcript variants (POU2F3-1, POU2F3-2, POU2F3-3, and POU2F3-4), encoding three POU2F3 protein isoforms (POU2F3-1, POU2F3-2, and POU2F3-3). However, the functional differences among the three POU2F3 isoforms remain unknown. The objective of this study was to determine the tissue expression pattern of the four POU2F3 transcript variants in sheep and to investigate the functional differences in cell proliferation among the three POU2F3 isoforms. Quantitative RT-PCR analysis showed that the four POU2F3 transcripts were ubiquitously expressed in all tested adult sheep tissues, and POU2F3-1 exhibited higher expression level than the other three POU2F3 transcript variants in skin (P < 0.05). Cell proliferation assay showed that overexpression of any one of the three POU2F3 isoforms significantly inhibited the proliferation of sheep fetal fibroblasts and HaCaT cells at 48 and 72 h after transfection (P < 0.05). POU2F3-3 had less inhibitory effect on cell proliferation than POU2F3-1 and POU2F3-2 (P < 0.05), and POU2F3-1 and POU2F3-2 had similar inhibitory effects (P > 0.05). Dual luciferase reporter assays demonstrated that overexpression of any one of the three POU2F3 isoforms significantly inhibited the promoter activities of keratin 14 (KRT14) and matrix metalloproteinase 19 (MMP19) genes (P < 0.05). POU2F3-3 had less inhibitory effect on the promoter activities of KRT14 and MMP19 genes than POU2F3-1 and POU2F3-2 (P < 0.05), and POU2F3-1 and POU2F3-2 had similar inhibitory effects (P > 0.05). These results suggest three sheep POU2F3 isoforms have similar functional effects, but to a different extent.

Complex mode-locking oscillations and Stern-Brocot derivation tree in a CSTR reaction with impulsive perturbations.

A complex mode-locking (entrainment) topology underlying the continuous stirred tank reactor reaction model subjected to impulsive perturbations is identified. Employing high-resolution stability diagrams, we exhibit the global structure of mode-locking oscillations and describe how they are interconnected and how their complexity unfolds with control parameters varying. The scenarios shown in the bi-parametric planes revealed that the skeleton of Arnold's tongues is organized according to the symmetric Stern-Brocot sum tree. Moreover, the mode-locking organization is controlled by an invariant torus (a pair of frequencies) initiated from Hopf bifurcations. Interestingly, the mode-locking order is unfolded in an elusive way, that is, in perfect agreement with the reciprocal of the Stern-Brocot sum tree. The findings reported here contribute to providing a description and classification of mode-locking oscillations for the impulsive system.

Upscale production of (R)-mandelic acid with a stereospecific nitrilase in an aqueous system.

(R)-Mandelic acid (R-MA) is a key precursor for the synthesis of semi-synthetic penicillin, cephalosporin, anti-obesity drugs, antitumor agents, and chiral resolving agents for the resolution of racemic alcohols and amines. In this study, an enzymatic method for the large-scale production of R-MA by a stereospecific nitrilase in an aqueous system was developed. The nitrilase activity of the Escherichia coli BL21(DE3)/pET-Nit whole cells reached 138.6 U/g in a 20,000-L fermentor. Using recombinant E. coli cells as catalyst, 500 mM R,S-mandelonitrile (R,S-MN) was resolved into 426 mM (64.85 g/L) R-MA within 8 h, and the enantiomeric excess (ee) value of R-MA reached 99%. During the purification process, pure R-MA with a recovery rate of 78.8% was obtained after concentration and crystallization. This study paved the foundation for the upscale production of R-MA using E. coli whole cells as biocatalyst.

Dual Separation of Krypton and Argon from Environmental Samples for Radioisotope Dating.

The noble gas radioisotopes 85Kr, 81Kr, and 39Ar are nearly ideal environmental tracers because of their chemical inertness and simple transport mechanisms. Recent advances in Atom Trap Trace Analysis have enabled measurements of 85Kr and 81Kr using 10-20 kg of water or ice, and 39Ar in only a few kilograms, making these tracers available to be applied in the earth sciences on a large-scale. To meet the resulting increase in demand, we have developed an automated process for the dual separation of krypton and argon from environmental samples based on titanium gettering and gas chromatography. 0.5-4 L STP air samples have been purified, demonstrating purities and recoveries of >90% for krypton and >99% for argon within 90-120 min of processing time. Samples of high methane admixtures, a challenge regularly encountered in groundwater applications, have been purified by exploiting the full potential of titanium gettering at high temperatures (>1000 °C). Samples with 0.4-48 L STP of methane admixture are processed in 2-5 h without compromising purity or recovery. The applicability of the purification system is further demonstrated using actual groundwater samples with carbon dioxide and methane content in the extracted gas up to 16 L STP and 42 L STP, respectively.