Femoral Tunnel Malposition, Increased Lateral Tibial Slope, and Decreased Notch Width Index Are Risk Factors for Non-Traumatic Anterior Cruciate Ligament Reconstruction Failure.

PURPOSE: To identify risk factors for patients who sustain nontraumatic anterior cruciate ligament reconstruction (ACLR) failure. METHODS: A retrospective analysis was performed on patients undergoing primary or revision ACLR in our institution between 2010 and 2018. Patients sustaining insidious-onset knee instability without history of trauma were identified as nontraumatic ACLR failure and assigned to the study group. The control group of subjects who showed no evidence of ACLR failure with minimum 48-month follow-up were matched in a 1:1 ratio based on age, sex, and body mass index. Anatomic parameters including tibial slope (lateral [LTS], medial [MTS]); tibial plateau subluxation (lateral [LTPsublx], medial [MTPsublx]); notch width index (NWI); and lateral femoral condyle ratio were measured with magnetic resonance imaging or radiography. Graft tunnel position was assessed using 3-dimensional computed tomography and reported in 4 dimensions: deep-shallow ratio (DS ratio) and high-low ratio for femoral tunnel, anterior-posterior ratio and medial-lateral ratio for tibial tunnel. Interobserver and intraobserver reliability were evaluated by the intraclass correlation coefficient (ICC). Patients' demographic data, surgical factors, anatomic parameters, and tunnel placements were compared between the groups. Multivariate logistic regression and receiver operating characteristic curve analysis was used to discriminate and assess the identified risk factors. RESULTS: A total of 52 patients who sustained nontraumatic ACLR failure were included and matched with 52 control subjects. Compared to patients with intact ACLR, those who sustained nontraumatic ACLR failure showed significantly increased LTS, LTPsublx, MTS, and deceased NWI (all P < .001). Moreover, the average tunnel position in the study group was significantly more anterior (P < .001) and superior (P = .014) at the femoral side and more lateral (P = .002) at the tibial side. Multivariate regression analysis identified LTS (odds ratio [OR] = 1.313; P = .028), DS ratio (OR = 1.091; P = .002), and NWI (OR = 0.813; P = .040) as independent predictors of nontraumatic ACLR failure. LTS appeared to be the best independent predictive factor (area under the curve [AUC] = 0.804; 95% confidence interval [CI], 0.721-0.887), followed by DS ratio (AUC = 0.803; 95% CI, 0.717-0.890), and NWI (AUC = 0.756; 95% CI, 0.664-0.847). The optimal cutoff values were 6.7° for increased LTS (sensitivity = 0.615, specificity = 0.923); 37.4% for increased DS ratio (sensitivity = 0.673, specificity = 0.885); and 26.4% for decreased NWI (sensitivity = 0.827, specificity = 0.596). Intraobserver and interobserver reliability was good to excellent, with ICCs ranging from 0.754 to 0.938 for all radiographical measurements. CONCLUSIONS: Increased LTS, decreased NWI, and femoral tunnel malposition are predictive risk factors for nontraumatic ACLR failure. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Precommitment low-level Neurog3 expression defines a long-lived mitotic endocrine-biased progenitor pool that drives production of endocrine-committed cells.

The current model for endocrine cell specification in the pancreas invokes high-level production of the transcription factor Neurogenin 3 (Neurog3) in Sox9(+) bipotent epithelial cells as the trigger for endocrine commitment, cell cycle exit, and rapid delamination toward proto-islet clusters. This model posits a transient Neurog3 expression state and short epithelial residence period. We show, however, that a Neurog3(TA.LO) cell population, defined as Neurog3 transcriptionally active and Sox9(+) and often containing nonimmunodetectable Neurog3 protein, has a relatively high mitotic index and prolonged epithelial residency. We propose that this endocrine-biased mitotic progenitor state is functionally separated from a pro-ductal pool and endows them with long-term capacity to make endocrine fate-directed progeny. A novel BAC transgenic Neurog3 reporter detected two types of mitotic behavior in Sox9(+) Neurog3(TA.LO) progenitors, associated with progenitor pool maintenance or derivation of endocrine-committed Neurog3(HI) cells, respectively. Moreover, limiting Neurog3 expression dramatically increased the proportional representation of Sox9(+) Neurog3(TA.LO) progenitors, with a doubling of its mitotic index relative to normal Neurog3 expression, suggesting that low Neurog3 expression is a defining feature of this cycling endocrine-biased state. We propose that Sox9(+) Neurog3(TA.LO) endocrine-biased progenitors feed production of Neurog3(HI) endocrine-committed cells during pancreas organogenesis.

Gold Nanoparticles in Neurological Diseases: A Review of Neuroprotection.

This review explores the diverse applications of gold nanoparticles (AuNPs) in neurological diseases, with a specific focus on Alzheimer's disease (AD), Parkinson's disease (PD), and stroke. The introduction highlights the pivotal role of neuroinflammation in these disorders and introduces the unique properties of AuNPs. The review's core examines the mechanisms by which AuNPs exert neuroprotection and anti-neuro-inflammatory effects, elucidating various pathways through which they manifest these properties. The potential therapeutic applications of AuNPs in AD are discussed, shedding light on promising avenues for therapy. This review also explores the prospects of utilizing AuNPs in PD interventions, presenting a hopeful outlook for future treatments. Additionally, the review delves into the potential of AuNPs in providing neuroprotection after strokes, emphasizing their significance in mitigating cerebrovascular accidents' aftermath. Experimental findings from cellular and animal models are consolidated to provide a comprehensive overview of AuNPs' effectiveness, offering insights into their impact at both the cellular and in vivo levels. This review enhances our understanding of AuNPs' applications in neurological diseases and lays the groundwork for innovative therapeutic strategies in neurology.

Prognostic-Related Biomarkers in Pancreatic Ductal Adenocarcinoma Correlating with Immune Infiltrates Based on Proteomics.

BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) accounts for 85% of pancreatic carcinoma cases. Patients with PDAC have a poor prognosis. The lack of reliable prognostic biomarkers makes treatment challenging for patients with PDAC. Using a bioinformatics database, we sought to identify prognostic biomarkers for PDAC. MATERIAL AND METHODS Using proteomic analysis of the Clinical Proteomics Tumor Analysis Consortium (CPTAC) database, we were able to identify core differential proteins between early and advanced pancreatic ductal adenocarcinoma tissue, and then we used survival analysis, Cox regression analysis, and area under the ROC curves to screen for more significant differential proteins. Additionally, the Kaplan-Meier plotter database was utilized to determine the relationship between prognosis and immune infiltration in PDAC. RESULTS We identified 378 differential proteins in early (n=78) and advanced stages (n=47) of PDAC (P<0.05). PLG, COPS5, FYN, ITGB3, IRF3, and SPTA1 served as independent prognostic factors of patients with PDAC. Patients with higher COPS5 expression had shorter overall survival (OS) and recurrence-free survival, and those with higher PLG, ITGB3, and SPTA1, and lower FYN and IRF3 expression had shorter OS. More importantly, COPS5, IRF3 were negatively associated with macrophages and NK cells, but PLG, FYN, ITGB3, and SPTA1 were positively related to the expression of CD8+ T cells and B cells. COPS5 affected the prognosis of PDAC patients by acting on B cells, CD8+ T cells, macrophages, and NK cells immune infiltration, while PLG, FYN, ITGB3, IRF3, and SPTA1 affected PDAC patient prognosis through some immune cells. CONCLUSIONS PLG, COPS5, FYN, IRF3, ITGB3 and SPTA1 could be potential immunotherapeutic targets and valuable prognostic biomarkers of PDAC.

Increased Lateral Femoral Condyle Ratio Measured by Magnetic Resonance Imaging Is Associated With Anterior Cruciate Ligament Rerupture.

PURPOSE: To investigate the association between lateral femoral condyle ratio (LFCR) measured by magnetic resonance imaging (MRI) and anterior cruciate ligament (ACL) rerupture after anatomic ACL reconstruction (ACLR) and to compare the diagnostic accuracy between MRI and radiograph measurements. METHODS: A retrospective review was conducted on patients who underwent anatomic ACLR in our institution between 2015 and 2018. Patients who experienced rerupture after ACLR were identified and matched 1:1 with control patients who showed no evidence of graft failure during a minimum 48-month follow-up. The matching criteria included age, sex, and body mass index. LFCR was measured on MRI scans and radiographs of the affected limb. Patients' characteristics, surgical features, and anatomic measurements were compared between groups. Conditional logistic regression was performed to investigate whether MRI-measured LFCR is a risk factor for ACL rerupture. The optimal cutoff value was determined by receiver operating characteristic curves (ROC). Delong's test was performed to compare the diagnostic accuracy between MRI and radiograph measurements. RESULTS: A total of 72 patients who sustained ACL rerupture were included and matched with 72 control subjects. Compared to patients with intact ACLR, those who sustained ACL rerupture showed a significant increase in LFCR on MRI scans (63.38% ± 2.26% [95% CI, 62.84%-63.91%] vs 61.10% ± 2.19% [95% CI, 60.59%-61.61%], P < .001). An MRI-measured LFCR >62.18% was set as the cutoff point to discern patients at a higher risk of graft failure after anatomic ACLR, with sensitivity and specificity of 75.0% and 70.8%, respectively. MRI-measured LFCR demonstrated superior diagnostic accuracy during ROC curve analysis, achieving a higher area under the curve compared to radiograph-measured LFCR (0.783 ± 0.051 vs 0.668 ± 0.060, P = .041). CONCLUSIONS: The study found that MRI-measured LFCR was associated with ACL rerupture. A cutoff value of 62.18% was determined, which can help identify patients at a higher risk of rerupture. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Comparison and analysis of skiing injuries at ski resorts in Chongli, China and Japan.

PURPOSE: The rapid development of winter sports requires investigation on injuries in Chongli district, Zhangjiakou city, one of the ski sites of the 2022 Winter Olympics. Careful evaluation is required to observe which injuries are caused under what circumstances, and then we can make corresponding preventive measures and recommendations based on the results. METHODS: In this retrospective study, the data of injury cases at ski resorts in China (Chongli district) and Japan were analyzed to provide a reference for the ongoing injury prevention at ski resorts. We collected data on injuries at Wanlong and Fulong ski resorts in Chongli district during the 2017-2018 and 2018-2019 ski seasons. We referred to the skiing injury report issued in February 2020 of a nationwide ski safety statistical service - Japan Ski Safety Association. The causes of injury and specific injured body parts were analyzed based on the data of Chinese and Japanese ski resorts. Statistical significance has been calculated using the Chi-square test. RESULTS: During the 2019-2020 ski season in Japanese ski resorts, the number of reported injuries per 10,000 skiers was 0.93, of which 457 (17.3%) were over 50 years old, accounting for a large proportion of injuries, meanwhile in Chongli ski resort, the injury rate of skiers aged 50 and over was 7.1%. The knee joint (23.7% at Wanlong ski resort and 28.4% in Japanese ski resorts) was the most injured body part among Chongli and Japanese skiers. Among snowboarders, shoulder joint injury (17.7% in Japanese ski resorts) was the most common, and injury on hands and fingers (16.3% in Wanlong ski resorts) was the most common. Head injury rates are similar in Chongli, China and Japanese ski resorts (8.2% and 8.7%, respectively). CONCLUSION: Our analysis demonstrated that injury data recorded among young skiers was higher in Chinese ski resorts (Chongli district) than that in Japanese ski resorts, and elderly skiers made up a larger proportion of skiing injuries in Japanese resorts. Thus, according to our research, the protection of knee joints, shoulder joints, and hands and fingers should be taken seriously. It should pay attention to the teaching of ski poles (for finger protection), and use protective devices such as knee pads, helmets, etc.

Homocysteine Suppresses Autophagy Through AMPK-mTOR-TFEB Signaling in Human THP-1 Macrophages.

ABSTRACT: Hyperhomocysteinemia is an independent risk factor for atherosclerosis. It is known that macrophage autophagy plays a protective role in atherosclerosis and that hyperhomocysteinemia is strongly linked to autophagy. Therefore, it is of great significance to study the molecular mechanisms underlying the effect of homocysteine (Hcy) on macrophage autophagy. This study aimed to investigate the effects of Hcy on autophagy in a human acute monocytic leukemia cell line (THP-1). The Hcy-treated THP-1 cells exhibited increased levels of the autophagy substrate SQSTM1 (p62) and decreased levels of the autophagy markers LC3 II/I and Beclin-1, indicating a decrease in autophagy in vitro. Furthermore, Western blotting showed that Hcy significantly increased the levels of p-mTOR and nuclear TFEB and decreased the levels of p-AMPK and cytoplasmic TFEB. These data suggest that Hcy inhibits autophagosome formation in human THP-1 macrophages through the AMPK-mTOR-TFEB signaling pathway. Our findings provide new insights into the mechanisms of atherosclerotic diseases caused by Hcy.

Facile high yield, excellent catalytic performance of polyoxometalate-based lanthanide phosphine oxide complexes: Syntheses, structures, photocatalysis and THz spectra.

Water pollution, which continuously threatens human health and the sustainable development of society, has become a major concern. Photocatalytic degradation is an effective strategy to remove organic dyes from wastewater. For this strategy, it is crucial to select the appropriate catalyst. Using triphenylphosphine oxide (OPPh3) as the ligand, phosphomolybdic acid as the anion template, three new lanthanide complexes [Ln(OPPh3)4(H2O)3](PMo12O40)∙4C2H5OH (1-3) (Ln = Sm, Gd, Tb) were synthesized. The raw materials for the reaction are cheap and readily available. The convenient synthesis method is environmentally friendly, with high yield (70%-80%). Complexes 1-3 are all seven-coordinated mononuclear structures centered on lanthanide ions, [PMo12O40]3- anions and solvent molecules are not coordinated with metal ions. These mononuclear structures eventually form complicated 3D supramolecular structures through hydrogen bonds, Mo-O … π or C-H … π weak interactions. Complexes 1-3 photocatalytic degradation of MB have high removal rates, as catalysts have enough stability to be reused, and can be used as excellent catalysts for the degradation of dye molecules in sewage. Among them, the removal rate of MB by photodegradation of complex 2 was highest (99.50%). In addition, the effects of different initial concentrations of MB solution and different types of organic dyes on the photocatalysis experiment were investigated. The photocatalytic reaction mechanism of complexes 1-3 was also studied. Due to the similar structures of complexes 1-3, they have almost the same THz absorption spectra with different absorption intensity, which may be attributed to the difference of the number of weak interactions. Therefore, terahertz spectroscopy can be used as a sensitive method to distinguish and determine small differences between lanthanide-organic complexes. This is the first time that this spectrum has been used to characterize lanthanide phosphine oxide complexes modified by [PMo12O40]3-.

Intermolecular interactions, photocatalysis and THz-TDS interrelationships for lanthanide phosphine oxide complexes based on {PW12}.

A series of rare earth complexes containing (α-PW12O40)3- and PO ligand are synthesized by water bath in 70 °C, [Ln(OPPh3)4(H2O)3](PW12O40)·4CH3CN (Ln = La, Pr, Nd, Sm, Gd, Tb, Ho 1-7) (OPPh3 = Triphenylphosphine oxide, {PW12} = phosphotungstic acid). The precise structures are confirmed by X-ray single crystal diffraction and the result shows all complexes are isostructural. Complexes 1-7 are fully characterized by PXRD, FT-IR, TGA, UV diffuse reflectance spectra and terahertz time-domain spectroscopy (THz-TDS). Complex 3 exhibits the highest photocatalytic degradation efficiency for methylene blue (MB) in this series of complexes. The experimental results showed that the photodegradation efficiency can remain constant at the level of 95% after five consecutive cycles. The photocatalytic reaction kinetics and mechanism of complexes were investigated. Additionally, complexes also exhibit photocatalytic hydrogen evolution activity. THz-TDS was used to characterize the complexes and its raw materials, the characteristic peaks of OPPh3 (broad peak at 1.20 THz) and phosphotungstic acid (sharp peaks at 0.23, 0.32 THz) were obtained.

Superficial chiral etching on an achiral metal-organic framework for high-performance liquid chromatography enantioseparations.

Chiral metal-organic frameworks have shown great potential in enantioselective separation and asymmetric catalysis due to their diverse and adjustable structures with abundant chiral recognition sites. Herein, a new chiral post-synthetic modification was used for preparing an achiral@chiral metal-organic frameworks core-shell composite [Cu3 (Btc)2 ]@[Cu2 ((+)-Cam)2 Dabco] by a superficial chiral etching method. The [Cu3 (Btc)2 ]@[Cu2 ((+)-Cam)2 Dabco] composite was utilized as a novel chiral stationary phase for HPLC enantioseparation. Various racemates were separated on the [Cu3 (Btc)2 ]@[Cu2 ((+)-Cam)2 Dabco]-packed column (column A). It exhibited good chiral resolving ability toward many different kinds of racemates, especially chiral drugs. Among them, the highest resolution value for 1,2-diphenyl-1,2-ethanediol reaches 2.70. The relative standard deviations of retention time and peak area for repeated separation of 1,2-diphenyl-1,2-ethanol were 0.45% and 0.81%, respectively. Compared with the resolution ability of [Cu2 ((+)-Cam)2 Dabco]-packed column (column B), column A shows higher column efficiency and better separation performance than those of column B. The results indicated that the [Cu3 (Btc)2 ]@[Cu2 ((+)-Cam)2 Dabco] as a stationary phase can greatly improve the column efficiency and chiral resolution ability of chiral metal-organic frameworks, which demonstrated that the superficial chiral etching as an economic and efficient strategy opens up a new way for the application of metal-organic frameworks.

A chiral porous organic polymer COP-1 used as stationary phase for HPLC enantioseparation under normal-phase and reversed-phase conditions.

A spherical chiral porous organic polymer (POPs) COP-1 is synthesized by the Friedel-Crafts alkylation reaction of Boc-3-(4-biphenyl)-L-alanine (BBLA) and 4,4'-bis(chloromethyl)-1,1'-biphenyl (BCMBP), which was used as a novel chiral stationary phase (CSPs) for mixed-mode high-performance liquid chromatography (HPLC) enantioseparation. The racemic compounds were resolved in normal-phase liquid chromatography (NPLC) using n-hexane/isopropanol as mobile phase and reversed-phase liquid chromatography (RPLC) using methanol/water as mobile phase. The COP-1-packed column exhibited excellent separation performance toward various racemic compounds including alcohols, amines, ketones, esters, epoxy compounds, organic acids, and amino acids in NPLC and RPLC modes. The effects of analyte mass and column temperature on the separation efficiency of racemic compounds were investigated. In addition, the chiral resolution ability of the COP-1-packed column not only can be complementary in RPLC/NPLC modes but also exhibit a good chiral recognition complementarity with Chiralpak AD-H column and chiral porous organic cage (POC) NC1-R column. The relative standard deviations (RSD) (n = 5) of the retention time, resolution value, and peak area by repeated separation of 1-(4-chiorophenyl)ethanol are all below 3.0%. The COP-1 column shows high column efficiency (e.g., 17,320 plates m-1 for 1-(4-chlorophenyl)ethanol on COP-1 column in NPLC), high enantioselectivity, and good reproducibility toward various racemates. This work demonstrates that chiral POPs microspheres are promising chiral materials for HPLC enantioseparation.

Meniscus repair with simultaneous anterior cruciate ligament reconstruction: Clinical outcomes, failure rates and subsequent processing.

PURPOSE: To retrospectively analyze the clinical outcomes of meniscus repair with simultaneous anterior cruciate ligament (ACL) reconstruction and explore the causes of failure of meniscus repair. METHODS: From May 2013 to July 2018, the clinical data of 165 patients who were treated with meniscus surgery and simultaneous ACL reconstruction, including 69 cases of meniscus repair (repair group) and 96 cases of partial meniscectomy (partial meniscectomy group) were retrospectively analyzed. The exclusion criteria were as follows: (1) ACL rupture associated with fracture, collateral ligament injury, or complex ligament injury; (2) a history of knee surgery; or (3) a significant degree of osteoarthritis. The 69 patients in the repair group were divided into the non-failure group (62 cases) and the failure group (7 cases) depending on the repair effect. Postoperative outcomes of the repair group and the partial meniscectomy group were compared. General conditions and postoperative outcomes of the failure group and the non-failure group were compared. During the median follow-up period of 28 months (range, 4 - 65 months) after the second arthroscopy, postoperative outcomes of seven patients in the failure group were summarized. SPSS 25.0 statistical software was used for statistical analysis. A p value less than 0.05 was considered statistically significant. RESULTS: Seven patients in the failure group who underwent the second arthroscopy were followed up for (30 ± 17.4) months and their postoperative outcomes were summarized. Compared with the partial meniscectomy group, the International Knee Documentation Committee scores of patients in the repair group improved significantly (p = 0.031). Compared with the non-failure group, more patients in the failure group were younger than 24 years (p = 0.030). The median follow-up period was 39.5 months. All patients recovered well after subsequent partial meniscectomy and relieved clinical symptoms. Visual analog scale scores decreased significantly (p = 0.026), and the International Knee Documentation Committee and Lysholm scores improved significantly (p = 0.046 for both). CONCLUSION: The failure rate of meniscus repair in this study was 10.1% (7/69), all of which were medial meniscus tears. However, the surgical outcomes of ACL reconstruction were not affected, and there might be a role for graft protection. Therefore, meniscus retears can be successful treated by performing subsequent partial meniscectomy in patients with repair failure.

PCAT6 may be a new prognostic biomarker in various cancers: a meta-analysis and bioinformatics analysis.

BACKGROUND: LncRNA prostate cancer-associated transcript 6 (PCAT6) has been reported to be dysregulated in several cancers and is associated with tumor progression. Here, we have performed a meta-analysis to assess the general prognostic role of PCAT6 in malignancies. METHODS: Four public databases (Embase, Pubmed, Web of Science, Cochrane Library) were used to identify eligible studies, then data was extracted and associations between prognostic indicators and clinical characteristics were combined to estimate hazard ratio (HR) or odds ratio (OR) with a 95% confidence interval (CI). Publication bias was measured using the Begg's test, and the stability of the combined results was measured using sensitivity analysis. Subsequently, results were validated using Gene Expression Profiling Interactive Analysis (GEPIA) and the National Genomics Data Center (NGDC). RESULTS: Ten studies were considered eligible for inclusion. In total, 937 patients and eight types of cancer were included. Our results revealed that overexpression of PCAT6 was significantly associated with a shorter OS (HR = 1.82; 95% CI, [1.40, 2.38]; P < 0.0001) and progression-free survival (PFS) (HR = 1.66; 95% CI, [1.22, 2.25]; P < 0.0001) in cancer patients, and that PCAT6 overexpression was significantly associated with individual tumor clinicopathological parameters, including TNM stage (OR = 0.29; 95% CI, [0.09, 0.94]; P = 0.04), gender (OR = 1.84; 95% CI, [1.31, 2.59]; P = 0.0005), and whether the tumor was metastatic (OR = 5.02; 95% CI, [1.36, 18.57]; P = 0.02). However, PCAT6 overexpression was not correlated with patient age and tumor differentiation. PCAT6 expression was significantly up-regulated in four types of cancer, which was validated using the GEPIA cohort. Combining OS and disease-free survival (DFS) of these four types of cancer revealed a shorter OS and DFS in patients with PCAT6 overexpression. PCAT6 expression in various types of cancer was also validated in NGDC. A total of eight cancers were analyzed and PCAT6 was highly expressed in all eight cancers. Further functional predictions suggest that PCAT6 is correlated with tumor prognosis, and that PCAT6 may be useful as a new tumor-specific marker. CONCLUSIONS: LncRNA PCAT6 is highly expressed in multiple cancer types and its upregulation was significantly associated with patient prognosis and poorer clinical features, thereby suggesting that PCAT6 may be a novel prognostic factor in multiple cancer types.

Design of a mediator-free, non-enzymatic electrochemical biosensor for glutamate detection.

A mediator-free, non-enzymatic electrochemical biosensor was constructed by covalent immobilization of a genetically engineered periplasmic glutamate binding protein onto gold nanoparticle-modified, screen-printed carbon electrodes (GluBP/AuNP/SPCE) for the purpose of direct measurement of glutamate levels. Glutamate serves as the predominant excitatory neurotransmitter in the central nervous system. As high levels of glutamate are an indicator of many neurologic disorders, there is a need for advancements in glutamate detection technologies. The biosensor was evaluated for glutamate detection by cyclic voltammetry. Binding of glutamate to the immobilized glutamate binding protein results in a conformational change of the latter that alters the microenvironment on the surface of the sensor, which is manifested as a change in signal. Dose-response plots correlating the electrochemical signal to glutamate concentration revealed a detection limit of 0.15 µM with a linear range of 0.1-0.8 µM. Selectivity studies confirmed a strong preferential response of the biosensor for glutamate against common interfering compounds.

The mammal-specific Pdx1 Area II enhancer has multiple essential functions in early endocrine cell specification and postnatal ß-cell maturation.

The transcription factor Pdx1 is required for multiple aspects of pancreatic organogenesis. It remains unclear to what extent Pdx1 expression and function depend upon trans-activation through 5' conserved cis-regulatory regions and, in particular, whether the mammal-specific Area II (-2139 to -1958 bp) affects minor or major aspects of organogenesis. We show that Area II is a primary effector of endocrine-selective transcription in epithelial multipotent cells, nascent endocrine progenitors, and differentiating and mature ß cells in vivo Pdx1ΔAREAII/- mice exhibit a massive reduction in endocrine progenitor cells and progeny hormone-producing cells, indicating that Area II activity is fundamental to mounting an effective endocrine lineage-specification program within the multipotent cell population. Creating an Area II-deleted state within already specified Neurog3-expressing endocrine progenitor cells increased the proportion of glucagon+ α relative to insulin+ ß cells, associated with the transcriptional and epigenetic derepression of the α-cell-determining Arx gene in endocrine progenitors. There were also glucagon and insulin co-expressing cells, and ß cells that were incapable of maturation. Creating the Pdx1ΔAREAII state after cells entered an insulin-expressing stage led to immature and dysfunctional islet ß cells carrying abnormal chromatin marking in vital ß-cell-associated genes. Therefore, trans-regulatory integration through Area II mediates a surprisingly extensive range of progenitor and ß-cell-specific Pdx1 functions.

Floralozone Ameliorated Atherosclerosis in Experimental Atherosclerotic Rats Involved with Sphingosine 1-Phosphate 1 Enhancement.

Atherosclerosis (AS) is a chronical pathological process of the arterial narrows due to the AS plaque formation. The aim of this study was to explore the therapeutic effect and the underlying mechanism of Floralozone on experimental atherosclerotic model rats. Experimental atherosclerotic model rats were induced by the right carotid artery balloon injury and intraperitoneal injection of vitamin D3 in rats after 4 weeks high-fat diet. The results exhibited that Floralozone could ameliorate vascular injury and vasorelaxation of descending aortas and increase the superoxide dismutase activity and the expression of sphingosine 1-phosphate (S1P) 1 and reduce the intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1, interleukin (IL)-1, IL-6 level, and the malondialdehyde activity in experimental atherosclerotic rats. However, Fingolimod, an S1P1 inhibitor, could reverse these Floralozone effects in experimental atherosclerotic rats. Our results indicated that Floralozone could inhibit the atherosclerotic plaque formation and improves arterial stenosis and reduces endothelial dysfunction in experimental atherosclerotic rats, which might be involved with S1P1 enhancement.

Context-specific α- to-ß-cell reprogramming by forced Pdx1 expression.

Using single transcription factors to reprogram cells could produce important insights into the epigenetic mechanisms that direct normal differentiation, or counter inappropriate plasticity, or even provide new ways of manipulating normal ontogeny in vitro to control lineage diversification and differentiation. We enforced Pdx1 expression from the Neurogenin-3-expressing endocrine commitment point onward and found during the embryonic period a minor increased ß-cell allocation with accompanying reduced α-cell numbers. More surprisingly, almost all remaining Pdx1-containing glucagon/Arx-producing cells underwent a fairly rapid conversion at postnatal stages, through glucagon-insulin double positivity, to a state indistinguishable from normal ß cells, resulting in complete α-cell absence. This α-to-ß conversion was not caused by activating Pdx1 in the later glucagon-expressing state. Our findings reveal that Pdx1 can work single-handedly as a potent context-dependent autonomous reprogramming agent, and suggest a postnatal differentiation evaluation stage involved in normal endocrine maturation.

Outcome of posterior wall blowout in anterior cruciate ligament (ACL) reconstruction via anteromedial portal approach: A retrospective research in 20 patients with 6 years follow-up.

PURPOSE: To evaluate the clinical outcome in patients who received anterior cruciate ligament (ACL) reconstruction via anteromedial portal with or without posterior wall blowout. METHODS: Twenty patients with ruptured ACL, who have received ACL reconstruction via anteromedial portal between Apr 2012 and Oct 2013 were enrolled. According to the conditions of posterior wall, the patients were divided into 2 groups: posterior wall blowout group (10 patients) and posterior wall intact group (10 patients). The median follow up time were 63 (range 19-75) months and 60.5 (range 25-64) months in the 2 groups respectively. The clinical outcome was evaluated by knee joint physical examination, magnetic resonance imaging (MRI), the International Knee Documentation Committee (IKDC) 2000 subjective score, Lysholm score, Tenger score, difference of thigh circumference, KT-2000 and Biodex isokinetic dynamometer system. RESULTS: No significant differences were found in terms of the IKDC score, Lysholm score, Tegner score, Lachman test positive rate or Pivot Shift test positive rate between the two groups. In KT-2000 and Biodex isokinetic dynamometer tests, the difference of muscle strength between affected knees and unaffected knees in posterior wall blowout group was not significant less than that of posterior wall intact group (p > 0.05). In addition, there is no statistical difference between the two groups in signal/noise quotient (SNQ) of the graft (p > 0.05) in post operative MRI. CONCLUSION: Blowout of posterior wall in ACL reconstruction via anteromedial portal does not affect the clinical outcome as long as reliable fixation is taken intraoperatively.

[Chemical constituents in chloroform fraction of Houttuynia cordata].

Nine compounds were isolated from chloroform fraction of Houttuynia cordata,and the isolates were identified as follows:( S)-5,6,6 a,7-tetrahydro-2,10-dimethoxy-4 H-dibenzo [DE,G] quinoline-1,9-diol( 1),( +)-isoboldine ß-N-oxide( 2),liriotulipiferine( 3),telitoxinone( 4),isoboldine( 5),(-)-clovane-2ß,9α-diol( 6),benzoic acid( 7),acantrifoside E( 8),and dibutyl phthalate( 9). Among them,compound 1 was new,and compounds 2-9 were reported from this species for the first time.

Origin of selenium-gold interaction in F2CSe⋯AuY (Y = CN, F, Cl, Br, OH, and CH3): Synergistic effects.

Selenium-gold interaction plays an important role in crystal materials, molecular self-assembly, and pharmacochemistry involving gold. In this paper, we unveiled the mechanism and nature of selenium-gold interaction by studying complexes F2CSe⋯AuY (Y = CN, F, Cl, Br, OH, and CH3). The results showed that the formation of selenium-gold interaction is mainly attributed to the charge transfer from the lone pair of Se atom to the Au-Y anti-bonding orbital. Energy decomposition analysis indicated that the polarization energy is nearly equivalent to or exceeds the electrostatic term in the selenium-gold interaction. Interestingly, the chalcogen-gold interaction becomes stronger with the increase of chalcogen atomic mass in F2CX⋯AuCN (X = O, S, Se, and Te). The cyclic ternary complexes are formed with the introduction of NH3 into F2CSe⋯AuY, in which selenium-gold interaction is weakened and selenium-nitrogen interaction is strengthened due to the synergistic effects.