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The transition from spermatogonia to spermatocytes and the initiation of meiosis are key steps in spermatogenesis and are precisely regulated by a plethora of proteins. However, the underlying molecular mechanism remains largely unknown. Here, we report that Src homology domain tyrosine phosphatase 2 (Shp2; encoded by the protein tyrosine phosphatase, nonreceptor type 11 [Ptpn11] gene) is abundant in spermatogonia but markedly decreases in meiotic spermatocytes. Conditional knockout of Shp2 in spermatogonia in mice using stimulated by retinoic acid gene 8 (Stra8)-cre enhanced spermatogonial differentiation and disturbed the meiotic process. Depletion of Shp2 in spermatogonia caused many meiotic spermatocytes to die; moreover, the surviving spermatocytes reached the leptotene stage early at postnatal day 9 (PN9) and the pachytene stage at PN11-13. In preleptotene spermatocytes, Shp2 deletion disrupted the expression of meiotic genes, such as disrupted meiotic cDNA 1 (Dmc1), DNA repair recombinase rad51 (Rad51), and structural maintenance of chromosome 3 (Smc3), and these deficiencies interrupted spermatocyte meiosis. In GC-1 cells cultured in vitro, Shp2 knockdown suppressed the retinoic acid (RA)-induced phosphorylation of extracellular-regulated protein kinase (Erk) and protein kinase B (Akt/PKB) and the expression of target genes such as synaptonemal complex protein 3 (Sycp3) and Dmc1. Together, these data suggest that Shp2 plays a crucial role in spermatogenesis by governing the transition from spermatogonia to spermatocytes and by mediating meiotic progression through regulating gene transcription, thus providing a potential treatment target for male infertility.

The transition from spermatogonia to spermatocytes and the initiation of meiosis are key steps in spermatogenesis and are precisely regulated by a plethora of proteins. However, the underlying molecular mechanism remains largely unknown. Here, we report that Src homology domain tyrosine phosphatase 2 (Shp2; encoded by the protein tyrosine phosphatase, nonreceptor type 11 [Ptpn11] gene) is abundant in spermatogonia but markedly decreases in meiotic spermatocytes. Conditional knockout of Shp2 in spermatogonia in mice using stimulated by retinoic acid gene 8 (Stra8)-cre enhanced spermatogonial differentiation and disturbed the meiotic process. Depletion of Shp2 in spermatogonia caused many meiotic spermatocytes to die; moreover, the surviving spermatocytes reached the leptotene stage early at postnatal day 9 (PN9) and the pachytene stage at PN11–13. In preleptotene spermatocytes, Shp2 deletion disrupted the expression of meiotic genes, such as disrupted meiotic cDNA 1 (Dmc1), DNA repair recombinase rad51 (Rad51), and structural maintenance of chromosome 3 (Smc3), and these deficiencies interrupted spermatocyte meiosis. In GC-1 cells cultured in vitro, Shp2 knockdown suppressed the retinoic acid (RA)-induced phosphorylation of extracellular-regulated protein kinase (Erk) and protein kinase B (Akt/PKB) and the expression of target genes such as synaptonemal complex protein 3 (Sycp3) and Dmc1. Together, these data suggest that Shp2 plays a crucial role in spermatogenesis by governing the transition from spermatogonia to spermatocytes and by mediating meiotic progression through regulating gene transcription, thus providing a potential treatment target for male infertility.

Porous materials such as cellular cytosol, hydrogels, and block copolymers have nanoscale features that determine macroscale properties. Characterizing the structure of nanopores is difficult with current techniques due to imaging, sample preparation, and computational challenges. We produce a super-resolution optical image that simultaneously characterizes the nanometer dimensions of and diffusion dynamics within porous structures by correlating stochastic fluctuations from diffusing fluorescent probes in the pores of the sample, dubbed here as "fluorescence correlation spectroscopy super-resolution optical fluctuation imaging" or "fcsSOFI". Simulations demonstrate that structural features and diffusion properties can be accurately obtained at sub-diffraction-limited resolution. We apply our technique to image agarose hydrogels and aqueous lyotropic liquid crystal gels. The heterogeneous pore resolution is improved by up to a factor of 2, and diffusion coefficients are accurately obtained through our method compared to diffraction-limited fluorescence imaging and single-particle tracking. Moreover, fcsSOFI allows for rapid and high-throughput characterization of porous materials. fcsSOFI could be applied to soft porous environments such hydrogels, polymers, and membranes in addition to hard materials such as zeolites and mesoporous silica.

The human endometrium plays a vital role in providing the site for embryo implantation and maintaining the normal development and survival of the embryo. Recent studies have shown that stress is a common factor for the development of unexplained reproductive disorders. The nonreceptive endometrium and disturbed early maternal-fetal interaction might lead to infertility including the repeated embryo implantation failure and recurrent spontaneous abortion, or late pregnancy complications, thereby affecting the quality of life as well as the psychological status of the affected individuals. Additionally, psychological stress might also adversely affect female reproductive health. In recent years, several basic and clinical studies have tried to investigate the harm caused by psychological stress to reproductive health, however, the mechanism is still unclear. Here, we review the relationship between psychological stress and endometrial dysfunction, and its consequent effects on female infertility to provide new insights for clinical therapeutic interventions in the future.

Abstract. Proper development of the human placenta is of vital importance for a successful pregnancy, and a series of pregnancy complications are considered originating from dysfunctional placentas. Like other organ system development, placentation requires large numbers of co-regulators, while the underlying molecular mechanisms orchestrating the placental formation and function are poorly understood. Although we have made many signs of progress in understanding the placental architectures and developments using mouse models, the species-specific differences impede our progress due to the lack of appropriate model systems. In the past few years, major progress has been made by the establishment of novel in-vitro self-renewing stem cell models, as well as identifying the full picture of the cellular organization of the maternal and fetal interface. Providing the tools for the investigation of placentation and reproductive-related regulation mechanism. In this review, we focus on the detailed progress of the human trophoblast stem cells culturing system, and the cellular and molecular terrain at the maternal-fetal interface, respectively, thus providing new insights into placental development.

Objective: To evaluate the relation between the expression of PD‐1, PD‐L1, CD3, CD8, Foxp3 and clinicopathological features in patients with oral leukoplakia (OLK) and oral squamous cell carcinomas (OSCC) as well as the malignant outcome in OLK patients, and to study the effect of PD‐1 and PD‐L1 on immune microenvironment in the progression of oral carcinogenesis. Methods: We evaluated the expression of PD‐1/PD‐L1 and composition of CD3+, CD8+and Foxp3+ T lymphocytes in OLK and OSCC samples by immunohistochemical (IHC) staining and analyzed their relation with clinical information and malignant transformation in OLK patients. Results: IHC staining demonstrated that the expression of PD‐1 was significantly increased in the high‐grade OLK group than in the low‐grade OLK group, while PD‐L1 was detected mainly in OSCC. The expression of CD3, CD8, and Foxp3 was found higher in the high‐grade OLK group than in the low‐grade OLK group, and the Foxp3+ cells were found more in the OSCC group than in the high‐grade OLK group. PD‐1 was significantly correlated with CD3 (p < 0.05, R = 0.52), CD8 (p < 0.05, R = 0.46), and Foxp3 (p < 0.05, R = 0.46), and the low PD‐1‐expression group showed a better malignant‐free survival than high PD‐1 expression group in the OLK (p < 0.05). Conclusion: The PD‐1/PD‐L1 may induce immune suppression in OLK and accelerate the progress of malignant transformation. [ABSTRACT FROM AUTHOR]

In clinical practice, early pregnancy loss has afflicted approximately 15%–25% women of reproductive age worldwide, which is partially attributed to defects associated with the endometrium. During pregnancy, the endometrial stromal cells experience remarkable tissue remodeling and transformation, termed as decidualization, to support embryonic development, placental formation, and the maintenance of normal pregnancy in both mice and human. During this process, a series of dynamic developmental events, including rapid stromal proliferation, increased stromal cell size, enhanced angiogenesis, taken place in a highly-ordered manner under the precise regulation of steroid hormones. Meanwhile, diverse molecules exhibit spatiotemporal-specific expression pattern, implying their unique roles in decidual development. To achieve a more comprehensive understanding of these biological events and explore the underlying causes of early pregnancy disorders, this review emphasizes on the detailed developmental progression of decidual transformation and patterning as well as related pregnancy complications at the early stage of pregnancy.

Objective To discuss the methods and strategies to identify the causes of dependents’ deaths, as well as provide the experiences that can be used for reference and scientific basis for the forensic identification of the potentially growing deaths of the same kind in the future. Methods The 13 cases concerning death of dependents accepted by Sun Yat-sen University Forensic Center were collected, and the basic information of the dependents were statistically described. The nutritional status, environmental condition and medical care condition were evaluated according to dietary energy, living space, environment and medical treatment condition. Results Among the 13 dependents, there were 11 males and 2 females, with the oldest 74 and the youngest 9 and dwelling time was from 0.4 to 5.6 years. Forensic pathological examination showed that 13 dependents had infectious diseases and 11 were severely dystrophic. There were no fatal mechanical injuries or poisoning in dependents. Molecular pathological screening of 4 cases revealed no pathogenic variants of sudden death susceptible genes. The poor status of the diet, nutrition, living environment and medical care of these dependents were discovered. The direct cause of death of all 13 dependents was identified to be disease. The lack of nutrition, poor living environment and lack of medical care were thought to play a dominant role in causing the deaths of 12 dependants. Conclusion The death identification should follow the judicial procedure. In identification of the causes of death and analysis of the proportion of the affecting factors resulting in death, all factors, including nutrition,environment, medical care, injury and diseases, need to be considered.

A considerable amount of surplus nitrogen (N), which primarily takes the form of nitrate, accumulates in the soil profile after harvesting crops from an intensive production system in the North China Plain. The residual soil nitrate (RSN) is a key factor that is included in the N recommendation algorithm. Quantifying the utilization and losses of RSN is a fundamental necessity for optimizing crop N management, improving N use efficiency, and reducing the impact derived from farmland N losses on the environment. In this study, a 15N-labeling method was introduced to study the fate of the RSN quantitatively during the winter wheat growing season by 15N tracer technique combined with a soil column study. A soil column with a 2 m height was vertically divided into 10 20-cm layers, and the RSN in each layer was individually labeled with a 15N tracer before the wheat was sown. The results indicated that approximately 17.68% of the crop N derived from RSN was located in the 0-2 m soil profile prior to wheat sowing. The wheat recovery proportions of RSN at various layers ranged from 0.21% to 33.46%. The percentages that still remained in the soil profile after the wheat harvest ranged from 47.08% to 75.44%, and 19.46-32.64% of the RSN was unaccounted for. Upward and downward movements in the RSN were observed, and the maximum upward and downward distances were 40 cm and 100 cm, respectively. In general, the 15N-labeling method contributes to a deeper understanding of the fates of the RSN. Considering the low crop recovery of the RSN from deep soil layers, water and N saving practices should be adopted during crop production.

This paper proposes a new measure for recommendation through integrating Triangle and Jaccard similarities. The Triangle similarity considers both the length and the angle of rating vectors between them, while the Jaccard similarity considers non co-rating users. We compare the new similarity measure with eight state-of-the-art ones on four popular datasets under the leave-one-out scenario. Results show that the new measure outperforms all the counterparts in terms of the mean absolute error and the root mean square error.

This study aimed to evaluate the effects of di-(2-ethylhexyl) phthalate (DEHP) on estrous cycle, sex hormone levels and ovary histological features. A total of 80 female SD rats were randomly divided into 8 groups (n=10 per group): short-course control group, short-course low-dose group, short-course medium-dose group, and short-course high-dose group, long-course control group, long-course low-dose group, long-course medium-dose group and longcourse high-dose group. Intragastrical DEHP was administrated at 1000 mg/kg/d (low dose), 2000 mg/kg/d (medium dose) and 3000 mg/kg/d (high dose) independently for 14 days (short course) or 28 days (long course). Rats in control groups were untreated. Vaginal smearing was used to detect the estrous cycle and rats were weighed at every Monday and Thursday to evaluate the growth status. At the end of study, rats were sacrificed and bilateral ovaries were obtained for histological examination. In addition, ELISA determined levels of serum progesterone, estradiol, testosterone, follicle stimulating hormone and luteinizing hormone. DEHP treatment limited body weight gain (P

The first genome-wide association study for coronary artery disease (CAD) in the Han Chinese population, we reported recently, had identified rs6903956 in gene ADTRP on chromosome 6p24.1 as a novel susceptibility locus for CAD. The risk allele of rs6903956 was associated with decreased mRNA expression of ADTRP. To further study the correlation of ADTRP expression and CAD, in this study we evaluated the associations of eight common variants in the expression-regulating regions of ADTRP with CAD in the Southern Han Chinese population. Rs169790 in 3'UTR, rs2076189 in 5'UTR, four SNPs (rs2076188, rs7753407, rs11966356 and rs1018383) in promoter, and two SNPs (rs3734273, rs80355771) in the last intron of ADTRP were genotyped in 1716 CAD patients and 1572 controls. The correlations between these loci and total or early-onset CAD were investigated. None of these loci was discovered to associate with total CAD (P > 0.05). However, with early-onset CAD, significant both allelic and genotypic associations of rs7753407, rs11966356 and rs1018383 were identified, after adjustment for risk factors of age, gender, hypertension, diabetes, lipid profiles and smoking (adjusted P < 0.05). A haplotype AGCG (constructed by rs2076188, rs7753407, rs11966356 and rs1018383) was identified to protect subjects from early-onset CAD (OR = 0.332, 95% CI = 0.105-0.879, adjusted P = 0.010). Real-time quantitative reverse transcription polymerase chain reaction assay showed that the risk alleles of the associated loci were significantly associated with decreased expression of ADTRP mRNA. Moreover, the average level of ADTRP mRNA expression in early-onset CAD cases was significantly lower than that in controls. Our results provide new evidence supporting the association of ADTRP with the pathogenesis of early-onset CAD.

In this article, a method of simultaneous sensorless rotor position and torque estimation is proposed for interior permanent magnet synchronous machines at standstill and low speed. The proposed method estimates the torque using high-frequency inductances identified from the current variations due to high-frequency square wave voltage injections in the estimated dq-axes, which are simultaneously used for sensorless rotor position estimation. The proposed method is not dependent on the fundamental model and has taken the cross-coupling effect into consideration, allowing for low cost and fast torque estimation at standstill and low speed. Both simulations and experiments are carried out to verify the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

In this article, we propose a novel switching-table-based direct torque control (ST-DTC) method to eliminate the current harmonics in dual-three-phase permanent-magnet synchronous machines due to the back electromotive force (back EMF) harmonics and voltage vector selection. By employing a novel space voltage vector selection strategy and the optimal action time for different groups of vectors, a novel ST-DTC method is developed. Furthermore, in order to implement standard pulsewidth modulation (PWM) switching sequence, a centralization PWM method for 36 voltage vectors is introduced. The proposed method can effectively reduce the phase current harmonics caused by both back EMF distortion and voltage vector selection, and still reserve the advantages of the conventional ST-DTC, such as fast torque response and simple structure. Its effectiveness is verified by simulations and experiments. [ABSTRACT FROM AUTHOR]

The human endometrium plays a vital role in providing the site for embryo implantation and maintaining the normal development and survival of the embryo. Recent studies have shown that stress is a common factor for the development of unexplained reproductive disorders. The nonreceptive endometrium and disturbed early maternal-fetal interaction might lead to infertility including the repeated embryo implantation failure and recurrent spontaneous abortion, or late pregnancy complications, thereby affecting the quality of life as well as the psychological status of the affected individuals. Additionally, psychological stress might also adversely affect female reproductive health. In recent years, several basic and clinical studies have tried to investigate the harm caused by psychological stress to reproductive health, however, the mechanism is still unclear. Here, we review the relationship between psychological stress and endometrial dysfunction, and its consequent effects on female infertility to provide new insights for clinical therapeutic interventions in the future. [ABSTRACT FROM AUTHOR]

Spoke array permanent magnet (PM) flux reversal machines (SAFRPMMs), which are suitable for low speed and high torque applications, are able to enhance torque density due to the flux focusing effect. In this paper, what influence both the number of PM per slot and the PM shape have on their electromagnetic performance are investigated. The results show that both the PM number and the PM shape have significant effects on the performance of SAFRPMMs, and proper selections are critical in designing high performance machines. When the PM number per slot is 2, the SAFRPMM exhibits the best electromagnetic performances, i.e., the highest torque, power, efficiency, and power factor. Meanwhile, by properly designing the PM shape, the torque can be further improved by around 11%. A prototype is made and tested to validate the analyses. [ABSTRACT FROM AUTHOR]

This article investigates the influence of two nonideal factors on zero-crossing-point-detection-based sensorless control of high-speed brushless dc (BLDC) motor, i.e., asymmetric machine parameters and the resistance tolerance of back electromotive force (EMF) measurement circuit. Influenced by the machine parameter asymmetry, the back EMF envelopes will shift horizontally from its ideal position. Furthermore, the acquisition accuracy of back EMF is limited by the resistance tolerance of measurement circuit. Inaccurate acquisition of back EMF will result in vertical deviation of the envelopes. These two nonideal factors decrease the commutation accuracy and deteriorate the control performance. In order to suppress the commutation errors, an adaptive threshold correction strategy, including horizontal and vertical corrections is proposed for eliminating the influence of these two nonideal factors, respectively. In addition, the proposed correction method does not depend on any parameters of the machine or the measurement circuit. Finally, the theoretical analysis and the proposed correction method are verified by experiment on a 54 000 r/min high-speed BLDC drive platform. [ABSTRACT FROM AUTHOR]

The majority of men with defects in spermatogenesis remain undiagnosed. Acephalic spermatozoa is one of the diseases causing primary infertility. However, the causes underlying over half of affected cases remain unclear. Here, we report by whole‐exome sequencing the identification of homozygous and compound heterozygous truncating mutations in PMFBP1 of two unrelated individuals with acephalic spermatozoa. PMFBP1 was highly and specifically expressed in human and mouse testis. Furthermore, immunofluorescence staining in sperm from a normal control showed that PMFBP1 localizes to the head‐flagella junction region, and the absence of PMFBP1 was confirmed in patients harboring PMFBP1 mutations. In addition, we generated Pmfbp1 knock‐out (KO) mice, which we found recapitulate the acephalic sperm phenotype. Label‐free quantitative proteomic analysis of testicular sperm from Pmfbp1 KO and control mice showed 124 and 35 proteins, respectively, increased or decreased in sperm from KO mice compared to that found in control mice. Gene ontology analysis indicates that the biological process of Golgi vesicle transport was the most highly enriched in differentially expressed proteins, indicating process defects related to Golgi complex function may disturb formation of the head‐neck junction. Collectively, our data indicate that PMFBP1 is necessary for sperm morphology in both humans and mice, and that biallelic truncating mutations in PMFBP1 cause acephalic spermatozoa. [ABSTRACT FROM AUTHOR]

Metabolic changes of Tan sheep meat maintained at 0°C for up to 8 d were identified based on gas chromatography time-of-flight mass spectrometry. Total viable counts (TVC), total volatile basic nitrogen (TVB-N) and pH were utilized as freshness indicators during meat storage. A relationship between meat freshness, metabolite accumulation and key metabolic pathways was postulated. Twenty-seven statistically significant metabolites were characterized. D-glyceric acid, phenylalanine, methionine, glucose-l-phosphate, D-(glycerol-phosphate), lysine, ribitol, asparagine and isomaltose were significantly (p < 0.01) correlated to the freshness indicators. A correlation coefficient with gluconic acid, citric acid and trans-4-hydroxy-L-proline and the freshness indicators ranged from 0.539 to 0.911. 1, 5-anhydroglucitol was significantly correlated with pH (p < 0.05) and TVC (p < 0.01). These metabolites were identified as potential spoilage biomarkers. Three major metabolic processes occurred during storage: metabolism of alanine, aspartate, and glutamate; an operational TCA cycle and metabolism of amino sugar and nucleotide sugar. [ABSTRACT FROM AUTHOR]

This paper proposes a new measure for recommendation through integrating Triangle and Jaccard similarities. The Triangle similarity considers both the length and the angle of rating vectors between them, while the Jaccard similarity considers non co-rating users. We compare the new similarity measure with eight state-of-the-art ones on four popular datasets under the leave-one-out scenario. Results show that the new measure outperforms all the counterparts in terms of the mean absolute error and the root mean square error. [ABSTRACT FROM AUTHOR]

Streptococcus mutans is a primary etiological agent of dental caries. Farnesol, as a potential antimicrobial agent, inhibits the development of S. mutans biofilm. In this study, we hypothesized that farnesol inhibits caries development in vitro and interferes with biofilm formation by regulating virulence-associated gene expression. The inhibitory effects of farnesol to S. mutans biofilms on enamel surfaces were investigated by determining micro-hardness and calcium measurements. Additionally, the morphological changes of S. mutans biofilms were compared using field emission scanning electron microscopy and confocal laser scanning microscopy, and the vitality and oxygen sensitivity of S. mutans biofilms were compared using MTT assays. To investigate the molecular mechanisms of farnesol's effects, expressions of possible target genes luxS, brpA, ffh, recA, nth, and smx were analyzed using reverse-transcription polymerase chain reaction (PCR) and quantitative PCR. Farnesol-treated groups exhibited significantly higher micro-hardness on the enamel surface and lower calcium concentration of the supernatants as compared to the-untreated control. Microscopy revealed that a thinner film with less extracellular matrix formed in the farnesol-treated groups. As compared to the-untreated control, farnesol inhibited biofilm formation by 26.4% with 500 μmol/L and by 37.1% with 1,000 μmol/L (P < 0.05). Last, decreased transcription levels of luxS, brpA, ffh, recA, nth, and smx genes were expressed in farnesol-treated biofilms. In vitro farnesol inhibits caries development and S. mutans biofilm formation. The regulation of luxS, brpA, ffh, recA, nth, and smx genes may contribute to the inhibitory effects of farnesol. [ABSTRACT FROM AUTHOR]

Background: Peutz-Jeghers syndrome (PJS) is a rare disorder characterized by multiple gastrointestinal hamartomatous polyps and mucocutaneous pigmentation. STK11 has been identified as a causative gene for this disease. Case presentation: Herein we report a Chinese Han kindred with PJS. Onset for the PJS signs in three of the patients was rarely as early as at birth. We identified a novel heterozygous mutation (c.440_441delGT, p.Arg147Leufs*15) in the gene STK11, causing a short frameshift followed by a deletion of 63% of the amino acids in the STK protein. This mutation co-segregated with the PJS phenotype, and was absent in two hundred of unrelated ethnicity-matched controls. The mutation led to expression decrease of unaffected STK11 protein in patients than in controls, as well in PJ polyps than in circulating leucocytes from the patients. Phosphorylation levels of the downstream kinase AMPKa altered according with the expression of STK11. These results indicated the possibility that haploinsufficiency and epigenetic reduction of STK11 contributed to the pathogenesis of the disease. Conclusion: This study identifies a novel mutation in the pathogenic gene STK11 leading to PJS. [ABSTRACT FROM AUTHOR]

A considerable amount of surplus nitrogen (N), which primarily takes the form of nitrate, accumulates in the soil profile after harvesting crops from an intensive production system in the North China Plain. The residual soil nitrate (RSN) is a key factor that is included in the N recommendation algorithm. Quantifying the utilization and losses of RSN is a fundamental necessity for optimizing crop N management, improving N use efficiency, and reducing the impact derived from farmland N losses on the environment. In this study, a 15N-labeling method was introduced to study the fate of the RSN quantitatively during the winter wheat growing season by 15N tracer technique combined with a soil column study. A soil column with a 2 m height was vertically divided into 10 20-cm layers, and the RSN in each layer was individually labeled with a 15N tracer before the wheat was sown. The results indicated that approximately 17.68% of the crop N derived from RSN was located in the 0–2 m soil profile prior to wheat sowing. The wheat recovery proportions of RSN at various layers ranged from 0.21% to 33.46%. The percentages that still remained in the soil profile after the wheat harvest ranged from 47.08% to 75.44%, and 19.46–32.64% of the RSN was unaccounted for. Upward and downward movements in the RSN were observed, and the maximum upward and downward distances were 40 cm and 100 cm, respectively. In general, the 15N-labeling method contributes to a deeper understanding of the fates of the RSN. Considering the low crop recovery of the RSN from deep soil layers, water and N saving practices should be adopted during crop production. [ABSTRACT FROM AUTHOR]

Aim: The role of hyperbaric oxygen therapy (HBOT) in the treatment of acute ischemic stroke is controversial. This study aims to investigate whether the peripheral insulin sensitivity of type 2 diabetes patients suffering from intracerebral hemorrhage can be increased after HBOT. Methods: Fifty-two type 2 diabetes participants were recruited after being diagnosed with intracerebral hemorrhage in our hospital. Insulin sensitivity was measured by the glucose infusion rate during a hyperinsulinemic euglycemic clamp (80 mU m-2 min-1) at baseline and 10 and 30 days after HBOT sessions. Serum insulin, fasting glucose, and hemoglobin A1C were measured in fasting serum at baseline and after HBOT sessions. In addition, early (~10 days after onset) and late (1 month after onset) outcomes (National Institutes of Health Stroke Scale, NIHSS scores) and efficacy (changes of NIHSS scores) of HBOT were evaluated. Results: In response to HBOT, the glucose infusion rate was increased by 37.8%±5.76% at 1 month after onset compared with baseline. Reduced serum insulin, fasting glucose, and hemoglobin A1C were observed after HBOT. Both early and late outcomes of the HBOT group were improved compared with baseline (P<0.001). In the control group, there was significant difference only in the late outcome (P<0.05). In the assessment of efficacy, there were statistically significant differences between the groups when comparing changes in NIHSS scores at 10 days and 1 month after onset (P<0.05). Conclusion: Peripheral insulin sensitivity was increased following HBOT in type 2 diabetes patients with intracerebral hemorrhage. The HBOT used in this study may be effective for diabetes patients with acute stroke and is a safe and harmless adjunctive treatment. [ABSTRACT FROM AUTHOR]

The first genome-wide association study for coronary artery disease (CAD) in the Han Chinese population, we reported recently, had identified rs6903956 in gene ADTRP on chromosome 6p24.1 as a novel susceptibility locus for CAD. The risk allele of rs6903956 was associated with decreased mRNA expression of ADTRP. To further study the correlation of ADTRP expression and CAD, in this study we evaluated the associations of eight common variants in the expression-regulating regions of ADTRP with CAD in the Southern Han Chinese population. Rs169790 in 3’UTR, rs2076189 in 5’UTR, four SNPs (rs2076188, rs7753407, rs11966356 and rs1018383) in promoter, and two SNPs (rs3734273, rs80355771) in the last intron of ADTRP were genotyped in 1716 CAD patients and 1572 controls. The correlations between these loci and total or early-onset CAD were investigated. None of these loci was discovered to associate with total CAD (P > 0.05). However, with early-onset CAD, significant both allelic and genotypic associations of rs7753407, rs11966356 and rs1018383 were identified, after adjustment for risk factors of age, gender, hypertension, diabetes, lipid profiles and smoking (adjusted P < 0.05). A haplotype AGCG (constructed by rs2076188, rs7753407, rs11966356 and rs1018383) was identified to protect subjects from early-onset CAD (OR = 0.332, 95% CI = 0.105–0.879, adjusted P = 0.010). Real-time quantitative reverse transcription polymerase chain reaction assay showed that the risk alleles of the associated loci were significantly associated with decreased expression of ADTRP mRNA. Moreover, the average level of ADTRP mRNA expression in early-onset CAD cases was significantly lower than that in controls. Our results provide new evidence supporting the association of ADTRP with the pathogenesis of early-onset CAD. [ABSTRACT FROM AUTHOR]

Thetunable nature of weak polyelectrolyte multilayers makes themideal candidates for drug loading and delivery, water filtration,and separations, yet the lateral transport of charged molecules inthese systems remains largely unexplored at the single molecule level.We report the direct measurement of the charge-dependent, pH-tunable,multimodal interaction of single charged molecules with a weak polyelectrolytemultilayer thin film, a 10 bilayer film of poly(acrylic acid) andpoly(allylamine hydrochloride) PAA/PAH. Using fluorescence microscopyand single-molecule tracking, two modes of interaction were detected:(1) adsorption, characterized by the molecule remaining immobilizedin a subresolution region and (2) diffusion trajectories characteristicof hopping (D∼ 10–9cm2/s). Radius of gyration evolution analysis and comparisonwith simulated trajectories confirmed the coexistence of the two transportmodes in the same single molecule trajectories. A mechanistic explanationfor the probe and condition mediated dynamics is proposed based ona combination of electrostatics and a reversible, pH-induced alterationof the nanoscopic structure of the film. Our results are in good agreementwith ensemble studies conducted on similar films, confirm a previously-unobservedhopping mechanism for charged molecules in polyelectrolyte multilayers,and demonstrate that single molecule spectroscopy can offer mechanisticinsight into the role of electrostatics and nanoscale tunability oftransport in weak polyelectrolyte multilayers. [ABSTRACT FROM AUTHOR]

Pien Tze Huang (PZH) is a well-known Chinese medicine that has been used as a therapeutic drug in the treatment of a number of diseases, such as hepatocellular carcinoma and colon cancer. However, few studies have analyzed the effects of PZH on ovarian cancer cell proliferation. In the present study, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphen-yltetrazolium bromide and Transwell assays, cell cycle and apoptosis rate analyses and western blotting were conducted to investigate the effects of PZH on the proliferation rate of ovarian cancer cells and its potential molecular pathway. The results showed that PZH inhibits the proliferation of the human ovarian cancer OVCAR-3 cell line by blocking the progression of the cell cycle from the G1 to S phase, however, PZH did not induce OVCAR-3 cell apoptosis. Increased PZH concentration may downregulate the expression of AKT, phos-phorylated (p)-AKT, mammalian target of rapamycin (mTOR) and p-mTOR proteins in the OVCAR-3 cell line. In addition, it was observed that PZH may suppress the protein expression of cyclin-dependent kinase (CDK)4 and CDK6. Overall, the results of the present study indicated that PZH may inhibit ovarian cancer cell proliferation by modulating the activity of the AKT-mTOR pathway. [ABSTRACT FROM AUTHOR]

Single particle tracking (SPT) techniques provide a microscopic approach to probe in vivo and in vitro structure and reactions. Automatic analysis of SPT data with high efficiency and accuracy spurs the development of SPT algorithms. In this perspective, we review a range of available techniques used in SPT analysis programs. In addition, we present an example SPT program step-by-step to provide a guide so that researchers can use, modify, and/or write a SPT program for their own purposes. [ABSTRACT FROM AUTHOR]

Two maximum likelihood estimation (MLE) methods weredevelopedfor optimizing the analysis of single-molecule trajectories that includephenomena such as experimental noise, photoblinking, photobleaching,and translation or rotation out of the collection plane. In particular,short, single-molecule trajectories with photoblinking were studied,and our method was compared to existing analytical techniques appliedto simulated data. The optimal method for various experimental caseswas established, and the optimized MLE method was applied to a realexperimental system: single-molecule diffusion of fluorescent molecularmachines known as nanocars. [ABSTRACT FROM AUTHOR]

An accurate 3-D nonlinear transient finite-element model of an eddy current brake (ECB) has been developed, with consideration of the skin effect, eddy current distribution, nonlinear magnetization-saturation and rotation. Based on the analysis of the eddy current path (ECP) and penetration depth, the influence of principal parameters related to the braking process is analyzed. After analysis and comparison with the common round pole, a novel pole with sector shape has been developed, which brings about a significant increase of braking torque. An eight-pole ECB device with a peak torque of 4220 N · m under an excitation current of 88 A has been designed and tested for use in high-speed trains. The test results agree well with simulations. [ABSTRACT FROM AUTHOR]

In order to identify the role of the port backup service elements in the development of the container port, the paper puts forward a system dynamics model between the container port and the port backup service. Firstly, the system dynamics causal relationship path between the container port and the port backup service was established, and the interaction effects of the units in the system were analyzed qualitatively. Then, the empirical analysis based on system dynamics was implemented. Results show that the system dynamics model of the container port and the port backup service is effective; the port backup service elements have positive effects on the development of the container port. [ABSTRACT FROM AUTHOR]

This article has been retracted: please see Elsevier Policy on Article Withdrawal ( https://www.elsevier.com/about/our-business/policies/article-withdrawal ). This article has been retracted at the request of Neuroscience Letters has learned that text throughout this paper duplicates, or nearly duplicates, text in an earlier paper by others (Rusyniak DE, Kirk MA, May JD, Kao LW, Brizendine EJ, Welch JL, Cordell WH, Alonso RJ; Hyperbaric Oxygen in Acute Ischemic Stroke Trial Pilot Study, Stroke . 2003 Feb;34(2):571-4). [ABSTRACT FROM AUTHOR]

Inflammation is closely related to oral squamous cell carcinoma (OSCC). However, its mechanism is still obscure. Toll-like receptor 2 (TLR2) plays an important role in oral chronic inflammatory diseases, but the role of TLR2 in OSCC is unclear. Here, we investigated the expression of TLR2 expression in OSCCs and examined the potential role of TLR2 in OSCC through its association with clinicopathological features and patient outcome. We used 4-nitroquinoline 1-oxide (4-NQO) to induce a tongue cancer model in TLR2-/- and wild type (WT) mice. Histological and clinical results both indicated that TLR2 played a protective role in oral tumorigenesis. The results of a cytometric bead array (CBA) indicated that TLR2 deficiency resulted in Th1 and Th2 cytokine abnormalities, especially Th2 abnormalities. Immunohistochemistry also showed that TLR2 deficiency increases the number of tongue-infiltrating M2 macrophages. Overall, our results demonstrated that TLR2 plays an important role in the prevention of oral tumorigenesis and affects the levels of Th2 cytokines and tongue-infiltrating M2 macrophages; therefore, it may be used to prevent the development of oral cancer., Competing Interests: None., (AJCR Copyright © 2019.)

Streptococcus mutans is a primary etiological agent of dental caries. Farnesol, as a potential antimicrobial agent, inhibits the development ofS. mutans biofilm. In this study, we hypothesized that farnesol inhibits caries development in vitro and interferes with biofilm formation by regulating virulence-associated gene expression. The inhibitory effects of farnesol to S. mutans biofilms on enamel surfaces were investigated by determining micro-hardness and calcium measurements. Additionally, the morphological changes ofS. mutans biofilms were compared using field emission scanning electron microscopy and confocal laser scanning microscopy, and the vitality and oxygen sensitivity ofS. mutans biofilms were compared using MTT assays. To investigate the molecular mechanisms of farnesol's effects, expressions of possible target genesluxS, brpA, ffh, recA, nth, and smx were analyzed using reverse-transcription polymerase chain reaction (PCR) and quantitative PCR. Farnesol-treated groups exhibited significantly higher micro-hardness on the enamel surface and lower calcium concentration of the supernatants as compared to the-untreated control. Microscopy revealed that a thinner film with less extracellular matrix formed in the farnesol-treated groups. As compared to the-untreated control, farnesol inhibited biofilm formation by 26.4% with 500 µmol/L and by 37.1% with 1,000 µmol/L (P<0.05). Last, decreased transcription levels of luxS, brpA, ffh, recA, nth, and smx genes were expressed in farnesol-treated biofilms. In vitrofarnesol inhibits caries development and S. mutans biofilm formation. The regulation of luxS, brpA, ffh, recA, nth, and smx genes may contribute to the inhibitory effects of farnesol.

After three decades of developments, single particle tracking (SPT) has become a powerful tool to interrogate dynamics in a range of materials including live cells and novel catalytic supports because of its ability to reveal dynamics in the structure-function relationships underlying the heterogeneous nature of such systems. In this review, we summarize the algorithms behind, and practical applications of, SPT. We first cover the theoretical background including particle identification, localization, and trajectory reconstruction. General instrumentation and recent developments to achieve two- and three-dimensional subdiffraction localization and SPT are discussed. We then highlight some applications of SPT to study various biological and synthetic materials systems. Finally, we provide our perspective regarding several directions for future advancements in the theory and application of SPT.

Background: Peutz-Jeghers syndrome (PJS) is a rare disorder characterized by multiple gastrointestinal hamartomatous polyps and mucocutaneous pigmentation. STK11 has been identified as a causative gene for this disease., Case Presentation: Herein we report a Chinese Han kindred with PJS. Onset for the PJS signs in three of the patients was rarely as early as at birth. We identified a novel heterozygous mutation (c.440&#95;441delGT, p.Arg147Leufs*15) in the gene STK11, causing a short frameshift followed by a deletion of 63% of the amino acids in the STK protein. This mutation co-segregated with the PJS phenotype, and was absent in two hundred of unrelated ethnicity-matched controls. The mutation led to expression decrease of unaffected STK11 protein in patients than in controls, as well in PJ polyps than in circulating leucocytes from the patients. Phosphorylation levels of the downstream kinase AMPKα altered according with the expression of STK11. These results indicated the possibility that haploinsufficiency and epigenetic reduction of STK11 contributed to the pathogenesis of the disease., Conclusion: This study identifies a novel mutation in the pathogenic gene STK11 leading to PJS.

Aim: The role of hyperbaric oxygen therapy (HBOT) in the treatment of acute ischemic stroke is controversial. This study aims to investigate whether the peripheral insulin sensitivity of type 2 diabetes patients suffering from intracerebral hemorrhage can be increased after HBOT., Methods: Fifty-two type 2 diabetes participants were recruited after being diagnosed with intracerebral hemorrhage in our hospital. Insulin sensitivity was measured by the glucose infusion rate during a hyperinsulinemic euglycemic clamp (80 mU m -2 min -1 ) at baseline and 10 and 30 days after HBOT sessions. Serum insulin, fasting glucose, and hemoglobin A1 C were measured in fasting serum at baseline and after HBOT sessions. In addition, early (∼10 days after onset) and late (1 month after onset) outcomes (National Institutes of Health Stroke Scale, NIHSS scores) and efficacy (changes of NIHSS scores) of HBOT were evaluated., Results: In response to HBOT, the glucose infusion rate was increased by 37.8%±5.76% at 1 month after onset compared with baseline. Reduced serum insulin, fasting glucose, and hemoglobin A1 C were observed after HBOT. Both early and late outcomes of the HBOT group were improved compared with baseline ( P <0.001). In the control group, there was significant difference only in the late outcome ( P <0.05). In the assessment of efficacy, there were statistically significant differences between the groups when comparing changes in NIHSS scores at 10 days and 1 month after onset ( P <0.05)., Conclusion: Peripheral insulin sensitivity was increased following HBOT in type 2 diabetes patients with intracerebral hemorrhage. The HBOT used in this study may be effective for diabetes patients with acute stroke and is a safe and harmless adjunctive treatment., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

A considerable amount of surplus nitrogen (N), which primarily takes the form of nitrate, accumulates in the soil profile after harvesting crops from an intensive production system in the North China Plain. The residual soil nitrate (RSN) is a key factor that is included in the N recommendation algorithm. Quantifying the utilization and losses of RSN is a fundamental necessity for optimizing crop N management, improving N use efficiency, and reducing the impact derived from farmland N losses on the environment. In this study, a 15N-labeling method was introduced to study the fate of the RSN quantitatively during the winter wheat growing season by 15N tracer technique combined with a soil column study. A soil column with a 2 m height was vertically divided into 10 20-cm layers, and the RSN in each layer was individually labeled with a 15N tracer before the wheat was sown. The results indicated that approximately 17.68% of the crop N derived from RSN was located in the 0-2 m soil profile prior to wheat sowing. The wheat recovery proportions of RSN at various layers ranged from 0.21% to 33.46%. The percentages that still remained in the soil profile after the wheat harvest ranged from 47.08% to 75.44%, and 19.46-32.64% of the RSN was unaccounted for. Upward and downward movements in the RSN were observed, and the maximum upward and downward distances were 40 cm and 100 cm, respectively. In general, the 15N-labeling method contributes to a deeper understanding of the fates of the RSN. Considering the low crop recovery of the RSN from deep soil layers, water and N saving practices should be adopted during crop production., Competing Interests: The authors have declared that no competing interests exist.

Interactions between fluorophores and plasmonic nanoparticles modify the fluorescence intensity, shape, and position of the observed emission pattern, thus inhibiting efforts to optically super-resolve plasmonic nanoparticles. Herein, we investigate the accuracy of localizing dye fluorescence as a function of the spectral and spatial separations between fluorophores (Alexa 647) and gold nanorods (NRs). The distance at which Alexa 647 interacts with NRs is varied by layer-by-layer polyelectrolyte deposition while the spectral separation is tuned by using NRs with varying localized surface plasmon resonance (LSPR) maxima. For resonantly coupled Alexa 647 and NRs, emission to the far field through the NR plasmon is highly prominent, resulting in underestimation of NR sizes. However, we demonstrate that it is possible to improve the accuracy of the emission localization when both the spectral and spatial separations between Alexa 647 and the LSPR are optimized.

Super-resolution microscopy typically achieves high spatial resolution, but the temporal resolution remains low. We report super temporal-resolved microscopy (STReM) to improve the temporal resolution of 2D super-resolution microscopy by a factor of 20 compared to that of the traditional camera-limited frame rate. This is achieved by rotating a phase mask in the Fourier plane during data acquisition and then recovering the temporal information by fitting the point spread function (PSF) orientations. The feasibility of this technique is verified with both simulated and experimental 2D adsorption/desorption and 2D emitter transport. When STReM is applied to measure protein adsorption at a glass surface, previously unseen dynamics are revealed.

Understanding and controlling protein adsorption on surfaces is critical to a range of biological and materials applications. Kinetic details that provide the equilibrium and nonequilibrium mechanisms are difficult to acquire. In this work, single-molecule fluorescence microscopy was used to study the adsorption of Alexa 555 labeled α-lactalbumin (α-LA) on two chemically identical but morphologically different polymer surfaces: flat and porous nylon-6,6 thin films. The adsorption kinetics of spatially resolved single molecule α-LA binding to nylon films were quantified by a monolayer adsorption model. The surface morphology of the porous nylon-6,6 films increased the number of adsorption sites but decreased the binding affinity compared to the flat films. Such single-molecule based kinetic studies may be extended to various protein-polymer interactions.