Search

Microbial proton-pump rhodopsin (PPR)-based phototrophy, a light-harvesting mechanism different from chlorophyll-based photosystems, may contribute significantly to solar energy entry into the marine ecosystem. PPR transforms solar energy into cellular energy that is used for various metabolic processes in the cells or flagellar movement. Although rhodopsins or their encoding genes have been documented in a wide phylogenetic range of cultured dinoflagellates, information is limited about how widespread and how spatiotemporally dynamical dinoflagellate PPR (DiPPR) are in natural marine ecosystems. In this study, we investigated DiPPR in Long Island Sound (LIS), a temperate estuary of the Atlantic Ocean between Connecticut and Long Island, New York, USA. We isolated six novel full-length dinoflagellate proton-pump rhodopsin cDNAs, expanding the DiPPR database that is crucial to PPR research. Based on these new sequences and existing sequences of DiPPR, we designed primers and conducted quantitative PCR and sequencing to determine the abundance and diversity of DiPPR genes spatially and temporally throughout a year in the water samples collected from LIS. DiPPR genes were found year-round and throughout LIS but with higher abundances in the eutrophic Western Sound and in April and July. The gene diversity data suggest that there are at least five distinct rhodopsin-harboring groups of dinoflagellates throughout the year. The abundance of DiPPR genes, measured as copy number per mL of seawater, appeared not to be influenced by water temperature or nitrogen nutrient concentration but exhibited weak negative correlations with orthophosphate concentration and salinity and a positive correlation with the abundance of DiPPR-harboring dinoflagellates. This first quantitative profiling of PPR in natural plankton reveals the prevalence and dynamics of this plastid-independent photoenergy harvesting mechanism in a temperate estuary and provides efficient DiPPR primers potentially useful for future research. Furthermore, this study shed light on the potential role of DiPPR in phosphor nutrition and dinoflagellate population, which warrants further studies.

Typical (peridinin-containing) dinoflagellates possess plastid genomes composed of small plasmids named "minicircles". Despite the ecological importance of dinoflagellate photosynthesis in corals and marine ecosystems, the structural characteristics, replication dynamics, and evolutionary forcing of dinoflagellate plastid genomes remain poorly understood. Here, we sequenced the plastid genome of the symbiodiniacean species Fugacium kawagutii and conducted comparative analyses. We identified psbT-coding minicircles, features previously not found in Symbiodiniaceae. The copy number of F. kawagutii minicircles showed a strong diel dynamics, changing between 3.89 and 34.3 copies/cell and peaking in mid-light period. We found that F. kawagutii minicircles are the shortest among all dinoflagellates examined to date. Besides, the core regions of the minicircles are highly conserved within genus in Symbiodiniaceae. Furthermore, the codon usage bias of the plastid genomes in Heterocapsaceae, Amphidiniaceae, and Prorocentraceae species are greatly influenced by selection pressure, and in Pyrocystaceae, Symbiodiniaceae, Peridiniaceae, and Ceratiaceae species are influenced by both natural selection pressure and mutation pressure, indicating a family-level distinction in codon usage evolution in dinoflagellates. Phylogenetic analysis using 12 plastid-encoded proteins and five nucleus-encoded plastid proteins revealed accelerated evolution trend of both plastid- and nucleus-encoded plastid proteins in peridinin- and fucoxanthin-dinoflagellate plastids compared to plastid proteins of nondinoflagellate algae. These findings shed new light on the structure and evolution of plastid genomes in dinoflagellates, which will facilitate further studies on the evolutionary forcing and function of the diverse dinoflagellate plastids. The accelerated evolution documented here suggests plastid-encoded sequences are potentially useful for resolving closely related dinoflagellates., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Proton-pump rhodopsin (PPR) in marine microbes can convert solar energy to bioavailable chemical energy. Whereas bacterial PPR has been extensively studied, counterparts in microeukaryotes are less explored, and the relative importance of the two groups is poorly understood. Here, we sequenced whole-assemblage metatranscriptomes and investigated the diversity and expression dynamics of PPR in microbial eukaryotes and prokaryotes at a continental shelf and a slope site in the northern South China Sea. Data showed the whole PPRs transcript pool was dominated by Proteorhodopsins and Xanthorhodopsins, followed by Bacteriorhodopsin-like proteins, dominantly contributed by prokaryotes both in the number and expression levels of PPR unigenes, although at the continental slope station, microeukaryotes and prokaryotes contributed similarly in transcript abundance. Furthermore, eukaryotic PPRs are mainly contributed by dinoflagellates and showed significant correlation with nutrient concentrations. Green light-absorbing PPRs were mainly distributed in >3 μm organisms (including microeukaryotes and their associated bacteria), especially at surface layer at the shelf station, whereas blue light-absorbing PPRs dominated the <3 μm (mainly bacterial) communities at both study sites, especially at deeper layers at the slope station. Our study portrays a comparative PPR genotype and expression landscape for prokaryotes and eukaryotes in a subtropical marginal sea, suggesting PPR's role in niche differentiation and adaptation among marine microbes., (© 2023. ISME Publications B.V.)

Objective: To investigate the association of bedtime with the risk of early-onset diabetes mellitus (DM) and islet beta cell function., Methods: 138 participants with treat-naïve DM were included in this study. All participants underwent a 75g oral glucose tolerance test. Sleep habit was obtained through a standardized questionnaire. Bedtime was categorized as < 22:00, 22:00-24:00, and ≥ 24:00 in this study. Multivariate logistic regression and multiple linear regression were used to estimate the association between bedtime and risk of early-onset DM and islet beta cell function, respectively., Results: Patients with early-onset DM had a later bedtime than those with late-onset DM. Individuals with bedtime ≥ 24:00 had a higher prevalence of early-onset DM than those with bedtime at 22:00-24:00 and < 22:00 (51.2% vs 29.3% vs 14.3%, respectively, p = 0.028). The multivariate logistic regression showed that per hour later in bedtime was associated with a 52% increased risk of early-onset DM (p = 0.023). Patients with bedtime after 24:00 had a 146% increased risk of early-onset DM compared to those went to bed between 22:00 to 24:00 (OR = 2.46, 95% CI 1.05 to 5.77, p = 0.039). The multiple linear regression showed that bedtime was independently negatively correlated with late-phase insulin secretion (assessed by disposition index, DI 120 )., Conclusion: Later bedtime was associated with worse late-phase insulin secretion and may be a risk factor for early-onset DM. Proper bedtime to lower risk of early-onset DM deserves further investigation., Competing Interests: All the authors declare no conflict of interest., (© 2023 Ma et al.)

The development and demise of a harmful algal bloom (HAB) are generally regulated by multiple processes; identifying specific critical drivers for a specific bloom is important yet challenging. Here, we conducted a whole-assemblage molecular ecological study on a dinoflagellate bloom to address the hypothesis that energy and nutrient acquisition, defense against grazing and microbial attacks, and sexual reproduction are critical to the rise and demise of the bloom. Microscopic and molecular analyses identified the bloom-causing species as Karenia longicanalis and showed that the ciliate Strombidinopsis sp. was dominant in a nonbloom plankton community, whereas the diatom Chaetoceros sp. dominated the after-bloom community, along with remarkable shifts in the community structure for both eukaryotes and prokaryotes. Metatranscriptomic analysis indicated that heightened energy and nutrient acquisition in K. longicanalis significantly contributed to bloom development. In contrast, active grazing by the ciliate Strombidinopsis sp. and attacks by algicidal bacteria ( Rhodobacteracea , Cryomorphaceae , and Rhodobacteracea ) and viruses prevented (at nonbloom stage) or collapsed the bloom (in after-bloom stage). Additionally, nutrition competition by the Chaetoceros diatoms plausibly contributed to bloom demise. The findings suggest the importance of energy and nutrients in promoting this K. longicanalis bloom and the failure of antimicrobial defense and competition of diatoms as the major bloom suppressor and terminator. This study provides novel insights into bloom-regulating mechanisms and the first transcriptomic data set of K. longicanalis , which will be a valuable resource and essential foundation for further elucidation of bloom regulators of this and related species of Kareniaceae in the future. IMPORTANCE HABs have increasingly occurred and impacted human health, aquatic ecosystems, and coastal economies. Despite great efforts, the factors that drive the development and termination of a bloom are poorly understood, largely due to inadequate in situ data about the physiology and metabolism of the causal species and the community. Using an integrative molecular ecological approach, we determined that heightened energy and nutrient acquisition promoted the bloom, while resource allocation in defense and failure to defend against grazing and microbial attacks likely prevented or terminated the bloom. Our findings reveal the differential roles of multiple abiotic and biotic environmental factors in driving the formation or demise of a toxic dinoflagellate bloom, suggesting the importance of a balanced biodiverse ecosystem in preventing a dinoflagellate bloom. The study also demonstrates the power of whole-assemblage metatranscriptomics coupled to DNA barcoding in illuminating plankton ecological processes and the underlying species and functional diversities., Competing Interests: The authors declare no conflict of interest.

Objective: To assess the correlation between body components with insulin resistance (IR) and islet beta cell function in patients with newly diagnosed type 2 diabetes mellitus (T2DM) or pre-diabetes mellitus (pre-DM) and to explore whether this correlation differs in males and females., Methods: 111 newly diagnosed diabetic or pre-diabetic patients were recruited in this cross-sectional study. 75g oral glucose tolerance test was used to determine the diagnosis of DM or pre-DM. Homeostasis model assessment of insulin resistance (HOMA-IR) and glucose disposition index (DI 30 ) was calculated to assess IR and islet beta cell function, respectively. Whole-body and regional lean mass (LM) and fat mass (FM) were obtained by dual-energy X-ray absorptiometry (DEXA). Partial correlation and multiple linear regression analyses were used to determine the associations between body composition, IR, and islet beta cell function., Results: More body fat and appendicular fat was observed in female patients than in male, though with similar BMI. Legs fat % was negatively correlated with HOMA-IR, whereas legs lean % was positively associated with HOMA-IR in females (r = -0.673, p = 0.017; r =0.664, p = 0.018, respectively). The regression analysis showed that legs LM was positively correlated with HOMA-IR in females. However, in male patients, android FM was positively correlated with HOMA-IR (r = 0.462, p = 0.007), and trunk LM was negatively associated with DI 30 (r = -0.458, p = 0.007). Nevertheless, no significant correlation was observed between body composition and islet beta cell function in female patients., Conclusion: Android FM was positively correlated with IR only in male patients but not in females. Besides, relative legs fat and LM were independently associated with IR in female patients but not in males. Further studies are needed to explore the underlying mechanism., Competing Interests: All the authors declare no conflicts of interest in this work., (© 2023 Ma et al.)

Trypsin is best known as a digestive enzyme in animals, but remains unexplored in phytoplankton, the major primary producers in the ocean. Here we report the prevalence of trypsin genes in global ocean phytoplankton and significant influences of environmental nitrogen (N) and phosphorus (P) on their expression. Using CRISPR/Cas9 mediated-knockout and overexpression analyses, we further reveal that a trypsin in Phaeodactylum tricornutum (PtTryp2) functions to repress N acquisition, but its expression decreases under N-deficiency to promote N acquisition. On the contrary, PtTryp2 promotes phosphate uptake per se, and its expression increases under P-deficiency to further reinforce P acquisition. Furthermore, PtTryp2 knockout led to amplitude magnification of the nitrate and phosphate uptake 'seesaw', whereas PtTryp2 overexpression dampened it, linking PtTryp2 to stabilizing N:P stoichiometry. Our data demonstrate that PtTryp2 is a coordinate regulator of N:P stoichiometric homeostasis. The study opens a window for deciphering how phytoplankton adapt to nutrient-variable marine environments., (© 2022. The Author(s).)

The different creep-aging forming processes of 2524 aluminum alloy were taken as the research object, and the effects of creep-aging temperature and creep stress on the fatigue-crack propagation properties of the alloy were studied. The research results showed the following under the same sintering time of 9 h, at creep-aging temperatures of 100 °C, 130 °C, 160 °C, and 180 °C, respectively, with an increase in creep-aging temperature: the fatigue-crack propagation rate was promoted, the spacing of fatigue striations increased, and the sizes of dimples decreased while the number was enlarged; this proves that the fatigue property of the alloy was weakened. Compared with the specimens with creep deformation radii of 1000 mm and 1500 mm, the creep deformation stress was the smallest when the forming radius was 1800 mm, with a higher threshold value of fatigue-crack growth in the near-threshold region of fatigue-crack propagation (Δ K ≤ 8 MPa·m 1/2 ). Under the same fatigue cycle, the specimens under the action of larger creep stress endured a longer fatigue stable-propagation time and a faster fracture speed. Comparing the effect of creep-aging temperature and creep stress, the creep-aging temperature plays a dominant role in the fatigue-crack propagation of creep-aged 2524 aluminum alloy.

Objective: To analyze the clinical characteristics of patients with pancreatic cancer (PC) and diabetes and to explore the impact of diabetes duration, weight loss, and hypoglycemic drugs on the tumor biological behavior of PC., Methods: This is a retrospective study on patients with PC and diabetes. Subjects were grouped according to the onset age of PC, distant metastasis, duration of diabetes, degree of weight loss (∆Wt), and type of hypoglycemic drugs. Logistic regression analysis was used to evaluate the association between diabetes duration, weight loss, hypoglycemic drugs, and early-onset PC, distant metastasis., Results: Compared with late-onset PC, patients with early-onset PC had a higher proportion of new-onset DM (35 [79.5%] vs. 217 [46.9%], p < 0.001), smoker, drinker, and more obvious weight loss (8.5 [3.8, 15] kg vs. 5 [0, 10] kg, p < 0.001). Patients with remote metastasis had an earlier diagnosis age, heavier weight loss, lower body mass index, and were more likely to be smokers but had cancer less likely to be localized in the head of pancreas. Regression analysis showed that new-onset diabetes and weight loss were independently correlated to early-onset PC: odds ratio (OR) = 3.38 (95% CI 1.36-8.4, p = 0.09; OR = 1.56 (95% CI 1.16-2.1), p = 0.003, respectively. In contrast, long-term diabetes, and heavy weight loss were independently associated with remote metastasis: OR = 3.38 (95% CI 1.36-8.4, p = 0.09; OR = 1.56 (95% CI 1.16-2.1), p = 0.003, respectively., Conclusion: New-onset diabetes and weight loss were common presentation and risk factors of early-onset PC, which required more attention. Long-term diabetes and heavy weight loss were risk factors contributing to distant metastases, indicating potential risk factors contributing to the adverse prognosis of patients with PC., (© 2022 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai JiaoTong University School of Medicine and John Wiley & Sons Australia, Ltd.)

This publisher's note contains corrections to Opt. Lett.46, 2738 (2021)OPLEDP0146-959210.1364/OL.423745.

We present the designs, theory, and experimental demonstrations of ultra-broadband, optical add-drop filters on the silicon-on-insulator platform, realized using period-chirped contra-directional couplers. Our fabricated devices have ultra-broad 3 dB bandwidths of up to 11 THz (88.1 nm), with flat-top responses at their drop ports. All of our devices were fabricated using a commercial, CMOS-compatible, 193 nm deep-ultraviolet lithography process. By using lithography-prediction models, the measured bandwidths, insertion losses, central wavelengths, and extinction ratios of our devices are all in good agreement with our predicted, simulated results. Such filters are necessary for photonic integrated circuits to operate over multiple optical bands.

Hydrocephalus may cause Parinaud's syndrome which consists of vertical gaze palsy, convergence palsy, lid retraction and pupil light-near dissociation. We are aware of only two prior reports of hydrocephalus presenting with bilateral ptosis. Both were cured by ventriculoperitoneal shunts. We report a 28-month-old girl who presented acute bilateral ptosis but full eye movements both sides. Neuroimages revealed chronic hydrocephalus and aqueductal stenosis. The bilateral ptosis resolved quickly after endoscopic third ventriculostomy (ETV).

To explore mechanisms underlying the discrepancy in anti-tumor effects of metformin on pancreatic cancer cells PANC-1 under different glucose conditions. We cultured PANC-1 cells in 25 mM and 5 mM glucose media, then treated with or without metformin. It showed that metformin significantly inhibited proliferation and viability, induced apoptosis of PANC-1 cells, which was more pronounced in low-glucose than in high-glucose group. Metformin up-regulated the expression of miR-210-5p in low glucose, but not in high glucose. miR-210-5p mimic inhibited the viability of PANC-1 cells and further enhanced the inhibitory effect of metformin. miR-210-5p down-regulated the expression of PFKFB2, a predicted target gene of miR-210-5p, reduced the activity of PFK1 and LDH. Metformin significantly inhibited the expression of phosphorylation-PFKFB2(p-PFKFB2) in the low-glucose group and inhibited the LDH activity both in the low and high glucose groups, thus inhibiting anaerobic glycolysis and inducing energy stress. Cells in the high glucose group could make a compensatory adaptation to the energy stress induced by metformin through increasing glucose consumption. However, due to the limited glucose supply and high dependence on anaerobic glycolysis of cells in the low glucose group, they couldn't make effective adaptive compensation. Therefore, cells in the low-glucose group were more vulnerable to the toxicity of metformin. In conclusion, the enhanced inhibitory effect of metformin on PANC-1 cells cultured in low glucose may be due to the up-regulation of the expression of miR-210-5p, then inhibiting anaerobic glycolytic flux and inducing energy stress via repressing the expression of p-PFKFB2 and activity of LDH., Abbreviations: PC: pancreatic cancer; DM: diabetes mellitus; PFKFB2: 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase2; PFK1: phosphofructokinases; LDH: lactate dehydrogenase; F-2,6-BP: fructose 2,6-bisphosphate.

Background: Previous studies on the effects of lipotoxicity and oxidative stress on islet beta cell function mainly focused on patients with diabetes, whereas studies on normal glucose tolerance (NGT) are few. The aim of this study was to explore the relationships among triglyceride (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), oxidative stress indicators, insulin resistance, and beta cell function in populations with different glucose and lipid metabolism states., Methods: A total of 517 individuals were recruited from a rural community in Beijing, China. Glucose metabolism status was defined according to the results of a 75-g oral glucose tolerance test (OGTT). Dyslipidemia was defined as abnormal TG, HDL-c, or LDL-c levels. The population was divided into four groups: individuals with normal glucose and lipid levels (group A, n = 62); those with dyslipidemia alone (group B, n = 82); those with dysglycemia alone (group C, n = 121); and those with dysglycemia and dyslipidemia (group D, n = 247). Oxidative stress indicators, including superoxide dismutase (SOD), glutathione reductase (GR) and 8-hydroxydeoxyguanosine (8-OHdG), were measured. Homeostasis model assessment of insulin resistance (HOMA-IR) and glucose disposition index (DI 30 , DI 120 ) were calculated to assess insulin resistance and islet beta cell function, respectively. Stratified multiple linear regression analysis was used to explore relationships between TG, HDL-c, LDL-c, oxidative stress indicators, and insulin resistance (natural log transformation of HOMA-IR, LnHOMA-IR) and beta cell function (natural log transformation of DI 30 , Ln DI 30 )., Results: Compared with the control group, populations with dyslipidemia and/or dysglycemia showed significantly increased insulin resistance. Dyslipidemia aggravated insulin resistance and beta cell dysfunction in individuals with dysglycemia. Stratified regression analysis showed that TG positively correlated with LnHOMA-IR in individuals with normal glucose levels (beta = 0.321, 0.327, P = 0.011, 0.003 in groups A and B, respectively) and negatively correlated with LnDI 30 in participants with dyslipidemia (beta = - 0.225, - 0.122, P = 0.035, 0.048 in groups B and D, respectively). Reduced serum SOD levels in individuals with dysglycemia plus dyslipidemia were observed, and a negative association between TG and SOD levels was found (r = - 0.461, P < 0.001)., Conclusion: TG correlated with both insulin resistance and beta cell function in individuals with dyslipidemia alone. SOD negatively correlated with TG, indicating a close relationship between oxidative stress and glucose-lipid metabolism. Due to the adverse effect of hypertriglyceridemia on insulin sensitivity and islet beta cell function, more attention should be paid to the detection and management of hypertriglyceridemia.

An erratum is presented to correct the caption of Fig. 1 and the citation number in Fig. 7(d) in the original article [Opt. Express 27, 17581 (2019)].

Objectives: In this study, we assessed the effects of dietary magnesium on leukocyte telomere length (LTL)., Designs: The current cross-sectional analysis was based on data collected within a type 2 diabetes project. Settings . Dietary magnesium intake is associated with peripheral blood leukocyte telomere length (LTL). However, few epidemiological studies have evaluated the effects of magnesium on LTL in the clinical setting. Participants . This cross-sectional analysis included 467 participants (34.8% men). Measurements . Serum blood lipid profile, HbA1c, oxidative stress, and proinflammatory mediator levels were measured. Detailed dietary data were obtained using a 24 h food recall. LTL was assessed using a real-time PCR assay. Regression models and simple regulatory models were used for data analysis., Results: There was an inverse relationship between dietary magnesium and LTL ( P < 0.001), with a between-extreme-quarter difference of -0.55. Conversely, there was a positive relationship between dietary magnesium and serum tumor necrosis factor (TNF) α , with an interquarter difference of 3.79 pmol/mL ( P  for trend = 0.006). Multivariate regression analysis revealed that the odds ratios (ORs) for shorter LTL and higher serum TNF α increased with magnesium intake, and the ORs of the differences between extreme quartiles were 2.60 (95% confidence interval (CI): 1.31-5.36; P = 0.003) and 1.98 (95% CI: 1.09-3.59; P = 0.008). There was a direct negative effect of dietary magnesium intake on LTL ( B = -0.002; P = 0.001), which appeared to be indirectly influenced by TNF α (-0.002 to -0.0005)., Conclusions: Dietary magnesium intake may be a critical component of the cellular aging process, and its effect could be partly mediated by TNF α ., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Jie Yu et al.)

We demonstrate greedy linear descent-based, basic gradient descent-based, two-point step size gradient descent-based, and two-stage optimization method-based automated control algorithms and examine their performance for use with a silicon photonic polarization receiver. With an active feedback loop control process, time-varying arbitrary polarization states from an optical fiber can be automatically adapted and stabilized to the transverse-electric (TE) mode of a single-mode silicon waveguide. Using the proposed control algorithms, we successfully realize automated adaptations for a 10 Gb/s on-off keying signal in the polarization receiver. Based on the large-signal measurement results, the control algorithms are examined and compared with regard to the iteration number and the output response. In addition, we implemented a long-duration experiment to track, adapt, and stabilize arbitrary input polarization states using the two-point step size gradient descent-based and two-stage optimization method-based control algorithms. The experimental results show that these control algorithms enable the polarization receiver to achieve real-time and continuous polarization management.

Background: Given that the dysregulation of iron homeostasis leads to genomic instability, iron has been linked to cellular aging. However, epidemiological research on dietary iron intake and cellular aging markers is scarce. The aim of this study was to explore the relationship between dietary iron intake and cellular aging markers and to investigate whether tumor necrosis factor- α (TNF α ) mediated this relationship., Methods: We conducted a cross-sectional analysis with a total of 467 subjects. Detailed dietary data were obtained using 24 h food recalls. Peripheral blood leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNAcn) were assessed using real-time PCR assay. The association between dietary iron intake and cellular aging markers and TNF α and superoxide dismutase (SOD) was analyzed by Pearson correlation analysis and regression models adjusted by covariates. Simple mediation models were generated to examine whether TNF α mediated the association between iron intake and cellular aging markers using PROCESS macro Version 3.3., Results: The study population contained more women than men, but their basic demographic and metabolic characteristics did not differ. After adjusting for age, LTL was the same for men and women, while mtDNAcn was lower in men. Multiple linear regression adjusted for confounding factors found that iron intake was negatively associated with LTL only in women and negatively associated with mtDNAcn only in men. Moreover, iron intake was positively associated with TNF α in both women and men but positively associated with SOD only in men. Path modeling showed that TNF α significantly mediated the indirect detrimental effect of iron intake on LTL only in women; in men, mediation of the indirect effect of iron intake on mtDNAcn by TNF α did not reach significance., Conclusions: The study found sex-specific negative associations between dietary iron intake and cellular aging markers in that iron intake had deleterious effects on LTL attrition in women and mtDNAcn in men; only the former was partly mediated by TNF α . Consequently, when dietary iron intake and iron supplementation is recommended, the effects of iron imbalance on genomic stability and cellular aging markers must be considered., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2019 Jie Yu et al.)

Objective: Previous studies have revealed dysregulated circulating microRNAs (miRNAs) in patients with type 1 diabetes (T1D). Here, we explored the serum levels of miR-21 , miR-25 , miR-146a , and miR-181a in patients with autoimmune diabetes (T1D and latent autoimmune diabetes of adults (LADA)) compared with type 2 diabetes (T2D) and nondiabetic individuals., Design Patients and Measurements: The serum levels of miR-21 , miR-25 , miR-146a , and miR-181a in patients with T1D ( n  = 29), LADA ( n  = 16), and T2D ( n  = 31) and in nondiabetic individuals ( n  = 19) were determined by quantitative real-time polymerase chain reaction, and receiver-operating characteristic (ROC) curves were evaluated to determine the discriminatory performances of these four miRNAs. Furthermore, target genes and pathways potentially modulated by these four miRNAs were predicted by bioinformatics analysis to investigate the possible functions of these miRNAs in autoimmune diabetes. Subsequently, multiple logistic regression analysis was performed to identify independent predictors for autoimmune diabetes, and a nomogram was established., Results: miR-21 , miR-25 , miR-146a , and miR-181a were significantly downregulated in the serum of patients with autoimmune diabetes compared with those in T2D patients and nondiabetic individuals ( p < 0.001). The areas under the ROC curves of these four miRNAs were greater than 0.80 ( p < 0.001). Bioinformatics analysis suggested that miR-21 , miR-25 , miR-146a , and miR-181a regulated multiple genes in pathways associated with immunity, inflammatory responses, hyperglycemia, and metabolism, which are involved in the pathogenesis of autoimmune diabetes. Multiple logistic regression analysis identified miR-25 (odds ratio (OR): 0.001, p < 0.05), miR-146a (OR: 0.136, p < 0.05), and fasting C-peptide levels (OR: 0.064, p < 0.05) as independent predictors of autoimmune diabetes., Conclusions: miR-25 and miR-146a may serve as potential circulating biomarkers and provide insights into the pathogenesis of autoimmune diabetes., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2019 Yiwen Liu et al.)

Sub-wavelength grating (SWG) metamaterials have been considered to provide promising solutions in the development of next-generation photonic integrated circuits. In recent years, increasied interest has been paid to silicon photonic planar biosensors based on SWG geometries for performance enhancement. In this work, we demonstrate a highly sensitive label-free phase-shifted Bragg grating (PSBG) sensing configuration, which consists of sub-wavelength block arrays in both propagation and transverse directions. By introducing salt serial dilutions and electrostatic polymers assays, bulk and surface sensitivities of the proposed sensor are characterized, obtaining measured results up to 579.2 nm/RIU and 1914 pm/nm, respectively. Moreover, the proposed multi-box PSBG sensor presents an improved quality factor as high as ∼ 8000 , roughly 3-fold of the microring-based counterpart, which further improves the detection limit. At last, by employing a biotin-streptavidin affinity assay, the capability for small molecule monitoring is exemplified with a minimum detectable concentration of biotin down to 2.28 × 10 - 8 M ., Competing Interests: The authors declare that there are no conflicts of interest related to this article., (© 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.)

We propose and demonstrate broadband, entirely mode-evolution-based, polarization splitter-rotators (PSR) using sub-wavelength grating (SWG) assisted adiabatic waveguides for two SOI platforms. Our PSRs are more compact than previously demonstrated entirely mode-evolution-based designs. The devices were fabricated using two fabrication processes and, in both cases, the measured spectra show close matches to the simulation results. One of the processes uses standard optical lithography and, hence, this is the first time that an SWG-based PSR has been experimentally implemented using such a process. Finally, measurements for arbitrary input polarizations on an active, automated polarization receiver, that uses one of our PSRs, are also presented.

A ring resonator based 4 channel wavelength division multiplexing (WDM) receiver with polarization diversity is demonstrated at 10 Gb/s per channel. By forming a waveguide loop between the two output ports of a polarization splitter-rotator (PSR), the input signals in the quasi-transverse-electric (quasi-TE) and the quasi-transverse-magnetic (quasi-TM) polarizations can be demultiplexed by the same set of ring resonator filters, thus reducing the number of required channel control circuits by half compared to methods which process the two polarizations individually. Large signal measurement results indicate that the design can tolerate a signal delay of up to 30% of the unit interval (UI) between the two polarizations, which implies that compensating for manufacturing variability with optical delay lines on chip is not necessary for a robust operation. The inter-channel crosstalk is found negligible down to 0.4nm (50 GHz) spacing, at which point the adjacent channel isolation is 17 dB, proving the design's compatibility for dense WDM application.

In this work, we present optical add/drop multiplexer (OADM) filters for coarse wavelength-division-multiplexing (CWDM) systems with high sidelobe suppressions that result in high adjacent channel isolations (A i ). The filters are realized by using a compact, series-cascaded configuration of apodized, contradirectional-coupling-based filters. We experimentally demonstrate a device with a measured A i of 53 dB (these devices hold the promise of achieving even higher A i s). While having large A i s, our devices have the wide bandwidths and low insertion losses required for CWDM applications. In addition, our demonstrated OADM has a nearly constant group delay, which results in low dispersion in the passband.

Object: Methylmalonic acidemia (MMA) with early-onset severe hydrocephalus is rare. In this paper, we described two cases of MMA with hydrocephalus and review the literature to elucidate the clinical features of the disease, treatment options, and follow-up results., Methods: The PubMed and Embase databases were searched for clinical reports on MMA with severe hydrocephalus, and two unreported cases were presented to illustrate the clinical spectrum., Results: Six cases of MMA with severe hydrocephalus were observed in the previous literature. Our two patients with severe hydrocephalus but not bulging fontanelle received a ventriculo-peritoneal shunt, and intracranial hypertension was confirmed in both cases during the operation. These patients' clinical symptoms significantly improved after the operation., Conclusions: Intracranial hypertension can exist in early-onset severe hydrocephalus in MMA, even if the bulging anterior fontanelle is not apparent. These patients could benefit from a ventriculo-peritoneal shunt.

Dinoflagellates undergo a typical eukaryotic cell cycle consisting of G1, S, G2, and M phases and some of the typical cell cycle related genes have been computationally identified. However, very few of these genes have been experimentally linked to the cell cycle phases. Besides, although thecate dinoflagellates are known to possess theca composed of cellulose, information on cellulose synthesis and degradation associated with the cell cycle is also limited. In this study, we isolated G1/S cyclin, cellulose synthase and cellulase encoding genes in dinoflagellate Prorocentrum donghaiense . Further, using reverse transcription quantitative PCR (RT-qPCR), we characterized the expression profiles of the three genes throughout the cell cycle. All three showed clear expression dynamics throughout the cell cycle, with fold changes of 26, 2.4 and 9.3 for G1/S cyclin, cellulose synthase and cellulase gene, respectively. The transcript abundance of G1/S cyclin increased in late G1 phase and dropped in early S phase, indicating that this protein is involved in the G1/S transition. Throughout the cell cycle, the average transcript level of cellulose synthase was 4.5-fold higher than that of cellulase. Cellulose synthase and cellulase gene expressions showed peak transcript abundances at middle G1 phase and G2M phase, respectively, indicating the respective roles of these enzymes in the growth of newly divided cells and in cytokinesis. Our results suggest that G1/S cyclin, cellulase, and cellulose synthase genes associated with G1/S transition, G2M, and G1 phases of the cell cycle and are candidates of biomarkers for assessing growth status of P. donghaiense .