Predictive Modeling Using a Composite Index of Sleep and Cognition in the Alzheimer's Continuum: A Decade-Long Historical Cohort Study.

Background: Sleep disturbances frequently affect Alzheimer's disease (AD), with up to 65% patients reporting sleep-related issues that may manifest up to a decade before AD symptoms. Objective: To construct a nomogram that synthesizes sleep quality and cognitive performance for predicting cognitive impairment (CI) conversion outcomes. Methods: Using scores from three well-established sleep assessment tools, Pittsburg Sleep Quality Index, REM Sleep Behavior Disorder Screening Questionnaire, and Epworth Sleepiness Scale, we created the Sleep Composite Index (SCI), providing a comprehensive snapshot of an individual's sleep status. Initially, a CI conversion prediction model was formed via COX regression, fine-tuned by bidirectional elimination. Subsequently, an optimized prediction model through COX regression, depicted as a nomogram, offering predictions for CI development in 5, 8, and 12 years among cognitively unimpaired (CU) individuals. Results: After excluding CI patients at baseline, our study included 816 participants with complete baseline and follow-up data. The CU group had a mean age of 66.1±6.7 years, with 36.37% males, while the CI group had an average age of 70.3±9.0 years, with 39.20% males. The final model incorporated glial fibrillary acidic protein, Verbal Fluency Test and SCI, and an AUC of 0.8773 (0.792-0.963). Conclusions: In conclusion, the sleep-cognition nomogram we developed could successfully predict the risk of converting to CI in elderly participants and could potentially guide the design of interventions for rehabilitation and/or cognitive enhancement to improve the living quality for healthy older adults, detect at-risk individuals, and even slow down the progression of AD.

10 kW tandem pumping fiber amplifier with good beam quality based on tapered ytterbium-doped fiber.

In this paper, we established a high power tandem pumped fiber amplifier based on tapered ytterbium-doped fiber (TYDF). The TYDF is developed in-house with a core/inner cladding diameter of 30/250 µm at the small-core region and 48/400 µm at the large-core region. The key parameters of the amplifier in a co-pumped and counter-pumped configuration are experimentally investigated, such as slope efficiency, stimulated Raman scattering (SRS) threshold, and beam quality evolution. Up to 10.28 kW laser free of SRS or transverse mode instability is obtained from the counter-pumped amplifier, and the beam quality factor M2 is 2.29, which is significantly improved compared with the 48/400 µm uniform YDF. To the best of our knowledge, this is the highest average output power achieved so far based on the TYDF. This work could provide a solution for balancing the SRS suppression and high order modes control in high power tandem pumped YDF lasers.

Mitigation of TMI in an 8†kW tandem pumped fiber amplifier enabled by inter-mode gain competition mechanism through bending control.

In this work, the impact of fiber bending and mode content on transverse mode instability (TMI) is investigated. Based on a modified stimulated thermal Rayleigh scattering (STRS) model considering the gain competition between transverse modes, we theoretically detailed the TMI threshold under various mode content and bending conditions in few-mode fibers. Our theoretical calculations demonstrate that larger bending diameters increase the high order mode (HOM) components in the amplifier, which in turn reduces the frequency-shifted Stokes LP11o mode due to the inter-mode gain competition mechanism, thus improving the TMI threshold of few-mode amplifiers. The experimental results agree with the simulation. Finally, by optimizing the bending, an 8.38 kW output tandem pumped fiber amplifier is obtained with a beam quality M2 of 1.8. Both TMI and stimulated Raman scattering (SRS) are well suppressed at the maximum power. This work provides a comprehensive analysis of the TMI in few-mode amplifiers and offers a practical method to realize high-power high-brightness fiber lasers.

PeriodNet: Noise-Robust Fault Diagnosis Method Under Varying Speed Conditions.

Rolling bearings are critical components in modern mechanical systems and have been extensively equipped in various rotating machinery. However, their operating conditions are becoming increasingly complex due to diverse working requirements, dramatically increasing their failure risks. Worse still, the interference of strong background noises and the modulation of varying speed conditions make intelligent fault diagnosis very challenging for conventional methods with limited feature extraction capability. To this end, this study proposes a periodic convolutional neural network (PeriodNet), which is an intelligent end-to-end framework for bearing fault diagnosis. The proposed PeriodNet is constructed by inserting a periodic convolutional module (PeriodConv) before a backbone network. PeriodConv is developed based on the generalized short-time noise resist correlation (GeSTNRC) method, which can effectively capture features from noisy vibration signals collected under varying speed conditions. In PeriodConv, GeSTNRC is extended to the weighted version through deep learning (DL) techniques, whose parameters can be optimized during training. Two open-source datasets collected under constant and varying speed conditions are adopted to assess the proposed method. Case studies demonstrate that PeriodNet has excellent generalizability and is effective under varying speed conditions. Experiments adding noise interference further reveal that PeriodNet is highly robust in noisy environments.

Bidirectional tandem-pumped high-brightness 6†kW level narrow-linewidth confined-doped fiber amplifier exploiting the side-coupled technique.

In this work, a bidirectional tandem-pumped high-power narrow-linewidth confined-doped ytterbium fiber amplifier is demonstrated based on side-coupled combiners. Benefiting from the large-mode-area design of the confined-doped fiber, the nonlinear effects, including stimulated Raman (SRS) and stimulated Brillouin scattering (SBS), are effectively suppressed. While the transverse mode instability (TMI) effect is also mitigated through the combination of confined-doped fiber design and the bidirectional tandem pumping scheme. As a result, narrow-linewidth fiber laser with 5.96 kW output power is obtained, the slope efficiency and the 3-dB linewidth of which are ∼81.7% and 0.42 nm, respectively. The beam quality is well maintained during the power scaling process, being around M2 = 1.6 before the TMI occurs, and is well kept (M2 = 2.0 at 5.96 kW) even after the onset of TMI. No SRS or SBS is observed at the maximum output power, and the signal-to-noise ratio reaches as high as ∼61.4 dB. To the best of our knowledge, this is the record power ever reported in narrow-linewidth fiber lasers. This work could provide a good reference for realizing high-power high-brightness narrow-linewidth fiber lasers.

More than 6 kW near single-mode fiber amplifier based on a bidirectional tandem pumping scheme.

We demonstrate the first all-fiber monolithic bidirectional tandem pumping amplifier, to the best of our knowledge, based on a 30/250 µm conventional ytterbium-doped double-clad fiber. By optimizing the bidirectional pumping power distribution, an output power of 6.22 kW is obtained with near single-mode beam quality (M2=1.53), and no transverse mode instability is observed. This work could provide an excellent reference for high-power, higher-brightness fiber lasers.

Prospective biomarkers of Alzheimer's disease: A systematic review and meta-analysis.

OBJECTIVE: Alzheimer's disease (AD) involves a series of pathological changes and some biomarkers were reported to assist in monitoring and predicting disease progression before the emergence of clinical symptoms. We aimed to identify prospective biomarkers and quantify their effect on AD progression. METHODS: PubMed, EMBASE and Web of Science databases were searched for prospective cohort studies published up to October 2021. Eligible studies were included, and the available data were extracted. Meta-analyses were conducted based on random-effect models. Relative risk (RR) with 95% confidence interval (CI) was adopted as the final effect size. RESULTS: Totally 48,769 articles were identified, of which 84 studies with 20 prospective biomarkers were included in meta-analyses. In the present study, 15 biomarkers were associated with AD progression, comprising CSF Aß42 (RR=2.49, 95%CI=1.68-3.69), t-tau (RR=1.88, 95%CI=1.49-2.37), p-tau (RR=1.74, 95%CI=1.37-2.21), tau/Aß42 ratio (RR=5.11, 95%CI=2.01-13.00); peripheral blood Aß42/Aß40 (RR=1.26, 95%CI=1.05-1.51), t-tau (RR=1.33, 95%CI=1.08-1.64), NFL (RR=1.75, 95%CI=1.07-2.87); whole, left and right hippocampal volume (HV) (whole: RR=1.65, 95%CI=1.39-1.95; left: RR=2.60, 95%CI=1.02-6.64; right: RR=1.43, 95%CI=1.23-1.66), entorhinal cortex (EC) volume (RR=1.69, 95%CI=1.24-2.30), medial temporal lobe atrophy (MTA) (RR=1.52, 95%CI=1.33-1.74), 18 F-FDG PET (RR=2.24, 95%CI=1.29-3.89), 11 C-labeled Pittsburgh Compound B PET (11 C-PIB PET) (RR=3.91, 95%CI=1.06-14.41); APOE ε4 (RR=2.16, 1.83-2.55). A total of 70 articles were included in the qualitative review, in which 61 biomarkers were additionally associated with AD progression. CONCLUSION: CSF Aß42, t-tau, p-tau, tau/Aß42; peripheral blood t-tau, Aß42/Aß40, NFL; whole, left and right HV, EC volume, MTA, 18 F-FDG PET, 11 C-PIB PET; APOE ε4 may be promising prospective biomarkers for AD progression.

Comprehensive investigations on the tandem pumping scheme employing the pump fiber laser operating at an extremely short wavelength.

In this work, with the aim of improving the nonlinearity threshold in tandem-pumped fiber amplifiers for higher output power, theoretical and experimental work was carried out to enhance the pump absorption and thereby decrease the required length of ytterbium-doped fiber by employing shorter-wavelength fiber lasers as the pump sources. Systematical simulations were first carried out to optimize the cavity parameters of a short-wavelength fiber oscillator at 1007 nm, and subsequently, the performance of the 1007 nm fiber laser in tandem pumping was simulated and compared with that of the 1018 nm fiber laser pumped results. Considerable absorption increment and efficiency improvement could be realized in the 1007 nm fiber laser pumped fiber amplifier relative to the 1018 nm fiber laser pumped one. Furthermore, according to the simulation results, a fiber laser operating at 1007.7 nm with the output power of ∼170 W and a slope efficiency of ∼72.90% was experimentally demonstrated. By applying this fiber laser in tandem pumping a 1080 nm fiber amplifier with different gain fiber lengths, improved performance was acquired in comparison with the 1018.6 nm tandem pumping scheme, the experimental results of which were coherent with the simulation results. This work could provide an effective approach for improving the nonlinearity threshold of tandem-pumped fiber amplifiers and paving the way for higher output power.

High-power tandem-pumped fiber amplifier with beam quality maintenance enabled by the confined-doped fiber.

The high absorption confined-doped ytterbium fiber with 40/250 µm core/inner-cladding diameter is proposed and fabricated, where the relative doping ratio of 0.75 is selected according to the simulation analysis. By employing this fiber in a tandem-pumped fiber amplifier, an output power of 6.2 kW with an optical-to-optical efficiency of ∼82.22% is realized. Benefiting from the large-mode-area confined-doped fiber design, the beam quality of the output laser is well maintained during the power scaling process with the beam quality factor of ∼1.7 of the seed laser to ∼ 1.89 at the output power of 5.07 kW, and the signal-to-noise ratio of the output spectrum reaches ∼40 dB under the maximum output power. In the fiber amplifier based on the 40/250 µm fully-doped ytterbium fiber, the beam quality factor constantly degrades with the increasing output power, reaching 2.56 at 2.45 kW. Moreover, the transverse mode instability threshold of the confined-doped fiber amplifier is ∼4.74 kW, which is improved by ∼170% compared with its fully-doped fiber amplifier counterpart.

Variation of representative rainfall time series length for rainwater harvesting modelling in different climatic zones.

Rainwater harvesting systems (RHS) have been increasingly used to mitigate urban water scarcity and flooding problems. Rainfall data with various lengths have been used for RHS modelling. However, short-term rainfall data with inadequate lengths used for the modelling of RHS may lead to considerable errors. In this study, a method that can be used to identify representative length of short-term rainfall data for RHS modelling was proposed and tested in 12 cities located in different climatic zones. The influences of local rainfall characteristics on the variation of representative time series lengths (RTSL) were revealed using linear regression and partial correlation analyses. The results show that RHS with larger storage capacity and located in more humid cities can provide higher water saving efficiency and reliability. Rainfall time series length has significant influence on the modelling results of RHS. The RTSL for the 12 cities vary from 6 to 21 years. The RTSL for the 12 cities are non-significantly correlated with mean annual rainfall (R2 = 0.32, n = 12, p > 0.05) and seasonality index (R2 = 0.28, n = 12, p > 0.05), but significantly correlated with variation coefficients of annual rainfall (R2 = 0.76, n = 12, p < 0.05). The partial correlation coefficient between RTSL and the variation coefficients of annual rainfall is 0.878, while the partial correlation coefficients between RTSL and the mean annual rainfall and seasonality index are -0.569 and -0.522, respectively. The results demonstrate the feasibility of using short-term rainfall data with adequate length instead of long-term rainfall data for RHS modelling and also provide insights into the variation of RTSL in different climatic zones.

Zinc supplement ameliorates phthalates-induced reproductive toxicity in male rats.

People are inevitably exposed to phthalates (PEs) ubiquitously existing in environment. Our previous studies, simulating the actual situations of people exposure to PEs, have shown that the sub-chronic exposure to low-doses PEs mixture (MIXPs) impaired reproductive function in male rats. Zinc is an important element in maintaining male reproductive functions. However, it is still unknown whether zinc supplement could mitigate PEs-induced male reproductive toxicity or not with sub-chronic low-dose mixture exposure. This study aimed to explore the effect of zinc supplement on the reproductive toxicity caused by sub-chronic MIXPs exposure (160 mg/(kg•body weight)/d, for 90 days) in male rats, and further to reveal the underlying mechanisms. Testosterone (T), FSH and LH in serum, early toxicity indicators in urine, PIWI proteins (PIWIL1 and PIWIL2) expression in testes and pathological examination were performed for toxicity evaluation. Steroidogenic proteins (17ß-HSD, StAR, CYP17A1, P450scc and SRD5A) were measured for mechanisms of exploration. The results indicated that zinc supplement could inhibit the T, LH, FSH level decreases in serum, abolish the effect of 5 early toxicity indicators' levels in urine, restrain the alteration of PIWI proteins expression and improve the constructional injury of testes. These effects might be relevant with the suppressed alteration of the expression of steroidogenic proteins induced by MIXPs in rat testicular cells. This work may offer further insights into reducing health risks of MIXPs exposure.

Simultaneous extraction of four plant growth regulators residues in vegetable samples using solid phase extraction based on thiol-functionalized nanofibers mat.

A simple and environmentally friendly sample pretreatment method was established for extraction of four plant growth regulators (PGRs) residues in vegetable samples. In order to effectively extract targets from complex sample matrices, three types of polar groups (COOH, NH2, or SH) functionalized polyacrylonitrile nanofibers mats (PAN NFsM) were prepared and evaluated, respectively. The superior -SH functionalized PAN NFsM was further selected as a novel adsorbent of solid phase extraction (SPE). Under optimal conditions, the proposed method could achieve high sensitivity (0.2-2 ng g-1) and acceptable recovery (88.94%-106.42%) by consuming lower amount of adsorbent (only 5 mg) and organic reagent (only 1.4 mL), and performing much fewer steps than current methods. In addition, the prepared SH-PAN NFsM possessed excellent reusability which could be reused for 6 times without degradation in adsorption capability. These results presented the great potential of the established method for environmental-friendly and efficiently detecting PGRs residues.

Nanofibers mat as sampling module of direct analysis in real time mass spectrometry for sensitive and high-throughput screening of illegally adulterated sulfonylureas in antidiabetic health-care teas.

In this work, novel ionic liquid (IL) functionalized polyacrylonitrile nanofibers mat (IL/PAN-NFsM) was firstly prepared through thiol-ene "click" reaction and evaluated for the establishment of a sensitive and high-throughput screening method. Because of its excellent pre-separation efficiency, IL/PAN-NFsM can adsorb trace-level targets from complex sample matrix within tens of seconds by performing a solid-phase extraction (SPE) process, and then served as sampling modules of direct analysis real time mass spectrometry (DART-MS) without any additional processing. This means the target analytes concentrated on IL/PAN-NFsM were directly desorbed, ionized, and detected by DART-MS. To verify the feasibility of the proposed method, three illegal added synthetic drugs (gliclazide, glimepiride, and gliquidone) were screened in six types of antidiabetic health-care tea samples. The results indicated that the sensitivity is in the level of ng g-1, while total analysis time does not exceed 1.0 min per sample. Moreover, the stability expressed as relative standard deviation (RSD) varies from 1.7% to 17.3%. We proposed a new screening mode based on the direct combination of functionalized NFsM and DART-MS, which is expected to become a universal method in food safety analysis.

Simple, efficient, and eco-friendly sample preparation for simultaneous determination of paracetamol and chloramphenicol in meat.

We have developed and validated a simple, eco-friendly, and reliable method to simultaneously determine paracetamol and chloramphenicol in meat with ultra performance liquid chromatography and tandem mass spectrometry. The samples were firstly extracted with ethylenediaminetetraacetic acid-McIlvaine's buffer and then purified by solid-phase extraction by using a novel core-shell polyaniline/polyacrylonitrile nanofibers mat. Compared with existing methods for the two analytes, the proposed method was simplified greatly with much fewer sample preparation steps, consumed much less time (< 2 min per sample) and organic solvent (0.7 mL per sample). Low detection levels (0.15-0.20 µg/kg for paracetamol, 0.01 µg/kg for chloramphenicol) with good precision and recoveries of the target compounds were obtained. The proposed method was applied to determine the residual paracetamol and chloramphenicol in pork, chicken, and beef samples, and the test results were consistent with those using the Chinese national standard methods, which demonstrates the reliability and practicality of the new method.

Novel nanofibers mat as an efficient, fast and reusable adsorbent for solid phase extraction of non-steroidal anti-inflammatory drugs in environmental water.

Core-shell polyaniline/polyacrylonitrile nanofibers mat (PANI/Pan NFsM) was prepared for extraction of hydrophilic non-steroidal anti-inflammatory drugs (NSAIDs) in environmental water. Superior adsorption and desorption performance of PANI/Pan NFsM was confirmed by both static and dynamic adsorption/desorption experiments. These properties proved PANI/Pan NFsM was a potentially efficient and fast solid phase extraction (SPE) adsorbent for NSAIDs. Under the optimized conditions, only 3 mg of PANI/Pan NFsM could easily extract eight target analytes in 10 mL of water sample without any pre-treatment, and the analytes retained on NFsM could be easily eluted by 500 µL of 1% acetic acid methanol for direct UPLC-MS/MS analysis. In addition, each piece of PANI/Pan NFsM could be reused for at least 20 times without performance decline. Possible adsorption mechanisms were also proposed. Practical feasibility was validated through the actual sample analysis.

Determination of Five Sex Hormones in Urine Samples for Early Evaluation of Male Reproductive Toxicity Induced by Phthalate Esters in Rats.

In this work, male rats were exposed to multiple phthalate esters (MIXPs) in a long-term low-dose model for the early evaluation of reproductive toxicity. An ananlysis method with better sensitivity, accuracy and precision was established to determine the five sex hormones (androstenedione, testosterone, dehydroepiandrosterone, dihydrotestosterone, and estrone) in collected urine samples. The results showed that all the analytes in the MIXPs treated group changed in a time-dependent manner. Specifically, estrone significantly decreased from the 30th day and the other four changed from the 30th day and then significantly increased on the 60th day, while no obvious changes were found in the control group. Therefore, a possible way was provided for the early evaluation of male reproductive toxicity induced by Phthalate esters (PEs) . The reliability of judgment was improved by observing the changes of five target hormones simultaneously. Furthermore, good compliance was predicted for the practical application due to the noninvasive and convenient urine sample collection.

Combined effects of simultaneous exposure to six phthalates and emulsifier glycerol monosterate on male reproductive system in rats.

Human beings are inevitably exposed to ubiquitous phthalate esters (PEs), and simultaneously ingesting high quantities of food emulsifiers via daily diet. Glycerin monostearate (GMS) is a widely used food emulsifier. The purposes of this study were to investigate the combined effects between the mixture of six frequently used PEs (MIXPs) and GMS on male rat reproductive system, and further to explore the underlying mechanisms. Male rats were orally administered either sodium carboxymethyl cellulose as controls or MIXPs at three different low-doses with or without GMS (200mg/kg/d) by gavage. The 15-week exposure of MIXPs caused male reproductive toxicity in a dose- and time-dependent manner, including the decrease of serum testosterone and morphological damage of testis. Metabonomics analyses of urine and Western blotting analyses of steroidogenic proteins (StAR, P450scc, CYP17A1, 17ß-HSD and P450arom) indicated that MIXPs exposure down-regulated the expression of steroidogenic proteins, and might alter androgen metabolism. The results also showed that the presence of GMS exacerbated the toxicities of MIXPs to male rat reproductive system. These findings suggest that food emulsifier GMS could enhance the toxic effects of MIXPs on male hormone biosynthesis.

Nanofibers mat-based solid-phase extraction method for the pretreatment of urine samples and its application in the primary study on the disposition of nonylphenol after long-term low-level exposure in rats.

A method was established for the analysis of nonylphenol (NP) in rat urine samples based on a solid-phase extraction (SPE) procedure with an amino functionalized polyacrylonitrile nanofibers mat (NH2-PAN NFSM) as sorbent coupled with high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The calibration curves prepared in three different days showed good linearity over a wide range of NP concentrations from 0.1 to 100.0ng/mL. It was remarkable that the proposed NH2-PAN NFsM based SPE method showed superior extraction efficiency with the consumption of only 4mg of sorbent and 500µL of eluent. The eluent without any further concentration was directly analyzed by HPLC-MS/MS. As a result, a simple and effective sample preparation was achieved. In addition, the notable lower detection limit (LOD) of 0.03ng/mL revealed the excellent sensitivity of the proposed method in comparison with that in literatures. The recoveries ranged from 85.0% to 114.8% with the relative standard deviations (RSDs) ranging from 7.5% to 13.7%, which were better than or comparable to those from the published methods, suggesting high accuracy of the proposed method. The proposed method was applied in primary study on the disposition of nonylphenol after long-term low-level exposure in rats, providing information for health risk assessment on the real scenarios of NP exposure. NH2-PAN NFsM shows great potential as a novel SPE sorbent for the analysis of biological samples.

414 W near-diffraction-limited all-fiberized single-frequency polarization-maintained fiber amplifier.

A high-power 1064 nm single-frequency polarization-maintained fiber amplifier based on an all-fiber master oscillator power amplifier configuration is demonstrated. To mitigate the stimulated Brillouin scattering (SBS) and the mode instability (MI) effect, a polarization-maintained Yb-doped fiber with a high dopant concentration and a 25 µm core diameter is adopted in the main amplifier stage; in addition, step-distributed longitudinal strain is imposed on the active fiber to broaden its effective SBS gain spectrum and further increase the SBS threshold. As a result, a pump-limited 414 W single-frequency fiber laser is obtained without signs of SBS and MI. Experimental results show that the SBS threshold is increased by at least two times. The slope efficiency of the main amplifier is about 80%. The polarization degree is higher than 98% at all the power levels. The beam quality is measured with a M2 of 1.34. To the best of our knowledge, this is the highest output power of single-frequency polarization-maintained fiber amplifier based on an all-fiber structure.

Characterization of an exo-inulinase from Arthrobacter: a novel NaCl-tolerant exo-inulinase with high molecular mass.

A glycoside hydrolase family 32 exo-inulinase gene was cloned from Arthrobacter sp. HJ7 isolated from saline soil located in Heijing town. The gene encodes an 892-residue polypeptide with a calculated mass of 95.1 kDa and a high total frequency of amino acid residues G, A, and V (30.0%). Escherichia coli BL21 (DE3) cells were used as hosts to express the exo-inulinase gene. The recombinant exo-inulinase (rInuAHJ7) showed an apparently maximal activity at pH 5.0-5.5 and 40-45°C. The addition of 1.0 and 10.0 mM Zn(2+) and Pb(2+) had little or no effect on the enzyme activity. rInuAHJ7 exhibited good salt tolerance, retaining more than 98% inulinase activity at a concentration of 3.0%-20.0% (w/v) NaCl. Fructose was the main product of inulin, levan, and Jerusalem artichoke tubers hydrolyzed by the enzyme. The present study is the first to report the identification and characterization of an Arthrobacter sp exo-inulinase showing a high molecular mass of 95.1 kDa and NaCl tolerance. These results suggest that the exo-inulinase might be an alternative material for potential applications in processing seafood and other foods with high saline contents, such as marine algae, pickles, and sauces.