High resolution acoustic sensing based on microcavity optomechanical oscillator.

In this paper, a simple sensing method based on a silicon oxide microcavity optomechanical oscillator (OMO) is proposed and demonstrated for the detection of acoustic signals. Firstly, the resonance damping was reduced by improving the optical quality factor (Qo) and increasing the sphere-to-neck ratio. After optimizing the process, a microsphere OMO was fabricated, which has an ultra-high mechanical quality factor (6.8 × 106) and greater sphere-to-neck ratio (∼11:1), based on which ultra-narrow linewidth phonon laser (∼1 Hz) is constructed. Secondly, by changing the refractive index of the coupling interval, the low-frequency acoustic pressure signal is efficiently coupled into the microcavity OMO to construct a high-resolution acoustic sensor. This sensing mechanism can not only measure the acoustic pressure, but also use the sideband signal in the modulation mechanism to measure the frequency of acoustic signals (15 Hz∼16 kHz), the sensitivity is 10.3 kHz/Pa, the minimum detectable pressure is 1.1 mPa, and noise-limited minimum detectable pressure is 28.8 µPa/Hz1/2. It is the highest detection resolution compared with the same type of low-frequency acoustic signal detection currently reported. This OMO-based acoustic sensing detection method opens up a new path for future miniaturized, ultra-high-precision, and cost-effective acoustic sensing.

Ultra-stable control near the EP in non-Hermitian systems and high-precision angular rate sensing applications.

In non-Hermitian systems, enhancing sensitivity under exceptional point (EP) conditions offers an ideal solution for reconciling the trade-off between sensitivity and size constraints in sensing applications. However, practical application is limited by undesired sensitivity to external fluctuations, noise, and errors in signal amplification synchronization. This paper presents a precisely controlled EP tracking and detection system (EPTDS) that achieves long-term rapid tracking and locking near the EP by constructing a second-order non-Hermitian optical sensing unit, employing an optical power adaptive control method, and utilizing a combinatorial demodulation-based dual-loop cascaded control (CDCC) technique to selectively suppress traditional noise at different frequencies. The system locking time is 10 ms, and in room temperature conditions, the output frequency error over 1 hour is reduced by more than 30 times compared to before locking. To assess its sensing capabilities, the EPTDS undergoes testing in a rotational experiment based on the Sagnac effect, with the output bias instability based on Allan deviation measured at 0.036 °/h. This is the best result for EP-enhanced angular rate sensing that we are aware of that has been reported. The EPTDS method can be extended to various sensing fields, providing a new path for transitioning non-Hermitian sensing from the laboratory to practical applications.

Evaluation of the Inhibition Potency of Nirmatrelvir against Main Protease Mutants of SARS-CoV-2 Variants.

SARS-CoV-2 continues to pose a threat to public health. Main protease (Mpro) is one of the most lucrative drug targets for developing specific antivirals against SARS-CoV-2 infection. By targeting Mpro, peptidomimetic nirmatrelvir is able to inhibit viral replication of SARS-CoV-2 and reduce the risk for progression to severe COVID-19. However, multiple mutations in the gene encoding Mpro of emerging SARS-CoV-2 variants raise a concern of drug resistance. In the present study, we expressed 16 previously reported SARS-CoV-2 Mpro mutants (G15S, T25I, T45I, S46F, S46P, D48N, M49I, L50F, L89F, K90R, P132H, N142S, V186F, R188K, T190I, and A191V). We evaluated the inhibition potency of nirmatrelvir against these Mpro mutants and solved the crystal structures of representative Mpro mutants of SARS-CoV-2 bound to nirmatrelvir. Enzymatic inhibition assays revealed that these Mpro variants remain susceptible to nirmatrelvir as the wildtype. Detailed analysis and structural comparison provided the inhibition mechanism of Mpro mutants by nirmatrelvir. These results informed the ongoing genomic surveillance of drug resistance of emerging SARS-CoV-2 variants to nirmatrelvir and facilitate the development of next-generation anticoronavirus drugs.

Structural basis of main proteases of HCoV-229E bound to inhibitor PF-07304814 and PF-07321332.

PF-07321332 and PF-07304814, inhibitors against SARS-CoV-2 developed by Pfizer, exhibit broad-spectrum inhibitory activity against the main protease (Mpro) from various coronaviruses. Structures of PF-07321332 or PF-07304814 in complex with Mpros of various coronaviruses reveal their inhibitory mechanisms against different Mpros. However, the structural information on the lower pathogenic coronavirus Mpro with PF-07321332 or PF-07304814 is currently scarce, which hinders our comprehensive understanding of the inhibitory mechanisms of these two inhibitors. Meanwhile, given that some immunocompromised individuals are still affected by low pathogenic coronaviruses, we determined the structures of lower pathogenic coronavirus HCoV-229E Mpro with PF-07321332 and PF-07304814, respectively, and analyzed and defined in detail the structural basis for the inhibition of HCoV-229E Mpro by both inhibitors. Further, we compared the crystal structures of multiple coronavirus Mpro complexes with PF-07321332 or PF-07304814 to illustrate the differences in the interaction of Mpros, and found that the inhibition mechanism of lower pathogenic coronavirus Mpro was more similar to that of moderately pathogenic coronaviruses. Our structural studies provide new insights into drug development for low pathogenic coronavirus Mpro, and provide theoretical basis for further optimization of both inhibitors to contain potential future coronaviruses.

Sandwich structure magnetometer with a high sensitivity and signal-to-noise ratio based on an ultrahigh-Q CaF2 resonator.

Whispering gallery mode (WGM) resonators with an ultrahigh quality (Q) factor provide an extremely high resolution for high-precision sensing. However, it is difficult to use them directly in magnetic sensors because of the transparency to the magnetic field. In this paper, a sandwich structure consisting of a neodymium iron boron magnet and calcium fluoride resonator with a Q factor of 109 is proposed. The experimental results show that, compared with the conventional magnetometer, the signal-to-noise ratio of the optical WGM magnetometer reaches 62 dB, with the direct current sensitivity of 42.59 MHz/mT and the AC sensitivity of 794p T H z -1/2 at 42 kHz.

Design of an ultra-broadband and low-loss 3 dB power splitter from the 1.25 to 2.04 µm wave band.

As a key component of the beam splitting and combining in photonic integrated circuits, an optical power splitter requires the characteristics of compactness, broadband, and low loss. Here, we propose a 1×2 ultra-broadband 3 dB power splitter with a 5 µm long beam splitting area, based on the structure of a subwavelength grating. The 0.45 dB bandwidth of the TE mode achieves 790 nm from 1.25 to 2.04 µm. This power splitter has a large fabrication tolerance, exceeding more than 30 nm (±15n m) and obtains the desired power ratio. It is suitable for high-speed and large-capacity communication, wavelength division multiplexing systems, and other multi-wave interconnection applications.

An incidental hepatic epithelioid hemangioendothelioma in a patient with chronic hepatitis: lost in the maze.

Hepatic epithelioid angioendotheliomas (HEHE) are rare vascular tumors with low to intermediate malignancy. Imaging plays an important role in the diagnosis of HEHE. However, imaging characterization of HEHE still remains challenging, since HEHE is commonly misdiagnosed as hepatocellular carcinoma, cholangiocarcinoma or metastases.

Analysis of blood coagulation indexes, thromboelastogram and autoantibodies in patients with recurrent pregnancy loss.

Objectives: Changes in coagulation indexes, thromboelastogram(TEG) and autoantibodies in patients with recurrent pregnancy loss (RPL) with different number of abortions were analyzed. Methods: Medical records of 48 patients with recurrent abortion, treated in Quzhou people's Hospital from November 2019 to October 2020, were collected as the observation group. Based on the number of abortions, patients were divided into Group-A (Two abortions, n=21), Group-B (Three abortions, n=16) and group C (Abortion ≥ four times, n=11). Records of 50 healthy pregnant women in our hospital in the same period were selected as the control group. Coagulation indexes [prothrombin time (PT), activated partial prothrombin time (APTT), fibrinogen (FIB), D-Dimer (DD)], thromboelastogram (TEG) parameters [reaction time (R), coagulation time(K), maximum thrombus amplitude (MA), coagulation angle (α)], changes in the levels of autoantibodies [anticardiolipin antibody (ACA), anti-endometrial antibody (EmAb), anti-thyroid antibody(ATA)] were compared between the groups. Results: There were significant differences in the levels of ATPP, Pt, FIB and DD among the groups. Higher number of abortions correlated with lower the levels of ATPP and Pt, and higher levels of FIB and DD (P<0.05). Compared to the control group, R and K in Group-A,B and C decreased, while α and MA increased (P<0.05). There were significant differences in α and MA indexes. The positive rates of ACA, EmAb and ATA in Group-A were higher than those in the control group, but the difference was not statistically significant (P>0.05), while the above indexes in groups B and C were significantly higher than those in the control group (P<0.05). The positive rates of ACA and ATA in group C were significantly higher than those in Group-A (P<0.05), but there was no significant difference in the positive rate of EmAb (P>0.05). Conclusion: RPL was related to the decrease of APTT, PT, and the increase of FIB and DD levels. TEG indicated that the increase of α and MA values indicated that the risk of multiple abortion was increased. The positive rates of ACA, EmAb and ATA were closely related to multiple abortions, especially the positive rates of ACA and ATA.

[Study on homeostasis and circadian rhythm of attention performance of different chronotypes in sleep deprivation].

Difference of chronotypes makes influence to cognitive performance of individuals in routine duties. In this paper, 55 subjects with different chronotypes were subjected to continuous sleep deprivation for 30 h by using the constant routine protocol, during which core body temperature was measured continuously, and subjective sleepiness self-rating and the performance of selective attention were measured hourly. The results showed that the phase difference of core body temperature has no significant difference, yet the amplitude and term difference among the three chronotypes are significant. There was an advance in phase between subjective sleepiness self-rating and core body temperature, and the self-rating sleepiness of evening type came the latest, and the self-rating sleepiness of morning type dissipated the fastest. The response time of selective attention showed a 2 h phase delay with subjective sleepiness self-rating. And the analysis of core body temperature showed that the later the chronotype was, the greater the phase delay was. The correct rate of selective attention of different chronotypes were inconsistent with delay of subjective sleepiness self-rating and core body temperature. We provide reference for industry, aviation, military, medical and other fields to make a more scientific scheduling/ shifting based on cognitive performance characteristics of different chronotypes.

Reducing backscattering and the Kerr noise in a resonant micro-optic gyro using two independent lasers.

In a resonator micro-optic gyroscope (R-MOG), backscattering noise and Kerr noise have been key issues affecting the optical gyro output that are difficult to completely suppress. A method is proposed to suppress backscattering noise in a R-MOG. It uses two independent lasers and, by locking the two optical signals at different resonance peaks, a differential output of the two optical signals is achieved that successfully suppresses the backscattering noise. At the same time, a light intensity feedback loop based on a light intensity modulator is added to the loop to ensure the same optical power into the cavity. Experimental results show that the light intensity fluctuation into the gyro system is reduced nearly two orders of magnitude and the bias stability is improved to 9.06 deg/h by using a light intensity feedback loop with two independent lasers.

Single-detecting-path high-resolution displacement sensor based onself-interference effect of a single submicrometer grating.

On the basis of the self-interference effect between ±1 st-order diffraction beams from a single optical submicrometer grating, we demonstrate a single-detecting-path optical displacement sensor with high resolution. Using a quadrant optoelectronic detector, a single-detecting-path system without any wave plates is realized experimentally. Combined with an interpolation circuit, we demonstrate the system for displacement measurement within a range of 200 µm. The results indicate a detecting sensitivity of 905.4°/µm and an accuracy of ±1.9µm. It is worth mentioning that, considering a maximum subdividing factor of 9674 used in experiment, the resolution goes down to 41.1 pm in principle. We demonstrate a compact optical sensor with high resolution, which is promising in developing miniaturized displacement systems.

ARGONAUTE SUBFAMILY GENES IN THE SMALL BROWN PLANTHOPPER, Laodelphax striatellus (HEMIPTERA: DELPHACIDAE).

Argonaute (AGO) proteins are essential catalytic components of the RNA-induced silencing complex and play central roles in RNA interference. Using a combination of bioinformatics and rapid amplification of cDNA ends (RACE) methods, putative AGO subfamily members, ls-AGO1 and ls-AGO2, were cloned and characterized from the small brown planthopper, Laodelphax striatellus. The open reading frame (ORF) of ls-AGO1 is 2,820 bp long, encoding a putative protein of 939 amino acid residues, and ls-AGO2 contains an ORF of 2,490 bp, encoding 829 amino acid residues. The expected conserved PAZ and PIWI domains, and the conserved Asp-Asp-His (DDH) catalytic triad motif in the PIWI domain were observed in both ls-AGO1 and ls-AGO2. Reverse transcription-qPCR (RT-qPCR) results showed that both ls-AGO1 and ls-AGO2 were expressed in all developmental stages of L. striatellus with highest mRNA abundance in eggs. Expression of ls-AGO1 and ls-AGO2 was significantly decreased in adult insects in response to acquisition of rice black-streaked dwarf virus by second instar nymphs. mRNA expression of ls-AGO1 was significantly downregulated in response to low and high temperatures, but expression of ls-AGO2 was only affected by low temperature. ls-AGO1 and ls-AGO2 were initially downregulated when insects were transferred from rice to maize and to the wild grass Brachypodium distachyon, but expression showed partial or complete recovery 7 days after transfer. These results document that AGO subfamily members of L. striatellus are ubiquitously expressed at different developmental stages and respond to various stresses. Thus, AGO subfamily may act in regulating the stress-response of L. striatellus by controlling related gene expression.

Unusual characteristics of dicistrovirus-derived small RNAs in the small brown planthopper, Laodelphax striatellus.

In this study, sequences of small RNA (sRNA) libraries derived from the insect vector Laodelphax striatellus were assembled into contigs and used as queries for database searches. A large number of contigs were highly homologous to the genome sequence of an insect dicistrovirus, himetobi P virus (HiPV). Interestingly, HiPV-derived sRNAs had a wide size distribution, and were relatively abundant throughout the 18-30 nt size range with only a slight peak at 22 nt. HiPV sRNAs had a strong bias towards the sense strand, whilst the antisense sRNAs were predominantly 21 and 22 nt. HiPV sRNAs do not have the typical features of PIWI-interacting RNAs, but their 3' ends were preferentially cleaved at UA-rich sequences. Our data suggest that HiPV sRNAs may be derived both from activities of the RNA interference pathway and from cleavage of the viral genome by other host RNases.

[Expression of heparanase in kidney of rats with respiratory syncytial virus nephropathy and its relationship with proteinurina].

OBJECTIVE: To explore the role of heparanase in the pathogenesis of respiratory syncytial virus (RSV) nephropathy in rats model. METHODS: Twenty 150-200 g Sprague-Dawley (SD) rats (n = 5 per group) were inoculated with 6 x 10(6) PFU RSV and sacrificed on days 4, 8, 14 and 28 postinoculation (RSV4, RSV8, RSV14 and RSV29). Five SD rats inoculated with Dulbecco's minimum essential medium were served as normal control. The expression levels of heparanase protein and mRNA in the rat renal tissue of each group were determined by immunohistochemical staining and real-time quantitative RT-PCR respectively. The proteinurina was also measured and then the relationship between the expression level of heparanase and the 24-hour urinary protein was studied. RESULTS: The rats with RSV nephropathy exhibited higher proteinuria in comparison with normal rats, and the 24-hour urinary protein level was significantly different between each RSV nephropathy group (RSV14 > RSV8 > RSV28 > RSV4, P < 0.05). Compared with normal control, the rats with RSV nephropathy showed up-regulated expression of heparanase protein in glomeruli. The expression levels of heparanase protein in RSV8 and RSV14 group were higher than those in RSV4 and RSV28 group (P < 0.05). There was a linear positive correlation between the expression level of glomerular heparanase protein and the quantity of 24-hour urinary protein (r = 0.783, P < 0.05). Compared with normal control group, the expression levels of heparanase mRNA in the kidney from RSV4, RSV8, RSV14, and RSV28 group were elevated (RSV14 > RSV8 > RSV4 > RSV28 , P < 0.05). There was a linear positive correlation between the expression level of renal heparanase mRNA and the quantity of 24-hour urinary protein (r = 0.725, P < 0.05). CONCLUSION: The increased expression of heparanase in kidney may be important to the loss of glomerular negative charge in glomerular basement membrane which is involved in the pathogenesis of RSV nephropathy in rats.

In vivo determination of the bioavailability of folic acid through the utilization of the PBPK model in conjunction with UPLC.

This paper employed a physiologically based pharmacokinetic model (PBPK) to investigate the transformations of folic acid and its metabolites in vivo. Additionally, an ultra-performance liquid chromatography (UPLC) method was developed to accurately measure the body's retention rate and conversion rate of folic acid, tetrahydrofolate, and 5-methyltetrahydrofolate. Furthermore, the bioavailability of folic acid in the body was assessed by combining this method with an evaluation technique for animal models. The study found that the gastric metabolism time was 2 h, while the small intestinal metabolism duration was 4 h. The maximum conversion rate was observed in plasma and liver after 6 h, and in the brain after 8 h. This serves as a framework for creating a model to assess the bioavailability of folic acid in living organisms, to enhance the safety and efficacy of folic acid intake.

Accelerated and precise identification of antioxidants and pesticides using a smartphone-based colorimetric sensor array.

The integration of smartphones with conventional analytical approaches plays a crucial role in enhancing on-site detection platforms for point-of-care testing. Here, we developed a simple, rapid, and efficient three-channel colorimetric sensor array, leveraging the peroxidase (POD)-like activity of polydopamine-decorated FeNi foam (PDFeNi foam), to identify antioxidants using both microplate readers and smartphones for signal readouts. The exceptional catalytic capacity of PDFeNi foam enabled the quick catalytic oxidation of three typical peroxidase substrates (TMB, OPD and 4-AT) within 3 min. Consequently, we constructed a colorimetric sensor array with cross-reactive responses, which was successfully applied to differentiate five antioxidants (i.e., glycine (GLY), glutathione (GSH), citric acid (CA), ascorbic acid (AA), and tannic acid (TAN)) within the concentration range of 0.1-10 µM, quantitatively analyze individual antioxidants (with AA and CA as model analytes), and assess binary mixtures of AA and GSH. The practical application was further validated by discriminating antioxidants in serum samples with a smartphone for signal readout. In addition, since pesticides could be absorbed on the surface of PDFeNi foam through π-π stacking and hydrogen bonding, the active sites were differentially masked, leading to featured modulation on POD-like activity of PDFeNi foam, thereby forming the basis for pesticides discrimination on the sensor array. The nanozyme-based sensor array provides a simple, rapid, visual and high-throughput strategy for precise identification of various analytes with a versatile platform, highlighting its potential application in point-care-of diagnostic, food safety and environmental surveillance.

Bridging techniques compared with direct endovascular therapy for stroke due to tandem occlusion: A systematic review and meta-analysis.

The superiority of the bridging strategy of intravenous thrombolysis (IVT) plus endovascular therapy (EVT) to EVT alone for the anterior circulation with tandem vascular occlusion (TO) has not been specifically addressed by a single randomized trial. Analysis of 15 studies (n = 1857 patients) revealed that 90 Day good functional outcomes (MRS≤2) were better for bridging therapy (IVT + EVT) than for dEVT (OR:1.39, 95%CI: 1.09-1.79, p = 0.008); 90-day mortality was lower for IVT + EVT than for dEVT (OR: 0.57; 95%CI: 0.40-0.81, p = 0.002) and rates of successful recanalization were higher for IVT + EVT than for dEVT (OR: 1.79, 95%CI: 1.36-2.36, p<0.0001). However, there was no significant difference in the incidence of symptomatic. intracranial hemorrhage (sICH) between groups (OR 0.91, 95%CI 0.64-1.31, p = 0.62).In conclusion, Patients receiving IVT + EVT have a better functional outcome, lower death rate and a higher rate of successful recanalization than those receiving dEVT but there was no difference in sICH risk between the two treatments.

Insight into the Mechanism Underlying the Reduction of Digestibility and IgG/IgE Binding Ability in Ovalbumin during Different High-Temperature Conduction Modes-Induced Glycation.

Effects of different high-temperature conduction modes [high-temperature air conduction (HAC), high-temperature contact conduction (HCC), high-temperature steam conduction (HSC)]-induced glycation on the digestibility and IgG/IgE-binding ability of ovalbumin (OVA) were studied and the mechanisms were investigated. The conformation in OVA-HSC showed minimal structural changes based on circular dichroism, fluorescence, and ultraviolet spectroscopy. The degree of hydrolysis analysis indicated that glycated OVA was more resistant to digestive enzymes. Liquid chromatography-Orbitrap mass spectrometry identified 11, 14, and 15 glycation sites in OVA-HAC, OVA-HCC, and OVA-HSC, respectively. The IgG/IgE-binding ability of OVA was reduced during glycation and digestion, and the interactions among glycation, allergenicity, and digestibility were further investigated. Glycation sites masked the IgG/IgE epitopes resulting in a reduction in allergenicity. Digestion enzymes destroyed the IgG/IgE epitopes thus reducing allergenicity. Meanwhile, the glycation site in proximity to the digestion site of pepsin was observed to cause a reduction in digestibility.

[Impact of baseline pulse pressure on new-onset cardio-and cerebrovascular events in diabetic population].

OBJECTIVE: To observe the association between baseline pulse pressure (PP) level and new-onset cardio-cerebrovascular events in diabetic population. METHODS: Physical examination data between July 2006 to October 2007 from a total of 101 510 employees of Kailuan Group were reviewed, 8306 subjects with a fasting plasma glucose level of ≥ 7.0 mmol/L or with confirmed diabetes diagnosis and were enrolled in this prospective cohort study. Subjects were followed up for 38-53 (48.1 ± 3.1) months and the cardio-cerebrovascular events were obtained every six months, association between baseline PP and new-onset cardio-cerebrovascular events in the diabetic population were analyzed. RESULTS: (1) Incidences of total cardio-cerebrovascular events in the PP groups were 3.4%, 2.8%, 4.5%, 6.4%, respectively. Incidences of cerebral infarction events and myocardial infarction were 2.1%, 1.6%, 2.9%, 3.9% and 1.1%, 0.7%, 1.0%, 1.7%, respectively. (2) Multivariate Cox's proportional hazards regression analysis indicated that baseline PP group was the risk factor for total cardio-cerebrovascular events, cerebral infarction events and myocardial infarction, and the risk for all the events of the PP ≥ 60 mm Hg (1 mm Hg = 0.133 kPa) group was increasing. The values of RR(95%CI) were 1.88 (95%CI 1.34-2.65, P < 0.01), 1.92 (95%CI 1.23-2.99, P < 0.01) and 1.52 (95%CI 0.82-2.81, P > 0.05) after adjust the other factors.(3) In line with increasing level of baseline PP, age, BMI, SBP, DBP, HDL-C, and hs-CRP levels significantly increased in this diabetic population (P < 0.01 or P < 0.05). CONCLUSION: The level of high baseline PP is a risk factor for new-onset cardio-cerebrovascular events in diabetic population.

The sustained attention characteristics of flight crews on exempt and non-exempt flights.

We analyzed the characteristics of sustained attention changes in flight crews during exempt and non-exempt flights. Fourteen pilots (aged 30-43 y) participated in this study, with seven involved in each flight type, all of which were intercontinental (China to North America). Pilots completed continuous performance tests (CPT) at the required flight stages without compromising safety while on duty. No significant differences in sleep and sustained attention emerged between the exempt and non-exempt flight crews. Pilots' fatigue was highest in the early morning hours. Their general stability of efficiency increased during the day and decreased at night. Non-exempt flight crews appeared to sacrifice reaction rate to improve accuracy. Exempt crews appeared to increase their test proficiency. The task stability time of the non-exempt flight crews was better than that of the exempt ones. Short-term stability was better for exempt inbound flights rather than for outbound ones. Pilots were more prone to error runs as their total time awake increased, especially on non-exempt flights. The addition of crew members to exempt flights, allowance for more in-flight rest shifts, and over-stop rest on non-exempt flights may alleviate pilot fatigue and preserve alertness.