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In this work, Flammulina velutipes was used as a novel protein and fibrous structure source to prepare animal-free patties, and transglutaminase (TGase) was added to improve their functional properties. The results showed that the addition of mushroom increased the gel strength, texture profile, and sensory property of animal-free patties. However, the presence of mushroom made the microstructure of patty become loose, with large holes. Interestingly, TGase (6–8 U/g) significantly decreased the size of holes in microstructure and induced to form a uniform and compact microstructure. Because TGase decreased the content of free amino acid group and soluble protein, and induced the formation of new protein polymers with high molecular weight in SDS-PAGE results. The covalent cross-linking catalyzed by TGase helped to form a stronger gel matrix in patty, leading to the formation of patty with higher hardness, adhesiveness, chewiness, water holding capacity, and sensory scores.

The relationship between venous congestion and acute kidney injury (AKI) in cardiac surgery after cardiopulmonary bypass has not thoroughly investigated. Vacuum-assisted venous drainage (VAVD) reduces venous congestion, so we hypothesized that it would reduce the incidence of AKI in cardiovascular surgery.Methods and Results: We used a retrospective propensity score-matched analysis to evaluate the effect of VAVD on AKI in adult patients undergoing cardiac surgery. The primary outcomes were AKI and renal replacement therapy (RRT). Multivariable logistic regression was used to explore the association between VAVD exposure and adverse kidney outcomes. Of 15,387 eligible subjects, 13,480 and 1,907 had gravity drainage (GD) or VAVD, respectively, during cardiopulmonary bypass. On the basis of propensity scores, there were 1,468 matched patient pairs for GD and VAVD. The average central venous pressure (CVP) in the GD group was higher than in the VAVD group (4.43±1.23 mmHg vs. 2.30±0.98 mmHg, P0.001). The occurrence of AKI and RRT was statistically significantly different in the 2 groups [(600/1,468, 40.87%) vs. (445/1,468, 30.31%), P0.001; (36/1,468, 2.45% vs. 8/1,468; 0.54%), P0.001, respectively)]. Multivariate logistic regression analysis revealed that VAVD was effective in protecting kidney function.VAVD was associated with a lower CVP and lower incidence of AKI, suggesting it protects adult cardiac patients from adverse renal outcomes.

The colors of copper-containing pigments, copper (II) oxide and malachite, and their origins in ceramic glazes were systematically examined over a wide firing temperature range using a suite of analytical and spectroscopy techniques including SEM, UV-Vis FORS, XRD, FTIR, and EPR to gain new insight into the structural and chemical transformations of the glaze during firing. The two colorants investigated were black copper (II) oxide (CuO) nanopowder and blue-green basic copper carbonate, or malachite (Cu2CO3(OH)2), both of which produce a final light blue color following firing. Additionally, silicon carbide (SiC) was used to locally reduce CuO to simulate firing glazes in a reductive environment and produce a final red color. At lower temperatures, malachite was found to decompose to form CuO at 550 °C, elucidating the reason that two different copper colorants could be used interchangeably to form the same “Robin’s Egg Blue” color. At 850 °C, a glaze sintering process occurred, resulting in the distribution of Cu2+ in a square planar geometry and an observed blue color. This structural change occurred at temperatures lower than the glaze’s melting point, indicating that complete vitrification of the glaze is not required for glaze coloration. Conversely, the reduction in Cu2+ to Cu+ through the addition of SiC did not occur until the glaze was fired above the melting temperature (1000 °C), signifying that high temperatures are required for the redox reaction to occur. This study sheds light on intermediate colorant-glaze interactions that are beneficial for understanding and predicting glaze coloring upon exposure to varying temperatures, and the results from this study can be applied to better-controlled glaze production for artists and a deeper appreciation of ceramic glaze chemistry and aesthetics.

The nitrate depletion and HNO3 release in internally mixed nitrate and dicarboxylic acid (DCA) particles have been widely detected in field and laboratory studies. Nevertheless, considerable discrepancies are still present among these measurements, and the influencing factors for this acid-displacement reaction have not yet been elucidated. In this work, the hygroscopic growth and chemical composition evolution of mixtures of NaNO3 and DCAs, i.e. oxalic acid (OA), malonic acid (MA), and glutaric acid (GA), were measured using attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and vacuum FTIR techniques. The nitrate depletion from NaNO3–OA mixtures was observed in both the measurements, owing to the relatively higher acidity of OA compared to MA and GA. At the same time, the NaNO3 phase state was found to act as a key regulator of nitrate depletion. Amorphous NaNO3 solids at relative humidity (RH) <5 % were inert to liquid OA. With increasing RH, the mixtures experienced three interesting stages of phase changes showing different HNO3 release rates; e.g. at around 15 % RH, the slow HNO3 release was detected by the vacuum IR spectra, potentially indicating the transformation of amorphous solids to semisolid NaNO3. In the second stage (sudden RH increase from ∼15 % to 61 %), the HNO3 release rate was increased by about an order of magnitude. When NaNO3 deliquescence occurred in the third stage, this displacement reaction proceeded due to more available NO3- ion formation. Compared to OA, MA and GA reacted with nitrate only in vacuum FTIR measurement, while in ATR-FTIR measurement, the mixtures tended to be effloresced completely without nitrate depletion. Further, the influences of ambient pressure, chemical composition, and water activity on HNO3 release rates were estimated via Maxwell steady-state diffusive mass transfer equation. The results showed that weaker acidity of MA and GA as well as relatively lower HNO3 diffusion rate in the ambient gas phase mainly contributed to the unobserved nitrate depletion in ATR-FTIR measurement. Our findings reveal that chemical component, phase state, and water activity of particles, as well as HNO3 gas-phase diffusion, play crucial roles in HNO3 release from nitrate and DCA mixtures. This work may provide a new perspective on nitrate depletion in the ageing processes during transport of tropospheric aerosols.

To review of our hospital's experiences in transvaginal natural orifice transluminal endoscopic surgery (vNOTES) and challenges we encountered in performance of the procedure, so as to provide help to medical institutions who are preparing to carry out vNOTES.We retrospectively analyzed the data of all patients receiving vNOTES in our hospital from April 2018 to May 2021. Data we collected cover the general characteristics, perioperative outcomes, and complications of the patients.A total of 1147 patients underwent vNOTES in the past 3 years at our hospital. The total numbers of adnexal surgery, myomectomy, hysterectomy, pelvic floor reconstruction surgery, and malignant tumor surgery performed via vNOTES were 902, 98, 82, 51, and 14, respectively. Eighteen patients were converted to transabdominal laparoscopic surgery. A total of 38 patients had complications according to Clavien-Dindo classification, and the total complication rate was 3.31%. Among these cases of complications, 27 were Grade I, 4 were Grade II, and 7 were Grade III. No complications of Grade IV or V were reported.The application of vNOTES is safe and feasible for most gynecological surgeries. Moreover, hospitals with traditional laparoscopic equipment are advised to try this technique as there is no need to purchase additional expensive equipment. However, since vNOTES represents a novel approach, the long-term complications and efficacy associated with this technique are pending to be verified through large-scale prospective multicenter randomized controlled studies.

Colon cancer is the third most common cancer and the second leading cause of cancer-related death worldwide. Dysregulated RNA splicing factors have been reported to be associated with tumorigenesis and development in colon cancer. In this study, we interrogated clinical and RNA expression data of colon cancer patients from The Cancer Genome Atlas (TCGA) dataset and the Gene Expression Omnibus (GEO) database. Genes regulating RNA splicing correlated with survival in colon cancer were identified and a risk score model was constructed using Cox regression analyses. In the risk model, RNA splicing factor peroxisome proliferator-activated receptor-γ coactivator-1α (PPARGC1) is correlated with a good survival outcome, whereas Cdc2-like kinase 1(CLK1), CLK2, and A-kinase anchor protein 8-like (AKAP8L) with a bad survival outcome. The risk model has a good performance for clinical prognostic prediction both in the TCGA cohort and the other two validation cohorts. In the tumor microenvironment (TME) analysis, the immune score was higher in the low-risk group, and TME-related pathway gene expression was also higher in low-risk group. We further verified the mRNA and protein expression levels of these four genes in the adjacent nontumor, tumor, and liver metastasis tissues of colon cancer patients, which were consistent with bioinformatics analysis. In addition, knockdown of AKAP8L can suppress the proliferation and migration of colon cancer cells. Animal studies have also shown that AKAP8L knockdown can inhibit tumor growth in colon cancer in vivo. We established a prognostic risk model for colon cancer based on genes related to RNA splicing regulation and uncovered the role of AKAP8L in promoting colon cancer progression.

The authors investigated the effectiveness of home-based transcutaneous electrical acupoint stimulation (TEAS) combined with lifestyle modification on blood pressure (BP) control and explored the feasibility of the trial design in this prospective, randomized controlled trial. The authors recruited individuals with high-normal BP who had a systolic blood pressure (SBP) of 120-139 mm Hg and a diastolic blood pressure (DBP) of 80-89 mm Hg, or both. Participants were randomly assigned to receive either lifestyle modification combined with TEAS four times weekly for 12 weeks at home (intervention group) or solely lifestyle modification (control group). The primary outcome was the change in mean SBP at week 12 from the baseline measurement. A total of 60 participants were randomized in a 1:1 ratio, and an intention-to-treat analysis was performed on all of the outcomes. The mean difference in the change in SBP for the intervention group (compared to the control) at week 12 was -3.85 mm Hg (95% CI: -7.58 to -.12; p = .043); for the DBP, the change was -2.27 mm Hg (95% CI: -5.76 to 1.23; p = .199). There was no difference in the proportion of progression to hypertension, quality of life, body mass index (BMI) or waist circumference. In addition, two participants reported TEAS-related adverse events. The authors found a reduction in SBP control in the pragmatic, home-based intervention by using TEAS combined with lifestyle modification in adults with high-normal BP. Trial Registration: The study was registered in the Chinese Clinical Trial Registry (ChiCTR 1900024982) on August 6, 2019.

BACKGROUND: This study developed and validated a viable model for the preoperative diagnosis of malignant distal gastric wall thickening based on dual-energy spectral computed tomography (DEsCT). METHODS: The imaging data of 208 patients who were diagnosed with distal gastric wall thickening using DEsCT were retrospectively collected and divided into a training cohort (n=151) and a testing cohort (n=57). The patient’s clinical data and pathological information were collated. The multivariable logistic regression model was built using 5 selected features, and subsequently, a 10-fold cross-validation was performed to identify the optimal model. A nomogram was established based on the training cohort. Finally, the diagnostic performance of the best model was compared to the existing conventional CT scheme through evaluating the discrimination ability in the testing cohort in terms of the receiver operating characteristic curve (ROC), calibration, and clinical usefulness. RESULTS: Stepwise regression analysis identified 5 candidate variables with the smallest Akaike information criteria (AIC), namely, the venous phase spectral curve [VP_ SC; odds ratio (OR) 8.419], focal enhancement (OR 3.741), arterial phase mixed (OR 1.030), tumor site (OR 0.573), and diphasic shape change (DP_shape change; OR 2.746). The best regression model with 10-fold cross-validation consisting of VP_SC and focal enhancement was built using the 5 candidate variables. The average area under the ROC curve (AUC) of the model from the 10-fold cross-validation was 0.803 (sensitivity of 69.2%, specificity of 94.1%, and accuracy of 74.8%). In the testing cohort, the DEsCT model identified using the regression model performed better (AUC 0.905, sensitivity 81.3%, specificity 85.4%, and accuracy 84.2%) than did the conventional CT scheme (AUC 0.852, sensitivity 80.0%, specificity 76.6%, and accuracy 77.2%). The nomogram based on the DEsCT model showed good calibration and provided a better net benefit for predicting malignancy of distal gastric wall thickening. CONCLUSIONS: Comprehensive assessment with the DEsCT-based model can be used to facilitate the individualized diagnosis of malignancy risk in patients presenting with distal gastric wall thickening.

The edible fungi have both edible and medicinal functions, in which terpenoids are one of the most important active ingredients. Terpenoids possess a wide range of biological activities and show great potential in the pharmaceutical and healthcare industries. In this review, the diverse biological activities of edible fungi terpenoids were summarized with emphasis on the mechanism of anti-cancer and anti-inflammation. Subsequently, this review focuses on advances in knowledge and understanding of the biosynthesis of terpenoids in edible fungi, especially in the generation of sesquiterpenes, diterpenes, and triterpenes. This paper is aim to provide an overview of biological functions and biosynthesis developed for utilizing the terpenoids in edible fungi.

Software testing guarantees the delivery of high-quality software products, and software defect prediction (SDP) has become an important part of software testing. Software defect prediction is divided into traditional software defect prediction and just-in-time software defect prediction (JIT-SDP). However, most of the existing software defect prediction frameworks are relatively simplified, which makes it extremely difficult to provide developers with more detailed reference information. To improve the effectiveness of software defect prediction and realize effective software testing resource allocation, this paper proposes a software defect prediction framework based on Nested-Stacking and heterogeneous feature selection. The framework includes three stages: data set preprocessing and feature selection, Nested-Stacking classifier, and model classification performance evaluation. The novel heterogeneous feature selection and nested custom classifiers in the framework can effectively improve the accuracy of software defect prediction. This paper conducts experiments on two software defect data sets (Kamei, PROMISE), and demonstrates the classification performance of the model through two comprehensive evaluation indicators, AUC, and F1-score. The experiment carried out large-scale within-project defect prediction (WPDP) and cross-project defect prediction (CPDP). The results show that the framework proposed in this paper has an excellent classification performance on the two types of software defect data sets, and has been greatly improved compared with the baseline models.

Inspired by the working principle of natural spiderweb and long-persistence phosphors, we have synthesized a spiderweb-like nanocomposite in which CoS quantum dots are confined in N-doped carbon frameworks/carbon nanotubes (CNTs). The intimate combination of three-dimensional conductive networks of CoS/CNTs with abundant active sites allows effective capture of sulfate radicals

The water extract of the fungal substance from Ganoderma resinaceum FQ23 solid-state fermentation with high-yield EGT (GSW) could ameliorate anxiety-like insomnia in mice by improving the antioxidant, neuroprotection and neuroendocrine regulation.

Angiotensin-converting enzyme 2 (ACE2) is a major cell entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Induction of ACE2 expression may represent an effective tactic employed by SARS-CoV-2 to facilitate its own propagation. However, the regulatory mechanisms of ACE2 expression after viral infection remain largely unknown. By employing an array of 45 different luciferase reporters, we identify that the transcription factor Sp1 positively and HNF4α negatively regulate the expression of ACE2 at the transcriptional levels in HPAEpiC cells, a human lung epithelial cell line. SARS-CoV-2 infection promotes and inhibits the transcription activity of Sp1 and HNF4α, respectively. The PI3K/AKT signaling pathway, which is activated by SARS-CoV-2 infection, is a crucial node for induction of ACE2 expression by increasing Sp1 phosphorylation, an indicator of its activity, and reducing HNF4α nuclear location. Furthermore, we show that colchicine could inhibit the PI3K/AKT signaling pathway, thereby suppressing ACE2 expression. Inhibition of Sp1 by either its inhibitor mithramycin A or colchicine reduces viral replication and tissue injury in Syrian hamsters infected with SARS-CoV-2. In summary, our study uncovers a novel function of Sp1 in regulating ACE2 expression and suggests that Sp1 is a potential target to reduce SARS-CoV-2 infection.

Quantum key distribution (QKD) networks are expected to enable information-theoretical secure (ITS) communication over a large-scale network. Most researches on relay-based QKD network assume that all relays are completely trustworthy, but the assumption is unrealistic in a complex network. The current study only analyzes the case of passive attacks by untrusted relays (e.g. eavesdropping). However, active attacks by untrusted relays (e.g. spoofing or interfering with the cooperation between honest nodes) are more serious threats and should not be ignored. Taking both passive and active attacks into account, we propose the ITSBFT-QKD networks to defend against untrusted nodes and achieve end-to-end key distribution. In end-to-end key distribution, multiple participating nodes are required to establish trust relationships and cooperate with each other. To prevent attackers from breaking trust relationship and gaining an unreasonable advantage, we incorporate a byzantine consensus scheme to establish and transmit trust relationships in a global QKD network perspective. Moreover, since the security of traditional consensus schemes is lower than the security requirement of QKD networks, we devise a byzantine fault tolerance (BFT) signature scheme to ensure the information-theoretic security of consensus. It provides a new way to construct signature schemes with point-to-point QKD keys in the presence of untrusted relays or nodes. The security of our scheme is analyzed thoroughly from multiple aspects. Our scheme can accommodate up to $ MIN\left( C-1,\lfloor \frac{N-1}{3} \rfloor \right) $ untrusted nodes, where $C$ is the node connectivity of the network and $N$ is the number of nodes in the network. Our scheme provides the highest level of security in currently relay-based QKD networks and will significantly promote the application of QKD networks., Comment: 13 pages,7 figures

We present an analysis of the ultraviolet luminosity function (UV LF) and star formation rate density of distant galaxies ($7.5 < z < 13.5$) in the `blank' fields of the Prime Extragalactic Areas for Reionization Science (PEARLS) survey combined with Early Release Science (ERS) data from the CEERS, GLASS and NGDEEP surveys/fields. We use a combination of SED fitting tools and quality cuts to obtain a reliable selection and characterisation of high-redshift ($z>6.5$) galaxies from a consistently processed set of deep, near-infrared imaging. Within an area of 110 arcmin$^{2}$, we identify 214 candidate galaxies at redshifts $z>6.5$ and we use this sample to study the ultraviolet luminosity function (UV LF) in four redshift bins between $7.5, 28 Pages, 4 Tables, 9 Figures, Submitted to ApJ

We report the large scale structure and clustering analysis of Ly$α$ emitters (LAEs) and Ly$α$ blobs (LABs) at $z=2.2-2.3$. Using 3,341 LAEs, 117 LABs, and 58 bright (Ly$α$ luminosity $L_{\rm Lyα}>10^{43.4}$ erg s$^{-1}$) LABs at $z=2.2-2.3$ selected with Subaru/Hyper Suprime-Cam (HSC), we calculate the LAE overdensity to investigate the large scale structure at $z=2$. We show that 74% LABs and 78% bright LABs locate in overdense regions, which is consistent with the trend found by previous studies that LABs generally locate in overdense regions. We find that one of our 8 fields dubbed J1349 contains $39/117\approx33\%$ of our LABs and $22/58\approx38\%$ of our bright LABs. A unique and overdense $24'\times12'$ ($\approx 40\times20$ comoving Mpc$^2$) region in J1349 has 12 LABs (8 bright LABs). By comparing to SSA22 that is one of the most overdense LAB regions found by previous studies, we show that the J1349 overdense region contains $\geq 2$ times more bright LABs than the SSA22 overdense region. We calculate the angular correlation functions (ACFs) of LAEs and LABs in the unique J1349 field and fit the ACFs with a power-law function to measure the slopes. The slopes of LAEs and LABs are similar, while the bright LABs show a $\approx 2$ times larger slope suggesting that bright LABs are more clustered than faint LABs and LAEs. We show that the amplitudes of ACFs of LABs are higher than LAEs, which suggests that LABs have a $\approx 10$ times larger galaxy bias and field-to-field variance than LAEs. The strong field-to-field variance is consistent with the large differences of LAB numbers in our 8 fields., 8 pages, 5 figures, and 1 table

Supplementary Material 2

The transport properties of matter have been widely investigated. In particular, shear viscosity over a wide parameter space is crucial for various applications, such as designing inertial confinement fusion (ICF) targets and determining the Rayleigh-Taylor instability. In this work, an extended random-walk shielding-potential viscosity model (RWSP-VM) [Phys. Rev. E 106, 014142] based on the statistics of random-walk ions and the Debye shielding effect is proposed to elevate the temperature limit of RWSP-VM in evaluating the shear viscosity of metals. In the extended model, we reconsider the collision diameter that is introduced by hard-sphere concept, hence, it is applicable in both warm and hot temperature regions (10^1-10^7 eV) rather than the warm temperature region (10^1-10^2 eV) in which RWSP-VM is applicable. The results of Be, Al, Fe, and U show that the extended model provides a systematic way to calculate the shear viscosity of arbitrary metals at the densities from about 0.1 to 10 times the normal density (the density at room temperature and 1 standard atmosphere). This work will help to develop viscosity model in wide region when combined with our previous low temperature viscosity model [AIP Adv. 11, 015043]., Comment: 6 pages, 5 figures

The formation of the first supermassive black holes is expected to have occurred in some most pronounced matter and galaxy overdensities in the early universe. We have conducted a sub-mm wavelength continuum survey of 54 $z\sim6$ quasars using the Submillimeter Common-User Bolometre Array-2 (SCUBA2) on the James Clerk Maxwell Telescope (JCMT) to study the environments around $z \sim 6$ quasars. We identified 170 submillimeter galaxies (SMGs) with above 3.5$\sigma$ detections at 450 or 850 \um\, maps. Their FIR luminosities are 2.2 - 6.4 $\times$ 10$^{12} L_{\odot}$, and star formation rates are $\sim$ 400 - 1200 M$_{\odot}$ yr$^{-1}$. We also calculated the SMGs differential and cumulative number counts in a combined area of $\sim$ 620 arcmin$^2$. To a $4\sigma$ detection (at $\sim$ 5.5 mJy), SMGs overdensity is $0.68^{+0.21}_{-0.19}$($\pm0.19$), exceeding the blank field source counts by a factor of 1.68. We find that 13/54 quasars show overdensities (at $\sim$ 5.5 mJy) of $\delta_{SMG}\sim$ 1.5 - 5.4. The combined area of these 13 quasars exceeds the blank field counts with the overdensity to 5.5 mJy of \dsmg $\sim$ $2.46^{+0.64}_{-0.55}$($\pm0.25$) in the regions of $\sim$ 150 arcmin$^2$. However, the excess is insignificant on the bright end (e.g., 7.5 mJy). We also compare results with previous environmental studies of Lyman alpha emitters (LAEs) and Lyman-Break Galaxies (LBGs) on a similar scale. Our survey presents the first systematic study of the environment of quasars at $z\sim6$. The newly discovered SMGs provide essential candidates for follow-up spectroscopic observations to test whether they reside in the same large-scale structures as the quasars and search for protoclusters at an early epoch., Comment: 12 pages, 8 figures and 2 tables, accepted for publication in ApJ

Supplementary Material 1

Supplementary Material 1

Additional file 1. Supplementary figures and tables.

Cosmic variance introduces significant uncertainties into galaxy number density properties when surveying the high-z Universe with a small volume, such uncertainties produce the field-to-field variance of galaxy number $σ_{g}$ in observational astronomy. This uncertainty significantly affects the Luminosity Functions (LF) measurement of Lya Emitters (LAEs). For most previous Lya LF studies, $σ_{g}$ is often adopted from predictions by cosmological simulations, but barely confirmed by observations. Measuring cosmic variance requires a huge sample over a large volume, exceeding the capabilities of most astronomical instruments. In this study, we demonstrate an observational approach for measuring the cosmic variance contribution for $z\approx2.2$ Lya LFs. The LAE candidates are observed using narrowband and broadband of the Subaru/Hyper Suprime-Cam (HSC), with 8 independent fields, making the total survey area $\simeq11.62$deg$^2$ and a comoving volume of $\simeq8.71\times10^6$Mpc$^3$. These eight fields are selected using the project of MAMMOTH. We report a best-fit Schechter function with parameters $α=-1.75$ (fixed), $L_{Lyα}^{*}=5.18_{-0.40}^{+0.43} \times 10^{42}$erg s$^{-1}$ and $ϕ_{Lya}^{*}=4.87_{-0.55}^{+0.54}\times10^{-4}$Mpc$^{-3}$ for the overall Lya LFs. After clipping out the regions that can bias the cosmic variance measurements, we calculate $σ_{g}$, by sampling LAEs within multiple pointings assigned on the field image. We investigate the relation between $σ_{g}$ and survey volume $V$, and fit a simple power law: $σ_g=k\times(\frac{V_{\rm eff}}{10^5 {\rm Mpc}^3})^β$. We find best-fit values of $-1.209_{-0.106}^{+0.106}$ for $β$ and $0.986_{-0.100}^{+0.108}$ for k. We compare our measurements with predictions from simulations and find that the cosmic variance of LAEs might be larger than that of general star-forming galaxies., 14 pages, 7 figures

Quantum key distribution (QKD) can provide fundamentally proven security for secure communication. Toward application, the secret key rate (SKR) is a key figure of merit for any QKD system. So far, the SKR has been limited to about a few megabit-per-second. Here we report a QKD system that is able to generate key at a record high SKR of 115.8 Mb/s over 10-km standard fibre, and to distribute key over up to 328 km of ultra-low-loss fibre. This attributes to a multi-pixel superconducting nanowire single-photon detector with ultrahigh counting rate, an integrated transmitter that can stably encode polarization states with low error, a fast post-processing algorithm for generating key in real time and the high system clock-rate operation. The results demonstrate the feasibility of practical high-rate QKD with photonic techniques, thus opening its possibility for widespread applications.

In this paper, we present a Ly$α$ halo extended to $\sim200$ kpc identified by stacking $\sim 3300$ Ly$α$ emitters at $z=2.2-2.3$. We carry out imaging observations and data reduction with Subaru/Hyper Suprime-Cam (HSC). Our total survey area is $\sim12$ deg$^2$ and imaging depths are $25.5-27.0$ mag. Using the imaging data, we select 1,240 and 2,101 LAE candidates at $z=2.2$ and 2.3, respectively. We carry out spectroscopic observations of our LAE candidates and data reduction with Magellan/IMACS to estimate the contamination rate of our LAE candidates. We find that the contamination rate of our sample is low (8%). We stack our LAE candidates with a median stacking method to identify the Ly$α$ halo at $z=2$. We show that the Ly$α$ halo is extended to $\sim200$ kpc at a surface brightness level of $10^{-20}$ erg s$^{-1}$ cm$^{-2}$ arcsec$^{-2}$. Comparing to previous studies, our Ly$α$ halo is more extended at radii of $\sim25-100$ kpc, which is not likely caused by the contamination in our sample but by different redshifts and fields instead. To investigate how central galaxies affect surrounding LAHs, we divide our LAEs into subsamples based on the Ly$α$ luminosity ($L_{\rm Lyα}$), rest-frame Ly$α$ equivalent width (EW$_0$), and UV magnitude (M$_{\rm uv}$). We stack the subsamples and find that higher $L_{\rm Lyα}$, lower EW$_0$, and brighter M$_{\rm uv}$ cause more extended halos. Our results suggest that more massive LAEs generally have more extended Ly$α$ halos., 9 pages, 7 figures, and 2 tables

Additional file 1: Figure S1. Preparation and Characterization of CLT-IR820 and stability of HCR NPs. (A) Schematic illustration of the synthesis of HA-HCQ. (B) 1H NMR results of HA-HCQ. (C) The Tyndall effect of HCR NPs at the indicated time points. (D) The Tyndall effect of CLT-IR820. (E) Size distribution of CLT-IR820. (F) UV-vis absorption spectra of CLT-IR820. (G) Zeta potential of CLT-IR820. (H) TEM image of CLT-IR820. Scale bar: 100 nm. Figure S2. Cytotoxicity of HCR NPs in vitro. (A-B) Quantification of DLD-1 and HCT116 cells co-cultured with CLT, CLT+IR820+Laser, CLT-IR820+Laser, and HCR NPs+Laser in the EDU assay. (λ=808 nm, P =1.0 W/cm2; 40 s). ***P < 0.001. (C-E) Representative images of the colony formation of DLD-1 and HCT116 cells treated with HA-HCQ, CLT, IR820+Laser, CLT+ IR820+Laser, CLT- IR820+Laser, and HCR NPs+Laser. (λ=808 nm, P =1 W/cm2; 60 s). ***P < 0.001. (F) Cell imaging showing the survival of DLD-1 and HCT116 cells treated with CLT, CLT+ IR820+Laser, CLT- IR820+Laser, and HCR NPs+Laser. Live cells were marked with Calcein-AM (green fluorescence), while dead cells were marked with propidium iodide (red fluorescence). Scale bar: 50 µm. (λ=808 nm, P =1 W/cm2; 2 min). Figure S3. Apoptosis and inhibition of autophagy. (A) Fluorescent images of JC-1-stained DLD-1 and HCT116 cells, including CLT, CLT+IR820+Laser, CLT-IR820+Laser, and HCR NPs+Laser treatments. Scale bar: 50 μm. (λ=808 nm, P=1 W/cm2; 2 min). (B) Fluorescent images of DQBSA-stained DLD-1 and HCT116 cells, including HA-CLT-IR820, and HCR NPs treatments. Scale bar: 50 μm. (λ=808 nm, P=1 W/cm2; 2 min). (C) Immunoblot analysis of p62 and LC3-II in DLD-1 and HCT116 cells treated with CLT, HA-CLT-IR820, and HCR NPs. (λ=808 nm, P=1 W/cm2; 2 min). Figure S4. HCR NPs-mediated ROS inhibited colorectal cancer cell survival. (A-B) Flow cytometry statistical analysis of intracellular ROS generation in DLD-1 and HCT116 cells treated with HCR NPs+Laser with or without NAC treatment using DCFH-DA as a probe. (λ=808 nm, P=1 W/cm2; 2 min). (C-E) The proliferation of DLD-1 and HCT116 cells treated with HCR NPs+Laser with or without NAC treatment as measured by EdU assay. Scale bar: 50 μm. (λ=808 nm, P =1 W/cm2; 40 s). ***P < 0.001. (F-G) Flow cytometry analysis of intracellular ROS generation in DLD-1 and HCT116 cells treated with IR820+Laser or HCR NPs+Laser using DCFH-DA as a probe. (λ=808 nm, P=1 W/cm2; 2 min). Figure S5. The photothermal capacity of HCR NPs in vivo. (A) Schematic illustration of the photothermal capacity of HCR NPs in vivo. (B) Fluorescence images of tumors and major organs at 24 h after injection with IR820, CLT-IR820, free HA+HCR NPs, and HCR NPs. (C) In vivo thermal analysis of different groups of treated mice. (λ=808 nm, P=1 W/cm2; 5 min).

Objectives To explore the level of active aging and correlates among rural elderly in Xiangtan County, China. Methods A cross-sectional survey was conducted from July to November 2019. A total of 945 rural elderly from 3 towns in Xiangtan County, China, were investigated by using the positive aging evaluation questionnaire (PAEQ), the activity of daily living scale (ADL), and the depression in old-age scale (DIA-S). Results The average score in the PAEQ among the rural elderly of Xiangtan County was 72.81 (range = 21–105). A moderate negative correlation was found between the score in the PAEQ and those in the ADL (r = −0.361) and DIA-S (r = −0.495). Symptoms of depression (β: −0.321, P = 0.001), number of chronic diseases (β: −0.281, P = 0.001), subjective economic status (β: 0.239, P = 0.001), ADL (β: −0.196, P = 0.001), education (β: 0.126, P = 0.001), number of children (β: 0.097, P = 0.001), and marital status (β: −0.060, P = 0.001) were significantly associated with levels of active aging in rural elderly, whereas gender and age were not independently related to active aging. Conclusions The level of active aging is at a moderately high level in the Chinese elderly in rural areas in Xiangtan County. The focus group of active aging in rural areas should be elderly people suffering from chronic diseases, physical decline, poor education and economic conditions, childlessness, and those without partners.

Background Current evidence suggests that acupuncture is an effective adjunctive therapy that can bring potential benefits to patients with cardiac arrhythmias. However, there are relevant gaps in the optimal therapeutic strategy, which may cause uncertainties on the best practice of acupuncture treatment for arrhythmia. We aim to develop consensus-based recommendations for clinical guidance on acupuncture treatment of cardiac arrhythmias. Methods A multidisciplinary panel of specialists was invited to participate in a two-round semi-open clinical issue investigation. Meanwhile, relevant literature reviews were searched in 3 databases to provide evidence. Subsequently, an initial consensus voting list on acupuncture as an adjunctive therapy for cardiac arrhythmias was derived from the clinical investigation and literature review. Finally, 30 authoritative experts reached a consensus on the key issues of the voting list by a three-round modified Delphi survey. Consensus was defined when >80% agreement was achieved. Results Following the three-round Delphi survey, there were 32 items (91.43%) finally reaching consensus, including the following 5 domains: (I) the benefits of acupuncture for the appropriate population; (II) the general therapeutic principle; (III) the acupuncture strategy; (IV) the relevant adverse events; (V) others. Conclusions Consensus was achieved on some key elements. Given the lack of guidelines and the substantial heterogeneity of previous studies, these recommendations are of value in providing guidance for clinical practice of acupuncturists and in assisting patients with arrhythmia to obtain standardized acupuncture treatment. It also pointed out some problems that need to be carefully explored in future studies.

Herein, a solid-state fermentation (SSF) system of

Background Both Response Evaluation Criteria in Solid Tumors (RECIST) and tumor regression grade (TRG) play key roles in evaluating tumor response. We analyzed the consistency of TRG and RECIST 1.1 for gastric cancer (GC) patients and compared their prognostic values. Methods Patients with GC who received preoperative chemotherapy or chemoimmunotherapy and had records of TRG from December 2013 to October 2021 were enrolled retrospectively. TRG 0–1 and 2–3 are considered as corresponding to complete response (CR)/partial response (PR) and stable disease (SD)/progress disease (PD) in RECIST 1.1, respectively. The primary endpoints were disease-free survival (DFS) and overall survival (OS). The consistency of RECIST and TRG was examined by kappa statistics. Survival analysis was performed using the Kaplan Meier method. Result One hundred fifty seven GC patients were enrolled, including 125 with preoperative chemotherapy and 32 with chemoimmunotherapy. Among them, 56 patients had measurable lesions. Only 19.6% (11/56) of the patients had consistent results between RECIST 1.1 and TRG. TRG was correlated with both OS and DFS (P = 0.02 and 0.03, respectively) while response according to RECIST1.1 was not (P = 0.86 and 0.23, respectively). The median DFS had not reached in the TRG 0–1 group and was 16.13 months in TRG 2–3 group. TRG 2–3 was associated with young age and peritoneal or liver metastasis. Besides, preoperative chemoimmunotherapy had a significantly higher pCR rate than chemotherapy alone (34.4% vs 8.0%, P Conclusion TRG was in poor agreement with RECIST 1.1. TRG was better than RECIST 1.1 in predicting DFS and OS for GC patients who received preoperative therapy.

Background Diarrhea-predominant irritable bowel syndrome (IBS-D) is the most common subtype of IBS. Acupuncture is commonly used to treat IBS-D, but its effect is uncertain because of the poor quality of prior studies. This trial aims to evaluate the efficacy and safety of acupuncture treatment for IBS-D through comparisons with sham acupuncture. Methods/design This is a large-scale, multi-center, randomized, two-arm interventional clinical trial. Participants will take part in a total of 20 weeks of study, which contained 3 phases: 2-week screening, 6-week treatment, and 12-week follow-up. Based on the composite response rate of the primary endpoint in our pilot study (a sham acupuncture response rate of 27% and a true acupuncture of approximately 45%), 280 randomly allocated participants were planned. Eligible participants will be randomly assigned to the true acupuncture group and sham acupuncture group according to a ratio of 1:1, and a total of 15 sessions of treatment overall 6-week treatment period will be brought. The primary endpoint is a composite response rate at week 6, and the responder is defined as who responses in both abdominal pain intensity and stool consistency. Furthermore, composite response rates at other weeks, IBS Symptom Severity Scale, IBS Quality of Life, Adequate Relief scale, and individual IBS symptoms (abdominal pain, bloating, stool frequency) are chosen as secondary endpoints. Discussion This trial may provide high-quality evidence for the efficacy and safety of acupuncture in the treatment of IBS-D. The results of this study will be published in peer-reviewed journals. Trial registration Chinese Clinical Trial Registry: ChiCTR2100044762. Registered on 26 March 2021.

Background Cordyceps militaris is a traditional medicinal fungus contains a variety of functional ingredients and has been developed as an important mushroom food recently. Ergothioneine, one of the antioxidative compounds in C. militaris, is benefits on aging-related diseases and therefore became a novel functional food nutritive fortifier. Currently, the main diet source of ergothioneine is mushroom food. However, the mushroom farming faces the problems such as rather low ingredient yield and spontaneous degeneration associated fruiting body that restricts large scale production of ergothioneine. Results In this study, we excavated the ergothioneine synthetases in mushroom and modified the genes in C. militaris to construct a new ergothioneine synthesis pathway. By further introducing this pathway into C. militaris genome, we succeeded to increase the ingredients’ production of engineering strain, the highest amount of ergothioneine and cordycepin were up to 2.5 g/kg dry weight and 2 g/L, respectively. Additionally, the expression of ergothioneine synthetase genes in the shape-mutated degenerative C. militaris could recover the ability of degenerative strain to produce high amount of ingredients, suggesting the metabolic regulation of ergothioneine might release the symptom of mushroom degeneration. Conclusion This study reveals a new pathway to fulfill the market needs of functional mushroom food and food fortifier ergothioneine. It implied the mycelium of C. militaris could be engineered as a novel medicinal mushroom food which could produce higher amount of valuable ingredients. Graphical abstract

The medicinal mushroom Cordyceps militaris contains abundant valuable bioactive ingredients that have attracted a great deal of attention in the pharmaceutical and cosmetic industries. However, the development of this valuable mushroom faces the obstacle of lacking powerful genomic engineering tools. Here, by excavating the endogenous tRNA-processed element, introducing the extrachromosomal plasmid and alongside with homologous template, we develop a marker-free CRISPR-Cas9-TRAMA genomic editing system to achieve the multiplex gene precise editing and large synthetic cluster deletion in C. militaris. We further operated editing in the synthetases of cordycepin and ergothioneine to demonstrate the application of Cas9-TRAMA system in protein modification, promoter strength evaluation and 10 kb metabolic synthetic cluster deletion. The Cas9-TRAMA system provides a scalable method for excavating the valuable metabolic resource of medicinal mushrooms and constructing a mystical cellular pathway to elucidate the complex cell behaviours of the edible mushroom.

To understand the morphological and structural characteristics of root nodules in Podocarpus macrophyllus and their development, this study prepared P. macrophyllus root nodule samples at the young, mature, and senescent stages. Optical microscopy and transmission electron microscopy (SEM) revealed that new nodules can be formed on roots and senescent nodules; new nodules formed on the roots are nearly spherical and have an internal structure similar to finite nodules; new nodules on senescent nodules are formed by extension and differentiation of the vascular cylinder of the original nodules; and these new nodules are nested at the base of the original nodules, which create growth space for new nodules by dissociating the cortical tissue; clusters of nodules are formed after extensive accumulation, and the growth pattern is similar to that of infinite nodules; the symbiotic bacteria of P. macrophyllus root nodules mainly invade from the epidermal intercellular space of the roots and migrate along the intercellular space of the nodule cortex; infected nodule cortex cells have a well-developed inner membrane system and enlarged and loose nuclei; and unique Frankia vesicles, and rhizobia cysts, and bacteriophages can all develop. Compared with common leguminous and nonleguminous plant nodules, P. macrophyllus root nodules are more complex in morphology, structure and composition. From the perspective of plant system evolution, the rhizobium nodules in leguminous angiosperms and Frankia nodules in nonleguminous angiosperms are most likely two branches derived from the nodules in gymnosperms, such as P. macrophyllus. The conclusions of this study can provide a theoretical basis for the developmental biology of P. macrophyllus root nodules and the evolutionary pattern of plant symbionts.HighlightsWe discuss from the perspective of cell developmental biology, the rhizobium nodules in leguminous angiosperms and Frankia nodules in nonleguminous angiosperms are most likely two branches derived from the nodules in gymnosperms, such as Podocarpus macrophyllus.

IntroductionHypertension is a common risk factor for cardiovascular disease. Transcutaneous electrical acupoint stimulation (TEAS) may be effective for hypertension, but the evidence remains limited. The aim of this study is to evaluate the effectiveness and safety of the smart phone-based TEAS as adjunctive therapy for hypertension.Methods and analysisThis study is a 52-week cluster randomised controlled trial with 1600 hypertension patients in 32 community health service centres. Patients who meet the inclusion criteria will be randomised into usual care group or TEAS group in a 1:1 ratio. All patients will be provided with usual care as recommended by the guidelines. In addition to this, patients in the TEAS group will receive non-invasive acupoint electrical stimulation for 30 min at home, 4 times weekly for 12 weeks. The primary outcome will be the mean difference in the changes in office systolic blood pressure from baseline to 12 weeks between TEAS and usual care groups. Secondary outcomes will include the change of mean diastolic blood pressure, proportion of patients with controlled blood pressure (blood pressure Ethics and disseminationThis study has been approved by ethics committee of Beijing University of Chinese Medicine (No. 2020BZHYLL0104). Written informed consent will be obtained from all patients before randomisation. Trial results will be disseminated in peer-reviewed publications.Trial registration numberChiCTR2000039400.

Purpose Acupuncture has been widely used in the treatment of knee osteoarthritis (KOA), but the selection of acupoints is indeterminate and lacks biological basis. The skin temperature of acupoints can reflect the state of local tissue and may be a potential factor for guiding acupoint selection. This study aims to compare the skin temperature of acupoints between KOA patients and the healthy population. Study design and methods This is a protocol for a cross-sectional case-control study with 170 KOA patients and 170 age- and gender-matched healthy individuals. Diagnosed patients aged 45 to 70 will be recruited in the KOA group. Participants in the healthy group will be matched with the KOA group based on mean age and gender distribution. Skin temperature of 11 acupoints (ST35, EX-LE5, GB33, GB34, EX-LE2, ST34, ST36, GB39, BL40, SP9, SP10) will be extracted from infrared thermography (IRT) images of the lower limbs. Other measurements will include demographic data (gender, age, ethnicity, education, height, weight, BMI) and disease-related data (numerical rating scale, pain sites, duration of pain, pain descriptors, pain activities). Discussion The results of this study will provide biological evidence for acupoint selection. This study is a precondition for follow-up studies, in which the value of optimized acupoint selection will be verified. Trial registration ChiCTR2200058867.

Acute pancreatitis (AP), an inflammatory disorder of the pancreas with a high hospitalization rate, frequently leads to systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). However, therapeutic targets for effective treatment and early intervention of AP are still urgently required to be identified. Here, we have observed that the expression of pancreatic lincRNA-EPS, a long intergenic non-coding RNA, is dynamically changed during both caerulein-induced AP (Cer-AP) and sodium taurocholate-induced severe AP (NaTc-SAP). The expression pattern of lincRNA-EPS is negatively correlated with the typical inflammatory genes such as IL-6, IL-1β, CXCL1, and CXCL2. Further studies indicate that knockout of lincRNA-EPS aggravates the pathological symptoms of AP including more induction of serum amylase and lipase, severe edema, inflammatory cells infiltration and acinar necrosis in both experimental AP mouse models. Besides these intrapancreatic effects, lincRNA-EPS also protects against tissue damages in the extra-pancreatic organs such as lung, liver, and gut in the NaTc-SAP mouse model. In addition, we have observed more serum pro-inflammatory cytokines TNF-α and IL-6 in the lincRNA-EPS-/- NaTc-SAP mice and more extracellular HMGB1 around injured acinar cells in the pancreas from lincRNA-EPS-/- NaTc-SAP mice, compared with their respective controls. Pharmacological inhibition of NF- κ B activity by BAY11-7082 significantly abolishes the suppressive effect of lincRNA-EPS on TLR4 ligand-induced inflammatory genes in macrophages. Our study has described a protective role of lincRNA-EPS in alleviating AP and SAP, outlined a novel pathway that lincRNA-EPS suppresses HMGB1-NF- κ B-dependent inflammatory response in pancreatic macrophages and provided a potential therapeutic target for SAP.

The interface failure (micro-annulus and de-bonding) at the first interface between cement sheath and formation, or at the second interface between cement sheath and casing can be easily caused by alternating change of internal pressure and temperature in the casing during large-scale multistage hydraulic fracturing in shale-gas well. It is likely to have a great impact on casing stress and pose a potential threat to casing failure, especially the casing under non-uniform in-situ stress (NUS). Hence, based on the generation mechanism of micro-annulus in the first and second interface, the mechanical model coupling the casing and cement sheath as well as formation under non-uniform in-situ stress is presented with due consideration of the effect of interface failure status on casing stress. In the model, the failure interface with micro-annulus is considered by adopting boundary conditions of smooth contact, and the interface without micro-annulus is considered by adopting boundary conditions of ideal complete contact. The stress and displacement equations are derived by the semi analytical method, and the linear algebra equations and analytical solution of the equations are obtained based on the different contact status. The associated calculating program to calculate stress distribution of casing and cement sheath is developed and programmed. The effects of physical parameter and geometrical parameters of formation, cement sheath and casing, contact status of cement sheath boundary and non-uniformity of in-situ stress on casing stress have been systematically investigated.

OBJECTIVE To assess the efficacy of intensive acupuncture (3 times weekly for 8 weeks) versus sham acupuncture for knee osteoarthritis (OA). METHODS In this multicenter, randomized, sham-controlled trial, patients with knee OA were randomly assigned to receive electroacupuncture (EA), manual acupuncture (MA), or sham acupuncture (SA) 3 times weekly for 8 weeks. Participants, outcome assessors, and statisticians were blinded with regard to treatment group assignment. The primary outcome measure was response rate, which is the proportion of participants who simultaneously achieved minimal clinically important improvement in pain and function by week 8. The primary analysis was conducted using a Z test for proportions in the modified intent-to-treat population, which included all randomized participants who had ≥1 post-baseline measurement. RESULTS Of the 480 participants recruited in the trial, 442 were evaluated for efficacy. The response rates at week 8 were 60.3% (91 of 151), 58.6% (85 of 145), and 47.3% (69 of 146) in the EA, MA, and SA groups, respectively. The between-group differences were 13.0% (97.5% confidence interval [97.5% CI] 0.2%, 25.9%; P = 0.0234) for EA versus SA and 11.3% (97.5% CI -1.6%, 24.4%; P = 0.0507) for MA versus SA. The response rates in the EA and MA groups were both significantly higher than those in the SA group at weeks 16 and 26. CONCLUSION Among patients with knee OA, intensive EA resulted in less pain and better function at week 8, compared with SA, and these effects persisted though week 26. Intensive MA had no benefit for knee OA at week 8, although it showed benefits during follow-up.