Correction: FoQDE2-dependent milRNA promotes Fusarium oxysporum f. sp. cubense virulence by silencing a glycosyl hydrolase coding gene expression.

[This corrects the article DOI: 10.1371/journal.ppat.1010157.].

FoQDE2-dependent milRNA promotes Fusarium oxysporum f. sp. cubense virulence by silencing a glycosyl hydrolase coding gene expression.

MicroRNAs (miRNAs) are small non-coding RNAs that regulate protein-coding gene expression primarily found in plants and animals. Fungi produce microRNA-like RNAs (milRNAs) that are structurally similar to miRNAs and functionally important in various biological processes. The fungus Fusarium oxysporum f. sp. cubense (Foc) is the causal agent of Banana Fusarium vascular wilt that threatens global banana production. It remains uncharacterized about the biosynthesis and functions of milRNAs in Foc. In this study, we investigated the biological function of milRNAs contributing to Foc pathogenesis. Within 24 hours post infecting the host, the Argonaute coding gene FoQDE2, and two Dicer coding genes FoDCL1 and FoDCL2, all of which are involved in milRNA biosynthesis, were significantly induced. FoQDE2 deletion mutant exhibited decreased virulence, suggesting the involvement of milRNA biosynthesis in the Foc pathogenesis. By small RNA sequencing, we identified 364 small RNA-producing loci in the Foc genome, 25 of which were significantly down-regulated in the FoQDE2 deletion mutant, from which milR-87 was verified as a FoQDE2-depedent milRNA based on qRT-PCR and Northern blot analysis. Compared to the wild-type, the deletion mutant of milR-87 was significantly reduced in virulence, while overexpression of milR-87 enhanced disease severity, confirming that milR-87 is crucial for Foc virulence in the infection process. We furthermore identified FOIG_15013 (a glycosyl hydrolase-coding gene) as the direct target of milR-87 based on the expression of FOIG_15013-GFP fusion protein. The FOIG_15013 deletion mutant displayed similar phenotypes as the overexpression of milR-87, with a dramatic increase in the growth, conidiation and virulence. Transient expression of FOIG_15013 in Nicotiana benthamiana leaves activates the host defense responses. Collectively, this study documents the involvement of milRNAs in the manifestation of the devastating fungal disease in banana, and demonstrates the importance of milRNAs in the pathogenesis and other biological processes. Further analyses of the biosynthesis and expression regulation of fungal milRNAs may offer a novel strategy to combat devastating fungal diseases.

Ultraviolet attenuates centromere-mediated meiotic genome stability and alters gametophytic ploidy consistency in flowering plants.

Ultraviolet (UV) radiation influences development and genome stability in organisms; however, its impact on meiosis, a special cell division essential for the delivery of genetic information across generations in eukaryotes, has not yet been elucidated. In this study, by performing cytogenetic studies, we reported that UV radiation does not damage meiotic chromosome integrity but attenuates centromere-mediated chromosome stability and induces unreduced gametes in Arabidopsis thaliana. We showed that functional centromere-specific histone 3 (CENH3) is required for obligate crossover formation and plays a role in the protection of sister chromatid cohesion under UV stress. Moreover, we found that UV specifically alters the orientation and organization of spindles and phragmoplasts at meiosis II, resulting in meiotic restitution and unreduced gametes. We determined that UV-induced meiotic restitution does not rely on the UV Resistance Locus8-mediated UV perception and the Tapetal Development and Function1- and Aborted Microspores-dependent tapetum development, but possibly occurs via altered JASON function and downregulated Parallel Spindle1. This study provides evidence that UV radiation influences meiotic genome stability and gametophytic ploidy consistency in flowering plants.

High-Precision Atom Interferometer-Based Dynamic Gravimeter Measurement by Eliminating the Cross-Coupling Effect.

A dynamic gravimeter with an atomic interferometer (AI) can perform absolute gravity measurements with high precision. AI-based dynamic gravity measurement is a type of joint measurement that uses an AI sensor and a classical accelerometer. The coupling of the two sensors may degrade the measurement precision. In this study, we analyzed the cross-coupling effect and introduced a recovery vector to suppress this effect. We improved the phase noise of the interference fringe by a factor of 1.9 by performing marine gravity measurements using an AI-based gravimeter and optimizing the recovery vector. Marine gravity measurements were performed, and high gravity measurement precision was achieved. The external and inner coincidence accuracies of the gravity measurement were ±0.42 mGal and ±0.46 mGal after optimizing the cross-coupling effect, which was improved by factors of 4.18 and 4.21 compared to the cases without optimization.

Dependence of the ellipse fitting noise on the differential phase between interferometers in atom gravity gradiometers.

Ellipse fitting is widely used in the extraction of the differential phase between atom interferometers amid substantial common phase noise. This study meticulously examines the dependency of extraction noise on the differential phase between atom interferometers during ellipse fitting. It reveals that the minimum extraction noise can manifest at distinct differential phases, contingent upon the dominance of different noise types. Moreover, the outcomes are influenced by whether the interferometers undergo simultaneous detection or not. Our theoretical simulations find empirical validation in a compact horizontal atom gravity gradiometer. The adjustment of the differential phase significantly enhances measurement sensitivity, culminating in a differential gravity resolution of 1.6 × 10-10 g @ 4800 s.

Transhepatectomy combined with arterial chemoembolization and transcatheter arterial chemoembolization in the treatment of hepatocellular carcinoma: a clinical prognostic analysis.

BACKGROUND: The prognosis of patients undergoing hepatectomy combined with transarterial chemoembolization (TACE) and TACE alone was examined in order to better understand the role of hepatectomy in the treatment of hepatocellular carcinoma (HCC). In this work, we also created a model and investigated the variables influencing overall survival (OS) in HCC patients. METHODS: Retrospective analysis of 1083 patients who received TACE alone as the control group and 188 patients who received TACE after surgery in a total of 1271 HCC patients treated with LR + TACE or TACE at three third-class hospitals in China. It was done using the Propensity Score Matching (PSM) technique. The differences in OS between the two groups were compared, and OS-influencing factors were looked at. The main endpoint is overall survival. In this study, the COX regression model was used to establish the nomogram. RESULTS: The median OS of the LR + TACE group was not attained after PSM. The median OS for the TACE group was 28.8 months (95% CI: 18.9-38.7). The median OS of the LR + TACE group was higher than that of the TACE group alone, indicating a significant difference between the two groups (χ2 = 16.75, P < 0.001). While it was not achieved in the LR + TACE group, the median OS for patients with lymph node metastases in the TACE group alone was 18.8 months. The two groups differed significantly from one another (χ2 = 4.105, P = 0.043). In patients with distant metastases, the median OS of the LR + TACE treatment group was not achieved, and the median OS of the TACE group alone was 12.0 months. The difference between the two groups was sizable (χ2 = 5.266, P = 0.022). The median OS for patients with PVTT following PSM was 30.1 months in the LR + TACE treatment group and 18.7 months in the TACE alone group, respectively. The two groups differed significantly from one another (χ2 = 5.178, P = 0.023); There was no discernible difference between the two groups in terms of median overall survival (OS), which was 30.1 months for patients with lymph node metastasis and 19.2 months for those without (P > 0.05); Regarding the median OS for patients with distant metastases, which was not achieved and 8.5 months, respectively, there was a significant difference between the two groups (χ2 = 5.759, P = 0.016). We created a new nomogram to predict 1-, 2-, and 3-year survival rates based on multiple independent predictors in COX multivariate analysis. The cohort's C-index is 0.705. The area under the curve (AUC value) for predicting 1-, 2-, and 3-year survival rates were shown by the subject operating characteristic (ROC) curve linked to the nomogram to be 0.730, 0.728, and 0.691, respectively. CONCLUSIONS: LR + TACE can increase OS, delay tumor recurrence, and improve prognosis in HCC patients when compared to TACE alone. Additionally, the nomogram we created does a good job of forecasting the 1-year survival rate of hepatocellular carcinoma.

Changes in brain functional networks in remitted major depressive disorder: a six-month follow-up study.

BACKGROUND: Patients with remitted major depressive disorder (rMDD) show abnormal functional connectivity of the central executive network (CEN), salience networks (SN) and default mode network (DMN). It is unclear how these change during remission, or whether changes are related to function. METHODS: Three spatial networks in 17 patients with rMDD were compared between baseline and the six-month follow-up, and to 22 healthy controls. Correlations between these changes and psychosocial functioning were also assessed. RESULTS: In the CEN, patients at baseline had abnormal functional connectivity in the right anterior cingulate, right dorsolateral prefrontal cortex (DLPFC) and inferior parietal lobule (IPL) compare with HCs. There were functional connection differences in the right DLPFC and left IPL at baseline during follow-up. Abnormal connectivity in the right DLPFC and medial prefrontal cortex (mPFC) were found at follow-up. In the SN, patients at baseline had abnormal functional connectivity in the insula, left anterior cingulate, left IPL, and right precuneus; compared with baseline, patients had higher connectivity in the right DLPFC at follow-up. In the DMN, patients at baseline had abnormal functional connectivity in the right mPFC. Resting-state functional connectivity of the IPL and DLPFC in the CEN correlated with psychosocial functioning. CONCLUSIONS: At six-month follow-up, the CEN still showed abnormal functional connectivity in those with rMDD, while anomalies in the SN and DMN has disappeared. Resting-state functional connectivity of the CEN during early rMDD is associated with psychosocial function. CLINICAL TRIALS REGISTRATION: Pharmacotherapy and Psychotherapy for MDD after Remission on Psychology and Neuroimaging. https://www. CLINICALTRIALS: gov/ , registration number: NCT01831440 (15/4/2013).

Accuracy Improvement of a Compact 85Rb Atom Gravimeter by Suppressing Laser Crosstalk and Light Shift.

We design and implement a compact 85Rb atom gravimeter (AG). The diameter of the sensor head is 35 cm and the height is 65 cm; the optical and electronic systems are installed in four standard 3U cabinets. The measurement accuracy of this AG is improved by suppress laser crosstalk and light shift. In addition, the angle of the Raman laser reflector is adjusted and locked, and the attitude of the sensing head is automatically adjusted, and the vibration noise is also compensated. The comparison measurement results between this AG and the superconducting gravimeter indicate that its long-term stability is 0.65 µGal @50000 s.

Feedback control of atom trajectories in a horizontal atom gravity gradiometer.

The coincidence between the atom trajectory and the Raman pulse sequence is very important for an intersection type atom interferometer. Here we present a feedback control technique for the atom trajectories in our horizontal gravity gradiometer, which improves the stabilities of the trajectories by about 2 orders of magnitude. Through the further study of the dependence of the interferometer contrasts on the atom trajectories, we lock the trajectories at optimal positions. And by this technique, the sensitivity of the gravity gradiometer is improved from 982 E/Hz1/2 to 763 E/Hz1/2, while the long-term stability is enhanced more significantly and reaches 8.9 E after an integration time of 6000 s. This work may provide hints to other experiments based on intersection type atom interferometers.

Balanced Coherence Times of Atomic Qubits of Different Species in a Dual 3×3 Magic-Intensity Optical Dipole Trap Array.

We construct a polarization-mediated magic-intensity (MI) optical dipole trap (ODT) array, in which the detrimental effects of light shifts on the mixed-species qubits are efficiently mitigated so that the coherence times of the mixed-species qubits are both substantially enhanced and balanced for the first time. This mixed-species magic trapping technique relies on the tunability of the coefficient of the third-order cross term and ground state hyperpolarizability, which are inherently dependent on the degree of circular polarization of the trapping laser. Experimentally, polarization of the ODT array for ^{85}Rb qubits is finely adjusted to a definite value so that its working magnetic field required for magic trapping amounts to the one required for magically trapping ^{87}Rb qubits in another ODT array with fully circular polarization. Ultimately, in such a polarization-mediated MI-ODT array, the coherence times of ^{87}Rb and ^{85}Rb qubits are, respectively, enhanced up to 891±47 ms and 943±35 ms. Moreover, we reveal that the noise of the elliptic polarization causes dephasing effect on the ^{85}Rb qubits but it could be efficiently mitigated by choosing the dynamical range of active polarization device. We also show that light shifts seen by qubits in an elliptically polarized MI-ODT can be more efficiently compensated due to the decrease in the ground state hyperpolarizability. It is anticipated that the novel mixed-species MI-ODT array is a versatile platform for building scalable quantum computers with neutral atoms.

Restoration of psychosocial functioning in remitted major depressive disorder patients: A 1-year longitudinal study.

BACKGROUND: The recovery of psychosocial functioning is an important treatment goal for patients with depression. The aim of the present study is to investigate psychosocial functioning restoration 1 year after major depressive disorder (MDD) remission. METHODS: Depression symptoms and psychosocial functioning were assessed in 167 remitted MDD patients at baseline, as well as 1, 2, 6, 9, and 12 months following remission, according to the Hamilton Depression Scale (HAMD-17) and Generic Quality of Life Inventory (GQOLI-74). RESULTS: Of the 167 MDD patients, 85 completed the final evaluation at 1 year, 32 relapsed, and 50 dropped out. The total relapse rate over 1 year was 27%. A rapid increase in psychosocial functioning was found in the first 2 months after remission in the non-relapse group. In the non-relapse group, psychosocial functioning was higher at 2 months than at baseline. At baseline and 2 months, psychosocial functioning was lower in the relapse group patients compared to those in the non-relapse group. CONCLUSIONS: Patients with MDD showed continuous improvement in psychosocial functioning during the first year after remission, though psychosocial functioning in the relapse group remained the same during the first two months, suggesting possible further relapse.

Realization of a compact one-seed laser system for atom interferometer-based gravimeters.

A simple and compact design of the laser system is important for realization of compact atom interferometers (AIs). We design and realize a simple fiber bench-based 780-nm laser system used for 85Rb AI-based gravimeters. The laser system contains only one 780 nm seed laser, and the traditional frequency-doubling-module is not used. The Raman beams are shared with one pair of the cooling beams by using a liquid crystal variable retarder based polarization control technique. This laser system is applied to a compact AI-based gravimeter, and a best gravity measurement sensitivity of 230 µGal/Hz1/2 is achieved. The gravity measurements for more than one day are also performed, and the long-term stability of the gravimeter is 5.5 µGal.

Compact portable laser system for mobile cold atom gravimeters.

We have designed and realized a compact portable laser system for high-sensitivity mobile cold atom interferometers. The laser system is mounted on a single module with dimensions of 45 cm×45 cm×16 cm and emits lights directly on up to 13 fiber ports for a two-dimensional magneto-optical trap, atom fountain, Raman transition, and normalized detection. A double-sided optical structure and mounts without kinematic adjustment are designed to achieve high-level integration and stability. The laser system is applied to a mobile atom gravimeter and achieves a sensitivity of 28 µGal/Hz1/2. Experiencing 1200-km-long truck transportation, the laser system could be restored to good operating status without internal realignment.

Measurement and control of the sideband to carrier ratio of an electro-optic modulator used in atom interferometers.

The sideband and carrier of an electro-optic modulator (EOM) are usually used as Raman lasers in atom interferometry. To eliminate AC-Stark shift in atom interferometry, the stability of sideband to carrier ratio (SCR) is of great significance. We present a beating method to accurately measure and control the SCR. The influence of imperfect frequency response of the beating system is avoided by chirping the reference laser with half chirping rate of the modulation frequency. Making use of this method, we performed a SCR locking by feedback to the modulation depth. The locked SCRs' variation is averaged to be less than 0.1% within 20 MHz chirping span, and the according error for gravity measurement with 180 ms free evolution time is 6.2×10-11g. Thus both the SCR variation and the estimated gravity measurement error are reduced by about 2 orders. This work may provide hints to other EOM involving experiments.

Normalized detection by using the blow-away signal in cold atom interferometry.

We propose and realize a simple normalized detection scheme for cold atom interferometry. The detection of population in final atomic states is normalized to the blow-away fluorescence during initial state preparation. In this way, the detection system and procedure are both simplified. The reduced sensitivity to amplitude noise in atom interference signal is experimentally verified. Both amplitude noise in atom source and short term phase noise of interference fringes are suppressed by more than a factor of 10 with normalized detection.

Synthesis of stable isotope labeled D9 -Mabuterol, D9 -Bambuterol, and D9 -Cimbuterol.

Three stable and simple synthetic routes of labeled D9 -Mabuterol, D9 -Bambuterol, and D9 -Cimbuterol were described with 98.5%, 99.7%, and 98.4% isotopic abundance and good purity. These structures and isotope-abundance were confirmed according to 1 H NMR and liquid chromatography-tandem mass spectrometry.

Test of Equivalence Principle at 10(-8) Level by a Dual-Species Double-Diffraction Raman Atom Interferometer.

We report an improved test of the weak equivalence principle by using a simultaneous 85Rb-87Rb dual-species atom interferometer. We propose and implement a four-wave double-diffraction Raman transition scheme for the interferometer, and demonstrate its ability in suppressing common-mode phase noise of Raman lasers after their frequencies and intensity ratios are optimized. The statistical uncertainty of the experimental data for Eötvös parameter η is 0.8×10(-8) at 3200 s. With various systematic errors corrected, the final value is η=(2.8±3.0)×10(-8). The major uncertainty is attributed to the Coriolis effect.

Association of antibiotic exposure with survival in patients with extensive-stage small cell lung cancer receiving immune checkpoint inhibitor therapy.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have dramatically shifted the therapeutic paradigm of extensive-stage small cell lung cancer (ES-SCLC). Antibiotic (ATB) exposure before or during ICI therapy can harm the integrity of the gut microbiome and lead to intestinal dysbiosis, which has a profoundly negative impact on the treatment response for various malignancies. Whether this is applicable to ES-SCLC remains unclear. METHODS: We retrospectively reviewed the electronic medical records of all patients diagnosed with ES-SCLC who were treated with ICI-based immunotherapies from July 2019 to December 2020 at Shandong Cancer Hospital and Institute, China. Outcomes with the use of ATBs before or after the first infusion of ICI, including progression-free survival (PFS) and overall survival (OS), were investigated using the Kaplan-Meier method. Multivariate analyses were also conducted using a Cox proportional hazards model. RESULTS: A total of 214 patients were included, among whom 41 (19.2%) received ATBs within 2 months before or after the first initiation of ICI therapy and were assigned to the ATB group. The ATB group showed a shorter median PFS (4.3 vs. 6.3 months; HR = 1.43, 95% CI: 0.97-2.11; p = 0.043) and a significantly shorter median OS (6.9 vs. 13 months; HR = 1.47, 95% CI: 0.98-2.20; p = 0.033) than the non-ATB group. In the multivariate analysis, ATB exposure was markedly associated with worse PFS (HR = 1.47, 95% CI: 1.03-2.09, p = 0.035) and OS (HR = 1.46, 95% CI: 1.01-2.11, p = 0.043). CONCLUSIONS: Our results demonstrate that ATB exposure was significantly associated with worse survival in ES-SCLC patients who received ICI therapy.

RBF neural network disturbance observer-based backstepping boundary vibration control for Euler-Bernoulli beam model with input saturation.

The main objective of this paper is to address the issue of vibration control for a class of Euler-Bernoulli beam systems that are subject to external disturbances and input saturation. The proposed controller differs from other backstepping methods in that it employs a radial basis function (RBF) neural network to accurately estimate boundary disturbances and incorporates the hyperbolic tangent function to ensure input constraints. The nonlinear partial differential equation (PDE) model is initially derived based on Hamilton's principle to capture the dominant dynamic characteristics of the flexible beam. In the framework of the Lyapunov direct approach, an adaptive RBF neural network-based law is subsequently designed to estimate the state-related boundary disturbances. The backstepping approach is then developed to propose sufficient conditions for ensuring the stability and convergence of closed-loop systems subject to input saturation. Finally, the effectiveness and superiority of the proposed methodology are further demonstrated by comparing the simulation results of constrained backstepping controllers.

Identification and Functional Characterization of PI3K/Akt/mTOR Pathway-Related lncRNAs in Lung Adenocarcinoma: A Retrospective Study.

OBJECTIVE: This paper aimed to investigate the PI3K/Akt/mTOR signal-pathway regulator factor-related lncRNA signatures (PAM-SRFLncSigs), associated with regulators of the indicated signaling pathway in patients with lung adenocarcinoma (LUAD) undergoing immunotherapy. MATERIALS AND METHODS: In this retrospective study, we employed univariate Cox, multivariate Cox, and least absolute shrinkage and selection operator (LASSO) regression analyses to identify prognostically relevant long non-coding RNAs (lncRNAs), construct prognostic models, and perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Subsequently, immunoassay and chemotherapy drug screening were conducted. Finally, the prognostic model was validated using the Imvigor210 cohort, and tumor stem cells were analyzed. RESULTS: We identified seven prognosis-related lncRNAs (AC084757.3, AC010999.2, LINC02802, AC026979.2, AC024896.1, LINC00941 and LINC01312). We also developed prognostic models to predict survival in patients with LUAD. KEGG enrichment analysis confirmed association of LUAD with the PI3K/Akt/mTOR signaling pathway. In the analysis of immune function pathways, we discovered three good prognostic pathways (Cytolytic_activity, Inflammation-promoting, T_cell_co-inhibition) in LUAD. Additionally, we screened 73 oncology chemotherapy drugs using the "pRRophetic" algorithm. CONCLUSION: Identification of seven lncRNAs linked to regulators of the PI3K/Akt/mTOR signaling pathway provided valuable insights into predicting the prognosis of LUAD, understanding the immune microenvironment and optimizing immunotherapy strategies.