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Purpose: To evaluate the impact anterior cruciate ligament reconstruction (ACLR) has on strike evasion rates, strike and landing rates, win percentage, and career longevity in Ultimate Fighting Championship (UFC) fighters. Methods: UFC fighters who underwent ACLR from 1993 to 2022 were matched 2:1 with uninjured controls. The percentage of each injured fighter’s career that occurred before ACLR was deemed the “index percentage.” Injured fighter performance pre-/post-ACLR was compared with control metrics pre-/postindex percentage. Results: Of the 82 patients with documented ACL injuries identified, 48 met the inclusion criteria. Of these, 27 returned for more than 2 fights and were paired with 54 controls. UFC fighters demonstrated return-to-sport rates of 81.25% and 56.25% for at least 1 and 2 fights, respectively. On average, it took 411.85 ± 174.73 (range, 165-879) days for fighters to return. All fighters had significantly lower evasion rates against total significant strikes, distance strikes, and head strikes, postindex (P < .05 for each). ACLR fighters had significantly lower submission attempts and evasion rates against clinch strikes, ground strikes, and total strikes, postindex (P < .05 for each). Controls had a significantly lower evasion rate against leg strikes, postindex. Both groups’ win percentages significantly declined (ACLR, P = .001; control, P = .012). No significant difference in total career fights was observed (P = .873). Conclusions: In this study, we found that most UFC fighters who undergo ACLR return to sport for at least 1 fight; however, just over half return for at least 2 fights. There was not a significant difference in career length between fighters who returned to sport following ACLR for at least 2 fights and their controls. Defensive performance, but not offensive performance, declined significantly following ACLR. All fighters demonstrated significant declines in their win percentage as their career progressed, irrespective of ACLR. Level of Evidence: Level III, retrospective comparative study.

The structural, magnetic, ferroelectric, dielectric and optical properties of Ba6MnNb9O30 (BMNO) and Ba6Mn0.5Co0.5Nb9O30 (BMCNO) ceramics were investigated. The samples can be indexed by a tetragonal lattice and the space group of P4bm with the presence of a tiny amount of impurity phase Ba1.04NbO3. The sample BMNO undergoes a short-range ferrimagnetic-like transition at 43 K originating from the spin canting of the antiferromagnetic coupling between the adjacent Mn2+ and Mn3+ based sublattices via the Dzyaloshinskii-Moriya interaction, whereas the sample BMCNO exhibits a local short-range antiferromagnetic state with the presence of weak ferromagnetic ordering. Both samples show the relaxor ferroelectric nature. The sample BMCNO possesses a superior energy storage property with a total energy density of 1.58 J/cm3 and a conversion efficiency of 74.5 %, which can be mainly ascribed to the improved densification and the reduced oxygen vacancies. Two different dielectric relaxations are discussed in term of the Vogel-Fulcher law. In addition, all samples have two different absorption edges and the optical band gaps are determined to be about 2.2 eV and 2.8 eV.

Kelvin–Helmholtz instability (KHI) is most likely to be the primary source for clear-air turbulence, which is of importance in pollution transfer and diffusion and aircraft safety. It is indicated by the critical value of the dimensionless Richardson (Ri) number, which is predicted to be 1/4 from linear stability analysis. However, Ri is fairly sensitive to the vertical resolution of the dataset; a higher resolution systematically leads to a finer structure. The study aims to evaluate the performance of ERA5 reanalysis in determining the spatial–temporal variabilities in subcritical Ri by comparing it against a near-global high-resolution radiosonde dataset during the years 2017 to 2022 and further highlights the global climatology and dynamical environment of subcritical Ri. Overall, the occurrence frequency of Ri<1/4 is inevitably underestimated by the ERA5 reanalysis over all climate zones at all heights from the near-ground atmosphere up to 30 km, compared to radiosonde, due directly to the severe underestimation in wind shears. Otherwise, the occurrence frequency of Ri in ERA5 is climatologically consistent with that from Ri<1/4 in radiosondes in the free troposphere, especially over the midlatitude and subtropics in the Northern Hemisphere and Southern Hemisphere. Therefore, we argue that the threshold value of Ri could be approximated as 1 rather than 1/4 when using ERA5-based Ri as a proxy for KHI. The occurrence frequency of subcritical Ri revealed by both datasets exhibits significant seasonal cycles over all climate zones. In addition, it is positively correlated with the standard derivation of orography at low levels and is exceptionally strong over the Niño-3 region at heights of 6–13 km. Furthermore, a high occurrence of subcritical Ri would likely be accompanied by strong wind speeds and intensive orographic or non-orographic gravity waves.

Abstract Temperature, particle number and volume are the independent variables of the Helmholtz free energy for a bulk fluid. For a fluid confined in a slit pore between two walls, they are usually complemented by the surface area. However, an alternative choice is possible with the volume replaced by the pore width. Although the formulations with such two sets of independent variables are different, we show they are equivalent and present their relations. Corresponding general statistical-mechanics results are also presented. When the pore width becomes very small, the system behaves rather like a two-dimensional (2D) fluid and one can wonder if thermodynamics still holds. We find it remains valid even in the limit of vanishing pore width and show how to treat the divergences in the normal pressure and the chemical potential so that the corresponding 2D results can be obtained. Thus, we show that the Gibbs surface thermodynamics is perfectly capable of describing small systems.

ABSTRACT Chronic wasting disease (CWD) is a naturally occurring prion disease in cervids that has been rapidly proliferating in the United States. Here, we investigated a potential link between CWD infection and gut microbiome by analyzing 50 fecal samples obtained from CWD-positive animals of different sexes from various regions in the USA compared to 50 CWD-negative controls using high throughput sequencing of the 16S ribosomal RNA and targeted metabolomics. Our analysis reveals promising trends in the gut microbiota that could potentially be CWD-dependent, including several bacterial taxa at each rank level, as well as taxa pairs, that can differentiate between CWD-negative and CWD-positive deer. Through machine-learning, these taxa and taxa pairs at each rank level could facilitate identification of around 70% of both the CWD-negative and the CWD-positive samples. Our results provide a potential tool for diagnostics and surveillance of CWD in the wild, as well as conceptual advances in our understanding of the disease.IMPORTANCEThis is a comprehensive study that tests the connection between the composition of the gut microbiome in deer in response to chronic wasting disease (CWD). We analyzed 50 fecal samples obtained from CWD-positive animals compared to 50 CWD-negative controls to identify CWD-dependent changes in the gut microbiome, matched with the analysis of fecal metabolites. Our results show promising trends suggesting that fecal microbial composition can directly correspond to CWD disease status. These results point to the microbial composition of the feces as a potential tool for diagnostics and surveillance of CWD in the wild, including non-invasive CWD detection in asymptomatic deer and deer habitats, and enable conceptual advances in our understanding of the disease.

Background. Immunosuppression in solid organ transplantation (SOT) increases the risk of Epstein–Barr virus (EBV) DNAemia, which may herald development of posttransplant lymphoproliferative disease (PTLD). Few studies have characterized the incidence, risk factors, and clinical impact of EBV DNAemia in adult SOT recipients (SOTR). Methods. A single-center, retrospective review of adult (≥18 years) SOTR between 01 January 2015 and 31 December 2019 was conducted. Patients were stratified by the primary study endpoint of development of EBV DNAemia (whole blood EBV DNA PCR > 200 copies/mL). Secondary endpoints included development of PTLD, reduction in immunosuppression (RIS), use of pre-emptive therapy, and all-cause mortality. Results. Among 442 adult SOTR, the predominant transplant organs were the kidney (258, 58%) and liver (141, 31.9%). EBV serostatus in most subjects (430, 97%) was classified as intermediate risk (R+). Eight subjects (2%) were high risk (donor (D+/R−), and 4 (1%) were low risk (D−/R−). The overall incidence of EBV DNAemia was 4.1% (18/442) with a median time to detection of 14 months (range 3–60). The highest proportion of DNAemia was observed in D+/R− subjects (37.5%; p

Matter behaves differently at the nanoscale. Here, the author introduces the concept of a disjoining chemical potential for nanoscale thermodynamics, showing that thermodynamic functions depend on the environment, and suggests possible experimental verifications.

IntroductionThere is increasing recognition of infections due to multidrug-resistant Gram negative (MDRGN) bacterial infections among children undergoing solid organ and hematopoietic cell transplantation, which may be associated with morbidity and mortality.MethodsWe present two vignettes that highlight the clinical challenges of evaluation, management, and prevention of MDRGN bacterial infections in children prior to and after transplantation. The goal of this discussion is to provide a framework to help develop an approach to evaluation and management of these infections.ResultsSource control remains the utmost priority in management of MDR infections and is paired with antibiotic selection guided by in vitro susceptibilities, adverse effect profiles, and clinical response. Identification and confirmation of resistance can be challenging and often requires additional testing for recognition of complex mechanisms. Current antimicrobial approaches to MDRGN infections include use of novel agents, prolonged infusion, and/or combination therapy. We also discuss preventative efforts including infection control, antimicrobial stewardship, targeted pre-emptive or prophylactic treatment, and decolonization.DiscussionThe impact of MDRGN infections on patient and graft survival highlights the need to optimize treatment and prevention strategies.

Unraveling the internal kinematics of open clusters is crucial for understanding their formation and evolution. However, there is a dearth of research on this topic, primarily due to the lack of high-quality kinematic data. Using the exquisite-precision astrometric parameters and radial velocities provided by Gaia data release 3, we investigate the internal rotation in three of the most nearby and best-studied open clusters, namely the Pleiades, Alpha Persei, and Hyades clusters. Statistical analyses of the residual motions of the member stars clearly indicate the presence of three-dimensional rotation in the three clusters. The mean rotation velocities of the Pleiades, Alpha Persei, and Hyades clusters within their tidal radii are estimated to be 0.24 ± 0.04, 0.43 ± 0.08, and 0.09 ± 0.03 km s ^−1 , respectively. Similar to the Praesepe cluster that we have studied before, the rotation of the member stars within the tidal radii of these three open clusters can be well interpreted by Newton’s theorem. No expansion or contraction is detected in the three clusters either. Furthermore, we find that the mean rotation velocity of open clusters may be positively correlated with the cluster mass, and the rotation is likely to diminish as open clusters age.

Scientific tasks aimed at decoding and characterizing complex systems and processes at high pressures set new challenges for modern X-ray diffraction instrumentation in terms of X-ray flux, focal spot size and sample positioning. Presented here are new developments at the Extreme Conditions beamline (P02.2, PETRA III, DESY, Germany) that enable considerable improvements in data collection at very high pressures and small scattering volumes. In particular, the focusing of the X-ray beam to the sub-micrometer level is described, and control of the aberrations of the focusing compound refractive lenses is made possible with the implementation of a correcting phase plate. This device provides a significant enhancement of the signal-to-noise ratio by conditioning the beam shape profile at the focal spot. A new sample alignment system with a small sphere of confusion enables single-crystal data collection from grains of micrometer to sub-micrometer dimensions subjected to pressures as high as 200 GPa. The combination of the technical development of the optical path and the sample alignment system contributes to research and gives benefits on various levels, including rapid and accurate diffraction mapping of samples with sub-micrometer resolution at multimegabar pressures.

The capsule endoscope, as one of important equipment in screening the entire spectrum of digestive tract disease diagnosis, has largely compensated for the limited of vision field and poor patient experience of wired endoscopes. In order to better develop the clinical application of capsule endoscope and assist doctors in the diagnosis and treatment of gastrointestinal diseases, there is an urgent need to solve a key scientific problem, that is obtaining the position information of capsule endoscope in the body. This article reviews the research evolution of the capsule endoscope based on magnetic localization through the last 10 years and describes notable problem, as well as technological challenges to overcome. Besides that, the article also presents the future development in capsule endoscopy localization technology based on magnetic sensors, for further developing capsule endoscopy localization and surgical navigation.

Global surface temperature observational datasets are the basis of global warming studies. In the context of increasing global warming and frequent extreme events, it is essential to improve the coverage and reduce the uncertainty in global surface temperature datasets. The China global Merged Surface Temperature Interim version (CMST-Interim) is updated to CMST 2.0 in this study. The previous CMST datasets were created by merging the China global Land Surface Air Temperature (C-LSAT) with sea surface temperature (SST) data from the Extended Reconstructed Sea Surface Temperature version 5 (ERSSTv5). The CMST 2.0 contains three variants: CMST 2.0 − Nrec (without reconstruction), CMST 2.0 − Imax, and CMST 2.0 − Imin (according to their reconstruction area of the air temperature over the sea ice surface in the Arctic region). The reconstructed datasets significantly improve data coverage, whereas CMST 2.0 − Imax and CMST 2.0 − Imin have improved coverage in the Northern Hemisphere, up to more than 95 %, and thus increased the long-term trends at global, hemispheric, and regional scales from 1850 to 2020. Compared to CMST-Interim, CMST 2.0 − Imax and CMST 2.0 − Imin show a high spatial coverage extended to the high latitudes and are more consistent with a reference of multi-dataset averages in the polar regions. The CMST 2.0 datasets presented here are publicly available at the website of figshare, https://doi.org/10.6084/m9.figshare.16929427.v4 (Sun and Li, 2021a), and the CLSAT2.0 datasets can be downloaded at https://doi.org/10.6084/m9.figshare.16968334.v4 (Sun and Li, 2021b). Both are also available at http://www.gwpu.net (last access: January 2022).

Abstract Background Alpha-synuclein (α-syn) exhibits pathological misfolding in many human neurodegenerative disorders. We previously showed that α-syn is arginylated in the mouse brain and that lack of arginylation leads to neurodegeneration in mice. Methods Here, we tested α-syn arginylation in human brain pathology using newly derived antibodies in combination with Western blotting, biochemical assays, and experiments in live neurons. Results We found that α-syn was arginylated in the human brain on E46 and E83, two sites previously implicated in α-syn pathology and familial cases of Parkinson’s disease. The levels of arginylation in different brain samples ranged between ~ 3% and ~ 50% of the total α-syn pool, and this arginylation nearly exclusively concentrated in the subcellular α-syn fraction that sedimented at low centrifugation speeds and appeared to be simultaneously targeted by multiple posttranslational modifications. Arginylated α-syn was less susceptible to S129 phosphorylation and pathological aggregation in neurons. The arginylation level inversely correlated with the overall α-syn levels and with patient age, suggesting a possible causal relationship between arginylation decline and α-syn-dependent neuropathology. Conclusion We propose that α-syn arginylation constitutes a potential neuroprotective mechanism that prevents its abnormal accumulation during neurodegeneration and aging in the human brain.

Summary: Cytoplasmic beta- and gamma-actin are ubiquitously expressed in every eukaryotic cell. They are encoded by different genes, but their amino acid sequences differ only by four conservative substitutions at the N-termini, making it difficult to dissect their individual regulation. Here, we analyzed actin from cultured cells and tissues by mass spectrometry and found that beta, unlike gamma actin, undergoes sequential removal of N-terminal Asp residues, leading to truncated actin species found in both F- and G-actin preparations. This processing affects up to ∼3% of beta actin in different cell types. We used CRISPR/Cas-9 in cultured cells to delete two candidate enzymes capable of mediating this type of processing. This deletion abolishes most of the beta actin N-terminal processing and results in changes in F-actin levels, cell spreading, filopodia formation, and cell migration. Our results demonstrate previously unknown isoform-specific actin regulation that can potentially affect actin functions in cells.

Abstract Background γδT cells play an important role in the mucosa inflammation and immunity-associated disorders. Our previous study reported that γδ T cells producing IL-17 were involved in the pathogenesis of post-infectious irritable bowel syndrome (PI-IBS). However, their subset characteristic profile in this kind of disease remains unclear. Thus the current study’s aim is to investigate the functionally predominant subset and its role in PI-IBS. Methods The total T cells were collected from the peripheral blood of patients with PI-IBS. The peripheral proportion of Vδ1 and Vδ2 subset was detected by FACS after stained with anti δ1-PE and anti δ2-APC. The local colonic proportion of this two subsets were measured under laser confocal fluorescence microscope. Vδ1 γδ T cells were enriched from the total peripheral T cells by minoantibody-immuno-microbeads (MACS) method and cultured, functionally evaluated by CCK-8 assay (proliferation), CD69/CD62L molecules expression assay (activation) and ELISA (IL-17 production) respectively. Results 1. Vδ1 γδ T cells significantly increased while Vδ2 γδ T cells remained unchanged in both the peripheral blood and local colonic tissue from PI-IBS patients (p

Abstract Regulator of G-protein signaling 7 (RGS7) is predominately present in the nervous system and is essential for neuronal signaling involving G-proteins. Prior studies in cultured cells showed that RGS7 is regulated via proteasomal degradation, however no protein is known to facilitate proteasomal degradation of RGS7 and it has not been shown whether this regulation affects G-protein signaling in neurons. Here we used a knockout mouse model with conditional deletion of arginyltransferase (Ate1) in the nervous system and found that in retinal ON bipolar cells, where RGS7 modulates a G-protein to signal light increments, deletion of Ate1 raised the level of RGS7. Electroretinographs revealed that lack of Ate1 leads to increased light-evoked response sensitivities of ON-bipolar cells, as well as their downstream neurons. In cultured mouse embryonic fibroblasts (MEF), RGS7 was rapidly degraded via proteasome pathway and this degradation was abolished in Ate1 knockout MEF. Our results indicate that Ate1 regulates RGS7 protein level by facilitating proteasomal degradation of RGS7 and thus affects G-protein signaling in neurons.

Introduction Previous Electronic Health Records (EHR) based studies adopted various definitions in identifying Treatment-Resistant Depression (TRD) patients. There is a lack of similar attempts among Chinese population which limits the understanding of TRD in China. Objectives Assess TRD identification using EHR from a major psychiatric hospital in China. Methods This study utilized a retrospective Major Depressive Disorder (MDD) cohort of patients who newly initiated pharmaceutical treatment (2010-2018); follow-up was ended upon 1-year or treatment discontinuation (≥120d without treatment). TRD was first identified based on common clinical definition of two prior regimen failures (change of regimen) with 4-week as regimen adequacy threshold (Def1). Alternative adequacy thresholds of 2-week and 6-week were applied. Based on Def1 (4-week), at least 3 distinctive regimens were additionally required in TRD identification (Def2). Further, a data-driven definition (Def3) based on drug count as having ≥3 antidepressants or ≥1 antipsychotic within 1 year was considered (Cepeda et al., 2018). Results From 12257 MDD patients included in the cohort, Def1 identified 633 (5.2%) TRD cases, whereas regimen adequacy thresholds of 2-week and 6-week identified 1772 (14.5%) and 61 (0.5%) cases, respectively. Further, Def2 identified 261 (2.4%) TRD cases. Finally, Def3 yielded 2449 (20.0%) TRD cases, including 1966 exclusive cases that were not identified by Def1. Conclusions This study showed different definitions for TRD identification had considerable impact on the number of patients identified among Chinese population, obscuring the comparability among EHR-based TRD studies. As first step, we found the criteria of regimen adequacy as major contributor to the observed variability in China. Disclosure No significant relationships.

Urban ecological space is a significant factor for sustainable urban development and ecological civilization construction. Traditional urban ecological space analysis mainly used medium-resolution image data at large scales and used high-resolution images at a typical urban scale. Few studies focused on the high-precision ecological space analysis at a national urban scale. In this study, high-precision urban boundary and land cover data were utilized to analyze the urban ecological space change and its reason from 2016 to 2017. Ecological space was extracted and merged from high-precision land cover data, which came from the National Geoinformation Survey data of China. Results showed that in 2017, the total urban ecological space area of 338 prefecture-level cities in China was 8514.2 square kilometers, accounting for 22.4% of the total urban area, which was far below the threshold of 40% for evaluating the urban green coverage in China. Urban ecological space of 184 cities declined. There were four principal reasons for the decrease of urban ecological space. First, the green space supporting the buildings was occupied. Second, the green landscape space near rivers and lakes was occupied. Third, blocks of woodland were occupied. Fourth, the water area was occupied. The reduced urban ecological space was mainly changed into construction sites, structures, and buildings. Urban ecological space of China was seriously insufficient, and it was heavily occupied. Adequate ecological space should be preserved not only in new urban development areas but also in the old urban areas to ensure people a more comfortable living environment.

To overcome the limitations of conventional bistable mechanisms, this paper proposes a novel type of bistable mechanism with linear negative stiffness and large in-plane lateral stiffness. By connecting the novel negative-stiffness mechanism in parallel with a positive-stiffness mechanism, a novel quasi-zero stiffness compliant mechanism is developed, which has good axial guidance capability and in-plane lateral anti-interference capability. Analytical models based on a comprehensive elliptic integral solution of bistable mechanism are established and then the stiffness curves of both conventional and novel bistable mechanisms are analyzed. The quasi-zero stiffness characteristic and High-Static-Low-Dynamic-Stiffness characteristic of the novel compliant mechanism are investigated and its application in constant-force mechanism and vibration isolator is discussed. A prototype with adjustable load-carrying capacity is designed and fabricated for experimental study. In the two experiments, the effectiveness of the proposed quasi-zero stiffness mechanism used in the field of constant-force output and vibration isolation is tested.

In a Francis turbine, the guide vanes are arranged in the direction of flow behind the stay vanes. And as it is generally believed that the outlet angle of water after it flows through the spiral case and stay vanes is fixed, the flow and flow circulation are altered by changing the opening of the guide vanes so as to change the output of the turbine. The rotor–stator interaction effect induced by the interaction between the guide vanes and the runner of the Francis turbine was one of the main causes of the pressure fluctuation. The effect of guide vanes placement on pressure fluctuation in vaneless zone of Francis turbine was studied. In this study, the commercial software ANSYS CFX16.0 was used for the three-dimensional numerical simulation of the whole flow passage of a Francis turbine model in a power station. The turbulence model used in the calculation was the shear stress transport (SST) model. The independence between the total number of computational meshes and the timestep was verified to ensure the reliability of the calculation results. Five schemes with different diameters of the guide vanes distribution circle were proposed including D0/D1 (guide vane pitch circle diameter /diameter of runner inlet) equaling to 1.119, 1.128, 1.138, 1.144, and 1.15. The steady calculation results showed that, when the turbine was operating under the design condition, D0/D1 increased from 1.119 to 1.15, and the turbine efficiency and output showed a monotonically increasing trend, with the efficiency increased by 0.17 percentage point and output increased by 3.91kw. Twenty monitoring points were set up in the vaneless zone between the guide vanes and the runner to collect pressure fluctuation signals in the vaneless zone. By analyzing the characteristics of unsteady pressure fluctuations in the vaneless zone under design conditions of the five schemes, the optimal position of the guide vanes was determined. The numerical results showed that the pressure fluctuation amplitude at monitoring points in the same axial direction increased gradually from the top cover to the bottom ring. When the unit operated under the design conditions, by increasing the guide vane pitch circle diameter, the rotor–stator interaction between the guide vanes and the runner domain was weakened, and the pressure fluctuation amplitude in the vaneless zone between the guide vanes and the runner was reduced, thereby the stability of unit operation was improved.

Abstract Objective: We developed an implementation plan to integrate diagnostic testing for coronavirus disease 2019 (COVID-19) into a public school system. Implementation barriers were identified and strategies were mapped to overcome them. Design: A COVID-19 diagnostic testing program leveraging a public–private partnership was developed for a public school system. Setting: A suburban school district and a local hospital during the 2020–2021 academic year. Methods: Using Consolidated Framework for Implementation Research (CFIR) constructs and evidenced-based implementation strategies, the program was designed as a “closed system” and was adapted based on stakeholder feedback. Implementation barriers and facilitators were identified and mapped to CFIR constructs to provide insights into factors influencing program adoption. Results: Preimplementation stages of engagement, feasibility, and readiness planning were completed. The program did not progress to implementation due to multiple factors, including changes in school leadership (inner setting and process-level constructs), improved access to outside testing, and lack of an existing paradigm for in-school testing (external constructs). Limited support from key stakeholders and opinion leaders was also a barrier (process-level construct). Conclusions: Although this locally initiated program did not progress beyond the preimplementation stage, the processes developed and barriers identified may be useful to inform planning efforts in other testing programs within public school systems. Future programs may consider incorporating multiplex diagnostic testing for influenza in addition to COVID-19. With relaxation of infection control measures, the prevalence of other respiratory viruses will increase. Actionable results will be needed to inform decisions about closures and quarantines.

Arginylation is a post-translational modification mediated by the arginyltransferase (Ate1). We recently showed that conditional deletion of Ate1 in the nervous system leads to increased light-evoked response sensitivities of ON-bipolar cells in the retina, indicating that arginylation regulates the G-protein signaling complexes of those neurons and/or photoreceptors. However, none of the key players in the signaling pathway were previously shown to be arginylated. Here we show that Gαt1, Gβ1, RGS6, and RGS7 are arginylated in the retina and RGS6 and RGS7 protein levels are elevated in Ate1 knockout, suggesting that arginylation plays a direct role in regulating their protein level and the G-protein-mediated responses in the retina.

Superoxide dismutase is a crucial reactive oxygen species (ROS) scavenger and converts the superoxide radical (O2-) to H2O2, so it is thought to enhance abiotic stress tolerance by reducing ROS accumulation and so avoiding oxidative damage. In this study, we isolated a salt- and oxidative stress-responsive Cu/Zn SOD gene TaSOD5 from wheat. The ectopic overexpression of TaSOD5 in Arabidopsis increased total and Cu/Zn SOD activities, and offered the plant tolerance to salt stress. Arabidopsis ectopically expressing TaSOD5 possessed a superior resistance to oxidative stress induced H2O2. The TaSOD5 ectopic overexpression elevated the activities of both ROS scavengers and O2- producer NADPH oxidase. These findings show that Cu/Zn SOD enhances salt tolerance via regulating the machinery of redox homeostasis rather than improving SOD activity alone.

The Community Atmosphere Model version 6 (CAM6), released in 2018 as part of the Community Earth System Model version 2 (CESM2), is a major upgrade over the previous CAM5 that has been used in numerous global and regional climate studies. Since CESM2–CAM6 will participate in the upcoming Coupled Model Intercomparison Project phase 6 (CMIP6) and is likely to be adopted in many future studies, its simulation fidelity needs to be thoroughly examined. Here we evaluate the performance of a developmental version of the Community Atmosphere Model with parameterizations that will be used in version 6 (CAM6α), with a default 1∘ horizontal resolution (0.9∘×1.25∘, CAM6α-1∘) and a high-resolution configuration (approximately 0.25∘, CAM6α-0.25∘), against various observational and reanalysis datasets of precipitation over Asia. CAM6α performance is compared with CAM5 at default 1∘ horizontal resolution (CAM5-1∘) and a high-resolution configuration at 0.25∘ (CAM5-0.25∘). With the prognostic treatment of precipitation processes and the new microphysics module, CAM6α is able to better simulate climatological mean and extreme precipitation over Asia, better capture the heaviest precipitation events, better reproduce the diurnal cycle of precipitation rates over most of Asia, and better simulate the probability density distributions of daily precipitation over Tibet, Korea, Japan and northern China. Higher horizontal resolution in CAM6α improves the simulation of mean and extreme precipitation over northern China, but the performance degrades over the Maritime Continent. Moisture budget diagnosis suggests that the physical processes leading to model improvement are different over different regions. Both upgraded physical parameterizations and higher horizontal resolution affect the simulated precipitation response to the internal variability of the climate system (e.g., Asian monsoon variability, El Niño–Southern Oscillation – ENSO, Pacific Decadal Oscillation – PDO), but the effects vary across different regions. For example, higher horizontal resolution degrades the model performance in simulating precipitation variability over southern China associated with the East Asian summer monsoon. In contrast, precipitation variability associated with ENSO improves with upgraded physical parameterizations and higher horizontal resolution. CAM6α-0.25∘ and CAM6α-1∘ show an opposite response to the PDO over southern China. Basically, the response to increases in horizontal resolution is dependent on the CAM version.

Cell division cycle 25A (CDC25A), a member of the CDC25 family of phosphatases, is required for progression from G1 to the S phase of the cell cycle. CDC25A provides an essential function during early embryonic development in mice, suggesting that it plays an important role in growth and development. In this study, we used mathematical expectation (ME) methods to identify a 20-bp insertion/deletion (indel) polymorphism of CDC25A gene in Shaanbei White Cashmere (SBWC) goats. We also investigated the association between this 20-bp indel and growth-related traits in SBWC goats. Association results showed that the indel was related to growth traits (height at hip cross, cannon circumference, and cannon circumference index) in SBWC goats. The height at hip cross of individuals with insertion/insertion (II) genotype was higher than those with insertion/deletion (ID) genotype (P=0.02); on the contrary, the cannon circumference and cannon circumference index of individuals with ID genotype were superior when compared with those with II genotype (P=0.017 and P=0.009). These findings suggest that the 20-bp indel in the CDC25A gene significantly affects growth-related traits, and could be utilized as a candidate marker for marker-assisted selection (MAS) in the cashmere goat industry.

In the case study of Guanghua Pavilion [光化楼] located in Jiayuguan [嘉峪关] City, Gansu province in China, the 3D laser scanning technology and leveling technology are used to analyze overall tilt, columns tilt and uneven settlement of the pavilion. It is found that Guanghua Pavilion [光化楼] tilted to the southeast; most of the columns from the first floor to the third floor tilted to the northeast and east directions, and all the tilted distance of the columns is within 100 mm.; a certain amount of uneven settlement happened on Guanghua Pavilion [光化楼], in which the east side sinks more obviously. In the process of analyzing the influencing factors of deformation, numerical wind tunnel simulation and Midas Gen modeling methods are used. It is concluded that the external wind load is the main cause of Jiayuguan [嘉峪关] pavilions’ deformation.

For the fatigue failure of 42CrMo, the tensile test was performed on the CT specimen at different load ratios using a fatigue tensile tester. Data on the fatigue crack growth rate of the material and the crack tip factor were obtained. Scanning electron microscopy (SEM) was used to observe the microstructure and crack initiation and propagation of fractures. The crack initiation and propagation path law during fatigue crack propagation were obtained. The fatigue crack life was calculated by Paris formula, and the fatigue crack growth test and microscopic observation were compared. The propagation law and fatigue crack life of different stages of crack propagation were analyzed. The results show that the stable propagation stage of fatigue crack propagation is the key stage to determine fatigue fracture, the rate of growth is related to the stress ratio.

β- and γ-cytoplasmic actins are ubiquitously expressed in every cell type and are nearly identical at the amino acid level but play vastly different roles in vivo. Their essential roles in embryogenesis and mesenchymal cell migration critically depend on the nucleotide sequences of their genes, rather than their amino acid sequences; however, it is unclear which gene elements underlie this effect. Here we address the specific role of the coding sequence in β- and γ-cytoplasmic actins’ intracellular functions, using stable polyclonal populations of immortalized mouse embryonic fibroblasts with exogenously expressed actin isoforms and their ‘codon-switched’ variants. When targeted to the cell periphery using β-actin 3′UTR; β-actin and γ-actin have differential effects on cell migration. These effects directly depend on the coding sequence. Single-molecule measurements of actin isoform translation, combined with fluorescence recovery after photobleaching, demonstrate a pronounced difference in β- and γ-actins’ translation elongation rates in cells, leading to changes in their dynamics at focal adhesions, impairments in actin bundle formation, and reduced cell anchoring to the substrate during migration. Our results demonstrate that coding sequence-mediated differences in actin translation play a key role in cell migration.

Introduction The antipsychotic dosage of Chinese schizophrenia patients has rarely been studied, although nonstandard dosage has impact on prognosis. Objectives To describe the dosage of antipsychotics in China routine practice. Methods This was a retrospective cohort study using de-identified data from a Chinese mental health hospital. The included patients were adults (≥18 years) with at least one diagnosis of schizophrenia (ICD-10: F20) and one prescription of any antipsychotic between 2014 and 2019. Date of first identified antipsychotic prescription was defined as index date, patients were followed up until last prescription of antipsychotics, end of 2019, or discontinuation (>60 days without antipsychotic prescription), whichever was earliest. Dosage was summarized using defined daily dose (DDD), calculated by cumulative average daily dose (CAD) with a unit of DDDs/day, i.e., total DDDs of all antipsychotics in follow-up period divided by total days of follow-up. CAD was categorized into low (1.5 DDDs/day) groups. Results 13554 patients were included with an average follow-up of 269.9 days. Median CAD was 0.8 DDDs/day (IQR=0.5-1.3), patients with hospitalization during follow-up and used multiple antipsychotics at the same time had larger median CAD, 1.0 DDDs/day and 1.2 DDDs/days, respectively. There were 3245 (23.9%), 7627 (56.3%), and 2682 (19.8%) patients in low, moderate, and high groups, respectively. The median CAD of high dosage group was 2.5 DDDs/day (IQR=1.9-10.5). Conclusions CAD of most Chinese schizophrenia patients was low or moderate. Association between CAD and hospitalization and multiple concurrent antipsychotics merit further research.

Introduction In China, the indications of paliperidone extended in schizophrenia adolescents (12-17 years) was approved by National Medical Products Administration (NMPA) in 2017. But, the utilization of paliperidone in this group needs to be further investigated. Objectives To assess paliperidone utilization in schizophrenia adolescents. Methods The study employed the electronic medical records (EMRs) database from a psychiatry specialized hospital (PH) and a general hospital (GH), respectively. General information, including birth date, gender, visit date, diagnosis (inpatient and outpatient) with ICD-10 coding, drug characterize, prescription date and dosage, was de-identified and standardized for analysis. Schizophrenia adolescents (ICD-10: F20.x) received at least one prescription of paliperidone between 2018 and 2019 were included in this study. Index date was defined as the date of first identified paliperidone prescription. The patients were followed up until the end of 2019 with the last record, or upon reaching 18 years. The database was analyzed based on days of supply, administration frequency, and daily dose. Results Overall, 112 and 117 eligible patients were included in the present study from PH and GH, respectively. The median drug supply was 179.0 days and 44.0 days, respectively, during which median number of prescriptions patients received was 6.0 and 3.0. Paliperidone was mostly initiated alone (57.1% and 88.9%) with frequency of once daily (97.3% and 88.9%), and the median of average daily dose during follow-up was 5.7 mg/day and 6.0 mg/day, respectively. Conclusions The duration of paliperidone usage was very different in two hospitals, but the dosages in both hospitals were generally agreed with prescribing information.

Mind wandering is often characterized by attention oriented away from an external task towards our internal, self-generated thoughts. This universal phenomenon has been linked to numerous disruptive functional outcomes, including performance errors and negative affect. Despite its prevalence and impact, studies to date have yet to identify robust behavioral signatures, making unobtrusive, yet reliable detection of mind wandering a difficult but important task for future applications. Here we examined whether electrophysiological measures can be used in machine learning models to accurately predict mind wandering states. We recorded scalp EEG from participants as they performed an auditory target detection task and self-reported whether they were on task or mind wandering. We successfully classified attention states both within (person-dependent) and across (person-independent) individuals using event-related potential (ERP) measures. Non-linear and linear machine learning models detected mind wandering above-chance within subjects: support vector machine (AUC = 0.715) and logistic regression (AUC = 0.635). Importantly, these models also generalized across subjects: support vector machine (AUC = 0.613) and logistic regression (AUC = 0.609), suggesting we can reliably predict a given individual's attention state based on ERP patterns observed in the group. This study is the first to demonstrate that machine learning models can generalize to "never-seen-before" individuals using electrophysiological measures, highlighting their potential for real-time prediction of covert attention states.

Water electrolysis in neutral media has attracted concerted research efforts because of its practical applications including microbial electrolysis of wastewater and large-scale hydrogen generation by direct electrolysis of seawater. Because the corrosion of electrochemical devices is effectively reduced in neutral environments, the associated cost is consequently lowered. In this context, two-dimensional transition metal compounds have enjoyed extensive applications in the field of renewable energy because of their abundant storage capacity, easily regulated electronic structure, and unique physical and chemical features. As such, this review summarizes recent advances in the use of two-dimensional transition metal compounds as hydrogen evolution, oxygen evolution, and bifunctional catalysts for neutral water splitting. Some engineering strategies to enhance electrocatalytic performances are also discussed. Finally, the current challenges and future opportunities in bifunctional electrocatalysts for full water splitting are presented.

The cation/H+ exchange is a basic process in transmembrane transport. The acquisition of genome sequences has now established that plants possess genes encoding a large number of cation/proton antiporter 1 (CPA1) proteins, few of which have been characterized with respect to their contribution to ion homeostasis. The CPA1s comprise plasma membrane, vacuolar, and endosomal forms, and they have been identified as important for a salinity tolerance. They are, however, also involved in both the control of cellular pH and K+ homeostasis, and regulate processes over a wide range of physiological events, from vesicle trafficking to development.

Immune checkpoint blockade (ICB) only induces tumour response in a subset of non-small cell lung carcinomas (NSCLC). Here the authors do whole genome sequencing and multiplexed quantitative immunofluorescence on patient samples and identify a “dormant” T-cell signature associated with sensitivity to ICB.

Continuum manipulators are widely used in minimally invasive surgical robot systems (MISRS) because of their flexibility and compliance, while their modelling and control are relatively difficult and complex. This paper proposes an improved hysteresis model of a notched continuum manipulator based on the classical Bouc–Wen model, which can reduce errors and increase the accuracy of the kinematic-mechanics coupled model. Then parameters are identified by the mean of genetic algorithm (GA). Hysteresis phenomenon of the mentioned manipulator is actually caused by many factors such as the hysteresis property of Hyperelastic Nitinol Alloy (HNA), the elastic deformation of tendon and the friction between the tendon and the tube. The results of both static and dynamic experiments show that the introduced hysteresis model can eliminate the positional difference between forward and reverse bending processes, and thus improve the forecast precision of deformation during motion. This model can also be used to compensate modelling errors caused by hysteresis of other similar systems.

Understanding physiological responses of organisms to warming and ocean acidification is the first step towards predicting the potential population- and community-level ecological impacts of these stressors. Increasingly, physiological plasticity is being recognized as important for organisms to adapt to the changing microclimates. Here, we evaluate the importance of physiological plasticity for coping with ocean acidification and elevated temperature, and its variability among individuals, of the intertidal limpet Cellana toreuma from the same population in Xiamen. Limpets were collected from shaded mid-intertidal rock surfaces. They were acclimated under combinations of different pCO2 concentrations (400 and 1000 ppm, corresponding to a pH of 8.1 and 7.8) and temperatures (20 and 24 °C) in a short-term period (7 days), with the control conditions (20 °C and 400 ppm) representing the average annual temperature and present-day pCO2 level at the collection site. Heart rates (as a proxy for metabolic performance) and expression of genes encoding inducible and constitutive heat-shock proteins (hsp70 and hsc70) at different heat-shock temperatures (26, 30, 34, and 38 °C) were measured. Hsp70 and Hsc70 play important roles in protecting cells from heat stresses, but have different expression patterns, with Hsp70 significantly increased in expression during stress and Hsc70 constitutively expressed and only mildly induced during stress. Analysis of heart rate showed significantly higher temperature coefficients (Q10 rates) for limpets at 20 °C than at 24 °C and post-acclimation thermal sensitivity of limpets at 400 ppm was lower than at 1000 ppm. Expression of hsp70 linearly increased with the increasing heat-shock temperatures, with the largest slope occurring in limpets acclimated under a future scenario (24 °C and 1000 ppm pCO2). These results suggested that limpets showed increased sensitivity and stress response under future conditions. Furthermore, the increased variation in physiological response under the future scenario indicated that some individuals have higher physiological plasticity to cope with these conditions. While short-term acclimation to reduced pH seawater decreases the ability of partial individuals against thermal stress, physiological plasticity and variability seem to be crucial in allowing some intertidal animals to survive in a rapidly changing environment.

A detailed analysis on the fluid flow distribution in the back shroud cavity is significant for accurately calculat-ing axial forces in the operation of centrifugal pumps. The numerical calculation results and the experimental results were basically consistent on the performance of the centrifugal pump and the fluid flow characteristics in the back shroud cavity. Distribution of velocity field was researched in the back shroud cavity. We plot the axial distribution curves of the dimensionless circumferential and radial components of velocity of the fluid inside the cavity with different angles and radii. We then analyze the fluid pressure distribution in the back shroud cavity and compare it with experimental results. Results show that the fluid flow in the back shroud cavity involves the core area and the fluid leakage. Results also show that the fluid in the core area behaves like a revolving rigid body. At the operating points of the same flow rate, the cross-sectional area of the volute directly affects the flow rate of the fluid in the back shroud cavity, significantly restricting the fluid flow in that component. How-ever, the flow pattern in the turbulent boundary layer is strongly affected by the leakage flow; hence, the distri-bution of velocity is not axially symmetric. When the flow rate increases from 0.8 Qsp to 1.2 Qsp, the radial dif-ferential pressure between the sealing ring and the volute decreases. Meanwhile, the disc friction loss of the impeller-to-wall inside the back shroud cavity tends to be more circumferentially or radially equal, whereas the radial leakage rate in the back shroud cavity tends to decrease. The fluid flow in the back shroud cavity compris-es the circumferential shear flow and radial differential pressure flow and is considered as a 2D viscous laminar flow.

Drought is a recurring extreme of the climate system with well-documented impacts on agriculture and water resources. The strong perturbation of drought to the land biosphere and atmospheric water cycle will affect atmospheric composition, the nature and extent of which are not well understood. Here we present observational evidence that US air quality is significantly correlated with drought severity. Severe droughts during the period of 1990–2014 were found associated with growth-season (March–October) mean enhancements in surface ozone and PM2.5 of 3.5 ppbv (8 %) and 1.6 µg m−3 (17 %), respectively. The pollutant enhancements associated with droughts do not appear to be affected by the decreasing trend of US anthropogenic emissions, indicating natural processes as the primary cause. Elevated ozone and PM2.5 are attributed to the combined effects of drought on deposition, natural emissions (wildfires, biogenic volatile organic compounds (BVOCs), and dust), and chemistry. Most climate–chemistry models are not able to reproduce the observed correlations of ozone and PM2.5 to drought severity. The model deficiencies are partly attributed to the lack of drought-induced changes in land–atmosphere exchanges of reactive gases and particles and misrepresentation of cloud changes under drought conditions. By applying the observed relationships between drought and air pollutants to climate model projected drought occurrences, we estimate an increase of 1–6 % for ground-level O3 and 1–16 % for PM2.5 in the US by 2100 compared to the 2000s due to increasing drought alone. Drought thus poses an important aspect of climate change penalty on air quality, and a better prediction of such effects would require improvements in model processes.

Abstract Linagliptin is a dipeptidyl Peptidase-4 (DPP-4) inhibitor that inhibits the degradation of glucagon-like peptide 1 (GLP-1), and has been approved for the treatment of type 2 diabetes (T2D) in clinic. Previous studies have shown linagliptin improves β cell function using animal models and isolated islets from normal subjects. Since β cell dysfunction occurs during diabetes development, it was not clear how human islets of T2D patients would respond to linagliptin treatment. Therefore, in this study we employed human islets isolated from donors with and without T2D and evaluated how they responded to linagliptin treatment. Our data showed that linagliptin significantly improved glucose-stimulated insulin secretion for both non-diabetic and diabetic human islets, but its effectiveness on T2D islets was lower than on normal islets. The differential effects were attributed to reduced GLP-1 receptor expression in diabetic islets. In addition, linagliptin treatment increased the relative GLP-1 vs glucagon production in both non-diabetic and diabetic islets, suggesting a positive role of linagliptin in modulating α cell function to restore normoglycemia. Our study indicated that, from the standpoint of islet cell function, linagliptin would be more effective in treating early-stage diabetic patients before they develop severe β cell dysfunction.

In this paper, a double compact elastic module is designed and implemented in the lower extremity exoskeleton. The double compact elastic module is composed of two parts, i.e., physical human robot interaction (pHRI) measurement and the elastic actuation system (EAS), which are called proximal elastic module (PEM) and distal elastic module (DEM) respectively. The PEM is used as the pHRI information collection device while the DEM is used as the compliance device. A novel compact parallelogram-like structure based torsional spring is designed and developed. An iterative finite element analysis (FEA) based optimization process was conducted to find the optimal parameters in the search space. In the PEM, the designed torsional spring has an outer circle with a diameter of 60 mm and an inner hole with a diameter of 12 mm, while in the DEM, the torsional spring has the outer circle with a diameter of 80 mm and the inner circle with a diameter of 16 mm. The torsional spring in the PEM has a thickness of 5 mm and a weight of 60 g, while that in the DEM has a thickness of 10 mm and a weight of 80 g. The double compact elastic module prototype is embedded in the mechanical joint directly. Calibration experiments were conducted on those two elastic modules to obtain the linear torque versus angle characteristic. The calibration experimental results show that this torsional spring in the PEM has a stiffness of 60.2 Nm rad−1, which is capable of withstanding a maximum torque of 4 Nm, while that in the DEM has a stiffness of 80.2 Nm rad−1, which is capable of withstanding a maximum torque of 30 Nm. The experimental results and the simulation data show that the maximum resultant errors are 6 % for the PEM and 4 % for the DEM respectively. In this paper, an assumed regression algorithm is used to learn the human motion intent (HMI) based on the pHRI collection. The HMI is defined as the angular position of the human limb joint. A closed-loop position control strategy is utilized to drive the robotic exoskeleton system to follow the human limb's movement. To verify the developed system, experiments are performed on healthy human subjects and experimental results show that this novel robotic exoskeleton can help human users walk, which can be extended and applied in the assistive wearable exoskeletons.

Histone modification is a ubiquitous regulator of gene transcription. Arabidopsis CUP-SHAPED COTYLEDON (CUC) genes serve as a marker for shoot apical meristem initiation, but how they are regulated during shoot regeneration from in vitro culture, it is not yet understood. Here, the histone modification status of CUC1, CUC2, and CUC3 was analysed using a combination of chromatin immunoprecipitation (ChIP) and real time quantitative PCR. The activation of CUC1 and CUC2 was associated with an increased level of histone H3K4 trimethylation and/or H3K9 acetylation, as well as a reduced level of H3K9 demethylation in various parts of their promoter and coding sequences. Histone modification is suggested to play an important role in regulating CUC1 and CUC2 expression during shoot regeneration.