Precipitation regime changes in High Mountain Asia driven by cleaner air.

High Mountain Asia (HMA) has experienced a spatial imbalance in water resources in recent decades, partly because of a dipolar pattern of precipitation changes known as South Drying-North Wetting1. These changes can be influenced by both human activities and internal climate variability2,3. Although climate projections indicate a future widespread wetting trend over HMA1,4, the timing and mechanism of the transition from a dipolar to a monopolar pattern remain unknown. Here we demonstrate that the observed dipolar precipitation change in HMA during summer is primarily driven by westerly- and monsoon-associated precipitation patterns. The weakening of the Asian westerly jet, caused by the uneven emission of anthropogenic aerosols, favoured a dipolar precipitation trend from 1951 to 2020. Moreover, the phase transition of the Interdecadal Pacific Oscillation induces an out-of-phase precipitation change between the core region of the South Asian monsoon and southeastern HMA. Under medium- or high-emission scenarios, corresponding to a global warming of 0.6-1.1 °C compared with the present, the dipolar pattern is projected to shift to a monopolar wetting trend in the 2040s. This shift in precipitation patterns is mainly attributed to the intensified jet stream resulting from reduced emissions of anthropogenic aerosols. These findings underscore the importance of considering the impact of aerosol emission reduction in future social planning by policymakers.

Pneumatic Structural Deformation to Enhance Resonance Behavior for Broadband and Adaptive Radar Stealth.

Ideal radar absorbing materials (RAMs) require instantaneous, programmable, and spontaneous adaptability to cope with a complex electromagnetic (EM) environment across the full working frequency. Despite various material systems and adaptive mechanisms having been demonstrated, it remains a formidable challenge to integrate these benefits simultaneously. Here, we present a pneumatic matrix that couples morphable MXene/elastomer conductors with dielectric spacers, which leverages controllable airflow to reconfigure the spatial structure between a flat sheet and a hemispherical crown while maintaining resistance stability via wrinkle folding and unfolding. The interdimensional reconfigurations drastically induce multiple resonance behavior, enabling the matrix remarkable frequency tunability (144.5%), ultrawide bandwidth (15 GHz), weak angular dependence (45° incidence), ultrafast responsiveness (∼30 ms), and excellent reproducibility (1000 cycles). With multichannel fluidic and conceptual automated control systems, the final pneumatic device demonstrates a multiplexed, programmable, and autonomous transformable mode that builds a promising platform for smart radar cloaking.

Single-cell transcriptomic analysis deciphers heterogenous cancer stem-like cells in colorectal cancer and their organ-specific metastasis.

OBJECTIVE: Metastasis is the major cause of cancer death. However, what types of heterogenous cancer cells in primary tumour and how they metastasise to the target organs remain largely undiscovered. DESIGN: We performed single-cell RNA sequencing and spatial transcriptomic analysis in primary colorectal cancer (CRC) and metastases in the liver (lCRC) or ovary (oCRC). We also conducted immunofluorescence staining and functional experiments to examine the mechanism. RESULTS: Integrative analyses of epithelial cells reveal a stem-like cell cluster with high protein tyrosine phosphatase receptor type O (PTPRO) and achaete scute-like 2 (ASCL2) expression as the metastatic culprit. This cell cluster comprising distinct subpopulations shows distinct liver or ovary metastatic preference. Population 1 (P1) cells with high delta-like ligand 4 (DLL4) and MAF bZIP transcription factor A (MAFA) expression are enriched in primary CRC and oCRC, thus may be associated with ovarian metastasis. P3 cells having a similar expression pattern as cholangiocytes are found mainly in primary CRC and lCRC, presuming to be likely the culprits that specifically metastasise to the liver. Stem-like cells interacted with cancer-associated fibroblasts and endothelial cells via the DLL4-NOTCH signalling pathway to metastasise from primary CRC to the ovary. In the oCRC microenvironment, myofibroblasts provide cancer cells with glutamine and perform a metabolic reprogramming, which may be essential for cancer cells to localise and develop in the ovary. CONCLUSION: We uncover a mechanism for organ-specific CRC metastasis.

A comparison of computational algorithms for the Bayesian analysis of clinical trials.

BACKGROUND: Clinical trials are increasingly using Bayesian methods for their design and analysis. Inference in Bayesian trials typically uses simulation-based approaches such as Markov Chain Monte Carlo methods. Markov Chain Monte Carlo has high computational cost and can be complex to implement. The Integrated Nested Laplace Approximations algorithm provides approximate Bayesian inference without the need for computationally complex simulations, making it more efficient than Markov Chain Monte Carlo. The practical properties of Integrated Nested Laplace Approximations compared to Markov Chain Monte Carlo have not been considered for clinical trials. Using data from a published clinical trial, we aim to investigate whether Integrated Nested Laplace Approximations is a feasible and accurate alternative to Markov Chain Monte Carlo and provide practical guidance for trialists interested in Bayesian trial design. METHODS: Data from an international Bayesian multi-platform adaptive trial that compared therapeutic-dose anticoagulation with heparin to usual care in non-critically ill patients hospitalized for COVID-19 were used to fit Bayesian hierarchical generalized mixed models. Integrated Nested Laplace Approximations was compared to two Markov Chain Monte Carlo algorithms, implemented in the software JAGS and stan, using packages available in the statistical software R. Seven outcomes were analysed: organ-support free days (an ordinal outcome), five binary outcomes related to survival and length of hospital stay, and a time-to-event outcome. The posterior distributions for the treatment and sex effects and the variances for the hierarchical effects of age, site and time period were obtained. We summarized these posteriors by calculating the mean, standard deviations and the 95% equitailed credible intervals and presenting the results graphically. The computation time for each algorithm was recorded. RESULTS: The average overlap of the 95% credible interval for the treatment and sex effects estimated using Integrated Nested Laplace Approximations was 96% and 97.6% compared with stan, respectively. The graphical posterior densities for these effects overlapped for all three algorithms. The posterior mean for the variance of the hierarchical effects of age, site and time estimated using Integrated Nested Laplace Approximations are within the 95% credible interval estimated using Markov Chain Monte Carlo but the average overlap of the credible interval is lower, 77%, 85.6% and 91.3%, respectively, for Integrated Nested Laplace Approximations compared to stan. Integrated Nested Laplace Approximations and stan were easily implemented in clear, well-established packages in R, while JAGS required the direct specification of the model. Integrated Nested Laplace Approximations was between 85 and 269 times faster than stan and 26 and 1852 times faster than JAGS. CONCLUSION: Integrated Nested Laplace Approximations could reduce the computational complexity of Bayesian analysis in clinical trials as it is easy to implement in R, substantially faster than Markov Chain Monte Carlo methods implemented in JAGS and stan, and provides near identical approximations to the posterior distributions for the treatment effect. Integrated Nested Laplace Approximations was less accurate when estimating the posterior distribution for the variance of hierarchical effects, particularly for the proportional odds model, and future work should determine if the Integrated Nested Laplace Approximations algorithm can be adjusted to improve this estimation.

Dual-Strategy Tailoring Molecular Structures of Dopant-Free Hole Transport Materials for Efficient and Stable Perovskite Solar Cells.

Dopant-free hole transport materials (HTMs) are ideal materials for highly efficient and stable n-i-p perovskite solar cells (PSCs), but most current design strategies for tailoring the molecular structures of HTMs are limited to single strategy. Herein, four HTMs based on dithienothiophenepyrrole (DTTP) core are devised through dual-strategy methods combining conjugate engineering and side chain engineering. DTTP-ThSO with ester alkyl chain that can form six-membered ring by the S⋅⋅⋅O noncovalent conformation lock with thiophene in the backbone shows good planarity, high-quality film, matching energy level and high hole mobility, as well as strong defect passivation ability. Consequently, a remarkable power conversion efficiency (PCE) of 23.3 % with a nice long-term stability is achieved by dopant-free DTTP-ThSO-based PSCs, representing one of the highest values for un-doped organic HTMs based PSCs. Especially, the fill factor (FF) of 82.3 % is the highest value for dopant-free small molecular HTMs-based n-i-p PSCs to date. Moreover, DTTP-ThSO-based devices have achieved an excellent PCE of 20.9 % in large-area (1.01 cm2) devices. This work clearly elucidates the structure-performance relationships of HTMs and offers a practical dual-strategy approach to designing dopant-free HTMs for high-performance PSCs.

The C2H2-type zinc-finger regulator AoKap5 is required for the growth and kojic acid synthesis in Aspergillus oryzae.

Aspergillus oryzae is an important filamentous fungus widely used for the industrial production of fermented foods and secondary metabolites. The clarifying of the mechanism of the growth and secondary metabolites in A. oryzae is important for its industrial production and utilization. Here, the C2H2-type zinc-finger protein AoKap5 was characterized to be involved in the growth and kojic acid production in A. oryzae. The Aokap5-disrupted mutants were constructed by the CRISPR/Cas9 system, which displayed increased colony growth but decreased conidial formation. Deletion of Aokap5 enhanced the tolerance to cell-wall and oxidative but not osmotic stress. The transcriptional activation assay revealed that AoKap5 itself didn't have transcriptional activation activity. Disruption of Aokap5 resulted in the reduced production of kojic acid, coupled with the reduced expression of the kojic acid synthesis genes kojA and kojT. Meanwhile, overexpression of kojT could rescue the decreased production of kojic acid in Aokap5-deletion strain, indicating that Aokap5 serves upstream of kojT. Furthermore, the yeast one-hybrid assay demonstrated that AoKap5 could directly bind to the kojT promoter. These findings suggest that AoKap5 regulates kojic acid production through binding to the kojT promoter. This study provides an insight into the role of zinc finger protein in the growth and kojic acid biosynthesis of A. oryzae.

Functional role of a novel zinc finger protein, AoZFA, in growth and kojic acid synthesis in Aspergillus oryzae.

Kojic acid (KA) is a valuable secondary metabolite that is regulated by zinc finger proteins in Aspergillus oryzae. However, only two such proteins have been characterized to function in kojic acid production of A. oryzae to date. In this study, we identified a novel zinc finger protein, AoZFA, required for kojic acid biosynthesis in A. oryzae. Our results showed that disruption of AozfA led to increased expression of kojA and kojR involved in kojic acid synthesis, resulting in enhanced kojic acid production, while overexpression of AozfA had the opposite effect. Furthermore, deletion of kojR in the AozfA disruption strain abolished kojic acid production, whereas overexpression of kojR enhanced it, indicating that AoZFA regulates kojic acid production by affecting kojR. Transcriptional activation assay revealed that AoZFA is a transcriptional activator. Interestingly, when kojR was overexpressed in the AozfA overexpression strain, the production of kojic acid failed to be rescued, suggesting that AozfA plays a distinct role from kojR in kojic acid biosynthesis. Moreover, we found that AozfA was highly induced by zinc during early growth stages, and its overexpression inhibited the growth promoted by zinc, whereas its deletion had no effect, suggesting that AoZFA is non-essential but has a role in the response of A. oryzae to zinc. Overall, these findings provide new insights into the roles of zinc finger proteins in the growth and kojic acid production of A. oryzae.IMPORTANCEKojic acid (KA) is an economically valuable secondary metabolite produced by Aspergillus oryzae due to its vast biological activities. Genetic modification of A. oryzae has emerged as an efficient strategy for enhancing kojic acid production, which is dependent on the mining of genes involved in kojic acid synthesis. In this study, we have characterized a novel zinc-finger protein, AoZFA, as a negative regulator of kojic acid production by affecting kojR. AozfA is an excellent target for improving kojic acid production without any effects on the growth of A. oryzae. Furthermore, the simultaneous modification of AozfA and kojR exerts a more significant promotional effect on kojic acid production than the modification of single genes. This study provides new insights for the regulatory mechanism of zinc finger proteins in the growth and kojic acid production of A. oryzae.

Cascaded parallel crowd counting network with multi-resolution collaborative representation.

Accurately estimating the size and density distribution of a crowd from images is of great importance to public safety and crowd management during the COVID-19 pandemic, but it is very challenging as it is affected by many complex factors, including perspective distortion and background noise information. In this paper, we propose a novel multi-resolution collaborative representation framework called the cascaded parallel network (CP-Net), consisting of three parallel scale-specific branches connected in a cascading mode. In the framework, the three cascaded multi-resolution branches efficiently capture multi-scale features through their specific receptive fields. Additionally, multi-level feature fusion and information filtering are performed continuously on each branch to resist noise interference and perspective distortion. Moreover, we design an information exchange module across independent branches to refine the features extracted by each specific branch and deal with perspective distortion by using complementary information of multiple resolutions. To further improve the robustness of the network to scale variance and generate high-quality density maps, we construct a multi-receptive field fusion module to aggregate multi-scale features more comprehensively. The performance of our proposed CP-Net is verified on the challenging counting datasets (UCF_CC_50, UCF-QNRF, Shanghai Tech A&B, and WorldExpo'10), and the experimental results demonstrate the superiority of the proposed method.

Elucidating the Role of Antisolvents on the Surface Chemistry and Optoelectronic Properties of CsPbBrxI3-x Perovskite Nanocrystals.

Colloidal lead-halide perovskite nanocrystals (LHP NCs) have emerged over the past decade as leading candidates for efficient next-generation optoelectronic devices, but their properties and performance critically depend on how they are purified. While antisolvents are widely used for purification, a detailed understanding of how the polarity of the antisolvent influences the surface chemistry and composition of the NCs is missing in the field. Here, we fill this knowledge gap by studying the surface chemistry of purified CsPbBrxI3-x NCs as the model system, which in itself is considered a promising candidate for pure-red light-emitting diodes and top-cells for tandem photovoltaics. Interestingly, we find that as the polarity of the antisolvent increases (from methyl acetate to acetone to butanol), there is a blueshift in the photoluminescence (PL) peak of the NCs along with a decrease in PL quantum yield (PLQY). Through transmission electron microscopy and X-ray photoemission spectroscopy measurements, we find that these changes in PL properties arise from antisolvent-induced iodide removal, which leads to a change in halide composition and, thus, the bandgap. Using detailed nuclear magnetic resonance (NMR) and Fourier-transform infrared spectroscopy (FTIR) measurements along with density functional theory calculations, we propose that more polar antisolvents favor the detachment of the oleic acid and oleylamine ligands, which undergo amide condensation reactions, leading to the removal of iodide anions from the NC surface bound to these ligands. This work shows that careful selection of low-polarity antisolvents is a critical part of designing the synthesis of NCs to achieve high PLQYs with minimal defect-mediated phase segregation.

Overexpression of a novel gene Aokap2 affects the growth and kojic acid production in Aspergillus oryzae.

BACKGROUND: Aspergillus oryzae is an industrially important filamentous fungus for the production of fermentative food, commercial enzyme and valuable secondary metabolites. Although the whole genome of A. oryzae has been sequenced in 2005, there is currently not enough research on functional genes that affect the growth and secondary metabolites of A. oryzae. This study aimed to identify and characterize functional genes involved in the growth and secondary metabolites of A. oryzae. METHODS AND RESULTS: Our previous work on the developmental transcriptome of A. oryzae found that an uncharacterized gene Aokap2 was repressed during the development of A. oryzae. In this study, the gene expression pattern was verified by qRT-PCR. Phylogenetic analysis revealed that AoKAP2 has the species specificity of Aspergillus. Furthermore, Aokap2 was overexpressed using the A. oryzae amyB promoter and overexpression of Aokap2 caused the inhibition in mycelium growth, conidia formation and biomass. Additionally, overexpression of Aokap2 increased the production of kojic acid. In accordance with the enhanced kojic acid, the overexpression of Aokap2 led to elevated transcription levels of the key kojic acid synthesis gene kojA and the global transcriptional regulator gene of secondary metabolism laeA. Moreover, the expression of Aokap2 was down-regulated significantly in the laeA mutant. Meanwhile, overexpression of Aokap2 in the kojA disrupted strain resulted in a ΔkojA strain-like phenotype with significant inhibition in kojic acid production. CONCLUSION: Taken together, these data suggest that a novel gene Aokap2 is involved in the growth and overexpression of Aokap2 increased kojic acid production through affecting the expression of laeA and kojA. The identification of Aokap2 provides a new target for genetic modification of the growth and the production of kojic acid in A. oryzae.

Phaeosphamides A and B, Cytotoxic Cyclodecadepsipeptides from the Mangrove-Derived Fungus Phaeosphaeriopsis sp. S296.

Chemical examination of the fermented broth of the mangrove-derived fungus Phaeosphaeriopsis sp. S296 resulted in the isolation of two new cyclodecadepsipeptides, namely phaeosphamides A (1) and B (2), as well as one known congener Sch 217048 (3). The structures of new metabolites, including absolute configurations, were established on the basis of extensive spectroscopic data analyses, chemical conversion, and Marfey's method. The 2-hydroxy-3-methylpentanoic acid (Hmp) moiety and pipecolic acid (Pip) unit in structures were rarely discovered in nature. Interestingly, compounds 1-3 are examples of peptides discovered from the fungal genus Phaeosphaeriopsis for the first time. All identified compounds were evaluated for their cytotoxicity against five tumor cell lines of AGS, BEL-7402, HepG2, B16, and BIU87. Among them, compound 1 showed inhibitory activities against these tumor cell lines with IC50 values ranging from 5.14 to 66.38 µM. A further mechanistic investigation found that 1 arrested AGS cells in the G2 phase and induced their apoptosis in a dose-dependent manner.

Binding-Induced Fibrillogenesis Peptides Recognize and Block Intracellular Vimentin Skeletonization against Breast Cancer.

Life is recognized as a sophisticated self-assembling material system. Cancer involves the overexpression and improper self-assembly of proteins, such as cytoskeleton protein vimentin, an emerging target related to tumor metastasis. Herein, we design a binding-induced fibrillogenesis (BIF) peptide that in situ forms fibrous networks, blocking the improper self-assembly of vimentin against cancer. The BIF peptide can bind to vimentin and subsequently perform fibrillogenesis to form fibers on vimentin. The resultant peptide fibrous network blocks vimentin skeletonization and inhibits the migration and invasion of tumor cells. In mouse models of tumor metastasis, the volume of tumor and the number of lung metastases are markedly decreased. Moreover, the efficacy of BIF peptide (5 mg/kg) is much higher than small molecular antimetastasis drug withaferin A (5 mg/kg) as a standard, indicating that the BIF peptide shows advantages over small molecular inhibitors in blocking the intracellular protein self-assembly.

Disruption of Aokap6 near the kojic acid gene cluster affects the growth and kojic acid production in Aspergillus oryzae.

The kojic acid gene cluster of Aspergillus oryzae plays a key role in kojic acid synthesis. Although the kojic acid gene cluster has been found in 2010, there is little information on the function of the genes located near the kojic acid gene cluster of A. oryzae and whether these genes affect the kojic acid gene cluster containing kojA, kojR and kojT. Here, Aokap6 near the kojic acid gene cluster of A. oryzae was identified and characterized. The Aokap6 disrupted mutants were constructed by the CRISPR/Cas9 system, which exhibited increased mycelium growth and conidial formation. Disruption of Aokap6 enhanced the tolerance to cell wall, oxidative and heat stress but not osmotic stress. Deletion of Aokap6 repressed kojic acid production, together with the reduced expression of kojA, kojR and kojT. Meanwhile, knockout of kojA, kojR and kojT led to the declined expression of Aokap6, indicating that Aokap6 is required for kojic acid production in coordination with kojA, kojR and kojT. Furthermore, overexpression of kojA, kojR and kojT had no effects on the transcript level of Aokap6, and overexpression of kojA in Aokap6 deletion strain could rescue the reduced yield of kojic acid, suggesting that Aokap6 is involved in kojic acid synthesis acting upstream of kojA. These findings provide new insight for the further understanding of kojic acid gene cluster and kojic acid production in A. oryzae.

Materials, photophysics and device engineering of perovskite light-emitting diodes.

Here we provide a comprehensive review of a newly developed lighting technology based on metal halide perovskites (i.e. perovskite light-emitting diodes) encompassing the research endeavours into materials, photophysics and device engineering. At the outset we survey the basic perovskite structures and their various dimensions (namely three-, two- and zero-dimensional perovskites), and demonstrate how the compositional engineering of these structures affects the perovskite light-emitting properties. Next, we turn to the physics underpinning photo- and electroluminescence in these materials through their connection to the fundamental excited states, energy/charge transport processes and radiative and non-radiative decay mechanisms. In the remainder of the review, we focus on the engineering of perovskite light-emitting diodes, including the history of their development as well as an extensive analysis of contemporary strategies for boosting device performance. Key concepts include balancing the electron/hole injection, suppression of parasitic carrier losses, improvement of the photoluminescence quantum yield and enhancement of the light extraction. Overall, this review reflects the current paradigm for perovskite lighting, and is intended to serve as a foundation to materials and device scientists newly working in this field.

Identification and characterization of a novel gene Aokap1 involved in growth and kojic acid synthesis in Aspergillus oryzae.

The elucidation of the mechanism for the growth and secondary metabolites in Aspergillus oryzae is important for industrial production and utilization. Here, we found that the expression of a novel gene Aokap1 was induced during the growth of A. oryzae. Sequence analysis revealed that AoKap1 has four transmembrane regions and is conserved in Aspergillus species. Disruption of Aokap1 caused the inhibition in mycelium growth and conidia formation, corresponding with reduced expression of brlA and abaA. Furthermore, deletion of Aokap1 resulted in elevated production of kojic acid, and the expression of kojA, kojR and kojT was up-regulated in Aokap1-disrupted strain. Meanwhile, overexpression of kojR resulted in the decreased expression of Aokap1, suggesting that disruption of Aokap1 increased kojic acid production by affecting the expression of kojA, kojR and kojT. The discovery of Aokap1 provides a new target for genetic modification of the growth and kojic acid production in A. oryzae.

Design and Analysis of an Intelligent Toilet Wheelchair Based on Planar 2DOF Parallel Mechanism with Coupling Branch Chains.

Due to the fixed size of the structure or the possibility of only simple manual adjustment, the traditional toilet wheelchair cannot easily be adapted to the size of the user or the toilet. In this paper, a planar two-degree-of-freedom parallel mechanism with coupling branch chains is proposed to enable both seat height adjustment and body posture adjustment of a toilet chair, solving the problems of posture adaptability between the user and the machine, and height matching in the process of using the wheelchair-assisted toilet. The model of the parallel mechanism was designed after analyzing the general rules of posture transformation in the human body before and after the toilet process, and the dimensions of each linkage were then determined according to the constraint conditions. By analyzing the degree of freedom, kinematics, workspace, singularity and position of the center of gravity, the rationality of the design was ensured. The weighted average function was used to find the optimal fixed point of the horizontal moving slider, and the actual trajectory at the end of the single driving mode was close to the ideal trajectory. The experimental results show that the adjustable seat height range is 290~550 mm and the adjustable angle range is 0~90°, which can enable disabled people to use the toilet independently.

Kinematics and Singularity Analysis of a 7-DOF Redundant Manipulator.

A new method of kinematic analysis and singularity analysis is proposed for a 7-DOF redundant manipulator with three consecutive parallel axes. First, the redundancy angle is described according to the self-motion characteristics of the manipulator, the position and orientation of the end-effector are separated, and the inverse kinematics of this manipulator is analyzed by geometric methods with the redundancy angle as a constraint. Then, the Jacobian matrix is established to derive the conditions for the kinematic singularities of the robotic arm by using the primitive matrix method and the block matrix method. Then, the kinematic singularities conditions in the joint space are mapped to the Cartesian space, and the singular configuration is described using the end poses and redundancy angles of the robotic arm, and a singularity avoidance method based on the redundancy angles and end pose is proposed. Finally, the correctness and feasibility of the inverse kinematics algorithm and the singularity avoidance method are verified by simulation examples.

A highly efficient identification of mutants generated by CRISPR/Cas9 using the non­functional DsRed assisted selection in Aspergillus oryzae.

The CRISPR/Cas9 system has become a great tool for target gene knock-out in filamentous fungi. It is laborious and time-consuming that identification mutants from a large number of transformants through PCR or enzyme-cut method. Here, we first developed a CRISPR/Cas9 system in Aspergillus oryzae using AMA1-based autonomously replicating plasmid and Cas9 under the control of the Aspergillus nidulans gpdA promoter. By the genome editing technique, we successfully obtained mutations within each target gene in Aspergillus oryzae. Then, we put the protospacer sequence of a target gene and its protospacer adjacent motif (PAM) behind the start codon "ATG" of DsRed, yielding the non­functional DsRed (nDsRed) reporter gene, and the nDsRed reporter gene could be rescued after successful targeted editing. Moreover, this method was also applied by targeting the kojic acid synthesis gene kojA, and the transformants with DsRed activity were found to harbor targeted mutations in kojA. These results suggest that the nDsRed can be used as a powerful tool to facilitate the identification of mutants generated by CRISPR/Cas9 in Aspergillus oryzae.

How to predict early clinical outcomes and evaluate the quality of primary total knee arthroplasty: a new scoring system based on lower-extremity angles of alignment.

BACKGROUND: A method that can accurately predict the outcome of surgery can give patients timely feedback. In addition, to some extent, an objective evaluation method can help the surgeon quickly summarize the patient's surgical experience and lessen dependence on the long wait for follow-up results. However, there was still no precise tool to predict clinical outcomes of total knee arthroplasty (TKA). This study aimed to develop a scoring system to predict clinical results of TKA and then grade the quality of TKA. METHODS: We retrospectively reviewed 98 primary TKAs performed between April 2013 and March 2017 to determine predictors of clinical outcomes among lower-extremity angles of alignment. Applying multivariable linear-regression analysis, we built Models (i) and (ii) to predict detailed clinical outcomes which were evaluated using the Knee Society Score (KSS). Multivariable logistic-regression analysis was used to establish Model (iii) to predict probability of getting a good clinical outcome (PGGCO) which was evaluated by Knee Injury and Osteoarthritis Outcome Score (KOOS) score. Finally, we designed a new scoring system consisting of 3 prediction models and presented a method of grading TKA quality. Thirty primary TKAs between April and December 2017 were enrolled for external validation. RESULTS: We set up a scoring system consisting of 3 models. The interpretations of Model (i) and (ii) were good (R2 = 0.756 and 0.764, respectively). Model (iii) displayed good discrimination, with an area under the curve (AUC) of 0.936, and good calibration according to the calibration curve. Quality of surgery was stratified as follows: "A" = PGGCO ≥0.8, "B" = PGGCO ≤0.6 but < 0.8, and "C" = PGGCO < 0.6. The scoring system performed well in external validation. CONCLUSIONS: This study first developed a validated, evidence-based scoring system based on lower-extremity angles of alignment to predict early clinical outcomes and to objectively evaluate the quality of TKA.

Natural Hydroxamate-Containing Siderophore Acremonpeptides A-D and an Aluminum Complex of Acremonpeptide D from the Marine-Derived Acremonium persicinum SCSIO 115.

Four new hydroxamate-containing natural product cyclopeptides designated acremonpeptides A-D (1-4), together with Al(III)-acremonpeptide D (5) were obtained from the marine fungus Acremonium persicinum SCSIO 115. The planar structures of 1-5 were established on the basis of HRMS as well as 1D and 2D NMR data sets. Moreover, the amino acid absolute configurations were determined using Marfey's method. Compounds 1-5 all feature three 2-amino-5-(N-hydroxyacetamido)pentanoic acid (N5-hydroxy-N5-acetyl-l-ornithine) metal ion chelating moieties. Beyond their discovery and structure elucidation, in vitro bioassays revealed acremonpeptides A (1), B (2), and Al(III)-acremonpeptide D (5) as moderate antiviral agents for herpes simplex virus 1 with EC50 values of 16, 8.7, and 14 µM, respectively.