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Abstract As our planet is entering into the “global boiling” era, understanding regional climate change becomes imperative. Effective downscaling methods that provide localized insights are crucial for this target. Traditional approaches, including computationally-demanding regional dynamical models or statistical downscaling frameworks, are often susceptible to the influence of downscaling uncertainty. Here, we address these limitations by introducing a diffusion probabilistic downscaling model (DPDM) into the meteorological field. This model can efficiently transform data from 1° to 0.1° resolution. Compared with deterministic downscaling schemes, it not only has more accurate local details, but also can generate a large number of ensemble members based on probability distribution sampling to evaluate the uncertainty of downscaling. Additionally, we apply the model to generate a 180-year dataset of monthly surface variables in East Asia, offering a more detailed perspective for understanding local scale climate change over the past centuries.

Summary: In recent years, two-dimensional (2D) materials have been extensively studied and applied in the field of catalysis on account of their high specific surface areas, high exposure of metal active sites, and readily tunable structures. This article introduces various 2D materials (including materials composed of a few atomic layers) and the related synthesis methods and discusses their catalytic performances for hydrogen fuel cells, in particular, for oxygen reduction reaction and hydrogen oxidation reaction. At the end of this review, the advantages and current challenges of 2D materials are summarized, and the prospects of 2D electrocatalytic materials are proposed.

ObjectiveInflammation is a central driver of atherogenesis and eventual plaque rupture. This study aimed to evaluate the association between residual inflammatory risk (RIR) and vulnerable plaques in the carotid artery in patients with ischemic stroke.MethodsPatients with acute ischemic stroke were enrolled from January 2021 to July 2022. They were divided into four groups: RIR only (LDL-C 1.1, which indicated a positive remodeling.ResultsOut of the 468 enrolled patients, 157 (33.5%) were detected to have vulnerable plaques. The proportion of patients with neither risk, RIR, RCR, and RCIR were 32.9%, 28.6%, 18.8%, and 19.7%, respectively. Patients with vulnerable plaques exhibited a higher prevalence of hyperlipidemia (P = 0.026), higher proportion of RIR (P = 0.015), a higher ratio of stroke subtypes of large artery atherosclerosis (P = 0.012), and high leukocyte counts (P < 0.001). The logistic regression analysis detected that RIR was associated with vulnerable plaques after adjusted for major confounding factors (OR 1.98, 95% CI 1.13–3.45, P = 0.016), especially in the large artery atherosclerosis subtype (OR 2.71, 95% CI 1.08–6.77, P = 0.034).ConclusionsIn patients with ischemic stroke, RIR is associated with the vulnerability of carotid plaques, especially for those with the large artery atherosclerosis subtype. Therefore, further studies investigating the interventions to modulate inflammation in these patients may be warranted.

Abstract Recently, many analysis tools have been devised to offer insights into data generated via cytometry by time-of-flight (CyTOF). However, objective evaluations of these methods remain absent as most evaluations are conducted against real data where the ground truth is generally unknown. In this paper, we develop Cytomulate, a reproducible and accurate simulation algorithm of CyTOF data, which could serve as a foundation for future method development and evaluation. We demonstrate that Cytomulate can capture various characteristics of CyTOF data and is superior in learning overall data distributions than single-cell RNA-seq-oriented methods such as scDesign2, Splatter, and generative models like LAMBDA.

In the exploration of deep-sea mineral resources and detection of extreme environments, the use of optical cameras mounted on mobile underwater platforms to obtain optical image data of the seafloor now becomes an important method of deep-sea fine detection. To meet the demand for high-precision detection of deep-sea microtopography, the high-precision three-dimensional(3D) reconstruction method of deep-sea microtopography based on a monocular camera was studied. The monocular camera mounted on the underwater remotely operated vehicle acquired many images of the hydrate-rich areas in China waters. On this basis, the 3D seafloor models of the sand wave area, carbonate rock area, and cold spring area in the typical sea area were constructed using the structure from motion(SFM) method, and the topographic and geomorphological features and bio-ecological information were finely delineated. The results show that this method can provide important support for the exploration of deep-sea epigenetic mineral resources and the detection of extreme environments.

Abstract Peculiar hierarchical microstructures in creatures inspire modern material design with distinct functionalities. Creatures can effortlessly construct sophisticated yet long‐range ordered microstructure across bio‐membrane through ion secretion and precipitation. However, microstructure biomimicry in current technology generally requires elaborate, point‐by‐point fabrication. Herein, a spontaneous yet controllable strategy is developed to achieve surface microstructure engineering through a natural surface phenomenon similar to ion secretion‐precipitation, that is, coupled dissolution‐precipitation. A series of hierarchical microstructures on mineral surfaces in fluids with tunable morphology, orientation, dimension, and spatial distribution are achieved by simply controlling initial dissolution and fluid chemistry. In seawater, long‐range ordered film of vertically aligned brucite flakes forms through interfacial dissolution, nucleation, and confinement‐induced orientation of flakes with vertically grown {110} plane, on the edge of which, fusiform aragonite epitaxially precipitates. With negligible initial surface dissolution, prismatic aragonite epitaxially grows on a calcite polyhedron‐packed surface. By tuning fluid chemistry, closely packed calcite polyhedron and loosely packed calcite micro‐pillars are engineered through rapid and retarded precipitation, respectively. Surprisingly, the spontaneously grown microstructures resemble those deliberately created by human or found in nature, and tremendously modulate surface functionality. These findings open new possibilities for facile and customizable engineering of microstructural surfaces, hierarchical heterostructures, and biomimetic materials.

Abstract Enzyme spatial organization is an evolved mechanism for facilitating multi‐step biocatalysis and can play an important role in the regulation of promiscuous enzymes. The latter function suggests that artificial spatial organization can be an untapped avenue for controlling the specificity of bioengineered metabolic pathways. A promiscuous terpene synthase (nerolidol synthase) is co‐localized and spatially organized with the preceding enzyme (farnesyl diphosphate synthase) in a heterologous production pathway, via translational protein fusion and/or co‐encapsulation in a self‐assembling protein cage. Spatial organization enhances nerolidol production by ≈11‐ to ≈62‐fold relative to unorganized enzymes. More interestingly, striking differences in the ratio of end products (nerolidol and linalool) are observed with each spatial organization approach. This demonstrates that artificial spatial organization approaches can be harnessed to modulate the product profiles of promiscuous enzymes in engineered pathways in vivo. This extends the application of spatial organization beyond situations where multiple enzymes compete for a single substrate to cases where there is competition among multiple substrates for a single enzyme.

Objective Autogenic bone grafts have shown successful fusion rates in the treatment of degenerative lumbar disorders, but taking too many autogenic bones may result in donor site ischemia or infection. This study aimed to evaluate the outcomes of single‐level oblique lumbar interbody fusion (OLIF) using pure allograft combined with posterior pedicle screw instrumentation through the Wiltse approach. Methods A retrospective case analysis was performed on a series of consecutive patients who received a single‐level OLIF procedure combined with posterior pedicle screw instrumentation through the Wiltse approach between July 1, 2017, and December 31, 2019, in which pure allogenic bone graft was used and filled in the large window of the cage. The patients were followed up as scheduled at 1 day and 3, 6, 12, 24 months after operation. Clinical outcome was assessed by multiple questionnaires, including Oswestry disability index (ODI), Japanese Orthopaedic Association (JOA) score rating system, short form‐36 health survey (SF‐36), and visual analog scale (VAS) for low back pain. Radiographic outcome was evaluated by measuring the parameters such as disc height, lumbar lordosis, and segmental angle on the standard standing lateral radiographs, and the space angle of the fusion level on the dynamic views of the lateral radiographs. Subsidence of the cage and intervertebral fusion status were evaluated on both the radiographic and CT scan images. Results A total of 34 patients were finally included in this study. At 2‐year follow‐up, the VAS for low back pain, ODI, JOA, and SF‐36 scores all had significant improvement (p

Hexokinase II (Hxk2) is a master protein in glucose-mediated transcriptional repression signaling pathway. Degrading Hxk2 through an auxin-inducible protein degradation previously doubled sesquiterpene (nerolidol) production at gram-per-liter levels in Saccharomyces cerevisiae. Global transcriptomics/proteomics profiles in Hxk2-deficient background are important to understanding genetic and molecular mechanisms for improved nerolidol production and guiding further strain optimization. Here, proteomic responses to Hxk2 depletion are investigated in the yeast strains harboring a GAL promoters-controlled nerolidol synthetic pathway, at the exponential and ethanol growth phases and in GAL80-wildtype and gal80Δ backgrounds. Carbon metabolic pathways and amino acid metabolic pathways show diversified responses to Hxk2 depletion and growth on ethanol, including upregulation of alternative carbon catabolism and respiration as well as downregulation of amino acid synthesis. De-repression of GAL genes may contribute to improved nerolidol production in Hxk2-depleted strains. Seventeen transcription factors associated with upregulated genes are enriched. Validating Ash1-mediated repression on the RIM4 promoter shows the variation on the regulatory effects of different Ash1-binding sites and the synergistic effect of Ash1 and Hxk2-mediated repression. Further validation of individual promoters shows that HXT1 promoter activities are glucose-dependent in hxk2Δ background, but much weaker than those in HXK2-wildtype background. In summary, inactivating HXK2 may relieve glucose repression on respiration and GAL promoters for improved bioproduction under aerobic conditions in S. cerevisiae. The proteomics profiles provide a better genetics overview for a better metabolic engineering design in Hxk2-deficient backgrounds.

Cashmere is the fine bottom hair produced by the secondary hair follicles of the skin. This hair is economically important. Previous studies by our research group have shown that exogenous melatonin (MT) can regulate the periodic growth of secondary hair follicles, induce the secondary development of villi, and alter the expression of some genes related to hair follicle development. Few studies on the regulation of villus growth by MT binding receptors have been published. In this study, MT was implanted subcutaneously behind the ear of Inner Mongolia cashmere goats. RT-qPCR, in situ hybridization, Western blot analysis, immunofluorescence and RNAi techniques were used to investigate the receptors and functions of MT in regulating the development of secondary hair follicles in Inner Mongolia cashmere goats. The results showed that MT binds to the nuclear receptor RORα on dermal papilla stimulates hair follicle development and promotes villus growth. The RORα mRNA expression in the skin of Inner Mongolia cashmere goats was periodic and showed a trend of first increasing and then decreasing. The expression began to increase in February, peaked in April, and reached the lowest level in May. RORα significantly affected the mRNA expression of β-catenin gene, a key gene in hair follicle development, in the presence of MT. It will lay a solid molecular foundation for further research on the regulation mechanism between MT receptor and villus growth and development and to achieve artificial regulation of villus growth time and yield to improve the effect of villus production.

Facing with the sustainable development of civil infrastructures in plateau regions, this paper begins with a brief description of the problems need to be overcome when concrete is under plateau harsh environment, and concisely reviews the current research on potential utilization of superabsorbent polymer (SAP) to reinforce concrete, and the limitations, improvement strategies and future perspectives of SAP on delivering the targeted shrinkage inhibition, mechanical enhancement and air-entrainment improvement of concrete in plateau region are discussed and proposed from sustainable perspectives.

Due to recent innovations in gene editing technology, great progress has been made in livestock breeding, with researchers rearing gene-edited pigs, cattle, sheep, and other livestock. Gene-editing technology involves knocking in, knocking out, deleting, inhibiting, activating, or replacing specific bases of DNA or RNA sequences at the genome level for accurate modification, and such processes can edit genes at a fixed point without needing DNA templates. In recent years, although clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system-mediated gene-editing technology has been widely used in research into the genetic breeding of animals, the system’s efficiency at inserting foreign genes is not high enough, and there are certain off-target effects; thus, it is not appropriate for use in the genome editing of large livestock such as cashmere goats. In this study, the development status, associated challenges, application prospects, and future prospects of CRISPR/Cas9-mediated precision gene-editing technology for use in livestock breeding were reviewed to provide a theoretical reference for livestock gene function analysis, genetic improvement, and livestock breeding that account for characteristics of local economies.

Gene dosage-based expression upregulation suffers from instability and random gene integration. Here, the authors report HapAmp, a method that uses haploinsufficiency as evolutionary force to drive in vivo gene amplification, and demonstrate its applications in protein and biochemical production in yeast.

Eukaryotic trans-regulatory mechanisms are exploited to synthesize a stringent tetracycline-repressible circuit and a heat-inducible circuit for negative/positive metabolic controls using the GAL system in Saccharomyces cerevisiae.

A cross-sectional census was conducted on all students at the campus of Inner Mongolia Medical University using a self-administered questionnaire. This study aimed to investigate their love from psychological pressure, behavioral characteristics, social cognition, etc. Our results show that all students cultivate feelings and become lifelong partners as their motivation for love. Among the population with various demographic characteristics, the prevalence of love among disadvantaged groups is low; that is, women are lower than men, and those from rural are lower than those from cities. After balancing areas and gender, mental working families have a high prevalence of love. Instead, students whose parents' high expectations pressure their children to have a high love prevalence. This is due to China's specific historical perspective. Our results suggested that although China has been deeply integrated with the world and has more frequent ideological and cultural exchanges, college students still inherit China's traditional outlook on love.