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The release of ChatGPT has triggered global attention on artificial intelligence (AI), and AI for science is thus becoming a hot topic in the scientific community. When we think about unleashing the power of AI to accelerate scientific research, the question coming to our mind first is whether there is a continuous supply of highly available data at a sufficiently large scale.

Snow density is one of the basic properties used to describe snow cover characteristics, and it is critical for remote sensing retrieval, water resources assessment and modeling inputs. There are many instruments available to measure snow density in situ. However, there are measurement errors of snow density for bulk and layers or gravimetric and electronic instruments, which may affect the accuracy of remote sensing retrieval and model simulation. Especially in China, due to the noticeable heterogeneity of snowpacks, it is necessary to evaluate in detail the performance and applicability of snow density instruments in different snowpack conditions. This study evaluated the performance of different snow density instruments: the Federal Sampler, the model VS–43 snow density cylinder (VS–43), the wedge snow density cutter (WC1000 and WC250), and the Snow Fork. The average bulk snow density of all instrument measurements was set as the reference value for evaluation. The results showed that as compared with the reference, the VS–43 cylinder presented the best performance for bulk snow density measurement in the measured range with the lowest RMSE (11 kg m−3), BIAS (3 kg m−3), and MRE (1.6%). For layer observation, bulk snow density was overestimated by 8.1% with WC1000 and underestimated by 11.4% with Snow Fork which was the worst performance compared with the reference value, and there were greater measurement errors of snow density in the depth hoar than other snow layers. Compared with grassland, the uncertainty of snow density measurements was slightly lower in forests. Overall, the Federal Sampler and VS–43 cylinder are more suitable for bulk snow density measurement in deep snowpack regions across China, and it is recommended to use WC1000, WC250 and Snow Fork to measure the snow density of snow layers in the snow stratigraphy.

A series of large-scale north-dipping faults and imbricate folding structures have developed in the Cretaceous ultra-deep tight sandstone reservoirs in Bozi-Dabei area of Kuqa Depression of Tarim Basin under the north-to-south thrust-nappe movement in this area. This complex structural morphology results in highly variable in-situ stress fields, leading to significant differences in reservoir modification effectiveness. Therefore, it is urgent to clarify the disturbance characteristics of the in-situ stress caused by the complex structures in the study area. In this study, multiple methods were combined for the accurate interpretation of the current in-situ stress of a single well. The disturbance effects of faults, folds, and fault-fold composite structures on the in-situ stress were analyzed separately. The relevant disturbance mechanisms were identified, and a zoning map of the disturbance characte-ristics of the in-situ stress for the study area was presented. Based on these disturbance characteristics, models of in-situ stress disturbance for different structures, as well as recommendations for well deployment and trajectory, were proposed. Faults exhibit an unloading effect on the in-situ stress, leading to varying degrees of reduction in the horizontal principal stress gradient near the faults, with the maximum reduced by about 0.3 MPa/hm. Near EW-oriented faults, the regional stress direction near SN exhibits a clockwise deflection, with the maximum deflection angle reaching 60°. The disturbance range of faults with different scales is approximately 60% of the fault throw. A disturbance of the in-situ stress appears when the strata curvature exceeds 0.4 km-1. The in-situ stress is lower than the regional stress in the upper tensile disturbance zone of the folded strata, while it increases in the lower compressive disturbance zone. In the tensile disturbance zone, the maximum decrease in the horizontal principal stress gradient is approximately 0.3 MPa/hm, with the stress direction deflecting counterclockwise, reaching a maximum deflection angle of 70°. The greater the fold deformation curvature, the thicker the tensile disturbance zone, and the more significant the disturbance. Under fault-fold composite structures, the superposition of fault disturbance zones and fold tensile disturbance zones further reduces the magnitude of the in-situ stress. After offsetting the disturbance effects of both, the in-situ stress direction deviates less or does not deviate at all from the regional stress. Considering the difficulty of reservoir modification and the characteristics of tight gas enrichment, drilling should be prioritized in the overlapping areas of faults and fold tensile disturbance zones within the fault-fold composite structure zone. It is recommended that the drilling depth should not exceed the neutral plane of the folds, and the horizontal well trajectory should be designed along the EW direction.

With the rapid advancement of 5G technology, the Internet of Things (IoT) has entered a new phase of applications and is rapidly becoming a significant force in promoting economic development. Due to the vast amounts of data created by numerous 5G IoT devices, the Ethereum platform has become a tool for the storage and sharing of IoT device data, thanks to its open and tamper-resistant characteristics. So, Ethereum account security is necessary for the Internet of Things to grow quickly and improve people's lives. By modeling Ethereum transaction records as a transaction network, the account types are well identified by the Ethereum account classification system established based on Graph Neural Networks (GNNs). This work first investigates the Ethereum transaction network. Surprisingly, experimental metrics reveal that the Ethereum transaction network is neither optimal nor even satisfactory in terms of accurately representing transactions per account. This flaw may significantly impede the classification capability of GNNs, which is mostly governed by their attributes. This work proposes an Adaptive Multi-channel Bayesian Graph Attention Network (AMBGAT) for Ethereum account classification to address this difficulty. AMBGAT uses attention to enhance node features, estimate graph topology that conforms to the ground truth, and efficiently extract node features pertinent to downstream tasks. An extensive experiment with actual Ethereum transaction data demonstrates that AMBGAT obtains competitive performance in the classification of Ethereum accounts while accurately estimating the graph topology.

Abstract The impact of wildfire smoke is largely determined by the height where they are injected into the atmosphere. Current plume rise models tend to underestimate the high smoke injection heights because the previous models and configurations were mainly constrained and validated by the plume height observation from Multi‐angle Imaging SpectroRadiometer (MISR), of which most cases inject low within the planetary boundary layer (PBL). Here we retrieve smoke injection heights from intense pyro‐convections based on pyrocumulonimbus satellite images in PYROCAST data set alongside meteorological reanalysis. It largely augments the MISR data set with smoke injection heights up to the upper troposphere and lower stratosphere (UTLS). Constrained by both MISR and PYROCAST, we show that a scaling down of factor 0.2 to the entrainment efficiency parameterized in the one‐dimensional plume‐rise model (1‐D PRM, Freitas et al. (2010, https://doi.org/10.5194/acp‐10‐585‐2010)) significantly improves the model performance for high injection cases without compromising the accuracy of low injection cases. We also found that the fire intensity input can be obtained through a simplified dependence on the biome and biomass burning emission flux. While being unable to represent high cases before, the improved 1‐D PRM model predicts similarly well in injection heights both low near the PBL height and high into the UTLS. The improved 1‐D PRM is then coupled into Community Atmosphere Model with Chemistry (CAM‐chem). The coupled CAM‐chem‐PRM, when predicting injection heights in tests imitating real BB emission, exhibited consistent predictive capabilities with the standalone 1‐D PRM while saw a mere 15% increase of computation time.

Background: Extranodal natural killer/T-cell lymphoma (ENKTCL) has a unique treatment principle. However, the optimal combination of drugs along with radiotherapy (RT) is unknown. Design: Retrospective cohort study. Objectives: We screened multiple drug combinations to identify the most efficacious therapeutic combinations. Methods: We reviewed 3105 patients who received 40 chemotherapy regimens with different combinations of 9 drug classes and/or RT. Least absolute shrinkage and selection operator and multivariable Cox regression analyses were used to screen efficacious single drugs and identify optimal combinations for overall survival (OS). Inverse probability of treatment weighting (IPTW) and multivariable analyses were used to compare survival between treatment regimens. Results: Screening and validation revealed RT, asparaginase (ASP), and gemcitabine (GEM) to be the most efficacious single modality/drug. RT remained an important component of first-line treatment, whereas ASP was a fundamental drug of non-anthracycline (ANT)-based regimens. Addition of RT to non-ANT-based or ASP/GEM-based regimens, or addition of an ASP-drug into ANT-based or GEM/platinum-based regimens, improved 5-year OS significantly. Use of ASP/GEM-based regimens was associated with significantly higher 5-year OS (79.9%) compared with ASP/ANT-based (69.2%, p = 0.001), ASP/methotrexate-based (63.5%, p = 0.011), or ASP/not otherwise specified-based (63.2%, p

BackgroundPulmonary fibrosis (PF) emerges as a significant pulmonary sequelae in the convalescent phase of coronavirus disease 2019 (COVID-19), with current strategies neither specifically preventive nor therapeutic. Licoricesaponin G2 (LG2) displays a spectrum of natural activities, including antibacterial, anti-inflammatory, and antioxidant properties, and has been effectively used in treating various respiratory conditions. However, the potential protective effects of LG2 against PF remain underexplored.MethodsNetwork analysis and molecular docking were conducted in combination to identify the core targets and pathways through which LG2 acts against PF. In the model of bleomycin (BLM)-induced C57 mice and transforming growth factor-β1 (TGF-β1)-induced A549 and MRC5 cells, techniques such as western blot (WB), quantitative Real-Time PCR (qPCR), Immunohistochemistry (IHC), Immunofluorescence (IF), and Transwell migration assays were utilized to analyze the expression of Epithelial-mesenchymal transition (EMT) and inflammation proteins. Based on the analysis above, we identified targets and potential mechanisms underlying LG2’s effects against PF.ResultsNetwork analysis has suggested that the mechanism by which LG2 combats PF may involve the TNF-α pathway. Molecular docking studies have demonstrated a high binding affinity of LG2 to TNF-α and MMP9. Observations from the study indicated that LG2 may mitigate PF by modulating EMT and extracellular matrix (ECM) remodeling. It is proposed that the therapeutic effect is likely arises from the inhibition of inflammatory expression through regulation of the TNF-α pathway.ConclusionLG2 mitigates PF by suppressing TNF-α signaling pathway activation, modulating EMT, and remodeling the ECM. These results provide compelling evidence supporting the use of LG2 as a potential natural therapeutic agent for PF in clinical trials.

RationaleRelapse to drug use is a major clinical challenge in the treatment of addictive disorders, including psychostimulant use and may be exacerbated by reduced sensitivity to natural, non-drug reward. Given the relatively limited set of outcomes, and short withdrawal time in rodent studies, we conducted a more detailed assessment of the response to natural rewards in methamphetamine (METH) naive versus exposed monkeys during long-term abstinence.MethodsThis study introduced an improved sucrose preference test (iSPT) to assess natural reward seeking and consumption in monkeys with long-term abstinence after methamphetamine (METH) use. The test was administered to sixteen naive monkeys and five METH exposed monkeys that had been abstinent for at least 3 months.ResultsMETH exposed monkeys showed a lower sucrose preference score in both the iSPT (z = -2.10, p = 0.036) and the sucrose preference test (z = -2.61, p = 0.009). The sucrose preference score was significantly correlated with the latency of the establishment of stable sucrose-preference (r = -0.76, df = 46, p < 0.001) but not with the other variables. Furthermore, water-sucrose switch latency and switch times were significantly negatively correlated (r = -0.50, df = 20, p = 0.02).ConclusionThese results show reductions in natural reward consumption during long-term methamphetamine abstinence.

The application of non-invasive brain stimulation (NIBS) in non-human primates (NHPs) is critical for advancing understanding of brain networks and developing treatments for neurological diseases. Improving the precision of targeting can significantly enhance the efficacy of these interventions. Here, we introduce a 3D-printed helmet designed to achieve repeatable and precise neuromodulation targeting in awake rhesus monkeys, eliminating the need of head fixation. Imaging studies confirmed that the helmet consistently targets the primary motor cortex (M1) with a margin of error less than 1 mm. Evaluations of stimulation efficacy revealed high resolution and stability. Additionally, physiological evaluations under propofol anesthesia showed that the helmet effectively facilitated the generation of recruitment curves for motor area, confirming successful neuromodulation. Collectively, our findings present a straightforward and effective method for achieving consistent and precise NIBS targeting in awake NHPs, potentially advancing both basic neuroscience research and the development of clinical neuromodulation therapies.

[Introduction] In recent years, as the installed capacity of the fusion device has been increasing, the power supply system of the device requires high-amplitude and long-pulse power output, which causes a strong power impact on the grid, and even power supply disconnection in severe cases to pose a serious threat to the safety of the fusion device. Additionally, the high-amplitude pulses also result in a lot of redundancy in the power supply system design. [Method] To solve these problems, this paper proposed a novel fusion power supply topology with energy storage, that is, the power supply system was designed with energy storage to mitigate the impact of pulse power on the grid. During the operation of the power supply, the grid provided steady-state power while the energy storage device delivered pulse power, effectively reducing the cost of the power supply. [Result] According to the experience in industrial power supply and distribution, this paper presents the calculation formulas for the selection of key components in different topologies and conducts a cost analysis and comparison for different power supply topologies based on simulation data. [Conclusion] The experimental results show that the new power supply topology not only reduces the power impact on the grid and improves the energy utilization of the power supply system, but also reduces transformer capacity, thus it is cost-efficient.

Abstract Based on the dual response of RhB@UiO-67 (1:6) to Cu2+ and Fe3+, a proportional fluorescent probe with (I 392 /I 581 ) as the output signal was developed to recognize Cu2+ and Fe3+. Developing highly sensitive and selective trace metal ions probes is crucial to human health and ecological sustainability. In this work, a series of ratio fluorescent probes (RhB@UiO-67) were successfully synthesized using a one-pot method to enable fluorescence sensing of Cu2+ and Fe3+ at low concentrations. The proportional fluorescent probe RhB@UiO-67 (1:6) exhibited simultaneous quenching of Cu2+ and Fe3+, which was found to be of interest. Furthermore, the limits of detection (LODs) for Cu2+ and Fe3+ were determined to be 2.76 μM and 0.76 μM, respectively, for RhB@UiO-67 (1:6). These values were significantly superior to those reported for previous sensors, indicating the probe’s effectiveness in detecting Cu2+ and Fe3+ in an ethanol medium. Additionally, RhB@UiO-67 (1:6) demonstrated exceptional immunity and reproducibility towards Cu2+ and Fe3+. The observed fluorescence quenching of Cu2+ and Fe3+ was primarily attributed to the mechanisms of fluorescence resonance energy transfer (FRET), photoinduced electron transfer (PET), and competitive absorption (CA). This work establishes a valuable foundation for the future study and utilization of Cu2+ and Fe3+ sensing technologies.

Abstract Objectives Invasive mucinous adenocarcinoma (IMA) has a rare incidence with better prognosis than nonmucinous adenocarcinoma. We aimed to investigate the prognosis between limited resection and lobectomy for patients with clinical stage IA IMA ≤ 2 cm. Methods Data were taken from two cohorts: In Shanghai Pulmonary Hospital (SPH) corhort, we identified 403 patients with clinical stage IA IMA who underwent surgery. In the SEER corhort, 480 patients with stage T1 IMA who after surgery were included. Recurrence-free survival (RFS) for SPH corhort, lung cancer–specific survival (LCSS) for the SEER corhort and overall survival (OS) for both corhort were compared between patients undergoing lobectomy and limited resection by Log-rank and Cox proportional hazard regression model. Results In SPH corhort, patients who underwent limited resection had equivalent prognosis than those underwent lobectomy (5-year RFS: 79.3% versus. 82.6%, p = 0.116; 5-year OS: 86.2% versus. 88.3%, p = 0.235). However, patients with IMA > 2 to 3 cm had worse prognosis than those with IMA ≤ 2 cm (5-year RFS: 73.7% versus. 86.1%, p = 0.007). In the analysis of IMA > 2 to 3 cm subgroup, multivariate analysis showed that limited resection was an independent risk factor of RFS (hazard ratio, 2.417; 95% confidence interval, 1.157–5.049; p = 0.019), while OS (p = 0.122) was not significantly different between two groups. For IMA ≤ 2 cm, limited resection was not a risk factor of RFS (p = 0. 953) and OS (p = 0.552). In the SEER corhort, IMA ≤ 2 cm subgroup, limited resection was equivalent prognosis in LCSS (p = 0.703) and OS (p = 0.830). Conclusions Limited resection could be a potential surgical option which comparable to lobectomy in patients with clinical stage IA IMA ≤ 2 cm.

Abstract This registration study assessed clinical outcomes of TQ-B3525, the dual phosphatidylinositol-3-kinase (PI3K) α/δ inhibitor, in relapsed and/or refractory follicular lymphoma (R/R FL). This phase II study (ClinicalTrials.gov NCT04324879. Registered March 27, 2020) comprised run-in stage and stage 2. R/R FL patients after ≥2 lines therapies received oral 20 mg TQ-B3525 once daily in a 28-day cycle until intolerable toxicity or disease progression. Primary endpoint was independent review committee (IRC)-assessed objective response rate (ORR). Based on results (ORR, 88.0%; duration of response [DOR], 11.8 months; progression-free survival [PFS], 12.0 months) in 25 patients at run-in stage, second stage study was initiated and included 82 patients for efficacy/safety analysis. Patients received prior-line (median, 3) therapies, with 56.1% refractory to previous last therapies; 73.2% experienced POD24 at baseline. At stage 2, ORR was 86.6% (71/82; 95% CI, 77.3–93.1%), with 28 (34.2%) complete responses. Disease control rate was 95.1% due to 7 (8.5%) stable diseases. Median time to response was 1.8 months. Among 71 responders, median DOR was not reached; 18-month DOR rate was 51.6%. with median follow-up of 13.3 months, median PFS was 18.5 (95% CI, 10.2-not estimable) months. Median overall survival (OS) was not reached by cutoff date; 24-month OS rate was estimated as 86.1%. Response rates and survival data were consistent across all subgroups. Grade 3 or higher treatment-related adverse events were observed in 63 (76.8%) cases, with neutropenia (22.0%), hyperglycemia (19.5%), and diarrhea (13.4%) being common. TQ-B3525 showed favorable efficacy and safety for R/R FL patients after ≥2 lines prior therapies.

The Pan-Eurasian Experiment Modelling Platform (PEEX-MP) is one of the key blocks of the PEEX Research Programme. The PEEX MP has more than 30 models and is directed towards seamless environmental prediction. The main focus area is the Arctic-boreal regions and China. The models used in PEEX-MP cover several main components of the Earth’s system, such as the atmosphere, hydrosphere, pedosphere and biosphere, and resolve the physical-chemical-biological processes at different spatial and temporal scales and resolutions. This paper introduces and discusses PEEX MP multi-scale modelling concept for the Earth system, online integrated, forward/inverse, and socioeconomical modelling, and other approaches with a particular focus on applications in the PEEX geographical domain. The employed high-performance computing facilities, capabilities, and PEEX dataflow for modelling results are described. Several virtual research platforms (PEEX-View, Virtual Research Environment, Web-based Atlas) for handling PEEX modelling and observational results are introduced. The overall approach allows us to understand better physical-chemical-biological processes, Earth’s system interactions and feedbacks and to provide valuable information for assessment studies on evaluating risks, impact, consequences, etc. for population, environment and climate in the PEEX domain. This work was also one of the last projects of Prof. Sergej Zilitinkevich, who passed away on 15 February 2021. Since the finalization took time, the paper was actually submitted in 2023 and we could not argue that the final paper text was agreed with him.

The relationship between CD276 and malignancies of the female reproductive system has previously been controversial. The purpose of this study was to evaluate the predictive value of CD276 expression in clinicopathological features and prognosis of female reproductive system malignant tumors through meta-analysis. PubMed, Embase, Cochrane Library, Web of Science, CNKI and Wanfang databases were searched for studies published up to December 2022 on the role of CD276 expression in the clinicopathological features and prognosis of female reproductive system malignancies. STATA 14.0 was used for meta-analysis. A total of 10 studies were included, involving 840 patients with malignant tumors of the female reproductive system. The results showed that in terms of clinicopathological features: CD276 expression was closely related to lymph node status [OR = 2.33， 95 %CI = 1.32–4.11， P = 0.003], tumor differentiation [OR = 2.15， 95 %CI = 1.27–3.63, P = 0.004], and FIGO stage [OR = 2.58， 95 %CI = 1.44–4.61, P = 0.001] of reproductive system malignant tumors. In terms of prognosis: CD276 expression is strongly associated with shorter OS in patients with female reproductive system malignancies [HR = 3.33, 95 % CI = 1.36–8.15, P = 0.01]. CD276 may be a new target for immunotherapy and a biomarker for predicting poor prognosis of female reproductive system malignancies.

The martensite start temperature (MS) plays a pivotal role in formulating heat treatment regimes for steel. This paper, through the compilation of experimental data from literature and the incorporation of expert knowledge to construct features, employs machine learning algorithms to predict the MS of steel. The study highlights that the ETR algorithm attains optimal prediction accuracy, and the inclusion of atomic features enhances the model’s performance. Feature selection is accomplished by evaluating linear and nonlinear relationships between data using the Pearson correlation coefficient (PCC), variance inflation factor (VIF), and maximum information coefficient (MIC). Subsequently, the performance of machine learning models on unknown data is compared to validate the model’s generalization ability. The introduction of SHAP values for model interpretability analysis unveils the influencing mechanisms between features and the target variable. Finally, utilizing a specific steel type as an illustration, the paper underscores the practical value of the model.

Abstract Multiphase oxidation of sulfur dioxide (SO2) is an important source of sulfate in the atmosphere. There are, however, concerns that protons produced during SO2 oxidation may cause rapid acidification of aerosol water and thereby quickly shut down the fast reactions favored at high pH. Here, we show that the sustainability of sulfate production is controlled by the competing effects of multiphase buffering and acidification, which can be well described by a characteristic buffering time, τbuff. Both GEOS‐Chem simulations and observations show that globally, τbuff is long enough (days) to sustain sulfate production over most populated regions, where the acidification of aerosol water is counteracted by the strong buffering effect of NH4+/NH3. Our results highlight the importance of anthropogenic ammonia emissions and pervasive human influences in shaping the chemical environment of the atmosphere.

Abstract Chemoselective modification of specific residues within a given protein poses a significant challenge, as the microenvironment of amino acid residues in proteins is variable. Developing a universal molecular platform with tunable chemical warheads can provide powerful tools for precisely labeling specific amino acids in proteins. Cysteine and lysine are hot targets for chemoselective modification, but current cysteine/lysine‐selective warheads face challenges due to cross‐reactivity and unstable reaction products. In this study, a versatile fluorescent platform is developed for highly selective modification of cysteine/lysine under biocompatible conditions. Chloro‐ or phenoxy‐substituted NBSe derivatives effectively labeled cysteine residues in the cellular proteome with high specificity. This finding also led to the development of phenoxy‐NBSe phototheragnostic for the diagnosis and activatable photodynamic therapy of GSH‐overexpressed cancer cells. Conversely, alkoxy‐NBSe derivatives are engineered to selectively react with lysine residues in the cellular environment, exhibiting excellent anti‐interfering ability against thiols. Leveraging a proximity‐driven approach, alkoxy‐NBSe probes are successfully designed to demonstrate their utility in bioimaging of lysine deacetylase activity. This study also achieves integrating a small photosensitizer into lysine residues of proteins in a regioselective manner, achieving photoablation of cancer cells activated by overexpressed proteins.

IntroductionCitrus canker, caused by Xanthomonas citri subsp. citri (Xcc), is a devastating disease worldwide. Previously, we successfully generated canker-resistant Citrus sinensis cv. Hamlin lines in the T0 generation. This was achieved through the transformation of embryogenic protoplasts using the ribonucleoprotein (RNP) containing Cas12a and one crRNA to edit the canker susceptibility gene, CsLOB1, which led to small indels.MethodsHere, we transformed embryogenic protoplasts of Hamlin with RNP containing Cas12a and three crRNAs.ResultsAmong the 10 transgene-free genome-edited lines, long deletions were obtained in five lines. Additionally, inversions were observed in three of the five edited lines with long deletions, but not in any edited lines with short indel mutations, suggesting long deletions maybe required for inversions. Biallelic mutations were observed for each of the three target sites in four of the 10 edited lines when three crRNAs were used, demonstrating that transformation of embryogenic citrus protoplasts with Cas12a and three crRNAs RNP can be very efficient for multiplex editing. Our analysis revealed the absence of off-target mutations in the edited lines. These cslob1 mutant lines were canker- resistant and no canker symptoms were observed after inoculation with Xcc and Xcc growth was significantly reduced in the cslob1 mutant lines compared to the wild type plants.DiscussionTaken together, RNP (Cas12a and three crRNAs) transformation of embryogenic protoplasts of citrus provides a promising solution for transgene-free multiplex genome editing with high efficiency and for deletion of long fragments.

Abstract The growth of newly formed particles through new particle formation (NPF) contributes a significant fraction to the cloud condensation nuclei, yet the driving mechanisms remain unclear, especially for polluted environments. To investigate the potential species contributing for nanoparticle growth in environments with significant anthropogenic influences, we measured the hygroscopicity of newly formed particles at 20–40 nm at a rural observational site in the North China Plain during winter 2018. Our results demonstrate that these particles were not very hygroscopic, with the mean hygroscopicity parameter κ of 0.13 ± 0.09. Clear differences in the inferred κ of the growing material responsible for the growth were observed among different events, indicating that even at the same region, the compounds driving particle growth may not be identical. This may be synergistically influenced by the NPF precursors, oxidants and meteorological conditions, suggesting complex mechanisms might co‐exist behind nanoparticle growth in polluted environments.

Abstract Ozone (O3) pollution is a severe air quality issue in China, posing a threat to human health and ecosystems. The climate change will affect O3 levels by directly changing physical and chemical processes of O3 and indirectly changing natural emissions of O3 precursors. In this study, near‐surface O3 concentrations in China in 2030 and 2060 are predicted using the process‐based interpretable Extreme Gradient Boosting (XGBoost) model integrated with multi‐source data. The results show that the climate‐driven O3 levels over eastern China are projected to decrease by more than 0.4 ppb in 2060 under the carbon neutral scenario (SSP1‐1.9) compared with the high emission scenario (SSP5‐8.5). Among this reduction, 80% is attributed to the changes in physical and chemical processes of O3 related to a cooler climate, while the remaining 20% is attributed to the reduced biogenic isoprene emissions.

Abstract On behalf of the AGU Advances editorial team, we would like to express our sincere gratitude to everyone who reviewed manuscripts for us in 2023. Peer review is time‐consuming, but it remains essential to the scientific process. Advances reviewers continue to help define the scope of our journal by commenting specifically on whether a paper is likely to have broad and immediate impact. We also appreciate the degree to which reviewers have embraced AGU's open data strategies, although this obviously takes more time.

Abstract Background TMPRSS2-ERG (T2E) fusion is highly related to aggressive clinical features in prostate cancer (PC), which guides individual therapy. However, current fusion prediction tools lacked enough accuracy and biomarkers were unable to be applied to individuals across different platforms due to their quantitative nature. This study aims to identify a transcriptome signature to detect the T2E fusion status of PC at the individual level. Methods Based on 272 high-throughput mRNA expression profiles from the Sboner dataset, we developed a rank-based algorithm to identify a qualitative signature to detect T2E fusion in PC. The signature was validated in 1223 samples from three external datasets (Setlur, Clarissa, and TCGA). Results A signature, composed of five mRNAs coupled to ERG (five ERG-mRNA pairs, 5-ERG-mRPs), was developed to distinguish T2E fusion status in PC. 5-ERG-mRPs reached 84.56% accuracy in Sboner dataset, which was verified in Setlur dataset (n = 455, accuracy = 82.20%) and Clarissa dataset (n = 118, accuracy = 81.36%). Besides, for 495 samples from TCGA, two subtypes classified by 5-ERG-mRPs showed a higher level of significance in various T2E fusion features than subtypes obtained through current fusion prediction tools, such as STAR-Fusion. Conclusions Overall, 5-ERG-mRPs can robustly detect T2E fusion in PC at the individual level, which can be used on any gene measurement platform without specific normalization procedures. Hence, 5-ERG-mRPs may serve as an auxiliary tool for PC patient management.

Abstract Machine learning with optical neural networks has featured unique advantages of the information processing including high speed, ultrawide bandwidths and low energy consumption because the optical dimensions (time, space, wavelength, and polarization) could be utilized to increase the degree of freedom. However, due to the lack of the capability to extract the information features in the orbital angular momentum (OAM) domain, the theoretically unlimited OAM states have never been exploited to represent the signal of the input/output nodes in the neural network model. Here, we demonstrate OAM-mediated machine learning with an all-optical convolutional neural network (CNN) based on Laguerre-Gaussian (LG) beam modes with diverse diffraction losses. The proposed CNN architecture is composed of a trainable OAM mode-dispersion impulse as a convolutional kernel for feature extraction, and deep-learning diffractive layers as a classifier. The resultant OAM mode-dispersion selectivity can be applied in information mode-feature encoding, leading to an accuracy as high as 97.2% for MNIST database through detecting the energy weighting coefficients of the encoded OAM modes, as well as a resistance to eavesdropping in point-to-point free-space transmission. Moreover, through extending the target encoded modes into multiplexed OAM states, we realize all-optical dimension reduction for anomaly detection with an accuracy of 85%. Our work provides a deep insight to the mechanism of machine learning with spatial modes basis, which can be further utilized to improve the performances of various machine-vision tasks by constructing the unsupervised learning-based auto-encoder.

Abstract HLX01 (HanliKang®) is a rituximab biosimilar that showed bioequivalence to reference rituximab in untreated CD20-positive diffuse large B-cell lymphoma (DLBCL) in the phase 3 HLX01-NHL03 study. Here, we report the 5-year follow-up results from the open-label extension part. Patients were randomised to either rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or HLX01 plus CHOP (H-CHOP) every 21 days for up to six cycles. The primary efficacy endpoint was overall survival (OS), and secondary efficacy endpoint was progression-free survival (PFS). Of the 407 patients enrolled in HLX01-NHL03, 316 patients (H-CHOP = 157; R-CHOP = 159) were included in the 5-year follow-up for a median duration of 65.1 (range, 2.2–76.5) months. 96.5% of the patients had an International Prognostic Index (IPI) of 1 or 2, and 17.7% had bone marrow involvement. The 5-year OS rates were 81.0% (95% CI: 74.9–87.5%) and 75.4% (95% CI: 68.9–82.6%)( HR: 0.75, 95% CI 0.47–1.20; p = 0.23) while 5-year PFS rates were 77.7% (95% CI: 71.4–84.6%) and 73.0% (95% CI: 66.3–80.3%) (HR: 0.84, 95% CI 0.54–1.30; p = 0.43) in the H-CHOP and R-CHOP groups, respectively. Treatment outcomes did not differ between groups regardless of IPI score and were consistent with the primary analysis. H-CHOP and R-CHOP provided no significant difference in 5-year OS or PFS in previously untreated patients with low or low-intermediate risk DLBCL.

ObjectivesThis study proposes a fixed-time trajectory tracking control strategy to address the challenges of unmodeled dynamics and external disturbances in underactuated unmanned surface vessels (USVs).MethodsFirst, the tracking error system is divided into two channels for controller design through model transformation. Next, in order to accommodate unknown system dynamics and external disturbances, a minimum-learning-parameter-based neural network is adopted to compensate for uncertainties. After that, a fixed-time sliding mode controller is proposed with the application of a hyperbolic tangent function to ensure the fast convergence of tracking errors.ResultsThe numerical simulation results show that fixed-time convergence for tracking errors can be guaranteed independent of the initial state.ConclusionsThe designed control scheme not only features the effective estimation of uncertainties within the system, but also demonstrates a robust disturbance rejection capability, providing valuable insights for the fixed-time control of USVs.

Although combination antiretroviral therapy (ART) has been a landmark achievement for the treatment of human immunodeficiency virus (HIV), an HIV cure has remained elusive. Elimination of latent HIV reservoirs that persist throughout HIV infection is the most challenging barrier to an HIV cure. The progressive HIV infection is marked by the increasing size and diversity of latent HIV reservoirs until an effective immune response is mobilized, which can control but not eliminate HIV infection. The stalemate between HIV replication and the immune response is manifested by the establishment of a viral set point. ART initiation during the early stage limits HIV reservoir development, preserves immune function, improves the quality of life, and may lead to ART-free viral remission in a few people living with HIV (PLWH). However, for the overwhelming majority of PLWH, early ART initiation alone does not cure HIV, and lifelong ART is needed to sustain viral suppression. A critical area of research is focused on determining whether HIV could be functionally cured if additional treatments are provided alongside early ART. Several HIV interventions including Block and Lock, Shock and Kill, broadly neutralizing antibody (bNAb) therapy, adoptive CD8+ T cell therapy, and gene therapy have demonstrated delayed viral rebound and/or viral remission in animal models and/or some PLWH. Whether or not their application during early infection can improve the success of HIV remission is less studied. Herein, we review the current state of clinical and investigative HIV interventions and discuss their potential to improve the likelihood of post-treatment remission if initiated during early infection.

In recent years, although the air quality in the Liaoning region has improved, heavy pollution weather is still caused by external pollution transportation. In order to study the influence of multi-directional long-distance pollution on the heavily polluted weather in Liaoning, this paper analyzes three types of transport channel (northerly, northwesterly, and southwesterly transport corridors) by combining ground observations, airborne observations, AQI and the concentration data of atmospheric pollutants such as PM2.5, PM10 and so on. The results show that both northerly and southwesterly winds caused widespread fog and haze in the Liaoning region. The PM2.5 concentration reached the second-highest value on record (1479 μg/m3) during the pollution period caused by northwesterly wind transport. Wind and sand transported from the northwest mainly caused dusty weather in Liaoning, with PM10 concentration reaching up to 1200 μg/m3 during the pollution period. Northeasterly and northwesterly wind transport mainly led to the accumulation of pollutants in high places to high pollution values. Convergence of winds due to southwesterly wind transport led to prolonged accumulation of pollutants in the Liaoning region, resulting in severe pollution. Long-distance pollution transport is now one of the main sources of heavy pollution in the Liaoning region.

BackgroundCatastrophic antiphospholipid syndrome (CAPS) is a multi-system autoimmune disease characterized by extensive thrombosis. Pediatric CAPS is extremely rare and associated with a high mortality rate, especially when midbrain infarction is involved. Hence, early diagnosis and prompt initiation of appropriate treatment for CAPS complicated by midbrain infarction are of utmost importance in achieving favorable outcomes.Case presentationIn this report, we present the case of a 14-year-old girl who presented with neurological symptoms and digestive system infection and was initially diagnosed with an “intracranial infection”. After a series of rigorous diagnostic procedures, the patient was ultimately diagnosed with primary CAPS and was immediately transferred to the intensive care unit where she was treated with anticoagulation, glucocorticoids, intravenous immunoglobulin (IVIG) therapy, and multiple plasma infusions. Twenty-seven days after admission, the patient's condition improved with standardized treatment, and she was discharged and followed up regularly.ConclusionThis case report provides a description of the clinical features observed in a pediatric patient with CAPS and concurrent midbrain infarction, highlighting the crucial role of early diagnosis and timely treatment in influencing patient prognosis.

The feed legislation allows the use of fish protein hydrolysates in feed for the same species in which it came from, since enzymatic hydrolysis degrades the proteins and eliminates potential prions, which have caused disease in mammals, but not in fish. In this trial, we investigated the effects of partially replacing dietary fishmeal (FM) with salmon protein hydrolysate (FPH) on the intestinal gene expression and microbiota. Atlantic salmon post smolts were either fed a control diet containing 30% fishmeal (FM), a 20% FM diet with 9% salmon hydrolysate (FPH-09) or a 10% FM diet with 18% salmon hydrolysate (FPH-18), until doubling of weight. Gene expression analysis by RNA sequencing of pyloric caeca (PC), midgut (MG) and hindgut (HG) revealed a downregulation of immunological genes involved in inflammation in the intestine of FPH-18 fed salmon compared to salmon fed the FM control. The gene expression of paralogous peptide transporters (PepT) was analyzed by real time quantitative PCR in PC, anterior midgut (AMG), posterior midgut (PMG) and HG of salmon fed all the three diets. The PepT1b paralog had highest relative expression levels in PC and AMG, suggesting that PepT1b is most important for peptide uptake in the anterior intestine. PepT1a was also mainly expressed in the PC and AMG, but at lower levels than PepT1b and PepT2b in the AMG. The PepT2b paralog had high levels of expression in AMG, PMG and HG indicating that it contributed significantly to peptide uptake in the posterior part of the gastrointestinal tract. The gut microbiota in the mucosa and digesta of the MG and HG, were dominated by the phyla Cyanobacteria and Proteobacteria, but also Firmicutes were present. The only dietary effect on the microbiota was the higher prevalence of the phyla Spirochaetes in the mucosa of FPH-18 fed salmon compared to the FM fed salmon. In conclusion, replacing FM with salmon hydrolysate reduced the expression of inflammatory markers in the Atlantic salmon intestine suggesting improved health benefits. The reduced inflammation may be related to the reduced FM content, potentially bioactive peptides in the hydrolysate and/or the altered gut microbial composition.

Abstract Nervonic acid benefits the treatment of neurological diseases and the health of brain. In this study, we employed the oleaginous yeast Yarrowia lipolytica to overproduce nervonic acid oil by systematic metabolic engineering. First, the production of nervonic acid was dramatically improved by iterative expression of the genes ecoding β-ketoacyl-CoA synthase CgKCS, fatty acid elongase gELOVL6 and desaturase MaOLE2. Second, the biosynthesis of both nervonic acid and lipids were further enhanced by expression of glycerol-3-phosphate acyltransferases and diacylglycerol acyltransferases from Malania oleifera in endoplasmic reticulum (ER). Third, overexpression of a newly identified ER structure regulator gene YlINO2 led to a 39.3% increase in lipid production. Fourth, disruption of the AMP-activated S/T protein kinase gene SNF1 increased the ratio of nervonic acid to lignoceric acid by 61.6%. Next, pilot-scale fermentation using the strain YLNA9 exhibited a lipid titer of 96.7 g/L and a nervonic acid titer of 17.3 g/L (17.9% of total fatty acids), the highest reported titer to date. Finally, a proof-of-concept purification and separation of nervonic acid were performed and the purity of it reached 98.7%. This study suggested that oleaginous yeasts are attractive hosts for the cost-efficient production of nervonic acid and possibly other very long-chain fatty acids (VLCFAs).

Abstract Streptomyces clavuligerus NRRL 3585 is a native producer of clavulanic acid (CA), a clinically used β-lactamase inhibitor, and is widely used as an industrial strain for the production of antibiotics. Selective random mutagenesis has successfully generated the improved CA-producing S. clavuligerus mutant strains as well as the strain with the loss of CA biosynthesis. To understand the molecular mechanisms associated with the improved CA-production potential, genome-scale RNA-sequencing-based transcriptional data were obtained for the wild-type S. clavuligerus strain and its three mutant strains. Total RNA samples for each strain were collected across four different growth stages, and all 32 sequencing data points exhibited an average Phred score of 36. The high-quality genome-scale transcriptional profile of S. clavuligerus strains with varied CA biosynthetic potential provides valuable insights and new opportunities for discovering efficient metabolic engineering strategies for the development of improved industrial strains.

Taxifolin loaded zein-caseinate nanoparticles (TZP) were fabricated by the anti-solvent method and were used as an oral delivery vehicle to improve their bioavailability in the rat. The formulations of TZP were optimized. With mass ratio of 1:1:2 between taxifolin, zein and sodium caseinate, the particle size and ζ-potential of TZP were (168.74 ± 0.35) nm and (−57.67 ± 0.25) mV, while the encapsulation and loading efficiency of taxifolin were (85.83 ± 0.89)% and (17.11 ± 0.88)%, respectively. After freeze-drying, TZP exhibited excellent redispersibility in water without aggregation. Physicochemical characterization showed that taxifolin existed in amorphous form in TZP and its interaction with the protein was observed. After encapsulating in TZP, the excellent dispersion of taxifolin in water significantly improve its diffusion velocity through a semi-permeable membrane. After oral administration, taxifolin and its five metabolites were identified in rat plasma by ultra high performance liquid chromatography (UPLC) with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). The dynamic variation of taxifolin and its metabolites in plasma were then quantified by UPLC with a triple-quadrupole typemass spectroscopy (UPLC-QqQ-MS/MS). A pharmacokinetic study showed that the bioavailability of taxifolin increased from 0.35 % to 0.52 % through TZP fabrication. The plasma concentration of taxifolin glucuronide and methylated taxifolin glucuronide was much higher than taxifolin. Glucuronidation was the dominating metabolism pathway of taxifolin in vivo.

Objective To investigate the mechanisms of nicotinamide phosphoribosyl transferase (NAMPT) in the pathogenesis of psoriasis and to elucidate the effect of NAMPT on the nicotinamide adenine dinucleotide (NAD+) metabolic pathway in psoriasis. Methods Mitophagy gene and psoriasis microarray datasets were downloaded from the human autophagy gene database and GEO database to screen differentially expressed genes (DEGs) of mitophagy. Validation and assessment were performed by differential expression and receiver operating characteristic (ROC) curve analysis. LASSO and COX regression models were used to screen signature genes. Gene correlation and functional analysis were performed using Pearson and gene enrichment analysis (GSEA). Results A total of 16 differentially expressed mitophagy genes were identified in psoriasis, which all were highly expressed in psoriasis with high diagnostic value. The DEGs of mitophagy were mainly associated with NOD-like receptor signaling pathway, autophagy-animal, influenza A, chemo carcinogenic-receptor activation and lipid/atherosclerotic pathways. NAMPT was identified as a signature gene of psoriasis, mainly associated with the proteasome, pyrimidine metabolism, ubiquitin-mediated proteolysis, DNA replication, antigen processing and presentation, aminoacyl tRNA biosynthesis, cytoplasmic DNA sensing pathway, oocyte meiosis, homologous recombination and TOLL-like receptor signaling pathway. In psoriasis, NAD metabolic pathways were activated and positively correlated with NAMPT. In the NAD+ metabolic pathway, expression levels of BST1 were low and negatively correlated with NAMPT. In contrast, expression levels of PARP9 and PNP were high and positively correlated with NAMPT. Conclusions In psoriasis, NAMPT is highly expressed and NAD+ metabolic pathway is activated. Expression levels of NAMPT are positively correlated with the activity of NAD+ metabolic pathway. NAMPT may be involved in the pathogenesis of psoriasis through BST1, PARP9 and PNP in the NAD+ metabolic pathway.

Breast cancer remains a significant public health issue, being a leading cause of cancer-related mortality among women globally. Timely diagnosis and efficient treatment are crucial for enhancing patient outcomes, reducing healthcare burdens and advancing community health. This systematic review, following the PRISMA guidelines, aims to comprehensively synthesize the recent advancements in computer-aided diagnosis and treatment for breast cancer. The study covers the latest developments in image analysis and processing, machine learning and deep learning algorithms, multimodal fusion techniques and radiation therapy planning and simulation. The results of the review suggest that machine learning, augmented and virtual reality and data mining are the three major research hotspots in breast cancer management. Moreover, this paper discusses the challenges and opportunities for future research in this field. The conclusion highlights the importance of computer-aided techniques in the management of breast cancer and summarizes the key findings of the review.

Considering the characteristics of carbonate reservoirs in the Middle East, a low-viscosity microemulsion acid that can be prepared on site and has an appropriate retardation ability was developed. It was compared with four conventional acid systems (hydrochloric acid, gelled acid, emulsified acid and surfactant acid) through experiments of rotating disk, multistage acid fracturing and core flooding with CT scanning. The micro-etching characteristics and conductivity of fracture surfaces were clarified, and the variation of saturation field during water invasion and flowback of spent acid and the recovery of oil phase relative permeability were quantitatively evaluated. The study shows that the addition of negatively charged agent to the oil core of microemulsion acid can enhance its adsorption capacity on the limestone surface and significantly reduce the H+ mass transfer rate. Moreover, the negatively charged oil core is immiscible with the Ca2 + salt, so that the microemulsion acid can keep an overall structure not be damaged by Ca2 + salt generated during reaction, with adjustable adsorption capacity and stable microemulsion structure. With high vertical permeability along the fracture walls, the microemulsion acid can penetrate into deep fracture wall to form network etching, which helps greatly improve the permeability of reservoirs around the fractures and keep a high conductivity under a high closure pressure. The spent microemulsion acid is miscible with crude oil to form microemulsion. The microemulsion, oil and water are in a nearly miscible state, with basically no water block and low flowback resistance, the flowback of spent acid and the relative permeability of oil are recovered to a high degree.

In order to reveal the mechanism of sleeved stud connectors, 15 push-out specimens were designed, and static loading tests were conducted to evaluate the mechanical performance. The shear performance differences between the novel sleeved studs and conventional welded studs were compared. Referring to the experimental results, an Abaqus nonlinear finite element model was established to study the shear mechanism of sleeved stud connectors. Parametric analysis was conducted to investigate the effects of stud height, sleeve filling material, and sleeve diameter on the mechanical performance of the connectors. The experimental and finite element analysis results indicated that the ultimate shear bearing capacity and shear stiffness of the sleeved stud connectors were higher than those of ordinary welded studs, and the maximum slip was relatively small. Compared to conventional welded studs, the ultimate bearing capacity of sleeved studs increased by 4% to 8%, and the shear stiffness increased by 25% to 35%. Since the shear behavior of sleeved studs mainly occurred at the base of the studs, the influence of stud height on shear performance was relatively small. However, sleeve and stud diameter have a great influence on bearing capacity and stiffness. As the Ultra-High Performance Concrete (UHPC) near the base of the stud effectively enhanced the shear carrying capacity of the sleeved stud connectors, the shear carrying capacity and shear stiffness increased with the increase in the sleeve diameter.

Abstract The COVID lockdown presented an interesting opportunity to study the anthropogenic emissions from different sectors under relatively cleaner conditions in India. The complex interplays of power production, industry, and transport could be dissected due to the significantly reduced influence of the latter two emission sources. Here, based on measurements of cloud condensation nuclei (CCN) activity and chemical composition of atmospheric aerosols during the lockdown, we report an episodic event resulting from distinct meteorological conditions. This event was marked by rapid growth and high hygroscopicity of new aerosol particles formed in the SO2 plume from a large coal-fired power plant in Southern India. These sulfate-rich particles had high CCN activity and number concentration, indicating high cloud-forming potential. Examining the sensitivity of CCN properties under relatively clean conditions provides important new clues to delineate the contributions of different anthropogenic emission sectors and further to understand their perturbations of past and future climate forcing.

Abstract Citrus canker caused by Xanthomonas citri subsp. citri (Xcc) is a destructive citrus disease worldwide. Generating disease-resistant cultivars is the most effective, environmentally friendly and economic approach for disease control. However, citrus traditional breeding is lengthy and laborious. Here, we develop transgene-free canker-resistant Citrus sinensis lines in the T0 generation within 10 months through transformation of embryogenic protoplasts with Cas12a/crRNA ribonucleoprotein to edit the canker susceptibility gene CsLOB1. Among the 39 regenerated lines, 38 are biallelic/homozygous mutants, demonstrating a 97.4% biallelic/homozygous mutation rate. No off-target mutations are detected in the edited lines. Canker resistance of the cslob1-edited lines results from both abolishing canker symptoms and inhibiting Xcc growth. The transgene-free canker-resistant C. sinensis lines have received regulatory approval by USDA APHIS and are exempted from EPA regulation. This study provides a sustainable and efficient citrus canker control solution and presents an efficient transgene-free genome-editing strategy for citrus and other crops.

We report a case of eosinophilic fasciitis. A 58-year-old man complained of muscle weakness and stiffness, and joint pain of the limbs for 11 months. Dermatological examination revealed groove sign, which became more prominent when raising the arm. The skin of the forearms and calves was waxy appearance and tight. Muscle weakness and pain were apparent. The laboratory examination showed the absolute eosinophil count was 1.51×109/L in December, 2020, and 0.45 ×109/L in June, 2021. The erythrocyte sedimentation rate was 104 mm/h. Other test results were immunoglobulin G (IgG) 32.7 g/L, C3 0.881 g/L, gamma globulin 36.5%, and the anti-Scl-70 antibody (negative). The histopathology of the lesion on the right forearm was manifested by epidermal atrophy, collagen thickening in the fascia, hyaline degeneration, perivascular infiltration of plasma cells, lymphocytes, and eosinophils, remarkable reduction in elastic fibers in the fascia, and alcian blue stain(+). Patient was diagnosed with eosinophilic fasciitis. The patient refused the treatment with baricitinib and was without follow up.

Using the air quality monitoring data from the Department of Ecology and Environment of Liaoning Province for the period from 2017 to 2022, the temporal and spatial changes in the concentrations of various air pollutants in the Liaoning region for the periods from 2017 to 2019 and 2020 to 2022 were analyzed by using the Evaluation on the meteorological condition index of PM2.5 pollution (EMI) and the ArcGIS Kriging Interpolation Method, and the contributions of pollution reduction to the changes in the air quality of the Liaoning region were assessed. The results show that after the implementation of emission reduction measures, the quality of the atmospheric environment in the Liaoning region has significantly improved, and the mean concentrations of PM2.5, PM10, SO2, NO2, CO and O3 are all reduced by a certain magnitude in the period 2020 to 2022 compared with the period 2017 to 2019; Based on the EMI index calculation, the average EMI index in Liaoning during the period 2020 to 2022 is about 1.7% lower than the average value of the region during the period 2017 to 2019, and the atmospheric dispersion conditions are relatively good; From the perspective of daily changes in pollutant concentrations, the trend of PM2.5 and PM10 concentrations changed from double peaks and single valleys to single peaks and single valleys, and there were no significant changes in the types of valleys for CO, SO2, NO2, and O3, whereas the peaks of O3 concentrations during the daytime were basically the same as in previous years, and the concentrations during the nighttime were slightly higher than in previous years. Classification by topographic areas revealed that the mean pollutant concentration for the period from 2017 to 2019 was more significant than the mean value for the period from 2020 to 2022, except for O3, where the air quality in the mountainous areas of Liaodong and Liaoxi was better than that of the Liaohe Plain, and regional classification by coastal and inland, where the air quality in the coastal areas was better than that of the inland areas.

Background: Previous studies demonstrated a controversial relationship between sarcopenia (SP) and osteoarthritis (OA) and their genetic causality is unclear. Thus, we conducted a Mendelian randomization (MR) analysis to evaluate the possible causal association between sarcopenia-related traits (appendicular lean mass (ALM), grip strength, usual walking pace) and OA.Method: We used pooled genetic data from the UK Biobank for ALM(n = 450,243), left-hand grip strength (n = 461,026), right-hand grip strength (n = 461,089) and usual walking pace (n = 459,915). Moreover, summary statistics for OA were obtained from the latest study conducted by the Genetics of Osteoarthritis Consortium, including all OA (n = 826,690), hand OA (n = 303,7782), hip OA (n = 353,388) and knee OA (n = 396,054). The primary method for estimating causal effects was the inverse-variance weighted (IVW) method, with the utilizing of false discovery rate adjusted p values (PFDR). Additional MR methods such as MR-Egger regression, MR pleiotropy residual sum and outlier (MR-PRESSO), weighted median were employed as supplementary analyses.Results: We discovered ALM (odds ratio (OR) = 1.103, 95% confidence interval (CI) = 1.052–1.156, PFDR = 2.87E-04), hand grip strength (left, IVW OR = 0.823, 95% CI = 0.712 to 0.952, PFDR = 0.020; right, OR = 0.826, 95% CI = 0.718 to 0.950, PFDR = 0.020), and usual walking pace (OR = 0.339, 95% CI = 0.204 to 0.564, PFDR = 2.38E-04) were causally associated with OA risk. In the reverse MR analysis, we identified a causal effect of OA on ALM (β = −0.258, 95% CI = −0.369 to 0.146, PFDR = 0.6.07E-06), grip strength (left, β = −0.064, 95% CI = −0.104 to 0.024, PFDR = 0.002; right, β = −0.055, 95% CI = −0.095 to 0.014, PFDR = 0.008), and usual walking pace (β = −0.104, 95% CI = −0.147 to 0.061, PFDR = 1.61E-05).Conclusion: This present study suggests an obvious causality of SP on OA, with condition exhibiting site-specific effects, while evidence was also provided for the causal effect of OA on SP.