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Phishing has been the primary means utilized by attackers to conduct cyber fraud. As national anti-cyber fraud efforts continue to increase, the technical confrontation of various phishing activities has also escalated, bringing significant pressure to phishing detection work. For instance, current phishing attacks often employ images in place of text and apply small-scale shifts or rotations to high-weight website logo images to evade traditional detection algorithms that rely on text or image features. To address the problem of escalating adversarial phishing technologies, a phishing detection algorithm based on the attention mechanism and feature fusion was proposed, and a hierarchical classification model was established. This model included two stages of fusion involving domain names, web structure, web text, and web icons, capable of effectively countering various technical adversarial strategies employed by attackers. In the first stage, the algorithm leveraged the lightweight characteristics of the machine learning model to pre-recall a subset of suspicious domain names from a multitude of domain names. This was achieved by fusing the structural features of domain names, text, and web pages. In the second stage, based on the candidate subset, the attention mechanism was introduced to enhance the extraction of global text association features between the samples and the counterfeited objects. Additionally, the contrast features between the samples and the icons of the counterfeited objects were intensified, and a deep classification model fusing text and image features was established. The effectiveness of the algorithm was ultimately verified. This hierarchical detection method effectively avoids the extraction of image data from a large number of domain names to be detected, significantly improving detection efficiency while ensuring the accuracy of detection.

Abstract Protein methylation is a functionally important post-translational modification that occurs on diverse amino acid residues. The current proteomics approaches are inefficient to discover the methylation on residues other than Arg and Lys, which hinders the deep understanding of the functional role of rare protein methylation. Herein, we present a methyl-specific metabolic labeling approach for global methylome mapping, which enable the acquisition of methylome dataset covering diverse methylation types. Interestingly, of the identified methylation events, His methylation is found to be preferably occurred in C3H1 zinc fingers (ZFs). These His methylation events are determined to be Nπ specific and catalyzed by CARNMT1. The His methylation is found to stabilize the structure of ZFs. U2AF1 is used as a proof-of-concept to highlight the functional importance of His methylation in ZFs in RNA binding and RNA metabolism. The results of this study enable novel understanding of how protein methylation regulates cellular processes.

Abstract Background Limited evidence demonstrated the potential relationship between dietary sugar intake and dementia. This association demands further clarification in a large-scale population. Methods A total of 210,832 participants from the UK Biobank cohort were included in this prospective cohort study. Absolute and relative sugar intake and high-sugar dietary scores were utilized to reflect dietary sugar intake. Absolute sugar intake was identified by the Oxford WebQ in the UK Biobank. Relative sugar intake was calculated by dividing the absolute sugar intake by total diet energy. High-sugar dietary pattern was identified using the method of reduced rank regression. Cox proportional hazards regression analyses and restricted cubic splines were performed to examine the longitudinal associations between dietary sugar intake and all-cause dementia and its main subtype, Alzheimer’s disease. Explorative mediation analyses were conducted to explore underlying mechanisms. Results Increased absolute sugar intake (g/day) was significantly associated with a higher risk of all-cause dementia (HR = 1.003, [95%CI: 1.002–1.004], p

Metabolic disease is a worldwide epidemic that has become a public health problem. Gut microbiota is considered to be one of the important factors that maintain human health by regulating host metabolism. As an abundant bacterium in the host gut, A. muciniphila regulates metabolic and immune functions, and protects gut health. Multiple studies have indicated that alterations in the abundance of A. muciniphila are associated with various diseases, including intestinal inflammatory diseases, obesity, type 2 diabetes mellitus, and even parasitic diseases. Beneficial effects were observed not only in live A. muciniphila, but also in pasteurized A. muciniphila, A. muciniphila-derived extracellular vesicles, outer membrane, and secreted proteins. Although numerous studies have only proven the simple correlation between multiple diseases and A. muciniphila, an increasing number of studies in animal models and preclinical models have demonstrated that the beneficial impacts shifted from correlations to in-depth mechanisms. In this review, we provide a comprehensive view of the beneficial effects of A. muciniphila on different diseases and summarize the potential mechanisms of action of A. muciniphila in the treatment of diseases. We provide a comprehensive understanding of A. muciniphila for improving host health and discuss the perspectives of A. muciniphila in the future studies.

To solve the privacy-preserving problem of both the user and the server in indoor positioning, outsourcing part of the calculation to cloud server in the process of using Paillier encryption was considered.The scheme not only protected the privacy of the user and the positioning server, but also avoided excessive computing and communication overhead.The main idea of the scheme was that the fingerprint database in the offline stage was established by the server firstly.The k-anonymity algorithm was combined with Paillier encryption in the online stage by the user, and the encrypted Wi-Fi fingerprints were sent to the positioning server.An aggregation of the received Wi-Fi fingerprints and database fingerprints were performed by the server.Then they were outsourced to the cloud server for decryption and distance calculation by the positioning server.Finally, the positioning result was obtained.Theoretical analysis and experimental results show that the proposed scheme is safe, effective and practical.

Partial reprogramming by cyclic short-term expression of Yamanaka factors holds promise for shifting cells to younger states and consequently delaying the onset of many diseases of aging. However, the delivery of transgenes and potential risk of teratoma formation present challenges for in vivo applications. Recent advances include the use of cocktails of compounds to reprogram somatic cells, but the characteristics and mechanisms of partial cellular reprogramming by chemicals remain unclear. Here, we report a multi-omics characterization of partial chemical reprogramming in fibroblasts from young and aged mice. We measured the effects of partial chemical reprogramming on the epigenome, transcriptome, proteome, phosphoproteome, and metabolome. At the transcriptome, proteome, and phosphoproteome levels, we saw widescale changes induced by this treatment, with the most notable signature being an upregulation of mitochondrial oxidative phosphorylation. Furthermore, at the metabolome level, we observed a reduction in the accumulation of aging-related metabolites. Using both transcriptomic and epigenetic clock-based analyses, we show that partial chemical reprogramming reduces the biological age of mouse fibroblasts. We demonstrate that these changes have functional impacts, as evidenced by changes in cellular respiration and mitochondrial membrane potential. Taken together, these results illuminate the potential for chemical reprogramming reagents to rejuvenate aged biological systems and warrant further investigation into adapting these approaches for in vivo age reversal.

IntroductionThe type VI secretion system (T6SS) is a crucial virulence factor in the nosocomial pathogen Acinetobacter baumannii. However, its association with drug resistance is less well known. Notably, the roles that different T6SS components play in the process of antimicrobial resistance, as well as in virulence, have not been systematically revealed.MethodsThe importance of three representative T6SS core genes involved in the drug resistance and virulence of A. baumannii, namely, tssB, tssD (hcp), and tssM was elucidated.ResultsA higher ratio of the three core genes was detected in drug-resistant strains than in susceptible strains among our 114 A. baumannii clinical isolates. Upon deletion of tssB in AB795639, increased antimicrobial resistance to cefuroxime and ceftriaxone was observed, alongside reduced resistance to gentamicin. The ΔtssD mutant showed decreased resistance to ciprofloxacin, norfloxacin, ofloxacin, tetracycline, and doxycycline, but increased resistance to tobramycin and streptomycin. The tssM-lacking mutant showed an increased sensitivity to ofloxacin, polymyxin B, and furazolidone. In addition, a significant reduction in biofilm formation was observed only with the ΔtssM mutant. Moreover, the ΔtssM strain, followed by the ΔtssD mutant, showed decreased survival in human serum, with attenuated competition with Escherichia coli and impaired lethality in Galleria mellonella.DiscussionThe above results suggest that T6SS plays an important role, participating in the antibiotic resistance of A. baumannii, especially in terms of intrinsic resistance. Meanwhile, tssM and tssD contribute to bacterial virulence to a greater degree, with tssM being associated with greater importance.

Abstract Background and aim Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder caused by CAG repeats expansion. Cognitive decline contributes to the loss of daily activity in manifest HD. We aimed to examine the cognition status in a Chinese HD cohort and explore factors influencing the diverse cognitive domains. Methods A total of 205 participants were recruited in the study with the assessment by neuropsychological batteries, including the mini–mental state examination (MMSE), Stroop test, symbol digit modalities test (SDMT), trail making test (TMT), verbal fluency test (VFT), and Hopkins verbal learning test–revised, as well as motor and psychiatric assessment. Pearson correlation and multiple linear regression models were applied to investigate the correlation. Results Only 41.46% of patients had normal global function first come to our center. There was a significantly difference in MMSE, Stroop test, SDMT, TMT, and VFT across each stage of HD patients (p

Background Somatic symptom disorder (SSD) commonly presents in general hospital settings, posing challenges for healthcare professionals lacking specialised psychiatric training. The Neuro-11 Neurosis Scale (Neuro-11) offers promise in screening and evaluating psychosomatic symptoms, comprising 11 concise items across three dimensions: somatic symptoms, negative emotions and adverse events. Prior research has validated the scale’s reliability, validity and theoretical framework in somatoform disorders, indicating its potential as a valuable tool for SSD screening in general hospitals.Aims This study aimed to establish the reliability, validity and threshold of the Neuro-11 by comparing it with standard questionnaires commonly used in general hospitals for assessing SSD. Through this comparative analysis, we aimed to validate the effectiveness and precision of the Neuro-11, enhancing its utility in clinical settings.Methods Between November 2020 and December 2021, data were collected from 731 patients receiving outpatient and inpatient care at Shenzhen People’s Hospital in China for various physical discomforts. The patients completed multiple questionnaires, including the Neuro-11, Short Form 36 Health Survey, Patient Health Questionnaire 15 items, Hamilton Anxiety Scale and Hamilton Depression Scale. Psychiatry-trained clinicians conducted structured interviews and clinical examinations to establish a gold standard diagnosis of SSD.Results The Neuro-11 demonstrated strong content reliability and structural consistency, correlating significantly with internationally recognised and widely used questionnaires. Despite its brevity, the Neuro-11 exhibited significant correlations with other questionnaires. A test-retest analysis yielded a correlation coefficient of 1.00, Spearman-Brown coefficient of 0.64 and Cronbach’s α coefficient of 0.72, indicating robust content reliability and internal consistency. Confirmatory factor analysis confirmed the validity of the three-dimensional structure (p

The modified carbapenem inactivation method (mCIM) recommended by the Clinical and Laboratory Standards Institute is not applicable for detecting carbapenemases in Acinetobacter baumannii. Four currently reported phenotypic detection methods, namely, the modified Hodge test, the mCIM, the adjusted mCIM, and the simplified carbapenem inactivation method (sCIM), did not perform well in our 90 clinical A. baumannii isolates. Thus, the minimal inhibitory concentrations (MICs) of carbapenems and the existence and expression of carbapenemase-encoding genes were detected to explain the results. According to the E-test, which was more accurate than the VITEK 2 system, 80.0 and 41.1% were resistant to imipenem (IPM) and meropenem (MEM), respectively, and 14.4 and 53.3% exhibited intermediate resistance, respectively. Five β-lactamase genes were found, of which blaOXA-51-like, blaTEM, and blaOXA-23-like were detected more frequently in 85 non-susceptible strains. The expression of blaOXA-23-like was positively correlated with the MIC values of IPM and MEM. Therefore, an improved approach based on the mCIM, designated the optimized CIM (oCIM), was developed in this study to detect carbapenemases more accurately and reproducibly. The condition was improved by evaluating the factors of A. baumannii inoculum, incubation broth volume, and MEM disk incubation time. Obvious high sensitivity (92.94%) and specificity (100.00%) were obtained using the oCIM, which was cost-effective and reproducible in routine laboratory work.

The accurate determination of the carbon-neutrality capacity (CNC) of a region is crucial for developing policies related to emissions and climate change. However, a systematic diagnostic method for determining the CNC that considers the rock chemical weathering carbon sink (RCS) is lacking. Moreover, it is challenging but indispensable to establish a fast and practical index model to determine the CNC. Here, we selected Guizhou as the study area, used the methods for different types of carbon sinks, and constructed a CNC index (CNCI) model. We found that: (1) the carbonate rock chemical weathering carbon sink flux was 30.3 t CO2 km−2 yr−1. Guizhou accounted for 1.8% of the land area and contributed 5.4% of the carbonate chemical weathering carbon sink; (2) the silicate rock chemical weathering carbon sink and its flux were 1.44 × 103 t CO2 and 2.43 t CO2 km−2 yr−1, respectively; (3) the vegetation-soil ecosystem carbon sink and its flux were 1.37 × 108 t CO2 and 831.70 t CO2 km−2 yr−1, respectively; (4) the carbon emissions (CEs) were 280 Tg CO2, about 2.8% of the total for China; and (5) the total carbon sinks in Guizhou were 160 Tg CO2, with a CNCI of 57%, which is 4.8 times of China and 2.1 times of the world. In summary, we conducted a systematic diagnosis of the CNC considering the RCS and established a CNCI model. The results of this study have a strong implication and significance for national and global CNC determination and gap analysis.

IntroductionFunctional neuroimaging could provide abundant information of underling pathophysiological mechanisms of the clinical triad including motor, cognitive and psychiatric impairment in Huntington's Disease (HD).MethodsWe performed a voxel-based meta-analysis using anisotropic effect size-signed differential mapping (AES-SDM) method.Results6 studies (78 symptomatic HD, 102 premanifest HD and 131 healthy controls) were included in total. Altered resting-state brain activity was primarily detected in the bilateral medial part of superior frontal gyrus, bilateral anterior cingulate/paracingulate gyrus, left insula, left striatum, right cortico-spinal projections area, right inferior temporal gyrus area, right thalamus, right cerebellum and right gyrus rectus area. Premanifest and symptomatic HD patients showed different alterative pattern in the subgroup analyses.DiscussionThe robust and consistent abnormalities in the specific brain regions identified in the current study could help to understand the pathophysiology of HD and explore reliable neuroimaging biomarkers for monitoring disease progression, or even predicting the onset of premanifest HD patients.

Presently, users usually register accounts on online social networks (OSNs). Identifying the same user in different networks is also known as interlayer link prediction. Most existing interlayer link prediction studies use embedding methods, which represent nodes in a common representation space by learning mapping functions. However, these studies often directly model links within the pre-embedding layer as equal weights, fail to effectively distinguish the strength of edge relationships, and do not fully utilize network topology information. In this paper, we propose an interlayer link prediction model based on weighted embedding of connected edges within the network layer, which models the links within the network layer as weighted graphs to better represent the network and then uses appropriate embedding methods to represent the network in a low-dimensional space. After embedding, vector similarity and distance similarity are used as comprehensive evaluation scores. This paper has conducted a large number of simulation experiments on actual networks. The results show that our proposed model has higher prediction accuracy in all aspects than current advanced models and can achieve the highest accuracy when the training frequency is low, which proves the validity of the proposed model.

HfO2-based ferroelectrics have evoked considerable interest owing to the complementary metal–oxide semiconductor compatibility and robust ferroelectricity down to a few unit cells. However, the unique wake-up effect of HfO2-based ferroelectric films severely restricts the improvement of their performance. In particular, the domain structure is an important characteristic of ferroelectric materials, which still has not been well understood in HfO2-based ferroelectrics. In this work, a Hf0.5Zr0.5O2 ferroelectric thin film is grown on a typical Si substrate buffered with TiN electrode. The 90° domains of the Pca21 ferroelectric phase with head-to-tail and tail-to-tail structures can be observed by Cs-corrected scanning transmission electron microscope under their pristine condition. After waking up, the 180° domain is displayed in the ferroelectric phase. The remarkable differences in domain walls for 90° and 180° domains are characterized by qualitatively mapping the polarization distributions at the atomic scale. The domain wall changes from the [Formula: see text] of the Hf0.5Zr0.5O2 film to the [001] of the Hf0.5Zr0.5O2 film. This result provides fundamental information for understanding the domain structure of HfO2-based ferroelectrics.

IntroductionAccurate assessment of the net ecosystem productivity (NEP) is very important for understanding the global carbon balance. However, it remains unknown whether climate change (CC) promoted or weakened the impact of human activities (HA) on the NEP from 1983 to 2018.MethodsHere, we quantified the contribution of CC and HA to the global NEP under six different scenarios based on a boosted regression tree model and sensitivity analysis over the last 40 years.Results and discussionThe results show that (1) a total of 69% of the areas showed an upward trend in the NEP, with HA and CC controlled 36.33 and 32.79% of the NEP growth, respectively. The contribution of HA (HA_con) far exceeded that of CC by 6.4 times. (2) The CO2 concentration had the largest positive contribution (37%) to NEP and the largest influence area (32.5%). It made the most significant contribution to the NEP trend in the range of 435–440 ppm. In more than 50% of the areas, the main loss factor was solar radiation (SR) in any control area of the climate factors. (3) Interestingly, CC enhanced the positive HA_con to the NEP in 44% of the world, and in 25% of the area, the effect was greater than 50%. Our results shed light on the optimal range of each climatic factor for enhancing the NEP and emphasize the important role of CC in enhancing the positive HA_con to the NEP found in previous studies.

Abstract Background Anticoagulation in hospitalized COVID-19 patients has been associated with survival benefit; however, the optimal anticoagulant strategy has not yet been defined. The objective of this meta-analysis was to investigate the effect of intermediate-to-therapeutic versus prophylactic anticoagulation for thromboprophylaxis on the primary outcome of in-hospital mortality and other patient-centered secondary outcomes in COVID-19 patients. Methods MEDLINE, EMBASE, and Cochrane databases were searched from inception to August 10th 2021. Cohort studies and randomized clinical trials that assessed the efficacy and safety of intermediate-to-therapeutic versus prophylactic anticoagulation in hospitalized COVID-19 patients were included. Baseline characteristics and relevant data of each study were extracted in a pre-designed standardized data-collection form. The primary outcome was all-cause in-hospital mortality and the secondary outcomes were incidence of thrombotic events and incidence of any bleeding and major bleeding. Pooled analysis with random effects models yielded relative risk with 95 % CIs. Results This meta-analysis included 42 studies with 28,055 in-hospital COVID-19 patients totally. Our pooled analysis demonstrated that intermediate-to-therapeutic anticoagulation was not associated with lower in-hospital mortality (RR=1.12, 95 %CI 0.99-1.25, p=0.06, I2=77 %) and lower incidence of thrombotic events (RR=1.30, 95 %CI 0.79-2.15, p=0.30, I2=88 %), but increased the risk of any bleeding events (RR=2.16, 95 %CI 1.79-2.60, p

To investigate the relationships among the chemical compositions of fog droplets, atmospheric pollutants, and the fog microphysical characteristics, four fog cases were sampled in a comprehensive field experiment conducted at the Donghai site in an agricultural city, China, in the winter of 2020. The pH, electrical conductivity (EC), total ion concentration (TIC), and chemical compositions of the fog water were all size-dependent. High concentrations of non-sea-salt calcium (nssCa2+) and NH4+ led to the alkaline pH of 6.13–7.32. The TIC of fog water was relatively high, especially in small droplets of diameter within 4–16 μm (463527.9 μeq/L). The relatively high NO2− concentration was also found in the fog water, dominated by the non-homogeneous chemical reaction between NO2 and fog droplets. An interesting finding is that the TIC of fog water measured on December 12 was much higher than that measured on December 11. Compared to the first fog, the stronger thermal inversion and local emissions led to the higher concentration of atmospheric particles in the second fog. Generally, the relatively high concentration of atmospheric particles resulted in a large number of small-sized droplets, which had fast liquid-phase oxidation reaction rates and high gas-liquid conversion efficiencies, leading to a higher TIC in the fog water during the second fog.

Abstract The Carbonate rock weathering Carbon Sink (CCS) and Silicate rock weathering Carbon Sink (SCS) play a significant role in the carbon cycle and global climate change. However, the spatial‐temporal patterns and trends of the CCS and SCS from 1950 to 2099 have not been systematically quantified. Thus, Supported by long‐term hydrometeorological data under the RCP8.5, we use the accepted Suchet and Hartmann models to determine the following. First, we found except for the difference in their weathering rates, the SCS covers 37.2 million km2 more area than the CCS. The CCS Flux (CCSF) and SCS Flux (SCSF) are 5.36 and 1.22 t/km2/yr, respectively. Similarly, the Full CCS (FCCS, 0.3 Pg/yr) is more than the Full SCS (FSCS, 0.08 Pg/yr). Furthermore, the CCS (7.01 kg/km2) and SCS (3.95 kg/km2) are in a state of overall increase. In addition, the mid‐to‐high latitudes of the northern hemisphere are aggravated by warming (0.03°C) and humidity (0.65 mm), while the decrease in runoff in the mid‐latitudes of the southern hemisphere reduces karstification. Specifically, by 2099, the CCSF in the mid‐latitudes of the southern hemisphere will decrease by 5.72%. Instead, the CCSF in the northern hemisphere and lower latitudes of the southern hemisphere will exhibit a gentle upward slope. Particularly, the peak regions of the global FCCS (65.63 Tg/yr) and FSCS (33.01 Tg/yr) are the tropical zone. In conclusion, this study contributes a high‐resolution and long‐time series CS datasets for the CCS and SCS. We provide data and a theory for solving terrestrial carbon sink loss.

This study investigated the effect of different fermentation humidities (55%, 65%, 75%, 85% and 95%) on congou black tea quality and bioactivity. Fermentation humidity mainly affected the tea′s appearance, aroma and taste quality. The tea fermented at low humidity (75% or below) showed a decrease in tightness, evenness and moistening degree, as well as a heavy grassy and greenish scent, plus a green, astringent and bitter taste. The tea fermented at a high humidity (85% or above) presented a sweet and pure aroma, as well as a mellow taste, plus an increase of sweetness and umami. With increasing fermentation humidity, the tea exhibited a drop in the content of flavones, tea polyphenols, catechins (EGCG, ECG) and theaflavins (TF, TF-3-G), contrasted by a rise in the content of soluble sugars, thearubigins and theabrownins, contributing to the development of a sweet and mellow taste. Additionally, the tea showed a gradual increase in the total amount of volatile compounds and in the content of alcohols, alkanes, alkenes, aldehydes, ketones and acids. Moreover, the tea fermented at a low humidity had stronger antioxidant activity against 2, 2-Diphenyl-1-picrylhydrazyl (DPPH) and a higher inhibiting capability on the activities of α-amylase and α-glucosidase. Overall results indicated the desirable fermentation humidity of congou black tea should be 85% or above.

Optimization efforts were devoted to discover novel PDE10A inhibitors in order to improve solubility and pharmacokinetics properties for a long-term therapy against pulmonary arterial hypertension (PAH) starting from the previously synthesized inhibitor A. As a result, a potent and highly selective PDE10A inhibitor, 14·3HCl (half maximal inhibitory concentration, IC50 = 2.8 nmol/L and >3500-fold selectivity) exhibiting desirable solubility and metabolic stability with a remarkable bioavailability of 50% was identified with the aid of efficient methods of binding free energy predictions. Animal PAH studies showed that the improvement offered by 14·3HCl [2.5 mg/kg, oral administration (p.o.)] was comparable to tadalafil (5.0 mg/kg, p.o.), verifying the feasibility of PDE10A inhibitors for the anti-PAH treatment. The crystal structure of the PDE10A−14 complex illustrates their binding pattern, which provided a guideline for rational design of highly selective PDE10A inhibitors.

ABSTRACT Acinetobacter baumannii is an important nosocomial pathogen that can develop various resistance mechanisms to many antibiotics. However, little is known about how it evolves from an antibiotic sensitive to a resistant phenotype. In this study, we investigated the transition of outer membrane proteins (OMPs) under antibiotic stress and identified YiaD as an OMP marker involved in the development of adaptive resistance to meropenem (MEM) in A. baumannii. Following stimulation of a carbapenem-sensitive strain AB5116 with sub-MIC of MEM, yiaD showed significantly decreased expression, and this decrease continued with prolonged stimulation for 8 h. The downregulation of yiaD was not only observed in clinically sensitive strains but also in 45 carbapenem-resistant isolates that produced the β-lactamases TEM and OXA-23. However, the extent of the reduction of yiaD expression in resistant strains was less than that in sensitive strains. Lack of yiaD resulted in a 4-fold increase in the MIC of AB5116 to MEM. The same level of depressed susceptibility induced by yiaD deletion was observed in both a growth curve test and a survival rate assay. Moreover, the colony shape became enlarged and irregular after loss of yiaD, and the biofilm formation ability of A. baumannii was influenced by YiaD. These results suggest that YiaD could respond to the stimulus of MEM in A. baumannii with a downregulation trend that kept pace with the prolonged stimulation time, indicating that it participates in various routes to benefit MEM resistance evolution in both carbapenem-sensitive and -resistant A. baumannii strains. IMPORTANCE Acinetobacter baumannii can develop various resistance mechanisms to carbapenems. However, the factors involved in the evolutionary process that leads from transition to the sensitive to resistant phenotype are not clear. The outer membrane protein YiaD of A. baumannii was downregulated under the stress of meropenem (MEM), and its expression level was continuously reduced with prolonged stimulation time. The downregulation of yiaD was not only observed in sensitive strains but also in carbapenem-resistant isolates producing the β-lactamases TEM and OXA-23. However, the extent of yiaD reduction was less in resistant strains than in sensitive strains. Lack of yiaD resulted in an increased MEM MIC, enlarged and irregular colonies, and decreased biofilm formation ability. These results suggest that YiaD responds to MEM stimulus in A. baumannii and participates in the adaptive resistance of MEM in both carbapenem-sensitive and -resistant strains.

With climate change, Nitrogen deposition (ND) and carbon dioxide (CO2) have increased significantly, but the effects of ND and CO2 fertilization on carbon-use efficiency (CUE) and water-use efficiency (WUE) are still unclear. Therefore, the effects of ND and CO2 on CUE and WUE are studied by means of trend analysis and partial derivatives. The results show the following: (1) From 2000 to 2020, the mean CUE in China was 0.533, and the WUE was 1.235 g C kg−1 H2O. (2) In the study area, a 53.8% CUE and 61.8% WUE showed an upward trend, and ND enhanced the positive contribution of CO2 to CUE and WUE by 15.9% and 19.3%, respectively. (3) ND explained 48.1% and 56% of the increase in CUE and WUE, respectively, and CO2 explained 45.8% and 50.1% of the increases in CUE and WUE, respectively. (4) The areas dominated by ND and CO2 accounted for 43.9% and 12.7% of the total area, respectively, highlighting the importance of ND in the driving mechanism of CUE and WUE. The research results are helpful to further research in CUE and WUE.

Infections led by Acinetobacter baumannii strains are of great concern in healthcare environments due to the strong ability of the bacteria to spread through different apparatuses and develop drug resistance. Severe diseases can be caused by A. baumannii in critically ill patients, but its biological process and mechanism are not well understood. Secretion systems have recently been demonstrated to be involved in the pathogenic process, and five types of secretion systems out of the currently known six from Gram-negative bacteria have been found in A. baumannii. They can promote the fitness and pathogenesis of the bacteria by releasing a variety of effectors. Additionally, antibiotic resistance is found to be related to some types of secretion systems. In this review, we describe the genetic and structural compositions of the five secretion systems that exist in Acinetobacter. In addition, the function and molecular mechanism of each secretion system are summarized to explain how they enable these critical pathogens to overcome eukaryotic hosts and prokaryotic competitors to cause diseases.

Capecitabine (CAP) is now widely used in the comprehensive treatment of digestive system tumors. Some clinical observations have shown that CAP may have immunosuppressive effects, but there is still a lack of clear experimental verification. In this study, different doses of CAP were administered to normal mice by gavage. Our results confirmed that CAP did not cause myelosuppression in bone marrow tissue; CAP selectively reduced the proportion of T cells and the concentration of related pro-inflammatory cytokines, while it increased the concentration of anti-inflammatory cytokines. Thymidylate phosphorylase (TP) is the key enzyme for the transformation of CAP in vivo; this study confirmed that T cells express TP, but the bone marrow tissue lacks TP expression, which explains the selectivity in pharmacodynamic effects of CAP. In addition, it was confirmed that CAP can induce T cell apoptosis in vivo and in vitro. In vitro experiments showed that CAP-induced T cell apoptosis was related to TP expression, endoplasmic reticulum stress (ERS) induction, reactive oxygen species (ROS) production, and mitochondria-mediated apoptosis activation. Therefore, this study confirmed that the differential expression of TP in cells and tissues explains why CAP avoids the toxic effects of myelosuppression while inducing T cell apoptosis to exert the immunosuppressive effect. Therefore, CAP may become an immunosuppressive agent with a simultaneous anti-cancer effect, which is worthy of further studies.

The district heating area in China is continuously increasing, which brings an increase in district heating load. In order to solve the shortage of heating power and realize the carbon neutral target, this study proposes two retrofit schemes for district heating system by integrating air source heat pump and water source heat pump, respectively. Mathematical models are established to study the performance of the integrated systems and a bilevel optimization model is proposed to optimize them. The results show that the air source heat pump combined district heating system has better performance compared to the conventional system, which reduces 50% energy consumption, 10.8% carbon emissions and achieves better economy. The dynamic coupling property of the district heating network and power grid are also considered, and the results indicate that the introduction of air source heat pump can effectively improve the efficiency and stability of power grid and reduce the seasonal fluctuation. The potential of large-scale application of air source heat pump combined system in Beijing is evaluated. The results reveal that retrofit scheme of integrating air source heat pumps into district heating system can cover 2930 MW heating load and bring 362 million Chinese Yuan profit by reducing 219,000 tons of carbon emissions and 539,000 tons of standard coal consumption in 2025.

Introduction: The association between systemic sclerosis (SSc) and sexual dysfunction was controversial. Aim: To explore the impacts of SSc on sexual function, the prevalence of sexual dysfunction in patients with SSc and associated risk factors. Methods: A systematic review of all published studies was performed. Studies exploring the association between SSc and sexual function were retrieved from PubMed, Web of Science, and EBSCO. All retrieved papers were selected according to the inclusion and exclusion criteria. Main Outcome Measure: The impacts of SSc on sexual function, the prevalence of sexual dysfunction in males and females with SSc and associated risk factors. Results: A total 12 studies were included in this study. The prevalence of sexual dysfunction in SSc males and SSc females were 76.9–81.4% and 46.7–86.6%, respectively. But the direct impacts of SSc on sexual function were controversial. EULAR SSc activity score ≥3, the number of complications ≥2, and the presence of anticardiolipin antibody and anti U1 ribonucleoprotein antibody in males and resistive index (RI) and the systolic/diastolic (S/D) ratio of clitoral blood in females have potential to be SSc-specific risk factors for sexual dysfunction. Clinical Implications: Clinicians need to pay more attention to the impacts of SSc on sexual function of patients especially in those with risk factors. Strengths & Limitations: Systematically explored the prevalence of sexual dysfunction in SSc males and females, and the risk factors of sexual dysfunction for SSc were explored innovatively. However, there were some limitations in included studies prevented exploring the impacts of SSc on sexual function deeply. Conclusion: Sexual dysfunction may be an important symptom of SSc, many risk factors may be associated with sexual dysfunction in males and females with SSc.Gao R, Qing P, Sun X, et al. Prevalence of Sexual Dysfunction in People With Systemic Sclerosis and the Associated Risk Factors: A Systematic Review. Sex Med 2021;9:100392.

Background: Increasing evidence demonstrates that repetitive transcranial magnetic stimulation (rTMS) treatment of the dorsolateral prefrontal cortex is beneficial for improving cognitive function in patients with Alzheimer’s disease (AD); however, the underlying mechanism of its therapeutic effect remains unclear.Objectives/Hypothesis: The aim of this study was to investigate the impact of rTMS to the dorsolateral prefrontal cortex on functional connectivity along with treatment response in AD patients with different severity of cognitive impairment.Methods: We conducted a 2-week treatment course of 10-Hz rTMS over the left dorsolateral prefrontal cortex in 23 patients with AD who were split into the mild or moderate cognitive impairment subgroup. Resting state electroencephalography and general cognition was assessed before and after rTMS. Power envelope connectivity was used to calculate functional connectivity at the source level. The functional connectivity of AD patients and 11 cognitively normal individuals was compared.Results: Power envelope connectivity was higher in the delta and theta bands but lower in the beta band in the moderate cognitive impairment group, compared to the cognitively normal controls, at baseline (p < 0.05). The mild cognitive impairment group had no significant abnormities. Montreal Cognitive Assessment scores improved after rTMS in the moderate and mild cognitive impairment groups. Power envelope connectivity in the beta band post-rTMS was increased in the moderate group (p < 0.05) but not in the mild group. No significant changes in the delta and theta band were found after rTMS in both the moderate and mild group.Conclusion: High-frequency rTMS to the dorsolateral prefrontal cortex modulates electroencephalographic functional connectivity while improving cognitive function in patients with AD. Increased beta connectivity may have an important mechanistic role in rTMS therapeutic effects.

Net biome productivity (NBP), which takes into account abiotic respiration and metabolic processes such as fire, pests, and harvesting of agricultural and forestry products, may be more scientific than net ecosystem productivity (NEP) in measuring ecosystem carbon sink levels. As one of the largest countries in global carbon emissions, in China, however, the spatial pattern and evolution of its NBP are still unclear. To this end, we estimated the magnitude of NBP in 31 Chinese provinces (except Hong Kong, Macau, and Taiwan) from 2000 to 2018, and clarified its temporal and spatial evolution. The results show that: (1) the total amount of NBP in China was about 0.21 Pg C/yr1. Among them, Yunnan Province had the highest NBP (0.09 Pg C/yr1), accounting for about 43% of China’s total. (2) NBP increased from a rate of 0.19 Tg C/yr1 during the study period. (3) At present, NBP in China’s terrestrial ecosystems is mainly distributed in southwest and south China, while northwest and central China are weak carbon sinks or carbon sources. (4) The relative contribution rates of carbon emission fluxes due to emissions from anthropogenic disturbances (harvest of agricultural and forestry products) and natural disturbances (fires, pests, etc.) were 70% and 9.87%, respectively. This study emphasizes the importance of using NBP to re-estimate the net carbon sink of China’s terrestrial ecosystem, which is beneficial to providing data support for the realization of China’s carbon neutrality goal and global carbon cycle research.

Identifying the impacts of climatic factors on runoff change has become a central topic in climate and hydrology research. This issue, however, has received minimal attention in karst watersheds worldwide. Multi-resolution analysis (MRA), continuous wavelet transform (CWT), cross wavelet transform (XWT) and wavelet transform coherence (WTC) are used to study the teleconnection in time and frequency between climate change and hydrological processes in a typical karst watershed at different time scales. The main results are: (1) All climatic factors exhibit a main cycle at 12-month time scales with runoff changes, but the main periodic bandwidth of rainfall on runoff changes is much wider than that of temperature and evaporation, indicating that rainfall is the main factor affecting runoff changes. (2) In other cycles, the impact of rainfall on runoff changes is the interlacing phenomena with positive and negative, but the impact of temperature and evaporation on runoff change is mainly negative. (3) The response of runoff to rainfall is in time in the high-energy region and the low-energy significant-correlation region and has shown a positive correlation with a smaller phase angle, but it is slightly lagged at 16-month time scales. Moreover, the runoff change lags behind temperature and evaporation for 1–2 months in those regions. (4) It has been found that there is a strong effect of rainfall over runoff, but a lesser effect of temperature and evaporation over runoff. The study sheds light on the main teleconnections between rainfall, evapotranspiration and surface runoff, which in turn might help to attain the better management of water resources in typical karst watersheds.

In recent decades, China has exhibited the fastest and most remarkable social-economic development in the world. As a result of such development, the forest cover of the country has undergone radical changes. This paper aims to develop a method for analyzing long-term and spatial changes in forest cover based on historical maps and remote sensing images. Moreover, we will focus on the reduction or restoration of forests distributed at different altitudes, slopes, soils, and lithologic types in different periods, to reveal the problems that should be paid attention to in forest restoration in karst areas. A typical county of China was selected as the study area. A historical military operation map was considered the principal source of basic data. These data were then combined with Landsat satellite images to conduct quantitative analysis on changes in the spatial area and location of forest cover with a long time series. The findings are as follows: in terms of time series, the forest area in the study area showed a trend of decreasing at first and then increasing, with the year 1986 as the turning point. In terms of spatial patterns, a considerable difference is observed in regions with changes in forest cover under different historical periods. Changes are obvious in limestone areas, rock soil areas, and areas with an elevation of 2000–2500 m and a slope gradient of 6°–15°. Spatial–temporal changes in forest cover reflect the effects of the war, national policy, and economic development to some extent. All these results indicate that, despite its limitations, a historical map is a valuable document for studying an ecological environment.

Abstract Silicate rock weathering maintains a stable and long‐term absorption of CO2. However, the magnitude, spatial pattern, and evolution characteristics of global silicate rock weathering carbon sink (SCS) remain unclear. To solve this problem, based on high‐precision hydrometeorological data (1996–2017) and CMIP5 data (2041–2060), using the Celine model, we calculated the global silicate rock weathering carbon sink flux (SCSF) magnitude and spatio‐temporal distribution for 1996–2017. We also predicted the SCSF under two future greenhouse gas emission scenarios (RCP 4.5 and RCP 8.5). Then, we produced a spatial data set (0.5 × 0.5) of global SCSF from 1996 to 2017 and found that the global average annual SCSF was 1.67 t/km2/yr, and the SCS was 127.11 Tg/yr. In particular, Brazil's silicate rock contribution accounts for nearly a quarter of the global SCS (24.41%). Although the GEM‐CO2 model is now widely used, the SCSF, without considering the temperature, may be overestimated by 5.4%, and the maximum contribution of temperature to it can reach 240 kg/km2/yr. Moreover, the global SCS is now showing a downward trend, but the global emission of greenhouse gases in the future (2041–2060) will continue to increase the carbon sink capacity (23.8%) due to temperature changes. In summary, we have produced a set of high‐resolution spatiotemporal data of the past and the future. The above results fill up the large‐scale data gap of SCSF and provide a scientific basis for quantitatively assessing the impact of climate change on SCS.

Background: RNA splicing defects are emerging molecular hallmarks of cancer. The gene encoding splicing factor RNA binding motif protein 10 (RBM10) has been found frequently mutated in various types of cancer, particularly lung adenocarcinoma (LUAD), but how RBM10 affects cancer pathogenesis remains to be determined. Moreover, the functional roles and clinical significance of RBM10 mutation-associated splicing events in LUAD are largely unknown. Methods: RBM10 mutations and their functional impacts were examined in LUAD patients from a Chinese patient cohort and The Cancer Genome Atlas (TCGA). Alternative splicing (AS) changes induced by RBM10 mutations in LUAD were identified by RNA sequencing and correlated with patient survival. Functions of RBM10 and the splice variants of eukaryotic translation initiation factor 4H containing or lacking exon 5 (EIF4H-L and EIF4H-S respectively) in LUAD development and progression were examined by cellular phenotypic assays and xenograft tumour formation. Findings: RBM10 mutations in LUAD generally lead to loss-of-function and cause extensive alterations in splicing events that can serve as prognostic predictors. RBM10 suppresses LUADprogression largely by regulating alternative splicing of EIF4H exon 5. Loss of RBM10 in LUAD enhances the expression of EIF4H-L in LUAD. EIF4H-L, but not EIF4H-S, is critical for LUAD cell proliferation, survival and tumourigenesis. Interpretation: Our study demonstrates a new molecular mechanism underlying RBM10 suppressive functions in lung cancer and the therapeutic value of RBM10-regulated AS events, providing important mechanistic and translational insights into splicing defects in cancer.

Colorectal carcinoma (CRC) is one of the major causes of cancer-related incidence and deaths. Here, we identified a novel antitumor peptide, P6, with a molecular weight of 2794.8 Da from a marine Chinese medicine, Arca inflata Reeve. The full amino acid sequence and secondary structure of P6 were determined by tandem mass de novo sequencing and circular dichroism spectroscopy, respectively. P6 markedly inhibited cell proliferation and colony formation, and induced apoptosis in CRC cells. Mechanistically, transcriptomics analysis and a serial functional evaluation showed that P6 induced colon cancer cell apoptosis through the activation of the p38-MAPK signaling pathway. Moreover, it was demonstrated that P6 exhibited antitumor effects in a tumor xenograft model, and induced cell cycle arrest in CRC cells in a concentration-dependent mode. These findings provide the first line of indication that P6 could be a potential therapeutic agent for CRC treatment.

Arteannuin B (AB) has been found to demonstrate obvious anti-tumor activity. However, AB is not available for clinical use due to its very low solubility and very short half-life. This study aimed to develop AB long sustained-release microspheres (ABMs) to improve the feasibility of clinical applications. Firstly, AB-polylactic-co-glycolic acid (PLGA) microspheres were prepared by a single emulsification method. In vitro characterization studies showed that ABMs had a low burst release and stable in vitro release for up to one week. The particle size of microspheres was 69.10 μm (D50). The drug loading is 37.8%, and the encapsulation rate is 85%. Moreover, molecular dynamics modeling was firstly used to simulate the preparation process of microspheres, which clearly indicated the molecular image of microspheres and provided in-depth insights for understanding several key preparation parameters. Next, in vivo pharmacokinetics (PK) study was carried out to evaluate its sustained release effect in Sprague-Dawley (SD) rats. Subsequently, the methyl thiazolyl tetrazolium (MTT) method with human lung cancer cells (A549) was used to evaluate the in vitro efficacy of ABMs, which showed the IC50 of ABMs (3.82 μM) to be lower than that of AB (16.03 μM) at day four. Finally, in vivo anti-tumor activity and basic toxicity studies were performed on BALB/c nude mice by subcutaneous injection once a week, four times in total. The relative tumor proliferation rate T/C of AMBs was lower than 40% and lasted for 21 days after administration. The organ index, organ staining, and tumor cell staining indicated the excellent safety of ABMs than Cis-platinum. In summary, the ABMs were successfully developed and evaluated with a low burst release and a stable release within a week. Molecular dynamics modeling was firstly applied to investigate the molecular mechanism of the microsphere preparation. Moreover, the ABMs possess excellent in vitro and in vivo anti-tumor activity and low toxicity, showing great potential for clinical applications.

The iterative closest point (ICP) algorithm is efficient and accurate for rigid registration but it needs the good initial parameters. It is easily failed when the rotation angle between two point sets is large. To deal with this problem, a new objective function is proposed by introducing a rotation invariant feature based on the Euclidean distance between each point and a global reference point, where the global reference point is a rotation invariant. After that, this optimization problem is solved by a variant of ICP algorithm, which is an iterative method. Firstly, the accurate correspondence is established by using the weighted rotation invariant feature distance and position distance together. Secondly, the rigid transformation is solved by the singular value decomposition method. Thirdly, the weight is adjusted to control the relative contribution of the positions and features. Finally this new algorithm accomplishes the registration by a coarse-to-fine way whatever the initial rotation angle is, which is demonstrated to converge monotonically. The experimental results validate that the proposed algorithm is more accurate and robust compared with the original ICP algorithm.