Mechanism of Abnormal Activation of MEK1 Induced by Dehydroalanine Modification.

Mitogen-activated protein kinase kinase 1 (MAPK kinase 1, MEK1) is a key kinase in the mitogen-activated protein kinase (MAPK) signaling pathway. MEK1 mutations have been reported to lead to abnormal activation that is closely related to the malignant growth and spread of various tumors, making it an important target for cancer treatment. Targeting MEK1, four small-molecular drugs have been approved by the FDA, including Trametinib, Cobimetinib, Binimetinib, and Selumetinib. Recently, a study showed that modification with dehydroalanine (Dha) can also lead to abnormal activation of MEK1, which has the potential to promote tumor development. In this study, we used molecular dynamics simulations and metadynamics to explore the mechanism of abnormal activation of MEK1 caused by the Dha modification and predicted the inhibitory effects of four FDA-approved MEK1 inhibitors on the Dha-modified MEK1. The results showed that the mechanism of abnormal activation of MEK1 caused by the Dha modification is due to the movement of the active segment, which opens the active pocket and exposes the catalytic site, leading to sustained abnormal activation of MEK1. Among four FDA-approved inhibitors, only Selumetinib clearly blocks the active site by changing the secondary structure of the active segment from α-helix to disordered loop. Our study will help to explain the mechanism of abnormal activation of MEK1 caused by the Dha modification and provide clues for the development of corresponding inhibitors.

Promoting Polysulfide Redox Reactions through Electronic Spin Manipulation.

Catalytic additives able to accelerate the lithium-sulfur redox reaction are a key component of sulfur cathodes in lithium-sulfur batteries (LSBs). Their design focuses on optimizing the charge distribution within the energy spectra, which involves refinement of the distribution and occupancy of the electronic density of states. Herein, beyond charge distribution, we explore the role of the electronic spin configuration on the polysulfide adsorption properties and catalytic activity of the additive. We showcase the importance of this electronic parameter by generating spin polarization through a defect engineering approach based on the introduction of Co vacancies on the surface of CoSe nanosheets. We show vacancies change the electron spin state distribution, increasing the number of unpaired electrons with aligned spins. This local electronic rearrangement enhances the polysulfide adsorption, reducing the activation energy of the Li-S redox reactions. As a result, more uniform nucleation and growth of Li2S and an accelerated liquid-solid conversion in LSB cathodes are obtained. These translate into LSB cathodes exhibiting capacities up to 1089 mA h g-1 at 1 C with 0.017% average capacity loss after 1500 cycles, and up to 5.2 mA h cm-2, with 0.16% decay per cycle after 200 cycles in high sulfur loading cells.

Gestational valproic acid exposure enhances facial stimulation-evoked cerebellar mossy fiber-granule cell transmission via GluN2A subunit-containing NMDA receptor in offspring mice.

Valproic acid (VPA) is one of the most effective antiepileptic drugs, and exposing animals to VPA during gestation has been used as a model for autism spectrum disorder (ASD). Numerous studies have shown that impaired synaptic transmission in the cerebellar cortical circuits is one of the reasons for the social deficits and repetitive behavior seen in ASD. In this study, we investigated the effect of VPA exposure during pregnancy on tactile stimulation-evoked cerebellar mossy fiber-granule cell (MF-GC) synaptic transmission in mice anesthetized with urethane. Three-chamber testing showed that mice exposed to VPA mice exhibited a significant reduction in social interaction compared with the control group. In vivo electrophysiological recordings revealed that a pair of air-puff stimulation on ipsilateral whisker pad evoked MF-GC synaptic transmission, N1, and N2. The evoked MF-GC synaptic responses in VPA-exposed mice exhibited a significant increase in the area under the curve (AUC) of N1 and the amplitude and AUC of N2 compared with untreated mice. Cerebellar surface application of the selective N-methyl-D-aspartate (NMDA) receptor blocker D-APV significantly inhibited facial stimulation-evoked MF-GC synaptic transmission. In the presence of D-APV, there were no significant differences between the AUC of N1 and the amplitude and AUC of N2 in the VPA-exposed mice and those of the untreated mice. Notably, blockade of the GluN2A subunit-containing, but not the GluN2B subunit-containing, NMDA receptor, significantly inhibited MF-GC synaptic transmission and decreased the AUC of N1 and the amplitude and AUC of N2 in VPA-exposed mice to levels similar to those seen in untreated mice. In addition, the GluN2A subunit-containing NMDA receptor was expressed at higher levels in the GC layer of VPA-treated mice than in control mice. These results indicate that gestational VPA exposure in mice produces ASD-like behaviors, accompanied by increased cerebellar MF-GC synaptic transmission and an increase in GluN2A subunit-containing NMDA receptor expression in the offspring.

Daily occupational exposure in swine farm alters human skin microbiota and antibiotic resistome.

Antimicrobial resistance (AMR) is a major threat to global public health, and antibiotic resistance genes (ARGs) are widely distributed across humans, animals, and environment. Farming environments are emerging as a key research area for ARGs and antibiotic resistant bacteria (ARB). While the skin is an important reservoir of ARGs and ARB, transmission mechanisms between farming environments and human skin remain unclear. Previous studies confirmed that swine farm environmental exposures alter skin microbiome, but the timeline of these changes is ill defined. To improve understanding of these changes and to determine the specific time, we designed a cohort study of swine farm workers and students through collected skin and environmental samples to explore the impact of daily occupational exposure in swine farm on human skin microbiome. Results indicated that exposure to livestock-associated environments where microorganisms are richer than school environment can reshape the human skin microbiome and antibiotic resistome. Exposure of 5 h was sufficient to modify the microbiome and ARG structure in workers' skin by enriching microorganisms and ARGs. These changes were preserved once formed. Further analysis indicated that ARGs carried by host microorganisms may transfer between the environment with workers' skin and have the potential to expand to the general population using farm workers as an ARG vector. These results raised concerns about potential transmission of ARGs to the broader community. Therefore, it is necessary to take corresponding intervention measures in the production process to reduce the possibility of ARGs and ARB transmission.

Highly efficient photocatalyst fabricated from the recycling of heavy metal ions in wastewater for dye degradation.

Water pollution and energy crisis are becoming global and strategic issues that people are closely concerned about. Green and energy-saving photocatalytic technology is developing rapidly in solving global energy crises and environmental pollution problems. Therefore, we propose the "kill two birds with one stone" strategy to design efficient photocatalysts for dye wastewater treatment by utilizing heavy metal ions in wastewater. The adsorption properties of Mordenite (MOR) were utilized to removal heavy metal ions (Cd2+ and Zn2+) from waste water, and the adsorbed heavy metal ions were dried and sulfurized to obtain CdS/ZnS/MOR(ZnCdM). Then, g-C3N4 was ultrasonically dispersed and composited with ZnCdM by self-assembly, 25 wt% ZnCdCM photocatalytic material was obtained with a degradation rate of 99.8% in 1.5 h for Rhodamine B(RhB). It was found that MOR can provid adequate support for active substances, and the surface of MOR with smaller sizes of CdS nanoparticles, ZnS nanoparticles and g-C3N4 nanosheets, which increased the specific surface area of the materials and improved the reactivity. The porous structure of MOR is favorable for the enrichment of RhB, and the electric field effect of MOR leads to the decrease of the photogenerated carrier complex rate in the semiconductor, which increases the catalytic efficiency. In addition, the double Z charge transfer mechanism formed by CdS, ZnS, g-C3N4 is favorable for separating photogenerated carriers. These synergistic effects improved the photocatalytic efficiency. This strategy will be a green and promising solution to water pollution and energy crisis.

[Source Apportionment and Health Risk Assessment of Heavy Metals in Dust Around Bus Stops in Kaifeng City Based on APCS-MLR Model].

In order to reveal the influence of urban transportation systems on the quality of urban ecological environment, this study selected surface dust from bus stops, which is strongly disturbed by transportation, as the research object. The contents of eight heavy metals (V, Cr, Co, Ni, Cu, Zn, Cd, and Pb) in the dust were determined through inductively coupled plasma mass spectrometry (ICP-MS) and inductively coupled plasma atomic emission spectroscopy (ICP-ASE). The spatial distribution characteristics and pollution levels of the eight heavy metals in the dust were analyzed using the geo-accumulation index method. A combined qualitative (correlation analysis and principal component analysis) and quantitative (absolute principal component scores-multiple linear regression model (APCS-MLR)) method was used to explore the sources of heavy metals in surface dust near bus stops. The spatial distribution characteristics of heavy metals from different sources were elucidated using the Kriging interpolation method. The health risk assessment model proposed by the United States Environmental Protection Agency was used to evaluate the human health risks. The results showed that the average values of ω(V), ω(Cr), ω(Co), ω(Ni), ω(Cu), ω(Zn), ω(Cd), ω(Pb), and ω(As) in the bus stop surface dust were 68.36, 59.73, 5.81, 19.34, 40.10, 208.32, 1.01, and 49.46 mg·kg-1, respectively. The concentrations of heavy metals (Cd, Zn, Pb, Cu, and Cr) in the dust were all higher than the background values in the surrounding dust, exceeding them by 3.37, 2.70, 2.01, 1.95, and 1.28 times, respectively. The order of the geo-accumulation index for the eight heavy metals was Cd > Zn > Pb > Cu > Cr > V > Ni > Co, with Cd, Zn, Cu, and Pb in the dust indicating mild pollution levels and the others showing no pollution. The source analysis results showed that Cr, Co, and Ni were natural sources, whereas Cu, Zn, Pb, and Cd were traffic sources, and V was derived from a combination of industrial and natural sources. The APCS-MLR results indicated that the average contribution rates of the four sources were as follows:natural source (34.17 %), traffic source (29.84 %), industrial-natural mixed source (14.64 %), and unknown source (21.35 %). The spatial distribution map of the contribution rate of the traffic source was consistent with the trends of traffic volume and bus route density distribution. According to the health risk assessment, the cancer risk and non-cancer risk for children were both higher than those for adults. Cr was the main non-cancer factor, and Cd was the main cancer-causing factor. Natural and traffic sources contributed the most to non-cancer risk and cancer risk, respectively.

[Effects of tramadol hydrochloride preemptive analgesia in kyphoplasty of thoracolumbar osteoporotic fractures under local anesthesia].

OBJECTIVE: To explore preemptive analgesic effect of preoperative intramural tramadol injection in percutaneous kyphoplasty (PKP) of vertebrae following local anesthesia. METHODS: From August 2019 to June 2021, 118 patients with thoraco lumbar osteoporotic fractures were treated and divided into observation group and control group, with 59 patients in each gruop. In observation group, there were 26 males and 33 females, aged from 57 to 80 years old with an average of (67.69±4.75)years old;14 patients on T11, 12 patients on T12, 18 patients on L1, 15 patients on L2;tramadol with 100 mg was injected intramuscularly half an hour before surgery in observation group. In control group, there were 24 males and 35 females, aged from 55 to 77 years old with an average of (68.00±4.43) years old;19 patients on T11, 11 patients on T12, 17patients on L1, 12 patients on L2;the same amount of normal saline was injected intramuscularly in control group. Observation indicators included operation time, intraoperative bleeding, visual analogue scale (VAS) evaluation and recording of preoperative (T0), intraoperative puncture(T1), and working cannula placement (T2) between two groups of patients, at the time of balloon dilation (T3), when the bone cement was injected into the vertebral body (T4), 2 hours after the operation (T5), and the pain degree at the time of discharge(T6);adverse reactions such as dizziness, nausea and vomiting were observed and recorded;the record the patient's acceptance of repeat PKP surgery. RESULTS: All patients were successfully completed PKP via bilateral pedicle approach, and no intravenous sedative and analgesic drugs were used during the operation. There was no significant difference in preoperative general data and VAS(T0) between two groups (P>0.05). There was no significant difference in operation time and intraoperative blood loss between the two groups (P>0.05). VAS of T1, T2, T3, T4 and T5 in observation group were all lower than those in control group(P<0.05), and there was no significant difference in T6 VAS (P>0.05). T6 VAS between two groups were significantly lower than those of T0, and the difference was statistically significant (P<0.05). There was no significant difference in incidence of total adverse reactions between two groups (P>0.05). There was a statistically significant difference in the acceptance of repeat PKP surgery (P<0.05). CONCLUSION: Half an hour before operation, intramuscular injection of tramadol has a clear preemptive analgesic effect for PKP of single-segment thoracolumbar osteoporotic fracture vertebral body under local anesthesia, which could increase the comfort of patients during operation and 2 hours after operation, and improve patients satisfaction with surgery.

Association between pretreatment emotional distress and immune checkpoint inhibitor response in non-small-cell lung cancer.

Emotional distress (ED), commonly characterized by symptoms of depression and/or anxiety, is prevalent in patients with cancer. Preclinical studies suggest that ED can impair antitumor immune responses, but few clinical studies have explored its relationship with response to immune checkpoint inhibitors (ICIs). Here we report results from cohort 1 of the prospective observational STRESS-LUNG study, which investigated the association between ED and clinical efficacy of first-line treatment of ICIs in patients with advanced non-small-cell lung cancer. ED was assessed by Patient Health Questionnaire-9 and Generalized Anxiety Disorder 7-item scale. The study included 227 patients with 111 (48.9%) exhibiting ED who presented depression (Patient Health Questionnaire-9 score ≥5) and/or anxiety (Generalized Anxiety Disorder 7-item score ≥5) symptoms at baseline. On the primary endpoint analysis, patients with baseline ED exhibited a significantly shorter median progression-free survival compared with those without ED (7.9 months versus 15.5 months, hazard ratio 1.73, 95% confidence interval 1.23 to 2.43, P = 0.002). On the secondary endpoint analysis, ED was associated with lower objective response rate (46.8% versus 62.1%, odds ratio 0.54, P = 0.022), reduced 2-year overall survival rate of 46.5% versus 64.9% (hazard ratio for death 1.82, 95% confidence interval 1.12 to 2.97, P = 0.016) and detriments in quality of life. The exploratory analysis indicated that the ED group showed elevated blood cortisol levels, which was associated with adverse survival outcomes. This study suggests that there is an association between ED and worse clinical outcomes in patients with advanced non-small-cell lung cancer treated with ICIs, highlighting the potential significance of addressing ED in cancer management. ClinicalTrials.gov registration: NCT05477979 .

Electronic Spin Alignment within Homologous NiS2/NiSe2 Heterostructures to Promote Sulfur Redox Kinetics in Lithium-Sulfur Batteries.

The catalytic activation of the Li-S reaction is fundamental to maximize the capacity and stability of Li-S batteries (LSBs). Current research on Li-S catalysts mainly focuses on optimizing the energy levels to promote adsorption and catalytic conversion, while frequently overlooking the electronic spin state influence on charge transfer and orbital interactions. Here, hollow NiS2/NiSe2 heterostructures encapsulated in a nitrogen-doped carbon matrix (NiS2/NiSe2@NC) are synthesized and used as a catalytic additive in sulfur cathodes. The NiS2/NiSe2 heterostructure promotes the spin splitting of the 3d orbital, driving the Ni3+ transformation from low to high spin. This high spin configuration raises the electronic energy level and activates the electronic state. This accelerates the charge transfer and optimizes the adsorption energy, lowering the reaction energy barrier of the polysulfides conversion. Benefiting from these characteristics, LSBs based on NiS2/NiSe2@NC/S cathodes exhibit high initial capacity (1458 mAh·g⁻1 at 0.1C), excellent rate capability (572 mAh·g⁻1 at 5C), and stable cycling with an average capacity decay rate of only 0.025% per cycle at 1C during 500 cycles. Even at high sulfur loadings (6.2 mg·cm⁻2), high initial capacities of 1173 mAh·g⁻1 (7.27 mAh·cm⁻2) are measured at 0.1C, and 1058 mAh·g⁻1 is retained after 300 cycles.

In Situ Electrochemical Rapid Induction of Highly Active γ-NiOOH Species for Industrial Anion Exchange Membrane Water Electrolyzer.

Limited by the strong oxidation environment and sluggish reconstruction process in oxygen evolution reaction (OER), designing rapid self-reconstruction with high activity and stability electrocatalysts is crucial to promoting anion exchange membrane (AEM) water electrolyzer. Herein, trace Fe/S-modified Ni oxyhydroxide (Fe/S-NiOOH/NF) nanowires are constructed via a simple in situ electrochemical oxidation strategy based on precipitation-dissolution equilibrium. In situ characterization techniques reveal that the successful introduction of Fe and S leads to lattice disorder and boosts favorable hydroxyl capture, accelerating the formation of highly active γ-NiOOH. The Density Functional Theory (DFT) calculations have also verified that the incorporation of Fe and S optimizes the electrons redistribution and the d-band center, decreasing the energy barrier of the rate-determining step (*O→*OOH). Benefited from the unique electronic structure and intermediate adsorption, the Fe/S-NiOOH/NF catalyst only requires the overpotential of 345 mV to reach the industrial current density of 1000 mA cm-2 for 120 h. Meanwhile, assembled AEM water electrolyzer (Fe/S-NiOOH//Pt/C-60 °C) can deliver 1000 mA cm-2 at a cell voltage of 2.24 V, operating at the average energy efficiency of 71% for 100 h. In summary, this work presents a rapid self-reconstruction strategy for high-performance AEM electrocatalysts for future hydrogen economy.

Depression and anxiety symptom network structure among patients with coronary heart disease and association with quality of life: protocol for a multicentre cross-sectional and prospective longitudinal study.

BACKGROUND: Anxiety and depression are critical mental health problems among persons with coronary heart disease (CHD). The range of symptoms is an important stressor for adverse cardiovascular events, and these symptoms can be involved in various ways during the course of CHD. However, the characteristics and mechanisms of comorbidity between the two mental states from the viewpoint of symptom interactions in patients with CHD remain unclear. Therefore, we aim to apply a symptom-oriented approach to identify core and bridge symptoms between anxiety and depression in a population with CHD and to identify differences in network structure over time and symptomatic link profiles. METHODS AND ANALYSIS: We designed a multicentre, cross-sectional, longitudinal study of anxiety and depression symptoms among patients with CHD. We will evaluate degrees of symptoms using the Generalized Anxiety Disorder Scale, the Patient Health Questionnaire and the WHO Quality of Life-Brief version. Patients will be followed up for 1, 3 and 6 months after baseline measurements. We will analyse and interpret network structures using R software and its packages. The primary outcomes of interest will include centrality, bridge connections, estimates, differences in network structures and profiles of changes over time. The secondary outcome measures will be the stability and accuracy of the network. By combining cross-sectional and longitudinal analyses, this study should elucidate the central and potential causative pathways among anxiety and depression symptom networks as well as their temporal stability in patients with CHD. ETHICS AND DISSEMINATION: The project conforms to the ethical principles enshrined in the Declaration of Helsinki (2013 amendment) and all local ethical guidelines. The ethics committee at the University of South China approved the study (Approval ID: 2023-USC-HL-414). The findings will be published and presented at conferences for widespread dissemination. TRIAL REGISTRATION NUMBER: ChiCTR2300075813.

Enhanced Electrochemical Hydrogenation of Benzaldehyde to Benzyl Alcohol on Pd@Ni-MOF by Modifying the Adsorption Configuration.

Electrocatalytic hydrogenation (ECH) approaches under ambient temperature and pressure offer significant potential advantages over thermal hydrogenation processes but require highly active and efficient hydrogenation electrocatalysts. The performance of such hydrogenation electrocatalysts strongly depends not only on the active phase but also on the architecture and surface chemistry of the support material. Herein, Pd nanoparticles supported on a nickel metal-organic framework (MOF), Ni-MOF-74, are prepared, and their activity toward the ECH of benzaldehyde (BZH) in a 3 M acetate (pH 5.2) aqueous electrolyte is explored. An outstanding ECH rate up to 283 µmol cm-2 h-1 with a Faradaic efficiency (FE) of 76% is reached. Besides, higher FEs of up to 96% are achieved using a step-function voltage. Materials Studio and density functional theory calculations show these outstanding performances to be associated with the Ni-MOF support that promotes H-bond formation, facilitates water desorption, and induces favorable tilted BZH adsorption on the surface of the Pd nanoparticles. In this configuration, BZH is bonded to the Pd surface by the carbonyl group rather than through the aromatic ring, thus reducing the energy barriers of the elemental reaction steps and increasing the overall reaction efficiency.

A Layered Bi2 Te3 @PPy Cathode for Aqueous Zinc-Ion Batteries: Mechanism and Application in Printed Flexible Batteries.

Low-cost, safe, and environmental-friendly rechargeable aqueous zinc-ion batteries (ZIBs) are promising as next-generation energy storage devices for wearable electronics among other applications. However, sluggish ionic transport kinetics and the unstable electrode structure during ionic insertion/extraction hamper their deployment. Herein, a new cathode material based on a layered metal chalcogenide (LMC), bismuth telluride (Bi2 Te3 ), coated with polypyrrole (PPy) is proposed. Taking advantage of the PPy coating, the Bi2 Te3 @PPy composite presents strong ionic absorption affinity, high oxidation resistance, and high structural stability. The ZIBs based on Bi2 Te3 @PPy cathodes exhibit high capacities and ultra-long lifespans of over 5000 cycles. They also present outstanding stability even under bending. In addition, here the reaction mechanism is analyzed using in situ X-ray diffraction, X-ray photoelectron spectroscopy, and computational tools and it is demonstrated that, in the aqueous system, Zn2+ is not inserted into the cathode as previously assumed. In contrast, proton charge storage dominates the process. Overall, this work not only shows the great potential of LMCs as ZIB cathode materials and the advantages of PPy coating, but also clarifies the charge/discharge mechanism in rechargeable ZIBs based on LMCs.

The Association between Magnesium Depletion Score and Hypertension in US Adults: Evidence from the National Health and Nutrition Examination Survey (2007-2018).

The magnesium depletion score (MDS) emerges as a new valuable predictor of the body's magnesium status index. This study aims to explore the link between MDS and hypertension (HTN) using the National Health and Nutrition Examination Survey (NHANES) data. A total of 9708 participants from NHANES (2007-2018) were enrolled to investigate MDS's connection with HTN. HTN was defined based on clinical guidelines. MDS classification (low, 0-1; middle, 2; high, 3-5) relied on alcohol consumption, diuretic use, proton-pump inhibitor (PPI) usage, and kidney disease. Multivariable logistic regression assessed MDS-HTN association. Subsequent analyses included interaction tests, subgroups, and sensitivity analysis. Each unit increase in MDS correlated with an 87% higher HTN risk (OR, 1.87; 95% CI, 1.64-2.13) after adjusting for confounders. High MDS participants exhibited significantly elevated HTN risk compared to low MDS counterparts (OR, 8.31; 95% CI, 4.81-14.36), with a significant trend across MDS groups (p < 0.001). Subgroup analyses supported a consistent positive correlation. Sensitivity analysis confirmed a robust association. The results indicated a positive correlation between MDS and the risk of developing HTN in US adults.

[Soil Heavy Metal Contamination, Sources, and Health Risk of Typical Drinking Water Sources in the Suspended Reach of the Lower Yellow River].

With the implementation of ecological protection and a high-quality development strategy in the Yellow River Basin, the environmental conditions around the Yellow River have attracted wide attention from scholars. In this study, the soil of drinking water sources(Heichi and Liuchi) in the typical suspended reach of the lower reaches of the Yellow River was selected as the research object. The geo-accumulation index and pollution load index were used to analyze the pollution characteristics of seven heavy metals(Cr, Ni, Cu, Zn, Cd, Pb, and As), and correlation analysis, principal component analysis, and absolute factor score-multiple linear regression(APCS-MLR) were employed to reveal the sources of soil heavy metals from both qualitative and quantitative perspectives. The health risk assessment model recommended by the United States Environmental Protection Agency(USEPA) was used to analyze the impact of soil heavy metals on human health, and the contribution rate of pollution sources to health risks was analyzed by combining the APCS-MLR model. The results showed that the average values of ω(Cr), ω(Ni), ω(Cu), ω(Zn), ω(Cd), ω(Pb), and ω(As) in the soil around the water source were 60.27, 30.00, 35.14, 77.75, 0.38, 21.74, and 9.70 mg·kg-1, respectively. Except for As, the contents of Cr, Ni, Cu, Zn, Cd, and Pb were higher than the background values of soil elements in the fluvo-aquic soil area of the lower Yellow River, whereas the contents of Cu and Zn in the soil around Liuchi were significantly higher than those in Heichi. Both the geo-accumulation index and the single-factor index showed that the black pond and the willow pond were slightly polluted by heavy metals, and Cd was the main pollution factor. The pollution load index model showed that the number of non-polluted and mildly polluted samples in the study area accounted for 5% and 95% of the total samples, respectively, indicating that the study area was at a mild pollution level. The source apportionment showed that Cr, Ni, Cu, and As were mainly affected by parent materials. The analysis results of the APCS-MLR model showed that the soil pollutants in the study area were mainly from natural sources, traffic sources, agricultural sources, and unknown sources, and their contribution rates were 42.95%, 23.39%, 16.95%, and 16.71%, respectively. The health risk assessment showed that As was the main non-carcinogenic factor, and Ni was the main carcinogenic factor. The non-carcinogenic risk of heavy metals to adults and children was negligible, and there was a tolerable carcinogenic risk to the human body. For both adults and children, the non-carcinogenic and carcinogenic risk contribution rates of the four pollution sources were:natural sources>unknown sources>traffic sources>agricultural sources, among which natural sources contributed the most to non-carcinogenic and carcinogenic risks. Therefore, it is of great significance to study the characteristics, sources, and effects of soil pollution on human health around the water source area of the suspended reach of the lower reaches of the Yellow River, which is of great significance for the protection of water sources and provides theoretical support for the high-quality development of the ecological environment along the Yellow River.

A segmentation model to detect cevical lesions based on machine learning of colposcopic images.

Background: Semantic segmentation is crucial in medical image diagnosis. Traditional deep convolutional neural networks excel in image classification and object detection but fall short in segmentation tasks. Enhancing the accuracy and efficiency of detecting high-level cervical lesions and invasive cancer poses a primary challenge in segmentation model development. Methods: Between 2018 and 2022, we retrospectively studied a total of 777 patients, comprising 339 patients with high-level cervical lesions and 313 patients with microinvasive or invasive cervical cancer. Overall, 1554 colposcopic images were put into the DeepLabv3+ model for learning. Accuracy, Precision, Specificity, and mIoU were employed to evaluate the performance of the model in the prediction of cervical high-level lesions and cancer. Results: Experiments showed that our segmentation model had better diagnosis efficiency than colposcopic experts and other artificial intelligence models, and reached Accuracy of 93.29 %, Precision of 87.2 %, Specificity of 90.1 %, and mIoU of 80.27 %, respectively. Conclution: The DeepLabv3+ model had good performance in the segmentation of cervical lesions in colposcopic post-acetic-acid images and can better assist colposcopists in improving the diagnosis.

Aryl Chloride-Directed Enantioselective C(sp2)-H Borylation Enabled by Iridium Catalysis.

We herein report the iridium-catalyzed enantioselective C-H borylation of aryl chlorides. A variety of prochiral biaryl compounds could be well-tolerated, affording a vast array of axially chiral biaryls with high enantioselectivities. The current method exhibits a high turnover number (TON) of 7000, which represents the highest in functional-group-directed asymmetric C-H activation. The high TON was attributed to a weak catalyst-substrate interaction that was caused by mismatched chirality between catalyst and substrate. We also demonstrated the synthetic application of the current method by C-B, ortho-C-H, and C-Cl bond functionalization, including programmed Suzuki-Miyaura coupling for the synthesis of axially chiral polyarenes.

RhoA Promotes Synovial Proliferation and Bone Erosion in Rheumatoid Arthritis through Wnt/PCP Pathway.

Ras homolog gene family member A (RhoA) plays a major role in the Wnt/planar cell polarity (PCP) pathway, which is significantly activated in patients with rheumatoid arthritis (RA). The function of RhoA in RA synovitis and bone erosion is still elusive. Here, we not only explored the impact of RhoA on the proliferation and invasion of RA fibroblast-like synoviocytes (FLSs) but also elucidated its effect on mouse osteoclast and a mouse model of collagen-induced arthritis (CIA). Results showed that RhoA was overexpressed in RA and CIA synovial tissues. Lentivirus-mediated silencing of RhoA increased apoptosis, attenuated invasion, and dramatically upregulated osteoprotegerin/receptor activator of nuclear factor-κB ligand (OPG/RANKL) ratio in RA-FLSs. Additionally, the silencing of RhoA inhibited mouse osteoclast differentiation in vitro and alleviated synovial hyperplasia and bone erosion in the CIA mouse model. These effects in RA-FLSs and osteoclasts were all regulated by RhoA/Rho-associated protein kinase 2 (ROCK2) and might interact with Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways.

Host ALDH2 deficiency aggravates nonalcoholic steatohepatitis through gut-liver axis.

Nonalcoholic steatohepatitis (NASH) is the major cause of liver dysfunction. Animal and population studies have shown that mitochondrial aldehyde dehydrogenase (ALDH2) is implicated in fatty liver disease. However, the role of ALDH2 in NASH and the underlying mechanisms remains unclear. To address this issue, ALDH2 knockout (ALDH2-/-) mice and wild-type littermate mice were fed a methionine-and choline-deficient (MCD) diet to induce a NASH model. Fecal, serum, and liver samples were collected and analyzed to investigate the impact of the gut microbiota and bile acids on this process. We found that MCD-fed ALDH2-/- mice exhibited increased serum pro-inflammation cytokines, hepatic inflammation and fat accumulation than their wild-type littermates. MCD-fed ALDH2-/- mice exhibited worsened MCD-induced intestinal inflammation and barrier damage, and gut microbiota disorder. Furthermore, mice receiving microbiota from MCD-fed ALDH2-/- mice had increased severity of NASH compared to those receiving microbiota from MCD-fed wild-type mice. Notably, the intestinal Lactobacillus was significantly reduced in MCD-fed ALDH2-/- mice, and gavage with Lactobacillus cocktail significantly improved MCD-induced NASH. Finally, we found that ALDH2-/- mice had reduced levels of bile salt hydrolase and specific bile acids, especially lithocholic acid (LCA), accompanied by downregulated expression of the intestinal FXR-FGF15 pathway. Supplementation of LCA in ALDH2-/- mice upregulated intestinal FXR-FGF15 pathway and alleviated NASH. In summary, ALDH2 plays a critical role in the development of NASH through modulation of gut microbiota and bile acid. The findings suggest that supplementing with Lactobacillus or LCA could be a promising therapeutic approach for treating NASH exacerbated by ALDH2 deficiency.

[Pollution Characteristics and Source Analysis of Heavy Metals in Soils in Yellow River Cultural Park Based on APCS-MLR and PMF Receptor Model].

With open spaces and good ecological environments, urban parks have become the first choice for the leisure and entertainment of many people. Therefore, the quality of park soil environments has gradually attracted the extensive attention of scholars. In this study, we take the Yellow River Cultural Park, a typical human disturbance area in the lower reaches of the Yellow River, as the research area to discuss the characteristics and sources of heavy metal pollution in the soil. Thirty-three soil surface samples were collected from the Yellow River Cultural Park, and the contents of seven heavy metals (Cr, Ni, Cu, Zn, Cd, Pb, and As) were determined using an inductively coupled plasma emission spectrometer (ICP-AES) and an inductively coupled plasma mass spectrometer (ICP-MS). The geo-accumulation index and geo-statistics method were used. Meanwhile, the absolute factor analysis-multiple linear regression (APCS-MLR) receptor model and positive matrix factorization (PMF) analysis model were employed to reveal the sources of soil heavy metals. The results showed that the average contents of heavy metals (Cd, Zn, Cu, Pb, and As) in the surface soil of the study area were 4.62, 1.78, 1.41, 1.08, and 1.03 times higher than the background values of soil elements in the tidal soil area of the lower reaches of the Yellow River, respectively. Except for Zn, the contents of other elements were lower than the corresponding values of soil elements in different regions along the Yellow River Basin. Among the seven heavy metal elements, the coefficients of variation of Cd and As were greater than 50%, showing obvious spatial variability. The decreasing trend of the accumulation index of the seven elements was Cd>Zn>Cu>Ni>Pb>As=Cr, and the element Cd belonged to the middle pollution category, which was obviously accumulated in the surface soil. The spatial distribution of heavy metals in the soil differed:the high contents of Cr, Cu, and Ni were distributed in the southwest and northeast, and the high-value areas of Cd and Pb were consistent with the areas of human activity intensity. The high-value areas of Zn and As were located in the center of lacustrine sediments. The combined results of the APCS-MLR and PMF models suggested that the first pollution source of soil heavy metal elements in the Yellow River Cultural Park could have been a natural source, the second pollution source may have been a transportation source, and the third source of pollution was judged as a mixed source. Human activities such as transportation sources and mixed sources were the main sources of heavy metal soil pollution, and Cr, Cu, and Ni were affected by natural factors. The contribution rates of APCS-MLR were 46.67%, 24.11%, 16.12%, and 13.10%, respectively, and the contribution rates of PMF were 35.50%, 35.48%, and 29.02%, respectively. This research can provide a basis for improving the ecological environment quality of the park and improving the health level of the population and can also provide support for the ecological environment risk management and comprehensive management along the Yellow River.