Iodoarene-directed photoredox ß-C(sp3)-H arylation of 1-(o-iodoaryl)alkan-1-ones with cyanoarenes via halogen atom transfer and hydrogen atom transfer.

Site selective functionalization of inert remote C(sp3)-H bonds to increase molecular complexity offers vital potential for chemical synthesis and new drug development, thus it has been attracting ongoing research interest. In particular, typical ß-C(sp3)-H arylation methods using chelation-assisted metal catalysis or metal-catalyzed oxidative/photochemical in situ generated allyl C(sp3)-H bond processes have been well developed. However, radical-mediated direct ß-C(sp3)-H arylation of carbonyls remains elusive. Herein, we describe an iodoarene-directed photoredox ß-C(sp3)-H arylation of 1-(o-iodoaryl)alkan-1-ones with cyanoarenes via halogen atom transfer (XAT) and hydrogen atom transfer (HAT). The method involves diethylaminoethyl radical-mediated generation of an aryl radical intermediate via XAT, then directed 1,5-HAT to form the remote alkyl radical intermediate and radical-radical coupling with cyanoarenes, and is applicable to a broad scope of unactivated remote C(sp3)-H bonds like ß-C(sp3)-H bonds of o-iodoaryl-substituted alkanones and α-C(sp3)-H bonds of o-iodoarylamides. Experimental findings are supported by computational studies (DFT calculations), revealing that this method operates via a radical-relay stepwise mechanism involving multiple SET, XAT, 1,5-HAT and radical-radical coupling processes.

High-Area-Capacity Cathode by Ultralong Carbon Nanotubes for Secondary Binder-Assisted Dry Coating Technology.

Thick electrodes with high mass loading and increased content of active materials are critical for achieving higher energy density in contemporary lithium-ion batteries (LIBs). Nonetheless, producing thick electrodes through the commonly used slurry coating technology remains a formidable challenge. In this study, we have addressed this challenge by developing a dry electrode technology by using ultralong multiwalled carbon nanotubes (MWCNT) as a conductive additive and secondary binder. The mixing process of electrode compositions and the fibrillation process of the polytetrafluoroethylene (PTFE) binder were optimized. The resulting LiCoO2 (LCO) electrode exhibited a remarkable mass loading of 48 mg cm-2 and an active material content of 95 wt %. Notably, the thick LCO electrode demonstrated a superior mechanical strength and electrochemical performance. After 100 cycles at a current density of 1/3 C, the electrode still exhibited a capacity retention of 91% of its initial capacity. This dry electrode technology provides a practicable and scalable approach to the powder-to-film LIB electrode manufacturing process.

Biomechanical evaluation of various rigid internal fixation modalities for condylar-base-associated multiple mandibular fractures: A finite element analysis.

Condylar-base-associated multiple mandibular fractures are more prevalent than single ones. Direct trauma to mandibular symphysis, body or angle are prone to induce indirect condylar fracture. However, little is known about the effects of various rigid internal fixation modalities in condylar base for relevant multiple mandibular fractures, especially when we are confused in the selection of operative approach. Within the finite element analysis, straight-titanium-plate implanting positions in condylar base contained posterolateral zone (I), anterolateral zone (II), and intermediate zone (III). Von Mises stress (SS) in devices and bone and mandibular displacement (DT) were solved, while maximum values (SSmax and DTmax) were documented. For rigid internal fixation in condylar-base-and-symphysis fractures, I + II modality exhibited least SSmax in screws and cortical bone and least DTmax, I + III modality exhibited least SSmax in plates. For rigid internal fixation in condylar-base-and-contralateral-body fractures, I + III modality exhibited least SSmax in screws and cortical bone, I + II modality exhibited least SSmax in plates and least DTmax. For rigid internal fixation in condylar-base-and-contralateral-angle fractures, I + III modality exhibited least DTmax. The findings suggest that either I + II or I + III modality is a valid guaranty for rigid internal fixation of condylar base fractures concomitant with symphysis, contralateral body or angle fractures.

Physical activity improves the visual-spatial working memory of individuals with mild cognitive impairment or Alzheimer's disease: a systematic review and network meta-analysis.

Objective: Our network meta-analysis aimed to ascertain the effect of physical activity on the visual-spatial working memory of individuals with mild cognitive impairment and Alzheimer's disease as well as to propose tailored exercise interventions for each group. Methods: Employing a frequentist approach, we performed a network meta-analysis to compare the effectiveness of different exercise interventions in improving the visual-spatial working memory of individuals with mild cognitive impairment and Alzheimer's disease. Subsequently, we explored the moderating variables influencing the effectiveness of the exercise interventions through a subgroup analysis. Results: We included 34 articles involving 3,074 participants in the meta-analysis, comprised of 1,537 participants from studies on mild cognitive impairment and 1,537 participants from studies on Alzheimer's disease. The articles included exhibited an average quality score of 6.6 (score studies) and 6.75 (reaction time [RT] studies), all passing the inconsistency test (p > 0.05). In the mild cognitive impairment literature, mind-body exercise emerged as the most effective exercise intervention (SMD = 0.61, 95% CI: 0.07-1.14). In Alzheimer's disease research, aerobic exercise was identified as the optimal exercise intervention (SMD = 0.39, 95% CI: 0.06-0.71). Conclusion: The results of the subgroup analysis suggest that the most effective approach to enhancing the visual-spatial working memory of individuals with mild cognitive impairment entails exercising at a frequency of three or more times per week for over 60 min each time and at a moderate intensity for more than 3 months. Suitable exercise options include mind-body exercise, multicomponent exercise, resistance exercise, and aerobic exercise. For individuals with Alzheimer's disease, we recommend moderately intense exercise twice per week for over 90 min per session and for a duration of 3 months or longer, with exercise options encompassing aerobic exercise and resistance exercise.

Global evapotranspiration from high-elevation mountains has decreased significantly at a rate of 3.923 %/a over the last 22 years.

Clarifying the responses of human activities and climate change to the water cycle under variable environments is crucial for accurately assessing regional water balance. An analysis of the changes in actual evapotranspiration and its driving factors was conducted in the global high-elevation mountains during the period from 2001 to 2022. Utilizing 18 formulas for calculating evapotranspiration, which are based on comprehensive, temperature, radiation, and mass transfer, and then simulated the variations in reference evapotranspiration. Furthermore, we optimized the ET simulation model based on the most effective simulation results and projected future changes using scenario simulation data. Our findings reveal that: 1) ET at high-elevation mountains has significantly decreased at an average rate of 3.923 %/a, with monthly values ranging from 31.179 to 33.652 mm and an average of 32.646 mm; 2) The radiation-based model of Irmark-Allen is particularly well-suited for simulating ET at high-elevation mountains, with precision analysis and the Taylor diagram confirming its superior simulation performance. After optimizing the model using the method of least squares, the value of R2 before and after the optimization were 0.633 and 0.853, respectively. 3) An upward trend in ET under both SSP245 and SSP585 scenario in future simulation projections. Attribution analysis has identified Vapor Pressure Deficit as the key positive driver influencing the change of ET in global high-elevation mountains. Structural equation modeling further reveals that variations in net radiation and precipitation play a significant role in altering evapotranspiration rates. Meanwhile，The water balance analysis reveals that ET has been declining from 2001 to 2022. This phenomenon can be largely attributed to the substantial decline in vapor pressure deficit, the rise in the Normalized Difference Vegetation Index signifying increased vegetation cover, and the reduction in shallow soil moisture during the same period. These factors collectively explain the notable decrease in ET observed in high-elevation mountains.

Corrigendum: Characterization of pannexin1, connexin32, and connexin43 in spotted sea bass (Lateolabrax maculatus): they are important neuro-related immune response genes involved in inflammation-induced ATP release.

[This corrects the article DOI: 10.3389/fimmu.2022.870679.].

Redoxhigh phenotype mediated by KEAP1/STK11/SMARCA4/NRF2 mutations diminishes tissue-resident memory CD8+ T cells and attenuates the efficacy of immunotherapy in lung adenocarcinoma.

Metabolism reprogramming within the tumor microenvironment (TME) can have a profound impact on immune cells. Identifying the association between metabolic phenotypes and immune cells in lung adenocarcinoma (LUAD) may reveal mechanisms of resistance to immune checkpoint inhibitors (ICIs). Metabolic phenotypes were classified by expression of metabolic genes. Somatic mutations and transcriptomic features were compared across the different metabolic phenotypes. The metabolic phenotype of LUAD is predominantly determined by reductase-oxidative activity and is divided into two categories: redoxhigh LUAD and redoxlow LUAD. Genetically, redoxhigh LUAD is mainly driven by mutations in KEAP1, STK11, NRF2, or SMARCA4. These mutations are more prevalent in redoxhigh LUAD (72.5%) compared to redoxlow LUAD (17.4%), whereas EGFR mutations are more common in redoxlow LUAD (19.0% vs. 0.7%). Single-cell RNA profiling of pre-treatment and post-treatment samples from patients receiving neoadjuvant chemoimmunotherapy revealed that tissue-resident memory CD8+ T cells are responders to ICIs. However, these cells are significantly reduced in redoxhigh LUAD. The redoxhigh phenotype is primarily attributed to tumor cells and is positively associated with mTORC1 signaling. LUAD with the redoxhigh phenotype demonstrates a lower response rate (39.1% vs. 70.8%, p = 0.001), shorter progression-free survival (3.3 vs. 14.6 months, p = 0.004), and overall survival (12.1 vs. 31.2 months, p = 0.022) when treated with ICIs. The redoxhigh phenotype in LUAD is predominantly driven by mutations in KEAP1, STK11, NRF2, and SMARCA4. This phenotype diminishes the number of tissue-resident memory CD8+ T cells and attenuates the efficacy of ICIs.

Correlation of distribution characteristics and dynamic changes of gut microbiota with the efficacy of immunotherapy in EGFR-mutated non-small cell lung cancer.

BACKGROUND: The effects of gut microbiota and metabolites on the responses to immune checkpoint inhibitors (ICIs) in advanced epidermal growth factor receptor (EGFR) wild-type non-small cell lung cancer (NSCLC) have been studied. However, their effects on EGFR-mutated (EGFR +) NSCLC remain unknown. METHODS: We prospectively recorded the clinicopathological characteristics of patients with advanced EGFR + NSCLC and assessed potential associations between the use of antibiotics or probiotics and immunotherapy efficacy. Fecal samples were collected at baseline, early on-treatment, response and progression status and were subjected to metagenomic next-generation sequencing and ultra-high-performance liquid chromatography-mass spectrometry analyses to assess the effects of gut microbiota and metabolites on immunotherapy efficacy. RESULTS: The clinical data of 74 advanced EGFR + NSCLC patients were complete and 18 patients' fecal samples were dynamically collected. Patients that used antibiotics had shorter progression-free survival (PFS) (mPFS, 4.8 vs. 6.7 months; P = 0.037); probiotics had no impact on PFS. Two dynamic types of gut microbiota during immunotherapy were identified: one type showed the lowest relative abundance at the response time point, whereas the other type showed the highest abundance at the response time point. Metabolomics revealed significant differences in metabolites distribution between responders and non-responders. Deoxycholic acid, glycerol, and quinolinic acid were enriched in responders, whereas L-citrulline was enriched in non-responders. There was a significant correlation between gut microbiota and metabolites. CONCLUSIONS: The use of antibiotics weakens immunotherapy efficacy in patients with advanced EGFR + NSCLC. The distribution characteristics and dynamic changes of gut microbiota and metabolites may indicate the efficacy of immunotherapy in advanced EGFR + NSCLC.

Whole-transcriptome RNA sequencing reveals CeRNA regulatory network under long-term space composite stress in Rats.

To systematically evaluate the effect of simulated long-term spaceflight composite stress (LSCS) in hippocampus and gain more insights into the transcriptomic landscape and molecular mechanism, we performed whole-transcriptome sequencing based on the control group (Ctrl) and the simulated long-term spaceflight composite stress group (LSCS) from six hippocampus of rats. Subsequently, differential expression analysis was performed on the Ctrl and LSCS groups, followed by enrichment analysis and functional interaction prediction analysis to investigate gene-regulatory circuits in LSCS. In addition, competitive endogenous RNA (ceRNA) network was constructed to gain insights into genetic interaction. The result showed that 276 differentially expressed messenger RNAs (DEmRNAs), 139 differentially expressed long non-coding RNAs (DElncRNAs), 103 differentially expressed circular RNAs (DEcircRNAs), and 52 differentially expressed microRNAs (DEmiRNAs) were found in LSCS samples compared with the controls, which were then subjected to enrichment analysis of Gene Ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways to find potential functions. PI3K-Akt signaling pathway and MAPK signaling pathway may play fundamental roles in the pathogenesis of LSCS. A ceRNA network was constructed with the predicted 340 DE pairs, which revealed the interaction roles of 220 DEmiRNA-DEmRNA pairs, 76 DEmiRNA-DElncRNA pairs, and 44 DEmiRNA-DEcircRNA pairs. Further, Thrombospondins2 was found to be a key target among those ceRNAs. Overall, we conducted for the first time a full transcriptomic analysis of the response of hippocampus to the LSCS that involved a potential ceRNA network, thus providing a basis to study the underlying mechanism of the LSCS.

Edaravone Dexborneol mitigates pathology in animal and cell culture models of Alzheimer's disease by inhibiting neuroinflammation and neuronal necroptosis.

BACKGROUND: Alzheimer's disease (AD) is the most prevalent neurodegenerative disease with limited disease-modifying treatments. Drug repositioning strategy has now emerged as a promising approach for anti-AD drug discovery. Using 5×FAD mice and Aß-treated neurons in culture, we tested the efficacy of Y-2, a compounded drug containing the antioxidant Edaravone (Eda), a pyrazolone and (+)-Borneol, an anti-inflammatory diterpenoid from cinnamon, approved for use in amyotrophic lateral sclerosis patients. RESULTS: We examined effects of Y-2 versus Eda alone by i.p. administered in 8-week-old 5×FAD mice (females) for 4 months by comparing cognitive function, Aß pathologies, neuronal necroptosis and neuroinflammation. Using primary neurons and astrocytes, as well as neuronal and astrocytic cell lines, we elucidated the molecular mechanisms of Y-2 by examining neuronal injury, astrocyte-mediated inflammation and necroptosis. Here, we find that Y-2 improves cognitive function in AD mice. Histopathological data show that Y-2, better than Eda alone, markedly ameliorates Aß pathologies including Aß burden, astrogliosis/microgliosis, and Tau phosphorylation. In addition, Y-2 reduces Aß-induced neuronal injury including neurite damage, mitochondrial impairment, reactive oxygen species production and NAD+ depletion. Notably, Y-2 inhibits astrocyte-mediated neuroinflammation and attenuates TNF-α-triggered neuronal necroptosis in cell cultures and AD mice. RNA-seq further demonstrates that Y-2, compared to Eda, indeed upregulates anti-inflammation pathways in astrocytes. CONCLUSIONS: Our findings infer that Y-2, better than Eda alone, mitigates AD pathology and may provide a potential drug candidate for AD treatment.

Development of a High-throughput Sequencing Platform for Detection of Viral Encephalitis Pathogens Based on Amplicon Sequencing.

Objective: Viral encephalitis is an infectious disease severely affecting human health. It is caused by a wide variety of viral pathogens, including herpes viruses, flaviviruses, enteroviruses, and other viruses. The laboratory diagnosis of viral encephalitis is a worldwide challenge. Recently, high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections. Thus, In this study, we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods: We designed nine pairs of specific polymerase chain reaction (PCR) primers for the 12 viruses by reviewing the relevant literature. The detection ability of the primers was verified by software simulation and the detection of known positive samples. Amplicon sequencing was used to validate the samples, and consistency was compared with Sanger sequencing. Results: The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×, and the sequence lengths were consistent with the sizes of the predicted amplicons. The sequences were verified using the National Center for Biotechnology Information BLAST, and all results were consistent with the results of Sanger sequencing. Conclusion: Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis. It is also a useful tool for the high-volume screening of clinical samples.

Identification of a risk score model based on tertiary lymphoid structure-related genes for predicting immunotherapy efficacy in non-small cell lung cancer.

BACKGROUND: Tertiary lymphoid structures (TLSs) affect the prognosis and efficacy of immunotherapy in patients with non-small cell lung cancer (NSCLC), but the underlying mechanisms are not well understood. METHODS: TLSs were identified and categorized online from the Cancer Digital Slide Archive (CDSA). Overall survival (OS) and disease-free survival (DFS) were analyzed. GSE111414 and GSE136961 datasets were downloaded from the GEO database. GSVA, GO and KEGG were used to explore the signaling pathways. Immune cell infiltration was analyzed by xCell, ssGSEA and MCP-counter. The analysis of WGCNA, Lasso and multivariate cox regression were conducted to develop a gene risk score model based on the SU2C-MARK cohort. RESULTS: TLS-positive was a protective factor for OS according to multivariate cox regression analysis (p = 0.029). Both the TLS-positive and TLS-mature groups exhibited genes enrichment in immune activation pathways. The TLS-mature group showed more activated dendritic cell infiltration than the TLS-immature group. We screened TLS-related genes using WGCNA. Lasso and multivariate cox regression analysis were used to construct a five-genes (RGS8, RUF4, HLA-DQB2, THEMIS, and TRBV12-5) risk score model, the progression free survival (PFS) and OS of patients in the low-risk group were markedly superior to those in the high-risk group (p < 0.0001; p = 0.0015, respectively). Calibration and ROC curves indicated that the combined model with gene risk score and clinical features could predict the PFS of patients who have received immunotherapy more accurately than a single clinical factor. CONCLUSIONS: Our data suggested a pivotal role of TLSs formation in survival outcome and immunotherapy response of NSCLC patients. Tumors with mature TLS formation showed more activated immune microenvironment. In addition, the model constructed by TLS-related genes could predict the response to immunotherapy and is meaningful for clinical decision-making.

Evaluation of the impact of antibody fragments on aggregation of intact molecules via size exclusion chromatography coupled with native mass spectrometry.

Aggregates are recognized as one of the most critical product-related impurities in monoclonal antibody (mAb)-based therapeutics due to their negative impact on the stability and safety of the drugs. So far, investigational efforts have primarily focused on understanding the causes and effects of mAb self-aggregation, including both internal and external factors. In this study, we focused on understanding mAb stability in the presence of its monovalent fragment, formed through hinge cleavage and loss of one Fab unit (referred to as "Fab/c"), a commonly observed impurity during manufacturing and stability. The Fab/c fragments were generated using a limited IgdE digestion that specifically cleaves above the IgG1 mAb hinge region, followed by hydrophobic interaction chromatographic (HIC) enrichment. Two IgG1 mAbs containing different levels of Fab/c fragments were incubated under thermally accelerated conditions. A method based on size exclusion chromatography coupled with native mass spectrometry (SEC-UV-native MS) was developed and used to characterize the stability samples and identified the formation of heterogeneous dimers, including intact dimer, mAb-Fab/c dimer, Fab/c-Fab/c dimer, and mAb-Fab dimer. Quantitative analyses on the aggregation kinetics suggested that the impact of Fab/c fragment on the aggregation rate of individual dimer differs between a glycosylated mAb (mAb1) and a non-glycosylated mAb (mAb2). An additional study of deglycosylated mAb1 under 25°C accelerated stability conditions suggests no significant impact of the N-glycan on mAb1 total aggregation rate. This study also highlighted the power of SEC-UV-native MS method in the characterization of mAb samples with regard to separating, identifying, and quantifying mAb aggregates and fragments.

Inversion of heavy metal content in soil using hyperspectral characteristic bands-based machine learning method.

The global concern regarding the adverse effects of heavy metal pollution in soil has grown significantly. Accurate prediction of heavy metal content in soil is crucial for environmental protection. This study proposes an inversion analysis method for heavy metals (As, Cd, Cr, Cu, Ni, Pb) in soil based on hyperspectral and machine learning algorithms for 21 soil reference materials from multiple provinces in China. On this basis, an integrated learning model called Stacked RF (the base model is XGBoost, LightGBM, CatBoost, and the meta-model is RF) was established to perform soil heavy metal inversion. Specifically, three popular algorithms were initially employed to preprocess the spectral data, then Random Forest (RF) was used to select the best feature bands to reduce the impact of noise, finally Stacking and four basic machine learning algorithms were used to establish comparisons and analysis of inversion model. Compared with traditional machine learning methods, the stacking model showcases enhanced stability and superior accuracy. Research results indicate that machine learning algorithms, especially ensemble learning models, have better inversion effects on heavy metals in soil. Overall, the MF-RF-Stacking model performed best in the inversion of the six heavy metals. The research results will provide a new perspective on the ensemble learning model method for soil heavy metal content inversion using data of hyperspectral characteristic bands collected from soil reference materials.

An investigation of neutron shielding and activation performances of four types of concrete for carbon ion therapy facility.

Carbon ions have unique physical and biological properties that allow for precise targeting of tumors while minimizing damage to surrounding healthy tissues. The emitted neutrons dominate the radiation field in the treatment room and pose challenges for radiological shielding. Concrete is extensively utilized in the construction of radiotherapy facilities due to its good shielding characteristics, and it can be easily poured into the desired shapes and thickness. The difference in composition of concrete affects the characteristics of neutron attenuation and activation performance. Therefore, the purpose of this study is to clarify the shielding properties and activation performances of four types of concrete for carbon ion therapy facilities. The Monte Carlo method is used to analyze the neutron spectra from thick targets upon carbon ion bombardment. Furthermore, the deep attenuation efficiency of the secondary neutron in different compositions of concrete is discussed. The shielding design is developed to ensure compliance with the prescribed dose limit outside the shielding during operation. Finally, the induced radioactivity in concrete is estimated for both short-term and long-term operation. The produced radionuclides inventories and depth profiling are determined. This study reveals the shielding and radioactivity issue of carbon ion therapy facilities and is expected to aid in the design or construction of similar facilities.

Abnormal interlimb coordination of motor developmental delay during infant crawling based on kinematic synergy analysis.

BACKGROUND: Previous studies have reported that abnormal interlimb coordination is a typical characteristic of motor developmental delay (MDD) during human movement, which can be visually manifested as abnormal motor postures. Clinically, the scale assessments are usually used to evaluate interlimb coordination, but they rely heavily on the subjective judgements of therapists and lack quantitative analysis. In addition, although abnormal interlimb coordination of MDD have been studied, it is still unclear how this abnormality is manifested in physiology-related kinematic features. OBJECTIVES: This study aimed to evaluate how abnormal interlimb coordination of MDD during infant crawling was manifested in the stability of joints and limbs, activation levels of synergies and intrasubject consistency from the kinematic synergies of tangential velocities of joints perspective. METHODS: Tangential velocities of bilateral shoulder, elbow, wrist, hip, knee and ankle over time were computed from recorded three-dimensional joint trajectories in 40 infants with MDD [16 infants at risk of developmental delay, 11 infants at high risk of developmental delay, 13 infants with confirmed developmental delay (CDD group)] and 20 typically developing infants during hands-and-knees crawling. Kinematic synergies and corresponding activation coefficients were derived from those joint velocities using the non-negative matrix factorization algorithm. The variability accounted for yielded by those synergies and activation coefficients, and the synergy weightings in those synergies were used to measure the stability of joints and limbs. To quantify the activation levels of those synergies, the full width at half maximum and center of activity of activation coefficients were calculated. In addition, the intrasubject consistency was measured by the cosine similarity of those synergies and activation coefficients. RESULTS: Interlimb coordination patterns during infant crawling were the combinations of four types of single-limb movements, which represent the dominance of each of the four limbs. MDD mainly reduced the stability of joints and limbs, and induced the abnormal activation levels of those synergies. Meanwhile, MDD generally reduced the intrasubject consistency, especially in CDD group. CONCLUSIONS: These features have the potential for quantitatively evaluating abnormal interlimb coordination in assisting the clinical diagnosis and motor rehabilitation of MDD.

An essential update on the inventory of landslides triggered by the Jiuzhaigou Mw6.5 earthquake in China on 8 August 2017, with their spatial distribution analyses.

On August 8, 2017, a magnitude Mw6.5 (Ms7.0) earthquake occurred in Jiuzhaigou County, Aba Prefecture, in the northern part of Sichuan Province, China, with a focal depth of 20 km and an epicenter located at (33.2°N, 103.8°E). Due to the significant magnitude of the earthquake, a large number of coseismic landslides were triggered. Despite previous research conducted by experts on the landslides caused by the Jiuzhaigou earthquake, the actual number of landslides has been severely underestimated in the previously published papers. Through field surveys and visual interpretation of high-resolution remote sensing images before and after the mainshock, we have established a detailed inventory of earthquake-induced landslides. The results indicate that the event caused a minimum of 9428 landslides covering a total area of 18.82 km2. These landslides are mainly distributed in the IX intensity area of the earthquake. The landslides mainly consist of medium-sized landslides and debris flows. They predominantly occur in areas with an altitude ranging from 2600 m to 3600 m, with slopes greater than 30° and facing east and southeast. The Lower Carboniferous and Middle Carboniferous formations are more prone to triggering landslides, and landslides are more concentrated within 1 km of roads and in forested areas. Additionally, as the distance from roads and the epicenter increases, the values of LAP and LND decrease, indicating a positive correlation between the two. There are more landslides within 2 km from the fault and within a range of 6 km-9 km from the epicenter. In conclusion, this study provides a comprehensive landslide inventory with broader coverage and increased accuracy. It also conducts a comprehensive analysis of the spatial distribution patterns of landslides. This contributes to a deeper understanding of the causes of coseismic landslides and further research on the impact of landslides in affected areas.

Plasma ddPCR for the detection of MET amplification in advanced NSCLC patients: a comparative real-world study.

Background: Mesenchymal-epithelial transition (MET) amplification is a crucial oncogenic driver and a resistance mechanism to epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) of non-small-cell lung cancer (NSCLC). Fluorescence in situ hybridization (FISH) is the gold standard for MET amplification detection. However, it is inapplicable when tissue samples are unavailable. Objective: This study assessed the performance of plasma droplet digital polymerase chain reaction (ddPCR) in MET amplification detection in NSCLC patients. Design and methods: A total of 87 NSCLC patients were enrolled, and 94 paired tissue and plasma samples were analyzed for the concordance between FISH and plasma ddPCR/tissue next-generation sequencing (NGS) in detecting MET amplification. In addition, the efficacy of patients with MET amplification using different detection methods who were treated with MET-TKIs was evaluated. Results: Plasma ddPCR showed substantial concordance with FISH (74.1% sensitivity, 92.5% specificity, and 87.2% accuracy with a kappa value of 0.68) and outperformed tissue NGS (kappa value of 0.64) in MET amplification detection. Combined plasma ddPCR and tissue NGS showed substantial concordance with FISH (92.3% sensitivity, 89.2% specificity, and an accuracy of 90.1% with a kappa value of 0.77). The efficacy is comparable in these NSCLC patients with MET amplification detected by FISH and plasma ddPCR who were treated with MET-TKIs. Conclusion: Plasma ddPCR is a potentially reliable method for detecting MET amplification in advanced NSCLC patients. Combined plasma ddPCR and tissue NGS might be an alternative or complementary method to MET amplification detection.

Nickel-Catalyzed Reductive Cross-Coupling of Propargylic Acetates with Chloro(vinyl)silanes: Access to Silylallenes.

Because of their various reactivities, propargyl acetates are refined chemical intermediates that are extensively applied in pharmaceutical synthesis. Currently, reactions between propargyl acetates and chlorosilanes may be the most effective method for synthesizing silylallenes. Nevertheless, owing to the adaptability and selectivity of substrates, transition metal catalysis is difficult to achieve. Herein, nickel-catalyzed reductive cross-coupling reactions between propargyl acetates and substituted vinyl chlorosilanes for the synthesis of tetrasubstituted silylallenes are described. Therein, metallic zinc is a crucial reductant that effectively enables two electrophilic reagents to selectively construct C(sp2)-Si bonds. Additionally, a Ni-catalyzed reductive mechanism involving a radical process is proposed on the basis of deuteration-labeled experiments.

Association of organ damage with predicted fat mass in a community-dwelling elderly: the Northern Shanghai study.

BACKGROUND: Body fat mass (FM) is associated with multiple organ damage. However, data regarding the relationship between various organ damage and FM are rare in the elderly. Therefore, we aim to perform an analysis on the relationship between organ damage and FM in a geriatric cohort. METHODS: 3331 participants were included in this analysis. Based on age, body height, body weight, waist circumference, and race, we calculated FM with the established formula. Organ damage, including arterial stiffening, lower extremity atherosclerosis, left ventricular hypertrophy (LVH), micro-albuminuria, and chronic kidney disease (CKD), were measured and calculated with standard methods. RESULTS: All organ damage parameters were significantly related to FM (all p < 0.001). In univariate logistics regression, the highest quartile of FM was tied to the increased risk of arterial stiffening, lower extremity atherosclerosis, LVH, micro-albuminuria, and CKD (all p < 0.05). After adjustment, participants with higher quantiles of FM had a significantly increased odd ratio (OR) for arterial stiffening [OR = 1.51, 95% confidence interval (CI): 1.15-1.99, p = 0.002] and LVH (OR = 1.99, 95% CI: 1.48-2.67, p < 0.001). Moreover, FM was linearly associated with arterial stiffening and LVH in total population and gender subgroups. Independent of confounders, FM was significantly correlated with arterial stiffening, lower extremity atherosclerosis, LVH and CKD in female, while was only related to LVH in male. CONCLUSIONS: Among various organ damage, elevated FM is significantly and independently associated with arterial stiffening and LVH in the elderly. Compared with men, women with increased FM are more likely to have multiple organ damage.