DSFE: Decoding EEG-based finger motor imagery using feature-dependent frequency, feature fusion and ensemble learning.

Accurate decoding finger motor imagery is essential for fine motor control using EEG signals. However, decoding finger motor imagery is particularly challenging compared with ordinary motor imagery. This paper proposed a novel EEG decoding method of featuredependent frequency band selection, feature fusion, and ensemble learning (DSFE) for finger motor imagery. First, a feature-dependent frequency band selection method based on correlation coefficient (FDCC) was proposed to select feature-specific effective bands. Second, a feature fusion method was proposed to fuse different types of candidate features to produce multiple refined sets of decoding features. Finally, an ensemble model using the weighted voting strategy was proposed to make full use of these diverse sets of final features. The results on a public EEG dataset of five fingers motor imagery showed that the DSFE method is effective and achieves the highest decoding accuracy of 50.64%, which is 7.64% higher than existing studies using exactly the same data. The experiments further revealed that both the effective frequency bands of different subjects and the effective frequency bands of different types of features are different in finger motor imagery. Furthermore, compared with two-hand motor imagery, the effective decoding information of finger motor imagery is transferred to the lower frequency. The idea and findings in this paper provide a valuable perspective for understanding fine motor imagery in-depth.

Exploration of Ginkgo biloba leaves on non-small cell lung cancer based on network pharmacology and molecular docking.

BACKGROUND: Pharmacological studies have found Ginkgo biloba leaves have the effect of inhibiting neoplasms, it is clinically used in treating various neoplasms. However, the mechanism of Ginkgo biloba leaves in treating non-small cell lung cancer (NSCLC) remains unclear. METHODS: The active components and corresponding targets of Ginkgo biloba leaves were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) database, and the targets of NSCLC were obtained from the GeneCards, OMIM, TTD, and DrugBank databases. The common targets of NSCLC and Ginkgo biloba leaves were obtained from VENNY 2.1.0. The STRING database was utilized to construct protein-protein intersections, by using the Cytoscape 3.7.1 software, the protein-protein intersection was optimized and the drug-disease network diagram was constructed. The DAVID database was utilized to perform GO and KEGG analysis. Finally, The Autodock Vina software was used to perform molecular docking of core components and targets. RESULTS: The key components of Ginkgo biloba leaves in treating NSCLC include quercetin, luteolin, and kaempferol, which may act on Tp53, AKT1, and TNF. Bioinformatic annotation analysis results suggest that Ginkgo biloba leaves may implicated in PI3K-AKT and MAPK signaling pathways. The molecular docking results show the firm affinity between key ingredients and targets. CONCLUSION: The potential mechanism of Ginkgo biloba leaves in treating NSCLC has been discussed in this study, which provides a theoretical basis for the clinical treatment of NSCLC and further experimental validation.

Exploration of kiwi root on non-small cell lung cancer based on network pharmacology and molecular docking.

BACKGROUND: Kiwi root is a Chinese herb clinically used in the treatment of lung neoplasm; however, the multi-target mechanism of kiwi root in the treatment of non-small cell lung cancer (NSCLC) remains to be elucidated. Thus, this study aimed to investigate the molecular mechanisms of kiwi root in the treatment of NSCLC through network pharmacology and molecular docking techniques. METHODS: The active components and targets of kiwi root were obtained from the TCMSP database, and NSCLC-related targets were obtained from the GeneCards, OMIM, and DrugBank databases. The intersection targets of NSCLC and kiwi root were obtained from VENNY 2.1.0. Then, the common targets were imported into the STRING database, and by using the Cytoscape 3.7.1 software, drug-disease network diagrams were created. Afterwards, the DAVID database was utilized to perform bioinformatic annotation. Finally, molecular docking of key components and key targets was performed by Autodock Tools. RESULTS: A total of 4083 NSCLC-related disease genes were collected from the GeneCards, OMIM,and DrugBank databases, and 177 non-duplicated drug targets were acquired from the TCMSP database. A total of 138 intersection target genes were obtained, in which TP53, AKT1, and TNF were the key targets. CONCLUSION: Through network pharmacology techniques, the mechanism of kiwi root in the treatment of NSCLC has been uncovered and provides a theoretical basis for the clinical treatment of NSCLC with kiwi root, which requires further experimental validation.

Ten-year clinical characteristics of patients with early-onset type 2 diabetes: A single-center experience in China.

AIMS: The incidence of type 2 diabetes in China has exhibited an increasing trend, including younger individuals, over the past years. Early-onset type 2 diabetes (EOT2D) refers to diabetes diagnosed before 40 years of age. These patients have poor metabolic control and are highly susceptible to diabetic complications, which poses challenges for treatment. However, few studies have reported on the treatment of EOT2D. We determined clinical features and trends in drug use in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: This retrospective study was performed at the Endocrinology Ward, Peking Union Medical College Hospital (PUMCH). "Diabetes" was used when searching PUMCH's Electronic Medical Record Analytical Database to obtain clinical data of patients between January 2013 and May 2022. RESULTS: The analysis included 1590 patients with T2DM. Among them, 609 (38.3%) had EOT2D. Compared with late-onset type 2 diabetes (LOT2D) patients, EOT2D patients exhibited worse glycemic control and higher body weight and lipid levels despite significant age differences. EOT2D patients also had a higher risk of diabetic retinopathy and nephropathy. Under the general trend of increasing use of dipeptidylpeptidase-4 inhibitors, sodium-glucose cotransporter-2 inhibitors, and glucagon-like peptide-1 agonists, patients with EOT2D were more likely to use organ-protective drugs. CONCLUSIONS: Compared with LOT2D patients, EOT2D patients have a longer course of diabetes, worse metabolic control, and a higher rate of developing microvascular complications. The administration of combined therapy, including new agents, may require consideration when selecting hypoglycemic agents for treating EOT2D.

Clinical outcome and molecular landscape of patients with ARID1A-loss gastric cancer.

Chromatin remodelers are commonly altered in human cancer. The mutation of AT-rich interactive domain 1A (ARID1A) in gastric cancer (GC), a component of the SWI/SNF chromatin remodeling complex, was proven associated with treatment response in our previous study. However, ARID1A loss of function was caused not only by mutations but also copy number deletions. The clinicopathologic, genomic, and immunophenotypic correlates of ARID1A loss is largely uncharacterized in GC. Here, 819 patients with clinicopathological information and sequencing data or formalin-fixed paraffin-embedded tissues from four cohorts, Zhongshan Hospital (ZSHS) cohort (n = 375), The Cancer Genome Atlas (TCGA) cohort (n = 371), Samsung Medical Center (SMC) cohort (n = 53), and ZSHS immunotherapy cohort (n = 20), were enrolled. ARID1A loss was defined by genome sequencing or deficient ARID1A expression by immunohistochemistry. We found that ARID1A mutation and copy number deletion were enriched in GC with microsatellite instability (MSI) and chromosomal-instability (CIN), respectively. In the TCGA and ZSHS cohorts, only CIN GC with ARID1A loss could benefit from fluorouracil-based adjuvant chemotherapy. In the SMC and ZSHS immunotherapy cohorts, ARID1A loss exhibited a tendency of superior responsiveness and indicated favorable overall survival after anti-PD-1 immunotherapy. ARID1A-loss tumors demonstrated elevated mutation burden, neoantigen load, and interferon gamma pathway activation. Moreover, in CIN GC, ARID1A loss was correlated with higher homologous recombination deficiency. ARID1A loss defines a distinct subtype of GC characterized by high levels of genome instability, neoantigen formation, and immune activation. These tumors show sensitivity to both chemotherapy and anti-PD-1 immunotherapy. This study provides valuable insights for precision treatment strategies in GC.

The effect of shear wave elastography in the diagnosis of delaminated partial-thickness rotator cuff tears.

AIM: To assess the effectiveness of shear wave elastography (SWE) in diagnosing delaminated partial-thickness rotator cuff tears (DPT-RCT). MATERIAL AND METHODS: A retrospective study was carried out on 137 patients with DPT-RCT. The study included complete clinical data, including the images of conventional ultrasound (US), SWE, Magnetic Resonance Imaging (MRI) and shoulder arthroscopic surgery. The features of US, SWE, and MRI were evaluated. The study analysed the Shear-Wave Velocity (SWV) among three types of DPT-RCT, and between the regions of tears, normal contralateral, and affected unilateral supraspinatus tendon. Furthermore, receiver operating characteristic (ROC) curves were evaluated. RESULTS:  The SWE detection rate was significantly higher (91.2%) compared to US (73.7%) and MRI (87.6%) for the overall diagnosis of DPT-RCT. Similarly, SWE yielded higher rates of detection for types 1 (89.5%) and 2 (92.3%) of DPT-RCT as compared to US (71.7%, 69.2%) and MRI (81.6%, 94.9%), respectively. However, there was no significant difference in the accuracy of diagnosing type 3 among the three methods. The SWV of the 137 supraspinatus tendon tears was 3.64±0.60 m/s, which was higher than that of the normal supraspinatus tendon (2.43±0.47 m/s, p<0.01) as well as the region of tears (1.61±0.54 m/s, p<0.01). Nevertheless, there was no significant difference in SWV among the three types of DPT-RCT. The cutoff thresholds of SWV for identifying normal tendon from DPT-RCT and for identifying DPT-RCT from the region of tears were 2.96m/s and 2.39m/s, respectively. CONCLUSIONS: SWE with SWV can provide both quantitative and qualitative diagnostic information for DPT-RCT, which can be used as a crucial supplement imaging method.

Targeting myeloid checkpoint Siglec-10 reactivates antitumor immunity and improves anti-programmed cell death 1 efficacy in gastric cancer.

OBJECTIVE: Immunotherapy has not yielded satisfactory therapeutic responses in gastric cancer (GC). However, targeting myeloid checkpoints holds promise for expanding the potential of immunotherapy. This study aims to evaluate the critical role of Siglec-10+ tumor-associated macrophages (TAMs) in regulating antitumor immunity and to explore the potential of the myeloid checkpoint Siglec-10 as an interventional target. DESIGN: Siglec-10+ TAMs were assessed based on immunohistochemistry on tumor microarrays and RNA-sequencing data. Flow cytometry, RNA sequencing, and single-cell RNA-sequencing analysis were employed to characterize the phenotypic and transcriptional features of Siglec-10+ TAMs and their impact on CD8+ T cell-mediated antitumor immunity. The effectiveness of Siglec-10 blockade, either alone or in combination with anti-programmed cell death 1 (PD-1), was evaluated using an ex vivo GC tumor fragment platform based on fresh tumor tissues. RESULTS: Siglec-10 was predominantly expressed on TAMs in GC, and associated with tumor progression. In Zhongshan Hospital cohort, Siglec-10+ TAMs predicted unfavorable prognosis (n=446, p<0.001) and resistance to adjuvant chemotherapy (n=331, p<0.001), which were further validated in exogenous cohorts. In the Samsung Medical Center cohort, Siglec-10+ TAMs demonstrated inferior response to pembrolizumab in GC (n=45, p=0.008). Furthermore, Siglec-10+ TAMs exhibited an immunosuppressive phenotype and hindered T cell-mediated antitumor immune response. Finally, blocking Siglec-10 reinvigorated the antitumor immune response and synergistically enhances anti-PD-1 immunotherapy in an ex vivo GC tumor fragment platform. CONCLUSIONS: In GC, the myeloid checkpoint Siglec-10 contributes to the regulation of immunosuppressive property of TAMs and promotes the depletion of CD8+ T cells, ultimately facilitating immune evasion. Targeting Siglec-10 represents a potential strategy for immunotherapy in GC.

C-type lectin receptor Dectin-1 blockade on tumour-associated macrophages improves anti-PD-1 efficacy in gastric cancer.

BACKGROUND: This study aimed to investigate the expression and clinical significance of Dendritic cell-associated C-type lectin-1 (Dectin-1) in gastric cancer (GC), and to explore the mechanism of Dectin-1 regulating tumour-associated macrophage (TAM)-mediated immune evasion in GC. METHODS: The association of Dectin-1+ cells with clinical outcomes was inspected by immunohistochemistry on tumour microarrays. Flow cytometry and RNA sequencing were applied to detect characteristics of T cells, phenotypic and transcriptional features of Dectin-1+ TAMs. The effect of Dectin-1 blockade was evaluated using an in vitro intervention experiment based on fresh GC tissues. RESULTS: High infiltration of intratumoral Dectin-1+ cells predicted poor prognosis in GC patients. Dectin-1+ cells were mainly composed of TAMs, and the accumulation of Dectin-1+ TAMs was associated with T-cell dysfunction. Notably, Dectin-1+ TAMs exhibited an immunosuppressive phenotype. Furthermore, blockade of Dectin-1 could reprogramme Dectin-1+ TAMs and reactivate anti-tumour effects of T cells, as well as enhanced PD-1 inhibitor-mediated cytotoxicity of CD8+ T cells against tumour cells. CONCLUSIONS: Dectin-1 could affect T-cell anti-tumour immune response by regulating the immunosuppressive function of TAMs, leading to poor prognosis and immune evasion in GC patients. Blockade of Dectin-1 can be used alone or in combination with current therapeutic strategies in GC.

Surgeons' mental distress and risks after severe complications following radical gastrectomy in China: a nationwide cross-sectional questionnaire.

BACKGROUND: This study was designed to investigate incidences of surgeons' mental distress following severe complications after radical gastrectomy. METHODS: A cross-sectional survey was conducted between 1 June 2021 and 30 September 2021 among Chinese general and/or gastrointestinal surgeons who experienced severe complications after radical gastrectomy. The clinical features collected in the questionnaire included: (i) feeling burnout, anxiety, or depression; (ii) avoiding radical gastrectomy or feeling stress, slowing down the process during radical gastrectomy operations; (iii) having physical reactions, including heart pounding, trouble breathing, or sweating while recalling; (iv) having urges to quit being a surgeon; (v) taking psychiatric medications; and (vi) seeking psychological counselling. Analyses were performed to identify risk factors of severe mental distress, which was defined as meeting three or more of the above-mentioned clinical features. RESULTS: A total of 1062 valid questionnaires were received. The survey showed that most of the participating surgeons (69.02%) had at least one clinical feature of mental distress following severe complications after radical gastrectomy, and more than 25% of the surgeons suffered from severe mental distress. Surgeons from non-university affiliated hospitals, the junior surgeons, and existing violent doctor-patient conflicts were recognized as independent risk factors for surgeons' severe mental distress related to the severe complications after radical gastrectomy. CONCLUSIONS: About 70% of surgeons had mental health problems following severe complications after radical gastrectomy, and more than 25% of the surgeons suffered from severe mental distress. More strategies and policies are needed to improve the mental well-being of these surgeons after such incidences.

Fertilizing-induced alterations of microbial functional profiles in soil nitrogen cycling closely associate with crop yield.

Fertilization and rhizosphere selection are key regulators for soil nitrogen (N) cycling and microbiome. Thus, clarifying how the overall N cycling processes and soil microbiome respond to these factors is a prerequisite for understanding the consequences of high inputs of fertilizers, enhancing crop yields, and formulating reasonable nitrogen management strategies under agricultural intensification scenarios. To do this, we applied shotgun metagenomics sequencing to reconstruct N cycling pathways on the basis of abundance and distribution of related gene families, as well as explored the microbial diversity and interaction via high throughput sequencing based on a two-decade fertilization experiment in Loess Plateau of China semiarid area. We found that bacteria and fungi respond divergent to fertilization regimes and rhizosphere selection, in terms of community diversity, niche breadth, and microbial co-occurrence networks. Moreover, organic fertilization decreased the complexity of bacterial networks but increased the complexity and stability of fungal networks. Most importantly, rhizosphere selection exerted more strongly influences on the soil overall nitrogen cycling than the application of fertilizers, accompanied by the increase in the abundance of nifH, NIT-6, and narI genes and the decrease in the abundance of amoC, norC, and gdhA genes in the rhizosphere soil. Furthermore, keystone families screening from soil microbiome (e.g., Sphingomonadaceae, Sporichthyaceae, and Mortierellaceae), which were affected by the edaphic variables, contributed greatly to crop yield. Collectively, our findings emphasize the pivotal roles of rhizosphere selection interacting with fertilization regimes in sustaining soil nitrogen cycling processes in response to decades-long fertilization, as well as the potential importance of keystone taxa in maintaining crop yield. These findings significantly facilitate our understanding of nitrogen cycling in diverse agricultural soils and lay a foundation for manipulating specific microorganisms to regulate N cycling and promote agroecosystem sustainability.

Management-induced changes in soil organic carbon and related crop yield dynamics in China's cropland.

Enhancing soil organic carbon (SOC) sequestration and food supply are vital for human survival when facing climate change. Site-specific best management practices (BMPs) are being promoted for adoption globally as solutions. However, how SOC and crop yield are related to each other in responding to BMPs remains unknown. Here, path analysis based on meta-analysis and machine learning was conducted to identify the effects and potential mechanisms of how the relationship between SOC and crop yield responds to site-specific BMPs in China. The results showed that BMPs could significantly enhance SOC and maintain or increase crop yield. The maximum benefits in SOC (30.6%) and crop yield (79.8%) occurred in mineral fertilizer combined with organic inputs (MOF). Specifically, the optimal SOC and crop yield would be achieved when the areas were arid, soil pH was ≥7.3, initial SOC content was ≤10 g kg-1 , duration was >10 years, and the nitrogen (N) input level was 100-200 kg ha-1 . Further analysis revealed that the original SOC level and crop yield change showed an inverted V-shaped structure. The association between the changes in SOC and crop yield might be linked to the positive role of the nutrient-mediated effect. The results generally suggested that improving the SOC can strongly support better crop performance. Limitations in increasing crop yield still exist due to low original SOC level, and in regions where the excessive N inputs, inappropriate tillage or organic input is inadequate and could be diminished by optimizing BMPs in harmony with site-specific conditions.

The value of percutaneous ultrasound-guided subacromial bursography in the diagnosis of rotator cuff tears.

AbstractPurpose To determine the feasibility and diagnostic value of percutaneous ultrasound-guided subacromial bursography (PUSB) in the diagnosis of rotator cuff tears.Methods Between July 2019 to October 2021, 78 patients who had suspected rotator cuff injury and who were admitted to the Second Affiliated Hospital of Xi'an Jiaotong University were selected, including 32 males and 46 females, aged 31-70 years (mean age 53.9±9.1 years), with a course of 1D-2 years. The MRI, US and PUSB images of patients were retrospectively analyzed to obtain the diagnostic and predictive indexes (sensitivity, specificity, positive predictive value，negative predictive value and accuracy) of these three methods for different rotator cuff tears types (full-thickness tears, partial-thickness tears and no tears of rotator cuff ). With the results of shoulder arthroscopy serving as the standard, PUSB results were compared with MRI and US results using the X2 -test (a=0.05, two-sided).Results In all 78 patients, the overall accuracy of MRI, US, and PUSB in diagnosing rotator cuff tears was 82.1% (64/78), 75.6% (59/78) and 96.2% (75/78), respectively (P < 0.001). Among 21 patients with full-thickness tears, the numbers of cases correctly diagnosed by MRI, US and PUSB were 19, 19 and 21, respectively. The sensitivity and specificity of MRI, US and PUSB in diagnosing full-thickness tears were 90.5%, 90.5%, 100% and 98.2%, 93.0%, 100%, respectively. The diagnostic accuracies of full-thickness rotator cuff tears were 90.5%, 90.5% and 100%, respectively, with no statistical difference (P = 0.344). Among 42 patients with partial-thickness tears, the numbers of patients whose cases were correctly diagnosed on MRI, US and PUSB were 32, 27 and 40, respectively. The sensitivity and specificity of MRI, US and PUSB in diagnosing partial-thickness tears were 76.2%, 64.3%, and 95.2% and 88.9%, 88.9%, and 97.2%, respectively. The diagnostic accuracies of partial-thickness rotator cuff tears were 76.2% (32/42), 64.3% (27/42) and 95.2% (40/42), respectively (P＜0.05). Among the 15 patients without tears, the numbers of misdiagnosed cases by MRI, US and PUSB were 2, 2, and 1, respectively, and they were all misdiagnosed as partial-thickness tears. The sensitivity and specificity of MRI, US and PUSB in the diagnosis of complete rotator cuff were 86.7%, 86.7%, and 93.3% and 85.7%, 82.5% and 96.8%, respectively, and the accuracies in diagnosing no tears were 86.7% (13/15), 86.7% (13/15) and 87.5% (14/15), respectively (P = 0.997).Conclusions It is feasible to diagnose rotator cuff tears by PUSB, which can be used as an important supplement imaging method to evaluate rotator cuff tears.

Complement receptor C5aR1 blockade reprograms tumor-associated macrophages and synergizes with anti-PD-1 therapy in gastric cancer.

In gastric cancer (GC), the therapeutic response of immune checkpoint blockade (ICB) remains suboptimal. Targeting myeloid cell checkpoints might be feasible as adjuvant to current ICB regimens. We sought to evaluate the crucial role of C5aR1+ TAMs in regulating antitumor immunity and the efficacy of combinatorial treatment with antiprogrammed cell death protein-1 (PD-1) and C5aR1 blockade. Here, we found that C5aR1 was predominantly expressed on macrophages and high level of C5aR1+ TAMs infiltration could predict poor prognosis and inferior chemotherapeutic response. The flow cytometry (FCM) and single-cell RNA-seq (scRNA-seq) data revealed that C5aR1+ TAMs exhibited immunosuppressive property which might contribute to CD8+ T cell dysfunction. Blockade of C5aR1 could diminish the immunosuppressive function of TAMs and led to reinvigorated CD8+ T cells mediated antitumor immunity. Moreover, using in vitro intervention experiment based on fresh GC surgical specimens, we discovered that C5aR1 blockade exert a synergistic effect when combined with PD-1 inhibitor for tumor clearance. Our study demonstrated that C5aR1 is a critical myeloid checkpoint and plays a crucial role in regulating the immunosuppressive property of TAMs and CD8+ T cell immune tolerance. C5aR1 blockade reprograms TAMs and reinvigorated the cytotoxicity of CD8+ T cells, thus improving the efficacy of anti-PD-1 therapy for tumor eradication in GC.

Weak environmental adaptation of rare phylotypes sustaining soil multi-element cycles in response to decades-long fertilization.

Deciphering the ecological role of soil communities in the maintenance of multiple ecosystem functions is pivotal for the conservation and sustainability of soil biodiversity. However, few studies have investigated niche differentiation of abundant and rare microbiota, as well as their contributions to multiple soil elemental cycles, particularly in agroecosystems that have received decades of intense fertilization. Here, we characterized the environmental thresholds and phylogenetic signals for the environmental adaptation of both abundant and rare microbial subcommunities via amplicon sequencing and metagenomic sequencing and explored their importance in sustaining soil multiple nutrient cycling in agricultural fields that were fertilized for two decades. The results showed that rare taxa exhibited narrower niche breadths and weaker phylogenetic signals than abundant species. The assembly of abundant subcommunity was shaped predominantly by dispersal limitation (explained 71.1 % of the variation in bacteria) and undominated processes (explained 75 % of the variation in fungi), whereas the assembly of rare subcommunity was dominated by homogeneous selection process (explained 100 % of the variation in bacteria and 60 % of the variation in fungi). Soil ammonia nitrogen was the leading factor mediating the balance between stochastic and deterministic processes in both abundant (R2 = 0.15, P < 0.001) and rare (R2 = 0.08, P < 0.001) bacterial communities. Notably, the rare biosphere largely contributed to key soil processes such as carbon (R2bacteria = 0.03, P < 0.05; R2fungi = 0.05, P < 0.05) and nitrogen (R2bacteria = 0.03, P < 0.05; R2fungi = 0.17, P < 0.001) cycling. Collectively, these findings facilitate our understanding of the maintenance of rhizosphere bacterial and fungal diversity in response to agricultural fertilization and highlight the key role of rare taxa in sustaining agricultural ecosystem functions.

Fertilization regimes affect crop yields through changes of diazotrophic community and gene abundance in soil aggregation.

Soil aggregates are extremely vulnerable to agricultural intensification and are important drivers of soil health, microbial diversity, and biogeochemical cycling. Despite its importance, there is a dearth of studies revealing how fertilization regimes influence diazotrophic community behind soil aggregates, as well as the potential consequences for crop yields. To do this, a two-decade fertilization of wheat-maize intercropping field experiment was conducted in Loess Plateau of China semiarid area under three treatments: no fertilizer, chemical and organic fertilizer. Moreover, we categorized soil aggregates as large macroaggregates (>2 mm), medium macroaggregates (1-2 mm), small macroaggregates (0.25-1 mm), microaggregates (< 0.25 mm) and rhizosphere soils aggregates. We found that soil aggregates exerted a much more influence on the nifH gene abundance than fertilization practices. Particularly, nifH gene abundance has been promoted with increasing the size of soil aggregates fraction without blank soil in the organic fertilization while its abundance presented contrast patterns in the chemical fertilization. Bipartite association networks indicated that different soil aggregates shaped niche differentiation of diazotrophic community behind fertilization regimes. Additionally, we found that organic fertilization strengthens the robustness of diazotrophic communities as well as increases the complexity of microbial networks by harboring keystone taxa. Mantel test results suggested that specific soil factors exerted more selective power on diazotrophic community and nifH gene abundance in the chemical fertilization. Furthermore, ß-diversity and nifH gene abundance of diazotrophic communities in the soil microaggregates jointly determine the crop yields. Collectively, our findings emphasize the key role of functional community diversity in sustaining soil cycling process and crop yields under long-term fertilization, and facilitate our understanding of the mechanisms underlying diazotrophic community in response to agricultural intensification, which could pave the way to sustainable agriculture through manipulating the functional taxa.

Somatic ARID1A mutation stratifies patients with gastric cancer to PD-1 blockade and adjuvant chemotherapy.

BACKGROUND: AT-rich interaction domain 1A (ARID1A) encodes a vital component of switch/sucrose non-fermentable chromatin-remodeling complex. Given its association with genomic instability, we conducted this study to determine whether ARID1A mutation status had an impact on therapeutic responsiveness in gastric cancer (GC), especially combinatory chemo-immunotherapy. METHODS: We retrospectively enrolled a total of 1162 patients from five independent cohorts. ZSHS Cohort and TCGA Cohort were designed to inform chemotherapeutic relevance and immunobiology of ARID1A-mutant GC based on tissue samples and sequencing data, respectively. MSKCC Cohort, mGC Cohort, and Melanoma Cohort were utilized to interrogate the predictive efficacy of ARID1A mutation to programmed cell death protein 1 (PD-1) blockade. RESULTS: ARID1A mutation was enriched in EBV-positive, hypermutated-single nucleotide variant and microsatellite-unstable subtype GC, and was predictive of responsiveness to both fluorouracil-based chemotherapy and PD-1 blockade. Specifically, ARID1A mutation score was a highly sensitive indicator (91%) of response to pembrolizumab. Mechanistically, ARID1A mutation correlated with extensive DNA damage repair deficiency and immunogenic tumor microenvironment (TME) featured by elevated activated subsets of CD8+ T cells, CD4+ T cells, and NK cells. Type 17T helper cells were typically abundant in ARID1A-mutant GC and might be a precondition for chemosensitivity conferred by ARID1A mutation. Furthermore, ARID1A mutation indicated elevated expression of VEGFA and CLDN18, as well as over-representation of ERBB2 and FGFR2 signaling pathway. CONCLUSIONS: ARID1A-mutant GC displayed immunogenic TME and might be a candidate for both monotherapy and the combination of frontline chemotherapy and PD-1 blockade.

Olfactory-auditory sensory integration in the lateral entorhinal cortex.

Multisensory integration plays an important role in animal cognition. Although many studies have focused on visual-auditory integration, studies on olfactory-auditory integration are rare. Here, we investigated neural activity patterns and odor decoding in the lateral entorhinal cortex (LEC) under uni-sensory and multisensory stimuli in awake, head-fixed mice. Using specific retrograde tracing, we verified that the LEC receives direct inputs from the primary auditory cortex (AC) and the medial geniculate body (MGB). Strikingly, we found that mitral/tufted cells (M/Ts) in the olfactory bulb (OB) and neurons in the LEC respond to both olfactory and auditory stimuli. Sound decreased the neural responses evoked by odors in both the OB and LEC, for both excitatory and inhibitory responses. Interestingly, significant changes in odor decoding performance and modulation of odor-evoked local field potentials (LFPs) were observed only in the LEC. These data indicate that the LEC is a critical center for olfactory-auditory multisensory integration, with direct projections from both olfactory and auditory centers.

Changes in cropland soil carbon through improved management practices in China: A meta-analysis.

Recommended management practices (RMPs, e.g., manuring, no-tillage, crop residue return) can increase soil organic carbon (SOC), reduce greenhouse gas emissions, and maintain soil health in croplands. However, there is no consensus on how RMPs affect the SOC storage potential of cropland soils for climate change mitigation. Here, based on 2301 comparisons from 158 peer-reviewed papers, a meta-analysis was conducted to explore management-induced SOC stock changes and their variations under different conditions. The results show that SOC stocks in the 0-20 cm layer were increased by 31.8% when chemical fertilization combined with manure application was compared with no fertilizer; 9.98% when no-tillage was compared with plow tillage; and 10.84% when straw return was compared with removal. The RMPs favorably increased SOC stock in arid areas, and in alkaline and fine-textured soils. Initial SOC, carbon-nitrogen ratio, and experimental duration could also affect SOC storage. Compared with the initial SOC stock, RMPs increased the SOC sequestration potential by 2.6-4.5% in the 0-20 cm soil depth, indicating that these practices can help China achieve targets to increase SOC by 4.0‰. Hence, it is essential to implement RMPs for climate change mitigation and soil fertility improvement.

Design of a large Stokes shift ratiometric fluorescent sensor with hypochlorite detection towards the potential application as invisible security ink.

Hypochlorite (ClO-) as a well-known highly reactive oxygen species (ROS), is widely used as preservative and household disinfectant in daily life. Although many fluorescence imaging sensors for ClO- have been reported, the development of ClO- ratio fluorescence sensors with large Stokes shift is still quite limited. This sensor shows obvious benefits including minimizing environmental intervention and improving signal-to-noise ratio. In the present project, we report an innovative conjugated pyrene-based system, 1-B, as a chlorine fluorescence sensor. The detector exhibits ratio detection performance, large Stokes and emission shifts. Furthermore, the system has desired sensitivity as well as selectivity for ClO-. Based on these excellent properties, the sensor 1-B was successfully used as ink to encrypt patterns and anti-counterfeiting information through inkjet printing technology. Compared with the existing probes, the probe shows some superior characteristics, which provides a promising tool for exploring the role of ClO- response sensor in the field of anti-counterfeiting.

Soil antibiotic abatement associates with the manipulation of soil microbiome via long-term fertilizer application.

The effects of different fertilization on microbial communities and resistome in agricultural soils with a history of fresh manure application remains largely unclear. Here, soil antibiotic resistance genes (ARGs), mobile genetic elements (MGEs) and microbial communities were deciphered using metagenomics approach from a long-term field experiment with different fertilizer inputs. A total of 541 ARG subtypes were identified, with Multidrug, Macrolides-Lincosamides-Streptogramins (MLS), and Bacitracin resistance genes as the most universal ARG types. The abundance of ARGs detected in manure (2.52 ARGs/16 S rRNA) treated soils was higher than chemical fertilizer (2.42 ARGs/16 S rRNA) or compost (2.37 ARGs/16 S rRNA) amended soils. The higher abundance of MGEs and the enrichment of Proteobacteria were observed in manure treated soils than in chemical fertilizer or compost amended soils. Proteobacter and Actinobacter were recognized as the main potential hosts of ARGs revealed by network analysis. Further soil pH was identified as the key driver in determining the composition of both microbial community and resistome. The present study investigated the mechanisms driving the microbial community, MGEs and ARG profiles of long-term fertilized soils with ARGs contamination, and our findings could support strategies to manage the dissemination of soil ARGs.