Genomic characterization and risk stratification of esophageal squamous dysplasia.

Objectives: The majority of esophageal squamous dysplasia (ESD) patients progress slowly, while a subset of patients can undergo recurrence rapidly or progress to invasive cancer even after proper treatment. However, the molecular mechanisms underlying these clinical observations are still largely unknown. Methods: By sequencing the genomic data of 160 clinical samples from 49 tumor-free ESD patients and 88 esophageal squamous cell carcinoma (ESCC) patients, we demonstrated lower somatic mutation and copy number alteration (CNA) burden in ESD compared with ESCC. Results: Cross-species screening and functional assays identified ACSM5 as a novel driver gene for ESD progression. Furthermore, we revealed that miR-4292 promoted ESD progression and could serve as a non-invasive diagnostic marker for ESD. Conclusions: These findings largely expanded our understanding of ESD genetics and tumorigenesis, which possessed promising significance for improving early diagnosis, reducing overtreatment, and identifying high-risk ESD patients.

Nlp-dependent ER-to-Golgi transport.

The mechanism that maintains ER-to-Golgi vesicles formation and transport is complicated. As one of the adapters, Ninein-like protein (Nlp) participated in assembly and transporting of partial ER-to-Golgi vesicles that contained specific proteins, such as ß-Catenin and STING. Nlp acted as a platform to sustain the specificity and continuity of cargoes during COPII and COPI-coated vesicle transition and transportation through binding directly with SEC31A as well as Rab1B. Thus, we proposed an integrated transport model that particular adapter participated in specific cargo selection or transportation through cooperating with different membrane associated proteins to ensure the continuity of cargo trafficking. Deficiency of Nlp led to vesicle budding failure and accumulation of unprocessed proteins in ER, which further caused ER stress as well as Golgi fragmentation, and PERK-eIF2α pathway of UPR was activated to reduce the synthesis of universal proteins. In contrast, upregulation of Nlp resulted in Golgi fragmentation, which enhanced the cargo transport efficiency between ER and Golgi. Moreover, Nlp deficient mice were prone to spontaneous B cell lymphoma, since the developments and functions of lymphocytes significantly depended on secretory proteins through ER-to-Golgi vesicle trafficking, including IL-13, IL-17 and IL-21. Thus, perturbations of Nlp altered ER-to-Golgi communication and cellular homeostasis, and might contribute to the pathogenesis of B cell lymphoma.

Effects of virtual reality-based rehabilitation on cognitive function and mood in multiple sclerosis: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Multiple sclerosis (MS) is a disabling neurological disease that causes cognitive impairment and mental problems that occur in all MS phenotypes but are most common in patients with secondary progressive MS. Various degrees of cognitive impairment and mental health concerns are common among patients with MS (PwMS). Virtual reality (VR)-based rehabilitation is an innovative approach aimed at enhancing cognitive function and mood in PwMS. This study aims to perform a meta-analysis to assess the effects of VR-based rehabilitation on cognitive function and mood in PwMS. METHODS: Using PubMed, Embase, the Cochrane Library, Web of Science, and the Physiotherapy Evidence Database (PEDro), a thorough database search was performed to identify randomized controlled trials (RCTs) examining the effects of VR on PwMS. Trials published until October 31, 2023, that satisfied our predetermined inclusion and exclusion criteria were included. Data were extracted, literature was examined, and the methodological quality of the included trials was assessed. StataSE version 16 was used for the meta-analysis. RESULTS: Our meta-analysis included 461 patients from 10 RCTs. PRIMARY OUTCOMES: The Montreal Cognitive Assessment (MoCA) (weighted mean difference [WMD]=1.93, 95 % confidence interval [CI]=0.51-3.36, P = 0.008, I² = 75.4 %) the Spatial Recall Test (SPART) (WMD=3.57, 95 % CI=1.65-5.50, P < 0.001, I² = 0 %), immediate recall (standard mean difference [SMD]=0.37, 95 % CI=0.10-0.64, P = 0.007, I² = 0 %) and delayed recall ([SMD]=0.30, 95 % CI=0.06-0.54, P = 0.013, I² = 35.4 %) showed improvements in comparison to the control group in terms of global cognitive function immediate recall, delayed recall, and visuospatial abilities. SECONDARY OUTCOMES: Compared to the control group, anxiety improved (standard mean difference [SMD]=0.36, 95 % CI=0.10-0.62, P = 0.007, I² = 43.1 %). However, there were no significant differences in processing speed, attention, working memory or depression. CONCLUSIONS: This systematic review provides valuable evidence for improving cognitive function and mood in PwMS through VR-based rehabilitation. In the future, VR-based rehabilitation may be a potential method to treat cognitive function and emotional symptoms of MS. SYSTEMATIC REVIEW REGISTRATION: PROSPERO; identifier: CRD42023474467.

Oral Administration of PLGA Nanoparticles to Deliver Antisense Oligonucleotides to Inflammatory Lesions in the Gastrointestinal Tract.

In this study, we prepared antisense oligonucleotide (ASO)-encapsulated nanoparticles (NPs) with a suitable profile for oral administration for the treatment of inflammatory bowel disease (IBD). We chose a water-in-oil-in-water (w/o/w) method to prepare the NPs using poly(lactide-co-glycolide) as a matrix and Pluronic as a stabilizer. The obtained NPs had a suitable diameter (158 nm) for the penetration of the mucus layer, endocytic uptake by enterocytes, and accumulation in inflammatory lesions in the intestine. The amount of ASOs in the NPs was relatively large (6.41% (w/w)). When the NPs were stably dispersed in solutions that mimicked gastrointestinal (GI) juice, minimal leakage of ASOs was demonstrated over the required period. The NPs were administered orally to mice with colitis induced by dextran sodium sulfate, which reduced target gene expression in the colons and rectums of the mice, whereas naked ASO administration caused no reduction in gene expression. Thus, the NPs have the potential of promising oral carriers of ASOs for the treatment of IBD that specifically target inflammatory lesions in the GI tract, thereby reducing the non-specific toxic effects of ASOs.

High-Precision Atom Interferometer-Based Dynamic Gravimeter Measurement by Eliminating the Cross-Coupling Effect.

A dynamic gravimeter with an atomic interferometer (AI) can perform absolute gravity measurements with high precision. AI-based dynamic gravity measurement is a type of joint measurement that uses an AI sensor and a classical accelerometer. The coupling of the two sensors may degrade the measurement precision. In this study, we analyzed the cross-coupling effect and introduced a recovery vector to suppress this effect. We improved the phase noise of the interference fringe by a factor of 1.9 by performing marine gravity measurements using an AI-based gravimeter and optimizing the recovery vector. Marine gravity measurements were performed, and high gravity measurement precision was achieved. The external and inner coincidence accuracies of the gravity measurement were ±0.42 mGal and ±0.46 mGal after optimizing the cross-coupling effect, which was improved by factors of 4.18 and 4.21 compared to the cases without optimization.

Psychological symptoms and quality of life in patients with inflammatory bowel disease in China: A multicenter study.

AIMS: To investigate the current situation of mental psychology and quality of life (QoL) in patients with inflammatory bowel disease (IBD) in China, and analyze the influencing factors. METHODS: A unified questionnaire was developed to collect clinical data on IBD patients from 42 hospitals in 22 provinces from September 2021 to May 2022. Multivariate Logistic regression analysis was conducted, and independent influencing factors were screened out to construct nomogram. The consistency index (C-index), receiver operating characteristic (ROC) curve, area under the ROC curve (AUC), calibration curve, and decision curve analysis (DCA) were used to evaluate the discrimination, accuracy, and clinical utility of the nomogram model. RESULTS: A total of 2478 IBD patients were surveyed, including 1371 patients with ulcerative colitis (UC) and 1107 patients with Crohn's disease (CD). Among them, 25.5%, 29.7%, 60.2%, and 37.7% of IBD patients had anxiety, depression, sleep disturbance and poor QoL, respectively. The proportion of anxiety, depression, and poor QoL in UC patients was significantly higher than that in CD patients (all p < 0.05), but there was no difference in sleep disturbance between them (p = 0.737). Female, higher disease activity and the first visit were independent risk factors for anxiety, depression and sleep disturbance in IBD patients (all p < 0.05). The first visit, higher disease activity, abdominal pain and diarrhea symptoms, anxiety, depression and sleep disturbance were independent risk factors for the poor QoL of patients (all p < 0.05). The AUC value of the nomogram prediction model for predicting poor QoL was 0.773 (95% CI: 0.754-0.792). The calibration diagram of the model showed that the calibration curve fit well with the ideal curve, and DCA showed that the nomogram model could bring clinical benefits. CONCLUSION: IBD patients have higher anxiety, depression, and sleep disturbance, which affect their QoL. The nomogram prediction model we constructed has high accuracy and performance when predicting QoL.

Dietary long-chain fatty acids promote colitis by regulating palmitoylation of STAT3 through CD36-mediated endocytosis.

The Western diet, characterized by its high content of long-chain fatty acids (LCFAs), is widely recognized as a significant triggering factor for inflammatory bowel disease (IBD). While the link between a high-fat diet and colitis has been observed, the specific effects and mechanisms remain incompletely understood. Our study provides evidence that the diet rich in LCFAs can disrupt the integrity of the intestinal barrier and exacerbate experimental colitis in mice. Mechanistically, LCFAs upregulate the signal transducer and activator of transcription-3 (STAT3) pathway in the inflammatory model, and STAT3 knockout effectively counters the pro-inflammatory effects of LCFAs on colitis. Specifically, palmitic acid (PA), a representative LCFA, enters intestinal epithelial cells via the cluster of differentiation 36 (CD36) pathway and participates in the palmitoylation cycle of STAT3. Inhibiting this cycle using pharmacological inhibitors like 2-Bromopalmitate (2-BP) and ML349, as well as DHHC7 knockdown, has the ability to alleviate inflammation induced by PA. These findings highlight the significant role of dietary LCFAs, especially PA, in the development and progression of IBD. Diet adjustments and targeted modulation offer potential therapeutic strategies for managing this condition. Model of LCFAs involvement in the palmitoylation cycle of STAT3 upon internalization into cells. Following cellular uptake through CD36, LCFAs are converted to palmitoyl-CoA. In the presence of DHHC7, palmitoyl-CoA binds to STAT3 at the C108 site, forming palmitoylated STAT3. Palmitoylation further promotes phosphorylation at the Y705 site of STAT3. Subsequently, palmitoylated STAT3 undergoes depalmitoylation by APT2 and translocates to the nucleus to exert its biological functions.

Exploring the role of gut microbiota in migraine risk: a two-sample Mendelian randomization study.

OBJECTIVES: The presence of intestinal flora in the gut has been linked to migraines in recent studies, but whether the association is causal or due to bias remains to be clarified. We aimed to explore whether there is a potential causal relationship between gut microbiota and migraine risk with this study. MATERIALS AND METHODS: We conducted a two-sample Mendelian randomized analysis study to explore whether gut microbiota has a causal relationship with migraine using publicly available data from large-scale genome-wide association studies. The inverse variance weighting was used as the main method, and weighted median and MR-Egger were used as supplementary methods for causal inference. Sensitivity analyses, including leave-one-out analysis, Cochran Q test, and MR-Egger intercept test, were used to verify the robustness of the results. RESULTS: After rigorous quality control of the results, we identified that genetic predisposition towards a higher abundance of genus.Lactobacillus was causally associated with higher of migraine (IVW OR = 1.10, 95% CI = 1.03 - 1.18, p = .004), whereas the higher abundance of family.Prvotellaceae predicted a decreased risk of migraine (IVW OR = 0.89, 95% CI = 0.80 - 0.98, p = .02). Sensitivity analyses indicated the results were not biased by pleiotropy. CONCLUSION: According to our research, there is evidence showing that gut microbiota may be involved in migraine development, which suggested that a stool examination might be helpful to recognize those with a higher risk of migraine. Further mechanisms remained to be elucidated in future studies.

2'-Fucosyllactose restores the intestinal mucosal barrier in ulcerative colitis by inhibiting STAT3 palmitoylation and phosphorylation.

BACKGROUND & AIMS: 2'-Fucosyllactose (2'-FL), the primary constituent of human milk oligosaccharides, has been identified as a potential regulator of inflammation in inflammatory bowel disease. Despite this recognition, the specific mechanisms through which 2'-FL alleviates ulcerative colitis (UC) remain ambiguous. This study seeks to investigate the potential anti-inflammatory properties of 2'-FL concerning intestinal inflammation and uncover the associated mechanisms. METHODS: C57BL/6J mice were orally administered a daily dose of 500 mg/kg 2'-FL for 11 consecutive days, followed by the induction of colitis using 3 % (wt/vol) dextran sulfate sodium (DSS) for the final 6 days. Subsequently, a comprehensive range of techniques, including an Acyl-biotin exchange assay, fluorescein-isothiocyanate-labeled dextran assay, histopathology, ELISA, quantitative real-time PCR, Western blot, immunofluorescence staining, immunohistochemistry staining, Alcian blue-periodic acid schiff staining, TdT-mediated dUTP nick end labeling, transmission electron microscopy, iTRAQ quantitative proteomics, bioinformatics analysis, and the generation of signal transducer and activator of transcription 3 (STAT3) knockout mice, were employed to explore the relevant molecular mechanisms. RESULTS: Administration of 2'-FL significantly ameliorated DSS-induced colitis in mice and enhanced the integrity of the intestinal mucosal barrier. 2'-FL downregulated the phosphorylation of STAT3 and inhibited STAT3-related signaling pathways in colon tissues, which, in turn, reduced inflammatory responses. Interestingly, knockdown of STAT3 attenuated the protective effects of 2'-FL, highlighting that 2'-FL-mediated inflammatory attenuation is dependent on STAT3 expression. Additionally, 2'-FL could influence STAT3 activation by modulating the palmitoylation and depalmitoylation of STAT3. CONCLUSIONS: 2'-FL promotes the recovery of the intestinal mucosal barrier and suppresses inflammation in ulcerative colitis by inhibiting the palmitoylation and phosphorylation of STAT3.

Altered Gene Expression of the Parasitoid Pteromalus puparum after Entomopathogenic Fungus Beauveria bassiana Infection.

Both parasitoids and entomopathogenic fungi are becoming increasingly crucial for managing pest populations. Therefore, it is essential to carefully consider the potential impact of entomopathogenic fungi on parasitoids due to their widespread pathogenicity and the possible overlap between these biological control tools during field applications. However, despite their importance, little research has been conducted on the pathogenicity of entomopathogenic fungi on parasitoids. In our study, we aimed to address this knowledge gap by investigating the interaction between the well-known entomopathogenic fungus Beauveria bassiana, and the pupal endoparasitoid Pteromalus puparum. Our results demonstrated that the presence of B. bassiana significantly affected the survival rates of P. puparum under laboratory conditions. The pathogenicity of B. bassiana on P. puparum was dose- and time-dependent, as determined via through surface spraying or oral ingestion. RNA-Seq analysis revealed that the immune system plays a primary and crucial role in defending against B. bassiana. Notably, several upregulated differentially expressed genes (DEGs) involved in the Toll and IMD pathways, which are key components of the insect immune system, and antimicrobial peptides were rapidly induced during both the early and late stages of infection. In contrast, a majority of genes involved in the activation of prophenoloxidase and antioxidant mechanisms were downregulated. Additionally, we identified downregulated DEGs related to cuticle formation, olfactory mechanisms, and detoxification processes. In summary, our study provides valuable insights into the interactions between P. puparum and B. bassiana, shedding light on the changes in gene expression during fungal infection. These findings have significant implications for the development of more effective and sustainable strategies for pest management in agriculture.

Safe and efficient oral allergy immunotherapy using one-pot-prepared mannan-coated allergen nanoparticles.

Allergen immunotherapy (AIT) is the only curative treatment for allergic diseases. However, AIT has many disadvantages related to efficiency, safety, long-term duration, and patient compliance. Dendritic cells (DCs) have an important role in antigen-specific tolerance induction; thus, DC-targeting strategies to treat allergies such as glutaraldehyde crosslinked antigen to mannoprotein (MAN) have been established. However, glutaraldehyde crosslinking may reduce the antigen presentation efficiency of DCs. To overcome this, we developed a MAN-coated ovalbumin (OVA) nanoparticle (MDO), which uses intermolecular disulfide bond to crosslink OVA and MAN. MDO effectively targeted DCs resulting in tolerogenic DCs, and promoted higher antigen presentation efficiency by DCs compared with OVA or glutaraldehyde crosslinked nanoparticles. In vitro and in vivo experiments showed that DCs exposed to MDO induced Treg cells. Moreover, MDO had low reactivity with anti-OVA antibodies and did not induce anaphylaxis in allergic mice, demonstrating its high safety profile. In a mouse model of allergic asthma, MDO had significant preventative and therapeutic effects when administered orally or subcutaneously. Therefore, MDO represents a promising new approach for the efficient and safe treatment of allergies.

Phellinus igniarius Polysaccharides Ameliorate Hyperglycemia by Modulating the Composition of the Gut Microbiota and Their Metabolites in Diabetic Mice.

Gut microbiota dysbiosis has been reported as a risk factor in the development of type 2 diabetes mellitus (T2DM). Polysaccharides from Phellinus igniarius (P. igniarius) possess various properties that help manage metabolic diseases; however, their underlying mechanism of action remains unclear. Therefore, in this study, we aimed to evaluate the effect of P. igniarius polysaccharides (SH-P) on improving hyperglycemia in mice with T2DM and clarified its association with the modulation of gut microbiota and their metabolites using 16S rDNA sequencing and liquid chromatography-mass spectrometry. Fecal microbiota transplantation (FMT) was used to verify the therapeutic effects of microbial remodeling. SH-P supplementation alleviated hyperglycemia symptoms in T2DM mice, ameliorated gut dysbiosis, and significantly increased the abundance of Lactobacillus in the gut. Pathway enrichment analysis indicated that SH-P treatment altered metabolic pathways associated with the occurrence and development of diabetes. Spearman's correlation analysis revealed that changes in the dominant bacterial genera were significantly correlated with metabolite levels closely associated with hyperglycemia. Additionally, FMT significantly improved insulin sensitivity and antioxidative capacity and reduced inflammation and tissue injuries, indicating improved glucose homeostasis. These results indicate that the ameliorative effects of SH-P on hyperglycemia are associated with the modulation of gut microbiota composition and its metabolites.

Complete genome sequence of a novel virus isolated from the phytopathogenic fungus Ceratobasidium sp. AG-A strain SHX-YJLC-1.

A novel mycovirus, Ceratobasidium bipartite virus 1 (CBV1), was identified in Ceratobasidium sp. AG-A strain SHX-YJLC-1 isolated from diseased potato stems. The complete genome of CBV1 consists of two double-stranded RNA (dsRNA) segments: dsRNA1 (2311 bp) and dsRNA2 (1761 bp). dsRNA1 contains a single open reading frame (ORF1) encoding an RNA-dependent RNA polymerase (RdRp), while dsRNA2 contains a single ORF (ORF2) encoding a hypothetical protein (HP) with unknown function. BLASTp analysis revealed that RdRp (75.04%) and HP (61.86%) encoded by the two ORFs have the highest sequence similarity to their counterparts in Rhizoctonia solani dsRNA virus 11 (RsRV11). The genome organization and phylogenetic analysis indicated that the closest relatives to CBV1 are members of the proposed family "Bipartitiviridae". Based on the collective results, CBV1 is inferred to be a new member of the proposed family "Bipartitiviridae". This is the first report on the complete genome sequence of the novel bipartitivirus CBV1, which infects Ceratobasidium sp. AG-A strain SHX-YJLC-1.

Cordyceps cicadae polysaccharides alleviate hyperglycemia by regulating gut microbiota and its mmetabolites in high-fat diet/streptozocin-induced diabetic mice.

Introduction: The polysaccharides found in Cordyceps cicadae (C. cicadae) have received increasing academic attention owing to their wide variety of therapeutic activities. Methods: This study evaluated the hypoglycemic, antioxidant, and anti-inflammatory effects of polysaccharides from C. cicadae (CH-P). In addition, 16s rDNA sequencing and untargeted metabolomics analysis by liquid chromatography-mass spectrometry (LC-MS) were used to estimate the changes and regulatory relationships between gut microbiota and its metabolites. The fecal microbiota transplantation (FMT) was used to verify the therapeutic effects of microbial remodeling. Results: The results showed that CH-P treatment displayed hypoglycemic, antioxidant, and anti-inflammatory effects and alleviated tissue damage induced by diabetes. The CH-P treatment significantly reduced the Firmicutes/Bacteroidetes ratio and increased the abundance of Bacteroides, Odoribacter, Alloprevotella, Parabacteroides, Mucispirillum, and significantly decreased the abundance of Helicobacter and Lactobacillus compared to the diabetic group. The alterations in the metabolic pathways were mostly related to amino acid biosynthesis and metabolic pathways (particularly those involving tryptophan) according to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Correlation analysis showed that Bacteroides, Odoribacter, Alloprevotella, Parabacteroides, and Mucispirillum were positively correlated with indole and its derivatives, such as 5-hydroxyindole-3-acetic acid. Indole intervention significantly improved hyperglycemic symptoms and insulin sensitivity, and increased the secretion of glucagon-like peptide-1 (GLP-1) in diabetic mice. FMT reduced blood glucose levels, improved glucose tolerance, and increased insulin sensitivity in diabetic mice. However, FMT did not significantly improve GLP-1 levels. Discussion: This indicates that C. cicadae polysaccharides alleviate hyperglycemia by regulating the production of metabolites other than indole and its derivatives by gut microbiota. This study provides an important reference for the development of novel natural products.

CDK7-YAP-LDHD axis promotes D-lactate elimination and ferroptosis defense to support cancer stem cell-like properties.

Reprogrammed cellular metabolism is essential for maintaining cancer stem cells (CSCs) state. Here, we report that mitochondrial D-lactate catabolism is a necessary initiating oncogenic event during tumorigenesis of esophageal squamous cell carcinoma (ESCC). We discover that cyclin-dependent kinase 7 (CDK7) phosphorylates nuclear Yes-associated protein 1 (YAP) at S127 and S397 sites and enhances its transcription function, which promotes D-lactate dehydrogenase (LDHD) protein expression. Moreover, LDHD is enriched significantly in ESCC-CSCs rather than differentiated tumor cells and high LDHD status is connected with poor prognosis in ESCC patients. Mechanistically, the CDK7-YAP-LDHD axis helps ESCC-CSCs escape from ferroptosis induced by D-lactate and generates pyruvate to satisfy energetic demands for their elevated self-renewal potential. Hence, we conclude that esophageal CSCs adopt a D-lactate elimination and pyruvate accumulation mode dependent on CDK7-YAP-LDHD axis, which drives stemness-associated hallmarks of ESCC-CSCs. Reasonably, targeting metabolic checkpoints may serve as an effective strategy for ESCC therapy.

Accuracy Improvement of a Compact 85Rb Atom Gravimeter by Suppressing Laser Crosstalk and Light Shift.

We design and implement a compact 85Rb atom gravimeter (AG). The diameter of the sensor head is 35 cm and the height is 65 cm; the optical and electronic systems are installed in four standard 3U cabinets. The measurement accuracy of this AG is improved by suppress laser crosstalk and light shift. In addition, the angle of the Raman laser reflector is adjusted and locked, and the attitude of the sensing head is automatically adjusted, and the vibration noise is also compensated. The comparison measurement results between this AG and the superconducting gravimeter indicate that its long-term stability is 0.65 µGal @50000 s.

The space cold atom interferometer for testing the equivalence principle in the China Space Station.

The precision of the weak equivalence principle (WEP) test using atom interferometers (AIs) is expected to be extremely high in microgravity environment. The microgravity scientific laboratory cabinet (MSLC) in the China Space Station (CSS) can provide a higher-level microgravity than the CSS itself, which provides a good experimental environment for scientific experiments that require high microgravity. We designed and realized a payload of a dual-species cold rubidium atom interferometer. The payload is highly integrated and has a size of [Formula: see text]. It will be installed in the MSLC to carry out high-precision WEP test experiment. In this article, we introduce the constraints and guidelines of the payload design, the compositions and functions of the scientific payload, the expected test precision in space, and some results of the ground test experiments.

The interspecific competition of tree plants in the presence of AM fungi and litter facilitates root morphological development and nutrition when compared with intraspecific competition.

Arbuscular mycorrhizal (AM) fungi can affect plant growth by regulating competition. Nutrient-deficient karst habitats contain abundant plants that compete for nutrients through interspecific or intraspecific competition, involving the nutritional transformation of litter decomposition. However, how plant competition in the presence of AM fungi and litter affects root development and nutrition remains unclear. A potted experiment was conducted, including AM fungus treatment with or without Glomus etunicatum, the competition treatment concerning intraspecific or interspecific competition through planting Broussonetia papyrifera and Carpinus pubescens seedlings, and the litter treatment with or without the mixture of B. papyrifera and C. pubescens litter leaves. The root morphological traits were analyzed, and nitrogen (N), phosphorus (P), and potassium (K) were measured. The results showed that AM fungus differently affected the root morphological development and nutrition of both competitive plants, significantly promoting B. papyrifera roots in the increase of dry weight, length, volume, surface area, tips, and branches as well as N, P, and K acquisitions regardless of litter addition. However, there was no apparent influence for C. pubescens roots, except for the diameter in the interspecific competition with litter. The root dry weight, length, volume, surface area, and tips of B. papyrifera under two competitive styles were significantly greater than C. pubescens regulated by AM fungus, presenting significant species differences. The responses of the relative competition intensity (RCI) on root morphological and nutritional traits indicated that AM fungus and litter both asymmetrically alleviated more competitive pressure for B. papyrifera than C. pubescens, and the interspecific competition facilitated more root morphological development and nutrition utilization by endowing B. papyrifera root superiority relative to C. pubescens compared with the intraspecific competition. In conclusion, interspecific competition is more beneficial for plant root development and nutrition than intraspecific competition in the presence of AM fungus and litter via asymmetrically alleviating competitive pressure for different plants.

Combined Wee1 and EGFR inhibition reveals synergistic antitumor effect in esophageal squamous cell carcinoma.

Epidermal growth factor receptor (EGFR) is one of the most common amplified and overexpressed oncogenes in esophageal squamous cell carcinoma (ESCC), while the clinical efficacy of EGFR-targeted therapy in ESCC is dismal. Here, we evaluated the efficacy of dual blockage using monoclonal antibody against EGFR (Nimotuzumab) and an Wee1 inhibitor (AZD1775) in ESCC. We found that the mRNA and protein expression of EGFR and Wee1 were positively correlated in ESCC. Nimotuzumab-AZD1775 co-treatment inhibited tumor growth in PDX models with different drug susceptibility. Transcriptome sequencing and mass spectrometry analysis indicated that higher sensitive models showed enrichment of the PI3K/Akt or MAPK signaling pathway in Nimotuzumab-AZD1775 group compared with control group. In vitro experiments showed that the combination further inhibit PI3K/Akt and MAPK pathways compared to their monotherapy as indicated by downregulation of pAKT, pS6, pMEK, pErk and p-p38 MAPK. Furthermore, AZD1775 potentiated Nimotuzumab's antitumor effect through inducing apoptosis. Meanwhile, the bioinformatics analysis suggests the POLR2A might be candidate molecule of EGFR/Wee1 downstream. In conclusion, our work uncovers that EGFR-mAb Nimotuzumab combined with Wee1 inhibitor AZD1775 elicited potentiated anticancer activity against ESCC cell line and PDXs partially through PI3K/Akt and MAPK pathways blockade. These preclinical data raise the promising that ESCC patients may benefit from dual target EGFR and Wee1.

The space cold atom interferometer for testing the equivalence principle in the China Space Station.

The precision of the weak equivalence principle (WEP) test using atom interferometers (AIs) is expected to be extremely high in microgravity environment. The microgravity scientific laboratory cabinet (MSLC) in the China Space Station (CSS) can provide a higher-level microgravity than the CSS itself, which provides a good experimental environment for scientific experiments that require high microgravity. We designed and realized a payload of a dual-species cold rubidium atom interferometer. The payload is highly integrated and has a size of 460 mm × 330 mm × 260 mm. It will be installed in the MSLC to carry out high-precision WEP test experiment. In this article, we introduce the constraints and guidelines of the payload design, the compositions and functions of the scientific payload, the expected test precision in space, and some results of the ground test experiments.