Multiomics integration reveals NETosis heterogeneity and TLR2 as a prognostic biomarker in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant neoplasm characterized by a poor prognosis and limited therapeutic strategy. The PDAC tumor microenvironment presents a complex heterogeneity, where neutrophils emerge as the predominant constituents of the innate immune cell population. Leveraging the power of single-cell RNA-seq, spatial RNA-seq, and multi-omics approaches, we included both published datasets and our in-house patient cohorts, elucidating the inherent heterogeneity in the formation of neutrophil extracellular traps (NETs) and revealed the correlation between NETs and immune suppression. Meanwhile, we constructed a multi-omics prognostic model that suggested the patients exhibiting downregulated expression of NETs may have an unfavorable outcome. We also confirmed TLR2 as a potent prognosis factor and patients with low TLR2 expression had more effective T cells and an overall survival extension for 6 months. Targeting TLR2 might be a promising strategy to reverse immunosuppression and control tumor progression for an improved prognosis.

Interplay between mesenchymal stem cells and macrophages: Promoting bone tissue repair.

The repair of bone tissue damage is a complex process that is well-orchestrated in time and space, a focus and difficulty in orthopedic treatment. In recent years, the success of mesenchymal stem cells (MSCs)-mediated bone repair in clinical trials of large-area bone defects and bone necrosis has made it a candidate in bone tissue repair engineering and regenerative medicine. MSCs are closely related to macrophages. On one hand, MSCs regulate the immune regulatory function by influencing macrophages proliferation, infiltration, and phenotype polarization, while also affecting the osteoclasts differentiation of macrophages. On the other hand, macrophages activate MSCs and mediate the multilineage differentiation of MSCs by regulating the immune microenvironment. The cross-talk between MSCs and macrophages plays a crucial role in regulating the immune system and in promoting tissue regeneration. Making full use of the relationship between MSCs and macrophages will enhance the efficacy of MSCs therapy in bone tissue repair, and will also provide a reference for further application of MSCs in other diseases.

SP6 controls human cytotrophoblast fate decisions and trophoblast stem cell establishment by targeting MSX2 regulatory elements.

The commitment and differentiation of human placental progenitor cytotrophoblast (CT) cells are crucial for a successful pregnancy, but the underlying mechanism remains poorly understood. Here, we identified the transcription factor (TF), specificity protein 6 (SP6), as a human species-specific trophoblast lineage TF expressed in human placental CT cells. Using pluripotent stem cells as a model, we demonstrated that SP6 controls CT generation and the establishment of trophoblast stem cells (TSCs) and identified msh homeobox 2 (MSX2) as the downstream effector in these events. Mechanistically, we showed that SP6 interacts with histone acetyltransferase P300 to alter the landscape of H3K27ac at targeted regulatory elements, thereby favoring transcriptional activation and facilitating CT cell fate decisions and TSC maintenance. Our results established SP6 as a regulator of the human trophoblast lineage and implied its role in placental development and the pathogenies of placental diseases.

Oridonin-induced ferroptosis and apoptosis: a dual approach to suppress the growth of osteosarcoma cells.

BACKGROUND: Osteosarcoma (OS) is one of the most common aggressive bone malignancy tumors in adolescents. With the application of new chemotherapy regimens, finding new and effective anti-OS drugs to coordinate program implementation is urgent for the patients of OS. Oridonin had been proved to mediate anti-tumor effect on OS cells, but its mechanism has not been fully elucidated. METHODS: The effects of oridonin on the viability, clonal formation and migration of 143B and U2OS cells were detected by CCK-8, colony formation assays and wound-healing test. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was used to explore the mechanism of oridonin on OS. Western blot (WB), real-time quantitative PCR (qRT-PCR) were used to detect the expression levels of apoptosis and ferroptosis-relative proteins and genes. Annexin V-FITC apoptosis detection kit and flow cytometry examination were used to detect the level of apoptosis. Iron assay kit was used to evaluate the relative Fe2+ content. The levels of mitochondrial membrane potential and lipid peroxidation production was determined by mitochondrial membrane potential detection kit and ROS assay kit. RESULTS: Oridonin could effectively inhibit the survival, clonal formation and metastasis of OS cells. The KEGG results indicated that oridonin is associated with the malignant phenotypic signaling pathways of proliferation, migration, and drug resistance in OS. Oridonin was capable of inhibiting expressions of BAX, cl-caspase3, SLC7A11, GPX4 and FTH1 proteins and mRNA, while promoting the expressions of Bcl-2 and ACSL4 in 143B and U2OS cells. Additionally, we found that oridonin could promote the accumulation of reactive oxygen species (ROS) and Fe2+ in OS cells, as well as reduce mitochondrial membrane potential, and these effects could be significantly reversed by the ferroptosis inhibitor ferrostatin-1 (Fer-1). CONCLUSION: Oridonin can trigger apoptosis and ferroptosis collaboratively in OS cells, making it a promising and effective agent for OS therapy.

A survey on puncture models and path planning algorithms of bevel-tipped flexible needles.

Percutaneous needle insertion is a minimally invasive surgery with broad medical application prospects, such as biopsy and brachytherapy. However, the currently adopted rigid needles have limitations, as they cannot bypass obstacles or correct puncture deviations and can only travel along a straight path. Bevel-tip flexible needles are increasingly being adopted to address these issues, owing to their needle body's ease of deformation and bending. Successful puncture of flexible needles relies on accurate models and path planning, ensuring the needle reaches the target while avoiding vital tissues. This review investigates puncture models and path-planning algorithms by reviewing recent literature, focusing on the path-planning part. According to the literature, puncture models can be divided into three types: mechanical, finite element method (FEM), and kinematic models, while path-planning algorithms are categorized and discussed following the division used for mobile robots, which differs from the conventional approach for flexible needles-an innovation in this review. This review systematically summarizes the following categories: graph theory search, sampling-based, intelligent search, local obstacle avoidance, and other algorithms, including their implementation, advantages, and disadvantages, to further explore the potential to overcome obstacles in path planning for minimally invasive puncture needles. Finally, this study proposes future development trends in path-planning algorithms, providing possible directions for subsequent research for bevel-tipped flexible needles. This research aims to provide a resource for researchers to quickly learn about common path-planning algorithms, their backgrounds, and puncture models.

Synaptotagmin-11 regulates immune functions of microglia in vivo.

Membrane trafficking pathways mediate key microglial activities such as cell migration, cytokine secretion, and phagocytosis. However, the underlying molecular mechanism remains poorly understood. Previously, we found that synaptotagmin-11 (Syt11), a non-Ca2+ -binding Syt associated with Parkinson's disease (PD) and schizophrenia, inhibits cytokine release and phagocytosis in primary microglia. Here we reported the in vivo function of Syt11 in microglial immune responses using an inducible microglia-specific Syt11-conditional-knockout (cKO) mouse strain. Syt11-cKO resulted in activation of microglia and elevated mRNA levels of IL-6, TNF-α, IL-1ß, and iNOS in various brain regions under both resting state and LPS-induced acute inflammation state in adult mice. In a PD mouse model generated by microinjection of preformed α-synuclein fibrils into the striatum, a reduced number of microglia migrated toward the injection sites and an enhanced phagocytosis of α-synuclein fibrils by microglia were found in Syt11-cKO mice. To understand the molecular mechanism of Syt11 function, we identified its direct binding proteins vps10p-tail-interactor-1a (vti1a) and vti1b. The linker domain of Syt11 interacted with both proteins and a peptide derived from it competitively inhibited the interaction of Syt11 with vti1a/vti1b in vitro and in cells. Importantly, application of this peptide induced more cytokine secretion in wild-type microglia upon LPS treatment, phenocopying defects in Syt11 knockdown cells. Altogether, we propose that Syt11 inhibits microglial activation in vivo and regulates cytokine secretion through interactions with vti1a and vti1b.

CircNOLC1 Promotes Colorectal Cancer Liver Metastasis by Interacting with AZGP1 and Sponging miR-212-5p to Regulate Reprogramming of the Oxidative Pentose Phosphate Pathway.

Liver metastasis is a common cause of death in progressive colorectal cancer patients, but the molecular mechanisms remain unclear. Here, it is reported that a conserved and oxidative pentose phosphate pathway-associated circular RNA, circNOLC1, plays a crucial role in colorectal cancer liver metastasis. It is found that circNOLC1 silencing reduces the oxidative pentose phosphate pathway-related intermediate metabolites and elevates NADP+ /NADPH ratio and intracellular ROS levels, thereby attenuating colorectal cancer cell proliferation, migration, and liver metastasis. circNOLC1 interacting with AZGP1 to activate mTOR/SREBP1 signaling, or sponging miR-212-5p to upregulate c-Met expression, both of which can further induce G6PD to activate oxidative pentose phosphate pathway in colorectal cancer liver metastasis. Moreover, circNOLC1 is regulated by the transcription factor YY1 and specifically stabilized HuR induces its parental gene mRNA expression. The associations between circNOLC1 and these signaling molecules are validated in primary CRC and corresponding liver metastasis tissues. These findings reveal that circNOLC1 interacting with AZGP1 and circNOLC1/miR-212-5p/c-Met axis plays a key role in oxidative pentose phosphate pathway-mediated colorectal cancer liver metastasis, which may provide a novel target for precision medicine of colorectal cancer.

High expression of NOLC1 as an independent prognostic factor for survival in patients with colorectal cancer.

BACKGROUND: As a phosphorylated protein, NOLC1 is mainly located in the nucleus and is highly expressed in a variety of tumors, participating in the regulation of cell proliferation and aging. This study further investigated the role of NOLC1 in colorectal cancer tumors, aiming to provide sufficient scientific evidence for the clinical treatment of colorectal cancer. METHODS: We used TCGA, GEO, TNMplot, GEPIA, and other databases to explore the expression level of NOLC1 in colorectal cancer patients, as well as the correlation between the clinical characteristics of colorectal cancer patients and their expression, and conducted the prognostic analysis. Immunohistofluorescence (IHF) staining verified the analytical results. Subsequently, KEGG and GO enrichment analysis was used to identify the potential molecular mechanism of NOLC1 promoting the occurrence and development of colorectal cancer. The influence of NOLC1 expression on the immune microenvironment of colorectal cancer patients was further investigated using the TIMER database. GDSC database analysis was used to screen out possible anti-colorectal cancer drugs against NOLC1. Finally, we demonstrated the effect of NOLC1 on the activity and migration of colorectal cancer cells by Edu Cell proliferation assay and Wound Healing assay in vitro. RESULTS: Our results suggest that NOLC1 is overexpressed in colorectal cancer, and that overexpression of NOLC1 is associated with relevant clinical features. NOLC1, as an independent risk factor affecting the prognosis of colorectal cancer patients, can lead to a poor prognosis of colorectal cancer. In addition, NOLC1 may be associated with MCM10, HELLS, NOC3L, and other genes through participating in Wnt signaling pathways and jointly regulate the occurrence and development of colorectal cancer under the influence of the tumor microenvironment and many other influencing factors. Related to NOLC1: Selumetinib, Imatinib, and targeted drugs such as Lapatinib have potential value in the clinical application of colorectal cancer. NOLC1 enhances the proliferation and migration of colorectal cancer cells. CONCLUSIONS: High expression of NOLC1 as an independent prognostic factor for survival in patients with colorectal cancer. NOLC1 enhances the proliferation and migration of colorectal cancer cells. Further studies and clinical trials are needed to confirm the role of NOLC1 in the development and progression of colorectal cancer.

An Organic Coordination Manganese Complex as Cathode for High-Voltage Aqueous Zinc-metal Battery.

Aqueous Zn-Mn battery has been considered as the most promising scalable energy-storage system due to its intrinsic safety and especially ultralow cost. However, the traditional Zn-Mn battery mainly using manganese oxides as cathode shows low voltage and suffers from dissolution/disproportionation of the cathode during cycling. Herein, for the first time, a high-voltage and long-cycle Zn-Mn battery based on a highly reversible organic coordination manganese complex cathode (Manganese polyacrylate, PAL-Mn) was constructed. Benefiting from the insoluble carboxylate ligand of PAL-Mn that can suppress shuttle effect and disproportionationation reaction of Mn3+ in a mild electrolyte, Mn3+ /Mn2+ reaction in coordination state is realized, which not only offers a high discharge voltage of 1.67 V but also exhibits excellent cyclability (100 % capacity retention, after 4000 cycles). High voltage reaction endows the Zn-Mn battery high specific energy (600 Wh kg-1 at 0.2 A g-1 ), indicating a bright application prospect. The strategy of introducing carboxylate ligands in Zn-Mn battery to harness high-voltage reaction of Mn3+ /Mn2+ well broadens the research of high-voltage Zn-Mn batteries under mild electrolyte conditions.

Hierarchical dandelion-like CoS2 hollow microspheres: self-assembly and controllable microwave absorption performance.

The emerging electromagnetic radiation and interference problems have promoted the rapid development of microwave absorption materials (MAMs). However, it remains a severe challenge to construct high-performance microwave absorption materials with broadband, lightweight and corrosion resistance within low filling contents. Herein, hierarchical dandelion-like CoS2 hollow microspheres were reasonably constructed via a solvothermal-hydrothermal etching-in situ vulcanization process. The structure morphology, composition and electromagnetic performance of all samples have been thoroughly tested. The research results demonstrated that the structure morphology of the prepared samples with a volume ratio of 1 : 1 between ethanol and H2O remained intact without serious damage. Notably, the as-obtained hierarchical dandelion-like CoS2 hollow microspheres (25 wt%) exhibited excellent microwave absorption capacity with a minimum reflection loss (RLmin) of -47.3 dB and the corresponding effective absorption bandwidth (EAB) of 8.4 GHz at 3.3 mm. Moreover, the broadest effective absorption bandwidth (EAB, RL < -10 dB) reached 9.0 GHz (9.0-18.0 GHz) at the matching thickness of 3.2 mm. The unparalleled multiple features including hierarchical hollow structure, tunable complex permittivity as well as the enhanced impedance matching endowed CoS2 great promise as high-performance microwave absorbers for solving the problem of electromagnetic pollution.

Medical text classification based on the discriminative pre-training model and prompt-tuning.

Medical text classification, as a fundamental medical natural language processing task, aims to identify the categories to which a short medical text belongs. Current research has focused on performing the medical text classification task using a pre-training language model through fine-tuning. However, this paradigm introduces additional parameters when training extra classifiers. Recent studies have shown that the "prompt-tuning" paradigm induces better performance in many natural language processing tasks because it bridges the gap between pre-training goals and downstream tasks. The main idea of prompt-tuning is to transform binary or multi-classification tasks into mask prediction tasks by fully exploiting the features learned by pre-training language models. This study explores, for the first time, how to classify medical texts using a discriminative pre-training language model called ERNIE-Health through prompt-tuning. Specifically, we attempt to perform prompt-tuning based on the multi-token selection task, which is a pre-training task of ERNIE-Health. The raw text is wrapped into a new sequence with a template in which the category label is replaced by a [UNK] token. The model is then trained to calculate the probability distribution of the candidate categories. Our method is tested on the KUAKE-Question Intention Classification and CHiP-Clinical Trial Criterion datasets and obtains the accuracy values of 0.866 and 0.861. In addition, the loss values of our model decrease faster throughout the training period compared to the fine-tuning. The experimental results provide valuable insights to the community and suggest that prompt-tuning can be a promising approach to improve the performance of pre-training models in domain-specific tasks.

Efficacy, safety, and tolerability of switching to long-acting cabotegravir plus rilpivirine versus continuing fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide in virologically suppressed adults with HIV, 12-month results (SOLAR): a randomised, open-label, phase 3b, non-inferiority trial.

BACKGROUND: Cabotegravir plus rilpivirine is the only approved complete long-acting regimen for the maintenance of HIV-1 virological suppression dosed every 2 months. The SOLAR study aimed to compare long-acting cabotegravir plus rilpivirine every 2 months with continued once-daily bictegravir, emtricitabine, and tenofovir alafenamide for the maintenance of HIV-1 virological suppression in adults living with HIV. METHODS: SOLAR is a randomised, open-label, multicentre, phase 3b, non-inferiority study. The study was done in 118 centres across 14 countries. Participants with HIV-1 RNA less than 50 copies per mL were randomly assigned (2:1), stratified by sex at birth and BMI, to either long-acting cabotegravir (600 mg) plus rilpivirine (900 mg) dosed intramuscularly every 2 months or to continue daily oral bictegravir (50 mg), emtricitabine (200 mg), and tenofovir alafenamide (25 mg). Participants randomly assigned to long-acting therapy had a choice to receive cabotegravir (30 mg) plus rilpivirine (25 mg) once daily as an optional oral lead-in for approximately 1 month. The primary efficacy endpoint was the proportion of participants with virological non-response (HIV-1 RNA ≥50 copies per mL; the US Food and Drug Administration snapshot algorithm, 4% non-inferiority margin; modified intention-to-treat exposed population) at month 11 (long-acting start with injections group) and month 12 (long-acting with oral lead-in group and bictegravir, emtricitabine, and tenofovir alafenamide group). The study is registered with ClinicalTrials.gov, NCT04542070, and is ongoing. FINDINGS: 837 participants were screened between Nov 9, 2020, and May 31, 2021, and 687 were randomly assigned to switch treatment or continue existing treatment. Of 670 participants (modified intention-to-treat exposed population), 447 (67%) switched to long-acting therapy (274 [61%] of 447 start with injections; 173 [39%] of 447 with oral lead-in) and 223 (33%) continued bictegravir, emtricitabine, and tenofovir alafenamide. Baseline characteristics were similar; median age was 37 years (range 18-74), 118 (18%) of 670 were female sex at birth, 207 (31%) of 670 were non-White, and median BMI was 25·9 kg/m2 (IQR 23·3-29·5). At month 11-12, long-acting cabotegravir plus rilpivirine showed non-inferior efficacy versus bictegravir, emtricitabine, and tenofovir alafenamide (HIV-1 RNA ≥50 copies per mL, five [1%] of 447 vs one [<1%] of 223), with an adjusted treatment difference of 0·7 (95% CI -0·7 to 2·0). Excluding injection site reactions, adverse events and serious adverse events were similar between groups. No treatment-related deaths occurred. More long-acting group participants had adverse events leading to withdrawal (25 [6%] of 454 vs two [1%] of 227). Injection site reactions were reported by 316 (70%) of 454 long-acting participants; most (98%) were grade 1 or 2. INTERPRETATION: These data support the use of long-acting cabotegravir plus rilpivirine dosed every 2 months as a complete antiretroviral regimen that has similar efficacy to a commonly used integrase strand transfer inhibitor-based first-line regimen, while addressing unmet psychosocial issues associated with daily oral treatment. FUNDING: ViiV Healthcare.

Potential biomarkers for the early detection of bone metastases.

The clinical manifestations of bone metastases are diversified while many sites remain asymptomatic at early stage. As the early diagnosis method is not perfect and the early symptoms of tumor bone metastasis are not typical, bone metastasis is not easy to be detected. Therefore, the search for bone metastasis-related markers is effective for timely detection of tumor bone metastases and the development of drugs to inhibit bone metastases. As a result, bone metastases can only be diagnosed when symptoms are found, increasing the risk of developing skeletal-related event (SREs), which significantly impairs the patient's quality of life. Therefore, the early diagnosis of bone metastases is of great importance for the treatment and prognosis of cancer patients. Changes of bone metabolism indexes appear earlier in bone metastases, but the traditional biochemical indexes of bone metabolism lack of specificity and could be interfered by many factors, which limits their application in the study of bone metastases. Some new biomarkers of bone metastases have good diagnostic value, such as proteins, ncRNAs, circulating tumor cells (CTCs). Therefore, this study mainly reviewed the initial diagnostic biomarkers of bone metastases which were expected to provide references for the early detection of bone metastases.

Pan-precancer and cancer DNA methylation profiles revealed significant tissue specificity of interrupted biological processes in tumorigenesis.

DNA methylation (DNAme) alterations are known to initiate from the precancerous stage of tumorigenesis. Herein, we investigated the global and local patterns of DNAme perturbations in tumorigenesis by analysing the genome-wide DNAme profiles of the cervix, colorectum, stomach, prostate, and liver at precancerous and cancer stages. We observed global hypomethylation in tissues of both two stages, except for the cervix, whose global DNAme level in normal tissue was lower than that of the other four tumour types. For alterations shared by both stages, there were common hyper-methylation (sHyperMethyl) and hypo-methylation (sHypoMethyl) changes, of which the latter type was more frequently identified in all tissues. Biological pathways interrupted by sHyperMethyl and sHypoMethyl alterations demonstrated significant tissue specificity. DNAme bidirectional chaos indicated by the enrichment of both sHyperMethyl and sHypoMethyl changes in the same pathway was observed in most tissues and was a common phenomenon, particularly in liver lesions. Moreover, for the same enriched pathways, different tissues may be affected by distinct DNAme types. For the PI3K-Akt signalling pathway, sHyperMethyl enrichment was observed in the prostate dataset, but sHypoMethyl enrichment was observed in the colorectum and liver datasets. Nevertheless, they did not show an increased possibility in survival prediction of patients in comparison with other DNAme types. Additionally, our study demonstrated that gene-body DNAme changes of tumour suppressor genes and oncogenes may persist from precancerous lesions to the tumour. Overall, we demonstrate the tissue specificity and commonality of cross-stage alterations in DNA methylation profiles in multi-tissue tumorigenesis.

Development of a responsive probe for colorimetric and fluorescent detection of bisulfite in food and animal serum samples in 100% aqueous solution.

Bisulfite (HSO3-) has the functions of bleaching, antiseptic, antioxidant, inhibiting bacterial growth, and controlling enzymatic reactions in food. However, long-term consumption of foods containing excessive amounts of bisulfite can be harmful to health. In addition, large doses of sulfur dioxide (SO2) can cause diarrhea, hypotension, allergic and asthmatic reactions in susceptible individuals. Therefore, it is urgent and essential to explore some rapid, reliable, and convenient tools to detect HSO3- in food and SO2 gas. Herein, we exploited a fluorescent probe, NPO, to detect HSO3- in 100 % aqueous solution. The probe has the advantages of easy synthesis, excellent water solubility, significant colorimetric change, good selectivity, high sensitivity, and fast response (within 1 min). Probe NPO was successfully applied for testing strips to visualize the behavior of HSO3- and SO2 gas. Moreover, the probe has been used to monitor the behavior of HSO3- in real food samples and animal serum samples.

Emerging Food Packaging Applications of Cellulose Nanocomposites: A Review.

Cellulose is the most abundant biopolymer on Earth, which is synthesized by plants, bacteria, and animals, with source-dependent properties. Cellulose containing ß-1,4-linked D-glucoses further assembles into hierarchical structures in microfibrils, which can be processed to nanocellulose with length or width in the nanoscale after a variety of pretreatments including enzymatic hydrolysis, TEMPO-oxidation, and carboxymethylation. Nanocellulose can be mainly categorized into cellulose nanocrystal (CNC) produced by acid hydrolysis, cellulose nanofibrils (CNF) prepared by refining, homogenization, microfluidization, sonification, ball milling, and the aqueous counter collision (ACC) method, and bacterial cellulose (BC) biosynthesized by the Acetobacter species. Due to nontoxicity, good biodegradability and biocompatibility, high aspect ratio, low thermal expansion coefficient, excellent mechanical strength, and unique optical properties, nanocellulose is utilized to develop various cellulose nanocomposites through solution casting, Layer-by-Layer (LBL) assembly, extrusion, coating, gel-forming, spray drying, electrostatic spinning, adsorption, nanoemulsion, and other techniques, and has been widely used as food packaging material with excellent barrier and mechanical properties, antibacterial activity, and stimuli-responsive performance to improve the food quality and shelf life. Under the driving force of the increasing green food packaging market, nanocellulose production has gradually developed from lab-scale to pilot- or even industrial-scale, mainly in Europe, Africa, and Asia, though developing cost-effective preparation techniques and precisely tuning the physicochemical properties are key to the commercialization. We expect this review to summarise the recent literature in the nanocellulose-based food packaging field and provide the readers with the state-of-the-art of this research area.

Single-nucleus RNA sequencing reveals the shared mechanisms inducing cognitive impairment between COVID-19 and Alzheimer's disease.

Alzheimer's disease (AD)-like cognitive impairment, a kind of Neuro-COVID syndrome, is a reported complication of SARS-CoV-2 infection. However, the specific mechanisms remain largely unknown. Here, we integrated single-nucleus RNA-sequencing data to explore the potential shared genes and pathways that may lead to cognitive dysfunction in AD and COVID-19. We also constructed ingenuity AD-high-risk scores based on AD-high-risk genes from transcriptomic, proteomic, and Genome-Wide Association Studies (GWAS) data to identify disease-associated cell subtypes and potential targets in COVID-19 patients. We demonstrated that the primary disturbed cell populations were astrocytes and neurons between the above two dis-eases that exhibit cognitive impairment. We identified significant relationships between COVID-19 and AD involving synaptic dysfunction, neuronal damage, and neuroinflammation. Our findings may provide new insight for future studies to identify novel targets for preventive and therapeutic interventions in COVID-19 patients.

Falsochrobactrum tianjinense sp. nov., a New Petroleum-Degrading Bacteria Isolated from Oily Soils.

The microbial remediation technology had great potential and attracted attention to total petroleum hydrocarbon pollution (TPH) remediation, but its efficiency is limited by its application in the field. In this study, a new TPH-degrading strain, TDYN1, was isolated from contaminated oil soil in Dagang Oilfield in Tianjin, China, and identified as Falsochrobactrum sp. by 16S rRNA sequence analysis. The physiological characterization of the isolate was observed. The orthogonal experiment was carried out for the optimum degradation conditions to improve its biodegradation efficiency. The strain was the gram-stain-negative, short rod-shaped, non-spore-forming, designated Falsochrobactrum tianjinense sp. nov (strain TDYN1); it had 3.51 Mb, and the DNA G + C content of the strain was 56.0%. The degradation rate of TDYN1 was 69.95% after 7 days of culture in optimal degradation conditions (temperature = 30 °C, pH = 8, salinity = 10 g L-1, petroleum concentration = 1 g L-1, and the inoculation dose of strain TDYN1 = 6%) and also reached more than 30% under other relatively extreme conditions. It suggested that the TDYN1 has great potential for TPH remediation in the soils of North China.

In Situ Formation of CoS2 Hollow Nanoboxes via Ion-Exchange for High-Performance Microwave Absorption.

Hollow nanoboxes structure have raised great attention as microwave absorption materials on account of their ultralow density and large specific area. By introducing an adjustable interior cavity structure, the dielectric loss and microwave absorption performance were affected by the tunable complex permittivity and impedance matching was improved. In our study, hollow CoS2 nanoboxes with designable interspaces were successfully fabricated based on the surfactant-assisted solution method and followed by an in situ ion-exchange process. The structure, elemental compositions and morphology of the products were characterized by XRD, XPS, EDX, SEM and TEM, respectively. In addition, microwave absorption performance and the intrinsic mechanism are investigated in-depth. The paraffin-based composites with 20 wt.% filling contents exhibited superior microwave absorption capacities in view of both maximum reflection loss value (RLmax, -54.48 dB) and effective absorption bandwidth (EAB, below -10 dB, 6.0 GHz), which can be ascribed to unique hollow structure and good impedance matching. With these considerations in mind, this study provides a reference for the construction of high-performance microwave absorbers with unique hollow structure.

Synaptotagmin-11 inhibits spontaneous neurotransmission through vti1a.

Recent work has revealed that spontaneous release plays critical roles in the central nervous system, but how it is regulated remains elusive. Here, we report that synaptotagmin-11 (Syt11), a Ca2+ -independent Syt isoform associated with schizophrenia and Parkinson's disease, suppressed spontaneous release. Syt11-knockout hippocampal neurons showed an increased frequency of miniature excitatory post-synaptic currents while over-expression of Syt11 inversely decreased the frequency. Neither knockout nor over-expression of Syt11 affected the average amplitude, suggesting the pre-synaptic regulation of spontaneous neurotransmission by Syt11. Glutathione S-transferase pull-down, co-immunoprecipitation, and affinity-purification experiments demonstrated a direct interaction of Syt11 with vps10p-tail-interactor-1a (vti1a), a non-canonical SNARE protein that maintains spontaneous release. Importantly, knockdown of vti1a reversed the phenotype of Syt11 knockout, identifying vti1a as the main target of Syt11 inhibition. Domain analysis revealed that the C2A domain of Syt11 bound vti1a with high affinity. Consistently, expression of the C2A domain alone rescued the phenotype of elevated spontaneous release in Syt11-knockout neurons similar to the full-length protein. Altogether, our results suggest that Syt11 inhibits vti1a-containing vesicles during spontaneous release.