Human intermediate prostate cancer stem cells contribute to the initiation and development of prostate adenocarcinoma.

BACKGROUND: Intermediate cells are present in the early stages of human prostate development and adenocarcinoma. While primary cells isolated from benign human prostate tissues or tumors exhibit an intermediate phenotype in vitro, they cannot form tumors in vivo unless genetically modified. It is unclear about the stem cell properties and tumorigenicity of intermediate cells. METHODS: We developed a customized medium to culture primary human intermediate prostate cells, which were transplanted into male immunodeficient NCG mice to examine tumorigenicity in vivo. We treated the cells with different concentrations of dihydrotestosterone (DHT) and enzalutamide in vitro and surgically castrated the mice after cell transplantation in vivo. Immunostaining, qRT-PCR, RNA sequencing, and western blotting were performed to characterize the cells in tissues and 2D and 3D cultures. RESULTS: We found intermediate cells expressing AR+PSA+CK8+CK5+ in the luminal compartment of human prostate adenocarcinoma by immunostaining. We cultured the primary intermediate cells in vitro, which expressed luminal (AR+PSA+CK8+CK18+), basal (CK5+P63+), intermediate (IVL+), and stem cell (CK4+CK13+PSCA+SOX2+) markers. These cells resisted castration in vitro by upregulating the expression of AR, PSA, and proliferation markers KI67 and PCNA. The intermediate cells had high tumorigenicity in vivo, forming tumors in immunodeficient NCG mice in a month without any genetic modification or co-transplantation with embryonic urogenital sinus mesenchyme (UGSM) cells. We named these cells human castration-resistant intermediate prostate cancer stem cells or CriPCSCs and defined the xenograft model as patient primary cell-derived xenograft (PrDX). Human CriPCSCs resisted castration in vitro and in vivo by upregulating AR expression. Furthermore, human CriPCSCs differentiated into amplifying adenocarcinoma cells of luminal phenotype in PrDX tumors in vivo, which can dedifferentiate into CriPCSCs in vitro. CONCLUSIONS: Our study identified and established methods for culturing human CriPCSCs, which had high tumorigenicity in vivo without any genetic modification or UGSM co-transplantation. Human CriPCSCs differentiated into amplifying adenocarcinoma cells of luminal phenotype in the fast-growing tumors in vivo, which hold the potential to dedifferentiate into intermediate stem cells. These cells resisted castration by upregulating AR expression. The human CriPCSC and PrDX methods hold significant potential for advancing prostate cancer research and precision medicine.

Establishment of a reverse genetics system for virulent systemic feline calicivirus using circular polymerase extension reaction.

Feline caliciviruses can cause oral and upper respiratory tract infections in cats. However, a virulent and systemic feline calicivirus (VS-FCV) variant implicated in multisystem lesions and death in cats has emerged recently. To date, the mechanism underlying virulence variations in VS-FCV remains unclear. The aim of the present study was to provide a tool for exploring genetic variation in VS-FCV, by constructing an infectious clone of VS-FCV SH/2014. First, a full-length cDNA molecular clone of VS-FCV SH/2014 strain, which contains an Xba I recognition site generated by mutating one base (A→T) as a genetic marker, was constructed using the circular polymerase extension reaction (CPER) method. Second, the full-length cDNA clone was introduced into Crandell-Rees feline kidney cells using liposomes to rescue recombinant VS-FCV SH/2014 (rVS-FCV SH/2014). Third, the rescued viruses were identified by real-time PCR, immunofluorescence assay, western blotting, and electron microscopy. The full-length cDNA molecular clone of the VS-FCV SH/2014 strain was successfully constructed and that rVS-FCV SH/2014 could be rescued efficiently. rVS-FCV SH/2014 had the expected genetic markers and morphology and growth characteristics similar to those of the parental virus. The reverse genetics system provides a research platform for future studies on VS-FCV genetic variation and pathogenesis.

Comparative mitochondrial genomics of Terniopsis yongtaiensis in Malpighiales: structural, sequential, and phylogenetic perspectives.

BACKGROUND: Terniopsis yongtaiensis, a member of the Podostemaceae family, is an aquatic flowering plant displaying remarkable adaptive traits that enable survival in submerged, turbulent habitats. Despite the progressive expansion of chloroplast genomic information within this family, mitochondrial genome sequences have yet to be reported. RESULTS: In current study, the mitochondrial genome of the T. yongtaiensis was characterized by a circular genome of 426,928 bp encoding 31 protein-coding genes (PCGs), 18 tRNAs, and 3 rRNA genes. Our comprehensive analysis focused on gene content, repeat sequences, RNA editing processes, intracellular gene transfer, phylogeny, and codon usage bias. Numerous repeat sequences were identified, including 130 simple sequence repeats, 22 tandem repeats, and 220 dispersed repeats. Phylogenetic analysis positioned T. yongtaiensis (Podostemaceae) within the Malpighiales order, showing a close relationship with the Calophyllaceae family, which was consistent with the APG IV classification. A comparative analysis with nine other Malpighiales species revealed both variable and conserved regions, providing insights into the genomic evolution within this order. Notably, the GC content of T. yongtaiensis was distinctively lower compared to other Malpighilales, primarily due to variations in non-coding regions and specific protein-coding genes, particularly the nad genes. Remarkably, the number of RNA editing sites was low (276), distributed unevenly across 27 PCGs. The dN/dS analysis showed only the ccmB gene of T. yongtaiensis was positively selected, which plays a crucial role in cytochrome c biosynthesis. Additionally, there were 13 gene-containing homologous regions between the mitochondrial and chloroplast genomes of T. yongtaiensis, suggesting the gene transfer events between these organellar genomes. CONCLUSIONS: This study assembled and annotated the first mitochondrial genome of the Podostemaceae family. The comparison results of mitochondrial gene composition, GC content, and RNA editing sites provided novel insights into the adaptive traits and genetic reprogramming of this aquatic eudicot group and offered a foundation for future research on the genomic evolution and adaptive mechanisms of Podostemaceae and related plant families in the Malpighiales order.

Mixed Bacillus subtilis and Lactiplantibacillus plantarum-fermented feed improves gut microbiota and immunity of Bamei piglet.

Antibiotics are widely used in the breeding production of Bamei pigs, affecting the quality and safety of pork and causing enormous harm to human health, the environment, and public health. The use of probiotic fermented feed to replace antibiotic feed is one of the solutions, which has the potential to improve the intestinal microbiota, promote animal growth, and enhance immunity. The purpose of this study was to evaluate the effect of fermented feed with Lactiplantibacillus (L.) plantarum QP28-1a or Bacillus (B.) subtilis QB8a on feed, growth performance, gut microbiota, and immunity of weaned piglets. A total of 60 freshly weaned piglets from the Tibetan Plateau were randomly divided into five groups and fed basal feed, L. plantarum fermented feed, B. subtilis fermented feed, mixed fermented feed, and antibiotic fermented feed for 60 days, respectively. The results showed fermented feed supplemented with L. plantarum QP28-1a or B. subtilis QB8a significantly lowered the pH of the feed (P < 0.05), produced lactic acid and acetic acid, inhibited the growth of harmful bacteria in the feed, and reduced the feed conversion rate in the group fed mixed fermented feed (P < 0.05). The fermented feed increased the α-diversity and prominently altered the ß-diversity of the intestinal microbiota, increasing the relative abundance of beneficial bacteria such as Lactobacillus and Turicibacter and decreasing the relative abundance of conditional pathogens such as Streptococcus and Clostridium, improving the intestinal microbiota of the Bamei piglets. Notably, the mixed fermented feed improved the immunity of Bamei piglets by modulating the production of pro-inflammatory cytokines, anti-inflammatory cytokines, and inflammatory-related signaling pathways. Spearman's correlation analysis revealed that the increased expression of immune-related cytokines may be associated with a significant enrichment of Lactobacillus, Prevotellaceae, Erysipelotrichaceae, and Ruminococcaceae in the gut. In conclusion, the probiotic fermented feed maintained an acidic environment conducive to suppressing pathogens, reduced the feed conversion ratio, optimized the intestinal microbiota, improved immunity, and alleviated intestinal inflammation that may be caused by weaning, demonstrating the excellent application prospects of L. plantarum QP28-1a and B. subtilis QB8a fermented feed in the feeding of Bamei piglets.

The super-resolution reconstruction algorithm of multi-scale dilated convolution residual network.

Aiming at the problems of traditional image super-resolution reconstruction algorithms in the image reconstruction process, such as small receptive field, insufficient multi-scale feature extraction, and easy loss of image feature information, a super-resolution reconstruction algorithm of multi-scale dilated convolution network based on dilated convolution is proposed in this paper. First, the algorithm extracts features from the same input image through the dilated convolution kernels of different receptive fields to obtain feature maps with different scales; then, through the residual attention dense block, further obtain the features of the original low resolution images, local residual connections are added to fuse multi-scale feature information between multiple channels, and residual nested networks and jump connections are used at the same time to speed up deep network convergence and avoid network degradation problems. Finally, deep network extraction features, and it is fused with input features to increase the nonlinear expression ability of the network to enhance the super-resolution reconstruction effect. Experimental results show that compared with Bicubic, SRCNN, ESPCN, VDSR, DRCN, LapSRN, MemNet, and DSRNet algorithms on the Set5, Set14, BSDS100, and Urban100 test sets, the proposed algorithm has improved peak signal-to-noise ratio and structural similarity, and reconstructed images. The visual effect is better.

Replacement of backfat with vegetable oils or their oleogels in emulsion-type sausage significantly change the digestibility of meat protein.

Replacing animal fat with vegetable oil occurred extensively in the meat products, but whether these replacements will affect the nutrition of meat protein was seldom revealed. Effect of substitution of back fat (BF) by vegetable oils or their oleogels in emulsion-type sausage on the digestion process of meat protein was investigated. Replacement of BF with vegetable oils and their oleogels decreased the G'/G" values of meat paste, and oleogels largely weakened the structure of sausages. The substitution significantly reduced the liberation of -NH2 during the initial gastric and intestinal digestion, and resulted in bigger digests in CLSM images. The reduced gastric digestibility induced by substitution was shown to be related to the reduced stability of gastric digests, which can be attributed to the larger particle size and reduced viscosity of digests. These results highlighted stability of digests as a key point changing the digestion process of meat protein.

Automated echocardiographic diastolic function grading: A hybrid multi-task deep learning and machine learning approach.

BACKGROUND: Assessing left ventricular diastolic function (LVDF) with echocardiography as per ASE guidelines is tedious and time-consuming. The study aims to develop a fully automatic approach of this procedure by a lightweight hybrid algorithm combining deep learning (DL) and machine learning (ML). METHODS: The model features multi-modality input and multi-task output, measuring LV ejection fraction (LVEF), left atrial end-systolic volume (LAESV), and Doppler parameters: mitral E wave velocity (E), A wave velocity (A), mitral annulus e' velocity (e'), and tricuspid regurgitation velocity (TRmax). The algorithm was trained and tested on two internal datasets (862 and 239 echocardiograms) and validated using three external datasets, including EchoNet-Dynamic and CAMUS. The ASE diastolic function decision tree and total probability theory were used to provide diastolic grading probabilities. RESULTS: The algorithm, named MMnet, demonstrated high accuracy in both test and validation datasets, with Dice coefficients for segmentation between 0.922 and 0.932 and classification accuracies between 0.9977 and 1.0. The mean absolute errors (MAEs) for LVEF and LAESV were 3.7 % and 5.8 ml, respectively, and for LVEF in external validation, MAEs ranged from 4.9 % to 5.6 %. The diastolic function grading accuracy was 0.88 with hard criteria and up to 0.98 with soft criteria which account for the top two probability in total probability theory. CONCLUSIONS: MMnet can automatically grade ASE diastolic function with high accuracy and efficiency by annotating 2D videos and Doppler images.

Cylindrical HPIII-SbIII-Templated Five-Layer Polyoxotungstate with Conspicuous Photochromism Triggered by UV or Visible Light.

The heteroanion (HA) component plays an important role in the templating of heteropolyoxometalate (HPA) structures, but polyoxometalates (POMs) formed from two different templates are rarely reported. Herein, we present a five-layer POM [H2N(CH3)2]14{[(HPO3)4W6O10][HPSbW15O54]2}·16H2O (1) prepared by two kinds of different HA templates. The multilayer heteropolyanion {[(HPO3)4W6O10][HPSbW15O54]2}14- in 1 consists of two trivacant diheteroatom-templated ([HPO3]2- and [SbO3]3-) [HPSbW15O54]11- subunits linked by one unusual [(HPO3)4W6O10]8+ subcluster via twelve corner-sharing oxygen atoms. Compound 1 was systematically characterized by IR, UV, PXRD, TGA, XPS, and Raman spectra. Compound 1 exhibits good photochromism under UV irradiation with a half-life (t1/2) of 42.5 s, and it also exhibits noteworthy photochromism under visible light irradiation with a half-life (t1/2) of 157.2 s. The possible photochromic mechanism is proposed and verified by the experimental results.

Female-Specific Association between the Apolipoprotein E E4 Allele and Age at Diagnosis of Glaucoma in UK Biobank.

OBJECTIVE: To explore the impact of the apolipoprotein E (APOE) E4 allele in the gender-specific aging process in glaucoma by illustrating the interaction between risk factors, including the APOE E4 allele, gender, and intraocular pressure (IOP), for age at diagnosis (AAD) of glaucoma. DESIGN: A cross-sectional study included UK Biobank participants with complete data (2006-2010) for analysis. Data were analyzed in December 2023. PARTICIPANTS: Two thousand two hundred thirty-six glaucoma patients and 103 232 controls. METHODS: We evaluated multivariable-adjusted associations of AAD of glaucoma, APOE E4 allele (0: absence; 1: presence), and IOP using linear mixed model (LMM) analyses across groups stratified by AAD of mean age of menopause (50 years) and gender. MAIN OUTCOMES MEASURES: Age at diagnosis of glaucoma, APOE E4 allele, and IOP. RESULTS: Patients with glaucoma were older and had a higher percentage of males and a higher mean IOP compared to controls (all P < 0.001). Further stratifying the patients with glaucoma by AAD of 50 and gender, lower IOP (model 1 adjusted by age, ßIOP = -0.096 ± 0.041, P = 0.019), and positive APOE E4 allele (model 2 adjusted by age and IOP, ße4 = 1.093 ± 0.488, P = 0.026) were associated with an older AAD in females with an AAD <50 years under univariate LMM. In multivariate LMM adjusted by age (model 3), the effect size of both factors increased in the multivariate model as the beta-value increased (ßIOP = -0.111 ± 0.040, P = 0.007; ße4 = 1.235 ± 0.485, P = 0.012) (model 1 vs. model 3: P = 0.011). In females with an AAD ≥50 years, only positive APOE E4 allele (adjusted by age and IOP, ße4 = -1.121 ± 0.412, P = 0.007) was associated with a younger AAD. In males, only higher IOP was associated with an older AAD in those with an AAD ≥50 years (ßIOP = 0.088 ± 0.032, P = 0.006). CONCLUSIONS: Apolipoprotein E E4 allele may initially delay and later accelerate the development of glaucoma in females around the transition period of 50 years, which is the mean age of menopause, and importantly, this is independent of IOP. Understanding the specific transition states and modifiable factors within each age phase is crucial for developing interventions or strategies that promote healthy aging. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Modulating Endothelial Cell Dynamics in Fat Grafting: The Impact of DLL4 siRNA via Adipose Stem Cell Extracellular Vesicles.

In the context of improving the efficacy of autologous fat grafts (AFG) in reconstructive surgery, this study delineates the novel use of adipose-derived mesenchymal stem cells (ADSCs) and their extracellular vesicles (EVs) as vehicles for delivering DLL4 siRNA. The aim was to inhibit DLL4, a gene identified through transcriptome analysis as a critical player in the vascular endothelial cells of AFG tissues, thereby negatively affecting endothelial cell functions and graft survival through the Notch signaling pathway. By engineering ADSC EVs to carry DLL4 siRNA (ADSC EVs-siDLL4), the research demonstrated a marked improvement in endothelial cell proliferation, migration, and lumen formation, as well as enhanced angiogenesis in vivo, leading to a significant increase in the survival rate of AFGs. This approach presents a significant advancement in the field of tissue engineering and regenerative medicine, offering a potential method to overcome the limitations of current fat grafting techniques.

Regulation of Electron Delocalization Region in 2D Heteroligand-Based Copper-Organic Framework to Enhance NH 4 + $ \rm {NH_{4}}{

The rechargeable aqueous ammonium ion battery shows great potential in low-cost energy storage system because of its long life and environmental friendliness. However, most inorganic host materials used in ammonium ion batteries are still limited by slow diffusion kinetics. Herein, it is identified that a 2D heteroligand-based copper-organic framework featuring numerous ammonium ion adsorption site in the π-conjugated periodic skeleton supplies multiple accessible redox-active sites for high-performance ammonium storage. Benefitting from the effective regulation of electron delocalization by heteroligand and the inherent hydrogen bond cage mechanism between ammonium ions, the resultant full battery delivers a large specific energy density of 211.84 Wh kg-1, and it can be stably operated for 12000 cycles at 5 A g-1 for over 80 days. This explanatory understanding provides a new idea for the rational design of high-performance MOF-based ammonium ion battery cathode materials for efficient energy storage and conversion in the future.

[Surgical technique and effect of the pulsatile tinnitus associated with sigmoid sinus on the dominant side of reflux].

Objective:To explore the effect of surgical treatment of the pulsatile tinnitus associated with sigmoid sinus on the dominant side of reflux. Methods:The clinical data of 43 patients with reflux dominant side pulsating tinnitus admitted by the same doctor from 2017 to 2023 were retrospectively studied to observe the curative effect of surgical treatment. Operation method: The sound insulation barrier was established by repair technique of bone wall defect of sigmoid sinus with "capping method", without changing the blood flow and blood vessel wall of sigmoid sinus. Results:No surgical complications occurred in all patients. During the follow-up period of 3 months to 6.9 years, 14 patients（32.6%） were cured, 18 patients（41.9%） were significantly effective, 4 patients（9.3%） were effective, and 7 patients（16.3%） were ineffective. The difference of tinnitus grade before and after surgery was statistically significant. Conclusion:In this group of cases, the sound insulation barrier was established by "capping method" technique of repairing bone wall defect of sigmoid sinus, which effectively avoided the disturbance of hemorheology status and vascular wall, thus avoiding the risk of venous wall stenosis and thrombosis on the dominant reflux side. The surgical method was easy to master, and the curative effect was significant, which was worthy of clinical promotion.

Airborne microbes: sampling, detection, and inactivation.

The human living environment serves as a habitat for microorganisms and the presence of ubiquitous airborne microbes significantly impacts the natural material cycle. Through ongoing experimentation with beneficial microorganisms, humans have greatly benefited from airborne microbes. However, airborne pathogens endanger human health and have the potential to induce fatal diseases. Tracking airborne microbes is a critical prerequisite for a better understanding of bioaerosols, harnessing their potential advantages, and mitigating associated risks. Although technological breakthroughs have enabled significant advancements in accurately monitoring airborne pathogens, many puzzles about these microbes remain unanswered due to their high variability and environmental diffusibility. Consequently, advanced techniques and strategies for special identification, early warning, and efficient eradication of microbial contamination are continuously being sought. This review presents a comprehensive overview of the research status of airborne microbes, concentrating on the recent advances and challenges in sampling, detection, and inactivation. Particularly, the fundamental design principles for the collection and timely detection of airborne pathogens are described in detail, as well as critical factors for eliminating microbial contamination and enhancing indoor air quality. In addition, future research directions and perspectives for controlling airborne microbes are also suggested to promote the translation of basic research into real products.

A risk prediction model based on machine learning algorithm for parastomal hernia after permanent colostomy.

OBJECTIVE: To develop a machine learning-based risk prediction model for postoperative parastomal hernia (PSH) in colorectal cancer patients undergoing permanent colostomy, assisting nurses in identifying high-risk groups and devising preventive care strategies. METHODS: A case-control study was conducted on 495 colorectal cancer patients who underwent permanent colostomy at the Second Affiliated Hospital of Anhui Medical University from June 2017 to June 2023, with a 1-year follow-up period. Patients were categorized into PSH and non-PSH groups based on PSH occurrence within 1-year post-operation. Data were split into training (70%) and testing (30%) sets. Variable selection was performed using Least Absolute Shrinkage and Selection Operator (LASSO) regression, and binary classification prediction models were established using Logistic Regression (LR), Support Vector Classification (SVC), K Nearest Neighbor (KNN), Random Forest (RF), Light Gradient Boosting Machine (LGBM), and Extreme Gradient Boosting (XgBoost). The binary classification label denoted 1 for PSH occurrence and 0 for no PSH occurrence. Parameters were optimized via 5-fold cross-validation. Model performance was evaluated using Area Under Curve (AUC), specificity, sensitivity, accuracy, positive predictive value, negative predictive value, and F1-score. Clinical utility was evaluated using decision curve analysis (DCA), model explanation was enhanced using shapley additive explanation (SHAP), and model visualization was achieved using a nomogram. RESULTS: The incidence of PSH within 1 year was 29.1% (144 patients). Among the models tested, the RF model demonstrated the highest discrimination capability with an AUC of 0.888 (95% CI: 0.881-0.935), along with superior specificity, accuracy, sensitivity, and F1 score. It also showed the highest clinical net benefit on the DCA curve. SHAP analysis identified the top 10 influential variables associated with PSH risk: body mass index (BMI), operation duration, history and status of chronic obstructive pulmonary disease (COPD), prealbumin, tumor node metastasis (TNM) staging, stoma site, thickness of rectus abdominis muscle (TRAM), C-reactive protein CRP, american society of anesthesiologists physical status classification (ASA), and stoma diameter. These insights from SHAP plots illustrated how these factors influence individual PSH outcomes. The nomogram was used for model visualization. CONCLUSION: The Random Forest model demonstrated robust predictive performance and clinical relevance in forecasting colonic PSH. This model aids in early identification of high-risk patients and guides preventive care.

Epidemiology of lipid disturbances in psoriasis: An analysis of trends from 2006 to 2023.

INTRODUCTION: A strong link has been established between psoriasis and lipid disturbances; however, no study has systematically examined their global epidemiology. METHODS: We searched six databases from their inception up to October 1, 2023. Data analysis was conducted using Stata SE 15.1. We performed subgroup, meta-regression, and sensitivity analyses to assess the heterogeneity of the pooled studies. RESULTS: Our review included 239 studies comprising 15,519,570 participants. The pooled prevalence rate of dyslipidemia among individuals with psoriasis was 38 %. CONCLUSION: Patients with severe psoriasis should undergo screening for lipid abnormalities. This can facilitate the early detection of lipid dysfunction and associated cardiovascular comorbidities.

Prostate cancer-induced endothelial-cell-to-osteoblast transition drives immunosuppression in the bone-tumor microenvironment through Wnt pathway-induced M2 macrophage polarization.

Immune checkpoint therapy has limited efficacy for patients with bone-metastatic castration-resistant prostate cancer (bmCRPC). To improve immunotherapy for bmCRPC, we aimed to identify the mechanism of bmCRPC-induced changes in the immune microenvironment. Among bmCRPC patients, higher levels of a 32-gene M2-like macrophage signature in bone metastasis samples correlated with shorter overall survival. Immunohistochemistry showed that CD206-positive (CD206+) macrophages were enriched in bmCRPC bone biopsy specimens compared with primary tumors or lymph node metastases. In preclinical osteogenic prostate cancer (Pca) xenograft models, CD206+ macrophages were recruited to areas with tumor-induced bone. RNA sequencing (RNAseq) analysis showed higher expression of an M2-like gene signature, with activated canonical and noncanonical Wnt pathways, in tumor-associated macrophages isolated from osteogenic tumors (bone-TAMs) than in TAMs isolated from nonosteogenic tumors (ctrl-TAMs). Mechanistic studies showed that endothelial cells (ECs) that had undergone EC-to-osteoblast (EC-to-OSB) transition, the precursors of tumor-induced OSBs, produced paracrine factors, including Wnts, CXCL14, and lysyl oxidase, which induced M2 polarization and recruited M2-like TAMs to the bone-tumor microenvironment (bone-TME). Bone-TAMs suppressed CD8+ T cells' proliferation and cytolytic activity, and these effects were partially reversed by treating bone-TAMs with Wnt inhibitors. Genetic or pharmacological inhibition of Pca-induced EC-to-OSB transition reduced the levels of M2-like macrophages in osteogenic tumors. Our study demonstrates that Pca-induced EC-to-OSB transition drives immunosuppression in the bone-TME, suggesting that therapies that reduce Pca-induced bone formation may improve immunotherapeutic outcomes for bmCRPC.

High-Yield Production of High-κ/Metal Gate Nanopattern Array for 2D Devices via Oxidation-Assisted Etching Approach.

2D materials with atomically thin nature are promising to develop scaled transistors and enable the extreme miniaturization of electronic components. However, batch manufacturing of top-gate 2D transistors remains a challenge since gate dielectrics or gate electrodes transferred from 2D material easily peel away as gate pitch decreases to the nanometer scale during lift-off processes. In this study, an oxidation-assisted etching technique is developed for batch manufacturing of nanopatterned high-κ/metal gate (HKMG) stacks on 2D materials. This strategy produces nano-pitch self-oxidized Al2O3/Al patterns with a resolution of 150 nm on 2D channel material, including graphene, MoS2, and WS2 without introducing any additional damage. Through a gate-first technology in which the Al2O3/Al gate stacks are used as a mask for the formation of source and drain, a short-channel HKMG MoS2 transistor with a nearly ideal subthreshold swing (SS) of 61 mV dec-1, and HKMG graphene transistor with a cut-off frequency of 150 GHz are achieved. Moreover, both graphene and MoS2 HKMG transistor arrays exhibit high uniformity. The study may bring the potential for the massive production of large-scale integrated circuits using 2D materials.

An artificial metabzyme for tumour-cell-specific metabolic therapy.

Metabolic dysregulation constitutes a pivotal feature of cancer progression. Enzymes with multiple metal active sites play a major role in this process. Here we report the first metabolic-enzyme-like FeMoO4 nanocatalyst, dubbed 'artificial metabzyme'. It showcases dual active centres, namely, Fe2+ and tetrahedral Mo4+, that mirror the characteristic architecture of the archetypal metabolic enzyme xanthine oxidoreductase. Employing spatially dynamic metabolomics in conjunction with the assessments of tumour-associated metabolites, we demonstrate that FeMoO4 metabzyme catalyses the metabolic conversion of tumour-abundant xanthine into uric acid. Subsequent metabolic adjustments orchestrate crosstalk with immune cells, suggesting a potential therapeutic pathway for cancer. Our study introduces an innovative paradigm in cancer therapy, where tumour cells are metabolically reprogrammed to autonomously modulate and directly interface with immune cells through the intervention of an artificial metabzyme, for tumour-cell-specific metabolic therapy.

Genetic risk factors for COVID-19 and influenza are largely distinct.

Coronavirus disease 2019 (COVID-19) and influenza are respiratory illnesses caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses, respectively. Both diseases share symptoms and clinical risk factors1, but the extent to which these conditions have a common genetic etiology is unknown. This is partly because host genetic risk factors are well characterized for COVID-19 but not for influenza, with the largest published genome-wide association studies for these conditions including >2 million individuals2 and about 1,000 individuals3-6, respectively. Shared genetic risk factors could point to targets to prevent or treat both infections. Through a genetic study of 18,334 cases with a positive test for influenza and 276,295 controls, we show that published COVID-19 risk variants are not associated with influenza. Furthermore, we discovered and replicated an association between influenza infection and noncoding variants in B3GALT5 and ST6GAL1, neither of which was associated with COVID-19. In vitro small interfering RNA knockdown of ST6GAL1-an enzyme that adds sialic acid to the cell surface, which is used for viral entry-reduced influenza infectivity by 57%. These results mirror the observation that variants that downregulate ACE2, the SARS-CoV-2 receptor, protect against COVID-19 (ref. 7). Collectively, these findings highlight downregulation of key cell surface receptors used for viral entry as treatment opportunities to prevent COVID-19 and influenza.