A whole-slide foundation model for digital pathology from real-world data.

Digital pathology poses unique computational challenges, as a standard gigapixel slide may comprise tens of thousands of image tiles1-3. Prior models have often resorted to subsampling a small portion of tiles for each slide, thus missing the important slide-level context4. Here we present Prov-GigaPath, a whole-slide pathology foundation model pretrained on 1.3 billion 256 × 256 pathology image tiles in 171,189 whole slides from Providence, a large US health network comprising 28 cancer centres. The slides originated from more than 30,000 patients covering 31 major tissue types. To pretrain Prov-GigaPath, we propose GigaPath, a novel vision transformer architecture for pretraining gigapixel pathology slides. To scale GigaPath for slide-level learning with tens of thousands of image tiles, GigaPath adapts the newly developed LongNet5 method to digital pathology. To evaluate Prov-GigaPath, we construct a digital pathology benchmark comprising 9 cancer subtyping tasks and 17 pathomics tasks, using both Providence and TCGA data6. With large-scale pretraining and ultra-large-context modelling, Prov-GigaPath attains state-of-the-art performance on 25 out of 26 tasks, with significant improvement over the second-best method on 18 tasks. We further demonstrate the potential of Prov-GigaPath on vision-language pretraining for pathology7,8 by incorporating the pathology reports. In sum, Prov-GigaPath is an open-weight foundation model that achieves state-of-the-art performance on various digital pathology tasks, demonstrating the importance of real-world data and whole-slide modelling.

Approaching the quantum limit in two-dimensional semiconductor contacts.

The development of next-generation electronics requires scaling of channel material thickness down to the two-dimensional limit while maintaining ultralow contact resistance1,2. Transition-metal dichalcogenides can sustain transistor scaling to the end of roadmap, but despite a myriad of efforts, the device performance remains contact-limited3-12. In particular, the contact resistance has not surpassed that of covalently bonded metal-semiconductor junctions owing to the intrinsic van der Waals gap, and the best contact technologies are facing stability issues3,7. Here we push the electrical contact of monolayer molybdenum disulfide close to the quantum limit by hybridization of energy bands with semi-metallic antimony ([Formula: see text]) through strong van der Waals interactions. The contacts exhibit a low contact resistance of 42 ohm micrometres and excellent stability at 125 degrees Celsius. Owing to improved contacts, short-channel molybdenum disulfide transistors show current saturation under one-volt drain bias with an on-state current of 1.23 milliamperes per micrometre, an on/off ratio over 108 and an intrinsic delay of 74 femtoseconds. These performances outperformed equivalent silicon complementary metal-oxide-semiconductor technologies and satisfied the 2028 roadmap target. We further fabricate large-area device arrays and demonstrate low variability in contact resistance, threshold voltage, subthreshold swing, on/off ratio, on-state current and transconductance13. The excellent electrical performance, stability and variability make antimony ([Formula: see text]) a promising contact technology for transition-metal-dichalcogenide-based electronics beyond silicon.

Anatomically distinct fibroblast subsets determine skin autoimmune patterns.

The skin serves as a physical barrier and an immunological interface that protects the body from the external environment1-3. Aberrant activation of immune cells can induce common skin autoimmune diseases such as vitiligo, which are often characterized by bilateral symmetric lesions in certain anatomic regions of the body4-6. Understanding what orchestrates the activities of cutaneous immune cells at an organ level is necessary for the treatment of autoimmune diseases. Here we identify subsets of dermal fibroblasts that are responsible for driving patterned autoimmune activity, by using a robust mouse model of vitiligo that is based on the activation of endogenous auto-reactive CD8+ T cells that target epidermal melanocytes. Using a combination of single-cell analysis of skin samples from patients with vitiligo, cell-type-specific genetic knockouts and engraftment experiments, we find that among multiple interferon-γ (IFNγ)-responsive cell types in vitiligo-affected skin, dermal fibroblasts are uniquely required to recruit and activate CD8+ cytotoxic T cells through secreted chemokines. Anatomically distinct human dermal fibroblasts exhibit intrinsic differences in the expression of chemokines in response to IFNγ. In mouse models of vitiligo, regional IFNγ-resistant fibroblasts determine the autoimmune pattern of depigmentation in the skin. Our study identifies anatomically distinct fibroblasts with permissive or repressive IFNγ responses as the key determinant of body-level patterns of lesions in vitiligo, and highlights mesenchymal subpopulations as therapeutic targets for treating autoimmune diseases.

The adaptor protein ECAP, the corepressor LEUNIG, and the transcription factor BEH3 interact and regulate microsporocyte generation in Arabidopsis.

Histospecification and morphogenesis of anthers during development in Arabidopsis (Arabidopsis thaliana) are well understood. However, the regulatory mechanism of microsporocyte generation at the pre-meiotic stage remains unclear, especially how archesporial cells are specified and differentiate into 2 cell lineages with distinct developmental fates. SPOROCYTELESS (SPL) is a key reproductive gene that is activated during early anther development and remains active. In this study, we demonstrated that the EAR motif-containing adaptor protein (ECAP) interacts with the Gro/Tup1 family corepressor LEUNIG (LUG) and the BES1/BZR1 HOMOLOG3 (BEH3) transcription factor to form a transcription activator complex, epigenetically regulating SPL transcription. SPL participates in microsporocyte generation by modulating the specification of archesporial cells and the archesporial cell-derived differentiation of somatic and reproductive cell layers. This study illustrates the regulation of SPL expression by the ECAP-LUG-BEH3 complex, which is essential for the generation of microsporocytes. Moreover, our findings identified ECAP as a key transcription regulator that can combine with different partners to regulate gene expression in distinct ways, thereby facilitating diverse processes in various aspects of plant development.

Downregulation of a transcription factor associated with resistance to Bt toxin Vip3Aa in the invasive fall armyworm.

Transgenic crops producing insecticidal proteins from Bacillus thuringiensis (Bt) have revolutionized control of some major pests. However, more than 25 cases of field-evolved practical resistance have reduced the efficacy of transgenic crops producing crystalline (Cry) Bt proteins, spurring adoption of alternatives including crops producing the Bt vegetative insecticidal protein Vip3Aa. Although practical resistance to Vip3Aa has not been reported yet, better understanding of the genetic basis of resistance to Vip3Aa is urgently needed to proactively monitor, delay, and counter pest resistance. This is especially important for fall armyworm (Spodoptera frugiperda), which has evolved practical resistance to Cry proteins and is one of the world's most damaging pests. Here, we report the identification of an association between downregulation of the transcription factor gene SfMyb and resistance to Vip3Aa in S. frugiperda. Results from a genome-wide association study, fine-scale mapping, and RNA-Seq identified this gene as a compelling candidate for contributing to the 206-fold resistance to Vip3Aa in a laboratory-selected strain. Experimental reduction of SfMyb expression in a susceptible strain using RNA interference (RNAi) or CRISPR/Cas9 gene editing decreased susceptibility to Vip3Aa, confirming that reduced expression of this gene can cause resistance to Vip3Aa. Relative to the wild-type promoter for SfMyb, the promoter in the resistant strain has deletions and lower activity. Data from yeast one-hybrid assays, genomics, RNA-Seq, RNAi, and proteomics identified genes that are strong candidates for mediating the effects of SfMyb on Vip3Aa resistance. The results reported here may facilitate progress in understanding and managing pest resistance to Vip3Aa.

Effect of Moniezia Benedeni infection on ileal transcriptome profile characteristics of sheep.

BACKGROUND: The intestinal mucosal immune system, renowned for its precise and sensitive regulation, can provide comprehensive and effective protection for the body, among which the ileum is a critical induction site for regulating mucosal immune homeostasis. Moniezia benedeni parasitizes the small intestine of sheep and can cause serious pathological damage or even death to the host when the infection is severe. In this study, 5 sheep infected with Moniezia benedeni were selected as the infected group, and 5 uninfected sheep were selected as the control group. The ileal transcriptome profile characteristics of Moniezia benedeni infection were analyzed based on RNA-seq sequencing technology, aiming to lay a foundation for further exploring the perception mechanism of sheep intestines to Moniezia benedeni infection and formulating effective prevention and control strategies. RESULTS: The results showed that a total of 3,891 differentially expressed genes (DEGs) were detected in the ileum tissues of sheep between the infected and control groups with 2,429 up-regulated genes and 1,462 down-regulated genes. GO and KEGG pathway enrichment analysis of differential genes, as well as Clue GO analysis showed that differential genes were significantly enriched in immune and metabolic-related biological processes and signaling pathways. Particularly, in immune-related signaling pathways, the B cell receptor signaling pathway was significantly down-regulated, while in metabolic regulation related signaling pathways, Bile secretion, Fat digestion and absorption and Vitamin digestion and absorption were notably up-regulated. On this basis, the differential core genes related to immune metabolism were verified by qRT-PCR method. The results showed that OVAR, CD3E, CD8A, CD4 and CD28 were significantly up-regulated (P < 0.05), while CIITA, BLNK, BCL6 and CD79A were significantly down-regulated (P < 0.05), which were consistent with transcriptome sequencing data. CONCLUSIONS: The results demonstrated that Moniezia benedeni infection significantly affected the immune and metabolic processes in sheep ileum, particularly, it significantly inhibited the activation process of host B cells, and also led to an overactive function of bile acid metabolism. This finding provides a solid foundation for further elucidating the response mechanism of Peyer's patches in sheep ileum to Moniezia tapeworm infection.

Knockout of the WD40 domain of ATG16L1 enhances foot and mouth disease virus replication.

The WD40 domain is one of the most abundant domains and is among the top interacting domains in eukaryotic genomes. The WD40 domain of ATG16L1 is essential for LC3 recruitment to endolysosomal membranes during non-canonical autophagy, but dispensable for canonical autophagy. Canonical autophagy was utilized by FMDV, while the relationship between FMDV and non-canonical autophagy is still elusive. In the present study, WD40 knockout (KO) PK15 cells were successfully generated via CRISPR/cas9 technology as a tool for studying the effect of non-canonical autophagy on FMDV replication. The results of growth curve analysis, morphological observation and karyotype analysis showed that the WD40 knockout cell line was stable in terms of growth and morphological characteristics. After infection with FMDV, the expression of viral protein, viral titers, and the number of copies of viral RNA in the WD40-KO cells were significantly greater than those in the wild-type PK15 cells. Moreover, RNA‒seq technology was used to sequence WD40-KO cells and wild-type cells infected or uninfected with FMDV. Differentially expressed factors such as Mx1, RSAD2, IFIT1, IRF9, IFITM3, GBP1, CXCL8, CCL5, TNFRSF17 were significantly enriched in the autophagy, NOD-like receptor signaling pathway, RIG-I-like receptor signaling pathway, Toll-like receptor signaling pathway, cytokine-cytokine receptor interaction and TNF signaling pathway, etc. The expression levels of differentially expressed genes were detected via qRT‒PCR, which was consistent with the RNA‒seq data. Here, we experimentally demonstrate for the first time that knockout of the WD40 domain of ATG16L1 enhances FMDV replication by downregulation innate immune factors. In addition, this result also indicates non-canonical autophagy inhibits FMDV replication. In total, our results play an essential role in regulating the replication level of FMDV and providing new insights into virus-host interactions and potential antiviral strategies.

Efficient Electrochemical Microsensor for the Simultaneous Measurement of Hydrogen Peroxide and Ascorbic Acid in Living Brains.

Hydrogen peroxide (H2O2) and ascorbic acid (AA), acting as two significant indicative species, correlate with the oxidative stress status in living brains, which have historically been considered to be involved mainly in neurodegenerative disorders such as Alzheimer's disease, Huntington's disease, and Parkinson's disease (PD). The development of efficient biosensors for the simultaneous measurement of their levels in living brains is vital to understand their roles played in the brain and their interactive relationship in the progress of these diseases. Herein, a robust ratiometric electrochemical microsensor was rationally designed to realize the determination of H2O2 and AA simultaneously. Therefore, a specific probe was designed and synthesized with both recognition units responsible for reacting with H2O2 to produce a detectable signal on the microsensor and linkage units helping the probe modify onto the carbon substrate. A topping ingredient, single-walled carbon nanotubes (SWCNTs) was added on the surface of the electrode, with the purpose of not only facilitating the oxidation of AA but also absorbing methylene blue (MB), prompting to read out the inner reference signal. This proposed electrochemical microsensor exhibited a robust ability to real-time track H2O2 and AA in linear ranges of 0.5-900 and 10-1000 µM with high selectivity and accuracy, respectively. Eventually, the efficient electrochemical microsensor was successfully applied to the simultaneous measurement of H2O2 and AA in the rat brain, followed by microinjection, and in the PD mouse brain.

Microfluidic Impedance Cytometry Enabled One-Step Sample Preparation for Efficient Single-Cell Mass Spectrometry.

Single-cell mass spectrometry (MS) is significant in biochemical analysis and holds great potential in biomedical applications. Efficient sample preparation like sorting (i.e., separating target cells from the mixed population) and desalting (i.e., moving the cells off non-volatile salt solution) is urgently required in single-cell MS. However, traditional sample preparation methods suffer from complicated operation with various apparatus, or insufficient performance. Herein, a one-step sample preparation strategy by leveraging label-free impedance flow cytometry (IFC) based microfluidics is proposed. Specifically, the IFC framework to characterize and sort single-cells is adopted. Simultaneously with sorting, the target cell is transferred from the local high-salinity buffer to the MS-compatible solution. In this way, one-step sorting and desalting are achieved and the collected cells can be directly fed for MS analysis. A high sorting efficiency (>99%), cancer cell purity (≈87%), and desalting efficiency (>99%), and the whole workflow of impedance-based separation and MS analysis of normal cells (MCF-10A) and cancer cells (MDA-MB-468) are verified. As a standalone sample preparation module, the microfluidic chip is compatible with a variety of MS analysis methods, and envisioned to provide a new paradigm in efficient MS sample preparation, and further in multi-modal (i.e., electrical and metabolic) characterization of single-cells.

High-Sensitive Uncooled Mid-Wave Infrared Detector Based on TiS3 Nanoribbon.

High-sensitive uncooled mid-wave infrared (MWIR) photodetection with fast speed is highly desired for biomedical imaging, optical communication, and night vision technology. Low-dimensional materials with low dark current and broadband photoresponse hold great promise for use in MWIR detection. Here, this study reports a high-performance MWIR photodetector based on a titanium trisulfide (TiS3) nanoribbon. This device demonstrates an ultra-broadband photoresponse ranging from the visible spectrum to the MWIR spectrum (405-4275 nm). In the MWIR spectral range, the photodetector achieves competitive high photoresponsivity (R) of 21.1 A W-1, and an impressive specific detectivity (D*) of 5.9 × 1010 cmHz1/2 W-1 in ambient air. Remarkably, the photoresponse speed in the MWIR with τr = 1.3 ms and τd = 1.5 ms is realized which is much faster than the thermal time constant of 15 ms. These findings pave the way for highly sensitive, room-temperature MWIR photodetectors with exceptionally fast response speed.

Environmental and molecular regulation of diapause formation in a scyphozoan jellyfish.

Understanding the mechanisms underlying diapause formation is crucial for gaining insight into adaptive survival strategies across various species. In this study, we aimed to uncover the pivotal role of temperature and food availability in regulating diapausing podocyst formation in the jellyfish Aurelia coerulea. Furthermore, we explored the cellular and molecular basis of diapause formation using single-cell RNA sequencing. Our results showed cell-type-specific transcriptional landscapes during podocyst formation, which were underscored by the activation of specific transcription factors and signalling pathways. In addition, we found that the heat shock protein-coding genes HSC70 and HSP90a potentially act as hub genes that regulate podocyst formation. Finally, we mapped the single-cell atlas of diapausing podocysts and identified cell types involved in metabolism, environmental sensing, defence and development that may collectively contribute to the long-term survival and regulated excystment of diapausing podocysts. Taken together, the findings of this study provide novel insights into the molecular mechanisms that regulate diapause formation and contributes to a better understanding of adaptive survival strategies in a variety of ecological contexts.

Clinical research progress of fruquintinib in the treatment of malignant tumors.

Malignant tumors represent an important cause of mortality within the global population. Tumor angiogenesis, recognized as one of the key hallmarks of malignant tumors, is crucial for supplying essential nutrients and oxygen for tumor growth. Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) are key drivers of tumor angiogenesis. Targeted therapeutic interventions not only effectively inhibit tumor growth by specifically blocking tumor angiogenesis but have also made breakthroughs in the treatment of malignant tumors. Fruquintinib, an anti-angiogenic small molecule drug developed independently in China, functions as a potent tyrosine kinase inhibitor with high selectivity. It effectively curtails tumor growth by binding to and inhibiting VEGFR-1, VEGFR-2, and VEGFR-3. Additionally, fruquintinib offers several advantages including minimal off-target toxicity, robust resistance profiles, and commendable efficacy. This agent can be used alone or in combination with other treatments. It has shown high effectiveness and survival benefits across various malignant tumors such as colorectal cancer, gastric cancer, non-small cell lung cancer, breast cancer, and other malignant tumors. Therefore, this article conducts a systematic review encompassing the mechanism of action, pharmacokinetics, clinical efficacy, and safety profile of fruquintinib. Through this review, we aimed to offer a reference for the clinical application and subsequent development of fruquintinib.

Validated enhancement and temperature modulated absorbance of a WS2 monolayer based on a planar structure.

Transition-metal dichalcogenides (TMDCs), as emerging optoelectronic materials, necessitate the establishment of an experimentally viable system to study their interaction with light. In this study, we propose and analyze a WS2/PMMA/Ag planar Fabry-Perot (F-P) cavity, enabling the direct experimental measurement of WS2 absorbance. By optimizing the structure, the absorbance of A exciton of WS2 up to 0.546 can be experimentally achieved, which matches well with the theoretical calculations. Through temperature and thermal expansion strain induced by temperature, the absorbance of the A exciton can be tuned in situ. Furthermore, temperature-dependent photocurrent measurements confirmed the consistent absorbance of the A exciton under varying temperatures. This WS2/PMMA/Ag planar structure provides a straightforward and practical platform for investigating light interaction in TMDCs, laying a solid foundation for future developments of TMDC-based optoelectronic devices.

A dosimetric comparison of brachytherapy sources for endometrial cancer: an electronic brachytherapy and an iridium-192 source with multichannel cylinders and a three-dimensional technique.

BACKGROUND AND PURPOSE: Ir192 vaginal brachytherapy (IBT) is commonly used for patients with postoperative endometrial cancer (EC). We devised a novel multichannel vaginal applicator that could be equipped with an electronic brachytherapy (EBT) device. We aimed to explore the differences in physical parameters between the EBT and IBT. MATERIALS AND METHODS: This retrospective study included 20 EC patients who received adjuvant IBT from March 1, 2023, to May 1, 2023. Multichannel vaginal cylinders were used, and three-dimensional plans were generated. We designed an electronic multichannel vaginal applicator model and simulated a three-dimensional EBT plan. In order to ensure comparability, D90 of the CTV for the EBT plan was normalized to be equivalent to that of the IBT plan for the same patient. RESULTS: Twenty EBT plans were compared with 20 IBT plans. Results showed, the mean D90 value of clinical target volume (CTV) was 536.1 cGy for both treatment plans. For the mean dose of CTV, the EBT was significantly greater (738.3 vs. 684.3 cGy, p = 0.000). There was no significant difference in CTV coverage between the EBT and IBT plans. For high-dose areas (V200% and V150%), the EBTs were significantly greater. There were no significant differences in the maximum doses to the vaginal mucosa between the EBT and IBT, whether at the apex or in the middle segment. For the bladder and rectum, both the low-dose area and high-dose area were significantly lower in the EBT plans. For the conformity index, there was no significant difference between the EBT and IBT plans. For the dose homogeneity index, the EBT value was lower. CONCLUSION: In conclusion, under the premise of a three-dimensional brachytherapy plan, for patients receiving multichannel vaginal applicator brachytherapy, compared with IBT, EBT could reduce the dose to the surrounding organs at risk while maintaining the dose in the target area.

Elevated Porcupine Disrupts Lipid Metabolism and Promotes Inflammatory Response in MASLD.

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) presents a high incidence globally and is a major cause of cirrhosis and hepatocellular carcinoma, lacking of efficient interventions. Patients with MASLD exhibit exceeded serum levels of palmitic acid (PA). However, the association between PA and MASLD remains obscure. METHODS: Gene expression omnibus dataset analysis, western blotting, mRNA-sequencing, RT-qPCR, a click chemistry-immunoprecipitation-immunofluorescence system, ELISA, lipid extraction and UHPLC-MS/MS analysis, CyTOF mass cytometry, gene knockdown via lentivirus-mediated shRNA, and high-fat methionine and choline-deficient diet-fed WT and db/db mice models were used to reveal the expression and functions of Porcupine in MASLD development both in vitro and in vivo. RESULTS: Our findings show that PA, as a crucial substrate for protein palmitoylation, induced the expression of palmitoyltransferase Porcupine in a time-dependent manner. This induction was closely associated with dysregulated lipid metabolism and stimulated inflammatory response observed in vitro. Porcupine protein levels were significantly increased in liver tissues from both MASLD mice models, which was predominantly localised in lipid droplet-rich hepatocytes. Pharmacological inhibition of Porcupine by Wnt974 markedly ameliorated the aberrant lipid accumulation and inflammatory response in mouse livers. Furthermore, increased Porcupine positively correlated with CD36 at protein levels, and its inhibition or knockdown decreased CD36 protein levels via mechanisms irrelevant to transcriptional regulation, but primarily dependent on protein palmitoylation. CONCLUSIONS: The current study reveals that PA-induced Porcupine disrupts lipid metabolism and promotes inflammatory response during MASLD development, which can be ameliorated by the Porcupine inhibitor Wnt974. Therefore, Porcupine may be a potential pharmacological target for the treatment of MASLD.

Adhesion between EVs and tumor cells facilitated EV-encapsulated doxorubicin delivery via ICAM1.

Doxorubicin (Dox) is an anti-tumor drug with a broad spectrum, whereas the cardiotoxicity limits its further application. In clinical settings, liposome delivery vehicles are used to reduce Dox cardiotoxicity. Here, we substitute extracellular vesicles (EVs) for liposomes and deeply investigate the mechanism for EV-encapsulated Dox delivery. The results demonstrate that EVs dramatically increase import efficiency and anti-tumor effects of Dox in vitro and in vivo, and the efficiency increase benefits from its unique entry pattern. Dox-loading EVs repeat a "kiss-and-run" motion before EVs internalization. Once EVs touch the cell membrane, Dox disassociates from EVs and directly enters the cytoplasm, leading to higher and faster Dox import than single Dox. This unique entry pattern makes the adhesion between EVs and cell membrane rather than the total amount of EV internalization the key factor for regulating the Dox import. Furthermore, we recognize ICAM1 as the molecule mediating the adhesion between EVs and cell membranes. Interestingly, EV-encapsulated Dox can induce ICAM1 expression by irritating IFN-γ and TNF-α secretion in TME, thereby increasing tumor targeting of Dox-loading EVs. Altogether, EVs and EV-encapsulated Dox synergize via ICAM1, which collectively enhances the curative effects for tumor treatment.

PRRSV hijacks DDX3X protein and induces ferroptosis to facilitate viral replication.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a severe disease with substantial economic consequences for the swine industry. The DEAD-box helicase 3 (DDX3X) is an RNA helicase that plays a crucial role in regulating RNA metabolism, immunological response, and even RNA virus infection. However, it is unclear whether it contributes to PRRSV infection. Recent studies have found that the expression of DDX3X considerably increases in Marc-145 cells when infected with live PRRSV strains Ch-1R and SD16; however, it was observed that inactivated viruses did not lead to any changes. By using the RK-33 inhibitor or DDX3X-specific siRNAs to reduce DDX3X expression, there was a significant decrease in the production of PRRSV progenies. In contrast, the overexpression of DDX3X in host cells substantially increased the proliferation of PRRSV. A combination of transcriptomics and metabolomics investigations revealed that in PRRSV-infected cells, DDX3X gene silencing severely affected biological processes such as ferroptosis, the FoxO signalling pathway, and glutathione metabolism. The subsequent transmission electron microscopy (TEM) imaging displayed the typical ferroptosis features in PRRSV-infected cells, such as mitochondrial shrinkage, reduction or disappearance of mitochondrial cristae, and cytoplasmic membrane rupture. Conversely, the mitochondrial morphology was unchanged in DDX3X-inhibited cells. Furthermore, silencing of the DDX3X gene changed the expression of ferroptosis-related genes and inhibited the virus proliferation, while the drug-induced ferroptosis inversely promoted PRRSV replication. In summary, these results present an updated perspective of how PRRSV infection uses DDX3X for self-replication, potentially leading to ferroptosis via various mechanisms that promote PRRSV replication.

Enantioselective α-Trifluoromethylthiolation of Carbonyl Compounds with AgSCF3 and Trichloroisocyanuric Acid.

We successfully developed an enantioselective trifluoromethylthiolation of structurally diverse carbonyl compounds. Trichloroisocyanuric acid and AgSCF3 were employed to generate active electrophilic trifluoromethylthio species in situ for asymmetric C-SCF3 bond formation. A broad variety of chiral SCF3-carbon nucleophiles (pyrazolones, ß-keto esters, and ß-keto amides) were obtained in excellent yields with high enantioselectivities (up to 92% ee) by Cinchona alkaloid derived squaramide catalysts. The reaction exhibits high efficiency, good enantioselectivity, and high functional group tolerance, which provided a novel and efficient way for asymmetric synthesis of trifluoromethylthiolated carbonyl compounds.

Broadband mid-infrared photodetectors utilizing two-dimensional van der Waals heterostructures with parallel-stacked pn junctions.

Optimizing the width of depletion region is a key consideration in designing high performance photovoltaic photodetectors, as the electron-hole pairs generated outside the depletion region cannot be effectively separated, leading to a negligible contribution to the overall photocurrent. However, currently reported photovoltaic mid-infrared photodetectors based on two-dimensional heterostructures usually adopt a single pn junction configuration, where the depletion region width is not maximally optimized. Here, we demonstrate the construction of a high performance broadband mid-infrared photodetector based on a MoS2/b-AsP/MoS2npn van der Waals heterostructure. The npn heterojunction can be equivalently represented as two parallel-stacked pn junctions, effectively increasing the thickness of the depletion region. Consequently, the npn device shows a high detectivity of 1.3 × 1010cmHz1/2W-1at the mid-infrared wavelength, which is significantly improved compared with its single pn junction counterpart. Moreover, it exhibits a fast response speed of 12 µs, and a broadband detection capability ranging from visible to mid-infrared wavelengths.

Bubble Turbulent Gas-Permeable Membrane for Ammonia Recovery from Swine Wastewater: Mass Transfer Enhancement and Antifouling Mechanisms.

Recovering ammonium from swine wastewater employing a gas-permeable membrane (GM) has potential but suffers from the limitations of unattractive mass transfer and poor-tolerance antifouling properties. Turbulence is an effective approach to enhancing the release of volatile ammonia from wastewater while relying on interfacial disturbance to interfere with contaminant adhesion. Herein, we design an innovative gas-permeable membrane coupled with bubble turbulence (BT-GM) that enhances mass transfer while mitigating membrane fouling. Bubbles act as turbulence carriers to accelerate the release and migration of ammonia from the liquid phase, increasing the ammonia concentration gradient at the membrane-liquid interface. In comparison, the ammonium mass transfer rate of the BT-GM process applied to real swine wastewater is 38% higher than that of conventional GM (12 h). Through a computational fluid dynamics simulation, the turbulence kinetic energy of BT-GM system is 3 orders of magnitude higher than that of GM, and the effective mass transfer area is nearly 3 times that of GM. Seven batches of tests confirmed that the BT-GM system exhibits remarkable antifouling ability, broadens its adaptability to complex water quality, and practically promotes the development of sustainable resource recycling.