Correlated Charge Density Wave Insulators in Chirally Twisted Triple Bilayer Graphene.

Electrons residing in a flat-band system can play a vital role in triggering spectacular phenomenology due to relatively large interactions and spontaneous breaking of different degeneracies. In this work, we demonstrate chirally twisted triple bilayer graphene, a new moiré structure formed by three pieces of helically stacked Bernal bilayer graphene, as a highly tunable flat-band system. In addition to the correlated insulators showing at integer moiré fillings, commonly attributed to interaction induced symmetry broken isospin flavors in graphene, we observe abundant insulating states at half-integer moiré fillings, suggesting a longer-range interaction and the formation of charge density wave insulators which spontaneously break the moiré translation symmetry. With weak out-of-plane magnetic field applied, as observed half-integer filling states are enhanced and more quarter-integer filling states appear, pointing toward further quadrupling moiré unit cells. The insulating states at fractional fillings combined with Hartree-Fock calculations demonstrate the observation of a new type of correlated charge density wave insulators in graphene and points to a new accessible twist manner engineering correlated moiré electronics.

Activation of a Silent Gene Cluster from the Endophytic Fungus Talaromyces sp. Unearths Cryptic Azaphilone Metabolites.

Fungal azaphilones have attracted widespread attention due to their significant potential as sources of food pigments and pharmaceuticals. Genome mining and gene cluster activation represent powerful tools and strategies for discovering novel natural products and bioactive molecules. Here, a putative azaphilone biosynthetic gene cluster lut from the endophytic fungus Talaromyces sp. was identified through genome mining. By overexpressing the pathway-specific transcription factor LutB, five new sclerotiorin-type azaphilones (1, 6, 8, and 10-11) together with seven known analogues (2-5, 7, 9, 12) were successfully produced. Compounds 8 and 9 exhibited antibacterial activity against Bacillus subtilis with MIC values of 64 and 16 µg/mL, respectively. Compound 11 showed cytotoxic activity against HCT116 and GES-1 with IC50 values of 10.9 and 4.9 µM, respectively, while 1, 4, 5, and 7-10 showed no obvious cytotoxic activity. Gene inactivation experiments confirmed the role of the lut cluster in the production of compounds 1-12. Subsequent feeding experiments unveiled the novel functional diversity of the dual megasynthase system. Furthermore, a LutC-LutD binary oxidoreductase system was discovered, and in combination with DFT calculations, the basic biosynthetic pathway of the sclerotiorin-type azaphilones was characterized. This study provided a good example for the discovery of new azaphilones and further uncovered the biosynthesis of these compounds.

Ultrasound-induced modifications of beef flavor characteristics during postmortem aging.

To investigate the effect of ultrasound treatment on the flavor profile of beef during postmortem aging, a comprehensive analysis of beef flavor was conducted at 0, 7, and 12 d of aging using sensory evaluation and electronic nose. Furthermore, the key volatile flavor compounds were identified using gas chromatography-mass spectrometry (GC-MS), and the odor activity value (OAV) was further evaluated. In addition, the primary pathway involved in flavor formation during beef aging after ultrasound treatment was explored. The results indicated that ultrasound enhanced the flavor profile of beef during postmortem aging by modifying the OAV of hexanal, heptanal, octanal, nonanal, decanal, (Z)-2-nonenal, dodecanal, pentanal, 1-octen-3-ol, octanoic acid, and 2-pentylfuran. Lipid oxidation was a crucial pathway through which ultrasound promoted the generation of volatile flavor compounds in beef, confirmed by the improved oxidation level of fatty acids, particularly monounsaturated ones. The study indicates that ultrasound technology can be regarded as an effective method for enhancing the beef flavor profile during postmortem aging.

Organophosphate esters uptake, translocation and accumulation in rice (Oryza sativa L.): impacts of lipid transporters and chemical properties.

To explore key factors involved in the uptake, translocation and accumulation of organophosphate esters (OPEs), computer simulation analysis and hydroponic experiments were executed. Lipid transporters with stocky-like active (SAC) cavities usually showed stronger binding affinities with the OPEs, especially when the SAC cavities belong to the Fish Trap model according to molecular docking. In our hydroponic trial, the binding affinity and gene expression of the lipid transporters and log Kow of the OPEs could be charged to the uptake, translocation and accumulation of the OPEs; however, these three factors played various important roles in roots and shoots. In detail, the effect of gene expression and binding affinity were stronger than log Kow in roots uptake and accumulation, but the result was the opposite in the shoots translocation. Transporters OsTIL and OsLTPL1 among all investigated transporters could play key roles in transporter-mediated OPE uptake, translocation and accumulation in the roots and shoots. OsMLP could be involved in the bidirected vertical translocation of the OPEs. OsLTP2 and OsLTP4 mainly acted as transporters of the OPEs in roots.

Biomechanical analysis of adjacent segments after correction surgery for adult idiopathic scoliosis: a finite element analysis.

The biomechanical aspects of adjacent segment degeneration after Adult Idiopathic Scoliosis (AdIS) corrective surgery involving postoperative changes in motion and stress of adjacent segments have yet to be investigated. The objective of this study was to evaluate the biomechanical effects of corrective surgery on adjacent segments in adult idiopathic scoliosis by finite element analysis. Based on computed tomography data of the consecutive spine from T1-S1 of a 28-year-old male patient with adult idiopathic scoliosis, a three-dimensional finite element model was established to simulate the biomechanics. Two posterior long-segment fixation and fusion operations were designed: Strategy A, pedicle screws implanted in all segments of both sides, and Strategy B, alternate screws instrumentation on both sides. The range of motion (ROM), Maximum von Mises stress value of intervertebral disc (IVD), and Maximum von Mises stress of the facet joint (FJ) at the fixation adjacent segment were calculated and compared with data of the preoperative AdIS model. Corrective surgery decreased the IVD on the adjacent segments, increased the FJ on the adjacent segments, and decreased the ROM of the adjacent segments. A greater decrease of Maximum von Mises stress was observed on the distal adjacent segment compared with the proximal adjacent segment. The decrease of Maximum von Mises stress and increment of Maximum von Mises stress on adjacent FJ in strategy B was greater than that in strategy A. Under the six operation modes, the change of the Maximum von Mises stress on the adjacent IVD and FJ was significant. The decrease in ROM in the proximal adjacent segment was greater than that of the distal adjacent segment, and the decrease of ROM in strategy A was greater than that in strategy B. This study clarified the biomechanical characteristics of adjacent segments after AdIS corrective surgery, and further biomechanical analysis of two different posterior pedicle screw placement schemes by finite element method. Our study provides a theoretical basis for the pathogenesis, prevention, and treatment of adjacent segment degeneration after corrective surgery for AdIS.

Microenvironment-Responsive Targeted Nanomedicine for a Collaborative Integration of Tumor Theranostics and Bone Defect Repair.

Despite advancements in breast cancer treatment, bone metastases remain a significant concern for advanced breast cancer patients. Current theranostics strategies face challenges in integrating tumor theranostics and bone formation. Herein, this work develops an activatable targeted nanomedicine AuMnCO@BSA-N3 (AMCBN) to enable a novel collaborative integration of second near-infrared (NIR-II) fluorescence imaging guided precise theranostics for breast cancer bone metastases and osteogenic microenvironment remolding. This strategy employs a chemical coordination between noble metal complex and metal carbonyl (MnCO), with surface modification of azide groups to enhance tumor affinity through passive and active targeting. The initiated respondent behavior of AMCBN by tumor microenvironment accelerate the degradation of coordinated MnCO, resulting in a rapid release of multifunctional agents for efficient chemodynamic therapy (CDT)/gas synergistic therapy. Meanwhile, the exceptional bone-binding properties enable the efficient and controlled release of Mn2+ ions and carbon monoxide (CO) in the bone microenvironment, thereby facilitating the expression of osteogenesis-related proteins and establishing a novel synchronous theranostics process for tumor-bone repair.

A landscape of methodology and implementation of adaptive designs in cancer clinical trials.

BACKGROUND: The use of adaptive designs in cancer trials has considerably increased worldwide in recent years, along with the release of various guidelines for their application. This systematic review aims to comprehensively summarize the key methodological and executive features of adaptive designs in cancer clinical trials. METHODS: A comprehensive search from PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials was conducted to screen eligible clinical trials that employed adaptive designs and were conducted in cancer patients. The methodological and executive characteristics of adaptive designs were the main measurements extracted. Descriptive analyses, primarily consisting of frequency and percentage, were employed to analyzed and reported the data. RESULTS: A total of 180 cancer clinical trials with adaptive designs were identified. The first three most common type of adaptive design was the group sequential design (n=114, 63.3 %), adaptive dose-finding design (n=22, 12.2 %), and adaptive platform design (n=16, 8.9 %). The results showed that 4.4 % (n=8) of trials conducted post hoc modifications, and around 29.4 % (n=53) did not provide the methods for controlling type I errors. Among phase II or above trials, 79.9 % (112/140) applied the surrogate endpoint as the primary outcome in these trials. Importantly, 27.2 % (49/180) of trials did not report clear information on the independent data monitoring committee (iDMC), and 13.3 % (n=24) without clear information on interim analyses. Interim analyses suggested 34.4 % (62/180) of trials being stopped for futility, 10.6 % (n=19) for efficacy, and 2.2 % (n=4) for safety concerns in the early stage. CONCLUSIONS: This study emphasizes adaptive designs in cancer trials face significant challenges in their design or strict implementation according to protocol, which might significantly compromise the validity and integrity of trials. It is thus important for researchers, sponsors, and policymakers to actively oversee and guide their application.

Four mutations identified in Chinese families with autosomal dominant congenital cataracts by next-generation sequencing.

BACKGROUND: Congenital cataracts, which can arise due to a combination of factors like environmental influences and genetic predisposition, significantly impact children's visual health globally. The occurrence rate of congenital cataracts varies from 0. 63 to 9.74 per 10,000 births. There are 7.4 instances per 10,000 children, with the highest occurrence seen in Asia. Symptoms of the disease include clouding of the lens and visual impairment. Timely identification of the condition plays a crucial role in the management and outlook of pediatric patients. OBJECTIVE: This investigation aimed to discover causative mutations in four separate Chinese family lineages. METHODS: The detailed clinical data and family history of four Chinese families with autosomal dominant congenital cataracts were carefully documented. Examination of the Whole Exome Sequencing was utilized to identify the genetic anomalies present in the familial cases. Subsequent validation of the identified mutations was carried out using PCR and Sanger sequencing. Following this, various computational predictive programs were utilized to evaluate how the mutations impact the structure and function of the protein. RESULTS: The sequencing results reveal four potential disease-causing mutations: c.436G > A (p.V146M) of CRYBB2 Family 1, c.26G > T (p.R9I) of GJA3 in family 2, c.227G > A (p.R76H) of GJA8 in family 3, c.-168G > T of FTL in family 4. Among them, the causative mutation in Family GJA3 is novel, and Family FTL is a rare cataract syndrome. These familial mutations showed complete co-segregation with the affected individuals, with no presence in unaffected family members or the 100 controls. Several bioinformatic prediction tools also support the likely pathogenicity of these mutations. CONCLUSION: Our findings expand the mutational and phenotypic spectrum of genes associated with congenital cataracts and provide clues to the pathogenesis of congenital cataracts. These data also demonstrate the importance of NGS technology for the molecular diagnosis of congenital cataract patients.

Investigating retinal explant models cultured in static and perfused systems to test the performance of exosomes secreted from retinal organoids.

BACKGROUND: Ex vivo cultures of retinal explants are appropriate models for translational research. However, one of the difficult problems of retinal explants ex vivo culture is that their nutrient supply needs cannot be constantly met. NEW METHOD: This study evaluated the effect of perfused culture on the survival of retinal explants, addressing the challenge of insufficient nutrition in static culture. Furthermore, exosomes secreted from retinal organoids (RO-Exos) were stained with PKH26 to track their uptake in retinal explants to mimic the efficacy of exosomal drugs in vivo. RESULTS: We found that the retinal explants cultured with perfusion exhibited significantly higher viability, increased NeuN+ cells, and reduced apoptosis compared to the static culture group at Days Ex Vivo (DEV) 4, 7, and 14. The perfusion-cultured retinal explants exhibited reduced mRNA markers for gliosis and microglial activation, along with lower expression of GFAP and Iba1, as revealed by immunostaining. Additionally, RNA-sequencing analysis showed that perfusion culture mainly upregulated genes associated with visual perception and photoreceptor cell maintenance while downregulating the immune system process and immune response. RO-Exos promoted the uptake of PKH26-labelled exosomes and the growth of retinal explants in perfusion culture. COMPARISON WITH EXISTING METHODS: Our perfusion culture system can provide a continuous supply of culture medium to achieve steady-state equilibrium in retinal explant culture. Compared to traditional static culture, it better preserves the vitality, provides better neuroprotection, and reduces glial activation. CONCLUSIONS: This study provides a promising ex vivo model for further studies on degenerative retinal diseases and drug screening.

Hydroxysafflor yellow A ameliorates alcohol-induced liver injury through PI3K/Akt and STAT3/NF-κB signaling pathways.

BACKGROUND: Alcohol-associated liver disease (ALD) is a prevalent liver ailment. It has escalated into a significant public health issue, imposing substantial burdens on medical, economic, and social domains. Currently, oxidative stress, inflammation, and apoptosis are recognized as crucial culprits in improving ALD. Consequently, mitigating these issues has emerged as a promising avenue for enhancing ALD. Hydroxysafflor yellow A (HSYA) is the main ingredient in safflower, showing excellent antioxidative stress, anti-inflammatory, and anti-apoptosis traits. However, there are limited investigations into the mechanisms by which HSYA ameliorates ALD PURPOSE: We investigated whether HSYA, a significant constituent of Asteraceae safflower, exerts antioxidant stress and attenuates inflammation and anti-apoptotic effects through PI3K/Akt and STAT3/NF-κB pathways, thereby ameliorating ALD METHODS: We established two experimental models: an ethanol-induced liver damage mouse model in vivo and a HepG2 cell alcohol injury model in vitro RESULTS: The results demonstrated that HSYA effectively ameliorated liver tissue damage, reduced levels of ALT, AST, LDL-C, TG, TC, and MDA, enhanced HDL-C levels, SOD and GSH activities, reduced ROS accumulation in cells, and activated the Nrf2 pathway, a transcription factor involved in antioxidant defense. By regulating the PI3K/Akt and STAT3/NF-κB pathways, HSYA exhibits notable antioxidative stress, anti-inflammatory, and anti-apoptotic effects, effectively impeding ALD's advancement. To further confirm the regulatory effect of HSYA on PI3K/Akt and downstream signaling pathways, the PI3K activator 740 Y-P was used and was found to reverse the downregulation of PI3K by HSYA CONCLUSION: This study supports the effectiveness of HSYA in reducing ALD by regulating the PI3K/Akt and STAT3/NF-κB pathways, indicating its potential medicinal value.

ChemFH: an integrated tool for screening frequent false positives in chemical biology and drug discovery.

High-throughput screening rapidly tests an extensive array of chemical compounds to identify hit compounds for specific biological targets in drug discovery. However, false-positive results disrupt hit compound screening, leading to wastage of time and resources. To address this, we propose ChemFH, an integrated online platform facilitating rapid virtual evaluation of potential false positives, including colloidal aggregators, spectroscopic interference compounds, firefly luciferase inhibitors, chemical reactive compounds, promiscuous compounds, and other assay interferences. By leveraging a dataset containing 823 391 compounds, we constructed high-quality prediction models using multi-task directed message-passing network (DMPNN) architectures combining uncertainty estimation, yielding an average AUC value of 0.91. Furthermore, ChemFH incorporated 1441 representative alert substructures derived from the collected data and ten commonly used frequent hitter screening rules. ChemFH was validated with an external set of 75 compounds. Subsequently, the virtual screening capability of ChemFH was successfully confirmed through its application to five virtual screening libraries. Furthermore, ChemFH underwent additional validation on two natural products and FDA-approved drugs, yielding reliable and accurate results. ChemFH is a comprehensive, reliable, and computationally efficient screening pipeline that facilitates the identification of true positive results in assays, contributing to enhanced efficiency and success rates in drug discovery. ChemFH is freely available via https://chemfh.scbdd.com/.

Challenging Aromaticity: Revealing a Thioesterase Domain in a Fungal Nonreducing Polyketide Synthase Governing the Production of 3-Methylene Isochromanone.

Thioesterase (TE) domain exerts a great influence over the structure of the final product and TE-released nonreduced polyketides (nrPKs) retain aromaticity. 3-Methylene isochromanones are lactones with a unique olefin at C3 that disrupts the aromaticity, whose biosynthetic details are speculative. Our study unveils the complete biosynthesis of ascochin, in which the construction of the 3-methylene isochromanone backbone is achieved by a nonreducing polyketide synthase (nrPKS) alone and two subsequent oxidations are involved. Intriguingly, the TEAscD serves as a gatekeeper to direct the product release toward formation of nonaromatic 3-methylene isochromanone, rather than the typical aromatic product.

Generation of New Synthons for Synthesis Through Activation of Nitromethane.

Nitromethane is used as a common solvent, stabilizer, and fuel additive. Nitromethane has also been used as a sustainable building block and convenient reagent in chemical synthesis. In this Minireview, we summarize the recent advances in activation of nitromethane, using nitromethane as the source of cyano group, nitrogen, methylamine, formyl group, C1, nitroso, and oxime.

NIR-II Absorption/Emission Dual Function Based 2D Targeted Nanotheranostics for Tunable Hydrogenothermal Therapy.

Photothermal therapy (PTT) is a promising approach for treating tumors that offers multiple advantages. Nevertheless, its practical use in clinical settings faces several limitations, such as suboptimal delivery efficiency, uneven heat distribution, and challenges in predicting optimal treatment duration. In addition, the localized hyperthermia generated by the PTT method to induce cell apoptosis can result in the production of excessive reactive oxygen species (ROS) and the release of inflammatory cytokines, which can pose a threat to the healthy tissues surrounding the tumor. To address the above challenges, this work designs an integrated H2 delivery nanoplatform for multimodal imaging H2 thermal therapy. The combination of the second near-infrared window (NIR-II) fluorescence imaging (FL) agent (CQ4T) and the photothermal and photoacoustic (PA) properties of Ti3C2 (TC) enables real-time monitoring of the tumor area and guides photothermal treatment. Simultaneously, due to the acid-responsive H2 release characteristics of the nanoplatform, H2 can be utilized for synergistic photothermal therapy to eradicate tumor cells effectively. Significantly, acting as an antioxidant and anti-inflammatory agent, Ti3C2-BSA-CQ4T-H2 (TCBCH) protects peritumoral normal cells from damage. The proposed technique utilizing H2 gas for combination therapies and multimodal imaging integration exhibits prospects for effective and secure treatment of tumors in future clinical applications.

Enhancing Molecular Property Prediction through Task-Oriented Transfer Learning: Integrating Universal Structural Insights and Domain-Specific Knowledge.

Precisely predicting molecular properties is crucial in drug discovery, but the scarcity of labeled data poses a challenge for applying deep learning methods. While large-scale self-supervised pretraining has proven an effective solution, it often neglects domain-specific knowledge. To tackle this issue, we introduce Task-Oriented Multilevel Learning based on BERT (TOML-BERT), a dual-level pretraining framework that considers both structural patterns and domain knowledge of molecules. TOML-BERT achieved state-of-the-art prediction performance on 10 pharmaceutical datasets. It has the capability to mine contextual information within molecular structures and extract domain knowledge from massive pseudo-labeled data. The dual-level pretraining accomplished significant positive transfer, with its two components making complementary contributions. Interpretive analysis elucidated that the effectiveness of the dual-level pretraining lies in the prior learning of a task-related molecular representation. Overall, TOML-BERT demonstrates the potential of combining multiple pretraining tasks to extract task-oriented knowledge, advancing molecular property prediction in drug discovery.

The optimal threshold of PD-L1 combined positive score to predict the benefit of PD-1 antibody plus chemotherapy for patients with HER2-negative gastric adenocarcinoma: a meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) combined with chemotherapy have become the first-line treatment of metastatic gastric and gastroesophageal adenocarcinomas (GEACs). This study aims to figure out the optimal combined positive score (CPS) cutoff value. METHODS: We searched for randomized phase III trials to investigate the efficacy of ICIs plus chemotherapy for metastatic GEACs compared with chemotherapy alone. Pooled analyses of hazard ratios (HRs) based on PD-L1 expression were performed. RESULTS: A total of six trials (KEYNOTE-062, KEYNOTE-590, KEYNOTE-859, ATTRACTION-04, CheckMate 649, and ORIENT-16) were included, comprising 5,242 patients. ICIs plus chemotherapy significantly improved OS (HR: 0.79, 95% CI 0.72-0.86 in global patients; HR: 0.75, 95% CI 0.57-0.98 in Asian patients) and PFS (HR: 0.74, 95% CI 0.68-0.82 in global patients; HR: 0.64, 95% CI 0.56-0.73 in Asian patients) compared with chemotherapy alone. The differences in OS (ratio of HR: 1.05, 95% CI 0.79-1.40; predictive value: - 5.1%) and PFS (ratio of HR: 1.16, 95% CI 0.98-1.36; predictive value: - 13.5%) were not statistically significant between the global and Asian patients. Subgroup analyses indicated that the optimal CPS threshold was at ≥ 5 for OS and ≥ 10 for PFS with the highest predictive values. CONCLUSIONS: The benefit derived from ICIs plus chemotherapy is similar between Asian and global GEAC patients. However, those with a PD-L1 CPS < 5 or CPS < 10 may not have significant benefits from ICIs therapy. Therefore, it is advisable to routinely assess PD-L1 expression in GEAC patients considered for ICIs treatment.

Elastic Properties of Low-Dimensional Single-Crystalline Dielectric Oxides through Controlled Large-Area Wrinkle Generation.

Freestanding single-crystalline SrTiO3 membranes, as high-κ dielectrics, hold significant promise as the gate dielectric in two-dimensional (2D) flexible electronics. Nevertheless, the mechanical properties of the SrTiO3 membranes, such as elasticity, remain a critical piece of the puzzle to adequately address the viability of their applications in flexible devices. Here, we report statistical analysis on plane-strain effective Young's modulus of large-area SrTiO3 membranes (5 × 5 mm2) over a series of thicknesses (from 6.5 to 32.2 nm), taking advantage of a highly efficient buckling-based method, which reveals its evident thickness-dependent behavior ranging from 46.01 to 227.17 GPa. Based on microscopic and theoretical results, we elucidate these thickness-dependent behaviors and statistical data deviation with a bilayer model, which consists of a surface layer and a bulk-like layer. The analytical results show that the ∼3.1 nm surface layer has a significant elastic softening compared to the bulk-like layer, while the extracted modulus of the bulk-like layer shows a variation of ∼40 GPa. This variation is considered as a combined contribution from oxygen deficiency presenting in SrTiO3 membranes, and the alignment between applied strain and the crystal orientation. Upon comparison of the extracted elastic properties and electrostatic control capability to those of other typical gate dielectrics, the superior performance of single-crystalline SrTiO3 membranes has been revealed in the context of flexible gate dielectrics, indicating the significant potential of their application in high-performance flexible 2D electronics.

A theoretical study of Lifshitz transition for 2H-TaS2.

Lifshitz transition was proposed to explain a change of the topology structure in a Fermi surface induced by continuous lattice deformation without symmetry breaking since 1960. It is well known that the anomalies of the kinetic coefficients (the coefficient of heat conduction and electrical conductivity, viscosity, sound absorption, etc.) are usually closely connected with the Lifshitz transition behavior. 2H-TaS2 is a typical representative to study its anomalies of temperature dependence of heat capacity, resistivity, Hall effect, and magnetic susceptibility. Its geometrical structure of the charge density wave (CDW) phase and layer number dependence of carrier-sign alternation upon cooling in the Hall measurements have not been well understood. The geometrical structure (T-Ts) of the CDW phase was predicted through first principles calculations for bulk and mono-layer 2H-TaS2. Driven by electron-lattice coupling, Ta atoms contract to form a partially gapped CDW phase. The CDW phase has a larger average interlayer separation of S-S atoms in the adjacent two layers compared with the metal phase, which results in a weaker chemical bonding among S-S atoms in the adjacent two layers and then a narrower bandwidth of the energy band. The narrower bandwidth of the energy band leads to a larger density of states (DOS) in the out-of-plane direction above the Fermi level for the CDW phase. As the Fermi level continually drops from the DOS region with a negative slope to that with a positive slope on cooling, the reversal of the p → n type carrier and the pocket-vanishing-type Lifshitz transition occur in the bulk 2H-TaS2. However, the Fermi level slightly drops by 6 meV and happens to be at the positions of pseudo band gaps, so the reduction of in-plane DOS and total DOS is responsible for the always p-type carrier in the mono-layer samples. Our CDW vector of the k-space separation between two saddle points is QSP ≈ 0.62 GK and can provide a theoretical support for the "saddle-point" CDW mechanism proposed by Rice and Scott. Our theoretical explanation gives a new understanding of both Lifshitz transition for symmetry breaking and reversal for the p-n carrier sign in the Hall measurements in various two-dimensional transition metal disulfides.

Single-Cell Transcriptomic Profiling Unveils Dynamic Immune Cell Responses during Haemonchus contortus Infection.

BACKGROUND: Haemonchus contortus is a parasite widely distributed in tropical, subtropical, and warm temperate regions, causing significant economic losses in the livestock industry worldwide. However, little is known about the genetics of H. contortus resistance in livestock. In this study, we monitor the dynamic immune cell responses in diverse peripheral blood mononuclear cells (PBMCs) during H. contortus infection in goats through single-cell RNA sequencing (scRNA-Seq) analysis. METHODS AND RESULTS: A total of four Boer goats, two goats with oral infection with the L3 larvae of H. contortus and two healthy goats as controls, were used in the animal test. The infection model in goats was established and validated by the fecal egg count (FEC) test and qPCR analysis of the gene expression of IL-5 and IL-6. Using scRNA-Seq, we identified seven cell types, including T cells, monocytes, natural killer cells, B cells, and dendritic cells with distinct gene expression signatures. After identifying cell subpopulations of differentially expressed genes (DEGs) in the case and control groups, we observed the upregulation of multiple inflammation-associated genes, including NFKBIA and NFKBID. Kyoto Encyclopedia of the Genome (KEGG) enrichment analysis revealed significant enrichment of NOD-like receptor pathways and Th1/Th2 cell differentiation signaling pathways in CD4 T cells DEGs. Furthermore, the analysis of ligand-receptor interaction networks showed a more active state of cellular communication in the PBMCs from the case group, and the inflammatory response associated MIF-(CD74 + CXCR4) ligand receptor complex was significantly more activated in the case group, suggesting a potential inflammatory response. CONCLUSIONS: Our study preliminarily revealed transcriptomic profiling characterizing the cell type specific mechanisms in host PBMCs at the single-cell level during H. contortus infection.

Highly Efficient and Stable Organic Photovoltaic Cells for Underwater Applications.

Organic photovoltaic (OPV) technology holds tremendous promise as a sustainable power source for underwater off-grid systems. However, research on underwater OPV cells is relatively scarce. Here, this gap is addressed by focusing on the exploration and development of OPV cells specifically designed for underwater applications. An acceptor, named ITO-4Cl, with excellent water resistance, is rationally designed and synthesized. Benefiting from its low energetic disorder and an absorption spectrum well-suited to the underwater environment, the ITO-4Cl-based OPV cell achieves an unprecedented power conversion efficiency (PCE) of over 25.6% at a water depth of 1 m. Additionally, under 660 nm laser irradiation, the cell demonstrates a notable PCE of 31.6%, indicating its potential for underwater wireless energy transfer. Due to the mitigation of thermal effects from solar irradiation, the lifetime of the ITO-4Cl-based OPV cell exceeds 7000 h. Additionally, a flexible OPV cell is fabricated that maintains its initial PCE even under exposure to high pressures of 5 MPa. A 32.5 cm2 flexible module achieves an excellent PCE of 17%. This work fosters a deeper understanding of underwater OPV cells and highlights the promising prospects of OPV cells for underwater applications.