Rhodium-catalyzed three-component C(sp3)/C(sp2)-H activation enabled by a two-fold directing group strategy.

Rh-catalyzed three-component C(sp3)/C(sp2)-H activation has been achieved through a two-directing group strategy. This protocol provides a convenient and efficient pathway for the construction of diverse 8-alkyl quinoline derivatives in one-pot. Furthermore, mechanistic studies revealed that the first C-H amidation was significantly faster than the sequential C-H alkylation.

A CARM1 Inhibitor Potently Suppresses Breast Cancer Both In Vitro and In Vivo.

CARM1, belonging to the protein arginine methyltransferase (PRMT) family, is intricately associated with the progression of cancer and is viewed as a promising target for both cancer diagnosis and therapy. However, the number of specific and potent CARM1 inhibitors is limited. We herein discovered a CARM1 inhibitor, iCARM1, that showed better specificity and activity toward CARM1 compared to the known CARM1 inhibitors, EZM2302 and TP-064. Similar to CARM1 knockdown, iCARM1 suppressed the expression of oncogenic estrogen/ERα-target genes, whereas activated type I interferon (IFN) and IFN-induced genes (ISGs) in breast cancer cells. Consequently, iCARM1 potently suppressed breast cancer cell growth both in vitro and in vivo. The combination of iCARM1 with either endocrine therapy drugs or etoposide demonstrated synergistic effects in inhibiting the growth of breast tumors. In summary, targeting CARM1 by iCARM1 effectively suppresses breast tumor growth, offering a promising therapeutic approach for managing breast cancers in clinical settings.

Identification of Microorganism in Infected Wounds by Positively Charged Selective Sensor Array and Deep Learning Algorithm.

Microorganism are ubiquitous and intimately connected with human health and disease management. The accurate and fast identification of pathogenic microorganisms is especially important for diagnosing infections. Herein, three tetraphenylethylene derivatives (S-TDs: TBN, TPN, and TPI) featuring different cationic groups, charge numbers, emission wavelengths, and hydrophobicities were successfully synthesized. Benefiting from distinct cell wall binding properties, S-TDs were collectively utilized to create a sensor array capable of imaging various microorganisms through their characteristic fluorescent signatures. Furthermore, the interaction mechanism between S-TDs and different microorganisms was explored by calculating the binding energy between S-TDs and cell membrane/wall constituents, including phospholipid bilayer and peptidoglycan. Using a combination of the fluorescence sensor array and a deep learning model of residual network (ResNet), readily differentiation of Gram-negative bacteria (G-), Gram-positive bacteria (G+), fungi, and their mixtures was achieved. Specifically, by extensive training of two ResNet models with large quantities of images data from 14 kinds of microorganism stained with S-TDs, identification of microorganism was achieved at high-level accuracy: over 92.8% for both Gram species and antibiotic-resistant species, with 90.35% accuracy for the detection of mixed microorganism in infected wound. This novel method provides a rapid and accurate method for microbial classification, potentially aiding in the diagnosis and treatment of infectious diseases.

Pore-Forming Toxin-Driven Recovery of Peroxidase-Mimicking Activity in Biomass Channels for Label-Free Electrochemical Bacteria Sensing.

The development of sensitive, selective, and rapid methods to detect bacteria in complex media is essential to ensuring human health. Virulence factors, particularly pore-forming toxins (PFTs) secreted by pathogenic bacteria, play a crucial role in bacterial diseases and serve as indicators of disease severity. In this study, a nanochannel-based label-free electrochemical sensing platform was developed for the detection of specific pathogenic bacteria based on their secreted PFTs. In this design, wood substrate channels were functionalized with a Fe-based metal-organic framework (FeMOF) and then protected with a layer of phosphatidylcholine (PC)-based phospholipid membrane (PM) that serves as a peroxidase mimetic and a channel gatekeeper, respectively. Using Staphylococcus aureus (S. aureus) as the model bacteria, the PC-specific PFTs secreted by S. aureus perforate the PM layer. Now exposed to the FeMOF, uncharged 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) molecules in the electrolyte undergo oxidation to cationic products (ABTS•+). The measured transmembrane ionic current indicates the presence of S. aureus and methicillin-resistant S. aureus (MRSA) with a low detection limit of 3 cfu mL-1. Besides excellent specificity, this sensing approach exhibits satisfactory performance for the detection of target bacteria in the complex media of food.

Phosphate phosphors with anti-thermal quenching properties for urban ecological lighting.

White light-emitting diode (LED) for night lighting disrupts photoperiod in plants, which affects the plant's photosynthesis. Therefore, it is necessary to find a new type of white LED with little effect on plant photosynthesis. In this study, a series of phosphate phosphors Ca9NaY2/3(PO4)7:Dy3+ (CNYP:Dy3+) were synthesized. Cation Li+ substitute Na+ were used to improve the luminescence properties of CNYP:Dy3+ phosphor. The CNYP:Dy3+ phosphor exhibits visible white light emission with emission peaks at 480 nm (blue light) and 570 nm (yellow light) excited by the near ultraviolet light 350 nm. The optimal concentration of Dy3+ was 0.10 mol, and the mechanism of concentration quenching was evaluated as energy migration among the nearest or next-nearest Dy3+. The substitution of Na+ by Li+ of CNYP:0.10Dy3+ improves the internal quantum efficiency from 30.24 % to 59.05 %, and presents good near-zero thermal quenching performance at 423 K. To assess the suitability of this phosphor for urban ecological lighting, the spectrum resemblance (SR) index between the electroluminescence spectrum of the prepared pc-LED and the absorption spectra of chlorophyll a and b was evaluated as 6.63 % and 18.61 %, respectively. This work exhibits a feasible scheme for the development of urban ecological lighting.

Electro-Induced Phase Transformation of a Conductive Metal-Organic Framework Film for Nonlinear Optical Switching.

Achieving metal-organic frameworks (MOFs) with nonlinear optical (NLO) switching is profoundly important. Herein, the conductive MOFs Cu-TCNQ phase I (Ph-I) and phase II (Ph-II) films were prepared using the liquid-phase-epitaxial layer-by-layer spin-coating method and steam heating method, respectively. Electronic experiments showed that the Ph-II film could be changed into the Ph-I film under an applied electric field. The third-order NLO results revealed that the Ph-I film had a third-order nonlinear reverse saturation absorption (RSA) response and the Ph-II film displayed a third-order nonlinear saturation absorption (SA) response. With increases in the heating time and applied voltage, the third-order NLO response realized the reversible transition between SA and RSA. The theoretical calculations indicated that Ph-I possessed more interlayer charge transfer, resulting in a third-order nonlinear RSA response that was stronger than that of Ph-II. This work applies phase-transformed MOFs to third-order NLO switching and provides new insights into the nonlinear photoelectric applications of MOFs.

Dietary protein restriction regulates skeletal muscle fiber metabolic characteristics associated with the FGF21-ERK1/2 pathway.

Under conditions of dietary amino acid balance, decreasing the dietary crude protein (CP) level in pigs has a beneficial effect on meat quality. To further elucidate the mechanism, we explored the alteration of muscle fiber characteristics and key regulators related to myogenesis in the skeletal muscle of pigs fed a protein restricted diet. Compared to pigs fed a normal protein diet, dietary protein restriction significantly increased the slow-twitch muscle fiber proportion in skeletal muscle, succinic dehydrogenase (SDH) activity, the concentrations of ascorbate, biotin, palmitoleic acid, and the ratio of s-adenosylhomocysteine (SAM) to s-adenosylhomocysteine (SAH), but the fast-twitch muscle fiber proportion, lactate dehydrogenase (LDH) activity, the concentrations of ATP, glucose-6-phosphate, SAM, and SAH in skeletal muscle, and the ratio of serum triiodothyronine (T3) to tetraiodothyronine (T4) were decreased. In conclusion, we demonstrated that dietary protein restriction induced skeletal muscle fiber remodeling association the regulation of FGF21-ERK1/2-mTORC1 signaling in weaned piglets.

Selenomethionine Alleviates Deoxynivalenol-Induced Oxidative Injury in Porcine Intestinal Epithelial Cells Independent of MAPK Pathway Regulation.

Deoxynivalenol (DON) is a prevalent contaminant in feed and food, posing a serious threat to the health of both humans and animals. The pig stands as an ideal subject for the study of DON due to its recognition as the most susceptible animal to DON. In this study, the IPEC-J2 cells were utilized as an in vitro model to explore the potential of SeMet in alleviating the intestinal toxicity and oxidative injury in intestinal epithelial cells when exposed to DON. Cells were treated either with or without 4.0 µM SeMet, in combination with or without a simultaneous treatment with 0.5 µg/mL DON, for a duration of 24 h. Then, cells or related samples were analyzed for cell proliferation, lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) level, gene expressions, and protein expressions. The results showed that SeMet mitigated the cellular toxicity caused by DON, evidenced by elevated cell proliferation and the reduced LDH release of IPEC-J2 cells in the SeMet + DON group vs. the DON group. Moreover, the SeMet treatment markedly promoted antioxidant functions and decreased the oxidative injury in IPEC-J2 cell, which is indicated by the decreased ROS level and up-regulated mRNA levels of GPX1, TXNRD1, Nrf2, and GCLC in IPEC-J2 cells in the SeMet + DON group vs. the DON group. However, in both the absence and presence of exposure to DON, the SeMet treatment did not affect the protein expression of MAPK (JNK, Erk1/2, and P38) and phosphorylated MAPK (p-JNK, p-Erk1/2, and p-P38) in IPEC-J2 cells. Collectively, SeMet alleviated the DON-induced oxidative injury in porcine intestinal epithelial cells independent of the MAPK pathway regulation.

When pyro(ptosis) meets palm(itoylation).

Pyroptosis, a programmed cell death process, is vital for the immune response against microbial infections and internal danger signals. Recent studies have highlighted the importance of protein palmitoylation, a modification that involves attaching palmitate to cysteine residues, in regulating key proteins involved in pyroptosis. Palmitoylation of cGAS at residue C474 by ZDHHC18 affects its enzymatic activity and DNA binding ability. Similarly, ZDHHC9 promotes cGAS activity through palmitoylation at residues C404/405. NLRP3 palmitoylation at residue C844, mediated by ZDHHC12, impacts its stability and interactions with other proteins, crucial for activating the NLRP3 inflammasome and triggering inflammation. However, the role of ZDHHC5 in NLRP3 palmitoylation remains uncertain due to conflicting findings. Palmitoylation at C88/91 is essential for STING activation and induction of type I interferons. It modulates the formation of multimeric complexes and downstream signaling pathways. GSDMD palmitoylation at C191 is necessary for pore formation and membrane translocation, while GSDME palmitoylation at C407/408 is associated with drug-induced pyroptosis. Moreover, palmitoylation of NOD1 and NOD2 influences their membrane recruitment and immune signaling pathways in response to bacterial peptidoglycans, acting as upstream regulators of pyroptosis. This review summarizes the important roles for palmitoylation in regulating the function of key pyroptosis-related proteins, shedding light on the intricate mechanisms governing immune responses and inflammation.

Identification of Pancreatic Metastasis Cells and Cell Spheroids by the Organelle-Targeting Sensor Array.

Pancreatic cancer is a highly malignant and metastatic cancer. Pancreatic cancer can lead to liver metastases, gallbladder metastases, and duodenum metastases. The identification of pancreatic cancer cells is essential for the diagnosis of metastatic cancer and exploration of carcinoma in situ. Organelles play an important role in maintaining the function of cells, the various cells show significant differences in organelle microenvironment. Herein, six probes are synthesized for targeting mitochondria, lysosomes, cell membranes, endoplasmic reticulum, Golgi apparatus, and lipid droplets. The six fluorescent probes form an organelles-targeted sensor array (OT-SA) to image pancreatic metastatic cancer cells and cell spheroids. The homology of metastatic cancer cells brings the challenge for identification of these cells. The residual network (ResNet) model has been proven to automatically extract and select image features, which can figure out a subtle difference among similar samples. Hence, OT-SA is developed to identify pancreatic metastasis cells and cell spheroids in combination with ResNet analysis. The identification accuracy for the pancreatic metastasis cells (> 99%) and pancreatic metastasis cell spheroids (> 99%) in the test set is successfully achieved respectively. The organelles-targeting sensor array provides a method for the identification of pancreatic cancer metastasis in cells and cell spheroids.

Functional interaction of abnormal beta and gamma oscillations on bradykinesia in parkinsonian rats.

Bradykinesia, a debilitating symptom characterized by impaired movement initiation and reduced speed in Parkinson's disease (PD), is associated with abnormal oscillatory activity in the motor cortex-basal ganglia circuit. We investigated the interplay between abnormal beta and gamma oscillations in relation to bradykinesia in parkinsonian rats. Our findings showed reduced movement activities in parkinsonian rats, accompanied by enhanced high beta oscillations in the motor cortex, which are closely associated with movement transitional difficulties. Additionally, gamma oscillations correlated with movement velocity in control rats but not in parkinsonian rats. We observed selective coupling between high beta oscillation phase and gamma oscillation amplitude in PD, as well as cortical high beta-broadband gamma phase-amplitude coupling (PAC) negatively influencing locomotor activities in control and PD rats. These findings suggest a collaborative role of cortical beta and gamma oscillations in facilitating movement execution, with beta oscillations being linked to movement initiation and gamma oscillations associated with movement speed. Importantly, the aberrant alterations of these oscillations are closely related to the development of bradykinesia. Furthermore, PAC hold promise as a biomarker for comprehensive assessment of movement performance in PD.

NaNO3-Promoted MgO-Based Adsorbents Prepared from Bischofite for CO2 Capture: Experimental and Density Functional Theory Study.

MgO has broad application potential in CO2 capture at intermedium temperatures. In this paper, the effects of NaNO3 doping on the properties of MgO prepared by using waste bischofite as the raw material were investigated to improve the performance of the CO2 capture. MgO-doped NaNO3 exhibited excellent CO2 capture performance at 320 °C with a maximum adsorption capacity of 36.62 wt %. MgO-doped NaNO3 has good cycling stability after 10 adsorption-desorption cycle experiments. In addition, CO2 adsorption on pure MgO and MgO-NaNO3 surfaces was investigated in accordance with density functional theory. Calculation results show that doping with NaNO3 allows more electrons to be transferred from the MgO substrate to the CO2 molecule. MgO-doped NaNO3 can lead to an increase in adsorption energy, resulting in a more stable structure after adsorption and thereby promoting adsorption. The result of this study provides an effective method for the comprehensive utilization of salt lake resources.

Evaluation of neck control strategies for oral squamous cell carcinoma of stage I: Neck dissection or potential immunotherapy.

The neck control strategies of early-stage oral squamous cell carcinoma (OSCC) patients with clinical node-negative neck remain uncertain. These patients could be benefit from elective neck dissection (END) alongside primary tumor excision; but current evidence on END versus observation for OSCC of stage I only is not yet analyzed collectively in detail. Herein, this short communication aimed to evaluate the neck control strategies of stage I OSCC, mainly END versus observation. A total of 740 patients with stage I OSCC, comprising 434 underwent END and 306 received observation, were identified from literature. The results showed that stage I OSCC patients would not be benefit from END based on the analysis of neck nodal recurrence and overall survival. An ideal strategy would likely be to avoid neck dissection for stage I OSCC patients with N0 neck. Immune checkpoint therapy is such a potential strategy, which aims at eliciting potent antitumor immune responses within lymph nodes hold promise for treating patients with early-stage OSCC and may prove more efficacious than lymphadenectomy in a variety of scenarios. Consequently, neck dissection for stage I OSCC could be approached with caution, particularly in patients receiving immune checkpoint therapy.

Ion Migration in Lead-Halide Perovskites: Cation Matters.

Metal halide perovskites exhibit remarkable properties for optoelectronic applications, yet their susceptibility to ion migration poses challenges for device stability. Previous research has predominantly focused on the migration of the halide ions. However, the migration of cations, which also has a significant influence on the device performance, is largely overlooked. In this Perspective, we review the migration of cations and their impacts on perovskite materials and devices. Special attention shall be devoted to recent insights into the migration of L-site organic cations in 2D/3D perovskites. We outline inspirations and directions for further research into the cation migration of perovskites, highlighting new possibilities in advancing perovskite optoelectronics.

Research Note: Preliminary functional analysis of EGF-like domains of Eimeria tenella microneme protein 7 identified in sporozoites and merozoites.

Eimeria tenella, an obligate intracellular apicomplexan parasite, is the major causative agent of chicken coccidiosis. Some epidermal growth factor (EGF)-like domain-containing proteins of other members of apicomplexan parasites have been reported to contribute to parasite survival. To date, however, EGF-like domain-containing proteins of E. tenella are not well studied. In this study, a gene fragment that encodes 4 EGF-like domains of E. tenella microneme protein 7 (EGF-EtMIC7) was amplified and expressed using an Escherichia coli expression system. Following generation of polyclonal antibodies that recognize recombinant EGF-EtMIC7 (rEGF-EtMIC7), the expression of EtMIC7 in sporozoites and merozoites was examined. Moreover, its roles in cellular regulation were investigated. The native EtMIC7 in E. tenella sporozoites and merozoites was detected by using Western blot and indirect immunofluorescence assays. rEGF-EtMIC7 could activate Akt, whereas blockade of EGF receptor (EGFR) failed to induce Akt phosphorylation. Compared with the control group, LMH cells treated with rEGF-EtMIC7 showed increased cell proliferation and expressed higher levels of B cell leukemia/lymphoma 2 (BCL-2). These findings contribute to the better understanding of parasite-host interactions at the molecular level during E. tenella infection.

Supramolecular host-guest interaction triggered dye extraction from metal-organic framework for dual-mode ATP sensing from serum.

Adenosine triphosphate (ATP) universally exists in all living organisms and holds a paramount role as a fundamental energy molecule in daily life. The abnormal concentration of ATP is closely related to many diseases, making the highly efficient detection of ATP very urgent. In this study, a dual-mode sensing system was developed to detect ATP sensitively and selectively via both DPV and fluorescence (FL) techniques, based on the strong interaction of ATP and Zn (II) nodes of zeolitic imidazolate framework-90 (ZIF-90). The disassembly of ZIF-90 further induced the subsequent release of pre-loaded rhodamine B (RhB). Benefitting from the robust host-guest recognition of ß-cyclodextrin (ß-CD) towards RhB, an enzyme-free and highly specific DPV detection strategy was established with the linear detecting range of 10.0-1.0 × 108 pM and the limit of detection (LOD) as low as 0.13 pM. Meanwhile, the FL sensing mode based on RhB exhibits comparable sensing performance with the linearity range of 10.0-1.0 × 107 pM and the LOD of 0.29 pM. Furthermore, the enzyme-free ATP sensing system exhibit outstanding long-term storage stability. The two-mode sensing platform was successfully applied to detect the ATP in human serum samples with the yielded result highly agree with the results of commercial ELISA kits. This dual-mode sensing platform is inspiring and paves the road for developing high-performance biosensor, demonstrating enormous potential for vitro diagnosis and practice clinic.

Precise Surface Profiling at the Nanoscale Enabled by Deep Learning.

Surface topography, or height profile, is a critical property for various micro- and nanostructured materials and devices, as well as biological systems. At the nanoscale, atomic force microscopy (AFM) is the tool of choice for surface profiling due to its capability to noninvasively map the topography of almost all types of samples. However, this method suffers from one drawback: the convolution of the nanoprobe's shape in the height profile of the samples, which is especially severe for sharp protrusion features. Here, we report a deep learning (DL) approach to overcome this limit. Adopting an image-to-image translation methodology, we use data sets of tip-convoluted and deconvoluted image pairs to train an encoder-decoder based deep convolutional neural network. The trained network successfully removes the tip convolution from AFM topographic images of various nanocorrugated surfaces and recovers the true, precise 3D height profiles of these samples.

Designed metal-organic π-clusters combining the aromaticity of the metal cluster and ligands for a third-order nonlinear optical response.

The pivotal role of clusters and aromaticity in chemistry is undeniable, but there remains a gap in systematically understanding the aromaticity of metal-organic clusters. Herein, this article presents a novel metal-organic π-cluster, melding both metal-organic chemistry and aromaticity, to guide the construction of structurally stable Os-organic π-clusters. An in-depth analysis of these clusters reveals their bonding attributes, π-electronic composition, and origins of aromaticity, thereby confirming their unique metal-organic π-cluster properties. Furthermore, the Os5 cluster exhibits a promising third-order nonlinear optical (NLO) response, attributable to its narrow band gap and uniform electron/hole distribution, suggesting its potential as an optical switching material. This research introduces a fresh perspective on clusters, centered on delocalization, and broadens the domain of aromaticity studies. It also presents a novel method for designing efficient third-order NLO materials through consideration of the structure-activity relationship.

Schizophrenia mediating the effect of smoking phenotypes on antisocial behavior: A Mendelian randomization analysis.

AIMS: Previous studies have indicated that smoking is linked to an increased risk of developing schizophrenia, and that individuals with schizophrenia are more prone to engaging in antisocial behavior. However, the causal effects of smoking behaviors on antisocial behavior and the potential mediating role of schizophrenia remains largely unclear. METHODS: In the present study, using the summary data from genome wide association studies of smoking phenotypes (N = 323,386-805,431), schizophrenia (Ncases = 53,386, Ncontrols = 77,258), and antisocial behavior (N = 85,359), we assessed bidirectional causality between smoking phenotypes and schizophrenia by the Mendelian randomization (MR) approach. Using a two-step MR approach, we further examined whether causal effects of smoking phenotypes/schizophrenia on antisocial behavior were mediated by schizophrenia/smoking phenotypes. RESULTS: The results showed that smoking initiation (SmkInit) and age of smoking initiation (AgeSmk) causally increase the risk of schizophrenia (SmkInit: OR = 2.06, 95% CI = 1.77-2.39, p = 4.36 × 10-21 ; AgeSmk: OR = 0.32, 95% CI = 0.16-0.62, p = 8.11 × 10-4 , Bonferroni corrected). However, there was no causal effect that liability to schizophrenia leads to smoking phenotypes. MR evidence also revealed causal influences of SmkInit and the amount smoked (CigDay) on antisocial behavior (SmkInit: OR = 1.28, 95% CI = 1.17-1.41, p = 2.53 × 10-7 ; CigDay: OR = 1.16, 95% CI = 1.06-1.27, p = 1.60 × 10-3 , Bonferroni corrected). Furthermore, the mediation analysis indicated that the relationship between SmkInit and antisocial behavior was partly mediated by schizophrenia (mediated proportion = 6.92%, 95% CI = 0.004-0.03, p = 9.66 × 10-3 ). CONCLUSIONS: These results provide compelling evidence for taking smoking interventions as a prevention strategy for schizophrenia and its related antisocial behavior.

OsALB3 Is Required for Chloroplast Development by Promoting the Accumulation of Light-Harvesting Chlorophyll-Binding Proteins in Rice.

ALBINO3 (ALB3) protein functions in the insertion and assembly of thylakoid membrane protein complexes and plays a critical role for chloroplast development in Arabidopsis. However, the biological function of ALB3 homologs in rice, OsALB3, remains elusive. Here, we identified a rice mutant, yellow leaf and lethal1 (yll1), that displayed yellow leaves and died at the seedling stage. The content of chlorophyll in yll1, compared with wild type, was significantly decreased. Transmission electron microscopy observation shows that the chloroplast of yll1 lacks thylakoid membranes. The causal mutation, which is located in OsALB3, was isolated by Mutmap+ combined with a simple mutation filtering process. Knockout of OsALB3 leads to yellow leaves and seedling lethality, mimicking the phenotype of yll1. OsALB3 is widely expressed and OsALB3 is chloroplast-localized. Moreover, the content of light-harvesting chlorophyll-binding proteins in yll1 is reduced. Together, our study demonstrated the essential role of OsALB3 in chloroplast development and provided clues to the possible conserved molecular function of ALB3 in rice.