Remote Activation of H-H Bonds by Platinum in Dilute Alloy Catalysts.

With heterogeneous catalysts, chemical promotion takes place at their surfaces. Even in the case of single-atom alloys, where small quantities of a reactive metal are dispersed within the main host, it is assumed that both elements are exposed and available to bond with the reactants. Here, we show, on the basis of in situ X-ray absorption spectroscopy data, that in alloy catalysts made from Pt highly diluted in Cu the Pt atoms are located at the inner interface between the metal nanoparticles and the silica support instead. Kinetic experiments indicated that these catalysts still display better selectivity for the hydrogenation of unsaturated aldehydes to unsaturated alcohols than the pure metals. Density functional theory calculations corroborated the stability of Pt at the metal-support interface and explained the catalytic performance as being due to a remote lowering of the activation barrier for the dissociation of H2 at Cu sites by the internal Pt atoms.

Thermal Conductivity and Sintering Mechanism of Aluminum/Diamond Composites Prepared by DC-Assisted Fast Hot-Pressing Sintering.

A novel DC-assisted fast hot-pressing (FHP) powder sintering technique was utilized to prepare Al/Diamond composites. Three series of orthogonal experiments were designed and conducted to explore the effects of sintering temperature, sintering pressure, and holding time on the thermal conductivity (TC) and sintering mechanism of an Al-50Diamond composite. Improper sintering temperatures dramatically degraded the TC, as relatively low temperatures (≤520 °C) led to the retention of a large number of pores, while higher temperatures (≥600 °C) caused unavoidable debonding cracks. Excessive pressure (≥100 MPa) induced lattice distortion and the accumulation of dislocations, whereas a prolonged holding time (≥20 min) would most likely cause the Al phase to aggregate into clusters due to surface tension. The optimal process parameters for the preparation of Al-50diamond composites by the FHP method were 560 °C-80 MPa-10 min, corresponding to a density and TC of 3.09 g cm-3 and 527.8 W m-1 K-1, respectively. Structural defects such as pores, dislocations, debonding cracks, and agglomerations within the composite strongly enhance the interfacial thermal resistance (ITR), thereby deteriorating TC performance. Considering the ITR of the binary solid-phase composite, the Hasselman-Johnson model can more accurately predict the TC of Al-50diamond composites for FHP technology under an optimal process with a 3.4% error rate (509.6 W m-1 K-1 to 527.8 W m-1 K-1). The theoretical thermal conductivity of the binary composites estimated by data modeling (Hasselman-Johnson Model, etc.) matches well with the actual thermal conductivity of the sintered samples using the FHP method.

The Effect Mechanism of N6-adenosine Methylation (m6A) in Melatonin Regulated LPS-induced Colon Inflammation.

Colon inflammation is characterized by disturbances in the intestinal microbiota and inflammation. Melatonin (Mel) can improve colon inflammation. However, the underlying mechanism remains unclear. Recent studies suggest that m6A methylation modification may play an important role in inflammatory responses. This study aimed to explore the effects of melatonin and LPS-mediated m6A methylation on colon inflammation. Our study found that melatonin inhibits M1 macrophages, activates M2 macrophages, inhibit the secretion of pro-inflammatory factors, maintain colon homeostasis and improves colon inflammation through MTNR1B. In addition, the increased methylation level of m6A is associated with the occurrence of colon inflammation, and melatonin can also reduce the level of colon methylation to improve colon inflammation. Among them, the main methylated protein METTL3 can be inhibited by melatonin through MTNR1B. In a word, melatonin regulates m6A methylation by improving abnormal METTL3 protein level to reshape the microflora and activate macrophages to improve colon inflammation, mainly through MTNR1B.

PRG ameliorates cognitive impairment in Alzheimer's disease mice by regulating ß-amyloid and targeting the ERK pathway.

BACKGROUND: PRG is derived from Phellinus ribis and is a homogeneous polysaccharide with well-defined structural information. PRG was found to have significant in vitro neurotrophic and neuroprotective activities. Thus, PRG might be a potential treatment for Alzheimer's disease. However, the related mechanisms of action are still unclear, so deeper in vivo experimental validation and the potential mechanisms need to be investigated. PURPOSE: The effects of PRG on AD mice were investigated using Senescence-accelerated SAMP8 mice as an AD model to elucidate the crucial molecular mechanisms. METHODS: PRG was obtained from Phellinus ribis by water-alcohol precipitation, column chromatography, and ultrafiltration. The Morris water maze and novel object recognition behavioral assays were used to evaluate the effects of PRG in AD mice. Nissl staining, the TUNEL apoptosis assay, and Golgi staining were used to assess brain neuronal cell damage, apoptosis, and neuronal status. Enzyme-linked immunosorbent assays, Western blotting, and immunofluorescence were used to explore the impacts of correlated factors and protein pathways under relevant mechanisms. RESULTS: The findings suggest that PRG improved learning ability and spatial memory capacity in SAMP8 mice. PRG hastened the disintegration of ß-amyloid, reduced the content and abnormal accumulation of the toxic Aß1-42 protein, and decreased apoptosis. PRG activated the BDNF/ERK/CREB signaling pathway through a cascade, exerted neurotrophic effects, regulated cell proliferation and differentiation, increased neuronal dendritic branching and spine density, and improved synaptic plasticity. CONCLUSION: PRG promoted ß-amyloid degradation to reduce neuronal damage and apoptosis. It exerted neurotrophic effects by activating the BDNF/ERK/CREB pathway, promoting neuronal dendritic branching and dendritic spine growth, regulating cell proliferation and differentiation, and improving synaptic plasticity, which improved AD. Taken together, as a novel natural active polysaccharide with a well-defined structure, PRG affected AD symptoms in senescence-accelerated mice by interacting with multiple targets. The results indicate that PRG is a promising potential anti-AD drug candidate.

Single-Cell multiomics reveals ENL mutation perturbs kidney developmental trajectory by rewiring gene regulatory landscape.

Cell differentiation during organogenesis relies on precise epigenetic and transcriptional control. Disruptions to this regulation can result in developmental abnormalities and malignancies, yet the underlying mechanisms are not well understood. Wilms tumors, a type of embryonal tumor closely linked to disrupted organogenesis, harbor mutations in epigenetic regulators in 30-50% of cases. However, the role of these regulators in kidney development and pathogenesis remains unexplored. By integrating mouse modeling, histological characterizations, and single-cell transcriptomics and chromatin accessibility profiling, we show that a Wilms tumor-associated mutation in the chromatin reader protein ENL disrupts kidney development trajectory by rewiring the gene regulatory landscape. Specifically, the mutant ENL promotes the commitment of nephron progenitors while simultaneously restricting their differentiation by dysregulating key transcription factor regulons, particularly the HOX clusters. It also induces the emergence of abnormal progenitor cells that lose their chromatin identity associated with kidney specification. Furthermore, the mutant ENL might modulate stroma-nephron interactions via paracrine Wnt signaling. These multifaceted effects caused by the mutation result in severe developmental defects in the kidney and early postnatal mortality in mice. Notably, transient inhibition of the histone acetylation binding activity of mutant ENL with a small molecule displaces transcriptional condensates formed by mutant ENL from target genes, abolishes its gene activation function, and restores developmental defects in mice. This work provides new insights into how mutations in epigenetic regulators can alter the gene regulatory landscape to disrupt kidney developmental programs at single-cell resolution in vivo . It also offers a proof-of-concept for the use of epigenetics-targeted agents to rectify developmental defects.

Association of aquatic food consumption, long-chain polyunsaturated n-3 fatty acid intake, and blood mercury levels with cognitive function in middle-aged and older adults.

BACKGROUND & AIMS: Aquatic food is rich in nutrients which benefit the human brain and cognitive health; however, concerns about heavy metal accumulation in aquatic food remain. This study evaluated the associations between aquatic food consumption, long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs) intake, and blood mercury levels with cognition in middle-aged and older adults. METHODS: This cross-sectional study used baseline data from the Lifestyle and Healthy Aging of Chinese Square Dancer Study. Aquatic food consumption and LC n-3 PUFAs intake were obtained from a food frequency questionnaire. Blood mercury levels were measured using inductively coupled plasma mass spectrometry. A composite z-score was developed to represent global cognition by averaging the z-scores for each cognitive domain. Participants with mild cognitive impairment (MCI) were diagnosed according to Petersen's criteria. Multivariate linear and logistic regression models were used to examine the association between the exposure factors and cognitive performance including cognitive scores and MCI. RESULTS: Of 2621 middle-aged and older adults, the mean (SD) age was 63.71 (5.15) years, and 85.73% were females. Compared with the lowest quartile, those in the highest quartile for aquatic food consumption were associated with higher composite z-scores (ß = 0.156, 95% CI: 0.088-0.225) and lower MCI odds (OR = 0.598, 95% CI: 0.425-0.841). A similar positive relationship between LC n-3 PUFAs intake and composite z-score and an inverse association between LC n-3 PUFAs intake and MCI were also observed. In addition, the participants in the highest quartile for blood mercury levels had higher composite z-scores than those in the lowest quartile. CONCLUSIONS: In this cross-sectional study, higher aquatic food consumption, LC n-3 PUFAs intake, and blood mercury levels were related to better cognitive function. Further studies in Chinese populations are required to confirm these findings.

Polyethyleneimine surface-modified silver-selenium nanocomposites for anti-infective treatment of wounds by disrupting biofilms.

Bacterial biofilm formation is associated with the pathogenicity of pathogens and poses a serious threat to human health and clinical therapy. Complex biofilm structures provide physical barriers that inhibit antibiotic penetration and inactivate antibiotics via enzymatic breakdown. The development of biofilm-disrupting nanoparticles offers a promising strategy for combating biofilm infections. Hence, polyethyleneimine surface-modified silver-selenium nanocomposites, Ag@Se@PEI (ASP NCs), were designed for synergistic antibacterial effects by destroying bacterial biofilms to promote wound healing. The results of in vitro antimicrobial experiments showed that, ASP NCs achieved efficient antibacterial effects against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) by disrupting the formation of the bacterial biofilm, stimulating the outbreak of reactive oxygen species (ROS) and destroying the integrity of bacterial cell membranes. The in-vivo bacterial infection in mice model showed that, ASP NCs further promoted wound healing and new tissue formation by reducing inflammatory factors and promoting collagen fiber formation which efficiently enhanced the antibacterial effect. Overall, ASP NCs possess low toxicity and minimal side effects, coupled with biocompatibility and efficient antibacterial properties. By disrupting biofilms and bacterial cell membranes, ASP NCs reduced inflammatory responses and accelerated the healing of infected wounds. This nanocomposite-based study offers new insights into antibacterial therapeutic strategies as potential alternatives to antibiotics for wound healing. .

Morphological and molecular characteristics of a Trypanosoma sp. from triatomines (Triatoma rubrofasciata) in China.

BACKGROUND: Triatomines (kissing bugs) are natural vectors of trypanosomes, which are single-celled parasitic protozoans, such as Trypanosoma cruzi, T. conorhini and T. rangeli. The understanding of the transmission cycle of T. conorhini and Triatoma rubrofasciata in China is not fully known. METHODS: The parasites in the faeces and intestinal contents of the Tr. rubrofasciata were collected, and morphology indices were measured under a microscope to determine the species. DNA was extracted from the samples, and fragments of 18S rRNA, heat shock protein 70 (HSP70) and glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH) were amplified and sequenced. The obtained sequences were then identified using the BLAST search engine, followed by several phylogenetic analyses. Finally, laboratory infections were conducted to test whether Tr. rubrofasciata transmit the parasite to rats (or mice) through bites. Moreover, 135 Tr. rubrofasciata samples were collected from the Guangxi region and were used in assays to investigate the prevalence of trypanosome infection. RESULTS: Trypanosoma sp. were found in the faeces and intestinal contents of Tr. rubrofasciata, which were collected in the Guangxi region of southern China and mostly exhibited characteristics typical of epimastigotes, such as the presence of a nucleus, a free flagellum and a kinetoplast. The body length ranged from 6.3 to 33.9 µm, the flagellum length ranged from 8.7 to 29.8 µm, the nucleus index was 0.6 and the kinetoplast length was -4.6. BLAST analysis revealed that the 18S rRNA, HSP70 and gGAPDH sequences of Trypanosoma sp. exhibited the highest degree of similarity with those of T. conorhini (99.7%, 99.0% and 99.0%, respectively) and formed a well-supported clade close to T. conorhini and T. vespertilionis but were distinct from those of T. rangeli and T. cruzi. Laboratory experiments revealed that both rats and mice developed low parasitaemia after inoculation with Trypanosoma sp. and laboratory-fed Tr. rubrofasciata became infected after feeding on trypanosome-positive rats and mice. However, the infected Tr. rubrofasciata did not transmit Trypanosoma sp. to their offspring. Moreover, our investigation revealed a high prevalence of Trypanosoma sp. infection in Tr. rubrofasciata, with up to 36.3% of specimens tested in the field being infected. CONCLUSIONS: Our study is the first to provide a solid record of T. conorhini from Tr. rubrofasciata in China with morphological and molecular evidence. This Chinese T. conorhini is unlikely to have spread through transovarial transmission in Tr. rubrofasciata, but instead, it is more likely that the parasite is transmitted between Tr. rubrofasciata and mice (or rats). However, there was a high prevalence of T. conorhini in the Tr. rubrofasciata from our collection sites and numerous human cases of Tr. rubrofasciata bites were recorded. Moreover, whether these T. conorhini strains are pathogenic to humans has not been investigated.

A BRD4-Targeting Photothermal Agent for Controlled Protein Degradation.

BRD4 protein plays a pivotal role in cell cycle regulation and differentiation. Disrupting the activity of BRD4 has emerged as a promising strategy for inhibiting the growth and proliferation of cancer cells. Herein, we introduced a BRD4-targeting photothermal agent for controlled protein degradation, aiming to enhance low-temperature photothermal therapy (PTT) for cancer treatment. By incorporating a BRD4 protein inhibitor into a cyanine dye scaffold, the photothermal agent specifically bond to the bromodomain of BRD4. Upon low power density laser irradiation, the agent induced protein degradation, directly destroying the BRD4 structure and inhibiting its transcriptional regulatory function. This strategy not only prolonged the retention time of the photothermal agent in cancer cells but also confined the targeted protein degradation process solely to the tumor tissue, minimizing side effects on normal tissues through the aid of exogenous signals. This work established a simple and feasible platform for future PTT agent design in clinical cancer treatment.

Automated segmentation and recognition of C. elegans whole-body cells.

MOTIVATION: Motivation: Accurate segmentation and recognition of Caenorhabditis elegans cells are critical for various biological studies, including gene expression, cell lineages and cell fates analysis at single-cell level. However, the highly dense distribution, similar shapes, and inhomogeneous intensity profiles of whole-body cells in 3D fluorescence microscopy images make automatic cell segmentation and recognition a challenging task. Existing methods either rely on additional fiducial markers or only handle a subset of cells. Given the difficulty or expense associated with generating fiducial features in many experimental settings, a marker-free approach capable of reliably segmenting and recognizing C. elegans whole-body cells is highly desirable. RESULTS: We report a new pipeline, called Automated Segmentation and Recognition (ASR) of cells, and applied it to 3D fluorescent microscopy images of L1-stage C. elegans with 558 whole-body cells. A novel displacement vector field based deep learning model is proposed to address the problem of reliable segmentation of highly crowded cells with blurred boundary. We then realize the cell recognition by encoding and exploiting statistical priors on cell positions and structural similarities of neighboring cells. To the best of our knowledge, this is the first method successfully applied to the segmentation and recognition of C. elegans whole-body cells. The ASR segmentation module achieves an F1-score of 0.8956 on a dataset of 116 C. elegans image stacks with 64728 cells (Accuracy 0.9880, AJI 0.7813). Based on the segmentation results, the ASR recognition module achieved an average accuracy of 0.8879. We also show ASR's applicability to other cell types, e.g. platynereis and rat kidney cells. AVAILABILITY: The code is available at https://github.com/reaneyli/ASR. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Pseudomonas aeruginosa two-component system LadS/PA0034 regulates macrophage phagocytosis via fimbrial protein cupA1.

Pseudomonas aeruginosa is one of the most common nosocomial pathogens worldwide, known for its virulence, drug resistance, and elaborate sensor-response network. The primary challenge encountered by pathogens during the initial stages of infection is the immune clearance arising from the host. The resident macrophages of barrier organs serve as the frontline defense against these pathogens. Central to our understanding is the mechanism by which bacteria modify their behavior to circumvent macrophage-mediated clearance, ensuring their persistence and colonization. To successfully evade macrophage-mediated phagocytosis, bacteria must possess an adaptive response mechanism. Two-component systems provide bacteria the agility to navigate diverse environmental challenges, translating external stimuli into cellular adaptive responses. Here, we report that the well-documented histidine kinase, LadS, coupled to a cognate two-component response regulator, PA0034, governs the expression of a vital adhesin called chaperone-usher pathway pilus cupA. The LadS/PA0034 system is susceptible to interference from the reactive oxygen species likely to be produced by macrophages and further lead to a poor adhesive phenotype with scantily cupA pilus, impairing the phagocytosis efficiency of macrophages during acute infection. This dynamic underscores the intriguing interplay: as macrophages deploy reactive oxygen species to combat bacterial invasion, the bacteria recalibrate their exterior to elude these defenses. IMPORTANCE: The notoriety of Pseudomonas aeruginosa is underscored by its virulence, drug resistance, and elaborate sensor-response network. Yet, the mechanisms by which P. aeruginosa maneuvers to escape phagocytosis during acute infections remain elusive. This study pinpoints a two-component response regulator, PA0034, coupled with the histidine kinase LadS, and responds to macrophage-derived reactive oxygen species. The macrophage-derived reactive oxygen species can impair the LadS/PA0034 system, resulting in reduced expression of cupA pilus in the exterior of P. aeruginosa. Since the cupA pilus is an important adhesin of P. aeruginosa, its deficiency reduces bacterial adhesion and changes their behavior to adopt a planktonic lifestyle, subsequently inhibiting the phagocytosis of macrophages by interfering with bacterial adhesion. Briefly, reactive oxygen species may act as environmental cues for the LadS/PA0034 system. Upon recognition, P. aeruginosa may transition to a poorly adhesive state, efficiently avoiding engulfment by macrophages.

Hydrothermal synthesis of high crystallinity ZSM-5 zeolite from coal gasification coarse slag and mother liquor circulation for efficient coal chemical wastewater purification.

A hydrothermal synthesis method was developed to produce high crystallinity ZSM-5 zeolite using coal gasification coarse slag (CGCS) as the raw material. Instead of the expensive NaOH(s.), Na2SiO3(s.) was utilized to activate, depolymerize, and recombine Si and Al elements in the CGCS. The mother liquor circulation technology was employed to recover and reuse raw materials and residual reagents (Na2SiO3(aq.) and TPABr), reducing waste emissions and enhancing resource utilization efficiency. The synthesized ZSM-5 had a specific surface area of 455.675 m2 g-1, pore volume of 0.284 cm3 g-1, and pore diameter of 2.496 nm. The influence of various factors on the morphology and crystallinity of ZSM-5 was investigated, resulting in the production of ZSM-5 with higher specific surface area and pore volume. Adsorption experiments showed that WU-ZSM-5 exhibited a removal efficiency of 85% for ammonia nitrogen (NH4+-N(aq.)), validating its effectiveness in coal chemical wastewater purification. The mother liquor recycling technology enabled zero-emission utilization of solid waste resources and improved the utilization rate of alkali and template to 90%. These results demonstrate the potential application of the developed method in the efficient treatment of coal chemical wastewater.

Three in one: An effective and universal vaccine expressing heterologous tandem RBD trimer by rabies virus vector protects mice against SARS-CoV-2.

The rapid emergence of Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2) variants, coupled with severe immune evasion and imprinting, has jeopardized the vaccine efficacy, necessitating urgent development of broad protective vaccines. Here, we propose a strategy employing recombinant rabies viruses (RABV) to create a universal SARS-CoV-2 vaccine expressing heterologous tandem receptor-binding domain (RBD) trimer from the SARS-CoV-2 Prototype, Delta, and Omicron strains (SRV-PDO). The results of mouse immunization indicated that SRV-PDO effectively induced cellular and humoral immune responses, and demonstrated higher immunogenicity and broader SARS-CoV-2 neutralization compared to the recombinant RABVs that only expressed RBD monomers. Moreover, SRV-PDO exhibited full protection against SARS-CoV-2 in the challenge assay. This study demonstrates that recombinant RABV expressing tandem RBD-heterotrimer as a multivalent immunogen could elicit a broad-spectrum immune response and potent protection against SARS-CoV-2, making it a promising candidate for future human or veterinary vaccines and offering a novel perspective in other vaccine design.

Impact of exogenous melatonin foliar application on physiology and fruit quality of wine grapes (Vitis vinifera) under salt stress.

Soil salinisation is an important abiotic stress faced in grape cultivating, leading to weakened plant vigour and reduced fruit quality. Melatonin as a novel hormone has shown positive exogenous application value. Therefore, this study used wine grape (Vitis vinifera ) 'Pinot Noir' as a test material to investigate the changes of foliar spraying with different concentrations of melatonin on the physiology and fruit quality of wine grapes in a field under simulated salt stress (200mmolL-1 NaCl). The results showed that foliar spraying of melatonin significantly increased the intercellular CO2 concentration, maximum photochemical quantum yield of PSII, relative chlorophyll and ascorbic acid content of the leaves, as well as the single spike weight, 100-grain weight, transverse and longitudinal diameters, malic acid, α-amino nitrogen and ammonia content of fruits, and decreased the initial fluorescence value of leaves, ascorbate peroxidase activity, glutathione content, fruit transverse to longitudinal ratio and tartaric acid content of plants under salt stress. Results of the comprehensive evaluation of the affiliation function indicated that 100µmolL-1 melatonin treatment had the best effect on reducing salt stress in grapes. In summary, melatonin application could enhance the salt tolerance of grapes by improving the photosynthetic capacity of grape plants under salt stress and promoting fruit development and quality formation, and these results provide new insights into the involvement of melatonin in the improvement of salt tolerance in crop, as well as some theoretical basis for the development and industrialisation of stress-resistant cultivation techniques for wine grapes.

Electroacupuncture stimulation modulates functional brain connectivity in the treatment of pediatric cerebral palsy: a case report.

Background: Pediatric cerebral palsy (CP) is a non-progressive brain injury syndrome characterized by central motor dysfunction and insufficient brain coordination ability. The etiology of CP is complex and often accompanied by diverse complications such as intellectual disability and language disorders, making clinical treatment difficult. Despite the availability of pharmacological interventions, rehabilitation programs, and spasticity relief surgery as treatment options for CP, their effectiveness is still constrained. Electroacupuncture (EA) stimulation has demonstrated great improvements in motor function, but its comprehensive, objective therapeutic effects on pediatric CP remain to be clarified. Methods: We present a case of a 5-year-old Chinese female child who was diagnosed with CP at the age of 4. The patient exhibited severe impairments in motor, language, social, and cognitive functions. We performed a 3-month period of EA rehabilitation, obtaining resting state functional magnetic resonance imaging (rs-fMRI) of the patient at 0 month, 3 months and 5 months since treatment started, then characterized brain functional connectivity patterns in each phase for comparison. Results: After a 12-month follow-up, notable advancements were observed in the patient's language and social symptoms. Changes of functional connectivity patterns confirmed this therapeutic effect and showed specific benefits for different recovery phase: starting from language functions then modulating social participation and other developmental behaviors. Conclusion: This is a pioneering report demonstrating the longitudinal effect of EA stimulation on functional brain connectivity in CP patients, suggesting EA an effective intervention for developmental disabilities (especially language and social dysfunctions) associated with pediatric CP.

Charting new paradigms for CAR-T cell therapy beyond current Achilles heels.

Chimeric antigen receptor-T (CAR-T) cell therapy has made remarkable strides in treating hematological malignancies. However, the widespread adoption of CAR-T cell therapy is hindered by several challenges. These include concerns about the long-term and complex manufacturing process, as well as efficacy factors such as tumor antigen escape, CAR-T cell exhaustion, and the immunosuppressive tumor microenvironment. Additionally, safety issues like the risk of secondary cancers post-treatment, on-target off-tumor toxicity, and immune effector responses triggered by CAR-T cells are significant considerations. To address these obstacles, researchers have explored various strategies, including allogeneic universal CAR-T cell development, infusion of non-activated quiescent T cells within a 24-hour period, and in vivo induction of CAR-T cells. This review comprehensively examines the clinical challenges of CAR-T cell therapy and outlines strategies to overcome them, aiming to chart pathways beyond its current Achilles heels.

Morphological Tracing and Functional Identification of Monosynaptic Connections in the Brain: A Comprehensive Guide.

Behavioral studies play a crucial role in unraveling the mechanisms underlying brain function. Recent advances in optogenetics, neuronal typing and labeling, and circuit tracing have facilitated the dissection of the neural circuitry involved in various important behaviors. The identification of monosynaptic connections, both upstream and downstream of specific neurons, serves as the foundation for understanding complex neural circuits and studying behavioral mechanisms. However, the practical implementation and mechanistic understanding of monosynaptic connection tracing techniques and functional identification remain challenging, particularly for inexperienced researchers. Improper application of these methods and misinterpretation of results can impede experimental progress and lead to erroneous conclusions. In this paper, we present a comprehensive description of the principles, specific operational details, and key steps involved in tracing anterograde and retrograde monosynaptic connections. We outline the process of functionally identifying monosynaptic connections through the integration of optogenetics and electrophysiological techniques, providing practical guidance for researchers.

Overexpression of Let-7a mitigates diploidization in mouse androgenetic haploid embryonic stem cells.

Mouse androgenetic haploid embryonic stem cells (mAG-haESCs) can be utilized to uncover gene functions, especially those of genes with recessive effects, and to produce semicloned mice when injected into mature oocytes. However, mouse haploid cells undergo rapid diploidization during long-term culture in vitro and subsequently lose the advantages of haploidy, and the factors that drive diploidization are poorly understood. In this study, we compared the small RNAs (sRNAs) of mAG-haESCs, normal embryonic stem cells (ESCs), and mouse round spermatids by high-throughput sequencing and identified distinct sRNA profiles. Several let-7 family members and miR-290-295 cluster microRNAs (miRNAs) were found significantly differentially transcribed. Knockdown and overexpression experiments showed that let-7a and let-7g suppress diploidization while miR-290a facilitates diploidization. Our study revealed the unique sRNA profile of mAG-haESCs and demonstrated that let-7a overexpression can mitigate diploidization in mAG-haESCs. These findings will help us to better understand mAG-haESCs and utilize them as tools in the future.

Surface segregation of rigid polyarylene ether amidoxime on polyurethane nanofiber into hierarchical membranes as substrate of flexible SERS nanosensor for sulfamethoxazole detection.

Electrospun polymeric nanofibrous membranes are emerging as the promising substrates for preparation of flexible SERS nanosensors due to their intrinsic nanoscale surface roughness, easy scalability as well as rich surface reactivity. Although the nanofiber membranes prepared from high performance thermoplastics exhibit good mechanical stability, the SERS nanosensors based on these substrates normally have lower signal-to-noise ratio because of the interference from background Raman signals of aromatic moieties. Herein, we synthesized an optically transparent polyurethane (PU) and rigid polyarylene ether amidoxime (PEA), which were electrospun into core-shell nanofibers membranes with a "beads-on-web" morphology. Furthermore, the PU-PEA membranes were coated with ultra-thin silver layer and thermally annealed to prepare the flexible SERS nanosensor without any background noises. In addition, the Raman enhancement of SERS nanosensor can be readily improved by tuning of PU-PEA composition, silver thickness as well as thermal annealing temperature. Finally, the optimized SERS nanosensor enables label-free detection of sulfamethoxazole as low as 0.1 nM with a good reproducibility and detection performance in real water sample. Meanwhile, the optimized SERS nanosensor shows long term anti-biofouling capacity. Thanks to its facile fabrication, competitive analytical performance and resistance to biofouling, the current work basically open new way for design of flexible SERS nanosensors for biomedical applications.

Efficacy of repetitive transcranial magnetic stimulation in post-stroke cognitive impairment: an overview of systematic reviews.

Objective: The reliability of clinical evidence depends on high-quality meta-analyses/ systematic reviews (MAs/SRs). However, there has been no assessment of the quality of MAs/SRs for repetitive transcranial magnetic stimulation (rTMS) in post-stroke cognitive impairment (PSCI), both nationally and internationally. This article seeks to use radar plotting to visually present the quality of MAs/SRs on rTMS for improving cognitive function in PSCI, aiming to offer an intuitive foundation for clinical research. Methods: Eight Chinese or English databases were systematically searched to collect comprehensive literature, and the retrieval time ranged from inception to 26 March 2024. Literature ranking was calculated using six dimensions: publication year, design type, AMSTAR-2 score, PRISMA score, publication bias, and homogeneity. Finally, radar plots were drafted to present a multivariate literature evaluation. The GRADE tool assessed the strength of evidence for the outcome indicators included in the MAs/SRs. Results: The 17 articles included had average scores of 12.29, 17, 9.88, 9.71, 12.88, and 12.76 for each dimension. The radar plot showed that an article published in 2023 had the highest rank and a large radar plot area, while an article published in 2021 had the lowest rank and a small radar plot area. The GRADE tool evaluation revealed that 51 pieces of evidence were of very low quality, 67 were of low quality, 12 were of moderate quality, and only one was of high quality. Conclusion: The average rank score of literature ranged from 8.50 to 17, with higher rankings indicating greater significance in literature reference. Variations in literature quality were attributed to inadequate study planning, irregular literature search and screening, insufficient description of inclusion criteria for studies, and inadequate consideration of bias risk in the included studies. Most MAs/SRs indicated that rTMS was more effective than the control group in enhancing the global cognitive function and activities of daily living in PSCI patients. However, the overall quality of the literature was generally low and needs validation from future high-quality evidence.Systematic review registration:https://www.crd.york.ac.uk/prospero/, identifier CRD42023491280.