Rapid detection of drugs in blood using "molecular hook" surface-enhanced Raman spectroscopy and artificial intelligence technology for clinical applications.

Accurate detection of cardiovascular drugs in blood is complicated by interference from serum biomolecules. This study introduces a novel surface-enhanced Raman spectroscopy (SERS) platform incorporating "molecular hooks" to capture small drug molecules while excluding larger biomolecules selectively. The self-assembled nanoparticles with the A13 molecule enhance Raman signals by creating dense electromagnetic "hotspot" regions, achieving detection limits of 10 pg/mL for dobutamine hydrochloride and 10 ng/mL for milrinone-substantially below therapeutic thresholds. Artificial intelligence (AI) integration enables automated spectral analysis, allowing rapid and precise drug detection in clinical blood samples. This approach offers a transformative solution for real-time diagnostics, significantly advancing personalized treatment strategies in clinical settings.

Botch improves cognitive impairment after cerebral ischemia associated with microglia-induced A1-type astrocyte activation.

Vascular cognitive impairment (VCI) is a clinical syndrome that arises from cerebrovascular issues and associated risk factors, resulting in difficulties in at least one area of cognitive function. VCI has emerged as the second most prevalent type of dementia following Alzheimer's disease, yet there is no effective clinical treatment. Botch, an endogenous Notch1 antagonist, demonstrates neuroprotective effects by inhibiting neuroinflammatory responses mediated through the Notch pathway. While its role in stroke-induced neuroinflammation is well-established, its involvement in VCI remains largely unexplored. This study investigates the role and potential mechanisms of Botch in a rat model of cognitive impairment caused by bilateral common carotid artery occlusion (BCCAO). Firstly, we observed that Botch levels were down-regulated in BCCAO rats, which correlated with increased release of inflammatory cytokines and neuronal damage. Microglia in BCCAO rats released interleukin-1α (IL-1α), tumor necrosis factor-α (TNF-α), and complement component 1q (C1q), leading to the activation of neurotoxic C3+ A1 reactive astrocytes. Then, the down-regulation of Botch exacerbated microglia-mediated inflammation, activated C3+ A1 astrocytes, worsened neuronal damage, and led to a decline in cognitive function. Conversely, the re-expression of Botch alleviated C3+ astrocyte activation, inhibited neuronal damage, and improved mental function. In conclusion, Botch plays a crucial role in inhibiting neuroinflammation induced by type A1 reactive astrocytes. It achieves this by blocking the activation of microglia triggered by the Notch pathway. Ultimately, it inhibits neuronal damage to play a neuroprotective role. These findings suggest that Botch may represent a novel potential target for treating VCI.

PET/CT Targeted Tissue Sampling Reveals Intravenously Administered HGN194 IgG1 Affects HIV Distribution after Rectal Exposure.

Neutralizing monoclonal antibodies hold great potential for prevention of human immunodeficiency virus (HIV) acquisition. IgG is the most abundant antibody in human serum, has a long half-life, and potent effector functions, making it a prime candidate for an HIV prevention therapeutic. We combined Positron Emission Tomography imaging and fluorescent microscopy of 64Cu-labeled, photoactivatable-green fluorescent protein HIV (PA-GFP-BaL) and fluorescently labeled HGN194 IgG1 to determine whether intravenously instilled IgG influences viral interaction with mucosal barriers and viral penetration in colorectal tissue 2 h after rectal viral challenge. Our results show that IgG1 did not alter the number of virions found throughout the colon or viral penetration into the epithelium of the rectum or descending colon. A minor increase in virions was observed in the transverse colon of IgG1 treated animals. Overall, the number of viral particles found in the mesenteric lymph nodes was low. However, IgG1 administration resulted in a significant reduction of virions found in mesenteric lymph nodes. Taken together, our results show that HGN194 IgG1 does not prevent virions from penetrating into the colorectal mucosa but may perturb HIV virion access to the lymphatic system.

Prognostic value of PD-L1 expression in patients with anal cancer: a meta-analysis.

Background: The present meta-analysis was performed to evaluate the prognostic and clinicopathological significance of PD-L1 in anal cancer (AC). Methods: Hazard ratios (HRs) and 95% CIs regarding overall survival (OS) and progression-free survival (PFS) were calculated based on PD-L1 levels. Results: According to the combined data, PD-L1 showed no significant relationship with OS (HR = 0.76; 95% CI = 0.35-1.67; p = 0.502) or PFS (HR = 0.88; 95% CI = 0.35-2.33; p = 0.789) in patients with AC. Based on subgroup analysis, PD-L1 overexpression significantly predicted prolonged OS (HR = 0.38; 95% CI = 0.17-0.84; p = 0.017) in tumor node metastasis stages I-III and inferior PFS (HR = 2.73; 95% CI = 1.32-5.65; p = 0.007) in patients with stage I-IV AC. Conclusion: PD-L1 level assessed by immunohistochemistry did not significantly predict survival outcomes in AC cases.

[Box: see text].

Relationships between obesity and functional outcome after ischemic stroke: a Mendelian randomization study.

BACKGROUND AND OBJECTIVES: Most previous studies suggested obesity deteriorates the functional outcome after ischemic stroke. But there are researches claiming that obesity is associated with lower mortality, recurrence, and readmission rates, which is known as the obesity paradox. Our current research aimed to investigate the correlation between genetically obesity and the post-stroke outcome with the Mendelian randomization (MR) method. METHODS: The UK Biobank and the GIANT consortium provided instrumental variables for body mass index (BMI, 806,834 individuals) and waist-to-hip ratio (WHR, 697,734 individuals). Data of functional outcome after ischemic stroke were obtained from the Genetics of Ischemic Stroke Functional Outcome network (6012 individuals). Inverse-variance weighted approach was utilized as the primary analyses. Sensitivity analyses involved the utilization of different MR methods. The heterogeneity among genetic variants was assessed by I2 and Q value statistics. RESULTS: In univariable analysis, there was a significant connection between genetic susceptibility to WHR and worse functional outcome (modified Rankin Scale 3) after ischemic stroke (OR [95%CI] = 1.47 [1.07, 2.02], P = 0.016). Genetic liability to BMI and was not associated with post-stroke functional outcome (all P > 0.05). The overall patterns between genetic liability to WHR and functional outcome post-ischemic outcome no longer existed in the multivariable MR analysis after adjusting for BMI (OR [95%CI] = 1.26[0.76,1.67], P = 0.56). CONCLUSION: The current MR study provided evidence that WHR was correlated to unfavorable outcome post-ischemic stroke. Exploring interventions against obesity may potentially improve recovery after ischemic stroke.

Advances in Aqueous Zinc Ion Batteries based on Conversion Mechanism: Challenges, Strategies, and Prospects.

Recently, aqueous zinc-ion batteries with conversion mechanisms have received wide attention in energy storage systems on account of excellent specific capacity, high power density, and energy density. Unfortunately, some characteristics of cathode material, zinc anode, and electrolyte still limit the development of aqueous zinc-ion batteries possessing conversion mechanism. Consequently, this paper provides a detailed summary of the development for numerous aqueous zinc-based batteries: zinc-sulfur (Zn-S) batteries, zinc-selenium (Zn-Se) batteries, zinc-tellurium (Zn-Te) batteries, zinc-iodine (Zn-I2) batteries, and zinc-bromine (Zn-Br2) batteries. Meanwhile, the reaction conversion mechanism of zinc-based batteries with conversion mechanism and the research progress in the investigation of composite cathode, zinc anode materials, and selection of electrolytes are systematically introduced. Finally, this review comprehensively describes the prospects and outlook of aqueous zinc-ion batteries with conversion mechanism, aiming to promote the rapid development of aqueous zinc-based batteries.

Interfacial assembled porous bismuthene/Ti3C2Tx MXene heterostructure for highly efficient capacitive deionization.

Capacitive deionization (CDI) is perceived as a promising technology for freshwater production owing to its environmentally friendly nature and low energy consumption. To date, the development of high-performance electrode materials represents the foremost challenge for CDI technology. In this work, the porous bismuthene/MXene (P-Bi-ene/MXene) heterostructure was synthesized using a simple interfacial self-assembly method with two-dimensional (2D) bismuthene and Ti3C2Tx MXene. Within the P-Bi-ene/MXene heterostructure, the porous structure can increase the active site and facilitate ion transport. Simultaneously, MXene effectively enhances the conductivity of the heterostructure, resulting in accelerating electron transport. Due to these attributes, the P-Bi-ene/MXene heterostructure demonstrates high desalination capacity (90.0 mg/g), fast desalination rate, and good cycling performance. The simple self-assembly strategy between 2D/2D materials described herein may offer inspirations for the synthesis of innovative electrode materials with high performance.

MoO2 Nanoclusters Embedded in Hierarchical Nitrogen Doped Carbon Nanoflower as Electrocatalytic Mediators in Aqueous Zinc-Tellurium Batteries: Enhancing Electrochemical Kinetics of Tellurium Redox Reaction.

Aqueous zinc-ion batteries (AZIBs) are considered to be one of the most promising devices for large-scale energy storage systems owing to their high theoretical capacity, environmental friendliness, and safety. However, the ionic intercalation or surface redox mechanisms in conventional cathode materials generally result in unsatisfactory capacities. Conversion-type aqueous zinc-tellurium (Zn-Te) batteries have recently gained widespread attention owing to their high theoretical specific capacities. However, it remains an enormous challenge to improve the slow kinetics of the aqueous Zn-Te batteries. Here, MoO2 nanoclusters embedded in hierarchical nitrogen-doped carbon nanoflower (MoO2 /NC) hosts are successfully synthesized and loaded with Te in aqueous Zn-Te batteries. Benefitting from the highly dispersed MoO2 nanoclusters and hierarchical nanoflower structure with a large specific surface area, the electrochemical kinetics of the Te redox reaction are significantly improved. As a result, the Te-MoO2 /NC electrode exhibits superior cycling stability and a high specific capacity of 493 mAh g-1 at 0.1 A g-1 . Meanwhile, the conversion mechanism is systematically explored using a variety of ex situ characterization methods. Therefore, this study provides a novel approach for enhancing the kinetics of the Te redox reaction in aqueous Zn-Te batteries.

Mechano-Driven Tribo-Electrophoresis Enabled Human-Droplet Interaction in 3D Space.

Electronically controlled droplet manipulation has widespread applications in biochemistry, life sciences, and industry. However, current technologies such as electrowetting, electrostatics, and surface charge printing rely on complex electrode arrays and external power supplies, leading to inefficient manipulation. In light of these limitations, a novel method is proposed, which leverages tribo-electrophoresis (TEP) to pipette in an oil medium, thereby enabling human-droplet interactions to be constructed with greater efficiency. The approach involves the rational design of a triboelectric nanogenerator-electrostatic tweezer that generates an electric field to charge the droplet and improves the maneuverability of the charged droplet, including aligned/non-aligned pipetting and stable transport in the clamped state, which can be accomplished solely by hand motion. The TEP method not only provides droplets with freedom to move in three dimensions but also offers a feasibility case for chemical reactions in the liquid phase and non-invasive sample extraction. This breakthrough establishes a cornerstone for human-droplet interactions capitalized on triboelectric nanogenerators, opening new avenues for research in droplet manipulation.

Strong interface coupling boosting hierarchical bismuth embedded carbon hybrid for high-performance capacitive deionization.

Capacitive deionization (CDI) is regarded as a promising desalination technology owing to its low cost and environmental friendliness. However, the lack of high-performance electrode materials remains a challenge in CDI. Herein, the hierarchical bismuth-embedded carbon (Bi@C) hybrid with strong interface coupling was prepared through facile solvothermal and annealing strategy. The hierarchical structure with strong interface coupling between the bismuth and carbon matrix afforded abundant active sites for chloridion (Cl-) capture, improved electrons/ions transfer and the stability of the Bi@C hybrid. As a result of these advantages, the Bi@C hybrid showed a high salt adsorption capacity (75.3 mg/g under 1.2 V), salt adsorption rate and good stability, making it a promising electrode material for CDI. Furthermore, the desalination mechanism of the Bi@C hybrid was elucidated through various characterizations. Therefore, this work provides valuable insights for the design of high-performance bismuth-based electrode materials for CDI.

Hierarchical amorphous vanadium oxide and carbon nanotubes microspheres with strong interface interaction for Superior performance aqueous Zinc-ion batteries.

Aqueous zinc-ion batteries have attracted more and more attention due to their safety, environmental benignity and high theoretical capacity. However, the lack of appropriate cathode materials with high capacity and long cycle life have become an obstacle to the development of aqueous zinc-ion batteries. Herein, the hierarchical amorphous vanadium oxide and carbon nanotubes (a-V2O5@CNTs) microspheres with strong interface interaction were successfully prepared by combing facile spray drying technique with annealing treatment. Benefiting from the a-V2O5 amorphous characters, CNTs framework high conductivity and hierarchical microspheres with strong interface interaction, the a-V2O5@CNTs exhibited abundant active sites, fast reaction kinetics as well as eminent structure stability. As a promising electrode material, the a-V2O5@CNTs displayed high specific capacity (480 mAh g-1 at 0.5 A g-1), good rate capability and long-term stability under high current density (158 mAh g-1 at 30 A g-1 over 1000 cycles). Meanwhile, the corresponding mechanism was further illustrated through different characterizations. Furthermore, the as-assembled flexible pouch battery based on the a-V2O5@CNTs delivered outstanding flexibility and feasibility. Hence, this work provides a new idea for developing high performance cathode materials of aqueous zinc-ion batteries.

Targeting small GTPases: emerging grasps on previously untamable targets, pioneered by KRAS.

Small GTPases including Ras, Rho, Rab, Arf, and Ran are omnipresent molecular switches in regulating key cellular functions. Their dysregulation is a therapeutic target for tumors, neurodegeneration, cardiomyopathies, and infection. However, small GTPases have been historically recognized as "undruggable". Targeting KRAS, one of the most frequently mutated oncogenes, has only come into reality in the last decade due to the development of breakthrough strategies such as fragment-based screening, covalent ligands, macromolecule inhibitors, and PROTACs. Two KRASG12C covalent inhibitors have obtained accelerated approval for treating KRASG12C mutant lung cancer, and allele-specific hotspot mutations on G12D/S/R have been demonstrated as viable targets. New methods of targeting KRAS are quickly evolving, including transcription, immunogenic neoepitopes, and combinatory targeting with immunotherapy. Nevertheless, the vast majority of small GTPases and hotspot mutations remain elusive, and clinical resistance to G12C inhibitors poses new challenges. In this article, we summarize diversified biological functions, shared structural properties, and complex regulatory mechanisms of small GTPases and their relationships with human diseases. Furthermore, we review the status of drug discovery for targeting small GTPases and the most recent strategic progress focused on targeting KRAS. The discovery of new regulatory mechanisms and development of targeting approaches will together promote drug discovery for small GTPases.

Vertically Aligned Bismuthene Nanosheets on MXene for High-Performance Capacitive Deionization.

Capacitive deionization has been considered as a promising solution to the challenge of freshwater shortage due to its high efficiency, low environmental footprint, and low energy consumption. However, developing advanced electrode materials to improve capacitive deionization performance remains a challenge. Herein, the hierarchical bismuthene nanosheets (Bi-ene NSs)@MXene heterostructure was successfully prepared by combining the Lewis acidic molten salt etching and the galvanic replacement reaction, which achieves the effective utilization of the molten salt etching byproducts (residual copper). The vertically aligned bismuthene nanosheets array evenly in situ grown on the surface of MXene, which not only facilitate ion and electron transport as well as offer abundant active sites but also provide strong interfacial interaction between bismuthene and MXene. Benefiting from the above advantages, the Bi-ene NSs@MXene heterostructure as a promising capacitive deionization electrode material exhibits high desalination capacity (88.2 mg/g at 1.2 V), fast desalination rate, and good long-term cycling performance. Moreover, the mechanisms involved were elaborated by systematical characterizations and density functional theory calculations. This work provides inspirations for the preparation of MXene-based heterostructures and their application for capacitive deionization.

Few-layered Ti3C2Tx MXene synthesized via water-free etching toward high-performance supercapacitors.

MXene has drawn considerable attention in energy storage due to particular physicochemical properties. At present, among most near-ambient temperature preparation methods, water is usually served as the main solvent. However, MXene is usually subjected to fast structural degradation on account of water molecules attacking in aqueous solution. Herein, we report a novel water-free etching strategy for synthesizing few-layered Ti3C2Tx MXenes in deep eutectic solvents at near-ambient temperature. Benefitting from the absence of water and macromolecular structure of deep eutectic solvents, the as-synthesized few-layered Ti3C2Tx (DES-Ti3C2Tx) MXene presents abundant -O terminations and low oxidation degree. As a consequence, the DES-Ti3C2Tx MXene displays excellent specific capacitance of 320 F/g at 2 mV/s. Impressively, the DES-Ti3C2Tx MXene exhibits splendid long-term stability that 97% specific capacitance retention can be acquired over 50 000 cycles at high current density of 50 A/g. Therefore, this study offers a new thought for preparing high performance MXene-based materials by water-free etching method.

Astrocyte-Derived Neuronal Transdifferentiation as a Therapy for Ischemic Stroke: Advances and Challenges.

After the onset of ischemic stroke, ischemia-hypoxic cascades cause irreversible neuronal death. Neurons are the fundamental structures of the central nervous system, and mature neurons do not renew or multiply after death. Functional and structural recovery from neurological deficits caused by ischemic attack is a huge task. Hence, there remains a need to replace the lost neurons relying on endogenous neurogenesis or exogenous stem cell-based neuronal differentiation. However, the stem cell source difficulty and the risk of immune rejection of the allogeneic stem cells might hinder the wide clinical application of the above therapy. With the advancement of transdifferentiation induction technology, it has been demonstrated that astrocytes can be converted to neurons through ectopic expression or the knockdown of specific components. The progress and problems of astrocyte transdifferentiation will be discussed in this article.

Hierarchical accordion-like manganese oxide@carbon hybrid with strong interaction heterointerface for high-performance aqueous zinc ion batteries.

Aqueous zinc ion batteries have attracted extensive concern as a promising candidate for large-scale energy storage because of their high theoretical specific capacity, low cost and inherent safety. However, the lacking of applicable cathode materials with outstanding electrochemical performance have severely hindered the further development of aqueous zinc ion batteries. Herein, we report a hierarchical accordion-like manganese oxide@carbon (MnO@C) hybrid with strong interaction heterointerface and comprehensively inquire into its electrochemical performance as cathode materials for aqueous zinc ion batteries. The unique hierarchical accordion-like layered structure coupling with strong interaction heterointerface between small MnO and carbon matrix efficaciously improve the ion/electron transfer process and enhance structure stability of the MnO@C hybrid. Benefitting from these unique advantages, the MnO@C hybrid bestows excellent specific capacity of 456 mAh g-1 at 50 mA g-1. Impressively, the MnO@C hybrid presents distinguished long-term cycling stability with fairly low decay rates of only 0.0079 % per cycle even over 2000 cycles at 2000 mA g-1. Moreover, comprehensive characterizations are executed to elucidate the mechanism involved. Therefore, this work affords a new idea for developing outstanding performance manganese-based cathode materials for aqueous zinc ion batteries.

Constructing titanium carbide MXene/reduced graphene oxide superlattice heterostructure via electrostatic self-assembly for high-performance capacitive deionization.

Capacitive deionization has attracted wide concern on accountof its high energy efficiency, low manufacturing cost and environmental friendliness. Nevertheless, the development of capacitive deionization is still impeded because of the scarcity of suitable electrode materials with superior performance. Herein, we successfully prepared the two-dimensional (2D) titanium carbide (Ti3C2Tx) MXene/ reduced graphene oxide (rGO) superlattice heterostructure by a facile electrostatic self-assembly strategy and systematically investigated its performance as capacitive deionized electrode materials. The unique 2D/2D superlattice heterostructure not only effectively alleviates the self-stacking problem of Ti3C2Tx MXene nanosheets, but also endows the heterostructure with superior conductivity and fast ion diffusion rate. As a result, the MXene/rGO superlattice heterostructure exhibits an outstanding salt (Na+) adsorption capacity (48 mg g-1) at 1.2 V significantly superior to pristine Ti3C2Tx MXene nanosheets, along with outstanding long-term cycling performance. Furthermore, the mechanism involved was elucidated through comprehensive characterizations. Therefore, this study offers a new pathway for designing high-performance electrode materials for capacitive deionization.

Antibody Light Chains: Key to Increased Monoclonal Antibody Yields in Expi293 Cells?

When constructing isogenic recombinant IgM-IgG pairs, we discovered that µ heavy chains strongly prefer partnering with λ light chains for optimal IgM expression in transiently cotransfected Expi293 cells. When µ chains were paired with κ light chains, IgM yields were low but increased by logs-up to 20,000 X-by using λ chains instead. Switching light chains did not alter epitope specificity. For dimeric IgA2, optimal expression involved pairing with λ chains, whereas light-chain preference varied for other immunoglobulin classes. In summary, recombinant IgM production can be drastically increased by using λ chains, an important finding in the use of IgM for mucosal immunoprophylaxis.

Constructing hollow nanotube-like amorphous vanadium oxide and carbon hybrid via in-situ electrochemical induction for high-performance aqueous zinc-ion batteries.

Aqueous zinc-ion batteries receive more and more attentions on account of their low cost, high theoretical density and inherent safety. Nevertheless, the lack of suitable cathode materials with excellent performance still severely impedes the development of aqueous zinc-ion batteries. Herein, an in-situ electrochemical induction strategy is developed to prepare hollow nanotube-like amorphous vanadium oxide and carbon (a-V2O5@C) hybrid and its electrochemical performance is investigated comprehensively as cathode materials for aqueous zinc-ion batteries. Benefitting from the unique amorphous structure of V2O5 and intimate contact between amorphous V2O5 and carbon, the a-V2O5@C hybrid possess the abundant ion storage sites, isotropic ion diffusion routes and excellent conductivity. As a result, the a-V2O5@C hybrid cathode shows outstanding specific capacity of 448 mAh g-1 at 0.15 A g-1. Impressively, the a-V2O5@C hybrid cathode exhibits superior cycling stability, even when cycling at high current density of 10 A g-1, that the 96.5% specific capacity retention can be gained over 1500 cycles, corresponding to an average specific capacity loss of only 0.0023% per cycle. Furthermore, the mechanism involved is illustrated by systematical characterizations. Therefore, this work affords a new way for developing high-performance cathode materials for aqueous zinc-ion batteries.

Iodine-Functionalized Titanium Carbide MXene with Ultra-Stable Pseudocapacitor Performance.

MXene has attracted a wide spread attention as promising supercapacitor electrode materials owing to excellent electronic conductivity and reversible surface redox capability. In fact, the supercapacitor performance strongly relies onsurface terminations of MXene. However, regulating the types of surface terminations for enhancing the electrochemical performance of MXene is still one of major challenge. Herein, we successfully prepared a MXene containing iodine terminations (I-Ti3C2 MXene) by facile Lewis-acidic-melt etching method and comprehensively investigated its supercapacitor performance. Benefiting from the presence of iodine terminations, the I-Ti3C2 MXene with pseudocapacitor property exhibits significantly higher specific capacitance than that of hydrofluoric acid etching MXene (HF-Ti3C2Tx MXene). Impressively, the I-Ti3C2 MXene shows extraordinary long-term cyclic performance, even when cycled at high current density of 50 A/g, that the specific capacitance retention of 91% can be obtained over 100,000 cycles, corresponding to an average specific capacitance loss of only 0.00009% per cycle. Furthermore, the mechanisms involved were clarfied by systematical characterizations. This work will provide new insights for enhancing the supercapacitor performance of MXene-based materials by surface chemistry modification.