Clinical efficacy and safety of combined anti-BCMA and anti-CD19 CAR-T cell therapy for relapsed/refractory multiple myeloma: a systematic review and meta-analysis.

Background: The low rates of durable response against relapsed/refractory multiple myeloma (RRMM) in recent studies prompt that chimeric antigen receptor (CAR)-T cell therapies are yet to be optimized. The combined anti-BCMA and anti-CD19 CAR-T cell therapy showed high clinical efficacy in several clinical trials for RRMM. We here conducted a meta-analysis to confirm its efficacy and safety. Methods: We collected data from Embase, Web of Science, PubMed, CNKI, Wanfang and Cochrane databases up to April 2023. We extracted and evaluated data related to the efficacy and safety of combined anti-BCMA and anti-CD19 CAR-T cell therapies in RRMM patients. The data was then analyzed using RevMan5.4 and StataSE-64 software. PROSPERO number was CRD42023455002. Results: Our meta-analysis included 12 relevant clinical trials involving 347 RRMM patients who were treated with combined anti-BCMA and anti-CD19 CAR-T cell therapies. For efficacy assessment, the pooled overall response rate (ORR) was 94% (95% CI: 91%-98%), the complete response rate (CRR) was 50% (95% CI: 29%-71%), and the minimal residual disease (MRD) negativity rate within responders was 73% (95% CI: 66%-80%). In terms of safety, the pooled all-grade cytokine release syndrome (CRS) rate was 98% (95% CI: 97%-100%), grade≥3 CRS rate was 9% (95% CI: 4%-14%), and the incidence of neurotoxicity was 8% (95% CI: 4%-11%). Of hematologic toxicity, neutropenia was 82% (95% CI: 75%-89%), anemia was 71% (95% CI: 53%-90%), thrombocytopenia was 67% (95% CI: 40%-93%) and infection was 42% (95% CI: 9%-76%). The median progression-free survival (PFS) was 12.97 months (95% CI: 6.02-19.91), and the median overall survival (OS) was 26.63 months (95% CI: 8.14-45.11). Conclusions: As a novel immunotherapy strategy with great potential, the combined anti-BCMA and anti-CD19 CAR-T cell therapy showed high efficacy in RRMM, but its safety needs further improvement. This meta-analysis suggests possible optimization of combined CAR-T therapy. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023455002.

Core-Shell Gold Nanoparticles@Pd-Loaded Covalent Organic Framework for In Situ Surface-Enhanced Raman Spectroscopy Monitoring of Catalytic Reactions.

A core-shell nanostructure of gold nanoparticles@covalent organic framework (COF) loaded with palladium nanoparticles (AuNPs@COF-PdNPs) was designed for the rapid monitoring of catalytic reactions with surface-enhanced Raman spectroscopy (SERS). The nanostructure was prepared by coating the COF layer on AuNPs and then in situ synthesizing PdNPs within the COF shell. With the respective SERS activity and catalytic performance of the AuNP core and COF-PdNPs shell, the nanostructure can be directly used in the SERS study of the catalytic reaction processes. It was shown that the confinement effect of COF resulted in the high dispersity of PdNPs and outstanding catalytic activity of AuNPs@COF-PdNPs, thus improving the reaction rate constant of the AuNPs@COF-PdNPs-catalyzed hydrogenation reduction by 10 times higher than that obtained with Au/Pd NPs. In addition, the COF layer can serve as a protective shell to make AuNPs@COF-PdNPs possess excellent reusability. Moreover, the loading of PdNPs within the COF layer was found to be in favor of avoiding intermediate products to achieve a high total conversion rate. AuNPs@COF-PdNPs also showed great catalytic activities toward the Suzuki-Miyaura coupling reaction. Taken together, the proposed core-shell nanostructure has great potential in monitoring and exploring catalytic processes and interfacial reactions.

Effective Management of Polycythemia Vera With Ropeginterferon Alfa-2b Treatment.

Background: Polycythemia vera (PV) is a myeloproliferative neoplasm. Ropeginterferon alfa-2b is a new-generation polyethylene glycol-conjugated proline-interferon. It is approved for the treatment of PV at a starting dose of 100 µg (50 µg for patients receiving hydroxyurea (HU)) and dose titrations up to 500 µg by 50 µg increments. The study was aimed at assessing its efficacy and safety at a higher starting dose and simpler intra-patient dose escalation. Methods: Forty-nine patients with PV having HU intolerance from major hospitals in China were treated biweekly with an initial dose of 250 µg, followed by 350 µg and 500 µg thereafter if tolerated. Complete hematological response (CHR) was assessed every 12 weeks based on the European LeukemiaNet criteria. The primary endpoint was the CHR rate at week 24. The secondary endpoints included CHR rates at weeks 12, 36 and 52, changes of JAK2V617F allelic burden, time to first CHR, and safety assessments. Results: The CHR rates were 61.2%, 69.4% and 71.4% at weeks 24, 36, and 52, respectively. Mean allele burden of the driver mutation JAK2V617F declined from 58.5% at baseline to 30.1% at 52 weeks. Both CHR and JAK2V617F allele burden reduction showed consistent increases over the 52 weeks of the treatment. Twenty-nine patients (63.0%) achieved partial molecular response (PMR) and two achieved complete molecular response (CMR). The time to CHR was rapid and median time was 5.6 months according to central lab results. The CHRs were durable and median CHR duration time was not reached at week 52. Mean spleen index reduced from 55.6 cm2 at baseline to 50.2 cm2 at week 52. Adverse events (AEs) were mostly mild or moderate. Most common AEs were reversible alanine aminotransferase and aspartate aminotransferase increases, which were not associated with significant elevations in bilirubin levels or jaundice. There were no grade 4 or 5 AEs. Grade 3 AEs were reversible and manageable. Only one AE led to discontinuation. No incidence of thromboembolic events was observed. Conclusion: The 250-350-500 µg dosing regimen was well tolerated and effectively induced CHR and MR and managed spleen size increase. Our findings demonstrate that ropeginterferon alfa-2b at this dosing regimen can provide an effective management of PV and support using this dosing regimen as a treatment option.

Age-stratified analysis of HTO and UKA clinical effects in cross-indicated anterior medial osteoarthritis.

PURPOSE: To compare clinical outcomes of high tibial osteotomy (HTO) and unicompartmental knee arthroplasty (UKA) for anterior medial osteoarthritis (AMOA) as well as offer surgical recommendations through age stratification. METHODS: Between May 2019 and May 2021, 68 cross-indicated AMOA patients were analyzed. The patients were divided into HTO and UKA groups and further into two age groups of 55-60 and 60-65 years. Additionally, general data, visual analog scale (VAS) score, and Hospital for Special Surgery knee score (HSS) were analyzed. RESULTS: All the patients were followed up for 18 months. Knee joint HSS significantly improved, and VAS score decreased in both groups (P < 0.05). In the 55-60 age group, HTO showed superior knee HSS at 1 and 3 months (P < 0.05), with no significant difference at 6, 12, and 18 months. HTO had a significantly lower VAS score at one month, and the VAS scores of the two groups decreased gradually with no significant difference. In the 60-65 age group, the UKA group showed superior knee joint HSS at one month, with no significant difference at 3, 6, 12, and 18 months. The UKA group had a significantly lower VAS score at one month, and both groups' VAS scores decreased gradually with no significant difference. CONCLUSION: Both methods yield satisfactory results for AMOA cross-indications, improving knee joint function. The observed recovery trends have implications for personalized surgical recommendations, guiding interventions based on age-specific considerations for optimal outcomes in anterior medial osteoarthritis cases.

Complement C1q-mediated microglial synaptic elimination by enhancing desialylation underlies sevoflurane-induced developmental neurotoxicity.

BACKGROUND: Repeated neonatal sevoflurane exposures led to neurocognitive disorders in young mice. We aimed to assess the role of microglia and complement C1q in sevoflurane-induced neurotoxicity and explore the underlying mechanisms. METHODS: Neonatal mice were treated with sevoflurane on postnatal days 6, 8, and 10, and the Morris water maze was performed to assess cognitive functions. For mechanistic explorations, mice were treated with minocycline, C1q-antibody ANX005, and sialidase-inhibitor N-acetyl-2,3-dehydro-2-deoxyneuraminic acid (NADNA) before sevoflurane exposures. Western blotting, RT-qPCR, Golgi staining, 3D reconstruction and engulfment analysis, immunofluorescence, and microglial morphology analysis were performed. In vitro experiments were conducted in microglial cell line BV2 cells. RESULTS: Repeated neonatal sevoflurane exposures resulted in deficiencies in learning and cognition of young mice, accompanied by microglial activation and synapse loss. Sevoflurane enhanced microglia-mediated synapse elimination through C1q binding to synapses. Inhibition of microglial activation and phagocytosis with minocycline significantly reduced the loss of synapses. We further revealed the involvement of neuronal sialic acids in this process. The enhanced activity of sialidase by sevoflurane led to the loss of sialic acids, which facilitated C1q binding to synapses. Inhibition of C1q with ANX005 or inhibition of sialidase with NADNA significantly rescued microglia-mediated synapse loss and improved neurocognitive function. Sevoflurane enhanced the engulfment of BV2 cells, which was reversed by ANX005. CONCLUSIONS: Our findings demonstrated that C1q-mediated microglial synaptic elimination by enhancing desialylation contributed to sevoflurane-induced developmental neurotoxicity. Inhibition of C1q or sialidase may be a potential therapeutic strategy for this neurotoxicity.

Single-cell analysis revealing the metabolic landscape of prostate cancer.

Tumor metabolic reprogramming is a hallmark of cancer development, and targeting metabolic vulnerabilities has been proven to be an effective approach for castration-resistant prostate cancer (CRPC) treatment. Nevertheless, treatment failure inevitably occurs, largely due to cellular heterogeneity, which cannot be deciphered by traditional bulk sequencing techniques. By employing computational pipelines for single-cell RNA sequencing, we demonstrated that epithelial cells within the prostate are more metabolically active and plastic than stromal cells. Moreover, we identified that neuroendocrine (NE) cells tend to have high metabolic rates, which might explain the high demand for nutrients and energy exhibited by neuroendocrine prostate cancer (NEPC), one of the most lethal variants of prostate cancer (PCa). Additionally, we demonstrated through computational and experimental approaches that variation in mitochondrial activity is the greatest contributor to metabolic heterogeneity among both tumor cells and nontumor cells. These results establish a detailed metabolic landscape of PCa, highlight a potential mechanism of disease progression, and emphasize the importance of future studies on tumor heterogeneity and the tumor microenvironment from a metabolic perspective.

Magneto-optical Properties of Chiral Co2Ln and Co3Ln2 (Ln = Dy and Er) Clusters.

A series of chiral heterometallic Ln-Co clusters, denoted as Co2Ln and Co3Ln2 (Ln = Dy and Er), were synthesized by reacting the chiral chelating ligand (R/S)-2-(1-hydroxyethyl)pyridine (Hmpm), CoAc2·4H2O, and Ln(NO3)3·6H2O. Co2Ln and Co3Ln2 exhibit perfect mirror images in circular dichroism within the 320-700 nm range. Notably, the Co2Er and Co3Er2 clusters display pronounced magnetic circular dichroism (MCD) responses of the hypersensitive f-f transitions 4I15/2-4G11/2 at 375 nm and 4I15/2-2H11/2 at 520 nm of ErIII ions. This study highlights the strong magneto-optical activity associated with hypersensitive f-f transitions in chiral 3d-4f magnetic clusters.

Advances in the study of tertiary lymphoid structures in the immunotherapy of breast cancer.

Breast cancer, as one of the most common malignancies in women, exhibits complex and heterogeneous pathological characteristics across different subtypes. Triple-negative breast cancer (TNBC) and HER2-positive breast cancer are two common and highly invasive subtypes within breast cancer. The stability of the breast microbiota is closely intertwined with the immune environment, and immunotherapy is a common approach for treating breast cancer.Tertiary lymphoid structures (TLSs), recently discovered immune cell aggregates surrounding breast cancer, resemble secondary lymphoid organs (SLOs) and are associated with the prognosis and survival of some breast cancer patients, offering new avenues for immunotherapy. Machine learning, as a form of artificial intelligence, has increasingly been used for detecting biomarkers and constructing tumor prognosis models. This article systematically reviews the latest research progress on TLSs in breast cancer and the application of machine learning in the detection of TLSs and the study of breast cancer prognosis. The insights provided contribute valuable perspectives for further exploring the biological differences among different subtypes of breast cancer and formulating personalized treatment strategies.

An advanced high-rate capability sodium-ion anode: Few-layered NbSe2 with a mechanism of parallel running intercalation and conversion.

The unique superconductivity and charge density wave transition characteristics of NbSe2 make it worthy of exploring its electrochemical performance and potential applications in the field of batteries. Herein, the bulk NbSe2 was successfully exfoliated into few-layered NbSe2 nanostructures by wet grinding exfoliation approach, which solved the issues of its long activation period and poor cycle stability. The strong Nb-Se bond in the plane and weak van der Waals force between the adjacent layers could render the fast Na+ diffusion, provide abundant reaction sites and multi-directional migration paths, thus accelerate the ionic conductivity. The theoretical calculations verified the high Na+ adsorption tendency between the NbSe2 interlayers stemming from the continuous region of charge accumulation. Thanks to the unique electronic and two-dimensional few-layered structures, the exfoliated NbSe2 exhibited a high cyclic stability with a capacity of 502 mA h g-1 over 2800 cycles at 10 A/g. In addition, the reaction mechanism was studied by in-situ X-ray diffraction and other tests, indicating a reaction mechanism containing of simultaneous intercalation (NbSe2↔NaxNbSe2↔NaNbSe2↔Na1+xNbSe2) and conversion processes in NbSe2. This parallelly running mechanism not only alleviates the volume change but also ensures a high specific capacity. Additionally, different lattice planes of the NaNbSe2 intermediate in the intercalation process experience varying degrees of contraction and expanding in d-spacing due to the influence of Coulombic force.

Tunable Emission of Low-Dimensional Organic Metal Halides by Stoichiometric Ratio and Metal Center.

Low-dimensional (LD) organic metal halides (OMHs) have a bright future due to their excellent photoelectric characteristics and unique structure. However, the synthesis and emission control of LD-OMHs are still unclear. Herein, the different dimensional (zero-dimensional (0D), one-dimensional (1D), and three-dimensional (3D)) of OMHs were obtained by the reaction of 1,4-diazabicyclo (2.2.2) octane with PbBr2 in different stoichiometric ratios. This discovery shows that the structure and properties of OMHs can be regulated while maintaining the functional organic cations of OMHs, which broadens the path for the development of functional LD-OMHs. Among them, 0D-OMH 1 and 1D-OMH 3 have narrow-band (full width at half-maximum (fwhm) = 74 nm) and broad-band (fwhm = 201 nm) emission, respectively. We found that when organic cations have no contribution to the formation of conduction band minimum and valence band maximum, and the distances between polyhedrons are larger than the van der Waals diameter of the halogen atom, the effect of phonons on exciton transitions can be reduced to achieve a narrow-band emission. Further, Cu(I)- and Mn (II)-based 0D-OMHs were synthesized, which have high photoluminescence quantum yield (PLQY) (33.97 and 47.33%, respectively). When the emitting of 0D-OMHs produced by the interaction of the metal-center and halogens, the asymmetric planar metal-halogen structure will result in a higher PLQY.

Preservative Effects of Curcumin on Semen of Hu Sheep.

Reactive oxygen species (ROS) are important factors that lead to a decline in sperm quality during semen preservation. Excessive ROS accumulation disrupts the balance of the antioxidant system in sperm and causes lipid oxidative damage, destroying its structure and function. Curcumin is a natural plant extract that neutralizes ROS and enhances the function of endogenous antioxidant enzymes. The effect of curcumin on the preservation of sheep semen has not been reported. This study aims to determine the effects of curcumin on refrigerated sperm (4 °C) and analyze the effects of curcumin on sperm metabolism from a Chinese native sheep (Hu sheep). The results showed that adding curcumin significantly improved (p < 0.05) the viability of refrigerated sperm at an optimal concentration of 20 µmol/L, and the plasma membrane and acrosome integrity in semen were significantly improved (p < 0.05). Adding curcumin to refrigerated semen significantly increased (p < 0.05) the levels of antioxidant enzymes (T-AOC, CAT, and SOD) and significantly decreased (p < 0.05) ROS production. A total of 13,796 metabolites in sperm and 20,581 metabolites in negative groups and curcumin-supplemented groups were identified using liquid chromatography-mass spectrometry. The proportion of lipids and lipid-like molecules among all metabolites in the sperm was the highest, regardless of treatment. We identified 50 differentially expressed metabolites (DEMs) in sperm between the negative control and curcumin-treated groups. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that DEMs were mainly enriched in the calcium signaling pathway, phospholipase D signaling pathway, sphingolipid metabolism, steroid hormone biosynthesis, 2-oxocarboxylic acid metabolism, and other metabolic pathways. The findings indicate that the addition of an appropriate concentration (20 µm/L) of curcumin to sheep semen can effectively suppress reactive oxygen species (ROS) production and extend the duration of cryopreservation (4 °C) by modulating the expression of sphingosine-1-phosphate, dehydroepiandrosterone sulfate, phytosphingosine, and other metabolites of semen. This discovery offers a novel approach to enhancing the cryogenic preservation of sheep semen.

The role of robotic-assisted surgery in the management of rectal cancer: a systematic review and meta-analysis.

BACKGROUND: Rectal cancer poses a significant global health burden. There is a lack of concrete evidence concerning the benefits of robotic-assisted surgery (RAS) for rectal cancer surgery as compared to laparoscopic and open techniques. To address this gap, we conducted a meta-analysis to assess the intraoperative, postoperative, and safety outcomes of robotic surgery in this context. METHODS: MEDLINE, Scopus, and the Cochrane library were searched till May 2023 for randomized and non-randomized studies comparing robotic surgery with either laparoscopic or open approach for rectal cancers. The outcomes of interest were operative time, blood loss, harvested lymph nodes, conversion rate, postoperative hospital stay, survival to hospital discharge, urinary retention rate, and anastomotic leakage rate. A random-effects meta-analysis was performed to pool means and dichotomous data to derive weighted mean differences and odds ratios, respectively. RESULTS: A total of 56 studies were shortlisted after the study selection process with a total of 25,458 rectal cancer patients. From the intraoperative outcomes, RAS was significantly associated with an increased operative time (WMD: 41.04, P <0.00001), decreased blood loss (WMD: -24.56, P <0.00001), decreased conversion rates (OR: 0.39, P <0.00001), lesser stay at the hospital (WMD: -1.93, P <0.00001), and no difference was found in lymph nodes harvested. Similarly, RAS group had a significantly greater survival to hospital discharge (OR: 1.90, P =0.04), decreased urinary retention rate (OR: 0.59, P =0.002), and no difference was seen in anastomotic leakage rate. CONCLUSION: Robotic-assisted surgery (RAS) demonstrates favourable outcomes for rectal cancer patients, contributing to global prevention and control efforts, health promotion, and addressing non-communicable disease risk factors. Further research and public awareness are needed to optimize RAS utilization in this context.

ROS-responsive & scavenging NO nanomedicine for vascular diseases treatment by inhibiting endoplasmic reticulum stress and improving NO bioavailability.

Vascular diseases seriously threaten human life and health. Exogenous delivery of nitric oxide (NO) represents an effective approach for maintaining vascular homeostasis during pathological events. However, the overproduction of reactive oxygen species (ROS) at vascular injury sites would react with NO to produce damaging peroxynitrite (ONOO-) species and limit the therapeutic effect of NO. Hence, we design a ROS-responsive NO nanomedicine (t-PBA&NO NP) with ROS scavenging ability to solve the dilemma of NO-based therapy. t-PBA&NO NP targets NO and anti-oxidant ethyl caffeate (ECA) to the injury sites via collagen IV homing peptide. The ROS-triggered ROS depletion and ECA release potently alleviate local oxidative stress via ROS scavenging, endoplasmic reticulum and mitochondrial regulation. It subsequently maximizes vascular modulation effects of NO, without production of harmful compounds, reactive nitrogen species (RNS). Therefore, it significantly increases competitiveness of human umbilical vein endothelial cells (HUVECs) over human aortic smooth muscle cells (HASMCs) both in vitro and in vivo. The strategy proved effective in inducing faster re-endothelialization, inhibiting neointimal formation and restoring vascular homeostasis. The synergy between ROS depletion and NO therapy served as a new inspiration for the treatment of cardiovascular diseases and other ROS-associated illnesses.

Spatial variation and controls of soil microbial necromass carbon in a tropical montane rainforest.

Soil microbial necromass carbon is an important component of the soil organic carbon (SOC) pool which helps to improve soil fertility and texture. However, the spatial pattern and variation mechanisms of fungal- and bacterial-derived necromass carbon at local scales in tropical rainforests are uncertain. This study showed that microbial necromass carbon and its proportion in SOC in tropical montane rainforest exhibited large spatial variation and significant autocorrelation, with significant high-high and low-low clustering patterns. Microbial necromass carbon accounted for approximately one-third of SOC, and the fungal-derived microbial necromass carbon and its proportion in SOC were, on average, approximately five times greater than those of bacterial-derived necromass. Structural equation models indicated that soil properties (SOC, total nitrogen, total phosphorus) and topographic features (elevation, convexity, and aspect) had significant positive effects on microbial necromass carbon concentrations, but negative effects on its proportions in SOC (especially the carbon:nitrogen ratio). Plant biomass also had significant negative effects on the proportion of microbial necromass carbon in SOC, but was not correlated with its concentration. The different spatial variation mechanisms of microbial necromass carbon and their proportions in SOC are possibly related to a slower accumulation rate of microbial necromass carbon than of plant-derived organic carbon. Geographic spatial correlations can significantly improve the microbial necromass carbon model fit, and low sampling resolution may lead to large uncertainties in estimating soil carbon dynamics at specific sites. Our work will be valuable for understanding microbial necromass carbon variation in tropical forests and soil carbon prediction model construction with microbial participation.

Age-Related Gut Microbiota Transplantation Disrupts Myocardial Energy Homeostasis and Induces Oxidative Damage.

BACKGROUND: Aging-related energy homeostasis significantly affects normal heart function and disease development. The relationship between the gut microbiota and host energy metabolism has been well established. However, the influence of an aged microbiota on energy metabolism in the heart remains unclear. OBJECTIVE: The objective of this was to explore the effects of age-related microbiota composition on energy metabolism in the heart. METHODS: In this study, we used the fecal microbiota transplantation (FMT) method. The fecal microbiota from young (2-3 mo) and aged (18-22 mo) donor mice were transplanted into separate groups of young (2-3 mo) recipient mice. The analysis utilized whole 16S rRNA sequencing and plasma metabolomics to assess changes in the gut microbiota composition and metabolic potential. Energy changes were monitored by performing an oral glucose tolerance test, biochemical testing, body composition analysis, and metabolic cage measurements. Metabolic markers and markers of DNA damage were assessed in heart samples. RESULTS: FMT of an aged microbiota changed the composition of the recipient's gut microbiota, leading to an elevated Firmicutes-to-Bacteroidetes ratio. It also affected overall energy metabolism, resulting in elevated plasma glucose concentrations, impaired glucose tolerance, and epididymal fat accumulation. Notably, FMT of an aged microbiota increased the heart weight and promoted cardiac hypertrophy. Furthermore, there were significant associations between heart weight and cardiac hypertrophy indicators, epididymal fat weight, and fasting glucose concentrations. Mechanistically, FMT of an aged microbiota modulated the glucose metabolic pathway and induced myocardial oxidative damage. CONCLUSIONS: Our findings suggested that an aged microbiota can modulate metabolism and induce cardiac injury. This highlights the possible role of the gut microbiota in age-related metabolic disorders and cardiac dysfunction.

The effect of sevoflurane exposure on cell-type-specific changes in the prefrontal cortex in young mice.

Sevoflurane, the predominant pediatric anesthetic, has been linked to neurotoxicity in young mice, although the underlying mechanisms remain unclear. This study focuses on investigating the impact of neonatal sevoflurane exposure on cell-type-specific alterations in the prefrontal cortex (PFC) of young mice. Neonatal mice were subjected to either control treatment (60% oxygen balanced with nitrogen) or sevoflurane anesthesia (3% sevoflurane in 60% oxygen balanced with nitrogen) for 2 hours on postnatal days (PNDs) 6, 8, and 10. Behavioral tests and single-nucleus RNA sequencing (snRNA-seq) of the PFC were conducted from PNDs 31 to 37. Mechanistic exploration included clustering analysis, identification of differentially expressed genes (DEGs), enrichment analyses, single-cell trajectory analysis, and genome-wide association studies (GWAS). Sevoflurane anesthesia resulted in sociability and cognition impairments in mice. Novel specific marker genes identified 8 distinct cell types in the PFC. Most DEGs between the control and sevoflurane groups were unique to specific cell types. Re-defining 15 glutamatergic neuron subclusters based on layer identity revealed their altered expression profiles. Notably, sevoflurane disrupted the trajectory from oligodendrocyte precursor cells (OPCs) to oligodendrocytes (OLs). Validation of disease-relevant candidate genes across the main cell types demonstrated their association with social dysfunction and working memory impairment. Behavioral results and snRNA-seq collectively elucidated the cellular atlas in the PFC of young male mice, providing a foundation for further mechanistic studies on developmental neurotoxicity induced by anesthesia.

Tailoring drug release in bilayer tablets through droplet deposition modeling and injection molding.

This study explores the innovative production of personalized bilayer tablets, integrating two advanced manufacturing techniques: Droplet Deposition Modeling (DDM) and Injection Molding (IM). Unlike traditional methods limited to customizing dense bilayer medicines, our approach uses Additive Manufacturing (AM) to effectively adjust drug release profiles. Focusing on Caffeine and Paracetamol, we found successful processing for both DDM and IM using Caffeine formulation. The high viscosity of Paracetamol formulation posed challenges during DDM processing. Integrating Paracetamol formulation for the over-molding process proved effective, demonstrating IM's versatility in handling complex formulations. Varying infill percentages in DDM tablets led to distinct porosities affecting diverse drug release profiles in DDM-fabricated tablets. In contrast, tablets with high-density structures formed through the over-molding process displayed slower and more uniform release patterns. Combining DDM and IM techniques allows for overcoming the inherent limitations of each technique independently, enabling the production of bilayer tablets with customizable drug release profiles. The study's results offer promising insights into the future of personalized medicine, suggesting new pathways for the development of customized oral dosage forms.

Highly Sensitive, Stable InP Quantum Dot Fluorescent Probes for Quantitative Immunoassay Through Nanostructure Tailoring and Biotin-Streptavidin Coupling.

Nontoxic, highly sensitive InP quantum dot (QD) fluorescent immunoassay probes are promising biomedical detection modalities due to their unique properties. However, InP-based QDs are prone to surface oxidation, and the stability of InP QD-based probes in biocompatible environments remains a crucial challenge. Although the thick shell can provide some protection during the phase transfer process of hydrophobic QDs, the photoluminescence quantum yield (PLQY) is generally decreased because of the contradiction between lattice stress relaxation and thick shell growth. Herein, we developed thick-shell InP-based core/shell QDs by inserting a ZnSeS alloy layer. The ternary ZnSeS intermediate shell could effectively facilitate lattice stress relaxation and passivate the defect states. The synthesized InP/ZnSe/ZnSeS/ZnS core/alloy shell/shell QDs (CAS-InP QDs) with nanostructure tailoring revealed a larger size, high PLQY (90%), and high optical stability. After amphiphilic polymer encapsulation, the aqueous CAS-InP QDs presented almost constant fluorescence attenuation and stable PL intensity under different temperatures, UV radiation, and pH solutions. The CAS-InP QDs were excellent labels of the fluorescence-linked immunosorbent assay (FLISA) for detecting C-reactive protein (CRP). The biotin-streptavidin (Bio-SA) system was first introduced in the FLISA to further improve the sensitivity, and the CAS-InP QDs-based SA-Bio sandwich FLISA realized the detection of CRP with an impressive limit of detection (LOD) of 0.83 ng/mL. It is believed that the stable and sensitive InP QD fluorescent probes will drive the rapid development of future eco-friendly, cost-effective, and sensitive in vitro diagnostic kits.