Mechanism of inflammatory response and therapeutic effects of stem cells in ischemic stroke: current evidence and future perspectives.

Ischemic stroke is a leading cause of death and disability worldwide, with an increasing trend and tendency for onset at a younger age. China, in particular, bears a high burden of stroke cases. In recent years, the inflammatory response after stroke has become a research hotspot: understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its treatment. This review summarizes several major cells involved in the inflammatory response following ischemic stroke, including microglia, neutrophils, monocytes, lymphocytes, and astrocytes. Additionally, we have also highlighted the recent progress in various treatments for ischemic stroke, particularly in the field of stem cell therapy. Overall, understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient outcomes. Stem cell therapy may potentially become an important component of ischemic stroke treatment.

Isolation and identification of specific Enterococcus faecalis phage C-3 and G21-7 against Avian pathogenic Escherichia coli and its application to one-day-old geese.

Colibacillosis caused by Avian pathogenic Escherichia coli (APEC), including peritonitis, respiratory tract inflammation and ovaritis, is recognized as one of the most common and economically destructive bacterial diseases in poultry worldwide. In this study, the characteristics and inhibitory potential of phages were investigated by double-layer plate method, transmission electron microscopy, whole genome sequencing, bioinformatics analysis and animal experiments. The results showed that phages C-3 and G21-7 isolated from sewage around goose farms infected multiple O serogroups (O1, O2, O18, O78, O157, O26, O145, O178, O103 and O104) Escherichia coli (E.coli) with a multiplicity of infection (MOI) of 10 and 1, respectively. According to the one-step growth curve, the incubation time of both bacteriophage C-3 and G21-7 was 10 min. Sensitivity tests confirmed that C-3 and G21-6 are stable at 4 to 50 °C and pH in the range of 4 to 11. Based on morphological and phylogenetic analysis, phages C-3 and G21-7 belong to Enterococcus faecalis (E. faecalis) phage species of the genus Saphexavirus of Herelleviridae family. According to genomic analysis, phage C-3 and G21-7 were 58,097 bp and 57,339 bp in size, respectively, with G+C content of 39.91% and 39.99%, encoding proteins of 97 CDS (105 to 3,993 bp) and 96 CDS (105 to 3,993 bp), and both contained 2 tRNAs. Both phages contained two tail proteins and holin-endolysin system coding genes, and neither carried resistance genes nor virulence factors. Phage mixture has a good safety profile and has shown good survival probability and feed efficiency in both treatment and prophylaxis experiments with one-day-old goslings. These results suggest that phage C-3 and G21-7 can be used as potential antimicrobials for the prevention and treatment of APEC.

Mapping the distribution of Nipah virus infections: a geospatial modelling analysis.

BACKGROUND: Nipah virus is a zoonotic paramyxovirus responsible for disease outbreaks with high fatality rates in south and southeast Asia. However, knowledge of the potential geographical extent and risk patterns of the virus is poor. We aimed to establish an integrated spatiotemporal and phylogenetic database of Nipah virus infections in humans and animals across south and southeast Asia. METHODS: In this geospatial modelling analysis, we developed an integrated database containing information on the distribution of Nipah virus infections in humans and animals from 1998 to 2021. We conducted phylodynamic analysis to examine the evolution and migration pathways of the virus and meta-analyses to estimate the adjusted case-fatality rate. We used two boosted regression tree models to identify the potential ecological drivers of Nipah virus occurrences in spillover events and endemic areas, and mapped potential risk areas for Nipah virus endemicity. FINDINGS: 749 people and eight bat species across nine countries were documented as being infected with Nipah virus. On the basis of 66 complete genomes of the virus, we identified two clades-the Bangladesh clade and the Malaysia clade-with the time of the most recent common ancestor estimated to be 1863. Adjusted case-fatality rates varied widely between countries and were higher for the Bangladesh clade than for the Malaysia clade. Multivariable meta-regression analysis revealed significant relationships between case-fatality rate estimates and viral clade (p=0·0021), source country (p=0·016), proportion of male patients (p=0·036), and travel time to health-care facilities (p=0·036). Temperature-related bioclimate variables and the probability of occurrence of Pteropus medius were important contributors to both the spillover and the endemic infection models. INTERPRETATION: The suitable niches for Nipah virus are more extensive than previously reported. Future surveillance efforts should focus on high-risk areas informed by updated projections. Specifically, intensifying zoonotic surveillance efforts, enhancing laboratory testing capacity, and implementing public health education in projected high-risk areas where no human cases have been reported to date will be crucial. Additionally, strengthening wildlife surveillance and investigating potential modes of transmission in regions with documented human cases is needed. FUNDING: The Key Research and Development Program of China.

Imbalance of mitochondrial quality control regulated by STING and PINK1 affects cyfluthrin-induced neuroinflammation.

Nervous system diseases are a global health problem, and with the increase in the elderly population around the world, their incidence will also increase. Harmful substances in the environment are closely related to the occurrence of nervous system diseases. China is a large agricultural country, and thus the insecticide cyfluthrin has been widely used. Cyfluthrin is neurotoxic, but the mechanism of this injury is not clear. Inflammation is an important mechanism for the occurrence of nervous system diseases. Mitochondria are the main regulators of the inflammatory response, and various cellular responses, including autophagy, directly affect the regulation of inflammatory processes. Mitochondrial damage is related to mitochondrial quality control (MQC) and PTEN-induced kinase 1 (PINK1). As an anti-inflammatory factor, stimulator of interferon genes (STING) participates in the regulation of inflammation. However, the relationship between STING and mitochondria in the process of cyfluthrin-induced nerve injury is unclear. This study established in vivo and in vitro models of cyfluthrin exposure to explore the role of MQC and to clarify the mechanism of action of STING and PINK1. Our results showed that cyfluthrin can increase the reactive oxygen species (ROS) level, resulting in mitochondrial damage and inflammation. In this process, an imbalance in MQC leads to the aggravation of mitochondrial damage, and high STING expression drives the occurrence of inflammation. We established a differential expression model of STING and PINK1 to further determine the underlying mechanism and found that the interaction between STING and PINK1 regulates MQC to affect the levels of mitochondrial damage and inflammation. When STING and PINK1 expression are downregulated, mitochondrial damage and STING-induced inflammation are significantly alleviated. In summary, a synergistic effect between STING and PINK1 on cyfluthrin-induced neuroinflammation may exist, which leads to an imbalance in MQC by inhibiting mitochondrial biogenesis and division/fusion, and PINK1 can reduce STING-driven inflammation.

N6-methyldeoxyadenosine modification difference contributes to homocysteine-induced mitochondrial perturbation in rat hippocampal primary neurons and PC12 cells.

Elevated homocysteine (Hcy) levels are detrimental to neuronal cells and contribute to cognitive dysfunction in rats. Mitochondria plays a crucial role in cellular energy metabolism. Interestingly, the damaging effects of Hcy in vivo and in vitro conditions exhibit distinct results. Herein, we aimed to investigate the effects of Hcy on mitochondrial function in primary neurons and PC12 cells and explore the underlying mechanisms involved. The metabolic intermediates of Hcy act as methyl donors and play important epigenetic regulatory roles. N6-methyldeoxyadenosine (6 mA) modification, which is enriched in mitochondrial DNA (mtDNA), can be mediated by methylase METTL4. Our study suggested that mitochondrial perturbation caused by Hcy in primary neurons and PC12 cells may be attributable to mtDNA 6 mA modification difference. Hcy could activate the expression of METTL4 within mitochondria to facilitate mtDNA 6 mA status, and repress mtDNA transcription, then result in mitochondrial dysfunction.

A trans-umbilical single-site plus one robotic-assisted surgery for choledochal cyst resection in children.

Objective: The purpose of this study is to compare the intraoperative and postoperative outcomes of a trans-umbilical single-site plus one robot-assisted surgery and a trans-umbilical single-site laparoscopic surgery in the treatment of choledochal cysts. Methods: We retrospectively analyzed clinical data from 49 children diagnosed with choledochal cysts who were admitted to our hospital between June 2020 and December 2023. Among these patients, 24 underwent a trans-umbilical single-site plus one Da Vinci robot-assisted surgery (the robot group) and 25 underwent a trans-umbilical single-site laparoscopic-assisted surgery (the laparoscopic group). We compared differences in intraoperative and postoperative outcomes between the two groups. Results: There was no significant difference between the two groups of patients in terms of gender, age, weight, clinical symptoms, maximum cyst diameter, type, postoperative complications, and facial expression, leg movement, activity, crying, and comfortability (FLACC) scoring (p > 0.05). Compared with the patients in the laparoscopic group, those in the robot group had less intraoperative bleeding [10 (8-12) vs. 15 (11.5-18) ml, p < 0.001] and required less postoperative drainage tube indwelling time [5 (4-6) vs. 7 (5.5-8) day, p < 0.001], less postoperative fasting time [4 (3-4) vs. 6 (5-7) days, p < 0.001], and less postoperative hospitalization time [6 (6-7) vs. 8 (6-10) days, p < 0.001], but they required more operative time [385.5 (317.0-413.3) vs. 346.0 (287.0-376.5) min, p = 0.050] and consumed more hospitalization expenses (79,323 ± 3,124 vs. 31,121 ± 2,918 yuan, p < 0.001). Conclusion: The results of this study showed a shorter hospitalization time, quicker postoperative recovery, and less tissue damage but a higher cost and a longer operation time in patients who chose robotic surgery rather than laparoscopic surgery. With the continuous expansion of the scale of installed robot-assisted surgical systems and the gradual accumulation of the technical experience of surgeons, robot-assisted surgery may slowly surpass, and shows a trend to replace, laparoscopy because of its advantages.

Exposure of women undergoing In-Vitro Fertilization to per-and polyfluoroalkyl substances: Evidence on negative effects on Fertilization and high-quality embryos.

In April 2023, the World Health Organization (WHO) reported that 17.5% of the global adult population experience infertility. What may be the contribution of per-and polyfluoroalkyl (PFAS) to this global public health problem? This study explored the associations between in vitro fertilization (IVF) outcomes and plasma concentrations of individual PFAS and PFAS mixtures in women undergoing in vitro fertilization and embryo transfer (IVF-ET) and how these exposures might affect IVF outcomes. We analyzed 8 PFASs in plasma samples from women (N=259) who underwent IVF treatment. In multivariable generalized linear mixed models, there were statistically significant associations of higher plasma concentrations of PFNA with reduced numbers of total retrieved oocytes [12.486 (95%CI:-0.446,25.418), p trend=0.017], 2PN zygotes [6.467(95%CI:-2.034,14.968), p trend=0.007], and cleavage embryos [6.039(95%CI:-2.162,14.240), p trend=0.008]. Similarly, there was a continuous decline in the numbers of retrieved 2PN zygotes and cleavage embryos with increasing concentration of PFOS [6.467(95%CI:-2.034,14.968), p trend=0.009 and 6.039(95%CI:-2.162,14.240), p trend=0.031,respectively] and a negative association between PFHxS concentrations and clinical pregnancy during the initial cycles of frozen ET [0.525(95%CI:0.410,0.640), p trend=0.021]. To investigate the joint effect of PFAS mixtures, a confounder-adjusted BKMR model analysis showed inverse relationship between PFAS mixtures and the number of high-quality embryos, 2PN zygotes and cleavage embryos, to which the greatest contributors to the mixture effect are PFDeA and PFBS, respectively. It demonstrated that PFAS exposure might exert negative effects on oocyte yield, fertilization and high-quality embryo in women undergoing IVF. These findings suggest that exposure to PFAS may increase the risk of female infertility and further studies are needed to uncover the potential mechanisms underlying the reproductive effects associated with PFAS.

Antibiotic resistance characterization, virulence factors and molecular characteristics of Bacillus species isolated from probiotic preparations in China.

OBJECTIVES: The aim of this study was to determine the phenotypic and molecular characteristics of antibiotic-resistant Bacillus spp. isolated from probiotic preparations in China. METHODS: Bacillus strains were isolated from probiotic preparations and then identified using 16S rDNA sequencing. Drug sensitivity tests were conducted to determine their susceptibility to seven antibiotics. Whole genome sequencing was performed on the most resistant strains, followed by analysis of their molecular characteristics, resistance genes, and virulence factors. RESULTS: In total, we isolated 21 suspected Bacillus species from seven compound probiotics, which were identified by 16S rDNA as 12 Bacillus licheniformis, six Bacillus subtilis and three Bacillus cereus. The determination of antimicrobial susceptibility showed widespread resistance to chloramphenicol (95.2%), erythromycin (85.7%) and gentamicin (42.9%). Whole genome sequencing of seven resistant strains revealed that J-6-A (Bacillus subtilis) and J-7-A (Bacillus cereus) contained a plasmid. The resistance gene analysis revealed that each strain contained more than ten resistance genes, among which J-7-A was the most. The streptomycin resistance gene strA was detected in all strains. The chloramphenicol resistance genes ykkC and ykkD were found in J-1-A to J-5-A and were first reported in Bacillus subtilis. The erythrocin resistance gene ermD was detected in strains J-1-A to J-4-A. There were also more than 15 virulence factors and gene islands (GIs) involved in each strain. CONCLUSIONS: These results confirm the potential safety risks of probiotics and remind us to carefully select probiotic preparations containing strains of Bacillus species, especially Bacillus cereus, to avoid the potential spread of resistance and pathogenicity.

Nonactivated Aziridine Synthesis by Intermolecular Polarity-Mismatched Carboamination of Unactivated Alkenes with Unactivated Alkyl Halides.

A general intermolecular polarity-mismatched carboamination reaction of unactivated alkenes with unactivated alkyl halides has been developed. A series of nonactivated alkyl-substituted aziridines were constructed in exclusive regioselectivity. The dual polarity-mismatched mechanism might be involved.

Development of an animal model of hypothyroxinemia during pregnancy in Wistar rats.

BACKGROUND: Hypothyroxinemia is a subclinical thyroid hormone deficiency in which the mother has inadequate levels of T4 during pregnancy. The fetus relies entirely on the mother's T4 hormone level for early neurodevelopment. Isolated maternal hypothyroxinemia (IMH) in the first trimester of pregnancy can lead to lower intelligence, lower motor scores, and a higher risk of mental illness in descendants. Here, we focus on the autism-like behavior of IMH offspring. METHODS: The animals were administered 1 ppm of propylthiouracil (PTU) for 9 weeks. Then, the concentrations of T3, T4, and thyroid-stimulating hormone (TSH) were detected using enzyme-linked immunosorbent assay (ELISA) to verify the developed animal model of IMH. We performed four behavioral experiments, including the marble burying test, open-field test, three-chamber sociability test, and Morris water maze, to explore the autistic-like behavior of 40-day-old offspring rats. RESULTS: The ELISA test showed that the serum T3 and TSH concentrations in the model group were normal compared with the negative control group, whereas the T4 concentration decreased. In the behavioral experiments, the number of hidden marbles in the offspring of IMH increased significantly, the frequency of entering the central compartment decreased, and the social ratio decreased significantly. CONCLUSION: The animal model of IMH was developed by the administration of 1 ppm of PTU for 9 weeks, and there were autistic-like behavior changes such as anxiety, weakened social ability, and repeated stereotyping in the IMH offspring by 40 days.

[Expression Levels and Regulation of Selenoprotein Genes in Patients With Coronavirus Disease 2019].

Objective To investigate the expression levels of selenoprotein genes in the patients with coronavirus disease 2019 (COVID-19) and the possible regulatory mechanisms.Methods The dataset GSE177477 was obtained from the Gene Expression Omnibus,consisting of a symptomatic group (n=11),an asymptomatic group (n=18),and a healthy control group (n=18).The dataset was preprocessed to screen the differentially expressed genes (DEG) related to COVID-19,and gene ontology functional annotation and Kyoto encyclopedia of genes and genomes enrichment analysis were performed for the DEGs.The protein-protein interaction network of DEGs was established,and multivariate Logistic regression was employed to analyze the effects of selenoprotein genes on the presence/absence of symptoms in the patients with COVID-19.Results Compared with the healthy control,the symptomatic COVID-19 patients presented up-regulated expression of GPX1,GPX4,GPX6,DIO2,TXNRD1,SELENOF,SELENOK,SELENOS,SELENOT,and SELENOW and down-regulated expression of TXNRD2 and SELENON (all P<0.05).The asymptomatic patients showcased up-regulated expression of GPX2,SELENOI,SELENOO,SELENOS,SELENOT,and SELENOW and down-regulated expression of SELP (all P<0.05).The results of multivariate Logistic regression analysis showed that the abnormally high expression of GPX1 (OR=0.067,95%CI=0.005-0.904,P=0.042) and SELENON (OR=56.663,95%CI=3.114-856.999,P=0.006) was the risk factor for symptomatic COVID-19,and the abnormally high expression of SELP was a risk factor for asymptomatic COVID-19 (OR=15.000,95%CI=2.537-88.701,P=0.003).Conclusions Selenoprotein genes with differential expression are involved in the regulation of COVID-19 development.The findings provide a new reference for the prevention and treatment of COVID-19.

[Ce3+-OV-Ce4+] Located Surface-Distributed Sheet Cu-Zn-Ce Catalysts for Methanol Production by CO2 Hydrogenation.

The metal-support interaction is crucial for the performance of Cu-based catalysts. However, the distinctive properties of the support metal element itself are often overlooked in catalyst design. In this paper, a sheet Cu-Zn-Ce with [Ce3+-OV-Ce4+] located on the surface was designed by the sol-gel method. Through EPR and X-ray photoelectron spectroscopy (XPS), the relationship between the content of oxygen vacancies and Ce was revealed. Ce itself induces the generation of [Ce3+-OV-Ce4+]. Through ICP-MS, XPS, and SEM-mapping, the Ce-induced formation of [Ce3+-OV-Ce4+] located on the catalyst surface was demonstrated. CO2-TPD and DFT calculations further revealed that [Ce3+-OV-Ce4+] enhanced CO2 adsorption, leading to a 10% increase in methanol selectivity compared to Cu-Zn-Ce synthesized via the coprecipitation method.

Spinal histamine H4 receptor mediates chronic pruritus via p-ERK in acetone-ether-water (AEW)-induced dry skin mice.

Dry skin is common to many pruritic diseases and is difficult to improve with oral traditional antihistamines. Recently, increasing evidence indicated that histamine H4 receptor (H4R) plays an important role in the occurrence and development of pruritus. Extracellular signal-regulated kinase (ERK) phosphorylation activation in the spinal cord mediates histamine-induced acute and choric itch. However, whether the histamine H4 receptor regulates ERK activation in the dry skin itch remains unclear. In the study, we explore the role of the histamine H4 receptor and p-ERK in the spinal cord in a dry skin mouse model induced by acetone-ether-water (AEW). q-PCR, Western blot, pharmacology and immunofluorescence  were applied in the study. We established a dry skin itch model by repeated application of AEW on the nape of neck in mice. The AEW mice showed typically dry skin histological change and persistent spontaneous scratching behaviour. Histamine H4 receptor, instead of histamine H1 receptor, mediated spontaneous scratching behaviour in AEW mice. Moreover, c-Fos and p-ERK expression in the spinal cord neurons were increased and co-labelled with GRPR-positive neurons in AEW mice. Furthermore, H4R agonist 4-methyhistamine dihydrochloride (4-MH)induced itch. Both 4-MH-induced itch and the spontaneous itch in AEW mice were blocked by p-ERK inhibitor U0126. Finally, intrathecal H4R receptor antagonist JNJ7777120 inhibited spinal p-ERK expression in AEW mice. Our results indicated that spinal H4R mediates itch via ERK activation in the AEW-induced dry skin mice.

The role and mechanism of action of miR-483-3p in mediating the effects of IGF-1 on human renal tubular epithelial cells induced by high glucose.

This study aimed to elucidate the influence of miR-483-3p on human renal tubular epithelial cells (HK-2) under high glucose conditions and to understand its mechanism. Human proximal tubular epithelial cells (HK-2) were exposed to 50 mmol/L glucose for 48 h to establish a renal tubular epithelial cell injury model, denoted as the high glucose group (HG group). Cells were also cultured for 48 h in a medium containing 5.5 mmol/L glucose, serving as the low glucose group. Transfection was performed in various groups: HK-2 + low glucose (control group), high glucose (50 mM) (HG group), high glucose + miR-483-3p mimics (HG + mimics group), high glucose +miR-483-3p inhibitor (HG + inhibitor group), and corresponding negative controls. Real-time quantitative polymerase chain reaction (qPCR) assessed the mRNA expression of miR-483-3p, bax, bcl-2, and caspase-3. Western blot determined the corresponding protein levels. Proliferation was assessed using the CCK-8 assay, and cell apoptosis was analyzed using the fluorescence TUNEL method. Western blot and Masson's staining were conducted to observe alterations in cell fibrosis post miR-483-3p transfection. Furthermore, a dual-luciferase assay investigated the targeting relationship between miR-483-3p and IGF-1. The CCK8 assay demonstrated that the HG + mimics group inhibited HK-2 cell proliferation, while the fluorescent TUNEL method revealed induced cell apoptosis in this group. Conversely, the HG + inhibitor group promoted cell proliferation and suppressed cell apoptosis. The HG + mimics group upregulated mRNA and protein expression of pro-apoptotic markers (bax and caspase-3), while downregulating anti-apoptotic marker (bcl-2) expression. In contrast, the HG + inhibitor group showed opposite effects. Collagen I and FN protein levels were significantly elevated in the HG + mimics group compared to controls (P < 0.05). Conversely, in the HG + inhibitor group, the protein expression of Collagen I and FN was notably reduced compared to the HG group (P < 0.05). The dual luciferase reporter assay confirmed that miR-483-3p could inhibit the luciferase activity of IGF-1's 3'-UTR region (P < 0.05). miR-483-3p exerts targeted regulation on IGF-1, promoting apoptosis and fibrosis in renal tubular epithelial cells induced by high glucose conditions.

Metabolic reprogramming in septic acute kidney injury: pathogenesis and therapeutic implications.

Acute kidney injury (AKI) is a frequent and severe complication of sepsis and is characterized by significant mortality and morbidity. However, the pathogenesis of septic acute kidney injury (S-AKI) remains elusive. Metabolic reprogramming, which was originally referred to as the Warburg effect in cancer, is strongly related to S-AKI. At the onset of sepsis, both inflammatory cells and renal parenchymal cells, such as macrophages, neutrophils and renal tubular epithelial cells, undergo metabolic shifts toward aerobic glycolysis to amplify proinflammatory responses and fortify cellular resilience to septic stimuli. As the disease progresses, these cells revert to oxidative phosphorylation, thus promoting anti-inflammatory reactions and enhancing functional restoration. Alterations in mitochondrial dynamics and metabolic reprogramming are central to the energetic changes that occur during S-AKI. In this review, we summarize the current understanding of the pathogenesis of metabolic reprogramming in S-AKI, with a focus on each cell type involved. By identifying relevant key regulatory factors, we also explored potential metabolic reprogramming-related therapeutic targets for the management of S-AKI.

Preparation and Mechanism Analysis of High-Performance Humidity Sensor Based on Eu-Doped TiO2.

TiO2 is a typical semiconductor material, and it has attracted much attention in the field of humidity sensors. Doping is an efficient way to enhance the humidity response of TiO2. Eu-doped TiO2 material was investigated in both theoretical simulations and experiments. In a simulation based on density functional theory, a doped Eu atom can increase the performance of humidity sensors by producing more oxygen vacancies than undoped TiO2. In these experiments, Eu-doped TiO2 nanorods were prepared by hydrothermal synthesis, and the results also confirm the theoretical prediction. When the doping mole ratio is 5 mol%, the response of the humidity sensor reaches 23,997.0, the wet hysteresis is 2.3% and the response/recovery time is 3/13.1 s. This study not only improves the basis for preparation of high-performance TiO2 humidity sensors, but also fills the research gap on rare earth Eu-doped TiO2 as a humidity-sensitive material.

An Insulin-Modified pH-Responsive Nanopipette Based on Ion Current Rectification.

The properties of nanopipettes largely rely on the materials introduced onto their inner walls, which allow for a vast extension of their sensing capabilities. The challenge of simultaneously enhancing the sensitivity and selectivity of nanopipettes for pH sensing remains, hindering their practical applications. Herein, we report insulin-modified nanopipettes with excellent pH response performances, which were prepared by introducing insulin onto their inner walls via a two-step reaction involving silanization and amidation. The pH response intensity based on ion current rectification was significantly enhanced by approximately 4.29 times when utilizing insulin-modified nanopipettes compared with bare ones, demonstrating a linear response within the pH range of 2.50 to 7.80. In addition, insulin-modified nanopipettes featured good reversibility and selectivity. The modification processes were monitored using the I-V curves, and the relevant mechanisms were discussed. The effects of solution pH and insulin concentration on the modification results were investigated to achieve optimal insulin introduction. This study showed that the pH response behavior of nanopipettes can be greatly improved by introducing versatile molecules onto the inner walls, thereby contributing to the development and utilization of pH-responsive nanopipettes.

Photonic crystal gas sensors based on metal-organic frameworks and polymers.

A photonic crystal (PC) is an optical microstructure with an adjustable dielectric constant. The PC sensor was deemed a powerful tool for gas molecule detection due to its excellent sensitivity, stability, online use and tailorable optical performance. The detection signals are generated by monitoring the changes of the photonic band gap when the sensing behavior occurs. Recently, many efforts have been devoted to improving the PC sensor's detection performance and reducing technical costs by selecting and refining functional materials. In this case, metal-organic frameworks (MOFs) with a large specific surface, tunable structural properties and polymers with unique swelling properties have attracted increasingly attention. In this review, a systematic review of PC gas sensors based on MOFs and polymers was carried out for the first time. Firstly, the optical properties and gas sensing mechanism of PCs were briefly summarized. Secondly, a detailed discussion of the structural properties and rapid preparation methods of distributed Bragg reflectors (DBRs), opals and inverse opals (IOPCs) was presented. Thirdly, the recent advances in MOF, polymer and MOF/polymer-based PC sensors over the past few years were summarized. It should be noted that the sensitivity and selectivity enhancement strategy by appropriate material species selection, organic ligand functionalization, metal-ion doping, diverse functional material arrays, and multi-component compounding were analyzed in detail. Finally, prospects on PC gas sensors are given in terms of preparation methods, material functionalization and future applications.

A self-calibrating flexible SERS substrate incorporating PB@Au assemblies for reliable and reproducible detection.

The precise quantitative analysis using surface-enhanced Raman spectroscopy (SERS) in an uncontrollable environment still faces a significant obstacle due to the poor reproducibility of Raman signals. Herein, we propose a facile method to fabricate a self-calibrating substrate based on a flexible polyvinyl alcohol (PVA) film comprising assemblies of Prussian blue (PB) and Au NPs (PB@Au) for reliable detection. PB cores were coated with an Au shell through simple electrostatic interaction, forming core-shell nanostructure PB@Au assemblies within the PVA film. The outer Au layer provided identical trends in enhancement for both the PB core and neighboring targets while PB cores served as an internal standard (IS) to correct signal fluctuations. The prevention of competitive adsorption on the metal surface between targets and ISs was achieved. The proposed PVA/PB@Au film exhibited enhanced stability of Raman signals after IS correction, resulting in improved spot-to-spot and batch-to-batch reproducibility with significantly reduced standard deviation (RSD) values from 11.42% and 25.02% to 4.43% and 9.39%, respectively. Simultaneously, a higher accuracy in the quantitative analysis of 4-mercaptobenzoic acid (4-MBA) and malachite green (MG) was achieved with fitting coefficient (R2) values improving from 0.9675 and 0.9418 to 0.9974 and 0.9832, respectively. Moreover, the PVA/PB@Au film was successfully applied to detect residual MG in real fish samples. This work opens up an avenue to improve the reproducibility of Raman signals for flexible SERS substrates in the detection of residues under various complex conditions.

Recent Advances in Targeted Cancer Therapy: Are PDCs the Next Generation of ADCs?

Antibody-drug conjugates (ADCs) comprise antibodies, cytotoxic payloads, and linkers, which can integrate the advantages of antibodies and small molecule drugs to achieve targeted cancer treatment. However, ADCs also have some shortcomings, such as non-negligible drug resistance, a low therapeutic index, and payload-related toxicity. Many studies have focused on changing the composition of ADCs, and some have even further extended the concept and types of targeted conjugated drugs by replacing the targeted antibodies in ADCs with peptides, revolutionarily introducing peptide-drug conjugates (PDCs). This Perspective summarizes the current research status of ADCs and PDCs and highlights the structural innovations of ADC components. In particular, PDCs are regarded as the next generation of potential targeted drugs after ADCs, and the current challenges of PDCs are analyzed. Our aim is to offer fresh insights for the efficient design and expedited development of innovative targeted conjugated drugs.