The application of phenylboronic acid pinacol ester functionalized ROS-responsive multifunctional nanoparticles in the treatment of Periodontitis.

Periodontitis is an inflammatory disease induced by the complex interactions between the host immune system and the microbiota of dental plaque. Oxidative stress and the inflammatory microenvironment resulting from periodontitis are among the primary factors contributing to the progression of the disease. Additionally, the presence of dental plaque microbiota plays a significant role in affecting the condition. Consequently, treatment strategies for periodontitis should be multi-faceted. In this study, a reactive oxygen species (ROS)-responsive drug delivery system was developed by structurally modifying hyaluronic acid (HA) with phenylboronic acid pinacol ester (PBAP). Curcumin (CUR) was encapsulated in this drug delivery system to form curcumin-loaded nanoparticles (HA@CUR NPs). The release results indicate that CUR can be rapidly released in a ROS environment to reach the concentration required for treatment. In terms of uptake, HA can effectively enhance cellular uptake of NPs because it specifically recognizes CD44 expressed by normal cells. Moreover, HA@CUR NPs not only retained the antimicrobial efficacy of CUR, but also exhibited more pronounced anti-inflammatory and anti-oxidative stress functions both in vivo and in vitro. This provides a good potential drug delivery system for the treatment of periodontitis, and could offer valuable insights for dental therapeutics targeting periodontal diseases.

Associations between sex hormones, receptors, binding proteins and inflammatory bowel disease: a Mendelian randomization study.

Background: Gender differences existed in inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). Observational studies have revealed associations between sex hormones and IBD, such as estrogen and testosterone. However, the exact relationship between these sex hormones and IBD is unclear. Method: Based on the genome-wide association studies data of eight sex hormones, two sex hormone receptors, sex hormone-binding globulin (SHBG), total IBD and its two subtypes, we performed a two-sample Mendelian randomization (MR) study to analyze their mutual relationship. For estradiol (E2), progesterone (PROG), bioavailable testosterone (BAT), total testosterone (TT) and SHBG, sex-stratified MR analyses were also performed. Inverse variance weighted method, MR-Egger regression and Weighted median method were used for causal analyses. Sensitivity analyses were conducted to test the stability of causal relationships. Besides, a reverse MR analysis was performed to estimate the reverse causation. Results: E2 (P=0.028) and TT (P=0.034) had protective effects on CD. Sex-stratified analyses revealed protective roles of E2 in males on total IBD (P=0.038) and CD (P=0.020). TT in females had protective effects on total IBD (P=0.025) and CD (P=0.029), and BAT in females decreased the risk of developing CD (P=0.047) and UC (P=0.036). Moreover, SHBG in males was also associated with a decreased risk of CD (P=0.021). The reversed MR analysis showed that CD was negatively correlated with estrogen receptor (P=0.046). UC was negatively correlated with PROG in females (P=0.015) and positively correlated with SHBG levels in males (P=0.046). Conclusion: Findings of this study revealed the mutual causal associations between sex hormones and the risk of developing IBD.

Loop PDE of viral capsid protein is involved in immune escape of the emerging novel variant infectious bursal disease virus.

Infectious bursa disease (IBD) is an acute, highly contactable, lethal, immunosuppressive infectious disease caused by the Infectious bursa disease virus (IBDV). Currently, the emerged novel variant IBDV (nVarIBDV) and the sustainedly prevalent very virulent IBDV (vvIBDV) are the two most prevalent strains of IBDV in China. The antigenic properties of the two prevalent strains differed significantly, which led to the escape of nVarIBDV from the immune protection provided by the existing vvIBDV vaccine. However, the molecular basis of the nVarIBDV immune escape remains unclear. In this study, we demonstrated, for the first time, that residues 252, 254, and 256 in the PDE of VP2 are involved in the immune escape of the emerging nVarIBDV. Firstly, the IFA-mediated antigen-antibody affinity assay showed that PBC and PDE of VP2 could affect the affinity of vvIBDV antiserum to VP2, of which PDE was more significant. The key amino acids of PDE influencing the antigen-antibody affinity were also identified, with G254N being the most significant, followed by V252I and I256V. Then the mutated virus with point or combined mutations was rescued by reverse genetics. it was further demonstrated that mutations of V252I, G254N, and I256V in PDE could individually or collaboratively reduce antigen-antibody affinity and interfere with antiserum neutralization, with G254N being the most significant. This study revealed the reasons for the widespread prevalence of nVarIBDV in immunized chicken flocks and provided innovative ideas for designing novel vaccines that match the antigen of the epidemic strain.

Interplay between mitochondrial dysfunction and lysosomal storage: challenges in genetic metabolic muscle diseases with a focus on infantile onset Pompe disease.

Background: Pompe disease (PD) is a rare, progressive autosomal recessive lysosomal storage disorder that directly impacts mitochondrial function, leading to structural abnormalities and potentially culminating in heart failure or cardiogenic shock. The clinical course and molecular mechanisms of the disease remain incompletely understood. Methods: We performed a retrospective analysis to examine the clinical manifestations, genetic traits, and the relationship between PD and mitochondrial function in a pediatric patient. This comprehensive evaluation included the use of ultrasound echocardiograms, computed tomography (CT) scans, electrocardiograms, mutagenesis analysis, and structural analysis to gain insights into the patient's condition and the underlying mechanisms of PD. For structural analysis and visualization, the structure of protein data bank ID 5KZX of human GAA was used, and VMD software was used for visualization and analysis. Results: The study revealed that a 5-month-old male infant was admitted due to fever, with physical examination finding abnormal cardiopulmonary function and hepatomegaly. Laboratory tests and echocardiography confirmed heart failure and hypertrophic cardiomyopathy. Despite a week of treatment, which normalized body temperature and reduced pulmonary inflammation, cardiac abnormalities did not show significant improvement. Further genetic testing identified a homozygous mutation c.2662G>T (p.E888) in the GAA gene, leading to a diagnosis of Infantile-Onset Pompe Disease (IOPD). Conclusions: Although enzyme replacement therapy can significantly improve the quality of life for patients with PD, enhancing mitochondrial function may represent a new therapeutic strategy for treating PD.

Targeting TYK2 alleviates Rab27A-induced malignant progression of non-small cell lung cancer via disrupting IFNα-TYK2-STAT-HSPA5 axis.

Rab27A is a small GTPase-mediating exosome secretion, which participates in tumorigenesis of multiple cancer types. Understanding the biological role of Rab27A in non-small cell lung cancer (NSCLC) is of great importance for oncological research and clinical treatment. In this study, we investigate the function and internal mechanism of Rab27A in NSCLC. Results show that Rab27A is overexpressed in NSCLC, and regulates the tumor proliferation, migration, invasion, and cell motility in vitro and in vivo, and is negatively regulated by miR-124. Further research reveals that upregulated Rab27A can induce the production of IFNα in the medium by mediating exosome secretion. Then IFNα activates TYK2/STAT/HSPA5 signaling to promote NSCLC cell proliferation and metastasis. This process can be suppressed by TYK2 inhibitor Cerdulatinib. These results suggest that Rab27A is involved in the pathogenesis of NSCLC by regulating exosome secretion and downstream signaling, and inhibitors targeting this axis may become a promising strategy in future clinical practice.

Association of follow-up neutrophil-to-lymphocyte ratio and systemic inflammation response index with stroke-associated pneumonia and functional outcomes in cerebral hemorrhage patients: a case controlled study.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) and systemic inflammation response index (SIRI) at admission are independent diagnostic biomarkers in stroke-associated pneumonia (SAP). Our study aimed to investigate the association between NLR, SIRI, specifically follow-up NLR and SIRI, and SAP, as well as their relationship with functional outcomes. MATERIALS AND METHODS: We retrospectively included 451 consecutive ICH patients from May 2017 to May 2019. We conducted univariate and multivariable analyses to identify the factors independently associated with SAP and poor functional outcomes. RESULTS: Compared to 127 (28.16%) patients diagnosed with SAP, those without SAP had both lower baseline and follow-up NLR and SIRI values (P<0.001). After adjustments, we found that baseline NLR (OR, 1.039 [95% CI, 1.003-1.077]; P=0.036) and follow-up NLR (OR, 1.054 [95% CI, 1.011-1.098]; P=0.012) were independently associated with SAP. The follow-up NLR was also associated with a higher mRS (OR, 1.124 [95% CI, 1.025-1.233]; P=0.013) and lower ADL-MBI score (OR, 1.167 [95% CI, 1.057-1.289]; P=0.002) at discharge. Multivariable analysis indicated that advanced age and nasogastric tube feeding were independently associated with SAP (P<0.05). We constructed a dynamic nomogram to identify SAP risk. Further subgroup analysis revealed that baseline NLR (OR, 1.062 [95% CI, 1.007-1.120]; P=0.026) is independently associated with SAP in the nasogastric feeding group, while follow-up NLR (OR, 1.080 [95% CI, 1.024-1.139]; P=0.005) was associated with the occurrence of SAP in non-nasogastric feeding patients. CONCLUSIONS: We found elevated baseline and follow-up NLR values were associated with SAP occurrence, and increasing follow-up NLR indicated poor functional outcomes. Inflammatory markers at different stages may offer individualized guidance for patients receiving various treatments.

Enantioselective Cross-[4 + 2]-Cycloaddition/Decarboxylation of 2-Pyrones by Cooperative Catalysis of the Pd(0)/NHC Complex and Chiral Phosphoric Acid.

Here, we describe a cooperative Pd(0)/chiral phosphoric acid catalytic system that allows us to realize the first chemo-, regio-, and enantioselective sequential cross-[4 + 2]-cycloaddition/decarboxylation reaction between 2-pyrones and unactivated acyclic 1,3-dienes. The key to the success of this transformation is the utilization of an achiral N-heterocyclic carbene (NHC) as the ligand and a newly developed chiral phosphoric acid as the cocatalyst. Experimental investigations and computational studies support the idea that the Pd(0)/NHC complex acts as a π-Lewis base to increase the nucleophilicity of 1,3-dienes via η2 coordination, while the chiral phosphoric acid simultaneously increases the electrophilicity of 2-pyrones by hydrogen bonding. By this synergistic catalysis, the sequential cross-[4 + 2]-cycloaddition and decarboxylation reaction proceeds efficiently, enabling the preparation of a wide range of chiral vinyl-substituted 1,3-cyclohexadienes in good yields and enantioselectivities. The synthetic utility of this reaction is demonstrated by synthetic transformations of the product to various valuable chiral six-membered carbocycles.

Cu-Pt/CrN Fuel Cell Gas Sensor Achieves ppb-Level H2S Detection at Room Temperature.

Fuel cell gas sensors have emerged as promising advanced sensing devices owing to their advantageous features of low power consumption and cost-effectiveness. However, commercially available Pt/C electrodes pose significant challenges in terms of stability and accurate detection of low concentrations of target gases. Here, we introduce an efficient Cu-Pt/CrN-based fuel cell gas sensor, designed specifically for the ultrasensitive detection of hydrogen sulfide (H2S) at room temperature. Compared to the commercial Pt/C sensor, the Cu-Pt/CrN sensor exhibits excellent sensitivity (0.26 µA/ppm), with an increase in the selectivity by a factor of 2.5, and demonstrates good stability over a 2 month period. The enhanced sensing performance can be attributed to the modulation of the electronic arrangement of Pt by Cu, resulting in an augmentation of H2S adsorption. The Cu-Pt/CrN fuel cell gas sensor provides an opportunity for detecting parts per billion-level H2S in various applications.

Identification of Volatile Compounds and Terpene Synthase (TPS) Genes Reveals ZcTPS02 Involved in ß-Ocimene Biosynthesis in Zephyranthes candida.

Zephyranthes candida is a frequently cultivated ornamental plant containing several secondary metabolites, including alkaloids, flavonoids, and volatile organic compounds (VOCs). However, extensive research has been conducted only on non-VOCs found in the plant, whereas the production of VOCs and the molecular mechanisms underlying the biosynthesis of terpenes remain poorly understood. In this study, 17 volatile compounds were identified from Z. candida flowers using gas chromatography-mass spectrometry (GC-MS), with 16 of them being terpenoids. Transcriptome sequencing resulted in the identification of 17 terpene synthase (TPS) genes; two TPS genes, ZcTPS01 and ZcTPS02, had high expression levels. Biochemical characterization of two enzymes encoded by both genes revealed that ZcTPS02 can catalyze geranyl diphosphate (GPP) into diverse products, among which is ß-ocimene, which is the second most abundant compound found in Z. candida flowers. These results suggest that ZcTPS02 plays a vital role in ß-ocimene biosynthesis, providing valuable insights into terpene biosynthesis pathways in Z. candida. Furthermore, the expression of ZcTPS02 was upregulated after 2 h of methyl jasmonate (MeJA) treatment and downregulated after 4 h of the same treatment.

Fed-batch performance profiles for mAb production using different intensified N - 1 seed strategies are CHO cell-line dependent.

Recent optimizations of cell culture processes have focused on the final seed scale-up step (N - 1 stage) used to inoculate the production bioreactor (N-stage bioreactor) to enable higher inoculation cell densities (2-20 × 106 cells/mL), which could shorten the production culture duration and/or increase the volumetric productivity. N - 1 seed process intensification can be achieved by either non-perfusion (enriched-batch or fed-batch) or perfusion culture to reach those higher final N - 1 viable cell densities (VCD). In this study, we evaluated how different N - 1 intensification strategies, specifically enriched-batch (EB) N - 1 versus perfusion N - 1, affect cell growth profiles and monoclonal antibody (mAb) productivity in the final N-stage production bioreactor operated in fed-batch mode. Three representative Chinese Hamster Ovary (CHO) cell lines producing different mAbs were cultured using either EB or perfusion N - 1 seeds and found that the N-stage cell growth and mAb productivities were comparable between EB N - 1 and perfusion N - 1 conditions for two of the cell lines but were very different for the third. In addition, within the two similar cell growth cell lines, differences in cell-specific productivity were observed. This suggests that the impact of the N - 1 intensification process on production was cell-line dependent. This study revealed that the N - 1 intensification strategy and the state of seeds from the different N - 1 conditions may affect the outcome of the N production stage, and thus, the choice of N - 1 intensification strategy could be a new target for future upstream optimization of mAb production.

Exosome lncRNA IFNG-AS1 derived from mesenchymal stem cells of human adipose ameliorates neurogenesis and ASD-like behavior in BTBR mice.

BACKGROUND: The transplantation of exosomes derived from human adipose-derived mesenchymal stem cells (hADSCs) has emerged as a prospective cellular-free therapeutic intervention for the treatment of neurodevelopmental disorders (NDDs), as well as autism spectrum disorder (ASD). Nevertheless, the efficacy of hADSC exosome transplantation for ASD treatment remains to be verified, and the underlying mechanism of action remains unclear. RESULTS: The exosomal long non-coding RNAs (lncRNAs) from hADSC and human umbilical cord mesenchymal stem cells (hUCMSC) were sequenced and 13,915 and 729 lncRNAs were obtained, respectively. The lncRNAs present in hADSC-Exos encompass those found in hUCMSC-Exos and are associated with neurogenesis. The biodistribution of hADSC-Exos in mouse brain ventricles and organoids was tracked, and the cellular uptake of hADSC-Exos was evaluated both in vivo and in vitro. hADSC-Exos promote neurogenesis in brain organoid and ameliorate social deficits in ASD mouse model BTBR T + tf/J (BTBR). Fluorescence in situ hybridization (FISH) confirmed lncRNA Ifngas1 significantly increased in the prefrontal cortex (PFC) of adult mice after hADSC-Exos intraventricular injection. The lncRNA Ifngas1 can act as a molecular sponge for miR-21a-3p to play a regulatory role and promote neurogenesis through the miR-21a-3p/PI3K/AKT axis. CONCLUSION: We demonstrated hADSC-Exos have the ability to confer neuroprotection through functional restoration, attenuation of neuroinflammation, inhibition of neuronal apoptosis, and promotion of neurogenesis both in vitro and in vivo. The hADSC-Exos-derived lncRNA IFNG-AS1 acts as a molecular sponge and facilitates neurogenesis via the miR-21a-3p/PI3K/AKT signaling pathway, thereby exerting a regulatory effect. Our findings suggest a potential therapeutic avenue for individuals with ASD.

Infectious bursal disease virus VP5 triggers host shutoff in a transcription-dependent manner.

Viruses have evolved intricate mechanisms to evade host antiviral responses and exploit cellular resources by manipulating the expression profile of host genes. During infection, viruses encode proteins with shutoff activity to globally inhibit host protein synthesis, which is an effective strategy for immune evasion. In this study, compelling evidence shows that infectious bursal disease virus (IBDV) infection triggers the suppression of host protein synthesis. Furthermore, using both in vitro and in vivo viral infection models, we have identified that IBDV specifically impedes the transcription of host genes via the shutoff activity of viral VP5, simultaneously conferring advantages to IBDV infection in these circumstances. The proposed mechanism suggests that VP5 competitively binds to RanBP1, disrupting the RanGDP/GTP gradient. This disruption interferes with cellular nucleocytoplasmic transport, impairing the nuclear import of proteins bearing nuclear localization signals. The nuclear transport of pivotal transcriptional regulatory factors, such as p65 and IFN regulatory factor 7, is also compromised, leading to the inhibition of pro-inflammatory cytokines and interferon expression. This newly discovered strategy employed by IBDV enables them to manipulate host gene expression, providing novel insights into how viruses evade host immune responses and establish infections.IMPORTANCEViruses manipulate host processes at various levels to regulate or evade both innate and adaptive immune responses, promoting self-survival and efficient transmission. The "host shutoff," a global suppression of host gene expression mediated by various viruses, is considered a critical mechanism for evading immunity. In this study, we have validated the presence of host shutoff during infectious bursal disease virus (IBDV) infection and additionally uncovered that the viral protein VP5 plays a pivotal role in inhibiting the overall synthesis of host proteins, including cytokines, through a transcription-dependent pathway. VP5 competitively binds with RanBP1, leading to disruption of the Ran protein cycle and consequently interfering with nucleocytoplasmic transport, which ultimately results in the suppression of host gene transcription. These findings unveil a novel strategy employed by IBDV to evade host innate immunity and rapidly establish infection. This study also suggests a novel supplement to understanding the pathway through which viruses inhibit host protein synthesis.

A Mendelian randomization study on the effects of plasma lipids on irritable bowel syndrome and functional dyspepsia.

Although functional gastrointestinal disorder (FGID) is a common clinical condition, its risk factors remain unclear. We performed a Mendelian randomization study to explore the association between plasma lipids and the risk of FGID. Instrumental variables closely related to six plasma lipids were obtained from the corresponding genome-wide association studies, and summary-level data on FGID, including irritable bowel syndrome (IBS) and functional dyspepsia (FD), were extracted from the FinnGen study. The primary inverse variance weighted method and other supplementary analyses were used to evaluate the causal relationship between diverse plasma lipids and FGID. For each increase in the standard deviation of triglyceride levels, there was a 12.0% increase in the risk of IBS rather than that of FD. Low- and high-density lipoprotein cholesterol, total cholesterol, apolipoprotein A, and apolipoprotein B levels were not associated with the risk of IBS or FD. Through this study, we identified the causal role of triglycerides in the pathogenesis of IBS, which could benefit further basic and clinical research.

Emulsion for stabilizing ß-carotene and curcumin prepared directly using a continuous phase of polysaccharide-rich Schizophyllum commune fermentation broth.

In this study, we examined the effect of Schizophyllum commune fermentation broth (SCFB) rich in polysaccharides (SCFP) on the stability and bioaccessibility of ß-carotene and curcumin. An SCFB-stabilized oil-in-water (o/w) emulsion (SCFBe) was prepared using SCFB as the continuous phase, and then evaluated for storage stability using an SCFP-based emulsion (SCFPe) as the control. The findings revealed that SCFBe is more stable at 60 °C than SCFPe, and stratification or droplet size varied at differing pH levels (3-9) and concentrations of Na+ (0.1-0.5 M) and Ca2+ (0.01-0.05 M). Since the absolute value of the zeta potential of SCFBe is much lower at 60 °C than that at 4 °C and 25 °C, a higher temperature (60 °C) may enhance the reactivity of polysaccharides and proteins in SCFB to improve the stability of SCFBe. Both the protective impact of SCFB on functional food molecules and their capacity to block lipid oxidation increased as polysaccharide content improved. The bioaccessibility of ß-carotene after in vitro simulated gastrointestinal digestion is 11.18 %-12.28 %, whereas that of curcumin is 31.64 %-33.00 %. By fermenting edible and medicinal fungi in liquid, we created a unique and environmentally friendly approach for getting food-grade emulsifiers without extraction.

RAI2 acts as a tumor suppressor with functional significance in gastric cancer.

Metastasis of gastric cancer (GC) is one of the major causes of death among GC patients. GC metastasis involves numerous biological processes, yet the specific molecular biological mechanisms have not been elucidated. Here, we report a novel tumor suppressor, retinoic acid-induced 2 (RAI2), which is located in the Xp22 region of the chromosome and plays a role in inhibiting GC growth and invasion. In this study, integrated analysis of The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) datasets and immunohistochemistry staining data suggested that RAI2 expression in GC samples was low. Moreover, the immune infiltration analysis indicated that low expression of RAI2 in GC was associated with a higher intensity of tumor-infiltrating lymphocytes (TILs) and an abundance of Programmed death ligand 1 (PD-L1) expression. Gene set enrichment analysis (GSEA) analysis further revealed that RAI2 regulated some pathways including the GAP junction, focal adhesion and ECM receptor interaction pathway, immune regulation, PI3K-Akt signaling, MAPK signaling, cell cycle, and DNA replication. Furthermore, the knockdown of RAI2 promoted GC cell proliferation, migration, and invasion in vitro. Taken together, these results suggest that the tumor suppressor RAI2 could be a potential target for the development of anti-cancer strategies in GC.

Total sleep deprivation reduces the table tennis anticipation performance of young men: A functional magnetic resonance imaging study.

This study explored whether and how sleep deprivation (SD) affects sport-related anticipation. Twenty table tennis players and 28 non-athletes completed a table tennis anticipation task before and after 36 h SD. Functional magnetic resonance imaging (fMRI) data were acquired simultaneously. The results showed that, compared with the non-athletes, table tennis players had higher neural efficiency, manifested by their higher anticipation accuracy and lower frontal lobe activation. SD impaired anticipation performance, accompanied by decreased activation of the occipital and temporal lobes. Compensatory activation occurred in the left hippocampus and orbital part of the right inferior frontal gyrus (IFG) after SD in the table tennis player group, but not in the non-athlete group. The decreased accuracy of non-athletes was positively correlated with decreased activation of orbital part of the right IFG. This study's findings improve the understanding of the cognitive neuroscience mechanisms by which SD affects sport-related anticipation.

Cognitive engagement of nursing undergraduates in blended learning: A parallel mixed method study.

BACKGROUND: Blended learning is being integrated into undergraduate nursing education at all levels and from all directions. Cognitive engagement is not only an embodiment and guarantee of students' engagement into the curriculum from a cognitive level, deep engagement and high-level thinking, but also an important indicator of whether students are effectively engaged in the blended learning curricula. However, no studies have been seen to investigate the cognitive engagement of nursing undergraduates in the blended learning curricula and its influential factors. OBJECTIVES: To explore nursing undergraduates' cognitive engagement during the blended learning curricula and its influential factors. DESIGN: A convergent parallel mixed-methods was used. Data were collected between November 2021 and May 2022, inclusive. SETTINGS AND PARTICIPANTS: The study was carried out in the nursing school at a university in China. Participants including students undertaking entry to the blended learning curricula. METHODS: In the quantitative component (n = 142), participants' cognitive engagement was investigated and factors associated with it were examined using univariate analysis, correlation analysis and multiple regression analysis. During this period, personal, semi-structured interviews were conducted with a subset of these participants (n = 15) to understand participants' cognitive engagement experiences. RESULTS: The cognitive engagement of nursing undergraduates was at a moderate level and the cognitive engagement experiences were reflected in the four themes of Reconstitution, Connection, Elaboration and Retention. The influential factors of cognitive engagement were learning activities (ß = 0.226, p = 0.004), autonomy (ß = 0.158, p = 0.047), academic self-efficacy (ß = 0.311, p < 0.001, ß = 0.271, p < 0.001) and social interaction (ß = 0.358, p < 0.001). CONCLUSIONS: The cognitive engagement of nursing undergraduates in the blended learning curricula needs to be improved. To maximize promote cognitive engagement of nursing undergraduates in the blended learning curricula, educators should design diverse learning activities, engage in high quality social interactions with students, and maximize students' autonomy and self-efficacy.

Multi-Stimuli-Responsive Nanoparticles Formed of POSS-PEG for the Delivery of Boronic Acid-Containing Therapeutics.

Polymeric vehicles often exhibit batch-to-batch variations due to polydispersity, limiting their reproducibility for biomedical applications. In contrast, polyhedral oligomeric silsesquioxane (POSS) has emerged as an attractive candidate for drug delivery due to its precise chemical structure and rigid molecular shape. A promising strategy to enhance drug efficacy while reducing systemic toxicity is the development of multi-stimuli-responsive delivery systems capable of targeted drug release at a disease site. Herein, we developed a drug delivery platform based on POSS-polymer conjugates. By functionalizing the POSS with amino groups and establishing B-N coordination with boronic acids, the nanoparticles (NPs) exhibit responsive behavior to stimuli, including adenosine-5'-triphosphate (ATP), acidic pH, and nucleophilic reagents. We successfully encapsulated two boronic acid-containing molecules: tetraphenylethylene (TPE), serving as a fluorescent probe, and bortezomib (BTZ), an anticancer drug. The TPE@NPs were employed to visualize the cellular uptake of NPs by tumor cells, while the BTZ@NPs exhibited increased cytotoxicity in tumor cells compared with normal cells. This POSS-PEG conjugate offers a nanoparticle platform for encapsulating versatile boronic acid-containing molecules, thereby enhancing drug efficacy while minimizing systemic toxicity. Given the wide-ranging applications of boronic acid-containing molecules in biomedicine, our platform holds significant promise for the development of intelligent drug delivery systems for diagnostics and therapeutics.

Towards energy conservation by constructing more transportation infrastructure?: An endogenous stochastic frontier analysis framework.

Whether constructing more transportation infrastructure can be helpful for the achievement of energy conservation is a long-running and debatable issue. To answer this question, the relationship between transportation infrastructure and energy efficiency must first be clarified. Nonetheless, the existence of the endogeneity problem poses a challenge to defining the relationship. In this paper, an endogenous stochastic frontier analysis method is used to investigate the influence of transportation infrastructure on energy efficiency. Based on the prefecture-city level panel data in China, we find that after addressing the endogeneity problem, the impact of transportation infrastructure on energy efficiency increases dramatically. Moreover, this impact is more pronounced in small-scale cities compared to large and medium-scale cities. Regardless of the measurement of transportation infrastructure, instrumental variable, or production function form, we get the similar conclusions, demonstrating the robustness of our findings. Additional simulation analysis shows that the energy conservation potential would be 1222-2935 million kilowatt hours if the level of transportation infrastructure could be optimized. We recommend accelerating the transportation infrastructure construction, particularly in the small-scale cities so as to boost the energy efficiency and achieve energy conservation targets.