Clinical efficacy of different therapeutic strategies in patients with spontaneous rupture of the esophagus: a multicenter retrospective cohort study.

BACKGROUND: The therapeutic strategy for patients with spontaneous rupture of the esophagus includes surgical repair, endoscopic therapy, supportive care, and others. However, no evidence exists to direct clinical decision-making regarding the choice of operative and nonoperative management. The aim of this study was to determine the clinical efficacy of different therapeutic strategies in both general and stratified patients. METHODS: This study retrospectively analyzed a consecutive cohort of 101 patients at nine tertiary referral hospital centers in China. Patients were divided into operative and nonoperative groups based on the initial treatment. Short-term outcomes, including 90-day mortality, length of hospital stay, and postoperative leakage were compared. Subgroup analysis was performed based on treatment timing and Pittsburgh perforation severity score (PSS). RESULTS: Of 101 patients, 60 (58.4%) underwent operative management. A significant difference of 90-day mortality between operative and nonoperative groups was observed (15.0% vs. 34.1%, P=0.031). Operative management tend to yield similar therapeutic benefits in timely (OR, 0.250; 95% CI, 0.05-1.14, P=0.073) and delayed (OR, 0.42; 95% CI, 0.12-1.47, P=0.175) treatment groups. Based on PSS stratification, operative management significantly decreased the risk of 90-day mortality (OR, 0.211; 95% CI, 0.064-0.701; P=0.011) for patients in low- and moderate-risk groups but may be detrimental for patients in high-risk group (OR, 1.333; 95% CI, 0.233-7.626; P=0.746). CONCLUSIONS: Operative management might be superior to nonoperative management for low- and moderate-risk patients with spontaneous rupture of the esophagus. However, for patients at high risks, operative management might not provide additional benefits compared with nonoperative management. Further research involving larger sample sizes is required for accurate patient stratification and conclusive evidence-based guideline.

Effect of ozone treatment on phenylpropanoid metabolism in harvested cantaloupes.

Phenylpropanoid metabolism plays an important role in cantaloupe ripening and senescence, but the mechanism of ozone regulation on phenylpropanoid metabolism remains unclear. This study investigated how ozone treatment modulates the levels of secondary metabolites associated with phenylpropanoid metabolism, the related enzyme activities, and gene expression in cantaloupe. Treating cantaloupes with 15 mg/m3 of ozone after precooling can help maintain postharvest hardness. This treatment also enhances the production and accumulation of secondary metabolites, such as total phenols, flavonoids, and lignin. These metabolites are essential components of the phenylpropanoid metabolic pathway, activating enzymes like phenylalanine ammonia-lyase, cinnamate 4-hydroxylase, 4CL, chalcone synthase, and chalcone isomerase. The results of the transcriptional expression patterns showed that differential gene expression related to phenylpropanoid metabolism in the peel of ozone-treated cantaloupes was primarily observed during the middle and late storage stages. In contrast, the pulp exhibited significant differential gene expression mainly during the early storage stage. Furthermore, it was observed that the level of gene expression in the peel was generally higher than that in the pulp. The correlation between the relative amount of gene changes in cantaloupe, activity of selected enzymes, and concentration of secondary metabolites could be accompanied by positive regulation of the phenylpropanoid metabolic pathway. Therefore, ozone stress induction positively enhances the biosynthesis of flavonoids in cantaloupes, leading to an increased accumulation of secondary metabolites. Additionally, it also improves the postharvest storage quality of cantaloupes.

The top 100 most cited articles on axon regeneration from 2003 to 2023: a bibliometric analysis.

Objective: In this study, we used a bibliometric and visual analysis to evaluate the characteristics of the 100 most cited articles on axon regeneration. Methods: The 100 most cited papers on axon regeneration published between 2003 and 2023 were identified by searching the Web of Science Core Collection database. The extracted data included the title, author, keywords, journal, publication year, country, and institution. A bibliometric analysis was subsequently undertaken. Results: The examined set of 100 papers collectively accumulated a total of 39,548 citations. The number of citations for each of the top 100 articles ranged from 215 to 1,604, with a median value of 326. The author with the most contributions to this collection was He, Zhigang, having authored eight papers. Most articles originated in the United States (n = 72), while Harvard University was the institution with the most cited manuscripts (n = 19). Keyword analysis unveiled several research hotspots, such as chondroitin sulfate proteoglycan, alternative activation, exosome, Schwann cells, axonal protein synthesis, electrical stimulation, therapeutic factors, and remyelination. Examination of keywords in the articles indicated that the most recent prominent keyword was "local delivery." Conclusion: This study offers bibliometric insights into axon regeneration, underscoring that the United States is a prominent leader in this field. Our analysis highlights the growing relevance of local delivery systems in axon regeneration. Although these systems have shown promise in preclinical models, challenges associated with long-term optimization, agent selection, and clinical translation remain. Nevertheless, the continued development of local delivery technologies represents a promising pathway for achieving axon regeneration; however, additional research is essential to fully realize their potential and thereby enhance patient outcomes.

Contribution of inwardly rectifying potassium channel 4.1 in orofacial neuropathic pain: Regulation of pannexin 3 via the reactive oxygen species-activated P38 MAPK signal pathway.

The involvement of inwardly rectifying potassium channel 4.1 (Kir4.1) in neuropathic pain has been established. However, there is limited understanding of the downstream mechanism through which Kir4.1 contributes to orofacial neuropathic pain. The objective of this study was to examine the regulation of Kir4.1 on the expression of pannexin 3 (Panx3) in the trigeminal ganglion (TG) and the underlying mechanism in the context of orofacial neuropathic pain caused by chronic constriction injury of the infraorbital nerve (CCI-ION). The study observed a significant increase in Panx3 expression in the TG of mice with CCI-ION. Inhibition of Panx3 in the TG of CCI-ION mice resulted in alleviation of orofacial mechanical allodynia. Furthermore, conditional knockdown (CKD) of Kir4.1 in the TG of both male and female mice led to mechanical allodynia and upregulation of Panx3 expression. Conversely, overexpression of Kir4.1 decreased Panx3 levels in the TG and relieved mechanical allodynia in CCI-ION mice. In addition, silencing Kir4.1 in satellite glial cells (SGCs) decreased Panx3 expression and increased the phosphorylation of P38 MAPK. Moreover, silencing Kir4.1 in SGCs increased the levels of reactive oxygen species (ROS). The elevated phosphorylation of P38 MAPK resulting from Kir4.1 silencing was inhibited by using a superoxide scavenger known as the tempol. Silencing Panx3 in the TG in vivo attenuated the mechanical allodynia caused by Kir4.1 CKD. In conclusion, these findings suggest that the reduction of Kir4.1 promotes the expression of Panx3 by activating the ROS-P38 MAPK signalling pathway, thus contributing to the development of orofacial neuropathic pain.

Understanding the preferences of young adults with type 2 diabetes mellitus with regard to diabetes self-management education: a qualitative study.

AIM: Young-onset type 2 diabetes (YOD) is associated with poorer clinical outcomes. To support the development of more effective diabetes self-management education (DSME) programmes, this study aimed to understand the preferences of young adults with YOD in relation to the modality, content and qualities of DSME. METHODS: Maximal variation sampling was employed to recruit participants of varied age, ethnicity and marital status. In-depth interviews using a semistructured questionnaire were conducted. Subsequently, thematic analysis with coding and conceptualisation of data was applied to identify the main themes regarding DSME. RESULTS: 21 young adult participants aged 22-39 years were interviewed from three polyclinics in Singapore. The most used modalities for DSME included education from healthcare providers, information and support from family and friends and information from internet sources. Participants were most interested in information regarding diet, age-specific diabetes-related conditions and medication effects. Additionally, participants valued DSME that was credible, accessible, individualised and empathetic. Conversely, absence of the above qualities and stigma hindered participants from receiving DSME. CONCLUSION: Our study explored the preferences of young adults with YOD with regard to DSME, identifying the most used modalities, preferred content and qualities that were valued by young adults. Our findings will help inform the development of DSME programmes that can better meet the needs and preferences of young adults with YOD.

Aspirin suppresses hepatocellular carcinoma progression by inhibiting platelet activity.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common malignant liver disease in the world. Platelets (PLTs) are known to play a key role in the maintenance of liver homeostasis and the pathophysiological processes of a variety of liver diseases. Aspirin is the most classic antiplatelet agent. However, the molecular mechanism of platelet action and whether aspirin can affect HCC progression by inhibiting platelet activity need further study. AIM: To explore the impact of the antiplatelet effect of aspirin on the development of HCC. METHODS: Platelet-rich plasma, platelet plasma, pure platelet, and platelet lysate were prepared, and a coculture model of PLTs and HCC cells was established. CCK-8 analysis, apoptosis analysis, Transwell analysis, and real-time polymerase chain reaction (RT-PCR) were used to analyze the effects of PLTs on the growth, metastasis, and inflammatory microenvironment of HCC. RT-PCR and Western blot were used to detect the effects of platelet activation on tumor-related signaling pathways. Aspirin was used to block the activation and aggregation of PLTs both in vitro and in vivo, and the effect of PLTs on the progression of HCC was detected. RESULTS: PLTs significantly promoted the growth, invasion, epithelial-mesenchymal transition, and formation of an inflammatory microenvironment in HCC cells. Activated PLTs promoted HCC progression by activating the mitogen-activated protein kinase/protein kinase B/signal transducer and activator of transcription three (MAPK/ AKT/STAT3) signaling axis. Additionally, aspirin inhibited HCC progression in vitro and in vivo by inhibiting platelet activation. CONCLUSION: PLTs play an important role in the pathogenesis of HCC, and aspirin can affect HCC progression by inhibiting platelet activity. These results suggest that antiplatelet therapy has promising application prospects in the treatment and combined treatment of HCC.

Quantifying periodontitis-associated oral dysbiosis in tongue and saliva microbiomes-An integrated data analysis.

BACKGROUND: Periodontitis is primarily driven by subgingival biofilm dysbiosis. However, the quantification and impact of this periodontal dysbiosis on other oral microbial niches remain unclear. This study seeks to quantify the dysbiotic changes in tongue and salivary microbiomes resulting from periodontitis by applying a clinically relevant dysbiosis index to an integrated data analysis. METHODS: The National Center for Biotechnology Information (NCBI) database was searched to identify BioProjects with published studies on salivary and tongue microbiomes of healthy and periodontitis subjects. Raw sequence datasets were processed using a standardized bioinformatic pipeline and categorized by their ecological niche and periodontal status. The subgingival microbial dysbiosis index (SMDI), a dysbiosis index originally developed using the subgingival microbiome, was computed at species and genus levels and customized for each niche. Its diagnostic accuracy for periodontitis was evaluated using receiver operating characteristic curves. RESULTS: Four studies, contributing 328 microbiome samples, were included. At both species and genus levels, periodontitis samples had a higher SMDI, but the differences were only significant for subgingival biofilm and saliva (p < 0.001). However, SMDI showed good diagnostic accuracy for periodontitis status for all three niches (area under curve ranging from 0.76 to 0.90, p < 0.05). The dysbiosis index of subgingival biofilm was positively correlated with saliva consistently (p < 0.001) and with the tongue at the genus level (p = 0.036). CONCLUSIONS: While the impact on the tongue microbiome requires further investigation, periodontitis-associated dysbiosis affects the salivary microbiome and is quantifiable using the dysbiosis index. The diagnostic potential of salivary microbial dysbiosis as a convenient periodontal biomarker for assessing periodontal status has potential public health and clinical applications. PLAIN LANGUAGE SUMMARY: Periodontitis, a severe inflammation of the gums which causes bone loss, is a disease caused by an imbalance of good and bad bacteria under the gums. However, it is unclear how this bacterial imbalance in the gums affects the bacterial balance of other distinct parts of the mouth, such as the saliva and tongue. This study uses bacteria datasets of four previously published studies, contributing a total of 328 bacterial samples. The data were processed using a uniform data analysis workflow, and a bacterial score, the subgingival microbial dysbiosis index (SMDI), previously shown to capture periodontitis-associated bacteria imbalance, was calculated separately for samples from under the gums, the saliva, and the tongue. The SMDI was able to distinguish between health and periodontitis within each oral location, and in general, the scores were higher for periodontitis samples, though this difference was significant only for bacteria under the gums and in saliva. Saliva scores were also consistently correlated with bacteria under the gums. This study shows that periodontitis-associated bacterial imbalances are observed in oral locations beyond just under the gums, particularly the saliva. Thus, saliva bacteria may be used as a convenient biomarker for assessing gum disease, allowing for potential public health and clinical applications.

Analysis of the seasonal water quality variation at the hydraulic junction of a dual-source water distribution system.

The implementation of a dual-source water supply system offers an increased level of reliability in water provision; however, intricate hydraulic dynamics introduce apprehensions regarding water safety at the hydraulic junction. In this study, we gathered data of the water quality at the hydraulic junction of a dual-source water supply system (plant A and plant B, sampling site A10 was near plant A, and sampling site A12 was near plant B) for one year in Suzhou Industrial Park. Our findings indicated that seasonal variations and water temperature exerted significant influence on the composition and formation of disinfection byproducts (DBPs). Notably, during the warmer months spanning from June to September, the concentration of trihalomethanes was the highest at the hydraulic junction, whereas the concentration of residual chloride was the lowest. The analysis on DBPs revealed that more Br-containing precursors in water in plant A resulted in the accumulation of more Br-containing DBPs at A10, whereas the highest concentration of Cl-containing DBPs accumulated at A12. The analysis of the dissolved organic matter (DOM) composition indicated an increase in concentration at A10 and A12 compared with that in plant A and plant B. The highest concentration of humic acids was observed at A10, whereas A12 accumulated the highest concentration of aromatic proteins and microbial metabolites. Owing to the fluctuations in water consumption patterns at the hydraulic junction, the water quality was susceptible to variability, thereby posing an elevated risk. Consequently, extensive efforts are warranted to ensure the maintenance of water safety and quality at this critical interface.

The Relationship between Low-Sodium Salt Intake and Both Blood Pressure Level and Hypertension in Chinese Residents.

Compared to common salt, low-sodium salt can reduce blood pressure to varying degrees. However, the exact dosage relationship remains unclear. We aimed to investigate the dose-response relationships between low-sodium salt intake and systolic blood pressure (SBP) and diastolic blood pressure (DBP), as well as the risk of hypertension, and to determine the optimal range for low-sodium salt intake. We investigated the basic characteristics and dietary profile of 350 individuals who consumed low-sodium salt. The samples were divided into three groups according to the 33.3rd and 66.6th percentiles of low-sodium salt intake in condiments (Q1: <4.72 g/d, Q2: ≥4.72 g/d, and <6.88 g/d, and Q3: ≥6.88 g/d). The restricted cubic spline results indicated that low-sodium salt intake decreased linearly with SBP and DBP, while low-sodium intake demonstrated a non-linear, L-shaped relationship with the risk of hypertension, with a safe range of 5.81 g to 7.66 g. The multiple linear regression analysis revealed that compared with group Q1, the DBP in group Q2 decreased by 2.843 mmHg (95%CI: -5.552, -0.133), and the SBP in group Q3 decreased by 4.997 mmHg (95%CI: -9.136, -0.858). Exploratory subgroup analyses indicated that low-sodium salt intake had a significant impact on reducing SBP in males, DBP in females, SBP in rural populations, and DBP in urban populations. The intake of low-sodium salt adheres to the principle of moderation, with 5.81-7.66 g potentially serving as a pivotal threshold.

Microneedle delivery system with rapid dissolution and sustained release of bleomycin for the treatment of hemangiomas.

Hemangioma of infancy is the most common vascular tumor during infancy and childhood. Despite the proven efficacy of propranolol treatment, certain patients still encounter resistance or face recurrence. The need for frequent daily medication also poses challenges to patient adherence. Bleomycin (BLM) has demonstrated effectiveness against vascular anomalies, yet its use is limited by dose-related complications. Addressing this, this study proposes a novel approach for treating hemangiomas using BLM-loaded hyaluronic acid (HA)-based microneedle (MN) patches. BLM is encapsulated during the synthesis of polylactic acid (PLA) microspheres (MPs). The successful preparation of PLA MPs and MN patches is confirmed through scanning electron microscopy (SEM) images. The HA microneedles dissolve rapidly upon skin insertion, releasing BLM@PLA MPs. These MPs gradually degrade within 28 days, providing a sustained release of BLM. Comprehensive safety assessments, including cell viability, hemolysis ratio, and intradermal reactions in rabbits, validate the safety of MN patches. The BLM@PLA-MNs exhibit an effective inhibitory efficiency against hemangioma formation in a murine hemangioma model. Of significant importance, RNA-seq analysis reveals that BLM@PLA-MNs exert their inhibitory effect on hemangiomas by regulating the P53 pathway. In summary, BLM@PLA-MNs emerge as a promising clinical candidate for the effective treatment of hemangiomas.

Exergoeconomic Analysis and Optimization of a Biomass Integrated Gasification Combined Cycle Based on Externally Fired Gas Turbine, Steam Rankine Cycle, Organic Rankine Cycle, and Absorption Refrigeration Cycle.

Adopting biomass energy as an alternative to fossil fuels for electricity production presents a viable strategy to address the prevailing energy deficits and environmental concerns, although it faces challenges related to suboptimal energy efficiency levels. This study introduces a novel combined cooling and power (CCP) system, incorporating an externally fired gas turbine (EFGT), steam Rankine cycle (SRC), absorption refrigeration cycle (ARC), and organic Rankine cycle (ORC), aimed at boosting the efficiency of biomass integrated gasification combined cycle systems. Through the development of mathematical models, this research evaluates the system's performance from both thermodynamic and exergoeconomic perspectives. Results show that the system could achieve the thermal efficiency, exergy efficiency, and levelized cost of exergy (LCOE) of 70.67%, 39.13%, and 11.67 USD/GJ, respectively. The analysis identifies the combustion chamber of the EFGT as the component with the highest rate of exergy destruction. Further analysis on parameters indicates that improvements in thermodynamic performance are achievable with increased air compressor pressure ratio and gas turbine inlet temperature, or reduced pinch point temperature difference, while the LCOE can be minimized through adjustments in these parameters. Optimized operation conditions demonstrate a potential 5.7% reduction in LCOE at the expense of a 2.5% decrease in exergy efficiency when compared to the baseline scenario.

Recent Advances in and Application of Fluorescent Microspheres for Multiple Nucleic Acid Detection.

Traditional single nucleic acid assays can only detect one target while multiple nucleic acid assays can detect multiple targets simultaneously, providing comprehensive and accurate information. Fluorescent microspheres in multiplexed nucleic acid detection offer high sensitivity, specificity, multiplexing, flexibility, and scalability advantages, enabling precise, real-time results and supporting clinical diagnosis and research. However, multiplexed assays face challenges like complexity, costs, and sample handling issues. The review explores the recent advancements and applications of fluorescent microspheres in multiple nucleic acid detection. It discusses the versatility of fluorescent microspheres in various fields, such as disease diagnosis, drug screening, and personalized medicine. The review highlights the possibility of adjusting the performance of fluorescent microspheres by modifying concentrations and carrier forms, allowing for tailored applications. It emphasizes the potential of fluorescent microsphere technology in revolutionizing nucleic acid detection and advancing health, disease treatment, and medical research.

Perfluorooctanoic acid triggers premature ovarian insufficiency by impairing NAD+ synthesis and mitochondrial function in adult zebrafish.

High-dose perfluorooctanoic acid (PFOA) impairs oocyte maturation and offspring quality. However, the physiological concentrations of PFOA in follicular fluids of patients with premature ovarian insufficiency (POI) were detected at lower levels, thus the relationship between physiological PFOA and reproductive disorders remains elusive. Here, we investigated whether physiological PFOA exposure affects gonad function in adult zebrafish. Physiological PFOA exposure resulted in POI-like phenotypes in adult females, which exhibited decreased spawning frequency, reduced number of ovulated eggs, abnormal gonadal index, and aberrant embryonic mortality. Meanwhile, oocytes from PFOA-exposed zebrafish showed mitochondrial disintegration and diminished mitochondrial membrane potential (MMP). Unlike the high-dose treated oocytes exhibiting high reactive oxygen species (ROS) levels and excessive apoptosis, physiological PFOA reduced the ROS levels and did not trigger apoptosis. Interestingly, physiological PFOA exposure would not affect testis function, indicating specific toxicity in females. Mechanistically, PFOA suppressed the NAD+ biosynthesis and impaired mitochondrial function in oocytes, thus disrupting oocyte maturation and ovarian fertility. Nicotinamide mononucleotide (NMN), a precursor for NAD+ biosynthesis, alleviated the PFOA-induced toxic effects in oocytes and improved the oocyte maturation and fertility upon PFOA exposure. Our findings discover new insights into PFOA-induced reproductive toxicity and provide NMN as a potential drug for POI therapy.

Pongamol Alleviates Neuroinflammation and Promotes Autophagy in Alzheimer's Disease by Regulating the Akt/mTOR Signaling Pathway.

Alzheimer's disease (AD), one of the neurodegenerative disorders, is highly correlated with the abnormal hyperphosphorylation of Tau and aggregation of ß-amyloid (Aß). Oxidative stress, neuroinflammation, and abnormal autophagy are key drivers of AD and how they contribute to neuropathology remains largely unknown. The flavonoid compound pongamol is reported to possess a variety of pharmacological activities, such as antioxidant, antibacterial, and anti-inflammatory. This study investigated the neuroprotective effect and its mechanisms of pongamol in lipopolysaccharide (LPS)-induced BV2 cells, d-galactose/sodium nitrite/aluminum chloride (d-gal/NaNO2/AlCl3)-induced AD mice, and Caenorhabditis elegans models. Our research revealed that pongamol reduced the release of inflammatory factors IL-1ß, TNF-α, COX-2, and iNOS in LPS-induced BV2 cells. Pongamol also protected neurons and significantly restored memory function, inhibited Tau phosphorylation, downregulated Aß aggregation, and increased oxidoreductase activity in the hippocampus of AD mice. In addition, pongamol reversed the nuclear transfer of NF-κB and increased the levels of Beclin 1 and LC3 II/LC3 I. Most importantly, the anti-inflammatory and promoter autophagy effects of pongamol may be related to the regulation of the Akt/mTOR signaling pathway. In summary, these results showed that pongamol has a potential neuroprotective effect, which greatly enriched the research on the pharmacological activity of pongamol for improving AD.

Thermodynamic Geometry of Nonequilibrium Fluctuations in Cyclically Driven Transport.

Nonequilibrium thermal machines under cyclic driving generally outperform steady-state counterparts. However, there is still lack of coherent understanding of versatile transport and fluctuation features under time modulations. Here, we formulate a theoretical framework of thermodynamic geometry in terms of full counting statistics of nonequilibrium driven transports. We find that, besides the conventional dynamic and adiabatic geometric curvature contributions, the generating function is also divided into an additional nonadiabatic contribution, manifested as the metric term of full counting statistics. This nonadiabatic metric generalizes recent results of thermodynamic geometry in near-equilibrium entropy production to far-from-equilibrium fluctuations of general currents. Furthermore, the framework proves geometric thermodynamic uncertainty relations of near-adiabatic thermal devices, constraining fluctuations in terms of statistical metric quantities and thermodynamic length. We exemplify the theory in experimentally accessible driving-induced quantum chiral transport and Brownian heat pump.

Enhancing the physicochemical properties and bioactivities of 2'-hydroxyflavanone through fungal biotransformation.

Flavonoids comprise a group of natural compounds with diverse bioactivities; however, their low water solubility and limited bioavailability often impede their potential health benefits for humans. In this study, five derivatives, namely 2',5'-dihydroxyflavanone (1), 2'-dihydroxyflavanone-5'-O-4″-O-methyl-ß-d-glucoside (2), 2'-dihydroxyflavanone-6-O-4″-O-methyl-ß-d-glucoside (3), 2'-dihydroxyflavanone-3'-O-4″-O-methyl-ß-d-glucoside (4) and hydroxyflavanone-2'-O-4″-O-methyl-ß-d-glucoside (5), were biosynthesized from 2'-hydroxyflavanone through microbial transformation using Beauveria bassiana ATCC 7159. Product 1 was identified as a known compound while 2-5 were structurally characterized as new structures through extensive 1D and 2D NMR analysis. The water solubility of biotransformed products 1-5 was enhanced by 30-280 times compared to the substrate 2'-hydroxyflavanone. Moreover, the antioxidant assay revealed that 1 and 2 exhibited improved 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity relative to the substrate, decreasing the logIC50 from 8.08 ± 0.11 µM to 6.19 ± 0.08 µM and 7.15 ± 0.08 µM, respectively. Compound 5 displayed significantly improved anticancer activity compared to the substrate 2'-hydroxyflavanone against Glioblastoma 33 cancer stem cells, decreasing the IC50 from 25.05 µM to 10.59 µM. Overall, fungal biotransformation represents an effective tool to modify flavonoids for enhanced water solubility and bioactivities.

Effect Modification of Heat-Related Mortality Risk by Air Pollutants in Shandong, China.

Although studies have reported the modification effect of air pollutants on heat-related health risk, little is known on the modification effect among various particulate matter with different particle size on mortality. We aimed to investigate whether the associations of hot temperatures with daily mortality were modified by different air pollutant levels in Shandong Province, China. Daily data of air pollutants, meteorological factors, and mortality of 1,822 subdistricts in Shandong province from 2013 to 2018 were collected. We used a time-stratified case-crossover model with an interaction term between the cross-basis term for ambient temperature and the linear function of particulate matter ≤1 µm (PM1), PM2.5, nitrogen dioxide (NO2), and ozone to obtain heat-mortality associations during the hot season. Results showed that the cumulative odds ratio of extreme heat on mortality over 0 to 10 days was 3.66 (95% CI: 3.10-4.31). The mortality risk during hot seasons was stronger at high air pollutant levels. The modification effect of particulate matters on heat-related mortality decreased by its aerodynamic diameter. Females and older adults over 75 years were more vulnerable to the modification effect of air pollutants, and significant differences were detected in the association between temperatures and mortality stratified by PM1 and PM2.5. Higher heat-related mortality risks were observed at high NO2 levels, especially for cardiorespiratory disease. The findings suggest that more consideration should be given to the combined effect of very fine particles and NO2 with ambient heat when developing healthcare strategies, and women and older adults should be given priority in health-related settings.

Engineered bacteria that self-assemble "bioglass" polysilicate coatings display enhanced light focusing.

Photonic devices are cutting-edge optical materials that produce narrow, intense beams of light, but their synthesis typically requires toxic, complex methodology. Here we employ a synthetic biology approach to produce environmentally-friendly, living microlenses with tunable structural properties. We engineered Escherichia coli bacteria to display the silica biomineralization enzyme silicatein from aquatic sea sponges. Our silicatein-expressing bacteria can self-assemble a shell of polysilicate "bioglass" around themselves. Remarkably, the polysilicate-encapsulated bacteria can focus light into intense nanojets that are nearly an order of magnitude brighter than unmodified bacteria. Polysilicate-encapsulated bacteria are metabolically active for up to four months, potentially allowing them to sense and respond to stimuli over time. Our data demonstrate that engineered bacterial particles have the potential to revolutionize the development of multiple optical and photonic technologies.

Achieving Circularly Polarized Phosphorescence through Noncovalent Clipping of Metallotweezers.

Circularly polarized phosphorescent materials, based on host-guest complexation, have received significant attention due to their outstanding emission performance in solutions. Recent studies have primarily focused on macrocyclic host-guest complexes. To broaden the scope of this research, there is a keen pursuit of developing novel chiral phosphorescent host-guest systems. Metallotweezers with square-planar d8 transition metal complexes emerge as promising candidates for achieving this objective. Specifically, metallotweezers, comprising platinum(II) terpyridine and gold(III) diphenylpyridine pincers on a diphenylpyridine scaffold, have been designed and synthesized. Due to the preorganization effect rendered by the diphenylpyridine scaffold, the resulting metallotweezers are capable of complexing with each other and forming quadruple stacking structures. The phosphorescent emission is enhanced owing to the synergistic rigidifying and shielding effects. Meanwhile, the steric effect of chiral (1R) pinene units on the platinum(II) terpyridine pincers results in a stereospecific twist for the quadruple stacking structures. Thus, the chirality transfers from the molecular to the supramolecular level. By a combination of phosphorescent enhancement and supramolecular chirality for the clipping complex, circularly polarized phosphorescent emission is achieved. Overall, noncovalent clipping of metallotweezers exemplified in the current study presents a novel and effective approach toward solution-processable circularly polarized phosphorescent materials.

Apoptosis-induced decline in hippocampal microglia mediates the development of depression-like behaviors in adult mice triggered by unpredictable stress during adolescence.

Depression triggered by harmful stress during adolescence is a common problem that can affect mental health. To date, the mechanisms underlying this type of depression remain unclear. One mechanism for the promotion of depression by chronic stress in adulthood is the loss of hippocampal microglia. Since deleterious stress in adolescence also activates microglia, we investigated the dynamic changes of microglia in the hippocampus in mice exposed to chronic unpredictable stress (CUS) in adolescence. Our results showed that 12 days of CUS stimulation in adolescence induced typical depression-like behaviors in adult mice, which were accompanied by a significant decrease and dystrophy of microglia in the dentate gyrus of the hippocampus. Further analysis showed that this decrease in microglia was mediated by the initial response of microglia to unpredictable stress in the dentate gyrus of the hippocampus and their subsequent apoptosis. Blocking the initial response of microglia to unpredictable stress by pretreatment with minocycline was able to prevent apoptosis and microglial decline as well as the development of depression-like behaviors in adult mice induced by adolescent CUS. Moreover, administration of lipopolysaccharide (LPS) or macrophage-colony stimulatory factor (M-CSF), two drugs that reversed microglia decline in the dentate gyrus, ameliorated the depression-like behaviors induced by CUS stimulation in adolescence. These findings reveal a novel mechanism for the development of depression-like behaviors in animals triggered by deleterious stress in adolescence and suggest that reversing microglial decline in the hippocampus may be a hopeful strategy for the treatment of depression triggered by deleterious stress in adolescence.