Inflammatory diet, gut microbiota and sensorineural hearing loss: a cross-sectional and Mendelian randomization study.

Aims: Inflammatory diets can trigger chronic inflammation and affect gut microbiota. However, the relationship between dietary preferences and sensorineural hearing loss (SNHL) remains unclear. This study aims to elucidate the relationship between different dietary preferences and sensorineural deafness. Methods: The Dietary Inflammation Index (DII) and SNHL were defined by data from the National Health and Nutrition Examination Survey (NHANES), and exploring their relationship. Using Mendelian randomization (MR) to analyze the relationship between 34 dietary preferences, 211 gut microbiota, and SNHL. Results: Smooth curve fitting indicated that the risk of SNHL increased with increasing DII score when the DII score was greater than 5.15. MR results suggest that a diet including both oily and non-oily fish can substantially reduce the risk of SNHL. Additionally, six specific gut microbiota were found to have significant causal relationship with SNHL. Conclusion: An inflammatory diet may increase the risk of developing SNHL. The observed relationship between fish consumption, gut microbiota, and SNHL suggests the existence of a gut-inner ear axis.

3D Bioprinting of Engineered Living Materials with Extracellular Electron Transfer Capability for Water Purification.

Attention is widely drawn to the extracellular electron transfer (EET) process of electroactive bacteria (EAB) for water purification, but its efficacy is often hindered in complex environmental matrices. In this study, the engineered living materials with EET capability (e-ELMs) were for the first time created with customized geometric configurations for pollutant removal using three-dimensional (3D) bioprinting platform. By combining EAB and tailored viscoelastic matrix, a biocompatible and tunable electroactive bioink for 3D bioprinting was initially developed with tuned rheological properties, enabling meticulous manipulation of microbial spatial arrangement and density. e-ELMs with different spatial microstructures were then designed and constructed by adjusting the filament diameter and orientation during the 3D printing process. Simulations of diffusion and fluid dynamics collectively showcase internal mass transfer rates and EET efficiency of e-ELMs with different spatial microstructures, contributing to the outstanding decontamination performances. Our research propels 3D bioprinting technology into the environmental realm, enabling the creation of intricately designed e-ELMs and providing promising routes to address the emerging water pollution concerns.

Anisomycin alleviates cognitive impairments and pathological features in 3xTg-AD mice.

Neuroinflammation plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). Anisomycin is a pyrrolidine antibiotic isolated from Streptomyces griseolus, which is an efficient anti-inflammatory agent that functions both in vivo and in vitro. However, it is not clear whether anisomycin can exert neuroprotective effect in AD. In the present study, anisomycin was intragastrically administrated to female triple-transgenic AD (3xTg-AD) model mice, then Morris water maze test was used to observe the long-term spatial memory of mice, the in vivo hippocampal field potential recording was performed to evaluate the synaptic plasticity, the western blot and immunofluorescence were employed to detect pathological changes, and the bioinformatics analysis was used to predict the potential target of anisomycin exerting effects in AD. The results showed that anisomycin ameliorated the long-term spatial memory deficits, improved LTP depression and increased the expression of PSD-95, reduced the Aß and tau pathologies, and alleviated the activation of microglia and astrocytes in the brains of 3xTg-AD mice. In addition, the results from bioinformatics analysis showed that the potential target of anisomycin focused on inflammatory pathway. These results indicated that anisomycin exerts neuroprotective effects in 3xTg-AD mice by alleviating neuroinflammation, but the potential mechanism of anisomycin exerting neuroprotective effects needs to be further investigated.

PEDOT-based stretchable optoelectronic materials and devices for bioelectronic interfaces.

The rapid development of wearable and implantable electronics has enabled the real-time transmission of electrophysiological signals in situ, thus allowing the precise monitoring and regulation of biological functions. Devices based on organic materials tend to have low moduli and intrinsic stretchability, making them ideal choices for the construction of seamless bioelectronic interfaces. In this case, as an organic ionic-electronic conductor, poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) has low impedance to offer a high signal-to-noise ratio for monitoring bioelectrical signals, which has become one of the most promising conductive polymers. However, the initial conductivity and stretchability of pristine PEDOT:PSS are insufficient to meet the application requirements, and there is a trade-off between their improvement. In addition, PEDOT:PSS has poor stability in aqueous environments due to the hygroscopicity of the PSS chains, which severely limits its long-term applications in water-rich bioelectronic interfaces. Considering the growing demands of multi-function integration, the high-resolution fabrication of electronic devices is urgent. It is a great challenge to maintain both electrical and mechanical performance after miniaturization, particularly at feature sizes below 100 µm. In this review, we focus on the combined improvement in the conductivity and stretchability of PEDOT:PSS, as well as the corresponding mechanisms in detail. Also, we summarize the effective strategies to improve the stability of PEDOT:PSS in aqueous environments, which plays a vital role in long-term applications. Finally, we introduce the reliable micropatterning technologies and PEDOT:PSS-based stretchable optoelectronic devices applied at bio-interfaces.

Inhibiting histone deacetylase 6 suppresses the proliferation of microvascular endothelial cells by epigenetically activating miR-375-3p, potentially contributing to bone loss during mechanical unloading.

BACKGROUND: Mechanical unloading-induced bone loss threatens prolonged spaceflight and human health. Recent studies have confirmed that osteoporosis is associated with a significant reduction in bone microvessels, but the relationship between them and the underlying mechanism under mechanical unloading are still unclear. METHODS: We established a 2D clinostat and hindlimb-unloaded (HLU) mouse model to simulate unloading in vitro and in vivo. Micro-CT scanning was performed to assess changes in the bone microstructure and mass of the tibia. The levels of CD31, Endomucin (EMCN) and histone deacetylase 6 (HDAC6) in tibial microvessels were detected by immunofluorescence (IF) staining. In addition, we established a coculture system of microvascular endothelial cells (MVECs) and osteoblasts, and qRT‒PCR or western blotting was used to detect RNA and protein expression; cell proliferation was detected by CCK‒8 and EdU assays. ChIP was used to detect whether HDAC6 binds to the miRNA promoter region. RESULTS: Bone mass and bone microvessels were simultaneously significantly reduced in HLU mice. Furthermore, MVECs effectively promoted the proliferation and differentiation of osteoblasts under coculture conditions in vitro. Mechanistically, we found that the HDAC6 content was significantly reduced in the bone microvessels of HLU mice and that HDAC6 inhibited the expression of miR-375-3p by reducing histone acetylation in the miR-375 promoter region in MVECs. miR-375-3p was upregulated under unloading and it could inhibit MVEC proliferation by directly targeting low-density lipoprotein-related receptor 5 (LRP5) expression. In addition, silencing HDAC6 promoted the miR-375-3p/LRP5 pathway to suppress MVEC proliferation under mechanical unloading, and regulation of HDAC6/miR-375-3p axis in MVECs could affect osteoblast proliferation under coculture conditions. CONCLUSION: Our study revealed that disuse-induced bone loss may be closely related to a reduction in the number of bone microvessels and that the modulation of MVEC function could improve bone loss induced by unloading. Mechanistically, the HDAC6/miR-375-3p/LRP5 pathway in MVECs might be a promising strategy for the clinical treatment of unloading-induced bone loss.

Brightening triplet excitons enable high-performance white-light emission in organic small molecules via integrating n-π*/π-π* transitions.

Luminescent materials that simultaneously embody bright singlet and triplet excitons hold great potential in optoelectronics, signage, and information encryption. However, achieving high-performance white-light emission is severely hampered by their inherent unbalanced contribution of fluorescence and phosphorescence. Herein, we address this challenge by pressure treatment engineering via the hydrogen bonding cooperativity effect to realize the mixture of n-π*/π-π* transitions, where the triplet state emission was boosted from 7% to 40% in isophthalic acid (IPA). A superior white-light emission based on hybrid fluorescence and phosphorescence was harvested in pressure-treated IPA, and the photoluminescence quantum yield was increased to 75% from the initial 19% (blue-light emission). In-situ high-pressure IR spectra, X-ray diffraction, and neutron diffraction reveal continuous strengthening of the hydrogen bonds with the increase of pressure. Furthermore, this enhanced hydrogen bond is retained down to the ambient conditions after pressure treatment, awarding the targeted IPA efficient intersystem crossing for balanced singlet/triplet excitons population and resulting in efficient white-light emission. This work not only proposes a route for brightening triplet states in organic small molecules, but also regulates the ratio of singlet and triplet excitons to construct high-performance white-light emission.

Highly Tunable Light Absorber Based on Topological Interface Mode Excitation of Optical Tamm State.

Optical absorbers based on Tamm plasmon states are known for their simple structure and high operational efficiency. However, these absorbers often have limited absorption channels, and it is challenging to continuously adjust their light absorption rates. Here, we propose a Tamm plasmon state optical absorber composed of a layered stack structure consisting of one-dimensional topological photonic crystals and graphene nano-composite materials. Using the four-by-four transfer matrix method, we investigate the structural relationship of the absorber. Our results reveal that topological interface states (TISs) effectively excite the optical Tamm state (OTS), leading to multiple absorption peaks. This expands the number of absorption channels, with the coupling number of the TIS determining the transmission quality of these channels-a value further adjustable by the period number of the photonic crystals. Tuning the filling factor, refractive index, and thickness of the graphene nano-composite material allows for a wide range of control over the device's absorption rate, from 0 to 1. Additionally, adjusting the defect layer thickness, incident angle, and Fermi energy enables us to control the absorber's operational bandwidth and the switching of its absorption effect. This work presents a new approach to expanding the tunability of optoelectronic devices.

Agent-Based Modeling of Virtual Tumors Reveals the Critical Influence of Microenvironmental Complexity on Immunotherapy Efficacy.

Since the introduction of the first immune checkpoint inhibitor (ICI), immunotherapy has changed the landscape of molecular therapeutics for cancers. However, ICIs do not work equally well on all cancers and for all patients. There has been a growing interest in using mathematical and computational models to optimize clinical responses. Ordinary differential equations (ODEs) have been widely used for mechanistic modeling in immuno-oncology and immunotherapy. They allow rapid simulations of temporal changes in the cellular and molecular populations involved. Nonetheless, ODEs cannot describe the spatial structure in the tumor microenvironment or quantify the influence of spatially-dependent characteristics of tumor-immune dynamics. For these reasons, agent-based models (ABMs) have gained popularity because they can model more detailed phenotypic and spatial heterogeneity that better reflect the complexity seen in vivo. In the context of anti-PD-1 ICIs, we compare treatment outcomes simulated from an ODE model and an ABM to show the importance of including spatial components in computational models of cancer immunotherapy. We consider tumor cells of high and low antigenicity and two distinct cytotoxic T lymphocyte (CTL) killing mechanisms. The preferred mechanism differs based on the antigenicity of tumor cells. Our ABM reveals varied phenotypic shifts within the tumor and spatial organization of tumor and CTLs despite similarities in key immune parameters, initial simulation conditions, and early temporal trajectories of the cell populations.

Theory-based and evidence-based nursing interventions for the prevention of ICU-acquired weakness in the intensive care unit: A systematic review.

OBJECTIVES: To synthesise and map the evidence of a theory- and evidence-based nursing intervention for the prevention of ICU-acquired weakness and evaluate its effectiveness in terms of the incidence of ICU-acquired weakness, incidence of delirium, and length of hospital stay. METHODS: We searched PubMed, CINAHL, MEDLINE, Academic Search Complete, Embase, Scopus, Web of Science and the Cochrane Library from database inception to November 2023. The eligible studies focused on critically ill patients in the intensive care unit, used a theory- and evidence-based nursing intervention, and reported the incidence of ICU-acquired weakness and/or used the Medical Research Council Scale. The methodological quality of the included studies was critically appraised by two authors using the appropriate Joanna Briggs Institute appraisal tool for randomised controlled trials, quasi-experimental studies, and cohort studies. Additionally, the weighted kappa coefficient was used to assess inter-rater agreement of the quality assessment. Data were reported using a narrative synthesis. This systematic review was registered by the International Prospective Register of Systematic Review (PROSPERO; CRD42023477011). RESULTS: A total of 5162 studies were initially retrieved, and 9 studies were eventually included after screening. This systematic review revealed that preventive nursing interventions for ICU-acquired weakness mainly include (a) physiotherapy, including neuromuscular electrical stimulation and early rehabilitation, and (b) nutritional support. In addition, (c) airway management, (d) sedation and analgesia management, (e) complication prevention (delirium, stress injury and deep vein thrombosis prevention), and (f) psychological care were also provided. The theories are dominated by goal-oriented theories, and the evidence is mainly the ABCDE bundle in the included studies. The results show that theory- or evidence-based nursing interventions are effective in reducing the incidence of ICU-acquired weakness (or improving the Medical Research Council Scale scores), decreasing the incidence of delirium, shortening the length of hospital stay, and improving patients' self-care and quality of life. CONCLUSION: Theory- and evidence-based nursing interventions have good results in preventing ICU-acquired weakness in critically ill patients. Current nursing interventions favour a combination of multiple interventions rather than just a single intervention. Therefore, preventive measures for ICU-acquired weakness should be viewed as complex interventions and should be based on theory or evidence. This systematic review is based on a small number of trials. Thus, more high-quality randomised controlled trials are needed to draw definitive conclusions about the impact of theory- and evidence-based nursing interventions on the prevention of ICU-acquired weakness.

"The Razor's Edge of Timing:" A Phenomenological Analysis of Decision-Making Processes Surrounding Medical Aid in Dying.

Objectives: The study aimed to explore how terminally ill individuals in the United States approach medical aid in dying (MAID), including personal, interpersonal and structural factors that influence their decision-making processes. Methods: This embodied phenomenological study incorporated semi-structured (N = 9) interviews with seven terminally ill adults who received a prescription for MAID. Interviews occurred over Zoom between October 2021-January 2023 and was guided by Ashworth's framework for exploring phenomenological lifeworlds. Participants were invited to share perceptions of their lifeworlds in pursuit of MAID including values; embodied health, ability, and emotions; space and place in society; reflections on time/timing; and political and cultural discourse. Data analysis integrated Wertz's phenomenological psychological analysis methods. Results: The phenomenon of choosing MAID is an intricate juggling of lifeworlds between participants' embodied relationships, values, time and agency which lead to co-existing experiences of uncertainty and hard-won relief. Conclusion: Our findings contribute cutting-edge knowledge of the decisional tensions and triumphs terminally ill individuals encounter as they approach MAID and highlight practical implications for health and mental health providers in preparing psychoeducational support for those seeking MAID.

Mechanistic characterisation of a fungal fusicoccane-type diterpene synthase involved in the biosynthesis of talaro-7,13-diene.

The cyclisation mechanism of the fungal fusicoccane (FC)-type diterpene synthase (DTS) TadA was investigated by extensive isotopic labelling experiments, and the pH-dependency of the product selectivity of this enzyme was explored. These studies provide new insights into the cyclisation mechanisms of FC-type DTSs.

Effect of concentration, temperature, and time on the stability of hepatitis C virus nucleic acid in serum.

To explore the influence of storage temperature and time on the stability of different concentrations of hepatitis C virus nucleic acid (HCV RNA) samples and to provide data reference for laboratory quality control. Serum samples of 10 patients with HCV RNA detection quantitation of 106-108 IU/mL were collected. The samples of each patient were diluted into three concentrations: high, medium, and low. Then the samples of each concentration were divided into 21, which were divided into three groups according to the storage conditions of -20°C, 4°C, and 25°C, with seven samples in each group. The samples were selected from each group for quantitative detection of HCV RNA on day 0, day 1, day 3, day 5, day 7, day 14, and day 30. The results of each concentration and storage temperature sample remained stable within 5 days. Based on the mixed-effect linear model, the main effects of temperature, time, and concentration were statistically significant (P < 0.01). There was an interaction effect between concentration and time (P = 0.0448), and there was also an interaction effect between temperature and time (P < 0.01). There was no interaction effect between concentration and temperature (P = 0.11) or between concentration, temperature, and time (P = 0.90). The results of serum samples with different concentrations of the HCV RNA remained stable within 5 days. The lower the initial concentration of HCV RNA serum sample, the worse the stability; the higher the storage temperature, the worse the stability. If conditions permit, the laboratory should store such samples at -20°C. IMPORTANCE: Previously, there were few reports about the influence of different concentrations of sample nucleic acid on the stability of samples at various temperatures and times in various literatures. Therefore, it is necessary to analyze the influence of concentration factors on the stability of samples and test results at different storage times and temperatures. This study took the concentration of hepatitis C virus nucleic acid as the research object to further understand the stability of hepatitis C virus nucleic acid test samples under various storage conditions, to provide data reference for the treatment of hepatitis C virus nucleic acid and RNA test samples before clinical laboratory test, and provide guidance and help for the improvement of laboratory quality control.

Effects of derivatization and probiotic transformation on the antioxidative activity of fruit polyphenols.

Fruits contain numerous polyphenols in the form of conjugates, which exhibit low antioxidant activity. Probiotic fermentation is a strategy to improve the antioxidant activity of these conjugated polyphenols by modifying their structure. However, the mechanisms underlying the effects of functional groups and derivatizations on the antioxidative activities of polyphenols and the antioxidation enhancement by probiotic biotransformation haven't been comprehensively explored. This review aimed to explore the structure-antioxidant activity relationships of four functional groups and three derivatizations in flavonoids and phenolic acids. Further, the review elucidated the antioxidant mechanisms underlying the biotransformation of flavonoids and phenolic acids as glycoside, methylated, and ester conjugates by probiotic biotransformation. Deglycosylation, demethylation, and hydrolysis catalyzed by enzymes produced by Bifidobacterium and Lactobacillus facilitated the conversion of conjugated polyphenols into flavonoids and phenolic acids with hydrolyzed forms and highly active functional groups, thereby increasing hydrogen supply and electron transfer capacity to enhance the antioxidant activity.

Effects of the teach-back method on the health status of patients with chronic obstructive pulmonary disease: a real-world community-based cluster-randomized controlled trial.

Background: The teach-back method (TBM), also known as the "show-me" method, is a technique for verifying patients' understanding of health-related information that has been recommended for improving health literacy. However, the research on TBM effect on the outcomes of chronic obstructive pulmonary disease (COPD) patients is limited. Therefore, the aim of this study was to examine the effect of a TBM intervention on the health status of COPD patients. Methods: This real-world community-based cluster-randomized controlled trial enrolled 1,688 patients with COPD from 18 communities in China. Participants received either TBM plus usual care (UC) or UC only. General practitioners were trained in TBM before the intervention. The primary outcomes were depression and anxiety symptoms, as measured by the Hospital Anxiety and Depression Scale (HADS). The secondary outcomes were health-related quality of life and dyspnea, as measured by the COPD Assessment Test (CAT). Dyspnea was assessed using the modified Medical Research Council (mMRC) dyspnea scale. Data on acute exacerbations and deaths were extracted from medical records. Lung function was expressed as the forced expiratory volume in 1 second as a percentage of the predicted value [FEV1 (% pred)]. Results: In total, 336 of the 853 COPD patients in the intervention group (TBM plus UC) had comorbid depression, compared with 329 of the 835 in the control group (UC only). The TBM group showed a significantly greater improvement in HADS depression and anxiety subscale scores (HADS-D and HADS-A, respectively) than the UC group at12 months (t =8.34, P<0.001; t=12.18, P<0.001). The CAT and mMRC scores were significantly lower in the TBM than UC group at 12 months (t=8.43, P<0.001; t=7.23, P<0.001). The numbers of acute exacerbations and deaths were significantly lower in the TBM than UC group at 12 months (mean MCF values were 0.35 and 0.56, respectively [difference of 0.22; 95% confidence interval (CI): -0.41, -0.02; χ2=9.63, P<0.001]. The FEV1 (% pred) was significantly higher in the TBM than UC group at 12 months (t=7.45, P<0.001). Conclusions: General practitioners can use TBM interventions to effectively reduce anxiety, depression, and dyspnea symptoms, decrease the frequency of exacerbations and likelihood of death, and improve health-related quality of life and pulmonary function in patients with COPD. Trial Registration: The trial was registered on the Chinese Clinical Trials Registry (reference: ChiCTR-TRC-12001958).

Impact of Donor-Recipient BMI Ratio on Survival Outcomes of Heart Transplant Recipients: A Retrospective Analysis Study.

OBJECTIVE: This study aimed to investigate the impact of the donor-recipient BMI ratio on the survival outcomes of heart transplant recipients. METHODS: A retrospective analysis was conducted on 641 heart transplant patients who underwent surgery between September 2008 and June 2021. The BMI ratio (donor BMI divided by recipient BMI) was calculated for each patient. Kaplan-Meier survival analysis and Cox proportional hazards regression were performed to evaluate survival rates and determine the hazard ratio (HR) for mortality. RESULTS: Significant differences were found in donor age and donor-recipient height ratio between the BMI ratio groups. The BMI ratio ≥ 1 group had a higher mean donor age (37.27 ± 10.54 years) compared to the BMI ratio < 1 group (34.72 ± 11.82 years, p = 0.008), and a slightly higher mean donor-recipient height ratio (1.02 ± 0.06 vs. 1.00 ± 0.05, p = 0.002). The Kaplan-Meier survival analysis indicated that the survival rate in the BMI ratio ≥ 1 group was significantly lower than in the BMI ratio < 1 group. Cox multivariate analysis, adjusted for confounding factors, revealed a HR of 1.50 (95% CI: 1.08-2.09) for mortality in patients with a BMI ratio ≥ 1. No significant differences were observed in ICU stay, postoperative hospitalization days, or total mechanical ventilation time between the groups. CONCLUSION: A higher donor-recipient BMI ratio was associated with an increased risk of mortality in heart transplant recipients.

The Utility of the Vasoactive-Inotropic Score and Its Nomogram in Guiding Postoperative Management in Heart Transplant Recipients.

Background: In the early postoperative stage after heart transplantation, there is a lack of predictive tools to guide postoperative management. Whether the vasoactive-inotropic score (VIS) can aid this prediction is not well illustrated. Methods: In total, 325 adult patients who underwent heart transplantation at our center between January 2015 and December 2018 were included. The maximum VIS (VISmax) within 24 h postoperatively was calculated. The Kaplan-Meier method was used for survival analysis. A logistic regression model was established to determine independent risk factors and to develop a nomogram for a composite severe adverse outcome combining early mortality and morbidity. Results: VISmax was significantly associated with extensive early outcomes such as early death, renal injury, cardiac reoperation and mechanical circulatory support in a grade-dependent manner, and also predicted 90-day and 1-year survival (p < 0.05). A VIS-based nomogram for the severe adverse outcome was developed that included VISmax, preoperative advanced heart failure treatment, hemoglobin and serum creatinine. The nomogram was well calibrated (Hosmer-Lemeshow p = 0.424) with moderate to strong discrimination (C-index = 0.745) and good clinical utility. Conclusion: VISmax is a valuable prognostic index in heart transplantation. In the early post-transplant stage, this VIS-based nomogram can easily aid intensive care clinicians in inferring recipient status and guiding postoperative management.

Motion sickness resistant people showed suppressed steady-state visually evoked potential (SSVEP) under vection-inducing stimulation.

Visual stimulation can generate illusory self-motion perception (vection) and cause motion sickness among susceptible people, but the underlying neural mechanism is not fully understood. In this study, SSVEP responses to visual stimuli presented in different parts of the visual field are examined in individuals with different susceptibilities to motion sickness to identify correlates of motion sickness. Alpha band SSVEP data were collected from fifteen university students when they were watching roll-vection-inducing visual stimulation containing: (1) an achromatic checkerboard flickering at 8.6 Hz in the central visual field (CVF) and (2) rotating dots pattern flickering at 12 Hz in the peripheral visual field. Rotating visual stimuli provoked explicit roll-vection perception in all participants. The motion sickness resistant participants showed reduced SSVEP response to CVF checkerboard during vection, while the motion sickness susceptible participants showed increased SSVEP response. The changes of SSVEP in the presence of vection significantly correlated with individual motion sickness susceptibility and rated scores on simulator sickness symptoms. Discussion on how the findings can support the sensory conflict theory is presented. Results offer a new perspective on vection and motion sickness susceptibility. Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-023-09991-7.

Tea polyphenols nanoparticles integrated with microneedles multifunctionally boost 5-aminolevulinic acid photodynamic therapy for skin cancer.

5-aminolevulinic acid photodynamic therapy (ALA-PDT) is an emerging therapeutic strategy for skin cancer due to its noninvasiveness and high spatiotemporal selectivity. However, poor skin penetration, poor intratumoral delivery, the instability of aqueous ALA, and the tumor's inherent hypoxia microenvironment are major hurdles hindering the efficacy of ALA-PDT. Herein, we aim to address these challenges by using microneedles (MNs) to assist in delivering nanoparticles based on natural polymeric tea polyphenols (TP NPs) to self-assemble and load ALA (ALA@TP NPs). The TP NPs specifically increase cellular uptake of ALA by A375 and A431 cells and reduce mitochondrial membrane potential. Subsequently, the photosensitizer protoporphyrin IX derived from ALA accumulates in the tumor cells in a dose-dependent manner with TP NPs, generating reactive oxygen species to promote apoptosis and necrosis of A375 and A431 cells. Interestingly, TP NPs can ameliorate the tumor's inherent hypoxia microenvironment and rapid oxygen consumption during PDT by inhibiting hypoxia inducible factor-1α, thereby boosting reactive oxygen species (ROS) generation and enhancing ALA-PDT efficacy through a positive feedback loop. After ALA@TP NPs are loaded into MNs to fabricate ALA@TP NPs@MNs, the MNs enhance skin penetration and storage stability of ALA. Importantly, they exhibit remarkable antitumor efficacy in A375-induced melanoma and A431-induced squamous cell carcinoma with a reduced dose of ALA and reverse hypoxia in vivo. This study provides a facile and novel strategy that integrates MNs and green NPs of TP for addressing the bottlenecks of ALA-PDT and enhancing the ALA-PDT efficacy against skin cancers for future clinical translation.

Win-win integration: A mitochondria targeted AIE photosensitizer for hypochlorite detection and type I & type II photodynamic therapy.

BACKGROUND: Photodynamic therapy (PDT) is a pioneering and effective anticancer modality with low adverse effects and high selectivity. Hypochlorous acid or hypochlorite (HClO/ClO-) is a type of inflammatory cytokine. The abnormal increase of ClO- in tumor cells is related to tumor pathogenesis and may be a "friend" for the design and synthesis of responsive phototherapy agents. However, preparing responsive phototherapy agents for all-in-one noninvasive diagnosis and simultaneous in situ therapy in a complex tumor environment is highly desirable but still remains an enormously demanding task. RESULTS: An acceptor-π bridge-donor-π bridge-acceptor (A-π-D-π-A) type photosensitizer TPTPy was designed and synthesized based on the phenothiazine structure which was used as the donor moiety as well as a ClO- responsive group. TPTPy was a multifunctional mitochondria targeted aggregation-induced emission (AIE) photosensitizer which could quickly and sensitively respond to ClO- with fluorescence "turn on" performance (19-fold fluorescence enhancement) and enhanced type I reactive oxygen species (ROS) generation to effectively ablate hypoxic tumor cells. The detection limit of TPTPy to ClO- was calculated to be 185.38 nM. The well-tailored TPTPy anchoring to mitochondria and producing ROS in situ could disrupt mitochondria and promote cell apoptosis. TPTPy was able to image inflammatory cells and tumor cells through ClO- response. In vivo results revealed that TPTPy was successfully utilized for PDT in tumor bearing nude mice and exhibited excellent biological safety for major organs. SIGNIFICANCE AND NOVELTY: A win-win integration strategy was proposed to design a tumor intracellular ClO- responsive photosensitizer TPTPy capable of both type I and type II ROS production to achieve photodynamic therapy of tumor. This work sheds light on the win-win integration design by taking full advantage of the characteristics of tumor microenvironment to build up responsive photosensitizer for in situ PDT of tumor.

The effect of convalescent plasma therapy on the rate of nucleic acid negative conversion in patients with persistent COVID-19 test positivity.

Objective: This study investigates the association between convalescent plasma therapy and the negative conversion rate in patients with persistent COVID-19 test positivity. Method: A retrospective analysis was conducted on patients with severe or mild to moderate COVID-19 whose viral nucleic acid tests remained positive for over 30 days. Patients were categorized into two groups: those who administered convalescent plasma therapy and those who were not. Data collected included information on therapy strategies used (convalescent plasma, corticosteroids, interferons, etc.), patients' demographic characteristics, comorbidities, therapeutic medications, and nucleic acid testing results. Patients in the convalescent plasma therapy group were matched 1:2 ratio with those in the non-convalescent plasma therapy group. Cumulative negative conversion rates on the fifth, tenth, and fifteenth days post-therapy initiation were analyzed as dependent variables. Independent variables included therapy strategies, demographic characteristics, comorbidities, and therapeutic medication usage. Univariate analysis was conducted, and factors with a p-value (P) less than 0.2 were included in a paired Cox proportional hazards model. Results: There was no statistically significant difference in the cumulative negative conversion rate between the convalescent plasma therapy group and the non-convalescent plasma therapy group on the fifth, tenth, and fifteenth days. Specifically, on day the fifth, the negative conversion rate was 41.46% in the convalescent plasma therapy group compared to 34.15% in the non-convalescent plasma therapy group (HR: 1.72, 95% CI: 0.82-3.61, P = 0.15). On the tenth day, it was 63.41% in the convalescent plasma therapy group and 63.41% in the non-convalescent plasma therapy group (HR: 1.25, 95% CI: 0.69∼2.26, P = 0.46). On the fifteenth day, the negative conversion rate was 85.37% in the convalescent plasma therapy group and 75.61% in the non-convalescent plasma therapy group (HR: 1.19, 95% CI: 0.71-1.97, P = 0.51). Conclusion: Our finding does not support the hypothesis that convalescent plasma therapy could accelerate the time to negative conversion in patients who consistently test positive for COVID-19.