miR-142-5p and miR-130a-3p regulate pulmonary macrophage polarization and asthma airway remodeling.

Macrophages are key regulators of the development and progression of asthma, facilitating deleterious airway remodeling in affected patients. Immune cell function is tightly regulated by microRNAs (miRNAs), but how these miRNAs impact macrophage-mediated airway remodeling in the context of asthma remains to be determined. In this study, we utilized an ovalbumin (OVA)-based murine model of asthma to evaluate the importance of miRNAs within these macrophages. We found that macrophages from mice that had been sensitized with and exposed to OVA expressed higher levels of M2-like phenotypic markers and exhibited significantly altered expression of both miR-142-5p and miR-130a-3p. When these isolated pulmonary macrophages were cultured in vitro, we determined that transfecting them with miR-142-5p antisense oligonucleotide (ASO) or miR-130a-3p mimics was sufficient to inhibit the ability of interleukin-4 to induce M2 cytokine production. We additionally confirmed the in vivo relevance of these miRNAs in a Ccr2-/- murine model system mimicking asthma. Specifically, we determined that transfecting monocytes with miR-142-5p ASO and/or miR-130a-3p mimics was sufficient to disrupt the ability of these cells to promote airway remodeling. As such, these findings reveal that miR-142-5p and miR-130a-3p dysregulation are important factors governing the polarization of macrophages and associated airway remodeling in OVA-sensitized mice.

MiR-23b controls TGF-ß1 induced airway smooth muscle cell proliferation via direct targeting of Smad3.

BACKGROUND: MicroRNAs are small yet versatile gene tuners that regulate a variety of cellular processes, including cell growth and proliferation. Here we report that miR-23b inhibited airway smooth muscle cells (ASMCs) proliferation through directly targeting of Smad3. METHODS: We obtained ASMCs by laser capture microdissection of normal and asthmatic mice lung tissues. Mice ASMCs were cultured and induced by TGF-ß1. The implication between TGF-ß1 and miR-23b in ASMCs were detected by RT-PCR. The effects of miR-23b on ASMCs proliferation and apoptosis were assessed by transient transfection of miR-23b mimics and inhibitor. The expression of Smad3 in ASMCs were detected by RT-PCR and Western blotting analysis. Dual-Luciferase Reporter Assay System will be applied to identify whether Smad3 is a target gene of miR-23b. RESULTS: TGF-ß1 and miR-23b mRNA expression of in-situ bronchial ASMCs collected by laser capture microdissection were increased in asthmatic mice compared to non-asthma controls. This is accompanied by an increase in miR-23b mRNA expression in TGF-ß1 induced ASMCs. miR-23b up-regulation significantly inhibited TGF-ß1-induced ASMCs proliferation and promoted apoptosis. MiR-23b negatively regulates the expression of Smad3 in ASMCs. Dual-Luciferase Reporter Assay System demonstrated that Smad3 was a direct target of miR-23b. CONCLUSIONS: MiR-23b may function as an inhibitor of asthma airway remodeling by suppressing ASMCs proliferation via direct targeting of Smad3.

Airway smooth muscle cells from ovalbumin-sensitized mice show increased proliferative response to TGFß1 due to upregulation of Smad3 and TGFßRII.

OBJECTIVE: This study aimed to elucidate the role of Transforming growth factor (TGF)-ß1 signaling in the proliferation of airway smooth muscle cells (ASMCs). BACKGROUND: TGF-ß1 is an important cytokine in airway remodeling in asthma. However, results of studies focusing on the effect of TGFß1 on proliferation of ASMCs are controversial. METHODS: An allergic model that mimics airway remodeling in chronic asthma was established and primary ASMCs were cultured. Cell proliferation was detected by viable cell counting and Cell Counting Kit (CCK)-8 analysis. Expression and phosphorylation of Smad3, type 1 TGFß receptor (TGFßRI), type 2 TGFß receptor (TGFßRII), extracellular signal-regulated kinase (ERK)-1/2, p38 mitogen-activated protein kinase (MAPK), C-Jun N-terminal kinase (JNK) and AKT were detected by western blot. siRNAs were used to knock down Smad3 and TGFßRII. RESULTS: Smad3 and TGFßRII were up-regulated in primary ASMCs isolated from ovalbumin (OVA)-sensitized mice as compared with ASMCs isolated from unsensitized control mice, which persisted for at least four passages. TGFß1 stimulated proliferation of ASMCs isolated from OVA-sensitized mice, which was inhibited by specific siRNA targeting Smad3 or TGFßRII. However ASMCs from control mice showed no proliferative response to TGFß1. TGFß1-induced proliferation of ASMCs from OVA-sensitized mice was markedly attenuated by PD-98059, a specific ERK1/2 inhibitor. TGFß1 induced ERK1/2 phosphorylation within 15 minute, which was partially blocked by specific inhibitor of Smad3 (SIS3). CONCLUSIONS: ASMCs isolated from OVA-sensitized mice showed hyper-proliferation upon TGFß1 stimulation. This might have been associated with up-regulated Smad3 and TGFßRII and mediated by ERK1/2 downstream to Smad3.

Triptolide inhibits TGF-ß1-induced cell proliferation in rat airway smooth muscle cells by suppressing Smad signaling.

BACKGROUND: We have reported that triptolide can inhibit airway remodeling in a murine model of asthma via TGF-ß1/Smad signaling. In the present study, we aimed to investigate the effect of triptolide on airway smooth muscle cells (ASMCs) proliferation and the possible mechanism. METHODS: Rat airway smooth muscle cells were cultured and made synchronized, then pretreated with different concentration of triptolide before stimulated by TGF-ß1. Cell proliferation was evaluated by MTT assay. Flow cytometry was used to study the influence of triptolide on cell cycle and apoptosis. Signal proteins (Smad2, Smad3 and Smad7) were detected by western blotting analysis. RESULTS: Triptolide significantly inhibited TGF-ß1-induced ASMC proliferation (P<0.05). The cell cycle was blocked at G1/S-interphase by triptolide dose dependently. No pro-apoptotic effects were detected under the concentration of triptolide we used. Western blotting analysis showed TGF-ß1 induced Smad2 and Smad3 phosphorylation was inhibited by triptolide pretreatment, and the level of Smad7 was increased by triptolide pretreatment. CONCLUSIONS: Triptolide may function as an inhibitor of asthma airway remodeling by suppressing ASMCs proliferation via negative regulation of Smad signaling pathway.

Triptolide inhibits TGF-ß1 induced proliferation and migration of rat airway smooth muscle cells by suppressing NF-κB but not ERK1/2.

BACKGROUND: Airway remodeling contributes to increased mortality in asthma. We have reported that triptolide can inhibit airway remodeling in a mouse asthma model. In this study, we aimed to investigate the effect of triptolide on airway smooth muscle cells (ASMCs) proliferation, migration and the possible mechanism. METHODS: Rat airway smooth muscle cells were cultured and made synchronized, then pretreated with different concentrations of triptolide before stimulated by TGF-ß1. Cell proliferation was evaluated by cell counting and MTT assay. Flow cytometry was used to study the influence of triptolide on cell cycle. Migration was measured by Transwell analysis. Signal proteins (NF-κB p65 and ERK1/2) were detected by western blotting analysis. LDH releasing test and flow cytometry analysis of apoptosis were also performed to explore the potential cytotoxic or pro-apoptotic effects of triptolide. RESULTS: Triptolide significantly inhibited TGF-ß1 induced ASMC proliferation and migration (p<0.05). The cell cycle was blocked at G1/S-interphase by triptolide dose dependently. Western blotting analysis showed TGF-ß1 induced NF-κB p65 phosphorylation was inhibited by triptolide pretreatment, but ERK1/2 was not affected. No cytotoxic or pro-apoptotic effects were detected under the concentration of triptolide we used. CONCLUSIONS: Triptolide may function as an inhibitor of asthma airway remodeling by suppressing ASMCs proliferation and migration through inactivation of NF-κB pathway. This article is protected by copyright. All rights reserved.

Inhibition of TRPM7 channels reduces degranulation and release of cytokines in rat bone marrow-derived mast cells.

BACKGROUND: mast cells play an important role in airway inflammation in asthma. The transient receptor potential melastatin-like 7 (TRPM7) channel is expressed in primary human lung mast cells and plays a critical role for cell survival. This study aimed to investigate the role of TRPM7 on degranulation and release of cytokines in rat bone marrow-derived mast cells (BMMCs). METHODS: the expression levels of TRPM7 were observed by immunocytochemistry and RT-PCR between normal and asthmatic rat BMMCs. TRPM7-specific shRNA and 2-aminoethoxydiphenyl borate (2-APB) and specific shTRPM7 were used to inhibit the function of TRPM7. Degranulation levels were analyzed by beta-hexosaminidase assay. Histamine, TNF-α, IL-6 and IL-13 levels were measured by ELISA. RESULTS: the expression of TRPM7 was significantly higher in asthmatic rat BMMCs than in the normal control group. After application of 2-APB and down-regulation of TRPM7, the beta-hexosaminidase activity and secretion of histamine, IL-6, IL-13 and TNF-α were significantly decreased in the asthmatic group compared to the control group. CONCLUSION: this study indicates that TRPM7 channels may be involved in the process of degranulation and release of cytokines in rat bone marrow-derived mast cells.

Recent Advancements in Ultrasound Contrast Agents Based on Nanomaterials for Imaging.

Ultrasound (US) is a type of mechanical wave that is capable of transmitting energy through biological tissues. By utilization of various frequencies and intensities, it can elicit specific biological effects. US imaging (USI) technology has been continuously developed with the advantages of safety and the absence of radiation. The advancement of nanotechnology has led to the utilization of various nanomaterials composed of both organic and inorganic compounds as ultrasound contrast agents (UCAs). These UCAs enhance USI, enabling real-time monitoring, diagnosis, and treatment of diseases, thereby facilitating the widespread adoption of UCAs in precision medicine. In this review, we introduce various UCAs based on nanomaterials for USI. Their principles can be roughly divided into the following categories: carrying and transporting gases, endogenous gas production, and the structural characteristics of the nanomaterial itself. Furthermore, the synergistic benefits of US in conjunction with various imaging modalities and their combined application in disease monitoring and diagnosis are introduced. In addition, the challenges and prospects for the development of UCAs are also discussed.

Thermal-Responsive Antibacterial Hydrogel with Photothermal Therapy and Improving Wound Microenvironment for Promote Healing.

Skin damage is one of the most prevalent human injuries, which affects the health of human beings. However, skin damage is often accompanied by bacterial infection and wound microenvironment changes, causing damage to normal cells and inhibiting wound healing. Herein, we designed a thermal-responsive antibacterial hydrogel (GAG hydrogel) loaded with catalase (CAT)-like Au@Pt@MgSiO3 nanoparticles (APM NPs) and gentamicin (GM) to promote wound healing. The GAG hydrogel was used in a photothermal therapy (PTT)/antibiotic combination to kill bacteria, reduce the use of antibiotics, improve the wound microenvironment, promote cell proliferation, and accelerate wound healing. Under near-infrared laser irradiation, APM NPs in the hydrogel generated local hyperthermia to kill bacteria. Meanwhile, the generated heat led to a change in the hydrogel's morphology, enabling it to release GM and APM NPs to prevent the overuse of antibiotics. Subsequently, the CAT-like ability of the APM NPs decreased the oxidative stress caused by hydrogen peroxide (H2O2), thus remodeling the wound microenvironment. Then, the weakly acidic microenvironment of the wound caused the decomposition of the APM NPs and the release of magnesium ions (Mg2+), promoting the growth and migration of cells for wound healing. Therefore, the studied thermal-responsive antibacterial (GAG) hydrogel has potential in the field of wound healing.

Construction of a Functional Nucleic Acid-Based Artificial Vesicle-Encapsulated Composite Nanoparticle and Its Application in Retinoblastoma-Targeted Theranostics.

Retinoblastoma (RB) is an aggressive tumor of the infant retina. However, the ineffective targeting of its theranostic agents results in poor imaging and therapeutic efficacy, which makes it difficult to identify and treat RB at an early stage. In order to improve the imaging and therapeutic efficacy, we constructed an RB-targeted artificial vesicle composite nanoparticle. In this study, the MnO2 nanosponge (hMNs) was used as the core to absorb two fluorophore-modified DNAzymes to form the Dual/hMNs nanoparticle; after loaded with the artificial vesicle derived from human red blood cells, the RB-targeted DNA aptamers were modified on the surface, thus forming the Apt-EG@Dual/hMNs complex nanoparticle. The DNA aptamer endows this nanoparticle to target the nucleolin-overexpressed RB cell membrane specifically and enters cells via endocytosis. The nanoparticle could release fluorophore-modified DNAzymes and supplies Mn2+ as a DNAzyme cofactor and a magnetic resonance imaging (MRI) agent. Subsequently, the DNAzymes can target two different mRNAs, thereby realizing fluorescence/MR bimodal imaging and dual-gene therapy. This study is expected to provide a reliable and valuable basis for ocular tumor theranostics.

Metabolite Profiling Reveals the Dynamic Changes in Non-Volatiles and Volatiles during the Enzymatic-Catalyzed Processing of Aijiao Oolong Tea.

The enzymatic reaction stage (ECS) of oolong tea processing plays an important role in the formation of the flavor quality of the oolong tea. To investigate the dynamic changes in the volatile and non-volatile components in the leaves of oolong tea during the ECS, metabolomic studies were carried out using the leaf samples collected at different stages of the ECS of Aijiao oolong tea. Out of the identified 306 non-volatile metabolites and 85 volatile metabolites, 159 non-volatile metabolites and 42 volatile metabolites were screened out as key differential metabolites for dynamic changes during the ECS. A multivariate statistical analysis on the key differential metabolites showed that the accumulations of most metabolites exhibited dynamic changes, while some amino acids, nucleosides, and organic acids accumulated significantly after turning-over treatment. The evolution characteristics of 27 key precursors or transformed VOCs during the ECS of Aijiao oolong tea were clarified, and it was found that the synthesis of aroma substances was mainly concentrated in lipids as precursors and glycosides as precursor pathways. The results revealed the dynamic changes in the flavor metabolites in the ECS during the processing of Aijiao oolong tea, which provided valuable information for the formation of the characteristic flavor of Aijiao oolong tea.

Ultrasound Activated Nanobowls with Deep Penetration for Enhancing Sonodynamic Therapy of Orthotopic Liver Cancer.

Owing to the high penetration ability and the safety of ultrasound (US) of sonodynamic therapy (SDT), it has gained significant attention in tumor treatment. However, its therapeutic efficiency depends on the performance of the sonosensitizers. The hypoxic microenvironment and abnormal stromal matrix restrict the full potential of sonosensitizers. In this study, a US-activated bowl-shaped nanobomb (APBN) is designed as a novel sonosensitizer to enhance the SDT effect through various means. This enhancement strategy combines three major characteristics: relieving tumor hypoxia, amplifying bubble cavitation damage, and US-movement-enhanced permeation. The unique bowl-shaped structure of APBN provides more favorable attachment sites for the generated oxygen gas bubbles. Thus, when catalase-like APBN catalyzes endogenous hydrogen peroxide to produce oxygen, bubbles accumulate at the groove, preventing the dissipation of oxygen and increasing the number of cavitation nuclei to improve the acoustic cavitation effect. This approach differs from traditional SDT strategies because it couples the sonodynamic effect with reactive oxygen species generation and bubble cavitation damage rather than a single action. Additionally, the asymmetric bowl-shaped structure generates a driving force under the US field, improving the distribution of sonosensitizers in the tumors. Using US and photoacoustic imaging for dual localization, these sonosensitizers can improve the accuracy of orthotopic liver tumor treatment, which presents a promising avenue for the treatment of deep tumors.

Effects of polysaccharide from Pueraria lobata on osteoarthritis in rats.

The effects of Pueraria lobata polysaccharide (PPL-1) on osteoarthritis (OA) disease were comprehensively evaluated by using chondrocytes and synoviocytes extracted from the joints of SD rats based on in vitro cell experiments and by establishing pathological models of OA rats. The results showed that concentrations of 1.25-10 and 0.2-1.6 µg/mL, PPL-1 did not inhibit or promote chondrocytes and synoviocytes in vitro. However, at concentrations of 1.25-10 and 0.2-1.6 µg/mL, it can promote cartilage and synovial membrane cells after LPS stimulation of cell activity and inhibite LPS-induced apoptosis. The results of animal experiments showed that PPL-1 can reduce the symptoms of joint swelling in OA rats, decrease the production of serum inflammatory cytokines TNF-α, IL-1ß, and IL-6, and slow down the occurrence of inflammation. Therefore, from the perspective of symptoms, inflammatory factors and pathology, PPL-1 has therapeutic effects on OA rats and alleviates the development of inflammation. It indicated that PPL-1 has the potential to be developed into an OA therapeutic drug with anti-inflammatory properties that protects and activates chondrocytes.

Allergic hyper-carcinoembryonic antigen syndrome: A syndrome summarized by case series.

Allergic respiratory diseases can increase serum carcinoembryonic antigen levels. We report three cases experiencing allergic symptoms that proved refractory to inhaled corticosteroids but exhibited a positive response to long-term treatment with oral corticosteroids. This response was characterized by a synchronous alteration in serum eosinophil counts and carcinoembryonic antigen levels. Immunofluorescence assays indicated localized carcinoembryonic antigen production within eosinophils. In addition, we conducted a systematic review of patients exhibiting similar characteristics on PubMed. After comprehensively reviewing this unique pathophysiological condition, we herein introduced a novel term "Allergic hyper-carcinoembryonic antigen syndrome," defined by the following criteria: (1) recurrent asthmatic attacks; (2) eosinophilia or pulmonary eosinophilic infiltrations accompanied by elevated serum carcinoembryonic antigen levels; (3) pulmonary lesions determined by imaging or biopsy; (4) exclusion of malignancy and infections; and (5) responsive to systemic corticosteroids. Allergic hyper-carcinoembryonic antigen syndrome suggests systemic corticosteroids should be introduced early when managing allergic patients with both eosinophilia and elevated serum carcinoembryonic antigen levels.

Radiomics features of computed tomography and magnetic resonance imaging for predicting response to transarterial chemoembolization in hepatocellular carcinoma: a meta-analysis.

Purpose: To examine the methodological quality of radiomics-related studies and evaluate the ability of radiomics to predict treatment response to transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). Methods: A systematic review was performed on radiomics-related studies published until October 15, 2022, predicting the effectiveness of TACE for HCC. Methodological quality and risk of bias were assessed using the Radiomics Quality Score (RQS) and Quality Assessment of Diagnostic Accuracy Studies-2 tools, respectively. Pooled sensitivity, pooled specificity, and area under the curve (AUC) were determined to evaluate the utility of radiomics in predicting the response to TACE for HCC. Results: In this systematic review, ten studies were eligible, and six of these studies were used in our meta-analysis. The RQS ranged from 7-21 (maximum possible score: 36). The pooled sensitivity and specificity were 0.89 (95% confidence interval (CI) = 0.79-0.95) and 0.82 (95% CI = 0.64-0.92), respectively. The overall AUC was 0.93 (95% CI = 0.90-0.95). Conclusion: Radiomics-related studies evaluating the efficacy of TACE in patients with HCC revealed promising results. However, prospective and multicenter trials are warranted to make radiomics more feasible and acceptable.

Lattice Boltzmann model for predicting frosting process on surfaces considering wettability.

The process of frosting is a multiscale problem, which leads to challenges of proposing accurate numerical methods. In this study, a lattice Boltzmann model for predicting frost formation and growth on surfaces of various wettabilities is proposed based on the heterogeneous nucleation and dendrite growth theories. Three lattice Boltzmann equations are used to calculate the velocity, humidity, and temperature distributions. Furthermore, the heterogeneous nucleation theory and dendrite growth theory are used to construct the equations that govern ice production during the frosting process, so that the surface wettability can be considered. After experimental validation, the model was used in the analysis of frosting behaviors on plates and in microchannels with different wettabilities. The effects of the intrinsic contact angles and roughness on the frost layer properties were evaluated. This study will likely facilitate a better understanding of frosting on the mesoscopic level.

Effects of lower-extremity explosive strength on youth judo athletes adopting different types of power-based resistance training.

Objective: The present study compared the effects of two different resistance types (pneumatic resistance and free weight) of 6-week squat training on the performance for young female judo athletes in linear speed and vertical jump by utilizing the maximum power of each set of squats in each training session as the monitoring vehicle. Monitoring data were used to assess the effects and trends of the two resistance types on 70% 1RM weight-bearing during the 6-week intervention training. Methods: In a 6 weeks squat training (2 reps/week with a constant load), 23 adolescent female judo athletes (Age span: 13-16 years, 14.58 ± 0.96) were randomly selected and then divided into the traditional barbell (FW) group (n = 12) and the pneumatic resistance (PN) (n = 11) group according to different resistance types (free weight and pneumatic resistance), with 10 in FW group and 9 in PN group actually completed the study. Before and after training, the 30-m Sprint time (T-30M), vertical jump height and relative power (countermovement jump, static-squat jump, and drop jump), reactive strength index (DJ-RSI), and maximal strength were assessed. One-Way ANOVA was used to examine the pre-test differences of groups (FW and PN). A 2-factor mixed-model analysis of variance was used to examine the independent effects of group (FW and PN) and time (pre and post) on each dependent measure. Scheffe post hoc comparisons were used to examine the differences. Pre- and post-experimental differences between the two groups were analyzed using independent samples t-tests and magnitude-based inferences (MBI) derived from their p values, and effect statistics were applied to compare the pre- and post-changes exhibited by each group to identify the potential beneficiary groups. Results: The PN group outperformed the FW group in terms of maximal power output per training session (822.5 ± 55.22 vs. 927.42 ± 48.15, conventional vs. pneumatic, p < 0.001, effect size = -2.02). After 6 weeks of training, the FW group showed significant increases in vertical jump height and relative strength (CMJ, SJ, DJ), with no significant gains observed in T-30 and maximal strength. The PN group showed significant improvements in maximal strength; however, no significant improvements were observed in the other tests. In addition, there was no significant difference in DJ-RSI between the two groups before and after training. Discussion: At 70% weight bearing, free weight resistance appears to be more conducive to vertical jump growth, while pneumatic resistance appears to be more conducive to maximal strength gains; however, the maximal strength gains from pneumatic resistance may not be well applied to athletic performance. In addition, the body adapts more quickly to pneumatic resistance than to free weight resistance.

Meta-analysis of the impact of physical activity on the recovery of physical function in COVID-19 patients.

Background: The decrease in physical function resulting from COVID-19 infection exerts a substantial negative influence on the quality of life of individuals. Physical activity plays a crucial and irreplaceable role in hastening the elimination of adverse effects on the body caused by acute and chronic diseases. Nevertheless, there have been reports of unfavorable events following physical activity post-COVID-19 infection, sparking debate regarding the efficacy of physical activity as a rehabilitation method to enhance the physical function of COVID-19 patients. Objective: The aim of this study is to investigate the impact of physical activity on promoting the restoration of physical function among individuals with COVID-19, and to offer guidance for the advancement and consideration of physical activity in the rehabilitation treatment of COVID-19 patients. Methods: A search was conducted on the PubMed and Web of Science core collection databases, with the search period set from January 1, 2020, to February 6, 2023. The included literature was assessed for risk of bias and methodological quality according to the Cochrane Handbook for Systematic Reviews of Interventions, utilizing Review Manager 5.1 software. The outcome measures from the included studies were analyzed, and the quality of evidence for the outcome measures was graded using the GRADE classification criteria. Results: The effect of physical activity intervention on improving the 6-Minute Walk Test score in COVID-19 patients was better than that of conventional treatment [WMD = 69.19(95%CI = 39.38, 98.99), I2 = 57%(p = 0.03)]. The effect of physical activity on improving the 30-Second Sit-to-Stand Test score was better than that of conventional treatment [WMD = 2.98(95%CI = 1.91, 4.04), I2 = 0%(p = 0.56)]. There was no significant difference between physical activity and conventional treatment in improving Grip strength in COVID-19 patients [WMD = 2.35(95%CI = -0.49, 5.20), I2 = 0%(p = 0.80)]. The effect of physical activity on improving the Timed Up and Go test score in COVID-19 patients was better than that of conventional treatment [WMD = -1.16(95%CI = -1.98, -0.34), I2 = 4%(p = 0.35)]. The effect of physical activity on improving Forced Vital Capacity in COVID-19 patients was better than that of conventional treatment [WMD = 0.14(95%CI = 0.08, 0.21), I2 = 0%(p = 0.45)]. The effect of physical activity on improving Forced Expiratory Volume in the first second in COVID-19 patients was better than that of conventional treatment [WMD = 0.08(95%CI = 0.02, 0.15), I2 = 52%(p = 0.10)]. Conclusions: Physical activity plays a crucial role in facilitating the recovery of exercise capacity and pulmonary function in COVID-19 patients, helping to expedite the restoration of overall physical health. It is crucial for COVID-19 patients to undergo an accurate assessment of their physical condition before engaging in any physical activity.

Recent theranostic applications of hydrogen peroxide-responsive nanomaterials for multiple diseases.

It is well established that hydrogen peroxide (H2O2) is associated with the initiation and progression of many diseases. With the rapid development of nanotechnology, the diagnosis and treatment of those diseases could be realized through a variety of H2O2-responsive nanomaterials. In order to broaden the application prospects of H2O2-responsive nanomaterials and promote their development, understanding and summarizing the design and application fields of such materials has attracted much attention. This review provides a comprehensive summary of the types of H2O2-responsive nanomaterials including organic, inorganic and organic-inorganic hybrids in recent years, and focused on their specific design and applications. Based on the type of disease, such as tumors, bacteria, dental diseases, inflammation, cardiovascular diseases, bone injury and so on, key examples for above disease imaging diagnosis and therapy strategies are introduced. In addition, current challenges and the outlook of H2O2-responsive nanomaterials are also discussed. This review aims to stimulate the potential of H2O2-responsive nanomaterials and provide new application ideas for various functional nanomaterials related to H2O2.

RNA Methylome Reveals the m6A-mediated Regulation of Flavor Metabolites in Tea Leaves under Solar-withering.

The epitranscriptomic mark N6-methyladenosine (m6A), which is the predominant internal modification in RNA, is important for plant responses to diverse stresses. Multiple environmental stresses caused by the tea-withering process can greatly influence the accumulation of specialized metabolites and the formation of tea flavor. However, the effects of the m6A-mediated regulatory mechanism on flavor-related metabolic pathways in tea leaves remain relatively uncharacterized. We performed an integrated RNA methylome and transcriptome analysis to explore the m6A-mediated regulatory mechanism and its effects on flavonoid and terpenoid metabolism in tea (Camellia sinensis) leaves under solar-withering conditions. Dynamic changes in global m6A level in tea leaves were mainly controlled by two m6A erasers (CsALKBH4A and CsALKBH4B) during solar-withering treatments. Differentially methylated peak-associated genes following solar-withering treatments with different shading rates were assigned to terpenoid biosynthesis and spliceosome pathways. Further analyses indicated that CsALKBH4-driven RNA demethylation can directly affect the accumulation of volatile terpenoids by mediating the stability and abundance of terpenoid biosynthesis-related transcripts and also indirectly influence the flavonoid, catechin, and theaflavin contents by triggering alternative splicing-mediated regulation. Our findings revealed a novel layer of epitranscriptomic gene regulation in tea flavor-related metabolic pathways and established a link between the m6A-mediated regulatory mechanism and the formation of tea flavor under solar-withering conditions.

Analysis of Characteristics in the Macro-Composition and Volatile Compounds of Understory Xiaobai White Tea.

Understory planting affects the growth environment of tea plants, regulating the tea plant growth and the formation of secondary metabolites, which in turn affects the flavor of Xiaobai white tea. The present research adopted biochemical composition determination, widely targeted volatilities (WTV) analysis, multivariate statistical analysis, and odor activity value (OAV) analysis to analyze the characteristics in the macro-composition and volatile compounds of understory white tea. The sensory evaluation results indicated that understory Xiaobai white tea (LWTs) was stronger than ordinary Xiaobai white tea (PWTs) in terms of the taste of smoothness, sweetness, and thickness as well as the aromas of the flower and sweet. Understory planting reduced light intensity and air temperature, increased air humidity, organic matter, total nitrogen, and available nitrogen contents, which improved the growth environment of tea plants. The phytochemical analysis showed that the water-extractable substances, caffeine, flavonoids, and soluble sugar contents of understory tea fresh-leaf (LF) were higher than those of ordinary fresh-leaf (PF). The phytochemical analysis showed that the free amino acids, theaflavins, thearubigins, water-extractable substances, and tea polyphenols contents of LWTs were significantly higher than those of PWTs, which may explain the higher smoothness, sweetness, and thickness scores of LWTs than those of PWTs. The 2-heptanol, 2-decane, damasone, and cedar alcohol contents were significantly higher in LWTs than in PWTs, which may result in stronger flowery and sweet aromas in LWTs than in PWTs. These results provide a firm experimental basis for the observed differences in the flavor of LWTs and PWTs.