Hydrangea serrata extract attenuates PM-exacerbated airway inflammation in the CARAS model by modulating the IL-33/ST2/NF-κB signaling pathway.

Particulate matter (PM) significantly contributes to the global health crisis of respiratory diseases. It is known to induce and exacerbate conditions such as asthma and respiratory infections. Long exposure to PM can increase the risk of combined allergic rhinitis and asthma syndrome (CARAS). Although therapeutic drugs can be used to improve symptoms of respiratory diseases caused by PM, their usage is often accompanied by side effects. Therefore, many studies are being conducted to discover functional food materials that can more effectively treat respiratory diseases while minimizing the side effects of these therapeutic drugs. This study was conducted to investigate the efficacy of Hydrangea serrata extract (HSE) in airway inflammation in a mouse model of CARAS exacerbated by PM. In the CARAS mouse model worsened by PM, the airway inflammation improvement effect of HSE was evaluated by analyzing allergic nasal symptoms, changes in inflammatory cells, OVA-specific immunoglobulin (Ig) levels, cytokines, mast cell activation, and histopathological findings of both nasal mucosa and lung tissue. HSE effectively reduced OVA-specific IgE and IgG1 and inhibited the production of T helper type 2 (Th2)-related cytokines such as IL-4 and IL-5. Importantly, HSE reduced IL-33 and ST2 expression and inhibited the activation of the NF-κB signaling pathway. In addition, HSE inhibited airway hypersensitivity, mucus production, and inflammatory cell infiltration. These results suggest that HSE may inhibit airway inflammation in CARAS/PM mice by regulating the IL-33/ST2/NF-κB signaling pathway, opening avenues for considering HSE as a potential material for treating allergic airway inflammation diseases in the future.

Supramolecular Switch for the Regulation of Antibacterial Efficacy of Near-Infrared Photosensitizer.

The global antibiotic resistance crisis has drawn attention to the development of treatment methods less prone to inducing drug resistance, such as antimicrobial photodynamic therapy (aPDT). However, there is an increasing demand for new photosensitizers capable of efficiently absorbing in the near-infrared (NIR) region, enabling antibacterial treatment in deeper sites. Additionally, advanced strategies need to be developed to avert drug resistance stemming from prolonged exposure. Herein, we have designed a conjugated oligoelectrolyte, namely TTQAd, with a donor-acceptor-donor (D-A-D) backbone, enabling the generation of reactive oxygen species (ROS) under NIR light irradiation, and cationic adamantaneammonium groups on the side chains, enabling the host-guest interaction with curcubit[7]uril (CB7). Due to the amphiphilic nature of TTQAd, it could spontaneously form nanoassemblies in aqueous solution. Upon CB7 treatment, the positive charge of the cationic adamantaneammonium group was largely shielded by CB7, leading to a further aggregation of the nanoassemblies and a reduced antibacterial efficacy of TTQAd. Subsequent treatment with competitor guests enables the release of TTQAd and restores its antibacterial effect. The reversible supramolecular switch for regulating the antibacterial effect offers the potential for the controlled release of active photosensitizers, thereby showing promise in preventing the emergence of drug-resistant bacteria.

A novel pH-sensitive hemi-cyanine containing tetrahydropyridine ring near-infrared fluorescence probe with lysosome-targeting ability.

In recent years, hemi-cyanine dyes have been widely used as biological probes due to their red-light emission characteristics and high fluorescence quantum yield. In this study, we synthesized a novel hemi-cyanine dye containing a tetrahydropyridine ring. A lysosomal target was introduced into its structure to create a new pH-sensitive near-infrared fluorescent probe that successfully targeted lysosomes. The results showed that when the probe solution was excited at the absorption wavelength of 650 nm, its fluorescence emission wavelength was about 700 nm, and the peak intensity changed with different pH values in a wide range. Therefore, this probe enabled non-invasive detection of changes in the acidic environment of lysosomes in living organisms and showed good imaging capabilities. Moreover, the probe displays high sensitivity and good stability. The theoretical calculation of a probe structure has also been completed to discuss the relationship between structure and property.

Tectorigenin inhibits oxidative stress by activating the Keap1/Nrf2/HO-1 signaling pathway in Th2-mediated allergic asthmatic mice.

Asthma is a chronic obstructive airway condition and one of the most common non-communicable illnesses worldwide. Tectorigenin (Tec) is an isoflavonoid found in plants that possesses significant antioxidative and anti-inflammatory abilities. Nevertheless, the antioxidative properties of Tec have not yet been documented in allergic asthma. In this study, we created an asthmatic BALB/c mouse model induced by ovalbumin (OVA) and used it to assess the efficacy of Tec as a possible therapy agent. Tec decreased the serum OVA-specific immunoglobulin (Ig) E and IgG1 secretion levels. The total number of cells and the distribution of inflammatory cells decreased significantly in bronchoalveolar lavage fluid (BALF), with weakened inflammatory reaction in pulmonary tissues. Additionally, Tec regulated the T helper 1(Th1)/Th2 balance by increasing the expression of Th1- related factors (interleukin (IL)-12 and T-bet) and decreasing the expression of Th2-related factors (IL-4, IL-5, IL-13, and GATA binding protein 3. In addition, the pro-inflammatory cytokines such as IL-6, tumor necrosis factor-alpha, and IL-1ß were also inhibited by Tec. Tec also dramatically increased antioxidant (catalase and superoxide dismutase) concentrations while lowering the intensity of the indicators of oxidative stress such as reactive oxygen species and malondialdehyde in BALF. Finally, Tec effectively activated the Keap1/Nrf2/HO-1 signaling pathway and prevented the epithelial-mesenchymal transition. The results of the current study show that Tec may be useful in relieving the inflammatory and oxidative stress responses associated with asthma.

Mental health survey among front-line medical workers after 2 years of supporting COVID-19 efforts in Hubei Province.

During the outbreak of COVID-19 in China, many health care workers have been involved in the front-line fight against the epidemic and have experienced major psychological challenges. This study was aimed at assessing the mental health of front-line health workers after 2 years of COVID-19 efforts. We recruited front-line health workers from Liaoning province who supported Hubei, the epicenter of the COVID-19 outbreak. The Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder scale (GAD-7), and Insomnia Severity Index (ISI) were used to assess psychological status. A total of 1101 of 1354 contacted individuals completed the survey (participation rate of 81.31%): 963 (87.5%) were 20-45 years of age, 919 (83.47%) were women, 845 (76.7%) were nurses, and 245 (22.3%) were physicians. After 2 years, the mental health symptoms among survey respondents were as follows: 46.6% had depression, 35.5% had anxiety, and 38.1% had insomnia. Thus, 2 years after the COVID-19 pandemic, the front-line health workers who had assisted Hubei province during the COVID­19 pandemic in China still had high levels of depression, anxiety, and insomnia. Our findings suggest that the pandemic has had significant long-term effects on the mental health of front-line health workers. Therefore, mental health policies should offer long-term rather than short-term services.

The Role of OH Cards in Psychological Interventions for Children With Fractures.

Context: Fractures are traumatic events, with psychological effects that can have a negative impact on children hospitalized with fractures. They can seriously affect children's physical rehabilitation and quality of life and even produce psychological disorders The OH card is a metaphorical card that allows access to an individual's inner world and can have a positive effect in psychotherapy. Objective: The study intended to investigate the use of OH Cards during psychological interventions with children with fractures and to provide a methodological reference for the use of OH Cards in therapy. Design: The research team performed a randomized controlled study. Setting: The study took place in the Department of Trauma Surgery at Children's Hospital of Hebei Province in Shijiazhuang, China. Participants: Participants were 74 children with fractures who had been admitted to the hospital between September 2020 and November 2021. Intervention: The research team randomly divided participants into two groups using a random number table: (1) 37 in the intervention group, who received a conventional nursing intervention and also an OH-card intervention, and (2) 37 in the control group, who received conventional nursing interventions only. Outcome Measures: At baseline and postintervention, the research team: (1) measured the participants' posttraumatic growth scores, using the children's version of the Post-Traumatic Growth Inventory (PTGI); (2) assessed their coping styles, using the Medical Coping Modes Questionnaire (MCMQ); (3) determined the existence of any stress disorders, using the Child Stress Disorder Checklist (CSDC); (4) evaluated their mental statuses using the Depression Self-Rating Scale (DSRSC) and the Screen for Child Anxiety-related Emotional Disorders (SCARED); and (5) measured participants' Fracture Knowledge Questionnaire scores. Results: At baseline, no significant differences existed between the groups for any outcome measure at baseline. Postintervention, the intervention group's scores: (1) on the PTGI, were significantly higher for mental change, appreciate life, individual force, new possibilities and personal relation than those of the control group; (2) on the MCMQ, were significantly higher for facing and significantly lower for avoidance and yield than those of the control group; (3) on the CSDC, were significantly lower for trauma incidents and acute response than the control group did; (4) on the DSRSC were significantly lower and on SCARED were significantly higher than those of the control group; and (5) on the Fracture Knowledge Questionnaire were significantly higher than those of the control group. Conclusions: OH Cards can increase the posttraumatic growth scores of children with fractures, improve their coping styles, reduce stress disorders, decrease depression and improve their psychological state, increase their knowledge about fractures, and promote their recovery.

Bergapten ameliorates combined allergic rhinitis and asthma syndrome after PM2.5 exposure by balancing Treg/Th17 expression and suppressing STAT3 and MAPK activation in a mouse model.

Combined allergic rhinitis and asthma syndrome (CARAS) causes chronic respiratory inflammation in allergic individuals. Long-term exposure to particulate matter 2.5 (PM2.5; particles 2.5 µm or less in diameter) can aggravate respiratory damage. Bergapten (5-methoxysporalen) is a furocoumarin mostly found in bergamot essential oil and has significant antioxidant, anticancer, and anti-inflammatory activity. This study created a model in which CARAS was exacerbated by PM2.5 exposure, in BALB/c mice and explored the potential of bergapten as a therapeutic agent. The bergapten medication increased ovalbumin (OVA)-specific immunoglobulin (Ig) G2a level in serum and decreased OVA-specific IgE and IgG1 expression. Clinical nasal symptoms diminished significantly, with weakened inflammatory reaction in both the nasal mucosa and lungs. Furthermore, bergapten controlled the T helper (Th)1 to Th2 ratio by increasing cytokines associated with Th1-like interleukin (IL)-12 and interferon gamma and decreasing the Th2 cytokines IL-4, IL-5, and IL-13. Factors closely related to the balance between regulatory T cells and Th17 (such as IL-10, IL-17, Forkhead box protein P3, and retinoic-related orphan receptor gamma) were also regulated. Notably, pro-inflammatory cytokines IL-6, IL-1ß, and tumor necrosis factor-alpha were reduced by bergapten, which suppressed the activation of both the signal transducer and activator of transcription 3 signaling pathway and the mitogen-activated protein kinase signaling pathway. Therefore, bergapten might have potential as a therapeutic agent for CARAS.

Recent Progress in Diboronic-Acid-Based Glucose Sensors.

Non-enzymatic sensors with the capability of long-term stability and low cost are promising in glucose monitoring applications. Boronic acid (BA) derivatives offer a reversible and covalent binding mechanism for glucose recognition, which enables continuous glucose monitoring and responsive insulin release. To improve selectivity to glucose, a diboronic acid (DBA) structure design has been explored and has become a hot research topic for real-time glucose sensing in recent decades. This paper reviews the glucose recognition mechanism of boronic acids and discusses different glucose sensing strategies based on DBA-derivatives-based sensors reported in the past 10 years. The tunable pKa, electron-withdrawing properties, and modifiable group of phenylboronic acids were explored to develop various sensing strategies, including optical, electrochemical, and other methods. However, compared to the numerous monoboronic acid molecules and methods developed for glucose monitoring, the diversity of DBA molecules and applied sensing strategies remains limited. The challenges and opportunities are also highlighted for the future of glucose sensing strategies, which need to consider practicability, advanced medical equipment fitment, patient compliance, as well as better selectivity and tolerance to interferences.

Overexpression of the Salix matsudana SmAP2-17 gene improves Arabidopsis salinity tolerance by enhancing the expression of SOS3 and ABI5.

BACKGROUND: Salix matsudana (Koidz.) is a widely planted ornamental allotetraploid tree species. Genetic engineering can be used to enhance the tolerance of this species to soil salinization, endowing varieties with the ability to grow along coastlines, thereby mitigating afforestation and protecting the environment. The AP2/ERF family of transcription factors (TFs) plays multidimensional roles in plant biotic/abiotic stress tolerance and plant development. In this study, we cloned the SmAP2-17 gene and performed functional analysis of its role in salt tolerance. This study aims to identify key genes for future breeding of stress-resistant varieties of Salix matsudana. RESULTS: SmAP2-17 was predicted to be a homolog of AP2-like ethylene-responsive transcription factor ANT isoform X2 from Arabidopsis, with a predicted ORF of 2058 bp encoding an estimated protein of 685 amino acids containing two conserved AP2 domains (PF00847.20). SmAP2-17 had a constitutive expression pattern and was localized to the nucleus. The overexpression of the native SmAP2-17 CDS sequence in Arabidopsis did not increase salt tolerance because of the reduced expression level of ectopic SmAP2-17, potentially caused by salt-induced RNAi. Transgenic lines with high expression of optimized SmAP2-17 CDS under salt stress showed enhanced tolerance to salt. Moreover, the expression of general stress marker genes and important salt stress signaling genes, including RD29A, ABI5, SOS3, AtHKT1, and RBohF, were upregulated in SmAP2-17-overexpressed lines, with expression levels consistent with that of SmAP2-17 or optimized SmAP2-17. Promoter activity analysis using dual luciferase analysis showed that SmAP2-17 could bind the promoters of SOS3 and ABI5 to activate their expression, which plays a key role in regulating salt tolerance. CONCLUSIONS: The SmAP2-17 gene isolated from Salix matsudana (Koidz.) is a positive regulator that improves the resistance of transgenic plants to salt stress by upregulating SOS3 and ABI5 genes. This study provides a potential functional gene resource for future generation of salt-resistant Salix lines by genetic engineering.

Transcriptome-based analysis reveals that the biosynthesis of anthocyanins is more active than that of flavonols and proanthocyanins in the colorful flowers of Lagerstroemia indica.

Mechanisms associated with the control of flower color in crape myrtle varieties have yet to be sufficiently elucidated, which has tended to hamper the use of modern molecular and genetic strategies in the breeding programs for this plant. The whole transcriptome of four L. indica varieties characterized by different flower colors (white, light purple, deep purplish pink, and strong red) was sequenced, and we performed bioinformatic, quantitative PCR, and co-expression analyses of R2R3 MYB transcription factor and anthocyanin/flavonol pathway genes. We obtained a total of 49,980 transcripts with full-length coding sequences. Both transcriptome and qPCR analyses revealed that anthocyanin/flavonol pathway genes were differentially expressed among the four different flowers types, with the expression of LiPAL, LiCHS, LiCHI, LiDFR, LiANS/LDOX, and LiUFGT being induced in colorful flowers, whereas that of LiF3´5´H, LiFLS, and LiLAR was found to be inhibited. Base on phylogenetic analysis, seven R2R3 MYB transcriptional factors were identified as putative regulators of flower color. The molecular characteristics and co-expression patterns indicated that these MYBs differentially modulate their target genes, with two probably acting as activators, three as repressors, and one contributing to the regulation of vacuolar pH. The findings of this study indicate that the anthocyanin biosynthesis is more active than the flavonol and proanthocyanin in the colorful flowers. These observations provide new genomic information on L. indica and contribute gene resources for the flower color-targeted breeding of crape myrtle.

Genome-wide investigation of the AP2/ERF superfamily and their expression under salt stress in Chinese willow (Salix matsudana).

AP2/ERF transcription factors (TFs) play indispensable roles in plant growth, development, and especially in various abiotic stresses responses. The AP2/ERF TF family has been discovered and classified in more than 50 species. However, little is known about the AP2/ERF gene family of Chinese willow (Salix matsudana), which is a tetraploid ornamental tree species that is widely planted and is also considered as a species that can improve the soil salinity of coastal beaches. In this study, 364 AP2/ERF genes of Salix matsudana (SmAP2/ERF) were identified depending on the recently produced whole genome sequencing data of Salix matsudana. These genes were renamed according to the chromosomal location of the SmAP2/ERF genes. The SmAP2/ERF genes included three major subfamilies: AP2 (55 members), ERF (301 members), and RAV (six members) and two Soloist genes. Genes' structure and conserved motifs were analyzed in SmAP2/ERF family members, and introns were not found in most genes of the ERF subfamily, some unique motifs were found to be important for the function of SmAP2/ERF genes. Syntenic relationships between the SmAP2/ERF genes and AP2/ERF genes from Populus trichocarpa and Salix purpurea showed that Salix matsudana is genetically more closely related to Populus trichocarpa than to Salix purpurea. Evolution analysis on paralog gene pairs suggested that progenitor of S. matsudana originated from hybridization between two different diploid salix germplasms and underwent genome duplication not more than 10 Mya. RNA sequencing results demonstrated the differential expression patterns of some SmAP2/ERF genes under salt stress and this information can help reveal the mechanism of salt tolerance regulation in Salix matsudana.

Genome sequencing and phylogenetic analysis of allotetraploid Salix matsudana Koidz.

Polyploidy is a common phenomenon among willow species. In this study, genome sequencing was conducted for Salix matsudana Koidz (also named Chinese willow), an important greening and arbor tree species, and the genome of this species was compared with those of four other tree species in Salicaceae. The total genome sequence of S. matsudana was 655.72 Mb in size, with repeated sequences accounting for 45.97% of the total length. In total, 531.43 Mb of the genome sequence could be mapped onto 38 chromosomes using the published genetic map as a reference. The genome of S. matsudana could be divided into two groups, the A and B genomes, through homology analysis with the genome of Populus trichocarpa, and the A and B genomes contained 23,985 and 25,107 genes, respectively. 4DTv combined transposon analysis predicted that allotetraploidy in S. matsudana appeared ~4 million years ago. The results from this study will help reveal the evolutionary history of S. matsudana and lay a genetic basis for its breeding.

Uncovering candidate genes responsive to salt stress in Salix matsudana (Koidz) by transcriptomic analysis.

Salix matsudana, a member of Salicaceae, is an important ornamental tree in China. Because of its capability to tolerate high salt conditions, S. matsudana also plays an important ecological role when grown along Chinese coastal beaches, where the salinity content is high. Here, we aimed to elucidate the mechanism of higher salt tolerance in S. matsudana variety '9901' by identifying the associated genes through RNA sequencing and comparing differential gene expression between the S. matsudana salt-tolerant and salt-sensitive samples treated with 150 mM NaCl. Transcriptomic comparison of the roots of the two samples revealed 2174 and 3159 genes responsive to salt stress in salt-sensitive and salt-tolerant sample, respectively. Real-time polymerase chain reaction analysis of 9 of the responsive genes revealed a strong, positive correlation with RNA sequencing data. The genes were enriched in several pathways, including carbon metabolism pathway, plant-pathogen interaction pathway, and plant hormone signal transduction pathway. Differentially expressed genes (DEGs) encoding transcription factors associated with abiotic stress responses and salt stress response network were identified; their expression levels differed between the two samples in response to salt stress. Hub genes were also revealed by weighted gene co-expression network (WGCNA) analysis. For functional analysis of the DEG encoding sedoheptulose-1,7-bisphosphatase (SBPase), the gene was overexpressed in transgenic Arabidopsis, resulting in increased photosynthetic rates, sucrose and starch accumulation, and enhanced salt tolerance. Further functional characterization of other hub DEGs will reveal the molecular mechanism of salt tolerance in S. matsudana and allow the application of S. matsudana in coastal afforestation.

Guillain-Barre syndrome induced by pembrolizumab and sunitinib: A case report.

Pembrolizumab, an immune checkpoint inhibitor against the programmed death-1 pathway, has been used in combination with acitinib for the first-line treatment of advanced renal cell carcinoma. Neurotoxicity is a rare immune-related adverse event (irAE). The present study reports a case of Guillain-Barre syndrome (GBS) induced by pembrolizumab and sunitinib, and reviews other previous studies to elucidate the clinical characteristics and suitable management of this rare irAE. An advanced renal cell carcinoma patient who received several cycles of pembrolizumab combined with sunitinib developed limb weakness and numbness of the extremities, and was diagnosed with GBS by electrodiagnostic and cerebrospinal fluid examination. The patient improved after treatment with intravenous immunoglobulin along with prednisone. To the best of our knowledge, this is the first case of GBS during treatment with pembrolizumab in combination with sunitinib in advanced renal cell carcinoma.

Cancer vaccines: Targeting KRAS-driven cancers.

Introduction: Mutant KRAS is a genetic driver of multiple cancers that has challenged clinical anti-cancer therapeutics in the last 3 decades. Neo-antigens encoded by KRAS mutations have been identified as tumor-specific with high immunogenicity and can be used to deliver precision cancer vaccines to promote anti-tumor immune responses. KRAS mutation-based cancer vaccines have produced encouraging preclinical and clinical results. Cancer vaccines represent a promising approach to treat KRAS-driven cancers.Areas covered: In this review, we summarize the development and progress of vaccines targeting KRAS and evaluate their potential benefits and obstacles in the current landscape of therapy for KRAS-driven cancers.Expert opinion: KRAS mutation-based cancer vaccines can induce immunogenicity in patients with KRAS-driven cancers. However, the mechanisms of tumor suppression including cellular and molecular factors within the tumor microenvironment may limit vaccine efficacy. Combining KRAS-driven therapeutic cancer vaccines with other methods and adjuvants can circumvent immunosuppression and promote therapeutic successes.

A promising treatment option for refractory male primary choriocarcinoma: report of two cases.

Male primary choriocarcinoma is a rare and invasive malignant neoplasm for which traditional chemotherapy has limited efficacy. Pembrolizumab is a humanized monoclonal anti-programmed death-1 antibody that has antitumor activity in numerous malignancies. The diagnosis and treatment of two cases of advanced male primary choriocarcinoma were retrospectively analyzed and relevant literature was reviewed to discuss the prognosis and the efficacy of different treatments, including pembrolizumab. The first patient, who presented with cough and hemoptysis, was diagnosed with primary mediastinal choriocarcinoma. He initially responded to the first-line chemotherapy of etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine, but eventually developed brain metastases. The patient did not respond to the second-line chemotherapy comprising paclitaxel and cisplatin, and he died 6.5 months after diagnosis. The second patient experienced repeated episodes of abdominal pain and was diagnosed with primary neck choriocarcinoma. He received chemotherapy regimens similar to those of the first patient. However, imaging showed no significant changes and his clinical symptoms were not improved. Immunohistochemistry showed that the expression of programmed death ligand 1 on the tumor cells was 40%, and he was administered pembrolizumab combined with chemotherapy. He achieved complete response and was subsequently switched to pembrolizumab maintenance monotherapy. He is still alive without evidence of disease 36 months after diagnosis. To our knowledge, this is the first case of advanced male primary choriocarcinoma successfully treated with pembrolizumab combined with chemotherapy. Advanced male primary choriocarcinoma is highly aggressive and insensitive to chemotherapy. Pembrolizumab may provide a promising treatment option to improve patient outcomes.