Supramolecular coordination platinum metallacycle-based multilevel wound dressing for bacteria sensing and wound healing.

The exploitation of novel wound healing methods with real-time infection sensing and high spatiotemporal precision is highly important for human health. Pt-based metal-organic cycles/cages (MOCs) have been employed as multifunctional antibacterial agents due to their superior Pt-related therapeutic efficiency, various functional subunits and specific geometries. However, how to rationally apply these nanoscale MOCs on the macroscale with controllable therapeutic output is still challenging. Here, a centimeter-scale Pt MOC film was constructed via multistage assembly and subsequently coated on a N,N'-dimethylated dipyridinium thiazolo[5,4-d]thiazole (MPT)-stained silk fabric to form a smart wound dressing for bacterial sensing and wound healing. The MPT on silk fabric could be used to monitor wound infection in real-time through the bacteria-mediated reduction of MPT to its radical form via a color change. The MPT radical also exhibited an excellent photothermal effect under 660 nm light irradiation, which could not only be applied for photothermal therapy but also induce the disassembly of the Pt MOC film suprastructure. The highly ordered Pt MOC film suprastructure exhibited high biosafety, while it also showed improved antibacterial efficiency after thermally induced disassembly. In vitro and in vivo studies revealed that the combination of the Pt MOC film and MPT-stained silk can provide real-time information on wound infection for timely treatment through noninvasive techniques. This study paves the way for bacterial sensing and wound healing with centimeter-scale metal-organic materials.

Naringenin restricts the colonization and growth of Ralstonia solanacearum in tobacco mutant KCB-1.

Bacterial wilt severely jeopardizes plant growth and causes enormous economic loss in the production of many crops, including tobacco (Nicotiana tabacum). Here, we first demonstrated that the roots of bacterial wilt-resistant tobacco mutant KCB-1 can limit the growth and reproduction of Ralstonia solanacearum. Secondly, we demonstrated that KCB-1 specifically induced an upregulation of naringenin content in root metabolites and root secretions. Further experiments showed that naringenin can disrupt the structure of R. solanacearum, inhibit the growth and reproduction of R. solanacearum, and exert a controlling effect on bacterial wilt. Exogenous naringenin application activated the resistance response in tobacco by inducing the burst of reactive oxygen species and salicylic acid deposition, leading to transcriptional reprogramming in tobacco roots. Additionally, both external application of naringenin in CB-1 and overexpression of the Nicotiana tabacum chalcone isomerase (NtCHI) gene, which regulates naringenin biosynthesis, in CB-1 resulted in a higher complexity of their inter-root bacterial communities than in untreated CB-1. Further analysis showed that naringenin could be used as a marker for resistant tobacco. The present study provides a reference for analyzing the resistance mechanism of bacterial wilt-resistant tobacco and controlling tobacco bacterial wilt.

Chaotropic Effect-Induced Sol-Gel Transition and Radical Stabilization for Bacterially Sensitive Near-Infrared Photothermal Therapy.

Deep-seated bacterial infections (DBIs) are stubborn and deeply penetrate tissues. Eliminating deep-seated bacteria and promoting tissue regeneration remain great challenges. Here, a novel radical-containing hydrogel (SFT-B Gel) cross-linked by a chaotropic effect was designed for the sensing of DBIs and near-infrared photothermal therapy (NIR-II PTT). A silk fibroin solution stained with 4,4',4″-(1,3,5-triazine-2,4,6-triyl)tris(1-methylpyridin-1-ium) (TPT3+) was employed as the backbone, which could be cross-linked by a closo-dodecaborate cluster (B12H122-) through a chaotropic effect to form the SFT-B Gel. More interestingly, the SFT-B Gel exhibited the ability to sense DBIs, which could generate a TPT2+• radical with obvious color changes in the presence of bacteria. The radical-containing SFT-B Gel (SFT-B★ Gel) possessed strong NIR-II absorption and a remarkable photothermal effect, thus demonstrating excellent NIR-II PTT antibacterial activity for the treatment of DBIs. This work provides a new approach for the construction of intelligent hydrogels with unique properties using a chaotropic effect.

Perimenopausal and Menopausal Mammary Glands In A 4-Vinylcyclohexene Diepoxide Mouse Model.

As both perimenopausal and menopausal periods are recognized critical windows of susceptibility for breast carcinogenesis, development of a physiologically relevant model has been warranted. The traditional ovariectomy model causes instant removal of the entire hormonal repertoire produced by the ovary, which does not accurately approximate human natural menopause with gradual transition. Here, we characterized the mammary glands of 4-vinylcyclohexene diepoxide (VCD)-treated animals at different time points, revealing that the model can provide the mammary glands with both perimenopausal and menopausal states. The perimenopausal gland showed moderate regression in ductal structure with no responsiveness to external hormones, while the menopausal gland showed severe regression with hypersensitivity to hormones. Leveraging the findings on the VCD model, effects of a major endocrine disruptor (polybrominated diphenyl ethers, PBDEs) on the mammary gland were examined during and after menopausal transition, with the two exposure modes; low-dose, chronic (environmental) and high-dose, subacute (experimental). All conditions of PBDE exposure did not augment or compromise the macroscopic ductal reorganization resulting from menopausal transition and/or hormonal treatments. Single-cell RNA sequencing revealed that the experimental PBDE exposure during the post-menopausal period caused specific transcriptomic changes in the non-epithelial compartment such as Errfi1 upregulation in fibroblasts. The environmental PBDE exposure resulted in similar transcriptomic changes to a lesser extent. In summary, the VCD mouse model provides both perimenopausal and menopausal windows of susceptibility for the breast cancer research community. PBDEs, including all tested models, may affect the post-menopausal gland including impacts on the non-epithelial compartments.

New isolate of sweet potato virus 2 from Ipomoea nil: molecular characterization, codon usage bias, and phylogenetic analysis based on complete genome.

BACKGROUND: Viral diseases of sweet potatoes are causing severe crop losses worldwide. More than 30 viruses have been identified to infect sweet potatoes among which the sweet potato latent virus (SPLV), sweet potato mild speckling virus (SPMSV), sweet potato virus G (SPVG) and sweet potato virus 2 (SPV2) have been recognized as distinct species of the genus Potyvirus in the family Potyviridae. The sweet potato virus 2 (SPV2) is a primary pathogen affecting sweet potato crops. METHODS: In this study, we detected an SPV2 isolate (named SPV2-LN) in Ipomoea nil in China. The complete genomic sequence of SPV2-LN was obtained using sequencing of small RNAs, RT-PCR, and RACE amplification. The codon usage, phylogeny, recombination analysis and selective pressure analysis were assessed on the SPV2-LN genome. RESULTS: The complete genome of SPV2-LN consisted of 10,606 nt (GenBank No. OR842902), encoding 3425 amino acids. There were 28 codons in the SPV2-LN genome with a relative synonymous codon usage (RSCU) value greater than 1, of which 21 end in A/U. Among the 12 proteins of SPV2, P3 and P3N-PIPO exhibited the highest variability in their amino acid sequences, while P1 was the most conserved, with an amino acid sequence identity of 87-95.3%. The phylogenetic analysis showed that 21 SPV2 isolates were clustered into four groups, and SPV2-LN was clustered together with isolate yu-17-47 (MK778808) in group IV. Recombination analysis indicated no major recombination sites in SPV2-LN. Selective pressure analysis showed dN/dS of the 12 proteins of SPV2 were less than 1, indicating that all were undergoing negative selection, except for P1N-PISPO. CONCLUSION: This study identified a sweet potato virus, SPV2-LN, in Ipomoea nil. Sequence identities and genome analysis showed high similarity between our isolate and a Chinese isolate, yu-17-47, isolated from sweet potato. These results will provide a theoretical basis for understanding the genetic evolution and viral spread of SPV2.

Laboratory, epidemiological and clinical characteristics of pertussis in children and close contacts: a cross-sectional study.

PURPOSE: To investigate the epidemiological and clinical characteristics of pertussis in children and close contacts. METHODS: Nasopharyngeal swabs and blood samples of clinically suspected children with pertussis and their close contacts from 2018 to 2022 were collected for pathogen detection of Bordetella pertussis. Questionnaires were designed to investigate the basic information and infection status of pertussis children cases and their close contacts. Descriptive epidemiological analysis was performed on the results. RESULTS: 1229 confirmed children cases of pertussis were collected and infants < 1 year old were the most affected (77.7%). Etiological data were collected from 587 close contacts of 269 confirmed cases and the infection rate was high (24.4%). The positive detection rate of parents, especially mothers, was significantly higher than that of other groups (32.2% vs. 18.4%, P < 0.001); The rates of misdiagnosis or missed diagnosis in pertussis children (92.2%) and close contacts (99.8%) were very high, and the distribution of symptoms between pertussis children and their close contacts was different (χ2 = 535.328, P < 0.001); The vast majority of pertussis children (84.0%) were diagnosed with upper respiratory tract infection or trachea/bronchitis while 91.0% of close contacts did not seek medical attention (χ2 = 685.373, P < 0.001). CONCLUSION: Infants < 1 year old are at high risk in pertussis. Pertussis infection in close contacts of confirmed children is underestimated. Caregivers who are positive for pertussis but missed or misdiagnosed seriously may be a main source of pertussis infections in children. Adjusting the current pertussis immunization strategy in China is necessary.

Desmoplastic fibroma of the pediatric cranium with CTNNB1 mutation: case report and literature review.

PURPOSE: Desmoplastic fibroma (DF) is an uncommon intermediate bone tumor rarely involving the skull with unidentified pathogenesis. We report the first case of pediatric temporoparietal cranial desmoplastic fibroma (DF) with a CTNNB1 gene mutation and review the previous literature. CASE PRESENTATION: A 3-year-old boy had a firm, painless mass on the right temporoparietal region for 22 months. The cranial CT scan showed isolated osteolytic destruction in the outer plate and diploe of the right temporoparietal bone. Gross total resection of the lesion and cranioplasty were performed. After that, a growing epidural hematoma was observed so another operation was performed to remove the artificial titanium plate. Postoperative pathology indicated a DF diagnosis and molecular pathology suggested a missense mutation in exon 3 of the CTNNB1 gene (c.100G > A,p.Gly34Arg). CONCLUSION: Pediatric cranial DF is rare and easy to be misdiagnosed before operation. For cranial DF, lesion resection can be performed and perioperative management should be strengthened. Mutations in the CTNNB1 gene might be one of the molecular pathologic features of DF.

Prognostic analysis of surgical treatment for T3 glottic laryngeal cancer based on different tumor extension patterns.

BACKGROUND AND OBJECTIVES: To investigate the prognostic impact of different tumor invasion patterns in the surgical treatment of T3 glottic laryngeal cancer. METHODS: We conducted a retrospective analysis of clinical data of 91 patients with T3 glottic laryngeal cancer. RESULTS: We found that the posterior invasion being significantly associated with involvement of the lamina of cricoid cartilage (P < 0.001), arytenoid cartilage (P = 0.001), and subglottic (P = 0.001). There was no statistical difference in survival outcomes between the total laryngectomy (TL) group and the partial laryngectomy (PL) group, but in the PL group, tumors with anterior invasion were associated with a better 5-year DFS than tumors with posterior invasion (HR: 4.681, 95% CI: 1.337-16.393, P = 0.016), and subglottic involvement was associated with worse LRRFS (HR: 3.931, 95% CI: 1.054-14.658, P = 0.041). At the same time, we found that involvement of the lamina of cricoid cartilage was an independent risk factor for postoperative laryngeal stenosis in PL patients (HR: 11.67, 95% CI: 1.89-71.98, P = 0.008). CONCLUSION: Selectively performed PL can also achieve favorable oncological outcomes comparable to those of TL. Posterior invasion and subglottic involvement are independent prognostic factors for recurrence after PL in T3 glottic laryngeal cancer, and involvement of the lamina of cricoid cartilage is associated with postoperative laryngeal stenosis. The tumor invasion pattern of patients with laryngeal cancer should be further subdivided to allow for selection of a more individualized treatment plan.

First Report of Leaf Spot on Cucumis melo L. Caused by Arcopilus aureus in China.

Cucumis melo L. is an important fruit with widespread consumption and commercial value. However, an undescribed disease affecting Hami melon (Cucumis melo L. var. Luhoutian) plants has consistently emerged in the Qihe region of Dezhou, Shandong Province of China since 2021. The disease can occur in both seedling and mature stages of Hami melon plants, and in severely diseased areas, the incidence rate was seen as 40 to 80%. During the seedling stage, the initial symptom is the appearance of water-soaked spots on the leaves. As the disease progresses, the leaves develop necrotic spots, and severely affected plants may exhibit stem rot and decay. In the mature stage, the disease primarily affects the leaves, causing necrotic spots and chlorosis. Under conditions of high humidity, black mold can be observed in the affected areas. Small pieces of symptomatic leaves from six different infected plants were collected and surface-sterilized with 5% NaClO for 3 min and 75% alcohol for 30 s for pathogen isolation (Wang et al., 2020). After rinsing with sterile water and blotted on sterile filter paper, the tissues were established on potato dextrose agar (PDA) media and incubated at 28℃ for 3-4 days. Pure isolates showed up at PDA were obtained through single-spore isolation. Colonies of all 16 isolates obtained by single-spore isolation had similar morphological characteristics on the PDA medium, the mycelium of the isolate appears dense and yellowish-brown on the PDA medium, and also secretes a brownish-red pigment on PDA. Under the opticalmicroscope, the perithecia from PDA media are subglobose spherical in shape, 80-100 µm in diameter, brownish by reflected light, wholly and densely hairy. Terminal hairs are very dense, greyish by reflected light, olive brown to reddish brown by transmitted light, thick-walled, arcuate, circinate, or spirally coiled at the apex. The ascospores within the perithecia are elliptical or droplet-shaped, initially colorless hyaline but later becoming subhyaline slightly gray, with dimensions of 7-9 µm × 4-5 µm. The morphological characteristics of the isolates were consistent with the description of Arcopilus aureus (Wang et.al. 2016). The internal transcribed spacer (ITS) region and ß-tubulin genes of three randomly selected isolates were PCR amplified and sequenced using primers ITS4/ITS5 and Bt2a/Bt2b. The sequences of ITS and ß-tubulin genes were submitted to NCBI with GenBank Accession No. OR539527 and OR640972, respectively. Based on morphological features and phylogenetic analysis, we concluded that the isolates belonged to A. aureus. Pathogenicity tests were conducted by placing agar plugs-containing fungal mycelia and agar blocks (control) on leaves of Hami melon seedlings (n=12) grown at 28°C with 60% humidity in a greenhouse, the assay was repeated three times. Symptoms appeared on the pathogen-inoculated leaves seven days after inoculation, whereas the control treatment remained symptomless. The pathogens were reisolated from diseased leaves and identified as A. aureus based on morphological, and molecular phylogenetic analysis, while Koch'sostulate was used to confirm its life mode. To the best of our knowledge, this is the first report of leaf spot caused by A. aureus on Cucumis melo L. in China.

Ultrasound-electrochemistry assisted liquid-phase co-exfoliation of phosphorene decorated by Au-Ag bimetallic nanoparticles as nanozyme for smartphone-based portable sensing of 4-nitrophenol.

The stability of black phosphorene (BP) and its preparation and modification for developing and applying devices have become a hot topic in the interdisciplinary field. We propose ultrasound-electrochemistry co-assisted liquid-phase exfoliation as an eco-friendly one-step method to prepare gold-silver bimetallic nanoparticles (Au-AgNPs)-decorated BP nanozyme for smartphone-based portable sensing of 4-nitrophenol (4-NP) in different water sources. The structure, morphology, composition, and properties of Au-AgNPs-BP nanozyme are characterized by multiple instrumental analyses. Bimetallic salts are induced to efficiently occupy oxidative sites of BP to form highly stable Au-AgNPs-BP nanozyme and guarantee the integrity of the lamellar BP. The electrochemistry shortens the exfoliation time of the BP nanosheet and contributes to the loading efficiency of bimetallic nanoparticles on the BP nanosheet. Au-AgNPs-BP-modified screen-printed carbon electrode coupled with palm-sized smartphone-controlled wireless electrochemical analyzer as a portable wireless intelligent sensing platform was applied to the determination of 4-NP in a linear range of 0.6-10 µM with a limit of detection of 63 nM. It enables on-site determination of 4-NP content in lake water, river water, and irrigation ditch water. This work will provide a reference for an eco-friendly one-step preparation of bimetallic nanoparticle-decorated graphene-like materials as nanozymes and their smartphone-based portable sensing application outdoors.

Similarities in Structure and Function of UDP-Glycosyltransferase Homologs from Human and Plants.

The uridine diphosphate glycosyltransferase (UGT) superfamily plays a key role in the metabolism of xenobiotics and metabolic wastes, which is essential for detoxifying those species. Over the last several decades, a huge effort has been put into studying human and mammalian UGT homologs, but family members in other organisms have been explored much less. Potentially, other UGT homologs can have desirable substrate specificity and biological activities that can be harnessed for detoxification in various medical settings. In this review article, we take a plant UGT homology, UGT71G1, and compare its structural and biochemical properties with the human homologs. These comparisons suggest that even though mammalian and plant UGTs are functional in different environments, they may support similar biochemical activities based on their protein structure and function. The known biological functions of these homologs are discussed so as to provide insights into the use of UGT homologs from other organisms for addressing human diseases related to UGTs.

Discovering New Substrates of a UDP-Glycosyltransferase with a High-Throughput Method.

UDP-glycosyltransferases (UGTs) form a large enzyme family that is found in a wide range of organisms. These enzymes are known for accepting a wide variety of substrates, and they derivatize xenobiotics and metabolites for detoxification. However, most UGT homologs have not been well characterized, and their potential for biomedical and environmental applications is underexplored. In this work, we have used a fluorescent assay for screening substrates of a plant UGT homolog by monitoring the formation of UDP. We optimized the assay such that it could be used for high-throughput screening of substrates of the Medicago truncatula UGT enzyme, UGT71G1, and our results show that 34 of the 159 screened compound samples are potential substrates. With an LC-MS/MS method, we confirmed that three of these candidates indeed were glycosylated by UGT71G1, which includes bisphenol A (BPA) and 7-Ethyl-10-hydroxycamptothecin (SN-38); derivatization of these toxic compounds can lead to new environmental and medical applications. This work suggests that UGT homologs may recognize a substrate profile that is much broader than previously anticipated. Additionally, it demonstrates that this screening method provides a new means to study UDP-glycosyltransferases, facilitating the use of these enzymes to tackle a wide range of problems.

miRNAs contributing to the repair of tendon injury.

Tendon injury is one of the most common disorders of the musculoskeletal system, with a higher likelihood of occurrence in elderly individuals and athletes. In posthealing tendons, two undesirable consequences, tissue fibrosis and a reduction in mechanical properties, usually occur, resulting in an increased probability of rerupture or reinjury; thus, it is necessary to propose an appropriate treatment. Currently, most methods do not sufficiently modulate the tendon healing process and restore the function and structure of the injured tendon to those of a normal tendon, since there is still inadequate information about the effects of multiple cellular and other relevant signaling pathways on tendon healing and how the expression of their components is regulated. microRNAs are vital targets for promoting tendon repair and can modulate the expression of biological components in signaling pathways involved in various physiological and pathological responses. miRNAs are a type of noncoding ribonucleic acid essential for regulating processes such as cell proliferation, differentiation, migration and apoptosis; inflammatory responses; vascularization; fibrosis; and tissue repair. This article focuses on the biogenesis response of miRNAs while presenting their mechanisms in tendon healing with perspectives and suggestions.

Substrate Specificity of LACCASE8 Facilitates Polymerization of Caffeyl Alcohol for C-Lignin Biosynthesis in the Seed Coat of Cleome hassleriana.

Catechyl lignin (C-lignin) is a linear homopolymer of caffeyl alcohol found in the seed coats of diverse plant species. Its properties make it a natural source of carbon fibers and high-value chemicals, but the mechanism of in planta polymerization of caffeyl alcohol remains unclear. In the ornamental plant Cleome hassleriana, lignin biosynthesis in the seed coat switches from guaiacyl lignin to C-lignin at ∼12 d after pollination. Here we found that the transcript profile of the laccase gene ChLAC8 parallels the accumulation of C-lignin during seed coat development. Recombinant ChLAC8 oxidizes caffeyl and sinapyl alcohols, generating their corresponding dimers or trimers in vitro, but cannot oxidize coniferyl alcohol. We propose a basis for this substrate preference based on molecular modeling/docking experiments. Suppression of ChLAC8 expression led to significantly reduced C-lignin content in the seed coats of transgenic Cleome plants. Feeding of 13C-caffeyl alcohol to the Arabidopsis (Arabidopsis thaliana) caffeic acid o-methyltransferase mutant resulted in no incorporation of 13C into C-lignin, but expressing ChLAC8 in this genetic background led to appearance of C-lignin with >40% label incorporation. These results indicate that ChLAC8 is required for C-lignin polymerization and determines lignin composition when caffeyl alcohol is available.

Crystal Structures of the C-Glycosyltransferase UGT708C1 from Buckwheat Provide Insights into the Mechanism of C-Glycosylation.

C-Glycosyltransferases (CGTs) catalyze the formation of C-glycosidic bonds for the biosynthesis of C-glycosides, but the underlying mechanism is unclear. This process improves the solubility and bioavailability of specialized metabolites, which play important roles in plant growth and development and represent rich resources for drug discovery. Here, we performed functional and structural studies of the CGT UGT708C1 from buckwheat (Fagopyrum esculentum). Enzymatic analysis showed that UGT708C1 is capable of utilizing both UDP-galactose and UDP-glucose as sugar donors. Our structural studies of UGT708C1 complexed with UDP-glucose and UDP identified the key roles of Asp382, Gln383, Thr151, and Thr150 in recognizing the sugar moiety of the donor substrate and Phe130, Tyr102, and Phe198 in binding and stabilizing the acceptor. A systematic site-directed mutagenesis study confirmed the important roles of these residues. Further structural analysis combined with molecular dynamics simulations revealed that phloretin binds to the acceptor binding pocket in a bent state with a precise spatial disposition and complementarity. These findings provide insights into a catalytic mechanism for CGTs.

Electroactive poly(thionine) as imprinted polymer and reference probe simultaneously for ratiometric ion imprinted electrochemical Pb2+sensor.

In this work, an electrochemical sensor based on ion-imprinted polymer/Au nanoparticles/porous biochar (IIP/AuNPs/PBC) composite was proposed for the highly selective and sensitive detection of Pb2+. In this work, poly (thionine) (pTHI) served simultaneously as imprinted polymer and reference probe. It could not only realize the specific detection of Pb2+, but also provide an internal reference signal to eliminate the influence of human and environmental factors on the detection signal and further improve the stability of the sensor. In addition, the AuNPs/PBC composite with large specific surface area, excellent electron transport and electrocatalytic performance could effectively enhance the detection signal as a carrier material. At the same time, the AuNPs on the PBC surface would promote the formation of uniform and stable IIP through Au-S bonds. The synergistic effect between IIP, AuNPs/PBC and ratiometric signal mode gave the Pb2+sensor excellent performance, including a wide linear range (0.1-1000µg l-1), low detection limit (0.03µg l-1, S/N = 3), excellent selectivity and stability. All these results indicate that the proposed sensor could provide a meaningful reference for highly selective detection of heavy metal ions (HMIs).

Highly Selective Nitrite Hydrogenation to Ammonia over Iridium Nanoclusters: Competitive Adsorption Mechanism.

Wet denitrification is a promising approach to control nitrogen oxides (NOx) produced in fossil fuel combustion. Yet, the highly concentrated nitrite (NO2-) wastewater generated poses a major threat to the aqueous environment. Here, iridium nanoclusters (d = 1.63 nm) deposited on TiO2 were applied for NO2- reduction to ammonia (NRA), showing an exceptional NH4+ selectivity of 95% and a production rate of 20.51 mgN·L-1·h-1, which held significant potential for NO2- wastewater purification and ammonia resource recovery. Notably, an interesting non-first-order NO2- hydrogenation kinetics was observed, which was further confirmed to result from the competitive adsorption mechanism between H2 and NO2- over iridium. The NRA pathways on the Ir(111) surface were explored via density functional theory calculations with the NO2-* → NO* → HNO* → HNOH* → H2NOH* → NH2* → NH3* identified as the most energetically favorable pathway and the NO* → HNO* confirmed as the rate-determining step. In situ DRIFTS further experimentally verified the generation of HNO* intermediate during NO* hydrogenation on Ir(111). To verify NRA kinetics at varied NO2- concentrations or H2 pressures, a kinetic model was derived based on the Langmuir-Hinshelwood competitive adsorption mechanism. These findings provide mechanistic insights into the NRA pathways on Ir nanocatalysts, which will be beneficial for wet denitrification waste stream decontamination and valorization.

Phenome-wide association study and precision medicine of cardiovascular diseases in the post-COVID-19 era.

SARS-CoV-2 infection causes injuries of not only the lungs but also the heart and endothelial cells in vasculature of multiple organs, and induces systemic inflammation and immune over-reactions, which makes COVID-19 a disease phenome that simultaneously affects multiple systems. Cardiovascular diseases (CVD) are intrinsic risk and causative factors for severe COVID-19 comorbidities and death. The wide-spread infection and reinfection of SARS-CoV-2 variants and the long-COVID may become a new common threat to human health and propose unprecedented impact on the risk factors, pathophysiology, and pharmacology of many diseases including CVD for a long time. COVID-19 has highlighted the urgent demand for precision medicine which needs new knowledge network to innovate disease taxonomy for more precise diagnosis, therapy, and prevention of disease. A deeper understanding of CVD in the setting of COVID-19 phenome requires a paradigm shift from the current phenotypic study that focuses on the virus or individual symptoms to phenomics of COVID-19 that addresses the inter-connectedness of clinical phenotypes, i.e., clinical phenome. Here, we summarize the CVD manifestations in the full clinical spectrum of COVID-19, and the phenome-wide association study of CVD interrelated to COVID-19. We discuss the underlying biology for CVD in the COVID-19 phenome and the concept of precision medicine with new phenomic taxonomy that addresses the overall pathophysiological responses of the body to the SARS-CoV-2 infection. We also briefly discuss the unique taxonomy of disease as Zheng-hou patterns in traditional Chinese medicine, and their potential implications in precision medicine of CVD in the post-COVID-19 era.

Changes in type 2 innate lymphoid cells and serum cytokines in sublingual immunotherapy in pediatric patients with allergic rhinitis.

BACKGROUND: Type 2 innate lymphoid cells (ILC2) are upregulated in childhood allergic rhinitis (AR) and are associated with AR severity. This study aimed to investigate changes in the ILC2 milieu in pediatric patients with AR after sublingual immunotherapy (SLIT). METHODS: Forty- pediatric patients with AR received house dust mite (HDM) allergen extract for SLIT group and thirty pediatric patients received placebo in the study, respectively. The levels of ILC2, ILC2-related cytokines (IL-5/IL-13) and their transcription factors (GATA binding protein 3, retinoic acid-related orphan receptor α) in the circulation were assessed after 1- and 2-year SLIT. Moreover, peripheral blood mononuclear cells (PBMCs) in patients were prepared and stimulated by recombinant thymic stromal lymphopoietin, IL-25, and IL-33 after 2-year SLIT. Subsequently, the levels of ILC2, IL-5, and IL-13 were tested. RESULTS: The frequency of ILC2 and the levels of their transcription factors in the circulation were significantly decreased after SLIT in the SLIT group. The levels of ILC2-related cytokines in the SLIT group showed the same trend. The frequency of ILC2 was positively correlated with transcription factors and cytokines after SLIT. SLIT was observed to reduce the ability of HDM sensitization to generate the ILC2 milieu in PBMCs. CONCLUSIONS: Changes in the ILC2 milieu may be correlated with the curative effect and immune regulation function of SLIT. Our results suggested that the regulatory effect on ILC2 is part of the therapeutic mechanism of SLIT.

Pedicled thoracoacromial artery compound flaps for circumferential hypopharyngeal reconstruction.

BACKGROUND: Total laryngeal and hypopharyngeal resection remained to be the mainly treatment option for advanced hypopharyngeal cancer, which resulted in complicated reconstructive challenge for circumferential hypopharyngeal defect. The pedicled thoracoacromial artery compound flaps included Thoracoacromial artery perforator (TAAP) flap and pectoralis major myocutaneous (PMMC) flap. This study is to evaluate the clinical application of the pedicled thoracoacromial artery compound flaps for circumferential hypopharyngeal reconstruction. METHODS: From May 2021 to April 2022, four hypopharyngeal cancer patients with circumferential hypopharyngeal defects were reconstructed by the pedicled thoracoacromial artery compound flaps. All patients were males. Patient age ranged from 35 to 62 years (average, 50 years). The Shoulder function were evaluated by SPADI. The average follow-up was 10.25 months (range from 4 to 18 months). RESULTS: All of the pedicled thoracoacromial artery compound flaps in our study survived. The defect length between tongue base and cervical esophagus ranged from 8 to 10 cm after total laryngeal and hypopharyngeal resection. The TAAP flap size ranged from 6 × 7 cm to 7 × 10 cm, and the PMMC flap size ranged from 6 × 7 cm to 9 × 12 cm. The pedicle length of TAAP and PMMC flaps varied, respectively, from 5 to 8 cm (mean 6.5 cm) and 7 cm to 11 cm (mean 8.75 cm). The mean time of TAAP and PMMC flaps harvest was, respectively, 82 min and 39 min. All patients were able to resume soft diet in the fourth week of postoperation, but one patient was operated by gastrostomy in the second month of postoperation because of pharyngeal cavity stenosis, and the patient successfully resumed oral soft diet by endoscopic balloon dilation after postoperation radiotherapy. All patients have resumed oral feeding at last. There were mild dysfunction for our patients according to SPADI during the mid-long follow-up. CONCLUSIONS: The pedicled thoracoacromial artery compound flaps have stable blood supply and provide adequate muscle coverage for greater protection during radiotherapy, and the microsurgical skills have no requirement. Therefore, the compound flaps provide a good choice for the reconstruction of circumferential hypopharyngeal defect, especially in the aged or patients with comorbidities who are not able to tolerate prolonged surgery.