[Application scenario design and prospect of generative artificial intelligence (AI) in intelligent manufacturing and supply chain of traditional Chinese medicine].

Intelligent manufacturing technologies, including databases, mathematical modeling, and information systems have played a significant role in process control, production management, and supply chain management in traditional Chinese medicine(TCM) industry. However, their ability to process and utilize unstructured data, such as research and development reports, batch production records, quality inspection records, and supplier documents, is relatively weak. For text, images, language, and other unstructured data, generative artificial intelligence(AI) technology has shown strong potential for development in extracting information, extracting knowledge, semantic retrieval, and content generation. Generative AI is expected to provide a feasible set of tools for the utilization of unstructured data resources in the TCM industry. Based on years of research and industrial application experience in TCM intelligent manufacturing technology, this study reviewed the current situation of intelligent manufacturing in TCM and the utilization of unstructured data, analyzed the application value of generative AI in the TCM manufacturing process and supply chain, summarized four typical application scenarios, including intelligent pharmaceutical knowledge base/knowledge graph, intelligent on-the-job trai-ning, intelligent production quality control, and intelligent supply chain. Furthermore, this study also explained the data collection and processing, business process design, application potential, and value of each scenario based on industry demands. Finally, based on the integration of generative AI and TCM industrial models, the study proposed a preliminary concept of a smart industrial brain for TCM, aiming to provide a reference for the application of AI technology in the field of TCM manufacturing.

Unraveling the role of BMI and blood markers in the relationship between plant-based diets and osteoporosis: A prospective cohort study.

BACKGROUND: The potential adverse effects of plant-based diets on bone health have raised significant concern, while the prospective evidence is limited. This study aimed to evaluate the association between plant-based diet indexes and incident osteoporosis while exploring the underlying mechanisms involved in this relationship. METHODS: The analysis included 202,063 UK Biobank participants conducted between 2006 and 2022. Plant-based diet indexes (hPDI and uPDI) were calculated using the 24-h dietary questionnaire. Cox proportional risk regression and mediation analysis were used to explore the associations of plant-based diet indexes with osteoporosis, estimating the contribution of BMI and blood markers. RESULTS: We found the highest quintile for hPDI (HR = 1.16; 95% CI: 1.05 to 1.28) and uPDI (HR = 1.15; 95% CI: 1.05 to 1.26) were associated with an increased risk of osteoporosis. BMI was identified as an important mediator in the association between hPDI and osteoporosis, with mediation proportions of 46.17%. For blood markers, the mediating (suppressing) effects of C-reactive protein, alkaline phosphatase, and insulin-like growth factor-1 on the association between uPDI (hPDI) and osteoporosis were significant, ranging from 5.63%-16.87% (4.57%-6.22%). CONCLUSION: Adherence to a plant-based diet is associated with a higher risk of osteoporosis, with BMI and blood markers potentially contributing to this relationship. Notably, even a healthy plant-based diet necessitates attention to weight management to mitigate its impact on bone loss. These findings emphasize the importance of personalized dietary recommendations and lifestyle interventions to decrease the risk of osteoporosis.

Analysis of Ginkgo biloba Root Exudates and Inhibition of Soil Fungi by Flavonoids and Terpene Lactones.

Ginkgo biloba is abundant in secondary metabolites, including flavonoids and terpenoids. While the majority of research has focused on the role of these compounds in disease resistance, their specific contribution to pathogen defense has been rarely explored. In this study, we collected root exudates from hydroponically cultivated ginkgo seedlings and conducted a metabolomic analysis. We identified several primary metabolites mainly comprising amino acids and nucleotides, while secondary metabolites consisted of various compounds, including bioactive compounds such as flavonoids and terpenoids. Focusing on the secondary metabolites with relatively higher abundance in the exudates, we selected a mixture of flavonoids and terpenoids for in vitro inhibition experiments against two soil-borne fungal pathogens, Fusarium oxysporum f. sp. cucumerinum that causes cucumber wilt and Rhizoctonia solani AG-8 that causes wheat root rot. The results indicated that the growth rate of both fungus cells was significantly reduced with the increasing concentration of the flavonoid and terpenoid mixture extracted from ginkgo and was completely inhibited at a concentration of 5 mg/mL. Further experiments revealed that this mixture of flavonoids and terpenoids had a destructive effect on the cellular structure of both fungi, thereby reducing cell viability and achieving an antifungal effect. These findings provide a foundation for further research into the use of ginkgo extracts in biological control.

A tilapia skin-derived gelatin hydrogel combined with the adipose-derived stromal vascular fraction for full-thickness wound healing.

Biomaterials are widely used in regenerative medicine to repair full-thickness skin defect wounds. The adipose-derived stromal vascular fraction (SVF) shows pro-regenerative properties, however, the ex vivo biological activity of SVF is suppressed due to the lack of an external scaffold. Tilapia skin, as a sustained and recyclable biomaterial with low immunogenicity, was applied in the preparation of a hydrogel. The mixture of tilapia skin-derived gelatin and methacrylic anhydride as a scaffold facilitated the paracrine function of SVF and exerted a synergistic effect with SVF to promote wound healing. In this study, 30% (w/v) SVF was added to methacrylate-functionalized tilapia skin gelatin and subsequently exposed to UV irradiation to form a three-dimensional nano-scaffolding composite hydrogel (FG-SVF-3). The effects of paracrine growth factors, neovascularization, and collagen production on wound healing were extensively discussed. FG-SVF-3 displayed a pronounced wound healing ability via in vivo wound models. The FG-SVF-3 hydrogel enhanced the biocompatibility and the expression of EGF, bFGF, and VEGF. FG-SVF-3, as a promising wound dressing, exhibited superior ability to accelerate wound healing, skin regeneration, and wound closure.

A novel AVPR2 gene mutation in a Chinese pedigree with nephrogenic diabetes insipidus.

Nephrogenic diabetes insipidus (NDI) is a rare genetic disorder primarily associated with mutations in the arginine vasopressin receptor 2 (AVPR2) gene or the aquaporin 2 (AQP2) gene, resulting in impaired water reabsorption in the renal tubules. This report describes a case of a young male patient with NDI from China with a history of polydipsia and polyuria for over 15 years. Laboratory examinations of the proband indicated low urine-specific gravity and osmolality. Urologic ultrasound revealed severe bilateral hydronephrosis in both kidneys, bilateral dilatation of the ureters, roughness of the bladder wall, and the formation of muscle trabeculae. The diagnosis of diabetes insipidus was confirmed by water deprivation tests. The administration of posterior pituitary hormone did not alter urine-specific gravity, and osmolality remained at a low level (<300 mOsm/kg). Based on these findings, and the genetic tests of the proband and his parents were performed. A missense mutation (c.616 G>C) in exon 3 of the AVPR2 gene of the proband was found, caused by the substitution of amino acid valine to leucine at position 206 [p.Val206Leu], which was a hemizygous mutation and consistent with X-chromosome recessive inheritance. The administration of oral hydrochlorothiazide improves the symptoms of polydipsia and polyuria in the proband. This novel AVPR2 gene mutation may be the main cause of NDI in this family, which induces a functional defect in AVPR2, and leads to reduced tubular reabsorption of water.

Polyamine Anabolism Promotes Chemotherapy-Induced Breast Cancer Stem Cell Enrichment.

Breast cancer patients may initially benefit from cytotoxic chemotherapy but experience treatment resistance and relapse. Chemoresistant breast cancer stem cells (BCSCs) play a pivotal role in cancer recurrence and metastasis, however, identification and eradication of BCSC population in patients are challenging. Here, an mRNA-based BCSC signature is developed using machine learning strategy to evaluate cancer stemness in primary breast cancer patient samples. Using the BCSC signature, a critical role of polyamine anabolism in the regulation of chemotherapy-induced BCSC enrichment, is elucidated. Mechanistically, two key polyamine anabolic enzymes, ODC1 and SRM, are directly activated by transcription factor HIF-1 in response to chemotherapy. Genetic inhibition of HIF-1-controlled polyamine anabolism blocks chemotherapy-induced BCSC enrichment in vitro and in xenograft mice. A novel specific HIF-1 inhibitor britannin is identified through a natural compound library screening, and demonstrate that coadministration of britannin efficiently inhibits chemotherapy-induced HIF-1 transcriptional activity, ODC1 and SRM expression, polyamine levels, and BCSC enrichment in vitro and in xenograft and autochthonous mouse models. The findings demonstrate the key role of polyamine anabolism in BCSC regulation and provide a new strategy for breast cancer treatment.

Association of geriatric nutritional risk index with bone mineral density and osteoporosis in postmenopausal elderly women with T2DM.

BACKGROUND AND OBJECTIVES: To investigate the relationship between geriatric nutritional risk index (GNRI) and osteoporosis (OP) in postmenopausal elderly women with type 2 diabetes mellitus (T2DM). METHODS AND STUDY DESIGN: A total of 141 postmenopausal elderly women with T2DM was divided into OP and normal bone mineral density (BMD) groups, the differences in GRNI levels between the two groups were compared. According to the tertile levels of GRNI, T2DM were divided into three groups (T1, T2, T3 groups), and the differences in OP prevalence and levels of BMD among the three groups were compared. RESULTS: Among postmenopausal elderly women with T2DM, GNRI levels were lower in the OP group compared to the nor-mal BMD group [(103±5.46) vs. (105±5.46), p<0.05)]. With elevated GNRI levels, the BMD levels of femoral, total hip, total body, and lumbar vertebrae (L) were gradually increased, which were higher in the T3 group than in the T1 group (all p< 0.05). GNRI levels were positively correlated with the BMD levels of femoral, spine, total hip, total body, L1, L2, L3, L4, and L1-L4. GNRI was an independent influencing factor for the occurrence of OP (OR=0.887, 95%CI [0.795,0.988]). The ROC curve showed that the GNRI combined with serum ALP and P levels had a high predictive value for OP, with an area under the curve of 0.725 (p<0.01). CONCLUSIONS: In postmenopausal elderly women with T2DM, GNRI was independently and positively correlated with BMD levels. GNRI may be a predictor development of OP.

Shearing-induced formation of Au nanowires.

Shearing-induced nucleation is known in our daily lives, yet rarely discussed in nano-synthesis. Here, we demonstrate an unambiguous shearing-induced growth of Au nanowires. While in static solution Au would predominately deposit on pre-synthesized triangular nanoplates to form nano-bowls, the introduction of stirring or shaking gives rise to nanowires, where an initial nucleation could be inferred. Under specific growth conditions, CTAB is responsible for stabilizing the growth materials and the resulting oversaturation promotes shearing-induced nucleation. At the same time, all Au surfaces are passivated by ligands, so that the growth materials are diverted to relatively fresher sites. We propose that the different degrees of "focused growth" in active surface growth could be represented by watersheds of different slopes, so that the subtle differences between neighbouring sites would set course to opposite pathways, with some sites becoming ever more active and others ever more inhibited. The shearing-induced nuclei, with their initially ligand-deficient surface and higher accessibility to growth materials, win the dynamic inter-particle competition against other sites, explaining the dramatic diversion of growth materials from the seeds to the nanowires.

HIV-1 Molecular Networks and Pretreatment Drug Resistance at the Frontier of Yunnan Province, China.

The border areas of Yunnan Province in China are severely affected by human immunodeficiency virus (HIV). To investigate the risk of HIV transmission and assess the prevalence of pretreatment drug resistance (PDR) in the border area, blood samples were collected from individuals with newly reported HIV in 2021 in three border counties (Cangyuan, Gengma, and Zhenkang) in Yunnan Province. Among the 174 samples successfully genotyped, eight circulating recombinant forms (CRFs), two subtypes, and several unique recombinant forms (URFs) were identified. CRF08_BC (56.9%, 99/174), URFs (14.4%, 25/174), CRF01_AE (10.9%, 19/174), and CRF07_BC (8.0%, 14/174) were the main genotypes. CRF08_BC and URFs were detected more frequently in Chinese and Burmese individuals, respectively. CRF07_BC was found more frequently in men who have sex with men. The proportion of individuals detected in HIV-1 networks was only associated with case-reporting counties. When stratified by county, individuals aged ≤40 years in Cangyuan and ≥41 years in Gengma were more likely to be found in these networks. Furthermore, 93.8% (15/16) of the links in Cangyuan and 79.4% (50/63) of those in Gengma were located within their own counties. The prevalence of PDR to any antiretroviral drug, nucleoside reverse transcriptase inhibitors (NRTIs), and non-nucleoside reverse transcriptase inhibitors (NNRTIs) were 10% (17/170), 0.6% (1/170), and 9.4% (16/170), respectively. The most frequent resistance-associated mutations (RAMs) were V179D/VD/E/T (22.9%, 39/170) and E138A/G/K/R (13.5%, 23/170). In the molecular networks, six clusters shared common RAMs. HIV-1 genetics has become more diverse in border areas. HIV-1 molecular network analysis revealed the different characteristics of the HIV-1 epidemic in the border counties. The prevalence of PDR showed an upward trend, and the PDR to NNRTIs was close to the public response threshold. These findings provide information for the development of AIDS prevention and treatment strategies.

Effects of different HIIT protocols on exercise performance, metabolic adaptation, and fat loss in middle-aged and older adults with overweight.

Introduction: There is evidence that aging and obesity are associated with increased oxidative stress and chronic inflammation. High-intensity interval training (HIIT) may be superior to moderate-intensity continuous training (MICT) in anti-inflammatory and anti-obesity benefits. Therefore, the objective of this study is to determine which HIIT prescriptions will be more effective in reducing fat accumulation, inflammation, and improving metabolic adaptation and exercise performance in middle-aged and older overweight adults. Methods: Thirty-six middle-aged with overweight adults were divided into one of three groups: 1. L-HIIT group: the long-interval HIIT group (4 × 4 min Exercise/4 min Rest), 2. M-HIIT group: the medium-interval HIIT group (8 × 2 min Exercise/2 min Rest), 3. Control group: no exercise training intervention. All groups underwent the training stage for eight weeks (three sessions per week), followed by a detraining stage of four weeks in order to investigate the effects induced by different HIIT interventions on inflammation, metabolic adaptation, anti-fatigue and exercise performance, and fat loss Results: There was a significant physiological response in the change rate of heart rate (HR) after an acute L-HIIT session compared with an acute M-HIIT session (ΔHR: ↑49.66±16.09% vs ↑33.22±14.37%, p=0.02); furthermore, systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased significantly following a single L-HIIT session. After an eight-week training stage, the L-HIIT and M-HIIT groups exhibited a significant increase in aerobic capacity (ΔVO2peak), with values of +27.93±16.79% (p<0.001) and +18.39±8.12% (p<0.001), respectively, in comparison to the control group. Furthermore, in the L-HIIT group, the anaerobic power of relative mean power (RMP) exhibited a significant increase (p=0.019). However, following a four-week detraining stage, the adiponectin concentration remained 1.78 times higher in the L-HIIT group than in the control group (p=0.033). The results of blood sugar, blood lipids, body composition, and inflammatory markers did not indicate any improved it did not indicate any improvements from the two different HIIT protocols. Conclusions: The results indicate that an eight-week L-HIIT or M-HIIT intervention (three sessions per week, 32 minutes per session) may be an effective approach for improving aerobic capacity. It can be posited that L-HIIT may be a more advantageous mode than M-HIIT for enhancing anaerobic power, adipokine levels, and improving blood pressure in an aged and overweight population due to the induced physiological responses.

Research on the Human Motion Recognition Method Based on Wearable.

The accurate analysis of human dynamic behavior is very important for overcoming the limitations of movement diversity and behavioral adaptability. In this paper, a wearable device-based human dynamic behavior recognition method is proposed. The method collects acceleration and angular velocity data through a six-axis sensor to identify information containing specific behavior characteristics in a time series. A human movement data acquisition platform, the DMP attitude solution algorithm, and the threshold algorithm are used for processing. In this experiment, ten volunteers wore wearable sensors on their bilateral forearms, upper arms, thighs, calves, and waist, and movement data for standing, walking, and jumping were collected in school corridors and laboratory environments to verify the effectiveness of this wearable human movement recognition method. The results show that the recognition accuracy for standing, walking, and jumping reaches 98.33%, 96.67%, and 94.60%, respectively, and the average recognition rate is 96.53%. Compared with similar methods, this method not only improves the recognition accuracy but also simplifies the recognition algorithm and effectively saves computing resources. This research is expected to provide a new perspective for the recognition of human dynamic behavior and promote the wider application of wearable technology in the field of daily living assistance and health management.

A highly sensitive and colorimetric fluorescent probe for visualizing hydroxylamine in immune cells.

BACKGROUND: Hydroxylamine (HA) is vital industrial raw material and pharmaceutical intermediate. In addition, HA is an important cellular metabolite, which is intermediate in the formation of nitric oxide and nitroxide. However, excessive amounts of HA are toxic to both animals and plants. Conventional methods for the detection of HA are cumbersome and complicated. The detection of HA with fluorescent probes is convenient and sensitive. There are few probes available for the detection of hydroxylamine. Therefore, a fluorescent probe for the sensitive and selective detection of HA was developed in this work. RESULTS: A coumarin derivative SWJT-22 was synthesized as a colorimetric fluorescent probe to detect hydroxylamine (HA), with high sensitivity and selectivity. The detection limit of the probe to HA was 0.15 µM, which was lower than most probes of HA. Upon the addition of HA to aqueous solution containing SWJT-22, the color of the solution changed from orange to yellow, and the fluorescence color also changed from orange to green. The reaction mechanism of SWJT-22 to HA was confirmed by 1H NMR titrations, mass spectrometry and round bottom flask experiments. Moreover, SWJT-22 had been fabricated into portable test strips for the detection of HA. SWJT-22 had been successfully used in cellular imaging and could detect both endogenous and exogenous HA in HeLa cells and RAW 264.7 cells. SIGNIFICANCE: Due to the physiological role of hydroxylamine in organisms, it is crucial to detect hydroxylamine selectively and sensitively. This work provided a convenient tool for the detection of hydroxylamine, not only to detect endogenous and exogenous HA in cells, but also made into portable test strips. The HA fluorescent probe SWJT-22 is expected to promote the study of HA in physiological processes.

Development of magnesium hydroxide-doped nanofibrous spheres for repairing infected skin wounds.

The healing of skin wounds is a continuous and coordinated process, typically accompanied by microbial colonization and growth. This may result in wound infection and subsequent delay in wound healing. Therefore, it is of particular importance to inhibit the growth of microorganisms in the wound environment. In this study, magnesium hydroxide-doped polycaprolactone (PCL/MH) nanofibrous spheres were fabricated by electrospinning and electrospray techniques to investigate their effects on infected wound healing. The prepared PCL/MH nanofibrous spheres had good porous structure and biocompatibility, providing a favorable environment for the delivery and proliferation of adipose stem cells. The incorporation of MH significantly enhanced the antimicrobial properties of the spheres, in particular, the inhibition of the growth of S. aureus and E. coli. We showed that such PCL/MH nanofibrous spheres had good antimicrobial properties and effectively promoted the regeneration of infected wound tissues, which provided a new idea for the clinical treatment of infected wounds.

Recommendations for managing adult acne and adolescent acne based on an epidemiological study conducted in China.

There are numerous differences between adult acne and adolescent acne in terms of causes, distribution, and characteristics of skin lesions, as well as treatment. This paper aims to summarize the differences between adult and adolescent acne in China, in order to propose more suitable ways to improve their quality of life. We collected basic information, acne-related information, acne-affecting factors, quality of life scores and treatment-related information of acne patients. A total of 552 questionnaires were collected. Adult acne is typically predominant on the cheeks, similar to adolescent acne, with a relatively lower incidence in other areas, apart from the jawline. Pigmentation and depressed scars are present in nearly half of acne patients, while hypertrophic scars are less frequently observed. Teenagers often have a higher consumption of dairy products, sugary drinks, and high-sugar and high-fat foods. Eczema is more common in adult acne. Additionally, more adults than teenagers experience stress and poor quality of life related to acne. Adolescents are more likely to seek treatment online and on social media. Clinicians must thoroughly evaluate diverse risk factors and formulate personalized acne management strategies for patients with different types of acne.

How Do Butterflies Use Silk to Attach their Pupae to Trees?

Butterflies constitute approximately 10% of lepidopteran insects, and along with silkworms, they can produce silk; however, this feature is often ignored. In the present study, we observed two primary methods used by butterflies to hang pupae on trees using silk: pupa adheraena (Danaus chrysippus) and pupa contigua (Papilio polytes). Anchoring the abdominal ends of pupae with a silk pad was the most common method used in both cases, whereas wrapping silk around the body using a silk girdle was a method unique to pupa contigua. The connection between the cremaster and silk pad was observed to be similar to that between the hook and loop of a Velcro fastener, except that the cremaster hook is anchor-shaped rather than being a single hook. Such a connection will remain secure, ensuring the safety of the pupae during exposure to wind and rain. Through determining the mechanical properties of silk, the performance of butterfly silk was found to be weaker than that of silkworm silk. Therefore, the P. polytes silk girdle adopts the strategy of merging a dozen silk threads to improve its strength and toughness, thereby making it difficult to break. In addition, we explained how the protein sequence and structure of butterfly silk impact its performance. In conclusion, we discovered that butterfly pupae develop unique body features to establish secure bonds with silk. This enables them to effectively undergo metamorphosis and endure harsh weather conditions and surroundings.

SMARCA4 mutation induces tumor cell-intrinsic defects in enhancer landscape and resistance to immunotherapy.

Cancer genomic studies have identified frequent alterations in components of the SWI/SNF (SWItch/Sucrose Non- Fermenting) chromatin remodeling complex including SMARCA4 and ARID1A . Importantly, clinical reports indicate that SMARCA4 -mutant lung cancers respond poorly to immunotherapy and have dismal prognosis. However, the mechanistic basis of immunotherapy resistance is unknown. Here, we corroborated the clinical findings by using immune-humanized, syngeneic, and genetically engineered mouse models of lung cancer harboring SMARCA4 deficiency. Specifically, we show that SMARCA4 loss caused decreased response to anti-PD1 immunotherapy associated with significantly reduced infiltration of dendritic cells (DCs) and CD4+ T cells into the tumor microenvironment (TME). Mechanistically, we show that SMARCA4 loss in tumor cells led to profound downregulation of STING, IL1ß and other components of the innate immune system as well as inflammatory cytokines that are required for efficient recruitment and activity of immune cells. We establish that this deregulation of gene expression is caused by cancer cell-intrinsic reprogramming of the enhancer landscape with marked loss of chromatin accessibility at enhancers of genes involved in innate immune response such as STING, IL1ß, type I IFN and inflammatory cytokines. Interestingly, we observed that transcription factor NF-κB binding motif was highly enriched in enhancers that lose accessibility upon SMARCA4 deficiency. Finally, we confirmed that SMARCA4 and NF-κB co-occupy the same genomic loci on enhancers associated with STING and IL1ß, indicating a functional interplay between SMARCA4 and NF-κB. Taken together, our findings provide the mechanistic basis for the poor response of SMARCA4 -mutant tumors to anti-PD1 immunotherapy and establish a functional link between SMARCA4 and NF-κB on innate immune and inflammatory gene expression regulation.

An AIE-active tetra-aryl imidazole-derived chemodosimeter for turn-on recognition of hydrazine and its bioimaging in living cells.

A new chemodosimeter SWJT-31 with an aggregation-induced emission (AIE) effect was designed and constructed. Upon increasing the water fraction in the solution, it exhibited typical AIE, which showed bright red fluorescence at 610 nm. SWJT-31 could sensitively and specifically recognize hydrazine by the TICT effect with an LOD of 33.8 nM, which was much lower than the standard of the USEPA. A portable test strip prepared using SWJT-31 was also developed for the visual detection of hydrazine. Eventually, it was successfully used for the detection of hydrazine in water samples and HeLa cells.

Functions, accumulation, and biosynthesis of important secondary metabolites in the fig tree (Ficus carica).

Ficus carica is an economically important horticultural plant. Due to its abundant secondary metabolites, F. carica has gained interest for its applications in medicine and as a nutritional supplement. Both external and internal factors affect the accumulation of secondary metabolites in F. carica. The assembly of the F. carica genome has facilitated functional analysis of key genes and transcription factors associated with the biosynthesis of secondary metabolites, particularly anthocyanin. In this review, we summarize the various types and functions of secondary metabolites, with a particular focus on flavonoids, coumarins, and terpenes. We also explore the factors influencing their biosynthesis and accumulation, including varieties, tissue, environmental factors (e.g., light), stresses (e.g., high temperature, low temperature, drought, nutrient deficiencies, salinity), hormonal treatments, and developmental factors. Furthermore, we discuss the involvement of structural genes and transcription factors in the biosynthesis of secondary metabolites, specifically anthocyanin and furanocoumarins, knowledge of which will promote the breeding and genetic engineering of novel F. carica varieties.

Air pollutants, seasonal influenza, and acute otitis media in children: a population-based analysis using 22-year hospitalization data.

BACKGROUND: Acute otitis media (AOM) is a prevalent childhood acute illness, with 13.6 million pediatric office visits annually, often stemming from upper respiratory tract infections (URI) and affected by environmental factors like air pollution and cold seasons. METHODS: Herein, we made use of territory-wide hospitalization data to investigate the relationships between meteorological factors, air pollutants, influenza infection, and AOM for children observed from 1998 to 2019 in Hong Kong. Quasi-Poisson generalized additive model, combined with a distributed-lag non-linear model, was employed to examine the relationship between weekly AOM admissions in children and weekly influenza-like illness-positive (ILI +) rates, as well as air pollutants (i.e., oxidant gases, sulfur dioxide, and fine particulate matter), while accounting for meteorological variations. RESULTS: There were 21,224 hospital admissions due to AOM for children aged ≤ 15 years throughout a 22-year period. The cumulative adjusted relative risks (ARR) of AOM were 1.15 (95% CI, 1.04-1.28) and 1.07 (95% CI, 0.97-1.18) at the 95th percentile concentration of oxidant gases (65.9 ppm) and fine particulate matter (62.2 µg/m3) respectively, with reference set to their medians of concentration. The ARRs exhibited a monotone increasing trend for all-type and type-specific ILI + rates. Setting the reference to zero, the cumulative ARRs of AOM rose to 1.42 (95% CI, 1.29-1.56) at the 95th percentile of ILI + Total rate, and to 1.07 (95% CI, 1.01-1.14), 1.19 (95% CI, 1.11-1.27), and 1.22 (95% CI, 1.13-1.32) for ILI + A/H1N1, A/H3N2, and B, respectively. CONCLUSIONS: Our findings suggested that policy on air pollution control and influenza vaccination for children need to be implemented, which might have significant implications for preventing AOM in children.

Chemerin attracts neutrophil reverse migration by interacting with C-C motif chemokine receptor-like 2.

Neutrophil reverse migration (rM) is a recently identified phenomenon in which neutrophils migrate away from the inflammatory site back into the vasculature following initial infiltration, which involved in the resolution of loci inflammatory response or dissemination of inflammation. Present study was aimed to explore the mechanisms in neutrophil rM. By scRNA-seq on the white blood cells in acute lung injury model, we found rM-ed neutrophils exhibited increased gene expression of C-C motif chemokine receptor-like 2 (Ccrl2), an atypical chemokine receptor. Furthermore, an air pouch model was established to directly track rM-ed neutrophils in vivo. Air pouches were generated by 3 ml filtered sterile air injected subcutaneously for 3 days, and then LPS (2 mg/kg) was injected into the pouches to mimic the inflammatory state. For the rM-ed neutrophil tracking system, cell tracker CMFDA were injected into the air pouch to stain the inflammatory loci cells, and after 6 h, stained cells in blood were regarded as the rM-ed neutrophil. Based on this tracking system, we confirmed that rM-ed neutrophils showed increased CCRL2. We also found that the concentrations of the CCRL2 ligand chemerin in plasma was increased in the late stage. Neutralizing chemerin decreased the rM-ed neutrophil ratio in the blood. These results suggest that circulating chemerin attracts neutrophils to leave inflammatory sites by interacting with CCRL2, which might involve in the dissemination of inflammation.