Dynamic processes of fate decision in inducible bistable systems.

The process of biological fate decision regulated by gene regulatory networks (GRNs) involves numerous complex dynamical interactions among many components. Mathematical modeling typically employed ordinary differential equations (ODEs) and steady-state analysis, which has yielded valuable quantitative insights. However, stable states predicted by theoretical models often fail to capture transient or metastable phenomena that occur during most observation periods in experimental or real biological systems. We attribute this discrepancy to the omission of dynamic processes of various complex interactions. Here, we demonstrate the influence of delays in gene regulatory steps and the time scales of the external induction on the dynamic processes of the fate decision in inducible bistable systems. We propose that steady-state parameters determine the landscape of fate decision. However, during the dynamic evolution along the landscape, the unequal delays of biochemical interactions as well as time scale of external induction cause deviations in the differentiation trajectories, leading to the formation of new transient distributions that persist long-term. Our findings emphasize the importance of considering dynamic processes in fate decision, instead of relying solely on steady-state analysis. We provide insights into the interpretation of experimental phenomena, and offer valuable guidance for future efforts in dynamical modeling and synthetic biology design.

Quantitative Characterization of Gene Regulatory Circuits Associated With Fungal Secondary Metabolism to Discover Novel Natural Products.

Microbial genetic circuits are vital for regulating gene expression and synthesizing bioactive compounds. However, assessing their strength and timing, especially in multicellular fungi, remains challenging. Here, an advanced microfluidic platform is combined with a mathematical model enabling precise characterization of fungal gene regulatory circuits (GRCs) at the single-cell level. Utilizing this platform, the expression intensity and timing of 30 transcription factor-promoter combinations derived from two representative fungal GRCs, using the model fungus Aspergillus nidulans are determined. As a proof of concept, the selected GRC combination is utilized to successfully refactor the biosynthetic pathways of bioactive molecules, precisely control their production, and activate the expression of the silenced biosynthetic gene clusters (BGCs). This study provides insights into microbial gene regulation and highlights the potential of platform in fungal synthetic biology applications and the discovery of novel natural products.

Efficacy and safety of drugs for psoriasis patients with mental disorders: A systematic review.

BACKGROUND: The emergence of biological agents and small molecule drugs has revolutionized the treatment landscape for psoriasis, yet there remains a lack of systematic reviews elucidating the efficacy and safety of drugs for patients with psoriasis and mental disorders (MDs). The aim was to systemically evaluate the efficacy and safety of FDA-approved psoriasis drugs on MD symptoms and MD drugs on psoriasis symptoms. METHODS: We conducted comprehensive literature searches of the PubMed, Embase, and Cochrane Library from inception to March 24, 2024, identifying 116 relevant studies for inclusion. RESULTS: Our review encompasses 62 clinical trials and 54 case reports/series. Analyses of clinical trials revealed a positive impact of psoriasis drugs on MD, with notable exceptions including lithium and benzodiazepine receptor agonists, which exhibited adverse effects on psoriasis. Furthermore, analysis of case reports/series highlighted the efficacy of drugs such as apremilast, etanercept, infliximab, and secukinumab in ameliorating MD symptoms, contrasting with detrimental effects observed with methotrexate (MTX), cyclosporine, adalimumab, and secukinumab. Notably, tumor necrosis factor alpha (TNF-α) inhibitors and interleukin inhibitors demonstrated superior efficacy compared to conventional treatments. In the anxiety group, secukinumab showed the largest effective size as assessed by the Hospital Anxiety and Depression Scale - Anxiety (HADS-A) index; In the depression group, ixekizumab showed the largest effective size assessed by the 16-item Quick Inventory of Depressive Symptomology - Self-Report (QIDS-SR16) index. LIMITATIONS: The extracted data cannot be meta-analyzed, as the measurement scale is not uniform. CONCLUSIONS: This systematic review provides robust evidence regarding treatment options for individuals with psoriasis and MD, emphasizing the potential benefits of specific drugs in managing both conditions concurrently.

Laboratory diagnosis and treatment of Mycoplasma pneumoniae infection in children: a review.

Mycoplasma pneumoniae (MP) is the cause of Mycoplasma pneumoniae pneumonia (MPP) in children and adolescents, with the clinical manifestations highlighted by intermittent irritating cough, accompanied by headache, fever and muscle pain. This paper aimed to study the research status and focal points in MP infection, especially the common laboratory diagnostic methods and clinical treatment of Mycoplasma pneumoniae. Laboratory diagnostic methods include molecular assay, serological antibody detection, rapid antigen detection and isolation and culture. Polymerase chain reaction (PCR) is the gold standard with high sensitivity and specificity. The serological antibody can detect various immune antibodies qualitatively or quantitatively in serum. Rapid antigen can be detected faster, with no equipment environment requirements, which can be used for the early diagnosis of MP infection. While the culture growth cycle is long and insensitive, not recommended for routine diagnosis. Macrolides were the preferred drug for children with MPP, while the drug resistance rate was rising in China. Tetracycline can be substituted but was not recommended for children under 8 years of age, quinolone drugs are not necessary, severe MPP can be combined with glucocorticoids, involving the nervous or immune system can choose gamma globulin. Other treatments for MPP including symptomatic treatment which can alleviate symptoms, improve lung function and improve prognosis. A safe and effective vaccine needed to be developed which can provide protective immunity to children and will reduce the incidence of MPP.

Mechanical stress-induced autophagy is cytoskeleton dependent.

The cytoskeleton is essential for mechanical signal transduction and autophagy. However, few studies have directly demonstrated the contribution of the cytoskeleton to mechanical stress-induced autophagy. We explored the role of the cytoskeleton in response to compressive force-induced autophagy in human cell lines. Inhibition and activation of cytoskeletal polymerization using small chemical molecules revealed that cytoskeletal microfilaments are required for changes in the number of autophagosomes, whereas microtubules play an auxiliary role in mechanical stress-induced autophagy. The intrinsic mechanical properties and special intracellular distribution of microfilaments may account for a large proportion of compression-induced autophagy. Our experimental data support that microfilaments are core components of mechanotransduction signals.

Wogonin ameliorates the proliferation, inflammatory response, and pyroptosis in keratinocytes via NOD-like receptor family pyrin domain containing 3/Caspase-1/Gasdermin-D pathway.

BACKGROUND: Psoriasis refers to a highly prevalent and immunologically mediated dermatosis with considerable deterioration in life quality. Wogonin, a sort of flavonoid, has been mentioned to elicit protective activities in skin diseases. However, whether Wogonin is implicated in the treatment of psoriasis and its specific mechanisms are not fully understood. AIM: The present work attempted to elaborate the role of Wogonin during the process of psoriasis and to concentrate on the associated action mechanism. METHODS: Cell counting kit-8 (CCK-8) method was initially applied to assay the viability of human keratinocyte HaCaT cells treated by varying concentrations of Wogonin. To mimic psoriasis in vitro, HaCaT cells were exposed to M5 cytokines. CCK-8 and 5-Ethynyl-2'-deoxyuridine  assays were adopted for the measurement of cell proliferation. Inflammatory levels were examined with enzyme-linked immunosorbent assay. Immunofluorescence staining tested nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) and Caspase-1 expressions. Western blot examined the protein expressions of proliferation-, inflammation-, pyroptosis-associated factors, and NLRP3. RESULTS: Wogonin treatment antagonized the proliferation, inflammatory response, and NLRP3/caspase-1/Gasdermin-D (GSDMD)-mediated pyroptosis in M5-challenged HaCaT cells. Besides, NLRP3 elevation partially abrogated the effects of Wogonin on M5-induced proliferation, inflammatory response, and NLRP3/caspase-1/GSDMD-mediated pyroptosis in HaCaT cells. CONCLUSION: In a word, Wogonin might exert anti-proliferation, anti-inflammatory and anti-pyroptosis activities in M5-induced cell model of psoriasis and the blockade of NLRP3/Caspase-1/GSDMD pathway might be recognized as a potential mechanism underlying the protective mechanism of Wogonin in psoriasis, suggesting Wogonin as a prospective anti-psoriasis drug.

Vagus Nerve and Gut-Brain Communication.

The vagus nerve, as an important component of the gut-brain axis, plays a crucial role in the communication between the gut and brain. It influences food intake, fat metabolism, and emotion by regulating the gut-brain axis, which is closely associated with the development of gastrointestinal, psychiatric, and metabolism-related disorders. In recent years, significant progress has been made in understanding the vagus-mediated regulatory pathway, highlighting its profound implications in the development of many diseases. Here, we summarize the latest advancements in vagus-mediated gut-brain pathways and the novel interventions targeting the vagus nerve. This will provide valuable insights for future research on treatment of obesity and gastrointestinal and depressive disorders based on vagus nerve stimulation.

Vitamin D Binding Protein: A Potential Factor in Geriatric COVID-19 Acute Lung Injury.

Background: Previous research indicated that vitamin D binding protein (VDBP) is an independent multifunctional protein that plays a vital role in acute inflammatory and tissue damage. However, its role in acute lung injury (ALI) due to coronavirus disease 2019 (COVID-19) is unclear, and studies are lacking. This study intends to investigate the difference in serum VDBP levels in COVID-19 patients with ALI or without ALI and further explore the role of VDBP in the inflammatory response of ALI through cellular models. Methods: The serum was collected from COVID-19 patients, and the concentration of serum VDBP was detected. Construct a VDBP gene-silencing plasmid and transfect it into human alveolar epithelial A549 cells. After 72 hours of lipopolysaccharide (LPS) intervention, The inflammatory factors interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) were detected, and cell counting kit-8 (CCK-8) assay was used to detect cell viability. Flow cytometry was used to detect cell apoptosis. Results: The serum concentration of VDBP was significantly higher in COVID-19 with ALI (P < 0.05). Correlation analysis indicated serum VDBP positively correlated with leukocyte (r=0.329, P = 0.002), c-reaction protein (r = 0.470, P < 0.001), serum amyloid A (r = 0.900, P < 0.001), procalcitonin (r = 0.670, P < 0.001), and interleukin 6 (r = 0.452, P < 0.001). Simultaneously, the logistic regression analysis showed that increased serum VDBP was an independent risk factor for ALI in COVID-19 patients (OR 1.003 95% CI 1.001-1.006, P = 0.002). In human alveolar epithelial A549 cells, after LPS intervention, the inflammatory factor IL-1ß and TNF-A significantly reduced in the VDBP gene silencing group compared to the negative control (NC) group (P < 0.05). The cell viability of the VDBP gene silencing group was significantly increased compared to the NC group, and the cell apoptosis rate was significantly reduced (P < 0.05). Conclusion: In COVID-19 patients, acute lung injury may lead to increased serum concentration of VDBP. VDBP plays a vital role in promoting inflammatory response and apoptosis of bronchial epithelial cells.

Effect of duloxetine on changes in serum proinflammatory cytokine levels in patients with major depressive disorder.

OBJECTIVE: Accumulating evidence supports the idea that inflammation may contribute to the pathophysiology of major depressive disorder (MDD). Duloxetine, a serotonin-norepinephrine reuptake inhibitor, exhibits anti-inflammatory effects both in vitro and in vivo. In this study, we investigated the impact of duloxetine on changes in serum proinflammatory cytokine levels among individuals diagnosed with MDD. METHODS: A cohort of 23 drug-naïve individuals diagnosed with MDD and 23 healthy controls were included in this study. The severity of depressive symptoms was evaluated using the 24-item Hamilton Depression Scale (HAMD-24). A panel of 7 proinflammatory cytokines, including interleukin-1ß (IL-1ß), IL-2, IL-6, IL-8, IL-12, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ), were quantified using multiplex Luminex assays. The levels of serum cytokines in healthy controls and patients with MDD were compared at baseline. All patients received duloxetine at a dosage range of 40-60 mg/day for a duration of 4 weeks. The HAMD-24 scores and serum cytokine levels were compared before and after duloxetine treatment. RESULTS: Compared with healthy controls, patients with MDD had significantly greater levels of IL-2, IL-6, IL-8, IL-12, TNF-α, and IFN-γ (P < 0.05). Moreover, there was a significant decrease in HAMD-24 scores observed pre- and post-treatment (t = 13.161, P < 0.001). Furthermore, after 4 weeks of treatment, the serum levels of IL-8 (t = 3.605, P = 0.002), IL-12 (t = 2.559, P = 0.018), and IFN-γ (t = 3.567, P = 0.002) decreased significantly. However, there were no significant differences in other cytokines, including IL-1ß, IL-2, IL-6, and TNF-α, before and after treatment (P > 0.05). CONCLUSIONS: These findings present compelling evidence, potentially for the first time, indicating that duloxetine treatment may effectively reduce the serum concentrations of IL-8, IL-12, and IFN-γ in individuals diagnosed with MDD. However, the precise mechanisms underlying this effect remain unclear and warrant further investigation.

The relationship between comprehensive geriatric assessment on the pneumonia prognosis of older adults: a cross-sectional study.

BACKGROUND: The mortality of pneumonia in older adults surpasses that of other populations, especially with the prevalence of coronavirus disease 2019 (COVID-19). Under the influence of multiple factors, a series of geriatric syndromes brought on by age is one of the main reasons for the poor prognosis of pneumonia. This study attempts to analyze the impact of geriatric syndrome on the prognosis of pneumonia. METHODS: This is a prospective cross-sectional study. Patients over 65 years old with COVID-19 and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-negative community-acquired pneumonia (SN-CAP) were included in the research. General characteristics, laboratory tests, length of stay (LOS), and comprehensive geriatric assessment (CGA) were collected. Multivariate regression analysis to determine the independent predictors of the severity, mortality, and LOS of COVID-19. At the same time, the enrolled subjects were divided into three categories by clustering analysis of 10 CGA indicators, and their clinical characteristics and prognoses were analyzed. RESULTS: A total of 792 subjects were included in the study, including 204 subjects of SN-CAP (25.8%) and 588 subjects (74.2%) of COVID-19. There was no significant difference between non-severe COVID-19 and SN-CAP regarding mortality, LOS, and CGA (P > 0.05), while severe COVID-19 is significantly higher than both (P < 0.05). The Barthel Index used to assess the activities of daily living was an independent risk factor for the severity and mortality of COVID-19 and linearly correlated with the LOS (P < 0.05). The cluster analysis based on the CGA indicators divided the geriatric pneumonia patients into three groups: Cluster 1 (n = 276), named low ability group, with the worst CGA, laboratory tests, severity, mortality, and LOS; Cluster 3 (n = 228), called high ability group with the best above indicators; Cluster 2 (n = 288), named medium ability group, falls between the two. CONCLUSION: The Barthel Index indicates that decreased activities of daily living are an independent risk factor for the severity, mortality, and LOS of geriatric COVID-19. Geriatric syndrome can help judge the prognosis of pneumonia in older adults.

Transcriptomic atlas for hypoxia and following re-oxygenation in Ancherythroculter nigrocauda heart and brain tissues: insights into gene expression, alternative splicing, and signaling pathways.

Hypoxia is a mounting problem that affects the world's freshwaters, with severe consequence for many species, including death and large economical loss. The hypoxia problem has increased recently due to the combined effects of water eutrophication and global warming. In this study, we investigated the transcriptome atlas for the bony fish Ancherythroculter nigrocauda under hypoxia for 1.5, 3, and 4.5 h and its recovery to normal oxygen levels in heart and brain tissues. We sequenced 21 samples for brain and heart tissues (a total of 42 samples) plus three control samples and obtained an average of 32.40 million raw reads per sample, and 95.24% mapping rate of the filtered clean reads. This robust transcriptome dataset facilitated the discovery of 52,428 new transcripts and 6,609 novel genes. In the heart tissue, the KEGG enrichment analysis showed that genes linked to the Vascular smooth muscle contraction and MAPK and VEGF signaling pathways were notably altered under hypoxia. Re-oxygenation introduced changes in genes associated with abiotic stimulus response and stress regulation. In the heart tissue, weighted gene co-expression network analysis pinpointed a module enriched in insulin receptor pathways that was correlated with hypoxia. Conversely, in the brain tissue, the response to hypoxia was characterized by alterations in the PPAR signaling pathway, and re-oxygenation influenced the mTOR and FoxO signaling pathways. Alternative splicing analysis identified an average of 27,226 and 28,290 events in the heart and brain tissues, respectively, with differential events between control and hypoxia-stressed groups. This study offers a holistic view of transcriptomic adaptations in A. nigrocauda heart and brain tissues under oxygen stress and emphasizes the role of gene expression and alternative splicing in the response mechanisms.

Impact of nomenclature as metabolic associated steatotic liver disease on steatotic liver disease prevalence and screening: a prospective population survey in Asians.

BACKGROUND AND AIM: The introduction of the latest nomenclature, metabolic associated steatotic liver disease (MASLD), proposed by the multi-society without Asian society consensus statement, aims to redefine the diagnostic criteria for metabolic associated fatty liver disease (MAFLD). However, its effect on the epidemiology in Asia remains unclear. METHOD: We conducted a population-based cross-sectional survey on fatty liver disease using multistage stratified random sampling of participants from Guangzhou, a representative area in China (ChiCTR2000033376). Demographic, socioeconomic, lifestyle, and laboratory data were collected. Hepatic steatosis and the severity of fibrosis were assessed using FibroScan. RESULTS: A total of 7388 individuals were recruited, the proportion of which meeting the definitions for nonalcoholic fatty liver disease (NAFLD), MAFLD, and MASLD were 2359 (31.9%), 2666 (36.1%), and 2240 (30.3%), respectively. One hundred and twenty (1.6%) patients had cryptogenic SLD, and 537 (7.3%) patients were diagnosed with MetALD. MASLD did not significantly differ from NAFLD and MAFLD, except that MAFLD patients had a lower proportion of males, hypertension, and diabetes and were less likely to consume tea (P < 0.05). Both cryptogenic SLD and MASLD non-MAFLD patients exhibited milder hepatic steatosis and a lower frequency of liver injury than NAFLD, MAFLD, or MASLD patients (all P < 0.05). An increased HOMA-IR (adjusted OR: 1.33, 95% CI: 1.10-2.03) was associated with higher risk of moderate-to-severe steatosis for MASLD non-MAFLD patients, while consuming more cups of tea (P for trend = 0.015) showed inverse associations. CONCLUSION: Irrespective of terminology used is that fatty liver disease is highly prevalent in the Han Chinese population. Differences in insulin resistance and lifestyle risk factors are associated with redefinition disparities.

Human monkeypox virus: Epidemiologic review and research progress in diagnosis and treatment.

Monkeypox virus (MPXV) is responsible for causing a zoonotic disease called monkeypox (mpox), which sporadically infects humans in West and Central Africa. It first infected humans in 1970 and, along with the variola virus, belongs to the genus Orthopoxvirus in the poxvirus family. Since the World Health Organization declared the MPXV outbreak a "Public Health Emergency of International Concern" on July 23, 2022, the number of infected patients has increased dramatically. To control this epidemic and address this previously neglected disease, MPXV needs to be better understood and reevaluated. In this review, we cover recent research on MPXV, including its genomic and pathogenic characteristics, transmission, mutations and mechanisms, clinical characteristics, epidemiology, laboratory diagnosis, and treatment measures, as well as prevention of MPXV infection in light of the 2022 and 2023 global outbreaks. The 2022 MPXV outbreak has been primarily associated with close intimate contact, including sexual activity, with most cases diagnosed among men who have sex with men. The incubation period of MPXV infection usually lasts from 6 to 13 days, and symptoms include fever, muscle pains, headache, swollen lymph nodes, and a characteristic painful rash, including several stages, such as macules, papules, blisters, pustules, scabs, and scab shedding involving the genitals and anus. Polymerase chain reaction (PCR) is usually used to detect MPXV in skin lesion material. Treatment includes supportive care, antivirals, and intravenous vaccinia immune globulin. Smallpox vaccines have been designed with four givens emergency approval for use against MPXV infection.

Relationship between vitamin D levels and pediatric celiac disease: a systematic review and meta-analysis.

BACKGROUND: The relationship between Vitamin D levels and pediatric celiac disease (CD) remains controversial. In this study, we conducted a systematic review and meta-analysis to examine the relationship between Vitamin D and pediatric CD. METHODS: We screened relevant studies from PubMed, EMBASE, and Web of Science published in English from January 1, 2000, to August 1, 2023. The included studies were assessed according to the STROBE checklist. Heterogeneity was quantified by Cochran's Q test and the I2 statistic. Publication bias was estimated by Begg's test and Egger's test. Meta-regression was used to detect potential sources of heterogeneity. RESULTS: A total of 26 studies were included in the meta-analysis. Nineteen articles compared 25(OH)D3 levels between CD patients and control groups, average 25-hydroxyvitamin D3 [25(OH)D3 or calcidiol], and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3 or calcitriol] levels, as the main forms of Vitamin D, there was a significant difference in CD patients and healthy controls (weighted mean difference (WMD) = - 5.77, 95% confidence interval (CI) = [- 10.86, - 0.69] nmol/L). Meanwhile, eleven articles reported the numbers of patients and controls with Vitamin D deficiency, there was a significant difference in the incidence of 25(OH)D3 deficiency between CD patients and healthy controls (odds ratio 2.20, 95% CI= [1.19, 4.08]). Nine articles reported changes in 25(OH)D3 levels before and after administering a GFD in patients with CD, the result of this study revealed the increase of 25(OH)D3 levels in CD patients after a gluten-free diet (GFD) (WMD = - 6.74, 95% CI = [- 9.78, - 3.70] nmol/L). CONCLUSIONS: Vitamin D levels in pediatric CD patients were lower than in healthy controls, and 25(OH)D3 deficiency was more prevalent in CD patients. We found that 25(OH)D3 levels were elevated in CD patients after GFD, which is consistent with previous research. Further well-designed, longitudinal, prospective cohort studies focusing on the role of Vitamin D in the pathogenesis of CD are therefore needed.

Cytokine profile in first-episode drug-naïve major depressive disorder patients with or without anxiety.

OBJECTIVE: It is known that cytokines play a role in both depression and anxiety. This study aimed to compare the levels of multiple cytokines in patients with first-episode drug-naive major depressive disorder (MDD) with or without anxiety and analyze the correlation between the level of depression or anxiety and the serum cytokine levels. METHODS: The study involved 55 patients with first-episode drug-naive MDD. To assess anxiety symptoms, the 14-item HAMA was used. MDD patients were divided into two groups: 23 MDD patients without anxiety and 32 MDD patients with anxiety. The measurement of 37 cytokines was conducted. Serum cytokine levels between patients with MDD without anxiety and anxiety were compared. In multiple linear regression models, the relationship between the group and abnormal cytokines was explored. The receiver operating characteristic (ROC) curve analysis was performed to estimate diagnostic performance of serum cytokines in discriminating MDD patients with anxiety from MDD patients without anxiety. A correlation was evaluated between the scores of HAMD or HAMA and the serum cytokine levels. RESULTS: In MDD patients with anxiety, IL-17 C and CCL17 levels were significantly lower than in MDD patients without anxiety (all P < 0.05). Multiple measurements were corrected with Benjamini-Hochberger corrections, but none of these differences persisted (all P > 0.05). The results of multiple linear regression models revealed that after controlling for other independent variables, group was not a significant independent predictor of serum IL-17 C or CCL17 (all P > 0.05). The AUC values of IL-17 C and CCL17 were 0.643 and 0.637, respectively, in discriminating MDD patients with anxiety from MDD patients without anxiety. The results of partial correlation analyses showed the scores of HAMD were negatively correlated with the IL-17 C (r = -0.314, P = 0.021) levels with sex as a covariate. CONCLUSIONS: The findings suggest that there is a potential absence of disparity in the levels of circulating cytokines among individuals diagnosed with first-episode drug-naïve MDD, regardless of the presence or absence of comorbid anxiety.

Effect of COVID-19 protective measures on the epidemiology characteristics of rotavirus, adenovirus, and coinfections among pediatric patients with acute gastroenteritis in Hangzhou, China.

Human rotavirus (RV) and adenovirus (AdV) have been recognized as common enteric viruses associated with viral acute gastroenteritis (AGE) in children aged<5 years. However, with the transmission of coronavirus disease 2019 (COVID-19) has been suppressed due to various aggressive and effective anti-epidemic measures, the prevalence of other viruses has also been affected. Therefore, this study aimed to investigate the impact of COVID-19 on the epidemiological characterization of RV, AdV, and coinfections among children with AGE in a hospital in Hangzhou from 2019 to 2023. The overall changes, seasonal distribution, and age distribution of enteroviruses were analyzed based on 5 years of records. All data were analyzed using SPSS 27.0. A total of 102,049 samples were analyzed from January 2019 to August 2023, and among them 15,911 (15.59%) were positive specimens, 11,646 (11.41%) were RV-positive, 4,057 (3.98%) were AdV-positive, and 208 (0.20%) were coinfection. The positive rate among males was 15.54%, while among females was 15.66% with a male-to-female ratio of 1.42:1. There was no significant difference in the positive rates of enterovirus infection between males and females. Significant associations were found between the month group and RV/AdV infection, with RV detection peaking in winter (74.18%) and early spring (29.22%), while AdV has a high prevalence in summer (16.03%) and spring (12.71%). The age group was also found to be significantly associated with RV/AdV infection, with RV being most prevalent in the 1-3-year-old age group (16.99%), while AdV was highest in the 3-5-year-old age group (8.10%).IMPORTANCEThis study highlights the epidemiological changes of rotavirus (RV), adenovirus (AdV), and coinfections in children with acute gastroenteritis (AGE) before, during, and after coronavirus disease 2019 (COVID-19) periods. There was a highly statistically significant difference in the positive rates of RV-positive, AdV-positive, and coinfection (P < 0.001), indicating that RV remains the main pathogen causing AGE. It emphasizes the importance of continuous surveillance of RV and AdV at both local and global levels. Regular surveillance of prevalent rotavirus strains will facilitate the development of new inactivated rotavirus vaccines and aid in disease prevention and control.

The dynamic-process characterization and prediction of synthetic gene circuits by dynamic delay model.

Differential equation models are widely used to describe genetic regulations, predict multicomponent regulatory circuits, and provide quantitative insights. However, it is still challenging to quantitatively link the dynamic behaviors with measured parameters in synthetic circuits. Here, we propose a dynamic delay model (DDM) which includes two simple parts: the dynamic determining part and the doses-related steady-state-determining part. The dynamic determining part is usually supposed as the delay time but without a clear formula. For the first time, we give the detail formula of the dynamic determining function and provide a method for measuring all parameters of synthetic elements (include 8 activators and 5 repressors) by microfluidic system. Three synthetic circuits were built to show that the DDM can notably improve the prediction accuracy and can be used in various synthetic biology applications.