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Background: A rapid screening test for urinary tract infections (UTIs) in children is needed to avoid unnecessary cultures and provide prompt reports to make appropriate clinical decisions. We have evaluated for the first time the performance of the Sysmex UF-5000 flow cytometer as a screening tool for UTIs in children. Methods: This study included 4445 pediatric patients, with urinary sediment and urine culture data collected from January 2020 to September 2023. The Sysmex UF-5000 analyzer was utilized to measure urine white blood cell (WBC) and bacteria (BACT), with the findings being compared to the culture results. Results: At ≥ 104 colony-forming unit (CFU)/mL, 513 samples were culture-positive (400 samples presented 104–105 CFU/mL, and 113 demonstrated ≥ 105 CFU/mL bacterial growth). Optimal indicators for positive cultures were BACT counts of 92.2/μL (AUC: 0.944) and WBC counts of 40.8/μL (AUC:0.863). False negative rate were 0.9% when using a 7.8 bacteria/μL cut-off and avoiding unnecessary cultures in 28.1%. The UF-5000 has a higher consistency rate for Gram-negative (GN) bacteria (90.3%) than Gram-positive (GP) bacteria (86.8%). For samples with 105 CFU/mL, UF-5000's Bacteria -Information flags showed superior concordance for samples with 104−105 CFU/mL bacteria. Conclusions: Screening pediatric urine cultures with the UF-5000 showed potential application value in identifying negative cultures and significant bacterial growth, although performance may vary depending on the study population. Furthermore, detecting Gram typing aids in guiding early clinical empirical medication, particularly for UTIs caused by GN bacteria. [ABSTRACT FROM AUTHOR]

Antimicrobial de-escalation refers to reducing the spectrum of antibiotics used in treating bacterial infections. This strategy is widely recommended in many antimicrobial stewardship programs and is believed to reduce patients' exposure to broad-spectrum antibiotics and prevent resistance. However, the ecological benefits of de-escalation have not been universally observed in clinical studies. This paper conducts computer simulations to assess the ecological effects of de-escalation on the resistance prevalence of Pseudomonas aeruginosa—a frequent pathogen causing nosocomial infections. Synthetic data produced by the models are then used to estimate the sample size and study period needed to observe the predicted effects in clinical trials. Our results show that de-escalation can reduce colonization and infections caused by bacterial strains resistant to the empiric antibiotic, limit the use of broad-spectrum antibiotics, and avoid inappropriate empiric therapies. Further, we show that de-escalation could reduce the overall super-infection incidence, and this benefit becomes more evident under good compliance with hand hygiene protocols among health care workers. Finally, we find that any clinical study aiming to observe the essential effects of de-escalation should involve at least ten arms and last for four years—a size never attained in prior studies. This study explains the controversial findings of de-escalation in previous clinical studies and illustrates how mathematical models can inform outcome expectations and guide the design of clinical studies. [ABSTRACT FROM AUTHOR]

Small antibacterial effectors, including lysozymes, lectins, and antimicrobial peptides, are key regulators of intestinal immunity. However, whether there is coordination among them during regulation is an interesting, but largely unknown, issue. In the present study, we revealed that small effectors synergistically regulate peptidoglycan-derived intestinal immunity in the kuruma shrimp, Marsupenaeus japonicus. A C-type lysozyme (LysC) was screened as a responsive factor for the intestine-bacteria interaction. LysC functions to restrict intestinal bacteria, mainly by cleaving Photobacterium damselae peptidoglycan to generate muropeptides which are powerful stimulators that induce anti-lipopolysaccharides factor B1 (AlfB1), an effective bactericidal peptide. The muropeptides also induce a C-type lectin (Ctl24), which recognizes peptidoglycan and coats bacteria. By counteracting LysC-mediated muropeptide release and AlfB1's bactericidal activity, Ctl24 prevents the continuous elimination of intestinal bacteria. Therefore, this study demonstrates a mechanism by which small immune effectors coordinate to achieve intestinal homeostasis, and provides new insights into peptidoglycan-derived intestinal immunity in invertebrates. Author summary: Intestinal homeostasis largely determines the healthy status of metazoan animals. Uncovering the mechanism for intestinal homeostasis would be helpful to develop new strategies for disease control. In this study, we demonstrated that small immune effectors, including lysozyme, lectin, and bactericidal peptide, collaborate to regulate shrimp intestinal homeostasis in shrimp. Intestinal bacterial peptidoglycan is digested by a lysozyme into muropeptides, which induce the expression of this lysozyme, a bactericidal peptide and a lectin. The former two effectors are able to restrict intestinal bacteria by generating muropeptides and killing bacteria, respectively, while the latter one counteracts their functions. By coating peptidoglycan, this lectin inhibits lysozyme-mediated muropeptides release, and bactericidal peptide-mediated killing of bacteria. Through controlling, but not eliminating intestinal bacteria, these small effectors together achieve a dynamic balance of intestinal bacteria in shrimp. Therefore, this study emphasized the significance of peptidoglycan as the driving force for intestinal homeostasis, and provides insights into generating a healthy intestinal microbiota by utilizing the synergy among small immune effectors. [ABSTRACT FROM AUTHOR]

Background: Atherosclerosis(AS) is widely recognized as a risk factor for incident cardiovascular and cerebrovascular diseases. Tetramethylpyrazine (TMP) is the active ingredient of Ligusticum wallichii that possesses a variety of biological activities against atherosclerosis. Objective: This systematic review and meta-analysis sought to study the impact of and mechanism of tetramethylpyrazine for atherosclerosis in animal models. Methods: A systematic search was conducted of PubMed, Embase, Cochrane Library, Web of Science database, Chinese Biomedical (CBM) database, China National Knowledge Infrastructure (CNKI), WanFang data, and Vip Journal Integration Platform, covering the period from the respective start date of each database to December 2021. We used SYRCLE's 10-item checklist and Rev-Man 5.3 software to analyze the data and the risk of bias. Results: Twelve studies, including 258 animals, met the inclusion criteria. Compared with the control group, TMP significantly reduced aortic atherosclerotic lesion area, and induced significant decreases in levels of TC (SMD = ‐2.67, 95% CI -3.68 to -1.67, P < 0.00001), TG (SMD = ‐2.43, 95% CI -3.39 to -1.47, P < 0.00001), and LDL-C (SMD = ‐2.87, 95% CI -4.16 to -1.58, P < 0.00001), as well as increasing HDL-C (SMD = 2.04, 95% CI 1.05 to 3.03, P = 0.001). TMP also significantly modulated plasma inflammatory responses and biological signals associated with atherosclerosis. In subgroup analysis, the groups of high-dose TMP (≥50 mg/kg) showed better results than those of the control group. No difference between various durations of treatment groups or various assessing location groups. Conclusion: TMP exerts anti-atherosclerosis functions in an animal model of AS mediated by anti-inflammatory action, antioxidant action, ameliorating lipid metabolism disorder, protection of endothelial function, antiplatelet activity, reducing the proliferation and migration of smooth muscle cells, inhibition of angiogenesis, antiplatelet aggregation. Due to the limitations of the quantity and quality of current studies, the above conclusions need to be verified by more high-quality studies. Trial registration number: PROSPERO registration no.CRD42021288874. [ABSTRACT FROM AUTHOR]

Background: Endometriosis, a complex gynecological condition, involves inflammation and immune dysregulation. The vaginal microbiota, characterized by its diversity, is an integral part of the vaginal microecology—interacting with vaginal anatomy, the endocrine system, and local mucosal immunity. Imbalances in this microecology are known to precipitate various inflammatory diseases. Despite extensive research, the connection between vaginal microbiota dysbiosis and endometriosis remains a subject of debate. Our study assesses the association between vaginal microecology dysbiosis and endometriosis. Methods: We systematically searched major electronic databases in English, including Embase, PubMed, The Cochrane Library, MEDLINE (Ovid), BIOSIS (Ovid), China National Knowledge Infrastructure (CNKI), and Wanfang, up to August 15, 2023. Selected articles underwent screening based on predefined inclusion and exclusion criteria. Normal vaginal microecology was defined as a negative Amsel/Spiegel test or Nugent score of 0–3, or Lactobacillus predominance determined by 16S rRNA gene amplification sequencing. Deviations from this norm were classified as dysbiosis, further categorized into bacterial vaginosis (BV) and intermediate BV. Data analysis utilized Revman 5.4, with effect sizes presented as Odds Ratios (OR) and 95% Confidence Intervals (CI). Results: Out of 1081 articles, eight met the inclusion criteria. Utilizing fixed-effect models due to low heterogeneity, the analysis revealed a positive association between dysbiosis and endometriosis (OR = 1.17, 95% CI 0.81–1.70; I2 = 0%), but showed a slight negative association between normal vaginal microecology with endometriosis (OR = 0.90, 95% CI 0.55–1.46; I2 = 29%). However, the association was not significant. Subgroup and sensitivity analyses corroborated the stability of these associations. Conclusion: A positive correlation exists between vaginal microecology dysbiosis and endometriosis, notably with intermediate BV. However, the mechanisms underpinning this relationship remain elusive, highlighting the need for further research to overcome limitations. Trial registration: Registration number: CRD42023445163. [ABSTRACT FROM AUTHOR]

Sisal is a leaf fiber crop with a high integrated value and a wide range of uses in the application of soil remediation of heavy metal contamination. This study provides a preliminary understanding of how sisal responds to Cd stress and presents a theoretical basis for exploring the potential of sisal in the remediation of Cd-contaminated soils. In this work, the activities of the antioxidant enzymes (SOD, POD, and CAT) of sisal were measured by hydroponics with the addition of CdCl2·2.5H2O and different concentrations of Cd stress. Whole transcriptome sequencing (RNA-Seq) analysis was performed with lllumina sequencing technology, and qRT-PCR was conducted to verify the differential genes. The results obtained were as follows: (1) Short-term low concentration of Cd stress (20 mg/kg) had a transient promotion effect on the growth of sisal roots, but Cd showed a significant inhibitory effect on the growth of sisal roots over time. (2) Under different concentrations of Cd stress, the Cd content in sisal root was greater than that in sisal leaf, and Cd accumulated mainly in sisal roots. (3) With the increase of Cd stress concentration, the antioxidant enzyme catalase activity increased, peroxidase activity showed a decreasing trend, and superoxide dismutase showed a trend of increasing and then decreasing. (4) Transcriptome sequencing analysis detected 123 differentially expressed genes (DEGs), among which 85 genes were up-regulated and 38 genes were down-regulated. The DEGs were mainly concentrated in flavonoid biosynthesis and glutathione metabolism, and both processes had some regulatory effects on the Cd tolerance characteristics of sisal. This study elucidated the physiological, biochemical and transcriptomic responses of sisal under cadmium stress, and provided a theoretical basis for the ecological restoration function of sisal. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of herbal medicine and acupuncture combination for pediatric epilepsy treatment. Methods: Databases were searched from their interception until October 2023 to identify randomized controlled trials focusing on the therapeutic efficacy of herbal medicine-acupuncture combination (intervention group) for pediatric epilepsy. The primary outcome was the risk of treatment failure, whereas the secondary outcomes included the risk of post-treatment electroencephalogram (EEG) abnormalities and adverse events. Subgroup analyses were conducted based on the type of herbal compound formulas. Meta-regression analysis was conducted to examine the influence of patient demographics and clinical history on the therapeutic efficacy of herbal medicine-acupuncture combination for pediatric epilepsy. To assess the cumulative evidence, trial sequential analysis (TSA) was performed. Results: The analysis included 10 trials involving a total of 882 pediatric patients. Meta-analysis revealed that the intervention group had a lower risk of treatment failure than the control group (risk ratio [RR] = 0.3, 95% confidence interval [CI]: 0.19–0.47, P<0.00001, I2 = 0%, 10 trials). Subgroup analyses showed that therapeutic efficacy was consistent among the different herbal compound formulas. Meta-regression analysis revealed that the efficacy of the treatments did not significantly vary with patient age, male sex, and duration of seizure history. TSA suggested that herbal medicine-acupuncture combination exerted a robust and conclusive effect on seizure treatment. Although the combined used of herbal medicine and acupuncture was not associated with a lower risk of post-treatment EEG abnormalities (RR = 0.82, 95%CI:0.6–1.11, P = 0.2, 3 trials), the risk of adverse events was reduced (RR = 0.27, 95%CI:0.18–0.41, P<0.00001, 4 trials). Conclusion: The meta-analysis suggested that combined use of herbal medicine and acupuncture is a promising and safe clinical approach for pediatric epilepsy treatment. Further large-scale studies are necessary to conclusively determine the efficacy and safety of herbal medicine and acupuncture in pediatric epilepsy treatment. [ABSTRACT FROM AUTHOR]

Competitive fitness assays in liquid culture have been a mainstay for characterizing experimental evolution of microbial populations. Growth of microbial strains has also been extensively characterized by colony size and could serve as a useful alternative if translated to per generation measurements of relative fitness. To examine fitness based on colony size, we established a relationship between cell number and colony size for strains of Saccharomyces cerevisiae robotically pinned onto solid agar plates in a high-density format. This was used to measure growth rates and estimate relative fitness differences between evolved strains and their ancestors. After controlling for edge effects through both normalization and agar-trimming, we found that colony size is a sensitive measure of fitness, capable of detecting 1% differences. While fitnesses determined from liquid and solid mediums were not equivalent, our results demonstrate that colony size provides a sensitive means of measuring fitness that is particularly well suited to measurements across many environments. [ABSTRACT FROM AUTHOR]

Since its initial discovery in the Hunan province of China, genomic DNA of porcine circovirus 4 (PCV4) has been detected in pigs across multiple provinces in China, as well as in South Korea. However, the prevalence of porcine circovirus type 4 in Gansu Province, China, remains unknown. To address this gap, we undertook an extensive study where we gathered 121 clinical samples displaying diverse clinical manifestations from pig farms in Gansu Province between 2022 and 2023. Employing a real-time fluorescence quantification method, we identified the presence of PCV4 genome. Out of the 121 clinical samples analyzed, 13 samples tested positive for PCV4, resulting in a positive rate of 10.74% (13/121). This finding confirms the presence of PCV4 in pig farms within Gansu Province, China. Furthermore, we successfully sequenced and analyzed the complete genomes of two distinct PCV4 strains, comparing them with 60 reference sequences archived in the GenBank database. The results revealed a high nucleotide homology (98.2–98.8%) between the strains obtained in this study and the PCV4 reference strains, indicating a relatively low evolutionary rate of the PCV4 genome. Phylogenetic analysis revealed that two strains in this study belong to PCV4a and PCV4c. As far as we know, this study marks the inaugural report on the molecular identification and genomic attributes of PCV4 in Gansu Province, China, offering valuable insights for devising preventive and control strategies against this emerging virus. [ABSTRACT FROM AUTHOR]

Tourist impact management in ecotourism destinations requires an accurate description of tourists' spatiotemporal behavior patterns and recreation preferences to minimize the ecological environmental impact and maximize the recreation experience. This study classified tourist behaviors into five typical behavior patterns based on the digital footprints of tourists visiting Ziwuyu of the Qinling Mountains, including 348 traveling tracks and 750 corresponding geotagged photographs: short-distance, traversing, reentrant, large loop, and small loop. Furthermore, each behavior pattern's recreation preference was identified using photograph analysis. Tourists with large-loop and reentrant behavior patterns have 89.8% and 30% chances of visiting Jianshanding, respectively. Key protected areas are faced with the risk of ecological environmental damage. Based on the behavior pattern differentiation and preference of tourists, this paper provides a decision-making basis for the classified management and guidance of tourists in ecotourism destinations. It has reference value for the management of similar ecotourism destinations. [ABSTRACT FROM AUTHOR]

Organoids have immense potential as ex vivo disease models for drug discovery and personalized drug screening. Dynamic changes in individual organoid morphology, number, and size can indicate important drug responses. However, these metrics are difficult and labor-intensive to obtain for high-throughput image datasets. Here, we present OrganoID, a robust image analysis platform that automatically recognizes, labels, and tracks single organoids, pixel-by-pixel, in brightfield and phase-contrast microscopy experiments. The platform was trained on images of pancreatic cancer organoids and validated on separate images of pancreatic, lung, colon, and adenoid cystic carcinoma organoids, which showed excellent agreement with manual measurements of organoid count (95%) and size (97%) without any parameter adjustments. Single-organoid tracking accuracy remained above 89% over a four-day time-lapse microscopy study. Automated single-organoid morphology analysis of a chemotherapy dose-response experiment identified strong dose effect sizes on organoid circularity, solidity, and eccentricity. OrganoID enables straightforward, detailed, and accurate image analysis to accelerate the use of organoids in high-throughput, data-intensive biomedical applications. Author summary: A recent advance in biomedical research is the use of connective tissue gels to grow cells into microscopic structures, called organoids, that preserve and exhibit the physical and molecular traits of a particular organ. Organoids have enabled researchers to study complex phenomena, such as the beating of the heart or the folds of the intestines, and the effects of drugs on these properties. Changes in the size and shape of organoids are important indicators of drug response, but these are tedious to measure in large drug screening experiments, where thousands of microscopy images must be analyzed. We developed a software tool named OrganoID that automatically traces the exact shape of individual organoids in an image, even when multiple organoids are clumped together, and measures organoid changes over time. To show our tool in action, we used OrganoID to analyze pancreatic cancer organoids and their response to chemotherapy. We also showed that our tool can handle images of many different types of organoids, even those derived from mouse cells. With this software, researchers will be able to easily analyze immense quantities of organoid images in large-scale experiments to discover new drug treatments for a range of diseases. [ABSTRACT FROM AUTHOR]

Background: Scrub typhus has become a serious public health concern in the Asia-Pacific region including China. There were new natural foci continuously recognized and dramatically increased reported cases in mainland China. However, the epidemiological characteristics and spatiotemporal patterns of scrub typhus in Fujian province have yet to be investigated. Objective: This study proposes to explore demographic characteristics and spatiotemporal dynamics of scrub typhus cases in Fujian province, and to detect high-risk regions between January 2012 and December 2020 at county/district scale and thereby help in devising public health strategies to improve scrub typhus prevention and control measures. Method: Monthly cases of scrub typhus reported at the county level in Fujian province during 2012–2020 were collected from the National Notifiable Disease Surveillance System. Time-series analyses, spatial autocorrelation analyses and space-time scan statistics were applied to identify and visualize the spatiotemporal patterns of scrub typhus cases in Fujian province. The demographic differences of scrub typhus cases from high-risk and low-risk counties in Fujian province were also compared. Results: A total of 11,859 scrub typhus cases reported in 87 counties from Fujian province were analyzed and the incidence showed an increasing trend from 2012 (2.31 per 100,000) to 2020 (3.20 per 100,000) with a peak in 2018 (4.59 per 100,000). There existed two seasonal peaks in June-July and September-October every year in Fujian province. A significant positive spatial autocorrelation of scrub typhus incidence in Fujian province was observed with Moran's I values ranging from 0.258 to 0.471 (P<0.001). Several distinct spatiotemporal clusters mainly concentrated in north and southern parts of Fujian province. Compared to low-risk regions, a greater proportion of cases were female, farmer, and older residents in high-risk counties. Conclusions: These results demonstrate a clear spatiotemporal heterogeneity of scrub typhus cases in Fujian province, and provide the evidence in directing future researches on risk factors and effectively assist local health authorities in the refinement of public health interventions against scrub typhus transmission in the high risk regions. Author summary: Scrub typhus is a vector-borne zoonotic disease caused by Orientia tsutsugamushi and is popular in the Asia-Pacific area. Nowadays scrub typhus has been recognized as a considerable burden on public health in Fujian province. We explored the epidemiological characteristics, spatiotemporal patterns and diffusion characteristics of scrub typhus, and detected high-risk regions at the county level in Fujian province between January 2012 and December 2020. Our results indicated that the majority of cases were reported in June-July and September-October and that that middle aged and elderly people were more prone to infection every year in Fujian province. The spatial autocorrelation analysis revealed clustering in geographic distribution of cases and several distinct spatiotemporal clusters were identified in north and southern parts of Fujian province. Compared with cases from low-risk areas, a higher proportion of cases were female, farmer, and older residents in high-risk counties. [ABSTRACT FROM AUTHOR]

Background: The study was designed to explore the risk factors for sitting-induced tachycardia syndrome (STS) in children and adolescents. Methods and results: In this case-control study, 46 children with STS and 184 healthy children and adolescents were recruited. Demographic characteristics, lifestyle habits, allergy history, and family history were investigated using a questionnaire. The changes in heart rate and blood pressure from supine to sitting were monitored using a sitting test. The possible differences between STS patients and healthy children were analyzed using univariate analysis. Logistic regression analysis was used to explore the independent risk factors for STS. Univariate analysis showed that the daily sleeping time of the STS children were significantly shorter than that of the control group [(8.8 ± 1.2) hours/day vs. (9.3 ± 1.0) hours/day, P = 0.009], and the proportion of positive family history of syncope in the STS patients was higher than the controls (4/42 vs. 3/181, P = 0.044). Multivariate logistic regression studies showed that reduced daily sleeping time was an independent risk factor of STS in children (P = 0.006). Furthermore, when daily sleeping time was prolonged by 1 h, the risk of STS was decreased by 37.3%. Conclusion: Reduced daily sleeping was an independent risk factor for STS in children and adolescents. [ABSTRACT FROM AUTHOR]

Meiosis is a complex process involving the expression and interaction of numerous genes in a series of highly orchestrated molecular events. Fam9b localized in Xp22.3 has been found to be expressed in testes. However, FAM9B expression, localization, and its role in meiosis have not been previously reported. In this study, FAM9B expression was evaluated in the human testes and ovaries by RT-PCR, qPCR, and western blotting. FAM9B was found in the nuclei of primary spermatocytes in testes and specifically localized in the synaptonemal complex (SC) region of spermatocytes. FAM9B was also evident in the follicle cell nuclei and diffusely dispersed in the granular cell cytoplasm. FAM9B was partly co-localized with SYCP3, which is essential for both formation and maintenance of lateral SC elements. In addition, FAM9B had a similar distribution pattern and co-localization as γH2AX, which is a novel biomarker for DNA double-strand breaks during meiosis. All results indicate that FAM9B is a novel meiosis-associated protein that is co-localized with SYCP3 and γH2AX and may play an important role in SC formation and DNA recombination during meiosis. These findings offer a new perspective for understanding the molecular mechanisms involved in meiosis of human gametogenesis. [ABSTRACT FROM AUTHOR]