Ultrasound-generated bubbles enhance osteogenic differentiation of mesenchymal stromal cells in composite collagen hydrogels.

Hydrogels can improve the delivery of mesenchymal stromal cells (MSCs) by providing crucial biophysical cues that mimic the extracellular matrix. The differentiation of MSCs is dependent on biophysical cues like stiffness and viscoelasticity, yet conventional hydrogels cannot be dynamically altered after fabrication and implantation to actively direct differentiation. We developed a composite hydrogel, consisting of type I collagen and phase-shift emulsion, where osteogenic differentiation of MSCs can be non-invasively modulated using ultrasound. When exposed to ultrasound, the emulsion within the hydrogel was non-thermally vaporized into bubbles, which locally compacted and stiffened the collagen matrix surrounding each bubble. Bubble growth and matrix compaction were correlated, with collagen regions proximal (i.e., ≤ ∼60 µm) to the bubble displaying a 2.5-fold increase in Young's modulus compared to distal regions (i.e., > ∼60 µm). The viability and proliferation of MSCs, which were encapsulated within the composite hydrogel, were not impacted by bubble formation. In vitro and in vivo studies revealed encapsulated MSCs exhibited significantly elevated levels of RUNX2 and osteocalcin, markers of osteogenic differentiation, in collagen regions proximal to the bubble compared to distal regions. Additionally, alkaline phosphatase activity and calcium deposition were enhanced adjacent to the bubble. An opposite trend was observed for CD90, a marker of MSC stemness. Following subcutaneous implantation, bubbles persisted in the hydrogels for two weeks, which led to localized collagen alignment and increases in nuclear asymmetry. These results are a significant step toward controlling the 3D differentiation of MSCs in a non-invasive and on-demand manner.

Effects of supplemental medusa (Rhopilema esculentum) on intestinal microbiota and metabolites in silver pomfret (Pampus argenteus).

Pampus argenteus demonstrates a preference for Rhopilema esculentum as prey, yet the ramifications of consuming supplemental medusa on fish microbiota and metabolism remain elusive. To elucidate these effects, 300 juvenile fish were divided into two groups: control group (C, given commercial food only) and supplemental medusa (SM) group (given supplemental medusa + commercial feed). After 15 days, fish in the SM group exhibited a significant increase in fatness, the amylase activity in the intestine significantly increased, and the intestinal microvilli were arranged more neatly. The comprehensive approach involving 16S rRNA amplicon sequencing and metabolomics was employed, leading to the identification of five genera within the SM group, namely Lactococcus, Cohaesibacter, Maritalea, Sulfitobacter, and Carnobacterium. Functional prediction analysis of the microbiota indicated that the consumption of supplemental medusa facilitated processes such as glycolysis/gluconeogenesis and amino acid absorption. Metabolomics analysis revealed significant enrichment of 85 differential metabolites, most of them belonging to fatty acids and conjugates. These differential metabolites primarily participated in processes such as amino acid metabolism, fatty acid synthesis, and disease. Notably, the consumption of medusa resulted in a significant reduction in nine lysophospholipids associated with cardiovascular disease and inflammation. Pearson's correlation coefficient analysis revealed associations between specific microorganisms and metabolites, indicating that Cobetia, Weissella, and Macrococcus exhibited an increased abundance in the SM group, positively correlating with apocynin, 12-Hete, and delta 9-THC-d3. The indicator bacteria Psychrobacter reduced in the SM group, exhibiting a negative correlation with cystathionine (a compound involved in glutathione synthesis). Overall, the supplementation of medusa may confer a beneficial effect on the immunity of the fish. This study contributes to the theoretical framework for fish feed development.

Effects of Illness Perception and Coping Style on Self-Management in Peritoneal Dialysis Patients: A Cross-Sectional Study.

Aim: Chronic disease self-management is critical to disease prognosis and patient quality of life. Several psychological factors influence this process of self-management. In this background, the present study investigated the impact of illness perceptions and coping style on self-management in people with peritoneal dialysis (PD). Methods: The study is a cross-sectional study. From May 2022 to January 2023, a convenience sampling method was used to recruit 246 peritoneal dialysis patients. General information questionnaire, brief illness perception questionnaire, medical coping style modes questionnaire and the self-management scale for peritoneal dialysis patients were used in this study. We used SPSS 24.0 to analyze the data, and the statistical methods included descriptive analysis, single factor analysis, Pearson correlation analysis and multiple linear regression analysis. Results: A total of 246 patients were included in this study (93.89% response rate). Cognitive representations and emotional representations were 30.40, 14.18, respectively. However, illness comprehensibility was 2.87. Illness perceptions were negative significantly correlated with self-management. With regard to coping style, our patients were more likely to adopt avoidance and resignation coping style. Confrontation and avoidance were positively related to self-management, while acceptance-resignation was negatively related. Conclusion: Self-management of peritoneal dialysis patients needs to be improved. Age, female sex, monthly income, illness perceptions and coping style were independently associated with self-management. Impact: These findings suggest that interventions that improve illness perceptions and coping style should be explored to ultimately improve their self-management. For example, patients can be provided with psychological counseling so that they can face the disease correctly, and we should pay attention to the positive role of social support.

The application of mass defect percentage in the evaluation of acute coronary syndrome.

OBJECTIVES: White blood cells, neutrophils, lymphocytes, and neutrophil-to-lymphocyte ratio (NLR) distribution patterns in patients with anatomic coronary disease have previously been associated with cardiac events such as myocardial infarct size, complications, and prognosis. However, it remains unknown whether myocardial perfusion mass defect percentage (MDP) obtained from gated myocardial perfusion imaging (G-MPI) correlates with these hematological parameters. Therefore, our research aimed to investigate the application of MDP in the evaluation of acute coronary syndrome (ACS). METHODS: Thirty-six patients with ACS underwent single-photon emission computed tomography/computed tomography using retrospective electrocardiography gating during the resting state. The primary outcome was the percentage of left ventricular mass with abnormal myocardial perfusion (i.e. MDP) in G-MPI. Furthermore, the correlation between myocardial perfusion MDP and lymphocyte count, neutrophil count, white blood cell count, and NLR was calculated. In addition, we explored the relationship of myocardial perfusion MDP with other cardiac function parameters obtained from G-MPI, such as summed rest score, left ventricular ejection fraction, end-systolic volume, and end-diastolic volume. RESULTS: Myocardial perfusion MDP significantly correlated with white blood cell count, neutrophil count, and NLR (P < 0.01). Furthermore, these hematological parameters were significantly different between low and high MDP groups. Additionally, myocardial perfusion MDP negatively correlated with end-systolic volume (r = -0.615) and left ventricular ejection fraction (r = -0.657). CONCLUSION: Myocardial perfusion MDP has a high correlation with inflammatory cell counts and cardiac function parameters obtained from G-MPI in ACS; this may be of help in the evaluation and treatment of these patients.

Clathrin-Mediated Endocytosis of Multiple Nanoparticles Tends to Be Less Cooperative: A Computational Study.

The internalization of nanoparticles is of great significance for their biological applications. Clathrin-mediated endocytosis (CME) is one of the main endocytic pathways. However, there is still a lack of a fundamental understanding regarding the internalization of multiple nanoparticles via CME. Therefore, in this study, we conducted computational investigations to uncover detailed molecular mechanisms and kinetic pathways for differently shaped nanoparticles in the presence of clathrin. Particular focus is given to understanding the CME of multiple-nanoparticle systems. We found that unlike receptor-mediated endocytosis, multiple nanoparticles did not get cooperatively wrapped by the membrane but tended to undergo independent endocytosis in the presence of clathrin. To further investigate the endocytosis mechanism, we studied the effects of clathrins, nanoparticle shape, nanoparticle size, nanoparticle arrangement, and membrane surface tension. The self-assembly of clathrin prefers independent endocytosis for multiple nanoparticles. Besides, the cooperative behavior is weak with increasing nanoparticle-shape anisotropy. However, when the membrane tension is reduced, the endocytosis pathway for multiple nanoparticles is cooperative endocytosis. Moreover, we found that the self-assembly of clathrins reduces the critical size of nanoparticles to undergo cooperative wrapping by the cell membrane. Our results provide valuable insights into the molecular mechanisms of multiple nanoparticles through CME and offer useful guidance for the design of nanoparticles as drug/gene delivery carriers.

Self-Illuminating Copper-Luminol Coordination Polymers for Bioluminescence Imaging of Oxidative Damage.

Timely detection of reactive oxygen species (ROS) accumulated during inflammation is essential for an early disease diagnosis. Compared to fluorescence probes with limited sensitivity and accuracy, chemiluminescence (CL) imaging offers the potential for highly sensitive molecular visualization of ROS by minimizing background interferences. However, the development of bright and easily manufacturable CL probes for ROS imaging remains challenging. In this study, a novel chemiluminescent nanoprobe named Cu-Lum@NPs for ROS imaging in inflammation was synthesized by using a one-step solvothermal method. The Cu-Lum@NPs, which are composed of coordination polymers containing copper ions and luminol (Lum), demonstrate intrinsic peroxidase-like activity that relies on Cu(I) as the catalytic active center to initiate the Fenton reaction. This catalytic process facilitates the decomposition of hydrogen peroxide (H2O2) into hydroxyl radicals (•OH) and superoxide anion radicals (O2•-), leading to the oxidation of Lum and inducing strong luminescence. Cu-Lum@NPs, displaying nanozyme characteristics, were observed to accelerate and enhance the ROS-responsive luminescence (10-1600-fold in solution and over 100-fold in neutrophils) and notably extend persistent luminescence. The Cu-Lum@NPs allowed for CL imaging of endogenous ROS in living cells and animals with an outstanding signal-to-noise ratio exceeding 96 and facilitated oxidative damage luminescence imaging for tissue-specific detection. The study presents Cu-Lum@NPs, a highly sensitive and easily manufacturable chemiluminescent nanoprobe for ROS imaging both in vitro and in vivo, exhibiting enhanced luminescence and prolonged persistence for ROS-related disease detection.

Synthesis of Porous Red Mud/Slag-Based Spherical Geopolymers for Efficient Methylene Blue and Ni2+ Removal from Water.

To reuse red mud and slag wastes as raw materials, a green type of porous spherical red mud/slag-based geopolymer (RSG) was synthesized by utilizing suspension curing and foaming techniques. Because methylene blue (MB) and nickel ion (Ni2+) were common and difficult to treat in wastewater, the adsorption characteristics of MB and Ni2+, as well as the phase and microstructure of the porous RSG spheres prior to and after adsorption, were thoroughly investigated. The porous RSG spheres showed a stable and mesoporous structure with a BET surface area of 31.36 m2/g. The spheres achieved the maximum removal efficiencies of 99.81% (MB) and 99.01% (Ni2+) at dosages of 16 and 10 g/L, respectively. The pseudo-second-order kinetic model and the Langmuir model could match the adsorption data of these spheres, with predicted maximum adsorption capacity (Qmax) values of 19.88 mg/g for MB and 12.39 mg/g for Ni2+, respectively. After three adsorption-desorption cycles, porous RSG spheres demonstrated good recycling capability with removal efficiencies of 98.10% (MB) and 54.60% (Ni2+). The spheres were also effective in adsorbing additional dyes (methyl orange (MO), crystal violet (CV), and malachite green (MG)) and heavy metal ions (Cd2+, Pb2+, Zn2+, and Cu2+). The spheres have potential use in water treatment.

Optimizing nitrogen fertilizer for improved root growth, nitrogen utilization, and yield of cotton under mulched drip irrigation in southern Xinjiang, China.

The root system plays a crucial role in water and nutrient absorption, making it a significant factor affected by nitrogen (N) availability in the soil. However, the intricate dynamics and distribution patterns of cotton (Gossypium hirsutum L.) root density and N nutrient under varying N supplies in Southern Xinjiang, China, have not been thoroughly understood. A two-year experiment (2021 and 2022) was conducted to determine the effects of five N rates (0, 150, 225, 300, and 450 kg N ha-1) on the root system, shoot growth, N uptake and distribution, and cotton yield. Compared to the N0 treatment (0 kg N ha-1), the application of N fertilizer at a rate of 300 kg N ha-1 resulted in consistent and higher seed cotton yields of 5875 kg ha-1 and 6815 kg ha-1 in 2021 and 2022, respectively. This N fertilization also led to a significant improvement in dry matter weight and N uptake by 32.4% and 53.7%, respectively. Furthermore, applying N fertilizer at a rate of 225 kg N ha-1 significantly increased root length density (RLD), root surface density (RSD), and root volume density (RVD) by 49.6-113.3%, 29.1-95.1%, and 42.2-64.4%, respectively, compared to the treatment without N fertilization (0 kg N ha-1). Notably, the roots in the 0-20 cm soil layers exhibited a stronger response to N fertilization compared to the roots distributed in the 20-40 cm soil layers. The root morphology parameters (RLD, RSD, and RVD) at specific soil depths (0-10 cm in the seedling stage, 10-25 cm in the bud stage, and 20-40 cm in the peak boll stage) were significantly associated with N uptake and seed cotton yield. Optimizing nitrogen fertilizer supply within the range of 225-300 kg N ha-1 can enhance root foraging, thereby promoting the interaction between roots and shoots and ultimately improving cotton production in arid areas.

Two high quality chromosome-scale genome assemblies of female and male silver pomfret (Pampus argenteus).

Pampus argenteus is a highly commercial marine fish whose population is declining sharply. Here, we generated a female P. argenteus genome, spanning 536.33 Mb with contig N50 of 1.79 Mb; 24070 genes (99.50% of 24,182) were functionally annotated. To improve quality of it, we assembled a 553.79 Mb genome of male fish with contig N50 of 24.75 Mb through HiFi and ultra-long ONT sequence technologies; 550.82 Mb were anchored onto 24 gap-free chromosomes; 22,892 genes (98.1% of 23,346) were functionally annotated; the QV value was 51.55 with 98.9% of BUSCO and 99.39% coverage of Illumina reads. Finally, we compared this genome with previous published one, revealing 37,301 SVs. 52.82 Mb and 18.05 Mb SDs were characterized in our and published assemblies, respectively, and 48.96 Mb PURs were constructed. Thus, this genome assembly exhibits excellent completeness, continuity and accuracy comparing to the published one, which can be current preferred reference genome. Overall, these works help aquaculture and wild resources recovery of P. argenteus and provide a valuable genetic resource for study.

Construction of frailty and risk prediction models in maintenance hemodialysis patients: a cross-sectional study.

Objective: As the prevalence of diabetic nephropathy and hypertensive nephropathy increases with age in mainland China, the number of patients with end-stage renal disease is increasing, leading to an increase in the number of patients receiving maintenance hemodialysis. Considering the harmful effects of frailty on the health of maintenance hemodialysis patients, this study aims to identify hemodialysis patients at risk for frailty at an early stage, in order to prevent or delay the progression of frailty in the early stage, so as to prevent the adverse consequences of frailty. Methods: A total of 479 patients admitted to the blood purification centers of two grade tertiary hospitals in Anhui Province, China, using convenient sampling. The Frailty Scale, the SARC-F questionnaire, the Simplified Food Appetite Questionnaire (SNAQ) and the mini nutritional assessment short-form (MNA-SF) were used in the study. Pearson correlation analysis was used to explore the correlation among the frailty influencing factors. Results: The incidence of frailty was 24.0% among 479 Chinese hemodialysis patients. Gender (p < 0.05), Malnutrition (p < 0.001), sarcopenia (p < 0.001), and feel tired after dialysis (p < 0.001) were highly correlated with frailty in Chinese hemodialysis patients. Serum albumin concentration (p < 0.05) was a protective factor of frailty. Conclusion: This survey shows that frailty was highly prevalent among Chinese hemodialysis patients. Medical staff and their families should make early judgments and carry out interventions on the risk of frailty.

In Situ Synthesis of Copper-Based Metal-Organic Frameworks with Ligand Defects for Electrochemical Reduction of CO2 into C2 Products.

Electrochemical reduction of CO2 into high-value-added products is a potential approach to solving environmental problems but is limited by poor product selectivity and low efficiency. Metal-organic framework (MOF) materials have been considered one of the most promising catalysts, but their application is limited by complicated preparation processes, especially during the synthesis of organic ligands. In this work, a new three-dimensional Cu-MOF (JXUST-301) with high porosity was constructed based on the naphthalene diimide (NDI) ligand. Furthermore, JXUST-301 with ligand defects (JXUST-301D) originating from the missing NDI unit was synthesized via an in situ reaction. The presence of ligand defects endows JXUST-301D with a better CO2RR performance with a FEC2 of 56.7% and a jC2 of -162.4 mA cm-2. Mechanistic studies revealed that the hierarchical pore structure and amino sites are created from the absence of the NDI unit, which promotes the exposure of catalytically active sites and CO2 enrichment. Furthermore, the electronic structure of the Cu sites is modulated to upshift the d-band center, facilitating chemical adsorption and activation of key reaction intermediates. This work provides new insight into the in situ preparation of efficient Cu-MOF catalysts by introducing defects for the CO2RR.

Study on Quality and Starch Characteristics of Powdery and Crispy Lotus Roots.

Nine varieties of lotus root (Suining, Xinhe, Zaohua, Zhonghua, L0014, L0013, Cuiyu, L0011, and Zhenzhu) were selected as the research materials to compare their differences in physical, chemical, and starch characteristics before and after boiling, frying, and microwaving. The results showed that Zhenzhu, Xinhe, L0013, Cuiyu, and Zhonghua belong to the crispy lotus root type, while L0011, L0014, Zaohua, and Suining belong to the powdery lotus root type. Furthermore, the nine varieties were characterized for their starch by optical micrograph (OM), polarized micrograph (PM), scanning electron micrograph (SEM), attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR), X-ray diffraction (XRD), carbon-13 cross-polarization/magic angle spinning nuclear magnetic resonance (13C CP/MAS NMR), and differential scanning calorimetry (DSC). The starch granule of powdery lotus root appeared to be larger than that of crispy lotus, and ATR-FTIR studies revealed that the outer layer of starch granules from nine different varieties of lotus root had a highly organized structure. Moreover, XRD and 13C CP/MAS NMR analyses revealed that starch from eight lotus varieties (Suining, Xinhe, Zaohua, Zhonghua, L0014, L0013, Cuiyu, L0011) belong to the A-crystal type, while starch from Zhenzhu belongs to the CA-crystal type. The starch from powdery lotus root exhibited higher crystallinity, as well as increased gelatinization temperature and enthalpy, indicating that its crystal structure was relatively superior compared to that of crispy lotus starch. The short-range order degree, crystallinity, gelatinization temperature, and heat enthalpy of lotus starch decreased after boiling and frying but increased to varying extents after microwaving. Additionally, the heat resistance and stability of starch particles from crispy lotus root were improved after microwave treatment.

Roles of Hypoxia-Inducible Factor-Prolyl Hydroxylases in Aging and Disease.

The prolyl hydroxylase domain-containing (PHD or EGL9-homologs) enzyme family is mainly known for its role in the cellular response to hypoxia. HIF-PH inhibitors can stabilize hypoxia-inducible factors (HIFs), activating transcriptional programs that promote processes such as angiogenesis and erythropoiesis to adapt to changes in oxygen levels. HIF-PH inhibitors have been clinically approved for treating several types of anaemia. While most discussions of the HIF-PH signalling axis focus on hypoxia, there is a growing recognition of its importance under normoxic conditions. Recent advances in PHD biology have highlighted the potential of targeting this pathway therapeutically for a range of aging-related diseases. In this article, we review these recent discoveries, situate them within the broader context of aging and disease, and explore current therapeutic strategies that target PHD enzymes for these indications.

Light signaling-dependent regulation of plastid RNA processing in Arabidopsis.

Light is a vital environmental signal that regulates the expression of plastid genes. Plastids are crucial organelles that respond to light, but the effects of light on plastid RNA processing following transcription remain unclear. In this study, we systematically examined the influence of light exposure on plastid RNA processing, focusing on RNA splicing and RNA editing. We demonstrated that light promotes the splicing of transcripts from the plastid genes rps12, ndhA, atpF, petB, and rpl2. Additionally, light increased the editing rate of the accD transcript at nucleotide 794 (accD-794) and the ndhF transcript at nucleotide 290 (ndhF-290), while decreasing the editing rate of the clpP transcript at nucleotide 559 (clpP-559). We have identified key regulators of signaling pathways, such as CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1), ELONGATED HYPOCOTYL 5 (HY5), and PHYTOCHROME-INTERACTING FACTORs (PIFs), as important players in the regulation of plastid RNA splicing and editing. Notably, COP1 was required for GENOMES UNCOUPLED1 (GUN1)-dependent repression of clpP-559 editing in the light. We showed that HY5 and PIF1 bind to the promoters of nuclear genes encoding plastid-localized RNA processing factors in a light-dependent manner. This study provides insight into the mechanisms underlying light-mediated post-transcriptional regulation of plastid gene expression.

Colorimetric aptasensing of microcystin-LR using DNA-conjugated polydiacetylene.

Polydiacetylene (PDA) holds promise as a versatile material for biosensing applications due to its unique optical properties and self-assembly capabilities. In this study, we developed a colorimetric detection biosensor system utilizing PDA and aptamer for the detection of microcystin-LR (MC-LR), a potent hepatotoxin found in cyanobacteria-contaminated environments. The biosensor was constructed by immobilizing MC-LR-specific aptamer on magnetic beads, where the aptamer was hybridized with a urease-labelled complementary DNA (cDNA-urease). Upon binding MC-LR, the aptamer undergoes a conformational change to release cDNA-urease. The released cDNA-urease is subsequently captured by PDA bearing a single-stranded DNA (ssDNA). The enzymatic reaction triggers a distinctive color transition of PDA from blue to red. The results demonstrate exceptional sensitivity, with a linear detection range of 5-100 ng/mL and a limit of detection as low as 1 ng/mL. The practicability of the colorimetric method was demonstrated by detecting different levels of MC-LR in spiked water samples. The recoveries ranged from 77.3 to 102% and the color change, visible to the naked eye, underscores the practical utility for on-site applications. Selectivity for MC-LR over other microcystin variants (MC-RR and MC-YR) was confirmed. The colorimetric detection platform capitalizes on the properties of PDA and nucleic acid, offering a robust method for detecting small molecules with potential applications in environmental monitoring and public health.

Analysis and validation of diagnostic biomarkers and immune cell infiltration characteristics in Crohn's disease by integrating bioinformatics and machine learning.

Crohn's disease (CD) presents significant diagnostic and therapeutic challenges due to its unclear etiology, frequent relapses, and limited treatment options. Traditional monitoring often relies on invasive and costly gastrointestinal procedures. This study aimed to identify specific diagnostic markers for CD using advanced computational approaches. Four gene expression datasets from the Gene Expression Omnibus (GEO) were analyzed, identifying differentially expressed genes (DEGs) through gene set enrichment analysis in R. Key biomarkers were selected using machine learning algorithms, including LASSO logistic regression, SVM­RFE, and Random Forest, and their accuracy was assessed using receiver operating characteristic (ROC) curves and nomogram models. Immune cell infiltration was analyzed using the CIBERSORT algorithm, which helped reveal associations between diagnostic markers and immune cell patterns in CD. From a training set of 605 CD samples and 82 normal controls, we identified eight significant biomarkers: LCN2, FOLH1, CXCL1, FPR1, S100P, IGFBP5, CHP2, and AQP9. The diagnostic model showed high predictive power (AUC=0.954) and performed well in external validation (AUC = 1). Immune cell infiltration analysis highlighted various immune cells involved in CD, with all diagnostic markers strongly linked to immune cell interactions. Our findings propose candidate hub genes and present a nomogram for CD diagnosis, providing potential diagnostic biomarkers for clinical applications in CD.

Experimental study on the synchronization mechanism and trigger characteristic density of vertical evacuation in crowds.

Due to simultaneous horizontal and vertical displacement during vertical evacuation, the consequences of stampede congestion accidents can be more severe. Generally, pedestrians trigger a synchronization mechanism at some point during the vertical evacuation process. This synchronization behavior helps prevent stampede congestion and improves evacuation efficiency. This paper designs a well-controlled single-file vertical evacuation experiment. After the experiment, the video footage is imported into the TRACKER system to extract the coordinates of pedestrian step movements, after which the experimental data undergo calculations and visual analysis. The research findings indicate the following: Firstly, when the crowd coordinates trigger the synchronization mechanism, this behavior remains stable as long as pedestrian speed and direction are unchanged; Secondly, the variation in footstep speed over time is not directly related to the footstep synchronization rate of the crowd; Lastly, this study calculated the characteristic density value most likely to trigger the synchronization mechanism during vertical evacuation. This research deepens our understanding of crowd dynamics, reveals the characteristics of pedestrian movement during vertical evacuation, and proposes evacuation guidance strategies based on these features.

The impact of the COVID-19 pandemic on RSV outbreaks in children: A multicenter study from China.

OBJECTIVE: The aim of the study is to describe the season of RSV prevalence in China during the COVID-19 pandemic. METHODS: This multicenter retrospective study analyzed the epidemiology of pediatric RSV infections and the possible factors contributing to its variations in China from January 1, 2019, to October 31, 2022. RESULTS: A total of 872,565 children were included. During the pandemic, RSV detection rate increased across various regions, including South China, East China, Central China, and Northeast China. From 2019 to 2021, the detection rates of RSV showed an increasing trend among children aged <1 year, 1-2 years, and 3-5 years, but decreased in 2022. Among those tested positive for RSV, the proportion of children under 1 year old significantly decreased during the pandemic. The spring season of RSV in China in 2020 was shortened, and most regions experienced a summer season of RSV in 2021. This shift led to a year-round RSV outbreak throughout 2021. After April 2022, RSV positive rate significantly decreased, and no clear seasonal pattern was observed. CONCLUSION: Our study found that the COVID-19 pandemic has disrupted the seasonal pattern of RSV outbreaks in China, leading to increased RSV positive rate and off-season outbreaks.

Discovery of Bis-imidazolecarboxamide Derivatives as Novel, Potent, and Selective TNIK Inhibitors for the Treatment of Idiopathic Pulmonary Fibrosis.

Traf2- and Nck-interacting kinase (TNIK) has been identified as a promising therapeutic target for the treatment of fibrosis-driven diseases. Utilizing a structure-based drug design workflow, we developed a series of potent TNIK inhibitors that modulate the conformation of the gatekeeper Met105 side chain and access the TNIK back pocket. The lead optimization efforts culminated in the discovery of the recently reported compound 4 (INS018_055), a novel TNIK inhibitor. This molecule demonstrated excellent activity in both enzymatic and cell-based assays, along with high selectivity in a kinome panel. Further, in vitro and in vivo preclinical studies revealed favorable in vitro and in vivo DMPK properties. Results from multiple cell-based and animal models proved that compound 4 exhibits considerable antifibrotic and anti-inflammatory efficacy. Currently, phase II clinical trials of compound 4 are underway for the treatment of idiopathic pulmonary fibrosis (IPF).

Establishment of cross-priming amplification for point-of-care detection of Mycobacterium tuberculosis and non-tuberculosis mycobacteria.

Objective: To simplify sputum sample preparation steps and achieve point-of-care testing (POCT) of Mycobacterium tuberculosis (MTB) and non-tuberculosis mycobacteria (NTM) using Cross-Priming Amplification (CPA) technology on portable devices, overcoming the challenges of existing nucleic acid detection technologies that cannot be widely promoted in grassroots settings in China. Methods: Evaluate the liquefying ability of high-concentration guanidine thiocyanate (GTC) for sputum and the effectiveness of MTB inactivation; establish a rapid detection system for MTB and NTM based on CPA technology using EasyNAT integrated detection tubes, with the left amplification zone specific to MTB CPA amplification and the right amplification zone specific to both MTB and NTM CPA amplification. Suspected pulmonary tuberculosis (PTB) patients or patients diagnosed as suspected NTM pulmonary infections specimens collected from the Second Hospital of Longyan, Fujian Province, from September 2022 to September 2023, acid-fast bacilli (AFB) smear, quantitative real-time PCR (RT-PCR) and CPA-POCT were performed. The kappa coefficients was used to evaluate the consistency between the RT-PCR and CPA-POCT. Results: The liquefaction effect of 6M GTC on sputum was equivalent to 4 % NaOH, and no MTB growth was observed in the Lowenstein-Jensen medium of sputum samples treated with 6M GTC incorporating the H37Rv strain. The newly established CPA-POCT method showed good agreement with RT-PCR with a positive compliance rate of 86.27 %, a negative compliance rate of 89.36 %, an overall compliance rate of 87.75 %, and a Kappa coefficients of 0.786 (P < 0.05). Conclusion: 6M GTC can liquefy sputum and render MTB non-viable, eliminating the need for Mycobacterium nucleic acid testing in BSL-2 laboratories; the newly established CPA method can rapidly and accurately distinguish MTB and NTM in the form of POCT, with simple and fast operation, suitable for promotion and application in grassroots medical institutions and remote rural areas.