KLRG1-expressing CD8+ T cells are exhausted and polyfunctional in patients with chronic hepatitis B.

Killer cell lectin-like receptor G1 (KLRG1) has traditionally been regarded as an inhibitory receptor of T cell exhaustion in chronic infection and inflammation. However, its exact role in hepatitis B virus (HBV) infection remains elusive. CD8+ T cells from 190 patients with chronic hepatitis B were analyzed ex vivo for checkpoint and apoptosis markers, transcription factors, cytokines and subtypes in 190 patients with chronic hepatitis B. KLRG1+ and KLRG1- CD8+ T cells were sorted for transcriptome analysis. The impact of the KLRG1-E-cadherin pathway on the suppression of HBV replication mediated by virus-specific T cells was validated in vitro. As expected, HBV-specific CD8+ T cells expressed higher levels of KLRG1 and showed an exhausted molecular phenotype and function. However, despite being enriched for the inhibitory molecules, thymocyte selection-associated high mobility group box protein (TOX), eomesodermin (EOMES), and Helios, CD8+ T cells expressing KLRG1 produced significant levels of tumour necrosis factor (TNF)-α, interferon (IFN)-γ, perforin, and granzyme B, demonstrating not exhausted but active function. Consistent with the in vitro phenotypic assay results, RNA sequencing (RNA-seq) data showed that signature effector T cell and exhausted T cell genes were enriched in KLRG1+ CD8+ T cells. Furthermore, in vitro testing confirmed that KLRG1-E-cadherin binding inhibits the antiviral efficacy of HBV-specific CD8+ T cells. Based on these findings, we concluded that KLRG1+ CD8+ T cells are not only a terminally exhausted subgroup but also exhibit functional diversity, despite inhibitory signs in HBV infection.

T2 mapping for quantitative assessment of ankle cartilage of weightlifters.

The research into the prevention of sports injuries among the population, particularly juveniles, has become crucial due to the increasing participation in physical exercises like fitness. To assess the difference in T2 values of ankle talar cartilage between weightlifters and healthy volunteers using quantitative magnetic resonance imaging (MRI) technique T2 mapping. Study design: Prospective. Prospective evaluation of T2 values of ankle cartilage of 50 weightlifters (30 adults and 20 juveniles) and 100 healthy volunteers (80 adults and 20 juveniles) using Siemens 3.0 T MRI with PDWI, T1WI, and T2 mapping sequences. Three physicians manually divided the talar cartilage of the ankle joint into six regions of interest. Three physicians utilized the anterior and posterior cut edges of the tibial cartilage as markers to identify the corresponding anterior and posterior cut edges of the talar cartilage on the sagittal MRI images. The medial and lateral sides were defined as half of the talar articular surface on the coronal plane. Differences in T2 values in each cartilage region were compared using independent sample T test or Mann-Whitney U test. The T2 values of talar cartilage were significantly increased in the athlete group relative to the volunteer group (35.11 and 31.99, P < 0.001), with the most significant difference observed in the juvenile athlete group compared to the volunteer group (34.42 and 28.73, P < 0.001). There was a significant difference in the T2 value of ankle talar cartilage between weightlifters and healthy volunteers, and juveniles may be more vulnerable to overuse sports injuries. This study contributes to understanding the cartilage health of juvenile athletes and the prevention of sports injuries.

Hyperglycemia-regulated tRNA-derived fragment tRF-3001a propels neurovascular dysfunction in diabetic mice.

Neurovascular dysfunction is a preclinical manifestation of diabetic complications, including diabetic retinopathy (DR). Herein, we report that a transfer RNA-derived RNA fragment, tRF-3001a, is significantly upregulated under diabetic conditions. tRF-3001a downregulation inhibits Müller cell activation, suppresses endothelial angiogenic effects, and protects against high-glucose-induced retinal ganglion cell injury in vitro. Furthermore, tRF-3001a downregulation alleviates retinal vascular dysfunction, inhibits retinal reactive gliosis, facilitates retinal ganglion cell survival, and preserves visual function and visually guided behaviors in STZ-induced diabetic mice and db/db diabetic mice. Mechanistically, tRF-3001a regulates neurovascular dysfunction in a microRNA-like mechanism by targeting GSK3B. Clinically, tRF-3001a is upregulated in aqueous humor (AH) samples of DR patients. tRF-3001a downregulation inhibits DR-induced human retinal vascular endothelial cell and Müller cell dysfunction in vitro and DR-induced retinal neurovascular dysfunction in C57BL/6J mice. Thus, targeting tRF-3001a-mediated signaling is a promising strategy for the concurrent treatment of vasculopathy and neuropathy in diabetes mellitus.

A New Method of Extracting Polygonatum sibiricum Polysaccharide with Antioxidant Function: Ultrasound-Assisted Extraction-Deep Eutectic Solvents Method.

Polygonatum sibiricum Polysaccharide (PsP) with antioxidant function is the main active component of Polygonatum sibiricum (P.sibiricum). The currently poor extraction yield and extraction methods of PsP cannot meet the application of that in food industrial production. In this research, an ultrasound-assisted extraction-deep eutectic solvents (UAE-DESs) method, which has never been used in the PsP industry, was first used to extract PsP. The extraction conditions were optimized by the response surface method (RSM). Both the extraction yield and antioxidant function were simultaneously considered during the optimization process. The indicators of PsP's level and antioxidant activity in vitro were used to present the extraction yield of the UAE-DESs method, the purity, and the antioxidant effect of PsP. Under the optimal conditions, which included a liquid-solid ratio of 26:1 (mL:g), extraction temperature of 80 °C, ultrasonic time of 51 min, and ultrasonic power of 82 W, the PsP extraction yield could reach (43.61 ± 0.09)%, which was obviously higher than single DESs (33.81%) and UAE (5.83%), respectively, and the PsP appeared favorably antioxidant function. This research proposed an efficient extraction method for PsP, filled the basic research gap, and further improved the development of PsP as a dietary supplement with antioxidant function in the food industry.

Using TikTok to Educate, Influence, or Inspire? A Content Analysis of Health-Related EduTok Videos.

This study explores how people engage with educational and motivational content on TikTok. We conducted a mixed-methods content analysis of N = 400 health videos from the prosocial EduTok campaign. Two theories guided our analysis of content: the motivational theory of role modeling and the health belief model. Our results revealed that audiences most frequently engaged with educational videos related to diet, exercise, and sexual health. Role model appeals were prominently featured and highly engaged with. However, these videos often framed health promotion through an ideal lens, without including information needed for behavior change attainability. The prevalence of constructs from the health belief model in videos varied. Videos emphasizing prevention, cues to action, and behavior antecedents including perceived benefits and severity attracted more views and engagement than videos that did not include these concepts. We further observed a trend in which content creators used severity in a sensational manner to elicit shock and outrage, which in turn boosted content virality. When included, videos featuring efficacy appeals garnered higher engagement. However, these appeals were less common and had limited reach. Overall, our findings provide implications for using role modeling and theory-driven appeals in social media eHealth communication.

Single-cell RNA sequencing reveals a unique pericyte type associated with capillary dysfunction.

Background: Capillary dysfunction has been implicated in a series of life- threatening vascular diseases characterized by pericyte and endothelial cell (EC) degeneration. However, the molecular profiles that govern the heterogeneity of pericytes have not been fully elucidated. Methods: Single-cell RNA sequencing was conducted on oxygen-induced proliferative retinopathy (OIR) model. Bioinformatics analysis was conducted to identify specific pericytes involved in capillary dysfunction. qRT-PCRs and western blots were conducted to detect Col1a1 expression pattern during capillary dysfunction. Matrigel co-culture assays, PI staining, and JC-1 staining was conducted to determine the role of Col1a1 in pericyte biology. IB4 and NG2 staining was conducted to determine the role of Col1a1 in capillary dysfunction. Results: We constructed an atlas of > 76,000 single-cell transcriptomes from 4 mouse retinas, which could be annotated to 10 distinct retinal cell types. Using the sub-clustering analysis, we further characterized retinal pericytes into 3 different subpopulations. Notably, GO and KEGG pathway analysis demonstrated that pericyte sub-population 2 was identified to be vulnerable to retinal capillary dysfunction. Based on the single-cell sequencing results, Col1a1 was identified as a marker gene of pericyte sub-population 2 and a promising therapeutic target for capillary dysfunction. Col1a1 was abundantly expressed in pericytes and its expression was obviously upregulated in OIR retinas. Col1a1 silencing could retard the recruitment of pericytes toward endothelial cells and aggravated hypoxia-induced pericyte apoptosis in vitro. Col1a1 silencing could reduce the size of neovascular area and avascular area in OIR retinas and suppressed pericyte-myofibroblast transition and endothelial-mesenchymal transition. Moreover, Col1a1 expression was up-regulated in the aqueous humor of the patients with proliferative diabetic retinopathy (PDR) or retinopathy of prematurity (ROP) and up-regulated in the proliferative membranes of PDR patients. Conclusions: These findings enhance the understanding of the complexity and heterogeneity of retinal cells and have important implications for future treatment of capillary dysfunction.

Tribological behaviors of laser textured surface under different lubrication conditions for rotary compressor.

Tribological behaviors of laser textured surface with elliptical dimples were experimentally compared with that of the smooth one under different lubrication conditions, including the poor-oil, rich-oil and dry lubrication. The lubrication regime was analyzed with the increasing operating load by ring-on-ring tribological tests. Finally, the performance impact of rolling piston rotary compressor with textures fabricated on the thrust surfaces was investigated. Results show that the tribological improvement strongly depends on lubrication condition. With the increase of applied loads under rich-oil and poor-oil lubrication, the effect of micro dimple promotes the critical load transforming lubrication regime, and expands the range of hydrodynamic lubrication, meanwhile maintains a similar minimum of friction coefficient as the smooth surface but enhances wear resistance. However, it is reverse to increase the friction coefficient and surface wear for the textured surfaces under dry lubrication. The compressor performance can be improved significantly by laser surface texturing with a 2% reduction of friction power consumption and a 2.5% enhancement of energy efficiency ratio.

Contactin-6-deficient male mice exhibit the abnormal function of the accessory olfactory system and impaired reproductive behavior.

INTRODUCTION: Contactin-6 (CNTN6), also known as NB-3, is a neural recognition molecule and a member of the contactin subgroup of the immunoglobulin superfamily. Gene encoding CNTN6 is expressed in many regions of the neural system, including the accessory olfactory bulb (AOB) in mice. We aim to determine the effect of CNTN6 deficiency on the function of the accessory olfactory system (AOS). METHODS: We examined the effect of CNTN6 deficiency on the reproductive behavior of male mice through behavioral experiments such as urine sniffing and mate preference tests. Staining and electron microscopy were used to observe the gross structure and the circuitry activity of the AOS. RESULTS: Cntn6 is highly expressed in the vomeronasal organ (VNO) and the AOB, and sparsely expressed in the medial amygdala (MeA) and the medial preoptic area (MPOA), which receive direct and/or indirect projections from the AOB. Behavioral tests to examine reproductive function in mice, which is mostly controlled by the AOS, revealed that Cntn6-/- adult male mice showed less interest and reduced mating attempts toward estrous female mice in comparison with their Cntn6+/+ littermates. Although Cntn6-/- adult male mice displayed no obvious changes in the gross structure of the VNO or AOB, we observed the increased activation of granule cells in the AOB and the lower activation of neurons in the MeA and the MPOA as compared with Cntn6+/+ adult male mice. Moreover, there were an increased number of synapses between mitral cells and granule cells in the AOB of Cntn6-/- adult male mice as compared with wild-type controls. CONCLUSION: These results indicate that CNTN6 deficiency affects the reproductive behavior of male mice, suggesting that CNTN6 participated in normal function of the AOS and its ablation was involved in synapse formation between mitral and granule cells in the AOB, rather than affecting the gross structure of the AOS.

[Study on the Biological Function of Abemecilib in Inhibiting the Proliferation, Invasion and
Migration of Small Cell Lung Cancer with High c-Myc Expression].

BACKGROUND: Small cell lung cancer (SCLC) with high c-Myc expression is prone to relapse and metastasis, leading to extremely low survival rate. Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor Abemaciclib plays a key role in the treatment of tumors, but the effects and mechanisms on SCLC remain unclear. This study was to analyze the effect and molecular mechanism of Abemaciclib in inhibiting proliferation, migration and invasion of SCLC with high c-Myc expression, with a view to expanding a new direction for reducing the recurrence and metastasis. METHODS: Proteins interacting with CDK4/6 were predicted using the STRING database. The expressions of CDK4/6 and c-Myc in 31 cases of SCLC cancer tissues and paired adjacent normal tissues were analyzed by immunohistochemistry. The effects of Abemaciclib on the proliferation, invasion and migration of SCLC were detected by CCK-8, colony formation assay, Transwell and migration assay. Western blot was used to detect the expressions of CDK4/6 and related transcription factors. Flow cytometry was used to analyze the effects of Abemaciclib on the cell cycle and checkpoint of SCLC. RESULTS: The expression of CDK4/6 was associated with c-Myc by STRING protein interaction network. c-Myc can directly modalize achaete-scute complex homolog 1 (ASCL1), neuronal differentiation 1 (NEUROD1) and Yes-associated protein 1 (YAP1). Moreover, CDK4 and c-Myc regulate the expression of programmed cell death ligand 1 (PD-L1). Immunohistochemistry showed that the expressions of CDK4/6 and c-Myc in cancer tissues were higher than those in adjacent tissues(P<0.0001). CCK-8, colony formation assay, Transwell and migration assay verified that Abemaciclib could effectively inhibit the proliferation, invasion and migration of SBC-2 and H446OE(P<0.0001). Western blot analysis further showed that Abemaciclib not only inhibited CDK4 (P<0.05) and CDK6 (P<0.05), but also affected c-Myc (P<0.05), ASCL1 (P<0.05), NEUROD1 (P<0.05) and YAP1 (P<0.05), which are related to SCLC invasion and metastasis. Flow cytometry showed that Abemaciclib not only inhibited the cell cycle progression of SCLC cells (P<0.0001), but also significantly increased PD-L1 expression on SBC-2 (P<0.01) and H446OE (P<0.001). CONCLUSIONS: Abemaciclib significantly inhibits the proliferation, invasion, migration and cell cycle progression of SCLC by inhibiting the expressions of CDK4/6, c-Myc, ASCL1, YAP1 and NEUROD1. Abemaciclib can also increase the expression of PD-L1 in SCLC.

A theoretical study on the photochemical generation of phenylborylene from phenyldiazidoborane.

Organic borylenes are a kind of highly reactive species, which play important roles in a lot of reactions as vigorous intermediates. In this work, we investigated the photochemical generation mechanisms of phenylborylene (PhB) together with the side product N-phenylnitrenoiminoborane (PhNBN) from phenyldiazidoborane (PhBN6) by extrusion of dinitrogen in the two lowest electronic singlet states (S0 and S1) based on the complete active space self-consistent field (CASSCF) and its second-order perturbation (CASPT2) methods combined with time-dependent density functional theory (TD-DFT) calculations. Our results show that the reaction PhBN6 → PhB + 3N2 involves stepwise N2 extrusion three times and the azido region rearrangement. Moreover, we found that the studied photo-induced processes are kinetically feasible because the highest energy barrier is only 0.36 eV and excitation with light of wavelength 254 nm can provide enough excess energy to overcome these energy barriers. Importantly, we revealed that several conical intersections between S1 and S0 states participate and facilitate the studied photochemical processes. Our results not only clarify the experimental observations, (H. F. Bettinger, J. Am. Chem. Soc. 2006, 128, 2534), but also provide valuable insights into borylene chemistry.

Derivation of copper water quality criteria in Bohai Bay for the protection of local aquatic life and the ecological risk assessment.

Developing effective marine water quality criteria (WQC) is crucial for controlling marine contamination and protecting marine life. The WQC for copper is urgently needed due to the toxicity and widespread of copper contamination. In this work, both short-term water quality criteria (SWQC) and long-term water quality criteria (LWQC) under 10 % effect endpoints were derived by using the model averaging of species sensitivity distribution (SSD10) method for Bohai Bay. The WQC values were obtained directly from the hazardous concentration for 5 % of species (HC5) values, which removes the influence of arbitrary assessment factor (AF). Modifications to the acute-chronic ratio (ACR) strategies and the inclusion of the test toxicity data of local species also improved the accuracy and applicability of the WQC values. The derived SWQC and LWQC were 2.21 and 0.45 µg/L, respectively. Furthermore, the overall risk level of copper in Bohai Bay was evaluated by using the risk quotient (RQ) method, and the results showed it was at a moderate-low level. This study provides a new approach for the derivation of the WQC for Cu and the risk assessment of Bohai Bay, which is essential for the protection of local aquatic life and provides guidance to the establishment of the national WQC.

Strategies to inTerrupt RAbies Transmission for the Elimination Goal by 2030 In China (STRATEGIC): a modelling study.

BACKGROUND: A global plan has been set to end human deaths from dog-mediated rabies by 2030 ("Zero-by-30"), but whether it could be achieved in some countries, such as China, remains unclear. Although elimination strategies through post-exposure prophylaxis (PEP) use, dog vaccination, and patient risk assessments with integrated bite case management (IBCM) were proposed to be cost-effective, evidence is still lacking in China. We aim to evaluate the future burdens of dog-mediated human rabies deaths in the next decade and provide quantitative evidence on the cost-effectiveness of different rabies-control strategies in China. METHODS: Based on data from China's national human rabies surveillance system, we used decision-analytic modelling to estimate dog-mediated human rabies death trends in China till 2035. We simulated and compared the expected consequences and costs of different combination strategies of the status quo, improved access to PEP, mass dog vaccination, and use of IBCM. RESULTS: The predicted human rabies deaths in 2030 in China will be 308 (95%UI: 214-411) and remain stable in the next decade under the status quo. The strategy of improved PEP access alone could only decrease deaths to 212 (95%UI: 147-284) in 2028, remaining unchanged till 2035. In contrast, scaling up dog vaccination to coverage of 70% could eliminate rabies deaths by 2033 and prevent approximately 3,265 (95%UI: 2,477-3,687) extra deaths compared to the status quo during 2024-2035. Moreover, with the addition of IBCM, the "One Health" approach through mass dog vaccination could avoid unnecessary PEP use and substantially reduce total cost from 12.53 (95%UI: 11.71-13.34) to 8.73 (95%UI: 8.09-9.85) billion US dollars. Even if increasing the total costs of IBCM from 100 thousand to 652.10 million US dollars during 2024-2035, the combined strategy of mass dog vaccination and use of IBCM will still dominate, suggesting the robustness of our results. CONCLUSIONS: The combined strategy of mass dog vaccination and IBCM requires collaboration between health and livestock/veterinary sectors, and it could eliminate Chinese rabies deaths as early as 2033, with more deaths averted and less cost, indicating that adding IBCM could reduce unnecessary use of PEP and make the "One Health" rabies-control strategy most cost-effective.

[Determination of 25-hydroxyvitamin D in serum by pre-column derivatization-stable isotope labeling-ultra performance liquid chromatography-quadrupole electrostatic field orbitrap high-resolution mass spectrometry].

OBJECTIVE: To establish a rapid and accurate method for the determination of 25-hydroxyvitamin D_3(25(OH)D_3) and 25-hydroxyvitamin D_2(25(OH)D_2)in serum by pre-column derivatization with stable isotope labeling and ultra performance liquid chromatography-quadrupole electrostatic field orbitrap high-resolution mass spectrometry, which could be used to diagnose vitamin deficiency and to assess the nutritional status of vitamin D in the population. METHODS: The serum samples with isotopic internal standard were extracted by mixed extraction solvent(ethyl acetate∶hexane = 2∶1, V/V), centrifuged and dried by the nitrogen blowing, and derivatized with 4-phenyl-1, 2, 4-triazoline-3, 5-dione(PTAD). The reaction products were separated on a BEH C_(18) column(2.1 mm×50 mm, 1.7 µm), and eluted with a 0.1% formic acid/water solution-acetonitrile gradient. The mass spectrometry was performed in positive electrospray ionization(ESI~+) and parallel reaction monitoring(PRM) for the detection of the targets, and quantified by isotope internal standard. RESULTS: The limits of detection both for 25(OH)D_3 and 25(OH)D_2 were 0.01 ng/mL and the limits of quantification were 0.03 ng/mL. The concentration series of 25(OH)D_2 ranged from 0.5 to 40.0 ng/mL and the concentration series of 25(OH)D_3 ranged from 2.5 to 200.0 ng/mL. The recoveries(n=5) were 95.7%-101.3% for 25(OH)D_3, and 98.7%-108.6% for 25(OH)D_2, with the relative standard deviations(RSDs) of 0.5%-4.9% and 2.2%-3.4%, respectively. The accuracy of the determination of 25(OH)D_3 and 25(OH)D_2 in Level 2 serum of the 25(OH)D standard reference material NIST SRM 972a was 104.8% and 94.9%, respectively. The M(P25, P75)serum levels of 25(OH)D_3 and 25(OH)D_2 for 116 pregnant women at the first trimester from Beijing were 25.7(20.8, 32.6) ng/mL and 0.8(0.4, 1.1) ng/mL, respectively. CONCLUSION: This method is highly sensitive, qualitatively accurate and suitable for evaluation and monitoring the nutritional status of vitamin D in the population.

Epidemic Characteristics, High-Risk Areas and Space-Time Clusters of Human Brucellosis - China, 2020-2021.

Introduction: Analyze the recent epidemiological and temporal-spatial characteristics of human brucellosis in China and provide information for adjusting strategies for brucellosis control. Methods: Human brucellosis data were obtained from the National Notifiable Disease Reporting System (NNDRS). A geographical information system (GIS) was used to visualize high-risk areas with annual incidence based on county (district) polygons. The space-time scan statistic (STSS) was applied to detect the space-time clusters of human brucellosis. Results: A total of 69,767 cases were reported from 2,083 counties in the mainland of China in 2021, a 47.7% increase from 2020 (47,425). About 95.5% of the total cases were centralized in northern China and 31.8% in Inner Mongolia (IM). The number of counties with an incidence exceeding 100 per 100,000 was 34 in 2020 and 65 in 2021. From 2020 to 2021, 24 space-time clusters were detected. The two primary clusters were located northeast of IM, including 109 counties. The secondary clusters affected 208 counties in 2020 and spread to 297 counties in 2021, the majority of which were located in the middle of IM, exhibiting a trend spreading west from IM to neighboring provincial-level administrative divisions (PLADs). Conclusions: From 2020 to 2021, the incidence of human brucellosis nationwide was exponential, demonstrating distinct spatiotemporal characteristics. Space-time clusters were located in IM and neighboring areas. Therefore, considerable efforts are required to curb this momentum.

Enriched environment during adolescence modulates lipid metabolism and emotion-related behaviors in mice.

Enriched environment (EE) is an important animal experimental paradigm to decipher gene-environment interaction. It is thought to be efficient in aiding recovery from certain metabolism disorders or cognitive impairments. Recently, the effects of EE during adolescence in mice gradually draw much attention. We first established an EE model in adolescent mice, dissected lipid metabolism, and further examined baseline level of anxiety and depression by multiple behavioral tests, including open field test (OFT), elevated zero maze (EZM), tail suspension test (TST), and forced swimming test (FST). EE mice exhibited lower weights, lower cholesterol than standard housing (SH) mice. Behaviorally, EE mice traveled more distance and had higher velocity than SH mice in OFT and EZM. Besides, EE mice showed reduced anxiety levels in OFT and EZM. Furthermore, EE mice also had less immobility time than SH mice in TST and FST. Thus, these results suggest that EE during adolescence has metabolic and behavioral benefits in mice.

tRNA-derived fragment tRF-1001: A novel anti-angiogenic factor in pathological ocular angiogenesis.

Transfer RNA-derived fragments (tRFs) are a novel class of non-coding RNA transcripts and play important roles in several physiological/pathological processes. However, the role of tRFs in ocular angiogenesis remains elusive. Herein, we investigate whether the intervention of tRF-1001 expression could suppress pathological ocular angiogenesis. The results show that the levels of tRF-1001 expression were reduced in the retinas of an oxygen-induced retinopathy (OIR) model, choroidal neovascularization model, and endothelial sprouting model in vitro. Increased tRF-1001 expression could suppress ocular angiogenesis and endothelial sprouting in vivo and reduce endothelial migration, specification, and sprouting in vitro. Mechanistically, tRF-1001 regulated endothelial angiogenic effects via tRF-1001/METTL3/RBPJ-MAML1 signaling. The levels of tRF-1001 expression were downregulated in the aqueous humor of age-related macular degeneration (AMD) patients. tRF-1001 upregulation could suppress AMD aqueous humor-induced endothelial sprouting and pathological angiogenesis. Collectively, tRF-1001 acts as an anti-angiogenic factor during ocular angiogenesis. Targeting tRF-1001-mediated signaling is a therapeutic option for ocular neovascular diseases.

Association of Dietary Patterns with Metabolic Syndrome in Chinese Children and Adolescents Aged 7-17: The China National Nutrition and Health Surveillance of Children and Lactating Mothers in 2016-2017.

This study aims to determine the associations of dietary patterns with metabolic syndrome (MetS) and its components in Chinese children and adolescents aged 7-17 in 2016-2017. Using the data from the China National Nutrition and Health Surveillance of Children and Lactating Mothers in 2016-2017, the sociodemographic information, diet, anthropometric measurements and clinical examinations of subjects were obtained, and a total of 13,071 school-aged children and adolescents were included in this study. The Cook criteria were used to define MetS and its components. Dietary intake was derived from 24-h dietary records for three consecutive days, combined with the weighing method. Factor analysis was used to identify major dietary patterns. The associations of dietary patterns with MetS and its components were examined by logistic regression analysis. Consequently, five distinct dietary patterns were identified by factor analysis, and the relationships between dietary patterns with MetS and its components were observed. After adjusting for covariates, the animal product and vegetable patterns may have a positive association with MetS; the condiment pattern was positively associated with low HDL-C; the fruit and junk food patterns had positive relationships with MetS, abdominal obesity and high TG; the cereals and tubers pattern was positively associated with MetS, abdominal obesity, high TG and low HDL-C; the beans pattern was positively associated with high TG.

Diversity of Ceftazidime-Avibactam Resistance Mechanism in KPC2-Producing Klebsiella pneumoniae Under Antibiotic Selection Pressure.

Purpose: The aim of this study was to understand the resistance mechanism of ceftazidime/avibactam (CZA) in carbapenem-resistant Klebsiella pneumoniae under antibiotic selection pressure. Patients and Methods: Four CZA-resistant Klebsiella pneumoniae strains were isolated from two patients, and six CZA-resistant strains that were produced in vitro were screened from 25 carbapenem-resistant Klebsiella pneumoniae strains. The mechanisms of resistance to CZA of these strains were characterized by PCR and Sanger sequencing. Results: CZA-resistant Klebsiella pneumoniae with different resistance mechanisms (including upregulation of the expression of efflux pumps and KPC variants (KPC-14, KPC-44)) were isolated from the same patient (patient 1). In patient 2, the resistance mechanism of CZA-resistant Klebsiella pneumoniae was the mutation of KPC-2 to KPC-33. In addition, among the CZA-resistant Klebsiella pneumoniae that were produced in vitro, we found 3 new KPC variants: KPC-86 (D179G), KPC-87 (GT241A) and KPC-88 (G523T). Conclusion: In this study, although the CZA-resistant bacteria originated from only two clinical patients, four different mechanisms of CZA resistance were detected. In the in vitro induction experiment, the mechanisms of resistance to CZA in strains from different patients were also different. The above result implies that the mechanisms of resistance to CZA are generally random and diverse. Therefore, elucidating the mechanism of resistance to CZA can provide a certain theoretical basis for the effective response of CZA-resistant strains and the selection of antibiotics.

Single-Cell Transcriptomic Analysis Reveals Neutrophil as Orchestrator during ß-Glucan-Induced Trained Immunity in a Teleost Fish.

Trained immunity defines long-term memory of innate immunity based on transcriptional, epigenetic, and metabolic modifications of myeloid cells, which are characterized by elevated proinflammatory responses toward homologous or heterologous secondary stimuli in mammals. However, the evidence of trained immunity-associated immune cells and its molecular mechanism in teleost fish remains largely unknown. In this study, we established a trained immunity activation model in turbot (Scophthalmus maximus) and found that administration with ß-glucan induces protection against a bacterial infection. Through single-cell RNA sequencing to annotate 14 clusters of innate and adaptive immune cells, as well as two clusters of blood cells, from head kidney and spleen, respectively, we characterized that neutrophil displays cardinal features of trained immunity by analyzing the expression abundance of trained immunity database-related genes at the single-cell level. Subsequently, through establishing an in vivo training and in vitro neutrophil challenge model, we found that the trained neutrophils exhibit a significant elevation of the IL-1R signaling pathway after Edwardsiella piscicida infection. Furthermore, inhibition of neutrophil's IL-1R signaling pathway through anakinra treatment impaired the heightened production of reactive oxygen, nitrogen species, lactate, as well as the neutrophil extracellular traps formation and bacterial killing ability. Taken together, these findings characterized neutrophil as the orchestrator to express features of trained immunity, and revealed that the IL-1R signaling pathway plays a critical role in induction of trained immunity for bacterial clearance in teleost fish.