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BACKGROUND: The dangerous inducers of muscle atrophy are inflammatory reaction, oxidative stress, and cachexia, etc. β‐Glucan, an important food derived active ingredient, has been reported to exert anti‐inflammatory effects, however, its effects on regulating myoblast differentiation and protein degradation are unclear. This study is aimed to investigate the mechanism of oat β‐glucan on alleviating muscle atrophy. RESULTS: The results showed that oat β‐glucan treatment reversed tumor necrosis factor‐α (TNF‐α) induced abnormal myoblast differentiation and reduced muscle atrophy related MuRF‐1 and Atrogin‐1 protein expression. The similar phenomenon was observed after using MCC950 (NLRP3 specific inhibitor) or AS1842856 (FoxO1 specific inhibitor) to suppress NLRP3 and FoxO1 expression, respectively. Exposure to β‐glucan or AS1842856 also inhibited TNF‐α induced the activation of TLR4/NF‐κB pathway by inactivating FoxO1, and subsequently suppressed the expression of NLRP3. CONCLUSION: Our results indicate that oat β‐glucan exerts essential roles in promoting myoblast differentiation and alleviating muscle atrophy via inactivating FoxO1 and NLRP3 inflammasome signal pathway. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Background: Preterm infants presented a high prevalence of congenital hypothyroidism (CH), while the optimal screening pattern is still under debate. This study aimed at evaluating the characteristics of thyroid function by conducting weekly screening during the first month of life in very preterm infants (VPIs) to achieve timely diagnosis and treatment of CH. Methods: A prospective cohort study was carried out on VPIs born with gestational age (GA) <32 weeks (w) and admitted to the participating institutes from January 1, 2019 to December 31, 2022. Serial serum thyroid hormone levels were measured weekly within the first month after birth, and at 36 w of corrected age, or before discharge. Datasets for serial thyroid hormone levels and general information were obtained. Results: A total of 5992 VPIs were enrolled in this study, of which 456 (7.6%) [95% confidence interval (CI), 6.9–8.3%] were diagnosed with CH. The incidence of CH increased with lower GA, moving from 4.8% [CI, 3.4–6.1%] at GA 31 w to 16.9% [CI, 8.3–25.4%] at GA <26 w. Among the CH subjects, 57.7% [CI, 53.1–62.2%] were identified after the first screening and classified as delayed thyrotropin elevation (dTSH). With the decrease of GA, the proportion of dTSH also increased, moving from 38.1% [CI, 27.5–48.7%] at GA 31 w to 82.6% [CI, 65.8–99.4%] at GA <26 w. Through conducting weekly screening of thyroid function, it was remarkable that only 42.3% [CI, 37.8–46.9%] of CH subjects were diagnosed during the first screening. The cumulative rate of CH identified by rescreening performed at the second, third, and fourth week was 76.1% [CI, 72.2–80.0%], 90.6% [CI, 87.9–93.3%], and 98.9% [CI, 97.9–99.9%], respectively. Conclusion: The incidence of CH and dTSH both increase with lower GA in VPIs. Dynamic screening of thyroid function by weeks within the first month of life is crucial for the timely diagnosis and treatment of CH in VPIs, and it might effectively reduce the implications of missed diagnosis and delayed treatment. Clinical Trials Registration: ChiCTR1900025234 and ChiCTR2000037918 (Registration number). [ABSTRACT FROM AUTHOR]

Influenza A virus (IAV) is a deadly zoonotic pathogen that remains a burden to global health systems despite continuous vaccinations, indicating the need for an improved vaccine strategy. In this work, we constructed a new recombinant influenza vaccine using Bacillus subtilis spores expressing M2e-FP protein (RSM2eFP) and assessed its potency and efficacy in BALB/c mouse immunized via aerosolized intratracheal inoculation (i.t.) or intragastric (i.g.) administration. Immunization via i.t. route conferred 100 % protection against 20 × LD 50 A/PR/8/34 (H1N1) virus compared with only 50 % via the i.g. route. Even when challenged with 40 × LD 50 virus, the RSM2eFP vaccine immunized via i.t. provided 80 % protection. Consistently, i.t. inoculation of RSM2eFP spore vaccine induced a stronger lung mucosal immune response and a greater cellular immune response than i.g. administration, as indicated by the high production of IgG and SIgA. In addition, the RSM2eFP spore vaccine diminished the yield of infectious virus in the lung of mice immunized via i.t. These results suggest that i.t. immunization of the RSM2eFP spore vaccine may be a promising strategy for the development of mucosal vaccines against IAV infections. [ABSTRACT FROM AUTHOR]

The Ice, Cloud, and Land Elevation Satellite–2 (ICESat–2) carries the Advanced Topographic Laser Altimeter System (ATLAS), enabling global canopy height measurements from forest canopy height models (CHMs). Topographic slope is a crucial factor affecting the accuracy of canopy height estimates from ICESat–2 CHMs, but it has not been sufficiently studied. This paper aims to eliminate the influence of slope on canopy height estimates from ICESat–2 data and establishes a method for correcting forest canopy heights based on high spatial resolution digital orthophoto maps (DOM). The cross-track photons are corrected horizontally to eliminate the estimation error. Multi-resolution segmentation is used to segment tree crowns in the DOM, and the distance and relative position between the top of canopy (TOC) photons and the center point of the crown are calculated. TOC photon correction rules are established for different terrains, and the vertical error of the TOC photons is corrected. The results indicate that the vertical error increases exponentially with the slope. The cross-track photon correction and the TOC photon correction method eliminate the effect of slope on canopy height estimates. The cross-track photon correction method reduces the mean absolute error (MAE) and root mean square error (RMSE) of the canopy height estimates by 35.71% and 35.98%, respectively. The TOC photon correction approach further reduces the MAE and RMSE by 23% and 19.23%, respectively. The proposed method has significantly higher accuracy for forest canopy height estimation using ICESat–2 data than the traditional method. [ABSTRACT FROM AUTHOR]

Coxiella burnetii is the etiological agent of the zoonotic disease Q fever, which is featured by its ability to replicate in acid vacuoles resembling the lysosomal network. One key virulence determinant of C. burnetii is the Dot/Icm system that transfers more than 150 effector proteins into host cells. These effectors function to construct the lysosome-like compartment permissive for bacterial replication, but the functions of most of these effectors remain elusive. In this study, we used an affinity tag purification mass spectrometry (AP-MS) approach to generate a C. burnetii-human protein-protein interaction (PPI) map involving 53 C. burnetii effectors and 3480 host proteins. This PPI map revealed that the C. burnetii effector CBU0425 (designated CirB) interacts with most subunits of the 20S core proteasome. We found that ectopically expressed CirB inhibits hydrolytic activity of the proteasome. In addition, overexpression of CirB in C. burnetii caused dramatic inhibition of proteasome activity in host cells, while knocking down CirB expression alleviated such inhibitory effects. Moreover, we showed that a region of CirB that spans residues 91–120 binds to the proteasome subunit PSMB5 (beta 5). Finally, PSMB5 knockdown promotes C. burnetii virulence, highlighting the importance of proteasome activity modulation during the course of C. burnetii infection. Author summary: As the causative agent of Q fever, C. burnetii colonizes host cells by transferring effector proteins into the host cytoplasm through its Dot/Icm secretion system to construct a replicative vacuole. The function of effectors remains largely unknown. Here, we performed a large-scale AP-MS screen to analyze the interactions among C. burnetii effectors and human proteins. These analyses found that CirB functions as an inhibitor of host proteasome activity, revealing that proteasome activity is important for intracellular survival of C. burnetii. Our data have laid the foundation for future exploring the molecular mechanisms underlying the roles of C. burnetii effectors in its virulence and for the identification of novel potential drug targets for the development of novel therapeutic treatment for C. burnetii infection. [ABSTRACT FROM AUTHOR]

Background: Coxiella burnetii (Cb) is the causative agent of the zoonotic disease Q fever which is distributed worldwide. Molecular typing of Cb strains is essential to find out the infectious source and prevent Q fever outbreaks, but there has been a lack of typing data for Cb strains in China. The aim of this study was to investigate the genotypes of Cb strains in wild rats in Yunnan Province, China. Results: Eighty-six wild rats (Rattus flavipectus) were collected in Yunnan Province and 8 of the 86 liver samples from the wild rats were positive in Cb-specific quantitative PCR (qPCR). The Cb strains from the 8 rats were then typed into 3 genotypes using 10-spacer multispacer sequence typing (MST), and 2 of the 3 genotypes were recognized as novel ones. Moreover, the Cb strains in the wild rats were all identified as genotype 1 using 6-loci multilocus variable number of tandem repeat analysis (MLVA). Conclusions: This is the first report of genotypic diversity of Cb strains from wild rats in China. Further studies are needed to explore the presence of more genotypes and to associate the genotypes circulating in the wildlife-livestock interaction with those causing human disease to further expand on the epidemiological aspects of the pathogen. [ABSTRACT FROM AUTHOR]

Objectives. To investigate whether hUC-MSCs attenuated severe burn-induced ALI and the effects were based on TSG-6 secreted from hUC-MSCs. Method. A rat model was established and evaluated as follows: cytokine expression was measured by ELISA, and both inflammatory cell infiltration and lung injury were assessed by immunohistochemistry assay. Results. In vitro, TSG-6 levels in serum from the burn group were significantly increased compared with those from the sham group. In vivo, TSG-6 levels of lung tissues and serum in the burn+hUC-MSC group were significantly increased compared with those in the burn group. Both in lung tissues and in serum, increased levels of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) were remarkably decreased, but the anti-inflammatory cytokine IL-10 increased after hUC-MSC administration (p < 0.05). These significant positive effects after hUC-MSC transplantation did not occur in the burn+siTSG-6 group. Conclusion. The intratracheal implantation of hUC-MSCs has been an effective treatment for severe burn-induced ALI via promoting TSG-6 secretion and inhibiting inflammatory reaction in lung tissue. [ABSTRACT FROM AUTHOR]

The WW and C2 domain containing (WWC) protein family functions as scaffolds regulating cell proliferation and organ growth control through the Hippo signaling pathway. However, their pan-cancer dysregulation and mechanistic roles in signaling transduction have remained unclear. We performed integrated pan-cancer analyses of WWC family gene expression using data from The Cancer Genome Atlas (TCGA) across 33 different cancer types. Prognostic relevance was evaluated by survival analyses. WWC genetic alterations, DNA methylation, pathway activities, drug response, and tumor immunology were analyzed using online databases. Furthermore, we examined the functional roles of WWCs in lung cancer cells. We observed aberrant WWC expression in various cancers, which associated with patient prognosis. WWC hypermethylation occurred in many cancers and exhibited negative correlation with expression, alongside mutations linked to poor outcomes. Pathway analysis implicated WWCs as Hippo pathway scaffolds, while drug sensitivity analysis suggested associations with diverse chemotherapies. Additionally, pan-cancer analyses elucidated vital immunomodulatory roles for WWC through heterogeneous correlations with immune cell infiltrates, checkpoint molecules, tumor mutation burden, microsatellite instability, and chemokine pathways across cancers. Experimentally, WWCs suppressed lung cancer cell proliferation, migration, and invasion while enhancing apoptosis and paclitaxel chemosensitivity. Mechanistically, WWCs bound large tumor suppressor 1 and 2 (LATS1/2) kinases to stimulate phosphorylation cascades, thereby inhibiting nuclear translocation of the Yes-associated protein (YAP) oncoprotein. Taken together, our multi-omics characterization provides comprehensive evidence for WWCs as putative tumor suppressors across cancers via Hippo pathway modulation. WWCs may serve as prognostic markers and therapeutic targets in lung cancer. • WWC genes exhibit abnormal expression patterns across cancers and correlate with prognosis. • WWC mutations link to poor prognosis; WWC methylation elevated and negatively correlates with WWC expression. • WWC overexpression in lung cancer reduces proliferation, migration, invasion, and promotes chemotherapy drug sensitivity. • WWC genes bind LATS1/2 kinases to stimulate phosphorylation cascades, inhibiting YAP oncoprotein nuclear translocation. [ABSTRACT FROM AUTHOR]

Uterine leiomyoma (UM) is the most common benign gynecological tumor and the leading indication for hysterectomy. Our study explored the roles of TRIM9 in leiomyoma formation and investigated the underlying molecular mechanisms. The relationship between TRIM9 expression and fibroids formation was deciphered from the GEO database after bioinformatics analysis and identified by qPCR in human leiomyoma tissues. Both TRIM9 mRNA and protein expression were further detected in primary cultured uterine leiomyoma cells (UMC). The tumorigenesis potentials of TRIM9 in cell proliferation, cell cycle, cell apoptosis; cyclin D1, survivin and cleaved-caspase 3 protein expressions in primary UMC with TRIM9 overexpression (UMC-oeTRIM9); and uterine smooth muscle cells (SMC) with TRIM9 knockdown (SMC-siTRIM9) were evaluated in vitro. NF-κB p65 and its phosphorylation were further examined by western blotting, and rescue experiments on cell proliferation, cell cycle and cell apoptosis were conducted. TRIM9 showed higher expression in UM tissue and UMC compared with normal myometrium. The overexpression of TRIM9 in UMC notably promoted UM growth via enhancement of cell proliferation, reduction of cell apoptosis, and regulation of cyclin D1, survivin, cleaved-caspase 3, and nuclear NF-κB expression, which were reversed in SMC-siTRIM9 and PDTC (an NF-κB inhibitor) intervention in UMC-oeTRIM9. To our knowledge, this was the first study demonstrating the roles of TRIM9 in cell growth progression of UM development. TRIM9 may be a potential therapeutic target for UM, by promoting leiomyoma cell proliferation and reducing cell apoptosis via activation of the NF-κB pathway. • Human uterine leiomyoma tissue has high TRIM9 compared with adjacent tissues. • TRIM9 overexpression promotes cell growth and reduces apoptotic protein expression. • NF-κB inhibition reverses the effects of TRIM9 overexpression. • The TRIM9/NF-κB axis may be a potential therapeutic target for uterine leiomyoma. [ABSTRACT FROM AUTHOR]

Catalytic wet peroxide oxidation (CWPO) enhanced by swirl flow (SF-CWPO) was developed for the first time to explore the degradation of m-cresol in 3%iron/activated carbon catalysed Fenton reaction. Under the conditions of catalyst dosage of 0.6 g/L, H 2 O 2 dosage of 1.5 mL/L, pH = 6 and reaction time of 20 min, the degradation rate of m-cresol and total organic carbon in 100 mg/L m-cresol solution reaches 81.5% and 82%, respectively. The reaction speed in the SF-CWPO system with an independently designed cyclone reactor was two times faster than the traditional CWPO systems. In addition, via liquid chromatography-mass spectrometry analysis of the degradation product, the possible degradation pathway for m-cresol was proposed. The proposed SF-CWPO can potentially be an efficient and economical method to treat organic pollutants in wastewaters. [Display omitted] • Swirl flow were introduced into catalytic wet peroxide oxidation system to improve the catalytic performance. • The SF-CWPO reactor was designed independently and can be scaled up step by step. • Centrifugal force and interfacial turbulence in SF-CWPO can improve reaction efficiency and reduce catalyst loss. [ABSTRACT FROM AUTHOR]

The new generation of satellite-borne laser radar Ice, Cloud, and land Elevation Satellite-2 (ICESat-2) data has been successfully used for ground information acquisition. However, when dealing with complex terrain and dense vegetation cover, the accuracy of the extracted understory Digital Terrain Model (DTM) is limited. Therefore, this paper proposes a photon correction data processing method based on ICESat-2 to improve the DTM inversion accuracy in complex terrain and high forest coverage areas. The correction value is first extracted based on the ALOS PALSAR DEM reference data to correct the cross-track photon data of ICESat-2. The slope filter threshold is then selected from the reference data, and the extracted possible ground photons are slope filtered to obtain accurate ground photons. Finally, the impacts of cross-track photon and slope filtering on fine ground extraction from the ICESat-2 data are discussed. The results show that the proposed photon correction and slope filtering algorithms help to improve the extraction accuracy of forest DTM in complex terrain areas. Compared with the forest DTM extracted without the photon correction and slope filtering methods, the MAE (Mean Absolute Error) and RMSE (Root Mean Square Error) are reduced by 51.90~57.82% and 49.37~53.55%, respectively. To the best of our knowledge, this is the first study demonstrating that photon correction can improve the terrain inversion ability of ICESat-2, while providing a novel method for ground extraction based on ICESat-2 data. It provides a theoretical basis for the accurate inversion of canopy parameters for ICESat-2. [ABSTRACT FROM AUTHOR]

Background: Hexavalent chromium [Cr(VI)] is recognized as a human carcinogen via inhalation. However, the molecular mechanisms by which Cr(VI) causes cancers are not well understood. Objectives: We evaluated cyclooxygenase-2 (COX-2) expression and the signaling pathway leading to this induction due to Cr(VI) exposure in cultured cells. Methods: We used the luciferase reporter assay and Western blotting to determine COX-2 induction by Cr(VI). We used dominant negative mutant, genetic knockout, gene knockdown, and chromatin immunoprecipitation approaches to elucidate the signaling pathway leading to COX-2 induction. Results: We found that Cr(VI) exposure induced COX-2 expression in both normal human bronchial epithelial cells and mouse embryonic fibroblasts in a concentration- and time-dependent manner. Deletion of IKKβ [inhibitor of transcription factor NFκB (IκB) kinase β; an upstream kinase responsible for nuclear factor κB (NFκB) activation] or overexpression of TAM67 (a dominant-negative mutant of c-Jun) dramatically inhibited the COX-2 induction due to Cr(VI), suggesting that both NFκB and c-Jun/AP-1 pathways were required for Cr(VI)-induced COX-2 expression. Our results show that p65 and c-Jun are two major components involved in NFκB and AP-1 activation, respectively. Moreover, our studies suggest crosstalk between NFκB and c-Jun/AP-1 pathways in cellular response to Cr(VI) exposure for COX-2 induction. Conclusion: We demonstrate for the first time that Cr(VI) is able to induce COX-2 expression via an NFκB/c-Jun/AP-1-dependent pathway. Our results provide novel insight into the molecular mechanisms linking Cr(VI) exposure to lung inflammation and carcinogenesis. [ABSTRACT FROM AUTHOR]

Objective: The guidelines recommend early caffeine administration for preterm infants requiring non-invasive mechanical ventilation since earlier treatment is associated with better outcomes. The objective was to evaluate the impact of early caffeine therapy (within 24 hours after birth) on respiratory outcomes in very preterm infants who were initially receiving invasive mechanical ventilation., Methods: This was an observation cohort study from 1 January 2018 to 31 December 2022 based on a database that was prospectively collected and maintained. Infants who initially received invasive mechanical ventilation were divided into two groups based on the timing of caffeine initiation: within the first 24 hours after birth (early) and within 48 hours of birth or later (late). Generalised linear mixed models with a random effect model for the centre were used to assess the impact of different caffeine initiation times on neonatal outcomes., Results: Among the cohort of 9880 infants born at <32 weeks gestation, 2381 were eligible for this study (early initiation: 1758 (73.8%) and late initiation: 623 (26.2%)). For infants born at more than 28 weeks of gestation, the adjusted generalised linear mixed model showed that the duration of invasive mechanical ventilation was 1.34 (95% CI -2.40 to -0.27) days shorter and the incidence of moderate-to-severe bronchopulmonary dysplasia (BPD) was lower (adjusted OR 0.63; 95% CI 0.41 to 0.96) in the early caffeine group compared with the late caffeine group., Conclusion: In very preterm infants who initially receive invasive mechanical ventilation, early administration of caffeine within 24 hours after birth can shorten the duration of invasive mechanical ventilation, reduce the incidence of moderate-to-severe BPD and improve respiratory outcomes. The very early initiation of caffeine treatment does not appear to be associated with any adverse outcomes., Trial Registration Number: ChiCTR1900025234., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Coxiella burnetii ( C. burnetii ) is the causative agent of Q fever, a zoonotic disease. Intracellular replication of C. burnetii requires the maturation of a phagolysosome-like compartment known as the replication permissive Coxiella -containing vacuole (CCV). Effector proteins secreted by the Dot/Icm secretion system are indispensable for maturation of a single large CCV by facilitating the fusion of promiscuous vesicles. However, the mechanisms of CCV maintenance and evasion of host cell clearance remain to be defined. Here, we show that C. burnetii secreted Coxiella vacuolar protein E (CvpE) contributes to CCV biogenesis by inducing lysosome-like vacuole (LLV) enlargement. LLV fission by tubulation and autolysosome degradation is impaired in CvpE-expressing cells. Subsequently, we found that CvpE suppresses lysosomal Ca 2+ channel transient receptor potential channel mucolipin 1 (TRPML1) activity in an indirect manner, in which CvpE binds phosphatidylinositol 3-phosphate [PI(3)P] and perturbs PIKfyve activity in lysosomes. Finally, the agonist of TRPML1, ML-SA5, inhibits CCV biogenesis and C. burnetii replication. These results provide insight into the mechanisms of CCV maintenance by CvpE and suggest that the agonist of TRPML1 can be a novel potential treatment that does not rely on antibiotics for Q fever by enhancing Coxiella-containing vacuoles (CCVs) fission.

Osteoporosis commonly occurs in the older people and severe patients, with the main reason of the imbalance of bone metabolism (the rate of bone resorption exceeding the rate of bone formation), resulting in a decrease in bone mineral density and destruction of bone microstructure and further leading to the increased risk of fragility fracture. Recent studies indicate that protein nutritional support is beneficial for attenuating osteoporosis and improving bone health. This review summarized the classical mechanisms of protein intervention for alleviating osteoporosis on both suppressing bone resorption and regulating bone formation related pathways (promoting osteoblasts generation and proliferation, enhancing calcium absorption, and increasing collagen and mineral deposition), as well as the potential novel mechanisms via activating autophagy of osteoblasts, altering bone related miRNA profiles, regulating muscle-bone axis, and modulating gut microbiota abundance. Protein nutritional intervention is expected to provide novel approaches for the prevention and adjuvant therapy of osteoporosis.

Ferulic acid (FA), predominantly existing in most cereals, can modulate the gut microbiome, but the influences of its metabolites on the microbial population and FA-transforming microorganisms are still unclear. In this study, FA and its potential phenolic metabolites were fermented in vitro for 24 h with the human fecal inoculum. A comparable short chain fatty acid (SCFA) production trend was observed in the presence and absence of substrates, suggesting limited contribution of FA mechanism to SCFA formation. Dihydroferulic acid, 3-(3,4-dihydroxyphenyl)propionic acid, and 3-(3-hydroxyphenyl)propionic acid were ascertained to be successive metabolites of FA, by tracking the intermediate variation. FA remarkably promoted the absolute abundances of total bacteria, while different metabolites affected bacterial growth of selective genera. Specific genera were identified as quantitatively correlating to the content of FA and its metabolites. Ultimately, FA-mediated gut microbiota modulation involves both the action of metabolizing microbes and the regulation effects of metabolites on bacterial growth.

Rickettsia rickettsii ( R. rickettsii ), the causative agent of Rocky Mountain spotted fever (RMSF), is the most pathogenic member among Rickettsia spp. Previous studies have shown that tripartite motif-containing 56 (TRIM56) E3 ligase-induced ubiquitination of STING is important for cytosolic DNA sensing and type I interferon production to induce anti-DNA viral immunity, but whether it affects intracellular replication of R. rickettsii remains uncharacterized. Here, we investigated the effect of TRIM56 on HeLa and THP-1 cells infected with R. rickettsii . We found that the expression of TRIM56 was upregulated in the R. rickettsii -infected cells, and the overexpression of TRIM56 inhibited the intracellular replication of R. rickettsii , while R. rickettsii replication was enhanced in the TRIM56-silenced host cells with the reduced phosphorylation of IRF3 and STING and the increased production of interferon-β. In addition, the mutation of the TRIM56 E3 ligase catalytic site impairs the inhibitory function against R. rickettsii in HeLa cells. Altogether, our study discovers that TRIM56 is a host restriction factor of R. rickettsii by regulating the cGAS-STING-mediated signaling pathway. This study gives new evidence for the role of TRIM56 in the innate immune response against intracellular bacterial infection and provides new therapeutic targets for RMSF., Importance: Given that Rickettsia rickettsii ( R. rickettsii ) is the most pathogenic member within the Rickettsia genus and serves as the causative agent of Rocky Mountain spotted fever, there is a growing need to explore host targets. In this study, we examined the impact of host TRIM56 on R. rickettsii infection in HeLa and THP-1 cells. We observed a significant upregulation of TRIM56 expression in R. rickettsii -infected cells. Remarkably, the overexpression of TRIM56 inhibited the intracellular replication of R. rickettsii , while silencing TRIM56 enhanced bacterial replication accompanied by reduced phosphorylation of IRF3 and STING, along with increased interferon-β production. Notably, the mutation of the TRIM56's E3 ligase catalytic site did not impede R. rickettsii replication in HeLa cells. Collectively, our findings provide novel insights into the role of TRIM56 as a host restriction factor against R. rickettsii through the modulation of the cGAS-STING signaling pathway., Competing Interests: The authors declare no conflict of interest.

Background: Recent advancements in China's perinatal and neonatal intensive care have significantly reduced neonatal mortality, yet preterm births before 32 weeks remain the primary cause of neonatal fatalities and contribute to long-term disabilities. The prognosis of very preterm infants (VPIs) is significantly affected by factors including the intrauterine environment, delivery method and neonatal intensive care. Cesarean section which often used for preterm births has implications that are not fully understood, particularly concerning the type of anesthesia used. This study examines the impact of general anesthesia (GA) during cesarean delivery on VPI outcomes, aiming to identify strategies for mitigating GA-associated risks., Methods: This cohort study analyzed 1,029 VPIs born via cesarean section under 32 weeks' gestation at our single-center from 1 January 2018, to 31 December 2022. Detailed medical records, encompassing perioperative information, maternal data and neonatal outcomes were meticulously examined. The primary aim of this investigation was to compare maternal characteristics and neonatal outcomes between VPIs delivered under GA and neuraxial anesthesia (NA). A significance level of p < 0.05 was established., Results: Of the 1,029 VPIs analyzed, 87.95% (n = 905) were delivered via NA and 12.05% (n = 124) via GA. Mothers with hypertensive pregnancy diseases and emergency operations were more inclined to choose GA. VPIs delivered under GA showed a lower Apgar score at one and 5 minutes ( p < 0.01), increased need for tracheal intubation resuscitation (32.2% vs. 12.2%, p < 0.01) and a greater incidence of severe neurological injury (SNI) (14.5% vs. 5%, p < 0.01). Multivariable analysis revealed GA was significantly associated with lower Apgar scores at one (OR 6.321, 95% CI 3.729-10.714; p < 0.01) and 5 minutes (OR 4.535, 95% CI 2.975-6.913; p < 0.01), higher risk of tracheal intubation resuscitation (OR = 3.133, 95% CI = 1.939-5.061; p < 0.01) and SNI (OR = 3.019, 95% CI = 1.615-5.643; p < 0.01). Furthermore, for VPIs delivered under GA, a prolonged interval from skin incision to fetus delivery was associated with a lower 5-min Apgar score ( p < 0.01)., Conclusion: This study revealed the significant impact of GA on adverse outcomes among VPIs. In cases when GA is required, proactive measures should be instituted for the care of VPIs such as expediting the interval from skin incision to fetal delivery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Liu, Wang, Zhu, Zhang, Wang and Yu.)

Objective: Bronchopulmonary dysplasia (BPD) is one of the most serious complications affecting extremely preterm infants. We aimed to evaluate temporal trends in BPD and administration of respiratory support among extremely preterm infants in China over a decade., Methods: This was a retrospective study using data from a multicenter database, which included infants born less than 28 weeks' gestation discharged from 68 tertiary neonatal care centers in China between 2010 and 2019. Changes in rates and severity of BPD, as well as modalities and duration of respiratory support, were evaluated., Results: Among 4808 eligible infants with gestational age (GA) of 21 +6/7  to 27 +6/7 weeks and a mean (SD) birth weight of 980 (177) g, no significant change of median GA was found over time. Overall, 780 (16.2%) infants died before 36 weeks' postmenstrual age, 2415 (50.2%) were classified as having no BPD, 917 (19.1%) developed Grade 1 BPD, 578 (12.0%) developed Grade 2 BPD, and 118 (2.5%) developed Grade 3 BPD. The rate of BPD increased from 20.8% in 2010 to 40.7% in 2019 (aRR for trend, 1.081; 95% confidence interval, 1.062-1.099), especially for Grade 1 and Grade 2. Although survival to discharge improved over the decade, the overall survival without BPD did not change during the study period. The use of invasive mechanical ventilation (IMV) remained unchanged. However, the use of noninvasive ventilation (NIV) increased from 71.5% in 2010 to 89.8% in 2019. Moreover, the median duration of NIV increased over time, from 17.0 (4.8, 34.0) days in 2010 to 33.0 (21.0, 44.0) days in 2019, without significant change in the duration of IMV., Conclusions: Although survival increased over the decade and respiratory support practices changed significantly between 2010 and 2019 in China, with increased use and duration of NIV, there was an increased rate of BPD and survival without BPD has not improved., (© 2023 Wiley Periodicals LLC.)

Coxiella burnetii is an obligate intracellular bacterium that causes Q fever, a zoonotic disease typically manifests as a severe flu-illness. After invading into the host cells, C. burnetii delivers effectors to regulate the vesicle trafficking and fusion events to form a large and mature Coxiella -containing vacuole (CCV), providing sufficient space and nutrition for its intracellular growth and proliferation. Lysosomal trafficking regulator (LYST) is a member of the Beige and Chediak-Higashi syndrome (BEACH) family, which regulates the transport of vesicles to lysosomes and regulates TLR signaling pathway, but the effect of LYST on C. burnetii infection is unclear. In this study, a series of experiments has been conducted to investigate the influence of LYST on intracellular growth of C. burnetii . Our results showed that lyst transcription was up-regulated in the host cells after C. burnetii infection, but there is no significant change in lyst expression level after infection with the Dot/Icm type IV secretion system (T4SS) mutant strain, while CCVs expansion and significantly increasing load of C. burnetii appeared in the host cells with a silenced lyst gene, suggesting LYST inhibits the intracellular proliferation of C. burnetii by reducing CCVs size. Then, the size of CCVs and the load of C. burnetii in the HeLa cells pretreated with E-64d were significantly decreased. In addition, the level of iNOS was decreased significantly in LYST knockout THP-1 cells, which was conducive to the intracellular replication of C. burnetii . This data is consistent with the phenotype of L-NMMA-treated THP-1 cells infected with C. burnetii . Our results revealed that the upregulation of lyst transcription after infection is due to effector secretion of C. burnetii and LYST inhibit the intracellular replication of C. burnetii by reducing the size of CCVs and inducing nos2 expression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wan, Zhang, Zhao, OuYang, Yu, Xiong, Zhao and Jiao.)

The Qinghai-Tibet Plateau is the main permafrost area in China. Concrete structures constructed on permafrost are affected by the early negative-temperature environment. In particular, the negative-temperature environment seriously affects the strength growth process and the frost resistance of concrete (FRC). Therefore, this study considered the influence of the gas content, water-binder ratio (w/b), age, and other factors on the strength variation law and FRC under -3 °C curing conditions. Nuclear magnetic resonance (NMR) was used to analyze the pore structure of concrete before and after freeze-thaw cycles (FTCs). The results showed that the compressive strength of the concrete (CSC) under -3 °C curing was only 57.8-86.4% of that cured under standard conditions. The CSC under -3 °C curing showed an obvious age-lag phenomenon. The FRC under -3 °C curing was much lower than that under standard curing. The porosity of the concrete under -3 °C curing was greater, with a higher percentage of harmful and multi-harmful pores than that under standard curing. The concrete properties deteriorated primarily because curing at -3 °C hindered the hydration reaction compared with standard methods. This hindrance resulted in diminished hydration development, weakening the concrete's structural integrity. Under both curing conditions, when the gas content was between 3.2% and 3.8%, the frost resistance was the best. This is because a gas content within this range effectively enhances the internal pore structure, therefore relieving the swelling pressure caused by FTCs. Based on the freeze-thaw damage (FTD) model proposed by previous authors, a new model for the CSC under -3 °C curing reaching that of the concrete under standard curing for 28 d was established in this study. This advanced model was capable of accurately assessing the FTD of concrete structures in permafrost regions. Finally, the life expectancy of concrete in Northwest China was predicted. The life of the concrete reached 46.9 years under standard curing, while the longest life of the concrete under -3 °C curing was only 12.9 years. Therefore, attention should be paid to constructing and curing concrete structures in cold environments.

Chinese steamed bread (CSB) is a traditional food of the Chinese nation, and the preservation of its quality and freshness during storage is very important for its industrial production. Therefore, it is necessary to study the storage characteristics of CSB. Non-destructive CT technology was utilized to characterize and visualize the microstructure of CSB during storage, and also to further study of quality changes. Two-dimensional and three-dimensional images of CSBs were obtained through X-ray scanning and 3D reconstruction. Morphological parameters of the microstructure of CSBs were acquired based on CT image using image processing methods. Additionally, commonly used physicochemical indexes (hardness, flexibility, moisture content) for the quality evaluation of CSBs were analyzed. Moreover, a correlation analysis was conducted based on the three-dimensional morphological parameters and physicochemical indexes of CSBs. The results showed that three-dimensional morphological parameters of CSBs were negatively correlated with moisture content (Pearson correlation coefficient range-0.86~-0.97) and positively correlated with hardness (Pearson correlation coefficient range-0.87~0.99). The results indicate the inspiring capability of CT in the storage quality evaluation of CSB, providing a potential analytical method for the detection of quality and freshness in the industrial production of CSB.

Background: The epithelial-mesenchymal transition (EMT) plays an indispensable role in the development and progression of Endometrial cancer (EC). Nevertheless, little evidence is reported to uncover the functionality and application of EMT-related molecules in the prognosis of EC. This study aims to develop novel molecular markers for prognosis prediction in patients with EC., Methods: RNA sequencing profiles of EC patients obtained from The Cancer Genome Atlas (TCGA) database were used to screen differential expression genes (DEGs) between tumors and normal tissues. The Cox regression model with the LASSO method was utilized to identify survival-related DEGs and to establish a prognostic signature whose performance was evaluated by Kaplan-Meier curve, receiver operating characteristic (ROC) and calibration curve. Eventually, functional enrichment analysis and cellular experiments were performed to reveal the roles of prognosis-related genes in EC progression., Results: A total of 540 EMT-related DEGs in EC were screened, and subsequently a four-gene risk signature comprising SIRT2, SIX1, CDKN2A and PGR was established to predict overall survival of EC. This risk signature could serve as a meaningfully independent indicator for EC prognosis via multivariate Cox regression (HR = 2.002, 95%CI = 1.433-2.798; P < 0.001). The nomogram integrating the risk signature and clinical characteristics exhibited robust validity and performance at predicting EC overall survival indicated by ROC and calibration curve. Functional enrichment analysis revealed that the EMT-related genes risk signature was associated with extracellular matrix organization, mesenchymal development and cellular component morphogenesis, suggesting its possible relevance to epithelial-mesenchymal transition and cancer progression. Functionally, we demonstrated that the silencing of SIX1, SIRT2 and CDKN2A expression could accelerate the migratory and invasive capacities of tumor cells, whereas the downregulation of PGR dramatically inhibited cancer cells migration and invasion., Conclusions: Altogether, a novel four-EMT-related genes signature was a potential biomarker for EC prognosis. These findings might help to ameliorate the individualized prognostication and therapeutic treatment of EC patients., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Milk, enriched with high-quality protein, is a healthy and nutritious food that meets people's needs. However, consumers are turning their attention to plant-based milk due to several concerns, such as lactose intolerance, allergies and some diseases caused by milk; carbon emission from cattle farming; economical aspects; and low access to vitamins and minerals. Oat milk, which is produced from whole grain oats, is lactose free and rich in a variety of nutrients and phytochemicals. With the significant development of food processing methods and advancement in milk simulation products, the production of plant-based milk, such as cereal milk, has greatly progressed. This review described some features of oat milk analogue versus traditional milk and compared the properties, processing technologies, health effects, environmental friendliness, and consumer acceptance of these products. It is expected to provide a reference for evaluating development trends and helping consumers choose between oat milk and traditional milk., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Ltd.)

Background: The miRNA profile is changed after burn or sepsis and is involved in regulating inflammatory reactions. However, the function and molecular mechanism of miRNAs in regulating burn sepsis-induced acute kidney injury (AKI) are still unclear., Methods: In this study, animal and cell sepsis models were established after burned rats were injected with lipopolysaccharide (LPS) or NRK-52E cells treated with LPS, respectively. Cytokine expression, inflammatory cell infiltration, serum creatinine (Scr) and kidney injury molecule-1 (KIM-1) levels were analysed after the indicated treatments., Results: Burn sepsis increased the expression of inflammatory factors (TNF-α and IL-1β) and chemokines (MIP-1α, MIP-2 and MCP-1). Moreover, burn sepsis promoted macrophage and neutrophil infiltration into the kidney and upregulated the levels of Scr and KIM-1 in the kidney and urine. Ectopic expression of miR-181c significantly reduced LPS-induced TLR4 protein expression, suppressed KIM-1 mRNA levels and subsequently inhibited the activation of inflammatory genes (TNF-α and IL-1β) and chemokine genes (MIP-1α, MIP-2 and MCP-1)., Conclusions: Our results demonstrated that miR-181c could suppress TLR4 expression, reduce inflammatory factor and chemokine secretion, mitigate inflammatory cell infiltration into the kidney and downregulate KIM-1 expression, which might ultimately attenuate burn sepsis-induced AKI., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

An insufficient intracellular H 2 O 2 level and overexpressed glutathione (GSH) are still the major challenges for effective chemodynamic therapy (CDT). Inspired by the unique glutamine metabolism pathway in cancer cells, herein, intelligent nanocatalytic theranostics is used to enhance intracellular reactive oxygen species (ROS) accumulation via the production of H 2 O 2 by a biomimetic nanozyme, and simultaneously reduce ROS consumption via the depression of GSH synthesis by the glutamine metabolic inhibitor. In this reactor, nano-sized Au and Fe 3 O 4 coloaded dendritic mesoporous silica nanoparticles (DMSN-Au-Fe 3 O 4 ) serve as the bifunctional nanozyme, where intracellular glucose is catalyzed into H 2 O 2 by the glucose oxidase-mimicking Au nanoparticles and then immediately transformed into ˙OH by the peroxidase-like Fe 3 O 4 nanoparticles. Then, CB839, the glutaminase (GLS) inhibitor, is grafted on the nanozyme, blocking the glutamine pathway and GSH biosynthesis. As a result, the as-designed nanoplatform with a three-pronged integration of Au-mediated H 2 O 2 self-supply, Fe 3 O 4 -triggered Fenton-like reaction, and glutamine pathway-mediated GSH depletion significantly boosts the CDT efficacy, achieving remarkable and specific antitumor properties both in vitro and in vivo . This work not only paves a new way for rationally designing multi-functional nanozymes for achieving high therapeutic efficacy, but also provides new insights into the construction of bioinspired synergetic therapy by combining CDT and a key anticancer pathway.

Oat is classified as a whole grain and contains high contents of protein, lipids, carbohydrates, vitamins, minerals, and phytochemicals (such as polyphenols, flavonoids, and saponins). In recent years, studies have focused on the effects of oat consumption on reducing the risk of a variety of diseases. Reports have indicated that an oat diet exerts certain biological functions, such as preventing cardiovascular diseases, reducing blood glucose, and promoting intestinal health, along with antiallergy, antioxidation, and cancer preventive effects. At present, cancer is the second leading cause of death worldwide. The natural products of oat are an important breakthrough for developing new strategies of cancer prevention, and their ability to interact with multiple cellular targets helps to combat the complexity of cancer pathogenesis. In addition, the comprehensive study of the cancer prevention activity and potential mechanism of oat nutrients and phytochemicals has become a research hotspot. In this Review, we focused on the potential functions of peptides, dietary fiber, and phytochemicals in oats on cancer prevention and further revealed novel mechanisms and prospects for clinical application. These findings might provide a novel approach to deeply understand the functions and mechanisms for cancer prevention of oat consumption.

Objectives: Osteoporosis is increasingly prevalent, especially among postmenopausal women, both in China and worldwide. In previous work, soy-whey dual-protein (DP) intervention improved muscle status via regulation of gut microbiota. However, little information is available about the relationship between DP supplementation and osteoporosis., Methods: In this study, the ovariectomized rat model was used to detect the effect of DP on improving osteoporosis., Results: Significant improvement was observed in bone mineral density, bone microstructure, and bone biomechanics with both DP and zoledronic acid (positive control) intervention. DP supplementation dramatically reduced the levels of serum osteocalcin and parathyroid hormone in ovariectomized rats. Ingestion of DP also resulted in a significant decrease in the number of bone marrow adipocytes and a marked increase in the number of osteoblasts, accompanied by elevated expression of the key regulator osteoprotegerin at both mRNA and protein levels. In the analysis of fecal metabolites and intestinal microbiota, the fat metabolism-related molecules chenodeoxycholate, 21-hydroxypregnenolone, and tetrahydrocorticosterone were markedly upregulated with DP treatment, whereas the content of fatty acids such as oleic acid were significantly downregulated. The abundance of three bacterial taxa (upregulated: Ruminococcaceae UCG&#95;002; downregulated: anaerobic digester metagenome and Enterorhabdus) dramatically changed with DP intervention and was closely associated with fat metabolism-related metabolite content CONCLUSION: These results suggest that DP intervention could improve osteoporosis via regulation of bone marrow adipose tissue content and mesenchymal stem cell lineage differentiation. Furthermore, this effect might be mediated by the interaction between intestinal microbiota and metabolites., (Copyright © 2022. Published by Elsevier Inc.)

Background/objectives: Previous studies have reported that protein supplementation contributes to the attenuation of inflammation. Serious trauma such as burn injury usually results in the excessive release of inflammatory factors and organs dysfunction. However, a few reports continued to focus on the function of protein ingestion in regulating burn-induced inflammation and organ dysfunction., Materials/methods: This study established the rat model of 30% total body surface area burn injury, and evaluated the function of blended protein (mixture of whey and soybean proteins). Blood routine examination, inflammatory factors, blood biochemistry, and immunohistochemical assays were employed to analyze the samples from different treatment groups., Results: Our results indicated a decrease in the numbers of white blood cells, monocytes, and neutrophils in the burn injury group administered with the blended protein nutritional support (Burn+BP), as compared to the burn injury group administered normal saline supplementation (Burn+S). Expressions of the pro-inflammatory factors (tumor necrosis factor-α and interleukin-6 [IL-6]) and chemokines (macrophage chemoattractant protein-1, regulated upon activation normal T cell expressed and secreted factor, and C-C motif chemokine 11) were dramatically decreased, whereas anti-inflammatory factors (IL-4, IL-10, and IL-13) were significantly increased in the Burn+BP group. Kidney function related markers blood urea nitrogen and serum creatinine, and the liver function related markers alanine transaminase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase were remarkably reduced, whereas albumin levels were elevated in the Burn+BP group as compared to levels obtained in the Burn+S group. Furthermore, inflammatory cells infiltration of the kidney and liver was also attenuated after burn injury administered with blended protein supplementation., Conclusions: In summary, nutritional support with blended proteins dramatically attenuates the burn-induced inflammatory reaction and protects organ functions. We believe this is a new insight into a potential therapeutic strategy for nutritional support of burn patients., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interests., (©2022 The Korean Nutrition Society and the Korean Society of Community Nutrition.)

Introduction: Early onset sepsis (EOS) remains a potentially fatal newborn condition, especially in very preterm infants. Data on the pathogen distribution and antibiotic susceptibility patterns of EOS among very preterm infants are scarce but essential for the choice of empirical antibiotic administration. We sought to assess the epidemiologic characteristics and antibiotic susceptibility patterns of pathogens causing EOS among a cohort of very preterm infants in China., Methods: This prospective, observational study included a cohort of infants born at a gestational age (GA) less than 32 weeks of 32 newborn intensive care units (NICUs) in China between January 1, 2018 and December 31, 2020. EOS was defined by isolation of pathogenic species from blood culture within 72 h of birth., Results: A total of 108 EOS cases (18.4 per 1000 admissions) were identified among 5865 very preterm infants. Incidence of EOS increased with the decrease of GA and birthweight. Escherichia coli (n = 44, 40.7%) was the most common pathogen, followed by Klebsiella spp. (n = 10, 9.3%). The distribution and proportion of pathogenic bacteria varied significantly by GA. E. coli and Klebsiella spp. showed high resistance to ampicillin and third-generation cephalosporins, while they showed good susceptibility to carbapenem antibiotics and piperacillin-tazobactam., Conclusion: Our data demonstrated that pathogens causing neonatal EOS showed high rates of resistance to ampicillin and third-generation cephalosporins. This raised questions about the best empirical antibiotic choice for preterm infants suspected of having EOS in low- and middle-income countries (LMICs)., (© 2022. The Author(s).)

Objective: To assess the risk of necrotizing enterocolitis (NEC) and explore the relationship between antibiotic overexposure and disease occurrence in a large prospective birth cohort. Methods: Based on a prospective birth cohort, the study collected hospitalization data of very preterm infants (VPIs) having gestational age of less than 32 weeks from January 1, 2018, to June 30, 2021 via the China Northern Neonatal Network. Infants diagnosed with NEC ≥ stage II were included in the case group, and each case was matched for GA and birth weight for the control group. Furthermore, the risk factors for NEC were determined by statistical analyses. Results: A total of 6425 VPIs were included in this study, and 167 (2.6%) of these subjects were diagnosed with NEC ≥ stage II. The study also included 984 extremely preterm infants (gestational age <28 weeks), including 50 (5.1%) infants diagnosed with NEC ≥ stage II. In the matched case-control study, subjects had a total of antibiotic days-of-therapy for 9015 days, of which broad-spectrum antibiotics (BSAs) accounted for 77%. The antibiotic spectrum index per antibiotic day in the case group was significantly higher and was an independent risk factor for the occurrence of NEC ( p = 0.001, OR = 1.13). Conclusion: The cohort of VPIs was overexposed to antiboitics. Unreasonable combination of antibiotics and overexposure to BSAs may increase the risk of NEC in preterm infants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pei, Gao, Kou, Ding, Li, Lei, Zuo, Liu, Miao, Reddy, Yu and Sun.)

Chemodynamic therapy (CDT) is a promising tumor-specific treatment, but still suffering insufficient reactive oxygen species (ROS) levels due to its limited efficacy of Fenton/Fenton-like reaction. Polyphenol, as a natural reductant, has been applied to promote the efficacy of Fenton/Fenton-like reactions; however, its intrinsic pro-apoptosis effects was ignored. Herein, a novel CDT/polyphenol-combined strategy was designed, based on Avenanthramide C-loaded dendritic mesoporous silica (DMSN)-Au/Fe 3 O 4 nanoplatforms with folic acid modification for tumor-site targeting. For the first time, we showed that the nanocomplex (DMSNAF-AVC-FA) induced ROS production in the cytoplasm via Au/Fe 3 O 4 -mediated Fenton reactions and externally damaged the mitochondrial membrane; simultaneously, the resultant increased mitochondrial membrane permeability can facilitate the migration of AVC into mitochondrial, targeting the DDX3 pathway and impairing the electron transport chain (ETC) complexes, which significantly boosted the endogenous ROS levels inside the mitochondrial. Under the elevated oxidative stress level via both intra- and extra-mitochondrial ROS production, the maximum mitochondrial membrane permeability was achieved by up-regulation of Bax/Bcl-2, and thereby led to massive release of Cytochrome C and maximum tumor cell apoptosis via Caspase-3 pathway. As a result, the as-designed strategy achieved synergistic cytotoxicity to 4T1 tumor cells with the cell apoptosis rate of 99.12% in vitro and the tumor growth inhibition rate of 63.3% in vivo , while very minor cytotoxicity to normal cells with cell viability of 95.4%. This work evidenced that natural bioactive compounds are powerful for synergistically boosting ROS level, providing new insight for accelerating the clinical conversion progress of CDT with minimal side effects., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Objectives: To explore the associations between higher antibiotic use rates (AURs) and adverse outcomes in very-low-birth-weight (VLBW) infants without culture-proven sepsis or necrotizing enterocolitis (NEC) in a multicenter of China., Methods: A prospective cohort study was performed on VLBW infants admitted to 24 neonatal intensive care units from January 1, 2018, to December 31, 2018. AUR was calculated as calendar days of antibiotic therapy divided by total hospital days. The composite primary outcome was defined as mortality or severe morbidity, including any of the following: severe neurologic injury, bronchopulmonary dysplasia (BPD), and stage 3 or higher retinopathy of prematurity., Results: A total of 1,034 VLBW infants who received antibiotics without culture-proven sepsis or NEC were included in this study. The overall AUR of eligible VLBW infants was 55%, and the AUR of each eligible VLBW infant ranged from 3 to 100%, with a median of 56% (IQR 33%, 86%). After generalized propensity score and logistic regression analysis of 4 groups of VLBW infants with different AUR range, infants in the higher quartile AUR, (Q3, 0.57~0.86) and (Q4, 0.87~1.00), had higher odds of composite primary outcome (adjusted OR: 1.81; 95% CI: 1.23-2.67; adjusted OR 2.37; 95% CI: 1.59-3.54, respectively) and BPD (adjusted OR: 3.09; 95% CI: 1.52-6.57; adjusted OR 3.17; 95% CI: 1.56-6.57, respectively) than those in the lowest AUR (Q1)., Conclusions: Antibiotic overexposure in VLBW infants without culture-proven sepsis or NEC was associated with increased risk of composite primary outcome and BPD. Rational empirical antibiotic use in VLBW infants is urgently needed in China., (© 2022. The Author(s).)

In this study, a new method was developed for feruloylated oligosaccharides (FOs) enzymatic hydrolysis extraction from corn bran, using ionic liquids (ILs) as the solvent for the depolymerization of dietary fiber. The 1-allyl-3-methylimidazolium acetate [Amim]Ac was the most effective IL among the eight evaluated ILs, which leads to a 1.5 times-higher total FOs content as compared with conventional non-pretreatment extraction. The optimum condition acquired by response surface methodology was 194.31 min, 143.08 °C, solid-liquid ratio of 1:20, and the concentration of 18.65%. The depolymerized biomass was characterized using SEM, FTIR and CLSM. The results confirmed that [Amim]Ac mainly enters the cavity among the lignocellulose and breaks linkages to release FOs by exposure binding sites of hemicellulose to hydrolysis enzymes. In particular, the linkages between ferulic acid and hemicellulose were not affected by ILs pretreatment. This study provides an efficient method for the preparation of conjugated phenols from lignocellulose., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Coxiella burnetii, the causative agent of zoonotic Q fever, is characterized by replicating inside the lysosome-derived Coxiella -containing vacuole (CCV) in host cells. Some effector proteins secreted by C. burnetii have been reported to be involved in the manipulation of autophagy to facilitate the development of CCVs and bacterial replication. Here, we found that the Coxiella plasmid effector B (CpeB) localizes on vacuole membrane targeted by LC3 and LAMP1 and promotes LC3-II accumulation. Meanwhile, the C. burnetii strain lacking the QpH1 plasmid induced less LC3-II accumulation, which was accompanied by smaller CCVs and lower bacterial loads in THP-1 cells. Expression of CpeB in the strain lacking QpH1 led to restoration in LC3-II accumulation but had no effect on the smaller CCV phenotype. In the severe combined immune deficiency (SCID) mouse model, infections with the strain expressing CpeB led to significantly higher bacterial burdens in the spleen and liver than its parent strain devoid of QpH1. We also found that CpeB targets Rab11a to promote LC3-II accumulation. Intratracheally inoculated C. burnetii resulted in lower bacterial burdens and milder lung lesions in Rab11a conditional knockout (Rab11a -/- CKO) mice. Collectively, these results suggest that CpeB promotes C. burnetii virulence by inducing LC3-II accumulation via a pathway involving Rab11a.

Chlamydia psittaci is the causative agent of psittacosis, a worldwide zoonotic disease. A rapid, specific, and sensitive diagnostic assay would be benefit for C. psittaci infection control. In this study, an assay combining recombinase-aided amplification and a lateral flow strip (RAA-LF) for the detection of active C. psittaci infection was developed. The RAA-LF assay targeted the CPSIT&#95;RS02830 gene of C. psittaci and could be accomplished in 15 min at a single temperature (39°C). The analytical sensitivity of the assay was as low as 1 × 10 0 copies/μl and no cross-reaction with some other intracellular pathogens was observed. Moreover, all feces samples from mice infected with C. psittaci at day-1 post-infection were positive in the RAA-LF assay. In conclusion, the RAA-LF assay provides a convenient, rapid, specific and sensitive method for detection of active C. psittaci infection and it is also suitable for C. psittaci detection in field., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jiao, Qi, He, Wan, OuYang, Yu, Wen and Xiong.)

Purpose: Significant antibiotic overuse due to prolonged antibiotic duration has not draw enough attention in developing countries with high antibiotic consumption. We aimed to describe the current status of prolonged early antibiotic duration in very-low-birth-weight (VLBW) infants in a large regional multicenter cohort in China., Patients and Methods: Institution-based prospective cohort study was conducted in all VLBW infants admitted to 16 Grade A tertiary hospitals between January 1, 2019 and December 31, 2020. Early antibiotic use was defined as antibiotic initiation within the first 3 days of life. Prolonged early antibiotic course was defined as early antibiotic initiation for more than 7 days in infants with early-onset sepsis (EOS) or more than 3 days in infants with unlikely EOS. Antibiotic use was described as days of therapy (DOT) per 1000 patient days (PD)., Results: Among 1684 eligible VLBW infants, 1544 (91.7%) infants were prescribed with prolonged early antibiotic course, including 618 infants with EOS and 926 infants with unlikely EOS. The median duration of early antibiotic course was 13 (IQR 8;20) days, with 78.0% of courses >7 days and 43.6% of courses >14 days. Total early antibiotic use was 408.3DOT/1000Pd, of which prolonged antibiotic courses accounted for 98.2% of all antibiotic use days. More than three antibiotics used, escalation antibiotic therapy, antibiotics for special use and the use of third generation cephalosporins and carbapenems were significantly common in prolonged courses compared to short courses in both infants with EOS and unlikely EOS group ( P <0.05)., Conclusion: A large proportion of VLBW infants had excessively prolonged early antibiotic durations in the regional multicenter in China. Timely discontinuation of antibiotics in VLBW infants according to standardized guidelines and limit on the use of third-generation cephalosporins and carbapenems may be key drivers in reducing the antibiotic overuse in developing countries like ours., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Hou et al.)

Oats are among the most commonly consumed whole grains and are widely grown worldwide, and they contain numerous nutrients, including proteins, lipids, vitamins, minerals, β-glucan, and unique phytochemical polyphenol avenanthramides (Avns). Recent studies have indicated that Avns play essential roles in mediating the health benefits of oats. This review systemically summarized the nomenclature and structures of Avns, effect of germination on promoting Avns production, and in vivo metabolites produced after Avns consumption. The classical functions and novel potential bioactivities of Avns were further elucidated. The classical functions of Avns in cancer prevention, antioxidative response, anti-inflammatory reaction, and maintaining muscle health were expounded, and the internal mechanisms of these functions were analyzed. The potential novel bioactivities of Avns in modulating gut microbiota, alleviating obesity, and preventing chronic diseases, such as atherosclerosis and osteoporosis, were further revealed. This review may provide new prospects and directions for the development and utilization of oat Avns.

Rice bran protein (RBP) is a plant protein obtained from rice bran, a byproduct produced during rice milling process. It has been proved to be a high quality protein due to containing all of the essential amino acids and the content closing to the FAO/WHO recommended ideal pattern. Recent studies indicated that RBP and rice bran protein hydrolysates (RBPH) served variety biological functions. In this review, we summarized the classical functions of RBP and RBPH mediating antioxidant activity, chronic diseases prevention (such as antihypertensive effect, anti-diabetic effect, cholesterol-lowering activity), and anti-cancer effect. We also proposed their potential novel functions on anti-obesity effect, attenuating sarcopenia, promoting wound healing. Furthermore, the potential benefit to coronavirus disease 2019 (COVID-19) patients was put forward, which might provide new strategy for development and utilization of RBP and RBPH.

Rhipicephalus microplus , a vector that can transmit many pathogens to humans and domestic animals, is widely distributed in Yunnan province, China. However, few reports on the prevalence of tick-borne pathogens (TBPs) in Rh. microplus in Yunnan are available. The aim of this study was to detect TBPs in Rh. microplus in Yunnan and to analyze the phylogenetic characterization of TBPs detected in these ticks. The adult Rh. microplus ( n = 516) feeding on cattle were collected. The pooled DNA samples of these ticks were evaluated using metagenomic next-generation sequencing (mNGS) and then TBPs in individual ticks were identified using genus- or group-specific nested polymerase chain reaction (PCR) combined with DNA sequencing assay. As a result, Candidatus Rickettsia jingxinensis (24.61%, 127/516), Anaplasma marginale (13.18%, 68/516), Coxiella burnetii (3.10%, 16/516), and Coxiella- like endosymbiont (CLE) (8.33%, 43/516) were detected. The dual coinfection with Ca. R. jingxinensis and A. marginale and the triple coinfection with Ca. R. jingxinensis , A. marginale , and CLE were most frequent and detected in 3.68% (19/516) and 3.10% (16/516) of these ticks, respectively. The results provide insight into the diversity of TBPs and their coinfections in Rh. microplus in Yunnan province of China, reporting for the first time that C. burnetii had been found in Rh. microplus in China. Multilocus variable number tandem repeat analysis with 6 loci (MLVA-6) discriminated the C. burnetii detected in Rh. microplus in Yunnan into MLVA genotype 1, which is closely related to previously described genotypes found primarily in tick and human samples from different regions of the globe, indicating a potential public health threat posed by C. burnetii in Rh. microplus in Yunnan., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Jiao, Zhang, He, OuYang, Yu, Wen, Sun, Yuan and Xiong.)

Myocardial ischemia resulting from psychological stress [mental stress-induced myocardial ischemia (MSIMI)] refers to the condition wherein psychosocial and psychological stimulations cause myocardial ischemia in patients with coronary heart disease, which is different from drug-induced myocardial ischemia. Therefore, this condition often escapes diagnosis, portends clinical risk, and affects the quality of life of MSIMI survivors. MSIMI is closely related to the poor prognosis of cardiovascular diseases, especially in young women, according to recent randomized, controlled trials (RCTs) on MSIMI. These RCTs involved different sample sizes, interventional measures, and detection techniques. Moreover, differences exist regarding the prevalence rate, distribution characteristics, possible pathogenesis, and clinical significance. Nevertheless, currently, the diagnostic criteria, pathogenesis, and treatment of MSIMI are still in the clinical exploration stage. Hence, considering recent RCTs, this paper summarizes the research status of MSIMI from the aspects of pathogenesis, diagnosis, and treatment strategies to provide a theoretical basis for the follow-up diagnostic methods and treatment guidelines for MSIMI.

Ginsenoside Re, an herbal ingredient from ginseng, has been demonstrated to protect the heart from various cardiovascular diseases. In this study, we investigated the protective effects and mechanisms of ginsenoside Re (Gin-Re) on cardiac function and left ventricular remodeling in a rat model of myocardial infarction (MI). After ligating the left anterior descending coronary artery, Wistar rats were treated with Gin-Re (135 mg/kg) by gavage everyday for 4 weeks. Serological detection showed that Gin-Re significantly inhibited myocardial injury and attenuated oxidative stress in MI rats. Echocardiographic observation showed that Gin-Re significantly improved cardiac function and prevented left ventricular dilatation induced by MI. Pathological observation found that Gin-Re significantly decreased interstitial fibrosis in the left ventricle of MI rats. Compared with the MI group, Gin-Re treatment promoted AMPKα phosphorylation, decreased TGF-β1 expression, and attenuated Smad2/3 activation. After Gin-Re treatment, the phosphorylation of FAK, PI3K p110α, and Akt was enhanced in MI rats, while PI3K p110β showed no difference compared with the MI group. These results indicate that Gin-Re may improve MI-induced cardiac dysfunction and mitigate ventricular remodeling through regulation of the AMPK/TGF-β1/Smad2/3 and FAK/PI3K p110α/Akt signaling pathways.

Introduction: Cell autophagy is an important material recycling process and is involved in regulating many vital activities under both physiological and pathological conditions. However, the mechanism of autophagy regulating burn-induced skeletal muscle wasting still needs to be elucidated., Methods: The rat burn model with 30% total body surface area and L6 cell line were used in this study. An immunofluorescence assay was used to detect autophagic levels. MicroRNA array and real-time PCR were employed to measure miR-190b levels, and its influence on PH domain and leucine-rich repeat protein phosphatase 1 (PHLPP1) protein translation was estimated using luciferase reporter assay. The expression levels of autophagy-related proteins were analyzed by Western blot. Skeletal muscle wasting was evaluated by the ratio of tibias anterior muscle weight to body weight., Results: Our study demonstrates that burn injury promotes expression of the autophagy-related proteins light chain 3 (LC3) and Beclin-1, suppresses expression of Akt and Forkhead box O (FoxO) 3a protein phosphorylation, and increases PHLPP1 protein level which is required for Akt dephosphorylation. miR-190b, the regulator of PHLPP1 protein translation, also significantly decreases after burn injury. Ectopic expression of miR-190b in L6 myoblast cell downregulates PHLPP1 protein expression, elevates Akt and FoxO3a phosphorylation, and subsequently reduces cell autophagy. Finally, suppressing autophagy with 3-methyladenine represses the protein expression of LC3 and Beclin-1 and mitigates burn-induced skeletal muscle wasting., Conclusion: Burn injury induced skeletal muscle cell autophagy and subsequently resulted in skeletal muscle wasting via regulating miR-190b/PHLPP1/Akt/FoxO3a signaling pathway.

Our recent studies demonstrate that X-linked inhibitor of apoptosis protein (XIAP) is essential for regulating colorectal cancer invasion. Here, we discovered that RhoGDIβ was a key XIAP downstream effector mediating bladder cancer (BC) invasion in vitro and in vivo. We found that both XIAP and RhoGDIβ expressions were consistently elevated in BCs of N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-treated mice in comparison to bladder tissues from vehicle-treated mice and human BCs in comparison to the paired adjacent normal bladder tissues. Knockdown of XIAP attenuated RhoGDIβ expression and reduced cancer cell invasion, whereas RhoGDIβ expression was attenuated in BBN-treated urothelium of RING-deletion knockin mice. Mechanistically, XIAP stabilized RhoGDIβ mRNA by its positively regulating nucleolin mRNA stability via Erks-dependent manner. Moreover, ectopic expression of GFP-RhoGDIβ in T24T(shXIAP) cells restored its lung metastasis in nude mice. Our results demonstrate that XIAP-regulated Erks/nucleolin/RhoGDIβ axis promoted BC invasion and lung metastasis., (© 2017 UICC.)

Background: Severe burn causes acute lung injury in many victims, but the related mechanisms have been barely investigated. microRNAs (miRNAs) important regulators in numerous physiological and pathophysiological process. However, the roles of miRNAs in burn lung injury are untested., Methods: Six healthy male Sprague-Dawley rats were randomly assigned into burn and sham groups. Lung injury was evaluated by hematoxylin and eosin (HE) staining at 24 h after injury. Differentially expressed miRNAs were determined by array hybridization and verified by real-time quantitative polymerase chain reaction (RT-qPCR). Bioinformatics analysis was undertaken to predict the target genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases were employed to identify potentially related biological processes and pathways, respectively. Neutrophil infiltration and apoptosis of the lung were confirmed by immunohistochemical staining of myeloperoxidase (MPO) and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)., Results: HE sections showed obvious lung injury, and 21 upregulated and three downregulated miRNAs were detected. Target genes of these miRNAs were most highly enriched in inflammation and apoptosis related GO biological processes and pathways. Inflammation and apoptosis were confirmed by MPO and TUNEL staining., Conclusion: The differentially expressed miRNAs most likely participate in burn-induced lung injury by being involved in inflammation and apoptosis.

Fibrosis, tightly associated with fibroblasts collagen synthesis, is related closely with inflammatory response. Our previously study found that acute downregulation of miR-155 at wound sites leads to a reduced fibrosis, however its particular mechanism is unclear. Herein, we aimed to explore the mechanism of miR-155 in reducing fibrosis. We first found that down-regulation of miR-155 inhibited macrophages transforming growth factor-β1 (TGF-β1) and IL-1β secretion. Next, we found that co-cultured with macrophages increased the proliferation and collagen synthesis of fibroblasts, and downregulation of miR-155 in macrophages could effectively attenuate the accelerative effects. We further identified SH2 domain containing inositol-5-phosphatase 1 (SHIP1) as a direct target of miR-155 in macrophages, and the expression of SHIP1 was negatively correlated with the level of miR-155. We further confirmed that PI3K/Akt pathway was involved in this process. Last, we found that downregulation of miR-155 leads to a reduced fibrosis in sever burn rat. Taken together, these results indicate that down-regulation of miR-155 leads to a reduced fibroblasts proliferation and collagen synthesis through attenuating macrophages TGF-β1 and IL-1β secretion by targeting SHIP1 via PI3K/Akt pathway, suggesting its potential therapeutic effects on the treatment of skin fibrosis.

The geographical origin and radiation of holarctica-type tularemia, which has spread across the northern hemisphere, is open to scientific debate. Here, through phylogenetics, we show that five Tibetan Francisella tularensis isolates subsp. holarctica cluster between basal-positioned Japanese isolates and all other subspecies strains in the world, providing evidence for a previously unknown intermediate lineage next to the Japanese isolates. Importantly, identification of this new intermediate lineage complements current knowledge of tularemia epidemiology, supporting a geographical origin and radiation of the subsp. holarctica in Asia. In addition, thirteen Tibetan isolates belonging to a clade previously found only in North America and Scandinavia, further increases the diversity of holarctica strains in Asia. In summary, this study provides evidence for an Asian origin and radiation of holarctica-type tularemia., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

Skeletal muscle atrophy, a conventional clinical feature in patients with cancer, chronic obstructive pulmonary disease, sepsis and severe burns, is defined as a reduction in muscle mass. During atrophy, the protein degradation is abnormally activated and the aberrance between protein synthesis and protein degradation results in muscle atrophy. Previous studies have demonstrated that miRNAs, small non-coding RNA molecules, serve an important role in the regulation of muscle atrophy. Further studies have indicated the implications of the ubiquitin-proteasome and PI3K/Akt/FoxO signaling pathways and myogenic regulatory factors in miRNA-mediated muscle atrophy. Therefore, in this review, the effects and molecular mechanisms of miRNAs on muscle atrophy are summarized, leading to the suggestion that miRNAs may serve as potential therapeutic targets in muscle atrophy.

Background: In this study, we will establish a stable and optimized rat model that can meet strictly diagnosed criteria and serve as a tool to investigate the potential of novel therapeutics in this preclinical model through comparative analysis of systemic alterations, levels of pro-inflammatory cytokines in serum and infiltrated numbers of inflammatory cells in distant organ between 30% and 50% TBSA with a full-thickness burn., Materials and Methods: The adult male Wistar rats were randomly divided into the following groups: control group, 30% TBSA with a full-thickness burn group, and 50% TBSA with a full-thickness burn group. The blood and serum samples in the 3 groups were collected and detected by blood routine examination and biochemical detection at 6 h, 12 h, 24 h and 48 h post burn. The levels of TNF-α, IL-1β and IL-6 in serum were detected by ELISA. The sections of lung, renal, liver and heart were analyzed by H&E and immunohistochemical staining detection., Results: Our results showed that temperature in 50% TBSA with a full-thickness burn group was always hypothermia, and lower than 36°C at defined timepoints post burn, that was in 30% TBSA with a full-thickness burn group was lower than 36°C only at 48 h post burn. The levels of TNF-α, IL-1β and IL-6 were significantly increased in 30% and 50% groups at 6 h, 12 h, 24 h and 48 h post burn. The apoptosis in distant organs and the biochemical parameters such as ALT, AST, troponin, CK, CK-MB, LDH, urea and creatinine in 30% and 50% groups were also increased at different degrees at defined timepoints after burn, but changes in 50% group were more obvious than that in 30% group., Conclusion: We choose 50% TBSA with a full-thickness burn to establish a stable and optimized rat model that can meet strictly diagnosed criteria and serve as a tool to investigate the potential of novel therapeutics in this preclinical model.