Shuganning Injection Suppresses Apoptosis for Protecting Against Cantharidin-Induced Liver Injury by Network Pharmacology and Experiment Validation.

Cantharidin (CTD) is a compound of mylabris with antitumor activity, and CTD can potentially cause toxicity, especially hepatotoxicity. The classical Traditional Chinese Medicine prescription Shuganning injection (SGNI) exerts notable anti-inflammatory and hepatoprotective effects. However, the protective property and mechanism of SGNI against CTD-induced liver injury (CTD-DILI) have not yet been elucidated. To investigate the effective compounds, potential targets, and molecular mechanism of SGNI against CTD-DILI, network pharmacology combined with experiments were performed. This study found that SGNI could act with 62 core therapeutic targets, regulate multiple biological processes such as apoptosis, and oxidative stress, and influence apoptotic and p53 signaling pathways to treat CTD-DILI. Subsequently, HepaRG cell experiments demonstrated that SGNI pretreatment significantly increased the levels of GSH-Px and SOD, inhibiting the apoptosis induced by CTD. In vivo, according to H&E staining, SGNI can reduce the degeneration of hepatocytes and cytoplasmic vacuolation in mice exposed to CTD. Western blot analysis results indicated that SGNI pretreatment significantly suppressed the expressions of Caspase-3 and Bax while increasing the expression of Bcl-2. In conclusion, SGNI acted as a protective agent against CTD-DILI by inhibiting apoptosis.

Association of maternal weight gain in early pregnancy with congenital heart disease in offspring: a China birth cohort study.

OBJECTIVES: Little study has reported the association of maternal weight gain in early pregnancy with fetal congenital heart disease (CHD). We aimed to explore the potential relationship based on a China birth cohort while adjusting by multiple factors. DESIGN: Cohort study. SETTING: China birth cohort study conducted from 2017 to 2021. PARTICIPANTS: The study finally included 114 672 singleton pregnancies in the 6-14 weeks of gestation, without missing data or outliers, loss to follow-up or abnormal conditions other than CHD. The proportion of CHD was 0.65% (749 cases). PRIMARY AND SECONDARY OUTCOME MEASURES: Association between maternal pre-pregnancy weight gain and CHD in the offspring were analysed by multivariate logistic regression, with the unadjusted, minimally adjusted and maximally adjusted methods, respectively. RESULTS: The first-trimester weight gain showed similar discrimination of fetal CHD to that period of maternal body mass index (BMI) change (DeLong tests: p=0.091). Compared with weight gain in the lowest quartile (the weight gain less than 0.0 kg), the highest quartile (over 2.0 kg) was associated with a higher risk of fetal CHD in unadjusted (OR 1.36, 95% CI: 1.08 to 1.72), minimally adjusted (adjusted OR (aOR) 1.29, 95% CI: 1.02 to 1.62) and maximally adjusted (aOR 1.29, 95% CI: 1.02 to 1.63) models. The association remains robust in pregnant women with morning sickness, normal pre-pregnancy BMI, moderate physical activity, college/university level, natural conception or with folic acid (FA) and/or multivitamin supplementation. CONCLUSIONS AND RELEVANCE: Although the association of maternal pre-pregnancy weight gain on fetal CHD is weak, the excessive weight gain may be a potential predictor of CHD in the offspring, especially in those with morning sickness and other conditions that are routine in the cohort, such as normal pre-pregnancy BMI, moderate physical activity, college/university level, natural conception or with FA and/or multivitamin supplementation.

Functional types of long trichoid sensilla responding to sex pheromone components in Plutella xylostella.

Sex pheromones, which consist of multiple components in specific ratios promote intraspecific sexual communications of insects. Plutella xylostella (L.) is a worldwide pest of cruciferous vegetables, the mating behavior of which is highly dependent on its olfactory system. Long trichoid sensilla on male antennae are the main olfactory sensilla that can sense sex pheromones. However, the underlying mechanisms remain unclear. In this study, 3 sex pheromone components from sex pheromone gland secretions of P. xylostella female adults were identified as Z11-16:Ald, Z11-16:Ac, and Z11-16:OH in a ratio of 9.4 : 100 : 17 using gas chromatography - mass spectrometry and gas chromatography with electroantennographic detection. Electrophysiological responses of 581 and 385 long trichoid sensilla of male adults and female adults, respectively, to the 3 components were measured by single sensillum recording. Hierarchical clustering analysis showed that the long trichoid sensilla were of 6 different types. In the male antennae, 52.32%, 5.51%, and 1.89% of the sensilla responded to Z11-16:Ald, Z11-16:Ac, and Z11-16:OH, which are named as A type, B type, and C type sensilla, respectively; 2.93% named as D type sensilla responded to both Z11-16:Ald and Z11-16:Ac, and 0.34% named as E type sensilla were sensitive to both Z11-16:Ald and Z11-16:OH. In the female antennae, only 7.53% of long trichoid sensilla responded to the sex pheromone components, A type sensilla were 3.64%, B type and C type sensilla were both 0.52%, D type sensilla were 1.30%, and 1.56% of the sensilla responded to all 3 components, which were named as F type sensilla. The responding long trichoid sensilla were located from the base to the terminal of the male antennae and from the base to the middle of the female antennae. The pheromone mixture (Z11-16:Ald : Z11-16:Ac : Z11-16:OH = 9.4 : 100 : 17) had a weakly repellent effect on female adults of P. xylostella. Our results lay the foundation for further studies on sex pheromone communications in P. xylostella.

A Noncentrosymmetric Metal-Free Borophosphate: Achieving a Large Birefringence and Excellent Stability by Covalent-Linkage.

Organic-inorganic hybrid linear and nonlinear optical (NLO) materials have received increasingly wide spread attention in recent years. Herein, the first hybrid noncentrosymmetric (NCS) borophosphate, (C5H6N)2B2O(HPO4)2 (4PBP), is rationally designed and synthesized by a covalent-linkage strategy. 4-pyridyl-boronic acid (4 PB) is considered as a bifunctional unit, which may effectively improve the optical properties and stability of the resultant material. On the one hand, 4 PB units are covalently linked with PO3(OH) groups via strong B-O-P connections, which significantly enhances the thermal stability of 4PBP (decomposition at 321, vs lower 200 °C of most of hybrid materials). On the other hand, the planar π-conjugated C5H6N units and their uniform layered arrangements represent large structural anisotropy and hyperpolarizability, achieving the largest birefringence (0.156 @ 546 nm) in the reported borophosphates and a second-harmonic generation response (0.7 × KDP). 4PBP also exhibits a wide transparency range (0.27-1.50 µm). This work not only provides a promising birefringent material, but also offers a practical covalent-attachment strategy for the rational design of new high-performance optical materials.

Divergent redistribution behavior of divalent metal cations associated with Fe(II)-mediated jarosite phase transformation.

The Fe(II)/Fe(III) cycle is an important driving force for dissolution and transformation of jarosite. Divalent heavy metals usually coexist with jarosite; however, their effects on Fe(II)-induced jarosite transformation and different repartitioning behavior during mineral dissolution-recrystallization are still unclear. Here, we investigated Fe(II)-induced (1 mM Fe(II)) jarosite conversion in the presence of Cd(II), Mn(II), Co(II), Ni(II) and Pb(II) (denoted as Me(II), 1 mM), respectively, under anaerobic condition at neutral pH. The results showed that all co-existing Me(II) retarded Fe(II)-induced jarosite dissolution. In the Fe(II)-only system, jarosite first rapidly transformed to lepidocrocite (an intermediate product) and then slowly to goethite; lepidocrocite was the main product. In Fe(II)-Cd(II), -Mn(II), and -Pb(II) systems, coexisting Cd(II), Mn(II) and Pb(II) retarded the above process and lepidocrocite was still the dominant conversion product. In Fe(II)-Co(II) system, coexisting Co(II) promoted lepidocrocite transformation into goethite. In Fe(II)-Ni(II) system, jarosite appeared to be directly converted into goethite, although small amounts of lepidocrocite were detected in the final product. In all treatments, the appearance or accumulation of lepidocrocite may be also related to the re-adsorption of released sulfate. By the end of reaction, 6.0 %, 4.0 %, 76.0 % 11.3 % and 19.2 % of total Cd(II), Mn(II), Pb(II) Co(II) and Ni(II) were adsorbed on the surface of solid products. Up to 49.6 %, 44.3 %, and 21.6 % of Co(II), Ni(II), and Pb(II) incorporated into solid product, with the reaction indicating that the dynamic process of Fe(II) interaction with goethite may promote the continuous incorporation of Co(II), Ni(II), and Pb(II).

Upregulation of circ_0076684 in osteosarcoma facilitates malignant processes by mediating miRNAs/CUX1.

Circular RNAs (circRNAs) are a newly appreciated type of endogenous noncoding RNAs that play vital roles in the development of various human cancers, including osteosarcoma (OS). In this study, we investigated three circRNAs (circ_0076684, circ_0003563, circ_0076691) from the RUNX Family Transcription Factor 2 (RUNX2) gene locus in OS. We found that the expression of circ_0076684, circ_0003563, circ_0076691, and RUNX2 mRNA is upregulated in OS, which is a consequence of CBX4-mediated transcriptional activation. Among these three RUNX2-circRNAs, only circ_0076684 is significantly associated with the clinical features and prognosis of OS patients. Functional experiments indicate that circ_0076684 promotes OS progression in vitro and in vivo. Circ_0076684 acts as a sponge for miR-370-3p, miR-140-3p, and miR-193a-5p, raising Cut Like Homeobox 1 (CUX1) expression by sponging these three miRNAs. Furthermore, we presented that circ_0076684 facilitates OS progression via CUX1. In conclusion, this study found that the expression of three circRNAs and RUNX2 mRNA from the RUNX2 gene locus is significantly upregulated in OS, as a result of CBX4-mediated transcriptional activation. Circ_0076684 raises CUX1 expression by sponging miR-370-3p, miR-140-3p, and miR-193a-5p, and facilitates OS progression via CUX1.

Evaluation of reference genes for quantitative expression analysis in Mylabris sibirica (Coleoptera, Meloidae).

Mylabris sibirica is a hypermetamorphic insect whose adults feed on oilseed rape. However, due to a shortage of effective and appropriate endogenous references, studies on molecular functional genes in Mylabris sibirica, have been tremendously limited. In this study, ten internal reference genes (ACT, ARF1, AK, EF1α, GAPDH, α-TUB, RPL6, RPL13, RPS3 and RPS18) were tested and assessed under four selected treatments including adult ages, adult tissues, temperatures, and sex by RT-qPCR based on five methods (Ct value, geNorm, NormFinder, BestKeeper and RefFinder). Our findings showed that RPL6 and RPL13 were the most optimal internal reference gene combination for gene expression during various adult ages and under diverse temperatures; The combination of RPL6 and RPS18 was recommended to test gene transcription levels under different adult tissues. AK and RPL6 were the best reference genes in male and female adults. RPL6 and RPL13 were the most appropriate reference gene pair to estimate gene expression levels under four different tested backgrounds. The relative transcript levels of a uridine diphosphate (UDP)-N-acetylglucosamine-pyrophosphorylase (MsUAP), varied greatly according to normalization with the two most- and least-suited reference genes. This study will lay the basis for further molecular physiology and biochemistry studies in M. sibirica, such as development, reproduction, sex differentiation, cold and heat resistance.

Pediatric Ménière's disease with disassociated cochlear and vestibular symptoms: a case report.

Background: Typical Ménière's disease (MD) rarely occurs in childhood. Compared to adults, age-associated changes in vestibular function can occur during infancy and childhood. Previous case reports may have lacked some audiovestibular tests in children. It is worthwhile to follow a child with MD to observe how vertigo and hearing loss could progress under an insufficient vestibular system. Case Description: A 14-year-old pediatric patient with disassociated episodes between vertigo and hearing loss was finally diagnosed with MD. He was diagnosed with probable MD due to lack of objective evidence of hearing loss in his first two admissions. However, in his third admission, he had hearing loss even without attack of vertigo and was finally diagnosed. By listing the patient's audiovestibular auxiliary tests in a chronological order, we might follow the progress of pediatric MD. Gadolinium-enhanced magnetic resonance imaging (Gd-MRI) might be sensitive to reflect endolymphatic hydrops (EH). Medications including corticosteroids might be effective for both hearing loss and vertigo. Conclusions: In pediatric MD, vestibular and cochlear symptoms may occur and progress independently. Audiovestibular evaluation, especially caloric tests and cervical vestibular evoked myogenic potential (cVEMP), can be useful for pediatric MD. Gd-MRI can be sensitive for detecting EH. Both systemic and postauricular administration of corticosteroids might be effective in alleviating vertigo and improving hearing. Prolongation of the follow-up period of pediatric MD is warranted.

Anatomical, chemical and endophytic fungal diversity of a Qi-Nan clone of Aquilaria sinensis (Lour.) Spreng with different induction times.

Recently, some new Qi-Nan clones of Aquilaria sinensis (Lour.) Spreng which intensively produces high-quality agarwood have been identified and propagated through grafting techniques. Previous studies have primarily focused on ordinary A. sinensis and the differences in composition when compared to Qi-Nan and ordinary A. sinensis. There are few studies on the formation mechanism of Qi-Nan agarwood and the dynamic changes in components and endophytic fungi during the induction process. In this paper, the characteristics, chemical composition, and changes in endophytic fungi of Qi-Nan agarwood induced after 1 year, 2 years, and 3 years were studied, and Qi-Nan white wood was used as the control. The results showed that the yield of Qi-Nan agarwood continued to increase with the induction time over a period of 3 years, while the content of alcohol extract from Qi-Nan agarwood reached its peak at two years. During the formation of agarwood, starch and soluble sugars in xylem rays and interxylary phloem are consumed and reduced. Most of the oily substances in agarwood were filled in xylem ray cells and interxylary phloem, and a small amount was filled in xylem vessels. The main components of Qi-Nan agarwood are also chromones and sesquiterpenes. With an increasing induction time, the content of sesquiterpenes increased, while the content of chromones decreased. The most abundant chromones in Qi-Nan agarwood were 2-(2-Phenethyl) chromone, 2-[2-(3-Methoxy-4-hydroxyphenyl) ethyl] chromone, and2-[2-(4-Methoxyphenyl) ethyl] chromone. Significant differences were observed in the species of the endophytic fungi found in Qi-Nan agarwood at different induction times. A total of 4 phyla, 73 orders, and 448 genera were found in Qi-Nan agarwood dominated by Ascomycota and Basidiomycota. Different induction times had a significant effect on the diversity of the endophytic fungal community in Qi-Nan. After the induction of agarwood formation, the diversity of Qi-Nan endophytic fungi decreased. Correlation analysis showed that there was a significant positive correlation between endophytic fungi and the yield, alcohol extract content, sesquiterpene content, and chromone content of Qi-Nan agarwood, which indicated that endophytic fungi play a role in promoting the formation of Qi-Nan agarwood. Qi-Nan agarwood produced at different induction times exhibited strong antioxidant capacity. DPPH free radical scavenging activity and reactive oxygen species clearance activity were significantly positively correlated with the content of sesquiterpenes and chromones in Qi-Nan agarwood.

The Heterogeneity of Symptom Burden and Fear of Progression Among Kidney Transplant Recipients: A Latent Class Analysis.

Purpose: Kidney transplant recipients (KTRs) may experience symptoms that increase their fear of progression (FoP), but a dearth of research examines the issue from a patient-centered perspective. Our study aimed to first determine the category of symptom burden, then to explore the differences in characteristics of patients in different subgroups, and finally to analyze the impact of symptom subgroup on FoP. Patients and Methods: Sociodemographic and Clinical Characteristics, Symptom Experience Scale, and Fear of Progression Questionnaire-Short Form were used. Latent class analysis was used to group KTRs according to the occurrence of symptoms. We used multivariate logistic regression to analyze the predictors of different subgroups. The differences in FoP among symptom burden subgroups were analyzed by hierarchical multiple regression. Results: Three subgroups were identified, designated all-high (20.5%), moderate (39.9%), and all-low (39.6%) according to their symptom occurrence. Multivariate logistic regression showed that gender, post-transplant time, per capita monthly income, and hyperuricemia were the factors that distinguished and predicted the all-high subgroup (P < 0.05). Hierarchical multiple regression showed that symptom burden had a significant effect on FoP (class1 vs class3: ß = 0.327, P < 0.001; class2 vs class3: ß = 0.104, P = 0.046), explaining the 8.0% variance of FoP (ΔR2 = 0.080). Conclusion: KTRs generally experience moderate or low symptom burden, and symptom burden is an influencing factor in FoP. Identifying the traits of KTRs with high symptom burden can help clinicians develop targeted management strategies and ease FoP of KTRs.

A transcribed ultraconserved noncoding RNA, uc.285+, promotes colorectal cancer proliferation through dual targeting of CDC42 by directly binding mRNA and protein.

The transcribed ultraconserved region (T-UCR) belongs to a new type of lncRNAs that are conserved in homologous regions of the rat, mouse and human genomes. A lot of research has reported that differential expression of T-UCRs can influence the development of various cancers, revealing the ability of T-UCRs as new therapeutic targets or potential cancer biomarkers. Most studies on the molecular mechanisms of T-UCRs in cancer have focused on ceRNA regulatory networks and interactions with target proteins, but the present study reveals an innovative dual-targeted regulatory approach in which T-UCRs bind directly to mRNAs and directly to proteins. We screened T-UCRs that may be related to colorectal cancer (CRC) by performing a whole-genome T-UCR gene microarray and further studied the functional mechanism of T-UCR uc.285+ in the development of CRC. Modulation of uc.285+ affected the proliferation of CRC cell lines and influenced the expression of the CDC42 gene. We also found that uc.285+ promoted the proliferation of CRC cells by directly binding to CDC42 mRNA and enhancing its stability while directly binding to CDC42 protein and affecting its stability. In short, our research on the characteristics of cell proliferation found that uc.285+ has a biological function in promoting CRC proliferation. uc.285+ may have considerable potential as a new diagnostic biomarker for CRC.

Comparisons of long-term clinical outcomes with left bundle branch pacing, left ventricular septal pacing, and biventricular pacing for cardiac resynchronization therapy.

BACKGROUND: Left bundle branch pacing (LBBP) and left ventricular septal pacing (LVSP) are referred to as left bundle branch area pacing. OBJECTIVE: This study investigated whether long-term clinical outcomes differ in patients undergoing LBBP, LVSP, and biventricular pacing (BiVP) for cardiac resynchronization therapy (CRT). METHODS: Consecutive patients with reduced left ventricular ejection fraction (LVEF <50%) undergoing CRT were prospectively enrolled if they underwent successful LBBP, LVSP, or BiVP. The primary composite end point was all-cause mortality or heart failure hospitalization. Secondary end points included all-cause mortality, heart failure hospitalization, and echocardiographic measures of reverse remodeling. RESULTS: A total of 259 patients (68 LBBP, 38 LVSP, and 153 BiVP) were observed for a mean duration of 28.8 ± 15.8 months. LBBP was associated with a significantly reduced risk of the primary end point by 78% compared with both BiVP (7.4% vs 41.2%; adjusted hazard ratio [aHR], 0.22 [0.08-0.57]; P = .002) and LVSP (7.4% vs 47.4%; aHR, 0.22 [0.08-0.63]; P = .004]. The adjusted risk of all-cause mortality was significantly higher in LVSP than in BiVP (31.6% vs 7.2%; aHR, 3.19 [1.38-7.39]; P = .007) but comparable between LBBP and BiVP (2.9% vs 7.2%; aHR, 0.33 [0.07-1.52], P = .155). Propensity score adjustment also obtained similar results. LBBP showed a higher rate of echocardiographic response (ΔLVEF ≥10%: 60.0% vs 36.2% vs 16.1%; P < .001) than BiVP or LVSP. CONCLUSION: LBBP yielded long-term clinical outcomes superior to those of BiVP and LVSP. The role of LVSP for CRT needs to be reevaluated because of its high mortality risk.

Confinement-enhanced electrochemiluminescence by Ru(dcbpy)32+-functionalized γ-CD-MOF@COF-LZU1 porous hybrid material as micro-reactor for CYFRA 21-1 detection.

The improvement of electrochemiluminescence (ECL) performance relies on the electron transfer efficiency between luminophore and coreactant. An ultrasensitive ECL micro-reactor with confinement-enhanced performance was prepared by using the covalent organic framework-LZU1-functionalized metal-organic framework (MOF@COF-LZU1) as a platform to assemble enormous N,N-dibutyl-2-hydroxyethylamine (DBAE) and tris(4,4'-dicarboxylic acid-2,2'-bipyridyl) ruthenium(II) [Ru(dcbpy)32+] into its pore channels. Compared to individual substances of γ-CD-MOF and COF-LZU1, the synergistic effects can conduce to the enhancement of the intensity, durability and sensitivity of the micro-reactor. Besides, COF-LZU1 can provide a mild environment to accommodate a certain amount of DBAE by concentrating them from the aqueous solution into its hydrophobic cavities and boost the oxidation efficiency of DBAE to generate more DBAE●+ and profited the survival of DBAE●, leading to an improved reaction efficiency with the Ru(dcbpy)32+ intermediate. Thanks to the confinement-enhanced strategy, engineered as high-functioning luminescent materials, Ru@γ-CD-MOF@COF-LZU1 micro-reactors decorated with Au NPs can facilitate electron transfer and capture primary antibodies (Ab1). Moreover, Au-Pd-Pt noble metal aerogels (NMAs) functionalized MoS2 NFs (Au-Pd-Pt NMAs@MoS2 NFs) were chosen as base material due to its large specific surface areas, high porosity, and excellent electrical conductivity. Based on above merits, the sensor demonstrated a sensitive response to CYFRA 21-1 detection in a linear concentration gradient from 10 fg/mL to 50 ng/mL with a detection limit of 0.0055 pg/mL (S/N = 3). The COF-LZU1 decorated ECL micro-reactors were constructed based on the signal amplification strategies to realize accurate CYFRA 21-1 detection.

Experimental analysis and model prediction of elbow pipe's erosion in water-cooled radiator.

The radiator with heat transfer capability is able to guarantee the stable operation of hydro generator set, while the long-term and continuous scouring on radiator pipes by cooling medium will lead to thinning or even perforation of pipe wall, which triggers wall failure. This paper analyzes and predicts the failure mechanism of radiator's pipe wall, and investigates the effects of water flow velocity, sand content and sand particle size on erosion damage of radiator pipe by establishing a test bench for pipe erosion. The results show that the increase of above parameters will lead to the increasing erosion rate, especially when the sand content is 1%, the velocity is 8 m/s and the sand particle size is 0.85 mm, the erosion damage will be particularly serious. Based on experimental data, BP and LSSVM models are employed to predict the pipe wall failure, and PSO algorithm is used to optimize the two models. The optimized PSO-BP has the highest accuracy with the mean absolute error (MAE) of 0.2070 and the mean absolute percentage error (MAPE) of 4.702%. The findings provide a reference for wall failure analysis of radiator, which is of great significance for unit's safe operation.

Acanthopanax senticosus cultures fermented by Lactobacillus rhamnosus enhanced immune response through improvement of antioxidant activity and inflammation in crucian carp (Carassius auratus).

Lactic acid bacteria (LAB) have been recognized as safe microorganism that improve micro-flora disturbances and enhance immune response. A well-know traditional herbal medicine, Acanthopanax senticosus (As) was extensively utilized in aquaculture to improve growth performance and disease resistance. Particularly, the septicemia, skin wound and gastroenteritis caused by Aeromonas hydrophila threaten the health of aquatic animals and human. However, the effects of probiotic fermented with A. senticosus product on the immune regulation and pathogen prevention in fish remain unclear. Here, the aim of the present study was to elucidate whether the A. senticosus fermentation by Lactobacillus rhamnosus improve immune barrier function. The crucian carp were fed with basal diet supplemented with L. rhamnosus fermented A. senticosus cultures at 2 %, 4 %, 6 % and 8 % bacterial inoculum for 8 weeks. After trials, the weight gain rate (WGR), specific growth rate (SGR) were significantly increased, especially in LGG-6 group. The results confirmed that the level of the CAT, GSH-PX, SOD, lysozyme, and MDA was enhanced in fish received with probiotic fermented product. Moreover, the L. rhamnosus fermented A. senticosus cultures could trigger innate and adaptive immunity, including the up-regulation of the C3, C4, and IgM concentration. The results of qRT-PCR revealed that stronger mRNA transcription of IL-1ß, IL-10, IFN-γ, TNF-α, and MyD88 genes in the liver, spleen, kidney, intestine and gills tissues of fish treated with probiotic fermented with A. senticosus product. After infected with A. hydrophila, the survival rate of the LGG-2 (40 %), LGG-4 (50 %), LGG-6 (60 %), LGG-8 (50 %) groups was higher than the control group. Meanwhile, the pathological damage of the liver, spleen, head-kidney, and intestine tissues of probiotic fermentation-fed fish could be alleviated after pathogen infection. Therefore, the present work indicated that L. rhamnosus fermented A. senticosus could be regard as a potential intestine-target therapy strategy to protecting fish from pathogenic bacteria infection.

Pristine and Fe-functionalized biochar for the simultaneous immobilization of arsenic and antimony in a contaminated mining soil.

This study examined the effectiveness of pristine biochar (BC) and Fe-functionalized biochar (FBC) in remediating As-Sb co-contaminated soil, and revealed the resulting impact on soil enzymatic activities and bacterial communities. Results from incubation experiments showed that the 1.5% FBC treatment reduced the bioavailable As and Sb concentration by 13.5% and 27.1%, respectively, in compared to the control, and reduced the proportion of specifically adsorbed and amorphous Fe-Mn oxide-bound metal(loid) fractions in the treated soil. Among the BC treatments, only the 1.5% BC treatment resulted in a reduction of bioavailable As by 11.7% and Sb by 21.4%. The 0.5% BC treatment showed no significant difference. The FBC achieved high As/Sb immobilization efficiency through Fe-induced electrostatic attraction, π-π electron donor-acceptor coordination, and complexation (Fe-O(H)-As/Sb) mechanisms. Additionally, the 1.5% FBC treatment led to a 108.2% and 367.4% increase in the activities of N-acetyl-ß-glucosaminidase and urease in soils, respectively, compared to the control. Furthermore, it significantly increased the abundance of Proteobacteria (15.2%), Actinobacteriota (37.0%), Chloroflexi (21.4%), and Gemmatimonadota (43.6%) at the phylum level. Co-occurrence network analysis showed that FBC was better than BC in increasing the complexity of bacterial communities. Partial least squares path modeling further indicated that the addition of biochar treatments can affect soil enzyme activities by altering soil bacterial composition. This study suggests that FBC application offers advantages in simultaneous As and Sb immobilization and restructuring the bacterial community composition in metal(loid)-contaminated soil.

Acidification Offset Warming-Induced Increase in N2O Production in Estuarine and Coastal Sediments.

Global warming and acidification, induced by a substantial increase in anthropogenic CO2 emissions, are expected to have profound impacts on biogeochemical cycles. However, underlying mechanisms of nitrous oxide (N2O) production in estuarine and coastal sediments remain rarely constrained under warming and acidification. Here, the responses of sediment N2O production pathways to warming and acidification were examined using a series of anoxic incubation experiments. Denitrification and N2O production were largely stimulated by the warming, while N2O production decreased under the acidification as well as the denitrification rate and electron transfer efficiency. Compared to warming alone, the combination of warming and acidification decreased N2O production by 26 ± 4%, which was mainly attributed to the decline of the N2O yield by fungal denitrification. Fungal denitrification was mainly responsible for N2O production under the warming condition, while bacterial denitrification predominated N2O production under the acidification condition. The reduced site preference of N2O under acidification reflects that the dominant pathways of N2O production were likely shifted from fungal to bacterial denitrification. In addition, acidification decreased the diversity and abundance of nirS-type denitrifiers, which were the keystone taxa mediating the low N2O production. Collectively, acidification can decrease sediment N2O yield through shifting the responsible production pathways, partly counteracting the warming-induced increase in N2O emissions, further reducing the positive climate warming feedback loop.

Phase separation of SHP2E76K promotes malignant transformation of mesenchymal stem cells by activating mitochondrial complexes.

Mesenchymal stem cells (MSCs), suffering from diverse gene hits, undergo malignant transformation and aberrant osteochondral differentiation. Src homology region 2-containing protein tyrosine phosphatase 2 (SHP2), a nonreceptor protein tyrosine phosphatase, regulates multicellular differentiation, proliferation, and transformation. However, the role of SHP2 in MSC fate determination remains unclear. Here, we showed that MSCs bearing the activating SHP2E76K mutation underwent malignant transformation into sarcoma stem-like cells. We revealed that the SHP2E76K mutation in mouse MSCs led to hyperactive mitochondrial metabolism by activating mitochondrial complexes I and III. Inhibition of complexes I and III prevented hyperactive mitochondrial metabolism and malignant transformation of SHP2E76K MSCs. Mechanistically, we verified that SHP2 underwent liquid-liquid phase separation (LLPS) in SHP2E76K MSCs. SHP2 LLPS led to its dissociation from complexes I and III, causing their hyperactivation. Blockade of SHP2 LLPS by LLPS-defective mutations or allosteric inhibitors suppressed complex I and III hyperactivation as well as malignant transformation of SHP2E76K MSCs. These findings reveal that complex I and III hyperactivation driven by SHP2 LLPS promotes malignant transformation of SHP2E76K MSCs and suggest that inhibition of SHP2 LLPS could be a potential therapeutic target for the treatment of activated SHP2-associated cancers.

A novel approach combining network pharmacology and experimental validation to study the protective effect of ginsenoside Rb1 against cantharidin-induced hepatotoxicity in mice.

Cantharidin (CTD) is a widely used anticancer compound, but its clinical use is mainly limited due to hepatotoxicity. Ginsenoside Rb1 (GRb1) shows potential hepatoprotective effects. Nonetheless, the protective effect and underlying mechanism of GRb1 against CTD-induced hepatotoxicity in mice have not been investigated. This study aims to elucidate the effect and mechanism of GRb1 on CTD-induced hepatotoxicity using network pharmacology and in vivo experiments. Network pharmacology studies have shown that 263 targets were the main mechanisms by which GRb1 alleviates CTD-induced hepatotoxicity. KEGG enrichment analysis revealed that 75 hub genes were mainly enriched in TNF, IL-17 and apoptosis signalling pathways. Molecular docking analysis showed that GRb1 exhibited high affinity with Akt1, Tnf, Il6, Bcl2 and Caspase3. In addition, results from animal studies demonstrated that GRb1 could ameliorate CTD-induced hepatotoxicity by inhibiting protein expression of Caspase-3, Caspase-8, Bcl-2/Bax, GRP78, ATF6, ATF4, CHOP, IRE1α and PERK. This research revealed the mechanism of GRb1 against CTD-induced hepatotoxicity by inhibiting apoptosis and endoplasmic reticulum stress (ERS) and it may provide a scientific rationale for the potential use of GRb1 in the treatment of hepatotoxicity induced by CTD.

Longitudinal relations between teacher support and academic achievement among Chinese children: Disentangling between­ and within-student associations.

This study investigated the longitudinal associations between teacher support (i.e., emotional and instrumental support) and academic (i.e., math) achievement at the between-student and within-student levels using random intercept cross-lagged panel models (RI-CLPMs). Data were collected from 694 elementary school students in China (44.9% girls; Mage = 10.53 years, SD = 0.70) over four waves across 2 school years. Results from the RI-CLPMs supported that higher academic achievement was significantly associated with higher teacher emotional and instrumental support at the between-student level. At the within-student level, the RI-CLPMs only supported the predictive effect of academic achievement on teacher instrumental support, but not emotional support. Further analysis utilizing cross-lagged panel models (CLPMs) demonstrated significant reciprocal effects between teacher emotional support and academic achievement, as well as instrumental support and academic achievement. No significant sex differences were observed in RI-CLPMs or CLPMs. The findings illustrate the importance of distinguishing the between-student and within-student associations in longitudinal relations concerning teacher support and academic achievement.