Long-term liver-related outcomes and liver stiffness progression of statin usage in steatotic liver disease.

BACKGROUND: Statins have multiple benefits in patients with metabolic-associated steatotic liver disease (MASLD). AIM: To explore the effects of statins on the long-term risk of all-cause mortality, liver-related clinical events (LREs) and liver stiffness progression in patients with MASLD. METHODS: This cohort study collected data on patients with MASLD undergoing at least two vibration-controlled transient elastography examinations at 16 tertiary referral centres. Cox regression analysis was performed to examine the association between statin usage and long-term risk of all-cause mortality and LREs stratified by compensated advanced chronic liver disease (cACLD): baseline liver stiffness measurement (LSM) of ≥10 kPa. Liver stiffness progression was defined as an LSM increase of ≥20% for cACLD and from <10 kPa to ≥10 or LSM for non-cACLD. Liver stiffness regression was defined as LSM reduction from ≥10 kPa to <10 or LSM decrease of ≥20% for cACLD. RESULTS: We followed up 7988 patients with baseline LSM 5.9 kPa (IQR 4.6-8.2) for a median of 4.6 years. At baseline, 40.5% of patients used statins, and cACLD was present in 17%. Statin usage was significantly associated with a lower risk of all-cause mortality (adjusted HR=0.233; 95% CI 0.127 to 0.426) and LREs (adjusted HR=0.380; 95% CI 0.268 to 0.539). Statin usage was also associated with lower liver stiffness progression rates in cACLD (HR=0.542; 95% CI 0.389 to 0.755) and non-cACLD (adjusted HR=0.450; 95% CI 0.342 to 0.592), but not with liver stiffness regression (adjusted HR=0.914; 95% CI 0.778 to 1.074). CONCLUSIONS: Statin usage was associated with a relatively lower long-term risk of all-cause mortality, LREs and liver stiffness progression in patients with MASLD.

Predictive value of serum alanine aminotransferase for fatty liver associated with metabolic dysfunction.

In this editorial, we offer commentary on the article published by Chen et al in a recent issue of the World Journal of Gastroenterology (2024; 30: 1346-1357). The study highlights a noteworthy association between persistently elevated, yet high-normal levels of alanine transaminase (ALT) and an escalated cumulative risk of developing metabolic dysfunction-associated fatty liver disease (MAFLD). MAFLD has emerged as a globally prevalent chronic liver condition, whose incidence is steadily rising in parallel with improvements in living standards. Left unchecked, MAFLD can progress from hepatic steatosis to liver fibrosis, cirrhosis, and even hepatocellular carcinoma, underscoring the importance of early screening and diagnosis. ALT is widely recognized as a reliable biomarker for assessing the extent of hepatocellular damage. While ALT levels demonstrate a significant correlation with the severity of fatty liver disease, they lack specificity. The article by Chen et al contributes to our understanding of the development of MAFLD by investigating the long-term implications of high-normal ALT levels. Their findings suggest that sustained elevation within the normal range is linked to an increased likelihood of developing MAFLD, emphasizing the need for closer monitoring and potential intervention in such cases.

Erratum: Corrigendum: Liu W-B, Wang C-Y, Tang Y-N, Wang Y, Pei W-X, Yan C-C (2024) Six new species of Cryptochironomus Kieffer (Diptera, Chironomidae) from the Nearctic region. ZooKeys 1200: 275-302. doi: 10.3897/zookeys.1200.119225.

[This corrects the article DOI: 10.3897/zookeys.1200.119225.].

Xylooligosaccharides alleviate the carbohydrate-enriched diet-induced intestinal barrier dysfunction in carp Megalobrama amblycephala by promoting intestinal development, immunity and gut microbiota.

To date, although the high-carbohydrate (HC) feed has been extensively adopted in the aquaculture industry, its effects on the intestinal function and development of aquatic animals still remain unclear. In addition, the corresponding nutritional intervention is still barely reported. This study aimed to evaluate the influence of xylooligosaccharides (XOS) on the intestinal health of Megalobrama amblycephala subjected to a HC feeding. Fish (average weight: 44.55 ±â€¯0.15 g) were randomly offered 3 diets, including a control one (29 % carbohydrate), a HC one (41 % carbohydrate), and a XOS supplemented one (HC + 1.0 % XOS, HCX) respectively for 12 weeks. The HC feeding caused morphological abnormalities of intestine, an increased intestinal permeability, and the intestinal immunosuppression, all of which were markedly reversed by XOS administration. In addition, compared with the HC group, HCX feeding remarkably promoted the intestinal activities of digestive and brush border enzymes, and the expressions of cell proliferation-related proteins (Wnt10b and Cyclin D1). The 16s rDNA sequencing also revealed that XOS administration increased the abundance of beneficial bacteria, and decreased that of pathogenic ones. In conclusion, dietary supplementation of XOS improved the intestinal histomorphology, barrier function, cell proliferation and bacterial communities of carbohydrate-overloaded fish Megalobrama amblycephala.

The relationship between trait anger and reactive aggressive behavior in middle school students: the mediating role and intervention of hostile attribution bias.

BACKGROUND: The reactive aggressive behavior in individuals typically shows a rapid growth trend as individuals enter adolescence, and peaks during middle-school period. According to the Comprehensive Cognitive Model of Trait Anger, trait anger and hostile attribution bias play important roles in the development of reactive aggressive behavior. Based on this, current study explored the relationship between trait anger and reactive aggressive behavior in middle school students, as well as the mediating role of hostile attribution bias and interventions. METHODS: The current study consisted of three sub-studies. Study 1 recruited 87 middle school students with an average age of 12.367 ± 0.889 years, investigated the relationship between trait anger and reactive aggressive behavior, as well as the mediating role of trait hostile attribution bias. Study 2 recruited 62 middle school students with an average age of 13.376 ± 0.963 years, investigated the relationship between trait anger and reactive aggressive behavior, as well as the mediating role of state hostile attribution bias. Study 3 recruited 80 middle school students with an average age of 13.392 ± 0.977 years, implemented an intervention targeting trait hostile attribution bias in middle school students with high trait anger to reduce their reactive aggressive behavior. In current study, data management was performed using SPSS 22.0. Descriptive statistics, independent samples t-test, paired samples t-test, repeated measures analysis of variance (ANOVA), and path analysis were used for statistical analysis. FINDINGS: The results of Study 1 showed that trait anger predicted reactive aggressive behavior through trait hostile attribution bias. The results of Study 2 indicated that trait and state hostile attribution bias played mediating role intermediary, and trait hostile attribution bias had a stronger mediating effect than state hostile attribution bias. The results of Study 3 suggested that the intervention effectively decreased trait hostile attribution bias and reactive aggressive behavior. CONCLUSIONS: Trait anger can predict the reactive aggressive behavior of junior high school students, with trait hostility attribution bias and state hostility attribution bias mediating this relationship. Intervening in the hostility attribution bias of high-anger junior high school students can effectively reduce their reactive aggressive behavior.

Stearoyl-CoA desaturase 1 is targeted by EBV-encoded miR-BART20-5p and regulates cell autophagy, proliferation, and migration in EBV-associated gastric cancer.

Epstein-Barr virus (EBV) is the first human oncogenic virus known to express microRNAs (miRNAs), which are closely associated with the development of various tumors, including nasopharyngeal and gastric cancers. Stearoyl-CoA Desaturase 1 (SCD1) is a key enzyme in fatty acid synthesis, highly expressed in numerous tumors, promoting tumor growth and metastasis, making it a potential therapeutic target. In this study, we found that SCD1 expression in EBV-associated gastric cancer (EBVaGC) was significantly lower than in EBV-negative gastric cancer (EBVnGC) at both cellular and tissue levels. In addition, EBV-miR-BART20-5p targets the 3'-UTR of SCD1, downregulating its expression. Moreover, overexpression of SCD1 in EBVaGC cells promoted cell migration and proliferation while inhibiting autophagy. These results suggest that EBV-encoded miRNA-BART20-5p may contribute to EBVaGC progression by targeting SCD1.

Mechanism underlying the sustained stimulatory effects of energization on biomethane recovery from food waste post-energization cessation.

Microbial electrolysis cell-assisted anaerobic digestion represents a promising approach for enhancing methanogenesis. This study investigated the impact of varying energy levels followed by long-term open circuit on biogas recovery from food waste. The results demonstrated that a mild voltage of 0.4 V resulted in 61.7% increase in methane yield, with a methane composition reaching 78.89% vol and a remarkable reduction in digestion time by 8 days. Additionally, the facilitated effects remained after prolonged periods of open-circuit. In-depth study revealed that energization significantly enhanced organic hydrolysis, redox proteins secretion and sludge electro-activity. Microbial communities showed that the ever-present energization enriched the hydrolytic bacterium and electrophiles. Subsequent investigations also revealed the upgradation of enzyme-encoding genes associated with hydrolysis and the synthesis of flavin and its homologs (i.e. ribE, ssuE and nfrA2). These findings collectively demonstrated the enduring benefits of energization were linked to the enhanced hydrolysis and regulated mediator-mediated electron transfer pathway.

A simulation study of irradiation effect on InAs/GaAsSb type II quantum dot structures.

Particles in space cause irradiation damage to the solar cells (SCs), resulting in the degradation of their performance. Quantum dot solar cells (QDSCs) have higher theoretical efficiency and better irradiation resistance than the conventional GaAs SCs, which makes them highly promising for application in space. In this paper, we study the proton irradiation effect on InAs/GaAs0.8Sb0.2 QDSCs by SRIM program. The simulation result shows that the InAs/GaAs0.8Sb0.2 QDSCs have fewer vacancies than GaAs SCs when irradiated with low-energy proton, which indicates that the InAs/GaAs0.8Sb0.2 QDSCs have better anti-irradiation characteristics. The study about displacements per atom and proton concentration in two SCs shows that protons with low energy and high irradiation fluences will cause more serious damage in InAs/GaAs0.8Sb0.2 QDSCs. In addition, the proton incident angle affects the vacancy distribution, while the number of QD layers has little effect on it.

Layer-by-Layer Nanoparticles for Calcium Overload in situ Enhanced Reactive Oxygen Oncotherapy.

Background: Challenges such as poor drug selectivity, non-target reactivity, and the development of drug resistance continue to pose significant obstacles in the clinical application of cancer therapeutic drugs. To overcome the limitations of drug resistance in chemotherapy, a viable treatment strategy involves designing multifunctional nano-platforms that exploit the unique physicochemical properties of tumor microenvironment (TME). Methods: Herein, layer-by-layer nanoparticles with polyporous CuS as delivery vehicles, loaded with a sonosensitizer (tetra-(4-aminophenyl) porphyrin, TAPP) and sequentially functionalized with pH-responsive CaCO3, targeting group hyaluronic acid (HA) were designed and synthesized for synergistic treatment involving chemodynamic therapy (CDT), sonodynamic therapy (SDT), photothermal therapy (PTT), and calcium overload. Upon cleavage in an acidic environment, CaCO3 nanoparticles released TAPP and Ca2+, with TAPP generating 1O2 under ultrasound trigger. Exposed CuS produced highly cytotoxic ·OH in response to H2O2 and also exhibited a strong PTT effect. Results: CuS@TAPP-CaCO3/HA (CTCH) delivered an enhanced ability to release more Ca2+ under acidic conditions with a pH value of 6.5, which in situ causes damage to HeLa mitochondria. In vitro and in vivo experiments both demonstrated that mitochondrial dysfunction greatly amplified the damage caused by reactive oxygen species (ROS) to tumor, which strongly confirms the synergistic effect between calcium overload and reactive oxygen therapy. Conclusion: Collectively, the development of CTCH presents a novel therapeutic strategy for tumor treatment by effectively responding to the acidic TME, thus holding significant clinical implications.

Aurantiacibacter hainanensis sp. nov. and Qipengyuania zhejiangensis sp. nov., two novel Erythrobacteraceae species isolated from tidal flat sediments.

Two Gram-stain-negative, rod-shaped, non-motile, aerobic and carotenoid-producing strains, belonging to the family Erythrobacteraceae, designated as H149T and Z2T, were isolated from tidal flat sediment samples collected in Hainan and Zhejiang, PR China, respectively. Growth of strain H149T occurred at 15-42 °C, 0-10.0 % (w/v) NaCl, and pH 6.0-8.5, with the optima at 35-37 °C, 3.0-3.5 % (w/v) NaCl and pH 7.0. Strain Z2T grew at 15-37 °C, 0-6.0 % (w/v) NaCl, and pH 6.0-9.5, with the optima at 25-30 °C, 0.5-1.0 % (w/v) NaCl and pH 6.0-6.5. Ubiquinone-10 was the sole ubiquinone in two strains. The predominant cellular fatty acids of strain H149T were C16 : 0, summed feature 3 and summed feature 8, while those of strain Z2T were C17 : 1 ω6c, summed feature 3 and summed feature 8. Strains H149T and Z2T shared diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine and sphingoglycolipid as major polar lipids. The 16S rRNA gene sequence identity analysis indicated that strain H149T had the highest sequence identity of 98.4 % with Aurantiacibacter odishensis KCTC 23981T, and strain Z2T had that of 98.2 % with Qipengyuania pacifica NZ-96T. Phylogenetic trees based on 16S rRNA gene and core-genome sequences revealed that strains H149T and Z2T formed two independent clades in the genera Aurantiacibacter and Qipengyuania, respectively. Strain H149T had average nucleotide identity values of 74.0-81.3 % and in silico DNA-DNA hybridization values of 18.5-23.1 % with Aurantiacibacter type strains, while strain Z2T had values of 73.3-78.7 % and 14.5-33.3 % with Qipengyuania type strains. The genomic DNA G+C contents of strains H149T and Z2T were 64.3 and 61.8 %, respectively. Based on the genetic, genomic, phylogenetic, physiological and chemotaxonomic results, strains H149T (=KCTC 8397T=MCCC 1K08920T) and Z2T (=KCTC 8396T=MCCC 1K08946T) are concluded to represent two novel Erythrobacteraceae species for which the names Aurantiacibacter hainanensis sp. nov. and Qipengyuania zhejiangensis sp. nov. are proposed, respectively.

MLH1 Inhibits Metastatic Potential of Pancreatic Ductal Adenocarcinoma via Downregulation of GPRC5C.

DNA mismatch repair gene MutL homolog-1 (MLH1) has divergent effects in many cancers; however, its impact on the metastasis of pancreatic ductal adenocarcinoma (PDAC) remains unclear. In this study, MLH1 stably overexpressed (OE) and knockdowned (KD) sublines were established. Wound healing and transwell assays were used to evaluate cell migration/invasion. In vivo metastasis was investigated in orthotopic implantation models (severe combined immunodeficiency mice). RT-qPCR and western blotting were adopted to show gene/protein expression. MLH1 downstream genes were screened by transcriptome sequencing. Tissue microarray-based immunohistochemistry was applied to determine protein expression in human specimens. In successfully generated sublines, OE cells presented weaker migration/invasion abilities, compared with controls, whereas in KD cells, these abilities were significantly stronger. The metastasis-inhibitory effect of MLH1 was also observed in mice. Mechanistically, G protein-coupled receptor, family C, group 5, member C (GPRC5C) was a key downstream gene of MLH1 in PDAC cells. Subsequently, transient GPRC5C silencing effectively inhibited cell migration/invasion and remarkably reversed the proinvasive effect of MLH1 knockdown in KD cells. In animal models and human PDAC tissues, tumoral GPRC5C expression, negatively associated with MLH1 expressions, was positively correlated with histologic grade, vessel invasion, and poor cancer-specific survival. In conclusion, MLH1 inhibits the metastatic potential of PDAC via downregulation of GPRC5C.

Multi-objective optimization of the spatial layout of green infrastructures with cost-effectiveness analysis under climate change scenarios.

Green infrastructure (GI) plays a significant role in alleviating urban flooding risk caused by urbanization and climate change. Due to space and financial limitations, the successful implementation of GI relies heavily on its layout design, and there is an increasing trend in using multi-objective optimization to support decision-making in GI planning. However, little is known about the hydrological effects of synchronously optimizing the size, location, and connection of GI under climate change. This study proposed a framework to optimize the size, location, and connection of typical GI facilities under climate change by combining the modified non-dominated sorting genetic algorithm-II (NSGA-II) and storm water management model (SWMM). The results showed that optimizing the size, location, and connection of GI facilities significantly increases the maximum reduction rate of runoff and peak flow by 13.4 %-24.5 % and 3.3 %-18 %, respectively, compared to optimizing only the size and location of GI. In the optimized results, most of the runoff from building roofs flew toward green space. Permeable pavement accounted for the highest average proportion of GI implementation area in optimal layouts, accounting for 29.8 %-54.2 % of road area. The average cost-effectiveness (C/E) values decreased from 16 %/105 Yuan under the historical period scenario to 14.3 %/105 Yuan and 14 %/105 Yuan under the two shared socioeconomic pathways (SSPs), SSP2-4.5 and SSP5-8.5, respectively. These results can help in understanding the optimization layout and cost-effectiveness of GI under climate change, and the proposed framework can enhance the adaptability of cities to climate change by providing specific cost-effective GI layout design.

Predictive accuracy of wideband absorbance in children with large vestibular aqueduct syndrome: A single-center retrospective study.

Objectives: This study aimed to assess the clinical significance of Wideband Absorbance (WBA) in children with Large Vestibular Aqueduct Syndrome (LVAS), which could potentially serve as diagnostic and predictive markers for LVAS in children. Design: This was a single-center retrospective case-control study. Audiological measurements and Wideband Acoustic Immittance (WAI) were performed. Propensity score matching (PSM) was considered to treat group imbalance. The Receiver Operating Characteristic (ROC) curves and area under the ROC curve (AUC) were used to evaluate the sensitivity and specificity of WBA. Study sample: Participants included 42 children with LVAS and 163 normal children aged 6 months -11 years recruited from clinical audiology settings between 2019 and 2021. Results: The WBA at Tympanometric Peak Pressure (WBATPP) and Ambient Pressure (WBAA) in the LVAS group were significantly lower than those of the control group at 1259-2000 Hz but higher at 4000-6349 Hz (p < 0.05, power >0.8). The WBAA (1587 Hz) AUC value was 0.805, identifying a score ≤0.565 as indicative of a LVAS risk. Conclusions: WBA holds promise in distinguishing LVAS from the normal condition and warrants further exploration as a tool to examine the influence of inner ear pressure on acoustic energy transmission in the middle ear.

Novel goose parvovirus VP1 targets IRF7 protein to block the type I interferon upstream signaling pathway.

Outbreaks of short beak and dwarfism syndrome (SBDS), caused by a novel goose parvovirus (NGPV), have occurred in China since 2015. The NGPV, a single-stranded DNA virus, is thought to be vertically transmitted. However, the mechanism of NGPV immune evasion remains unclear. In this study, we investigated the impact of NGPV infection on the Cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway in duck embryonic fibroblast (DEF) cells. Our findings demonstrate that NGPV infection stimulates the mRNA expression of cGAS but results in weak IFN-ß induction. NGPV impedes the expression of IFN-ß and downstream interferon-stimulated genes, thereby reducing the secretion of IFN-ß induced by interferon-stimulating DNA (ISD) and poly (I: C). RNA-seq results show that NGPV infection downregulates interferon mRNA expression while enhancing the mRNA expression of inflammatory factors. Additionally, the results of viral protein over-expression indicate that VP1 exhibits a remarkable ability to inhibit IFN-ß expression compared to other viral proteins. Results indicated that only the intact VP1 protein could inhibit the expression of IFN-ß, while the truncated proteins VP1U and VP2 do not possess such characteristics. The immunoprecipitation experiment showed that both VP1 and VP2 could interact with IRF7 protein, while VP1U does not. In summary, our findings indicate that NGPV infection impairs the host's innate immune response by potentially modulating the expression and secretion of interferons and interferon-stimulating factors via IRF7 molecules, which are regulated by the VP1 protein.

Molecular mechanism of basolateral amygdala involved in electroacupuncture-induced amelioration of cancer pain and concomitant depression based on transcriptomics techniques. / åŸºäºŽè½¬å½•ç»„å­¦æŠ€æœ¯æŽ¢è®¨åŸºåº•å¤–ä¾§æä»æ ¸å‚ä¸Žç”µé’ˆæ²»ç–—ç™Œç—›åŠå ¶è¯±å‘çš„æŠ‘éƒæƒ ç»ªçš„åˆ†å­æœºåˆ¶.

OBJECTIVES: To observe the effect of electroacupuncture (EA) of "Zusanli" (ST36) and "Sanyinjiao" (SP6) on cancer pain and concomitant negative emotion in cancer pain model mice, and to explore its molecular mechanisms in the basolateral amygdala (BLA) by using transcriptomics techniques. METHODS: C57BL/6 mice were randomized into sham operation, model and EA groups, with 10 mice in each group. The cancer pain model was established by injecting PBS suspension containing Lewis lung cancer cells into the femur. The mice in the EA group received EA stimulation(1 mA, 2 Hz) on ST36 and SP6 from the 10th day after modeling, 20 min per day for 12 successive days. The bone damage of the distal femur was observed with X-ray and H.E. staining, respectively. The mechanical pain threshold (MPT) was detected by using von Frey. The depression-like behavior was detected by using sucrose-preference test (sucrose preference index in 12 h), and the immobility (feeling of despair) duration of forced swimming within 4 min. The BLA tissue was extracted for RNA sequencing (RNA library construction, and screening differential gene profiling by transcriptomic sequencing) and bioinformatics analysis. The real-time PCR was used to validate the mRNA expression of differentially expressed genes：tumor necrosis factor superfamily 8 (Tnfsf8), bone marrow stromal cell antigen 1 (Bst1), prodynorphin (Pdyn) and voltage-gated sodium channelß4 (Scn4b). RESULTS: H.E. staining and X-ray showed significant bone damage in the distal femur in cancer pain mice. In contrast to the sham operation group, the MPT on the 1st , 4th, 7th , 10th, 14th and 21st day after modeling and sucrose preference index were significantly decreased (P<0.001, P<0.000 1), and the immobility time of the forced swimming was considerably increased in the model group (P<0.001). In contrast to the model group, the MPT values on the 14th and 21st day and sucrose preference index were obviously increased (P<0.000 1, P<0.05), and the immobility time was strikingly decreased in the EA group (P<0.01). RNA sequencing showed that a total of 404 differentially expressed genes (205 up-regulated, 199 down-regulated) were screened in the model group compared with the sham operation group, and a total of 329 differentially expressed genes (206 up-regulated and 123 down-regulated) were screened in the EA group compared with the model group. Venn diagram analysis of the differentially expressed genes showed that 45 up-regulated and 28 down-regulated genes in the model group were completely reversed by EA. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the screened differentially expressed genes revealed that the above differential genes were mainly enriched in the ligand receptor activity, cytokine receptor binding, and cytokine activity related to neuro-inflammation, as well as in neuropeptide signaling pathways related to neuronal excitability, and calcium ion mediated signal transduction. The analysis of KEGG pathway showed that the differentially expressed genes were mainly enriched in the inflammation-related pathways, such as interleukin-17 pathway. Validation analysis of the differentially expressed genes showed that the expression levels of Tnfsf8 and Bst1 were significantly up-regulated in the model group compared with the sham operation group (P<0.01, P<0.05), and down-regulated by EA (P<0.01, P<0.05), while the expression levels of Pdyn and Scn4b were down-regulated in the model group in comparison with the sham operation group (P<0.01), and up-regulated by EA (P<0.05, P<0.01), which was consistent with the changing trend of the gene sequencing results. CONCLUSIONS: Acupuncture of ST36 and SP6 can significantly relieve cancer pain and concomitant negative emotion in cancer pain mice, which may be related to its functions in alleviating neuro-inflammation and relieving the abnormal activities of specific neurons in the BLA.

Mechanism of acupuncture and moxibustion in ameliorating liver injury induced by cisplatin by regulating IRE-1 signaling pathway. / "扶正益肝"é’ˆç¸ç©´æ–¹åŸºäºŽè‚Œé†‡éœ€æ±‚é ¶1ä¿¡å·é€šè·¯æ”¹å–„é¡ºé“‚è‡´å°é¼ è‚æŸä¼¤çš„æœºåˆ¶.

OBJECTIVES: To investigate the mechanism of the effect of acupuncture and moxibustion on improving liver injury in cisplatin (DDP) induced liver injury model mice by observing the changes of inositol-requiring enzyme (IRE) -1 signaling pathway. METHODS: Forty KM mice were randomly divided into control, model, acupuncture and moxibustion groups, with 10 mice in each group. The liver injury model was replicated by intraperitoneal injection of DDP (10 mg/kg). In the acupuncture group and the moxibustion group, acupuncture and moxibustion were performed at "Dazhui"(GV14), and bilateral "Ganshu"(BL18), "Shenshu" (BL23), and "Zusanli"(ST36), respectively for 6 min, once per day for 7 d. The apoptosis of hepatocytes was detected by TUNEL staining. The expression of phosphorylation(p)-IRE-1α, glucose-regulated protein (Grp) 78 and cysteine aspartic protease (Caspase) -12 in liver tissue were detected by immunohistochemistry and Western blot, respectively. The expression levels of Grp78 and Caspase-12 mRNA in liver tissue were detected by quantitative real-time PCR. RESULTS: Compared with the control group, the apoptosis rate of hepatocytes was increased (P<0.05), the positive expression and protein expression of p-IRE-1α, Grp78, and Caspase-12 were increased (P<0.05), the expression levels of Grp78 and Caspase-12 mRNA were increased (P<0.05) in the model group. Compared with the model group, all these indicators showed opposite trends (P<0.05) in the acupuncture and moxibustion groups. CONCLUSIONS: Acupuncture and moxibustion can reduce liver injury due to DDP chemotherapy by modulating IRE-1 signaling pathway, inhibiting the excessive activation of endoplasmic reticulum stress, and reducing liver cell apoptosis.

[Rapid Start-up of Continuous Autotrophic Nitrogen Removal Reactor by Hybrid-inoculating PN and PN/A Granular Sludges].

The rapid cultivation of partial nitritation/ANAMMOX （PN/A） granular sludge in a continuous-flow mode is one of the key technologies for efficient biological nitrogen removal in domestic wastewater treatment. Compared with that in PN/A granular sludge, PN granular sludge demonstrates a shorter incubation period and suitability for batch culture. It is also a good carrier for enriching ANAMMOX （AMX） bacteria. In this study, we established a continuous-flow autotrophic nitrogen removal process in three continuously stirred tank reactors （CSTR） （R1-R3） by hybrid-inoculating PN/A and PN granular sludge at the mass ratios of 3∶1, 1∶1, and 1∶3, respectively. By implementing high ammonium nitrogen loading and short hydraulic retention time, continuous autotrophic nitrogen removal processes were successfully started up in the three CSTRs. The results showed that compared with that of R1 and R2, R3 had a longer start-up time but a similar steady-state nitrogen removal performance. The total nitrogen removal load of R3 could be more than 2.6 kg·ï¼ˆm3·d）-1. Intriguingly, the inoculated PN granular sludge served as a precursor for PN/A granular sludge cultivation. This approach facilitated the enrichment of anaerobic ammonia-oxidizing bacteria （AMX） by introducing abundant ammonium-oxidizing bacteria （AOB） and nitrite nitrogen substrates into the CSTR. According to the results of high-throughput sequencing, the microbial abundance and diversity of the mature granules in R1-R3 were significantly higher than those of the inoculation sludge. AOB （genus Nitrosomonas）, AMX （genera Candidatus Kuenenia and Candidatus Brocadia）, and symbiotic heterotrophs, such as Chloroflexi, Bacteroidetes, and Chlorobi, drove the autotrophic nitrogen removal process and maintained the stability of the granular structure. In summary, a novel start-up strategy of hybrid-inoculating granular sludge was provided for a continuous-flow autotrophic nitrogen removal in engineering application.

Synthetic macrolides overcoming MLSBK-resistant pathogens.

Conventional macrolide-lincosamide-streptogramin B-ketolide (MLSBK) antibiotics are unable to counter the growing challenge of antibiotic resistance that is conferred by the constitutive methylation of rRNA base A2058 or its G2058 mutation, while the presence of unmodified A2058 is crucial for high selectivity of traditional MLSBK in targeting pathogens over human cells. The absence of effective modes of action reinforces the prevailing belief that constitutively antibiotic-resistant Staphylococcus aureus remains impervious to existing macrolides including telithromycin. Here, we report the design and synthesis of a novel series of macrolides, featuring the strategic fusion of ketolide and quinolone moieties. Our effort led to the discovery of two potent compounds, MCX-219 and MCX-190, demonstrating enhanced antibacterial efficacy against a broad spectrum of formidable pathogens, including A2058-methylated Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, and notably, the clinical Mycoplasma pneumoniae isolates harboring A2058G mutations which are implicated in the recent pneumonia outbreak in China. Mechanistic studies reveal that the modified quinolone moiety of MCX-190 establishes a distinctive secondary binding site within the nascent peptide exit tunnel. Structure-activity relationship analysis underscores the importance of this secondary binding, maintained by a sandwich-like π-π stacking interaction and a water-magnesium bridge, for effective engagement with A2058-methylated ribosomes rather than topoisomerases targeted by quinolone antibiotics. Our findings not only highlight MCX-219 and MCX-190 as promising candidates for next-generation MLSBK antibiotics to combat antibiotic resistance, but also pave the way for the future rational design of the class of MLSBK antibiotics, offering a strategic framework to overcome the challenges posed by escalating antibiotic resistance.