G3BP1 promotes DNA binding and activation of cGAS.

Cyclic GMP-AMP synthase (cGAS) is a key sensor responsible for cytosolic DNA detection. Here we report that GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) is critical for DNA sensing and efficient activation of cGAS. G3BP1 enhanced DNA binding of cGAS by promoting the formation of large cGAS complexes. G3BP1 deficiency led to inefficient DNA binding by cGAS and inhibited cGAS-dependent interferon (IFN) production. The G3BP1 inhibitor epigallocatechin gallate (EGCG) disrupted existing G3BP1-cGAS complexes and inhibited DNA-triggered cGAS activation, thereby blocking DNA-induced IFN production both in vivo and in vitro. EGCG administration blunted self DNA-induced autoinflammatory responses in an Aicardi-Goutières syndrome (AGS) mouse model and reduced IFN-stimulated gene expression in cells from a patient with AGS. Thus, our study reveals that G3BP1 physically interacts with and primes cGAS for efficient activation. Furthermore, EGCG-mediated inhibition of G3BP1 provides a potential treatment for cGAS-related autoimmune diseases.

Integrated analyses for identification of a three-gene signature associated with Chaihu Shugan San formula for hepatocellular carcinoma treatment.

Chaihu Shugan San (CSS) is a well-known traditional herbal formula that has the potential to ameliorate hepatocellular carcinoma (HCC); however, its mechanism of action remains unknown. Here, we identified the key targets of CSS against HCC and developed a prognostic model to predict the survival of patients with HCC. The effect of CSS plus sorafenib on HCC cell proliferation was evaluated using the MTT assay. LASSO-Cox regression was used to establish a three-gene signature model targeting CSS. Correlations between immune cells, immune checkpoints and risk score were determined to evaluate the immune-related effects of CSS. The interactions between the components and targets were validated using molecular docking and Surface Plasmon Resonance (SPR) assays. CSS and sorafenib synergistically inhibited HCC cell proliferation. Ten core compounds and 224 targets were identified using a drug compound-target network. The prognostic model of the three CSS targets (AKT1, MAPK3 and CASP3) showed predictive ability. Risk scores positively correlated with cancer-promoting immune cells and high expression of immune checkpoint proteins. Molecular docking and SPR analyses confirmed the strong binding affinities of the active components and the target genes. Western blot analysis confirmed the synergistic effect of CSS and sorafenib in inhibiting the expression of these three targets. In conclusion, CSS may regulate the activity of immune-related factors in the tumour microenvironment, reverse immune escape, enhance immune responses through AKT1, MAPK3, and CASP3, and synergistically alleviate HCC. The co-administration of sorafenib with CSS has a strong clinical outlook against HCC.

UBC9-mediated SUMOylation of Lamin B1 enhances DNA-damage-induced nuclear DNA leakage and autophagy after spinal cord injury.

Recent studies have shown that nucleophagy can mitigate DNA damage by selectively degrading nuclear components protruding from the nucleus. However, little is known about the role of nucleophagy in neurons after spinal cord injury (SCI). Western blot analysis and immunofluorescence were performed to evaluate the nucleophagy after nuclear DNA damage and leakage in SCI neurons in vivo and NSC34 expression in primary neurons cultured with oxygen-glucose deprivation (OGD) in vitro, as well as the interaction and colocalization of autophagy protein LC3 with nuclear lamina protein Lamin B1. The effect of UBC9, a Small ubiquitin-related modifier (SUMO) E2 ligase, on Lamin B1 SUMOylation and nucleophagy was examined by siRNA transfection or 2-D08 (a small-molecule inhibitor of UBC9), immunoprecipitation, and immunofluorescence. In SCI and OGD injured NSC34 or primary cultured neurons, neuronal nuclear DNA damage induced the SUMOylation of Lamin B1, which was required by the nuclear Lamina accumulation of UBC9. Furthermore, LC3/Atg8, an autophagy-related protein, directly bound to SUMOylated Lamin B1, and delivered Lamin B1 to the lysosome. Knockdown or suppression of UBC9 with siRNA or 2-D08 inhibited SUMOylation of Lamin B1 and subsequent nucleophagy and protected against neuronal death. Upon neuronal DNA damage and leakage after SCI, SUMOylation of Lamin B1 is induced by nuclear Lamina accumulation of UBC9. Furthermore, it promotes LC3-Lamin B1 interaction to trigger nucleophagy that protects against neuronal DNA damage.

The stress granule protein G3BP1 promotes pre-condensation of cGAS to allow rapid responses to DNA.

Cyclic GMP-AMP synthase (cGAS) functions as a key sensor for microbial invasion and cellular damage by detecting emerging cytosolic DNA. Here, we report that GTPase-activating protein-(SH3 domain)-binding protein 1 (G3BP1) primes cGAS for its prompt activation by engaging cGAS in a primary liquid-phase condensation state. Using high-resolution microscopy, we show that in resting cells, cGAS exhibits particle-like morphological characteristics, which are markedly weakened when G3BP1 is deleted. Upon DNA challenge, the pre-condensed cGAS undergoes liquid-liquid phase separation (LLPS) more efficiently. Importantly, G3BP1 deficiency or its inhibition dramatically diminishes DNA-induced LLPS and the subsequent activation of cGAS. Interestingly, RNA, previously reported to form condensates with cGAS, does not activate cGAS. Accordingly, we find that DNA - but not RNA - treatment leads to the dissociation of G3BP1 from cGAS. Taken together, our study shows that the primary condensation state of cGAS is critical for its rapid response to DNA.

Spatially and Temporally Differentiated NOx and VOCs Emission Abatement Could Effectively Gain O3-Related Health Benefits.

The increasing level of O3 pollution in China significantly exacerbates the long-term O3 health damage, and an optimized health-oriented strategy for NOx and VOCs emission abatement is needed. Here, we developed an integrated evaluation and optimization system for the O3 control strategy by merging a response surface model for the O3-related mortality and an optimization module. Applying this system to the Yangtze River Delta (YRD), we evaluated driving factors for mortality changes from 2013 to 2017, quantified spatial and temporal O3-related mortality responses to precursor emission abatement, and optimized a health-oriented control strategy. Results indicate that insufficient NOx emission abatement combined with deficient VOCs control from 2013 to 2017 aggravated O3-related mortality, particularly during spring and autumn. Northern YRD should promote VOCs control due to higher VOC-limited characteristics, whereas fastening NOx emission abatement is more favorable in southern YRD. Moreover, promotion of NOx mitigation in late spring and summer and facilitating VOCs control in spring and autumn could further reduce O3-related mortality by nearly 10% compared to the control strategy without seasonal differences. These findings highlight that a spatially and temporally differentiated NOx and VOCs emission control strategy could gain more O3-related health benefits, offering valuable insights to regions with severe ozone pollution all over the world.

Rapid hydrolysis of NO2 at High Ionic Strengths of Deliquesced Aerosol Particles.

Nitrogen dioxide (NO2) hydrolysis in deliquesced aerosol particles forms nitrous acid and nitrate and thus impacts air quality, climate, and the nitrogen cycle. Traditionally, it is considered to proceed far too slowly in the atmosphere. However, the significance of this process is highly uncertain because kinetic studies have only been made in dilute aqueous solutions but not under high ionic strength conditions of the aerosol particles. Here, we use laboratory experiments, air quality models, and field measurements to examine the effect of the ionic strength on the reaction kinetics of NO2 hydrolysis. We find that high ionic strengths (I) enhance the reaction rate constants (kI) by more than an order of magnitude compared to that at infinite dilution (kI=0), yielding log10(kI/kI=0) = 0.04I or rate enhancement factor = 100.04I. A state-of-the-art air quality model shows that the enhanced NO2 hydrolysis reduces the negative bias in the simulated concentrations of nitrous acid by 28% on average when compared to field observations over the North China Plain. Rapid NO2 hydrolysis also enhances the levels of nitrous acid in other polluted regions such as North India and further promotes atmospheric oxidation capacity. This study highlights the need to evaluate various reaction kinetics of atmospheric aerosols with high ionic strengths.

Methylobacterium nigriterrae sp. nov., isolated from black soil.

An aerobic, Gram-stain-negative, motile rod bacterium, designated as SYSU BS000021T, was isolated from a black soil sample in Harbin, Heilongjiang province, China. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the isolate belongs to the genus Methylobacterium, and showed the highest sequence similarity to Methylobacterium segetis KCTC 62267 T (98.51%) and Methylobacterium oxalidis DSM 24028 T (97.79%). Growth occurred at 20-37℃ (optimum, 28 °C), pH 6.0-8.0 (optimum, pH 7.0) and in the presence of 0% (w/v) NaCl. Polar lipids comprised of phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, one unidentified aminolipid and one unidentified polar lipid. The major cellular fatty acids (> 5%) were C18:0 and C18:1 ω7c and/or C18:1 ω6c. The predominant respiratory quinone was Q-10. The genomic G + C content was 68.36% based on the whole genome analysis. The average nucleotide identity (≤ 83.5%) and digital DNA-DNA hybridization (≤ 27.3%) values between strain SYSU BS000021T and other members of the genus Methylobacterium were all lower than the threshold values recommended for distinguishing novel prokaryotic species. Based on the results of phenotypic, chemotaxonomic and phylogenetic analyses, strain SYSU BS000021T represents a novel species of the genus Methylobacterium, for which the name Methylobacterium nigriterrae sp. nov. is proposed. The type strain of the proposed novel species is SYSU BS000021T (= GDMCC 1.3814 T = KCTC 8051 T).

The safety and short-term effect of mixed approach in laparoscopic right hemicolectomy for right colon cancer compared with middle approach: a retrospective study.

PURPOSE: To investigate whether the mixed approach is a safe and advantageous way to operate laparoscopic right hemicolectomy. METHODS: A retrospective study was performed on 316 patients who underwent laparoscopic right hemicolectomy in our center. They were assigned to the middle approach group (n = 158) and the mixed approach group (n = 158) according to the surgical approaches. The baseline data like gender、age and body mass index as well as the intraoperative and postoperative conditions including operation time, blood loss, postoperative hospital stay and complications were analyzed. RESULTS: There were no significant differences in age, sex, BMI, ASA grade and tumor characteristics between the two groups. Compared with the middle approach group, the mixed approach group was significantly lower in terms of operation time (217.61 min vs 154.31 min, p < 0.001), intraoperative blood loss (73.8 ml vs 37.97 ml, p < 0.001) and postoperative drainage volume. There was no significant difference in the postoperative complications like postoperative anastomotic leakage, postoperative infection and postoperative intestinal obstruction. CONCLUSIONS: Compared with the middle approach, the mixed approach is a safe and advantageous way that can significantly shorten the operation time, reduce intraoperative bleeding and postoperative drainage volume, and does not prolong the length of hospital stay or increase the morbidity postoperative complications.

Involvement of YTHDF1 in renal fibrosis progression via up-regulating YAP.

Renal fibrosis is a progressive, fatal renal disease characterized by the aberrant accumulation of myofibroblasts that produce excess extracellular matrix (ECM) in the renal interstitium and glomeruli. Yes-associated protein (YAP) has been regarded as a crucial modulator in myofibroblast transformation, but its upstream regulator remains a mystery. In the present study investigating the participation of m6A methylation during renal fibrosis through bioinformatics analysis, we identified YTHDF1, a modulator of m6A methylation, as a key contributor for renal fibrosis because it was highly expressed in human fibrotic kidneys and had a significant correction with YAP. Their co-localization in human fibrotic kidneys was additionally shown by immunofluorescence. We then found that YTHDF1 was also up-regulated in fibrotic mouse kidneys induced by unilateral ureteral obstruction (UUO), high-dose folic acid administration, or the unilateral ischemia-reperfusion injury, further supporting a causal role of YTHDF1 during renal fibrosis. Consistent with this notion, YTHDF1 knockdown alleviated the progression of renal fibrosis both in cultured cells induced by transforming growth factor-beta administration and in the UUO mouse model. Meanwhile, YAP was accordingly down-regulated when YTHDF1 was inhibited. Furthermore, the specific binding of YTHDF1 to YAP mRNA was detected using RNA Binding Protein Immunoprecipitation, and the up-regulation of fibrotic related molecules in cultured cells induced by YTHDF1 over-expression plasmid was attenuated by YAP siRNA. Taken together, our data highlight the potential utility of YTHDF1 as an indicator for renal fibrosis and suggest that YTHDF1 inhibition might be a promising therapeutic strategy to alleviate renal fibrosis via downregulating YAP.

Extreme Emission Reduction Requirements for China to Achieve World Health Organization Global Air Quality Guidelines.

A big gap exists between current air quality in China and the World Health Organization (WHO) global air quality guidelines (AQG) released in 2021. Previous studies on air pollution control have focused on emission reduction demand in China but ignored the influence of transboundary pollution, which has been proven to have a significant impact on air quality in China. Here, we develop an emission-concentration response surface model coupled with transboundary pollution to quantify the emission reduction demand for China to achieve WHO AQG. China cannot achieve WHO AQG by its own emission reduction for high transboundary pollution of both PM2.5 and O3. Reducing transboundary pollution will loosen the reduction demand for NH3 and VOCs emissions in China. However, to meet 10 µg·m-3 for PM2.5 and 60 µg·m-3 for peak season O3, China still needs to reduce its emissions of SO2, NOx, NH3, VOCs, and primary PM2.5 by more than 95, 95, 76, 62, and 96% respectively, on the basis of 2015. We highlight that both extreme emission reduction in China and great efforts in addressing transboundary air pollution are crucial to reach WHO AQG.

Mismatched Social Welfare Allocation and PM2.5-Related Health Damage along Value Chains within China.

Value chains have played a critical part in the growth. However, the fairness of the social welfare allocation along the value chain is largely underinvestigated, especially when considering the harmful environmental and health effects associated with the production processes. We used fine-scale profiling to analyze the social welfare allocation along China's domestic value chain within the context of environmental and health effects and investigated the underlying mechanisms. Our results suggested that the top 10% regions in the value chain obtained 2.9 times more social income and 2.1 times more job opportunities than the average, with much lower health damage. Further inspection showed a significant contribution of the "siphon effect"─major resource providers suffer the most in terms of localized health damage along with insufficient social welfare for compensation. We found that inter-region atmosphere transport results in redistribution for 53% health damages, which decreases the welfare-damage mismatch at "suffering" regions but also causes serious health damage to more than half of regions and populations in total. Specifically, around 10% of regions have lower social welfare and also experienced a significant increase in health damage caused by atmospheric transport. These results highlighted the necessity of a value chain-oriented, quantitative compensation-driven policy.

Sources of Organic Aerosol in China from 2005 to 2019: A Modeling Analysis.

Organic aerosol (OA) is a key component of fine particulate matter (PM2.5) and affects the human health and leads to climate change. With strict control measures for air pollutants during the last decade, the OA concentration in China declined slowly, while its sources remain unclear. In this study, we simulate the primary OA (POA) and secondary OA (SOA) concentrations from 2005 to 2019 with a state-of-the-art air quality model, Community Multiscale Air Quality (CMAQ, version 5.3.2) coupled with a Two-Dimensional Volatility Basis Set (2D-VBS) module, and a long-term emission inventory of full-volatility organic compounds in China and conduct source apportionment and sensitivity analysis. The simulation results show that, from 2005 to 2019, the OA concentration in China decreased from 24.0 to 12.8 µg/m3 with most of the reduction from POA. The OA pollution from residential biomass burning declined 75% from 2005 to 2019, while it is still the major OA source in China. OA pollution from VCP increased by more than 2-fold and became the largest SOA source in China. From 2014 to 2019, the NOx control in China slightly offset the decrease of SOA concentration due to elevated oxidation capacity.

Drivers of High Concentrations of Secondary Organic Aerosols in Northern China during the COVID-19 Lockdowns.

During the COVID-19 lockdown in early 2020, observations in Beijing indicate that secondary organic aerosol (SOA) concentrations increased despite substantial emission reduction, but the reasons are not fully explained. Here, we integrate the two-dimensional volatility basis set into a state-of-the-art chemical transport model, which unprecedentedly reproduces organic aerosol (OA) components resolved by the positive matrix factorization based on aerosol mass spectrometer observations. The model shows that, for Beijing, the emission reduction during the lockdown lowered primary organic aerosol (POA)/SOA concentrations by 50%/18%, while deteriorated meteorological conditions increased them by 30%/119%, resulting in a net decrease in the POA concentration and a net increase in the SOA concentration. Emission reduction and meteorological changes both led to an increased OH concentration, which accounts for their distinct effects on POA and SOA. SOA from anthropogenic volatile organic compounds and organics with lower volatility contributed 28 and 62%, respectively, to the net SOA increase. Different from Beijing, the SOA concentration decreased in southern Hebei during the lockdown because of more favorable meteorology. Our findings confirm the effectiveness of organic emission reductions and meanwhile reveal the challenge in controlling SOA pollution that calls for large organic precursor emission reductions to rival the adverse impact of OH increase.

m6A-dependent mevalonate kinase in juvenile hormone synthesis pathway regulates the diapause process of bivoltine silkworm (Bombyx mori).

BACKGROUND: Research has shown that epigenetic modification are involved the regulation of diapause in bivoltine silkworms (Bombyx mori), but it remains unclear how epigenetic modification in response to environmental signals precisely to regulate the diapause processing of bivoltine B. mori. METHODS AND RESULTS: In this study, the diapause terminated eggs of bivoltine B. mori, Qiufeng (QF) were divided into two groups: a QFHT group incubated at 25 °C with a natural day/night cycle to produce diapause eggs, and a QFLT group incubated at 16.5 °C in darkness to produce non-diapause eggs. On the 3rd day of the pupal stage, the total RNAs of the eggs were extracted and their N6-adenosine methylation (m6A) abundances were analyzed to explore the effects of m6A methylation on diapause in the silkworm. The results showed that 1984 m6A peaks are shared, 1563 in QFLT and 659 in QFHT. The m6A methylation level of the QFLT group was higher than that of the QFHT one in various signaling pathways. The m6A methylation rate of mevalonate kinase (MK) in the insect hormone synthesis pathway was significantly different between the two groups. The knockdown of MK by RNA interference in the pupae of QFLT resulted in females laying diapause eggs rather than non-diapause eggs after mating. CONCLUSIONS: m6A methylation involves in the diapause regulation of bivoltine B. mori by changing the expression levels of MK. This result provides a clearer image of the environmental signals on the regulation of diapause in bivoltine silkworms.

Downregulated lncRNA HOTAIR inhibits the proliferation of granulosa cells in endometriosis by upregulating p21.

This study was carried out to elucidate the biological function of HOTAIR in granulosa cells of endometriosis and the underlying mechanism. Granulosa cells were extracted from endometriosis patients and subjects with fallopian tube factor alone who received IVF-ET. Relative levels of HOTAIR and p21 in the extracted granulosa cells were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Moreover, HOTAIR level in endometriosis patients in stage I-II or III-IV was determined. Regulatory effects of HOTAIR on the proliferation of KGN cells were evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide), 5-Ethynyl-2'- deoxyuridine (EdU) and colony formation assay. Flow cytometry was conducted to evaluate the potential influence of HOTAIR on apoptosis of KGN cells. The interaction between HOTAIR and EZH2, SUV12 was detected by RNA binding protein immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assay. Finally, the potential role of the HOTAIR/p21 axis in mediating cellular behaviors of KGN cells was explored. HOTAIR was downregulated in granulosa cells extracted from endometriosis patients relative to those with fallopian tube factor alone who received IVF-ET. Knockdown of HOTAIR suppressed the proliferative ability and induced apoptosis of KGN cells. RIP and ChIP assay showed that silence of HOTAIR released EZH2 to suppress the DNA methylation of p21. Knockdown of p21 could reverse the regulatory effect of HOTAIR on the proliferative change of KGN cells. Downregulated HOTAIR suppresses the proliferative ability and induces apoptosis of granulosa cells in endometriosis by upregulating p21.

Causal effects of prenatal and chronic PM2.5 exposures on cognitive function.

Growing evidence indicated an association between PM2.5 exposure and cognitive function, but the causal effect and the cognitive effect of prenatal PM2.5 exposure remain elusive. We obtained 15,099 subjects from a nationally representative sample of China and measured their cognitive performance. We ascertained subjects' prenatal PM2.5 exposure and chronic PM2.5 exposure of the recent two years. Using this national sample, we found that PM2.5 exposure during the mid- to late-pregnancy was significantly associated with declined cognition and income; chronic PM2.5 exposure was also independently associated with cognition and income measured at adulthood with greater magnitude. Negative effect modification was observed between prenatal and chronic PM2.5 exposure. Instrumental variable approach and difference-in-difference study verified causal effects: every 1 µg/m3 increase in prenatal and chronic PM2.5 exposures were causally associated with -0.22% (-0.38%, -0.06%) and -0.17% (-0.31%, -0.03%) changes in cognitive function, respectively. People with low cognition and low income were more vulnerable to PM2.5 exposure with greater cognitive and income decline. In the future, although China's improved air quality continues to benefit people and reduce cognitive decline induced by chronic PM2.5 exposure, high prenatal PM2.5 exposure will continue to hurt the overall cognition of Chinese population, since in total 360 million people were born during the 2000-2020 polluted era. Prenatal PM2.5-induced cognitive decline would remain largely unchanged before 2050 and gradually reduce after 2065, regardless of environmental policy scenarios. The long-lasting cognitive impact of PM2.5 is worth considering while enacting environmental policies.

RNA N6-methyladenosine of DHAPAT and PAP involves in regulation of diapause of Bombyx mori via the lipid metabolism pathway.

Environment-induced epigenetics are involved in diapause regulation, but the molecular mechanism that epigenetically couples nutrient metabolism to diapause regulation remains unclear. In this study, we paid special attention to the significant differences in the level of N6-adenosine methylation (m6A) of dihydroxyacetone phosphate acyltransferase (DHAPAT) and phosphatidate phosphatase (PAP) genes in the lipid metabolism pathway of the bivoltine silkworm (Bombyx mori) strain Qiufeng developed from eggs incubated at a normal temperature (QFHT, diapause egg producer) compared to those from eggs incubated at a low temperature (QFLT, non-diapause egg producer). We knocked down DHAPAT in the pupal stage of the QFLT group, resulting in the non-diapause destined eggs becoming diapausing eggs. In the PAP knockdown group, the colour of the non-diapause destined eggs changed from light yellow to pink 3 days after oviposition, but they hatched as normal. Moreover, we validated that YTHDF3 binds to m6A-modified DHAPAT and PAP mRNAs to promote their stability and translation. These results suggest that RNA m6A methylation participates in the diapause regulation of silkworm by changing the expression levels of DHAPAT and PAP and reveal that m6A epigenetic modification can be combined with a lipid metabolism signal pathway to participate in the regulation of insect diapause traits, which provides a clearer image for exploring the physiological basis of insect diapause.

The quest for improved air quality may push China to continue its CO2 reduction beyond the Paris Commitment.

China is challenged with the simultaneous goals of improving air quality and mitigating climate change. The "Beautiful China" strategy, launched by the Chinese government in 2020, requires that all cities in China attain 35 µg/m3 or below for annual mean concentration of PM2.5 (particulate matter with aerodynamic diameter less than 2.5 µm) by 2035. Meanwhile, China adopts a portfolio of low-carbon policies to meet its Nationally Determined Contribution (NDC) pledged in the Paris Agreement. Previous studies demonstrated the cobenefits to air pollution reduction from implementing low-carbon energy policies. Pathways for China to achieve dual targets of both air quality and CO2 mitigation, however, have not been comprehensively explored. Here, we couple an integrated assessment model and an air quality model to evaluate air quality in China through 2035 under the NDC scenario and an alternative scenario (Co-Benefit Energy [CBE]) with enhanced low-carbon policies. Results indicate that some Chinese cities cannot meet the PM2.5 target under the NDC scenario by 2035, even with the strictest end-of-pipe controls. Achieving the air quality target would require further reduction in emissions of multiple air pollutants by 6 to 32%, driving additional 22% reduction in CO2 emissions relative to the NDC scenario. Results show that the incremental health benefit from improved air quality of CBE exceeds 8 times the additional costs of CO2 mitigation, attributed particularly to the cost-effective reduction in household PM2.5 exposure. The additional low-carbon energy polices required for China's air quality targets would lay an important foundation for its deep decarbonization aligned with the 2 °C global temperature target.

Long-term outcomes of endoscopic papillary large-balloon dilation (12-15 mm) with or without limited sphincterotomy for removal of bile duct stones.

BACKGROUND: Limited endoscopic sphincterotomy with large balloon dilation (ES-LBD) and endoscopic papillary large-balloon dilation (EPLBD) have been proven safe and effective for removal of bile duct stones. However, the long-term outcomes are not clear. The aim of this study was to assess the long-term outcomes of EPLBD (12-15 mm) with or without limited sphincterotomy for removal of common bile duct (CBD) stones. METHODS: Patients with EPLBD or ES-LBD referred for the removal of bile-duct stones between June 2008 and August 2020 were retrospectively reviewed. Complete stone clearance, endoscopic retrograde cholangiopancreatography (ERCP)-related adverse events, and late biliary complications during long-term follow-up were analyzed. RESULTS: Basic patient characteristics were not significantly different between the groups that underwent EPLBD (n = 168) and ES-LBD (n = 57). EPLBD compared with ES-LBD resulted in similar outcomes in terms of overall successful stone removal (99.4% vs. 100%, P = 1.00) and ERCP-related adverse events (7.7% vs. 5.3%, P = 0.77). The mean duration of the follow-up were 113.6 months and 106.7 months for patients with EPLBD and ES-LBD, respectively (P = 0.13). There was no significant difference between EPLBD and ES-LBD in the incidence of stone recurrence [20 (11.9%) vs. 9 (15.8%); P = 0.49]. Multivariate analysis showed that a diameter of CBD ≥ 15 mm (OR = 3.001; 95% CI: 1.357-6.640; P = 0.007) was an independent risk factor for stone recurrence. CONCLUSIONS: The application of a large balloon (12-15 mm) via EPLBD is an effective and safe alternative to ES-LBD for extraction of large CBD stones. Endoscopic sphincterotomy prior to EPLBD may be unnecessary. A diameter of CBD ≥ 15 mm is a risk factor of stone recurrence.

Exorista sorbillans (Diptera: Tachinidae) parasitism shortens host larvae growth duration by regulating ecdysone and juvenile hormone titers in Bombyx mori (Lepidoptera: Bombycidae).

The tachinid fly, Exorista sorbillans, is a notorious ovolarviparous endoparasitoid of the silkworm, Bombyx mori, causing severe damage to silkworm cocoon industry. Silkworm larvae show typically precocious wandering behavior after being parasitized by E. sorbillans; however, the underlying molecular mechanism remains unexplored. Herein, we investigated the changes in the levels of 20-hydroxyecdysone (20E) and juvenile hormone (JH) titer, and they both increased in the hemolymph of parasitized silkworms. Furthermore, we verified the expression patterns of related genes, which showed an upregulation of 20E signaling and biosynthesis genes but a significant downregulation of ecdysone oxidase (EO), a 20E inactivation enzyme, in parasitized silkworms. In addition, related genes of the JH signaling were activated in parasitized silkworms, while related genes of the JH degradation pathway were suppressed, resulting in an increase in JH titer. Notably, the precocious wandering behavior of parasitized silkworms was partly recoverable by silencing the transcriptions of BmCYP302A1 or BmCYP307A1 genes. Our findings suggest that the developmental duration of silkworm post parasitism could be shortened by regulation of 20E and JH titers, which may help silkworm to resist the E. sorbillans infestation. These findings provide a basis for deeper insight into the interplay between silkworms and E. sorbillans and may serve as a reference for the development of a novel approach to control silkworm myiasis.