Adenine base editing-mediated exon skipping restores dystrophin in humanized Duchenne mouse model.

Duchenne muscular dystrophy (DMD) affecting 1 in 3500-5000 live male newborns is the frequently fatal genetic disease resulted from various mutations in DMD gene encoding dystrophin protein. About 70% of DMD-causing mutations are exon deletion leading to frameshift of open reading frame and dystrophin deficiency. To facilitate translating human DMD-targeting CRISPR therapeutics into patients, we herein establish a genetically humanized mouse model of DMD by replacing exon 50 and 51 of mouse Dmd gene with human exon 50 sequence. This humanized mouse model recapitulats patient's DMD phenotypes of dystrophin deficiency and muscle dysfunction. Furthermore, we target splicing sites in human exon 50 with adenine base editor to induce exon skipping and robustly restored dystrophin expression in heart, tibialis anterior and diaphragm muscles. Importantly, systemic delivery of base editor via adeno-associated virus in the humanized male mouse model improves the muscle function of DMD mice to the similar level of wildtype ones, indicating the therapeutic efficacy of base editing strategy in treating most of DMD types with exon deletion or point mutations via exon-skipping induction.

Visible-ultraviolet dual-band photodetectors based on an all-inorganic CsPbCl3/p-GaN heterostructure.

All-inorganic metal halide perovskites (MHPs) have attracted increasing attention because of their high thermal stability and band gap tunability. Among them, CsPbCl3 is considered a promising semiconductor material for visible-ultraviolet dual-band photodetectors because of its excellent photoelectric properties and suitable band gap value. In this work, we fabricated a visible-ultraviolet dual-band photodetector based on a CsPbCl3/p-GaN heterojunction using the spin coating method. The formation of the heterojunction enables the device to exhibit obvious dual-band response behavior at positive and negative bias voltages. At the same time, the dark current of the device can be as low as 2.42 × 10-9 A, and the corresponding detection rate can reach 5.82 × 1010 Jones. In addition, through simulation calculations, it was found that the heterojunction has a type II energy band arrangement, and the heterojunction response band light absorption is significantly enhanced. The type II energy band arrangement will separate electron-hole pairs more effectively, which will help improve device performance. The successful implementation of visible-ultraviolet dual-band photodetectors based on a CsPbCl3/p-GaN heterojunction provides guidance for the application of all-inorganic MHPs in the field of multi-band photodetectors.

Bronchial artery chemoembolization in the treatment of refractory central lung cancer with atelectasis.

Objective: This study aims to explore the clinical application of bronchial artery chemoembolization (BACE) in managing refractory central lung cancer with atelectasis. Methods: The retrospective case series includes patients diagnosed with refractory central lung cancer and atelectasis who underwent BACE treatment at Yueyang Integrated Traditional Chinese and Western Medicine Hospital, affiliated with Shanghai University of Traditional Chinese Medicine, from January 2012 to December 2021. Results: All 30 patients with lung cancer successfully underwent BACE procedures. Their ages ranged from 62 to 88 years, with an average age of 67.53. The treatment interval was 21 days, and the treatment cycle ranged from 2 to 12 times, averaging 4.13 times. During the BACE procedures, the Karnofsky Performance Status (KPS) score after 2 to 3 BACE cycles showed a significant improvement (82.0 ± 10.1 vs 68.3 ± 14.0, P < 0.001) than that of before BACE. Only nutritional support and symptomatic treatment were performed after BACE, and no major hemoptysis were observed. During follow-up, 23 cases resulted in mortality, while seven survived. The median progression-free survival (PFS) and overall survival (OS) were 7.0 (95% CI: 4.6-9.4) and 10.0 (95% CI: 6.2-13.8) months, respectively, with 1-, 2-, and 3-year survival rates of 84.0%, 53.5%, and 11.3%, respectively. Eight cases exhibited bronchial recanalization and relief of atelectasis. According to the RECIST scale, there were 4 cases of complete response (CR), 16 cases of partial response (PR), 9 cases of stable disease (SD), and 1 case of progressive disease (PD). No serious adverse events were reported. Conclusion: BACE might be a safe intervention for refractory central lung cancer accompanied by atelectasis. The procedure exhibits satisfactory outcomes in tumor control, atelectasis relief, and enhancement of quality of life, warranting further investigation.

Analysis of the Distribution Characteristics of Jellyfish and Environmental Factors in the Seawater Intake Area of the Haiyang Nuclear Power Plant in China.

In recent years, there have been frequent jellyfish outbreaks in Chinese coastal waters, significantly impacting the structure, functionality, safety, and economy of nuclear power plant cooling water intake and nearby ecosystems. Therefore, this study focuses on jellyfish outbreaks in Chinese coastal waters, particularly near the Shandong Peninsula. By analyzing jellyfish abundance data, a Generalized Additive Model integrating environmental factors reveals that temperature and salinity greatly influence jellyfish density. The results show variations in jellyfish density among years, with higher densities in coastal areas. The model explains 42.2% of the variance, highlighting the positive correlation between temperature (20-26 °C) and jellyfish density, as well as the impact of salinity (27.5-29‱). Additionally, ocean currents play a significant role in nearshore jellyfish aggregation, with a correlation between ocean currents and site coordinates. This study aims to investigate the relationship between jellyfish blooms and environmental factors. The results obtained from the study provide data support for the prevention and control of blockages in nuclear power plant cooling systems, and provide a data basis for the implementation of monitoring measures in nuclear power plants.

Engineered Probiotic Bio-Heterojunction with Robust Antibiofilm Modality via "Eating" Extracellular Polymeric Substances for Wound Regeneration.

The compact three-dimensional (3D) structure of extracellular polymeric substances (EPS) within biofilms significantly hinders the penetration of antimicrobial agents, making biofilm eradication challenging and resulting in persistent biofilm-associated infections. To address this challenge, a solution is proposed: a probiotic bio-heterojunction (P-bioHJ) combining Lactobacillus rhamnosus with MXene (Ti3C2) quantum dots (MQDs)/FeS heterojunction. This innovation aims to break down the saccharides in EPS, enabling effective combat against biofilm-associated infections. Initially, the P-bioHJ targets saccharides through metabolic processes, causing the collapse of EPS and allowing infiltration into bacterial colonies. Simultaneously, upon exposure to near-infrared (NIR) irradiation, the P-bioHJ produces reactive oxygen species (ROS) and thermal energy, deploying physical mechanisms to combat bacterial biofilms effectively. Following antibiofilm treatment, the P-bioHJ adjusts the oxidative environment, reduces wound inflammation by scavenging ROS, boosts antioxidant enzyme activity, and mitigates the NF-κB inflammatory pathway, thereby accelerating wound healing. In vitro and in vivo experiments confirm the exceptional antibiofilm, antioxidant/anti-inflammatory, and wound-regeneration properties of P-bioHJ. In conclusion, this study provides a promising approach for treating biofilm-related infections.

The association between diets and periodontitis: a bidirectional two-sample Mendelian randomization study.

Background: Periodontitis, a complex inflammatory condition, has been associated with dietary habits and antioxidants. While the association between certain dietary patterns and periodontitis has been documented, the bidirectional relationship remains unclear. This study utilizes Mendelian randomization (MR) analysis to investigate the bidirectional associations between dietary factors comprising dietary antioxidants, and periodontitis. Methods: Employing a two-sample MR approach, this study analyzed genome-wide association study (GWAS) data on diets and periodontitis from large databases and published literature. Instrumental variables (IVs) were selected and filtered based on genetic variants associated with dietary factors and periodontitis, respectively. Various MR methods, including Inverse Variance Weighted, MR-Egger, Weighted Median, Weighted Mode, and Simple Mode were applied to assess the bidirectional associations. Sensitivity analyses were conducted to validate the robustness of the findings. Results: Our analysis revealed significant associations between certain dietary factors and the risk of periodontitis. Specifically, higher intake of filtered coffee, low-calorie drinks, and other cereals, as well as increased metabolic circulating levels of gamma-tocopherol, were associated with an elevated risk of periodontitis. Conversely, consumption of cheese, white rice, chocolate bars, unsalted peanuts, and higher absolute circulating levels of vitamin C were linked to a reduced risk. Additionally, the study suggests that periodontitis may influence dietary habits, indicating a bidirectional relationship. Conclusion: This study provides additional evidence of a bidirectional association between dietary factors and periodontitis. It highlights the importance of dietary interventions in the prevention and management of periodontitis. The findings underscore the need for incorporating dietary counseling into periodontal disease management protocols and suggest the potential of personalized dietary strategies for periodontitis patients. Further research is warranted to explore the mechanisms underlying these associations and to confirm these findings in diverse populations.

Exogenous sulfide regulates hypoxia/reoxygenation stress through the intrinsic apoptotic pathway in the blood clam (Tegillarca granosa).

The intertidal organism Tegillarca granosa can survive under frequent hypoxia/reoxygenation (H/R) exposure. Sulfides as accompanying products in benthic hypoxic environments, may play an important regulatory role, but the mechanisms are not well understood. This article investigated the physiological and molecular changes of T. granosa after adding different concentrations of sulfides (0.1, 0.5, 1 mM) at 72 h into a 120-h exposure to hypoxia, as well as the recovery state of 24 h of reoxygenation. The results indicated that H/R stress induces ROS production and mild mitochondrial depolarization in clams, and sulfide can participate in its regulation. Among them, a low concentration of sulfide up-regulated glutathione content and alternative oxidase activity, maintained the stability of antioxidant enzymes, and up-regulated the expression of the survival genes XIAP/BCL-xl which mediate cell survival via the NFκB signaling pathway. High concentrations of sulfide had a significant inhibitory effect on the p38/MPAK pathway and inhibited intrinsic apoptosis caused by ROS accumulation during reoxygenation. Taken together, our study suggested that different concentrations of sulfides are involved in regulating the endogenous apoptosis of clams during H/R.

Disparities in Body Color Adaptability and Ambient Light Color Preference between Wild and Hatchery-Reared Marbled Rockfish (Sebastiscus marmoratus).

Hatchery rearing significantly influences the phenotypic development of fish, with potential adverse effects for the post-release performance of hatchery-reared individuals in natural environments, especially when targeted for stock enhancement. To assess the suitability of releasing hatchery-reared fish, a comprehensive understanding of the phenotypic effects of captive rearing, through comparisons with their wild conspecifics, is essential. In this study, we investigated the divergence in body coloration between wild and hatchery-reared marbled rockfish Sebastiscus marmoratus. We examined the selection preferences for different light colors and assessed the impact of different ambient light colors on the morphological color-changing ability of juvenile marbled rockfish. Our findings revealed significant differences in body color between wild and hatchery-reared marbled rockfish. The hue and saturation values of wild marbled rockfish were significantly higher than those of their hatchery-reared counterparts, indicative of deeper and more vibrant body coloration in the wild population. Following a ten-day rearing period under various light color environments, the color of wild marbled rockfish remained relatively unchanged. In contrast, hatchery-reared marbled rockfish tended to change their color, albeit not reaching wild-like coloration. Light color preference tests demonstrated that wild juvenile marbled rockfish exhibited a preference for a red-light environment, while hatchery-reared individuals showed a similar but weaker response. Both wild and hatchery-reared marbled rockfish displayed notable negative phototaxis in the presence of yellow and blue ambient light. These results highlight the impact of hatchery rearing conditions on the body color and morphological color-changing ability, and provide insight into light color selection preferences of marbled rockfish. To mitigate the divergence in phenotypic development and produce more wild-like fish for stocking purposes, modifications to the hatchery environment, such as the regulation of ambient light color, should be considered.

Population Genomics of Commercial Fish Sebastes schlegelii of the Bohai and Yellow Seas (China) Using a Large SNP Panel from GBS.

Sebastes schlegelii is one of the most commercially important marine fish in the northwestern Pacific. However, little information about the genome-wide genetic characteristics is available for S. schlegelii individuals from the Bohai and Yellow Seas. In this study, a total of 157,778, 174,480, and 188,756 single-nucleotide polymorphisms from Dalian (DL), Yantai (YT), and Qingdao (QD) coastal waters of China were, respectively, identified. Sixty samples (twenty samples per population) were clustered together, indicating shallow structures and close relationships with each other. The observed heterozygosity, expected heterozygosity, polymorphism information content, and nucleotide diversity ranged from 0.14316 to 0.17684, from 0.14035 to 0.17145, from 0.20672 to 0.24678, and from 7.63 × 10-6 to 8.77 × 10-6, respectively, indicating the slight difference in genetic diversity among S. schlegelii populations, and their general genetic diversity was lower compared to other marine fishes. The population divergence showed relatively low levels (from 0.01356 to 0.01678) between S. schlegelii populations. Dispersing along drifting seaweeds, as well as the ocean current that flows along the western and northern coasts of the Yellow Sea and southward along the eastern coast of China might be the major reasons for the weak genetic differentiation. These results form the basis of the population genetic characteristics of S. schlegelii based on GBS (Genotyping by Sequencing). In addition to basic population genetic information, our results provid a theoretical basis for further studies aimed at protecting and utilizing S. schlegelii resources.

Observations of the effectiveness, dosage, and prognosis of intensity-modulated radiation therapy under ultrasonic guidance for cervical cancer patients.

BACKGROUND: Volumetric modulated arc therapy (VMAT) guided by ultrasound is a novel radiation therapy technique that facilitates the delineation of the tumor target area under image guidance, enhancing the precision of radiation therapy and maximizing the protection of surrounding tissues. OBJECTIVE: The objective of this paper is to investigate the effectiveness of VMAT under ultrasonic guidance for cervical cancer patients and its impact on radiotherapy dosage and prognosis. METHODS: A retrospective analysis encompassed 128 instances of cervical cancer patients who were admitted to our medical facility between April 2019 and April 2021. The patients were categorized into an observation cohort and a control cohort, depending on variations in treatment modalities post-admission. The control group underwent conventional radiotherapy, whereas the observation group received VMAT guided by ultrasound. Clinical efficacy, average radiation dosages (in the radiotherapy target area, rectum, and bladder), radiotherapy-related toxicities during treatment, and one-year survival rates were compared between the two groups. Additionally, variances in pre- and post-treatment serum levels of squamous cell carcinoma antigen (SCC-Ag), carcinoembryonic antigen (CEA), and carbohydrate antigen 724 (CA724) were subjected to assessment. RESULTS: When compared to the control group (64.52%), the observation cohort's comprehensive effectiveness rate was considerably greater (80.30%). The observation group saw lower average radiation exposures and a reduction in the post-treatment concentrations of CEA, SCC-Ag, and CA724. The overall incidence of adverse effects from radiation treatment also declined. The observation group had a greater one-year survival rate (90.48%) than the control group (73.33%). When comparing the observation cohort to the control group, Kaplan-Meier survival analysis showed a significantly higher one-year survival rate (Log-Rank = 6.530, P= 0.011). CONCLUSION: VMAT guided by ultrasound for patients with cervical cancer demonstrates promising short- and long-term treatment outcomes. It also leads to improvements in serum CEA, SCC-Ag, and CA724 levels, as well as reductions in the average radiation dosages to the radiotherapy target area, rectum, and bladder. This approach warrants attention from clinicians in clinical practice.

Correction of human nonsense mutation via adenine base editing for Duchenne muscular dystrophy treatment in mouse.

Duchenne muscular dystrophy (DMD) is the most prevalent herediatry disease in men, characterized by dystrophin deficiency, progressive muscle wasting, cardiac insufficiency, and premature mortality, with no effective therapeutic options. Here, we investigated whether adenine base editing can correct pathological nonsense point mutations leading to premature stop codons in the dystrophin gene. We identified 27 causative nonsense mutations in our DMD patient cohort. Treatment with adenine base editor (ABE) could restore dystrophin expression by direct A-to-G editing of pathological nonsense mutations in cardiomyocytes generated from DMD patient-derived induced pluripotent stem cells. We also generated two humanized mouse models of DMD expressing mutation-bearing exons 23 or 30 of human dystrophin gene. Intramuscular administration of ABE, driven by ubiquitous or muscle-specific promoters could correct these nonsense mutations in vivo, albeit with higher efficiency in exon 30, restoring dystrophin expression in skeletal fibers of humanized DMD mice. Moreover, a single systemic delivery of ABE with human single guide RNA (sgRNA) could induce body-wide dystrophin expression and improve muscle function in rotarod tests of humanized DMD mice. These findings demonstrate that ABE with human sgRNAs can confer therapeutic alleviation of DMD in mice, providing a basis for development of adenine base editing therapies in monogenic diseases.

How positive childhood experiences foster college students' adjustment: the role of sibling number and self-esteem.

Introduction: In recent years, growing concern has emerged regarding the mental health and well-being of college students who confront numerous challenges and transitions during their higher education journey. This research aims to investigate the influence of positive childhood experiences on the adaptability of college students and the underlying mechanisms. Methods: A cross-sectional survey was conducted with 5,787 college students from Chinese universities. Participants completed an online questionnaire assessing positive childhood experiences, self-esteem, the number of siblings, and China college students' adjustment. Results: The results revealed that positive childhood experiences positively predicted the adjustment of China college students, with self-esteem playing a mediating role in this positive effect. Moreover, siblings played an antagonistic moderating role in the positive effect of positive childhood experiences on China college students' adjustment. Discussion: It is recommended to enhance positive childhood experiences, improve self-esteem, and provide additional care and support to students from multi-sibling families to enhance China college students' adjustment.

Transcriptional and physiological profiles reveal the respiratory, antioxidant and metabolic adaption to intermittent hypoxia in the clam Tegillarca granosa.

Tegillarca granosa can survive intermittent hypoxia for a long-term. We used the clam T. granosa as model to investigate the respiratory, antioxidant and metabolic responses to consecutive hypoxia-reoxygenation (H/R) stress at both physiological and transcriptional levels. The results showed that the clams were able to rapidly regulate oxygen consumption and ammonia excretion during H/R stress, and alleviate oxidative stress during the second-time challenge. The clams also efficiently balanced energy metabolism through the rapid conversion and decomposition of glycogen. According to the transcriptome profile, KEGG pathways of starch and sucrose metabolism, ECM-receptor interaction, and protein processing in endoplasmic reticulum were significantly enriched in H group (the second-time 24 h hypoxia exposure), while pathways associated with lipid metabolism were significantly enriched in h group (the first-time 24 h hypoxia exposure). DEGs including hspa5, birc2/3, and map3k5 might play important roles in alleviating endoplasmic reticulum stress, cpla2 and pla2g16 might mitigate oxidative stress by adjusting the composition of cellular membrane. In conclusions, our findings suggest that rapid adjustment of oxygen consumption, ammonia metabolism, glycogen metabolism, and the ability to adjust the composition of the membrane lipid may be critical for T. granosa in maintaining energy homeostasis and reducing oxidative damage during intermittent H/R exposure. This study preliminarily clarified the response of T. granosa to intermittent hypoxia stress on the physiological and molecular levels, offering insights into the hypoxia-tolerant mechanisms in this species and providing a reference for the following study on the other hypoxic-tolerant species.

The effects of different doses of lanthanum-modified bentonite in combination with a submerged macrophyte (Vallisneria denseserrulata) on phosphorus inactivation and macrophyte growth: A mesocosm study.

The combination of chemical phosphorus (P) inactivation and submerged macrophyte transplantation has been widely used in lake restoration as it yields stronger effects than when applying either method alone. However, the dose effect of chemical materials on P inactivation when used in combination with submerged macrophytes and the influences of the chemicals used on the submerged macrophytes growth remain largely unknown. In this study, we investigated P inactivation in both the water column and the sediment, and the responses of submerged macrophytes to Lanthanum modified bentonite (LMB) in an outdoor mesocosm experiment where Vallisneria denseserrulata were transplanted into all mesocosms and LMB was added at four dosage levels, respectively: control (LMB-free), low dosage (570 g m-2), middle dosage (1140 g m-2), and high dosage (2280 g m-2). The results showed that the combination of LMB dosage and V. denseserrulata reduced TP in the water column by 32%-38% compared to V. denseserrulata alone, while no significant difference was observed among the three LMB treatments. Porewater soluble reactive P, two-dimensional diffusive gradient in thin films (DGT)-labile P concentrations, and P transformation in the 0-1 cm sediment layer exhibited similar trends along the LMB dosage gradient. Besides, LMB inhibited plant growth and reduced the uptake of mineral elements (i.e., calcium, manganese, iron, and magnesium) in a dosage-dependent manner with LMB. LMB may reduce plant growth by creating a P deficiency risk for new ramets and by interfering with the uptake of mineral elements. Considering both the dose effect of LMB on P inactivation and negative effect on macrophyte growth, we suggest a "small dosage, frequent application" method for LMB application to be used in lake restoration aiming to recover submerged macrophytes and clear water conditions.

Integrated analysis of transcriptome and metabolome reveals the regulatory mechanism of largemouth bass (Micropterus salmoides) in response to Nocardia seriolae infection.

Nocardia seriolae is a severe bacterial pathogen that has seriously affected the development of aquaculture industry. Largemouth bass (Micropterus salmoides) is a commercially significant freshwater fish that suffers a variety of environmental threats, including bacterial pathogens. However, the immune responses and metabolic alterations of largemouth bass to N. seriolae infection remain largely unclear. We discovered that N. seriolae caused pathological alterations in largemouth bass and shifted the transcript of immune-related and apoptotic genes in head kidney after infection. To answer the aforementioned question, a combined transcriptome and metabolome analysis was employed to explore the alterations in genes, metabolites, and metabolic pathways in largemouth bass following bacterial infection. A total of 3579 genes and 1929 metabolites are significant differentially changed in the head kidney post infection. In response to N. seriolae infection, host modifies the PI3K-Akt signaling pathway, TCA cycle, glycolysis, and amino acid metabolism. The integrated analysis of transcriptome and metabolome suggested that with the arginine metabolism pathway as the core, multiple biomarkers (arg gene, arginine) are involved in the antibacterial and immune functions of largemouth bass. Thus, we hypothesized that arginine plays a crucial role in the immune responses of largemouth bass against N. seriolae infection, and increasing arginine levels suitably is beneficial for the host against bacterial infection. Our results shed light on the regulatory mechanism of largemouth bass resistance to N. seriolae infection and contributed to the development of more effective N. seriolae resistance strategies.

Integrative Analysis of Metabolome and Transcriptome Provides Insights into the Mechanism of Flower Induction in Pineapple (Ananas comosus (L.) Merr.) by Ethephon.

Exogenous ethylene is commonly utilized to initiate flower induction in pineapple (Ananas comosus (L.) Merr.). However, the molecular mechanisms and metabolic changes involved are not well understood. In this study, we explored the genetic network and metabolic shifts in the 'Comte de Paris' pineapple variety during ethylene-induced flowering. This was achieved through an integrative analysis of metabolome and transcriptome profiles at vegetative shoot apexes (0 d after ethephon treatment named BL_0d), the stage of bract primordia (8 d after ethephon treatment named BL_8d), stage of flower primordia (18 d after ethephon treatment named BL_18d), and the stage of stopped floret differentiation (34 d after ethephon treatment named BL_34d). We isolated and identified 804 metabolites in the pineapple shoot apex and inflorescence, categorized into 24 classes. Notably, 29, 31, and 46 metabolites showed significant changes from BL_0d to BL_8d, BL_8d to BL_18d, and BL_18d to BL_34d, respectively. A marked decrease in indole was observed, suggesting its role as a characteristic metabolite during flower induction. Transcriptomic analysis revealed 956, 1768, and 4483 differentially expressed genes (DEGs) for BL_0d vs. BL_8d, BL_8d vs. BL_18d, and BL_18d vs. BL_34d, respectively. These DEGs were significantly enriched in carbohydrate metabolism and hormone signaling pathways, indicating their potential involvement in flower induction. Integrating metabolomic and transcriptomic data, we identified several candidate genes, such as Agamous-Like9 (AGL9), Ethylene Insensitive 3-like (ETIL3), Apetala2 (AP2), AP2-like ethylene-responsive transcription factor ANT (ANT), and Sucrose synthase 2 (SS2), that play potentially crucial roles in ethylene-induced flower induction in pineapple. We also established a regulatory network for pineapple flower induction, correlating metabolites and DEGs, based on the Arabidopsis thaliana pathway as a reference. Overall, our findings offer a deeper understanding of the metabolomic and molecular mechanisms driving pineapple flowering.

Polyphyllin I inhibits endometriosis in vitro by inducing apoptosis and autophagy via the inactivation of AKT/mTOR signalling pathway.

Previous research has indicated that Polyphyllin I (PPI) possesses potent anticancer properties. However, its impact on endometriosis remains unexplored. This study aims to investigate the inhibitory effects of PPI on ectopic endometrial stromal cells (EESCs). The CCK-8 and flow cytometry results respectively showed that the cell viability of EESCs decreased and the number of apoptotic cells increased in a dosage dependent of PPI. Wound healing and transwell assays demonstrated a notable reduction in cell motility and migration ability in the PPI group. Moreover, the Western blot analysis revealed a decrease in p62 levels and an increase in LC3-II expression following PPI administration. Additionally, the protein levels of p-Akt and p-mTOR were observed to decrease with increasing concentrations of PPI, indicating the potential of PPI to induce autophagy in EESCs through modulation of the Akt/mTOR signalling pathway. Consequently, PPI holds promise as a targeted therapeutic agent for the management of endometriosis.

A gonadal gap junction INX-14/Notch GLP-1 signaling axis suppresses gut defense through an intestinal lysosome pathway.

Gap junctions mediate intercellular communications across cellular networks in the nervous and immune systems. Yet their roles in intestinal innate immunity are poorly understood. Here, we show that the gap junction/innexin subunit inx-14 acts in the C. elegans gonad to attenuate intestinal defenses to Pseudomonas aeruginosa PA14 infection through the PMK-1/p38 pathway. RNA-Seq analyses revealed that germline-specific inx-14 RNAi downregulated Notch/GLP-1 signaling, while lysosome and PMK-1/p38 pathways were upregulated. Consistently, disruption of inx-14 or glp-1 in the germline enhanced resistance to PA14 infection and upregulated lysosome and PMK-1/p38 activity. We show that lysosome signaling functions downstream of the INX-14/GLP-1 signaling axis and upstream of PMK-1/p38 pathway to facilitate intestinal defense. Our findings expand the understanding of the links between the reproductive system and intestinal defense, which may be evolutionarily conserved in higher organism.

Optimizing surgical outcomes for elderly gallstone patients with a high body mass index using enhanced recovery after surgery protocol.

BACKGROUND: Rehabilitation of elderly patients with a high body mass index (BMI) after cholecystectomy carries risks and requires the adoption of effective perioperative management strategies. The enhanced recovery after surgery (ERAS) protocol is a comprehensive treatment approach that facilitates early patient recovery and reduces postoperative complications. AIM: To compare the effectiveness of traditional perioperative management methods with the ERAS protocol in elderly patients with gallbladder stones and a high BMI. METHODS: This retrospective cohort study examined data from 198 elderly patients with a high BMI who underwent cholecystectomy at the Shanghai Fourth People's Hospital from August 2019 to August 2022. Among them, 99 patients were managed using the traditional perioperative care approach (non-ERAS protocol), while the remaining 99 patients were managed using the ERAS protocol. Relevant indicator data were collected for patients preoperatively, intraoperatively, and postoperatively, and surgical outcomes were compared between the two groups. RESULTS: The comparison results between the two groups of patients in terms of age, sex, BMI, underlying diseases, surgical type, and preoperative hospital stay showed no statistically significant differences. However, the ERAS group had a significantly shorter preoperative fasting time than the non-ERAS group (4.0 ± 0.9 h vs 7.6 ± 0.9 h). Regarding intraoperative indicators, there were no significant differences between the two groups of patients. However, in terms of postoperative recovery, the ERAS protocol group exhibited significant advantages over the non-ERAS group, including a shorter hospital stay, lower postoperative pain scores and postoperative hunger scores, and higher satisfaction levels. The readmission rate was lower in the ERAS protocol group than in the non-ERAS group (3.0% vs 8.1%), although the difference was not significant. Furthermore, there were significant differences between the two groups in terms of postoperative nausea and vomiting severity, postoperative abdominal distention at 24 h, and daily life ability scores. CONCLUSION: The findings of this study demonstrate that the ERAS protocol confers significant advantages in postoperative outcomes following cholecystectomy, including reduced readmission rates, decreased postoperative nausea and vomiting, alleviated abdominal distension, and enhanced functional capacity. While the protocol may not exhibit significant improvement in early postoperative symptoms, it does exhibit advantages in long-term postoperative symptoms and recovery. These findings underscore the importance of implementing the ERAS protocol in the postoperative management of cholecystectomy patients, as it contributes to improving patients' recovery and quality of life while reducing health care resource utilization.