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Most of the current literature on the experiences of Chinese international students tends to adopt a deficit-based approach, focusing on the weaknesses, problems, and challenges Chinese students face while studying overseas. In other words, they tend to focus on struggling Chinese students, "problem" Chinese students, and Chinese students who are failing their overseas studies. Though the intention may be good, these studies may strengthen a negative stereotypical image of Chinese international students that is problem ridden. This study aims to introduce some positive psychology in international student development by focusing on successful Chinese students, their success stories, and what success secrets they can share with future Chinese students studying abroad. With the completion of an undergraduate program adopted as a minimum threshold of student success, this study aims to glean the experiences of successful Chinese students in the United Kingdom and disseminate them as lessons for future students. The study finds that proactiveness in networking and seeking support, open and adaptive attitude toward learning and life, and metacognitive skills in self-management are the most important factors contributing to Chinese students' success in overseas studies.

International student mobility is a complex phenomenon influenced by numerous factors. This study examines the prospect of China as a destination country for international students in the post-COVID-19 era. With qualitative data from 30 frontline international educators (support staff in international student recruitment and services) from 30 Chinese universities, this study has determined a set of "pull" factors that serve to attract international students to study in China and a set of "repel" factors that discourage students from going. On the basis of both the "pull" and "repel" factors identified, the participants anticipate important challenges for China's international enrollment in the short term, but stay optimistic about the long-term prospect. The "pull and repel" factors analysis is found to be a useful approach to examining the attractiveness of a host country to international students in a focused manner.

This research paper investigates the intersection of the maker movement and educational innovation, using the China-U.S. Young Maker Competition as a foundational example. It examines how maker education, fueled by hands-on learning and a curiosity-driven approach, can evolve and influence. The study explores the roles and impacts of Human-Computer Interaction (HCI), Design-Driven Innovation (DDI), and Cross-Cultural Perspectives (CCP) within maker education. It highlights HCI's connection of technology with learning, DDI's focus on user-centered solutions, and the significance of CCP in enhancing cultural collaboration, vital for fostering an innovative and creative future. This paper offers a detailed perspective on the current state and future potential of maker education. It proposes a roadmap for the coming decade, emphasizing collaborative learning and creative endeavors, all set within the engaging environment of the competition.

Abstract Background Spinal orthoses are commonly prescribed for adolescent idiopathic scoliosis (AIS), yet their three-dimensional correction was not fully understood. The amount of deformity control largely depends on the corrective forces applied, which remain empirically based due to a lack of consensus on optimal force application. This study investigated the effects of different corrective force directions exerted by spinal orthoses on patients with AIS. Methods A retrospective analysis was conducted on 78 subjects. The trunk was segmented into four quadrants using coronal and sagittal planes from a top-down perspective. Each left or right posterolateral quadrant (with 90°) was further subdivided into zones 1–4, from the sagittal to coronal planes. Based on the zone where the resultant corrective force direction fell, the subjects were categorized into Group 1 (zone 1), Group 2 (zone 2), Group 3 (zone 3), or Group 4 (zone 4). The direction of the corrective force was estimated using modified models of the subjects’ bodies, designed through a computer-aided design and manufacturing system integral to the orthosis fabrication process. The effects of corrective forces in different zones on scoliotic spine were assessed. Results Among the subjects, 3 were in Group 1, 17 in Group 2, 52 in Group 3, and 6 in Group 4. Due to the limited number of subjects, data from Groups 1 and 4 were not analysed. Groups 2 and 3 showed significant reductions in Cobb angle in the coronal plane and plane of maximum curvature (PMC) following orthosis fitting (p 5º in thoracic kyphosis (p 0.05) but was notably higher in Group 2 after orthosis fitting (p

Abstract Introduction Type IV-A choledochal cyst (CDC) has been considered to have a poor prognosis due to the high incidence of postoperative anastomotic strictures and intrahepatic stones. This study aimed to evaluate the surgical outcomes of children with type IV-A CDC and to provide insights for clinical diagnosis and treatment. Methods The study retrospectively analyzed patients from June 2015 to December 2018 at our center, 76 children were diagnosed with type IV-A CDC. All patients underwent single-incision laparoscopic choledochal cyst excision and Roux-en-Y hepaticojejunostomy. The decision to perform ductoplasty was made by comprehensively considering the intrahepatic duct dilatation (IHDD) and stricture. All patients were followed up 1, 3, and 6 months postoperatively, and then every 1 year thereafter. Patients were categorized into two groups based on IHDD changes postoperatively: the long-term group (LTG), with IHDD persisting for over a year, and the short-term group (STG), where IHDD normalized within a year. Single/multiple factor logistic regression was used to analyse the factors influencing postoperative IHDD. Results The median follow-up period was 80 months, with a range from 64 to 101 months. The decrease in postoperative liver function parameters, compared to preoperative levels, was statistically significant. Two patients (2.63%) developed bile leaks. One patient (1.32%) developed anastomotic stricture. All patients’ IHDD returned to normal size. Fifty-six (73.7%) patients showed normalization of IHDD within one-year postoperatively. The median recovery time for IHDD in patients was 1.65 months, ranging from 3 days to 74 months postoperatively. There were significant differences in intrahepatic biliary sludge and stones and maximum diameter of IHDD between STG and LTG. Logistic regression was used to analyse the factors and found that intrahepatic biliary sludge and a wider maximum diameter of IHDD were risk factors for postoperative long-term IHDD in patients. Conclusion Single-incision laparoscopic hepaticojejunostomy with selective ductoplasty are safe and effective for children with Type IV-A CDC. Long-term follow-up is recommended for children presenting with intrahepatic biliary sludge and larger IHDD.

Abstract Background Combination therapy is required for the treatment of moderate acne vulgaris. However, patient compliance in applying multiple topical formulations is poor. Objective To assess the efficacy and safety of a fixed-dose combination gel with adapalene 0.1% and clindamycin 1% (adapalene-clindamycin) relative to adapalene 0.1% monotherapy and clindamycin 1% monotherapy in patients with moderate facial acne vulgaris. Methods This was a randomized, controlled, assessor-blind, phase III study conducted in patients with moderate facial acne vulgaris. Results A total of 1617 patients were enrolled. At week 12, patients in the adapalene–clindamycin gel treatment group showed a significant reduction in the percentage change from baseline in total lesion count (− 66.85%), compared with adapalene alone (− 50.82%) or clindamycin gel alone (− 57.61%). The difference in the least square means of the adapalene–clindamycin gel group and adapalene group, or clindamycin gel group was − 16.08% (95% CI − 19.95% to − 12.21%) and − 9.38% (95% CI − 13.25% to − 5.51%;), respectively. At week 12, 19.28% of participants who received adapalene–clindamycin gel achieved at least 2-grade improvement in IGA, versus 7.74% with adapalene gel (OR 3.05, 95% CI 1.93, 4.80) and 14.77% with clindamycin gel (OR 1.42, 95% CI 0.97, 2.07). The study also achieved all its secondary endpoints. Adverse event rates were mostly mild to moderate and comparable across the three treatment groups. Conclusion Adapalene 0.1%–clindamycin 1% combination gel is well tolerated and demonstrated superior efficacy over 0.1% adapalene gel monotherapy and 1% clindamycin gel monotherapy for the treatment of moderate acne vulgaris. Trial Registration ClinicalTrials.gov identifier NCT03615768.

Abstract This study aims to clarify the impact of tumor size on the prognosis of patients diagnosed with thymoma and thymic carcinoma, leveraging data from a population-based registry. Utilizing the SEER database, this retrospective analysis identified patients diagnosed with thymoma and thymic carcinoma from 2000 to 2020. Propensity score matching was employed to mitigate potential statistical biases between groups categorized by tumor size (≤ 6.5 cm and > 6.5 cm). The study included a total of 3857 patients, comprising 2688 with thymoma and 1169 with thymic carcinoma. Multivariate analysis demonstrated that tumors ≤ 6.5 cm independently correlated with improved Cancer-Specific Survival (CSS) (p = 0.001; p

Abstract Background Acetate is an important chemical feedstock widely applied in the food, chemical and textile industries. It is now mainly produced from petrochemical materials through chemical processes. Conversion of lignocellulose biomass to acetate by biotechnological pathways is both environmentally beneficial and cost-effective. However, acetate production from carbohydrate in lignocellulose hydrolysate via glycolytic pathways involving pyruvate decarboxylation often suffers from the carbon loss and results in low acetate yield. Results Escherichia coli BL21 (DE3) was confirmed to have high tolerance to acetate in this work. Thus, it was selected from seven laboratory E. coli strains for acetate production from lignocellulose hydrolysate. The byproduct-producing genes frdA, ldhA, and adhE in E. coli BL21 (DE3) were firstly knocked out to decrease the generation of succinate, lactate, and ethanol. Then, the genes pfkA and edd were also deleted and bifunctional phosphoketolase and fructose-1,6-bisphosphatase were overexpressed to construct an EP-bifido pathway in E. coli BL21 (DE3) to increase the generation of acetate from glucose. The obtained strain E. coli 5K/pFF can produce 22.89 g/L acetate from 37.5 g/L glucose with a yield of 0.61 g/g glucose. Finally, the ptsG gene in E. coli 5K/pFF was also deleted to make the engineered strain E. coli 6K/pFF to simultaneously utilize glucose and xylose in lignocellulosic hydrolysates. E. coli 6K/pFF can produce 20.09 g/L acetate from corn stover hydrolysate with a yield of 0.52 g/g sugar. Conclusion The results presented here provide a promising alternative for acetate production with low cost substrate. Besides acetate production, other biotechnological processes might also be developed for other acetyl-CoA derivatives production with lignocellulose hydrolysate through further metabolic engineering of E. coli 6K/pFF.

Abstract Background Acute lung injury (ALI) is the most lethal disease associated with sepsis, and there is a lack of effective drug treatment. As the major cells of sepsis-induced ALI, macrophages polarize toward the proinflammatory M1 phenotype and secrete multiple inflammatory cytokines to accelerate the disease process through nuclear factor kappa-B (NF-κB) and NLR family pyrin domain containing 3 (NLRP3) inflammasome signaling pathways. Taraxerone, the main component of the Chinese medicinal Sedum, possesses numerous biological activities. However, uncertainty remains regarding the potential of taraxerone to protect against sepsis-induced ALI. This study aimed to investigate the effects and mechanisms of taraxerone against ALI. Methods An animal model for ALI was established by cecal ligation and puncture and treated with taraxerone via intraperitoneal administration. The protective effect of taraxerone on the lungs was analyzed using H&E staining, dihydroethidium staining, ELISA kits, cell counting, myeloperoxidase kit, malondialdehyde kit, glutathione kit, superoxide dismutase kit and flow cytometry. Western blotting, RT-PCR, flow cytometry, co-immunoprecipitation, and immunofluorescence were used to investigate the regulatory of taraxerone on SIRT1. Results Our study demonstrates for the first time that taraxerone can activate SIRT1 in macrophages, promoting SIRT1 activity. This activation inhibited the NF-κB signaling pathway primarily through the dephosphorylation and deacetylation of p65. Simultaneously, taraxerone disrupted the NLRP3 inflammasome signaling pathway, thereby alleviating M1 polarization of macrophages and mitigating sepsis-induced pulmonary inflammation and oxidative stress. In vivo, EX527 was used to validate the anti-inflammatory and anti-oxidative stress effects of taraxerone mediated by SIRT1. Conclusion SIRT1-mediated anti-inflammatory and anti-oxidative stress effects may be important targets for taraxerone in treating ALI.

Abstract Background Overcoming resistance to Osimertinib in epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) is clinically challenging because the underlying mechanisms are not fully understood. The murine double minute 2 (MDM2) has been extensively described as a tumor promotor in various malignancies, mainly through a negative regulatory machinery on the p53 tumor suppressor. However, the significance of MDM2 on the sensitivity to Osimertinib has not been described. Methods Osimertinib resistant cells were generated by standard dose escalation strategy and individual resistant clones were isolated for MDM2 testing. The MDM2 and its mutant constructs (ΔPBD, ΔRING, C464A) were introduced into PC-9, HCC827 and H1975 cells and evaluated for the sensitivity to Osimertinib by MTT assay, colony formation, EdU assay and TUNEL assay. MDM2 expression in resistant cells was manipulated by pharmacological and molecular approaches, respectively. Proteins that were implicated in PI3K/Akt, MAPK/Erk and apoptosis signaling were measured by Western blot analysis. Candidate proteins that interacted with MDM2 were captured by immunoprecipitation and probed with indicated antibodies. Results In comparison with parental PC-9 cells, the PC-9 OR resistant cells expressed high level of MDM2. Ectopic expression of MDM2 in PC-9, HCC827 and H1975 sensitive cells generated an Osimertinib resistant phenotype, regardless of p53 status. MDM2 promoted resistance to Osimertinib through a PI3K/Akt and MAPK/Erk-independent machinery, in contrast, MDM2 selectively stabilized MCL-1 protein to arrest Osimertinib-induced cancer cell apoptosis. Mechanistically, MDM2 acted as a E3 ligase to ubiquitinate FBW7, a well-established E3 ligase for MCL-1, at Lys412 residue, which resulted in FBW7 destruction and MCL-1 stabilization. Targeting MDM2 to augment MCL-1 protein breakdown overcame resistance to Osimertinib in vitro and in vivo. Finally, the clinical relevance of MDM2-FBW7-MCL-1 regulatory axis was validated in mouse xenograft tumor model and in NSCLC specimen. Conclusion Overexpression of MDM2 is a novel resistant mechanism to Osimertinib in EGFR mutant NSCLC. MDM2 utilizes its E3 ligase activity to provoke FBW7 destruction and sequentially leads to MCL-1 stabilization. Cancer cells with aberrant MDM2 state are refractory to apoptosis induction and elicit a resistant phenotype to Osimertinib. Therefore, targeting MDM2 would be a feasible approach to overcome resistance to Osimertinib in EGFR mutant NSCLC.

Abstract Conventional mini percutaneous nephrolithotomy (mPCNL) typically necessitates the pre-operative placement of ureteral catheters. With the development of enhanced recovery after surgery (ERAS), we introduce a novel approach: no ureteral catheter mini percutaneous nephrolithotomy (NUC-mPCNL). To evaluate the efficacy and safety of this innovative procedure compared to mPCNL, we compared the total operative time, stone clearance rate (SCR), stone-free rate (SFR), and complications among patients undergoing either modality from January to September 2021. Our findings revealed a statistically significant reduction in the mean total operative time for the NUC-mPCNL group (42.6 ± 2.4 vs. 60.2 ± 3.4 min, p

Abstract Background The prevalence of high body mass index (BMI) is increasing in both children and adults worldwide. However, it is unclear whether vulnerabilities to maintenance and transition of weight status vary throughout the lifespan. Objective We aimed to characterize dynamic transitions of weight statuses across different life stages and to identify the sensitive periods for maintenance, onset, and resolution of obesity. Methods This longitudinal study included a total of 23,179 participants aged 6–80 years with 95,994 BMI measurements from the China Health and Nutrition Survey 1989–2015. To examine the heterogeneity in transitions of weight statuses across different life stages, we divided participants into 8 sub-cohorts based on baseline ages by 10-year intervals, i.e., 6–10 years, 11–20 years, 21–30 years, 31–40 years, 41–50 years, 51–60 years, 61–70 years, and 71–80 years. We estimated the probabilities of transitioning between weight statuses at a given follow-up year by baseline age using generalized linear mixed-effects models. Results The predicted prevalence of obesity decreased from 6 years, bottomed at around 20 years, increased thereafter, peaked at around 55 years, and then decreased gradually. In general, participants with underweight had lower probabilities of maintaining the same status compared to those with normal weight, overweight, or obesity for all age groups. For 10-year follow-up, individuals aged 21–30 years had the highest probabilities of transitioning from normal weight to obesity and transitioning from overweight to obesity compared to those in other age groups. Individuals aged 6–20 years had the highest probabilities of transitioning from obesity to normal weight and transitioning from overweight to normal weight. Individuals in all adult age groups had higher probabilities of maintaining obesity status than children and adolescents. Conclusions Young adulthood is the most sensitive period for obesity onset, whereas childhood and adolescence are the most sensitive periods for obesity resolution. The findings suggest the heterogeneity of susceptibilities to weight status transitions across different life stages and highlight the importance of the development of age-appropriate approaches for the prevention and intervention of obesity.

Abstract Direct oxidation of KA oil (the mixture of cyclohexanone and cyclohexanol) toward ε-caprolactone is in high demand yet hard to implement in need of juggling the activation of both methyne C-H bond of cyclohexanol and α-C-C bond of cyclohexanone. Here we demonstrate that in situ formed Cu1+δ-Oδ-• active site, which originates from relay reaction at Ni(II) and Cu(I) pairs in a metal-organic framework (known as NiCu-MOF-74) with O2 and benzaldehyde (PhCHO), efficiently oxidizes KA oil toward ɛ-caprolactone along with good stability. Mechanism investigation discloses that the auxiliary Ni(II) site first adsorbs O2 for abstracting formyl hydrogen in PhCHO followed by transfer of PhCO· to react with another O2 over the major Cu(I) site, leading to formation of Cu1+δ-Oδ-• and PhCOOH. This major-auxiliary cooperative strategy will be particularly suitable for multivariate MOFs as next generation catalysts towards complex reactions.

Abstract Adaptive behavior requires the ability to shift responding within (intra-dimensional) or between (extra-dimensional) stimulus dimensions when reward contingencies change. Studies of shifting in humans have focused mainly on the prefrontal cortex and/ or have been restricted to indirect measures of neural activity such as fMRI and lesions. Here, we demonstrate the importance of the amygdala and hippocampus by recording local field potentials directly from these regions intracranially in human epilepsy patients. Reward signals were coded in the high frequency gamma activity (HFG; 60-250 Hz) of both regions and synchronised via low frequency (3-5 Hz) phase-locking only after a shift when patients did not already know the rule and it signalled to stop shifting (“Win-Stay”). In contrast, HFG punishment signals were only seen in the amygdala when the rule then changed and it signalled to start shifting (“Lose-Shift”). During decision-making, hippocampal HFG was more inhibited on non-shift relative to shift trials, suggesting a role in preventing interference in rule representation and amygdala HFG was sensitive to stimulus novelty. The findings expand our understanding of human amygdala-hippocampal function and shifting processes, the disruption of which could contribute to shifting deficits in neuropsychiatric disorders.

Abstract Coronavirus disease 2019 (COVID-19) represents the novel respiratory infectious disorder caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is characterized by rapid spread throughout the world. Reactive oxygen species (ROS) account for cellular metabolic by-products, and excessive ROS accumulation can induce oxidative stress due to insufficient endogenous antioxidant ability. In the case of oxidative stress, ROS production exceeds the cellular antioxidant capacity, thus leading to cell death. SARS-CoV-2 can activate different cell death pathways in the context of infection in host cells, such as neutrophil extracellular trap (NET)osis, ferroptosis, apoptosis, pyroptosis, necroptosis and autophagy, which are closely related to ROS signalling and control. In this review, we comprehensively elucidated the relationship between ROS generation and the death of host cells after SARS-CoV-2 infection, which leads to the development of COVID-19, aiming to provide a reasonable basis for the existing interventions and further development of novel therapies against SARS-CoV-2. Graphical Abstract

Abstract Beneficial rhizosphere microorganisms are widely employed to shield crops from underground pathogen infections. In this study, we challenge this conventional idea by employing rhizosphere soil bacteria to safeguard kiwi plants against the above-ground canker, caused by Pseudomonas syringae pv. actinidiae (Psa). Microbiome comparisons were conducted in different resistant cultivars Actinidia chinensis var. deliciosa ‘Hayward’ and A. chinensis var. chinensis ‘Hongyang’. Our findings reveal the most notable disparity in the rhizosphere soil microbiome, with the Flavobacterium significantly enriched in the rhizosphere soil of more resistant cultivar, ‘Hayward’. We isolated Flavobacterium isolates and observed their efficacy in preventing Psa infection, which is further confirmed in field trial by using a representative strain Flavobacterium soyae F55. Furthermore, undescribed gene clusters responsible for antimicrobial metabolite biosynthesis were identified in F. soyae F55, and F. soyae F55 growth was evidently promoted by the root exudates of ‘Hayward’. The results underscore the potential of beneficial rhizosphere soil bacteria in protection against above-ground disease.

Abstract Background Decision-making in the management of Crohn’s disease (CD)-related spontaneous intra-abdominal abscess (IAA) is challenging. This study aims to reveal predictive factors for percutaneous drainage and/or surgery in the treatment of CD-related spontaneous IAA through long-term follow-up. Methods Data were collected, including clinical manifestations, radiography and treatment strategies, in Chinese patients with CD-related IAA in a tertiary medical center. Univariate and Multivariate Cox analysis were conducted to identify predictors for invasive therapy. Results Altogether, 48 CD patients were identified as having IAA through enhanced CT scans. The median follow-up time was 45.0 (23.3, 58.0) months. 23 (47.9%) patients underwent conservative medical treatment, and 25 (52.1%) patients underwent percutaneous drainage and/or surgical intervention (invasive treatment group). The 1-, 2-, and 5-year overall survival rates without invasive treatment were 75.0%, 56.1%, and 46.1%, respectively. On univariate Cox analysis, the computerized tomography (CT) features including nonperienteric abscess (HR: 4.22, 95% CI: 1.81–9.86, p = 0.001), max abscess diameter (HR: 1.01, 95% CI: 1.00-1.02, p

Abstract The interaction between the shock wave and boundary layer of transonic wings can trigger periodic self-excited oscillations, resulting in transonic buffet. Buffet severely restricts the flight envelope of civil aircraft and is directly related to their aerodynamic performance and safety. Developing efficient and reliable techniques for buffet onset prediction is crucial for the advancement of civil aircraft. In this study, utilizing a comprehensive database of supercritical airfoils generated through numerical simulations, a convolutional neural network (CNN) model is firstly developed to perform buffet classification based on the flow fields. After that, employing explainable machine learning techniques, including Gradient-weighted Class Activation Mapping (Grad-CAM), random forest algorithms, and statistical analysis, the research investigates the correlations between supervised CNN features and key physical characteristics related with the separation region, shock wave, leading edge suction peak, and post-shock loading. Finally, physical buffet onset metric is established with good generalization and accuracy, providing valuable guidance for engineering design in civil aircraft.

Abstract Colorectal cancer (CRC) is a prevalent malignant tumor of the gastrointestinal system, with the third and second highest incidence and mortality rates globally in 2020, respectively. Immunotherapy has developed rapidly in recent years. Natural killer (NK) cells have received increasing attention in the field of tumor immunotherapy due to their recognition and killing tumor cells without the limitations of major histocompatibility complexes. However, constraints within the tumor microenvironment that impede the infiltration and proliferation of NK cells result in poor efficacy of NK cell therapy for solid tumors. Oncolytic viral therapy is an immunogenic treatment with the potential to enhance anti-tumour immune responses and promote immune cell infiltration. In this study, we synergistically combine NK cells with an oncolytic adenovirus carrying Decorin (rAd.DCN) for the treatment of colorectal cancer (CRC) in a xenograft mouse model. By using Flow cytometry, real-time quantitative PCR and Calcein-AM release assay, we found that rAd.DCN could effectively promote proliferation, activation and degranulation of NK cells, up-regulate expression and secretion of NK cell killing activity-related factors, and enhance their killing activity. The efficacy is better than that of the blank control oncolytic virus rAd.Null. Combined treatment significantly inhibited tumor growth, increased the number of NK cells in peripheral blood, promoted the killing function of NK cells, and increased the expression levels of perforin and IFN-γ. At the same time, more NK cells were recruited to infiltrate tumor tissue. Our study established the feasibility of combination NK cells and oncolytic adenovirus application, thus expanding the scope of potentially curative treatments for NK cells in CRC.

Lignin serves as a promising Ultraviolet (UV) absorber within sunscreen industry. However, the commercial development of lignin-containing sunscreens faces challenges due to their low sun protection factor (SPF) and dark color in cosmetics industry. In this study, dual modifications on the chemical and physical structures of lignin were conducted to address these challenges. Initially, methylene bis-benzotriazolyl tetramethylbutylphenol (MBBT) was grafted onto alkali lignin (AL) through an atom transfer radical polymerization reaction, resulting in a polymer of AL-graft-MBBT3 (AL-g-MBBT3). The sunscreen prepared with 10% AL-g-MBBT3 displays outstanding sun protection performance with a SPF of 42.93 and a light color with a color difference value (ΔE) of 45.6, in contrast to 10% AL with a SPF of 4.74 and a ΔE value of 49.5. Subsequently, AL-g-MBBT3 was transformed into normal submicron spheres (AL-g-MBBT3 N) and TiO2-loading submicron spheres (AL-g-MBBT3/TiO2). The sun protection performances of 10% AL-g-MBBT3 N@C and AL-g-MBBT3/TiO2@C sunscreens obviously surpass that of AL-g-MBBT3@C sunscreen, achieving SPFs of 60.38 and 66.20, respectively. Additionally, there is a considerable improvement in the color of these sunscreens, with ΔE values of 41.8 and 36.3, respectively. These results provide valuable insights into exploring lignin's high-value applications in sunscreen.

Introduction: Ovarian cancer (OC) is known for its high mortality rate. Although sodium citrate has anti-tumor effects in various cancers, its effect and mechanism in OC remain unclear. Objectives: To analyze the inhibitory effect of sodium citrate on ovarian cancer cells and the underlying mechanism. Methods: Cell apoptosis was examined by TUNEL staining, flow cytometry, and ferroptosis was examined intracellular Fe2+, MDA, LPO assays, respectively. Cell metabolism was examined by OCR and ECAR measurements. Immunoblotting and immunoprecipitation were used to elucidate the mechanism. Results: This study suggested that sodium citrate not only promoted ovarian cancer cell apoptosis but also triggered ferroptosis, manifested as elevated levels of Fe2+, LPO, MDA and lipid ROS production. On one hand, sodium citrate treatment led to a decrease of Ca2+ content in the cytosol by chelating Ca2+, which further inhibited the Ca2+/CAMKK2/AKT/mTOR signaling, thereby suppressing HIF1α-dependent glycolysis pathway and inducing cell apoptosis. On the other hand, the chelation of Ca2+ by sodium citrate resulted in inactivation of CAMKK2 and AMPK, leading to increase of NCOA4-mediated ferritinophagy, causing increased intracellular Fe2+ levels. More importantly, the inhibition of Ca2+/CAMKK2/AMPK signaling pathway reduced the activity of the MCU and Ca2+ concentration within the mitochondria, resulting in an increase in mitochondrial ROS. Additionally, metabolomic analysis indicated that sodium citrate treatment significantly increased de novo lipid synthesis. Altogether, these factors contributed to ferroptosis. As expected, Ca2+ supplementation successfully reversed the cell death and decreased tumor growth induced by sodium citrate. Inspiringly, it was found that coadministration of sodium citrate increased the sensitivity of OC cells to chemo-drugs. Conclusion: These results revealed that the sodium citrate exerted its anti-cancer activity by inhibiting Ca2+/CAMKK2-dependent cell apoptosis and ferroptosis. Sodium citrate will hopefully serve as a prospective compound for OC treatment and for improving the efficacy of chemo-drugs.

Abstract The levels of fasting-state serum bile acids (BAs) in individuals with polycystic ovary syndrome (PCOS) differ from those of control subjects. However, there is a lack of research on the BAs profile in lean women with PCOS and whether these changes are linked to the host metabolism. Therefore, our objective was to investigate the synthesis and metabolism of serum BAs in lean women with PCOS and assess the correlation between BAs and clinical characteristics. This study employed a cross-sectional design of lean women with PCOS (n = 240) in comparison to a control group (n = 80) consisting of healthy lean women. The findings revealed significant increases in the levels of non-12-OH BAs and chenodeoxycholic acid (CDCA)% (both P

Abstract Numerosity adaptation is a phenomenon in which prolonged exposure to a stimulus of greater numerosity makes subsequent stimuli appear less numerous, and vice versa. It has been confined to moderated numerosities outside the subitizing range (> 4). This study investigated whether the estimation of small numerosities (1–4), which is performed rapidly and accurately due to the mechanism of subitizing, is susceptible to adaptation. After adapting to a 50-dot stimulus, participants were presented with stimuli consisting of 1–5 color sets. In some trials, participants were informed of the target color-set before the presentation of stimuli, while in others, they were instructed afterwards. When estimating 1–4 dots in the single-color set or superset (the total dots), no adaptation effect was observed. The coefficient of variation (CV) was below 0.05, indicating the effective function of subitizing. However, when enumerating subsets in parallel, adaptation biased the estimation. The CV in estimating subitized numerosities was comparable to and correlated with that of estimating moderate numerosities (5–12), suggesting that subitizing was superseded by numerosity estimation. Greater effects arise when the targets were probed afterwards, with elevated CV. The prior adaptor may be more weighted to optimize detection of number deviations, especially under higher perceptual uncertainty.

Abstract To explore the performance of 99mTc-diethylene triaminepentaacetic acid (DTPA) SPECT/CT texture analysis in evaluating the activity of thyroid-associated ophthalmopathy (TAO) . This retrospective study examined 115 TAO patients from a single institution as an internal cohort and 58 TAO patients from another institution as an external validation set. Patients in the internal cohort were randomly divided into training (n = 81) and internal validation sets (n = 34). Radiomics signatures were constructed with the minimal redundancy maximal relevance and least absolute shrinkage and selection operator algorithms in training set. Multivariate logistic regression analysis was used to develop a clinical model and a combined clinical–radiomics model. Diagnostic performance of models was evaluated using receiver operating characteristic curve analysis, calibration curves and decision curve analysis. Compared with CT and SPECT radiomics models, Rad-scoreSPECT/CT demonstrated the best performance with areas under the receiver operating characteristic curve of 0.94 and 0.91 in the training and test sets, respectively. The combined clinical-radiomics model exhibited significantly better performance in evaluating TAO activity. Our results demonstrate the validity of a multimodal radiomic model of 99mTc-DTPA-SPECT/CT to assess TAO activity. The combined clinical-radiomics model exhibited significantly better diagnostic performance than the clinical model.

Abstract In the field of oil drilling, accurately predicting the Rate of Penetration (ROP) is crucial for improving drilling efficiency and reducing costs. Traditional prediction methods and existing machine learning approaches often lack accuracy and generalization capabilities, leading to suboptimal results in practical applications. This study proposes an end-to-end ROP prediction model based on BiLSTM-SA-IDBO, which integrates Bidirectional Long Short-Term Memory (BiLSTM), a Self-Attention mechanism (SA), and an Improved Dung Beetle Optimization algorithm (IDBO), incorporating the Bingham physical equation.We enhanced the DBO algorithm by using Sobol sequences for population initialization and integrating the Golden Sine algorithm and dynamic subtraction factors to develop a more robust IDBO. This optimized the BiLSTM-SA model, resulting in a BiLSTM-SA-IDBO model with an RMSE of 0.065, an R² of 0.963, and an MAE of 0.05 on the test set. Compared to the original BiLSTM-SA model, these metrics improved by 78%, 21%, and 83%, respectively. Additionally, we compared this model with BP Neural Network, Random Forest, XGBoost, and LSTM models, and found that our proposed model significantly outperformed these traditional models. Finally, through practical testing, the model’s excellent predictive ability and generalization were verified, demonstrating its great potential for practical applications.

Abstract Background The aim of this study is to investigate the real-world efficacy and safety of nivolumab in combination with chemotherapy for patients with advanced human epidermal growth factor receptor 2 (HER2)-negative gastric cancer (GC). Methods We enrolled patients diagnosed with unresectable advanced or metastatic GC who received nivolumab plus chemotherapy as first-line systemic treatment. The combined positive score (CPS), indicating the number of programmed cell death-ligand 1 (PD-L1)-stained cells, was utilized. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan–Meier method. Adverse events (AEs) were graded, and treatment was ceased upon disease progression or intolerance. Results A total of 27 patients were included in the study, comprising 15 patients with CPS ≥ 5 and 12 patients with CPS

Abstract Magnesium (Mg) metal is a promising anode candidate for high-energy and cost-effective multivalent metal batteries, but suffers from severe surface passivation in conventional electrolytes, especially aqueous solutions. Here, we uncover that MgH2, in addition to the well-known MgO and Mg(OH)2, can be formed during the passivation of Mg by water. The formation mechanism and spatial distribution of MgH2, and its detrimental effect on interfacial dynamics and stability of Mg anode are revealed by comprehensive experimental and theoretical investigations. Furthermore, a graphite-based hydrophobic and Mg2+-permeable water-tolerant interphase is drawn using a pencil on the surface of Mg anodes, allowing them to cycle stably in symmetric (> 900 h) and full cells (> 500 cycles) even after contact with water. The mechanistic understanding of MgH2-involved Mg passivation and the design of pencil-drawn waterproof Mg anodes may inspire the further development of Mg metal batteries with high water resistance.

In the context of the development of new power systems, a three-dimensional spatio-temporal adaptation assessment model based on grid satisfaction, spatio-temporal resources, and effectiveness improvement is proposed to address the problems of distribution network planning and construction, the adaptability of key distribution network technologies to the space and time in which they are applied, and the difficulty of quantifying application defects. Subjective assignment in hierarchical analysis is improved using continuous interval ordered weighted average operator, and the problem of bias of the single assignment method is solved by the introduction of a subjective-objective combination assignment method constructed by the conflicting correlation among criteria method. The degree of affiliation of each indicator is determined using the fuzzy integrated evaluation method and the evaluation level is then obtained. The case studies show that the proposed method can quantify the degree of fit between the key technologies of the distribution network and the space-time, identify the adaptability of the key technologies to different space-times and the degree of satisfaction of the application of the technologies in different space-times, and reveal the weaknesses of the key technologies of the distribution network, which can help improve the efficiency and effectiveness of the investment in the distribution network and better serve the high-quality development of the economy and society.

Abstract Background Resection of intrathoracic tumor with cardiopulmonary bypass (CPB) remains a relatively under-reported intervention in literature, and its role in managing locally advanced mediastinal and lung cancers is a topic of ongoing debate. Our aim was to review our experience and assess the role of CPB for treating locally advanced mediastinal and lung cancers. Methods Between 2015 and 2020, this study initially included 10 patients with primary locally advanced thoracic malignancies with apparent adjacent cardiovascular invasion demonstrated by thoracic imaging scans. Operation was performed based on a multidisciplinary tumor board consensus. Eventually, 8 patients (3 primary lung cancers and 5 mediastinal cancers) received either salvage or elective resection with CPB; two completed surgery without requiring CPB. Results Regarding the extent of adjacent structure involvement, 4 patients presented with involvement of the superior vena cava (SVC), 1 involved the right atrium (RA), 2 involved the SVC and RA, and 1 involved the SVC, the origin of main pulmonary artery, and the ascending aorta. Thirty-day mortality occurred in two of three patients receiving salvage surgery due to respiratory insufficiency. With the long-term follow-up, one patient died of recurrence 25 months postoperatively, one survived with recurrence 30 months postoperatively, and four were alive without recurrence for 35, 36, 49, and 107 months after operations. Conclusion In certain patients, particularly for elective surgical candidates rather than salvage resection, CPB allows for extended resection of locally advanced thoracic cancers with acceptable perioperative safety and survival.

Abstract This study aimed to elucidate the role and underlying mechanisms of Peroxisome proliferator-activated receptor gamma (PPARγ) and its m6A methylation in renal ischemia-reperfusion (I/R) injury and ferroptosis of tubular epithelial cells (TECs). High-throughput transcriptome sequencing was performed on renal tissue samples from I/R injury models and sham-operated mice, complemented by in vivo and in vitro experiments focusing on the PPARγ activator Rosiglitazone and the manipulation of METTL14 and IGF2BP2 expression. Key evaluations included renal injury assessment, ferroptosis indicator measurement, and m6A methylation analysis of PPARγ. Our findings highlight the critical role of the PPARγ pathway and ferroptosis in renal I/R injury, with Rosiglitazone ameliorating renal damage and TEC ferroptosis. METTL14-mediated m6A methylation of PPARγ, dependent on IGF2BP2, emerged as a pivotal regulator of PPARγ expression, renal injury, and ferroptosis. This study reveals that PPARγ m6A methylation, orchestrated by METTL14 through an IGF2BP2-dependent mechanism, plays a crucial role in mitigating renal I/R injury and TEC ferroptosis. These insights offer promising avenues for therapeutic strategies targeting acute kidney injury.

Abstract Background Gastroesophageal reflux disease (GERD) is among the most common complications of bariatric surgery. This study aimed to analyse the risk factors affecting the worsening of GERD symptoms after laparoscopic sleeve gastrectomy (LSG), and to establish and validate a related nomogram model. Methods The study recruited 236 participants and randomly divided them into training and validation sets in a ratio of 7:3. LASSO regression technique was used to select the optimal predictive features, and multivariate logistic regression was used to construct the column line graphs. The performance of the nomogram was evaluated and validated by analyzing the area under the receiver operating characteristic (ROC) curve, calibration curve, and decision curve. Results In this study, Lasso-logistic regression was applied to select 5 predictors from the relevant variables, which were body mass index (BMI), diabetes, hiatal hernia, GERD, and triglyceride levels. These 5 predictor variables constructed a model with moderate predictive power, with an area under the ROC curve of 0.779 for the training set and 0.796 for the validation set. Decision curve analysis showed that in external validation, if the risk thresholds were between 4 and 98% and 14–95%, then the nomogram can be applied to the clinic. Conclusions We have developed and validated a nomogram that effectively predicts the risk of worsening gastroesophageal reflux symptoms following LSG.

Abstract The aim of the study was to analyze and discuss the value of preoperative systemic immune inflammation index (SII) and prognostic nutritional index (PNI) in predicting the prognosis of patients with renal cell carcinoma (RCC) after operation, and to establish a nomogram prediction model for patients with RCC after operation based on SII and PNI. From January 2014 to December 2018, 210 patients with RCC who underwent surgical treatment at the Xuzhou Central Hospital were selected as the research object. The receiver operating characteristic curve (ROC) was used to determine the optimal cut-off value for preoperative SII, PNI, LMR, PLR, NLR and the patients were divided into groups according to the optimal cutoff values. The survival rate of patients was evaluated. The risk factors that affect the prognosis of patients with RCC were determined by LASSO and Cox regression analysis, and a prognostic nomogram was constructed based on this result. The bootstrap method was used for internal verification of the nomogram model. The prediction efficiency and discrimination of the nomogram model were evaluated by the calibration curve and index of concordance (C-index), respectively. The average overall survival (OS) of all patients was 75.385 months, and the 1-, 2-and 3-year survival rates were 95.5%, 86.6% and 77.2%, respectively. The survival curve showed that the 5-year OS rate of low SII group was significantly higher than that of high SII group (89.0% vs. 64.5%; P

Abstract In the field of intelligent fault diagnosis, particularly concerning rotating machinery, convolutional neural networks (CNNs) face significant challenges when applied to real industrial vibration data. These data are not only contaminated by various types of noise but also exhibit fault features that vary across different scales. Consequently, the effective suppression of extraneous noise and accurate extraction of multi-scale fault features are crucial issues. To address these challenges, this study proposes a novel deep neural network framework, termed the Multidimensional Fusion Residual Attention Network (MFRANet), for gearbox fault diagnosis. The MFRANet employs a multi-scale deep separable convolution module to thoroughly investigate the fundamental characteristics of the original vibration signals in both the time and time-frequency domains. To enhance the detailed analysis of diagnostic data and mitigate the risks of overfitting and noise interference, an efficient residual channel attention module is incorporated to weight and denoise the feature maps. Additionally, an external attention module is introduced to create implicit connections between the denoised multi-scale feature maps and to highlight potential correlations within the sample data, thereby improving the accuracy of fault diagnosis. Experimental evaluations on a gearbox fault dataset demonstrate that the proposed method surpasses several benchmark and state-of-the-art techniques in terms of diagnostic performance, exhibiting robust noise resilience across various noise levels. This indicates enhanced reliability and accuracy in gearbox fault diagnosis, providing an innovative and efficient solution for fault diagnosis in rotating machinery. The study underscores the contributions of artificial intelligence through the innovative structure of the method and the integration of advanced deep learning modules, while its engineering application is evidenced by addressing practical challenges in rotating machinery fault diagnosis. This work meets the urgent need for reliable diagnostic methods in industrial environments.

Abstract Chemotherapy resistance has been a great challenge in pancreatic ductal adenocarcinoma(PDAC) treatments. Current first-line chemotherapy regimens for PDAC include gemcitabine-based regimens such as AG regimen (albumin paclitaxel and gemcitabine), fluorouracil-based regiments such as FOLFIRINOX regimen ((5-fluorouracil5-FU), oxaliplatin, Irinotecan) and platinum-based regimens for patients with BRCA mutations. large amounts of work have been done on exploring the mechanism underlying resistance of gemcitabine-based and platinum-based regimens, while little research has been achieved on the mechanism of FOLFIRINOX regimens resistance. Hence, we identified Polypeptide N-Acetylgalactosaminyltransferase 5, (GALNT5) as a vital regulator and a potential therapeutic target in FOLFIRINOX regimens resistance. Colony formation assays and flow cytometry assays were performed to explore the roles of GALNT5 in cell proliferation and apoptosis in PDAC treated with FOLFIRINOX. IC50 alterations were calculated in GALNT5 knockdown and overexpressed cell lines. RNA-seq followed by GSEA (gene set enrichment analysis) was displayed to explore the potential mechanism. WB (western blotting), real-time PCR, and IF (immunofluorescence) were performed to validate relative pathways. The mouse orthotopic xenograft PDAC model was established to examine GALNT5 functions in vivo. GALNT5 was highly expressed in PDAC tissues and predicted poor prognosis in PDAC. Upregulation of GALNT5 in PDAC cells conferred FOLFIRINOX resistance on PDAC by inhibiting DNA damage. Moreover, GALNT5 interacted with MYH9, thus participating in the activation of the NOTCH pathways, resulting in hampering FOI-induced DNA damage. Functions of GALNT5 promoting FOLFIRINOX resistance were validated in vivo. In this study, we found that aberrantly overexpressed GALNT5 in PDAC took part in the activation of the NOTCH pathway by interacting with MYH9, thus inhibiting the DDR to achieve FOLFIRINOX resistance and causing poor prognosis. We identified GALNT5 as a potential therapeutic target for PDAC patients resistant to FOLFIRINOX chemotherapy.

Abstract High‐precision relative position and attitude measurement technology has a wide range of applications in aerospace and industrial production. Currently, the commonly used method for measurement is based on visual cooperative signs. However, its accuracy significantly decreases as the distance increases. Therefore, a relative positioning system is designed based on light field spatial coding and visual recognition. The projector emits spatially encoded structured light within the coverage of the light field, while the receiving end captures, identifies, measures the code, and calculates its pose in the light field coordinate system. Compared with the traditional measurement method, the measurement accuracy of this system does not decrease greatly with the increase in distance, the measurement distance can be adjusted in real‐time and does not depend on an external light source. By changing the projection pattern with different resolutions without changing hardware systems, it can adjust effective measurement distance accordingly. Theoretical and experimental results show that the proposed method can maintain measurement accuracy with the increase in distance.

The 25th Annual Western Canadian Gastrointestinal Cancer Consensus Conference (WCGCCC) was held in Winnipeg, Manitoba, on 26–27 October 2023. The WCGCCC is an interactive multidisciplinary conference that was attended by healthcare professionals from across Western Canada (British Columbia, Alberta, and Manitoba) who are involved in the care of patients with gastrointestinal cancer. Surgical, medical, and radiation oncologists; pathologists; oncology nurses; pharmacists; and a family physician in oncology (FPO) participated in presentation and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of gastroesophageal cancers.

G protein-coupled receptors (GPCRs) are pivotal in mediating diverse physiological and pathological processes, rendering them promising targets for drug discovery. GPCRs account for about 40% of FDA-approved drugs, representing the most successful drug targets. However, only approximately 15% of the 800 human GPCRs are targeted by market drugs, leaving numerous opportunities for drug discovery among the remaining receptors. Cell expression systems play crucial roles in the GPCR drug discovery field, including novel target identification, structural and functional characterization, potential ligand screening, signal pathway elucidation, and drug safety evaluation. Here, we discuss the principles, applications, and limitations of widely used cell expression systems in GPCR-targeted drug discovery, GPCR function investigation, signal pathway characterization, and pharmacological property studies. We also propose three strategies for constructing genome-wide pan-GPCR cell libraries, which will provide a powerful platform for GPCR ligand screening, and facilitate the study of GPCR mechanisms and drug safety evaluation, ultimately accelerating the process of GPCR-targeted drug discovery.

Abstract The recent measurements of h → Zγ from ATLAS and CMS show an excess of the signal strength μ Z = σ · B obs / σ · B SM $$ {\left(\sigma \cdotp \mathcal{B}\right)}_{\textrm{obs}}/{\left(\sigma \cdotp \mathcal{B}\right)}_{\textrm{SM}} $$ = 2.2 ± 0.7, normalized as 1 in the standard model (SM). If confirmed, it would be a signal of new physics (NP) beyond the SM. We study NP explanation for this excess. In general, for a given model, it also affects the process h → γγ. Since the measured branching ratio for this process agrees well with the SM prediction, the model is severely constrained. We find that a minimally fermion singlets and doublet extended NP model can explain simultaneously the current data for h → Zγ and h → γγ. There are two solutions. Although both solutions enhance the amplitude of h → Zγ to the observed one, in one of the solutions the amplitude of h → γγ flips sign to give the observed branching ratio. This seems to be a contrived solution although cannot be ruled out simply using branching ratio measurements alone. However, we find another solution that naturally enhances h → Zγ to the measured value, but keeps the amplitude of h → γγ close to its SM prediction. We also comment on the phenomenology associated with these new fermions.

Abstract Dental and maxillofacial diseases are always accompanied by complicated hard and soft tissue defects, involving bone, teeth, blood vessels and nerves, which are difficult to repair and severely affect the life quality of patients. Recently, extracellular vesicles (EVs) secreted by all types of cells and extracted from body fluids have gained more attention as potential solutions for tissue regeneration due to their special physiological characteristics and intrinsic signaling molecules. Compared to stem cells, EVs present lower immunogenicity and tumorigenicity, cause fewer ethical problems, and have higher stability. Thus, EV therapy may have a broad clinical application in regenerative dentistry. Herein, we reviewed the currently available literature regarding the functional roles of EVs in oral and maxillofacial tissue regeneration, including in maxilla and mandible bone, periodontal tissues, temporomandibular joint cartilage, dental hard tissues, peripheral nerves and soft tissues. We also summarized the underlying mechanisms of actions of EVs and their delivery strategies for dental tissue regeneration. This review would provide helpful guidelines and valuable insights into the emerging potential of EVs in future research and clinical applications in regenerative dentistry.

Abstract Testosterone (T) is a critical predictor of polycystic ovary syndrome (PCOS) but the genetic overlap between T and PCOS has not been established. Here by leveraging genetic datasets from large-scale genome-wide association studies, we assessed the genetic correlation and polygenic overlap between PCOS and three T-related traits using linkage disequilibrium score regression and the bivariate causal mixture model methods. The conjunctional false discovery rate (conjFDR) method was employed to identify shared causal variants. Functional annotation of variants was conducted using FUMA. Total T and bioavailable T exhibited positive correlations with PCOS, while sex hormone-binding globulin (SHBG) showed a negative correlation. All three traits demonstrated extensive genetic overlap with PCOS, with a minimum of 68% of T-related variants influencing PCOS. The conjFDR revealed 4 to 6 causal variants within joint genomic loci shared between PCOS and T-related traits. Functional annotations suggested that these variants might impact PCOS by modulating nearby genes, such as FSHB. Our findings support the hypothesis that PCOS is significantly influenced by androgen abnormalities. Additionally, this study identified several causal variants potentially involved in shared biological mechanisms between PCOS and T regulation.

Abstract Background Missing data in confounding variables present a frequent challenge in generating evidence using real-world data, including electronic health records (EHR). Our objective was to apply a recently published toolkit for characterizing missing data patterns and based on the toolkit results about likely missingness mechanisms, illustrate the decision-making process for analyses in an empirical case example. Methods We utilized the Structural Missing Data Investigations (SMDI) toolkit to characterize missing data patterns in the context of a pharmacoepidemiology study comparing cardiovascular outcomes of initiating sodium-glucose-cotransporter-2 inhibitors (SGLT2i) and dipeptidyl peptidase‐4 inhibitors (DPP‐4i) among older adults. The study used a linked EHR-Medicare claims dataset from Duke Health patients (2015–2017), focusing on partially observed confounders from EHR data (HbA1c lab and body mass index [BMI] values). Our analysis incorporated SMDI's descriptive functions and diagnostic tests to explore missingness patterns and determine missingness mitigation approaches. We used findings from these investigations to inform estimation of adjusted hazard ratios comparing the two classes of medications. Results High levels of missingness were noted for important confounding variables including HbA1c (63.6%) and BMI (16.5%). Diagnostic tests resulted in output that described: 1) the distributions of patient characteristics, exposure, and outcome between patients with or without an observed value of the partially observed covariate, 2) the ability to predict missingness based on observed covariates, and 3) estimate if the missingness of a partially observed covariate is differential with respect to the outcome. There was evidence that missingness could be sufficiently described using observed data, which allowed multiple imputation by chained equations using random forests to address missing confounder data in estimating treatment effects. Multiple imputation resulted in improved alignment of effect estimates with previous studies. Conclusions We were able to demonstrate the practical application of the SMDI toolkit in a real-world setting. Application of the SMDI toolkit and the resulting insights of potential missingness patterns can inform the choice of appropriate analytic methods and increase transparency of research methods in handling missing data. This type of approach can inform analytic decision making and may increase our ability to generate evidence from real-world data.

Abstract Background Saline-alkaline water aquaculture has become a key way to mitigate the reduction of freshwater aquaculture space and meet the increasing global demand for aquatic products. To enhance the comprehensive utilization capability of saline-alkaline water, it is necessary to understand the regulatory mechanisms of aquatic animals coping with saline-alkaline water. In this study, our objective was to elucidate the function of proline metabolism in the alkaline adaptation of Nile tilapia (Oreochromis niloticus). Results Expose Nile tilapia to alkaline water of different alkalinity for 2 weeks to observe changes in its growth performance and proline metabolism. Meanwhile, to further clarify the role of proline metabolism, RNA interference experiments were conducted to disrupt the normal operation of proline metabolic axis by knocking down pycr (pyrroline-5-carboxylate reductases), the final rate-limiting enzyme in proline synthesis. The results showed that both the synthesis and degradation of proline were enhanced under carbonate alkalinity stress, and the environmental alkalinity impaired the growth performance of tilapia, and the higher the alkalinity, the greater the impairment. Moreover, environmental alkalinity caused oxidative stress in tilapia, enhanced ion transport, ammonia metabolism, and altered the intensity and form of energy metabolism in tilapia. When the expression level of the pycr gene decreased, the proline metabolism could not operate normally, and the ion transport, antioxidant defense system, and energy metabolism were severely damaged, ultimately leading to liver damage and a decreased survival rate of tilapia under alkalinity stress. Conclusions The results indicated that proline metabolism plays an important role in the alkaline adaptation of Nile tilapia and is a key regulatory process in various biochemical and physiological processes.

Abstract Background Vital pulp therapy (VPT) is recommended as an alternative treatment to root canal therapy (RCT) for management of teeth with carious pulp exposure. This randomized clinical trial aimed to compare the outcomes and postoperative pain, and to evaluate the time and cost after full pulpotomy (FP) and RCT in mature molar teeth with irreversible pulpitis (IP). Methods A total of 160 mature molar teeth with IP were randomly divided into two treatment groups. The FP group (test group) was treated with FP using iRoot BP Plus by an endodontist, the RCT group (control group) was treated with RCT using iRoot SP as sealer by the same endodontist. Pain was recorded preoperatively and daily until day 7 postoperatively. The treatment time and cost were recorded. Clinical and radiographic assessments were collected, and pulp sensibility tests were done by electric pulp test (EPT) at 3-, 6-, 12- month postoperatively. Data were analyzed through chi-square test, Mann-Whitney U test, Fisher exact and independent t test. Results FP and RCT had comparable success rates (Clinical, 97.3% vs. 98.6%; radiographic, 93.3% vs. 94.6%) (P > 0.05). Pain levels decreased over time from day 1 to day 7 postoperative in both groups, and the FP group had larger reductions in pain intensity than RCT at day 1 (P