Association analyses between the variants of SNAP25, SV2C and ST3GAL2 and the efficacy of botulinum toxin A in the treatment of the primary Meige syndrome.

Objective: Individual differences were observed in the clinical efficacy of Botulinum toxin A (BoNT-A) in the treatment of the primary Meige syndrome. Our study aimed to explore the potential associations between the clinical efficacy of BoNT-A in the treatment of the primary Meige syndrome and variants of SNAP25, SV2C and ST3GAL2, which are involving in the translocation of the BoNT-A in vivo. Methods: Patients with the primary Meige syndrome treated with BoNT-A were enrolled. Clinical efficacy was evaluated by the maximum improvement rate of motor symptoms and the duration of efficacy. Variants of SNAP25, SV2C and ST3GAL2 were obtained by Sanger sequencing. Another cohort diagnosed with primary cervical dystonia was also enrolled in the replication stage. Results: Among the 104 primary Meige syndrome patients, 80 patients (76.9%) had a good efficacy (the maximum improvement rate of motor symptoms ≥30%) and 24 (23. 1%) had a poor (the maximum improvement rate of motor symptoms <30%). As to the duration of efficacy, 52 patients (50.0%) had a long duration of efficacy (≥4 months), and 52 (50.0%) had a short (<4 months). In terms of primary Meige syndrome, SNAP25 rs6104571 was found associating with the maximum improvement rate of motor symptoms (Genotype: P = 0.02, OR = 0.26; Allele: P = 0.013, OR = 0.29), and SV2C rs31244 was found associating with the duration of efficacy (Genotype: P = 0.024, OR = 0.13; Allele: P = 0.012, OR = 0.13). Besides, we also conducted the association analyses between the variants and BoNT-A-related adverse reactions. Although, there was no statistical difference between the allele of SV2C rs31244 and BoNT-A-related adverse reactions, there was a trend (P = 0.077, OR = 2.56). In the replication stage, we included 39 patients with primary cervical dystonia to further expanding the samples' size. Among the 39 primary cervical dystonia patients, 25 patients (64.1%) had a good efficacy (the maximum improvement rate of motor symptoms ≥50%) and 14 (35.9%) had a poor (the maximum improvement rate of motor symptoms <50%). As to the duration of efficacy, 32 patients (82.1%) had a long duration of efficacy (≥6 months), and 7 (17.9%) had a short (<6 months). Integrating primary Meige syndrome and primary cervical dystonia, SV2C rs31244 was still found associating with the duration of efficacy (Genotype: P = 0.002, OR = 0. 23; Allele: P = 0.001, OR = 0. 25). Conclusion: In our study, SNAP25 rs6104571 was associated with the maximum improvement rate of motor symptoms in patients with primary Meige syndrome treated with BoNT-A, and patients carrying this variant had a lower improvement rate of motor symptoms. SV2C rs31244 was associated with duration of treatment in patients with primary Meige syndrome treated with BoNT-A and patients carrying this variant had a shorter duration of treatment. Patients with primary Meige syndrome carrying SV2C rs31244 G allele have an increase likelihood of BoNT-A-related adverse reactions. Involving 39 patients with primary cervical dystonia, the results further verify that SV2C rs31244 was associated with duration of treatment and patients carrying this variant had a shorter duration of treatment.

Hope experiences in parents of children with cancer: A qualitative meta-synthesis.

PURPOSE: To synthesise qualitative research on the parental hope experiences for children with cancer and identify the levels of parental hope experiences and psychosocial adjustment during cancer events. METHODS: Five electronic databases (Cochrane Library, PubMed, Embase, Web of Science, and CINAHL) and three Chinese databases (CNKI, Wanfang, and VIP) were used to retrieve qualitative studies on the hope experiences of parents of children with cancer from inception to February 2023. The Joanna Briggs Institute Qualitative Assessment and Review Instrument (JBI-QARI) was used to assess the methodological quality of the included studies. Data were synthesised using a thematic analysis. RESULTS: Four analytical themes were identified: the process and way hope exists, sources of hope, positive effects of hope, and obstacles to hope maintenance. CONCLUSIONS: Maintaining hope is crucial for parents who are caring for their children with cancer. There are different sources of hope, and targeted interventions can enhance the experience of hope for parents of children with cancer. Families, healthcare providers, and society should pay more attention to the parents of children with cancer and provide them with psychological, social, and financial support to improve their level of hope and quality of care.

Epidemiology and antimicrobial susceptibility profiles of Enterobacterales causing bloodstream infections before and during COVID-19 pandemic: Results of the Study for Monitoring Antimicrobial Resistance Trends (SMART) in Taiwan, 2018-2021.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has contributed to the spread of antimicrobial resistance, including carbapenem-resistant Enterobacterales. METHODS: This study utilized data from the Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance program in Taiwan. Enterobacterales from patients with bloodstream infections (BSIs) were collected and subjected to antimicrobial susceptibility testing and ß-lactamase gene detection using a multiplex PCR assay. Statistical analysis was conducted to compare susceptibility rates and resistance genes between time periods before (2018-2019) and during the COVID-19 pandemic (2020-2021). RESULTS: A total of 1231 Enterobacterales isolates were collected, predominantly Escherichia coli (55.6%) and Klebsiella pneumoniae (29.2%). The proportion of nosocomial BSIs increased during the COVID-19 pandemic (55.5% vs. 61.7%, p < 0.05). Overall, susceptibility rates for most antimicrobial agents decreased, with Enterobacterales from nosocomial BSIs showing significantly lower susceptibility rates than those from community-acquired BSIs. Among 123 Enterobacterales isolates that underwent molecular resistance mechanism detection, ESBL, AmpC ß-lactamase, and carbapenemase genes were detected in 43.1%, 48.8% and 16.3% of the tested isolates, respectively. The prevalence of carbapenemase genes among carbapenem-resistant Enterobacterales increased during the pandemic, although the difference was not statistically significant. Two novel ß-lactamase inhibitor combinations, imipenem-relebactam and meropenem-vaborbactam, preserved good efficacy against Enterobacterales. However, imipenem-relebactam showed lower in vitro activity against imipenem-non-susceptible Enterobacterales than that of meropenem-vaborbactam. CONCLUSIONS: The COVID-19 pandemic appears to be associated with a general decrease in antimicrobial susceptibility rates among Enterobacterales causing BSIs in Taiwan. Continuous surveillance is crucial to monitor antimicrobial resistance during the pandemic and in the future.

Dynamic change of metabolic dysfunction-associated steatotic liver disease in patients with hepatitis C virus infection after achieving sustained virologic response with direct-acting antivirals.

BACKGROUND: Information on the dynamics of metabolic dysfunction-associated steatotic liver disease (MASLD) among hepatitis C virus patients achieving sustained virologic response (SVR12) with direct-acting antivirals (DAAs) is limited. METHODS: We enrolled 1512 eligible participants in this prospective study. MASLD was defined by a controlled attenuation parameter (CAP) of ≥248 dB/m utilizing vibration-controlled transient elastography in conjunction with presence of ≥1 cardiometabolic risk factor. The distribution of MASLD and the changes in CAP were evaluated before treatment and at SVR12. Forward stepwise logistic regression analyses were performed to determine factors significantly associated with the regression or emergence of MASLD. RESULTS: The prevalence of MASLD decreased from 45.0% before treatment to 36.1% at SVR12. Among 681 participants with MASLD before treatment, 144 (21%) exhibited MASLD regression at SVR12. Conversely, among 831 participants without MASLD before treatment, 9 (1.1%) developed MASLD at SVR12. Absence of type 2 diabetes (T2D) [odds ratio (OR): 1.73, 95% confidence interval (CI): 1.13-2.65, p = 0.011], age > 50 years (OR: 1.73, 95% CI: 1.11-2.68, p = 0.015), and alanine transaminase (ALT) ≤ 2 times the upper limit of normal (ULN) (OR: 1.56; 95% CI: 1.03-2.37, p = 0.035) were associated with the regression of MASLD. Presence of T2D was associated with the emergence of MASLD (OR: 5.83, 95% CI: 1.51-22.56, p = 0.011). CONCLUSIONS: The prevalence of MASLD decreased after achieving SVR12 with DAAs. Patients with pre-existing T2D showed a diminished probability of MASLD regression and a heightened risk of MASLD emergence post-SVR12.

A first-principles study of the BC3N2 monolayer and a BC3N2/graphene heterostructure as promising anode materials for sodium-ion batteries.

High-performance sodium-ion batteries (SIBs) require anode materials with high capacity and fast kinetics. Based on first-principles calculations, we propose BC3N2 and BC3N2/graphene (B/G) heterostructure as potential SIB anode materials. The BC3N2 monolayer exhibits intrinsic metallic behavior. In addition, BC3N2 possesses a low Na+ diffusion barrier (0.15 eV), a high storage capacity (777 mA h g-1), a low open-circuit voltage (0.72 V), and a tiny axial expansion (0.36%). Compared with the BC3N2 monolayer, the B/G heterostructure exhibits a lower diffusion barrier of 0.027 eV, suggesting a much faster diffusion. More importantly, although the B/G heterostructure possesses heavier molar weight, its theoretical capacity (689 mA h g-1) is comparable to that of the BC3N2 monolayer. Based on the above-mentioned properties, we hope both the BC3N2 monolayer and the B/G heterostructure would be promising anodes for SIBs.

Development of an attenuated potato virus Y mutant carrying multiple mutations in helper-component protease for cross-protection.

Tobacco (Nicotiana tabacum) is one of the major cash crops in China. Potato virus Y (PVY), a representative member of the genus Potyvirus, greatly reduces the quality and yield of tobacco leaves by inducing veinal necrosis. Mild strain-mediated cross-protection is an attractive method of controlling diseases caused by PVY. Currently, there is a lack of effective and stable attenuated PVY mutants. Potyviral helper component-protease (HC-Pro) is a likely target for the development of mild strains. Our previous studies showed that the residues lysine at positions 124 and 182 (K124 and K182) in HC-Pro were involved in PVY virulence, and the conserved KITC motif in HC-Pro was involved in aphid transmission. In this study, to improve the stability of PVY mild strains, K at position 50 (K50) in KITC motif, K124, and K182 were separately substituted with glutamic acid (E), leucine (L), and arginine (R), resulting in a triple-mutant PVY-HCELR. The mutant PVY-HCELR had attenuated virulence and did not induce leaf veinal necrosis symptoms in tobacco plants and could not be transmitted by Myzus persicae. Furthermore, PVY-HCELR mutant was genetically stable after six serial passages, and only caused mild mosaic symptoms in tobacco plants even at 90 days post inoculation. The tobacco plants cross-protected by PVY-HCELR mutant showed high resistance to the wild-type PVY. This study showed that PVY-HCELR mutant was a promising mild mutant for cross-protection to control PVY.

Packaged structure optimization for enhanced light extraction efficiency and reduced thermal resistance of ultraviolet B LEDs.

Ultraviolet B light-emitting diodes (UVB LEDs) hold promise in medical and agricultural applications. The commonly used sapphire substrate for their epitaxy growth possesses a high refractive index and excellent UV light absorption characteristics. However, this high refractive index can induce total internal reflection (TIR) within the substrate, leading to decreased Light Extraction Efficiency (LEE) due to light absorption within the material. In this study, UVB LED chips were detached from the sub-mount substrate and directly affixed onto an aluminum nitride (AlN) substrate with superior heat dissipation using a eutectic process. This was undertaken to diminish packaged thermal resistance (PTR). Simultaneously, optimization of the UVB LED packaging structure was employed to alleviate LEE losses caused by the TIR phenomenon, with the overarching goal of enhancin external quantum efficiency (EQE). The final experimental findings suggest that optimal LEE is achieved with packaging dimensions, including a length (ELL) of 2 mm, a width (ELW) of 1.62 mm, and a height (ELH) of 0.52 mm. At an input current of 200 mA, the output power reaches 50 mW, resulting in an EQE of 6.3%. Furthermore, the packaged thermal resistance from the chip to the substrate surface can be reduced to 4.615 K/W.

Full-angle chip scale package of mini LEDs with a V-shape packaging structure.

The light distribution of light-emitting diodes (LEDs) generally resembles that of a Lambertian light source. When used as large-area light sources, the light distribution angle of LEDs must be modified through secondary optics design to achieve uniformity and minimize the number of light sources. However, secondary optical components pose several challenges such as demanding alignment accuracy, material aging, detachment, and lower reliability. Therefore, this paper proposes a primary optical design approach to achieve full-angle emission in LEDs without the need for lenses. The design employs a flip-chip as the light source and incorporates a V-shaped packaged structure, including a white wall layer, optical structure layers, and a V-shaped diffuse structure. With this design, the LEDs achieve full-angle emission without relying on lenses. Our experimental results demonstrated a peak intensity angle of 77.7°, a 20.3% decrease in the intensity of the central point ratio, and a full width at half maximum (FWHM) of the light distribution of 175.5°. This design is particularly suitable for thin, large-area, and flexible backlight light sources. Moreover, the absence of secondary optical components allows for a thinner light source module.

LIKE EARLY STARVATION 1 interacts with amylopectin during starch biosynthesis.

Starch is the major energy storage compound in plants. Both transient starch and long-lasting storage starch accumulate in the form of insoluble, partly crystalline granules. The structure of these granules is related to the structure of the branched polymer amylopectin: linear chains of glucose units organized in double helices that align to form semi-crystalline lamellae, with branch points located in amorphous regions between them. EARLY STARVATION 1 (ESV1) and LIKE EARLY STARVATION 1 (LESV) proteins are involved in the maintenance of starch granule structure and in the phase transition of amylopectin, respectively, in Arabidopsis (Arabidopsis thaliana). These proteins contain a conserved tryptophan-rich C-terminal domain folded into an antiparallel ß-sheet, likely responsible for binding of the proteins to starch, and different N-terminal domains whose structure and function are unknown. In this work, we combined biochemical and biophysical approaches to analyze the structures of LESV and ESV1 and their interactions with the different starch polyglucans. We determined that both proteins interact with amylopectin but not with amylose and that only LESV is capable of interacting with amylopectin during starch biosynthesis. While the C-terminal domain interacts with amylopectin in its semi-crystalline form, the N-terminal domain of LESV undergoes induced conformational changes that are probably involved in its specific function of mediating glucan phase transition. These results clarify the specific mechanism of action of these two proteins in the biosynthesis of starch granules.

Latent profiles of academic resilience in undergraduate nursing students and their association with resilience and self-efficacy.

AIM: This study aimed to investigate the heterogeneity of academic resilience among nursing students using latent profile analysis and its associated influencing factors. BACKGROUND: Nursing students experience higher levels of stress compared to their peers in other professions, and the cultivation of academic resilience plays a pivotal role in their ability to effectively cope with this stress. Academic resilience not only facilitates success in the face of academic adversity but also contributes to the promotion of mental well-being among nursing students. However, the current research on the academic resilience of nursing students has predominantly focused on a scale-centered total score approach, disregarding individual variability, and hindering the development to inform personalized interventions for enhancing academic resilience. DESIGN: A cross-sectional study. METHODS: A convenience sampling method was used to collect a total of 644 nursing students from two medical schools in Guangzhou City. The participants were recruited through an online survey conducted from January to March 2023. The questionnaires consisted of a general information form, the Chinese version of the Academic Resilience Scale-30 (C-ARS-30), the 10-item Connor Davidson Resilience Scale (CD-RISC-10), and the General Self-Efficacy Scale (GSES). Latent profile analysis was used to identify distinct categories of academic resilience among nursing students, and influencing factors were examined through ordinal logistic regression analysis. RESULTS: The academic resilience levels of nursing students can be divided into three potential categories: 'low academic resilience' (13.0%), 'moderate academic resilience' (70.0%), and 'high academic resilience' (17.0%). Level of grade, GPA, self-reported physical health level, resilience and self-efficacy were significantly influenced the different categories of academic resilience of nursing students (P<0.05). CONCLUSIONS: The majority of undergraduate nursing students were placed in the moderate academic resilience group, however, educational institutions should pay special attention to nursing students demonstrating low levels. Regular assessments of academic resilience are recommended, and personalized interventions should be tailored to address specific academic resilience characteristics across different grades of nursing students. Strategies aimed at enhancing academic resilience among nursing students may include improvements in GPA performance, attention to physical health, and the reinforcement of resilience and self-efficacy.

Effectiveness of WeChat-assisted preoperative education to reduce perioperative anxiety in breast cancer patients: a prospective randomized controlled study protocol.

BACKGROUND: Breast cancer is the most prevalent cancer among women globally, and surgical procedures continue to be the primary treatment. However, over 50% of patients experience preoperative anxiety due to the unknown and fear associated with surgery. Although drug therapy is commonly used to address this anxiety, its side effects have led to a heated debate regarding its effectiveness. Consequently, non-pharmacological therapies, such as preoperative education, have emerged as an alternative approach to alleviate anxiety. WeChat, a widely popular social media platform, offers a public platform that can potentially be utilized for effective preoperative education. This study aims to evaluate the use of WeChat public platform as a tool for preoperative education in patients undergoing breast surgery. METHODS: This is a prospective, randomized, and controlled trial will involve 392 adult women scheduled for breast cancer resection. Participants will be randomly assigned to either the WeChat education group or the regular group. In addition to regular preoperative visits, the WeChat education group will also watch science videos through the WeChat public platform. The regular group will only receive education from ward nurses during preoperative visits. The primary outcome measure will be the incidence of preoperative anxiety, defined by scores of the State Anxiety Inventory (SAI) exceeding 40 points. Secondary outcome measures include the incidence of severe anxiety (SAI > 44) on the day before surgery, incidence of anxiety 72 h after surgery, incidence of severe anxiety 72 h after surgery, NRS scores for pain at rest and during activity 24, 48, and 72 h after surgery, incidence of nausea and vomiting within 24 h after surgery, subjective sleep score at 1 week postoperatively, quality of life QoR-15 scores at 1 and 3 months postoperatively, incidence of chronic pain at 3 months postoperatively, bowel function recovery, length of hospital stay, and hospitalization expenses. DISCUSSION: This is the first clinical trial to investigate the use of WeChat public platform for delivering preoperative education on perioperative anxiety in breast cancer patients. By utilizing the renowned WeChat public platform, our study aims to improve patient outcomes by providing video education that explains the disease, surgery, and anesthesia in a more accessible manner, thereby reducing the incidence of perioperative anxiety. If our hypothesis is confirmed, this non-pharmacological approach can be universally acknowledged as a cost-effective and practical method in clinical care. Its application can also be extended to other medical fields beyond breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05291494. Registered on 29 December 2021.

Emission of CO2 and its related carbonate system dynamics in a hotspot area during winter and summer: The Changjiang River estuary.

The carbonate chemistry in river-dominated marginal seas is highly heterogeneous, and there is ongoing debate regarding the definition of atmospheric CO2 source or sink. On this basis, we investigated the carbonate chemistry and air-sea CO2 fluxes in a hotspot estuarine area: the Changjiang Estuary during winter and summer. The spatial characteristics of the carbonate system were influenced by water mixing of three end-members in winter, including the Changjiang freshwater with low total alkalinity (TA) concentration, the less saline Yellow Sea Surface Water with high TA, and the saline East China Sea (ECS) offshore water with moderate TA. While in summer with increased river discharge, the carbonate system was regulated by simplified two end-member mixing between the Changjiang freshwater and the ECS offshore water. By performing the end-member mixing model on DIC variations in the river plume region, significant biological addition of DIC was found in winter with an estimation of -120 ± 113 µmol kg-1 caused by wintertime organic matter remineralization from terrestrial source. While this biological addition of DIC shifted to DIC removal due to biological production in summer supported by the increased nutrient loading from Changjiang River. The pCO2 dynamics in the river plume and the ECS offshore were both subjected to physical mixing of freshwater and seawater, whether in winter and summer. In the inner estuary without horizontal mixing, the pCO2 dynamics were mainly influenced by biological uptake in winter and temperature in summer. The inner estuary, the river plume, and the ECS offshore were sources of atmospheric CO2, with their contributions varying seasonally. The Changjiang runoff enhanced the inner estuary's role as a CO2 source in summer, while intensive biological uptake reduced the river plume's contribution.

Unveiling clinical applications of bacterial extracellular vesicles as natural nanomaterials in disease diagnosis and therapeutics.

Bacterial extracellular vesicles (BEVs) are naturally occurring bioactive membrane-bound nanoparticles released by both gram-negative and positive bacterial species, exhibiting a multifaceted role in mediating host-microbe interactions across various physiological conditions. Increasing evidence supports BEVs as essential mediators of intercellular exchange, influencing bacterial pathogenicity, disease mechanisms, and modulating the host immune response. However, the extent to which these BEV-mediated actions can be leveraged to predict disease onset, guide treatment strategies, and determine clinical outcomes remains uncertain, particularly in terms of their clinical translation potentials. This review briefly describes BEV biogenesis and their internalisation by recipient cells and summarises methods for isolation and characterization, essential for understanding their composition and cargo. Further, it discusses the potential of biofluid-associated BEVs as biomarkers for various diseases, spanning both cancer and non-cancerous conditions. Following this, we also outline the ongoing human clinical trials of using BEVs for vaccine development. In addition to disease diagnostics, this review explores the emerging research of using natural or engineered BEVs as smart nanomaterials for applications in anti-cancer therapy and bone regeneration. This discussion extends to key factors for unlocking the clinical potential of BEVs, such as standardization of BEVs isolation and characterisation, as well as other hurdles in translating these findings to the clinical setting. We propose that addressing these hurdles through collaborative research efforts and well-designed clinical trials holds the key to fully harnessing the clinical potential of BEVs. As this field advances, this review suggests that BEV-based nanomedicine has the potential to revolutionize disease management, paving the way for innovative diagnosis, therapeutics, and personalized medicine approaches. STATEMENT OF SIGNIFICANCE: Extracellular vesicles (EVs) from both host cells and bacteria serve as multifunctional biomaterials and are emerging in the fields of biomedicine, bioengineering, and biomaterials. However, most of the current studies focus on host-derived EVs, leaving a gap in comprehensive research on bacteria-derived EVs (BEVs). Although BEVs offer an attractive option as nanomaterials for drug delivery systems, their unique nanostructure and easy-to-modify functions make them a potential method for disease diagnosis and treatment as well as vaccine development. Our work among the pioneering studies investigating the potential of BEVs as natural nanobiomaterials, plays a crucial role in both understanding the development of diseases and therapeutic interventions.

Targeting epigenetic and post-translational modifications regulating pyroptosis for the treatment of inflammatory diseases.

Inflammatory diseases, including infectious diseases, diabetes-related diseases, arthritis-related diseases, neurological diseases, digestive diseases, and tumor, continue to threaten human health and impose a significant financial burden despite advancements in clinical treatment. Pyroptosis, a pro-inflammatory programmed cell death pathway, plays an important role in the regulation of inflammation. Moderate pyroptosis contributes to the activation of native immunity, whereas excessive pyroptosis is associated with the occurrence and progression of inflammation. Pyroptosis is complicated and tightly controlled by various factors. Accumulating evidence has confirmed that epigenetic modifications and post-translational modifications (PTMs) play vital roles in the regulation of pyroptosis. Epigenetic modifications, which include DNA methylation and histone modifications (such as methylation and acetylation), and post-translational modifications (such as ubiquitination, phosphorylation, and acetylation) precisely manipulate gene expression and protein functions at the transcriptional and post-translational levels, respectively. In this review, we summarize the major pathways of pyroptosis and focus on the regulatory roles and mechanisms of epigenetic and post-translational modifications of pyroptotic components. We also illustrate these within pyroptosis-associated inflammatory diseases. In addition, we discuss the effects of novel therapeutic strategies targeting epigenetic and post-translational modifications on pyroptosis, and provide prospective insight into the regulation of pyroptosis for the treatment of inflammatory diseases.

Metformin and statins reduce hepatocellular carcinoma risk in chronic hepatitis C patients with failed antiviral therapy.

Backgrounds and Aim: Chronic hepatitis C (CHC) patients who fail antiviral therapy have a high risk of developing hepatocellular carcinoma (HCC). We investigated the effects of metformin and statins, commonly used to treat diabetes mellitus (DM) and hyperlipidemia (HLP), on HCC risk in CHC patients who failed antiviral therapy. Methods: CHC patients with failed interferon-based therapy were enrolled in a large-scale multicenter cohort study in Taiwan (T-COACH). HCC occurrence 1.5 years after the end of antiviral therapy was identified by linking to the cancer registry databases from 2003 to 2019. After considering death and liver transplantation as competing risks, Gray's cumulative incidence and Cox sub-distribution hazards for HCC development were used. Results: Among the 2,779 CHC patients, 480 (17.3%) developed new-onset HCC and 238 (8.6%) died after antiviral therapy. Metformin non-users with DM had a 51% higher risk of liver cancer than patients without DM, while statin users with HLP had a 50% lower risk of liver cancer than patients without HLP. The 5-year cumulative incidence of HCC was 16.5% in metformin non-users, significantly higher in metformin non-users than in patients without DM (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Conversely, HLP statin users had a significantly lower HCC risk than patients without HLP (3.8% vs. 12.5%; aSHR=0.50; P<0.001). Notably, the unfavorable effect of non-metformin use on increased HCC risk was mainly observed among patients without cirrhosis but not in patients with cirrhosis. In contrast, a favorable effect of statins reduced the risk of HCC in both cirrhotic and non-cirrhotic patients. Conclusion: Metformin for DM and statins for HLP have chemopreventive effects on HCC risk in CHC patients who failed antiviral therapy. These findings emphasize the importance of personalized preventive strategies for managing patients with these clinical profiles.

Combined strategies for improving the heterologous expression of a novel xylanase from Fusarium oxysporum Fo47 in Pichia pastoris.

Xylanase, an enzyme capable of hydrolyzing non-starch polysaccharides found in grain structures like wheat, has been found to improve the organizational structure of dough and thus increase its volume. In our past work, one promising xylanase FXYL derived from Fusarium oxysporum Fo47 and first expressed 779.64 U/mL activity in P. pastoris. It has shown significant potential in improving the quality of whole wheat bread, making it become a candidate for development as a new flour improver. After optimization of expression elements and gene dose, the xylanase activity of FXYL strain carrying three-copies reached 4240.92 U/mL in P. pastoris. In addition, 12 factors associated with the three stages of protein expression pathway were co-expressed individually in order in three-copies strain, and the translation factor Pab1 co-expression increased FXYL activity to 8893.53 U/mL. Nevertheless, combining the most effective or synergistic factors from three stages did not exhibit better results than co-expressing them alone. To further evaluate the industrial potential, the xylanase activity and protein concentration reached 81184.51 U/mL and 11.8 g/L in a 5 L fed-batch fermenter. These engineering strategies improved the expression of xylanase FXYL by more than 104-fold, providing valuable insights for the cost-effective industrial application of FXYL in the baking field.

Genome-wide association studies identified OsTMF as a gene regulating rice seed germination under salt stress.

Introduction: Salt tolerance during seed germination is an important trait for direct seeding and low-cost rice production. Nevertheless, it is still not clear how seed germination under salt stress is regulated genetically. Methods: In this study, genome-wide association studies (GWAS) were performed to decipher the genetic basis of seed germination under salt stress using 541 rice varieties collected worldwide. Results and discussion: Three quantitative trait loci (QTLs) were identified including qGRG3-1 on chromosome 3, qGRG3-2 on chromosome 5, and qGRG4 on chromosome 4. Assessment of candidate genes in these loci for their responses to salt stress identified a TATA modulatory factor (OsTMF) in qGRG3-2. The expression of OsTMF was up-regulated in both roots and shoots after exposure to salt stress, and OsTMF knockout mutants exhibited delayed seed germination under salt stress. Haplotype analysis showed that rice varieties carrying OsTMF-Hap2 displayed elevated salt tolerance during seed germination. These results provide important knowledge and resources to improve rice seed germination under salt stress in the future.

Icodextrin-induced acute generalized exanthematous pustulosis in a patient with peritoneal dialysis.

Icodextrin has been widely prescribed for peritoneal dialysis (PD) patients with inadequate ultrafiltration, but icodextrin induced acute generalized exanthematous pustulosis (AGEP) has been not well recognized in clinical practice. We described a young-aged female with IgA nephropathy and end stage kidney disease under continuous automated peritoneal dialysis. She developed skin erythema with exfoliation over the groin 7th day after initiation of icodextrin based PD dialysate. Initially, her scaling skin lesion with pinhead-sized pustules affected the bilateral inguinal folds, and then it extended to general trunk accompanied by pruritus. She was admitted because of deterioration of skin lesion on 14th day of icodextrin exposure. She was afebrile and physical examination was notable for widespread erythematous papules with pruritus extending over her groins and trunk. Pertinent laboratory examination showed leukocytosis of 18 970 cells/µL with neutrophile count of 17 642 cells/µL (92.3%), and c-reactive-protein: 3.39 mg/dL. Skin biopsy revealed multifocal sub corneal abscess with papillary dermal edema, and upper-dermal neutrophilia with perivascular accentuation, consistent with the diagnosis of AGEP. After discontinuation of PD, she underwent temporary high-flux haemodialysis with treatment of steroid and antihistamine. Her dermatologic lesion resolved without any skin sequalae completely within 4 days, and she underwent icodextrin-free peritoneal dialysis at 17th day. This case highlighted the fact that icodextrin-induced AGEP should be early recognized to avoid inappropriate management.

[Transcriptome data mining combined with clinical and animal experiments for identification of syndrome element marker genes during entire course of steroid-induced osteonecrosis of femoral head].

A research strategy combining transcriptome data mining and experimental verification was adopted to identify the marker genes characterizing the syndrome elements of phlegm, stasis, and deficiency in steroid-induced osteonecrosis of the femoral head(SONFH). Firstly, the common differentially expressed gene sets of SONFH with the syndromes of phlegm-stasis obstructing collaterals, vessel obstruction, and liver-kidney deficiency were obtained from the clinical transcriptomic analysis of a previous study. The differential expression trend analysis and functional gene mining were then employed to predict the candidate marker gene sets representing phlegm, stasis, and deficiency. The whole blood samples from SONFH patients, whole blood samples from SONFH rats, and affected femoral head tissue samples were collected for qPCR, which aimed to determine the expression levels of the candidate marker genes mentioned above. Furthermore, the receiver operating characteristic curve(ROC) was established to objectively evaluate the syndrome differentiation effectiveness of the candidate marker genes mentioned above. The transcriptome data analysis results showed that the candidate marker genes for phlegm was ELOVL fatty acid elongase 6(ELOVL6), and those for stasis were ankyrin 1(ANK1), glycophorin A/B(GYPA/B), and Rh-associated glycoprotein(RHAG). The candidate marker genes for deficiency were solute carrier family 2 member 1(SLC2A1) and stomatin(STOM). The qPCR results showed that compared with that in the non-SONFH group, ELOVL6 had the lowest expression level in the peripheral blood of the SONFH patients with the syndrome of phlegm-stasis obstructing collaterals(P<0.05). Compared with that in the normal control group, ELOVL6 had the lowest expression level in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 4 weeks(P<0.01), and it showed better syndrome differentiation effectiveness of rats modeled for 4 weeks(AUC=0.850, P=0.006) than at other modeling time points(8, 12, 16, and 21 weeks, AUC of 0.689, 0.766, 0.588, and 0.662, respectively). Compared with that in the non-SONFH group, the expression levels of ANK1, GYPA, and RHAG were the lowest in the peripheral blood of SONFH patients with the vessel obstruction syndrome(P<0.05). The expression levels of the three genes were the lowest in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 12 weeks(P<0.05, P<0.01), and their syndrome differentiation effectiveness in the rats modeled for 12 weeks(GYPA: AUC=0.861, P=0.012; ANK1: AUC=0.855, P=0.006; RHAG: AUC=0.854, P=0.009) was superior to that for 4, 8, 16, and 21 weeks(GYPA: AUC=0.646, 0.573, 0.691, and 0.617, respectively; ANK: AUC1=0.630, 0.658, 0.657, and 0.585, respectively; RHAG: AUC=0.592, 0.511, 0.515, and 0.536, respectively). Compared with the non-SONFH group, both SLC2A1 and STOM had the lowest expression levels in the peripheral blood of patients with the syndrome of liver and kidney deficiency(P<0.05). Compared with the normal control group, their expression levels were the lowest in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 21 weeks(P<0.05, except STOM in the peripheral blood of rats). Moreover, the syndrome differentiation effectiveness of SLC2A1 in the rats modeled for 21 weeks(AUC=0.806, P=0.009) was superior to that for 4, 8, 12, and 16 weeks(AUC=0.520, 0.580, 0.741, 0.774, respectively), and STOM was meaningless in syndrome differentiation. In summary, the candidate marker gene for phlegm in SONFH is ELOVL6; the candidate marker genes for stasis are GYPA, RHAG, and ANK1; the candidate marker gene for deficiency is SLC2A1. The results help to reveal the biological connotations of phlegm, stasis, and deficiency in SONFH at the genetic level.