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BACKGROUND: Mothers play a crucial role in influencing their daughters' HPV vaccination decisions. Addressing barriers to receiving HPV vaccination among mothers of girls may achieve two goals in one strike: increasing vaccination coverage among both mothers and their daughters. This study aims to examine the HPV vaccination uptake and its determinants among mothers of girls in China at both the individual and interpersonal levels. METHODS: From July to October 2023, a cross-sectional online study was conducted to investigate HPV vaccine refusal for daughters aged 9-17 years among 11,678 mothers in Shenzhen, China. A randomized selection method was employed, targeting 11 primary schools and 13 secondary schools in Shenzhen. The research team invited mothers of girls to participate in an anonymous online survey. Multilevel logistic regression models (level 1: schools; level 2: individual participants) were employed to analyze the data. RESULTS: Among 11,678 mothers, 41.1% self-reported receiving at least one dose of HPV vaccination. Through multilevel logistic regression analysis, eight items measuring illness representations of HPV, which refers to how people think about HPV, were associated with higher HPV vaccination uptake (AOR: 1.02-1.14). These items included identity (identifying symptoms of HPV), timeline (whether HPV is acute/chronic), negative consequences, personal and treatment control (whether HPV is under volitional control), concern, negative emotions, and coherence (overall understanding of HPV). In addition, participants refusing HPV vaccines for the index daughters (AOR: 0.82, 95%CI: 0.76, 0.89) had lower vaccine uptake. Perceived more difficulties in accessing the 9-valent vaccines (AOR: 1.06, 95%CI: 1.04, 1.08) and more satisfaction with vaccine-related promotional materials (AOR: 1.50, 95%CI: 1.46, 1.54) at the individual level were associated with higher vaccine uptake. At the interpersonal factors, higher frequency of exposure to testimonials given by others about HPV vaccination on social media (AOR: 1.19, 95%CI: 1.14, 1.25) and thoughtful consideration of the veracity of the information (AOR: 1.11, 95%CI: 1.07, 1.16) were correlated with higher HPV vaccination uptake. CONCLUSIONS: These findings offer essential implications for modifying HPV disease perceptions, addressing difficulties in accessing the 9-valent HPV vaccines, and enhancing health communication needs to improve HPV vaccine uptake among mothers of girls.
Subject(s)
Mothers , Papillomavirus Infections , Papillomavirus Vaccines , Social Media , Humans , Cross-Sectional Studies , Female , Adolescent , China , Papillomavirus Vaccines/administration & dosage , Papillomavirus Infections/prevention & control , Child , Mothers/psychology , Adult , Vaccination/psychology , Health Knowledge, Attitudes, Practice , Nuclear Family , Patient Acceptance of Health Care , Middle Aged , Surveys and QuestionnairesABSTRACT
Pharyngitis can be caused by various pathogens, including viruses and bacteria. Group A streptococcus (GAS) is the most common bacterial cause of pharyngitis. However, distinguishing GAS pharyngitis from other types of upper respiratory tract infections is challenging in clinical settings. This often leads to empirical treatments and, consequently, the overuse of antimicrobial drugs. With the advancement of antimicrobial drug management and healthcare payment reform initiatives in China, reducing unnecessary testing and prescriptions of antimicrobial drugs is imperative. To promote standardized diagnosis and treatment of GAS pharyngitis, this article reviews various international guidelines on the clinical diagnosis and differential diagnosis of GAS pharyngitis, particularly focusing on clinical scoring systems guiding laboratory testing and antimicrobial treatment decisions for GAS pharyngitis and their application recommendations, providing a reference for domestic researchers and clinical practitioners.
Subject(s)
Pharyngitis , Streptococcal Infections , Streptococcus pyogenes , Humans , Pharyngitis/microbiology , Pharyngitis/drug therapy , Pharyngitis/diagnosis , Streptococcal Infections/diagnosis , Streptococcal Infections/drug therapyABSTRACT
Robotic pyelolithotomy continues to gain attention as an alternative to percutaneous nephrolithotomy (PCNL) for managing complex renal stones. We performed a single-arm meta-analysis and systematically searched the English-language literature published in PubMed, Web of Science, Scopus, and Google Scholar databases up to June 2024. The risk of non-randomized bias was assessed using ROBINS-I, and the quality of the literature was assessed using MINORS (Methodological Index for Non-Randomized Studies). Merger parameters were calculated using Stata16/SE under a random-effects model. Five non-comparative single-arm studies were included in the meta-analysis. Results showed that the operative time for robotic pyelolithotomy was 168.10 min (95% CI 133.63, 202.56). The hospital stay was 2.63 days (95% CI 0.96, 4.29), and blood loss was 44.13 ml (95% CI 19.76, 68.51). The stone clearance rate was 87% (95% CI 79-93%). The incidence of minor postoperative complications (Clavien grade I-II) was 23.7% (95% CI 13.4-35.8%), and the incidence of major complications (Clavien grade ≥ III) was 7% (95% CI 0.3-20.7%).The safety and efficacy of robotic pyelolithotomy in treating complex renal stones are acceptable, but future large prospective cohort studies are needed to validate the treatment.
Subject(s)
Kidney Calculi , Operative Time , Robotic Surgical Procedures , Humans , Kidney Calculi/surgery , Robotic Surgical Procedures/methods , Robotic Surgical Procedures/adverse effects , Treatment Outcome , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Nephrolithotomy, Percutaneous/methods , Nephrolithotomy, Percutaneous/adverse effects , Length of Stay/statistics & numerical data , Kidney Pelvis/surgery , Blood Loss, Surgical/statistics & numerical data , Female , MaleABSTRACT
BACKGROUND: Although immune checkpoint inhibitors (ICIs) have revolutionized the landscape of cancer treatment, only a minority of colorectal cancer (CRC) patients respond to them. Enhancing tumor immunogenicity by increasing major histocompatibility complex I (MHC-I) surface expression is a promising strategy to boost the antitumor efficacy of ICIs. METHODS: Dual luciferase reporter assays were performed to find drug candidates that can increase MHC-I expression. The effect of nilotinib on MHC-I expression was verified by dual luciferase reporter assays, qRT-PCR, flow cytometry and western blotting. The biological functions of nilotinib were evaluated through a series of in vitro and in vivo experiments. Using RNA-seq analysis, immunofluorescence assays, western blotting, flow cytometry, rescue experiments and microarray chip assays, the underlying molecular mechanisms were investigated. RESULTS: Nilotinib induces MHC-I expression in CRC cells, enhances CD8+ T-cell cytotoxicity and subsequently enhances the antitumor effects of anti-PDL1 in both microsatellite instability and microsatellite stable models. Mechanistically, nilotinib promotes MHC-I mRNA expression via the cGAS-STING-NF-κB pathway and reduces MHC-I degradation by suppressing PCSK9 expression in CRC cells. PCSK9 may serve as a potential therapeutic target for CRC, with nilotinib potentially targeting PCSK9 to exert anti-CRC effects. CONCLUSION: This study reveals a previously unknown role of nilotinib in antitumor immunity by inducing MHC-I expression in CRC cells. Our findings suggest that combining nilotinib with anti-PDL1 therapy may be an effective strategy for the treatment of CRC.
Subject(s)
Colorectal Neoplasms , Pyrimidines , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Colorectal Neoplasms/immunology , Colorectal Neoplasms/metabolism , Humans , Pyrimidines/pharmacology , Pyrimidines/therapeutic use , Animals , Cell Line, Tumor , Gene Expression Regulation, Neoplastic/drug effects , B7-H1 Antigen/metabolism , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/drug effects , Histocompatibility Antigens Class I/metabolism , Histocompatibility Antigens Class I/genetics , Mice , Microsatellite Instability/drug effects , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , Signal Transduction/drug effectsABSTRACT
Epidermal growth factor receptor (EGFR) mutation status is pivotal in predicting the efficacy of tyrosine kinase inhibitor treatments against tumors. Among EGFR mutations, the E746-A750 deletion is particularly common and accurately quantifying it can guide targeted therapies. This study introduces a novel visual sensing technology using the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12a system guided by ligation-initiated loop-mediated isothermal amplification (LAMP) to detect the del E746-A750 mutation in EGFR. Conventional LAMP primers were simplified by designing a pair of target-specific stem-loop DNA probes, enabling selective amplification of the target DNA. The CRISPR/Cas12a system was employed to identify the target nucleic acid and activate Cas12a trans-cleavage activity, thereby enhancing the specificity of the assay. Furthermore, the biosensor utilized high-performance nanomaterials such as triangular gold nanoparticles and graphdiyne, known for their large specific surface area, to enhance sensitivity effectively as a sensing platform. The proposed biosensor demonstrated outstanding specificity, achieving a low detection limit of 17 fM (S/N = 3). Consequently, this innovative strategy not only expands the application scope of CRISPR/Cas12a technology but also introduces a promising approach for clinical diagnostics in modern medicine.
Subject(s)
Biosensing Techniques , CRISPR-Cas Systems , ErbB Receptors , Nucleic Acid Amplification Techniques , Biosensing Techniques/methods , CRISPR-Cas Systems/genetics , Nucleic Acid Amplification Techniques/methods , Humans , ErbB Receptors/genetics , Electrochemical Techniques/methods , Limit of Detection , Gold/chemistry , Metal Nanoparticles/chemistry , Sequence Deletion , Bacterial Proteins , Endodeoxyribonucleases , Molecular Diagnostic Techniques , CRISPR-Associated ProteinsABSTRACT
Background: China started to implement the HPV vaccination program for females in 2016. This study investigated associations between mothers' decisional conflicts, satisfaction with governmental health promotion materials, and their daughters' HPV vaccination uptake. Methods: A cross-sectional online survey was conducted between July and October 2023 among mothers of girls aged 9-17 years in Shenzhen, China. Participants were mothers having a daughter aged 9-17 years at the survey date and a smartphone with internet access. About 3 % of all primary and secondary schools in Shenzhen were randomly selected by the research team (11 primary schools and 13 secondary schools). Teachers at the selected schools invited mothers of female students aged 9-17 years to complete an anonymous online questionnaire. Multivariate logistic regression was fitted. Results: Among 11,728 mothers who completed the survey, 18.9% of their index daughters received at least one dose of HPV vaccination. In multivariate analysis, less decisional conflict about the choice of HPV vaccines for their daughters (AOR: 1.07, 95%CI: 1.05, 1.10), more satisfaction with the government's health promotional materials related to HPV vaccines (AOR: 1.15, 95%CI: 1.12, 1.19), receiving more cue to action from significant others (AOR: 1.23, 95%CI: 1.19, 1.27), and perceived higher self-efficacy related to HPV vaccines (AOR: 1.79, 95%CI: 1.67, 1.92) were associated with a higher uptake of HPV vaccines. Perceived susceptibility to HPV (AOR: 0.79, 95%CI: 0.74, 0.85), perceived barriers to having the index daughter receive HPV vaccines (AOR: 0.82, 95%CI: 0.80, 0.84), and mothers who were hesitant to receive HPV vaccination (AOR: 0.75, 95%CI: 0.68, 0.84) were associated with a lower uptake. Conclusion: HPV vaccination uptake was low among girls in China. Future health promotion should address mothers' decisional conflicts about the choice of HPV vaccines for their daughters and improve the health promotional materials. School-based HPV vaccination programs might be useful.
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Background: Acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) carries a high mortality risk. Inflammation and nutrition are involved in the pathogenesis and prognosis of both AMI and CS. The advanced lung cancer inflammation index ratio (ALI) combines the inflammatory and nutritional status. Our present study aimed to explore the prognostic value of ALI in patients with CS following AMI. Methods: In total, 217 consecutive patients with AMI complicated by CS were divided into two groups based on the ALI admissions cut-off: ≤ 12.69 and > 12.69. The primary endpoint of this study was 30-day all-cause mortality. The secondary endpoints were gastrointestinal hemorrhage and major adverse cardiovascular events (MACEs), including 30-day all-cause mortality, atrioventricular block, ventricular tachycardia/ventricular fibrillation, and nonfatal stroke. The association of ALI with the study endpoints was analyzed by Cox regression analysis. Results: During the 30-day follow-up period after admission, 104 (47.9%) patients died and 150 (69.1%) suffered MACEs. The Kaplan-Meier analysis revealed significantly higher cumulative mortality and lower MACE rates in the low-ALI group compared to the high-ALI group (both log-rank p < 0.001). The 30-day mortality rate was significantly higher in patients with ALI ≤ 12.69 compared to ALI > 12.69 (72.1% vs. 22.6%; p < 0.001). Furthermore, the incidence of MACEs was higher in patients with ALI ≤ 12.69 (85.6% vs. 51.9%; p < 0.001). The receiver operating curve showed that ALI had a modest predictive value (area under the curve [AUC]: 0.789, 95% confidence interval [CI]: 0.729, 0.850). After multivariable adjustment, ALI ≤ 12.69 was an independent predictor for both 30-day all-cause mortality (hazard ratio [HR]: 3.327; 95% CI: 2.053, 5.389; p < 0.001) and 30-day MACEs (HR: 2.250; 95% CI 1.553, 3.260; p < 0.001). Furthermore, the addition of ALI to a base model containing clinical and laboratory data statistically improved the predictive value. Conclusions: Assessing ALI levels upon admission can provide important information for the short-term prognostic assessment of patients with AMI complicated by CS. A lower ALI may serve as an independent predictor of increased 30-day all-cause mortality and MACEs.
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OBJECTIVE: To compare the efficacy and safety of different asparaginase formulations in the treatment of acute lymphoblastic leukemia (ALL) based on nano-magnetic bead immunoassay. METHODS: Retrospective analysis of adult ALL patients' clinical data who admitted to The Affiliated Hospital of Changsha Health Vocational College from August 2020 to August 2023. Finally, 65 adult ALL patients were included in this study, including the polyethylene glycol conjugated asparaginase (PEG-ASNase) group (n = 32) and the L-asparaginase (L-ASNase) group (n = 33). Enzyme-linked immunosorbent assay (ELISA) based on magnetic nanoparticles was used to determine the activity of ASNase in both groups. The levels of asparagine or glutamine in two groups were detected by automatic biochemical analyzer during induction therapy, and the adverse events of the two groups were observed during the treatment. RESULTS: PEG-ASNase demonstrated a slower decrease in enzyme activity, longer action duration, and higher safety profile compared to L-ASNase. PEG-ASNase group and L-ASNase group demonstrated a similar complete remission rate (71.88% vs. 60.61%). Event-free survival was higher in patients receiving PEG-ASNase than those receiving L-ASNase (42.4% and 18.7%). The observed adverse reactions included allergic reactions, pancreatic lesions, gastrointestinal reactions and liver function damage. The incidence of gastrointestinal reactions and liver function damage was higher in the L-ASNase group than that in PEG-ASNase group (45.45% and 33.33%). CONCLUSION: This study provides valuable insights into the asparaginase treatments in clinical, highlighting the importance of PEG-ASNase for improving treatment protocols in adult ALL patients.
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Abrupt dietary change can disrupt the intestinal balance in felines. This study aimed to assess the impact of heat-treated Bifidobacterium longum CECT-7384 combined with Fibersol-2 on the intestinal health of adult cats before and after dietary change. We selected 24 British shorthair cats, dividing them into two groups. From day 1 to day 14, the control group received a lower protein (33%) concentration (LPF) diet, while the treated group received the same LPF diet supplemented with 0.16% functional additives, consisting of Bifidobacterium longum CECT-7384 combined with Fibersol-2. Subsequently, from day 15 to day 28, the control group transitioned to a higher protein (40%) concentration (HPF) diet, while the treated group received the same HPF diet supplemented with 0.16% functional additives. Blood and fresh feces were collected on day 0, 14, 17, 21, and 28 of the experiment. The results suggest that the use of heat-treated Bifidobacterium longum CECT-7384 combined with Fibersol-2 may improve gastrointestinal function in cats by reducing serum LPS levels and fecal pH, while increasing fecal sIgA levels. In addition, the functional additive regulates the fecal microbiota and its function, promoting intestinal homeostasis and colonization with beneficial bacteria such as Blautia. Furthermore, on day 28, there was a significant difference in fecal microbiota beta diversity between the two groups. In summary, the addition of heat-treated Bifidobacterium longum CECT-7384 combined with Fibersol-2 contributes to improving the intestinal health of adult cats affected by abrupt dietary change.
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Hydrogel devices with mechanical toughness and tunable functionalities are highly desirable for practical long-term applications such as sensing and actuation elements for soft robotics. However, existing hydrogels have poor mechanical properties, slow rates of response, and low functionality. In this work, two-dimensional hydrogel actuators are proposed and formed on the self-assembly of graphene oxide (GO) and deoxynucleic acid (DNA). The self-assembly process is driven by the GO-induced transition of double stranded DNA (dsDNA) into single stranded DNA (ssDNA). Thus, the hydrogel's structural unit consists of two layers of GO covered by ssDNA and a layer of dsDNA in between. Such heterogeneous architectures stabilized by multiple hydrogen bondings have Young's modulus of up to 10 GPa and rapid swelling rates of 4.0 × 10-3 to 1.1 × 10-2 s-1, which surpasses most types of conventional hydrogels. It is demonstrated that the GO/DNA hydrogel actuators leverage the unique properties of these two materials, making them excellent candidates for various applications requiring sensing and actuation functions, such as artificial skin, wearable electronics, bioelectronics, and drug delivery systems.
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The objective of this study was to perform a comprehensive pooled analysis aimed at comparing the efficacy and safety of percutaneous ablation (PCA) versus minimally invasive partial nephrectomy (MIPN), including robotic and laparoscopic approaches, in patients diagnosed with cT1 renal tumors. We conducted a comprehensive search across four major electronic databases: PubMed, Embase, Web of Science, and the Cochrane Library, targeting studies published in English up to April 2024. The primary outcomes evaluated in this analysis included perioperative outcomes, functional outcomes, and oncological outcomes. A total of 2449 patients across 17 studies were included in the analysis. PCA demonstrated superior outcomes compared to MIPN in terms of shorter hospital stays (WMD: - 2.13 days; 95% Confidence Interval [CI]: - 3.29, - 0.97; p = 0.0003), reduced operative times (WMD: - 109.99 min; 95% CI: - 141.40, - 78.59; p < 0.00001), and lower overall complication rates (OR: 0.54; 95% CI: 0.40, 0.74; p = 0.0001). However, PCA was associated with a higher rate of local recurrence when compared to MIPN (OR: 3.81; 95% CI: 2.45, 5.92; p < 0.00001). Additionally, no significant differences were observed in major complications, estimated glomerular filtration rate decline, creatinine variation, overall survival, recurrence-free survival, and disease-free survival between the two treatment modalities. PCA presents a notable disadvantage regarding local recurrence rates in comparison to MIPN. However, PCA offers several advantages over MIPN, including shorter durations of hospital stay, reduced operative times, and lower complication rates, while achieving similar outcomes in other oncologic metrics.
Subject(s)
Kidney Neoplasms , Nephrectomy , Robotic Surgical Procedures , Humans , Nephrectomy/methods , Kidney Neoplasms/surgery , Kidney Neoplasms/pathology , Treatment Outcome , Robotic Surgical Procedures/methods , Robotic Surgical Procedures/adverse effects , Length of Stay/statistics & numerical data , Minimally Invasive Surgical Procedures/methods , Operative Time , Laparoscopy/methods , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Neoplasm Staging , Neoplasm Recurrence, LocalABSTRACT
Bladder cancer (BC) is the tenth most common cancer globally, predominantly affecting men. Early detection and treatment are crucial due to high recurrence rates and poor prognosis for advanced stages. Traditional diagnostic methods like cystoscopy and imaging have limitations, leading to the exploration of noninvasive methods such as liquid biopsy. This review highlights the application of biosensors in BC, including electrochemical and optical sensors for detecting tumor markers like proteins, nucleic acids, and other biomolecules, noting their clinical relevance. Emerging therapeutic approaches, such as antibody-drug conjugates, targeted therapy, immunotherapy, and gene therapy, are also explored, the role of biosensors in detecting corresponding biomarkers to guide these treatments is examined. Finally, the review addresses the current challenges and future directions for biosensor applications in BC, highlighting the need for large-scale clinical trials and the integration of advanced technologies like deep learning to enhance diagnostic accuracy and treatment efficacy.
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BACKGROUND AND AIM: Clinical evidence for early identification and diagnosis of liver cirrhosis (LC) caused by different types of liver disease is limited. We investigated this topic through a meta-analysis of quantitative metabolomics. METHODS: Four databases were searched until October 31, 2022 for studies comparing metabolite levels between patients with different types of liver disease and control individuals. A random-effects model was applied for the meta-analysis. RESULTS: This study included 55 studies with 8266 clinical participants, covering 348 metabolites. In LC related to drug-induced liver injury (DILI), hepatitis B virus (HBV) infection, and non-alcoholic fatty liver disease (NAFLD), the primary bile acid biosynthesis (taurocholic acid: SMD, 1.08[0.81, 1.35]; P < 0.00001; glycocholic acid: SMD, 1.35[1.07, 1.62]; P < 0.00001; taurochenodeoxycholic acid: SMD, 1.36[0.94, 1.78]; P < 0.00001; glycochenodeoxycholic acid: SMD, 1.49[0.93, 2.06]; P < 0.00001), proline and arginine (l-proline: SMD, 1.06[0.53, 1.58]; P < 0.0001; hydroxyproline: SMD, 0.81[0.30, 1.33]; P = 0.002), and fatty acid biosynthesis (palmitic acid: SMD, 0.44[0.21, 0.67]; P = 0.0002; oleic acid: SMD, 0.46[0.19, 0.73]; P = 0.0008; stearic acid: SMD, 0.37[0.07, 0.68]; P = 0.02) metabolic pathways were significantly altered. CONCLUSION: We identified key biomarkers and metabolic characteristics for distinguishing and identifying LC related to different types of liver disease, providing a new perspective for early diagnosis, disease monitoring, and precise treatment.
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Objective:To investigate the changes in hearing threshold of the acquired primary cholesteatoma of the middle ear with different degrees of eustachian tube dysfunction after balloon eustachian tuboplasty. Methods:This retrospective study included forty cases with middle ear cholesteatoma and eustachian tube dysfunction who underwent open mastoidectomy + tympanoplasty + balloon eustachian tuboplasty were enrolled. All patients were admitted from November 2020 to April 2022. The preoperative eustachian tube score of 0-2 were defined as the lower group, and the scores of 3-5 were defined as the higher group. Pure tone audiometry was measured preoperatively and 1, 3, 6 and 12 months postoperatively. The average value of bone conduction threshold and air conduction threshold of 250-4 000 Hz were calculated, and the air-bone gap was calculated simultaneously. SPSS 25.0 was used for statistical analysis. P<0.05 was considered statistically significant. Results:In the lower group, the air conduction threshold and air-bone gap at 3 months postoperatively were significantly decreased in comparison with those preoperativelyï¼P<0.05ï¼ï¼as was the air-bone gap at 6 months postoperativelyï¼P<0.05ï¼. In the higher group, the air conduction threshold and air-bone gap were significantly decreased at 3, 6 and 12 months postoperativelyï¼P<0.05ï¼. Conclusion:The air conduction threshold and air-bone gap of patients with the acquired primary cholesteatoma of the middle ear and eustachian tube dysfunction were significantly decreased after eustachian tube balloon dilatation. Hearing improvement lasted longer in patients with slight eustachian tube dysfunction.
Subject(s)
Audiometry, Pure-Tone , Cholesteatoma, Middle Ear , Eustachian Tube , Tympanoplasty , Humans , Eustachian Tube/physiopathology , Eustachian Tube/surgery , Retrospective Studies , Female , Cholesteatoma, Middle Ear/surgery , Male , Tympanoplasty/methods , Adult , Middle Aged , Auditory Threshold , Mastoidectomy/methods , Bone ConductionABSTRACT
Parkinson's Disease (PD) is the second most common neurodegenerative disorder. Mutations in leucine-rich repeat kinase 2 (LRRK2), a multi-domain protein containing both a kinase and a GTPase, are a leading cause of the familial form of PD. Pathogenic LRRK2 mutations increase LRRK2 kinase activity. While the bulk of LRRK2 is found in the cytosol, the protein associates with membranes where its Rab GTPase substrates are found, and under certain conditions, with microtubules. Integrative structural studies using single-particle cryo-electron microscopy (cryo-EM) and in situ cryo-electron tomography (cryo-ET) have revealed the architecture of microtubule-associated LRRK2 filaments, and that formation of these filaments requires LRRK2's kinase to be in the active-like conformation. However, whether LRRK2 can interact with and form filaments on microtubules in its autoinhibited state, where the kinase domain is in the inactive conformation and the N-terminal LRR domain covers the kinase active site, was not known. Using cryo-ET, we show that full-length LRRK2 can oligomerize on microtubules in its autoinhibited state. Both WT-LRRK2 and PD-linked LRRK2 mutants formed filaments on microtubules. While these filaments are stabilized by the same interfaces seen in the active-LRRK2 filaments, we observed a new interface involving the N-terminal repeats that were disordered in the active-LRRK2 filaments. The helical parameters of the autoinhibited-LRRK2 filaments are different from those reported for the active-LRRK2 filaments. Finally, the autoinhibited-LRRK2 filaments are shorter and less regular, suggesting they are less stable.
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BACKGROUND: Exercise therapy can effectively manage chronic kidney disease (CKD) risk factors and improve renal function and physical fitness, but the challenge lies in choosing the right exercise type tailored to patients' condition. METHODS: An electronic search of databases including PubMed, The Cochrane Library, EMBASE, Web of Science, VIP, WanFang, and CNKI was performed. The random effects model was used. Mean difference was employed as the effect size for continuous variables, with 95% confidence interval (CI) provided. RESULTS: A total of 36 RCTs were included in this study. Compared to conventional therapy (CT), the combination of three exercise therapies with CT resulted in notable benefits in enhancing six minutes walk test (6MWT) capacity, 24-h urinary protein quantity (24hUTP), systolic blood pressure (SBP), diastolic blood pressure (DBP). Resistance exercise therapy (RT) + CT were more effective than CT to reduce serum creatinine (Scr), body mass index (BMI), and hemoglobin A1c (HbA1c) and improve estimated glomerular filtration rate (eGFR). In terms of improving peak oxygen uptake (VO2 peak), only two exercise modalities were involved, aerobic exercise therapy (AT) and combined (Resistance-Aerobic) exercise therapy (CBT), both of which were more efficacious than CT. The efficacy ranking overall demonstrated clear benefits for RT in enhancing eGFR and 6MWT, decreasing Scr, BMI, SBP, DBP, and HbA1c, while AT was more suitable for boosting VO2 peak, and CBT had greater potential for reducing 24hUTP. CONSLUSIONS: Exercise therapy combined with CT offers significant advantages over CT in many cases, but no single exercise modality is universally effective for all indicators.
Subject(s)
Exercise Therapy , Glomerular Filtration Rate , Network Meta-Analysis , Renal Insufficiency, Chronic , Humans , Renal Insufficiency, Chronic/therapy , Renal Insufficiency, Chronic/physiopathology , Renal Insufficiency, Chronic/complications , Exercise Therapy/methods , Risk Factors , Blood Pressure , Randomized Controlled Trials as Topic , Creatinine/blood , Glycated Hemoglobin/analysis , Glycated Hemoglobin/metabolismABSTRACT
Ficus carica is an economically important horticultural plant. Due to its abundant secondary metabolites, F. carica has gained interest for its applications in medicine and as a nutritional supplement. Both external and internal factors affect the accumulation of secondary metabolites in F. carica. The assembly of the F. carica genome has facilitated functional analysis of key genes and transcription factors associated with the biosynthesis of secondary metabolites, particularly anthocyanin. In this review, we summarize the various types and functions of secondary metabolites, with a particular focus on flavonoids, coumarins, and terpenes. We also explore the factors influencing their biosynthesis and accumulation, including varieties, tissue, environmental factors (e.g., light), stresses (e.g., high temperature, low temperature, drought, nutrient deficiencies, salinity), hormonal treatments, and developmental factors. Furthermore, we discuss the involvement of structural genes and transcription factors in the biosynthesis of secondary metabolites, specifically anthocyanin and furanocoumarins, knowledge of which will promote the breeding and genetic engineering of novel F. carica varieties.
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Wood-decay macrofungi play a vital role in forest ecosystems by promoting nutrient cycling and soil structure, and their evolution is closely related to their host plants. This study investigates the potential evolutionary adaptation of wood-decay macrofungi to their host plants, focusing on whether these relationships differ between gymnosperms and angiosperms. While previous research has suggested non-random associations between specific fungi and plant deadwood, direct evidence of evolutionary adaptation has been lacking. Our study, conducted in a subtropical region, utilized metabarcoding techniques to identify deadwood species and associated fungi. We found significant evidence of evolutionary adaptation when considering all sampled species collectively. However, distinct patterns emerged when comparing angiosperms and gymnosperms: a significant evolutionary adaptation was observed of wood-decay macrofungi to angiosperms, but not to gymnosperms. This variation may be due to the longer evolutionary history and more stable species interactions of gymnosperms, as indicated by a higher modularity coefficient (r = .452), suggesting greater specialization. In contrast, angiosperms, being evolutionarily younger, displayed less stable and more coevolving interactions with fungi, reflected in a lower modularity coefficient (r = .387). Our findings provide the first direct evidence of differential evolutionary adaptation dynamics of these fungi to angiosperms versus gymnosperms, enhancing our understanding of forest ecosystem carbon cycling and resource management.
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Electronic waste (e-waste) and diabetes are global challenges to modern societies. However, solving these two challenges together has been challenging until now. Herein, we propose a laser-induced transfer method to fabricate portable glucose sensors by recycling copper from e-waste. We bring up a laser-induced full-automatic fabrication method for synthesizing continuous heterogeneous CuxO (h-CuxO) nano-skeletons electrode for glucose sensing, offering rapid (< 1 min), clean, air-compatible, and continuous fabrication, applicable to a wide range of Cu-containing substrates. Leveraging this approach, h-CuxO nano-skeletons, with an inner core predominantly composed of Cu2O with lower oxygen content, juxtaposed with an outer layer rich in amorphous CuxO (a-CuxO) with higher oxygen content, are derived from discarded printed circuit boards. When employed in glucose detection, the h-CuxO nano-skeletons undergo a structural evolution process, transitioning into rigid Cu2O@CuO nano-skeletons prompted by electrochemical activation. This transformation yields exceptional glucose-sensing performance (sensitivity: 9.893 mA mM-1 cm-2; detection limit: 0.34 µM), outperforming most previously reported glucose sensors. Density functional theory analysis elucidates that the heterogeneous structure facilitates gluconolactone desorption. This glucose detection device has also been downsized to optimize its scalability and portability for convenient integration into people's everyday lives.