A small molecule compound targeting hemagglutinin inhibits influenza A virus and exhibits broad-spectrum antiviral activity.

Influenza A virus (IAV) is a widespread pathogen that poses a significant threat to human health, causing pandemics with high mortality and pathogenicity. Given the emergence of increasingly drug-resistant strains of IAV, currently available antiviral drugs have been reported to be inadequate to meet clinical demands. Therefore, continuous exploration of safe, effective and broad-spectrum antiviral medications is urgently required. Here, we found that the small molecule compound J1 exhibited low toxicity both in vitro and in vivo. Moreover, J1 exhibits broad-spectrum antiviral activity against enveloped viruses, including IAV, respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human coronavirus OC43 (HCoV-OC43), herpes simplex virus type 1 (HSV-1) and HSV-2. In this study, we explored the inhibitory effects and mechanism of action of J1 on IAV in vivo and in vitro. The results showed that J1 inhibited infection by IAV strains, including H1N1, H7N9, H5N1 and H3N2, as well as by oseltamivir-resistant strains. Mechanistic studies have shown that J1 blocks IAV infection mainly through specific interactions with the influenza virus hemagglutinin HA2 subunit, thereby blocking membrane fusion. BALB/c mice were used to establish a model of acute lung injury (ALI) induced by IAV. Treatment with J1 increased survival rates and reduced viral titers, lung index and lung inflammatory damage in virus-infected mice. In conclusion, J1 possesses significant anti-IAV effects in vitro and in vivo, providing insights into the development of broad-spectrum antivirals against future pandemics.

Effect of electroacupuncture of "Zusanli" (ST36) combined with capeOX on apoptosis and ferroptosis in nude mice with colorectal cancer. / 电针"足三里"联合capeOXæ–¹æ¡ˆå¯¹ç»“ç›´è‚ ç™Œè£¸é¼ è‚¿ç˜¤ç»†èƒžå‡‹äº¡å’Œé“æ­»äº¡çš„å½±å“.

OBJECTIVES: To investigate the impact of combined treatment of colorectal cancer (CRC) with electroacupuncture (EA) and capeOX (combined administration of fluorouracil, oxaliplatin and capecitabine) on the tumor volume, weight, spleen coefficient, apoptosis and ferroptosis of tumor tissue, and liver and kidney functions in nude mice with CRC, so as to explore its mechanisms underlying inhibiting CRC and alleviating toxic reactions of capeOX. METHODS: Female Balb/c nude mice were randomly assigned to 3 groups：model, capeOX, and EA+capeOX, with 8 nude mice in each group. The CRC model was established by subcutaneous injection of colon cancer cells at the right inguinal region. Nude mice of the capeOX group received intraperitoneal injection of oxaliplatin for 1 day and gavage of capecitabine from day 2 to day 7. EA (1 mA, 2 Hz/100 Hz) was applied to bilateral "Zusanli" (ST36) for 20 min, once daily for 7 days. During the interven-tion, the tumor volume and weight were measured every day, and at the end of intervention, the weight of the tumor tissue and spleen were measured, with tumor volume difference and spleen coefficient calculated. The proportion of apoptotic cells was measured by flow cytometry, and the contents of serum malondialdehyde (MDA), alanine aninotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine (Cr) were detected using ELISA. The expression level of glutathione peroxidase 4 (GPX4, a key regulator for ferroptosis) protein of the tumor tissue was determined using Western blot. RESULTS: Compared to the model group, both the capeOX group and EA+capeOX group showed a decrease in the tumor volume (on day 3 and 4 in the capeOX group, and from day 2 to 7 in the EA+capeOX group) and body weight (P<0.05, on day 3 to 7 in the EA+capeOX group and on day 2 to 7 in the capeOX group), being evidently lower in the tumor volume on day 7 in the EA+capeOX than in the capeOX group (P<0.05), and evidently higher in the body weight on day 6 and 7 in the EA+capeOX group than in the capeOX group (P<0.05). In comparison with the model group, the tumor volume difference, tumor weight and spleen coefficient in both capeOX and EA+capeOX groups were significantly decreased (P<0.05), and MDA content in EA+capeOX group was significantly decreased (P<0.05), while the contents of ALT, BUN and Cr in the capeOX group, the proportion of apoptotic cells in both capeOX and EA+capeOX groups, and the GPX4 expression level in the EA+capeOX group were all significantly increased (P<0.05). The tumor volume difference, tumor weight, and contents of MDA, ALT, AST, BUN and Cr in the EA+capeOX group were markedly lower than in the capeOX group (P<0.05), while the spleen coefficient, proportion of apoptotic cells and GPX4 expression level in the EA+capeOX group were markedly higher than those in the capeOX group (P<0.05). CONCLUSIONS: EA of ST36 can enhance the effect of capeOX in inhibiting colorectal cancer growth in nude mice with CRC, which may be related with its functions in promoting tumor cell apoptosis, inhibiting ferroptosis, and modulating immune tolerance. In addition, EA can lower the side effects of capeOX in hematopoietic and immune, liver, and kidney functions.

Examining the 2021 Cash Value Benefit Increase and WIC Participant Food Purchases.

INTRODUCTION: The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) provides nutritious foods to more than six million low-income families. In June 2021, WIC increased the amount of money provided for fruits and vegetables (FV), but studies have not investigated whether this increase changed WIC participant FV purchases. The objective was to estimate the association between the FV funding increase and WIC shopper FV purchases. METHODS: This evaluation uses longitudinal food transaction data from 496 stores in a grocery store chain in North Carolina between June 2020 and April 2022 and a propensity score weighted difference-in-differences (DID) approach to estimate the association between the FV funding increase and FV and other food group purchases. Analyses were conducted in 2023 and 2024. RESULTS: WIC shoppers' WIC-eligible FV purchases increased by $12.4 per shopper per month (Adjusted Confidence Interval (ACI), $12.0 to $12.9) after the FV benefit increase, which was $9.3 (ACI, $8.7 to $10.0) more than non-WIC shoppers. The monthly volume and unique varieties of FV purchased also increased more among WIC shoppers relative to non-WIC shoppers (DID 67.1 ounces (ACI, 61.9 to 72.3) and DID 2.1 varieties (ACI, 2.0 to 2.3)). There were also increases in the volume of processed foods (DID 22.0 ounces (ACI, 17.2, 26.9)) and sugar-sweetened beverages (DID 49.1 ounces (ACI, 33.4, 64.9)) purchased among WIC shoppers relative to non-WIC shoppers. CONCLUSIONS: Increased WIC FV funding was associated with greater FV purchases. Research is needed to understand the effects of this policy on total dietary intake.

Psychological factors associated with exercise self-efficacy in the recipients of an implantable cardioverter defibrillator.

BACKGROUND: Insufficient exercise affects the health of patients who have implantable cardioverter defibrillators (ICD). The purpose of this study was to investigate the correlations between exercise self-efficacy (ESE) and its associated psychological factors in ICD recipients. METHODS: This cross-sectional study included individuals who had undergone ICD implantation at the cardiology department of a medical centre in Taiwan. A face-to-face survey was conducted. The survey questionnaire included questions regarding the participants' demographics, perceived health (PH), ICD shock-related anxiety (ICD-SRA), self-care self-efficacy (SSE), perceived exercise benefit (PE-benefit), perceived exercise barrier (PE-barrier), and ESE. Data were analysed using SPSS 20.0 Software. Stepwise multiple regression analyses were also performed to evaluate the predictive effects of the aforementioned factors on ESE. RESULTS: A total of 52 ICD recipients were enrolled. ESE was negatively correlated with ICD-SRA (r = -0.511; p < 0.01) and PE-barrier (r = -0.563; p < 0.01), but positively correlated with SSE (r = 0.339; p < 0.05) and PE-benefit (r = 0.464; p < 0.01). The stepwise multiple regression analysis revealed that PE-barrier, PE-benefit, and ICD-SRA effectively predicted ESE in the participants. CONCLUSIONS: ESE may be improved by overcoming PE-barrier, ICD-SRA and enhancing PE-benefit. Consequently, improving ESE may enhance the health benefits of exercise.

Artemisinins ameliorate polycystic ovarian syndrome by mediating LONP1-CYP11A1 interaction.

Polycystic ovary syndrome (PCOS), a prevalent reproductive disorder in women of reproductive age, features androgen excess, ovulatory dysfunction, and polycystic ovaries. Despite its high prevalence, specific pharmacologic intervention for PCOS is challenging. In this study, we identified artemisinins as anti-PCOS agents. Our finding demonstrated the efficacy of artemisinin derivatives in alleviating PCOS symptoms in both rodent models and human patients, curbing hyperandrogenemia through suppression of ovarian androgen synthesis. Artemisinins promoted cytochrome P450 family 11 subfamily A member 1 (CYP11A1) protein degradation to block androgen overproduction. Mechanistically, artemisinins directly targeted lon peptidase 1 (LONP1), enhanced LONP1-CYP11A1 interaction, and facilitated LONP1-catalyzed CYP11A1 degradation. Overexpression of LONP1 replicated the androgen-lowering effect of artemisinins. Our data suggest that artemisinin application is a promising approach for treating PCOS and highlight the crucial role of the LONP1-CYP11A1 interaction in controlling hyperandrogenism and PCOS occurrence.

RETRACTED: Cheng et al. Using Comorbidity Pattern Analysis to Detect Reliable Methylated Genes in Colorectal Cancer Verified by Stool DNA Test. Genes 2021, 12, 1539.

The Genes journal retracts the article "Using Comorbidity Pattern Analysis to Detect Reliable Methylated Genes in Colorectal Cancer Verified by Stool DNA Test" [...].

Integrative omics analysis reveals insights into small colony variants of Staphylococcus aureus induced by sulfamethoxazole-trimethoprim.

BACKGROUND: Long-term treatment with trimethoprim-sulfamethoxazole (SXT) can lead to the formation of small-colony variants (SCVs) of Staphylococcus aureus. However, the mechanism behind SCVs formation remains poorly understood. In this study, we explored the phenotype and omics-based characterization of S. aureus SCVs induced by SXT and shed light on the potential causes of SCV formation. METHODS: Stable SCVs were obtained by continuously treating S. aureus isolates using 12/238 µg/ml of SXT, characterized by growth kinetics, antibiotic susceptibility testing, and auxotrophism test. Subsequently, a pair of representative strains (SCV and its parental strain) were selected for genomic, transcriptomic and metabolomic analysis. RESULTS: Three stable S. aureus SCVs were successfully screened and proven to be homologous to their corresponding parental strains. Phenotypic tests showed that all SCVs were non-classical mechanisms associated with impaired utilization of menadione, heme and thymine, and exhibited slower growth and higher antibiotic minimum inhibitory concentrations (MICs), compared to their corresponding parental strains. Genomic data revealed 15 missense mutations in 13 genes in the representative SCV, which were involved in adhesion, intramolecular phosphate transfer on ribose, transport pathways, and phage-encoded proteins. The combination analysis of transcriptome and metabolome identified 35 overlapping pathways possible associated with the phenotype switching of S. aureus. These pathways mainly included changes in metabolism, such as purine metabolism, pyruvate metabolism, amino acid metabolism, and ABC transporters, which could play a crucial role in promoting SCVs development by affecting nucleic acid synthesis and energy metabolism in bacteria. CONCLUSION: This study provides profound insights into the causes of S. aureus SCV formation induced by SXT. The findings may offer valuable clues for developing new strategies to combat S. aureus SCV infections.

Landform and lithospheric development contribute to the assembly of mountain floras in China.

Although it is well documented that mountains tend to exhibit high biodiversity, how geological processes affect the assemblage of montane floras is a matter of ongoing research. Here, we explore landform-specific differences among montane floras based on a dataset comprising 17,576 angiosperm species representing 140 Chinese mountain floras, which we define as the collection of all angiosperm species growing on a specific mountain. Our results show that igneous bedrock (granitic and karst-granitic landforms) is correlated with higher species richness and phylogenetic overdispersion, while the opposite is true for sedimentary bedrock (karst, Danxia, and desert landforms), which is correlated with phylogenetic clustering. Furthermore, we show that landform type was the primary determinant of the assembly of evolutionarily older species within floras, while climate was a greater determinant for younger species. Our study indicates that landform type not only affects montane species richness, but also contributes to the composition of montane floras. To explain the assembly and differentiation of mountain floras, we propose the 'floristic geo-lithology hypothesis', which highlights the role of bedrock and landform processes in montane floristic assembly and provides insights for future research on speciation, migration, and biodiversity in montane regions.

Recurrence of Diabetic Foot Complications: A Domino Effect Leading to Lethal Consequences-Insights From a National Longitudinal Study.

Background: Foot complications are common in people with diabetes mellitus (DM), leading to increased health care utilization, heightened mortality risk, and notable recurrence rates even after treatment. This retrospective cohort study aimed to investigate the impact of repeated occurrence of DM-related foot complications on the risk of all-cause mortality and to identify the potential risk factors associated with repeated events. Methods: People with DM admitted with foot complications (ulcer, skin and soft tissue infection, or osteomyelitis) from 2012 to 2014 were identified from Taiwan's National Health Insurance Research Database, with a 3-year follow-up for repeated events. We categorized the study subjects based on their cumulative number of hospital admissions with foot complications. Logistic regression was conducted to explore the potential risk factors associated with repeated diabetic foot events. Kaplan-Meier curves and Cox proportional hazard models were used to examine the associations between repeated diabetic foot events and all-cause mortality. Results: In this study, 28 754 eligible individuals were enrolled and classified into 3 groups: no repeated diabetic foot events (76.1%), 1 repeated event (16.0%), and 2 or more repeated events (7.9%). Logistic regression revealed that advanced age, male sex, congestive heart failure, dyslipidemia, hypertension, nephropathy, retinopathy, neuropathy, peripheral vascular disease, diabetes-related preventable hospitalizations, and outpatient visits due to diabetic foot were significantly associated with repeated events of diabetic foot complications. Compared with those with no repeated events, the adjusted hazard ratios for all-cause mortality were 1.26 (95% CI, 1.19-1.34) for 1 repeated event and 1.36 (95% CI, 1.26-1.47) for 2 or more repeated events. Conclusions: The significant association between repeated diabetic foot and elevated mortality risk highlights the critical necessity for proactive and targeted patient care within clinical practice. More research to delve into the predictive factors related to the repeated occurrence of diabetic foot is needed to provide additional insights for prevention strategies.

Early Therapeutic Drug Monitoring Optimizes Teicoplanin Use in Febrile Neutropenic Patients with Hematological Malignancies.

INTRODUCTION: A target trough concentration (Cmin) of teicoplanin ≥ 15-20 mg/L between the fourth and sixth day has been suggested for severe infections or management of febrile neutropenia (FN). Owing to no reports discussing the impact of early target attainment on treatment outcomes, this study aimed to evaluate the dose-Cmin relationship and clinical outcome and estimate the optimal early target Cmin for FN in patients with hematological malignancies. METHODS: This single-center, prospective study enrolled patients with hematological malignancies who were treated with teicoplanin either as an empirical antibiotic for FN or as targeted treatment for Gram-positive bacteria. Blood samples were collected on day three (48 h) post-loading doses, day 5 (96 h), and day 8 (when applicable) and determined by ultrahigh-pressure liquid chromatography-triple quadruple mass spectrometry. A total of 117 samples from 47 patients with FN (27 men, 20 women) were consecutively analyzed. A two-tailed α value of 0.05 was considered statistically significant. RESULTS: The mean Cmin values at 48 h, 96 h, and on day 8 were 23.4, 21.4, and 27.8 mg/L, respectively. The patients achieving Cmin ≥ 20 mg/L at 48 h had a higher likelihood of treatment success. The areas under the receiver operating characteristic curves were 0.71 for clinical efficacy and the cutoff value of Cmin at 48 h was 18.85 mg/L (95% confidence interval 0.55-0.87; P = 0.018). CONCLUSIONS: The Cmin of teicoplanin after completion of loading doses could predict the treatment response, with a target concentration ≥ 18.85 mg/L.

Aberrant Expression of SLC7A11 Impairs the Antimicrobial Activities of Macrophages in Staphylococcus Aureus Osteomyelitis in Mice.

Staphylococcus aureus (S. aureus) persistence in macrophages, potentially a reservoir for recurrence of chronic osteomyelitis, contributes to resistance and failure in treatment. As the mechanisms underlying survival of S. aureus in macrophages remain largely unknown, there has been no treatment approved. Here, in a mouse model of S. aureus osteomyelitis, we identified significantly up-regulated expression of SLC7A11 in both transcriptomes and translatomes of CD11b+F4/80+ macrophages, and validated a predominant distribution of SLC7A11 in F4/80+ cells around the S. aureus abscess. Importantly, pharmacological inhibition or genetic knockout of SLC7A11 promoted the bactericidal function of macrophages, reduced bacterial burden in the bone and improved bone structure in mice with S. aureus osteomyelitis. Mechanistically, aberrantly expressed SLC7A11 down-regulated the level of intracellular ROS and reduced lipid peroxidation, contributing to the impaired bactericidal function of macrophages. Interestingly, blocking SLC7A11 further activated expression of PD-L1 via the ROS-NF-κB axis, and a combination therapy of targeting both SLC7A11 and PD-L1 significantly enhanced the efficacy of clearing S. aureus in vitro and in vivo. Our findings suggest that targeting both SLC7A11 and PD-L1 is a promising therapeutic approach to reprogram the bactericidal function of macrophages and promote bacterial clearance in S. aureus osteomyelitis.

WSSV early protein WSSV004 enhances viral replication by suppressing LDH activity.

White spot syndrome virus (WSSV) is known to upregulate glycolysis to supply biomolecules and energy for the virus's replication. At the viral genome replication stage, lactate dehydrogenase (LDH), a glycolytic enzyme, shows increased activity without any increase in expression. In the present study, yeast 2-hybrid screening was used to identify WSSV proteins that interacted with LvLDH isoform 1 and 2, and these included the WSSV early protein WSSV004. The interaction between WSSV004 and LvLDH1/2 was confirmed by co-immunoprecipitation. Immunofluorescence showed that WSSV004 co-localized with LvLDH1/2 in the cytoplasm. dsRNA silencing experiments showed that WSSV004 was crucial for WSSV replication. However, although WSSV004 silencing led to the suppression of total LvLDH gene expression during the viral late stage, there was nevertheless a significant increase in LvLDH activity at this time. We also used affinity purification-mass spectrometry to identify cellular proteins that interact with WSSV004, and found a total of 108 host proteins and 3 WSSV proteins with which it potentially interacts. Bioinformatics analysis revealed that WSSV004 and its interacting proteins might be responsible for various biological pathways during infection, including vesicular transport machinery and RNA-related functions. Collectively, our study suggests that WSSV004 serves as a multifunctional modulator to facilitate WSSV replication.

Establishment and characterization of Lesch-Nyhan syndrome rabbit model.

Lesch-Nyhan syndrome (LNS) is a congenital defect disease that results in defective purine metabolism. It is caused by pathogenic variants of the HPRT gene. Its clinical symptoms mainly include high uric acid levels, gout, and kidney stones and damage. The mechanism of LNS has not been fully elucidated, and no cure exists. Animal models have always played an important role in exploring causative mechanisms and new therapies. This study combined CRISPR/Cas9 and microinjection to knock out the HPRT gene to create an LNS rabbit model. A sgRNA targeting exon 3 of HPRT gene was designed. Subsequently, Cas9 mRNA and sgRNA were injected into rabbit zygotes, and injected embryos were transferred to the uterus. The genotype and phenotype of rabbits were analyzed after birth. Four infant rabbits (named R1, R2, R3 and R4), which showed varying levels of gene modification, were born. The gene-editing efficiency was 100%. No wild-type sequences at the target HPRT gene were detected in R4 rabbit. Next, 6-thioguanine drug testing confirmed that HPRT enzymatic activity was deficient in R4 infant rabbit. HE staining revealed kidney abnormalities in all infant rabbits. Overall, an sgRNA capable of knocking out the HPRT gene in rabbits was successfully designed, and HPRT gene-modified rabbits were successfully constructed by using CRISPR/Cas9 technology and microinjection. This study provides a new nonrodent animal model for studying LNS syndrome.

Electroacupuncture improves low-grade duodenal inflammation in FD rats by reshaping intestinal flora through the NF-κB p65/NLRP3 pyroptosis pathway.

Electroacupuncture (EA) is an effective alternative for the treatment of functional dyspepsia (FD). It reduces low-grade duodenal inflammation and improves the symptoms of FD by downregulating the expression of NF-κB p65 and NLRP3, but its mechanism needs to be elucidated. To examine the regulatory effect of electroacupuncture (EA) on intestinal flora and NF-κB p65/NLRP3 pyroptosis pathway in FD rats. The FD rat model was established via multi-factor stress intervention for two weeks. The rats were randomly divided into the NC group, model group, NF-kB inhibitor group (NF-κB inhibitor BAY 11-7082 was administered), EA group, and EA + NF-kB inhibitor group. After 14 days of treatment, the rats were sacrificed, and the protein and mRNA levels of NF-κB p65, IκB, and NLRP3 in the duodenum were evaluated by Western blotting assays and real-time fluorescent quantitative PCR. The Illumina MiSeq sequencing platform was used to analyze the V4 region of the 16S rRNA gene of intestinal flora and predict functional genes. The concentration of short-chain fatty acids (SCFAs) in feces was assessed by metabolomics. EA can decrease low-grade duodenal inflammation and promote gastrointestinal motility in FD rats. This effect is mediated by inhibition of the NF-κB p65/NLRP3 pyroptosis pathway, an increase in the alpha and beta diversity of gut microbiota in the duodenum, an increase in the abundance of beneficial bacteria at the phylum and genus levels, and an increase in the content of SCFAs. The protective effect of EA against FD might involve multiple hierarchy and pathways. EA may remodel intestinal flora by inhibiting the NF-κB p65/NLRP3 pyroptosis pathway, thereby improving low-grade duodenal inflammation in FD rats.

Reversing Metabolic Dysfunction-Associated Steatotic Liver Disease Promotes Healthy Pediatric Cardiovascular Structures: The PROC Study.

INTRODUCTION: We investigated the impact of metabolic dysfunction-associated steatotic liver disease (MASLD) on cardiovascular structure development in children. METHODS: We followed 1,356 children with the mean age of 6.6 years for 4.5 years in Beijing, China. We assessed the association of MASLD with cardiovascular structure (carotid intima-media thickness and left ventricular mass) outcomes at baseline and follow-up. RESULTS: Over follow-up, 59 children had persistent MASLD, 109 had incident MASLD (progression), and 35 had normalization of liver health. Children with MASLD normalization showed a significantly lower mean development in carotid intima-media thickness (0.161 vs 0.188 mm) and left ventricular mass (4.5 vs 12.4 g) than children with persistent MASLD. DISCUSSION: The control of MASLD was associated with improved cardiovascular structure development.

Assessment of causal associations between obesity and peripheral artery disease: a bidirectional Mendelian randomization study.

Background: Several observational studies have documented a potential link between obesity and peripheral artery disease (PAD), although conflicting findings exist. The causal relationship between obesity and PAD continues to be a subject of ongoing debate in the medical community. Objectives: In this study, we employed a bidirectional Mendelian randomization (MR) analysis to explore the potential causal relationship between obesity and the risk of PAD. Methods: To investigate these causal relationships, we conducted bidirectional MR analysis using publicly available genome-wide association study (GWAS) data. Effect estimates were calculated using the random-effects inverse variance-weighted (IVW) method. Results: We identified eight independent single nucleotide polymorphisms (SNPs) associated with obesity in 218,735 samples involving 16,380,465 SNPs, all of which met the genome-wide significance threshold (p < 5 × 10-8). The IVW analysis indicates a significant positive association between genetic obesity and multiple datasets with PAD as the outcome: Queue-1 (GWAS ID: finn-b-I9_PAD) (OR = 1.138, 95% CI: 1.027-1.261, p = 0.013), Queue-2 (GWAS ID: bbj-a-144) (OR = 1.190, 95% CI: 1.019-1.390, p = 0.028), Queue-3 (GWAS ID: ebi-a-GCST90018670) (OR = 1.174, 95% CI: 1.014-1.360, p = 0.032), and Queue-4 (GWAS ID: ebi-a-GCST90018890) (OR = 1.194, 95% CI: 1.099-1.296, p < 0.001). However, we did not observe a significant genetic-level association between obesity and PAD for Queue-5 (GWAS ID: ukb-d-I9_PAD) (OR = 1.001, 95% CI: 1.000-1.002, p = 0.071). Furthermore, we conducted a reverse causal MR analysis to explore the potential reverse causal relationship between obesity and PAD. This comprehensive analysis did not provide evidence of a reverse causal association between these two factors. Conclusions: In summary, our study offers genetic evidence suggesting a possible causal link between obesity and PAD. While we did not find evidence supporting the "obesity paradox", prudent weight management remains crucial, as lower weight does not necessarily guarantee better outcomes. As with any study, caution is required in interpreting the findings. Further research is essential to assess the clinical relevance of weight in preventing PAD, which could inform the development of more precise intervention strategies.

Evaluating the performance of an AI-powered VBAC prediction system within a decision-aid birth choice platform for shared decision-making.

Background: Vaginal birth after cesarean (VBAC) is generally regarded as a safe and viable birthing option for most women with prior cesarean delivery. Nonetheless, concerns about heightened risks of adverse maternal and perinatal outcomes have often dissuaded women from considering VBAC. This study aimed to assess the performance of an artificial intelligence (AI)-powered VBAC prediction system integrated into a decision-aid birth choice platform for shared decision-making (SDM). Materials and Methods: Employing a retrospective design, we collected medical records from a regional hospital in northern Taiwan from January 2019 to May 2023. To explore a suitable model for tabular data, we compared two prevailing modeling approaches: tree-based models and logistic regression models. We subjected the tree-based algorithm, CatBoost, to binary classification. Results: Forty pregnant women with 347 records were included. The CatBoost model demonstrated a robust performance, boasting an accuracy rate of 0.91 (95% confidence interval (CI): 0.86-0.94) and an area under the curve of 0.89 (95% CI: 0.86-0.93), surpassing both regression models and other boosting techniques. CatBoost captured the data characteristics on the significant impact of gravidity and the positive influence of previous vaginal birth, reinforcing established clinical guidelines, as substantiated by the SHapley Additive exPlanations analysis. Conclusion: Using AI techniques offers a more accurate assessment of VBAC risks, boosting women's confidence in selecting VBAC as a viable birthing option. The seamless integration of AI prediction systems with SDM platforms holds a promising potential for enhancing the effectiveness of clinical applications in the domain of women's healthcare.

Analysis of nearly 3000 archaeal genomes from terrestrial geothermal springs sheds light on interconnected biogeochemical processes.

Terrestrial geothermal springs are physicochemically diverse and host abundant populations of Archaea. However, the diversity, functionality, and geological influences of these Archaea are not well understood. Here we explore the genomic diversity of Archaea in 152 metagenomes from 48 geothermal springs in Tengchong, China, collected from 2016 to 2021. Our dataset is comprised of 2949 archaeal metagenome-assembled genomes spanning 12 phyla and 392 newly identified species, which increases the known species diversity of Archaea by ~48.6%. The structures and potential functions of the archaeal communities are strongly influenced by temperature and pH, with high-temperature acidic and alkaline springs favoring archaeal abundance over Bacteria. Genome-resolved metagenomics and metatranscriptomics provide insights into the potential ecological niches of these Archaea and their potential roles in carbon, sulfur, nitrogen, and hydrogen metabolism. Furthermore, our findings illustrate the interplay of competition and cooperation among Archaea in biogeochemical cycles, possibly arising from overlapping functional niches and metabolic handoffs. Taken together, our study expands the genomic diversity of Archaea inhabiting geothermal springs and provides a foundation for more incisive study of biogeochemical processes mediated by Archaea in geothermal ecosystems.

Promoting Healthier Purchases: Ultraprocessed Food Taxes and Minimally Processed Foods Subsidies for the Low Income.

INTRODUCTION: Fiscal policies can shift relative food prices to encourage the purchase and consumption of minimally processed foods while discouraging the purchase and consumption of unhealthy ultraprocessed foods, high in calories and nutrients of concern (sodium, sugar, and saturated fats), especially for low-income households. METHODS: The 2017-2018 packaged food purchase data among U.S. households were used to derive household income- and composition-specific demand elasticities across 22 food and beverage categories. Policy simulations, conducted in 2022-2023, assessed the impact of national taxes on unhealthy ultraprocessed food and beverage purchases, both separately and alongside subsidies for minimally processed foods and beverages targeted to low-income households. Resultant nutritional implications are reported on the basis of changes in purchased calories and nutrients of concern. In addition, financial implications for both households and the federal government are projected. RESULTS: A sugar-based tax on sugar-sweetened beverages would lower both volume and calories purchased with the largest impact on low-income households without children. Meanwhile, targeted subsidies would increase fruit, vegetable, and healthier drink purchases without substantially increasing calories. Under tax simulations, low-income households would make larger reductions in their absolute volume and calorie purchases of taxed foods and beverages than their higher-income counterparts, suggesting that these policies, if implemented, could help narrow nutritional disparities. CONCLUSIONS: Levying national taxes on unhealthy ultraprocessed foods/beverages and offering targeted subsidies for minimally processed foods/beverages could promote healthier food choices among low-income households. Such policies have the potential to benefit low-income households financially and at a relatively low cost for the federal government annually.

Subjective experience of parent-child relationship in adolescents with congenital heart disease: A qualitative study.

PURPOSE: To explore the parent-child relationship through the subjective experience of adolescents with congenital heart disease (CHD). DESIGN AND METHODS: A descriptive phenomenology approach was adopted. Twelve adolescents aged from 12 to 18 years with CHD were recruited from the pediatric cardiology clinics at two medical centers in Taiwan. Data were collected through in-depth interviews. Data were analyzed using Colaizzi's phenomenological analysis method, and results were reported in accordance with the Consolidated Criteria for Reporting Qualitative Research guidelines. RESULTS: The experiences of the adolescents with CHD revealed five themes: 1. the enhancement of self-worth through parents' love; 2. the importance of parental support in desperate situations; 3. the development of a sense of security through mutual understanding; 4. growth under parental expectations; and 5. parental overcontrol disguised as love. CONCLUSIONS: The parent-child relationship encompasses both positive and negative experiences. Adolescents prioritize their relationship with parents over that with peers. PRACTICE IMPLICATIONS: Nurses caring for adolescents with CHD can improve care by recognizing the influence of parental love, support in challenges, mutual understanding, parental expectations, and potential negative consequences of overcontrol. This insight guides effective guidance for adolescents, enhancing parent-child interactions and overall well-being.