Cost-effectiveness analysis of first-line sintilimab plus chemotherapy vs. chemotherapy alone for unresectable advanced or metastatic gastric or gastroesophageal junction cancer in China.

Background: The Chinese Society of Clinical Oncology (CSCO) has recommended sintilimab plus chemotherapy (SINT + Chemo) as a standard first-line therapy for advanced gastric cancer or gastroesophageal junction cancer (GC/GEJC), based on the proven effectiveness and safety in the ORINT-16 trail. Its cost-effectiveness, however, remains to be evaluated. Methods: We established a partitioned survival approach (PartSA) model with a 10-year time horizon to determine whether SINT + Chemo (vs. chemotherapy) was more cost-effective as a first-line treatment for unresectable advanced or metastatic GC/GEJC. Survival data was generated from the ORIENT-16 trail. Cost calculation was limited to direct medical costs. Database of Hunan Public Resources Trading Service Platform was used as the source for obtaining drug prices. Other cost and utility values were gathered from established literature. Incremental cost-effectiveness ratio (ICER) was the primary output. Additionally, we conducted sensitivity analysis, subgroup analysis, and scenario analysis. Results: In the base-case analysis, group SINT + Chemo showed an increase in utility value by 0.32 quality-adjusted life-years (QALYs) at an extra cost of $7988.43, resulting in an ICER of $25239.29/QALY, below the Chinese cost-effective willingness-to-pay (WTP) threshold of $38223.34. Upon further subgroup analysis according to patients' programmed death 1 ligand (PD-L1) combined positive score (CPS), the ICERs were $26341.01/QALY for patients highly expressing PD-L1 (CPS ≥5) and $17658.26/QALY for patients lowly expressing PD-L1 (CPS <5). Based on the sensitivity analysis, we found the PFS utility was the parameter that had the most significant impact on the model's outcomes. Moreover, in scenario analysis, the results remained consistent despite variations in the model's time frame. Conclusion: In China, SINT + Chemo is a more cost-effective option (vs. chemotherapy) as a first-line therapy for unresectable advanced or metastatic GC/GEJC, irrespective of PD-L1 expression levels.

The developmental dyslexia scale for standard mandarin: A study among early primary students.

BACKGROUND: Developmental dyslexia (DD) is a prevalent neurodevelopmental disease that poses challenges in both early intervention and long-term development for children with DD. However, there is a lack of a standardized and comprehensive tool for the diagnosis of DD in Mainland China. AIM: To develop a standardized tool (i.e., Developmental Dyslexia Scale for Standard Mandarin [DDSSM]) for the diagnosis of DD in Mainland China and evaluate its reliability and validity. METHODS AND PROCEDURES: DDSSM consists of 10 subtests. The initial draft was created after Delphi expert consultation, and the final version was revised to improve discriminability with a pilot study involving 450 children from grades 1-3. The reliability and validity were then confirmed with 53 children from grades 1-2. OUTCOMES AND RESULTS: The Delphi expert consultation demonstrated that the expert panel had good authority, and that all agreed on the subtest setup. The DDSSM exhibited great internal consistency. Confirmatory factor analysis revealed that the model aligns with the theoretical structure (P > 0.05, χ2/df < 2.00, root-mean-square error of approximation (RMSEA) < 0.08, comparative fit index (CFI) > 0.90, TLI > 0.90). The Dyslexia Checklist for Chinese Children and children's academic performance agreed well with the DDSSM. CONCLUSIONS AND IMPLICATIONS: The DDSAM is reliable and valid for assessing and diagnosing DD in Standard Mandarin-speaking primary school children from grades 1-2. WHAT THIS PAPER ADDS?: Although a number of scales and tools have been proposed for assessing developmental dyslexia (DD) in Chinese, there is still a lack of diagnostic tools for Mandarin Chinese in Mainland China. In this study, we developed one of the most comprehensive diagnostic tools for DD in Mandarin Chinese for lower graders. We included visual-spatial attention (VA) and compounding awareness (CA), two tests that have been recently suggested as reliable measures for identifying DD in the Chinese language. This assessment tool has been verified for robust reliability and validity. This study also provided confirmation of the core deficits of DD in Chinese, which were orthographic awareness (OA). In addition, VA, rapid automatized naming (RAN) and morphological awareness (MA) were found to be the most important cognitive abilities for word reading in Chinese lower graders in this study.

Serum cotinine levels and adolescents' sleep health outcomes from NHANES 2005 to 2018.

The association between tobacco smoke exposure and sleep has been widely discussed, but the correlation between serum cotinine levels and sleep health outcomes in adolescents has not been well described. This study aimed to further evaluate the association between serum cotinine levels and sleep health outcomes in adolescents using data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. This cross-sectional study included participants aged 16-19 years from the NHANES 2005-2018. A weighted multivariate logistic regression model was used for the primary analysis. A restricted cubic spline (RCS) model was employed to investigate the non-linear association between serum cotinine levels and trouble sleeping. Subgroup analyses based on population characteristics were also conducted. In total, 2630 participants were included, which are representative of the 11.5 million US adolescents. Higher serum cotinine levels (≥ 3 ng/ml) were significantly associated with trouble sleeping in the fully adjusted model (odds ratio [OR] 1.817). The RCS model revealed a non-linear relationship between serum cotinine levels and trouble sleeping. Subgroup analyses indicated that this relationship was consistent and stable across various population characteristics. Serum cotinine levels are associated with sleep health outcomes in adolescents, with high serum cotinine levels being linked to increased trouble sleeping and longer or shorter sleep duration.

Chromosome-level genome assembly of Chinese water Scorpion Ranatra chinensis (Heteroptera: Nepidae).

Heteroptera (the true bugs), one of the most diverse lineages of insects, diversified in feeding strategies and living habitats, and thus become an ideal lineage for studies on adaptive evolution. Chinese water scorpion Ranatra chinensis (Heteroptera: Nepidae) is a predaceous bug living in lentic water systems, representing an ideal model for studying habitat transition and adaptation to water environment. However, genetic studies on this water bug remain limited. Here, we obtained a chromosome-level genome of R. chinensis using PacBio HiFi long reads and Hi-C sequencing reads. The total assembly size of genome is 867.89 Mb, with a scaffold N50 length of 26.48 Mb and the GC content of 39.50%. All contigs were assembled into 23 pseudo-chromosomes (N = 19 A + X1X2X3X4), and we predicted 18,424 protein-coding genes in this genome. This study will provide valuable genomic resources for future studies on the biology, water adaptation, and genome evolution of water bugs.

An orthology-based methodology as a complementary approach to retrieve evolutionarily conserved A-to-I RNA editing sites.

Adar-mediated adenosine-to-inosine (A-to-I) mRNA editing is a conserved mechanism that exerts diverse regulatory functions during the development, evolution, and adaptation of metazoans. The accurate detection of RNA editing sites helps us understand their biological significance. In this work, with an improved genome assembly of honeybee (Apis mellifera), we used a new orthology-based methodology to complement the traditional pipeline of (de novo) RNA editing detection. Compared to the outcome of traditional pipeline, we retrieved many novel editing sites in CDS that are deeply conserved between honeybee and other distantly related insects. The newly retrieved sites were missed by the traditional de novo identification due to the stringent criteria for controlling false-positive rate. Caste-specific editing sites are identified, including an Ile>Met auto-recoding site in Adar. This recoding was even conserved between honeybee and bumblebee, suggesting its putative regulatory role in shaping the phenotypic plasticity of eusocial Hymenoptera. In summary, we proposed a complementary approach to the traditional pipeline and retrieved several previously unnoticed CDS editing sites. From both technical and biological aspects, our works facilitate future researches on finding the functional editing sites and advance our understanding on the connection between RNA editing and the great phenotypic diversity of organisms.

Embryonic Genome Activation (EGA) Occurred at 1-Cell Stage of Embryonic Development in the Mud Crab, Scylla paramamosain, Revealed by RNA-Seq.

As a prerequisite for the success of embryo development, embryonic genome activation (EGA) is an important biological event in which zygotic gene products in the embryo are activated to replace maternal-derived transcripts. Although EGA has been extensively studied in a large number of vertebrates and invertebrates, there is a lack of information regarding this event in crustacean crab. In this study, the timing of EGA was confirmed by examining a transcriptomic dataset of early embryonic development, including mature oocytes and embryos through six early developmental stages, and signaling pathways associated with EGA were identified in the mud crab, S. paramamosain. The comprehensive transcriptomic data identified a total of 53,915 transcripts from these sequencing samples. Notable transcriptomic change was evident at the 1-cell stage, indicated by a 36% transcript number shift and a reduction in transcript fragment length, compared to those present in the mature oocytes. Concurrently, a substantial increase in the expression of newly transcribed transcripts was observed, with gene counts reaching 3485 at the 1-cell stage, indicative of the onset of EGA. GO functional enrichment revealed key biological processes initiated at the 1-cell stage, such as protein complex formation, protein metabolism, and various biosynthetic processes. KEGG analysis identified several critical signaling pathways activated during EGA, including the "cell cycle," "spliceosome," "RNA degradation", and "RNA polymerase", pathways. Furthermore, transcription factor families, including zinc finger, T-box, Nrf1, and Tub were predominantly enriched at the 1-cell stage, suggesting their pivotal roles in regulating embryonic development through the targeting of specific DNA sequences during the EGA process. This groundbreaking study not only addresses a significant knowledge gap regarding the developmental biology of S. paramamosain, especially for the understanding of the mechanism underlying EGA, but also provides scientific data crucial for the research on the individual synchronization of seed breeding within S. paramamosain aquaculture. Additionally, it serves as a reference basis for the study of early embryonic development in other crustacean species.

Design and validation of a high-speed hyperspectral laparoscopic imaging system.

Significance: Minimally invasive surgery (MIS) has shown vast improvement over open surgery by reducing post-operative stays, intraoperative blood loss, and infection rates. However, in spite of these improvements, there are still prevalent issues surrounding MIS that may be addressed through hyperspectral imaging (HSI). We present a laparoscopic HSI system to further advance the field of MIS. Aim: We present an imaging system that integrates high-speed HSI technology with a clinical laparoscopic setup and validate the system's accuracy and functionality. Different configurations that cover the visible (VIS) to near-infrared (NIR) range of electromagnetism are assessed by gauging the spectral fidelity and spatial resolution of each hyperspectral camera. Approach: Standard Spectralon reflectance tiles were used to provide ground truth spectral footprints to compare with those acquired by our system using the root mean squared error (RMSE). Demosaicing techniques were investigated and used to measure and improve spatial resolution, which was assessed with a USAF resolution test target. A perception-based image quality evaluator was used to assess the demosaicing techniques we developed. Two configurations of the system were developed for evaluation. The functionality of the system was investigated in a phantom study and by imaging ex vivo tissues. Results: Multiple configurations of our system were tested, each covering different spectral ranges, including VIS (460 to 600 nm), red/NIR (RNIR) (610 to 850 nm), and NIR (665 to 950 nm). Each configuration is capable of achieving real-time imaging speeds of up to 20 frames per second. RMSE values of 3.51 ± 2.03 % , 3.43 ± 0.84 % , and 3.47% were achieved for the VIS, RNIR, and NIR systems, respectively. We obtained sub-millimeter resolution using our demosaicing techniques. Conclusions: We developed and validated a high-speed hyperspectral laparoscopic imaging system. The HSI system can be used as an intraoperative imaging tool for tissue classification during laparoscopic surgery.

Functional roles of the interaction of Moa1 with CENP-C and Rec8 in meiosis of Schizosaccharomyces pombe.

The localization of the meiotic specific regulatory molecule Moa1 to the centromere is regulated by the kinetochore protein CENP-C, and participates in the cohesion of sister chromatids in the centromere region mediated by the cohesin Rec8. To examine the interaction of these proteins, we analyzed the interactions between Moa1 and Rec8, CENP-C by yeast two-hybrid assays and identified several amino acid residues in Moa1 required for the interaction with CENP-C and Rec8. The results revealed that the interaction between Moa1 and CENP-C is crucial for the Moa1 to participate in the regulation of monopolar attachment of sister kinetochores. However, mutation at S143 and T150 of Moa1, which are required for interaction with Rec8 in the two-hybrid assay, did not show significant defects. Mutations in amino acid residues may not be sufficient to interfere with the interaction between Moa1 and Rec8 in vivo. Further research is needed to determine the interaction domain between Moa1 and Rec8. This study revealed specific amino acid sites at which Moa1 affects the meiotic homologous chromosome segregation, providing a deeper understanding of the mechanism of meiotic chromosome segregation.

Explore the Role of Frailty as a Contributor to the Association Between AT(N) Profiles and Cognition in Alzheimer's Disease.

Background: The relationship between Alzheimer's disease (AD)-related pathology and cognition was not exactly consistent. Objective: To explore whether the association between AD pathology and cognition can be moderated by frailty. Methods: We included 1711 participants from the Alzheimer's Disease Neuroimaging Initiative database. Levels of cerebrospinal fluid amyloid-ß, p-tau, and t-tau were identified for AD-related pathology based on the amyloid-ß/tau/neurodegeneration (AT[N]) framework. Frailty was measured using a modified Frailty Index-11 (mFI-11). Regression and interaction models were utilized to assess the relationship among frailty, AT(N) profiles, and cognition. Moderation models analyzed the correlation between AT(N) profiles and cognition across three frailty levels. All analyses were corrected for age, sex, education, and APOEɛ4 status. Results: In this study, frailty (odds ratio [OR] = 1.71, p < 0.001) and AT(N) profiles (OR = 2.00, p < 0.001) were independently associated with cognitive status. The model fit was improved when frailty was added to the model examining the relationship between AT(N) profiles and cognition (p < 0.001). There was a significant interaction between frailty and AT(N) profiles in relation to cognitive status (OR = 1.12, pinteraction = 0.028). Comparable results were obtained when Mini-Mental State Examination scores were utilized as the measure of cognitive performance. The association between AT(N) profiles and cognition was stronger with the levels of frailty. Conclusions: Frailty may diminish patients' resilience to AD pathology and accelerate cognitive decline resulting from abnormal AD-related pathology. In summary, frailty contributes to elucidating the relationship between AD-related pathology and cognitive impairment.

Comparative genomic analyses on assassin bug Rhynocoris fuscipes (Hemiptera: Reduviidae) reveal genetic bases governing the diet-shift.

Genetic basis underlying the biodiversity and phenotypic plasticity are fascinating questions in evolutionary biology. Such molecular diversity can be achieved at multi-omics levels. Here, we sequenced the first chromosome-level genome of assassin bug Rhynocoris fuscipes, a polyphagous generalist predator for biological control of agroecosystems. Compared to non-predatory true bugs Apolygus lucorum and Riptortus pedestris, the R. fuscipes-specific genes were enriched in diet-related genes (e.g., serine proteinase, cytochrome P450) which had higher expression level and more exons than non-diet genes. Extensive A-to-I RNA editing was identified in all three species and showed enrichment in genes associated with diet in R. fuscipes, diversifying the transcriptome. An extended analysis between five predaceous and 27 phytophagous hemipteran species revealed an expansion of diet-related genes in R. fuscipes. Our findings bridge the gap between genotype and phenotype, and also advance our understanding on genetic and epigenetic bases governing the diet shifts in ture bugs.

Efficacy of Tilt-Angle and Low-Dose CT Scan Guidance in Percutaneous plasma Radiofrequency Treatment for Lumbar 5-Sacrum 1 Disc Herniation.

Objective: To investigate the application effect of tilt-angle low-dose ComputedTomography (CT) scanning guidance technology in the plasma radiofrequency treatment of lumbar 5-sacrum 1 (L5-S1) intervertebral disc herniation. Methods: A total of 43 patients with L5-S1 disc herniation were included in this study and categorized into vertical-angle-guided CT (Group A, n = 21) and tilt-angle-guided CT (Group B, n = 22) groups. Percutaneous plasma L5-S1 disc radiofrequency treatment was administered. The total number of punctures and scans, operation times, and Numerical Rating Scale (NRS) pain scores (preprocedure and 3 and 30 days postprocedure) were documented. Results: Compared with Group A, punctures and scans were fewer in Group B, and the differences were statistically significant (P = 0.0001). Moreover, the CT scan-guided total surgery time was significantly shorter in Group B than in Group A (P = 0.0001). In addition, the NRS score exhibited a statistically significant difference among preprocedure (T0), 3 day postprocedure (T1), and 30 days (T2) in Groups A (P < 0.05). The NRS score exhibited a statistically significant difference between T0 and T1 and between T0 and T2 in Group B (P < 0.05), but not between T1 and T2 in Group B (P = 0.084). At three time points (T0, T1, T2), there was no statistically significant difference between the two groups (P > 0.05). Conclusion: The tilt-angle low-dose CT scanning technique for L5-S1 disc herniation offers the advantages of high efficiency, low damage, and low radiation, and its clinical application is recommended.

CT-guided plasma surgery for intervertebral discs has gradually shown its importance in clinical practice. We found that the protrusion of the intervertebral disc in the lumbar 5/sacral 1 region often leads to difficulty in puncture due to its anatomical position. By adjusting the tilt angle of the CT, we increase the success rate of puncture and significantly reduce the radiation exposure to patients. The tilt-angle low-dose CT scanning technique for L5-S1 disc herniation offers the advantages of high efficiency, low damage, and low radiation. It can avoid surgical failures caused by puncture difficulties and also reduce patient exposure to radiation, strengthen awareness of patient protection during treatment.

Genome-wide meta-analysis identifies ancestry-specific loci for Alzheimer's disease.

INTRODUCTION: Alzheimer's disease (AD) is a devastating neurological disease with complex genetic etiology. Yet most known loci have only identified from the late-onset type AD in populations of European ancestry. METHODS: We performed a two-stage genome-wide association study (GWAS) of AD totaling 6878 Chinese and 63,926 European individuals. RESULTS: In addition to the apolipoprotein E (APOE) locus, our GWAS of two independent Chinese samples uncovered three novel AD susceptibility loci (KIAA2013, SLC52A3, and TCN2) and a novel ancestry-specific variant within EGFR (rs1815157). More replicated variants were observed in the Chinese (31%) than in the European samples (15%). In combining genome-wide associations and functional annotations, EGFR and TCN2 were prioritized as two of the most biologically significant genes. Phenome-wide Mendelian randomization suggests that high mean corpuscular hemoglobin concentration might protect against AD. DISCUSSION: The current study reveals novel AD susceptibility loci, emphasizes the importance of diverse populations in AD genetic research, and advances our understanding of disease etiology. HIGHLIGHTS: Loci KIAA2013, SLC52A3, and TCN2 were associated with Alzheimer's disease (AD) in Chinese populations. rs1815157 within the EGFR locus was associated with AD in Chinese populations. The genetic architecture of AD varied between Chinese and European populations. EGFR and TCN2 were prioritized as two of the most biologically significant genes. High mean corpuscular hemoglobin concentrations might have protective effects against AD.

Laparoscopy is non-inferior to open surgery for rectal cancer: A systematic review and meta-analysis.

BACKGROUND: Laparoscopic surgery has been endorsed by clinical guidelines for colon cancer, but not for rectal cancer on account of unapproved oncologic equivalence with open surgery. AIMS: We started this largest-to-date meta-analysis to comprehensively evaluate the safety and efficacy of laparoscopy in the treatment of rectal cancer compared with open surgery. MATERIALS & METHODS: Both randomized and nonrandomized controlled trials comparing laparoscopic proctectomy and open surgery between January 1990 and March 2020 were searched in PubMed, Cochrane Library and Embase Databases (PROSPERO registration number CRD42020211718). The data of intraoperative, pathological, postoperative and survival outcomes were compared between two groups. RESULTS: Twenty RCTs and 93 NRCTs including 216,615 patients fulfilled the inclusion criteria, with 48,888 patients received laparoscopic surgery and 167,727 patients underwent open surgery. Compared with open surgery, laparoscopic surgery group showed faster recovery, less complications and decreased mortality within 30 days. The positive rate of circumferential margin (RR = 0.79, 95% CI: 0.72 to 0.85, p < 0.0001) and distal margin (RR = 0.75, 95% CI: 0.66 to 0.85 p < 0.0001) was significantly reduced in the laparoscopic surgery group, but the completeness of total mesorectal excision showed no significant difference. The 3-year and 5-year local recurrence, disease-free survival and overall survival were all improved in the laparoscopic surgery group, while the distal recurrence did not differ significantly between the two approaches. CONCLUSION: Laparoscopy is non-inferior to open surgery for rectal cancer with respect to oncological outcomes and long-term survival. Moreover, laparoscopic surgery provides short-term advantages, including faster recovery and less complications.

Complex Pulmonary Arteriovenous Fistula Presented With Ventricular Tachycardia and Type 2 Acute Myocardial Infarction.

Pulmonary arteriovenous fistula (PAVF) is a rare congenital vascular malformation primarily manifested as dyspnea, migraine, ischemic stroke, hemoptysis, and nervous system complications. However, in our case, an 18-year-old male patient with PAVF presented with sudden onset of ventricular tachycardia and type 2 acute myocardial infarction as initial symptoms. A diagnosis was achieved through pulmonary artery computer tomography angiography (CTA) and three-dimensional (3D) computed tomography (CT) reconstruction, revealing a complex and giant PAVF. Following multidisciplinary team (MDT) consultation, the patient underwent thoracoscopic surgery and experienced a successful recovery during follow-up.

The determination of 11 sulfonamide antibiotics in water and foods by developing a N-rich magnetic covalent organic framework combined with ultra-high performance liquid chromatography-tandem mass spectrometry.

The concentration of antibiotic residues in water and animal-derived foods is low and the matrix is complex, and effective extraction of antibiotic residues in them is a key factor for accurate quantification. It is important to establish a rapid and effective method for the analytical determination of antibiotics in water and foods. In this study, a type of novel magnetic COF (Fe3O4@SiO2@PDE-TAPB-COF) was synthesized and characterized. Moreover, Fe3O4@SiO2@PDE-TAPB-COF combined with ultra-high performance liquid chromatography-tandem mass spectrometry was used to determine the 11 sulfonamide antibiotics (SAs) in water and food. The parameters including pH, adsorption amount, adsorption time, type of elution solvent and elution time were optimized. Under the optimal conditions, the standard curves of 11 SAs showed good linearity (R 2 > 0.999) in their respective concentration ranges and had lower detection and quantification limits. The spiked recoveries of the developed MSPE-UPLC-MS/MS method for the 11 SAs in water and foods were 74.3-107.2% and 75.1-102.5%, respectively. And the relative standard deviations (RSDs) were less than 9.56% (n = 7). The results indicated that the method can be used for the determination of SAs in foods and water with low detection limits and high sensitivity.

The relationship between depression and lipid accumulation product: a population-based study.

Background: Lipid Accumulation Product (LAP) is a new type of obesity index. The relationship between LAP and depression is unclear, and this cross-sectional study was conducted to explore the relationship between LAP and depression using the National Health and Nutrition Examination Survey (NHANES) database from 2005-2018. Methods: In our study, logistic regression analysis was used to calculate the odds ratio between depression and LAP, and subgroup analysis and sensitivity analysis were also performed to verify the robustness of the results. Results: The analysis included 13,240 participants aged 20 years or older. After adjusting for multiple variables, LAP was positively associated with depression, OR 1. 50 (95% CI, 1. 05-2. 12). In subgroup analysis, LAP was significantly positively, associated with depression among male (2. 52, OR; 95% CI, 1. 39,4. 57), non-Hispanic Black (2. 55, OR; 95% CI, 1. 49,4. 36), those without diabetes (1. 67, OR; 95% CI, (1. 06,2. 61) or in the overweight (2. 09, OR; 95% CI, (1. 23,3. 54) subgroups. After inverse probability of treatment weighting (IPTW), the OR for the highest versus lowest quartile was 1. 55 (95% CI: 1. 24 - 1. 95). Conclusion: There are positive results between LAP and depression after adjusting for multiple potential variables, and prospective studies are needed to verify the results.

Design of novel broad-spectrum antiviral nucleoside analogues using natural bases ring-opening strategy.

The global prevalence of RNA virus infections has presented significant challenges to public health in recent years, necessitating the expansion of its alternative therapeutic library. Due to its evolutional conservation, RNA-dependent RNA polymerase (RdRp) has emerged as a potential target for broad-spectrum antiviral nucleoside analogues. However, after over half a century of structural modification, exploring unclaimed chemical space using frequently-used structural substitution methods to design new nucleoside analogues is challenging. In this study, we explore the use of the "ring-opening" strategy to design new base mimics, thereby using these base mimics to design new nucleoside analogues with broad-spectrum antiviral activities. A total of 29 compounds were synthesized. Their activity against viral RdRp was initially screened using an influenza A virus RdRp high-throughput screening model. Then, the antiviral activity of 38a was verified against influenza virus strain A/PR/8/34 (H1N1), demonstrating a 50% inhibitory concentration (IC50) value of 9.95 µM, which was superior to that of ribavirin (the positive control, IC50 = 11.43 µM). Moreover, 38a also has inhibitory activity against coronavirus 229E with an IC50 of 30.82 µM. In addition, compounds 42 and 46f exhibit an 82% inhibition rate against vesicular stomatitis virus at a concentration of 20 µM and hardly induce cytotoxicity in host cells. This work demonstrates the feasibility of designing nucleoside analogues with "ring-opening" bases and suggests the "ring-opening" nucleosides may have greater polarity, and designing prodrugs is an important aspect of optimizing their antiviral activity. Future research should focus on enhancing the conformational restriction of open-loop bases to mimic Watson-Crick base pairing better and improve antiviral activity.

Early life malnutrition and risk of T2DM adulthood: evidence from the lower socioeconomic status of northwest Chinese population.

Objective: This study aimed to explore whether famine exposure during early life are associated with a high risk of Type 2 Diabetes Mellitus (T2DM) in adulthood and the role of socioeconomic status (SES) on this effect. Materials and methods: We conducted a secondary data analysis based on data from a cross-sectional survey, collected 3,355 participants born between January 1, 1941 and December 31, 1966. Participants were categorized into four groups based on their date of birth, unexposed (individuals born in 1963-1966), infant exposed (individuals born in 1959-1962), childhood exposed (individuals born in 1949-1958), and adolescent exposed (born in 1941-1948). The association of famine exposure with T2DM risk in adults and conducted separately in plain area and mountain area was assessed using logistics regression model. Result: 22.35% of participants were diagnosed with T2DM, of which 43.47% were from the childhood famine-exposed group, representing the highest proportion among all subgroups (p < 0.001). Participants exposed to famine during childhood and adolescence from the lower SES mountain areas showed a significantly higher prevalence of T2DM in adulthood than those from the plain areas (p < 0.001). The adolescence stage exposed famine will increase the risk of T2DM in the mountain area (OR 2.46, 95% CI 1.61, 3.77). Conclusion: No strong evidence demonstrates that exposure to famine during the early life stage increases the risk of developing T2DM in adulthood. However, populations with lower SES are likely to be exposed to more risk factors for T2DM.

Association between Body Mass Index or Serum Albumin and Different Dementia Populations.

INTRODUCTION: There is limited understanding of body mass index (BMI) and serum albumin levels in patients with dementia. This study aimed to investigate the association between BMI, serum albumin levels, and dementia in patients with Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and Parkinson's disease with dementia (PDD). METHODS: A total of 336 patients with dementia (173 with AD, 112 with DLB, 51 with PDD) and 220 healthy controls were recruited. Pearson and Spearman correlation analyses were performed to examine the relationships between BMI or serum albumin and MMSE scores, as well as neuropathological markers. Logistic regression models were used to analyze the data, adjusting for confounding variables. RESULTS: Using the highest BMI quartile (≥26.04 kg/m2) and serum albumin quartile (≥41.21 g/L) as reference groups, the lowest BMI quartile (<21.91 kg/m2) was significantly associated with AD (p < 0.001) and DLB (p = 0.003). The lowest serum albumin quartile (≤37.60 g/L) was independently associated with DLB (p < 0.001) and AD (p = 0.006). In AD patients, BMI was associated with Aß1-42 and p-Tau181 in cerebrospinal fluid after controlling for confounders, while serum albumin was correlated with T-Tau and T-tau/Aß1-42 (p < 0.05). CONCLUSION: Decreased serum albumin and BMI levels are associated with DLB and AD in dementia patients. Although no correlation was found between BMI or serum albumin and MMSE scores, there was a significant association with AD cerebrospinal fluid pathologic markers.