Objectives/Goals: Pharmacogenomic (PGx) testing identifies genetic variations affecting medication response but is not yet in routine clinical whole-genome sequencing (WGS) workflows. We aimed to establish a streamlined bioinformatics pipeline for incorporating PGx reporting into clinical WGS and to determine clinical implications for medication treatment. Methods/Study Population: A PGx profiling pipeline based on existing WGS data was developed, integrating three WGS-based PGx calling tools: Aldy, PyPGx, and Cyrius (CYP2D6 only), to provide genotype calls for 17 key pharmacogenes. The pipeline was validated using WGS data from 70 individuals with diverse backgrounds (36% European, 27% African, 27% Asian, and 10% admixed) from the Genetic Testing Reference Materials Coordination Program (GeT-RM). Results were manually reviewed against published data. The validated pipeline was then applied to 144 clinical patients previously screened for neurodevelopmental disorders or suspected hereditary diseases, followed by diplotype-to-phenotype translation and preemptive PGx-guided medication recommendations based on consensus guidelines and FDA labeling for commonly used medications. Results/Anticipated Results: Congruent phenotype call rates for GeT-RM samples were 100% for 13 genes (CFTR, CYP2B6, CYP2C19, CYP2C9, CYP3A4, CYP4F2, DPYD, G6PD, IFNL3, NAT2, NUDT15, TPMT, and VKORC1), 99% for three genes (CYP3A5, SLCO1B1, UGT1A1), and 97% for CYP2D6, indicating strong pipeline performance. Among 144 clinical patients, 99.3% had at least one clinically actionable PGx results relevant to 36 of top 300 medications in the USA across psychotropic, cardiovascular, musculoskeletal, gastrointestinal, and other therapeutic areas. The most prevalent drug–gene interactions involved sertraline and CYP2B6, affecting 49% patients: 41% were intermediate metabolizers who may require slower titration and lower maintenance doses, while 8% poor metabolizers may benefit from a lower starting dose or alternative antidepressants. Discussion/Significance of Impact: Our validated WGS-based PGx profiling pipeline successfully extracted actionable PGx data from clinical WGS. By aligning PGx profiles with guideline-recommended clinical actions, we demonstrated the clinical value of integrating PGx reporting in WGS workflows, improving personalized medication management.

When an oblate droplet translates through a viscous fluid under linear shear, it experiences a lateral lift force whose direction and magnitude are influenced by the Reynolds number, the droplet’s viscosity and its aspect ratio. Using a recently developed sharp interface method, we perform three-dimensional direct numerical simulations to explore the evolution of lift forces on oblate droplets across a broad range of these parameters. Our findings reveal that in the low-but-finite Reynolds number regime, the Saffman mechanism consistently governs the lift force. The lift increases with the droplet’s viscosity, aligning with the analytical solution derived by Legendre & Magnaudet (Phys. Fluids, vol. 9, 1997, p. 3572), and also rises with the droplet’s aspect ratio. We propose a semi-analytical correlation to predict this lift force. In the moderate- to high-Reynolds-number regime, distinct behaviours emerge: the $L\hbox{-}$ and $S\hbox{-}$mechanisms, arising from the vorticity contained in the upstream shear flow and the vorticity produced at the droplet surface, dominate for weakly and highly viscous droplets, respectively. Both mechanisms generate counter-rotating streamwise vortices of opposite signs, leading to observed lift reversals with increasing droplet viscosity. Detailed force decomposition based on vorticity moments indicates that in the $L\hbox{-}$mechanism-dominated regime for weakly to moderately viscous droplets, the streamwise vorticity-induced lift approximates the total lift. Conversely, in the $S\hbox{-}$mechanism-dominated regime, for moderately to highly viscous droplets, the streamwise vorticity-induced lift constitutes only a portion of the total lift, with the asymmetric advection of azimuthal vorticity at the droplet interface contributing additional positive lift to counterbalance the $S\hbox{-}$mechanism’s effects. These insights bridge the understanding between inviscid bubbles and rigid particles, enhancing our comprehension of the lift force experienced by droplets in different flow regimes.

This paper provides an overview of the current status of ultrafast and ultra-intense lasers with peak powers exceeding 100 TW and examines the research activities in high-energy-density physics within China. Currently, 10 high-intensity lasers with powers over 100 TW are operational, and about 10 additional lasers are being constructed at various institutes and universities. These facilities operate either independently or are combined with one another, thereby offering substantial support for both Chinese and international research and development efforts in high-energy-density physics.

Despite being almost 4000m above sea level, cereal crops have been grown in the Ngari Prefecture on the Tibetan Plateau for thousands of years. Where and when domestic crop species adapted to high-altitude growing conditions is a matter of ongoing debate. Here, the authors present a new radiocarbon date from the Gepa serul cemetery, providing the earliest evidence of naked six-rowed barley in Tibet (c. 3500 BP). Evaluating the available evidence for barley cultivation and interregional connections in central Asia at this time, two hypotheses are considered—a generational advance with farmers migrating up river valleys or rapid, long-distance trade through mountain corridors.

In this paper, on–off switching digitization of a W-band variable gain power amplifier (VGPA) with above 60 dB dynamic range is introduced for large-scale phased array. Digitization techniques of on–off switching modified stacking transistors with partition are proposed to optimize configuration of control sub-cells. By the proposed techniques, gain control of a radio frequency variable gain amplifier (VGA) could be highly customized for both coarse and fine switching requirements instead of using additional digital-to-analog converters to tune the overall amplifier bias. The designed VGA in 130 nm SiGe has achieved switchable gain range from −46.4 to 20.6 dB and power range from −25.0 to 15.7 dBm at W band. The chip size of the fabricated VGPA is about 0.31 mm × 0.1 mm.

In laser systems requiring a flat-top distribution of beam intensity, beam smoothing is a critical technology for enhancing laser energy deposition onto the focal spot. The continuous phase modulator (CPM) is a key component in beam smoothing, as it introduces high-frequency continuous phase modulation across the laser beam profile. However, the presence of the CPM makes it challenging to measure and correct the wavefront aberration of the input laser beam effectively, leading to unwanted beam intensity distribution and bringing difficulty to the design of the CPM. To address this issue, we propose a deep learning enabled robust wavefront sensing (DLWS) method to achieve effective wavefront measurement and active aberration correction, thereby facilitating active beam smoothing using the CPM. The experimental results show that the average wavefront reconstruction error of the DLWS method is 0.04 μm in the root mean square, while the Shack–Hartmann wavefront sensor reconstruction error is 0.17 μm.

The current scholarship on Ku Hung-Ming (1857–1928) as a translator and a historical figure has been constrained by identity politics and has viewed his translations and writings as a passive response to the challenge of the Western powers from a Chinese nationalist, or as a process of Ku's identity-building. This article goes beyond these constraints and recognises Ku as an active critic of Western modernity. By drawing on narrative theory, it investigates Ku's three broad choices regarding his translated Confucian classics—translation directionality, the invocation of Goethe, and the use of language mixing on the title pages and/or in the front matter—to demonstrate that Ku's translation agenda was to critique Western modernity. This article constitutes a paradigm shift in the research on Ku's translation of Confucian classics, and challenges what I call the ‘eccentricity thesis’ in Ku Hung-Ming studies to raise awareness of Ku as a critic of modernity.

The incidence of obesity-related glomerulopathy (ORG) is rising worldwide with very limited treatment methods. Paralleled with the gut–kidney axis theory, the beneficial effects of butyrate, one of the short-chain fatty acids (SCFA) produced by gut microbiota, on metabolism and certain kidney diseases have gained growing attention. However, the effects of butyrate on ORG and its underlying mechanism are largely unexplored. In this study, a mice model of ORG was established with a high-fat diet feeding for 16 weeks, and sodium butyrate treatment was initiated at the 8th week. Podocyte injury, oxidative stress and mitochondria function were evaluated in mice kidney and validated in vitro in palmitic acid-treated-mouse podocyte cell lines. Further, the molecular mechanisms of butyrate on podocytes were explored. Compared with controls, sodium butyrate treatment alleviated kidney injuries and renal oxidative stress in high-fat diet-fed mice. In mouse podocyte cell lines, butyrate ameliorated palmitic acid-induced podocyte damage and helped maintain the structure and function of the mitochondria. Moreover, the effects of butyrate on podocytes were mediated via the GPR43-Sirt3 signal pathway, as evidenced by the diminished effects of butyrate with the intervention of GPR43 or Sirt3 inhibitors. In summary, we conclude that butyrate has therapeutic potential for the treatment of ORG. It attenuates high-fat diet-induced ORG and podocyte injuries through the activation of the GPR43-Sirt3 signalling pathway.

Foodborne diseases are ongoing and significant public health concerns. This study analysed data obtained from the Foodborne Outbreaks Surveillance System of Wenzhou to comprehensively summarise the characteristics of foodborne outbreaks from 2012 to 2022. A total of 198 outbreaks were reported, resulting in 2,216 cases, 208 hospitalisations, and eight deaths over 11 years. The findings suggested that foodborne outbreaks were more prevalent in the third quarter, with most cases occurring in households (30.8%). Outbreaks were primarily associated with aquatic products (17.7%) as sources of contamination. The primary transmission pathways were accidental ingestion (20.2%) and multi-pathway transmission (12.1%). Microbiological aetiologies (46.0%), including Vibrio parahaemolyticus, Salmonella ssp., and Staphylococcus aureus, were identified as the main causes of foodborne outbreaks. Furthermore, mushroom toxins (75.0%), poisonous animals (12.5%), and poisonous plants (12.5%) were responsible for deaths from accidental ingestion. This study identified crucial settings and aetiologies that require the attention of both individuals and governments, thereby enabling the development of effective preventive measures to mitigate foodborne outbreaks, particularly in coastal cities.

Emotion regulation, as a typical “top-down” emotional self-regulation, has been shown to play an important role in children’s oppositional defiant disorder (ODD) development. However, the association between other self-regulation subcomponents and the ODD symptom network remains unclear. Meanwhile, while there are gender differences in both self-regulation and ODD, few studies have examined whether their relation is moderated by gender. Five hundred and four children (age 6–11 years; 207 girls) were recruited from schools with parents and classroom teachers completing questionnaires and were followed up for assessment six months later. Using moderation network analysis, we analyzed the relation between self-regulation and ODD symptoms, and the moderating role of gender. Self-regulation including emotion regulation, self-control, and emotion lability/negativity had broad bidirectional relations with ODD symptoms. In particular, the bidirectional relations between emotion regulation and ODD3 (Defies) and between emotion lability/negativity and ODD4 (Annoys) were significantly weaker in girls than in boys. Considering the important role of different self-regulation subcomponents in the ODD symptom network, ODD is better conceptualized as a self-regulation disorder. Each ODD symptom is associated with different degrees of impaired “bottom-up” and “top-down” self-regulation, and several of the associations vary by gender.

Saccharin is a widely used sugar substitute, but little is known about the long-term health effects of saccharin intake. Our study aimed to examine the association between saccharin intake and mortality in diabetic and pre-diabetic population and overweight population from NHANES 1988–1994. Cox proportional hazard models were used to evaluate the association between saccharin intake and CVD, cancer and all-cause mortality. After multivariable adjustment, increased absolute saccharin intake was associated with the risk of all-cause mortality (hazard ratio (HR): 1·41, 95 % CI: 1·05, 1·90), CVD mortality (HR: 1·93, 95 % CI: 1·15, 3·25) and cancer mortality (HR: 2·26, 95 % CI: 1·10, 4·45) in diabetic and pre-diabetic population. Among overweight population, higher absolute saccharin intake was associated with the risk of cancer mortality (HR: 7·369, 95 % CI: 2·122, 25·592). Replacing absolute saccharin intake with total sugar significantly reduced all-cause mortality by 12·5 % and CVD mortality by 49·7 % in an equivalent substitution analysis in the diabetic and pre-diabetic population. Aspartame substitution reduced all-cause mortality by 29·2 % and cancer mortality by 30·2 %. Notably, the relative daily intake of saccharin also had similar effects as the absolute intake on all-cause, cardiovascular and cancer mortality in all analyses. This was despite the fact that the relative daily intake in our study was below the Food and Drug Administration limit of 15 mg/kg. In conclusion, our study showed a considerable risk of increased saccharin intake on the all-cause, CVD mortality and cancer mortality.

Hydrogen sulfide (H2S) has been shown to play a significant role in oxidative stress across various tissues and cells; however, its role in sperm function remains poorly understood. This study aimed to investigate the protective effect of GYY4137, a slow-releasing H2S compound, on sperm damage induced by H2O2. We assessed the effects of GYY4137 on motility, viability, lipid peroxidation and caspase-3 activity in human spermatozoa in vitro following oxidative damage mediated by H2O2. Spermatozoa from 25 healthy men were selected using a density gradient centrifugation method and cultured in the presence or absence of 10 μM H2O2, followed by incubation with varying concentrations of GYY4137 (0.625–2.5 μM). After 24 h of incubation, sperm motility, viability, lipid peroxidation, and caspase-3 activity were evaluated. The results indicated that H2O2 adversely affected sperm parameters, reducing motility and viability, while increasing oxidative stress, as evidenced by elevated lipid peroxidation and caspase-3 activity. GYY4137 provided dose-dependent protection against H2O2-induced oxidative stress (OS). We concluded that supplementation with GYY4137 may offer antioxidant protection during in vitro sperm preparation for assisted reproductive technology.

Paranosema locustae is an environmentally friendly parasitic predator with promising applications in locust control. In this study, transcriptome sequencing was conducted on gonadal tissues of Locusta migratoria males and females infected and uninfected with P. locustae at different developmental stages. A total of 18,635 differentially expressed genes (DEGs) were identified in female ovary tissue transcriptomes, with the highest number of DEGs observed at 1 day post-eclosion (7141). In male testis tissue transcriptomes, a total of 32,954 DEGs were identified, with the highest number observed at 9 days post-eclosion (11,245). Venn analysis revealed 25 common DEGs among female groups and 205 common DEGs among male groups. Gene ontology and Kyoto Encyclopaedia of Genes and Genome analyses indicated that DEGs were mainly enriched in basic metabolism such as amino acid metabolism, carbohydrate metabolism, lipid metabolism, and immune response processes. Protein–protein interaction analysis results indicated that L. migratoria regulates the expression of immune- and reproductive-related genes to meet the body's demands in different developmental stages after P. locustae infection. Immune- and reproductive-related genes in L. migratoria gonadal tissue were screened based on database annotation information and relevant literature. Genes such as Tsf, Hex1, Apolp-III, Serpin, Defense, Hsp70, Hsp90, JHBP, JHE, JHEH1, JHAMT, and VgR play important roles in the balance between immune response and reproduction in gonadal tissues. For transcriptome validation, Tsf, Hex1, and ApoLp-III were selected and verified by quantitative real-time polymerase chain reaction (qRT-PCR). Correlation analysis revealed that the qRT-PCR expression patterns were consistent with the RNA-Seq results. These findings contribute to further understanding the interaction mechanisms between locusts and P. locustae.

This study aimed to explore the combined association between the dietary antioxidant quality score (DAQS) and leisure-time physical activity on sleep patterns in cancer survivors. Data of cancer survivors were extracted from the National Health and Nutrition Examination Surveys database in 2007–2014 in this cross-sectional study. Weighted multivariable logistic regression models were used to estimate OR and 95 % CI for the association of DAQS and leisure-time physical activity on sleep patterns. The combined association was also assessed in subgroups of participants based on age and use of painkillers and antidepressants. Among the eligible participants, 1133 had unhealthy sleep patterns. After adjusting for covariates, compared with low DAQS level combined with leisure-time physical activity level < 600 MET·min/week, high DAQS level combined with leisure-time physical activity ≥ 600 MET·min/week was associated with lower odds of unhealthy sleep patterns (OR = 0·41, 95 % CI: 0·23, 0·72). Additionally, the association of high DAQS level combined with high leisure-time physical activity with low odds of unhealthy sleep patterns was also significant in < 65 years old (OR = 0·30, 95 % CI: 0·13, 0·70), non-painkiller (OR = 0·39, 95 % CI: 0·22, 0·71), non-antidepressant (OR = 0·49, 95 % CI: 0·26, 0·91) and antidepressant (OR = 0·11, 95 % CI: 0·02, 0·50) subgroups. DAQS and leisure-time physical activity had a combined association on sleep patterns in cancer survivors. However, the causal associations of dietary nutrient intake and physical activity with sleep patterns in cancer survivors need further clarification.