Iodine enrichment in the groundwater in South China and its hydrogeochemical control.

In North China, iodine-rich groundwater has been extensively studied, but few in South China. This study aimed to investigate the characteristics of iodine-rich groundwater in South China and identify potential contamination sources. The results revealed that the average concentration of iodine in groundwater was 890 µg/L, with a maximum concentration of 6350 µg/L, exceeding the permitted levels recommended by the World Health Organization (5-300 µg/L). Notably, the enrichment of iodide occurred in acidic conditions (pH = 6.6) and a relatively low Eh environment (Eh = 198.4 mV). Pearson correlation and cluster analyses suggested that the enrichment of iodide could be attributed to the intensified redox process involving Mn(II), iodine (I2), or iodate (IO3-) in the soil. The strong affinity between Mn(II) and I2/IO3- facilitated their interaction, resulting in the formation and mobilization of I- from the soil to the groundwater. Leaching experiments further confirmed that reducing substances (such as sodium sulfides, ascorbic acids, and fulvic acids) in the soil with low dissolved oxygen (DO) levels (< 1.0 mg/L) enhanced the dissolution of iodine species. Conversely, higher DO content (> 3.8 mg/L) promoted the oxidation of I- into I2 or IO3-, leading to its stabilization. This research provides new insights into the characteristics and mechanisms of I- enrichment in groundwater in South China, and emphasizes the significance of the redox reactions involving Mn(II) and I2/IO3-, as well as the influence of soil properties in regulating the occurrence and transportation of iodine species within groundwater systems.

Capecitabine induces hand-foot syndrome through elevated thymidine phosphorylase-mediated locoregional toxicity and GSDME-driven pyroptosis that can be relieved by tipiracil.

BACKGROUND: Hand-foot syndrome (HFS) is a serious dose-limiting cutaneous toxicity of capecitabine-containing chemotherapy, leading to a deteriorated quality of life and negative impacts on chemotherapy treatment. The symptoms of HFS have been widely reported, but the precise molecular and cellular mechanisms remain unknown. The metabolic enzyme of capecitabine, thymidine phosphorylase (TP) may be related to HFS. Here, we investigated whether TP contributes to the HFS and the molecular basis of cellular toxicity of capecitabine. METHODS: TP-/- mice were generated to assess the relevance of TP and HFS. Cellular toxicity and signalling mechanisms were assessed by in vitro and in vivo experiments. RESULTS: TP-/- significantly reduced capecitabine-induced HFS, indicating that the activity of TP plays a critical role in the development of HFS. Further investigations into the cellular mechanisms revealed that the cytotoxicity of the active metabolite of capecitabine, 5-DFUR, was attributed to the cleavage of GSDME-mediated pyroptosis. Finally, we demonstrated that capecitabine-induced HFS could be reversed by local application of the TP inhibitor tipiracil. CONCLUSION: Our findings reveal that the presence of elevated TP expression in the palm and sole aggravates local cell cytotoxicity, further explaining the molecular basis underlying 5-DFUR-induced cellular toxicity and providing a promising approach to the therapeutic management of HFS.

Temporal coexistence mechanisms contribute to the latitudinal gradient in forest diversity.

The tropical forests of Borneo and Amazonia may each contain more tree species diversity in half a square kilometre than do all the temperate forests of Europe, North America, and Asia combined. Biologists have long been fascinated by this disparity, using it to investigate potential drivers of biodiversity. Latitudinal variation in many of these drivers is expected to create geographic differences in ecological and evolutionary processes, and evidence increasingly shows that tropical ecosystems have higher rates of diversification, clade origination, and clade dispersal. However, there is currently no evidence to link gradients in ecological processes within communities at a local scale directly to the geographic gradient in biodiversity. Here, we show geographic variation in the storage effect, an ecological mechanism that reduces the potential for competitive exclusion more strongly in the tropics than it does in temperate and boreal zones, decreasing the ratio of interspecific-to-intraspecific competition by 0.25% for each degree of latitude that an ecosystem is located closer to the Equator. Additionally, we find evidence that latitudinal variation in climate underpins these differences; longer growing seasons in the tropics reduce constraints on the seasonal timing of reproduction, permitting lower recruitment synchrony between species and thereby enhancing niche partitioning through the storage effect. Our results demonstrate that the strength of the storage effect, and therefore its impact on diversity within communities, varies latitudinally in association with climate. This finding highlights the importance of biotic interactions in shaping geographic diversity patterns, and emphasizes the need to understand the mechanisms underpinning ecological processes in greater detail than has previously been appreciated.

Reverse Phase Protein Array Reveals Correlation of Retinoic Acid Metabolism With Cardiomyopathy in Friedreich's Ataxia.

Identifying biomarkers is important for assessment of disease progression, prediction of symptom development, and determination of treatment effectiveness. While unbiased analyses of differential gene expression using next-generation sequencing methods are now routinely conducted, proteomics studies are more challenging because of traditional methods predominantly being low throughput and offering a limited dynamic range for simultaneous detection of hundreds of proteins that drastically differ in their intracellular abundance. We utilized a sensitive and high-throughput proteomic technique, reverse phase protein array (RPPA), to attain protein expression profiles of primary fibroblasts obtained from patients with Friedreich's ataxia (FRDA) and unaffected controls (CTRLs). The RPPA was designed to detect 217 proteins or phosphorylated proteins by individual antibody, and the specificity of each antibody was validated prior to the experiment. Among 62 fibroblast samples (44 FRDA and 18 CTRLs) analyzed, 30 proteins/phosphoproteins were significantly changed in FRDA fibroblasts compared with CTRL cells (p < 0.05), mostly representing signaling molecules and metabolic enzymes. As expected, frataxin was significantly downregulated in FRDA samples, thus serving as an internal CTRL for assay integrity. Extensive bioinformatics analyses were conducted to correlate differentially expressed proteins with critical disease parameters (e.g., selected symptoms, age of onset, guanine-adenine-adenine sizes, frataxin levels, and Functional Assessment Rating Scale scores). Members of the integrin family of proteins specifically associated with hearing loss in FRDA. Also, RPPA data, combined with results of transcriptome profiling, uncovered defects in the retinoic acid metabolism pathway in FRDA samples. Moreover, expression of aldehyde dehydrogenase family 1 member A3 differed significantly between cardiomyopathy-positive and cardiomyopathy-negative FRDA cohorts, demonstrating that metabolites such as retinol, retinal, or retinoic acid could become potential predictive biomarkers of cardiac presentation in FRDA.

Demographic composition, not demographic diversity, predicts biomass and turnover across temperate and tropical forests.

The growth and survival of individual trees determine the physical structure of a forest with important consequences for forest function. However, given the diversity of tree species and forest biomes, quantifying the multitude of demographic strategies within and across forests and the way that they translate into forest structure and function remains a significant challenge. Here, we quantify the demographic rates of 1961 tree species from temperate and tropical forests and evaluate how demographic diversity (DD) and demographic composition (DC) differ across forests, and how these differences in demography relate to species richness, aboveground biomass (AGB), and carbon residence time. We find wide variation in DD and DC across forest plots, patterns that are not explained by species richness or climate variables alone. There is no evidence that DD has an effect on either AGB or carbon residence time. Rather, the DC of forests, specifically the relative abundance of large statured species, predicted both biomass and carbon residence time. Our results demonstrate the distinct DCs of globally distributed forests, reflecting biogeography, recent history, and current plot conditions. Linking the DC of forests to resilience or vulnerability to climate change, will improve the precision and accuracy of predictions of future forest composition, structure, and function.

Vocal repertoire and sound characteristics in the variegated cardinalfish, Fowleria variegata (Pisces: Apogonidae).

The variegated cardinalfish Fowleria variegata produces grunt and hoot calls during agonistic and courtship interactions. Both sounds are tonal and occur as single and multiunit calls. Grunts are of short duration with variable frequency spectra. Hoots are longer, have a higher fundamental frequency, and a more developed harmonic structure. Agonistic grunt calls and short hoot calls (1-2 hoots) are produced during chases and when striking an individual or a mirror. Grunts are produced primarily in male-female and mirror-image encounters, and short hoot calls are produced primarily in male-male interactions. During the reproductive period, long hoot calls (three and four hoots) are the main sound type in a mix-sexed tank and at Dongsha Atoll. These are likely produced by males because isolated females are silent, and isolated males emit long hoot calls. Courtship interactions are mostly silent, and males are silent after capturing eggs for oral brooding. Tank sounds peak at dusk to early evening with a smaller peak at noon, although there are dusk and dawn peaks at Dongsha Atoll. Tank sounds exhibit a semilunar rhythm with peaks at the new and full moon. Other cardinalfish species from the atoll produce grunts but not hoot calls.

Phenolic compounds in water, suspended particulate matter and sediment from Weihe River in Northwest China.

The distribution and ecological risks of 11 phenolic compounds were studied in Weihe River, Northwest China. The concentrations of phenolic compounds were determined by ultra-high performance liquid chromatography (UPLC). The total concentration of 11 phenolic compounds (∑PC11) ranged from 0.06 to 14.12 µg/L with an average of 5.22 µg/L in water, from 0.92 to 34,885 µg/g with an average of 4,446 µg/g in suspended particulate matter (SPM), and from 3.54 to 34.09 µg/g with an average of 11.09 µg/g in sediment. For individual phenolic compound, the mean concentration of pentachlorophenol was the highest in water (2.65 µg/L) and in SPM (3,865 µg/g), while in sediment the mean concentration of 2,4,6-trichlorophenol was the highest (3.05 µg/g). The total concentration of 5 chlorophenols (∑CP5) was significantly higher than that of 6 non-chlorophenols (∑NCP6) in all three studied compartments. The phenolic compounds in Weihe River were at moderate levels in water and at high levels in sediment. The ecological risk assessment results indicated that phenolic compounds exhibited a high ecological risk in Weihe River water. In most sites, the distribution coefficient (Kd) (SPM) was much higher than Kd (sediment), which probably suggested fresh phenolic compounds input in Weihe River.

Comparative Reactogenicity of Enhanced Influenza Vaccines in Older Adults.

BACKGROUND: We analyzed data from a randomized controlled trial on the reactogenicity of 3 enhanced influenza vaccines compared with standard-dose (SD) inactivated influenza vaccine. METHODS: We enrolled community-dwelling older adults in Hong Kong, and we randomly allocated them to receive 2017-2018 northern hemisphere formulations of SD vaccine (FluQuadri; Sanofi Pasteur), MF59-adjuvanted vaccine (FLUAD; Seqirus), high-dose (HD) vaccine (Fluzone High-Dose; Sanofi Pasteur), or recombinant hemagglutinin vaccine (Flublok; Sanofi Pasteur). Local and systemic reactions were evaluated at days 1, 3, 7, and 14 after vaccination. RESULTS: Reported reactions were generally mild and short-lived. Systemic reactions occurred in similar proportions of participants by vaccine. Some local reactions were slightly more frequently reported among recipients of the MF59-adjuvanted and HD vaccines than among SD vaccine recipients. Participants reporting feverishness 1 day after vaccination had mean fold rises in postvaccination hemagglutination inhibition titers that were 1.85-fold higher (95% confidence interval, 1.01-3.38) for A(H1N1) than in those who did not report feverishness. CONCLUSIONS: Some acute local reactions were more frequent after vaccination with MF59-adjuvanted and HD influenza vaccines, compared with SD inactivated influenza vaccine, whereas systemic symptoms occurred at similar frequencies in all groups. The association between feverishness and immunogenicity should be further investigated in a larger population. CLINICAL TRIALS REGISTRATION: NCT03330132.

Landmark-Based Inertial Navigation System for Autonomous Navigation of Missile Platform.

As a new information provider of autonomous navigation, the on-orbit landmark observation offers a new means to improve the accuracy of autonomous positioning and attitude determination. A novel autonomous navigation method based on the landmark observation and the inertial system is designed to achieve the high-accuracy estimation of the missile platform state. In the proposed method, the navigation scheme is constructed first. The implicit observation equation about the deviation of the inertial system output is derived and the Kalman filter is applied to estimate the missile platform state. Moreover, the physical observability of the landmark and the mathematical observability of the navigation system are analyzed. Finally, advantages of the proposed autonomous navigation method are demonstrated through simulations compared with the traditional celestial-inertial navigation system and the deeply integrated celestial-inertial navigation system.

Electronic and Morphological Dual Modulation of Cobalt Carbonate Hydroxides by Mn Doping toward Highly Efficient and Stable Bifunctional Electrocatalysts for Overall Water Splitting.

Developing bifunctional efficient and durable non-noble electrocatalysts for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) is highly desirable and challenging for overall water splitting. Herein, Co-Mn carbonate hydroxide (CoMnCH) nanosheet arrays with controllable morphology and composition were developed on nickel foam (NF) as such a bifunctional electrocatalyst. It is discovered that Mn doping in CoCH can simultaneously modulate the nanosheet morphology to significantly increase the electrochemical active surface area for exposing more accessible active sites and tune the electronic structure of Co center to effectively boost its intrinsic activity. As a result, the optimized Co1Mn1CH/NF electrode exhibits unprecedented OER activity with an ultralow overpotential of 294 mV at 30 mA cm-2, compared with all reported metal carbonate hydroxides. Benefited from 3D open nanosheet array topographic structure with tight contact between nanosheets and NF, it is able to deliver a high and stable current density of 1000 mA cm-2 at only an overpotential of 462 mV with no interference from high-flux oxygen evolution. Despite no reports about effective HER on metal carbonate hydroxides yet, the small overpotential of 180 mV at 10 mA cm-2 for HER can be also achieved on Co1Mn1CH/NF by the dual modulation of Mn doping. This offers a two-electrode electrolyzer using bifunctional Co1Mn1CH/NF as both anode and cathode to perform stable overall water splitting with a cell voltage of only 1.68 V at 10 mA cm-2. These findings may open up opportunities to explore other multimetal carbonate hydroxides as practical bifunctional electrocatalysts for scale-up water electrolysis.

Crystallinity-Modulated Electrocatalytic Activity of a Nickel(II) Borate Thin Layer on Ni3 B for Efficient Water Oxidation.

The exploration of new efficient OER electrocatalysts based on nonprecious metals and the understanding of the relationship between activity and structure of electrocatalysts are important to advance electrochemical water oxidation. Herein, we developed an efficient OER electrocatalyst with nickel boride (Ni3 B) nanoparticles as cores and nickel(II) borate (Ni-Bi ) as shells (Ni-Bi @NB) via a very simple and facile aqueous reaction. This electrocatalyst exhibited a small overpotential of 302 mV at 10 mA cm-2 and Tafel slope of 52 mV dec-1 . More interestingly, it was found that the OER activity of Ni-Bi @NB was closely dependent on the crystallinity of the Ni-Bi shells. The partially crystalline Ni-Bi catalyst exhibited much higher activity than the amorphous or crystalline analogues; this higher activity originated from the enhanced intrinsic activity of the catalytic sites. These findings open up opportunities to explore nickel(II) borates as a new class of efficient nonprecious metal OER electrocatalysts, and to improve the electrocatalyst performance by modulating their crystallinity.

Long-term changes in liana loads and tree dynamics in a Malaysian forest.

The importance of lianas through time and their effect on tree reproduction are evaluated for the first time in a Southeast Asian Dipterocarp forest. We quantified flower and seed production by lianas and trees for 13 years, assessed liana loads in the crowns of all trees larger than 30 cm in diameter at breast height (1.3 m) in 2002 and 2014, and assessed levels of reproduction for the same trees during a strong general flowering event in 2014 for the 50-ha forest dynamics plot at the Pasoh Forest Reserve, Malaysia. General flowering refers to synchronous reproduction by hundreds of plant species at irregular, multiyear intervals and only occurs in Southeast Asian Dipterocarp forests. Overall, lianas were present in 50% of tree crowns and comprised 31% of flower production and 46% of seed production. Lianas reduced growth, survival, and reproduction by their host trees. Lianas were less frequent in canopy- emergent trees, Dipterocarps comprised a disproportionately large proportion of canopy emergents, and, as a consequence, lianas were less frequent in Dipterocarps than in trees from other plant families. Lianas infested the crowns of significantly fewer trees in 2014 (47.9%) than in 2002 (52.3%); however, the decrease was restricted to trees with the lightest liana loads and sample sizes and statistical power were enormous. Lianas comprised a stable proportion of flower production and a highly variable proportion of seed production from 2002 through 2013. We conclude lianas have a huge impact on trees in this forest and were a stable component of the forest between 2002 and 2014. The emergent habit and associated ability to avoid lianas might contribute to the success of the Dipterocarpaceae.

Temporal variability of forest communities: empirical estimates of population change in 4000 tree species.

Long-term surveys of entire communities of species are needed to measure fluctuations in natural populations and elucidate the mechanisms driving population dynamics and community assembly. We analysed changes in abundance of over 4000 tree species in 12 forests across the world over periods of 6-28 years. Abundance fluctuations in all forests are large and consistent with population dynamics models in which temporal environmental variance plays a central role. At some sites we identify clear environmental drivers, such as fire and drought, that could underlie these patterns, but at other sites there is a need for further research to identify drivers. In addition, cross-site comparisons showed that abundance fluctuations were smaller at species-rich sites, consistent with the idea that stable environmental conditions promote higher diversity. Much community ecology theory emphasises demographic variance and niche stabilisation; we encourage the development of theory in which temporal environmental variance plays a central role.

The Potential Value of Mean Platelet Volume and Platelet Distribution Width as Inflammatory Indicators in Surgical Necrotizing Enterocolitis.

Background: This study aims to investigate the potential significance of mean platelet volume (MPV) and platelet distribution width (PDW) in predicting surgical neonatal necrotizing enterocolitis (NEC) and establish the correlation between MPV/PDW levels and the severity/prognosis of NEC. Methods: A retrospective study was conducted on a cohort of 372 patients diagnosed with NEC. The patients were categorized into two groups based on whether they underwent surgical therapy. Univariate /multivariate analysis were employed to compare the MPV and PDW between the two groups. Moreover, patients in surgical group were categorized into multiple subgroups based on intraoperative findings and postoperative prognosis, and the levels of MPV and PDW were compared among these subgroups. Results: Of the 372 patients, the operative group exhibited significantly higher levels of MPV and PDW than the nonoperative group (P < 0.05). Logistic regression analysis revealed that MPV (OR = 4.895, P < 0.001) and PDW (OR = 1.476, P < 0.001) independently associated with surgical NEC. The analysis of the receiver operating characteristic (ROC) curve revealed that the area under the curve (AUC) was 0.706 for MPV alone, with a cut-off value of 11.8 fL. Similarly, the AUC was 0.728 for PDW alone, with a cut-off value of 16%. However, when MPV and PDW were combined, the AUC increased to 0.906 for predicting surgical NEC. In accordance with the intraoperative findings, the levels of MPV and PDW were found to be higher in the large area necrosis group than in the partial or mild necrosis group (P < 0.01). Furthermore, the MPV and PDW values in the death group were significantly greater than those in the survival group (P =0.040, P =0.008). Conclusion: MPV and PDW may serve as potentially valuable indicators for determining the need for surgical intervention and predicting the prognosis of patients with NEC.

Managing intraoperative rupture of internal carotid pseudoaneurysms during endoscopic transnasal optic canal decompression: a case report.

Background: Endoscopic transnasal optic canal decompression is widely used in the treatment of traumatic optic neuropathy (TON) following head and craniofacial trauma. Intraoperative hemorrhage is a catastrophic surgical complication during optic canal decompression. Case description: We present two cases of patients with TON who suffered unexpected intra-operative massive bleeding during endoscopic transnasal optic canal decompression. After intraoperative hemostasis was achieved, emergent cerebral angiograms demonstrated the formation of internal carotid pseudoaneurysms, which were immediately embolized with coils combined with or without Onyx with balloon assistance. One of these cases was also complicated by a postoperative cerebrospinal fluid leak, which failed to be treated with lumbar drainage but was successfully repaired with endoscopic transnasal surgery. Conclusion: The intra-operative rupture of ICA pseudoaneurysm is a rare but catastrophic complication in TON patients. Intraoperative massive bleeding indicates rupture of ICA pseudoaneurysm. Postoperative emergency angiography and endovascular therapy should be arranged to evaluate and repair the cerebral vascular injury. Endoscopic trans-nasal surgery repairing CSF leaks resistant to lumbar drainage could be efficient and safe following pseudoaneurysm embolization.

Novel biodegradable electrospun nanofibrous P(DLLA-CL) balloons for the treatment of vertebral compression fractures.

Significant interest has been expressed by the spinal surgeon community for the use of calcium phosphate cement (CPC) in the treatment of vertebral compression fractures (VCFs), but the water-induced collapsibility and poor mechanical properties limit its clinical use. Here we fabricated novel electrospun nanofibrous P(DLLA-CL) balloons (ENPBs) using the nanotechnique of electrospinning. The ENPBs could separate the cements from the surrounding environment, and therefore can prevent the water-induced collapsibility of CPC and eliminate cement leakage. The ENPBs filling with CPC had enough load-bearing ability to restore the height of the fractured vertebral body and had no obvious effects on the initial strength and stiffness of natural bones. Further, the ENPBs had good biodegradability and cell proliferation ability. Calcium can be released from ENPBs filling with CPC. All these results strongly demonstrate ENPBs can be potentially used as CPC filling containers that keep the advantages and eliminate the disadvantages of CPC. FROM THE CLINICAL EDITOR: Calcium phosphate cement (CPC) is a promising modality in vertebral compression fracture treatment, but its water-induced collapsibility limits clinical applications. This team of investigators fabricated novel nanofibrous balloons using electrospinning, which enabled the separation of CPC from its surrounding environment, and therefore prevented water-induced collapsibility of CPC and eliminated cement leakage while maintaining all the advantages of CPC treatment.

Parvalbumin characteristics in the sonic muscle of a freshwater ornamental grunting toadfish (Allenbatrachus grunniens).

The grunting toadfish, Allenbatrachus grunniens, is an ornamental fish in freshwater aquariums, and it has the ability to produce sounds. The sonic muscle of the toadfish is the fastest vertebrate muscle ever measured, and the rates of Ca(2+) transport and cross-bridge dissociation are also the fastest. Parvalbumins (PAs) are Ca(2+)-binding proteins that help in muscle relaxation in vertebrates. Several PA isoforms have been identified in variable ratios in different muscle types. Both male and female grunting toadfish have intrinsic sonic muscles attached to their swim bladders, but no significant difference in morphology between male and female sonic muscles has been observed. In this study, we used SDS-PAGE and western blotting to characterize the total PA expression and to identify the PAs from the sonic muscle and the white body muscle of A. grunniens. Although the total PA concentrations were similar in sonic and white muscles, there were differences in the isoform percentages. Two and four PA isoforms were identified from sonic muscle and white muscle, respectively. The estimated sizes of PA1, PA2, and PA3 in the sonic muscle of the grunting toadfish were 10, 10.5, and 10.5 kDa, respectively, and the isoelectric points of PA1, PA2, and PA3 in the grunting toadfish were 4.77, 4.58, and 4.42, respectively. In the sonic muscle, the primary PA isoform was PA1, which comprised more than 94 % of total PA, whereas PA2 comprised only 5 % of the total PA content. In contrast, in white muscle, the primary isoform was PA2, which comprised 58 % of the total PA. Both PA1 (with PA1a) and PA3 represented approximately 20 % of the total PA in white muscle. These results indicate that there is no positive correlation between a high PA content and the speed of muscle relaxation; however, PA1 might have the greatest effect on the relaxation of the grunting toadfish's sonic muscle.

Genetic structure and relatedness of juvenile sicklefin lemon shark (Negaprion acutidens) at Dongsha Island.

Negaprion acutidens (sicklefin lemon shark) is distributed in the Indo-Pacific and in close association with coral reefs. Under the protection of the Dongsha Atoll National Park, a small but well-established juvenile population of N. acutidens inhabiting coastal areas of Dongsha Island was recently observed to display site fidelity by using acoustic telemetry. This study was designed to reveal the fine scale genetic structure and relatedness within and among 5 juvenile shark cohorts inhabiting 3 sampling sites at Dongsha Island. A total 188 juveniles were caught and sampled between 2016 and 2017, and genotyped with twelve loci. They were assigned to 5 year cohorts (2013-2017) based on the body length and date they were caught, also assigned to 3 sites based on where they were caught. Among five cohorts, the percentage of unrelated pairs within a cohort is more than 62% in average, suggesting a potential high mortality during their early life stage. The results of Fst and assignment testing showed that there was no significant genetic structure between sites and cohorts indicating that there was no fine scale genetic structure, even though the juveniles possessed strong site fidelity. A small effective population size (Ne) was detected (Ne = 86.7) which indicates the presence of a potentially isolated and vulnerable population at Dongsha. These results provide the genetic diversity as a baseline for future management and conservation of N. acutidens in the South China Sea.

Comparison of Intergrowth-21st and Fenton growth standards to evaluate and predict the postnatal growth in eastern Chinese preterm infants.

Objectives: The aim of this article was to compare the differences between Intergrowth-21st (IG-21) and Fenton growth standards in the classification of intrauterine and extrauterine growth restriction (EUGR) in eastern Chinese preterm infants, and detect which one can better relate to neonatal diseases and predict the physical growth outcomes at 3-5 years old. Methods: Premature infants admitted to a tertiary pediatric hospital in Shanghai, China, from 2016 to 2018 were enrolled. Prenatal information, neonatal diseases during hospitalization, and anthropometric data (weight, height, and head circumference) at birth and at discharge were collected and analyzed. Physical growth outcomes (short stature, thinness, and overweight) were examined by telephone investigations in 2021 at age 3-5 years. Results: The medium gestational age and birth weight of the included 1,065 preterm newborns were 33.6 weeks and 1,900 g, respectively. The IG-21 curves diagnosed more newborns with small for gestational age (SGA) (19% vs. 14.7%) and fewer newborns with longitudinal EUGR on height (25.5% vs. 27.9%) and head circumference (17.9% vs. 24.7%) compared to Fenton curves. Concordances between Fenton and IG-21 standards were substantial or almost perfect in the classification of SGA and longitudinal EUGR, but minor in cross-sectional EUGR. EUGR identified by Fenton curves was better related to neonatal diseases than IG-21 curves. There were no statistical significances in the prediction of short stature, thinness, and overweight at 3-5 years old between the two charts. Conclusions: IG-21 growth standards are not superior to Fenton in assessing preterm growth and development in the eastern Chinese population.

DNA damage-mediated cellular senescence promotes hand-foot syndrome that can be relieved by thymidine prodrug.

Hand-foot syndrome (HFS) is a widely recognized dose-limiting cutaneous toxicity effect of fluoropyrimidine chemotherapy agents that impairs clinical benefits and treatment outcomes. Even though the cause and pathophysiology of HFS are relatively widely reported, how the toxicity of fluoropyrimidine translates into persistent inflammation has not been studied. Additionally, prevention and treatment strategies for HFS based on its mechanistic occurrence and development are scarce. In our study, we demonstrated that cGAS-STING signaling pathway-mediated cellular senescence played a critical role in the inflammatory reaction and provided a therapeutic solution for HFS. Mechanistically, DNA damage, as the primary cytotoxic cause, in keratinocytes induces cell cycle arrest, activates the cGAS-STING signaling pathway, and subsequently mediates cellular senescence, ultimately fueling a robust secondary inflammatory response that results in HFS. More importantly, the thymidine prodrug thymidine diacetate was proven to be effective in preventing HFS by compensating for thymidylate deficiency to facilitate the replication and repair of DNA and thus causing the escape from cellular senescence. These data highlight the importance of DNA damage-mediated cellular senescence in the etiology of HFS and provide a potential therapeutic anchor point for fluoropyrimidine-induced HFS.