Study on the Synthesis of Nano Zinc Oxide Particles under Supercritical Hydrothermal Conditions.

The supercritical hydrothermal synthesis of nanomaterials has gained significant attention due to its straightforward operation and the excellent performance of the resulting products. In this study, the supercritical hydrothermal method was used with Zn(CH3COO)2·2H2O as the precursor and deionized water and ethanol as the solvent. Nano-ZnO was synthesized under different reaction temperatures (300~500 °C), reaction times (5~15 min), reaction pressures (22~30 MPa), precursor concentrations (0.1~0.5 mol/L), and ratios of precursor to organic solvent (C2H5OH) (2:1~1:4). The effects of synthesis conditions on the morphology and size of ZnO were studied. It was found that properly increasing hydrothermal temperature and pressure and extending the hydrothermal time are conducive to the more regular morphology and smaller size of ZnO particles, which is mainly achieved through the change of reaction conditions affecting the hydrothermal reaction rate. Moreover, the addition of ethanol makes the morphology of nano-zno more regular and significantly inhibits the agglomeration phenomenon. In addition to the change in physical properties of the solvent, this may also be related to the chemical bond established between ethanol and ZnO. The results show that the optimum synthesis conditions of ZnO are 450 °C, 26 MPa, 0.3 mol/L, 10 min, and the molar ratio of precursor to ethanol is 1:3.

Synergistic Pore Structure and Active Site Modulation in Co-N-C Catalysts Enabling Stable Zinc-Air Batteries.

Development of cheap, highly active, and durable nonprecious metal-based oxygen electrocatalysts is essential for metal-air battery technology, but achieving the balance of oxygen evolution reaction (OER)/oxygen reduction reaction (ORR) bifunctional performance and long-term durability is still a great challenge. Using a typical Co-N-C catalyst as a model, herein, we introduced ammonium chloride into nitrogen-doped carbon materials containing metal elements during the pyrolysis process (Co-N-C/AC), which not only increases the active area but also realizes the accurate customization of the active site (pyridine nitrogen and cobalt oxide species) so as to achieve the balance of the OER/ORR bifunctional sites. The synthesized Co-N-C/AC bifunctional catalyst with a three-dimensional porous structure exhibits a smaller potential gap of 0.72 V. The peak power density of the aqueous cell at a current density of 308 mA cm-2 is 203 mW cm-2. The cycle life (≈3900 h) is longer than those of other recently reported aqueous Zn-air batteries (ZABs). The peak power density of the Co-N-C/AC-based quasi-solid-state ZAB reaches 550 mW cm-2 for ∼72 h. This work shows a feasible path for the practical application of ZABs by balancing the bifunctional electrocatalysts by tailoring the active site reasonably.

Co-Assembled Supramolecular Organohydrogels of Amphiphilic Zwitterion and Polyoxometalate with Controlled Microstructures.

The organization of modifiable and functional building components into various superstructures is of great interest due to their broad applications. Supramolecular self-assembly, based on rationally designed building blocks and appropriately utilized driving forces, is a promising and widely used strategy for constructing superstructures with well-defined nanostructures and diverse morphologies across multiple length scales. In this study, two homogeneous organohydrogels with distinct appearances were constructed by simply mixing polyoxometalate (phosphomolybdic acid, HPMo) and a double-tailed zwitterionic quaternary ammonium amphiphile in a binary solvent of water and dimethyl sulfoxide (DMSO). The delicate balance between electrostatic attraction and repulsion of anionic HPMo clusters and zwitterionic structures drove them to co-assemble into homogeneous organohydrogels with diverse microstructures. Notably, the morphologies of the organohydrogels, including unilamellar vesicles, onion-like vesicles, and spherical aggregates, can be controlled by adjusting the ionic interactions between the zwitterionic amphiphiles and phosphomolybdic acid clusters. Furthermore, we observed an organohydrogel fabricated with densely stacked onion-like structures (multilamellar vesicles) consisting of more than a dozen layers at certain proportions. Additionally, the relationships between the self-assembled architectures and the intermolecular interactions among the polyoxometalate, zwitterionic amphiphile, and solvent molecules were elucidated. This study offers valuable insights into the mechanisms of polyoxometalate-zwitterionic amphiphile co-assembly, which are essential for the development of materials with specific structures and emerging functionalities.

Designing 3d Transition Metal Cation-Doped MRuOx As Durable Acidic Oxygen Evolution Electrocatalysts for PEM Water Electrolyzers.

The continuous dissolution and oxidation of active sites in Ru-based electrocatalysts have greatly hindered their practical application in proton exchange membrane water electrolyzers (PEMWE). In this work, we first used density functional theory (DFT) to calculate the dissolution energy of Ru in the 3d transition metal-doped MRuOx (M = Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, and Zn) to evaluate their stability for acidic oxygen evolution reaction (OER) and screen out ZnRuOx as the best candidate. To confirm the theoretical predictions, we experimentally synthesized these MRuOx materials and found that ZnRuOx indeed displays robust acidic OER stability with a negligible decay of η10 after 15 000 CV cycles. Of importance, using ZnRuOx as the anode, the PEMWE can run stably for 120 h at 200 mA cm-2. We also further uncover the stability mechanism of ZnRuOx, i.e., Zn atoms doped in the outside of ZnRuOx nanocrystal would form a "Zn-rich" shell, which effectively shortened average Ru-O bond lengths in ZnRuOx to strengthen the Ru-O interaction and therefore boosted intrinsic stability of ZnRuOx in acidic OER. In short, this work not only provides a new study paradigm of using DFT calculations to guide the experimental synthesis but also offers a proof-of-concept with 3d metal dopants as RuO2 stabilizer as a universal principle to develop high-durability Ru-based catalysts for PEMWE.

Epidemic Features and Megagenomic Analysis of Childhood Mycoplasma Pneumoniae post COVID-19 Pandemic: A 6-year Study in Southern China.

With the atypical rise of Mycoplasma pneumoniae infection (MPI) in 2023, prompt studies are needed to determine the current epidemic features and risk factors with emerging trends of MPI to furnish a framework for subsequent investigations. This multicentre, retrospective study was designed to analyse the epidemic patterns of MPI before and after the COVID-19 pandemic, as well as genotypes and the macrolide resistance-associated mutations in MP sampled from pediatric patients in Southern China. Clinical data was collected from 133674 patients admitted into investigational hospitals from June 1, 2017, to November 30, 2023. Metagenomic next-generation sequencing (mNGS) data were retrieved based on MP sequence positive samples from 299 pediatric patients for macrolide resistance-associated mutations analysis. Pearson's chi-squared test was used to compare categorical variables between different time frames. The monthly average cases of pediatric common respiratory infection diseases were increased without enhanced public health measures after the pandemic, especially for influenza, respiratory syncytial virus infection, and MPI. The contribution of MPI to pneumoniae was similar to that in the outbreak in 2019. Compared mNGS data between 2019-2022 and 2023, the severity of MP did not grow stronger despite higher rates of macrolide-resistance hypervariable sites, including loci 2063 and 2064, were detected in childhood MP samples of 2023. Our findings indicated ongoing surveillance is necessary to understand the impact of post pandemic on MP transmission disruption on epidemic season and severity of clinical outcomes in different scenarios.

A ratiometric fluorescent probe revealing the abnormality of acetylated tau by visualizing polarity in Alzheimer's disease.

Abnormal neuronal polarity leads to early deficits in Alzheimer's disease (AD) by affecting the function of axons. Precise and rapid evaluation of polarity changes is very important for the early prevention and diagnosis of AD. However, due to the limitations of existing detection methods, the mechanism related to how neuronal polarity changes in AD is unclear. Herein, we reported a ratiometric fluorescent probe characterized by neutral molecule to disclose the polarity changes in nerve cells and the brain of APP/PS1 mice. Cy7-K showed a sensitive and selective ratiometric fluorescence response to polarity. Remarkably, unlike conventional intramolecular charge transfer fluorescent probes, the fluorescence quantum yield of Cy7-K in highly polar solvents is higher than that in low polar solvents due to the transition of neutral quinones to aromatic zwitterions. Using the ratiometric fluorescence imaging, we found that beta-amyloid protein (Aß) inhibits the expression of histone deacetylase 6, thereby increasing the amount of acetylated Tau protein (AC-Tau) and ultimately enhancing cell polarity. There was a high correlation between polarity and AC-Tau. Furthermore, Cy7-K penetrated the blood-brain barrier to image the polarity of different brain regions and confirmed that APP/PS1 mice had higher polarity than Wild-type mice. The probe Cy7-K will be a promising tool for assessing the progression of AD development by monitoring polarity.

Direct Measurement of Dissolved Gas Using a Tapered Single-Mode Silica Fiber.

Dissolved gases in the aquatic environment are critical to understanding the population of aquatic organisms and the ocean. Currently, laser absorption techniques based on membrane separation technology have made great strides in dissolved gas detection. However, the prolonged water-gas separation time of permeable membranes remains a key obstacle to the efficiency of dissolved gas analysis. To mitigate these limitations, we demonstrated direct measurement of dissolved gas using the evanescent-wave absorption spectroscopy of a tapered silica micro-fiber. It enhanced the analysis efficiency of dissolved gases without water-gas separation or sample preparation. The feasibility of this sensor for direct measurement of dissolved gases was verified by taking the detection of dissolved ammonia as an example. With a sensing length of 5 mm and a consumption of ~50 µL, this sensor achieves a system response time of ~11 min and a minimum detection limit (MDL) of 0.015%. Possible strategies are discussed for further performance improvement in in-situ applications requiring fast and highly sensitive dissolved gas sensing.

Dietary supplementation of osthole and icariin improves the production performance of laying hens by promoting follicular development.

Osthole (Ost) and icariin (Ica) are extracted from traditional Chinese medicine Cnidium monnieri and Epimedii Folium, respectively, and both exhibit estrogen-like biological activity. This study aimed to determine the efficacy and safety of combining Ost with Ica on the production performance of laying hens and to explore their possible mechanisms. The production performance, egg quality, residues of Ost and Ica in eggs, serum reproductive hormone levels, expression of ovarian reproductive hormone receptor, proliferation of granulosa cells in small yellow follicles (SYF), and progesterone secretion in large yellow follicles (LYF) related genes and proteins expression were detected. The results showed that adding 2 mg/kg Ost + 2 mg/kg Ica to the feed increased the laying rate, average egg weight, Haugh unit, and protein height of laying hens. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and progesterone (P4) levels increased, and the expression of ovarian estrogen receptor (ER), follicle-stimulating hormone receptor (FSHR), and progesterone receptor (PGR) mRNA was up-regulated. Additionally, the mRNA and protein levels of steroidogenesis acute regulatory protein (StAR), cytochrome P450 side-chain cleavage (P450scc), and 3ß-hydroxysteroid dehydrogenase (3ß-HSD) increased in LYF. Furthermore, mRNA and protein levels of proliferating cell nuclear antigen (PCNA), cyclin E1, and cyclin A2 were up-regulated in SYF. The residues of Ost and Ica in egg samples were not detected by high-performance liquid chromatography (HPLC). In conclusion, dietary supplementation of Ost and Ica increased granulosa cells proliferation in SYF and increased P4 secretion in granulosa cells of LYF, ultimately improving the production performance of laying hens.

Baicalin ameliorates the gut barrier function and intestinal microbiota of broiler chickens.

The deoxynivalenol (DON)-contaminated feeds can impair chicken gut barrier function, disturb the balance of the intestinal microbiota, decrease chicken growth performance and cause major economic loss. With the aim of investigating the ameliorating effects of baicalin on broiler intestinal barrier damage and gut microbiota dysbiosis induced by DON, a total of 150 Arbor Acres broilers are used in the present study. The morphological damage to the duodenum, jejunum, and ileum caused by DON is reversed by treatment with different doses of baicalin, and the expression of tight junction proteins (ZO-1, claudin-1, and occludin) is also significantly increased in the baicalin-treated groups. Moreover, the disturbance of the intestinal microbiota caused by DON-contaminated feed is altered by baicalin treatment. In particular, compared with those in the DON group, the relative abundances of Lactobacillus, Lachnoclostridium, Ruminiclostridium and other beneficial microbes in the baicalin-treated groups are significantly greater. However, the percentage of unclassified_f__Lachnospiraceae in the baicalin-treated groups is significantly decreased in the DON group. Overall, the current results demonstrate that different doses of baicalin can improve broiler intestinal barrier function and the ameliorating effects on broiler intestinal barrier damage may be related to modulations of the intestinal microbiota.

Cocatalyst Modified Polymeric Carbon Nitride Photoanode for Enhanced Photoelectrochemical Properties.

As a new organic photocatalyst, polymeric carbon nitride (CN) has shown good application potential in the field of photoelectrochemistry due to its unique physical and chemical properties, but its application has been seriously hindered due to its inherent characteristics such as the difficulty in charge separation. In this study, FeOOH modified CN photoanode (CN-Fe) was constructed to investigate the effect of the cocatalyst on the charge injection capacity of organic semiconductor photoelectrodes. The experimental results demonstrate significant improvement in the charge injection efficiency of the photoanode due to the introduction of FeOOH cocatalyst, leading to enhanced photoelectrochemical performance with approximately 2.4 times increase in photocurrent density. By thoroughly investigating the mechanism behind the loading of FeOOH on the polymeric carbon nitride photoanode, we gained profound insights into the behavior of charge carriers and reaction kinetics during the photoelectrocatalytic process.

Integration of hydrothermal liquefaction of Cyanophyta and supercritical water oxidation of its aqueous phase products: Biocrude production and nutrient removal.

Cyanophyta has the potential to produce biocrude via hydrothermal liquefaction (HTL). However, aqueous phase products (APs), as by-products of HTL, pose a risk of eutrophication for the high levels of carbon, nitrogen, and phosphorus. Supercritical water oxidation (SCWO) can efficiently convert organics into small molecules, offering a technique for the harmless treatment of APs. Effects of holding time, pressure, and moisture content on the biocrude yields from isothermal HTL (300 °C) and fast HTL (salt bath temperature of 500 °C) were comprehensively investigated. Biocrude properties were characterized by elemental analysis, FT-IR and GC-MS. Subsequently, the APs obtained under the conditions producing the highest biocrude yield were subjected to SCWO at 550 °C with different oxidation coefficients (n) from 0 to 2. Removal rates of chemical oxygen demand (COD), ammonia nitrogen (NH3-N), and total phosphorus (TP) were further explored. The results show that the highest biocrude yields from isothermal HTL and fast HTL were 24.2 wt% (300 °C, 1800 s, 25 MPa, and 80 wt% moisture content) and 21.9 wt% (500 °C, 40 s, 25 MPa, and 80 wt% moisture content), respectively. The biocrude primarily consisted of N-containing heterocyclic compounds, amides, and acids. SCWO effectively degraded the COD and TP in APs, while the NH3-N required further degradation. At n = 2, the highest removal rates of COD, NH3-N and TP were 98.5 %, 22.6 % and 89.1 %, respectively.

U-shaped relationship between ozone exposure and preterm birth risk associated with preconception telomere length.

There are conflicting findings regarding the association of ozone (O3) exposure with preterm birth (PTB) occurrence. In the present study, two cohorts were combined to explore the relationship between maternal O3 exposure during pregnancy and PTB risk, and analyze the underlying mechanisms of this relationship in terms of alterations in the preconception telomere length. Cohort 1 included mothers who participated in the National Free Preconception Health Examination Project in Henan Province from 2014 to 2018 along with their newborns (n = 1,066,696). Cohort 2 comprised mothers who conceived between 2016 and 2018 and their newborns (n = 1871) from six areas in Henan Province. The telomere length was assessed in the peripheral blood of mothers at the preconception stage. Data on air pollutant concentrations were collected from environmental monitoring stations and individual exposures were assessed using an inverse distance-weighted model. O3 concentrations (100.60 ± 14.13 µg/m3) were lower in Cohort 1 than in Cohort 2 (114.09 ± 15.17 µg/m3). Linear analyses showed that PTB risk decreased with increasing O3 exposure concentrations in Cohort 1 but increased with increasing O3 exposure concentrations in Cohort 2. Nonlinear analyses revealed that PTB risk tended to decrease and then increase with increasing O3 exposure concentrations in both cohorts. Besides, PTB risk was reduced by 88% for each-unit increase in telomere length in those exposed to moderate O3 concentrations (92.4-123.7 µg/m3, P < 0.05). While no significant association was observed between telomere length and PTB at extreme O3 concentration exposure during entire pregnancy (<92.4 or >123.7 µg/m3, P > 0.05) in Cohort 2. These findings reveal a nonlinear (U-shaped) relationship between O3 exposure and PTB risk. Furthermore, telomere with elevated length was associated with decreased risk of PTB only when exposed to moderate concentrations of O3, but not when exposed to extreme concentrations of O3 during pregnancy.

Kinetically Controlled Structural Modulation of the Self-Assembled Silver Nanoclusters.

Metal nanoclusters (NCs) with atomic precision are growing into a fascinating class of building blocks for supramolecular chemistry. What makes it more interesting is the enhanced optical properties of the ordered structures, including aggregation-induced emission (AIE). However, algorithm dictating the self-assembly of metal NCs in multicomponent environment remains largely unknown, and effective means to manipulate the self-assembly is still lacking, especially under kinetic control. Herein, nanofibers which contain sub-1 nm nanowires and exhibit circularly polarized phosphorescence (CPP) are obtained from crystallization-induced self-assembly (CISA) of water-soluble, negatively charged silver NCs (Ag9 -NCs) in the presence of glutamic acid (Glu). By the introduction of a positively-charged additive (choline chloride, CC), the structure of the nanowires is modulated and the lateral interaction between adjacent nanofibers is adjusted, leading to simultaneous improvement of the phosphorescence and chirality which finally enhances CPP. Importantly, changing the time at which CC is introduced altered the kinetic pathway of the CISA, which enables to effectively manipulate both the final structures of the self-assembled Ag9 -NCs and the output of the optical signals.

High-performance aqueous rechargeable NiCo//Zn battery with molybdate anion intercalated CoNi-LDH@CP bilayered cathode.

Seeking cathode materials with high areal capacity and excellent cycling tolerance is a key step to develop aqueous rechargeable zinc-based alkaline batteries with high energy density, power density and excellent stability. Here, the bilayered cathode composite (MCN-LDH@CP) of molybdate intercalated cobalt-nickel layered hydroxide nanosheets (MCN-LDH) grown on cobalt phosphate octahydrate microsheet (CP) was prepared by a two-step hydrothermal process. Molybdate intercalation significantly reduces the thickness of cobalt-nickel layered hydroxide, greatly increases its specific surface area, regulates its pore distribution, increases the crystal plane spacing, promotes the diffusion rate of hydroxide in it, and increases its specific capacity. Meanwhile, the bilayered MCN-LDH@CP electrode significantly improved the areal energy density (2.89 mWh/cm2) and peak power density (111.22 mW/cm2) and cycle stability (97.8 % after 7000 cycles) of the CoNi//Zn battery. The excellent stability is mainly due to the fact that the MCN-LDH overlay inhibits the loss of P element of CP and improves the structural stability of the sample. The quasi-solid-state MCN-LDH@CP//Zn battery can still charge a mobile phone even when hammered and pierced, showing excellent safety and reliability. This work opens a new avenue to develop CoNi//Zn batteries with high energy density, power density and excellent tolerance.

Scutellarin targets Wnt5a against zearalenone-induced apoptosis in mouse granulosa cells in vitro and in vivo.

Zearalenone (ZEA) poses severe reproductive toxicity to both humans and animals. Scutellarin has been demonstrated to rescue ZEA-induced apoptosis in mouse ovarian granulosa cells (GCs), but its specific targets remain unclear. In the present study, the potential targets of scutellarin were determined to clarify the mechanisms of scutellarin against ZEA-induced ovarian damage. 287 targets of scutellarin in mouse ovarian GCs were obtained by magnetic nano-probe-based fishing assay and liquid chromatography-tandem mass spectrometry. Wnt5a had the lowest binding free energy with scutellarin at - 8.3 kcal/mol. QRT-PCR and western blot showed that scutellarin significantly increased the Wnt5a and ß-catenin expression compared with the ZEA-treated group, and cleaved-caspase-3 expression was significantly increased in the scutellarin-treated group after interfering with the expression of Wnt5a. The affinity constant (KD) of Wnt5a and scutellarin was 1.7 × 10-5 M. The pull-down assay also demonstrated that scutellarin could specifically bind to Wnt5a protein. Molecular docking results showed that scutellarin could form hydrogen bonds with TRY52, GLN56, and SER90 on Wnt5a protein, and western blot assay confirmed SER90 was an important site for the binding. Scutellarin significantly increased Wnt5a and ß-catenin expression and decreased cleaved-caspase-3 expression in ovarian tissues of mice. In conclusion, scutellarin exerted anti-apoptotic effects on ZEA-induced mouse ovarian GCs by targeting Wnt5a.

Matrine Targets Intestinal Lactobacillus acidophilus to Inhibit Porcine Circovirus Type 2 Infection in Mice.

Porcine circovirus type 2 (PCV2) has caused huge economic losses to the pig industry across the world. Matrine is a natural compound that has been shown to regulate intestinal flora and has anti-PCV2 activity in mouse models. PCV2 infection can lead to changes in intestinal flora. The intestinal flora has proved to be one of the important pharmacological targets of the active components of Traditional Chinese Medicine. This study aimed to determine whether matrine exerts anti-PCV2 effects by regulating intestinal flora. In this study, fecal microbiota transplantation (FMT) was used to evaluate the effect of matrine on the intestinal flora of PCV2-infected Kunming (KM) mice. The expression of the Cap gene in the liver and the ileum, the relative expression of IL-1ß mRNA, and the Lactobacillus acidophilus (L. acidophilus) gene in the ileum of mice were determined by real-time quantitative polymerase chain reaction (qPCR). ELISA was used to analyze the content of secretory immunoglobulin A (SIgA) in small intestinal fluid. L. acidophilus was isolated and identified from the feces of KM mice in order to study its anti-PCV2 effect in vivo. The expression of the Cap gene in the liver and the ileum and the relative expression of L. acidophilus and IL-1ß mRNA in the ileum were determined by qPCR. The results showed that matrine could reduce the relative expression of IL-1ß mRNA by regulating intestinal flora, and that its pharmacological anti-PCV2 and effect may be related to L. acidophilus. L. acidophilus was successfully isolated and identified from the feces of KM mice. The in vivo experiment revealed that administration of L. acidophilus also reduced the relative expression of IL-1ß mRNA, and that it had anti-PCV2 effects in PCV2-infected mice. It was found that matrine could regulate the abundance of L. acidophilus in the gut of mice to exert an anti-PCV2 effect and inhibit PCV2-induced inflammatory response.

Atomically Precise Copper Nanoclusters for Highly Efficient Electroreduction of CO2 towards Hydrocarbons via Breaking the Coordination Symmetry of Cu Site.

We propose an effective highest occupied d-orbital modulation strategy engendered by breaking the coordination symmetry of sites in the atomically precise Cu nanocluster (NC) to switch the product of CO2 electroreduction from HCOOH/CO to higher-valued hydrocarbons. An atomically well-defined Cu6 NC with symmetry-broken Cu-S2 N1 active sites (named Cu6 (MBD)6 , MBD=2-mercaptobenzimidazole) was designed and synthesized by a judicious choice of ligand containing both S and N coordination atoms. Different from the previously reported high HCOOH selectivity of Cu NCs with Cu-S3 sites, the Cu6 (MBD)6 with Cu-S2 N1 coordination structure shows a high Faradaic efficiency toward hydrocarbons of 65.5 % at -1.4 V versus the reversible hydrogen electrode (including 42.5 % CH4 and 23 % C2 H4 ), with the hydrocarbons partial current density of -183.4 mA cm-2 . Theoretical calculations reveal that the symmetry-broken Cu-S2 N1 sites can rearrange the Cu 3d orbitals with d x 2 - y 2 ${d_{x^2 - y^2 } }$ as the highest occupied d-orbital, thus favoring the generation of key intermediate *COOH instead of *OCHO to favor *CO formation, followed by hydrogenation and/or C-C coupling to produce hydrocarbons. This is the first attempt to regulate the coordination mode of Cu atom in Cu NCs for hydrocarbons generation, and provides new inspiration for designing atomically precise NCs for efficient CO2 RR towards highly-valued products.

Predictive model containing gene signature and shear wave elastography to predict patient outcomes after Kasai surgery in biliary atresia.

AIMS: Infants with biliary atresia (BA) are treated with Kasai portoenterostomy (KPE) surgery, but many BA patients need subsequent salvage liver transplants. The aim of this study is to develop a comprehensive gene-clinical model based on two-dimensional shear wave elastography (2DSWE), liver gene expression, and other clinical parameters to predict response to KPE for BA patients. METHODS: Differentially expressed gene patterns between liver samples of BA (n = 102) and non-BA control (n = 14) were identified using RNA sequencing analysis. Biliary atresia patients were then randomly assigned to training and validation cohorts. Gene classifier based on the differentially expressed genes was built in the training cohort. Nomogram models with and without gene classifier were further constructed and validated for predicting native liver survival of BA patients. The utility of the nomograms was compared by C-index. RESULTS: Using the least absolute shrinkage and selection operator model, we generated a nine-gene prognostic classifier. The nomogram based on the nine-gene classifier, age, preoperative 2DSWE, and albumin had the better C-index compared to gene classifier alone in the training cohort (0.83 [0.76-0.90] vs. 0.69 [0.61-0.77], p = 0.003) and the validation cohort (0.74 [0.67-0.82] vs. 0.62 [0.55-0.70], p = 0.001). Using risk scores developed from the nomogram, the 12-month survival rates of BA patients with native liver were 35.7% (95% confidence interval [CI], 22.7-56.3) in the high-risk group and 80.8% (95% CI, 63.4-100.0) in the low-risk group in the validation cohort. CONCLUSIONS: The comprehensive genetic-clinical nomogram based on preoperative 2DSWE, liver gene expression, and other clinical parameters can accurately predict response to KPE.

Association between baseline C­reactive protein level and survival outcomes for cancer patients treated with immunotherapy: A meta­analysis.

The prognostic impact of baseline C-reactive protein (CRP) in patients with cancer receiving immune checkpoint inhibitors (ICIs) is unclear. The present meta-analysis aimed to review the prognostic value of baseline C-reactive protein (CRP) levels for patients with cancer receiving immunotherapy. Electronic databases, including PubMed, EMbase, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure, WanFang, Chinese Literature Biomedical Database and Weipu Database, were used to identify cohort studies on the relationship between the baseline CRP levels and ICI survival outcomes from inception to November 2020. Literature screening, data extraction and quality evaluation of studies were independently performed by two reviewers. Subsequently, a meta-analysis was performed using STATA 14.0. A total of 13 cohort studies comprising 2,387 patients with cancer were included in the present meta-analysis. The results indicated that high baseline CRP levels (serum CRP measured within 2 weeks before ICI treatment) were associated with low overall survival (OS) and progression-free survival (PFS) rate among patients treated with ICIs. The subgroup analysis based on cancer type showed that high baseline CRP levels were associated with poor survival outcomes of multiple types of cancer, such as non-small cell lung cancer (6/13; 46.2%), melanoma (2/13; 15.4%), renal cell (3/13; 23.0%) and urothelial carcinoma (2/13; 15.4%). Similar results were observed in subgroup analysis based on the CRP cut-off value of 10 mg/l. In addition, a higher mortality risk was reported in patients with cancer and CRP ≥10 mg/l (hazard ratio, 2.76; 95% CI, 1.70-4.48; P<0.001). Compared with patients with low baseline CRP levels, increased baseline CRP levels were associated with low OS and PFS rate in patients with cancer receiving ICIs. Furthermore, CRP ≥10 mg/l indicated a worse prognosis. Therefore, baseline CRP levels may serve as a marker for the prognosis of patients with certain types of solid tumor treated with ICIs. Due to the limited quality and quantity of included studies, more prospective well-designed studies are required to verify the present findings.