Research on Mechanism and Effect of Enhancing Gas Recovery by CO2 Huff-n-Puff in Shale Gas Reservoir.

The technology of CO2-enhanced gas recovery (CO2-EGR) plays a pivotal role in the CCUS (Carbon Capture, Utilization, and Storage) industry, which helps to achieve a win-win situation of economic benefit and environmental benefit for gas fields. Shale gas reservoirs, with their unique geological and surface engineering advantages, are one of the most promising options for CCUS implementation. Focusing on shale formations within the mid-deep blocks of the Sichuan Basin, this study conducted competitive adsorption experiments using multicomponent gases. Through physical simulations and single-well numerical modeling, factors such as injection volume, timing, shut-in time, and huff-n-puff rounds were examined for their impact on recovery. The results show that the higher the CO2 content in the injected medium, the more pronounced advantage in gas adsorption on shale surfaces. Optimal performance was achieved with a CO2 content in the injection medium of 80% to 100%, an injection volume of 0.2-0.3 PV, a shut-in time exceeding 6 h, and a relatively delayed injection timing. The recovery in the first round of huff-n-puff was increased by 24.2% to 47.8%, which gave a full play to the role of huff-n-puff and achieved favorable benefits. Based on the middle-deep geological parameters, a single-well numerical simulation was established, which demonstrates that single-well EUR (estimated ultimate recovery) can be increased by 14.2% to 19.8% compared to gas wells without CO2 injection. This study provides essential guidance for the enhanced recovery in shale gas reservoirs through CO2 huff-n-puff.

Combining Fast Pure Shift NMR and GEMSTONE-Based Selective TOCSY for Efficient NMR Analysis of Complex Systems.

As one of the commonly used intact detection techniques, liquid NMR spectroscopy offers unparalleled insights into the chemical environments, structures, and dynamics of molecules. However, it generally encounters the challenges of crowded or even overlapped spectra, especially when probing complex sample systems containing numerous components and complicated molecular structures. Herein, we exploit a general NMR protocol for efficient NMR analysis of complex systems by combining fast pure shift NMR and GEMSTONE-based selective TOCSY. First, this protocol enables ultrahigh-selective observation on the coupling networks that are totally correlated with targeted resonances or components, even where they are situated in severely overlapped spectral regions. Second, pure shift simplification is introduced to enhance the spectral resolution and further resolve the subspectra containing spectral congestion, thus facilitating the dissection of overlapped spectra. Additionally, sparse sampling accompanied by spectral reconstruction is adopted to significantly accelerate acquisition and improve spectral quality. The advantages of this protocol were demonstrated on different complex sample systems, including a challenging compound of estradiol, a mixture of sucrose and d-glucose, and natural grape juice, verifying its feasibility and power, and boosting the potential application landscapes in various chemical fields.

AbdomenAtlas: A large-scale, detailed-annotated, & multi-center dataset for efficient transfer learning and open algorithmic benchmarking.

We introduce the largest abdominal CT dataset (termed AbdomenAtlas) of 20,460 three-dimensional CT volumes sourced from 112 hospitals across diverse populations, geographies, and facilities. AbdomenAtlas provides 673 K high-quality masks of anatomical structures in the abdominal region annotated by a team of 10 radiologists with the help of AI algorithms. We start by having expert radiologists manually annotate 22 anatomical structures in 5,246 CT volumes. Following this, a semi-automatic annotation procedure is performed for the remaining CT volumes, where radiologists revise the annotations predicted by AI, and in turn, AI improves its predictions by learning from revised annotations. Such a large-scale, detailed-annotated, and multi-center dataset is needed for two reasons. Firstly, AbdomenAtlas provides important resources for AI development at scale, branded as large pre-trained models, which can alleviate the annotation workload of expert radiologists to transfer to broader clinical applications. Secondly, AbdomenAtlas establishes a large-scale benchmark for evaluating AI algorithms-the more data we use to test the algorithms, the better we can guarantee reliable performance in complex clinical scenarios. An ISBI & MICCAI challenge named BodyMaps: Towards 3D Atlas of Human Body was launched using a subset of our AbdomenAtlas, aiming to stimulate AI innovation and to benchmark segmentation accuracy, inference efficiency, and domain generalizability. We hope our AbdomenAtlas can set the stage for larger-scale clinical trials and offer exceptional opportunities to practitioners in the medical imaging community. Codes, models, and datasets are available at https://www.zongweiz.com/dataset.

Screening of polyurethane-degrading microbes using a quenching fluorescence probe by microfluidic droplet sorting.

Excessive use of polyurethane (PU) polymers has led contributed to serious environmental pollution. The plastic recycling technology using microorganisms and enzymes as catalysts offers a promising green and low-carbon approach for managing plastic waste. However, current methods for screening PU-degrading strains suffer from drawbacks such as being time-consuming and inefficient. Herein, we present a novel approach for screening PU-degrading microorganisms using a quenching fluorescent probe along with the fluorescence-activated droplet sorting (FADS). The FPAP could specifically recognize the 4,4'-methylenedianiline (MDA) derivates released from PU degradation, with fluorescence quenching as a response. Based on the approach, we successfully screen two PU-degrading strains (Burkholderia sp. W38 and Bacillus sp. C1). After 20 d of cultivation, strain W38 and C1 could degrade 41.58% and 31.45% of polyester-PU film, respectively. Additionally, three metabolites were identified during the degradation of PU monomer (2,4-toluene diamine, 2,4-TDA) and a proposed degradation pathway was established. Consequently, the fluorescence probe integrated with microfluidic droplet systems, demonstrates potential for the development of innovative PU-biocatalysts. Furthermore, the identification of the 2,4-TDA degradation pathway provides valuable insights that can propel advancements in the field of PU biodegradation.

The dual role of microglia in intracerebral hemorrhage.

Intracerebral hemorrhage has the characteristics of high morbidity, disability and mortality, which has caused a heavy burden to families and society. Microglia are resident immune cells in the central nervous system, and their activation plays a dual role in tissue damage after intracerebral hemorrhage. The damage in cerebral hemorrhage is embodied in the following aspects: releasing inflammatory factors and inflammatory mediators, triggering programmed cell death, producing glutamate induced excitotoxicity, and destroying blood-brain barrier; The protective effect is reflected in the phagocytosis and clearance of harmful substances by microglia, and the secretion of anti-inflammatory and neurotrophic factors. This article summarizes the function of microglia and its dual regulatory mechanism in intracerebral hemorrhage. In the future, drugs, acupuncture and other clinical treatments can be used to intervene in the activation state of microglia, so as to reduce the harm of microglia.

A fatty acid elongase complex regulates cell membrane integrity and septin-dependent host infection by the rice blast fungus.

Very-long-chain fatty acids (VLCFAs) regulate biophysical properties of cell membranes to determine growth and development of eukaryotes, such as the pathogenesis of the rice blast fungus Magnaporthe oryzae. The fatty acid elongase Elo1 regulates pathogenesis of M. oryzae by modulating VLCFA biosynthesis. However, it remains unknown whether and how Elo1 associates with other factors to regulate VLCFA biosynthesis in fungal pathogens. Here, we identified Ifa38, Phs1 and Tsc13 as interacting proteins of Elo1 by proximity labelling in M. oryzae. Elo1 associated with Ifa38, Phs1 and Tsc13 on the endoplasmic reticulum (ER) membrane to control VLCFA biosynthesis. Targeted gene deletion mutants Δifa38, Δphs1 and Δtsc13 were all similarly impaired as Δelo1 in vegetative growth, conidial morphology, stress responses in ER, cell wall and membrane. These deletion mutants also displayed severe damage in cell membrane integrity and failed to organize the septin ring that is essential for penetration peg formation and pathogenicity. Our study demonstrates that M. oryzae employs a fatty acid elongase complex to regulate VLCFAs for maintaining or remodelling cell membrane structure, which is important for septin-mediated host penetration.

Highly sensitive turn-on electrochemical sensing of organophosphorus pesticides by integration of homogeneous reaction and heterogeneous catalytic signal amplification.

Enzyme-inhibited electrochemical sensor is a promising strategy for detecting organophosphorus pesticides (OPs). However, the poor stability of enzymes and the high oxidation potential of thiocholine signal probe limit their potential applications. To address this issue, an indirect strategy was proposed for highly sensitive and reliable detection of chlorpyrifos by integrating homogeneous reaction and heterogeneous catalysis. In the homogeneous reaction, Hg2+ with low oxidation potential was employed as signal probe for chlorpyrifos detection since its electroactivity can be inhibited by thiocholine, which was the hydrolysate of acetylthiocholine catalyzed by acetylcholinesterase. Additionally, Co,N-doped hollow porous carbon nanocage@carbon nanotubes (Co,N-HPNC@CNT) derived from ZIF-8@ZIF-67 was utilized as high-performance electrode material to amplify the stripping voltammetry signal of Hg2+. Thanks to their synergistic effect, the sensor exhibited outstanding sensing performance, excellent stability and good anti-interference ability. This strategy paves the way for the development of high-performance OP sensors and their application in food safety.

A nomogram combining neutrophil to lymphocyte ratio (NLR) and prognostic nutritional index (PNI) to predict distant metastasis in gastric cancer.

In this study, We aim to explore the association between the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), systemic immune-inflammatory index (SII), lymphocyte to monocyte ratio (LMR) and prognostic nutritional index (PNI) and distant metastasis of gastric cancer and develop an efficient nomogram for screening patients with distant metastasis. A total of 1281 inpatients with gastric cancer were enrolled and divided into the training and validation set.Univariate, Lasso regression and Multivariate Logistic Regression Analysis was used to identify the risk factors of distant metastasis. The independent predictive factors were then enrolled in the nomogram model. The nomogram's predictive perform and clinical practicality was evaluated by receiver operating characteristics (ROC) curves, calibration curves and decision curve analysis. Multivariate Logistic Regression Analysis identified D-dimer, CA199, CA125, NLR and PNI as independent predictive factors. The area under the curve of our nomogram based on these factors was 0.838 in the training cohort and 0.811 in the validation cohort. The calibration plots and decision curves demonstrated the nomogram's good predictive performance and clinical practicality in both training and validation cohort. Therefore,our nomogram could be an important tool for clinicians in screening gastric cancer patients with distant metastasis.

Emergency preparedness in the central sterile supply department: a multicenter cross-sectional survey.

OBJECTIVE: To investigate the current situation of emergency preparation and emergency drill in the CSSD, and analyze its influence on the nurses' emergency attitude and ability. METHODS: This study employed a multicenter stratified sampling method, conducted from January to June 2023 using the online survey, participants completed the general data, emergency preparedness and drill questionnaire, public health emergency response questionnaire and emergency capacity scale. An independent samples t test or Kruskal-Wallis test was used to analyse differences in nurses' emergency capacity and attitudes. RESULTS: The data from 15 provinces 55 hospitals in China. Overall, 77.58% of participants' institutions set up emergency management teams, 85.45% have an emergency plan and revise it regularly. 92.12% store emergency supplies. All survey staff participated in the emergency drill, which predominantly consisted of individual drills (51.52%), with 90.30% being real combat drills, 49.09% of participants engaging in drills every quarter, and 91.52% of the drill's participants exceeding 50%. The respondents' emergency attitude score was (29.346 ± 6.029), their emergency ability score was (63.594 ± 10.413), and those with rescue experience showed a more positive attitude (Z = -2.316, P = 0.021). Different titles, education levels, rescue experience and the frequency of emergency drill affected the emergency rescue ability of the respondents (P < 0.05). CONCLUSIONS: Most medical institutions establish emergency management systems and plans, yet the content lacks geographical specificity.The duration and participation of emergency drills are high, but the effectiveness of the drills needs to be further improved, and the response capacity and attitudes of CSSD nurses are low. It is recommended that agencies develop comprehensive and targeted contingency plans to strengthen the inspection and evaluation of team strength, equipment and safeguards against the contingency plans, so as to ensure that the measures mandated by the contingency plans can be implemented promptly after the emergency response is initiated.

Cascade Electrocatalytic Nitrate Reduction Reaching 100% Nitrate-N to Ammonia-N Conversion over Cu2O@CoO Yolk-Shell Nanocubes.

The electroreduction of nitrate to ammonia via a selective eight-electron transfer nitrate reduction reaction offers a promising, low energy consumption, pollution-free, green NH3 synthesis strategy alternative to the Haber-Bosch method. However, it remains a great challenge to achieve high NH4+ selectivity and complete conversion from NO3--N to NH4+-N. Herein, we report ingredients adjustable Cu2O@CoO yolk-shell nanocubes featured with tunable inner void spaces and diverse activity centers, favoring the rapid cascade conversion of NO3- into NO2- on Cu2O and NO2- into NH4+ on CoO. Cu2O@CoO yolk-shell nanocubes exhibit super NH4+ Faradaic efficiencies (>99%) over a wide potential window (-0.2 V to -0.9 V versus RHE) with a considerable NH4+ yield rate of 15.27 mg h-1 cm-2 and fantastic cycling stability and long-term chronoamperometric durability. Cu2O@CoO yolk-shell nanocubes exhibited glorious NO3--N to NH4+-N conversion efficiency in both dilute (500 ppm) and highly concentrated (0.1 and 1 M) NO3- electrolytes, respectively. The nitrate electrolysis membrane electrode assembly system equipped with Cu2O@CoO yolk-shell nanocubes delivers over 99.8% NH4+ Faradaic efficiency at cell voltages of 1.9-2.3 V.

Recent Advances in Targeted Cancer Therapy: Are PDCs the Next Generation of ADCs?

Antibody-drug conjugates (ADCs) comprise antibodies, cytotoxic payloads, and linkers, which can integrate the advantages of antibodies and small molecule drugs to achieve targeted cancer treatment. However, ADCs also have some shortcomings, such as non-negligible drug resistance, a low therapeutic index, and payload-related toxicity. Many studies have focused on changing the composition of ADCs, and some have even further extended the concept and types of targeted conjugated drugs by replacing the targeted antibodies in ADCs with peptides, revolutionarily introducing peptide-drug conjugates (PDCs). This Perspective summarizes the current research status of ADCs and PDCs and highlights the structural innovations of ADC components. In particular, PDCs are regarded as the next generation of potential targeted drugs after ADCs, and the current challenges of PDCs are analyzed. Our aim is to offer fresh insights for the efficient design and expedited development of innovative targeted conjugated drugs.

Patterns of neurogenic lower urinary tract dysfunction management and associated factors among Chinese community-dwelling individuals with spinal cord injury.

To identify different patterns of neurogenic lower urinary tract dysfunction management among Chinese community-dwelling individuals with spinal cord injury and explore the factors associated with latent classes. This was a cross-sectional study conducted in communities throughout China Mainland. Participants were recruited through the China Association of Persons with Physical Disability and a total of 2582 participants was included in the analysis. The data were collected by a questionnaire consisting of socio-demographic factors, disease-related factors, and a list of 8 bladder management methods. Latent class analysis was used to identify different latent classes of neurogenic lower urinary tract dysfunction management. Then the multinomial logistic regression was applied to analyze the relationship between neurogenic lower urinary tract dysfunction management patterns and socio-demographic and disease-related factors. Neurogenic lower urinary tract dysfunction management pattern among community-dwelling individuals with spinal cord injury was divided into four latent classes: "urinal collecting apparatus dominated pattern" (40.3%), "bladder compression dominated pattern" (30.7%), "intermittent catheterization dominated pattern" (19.3%) and "urethral indwelling catheterization dominated pattern" (9.6%). Multinomial logistic regression analysis found that the employment status, residential region, nursing need, payment method for catheterization products, hand function, time since spinal cord injury, urinary incontinence and concerns about social interaction affected by urination problems were significantly associated with latent classes. Only 19.3% of people used the intermittent catheterization as their main neurogenic lower urinary tract dysfunction management method. More attention needs to be paid to the promotion of the standardization process of intermittent catheterization in community-dwelling individuals with spinal cord injury. The associated factors of the four classes can be used for tailored and targeted interventions to increase the use of intermittent catheterization.

[Recent progress of chromatographic techniques for antibody purification].

Antibody drugs are becoming increasingly popular in disease diagnosis, targeted therapy, and immunoprevention owing to their characteristics of high targeting ability, strong specificity, low toxicity, and mild side effects. The demand for antibody drugs is steadily increasing, and their production scale is expanding. Upstream cell culture technology has been greatly improved by the high-capacity production of monoclonal antibodies. However, the downstream purification of antibodies presents a bottleneck in the production process. Moreover, the purification cost of antibodies is extremely high, accounting for approximately 50%-80% of the total cost of antibody production. Chromatographic technology, given its selectivity and high separation efficiency, is the main method for antibody purification. This process usually involves three stages: antibody capture, intermediate purification, and polishing. Different chromatographic techniques, such as affinity chromatography, ion-exchange chromatography, hydrophobic interaction chromatography, mixed-mode chromatography, and temperature-responsive chromatography, are used in each stage. Affinity chromatography, mainly protein A affinity chromatography, is applied for the selective capture and purification of antibodies from raw biofluids or harvested cell culture supernatants. Other chromatographic techniques, such as ion-exchange chromatography, hydrophobic interaction chromatography, and mixed-mode chromatography, are used for intermediate purification and antibody polishing. Affinity biomimetic chromatography and hydrophobic charge-induction chromatography can produce antibodies with purities comparable with those obtained through protein A chromatography, by employing artificial chemical/short peptide ligands with good selectivity, high stability, and low cost. Temperature-responsive chromatography is a promising technique for the separation and purification of antibodies. In this technique, antibody capture and elution is controlled by simply adjusting the column temperature, which greatly eliminates the risk of antibody aggregation and inactivation under acidic elution conditions. The combination of different chromatographic methods to improve separation selectivity and achieve effective elution under mild conditions is another useful strategy to enhance the yield and quality of antibodies. This review provides an overview of recent advances in the field of antibody purification using chromatography and discusses future developments in this technology.

SNP-slice resolves mixed infections: simultaneously unveiling strain haplotypes and linking them to hosts.

MOTIVATION: Multi-strain infection is a common yet under-investigated phenomenon of many pathogens. Currently, biologists analyzing SNP information sometimes have to discard mixed infection samples as many downstream analyses require monogenomic inputs. Such a protocol impedes our understanding of the underlying genetic diversity, co-infection patterns, and genomic relatedness of pathogens. A scalable tool to learn and resolve the SNP-haplotypes from polygenomic data is an urgent need in molecular epidemiology. RESULTS: We develop a slice sampling Markov Chain Monte Carlo algorithm, named SNP-Slice, to learn not only the SNP-haplotypes of all strains in the populations but also which strains infect which hosts. Our method reconstructs SNP-haplotypes and individual heterozygosities accurately without reference panels and outperforms the state-of-the-art methods at estimating the multiplicity of infections and allele frequencies. Thus, SNP-Slice introduces a novel approach to address polygenomic data and opens a new avenue for resolving complex infection patterns in molecular surveillance. We illustrate the performance of SNP-Slice on empirical malaria and HIV datasets and provide recommendations for using our method on empirical datasets. AVAILABILITY AND IMPLEMENTATION: The implementation of the SNP-Slice algorithm, as well as scripts to analyze SNP-Slice outputs, are available at https://github.com/nianqiaoju/snp-slice.

Associations between news coverage, social media discussions, and search trends about celebrity deaths, screening, and other colorectal cancer-related events.

OBJECTIVE: Colorectal cancer (CRC) is the third leading cause of cancer death among both men and women in the United States. CRC-related events may increase media coverage and public attention, boosting awareness and prevention. This study examined associations between several types of CRC events (including unplanned celebrity cancer deaths and planned events like national CRC awareness months, celebrity screening behavior, and screening guideline changes) and news coverage, Twitter discussions, and Google search trends about CRC and CRC screening. METHODS: We analyzed data from U.S. national news media outlets, posts scraped from Twitter, and Google Trends on CRC and CRC screening during a three-year period from 2020 to 2022. We used burst detection methods to identify temporal spikes in the volume of news, tweets, and search after each CRC-related event. RESULTS: There is a high level of heterogeneity in the impact of celebrity CRC events. Celebrity CRC deaths were more likely to precede spikes in news and tweets about CRC overall than CRC screening. Celebrity screening preceded spikes in news and tweets about screening but not searches. Awareness months and screening guideline changes did precede spikes in news, tweets, and searches about screening, but these spikes were inconsistent, not simultaneous, and not as large as those events concerning most prominent public figures. CONCLUSIONS: CRC events provide opportunities to increase attention to CRC. Media and public health professionals should actively intervene during CRC events to increase emphasis on CRC screening and evidence-based recommendations.

Fast Pure Shift NMR Spectroscopy Using Attention-Assisted Deep Neural Network.

Pure shift NMR spectroscopy enables the robust probing on molecular structure and dynamics, benefiting from great resolution enhancements. Despite extensive application landscapes in various branches of chemistry, the long experimental times induced by the additional time dimension generally hinder its further developments and practical deployments, especially for multi-dimensional pure shift NMR. Herein, this study proposes and implements the fast, reliable, and robust reconstruction for accelerated pure shift NMR spectroscopy with lightweight attention-assisted deep neural network. This deep learning protocol allows one to regain high-resolution signals and suppress undersampling artifacts, as well as furnish high-fidelity signal intensities along with the accelerated pure shift acquisition, benefitting from the introduction of the attention mechanism to highlight the spectral feature and information of interest. Extensive results of simulated and experimental NMR data demonstrate that this attention-assisted deep learning protocol enables the effective recovery of weak signals that are almost drown in the serious undersampling artifacts, and the distinction and recognition of close chemical shifts even though using merely 5.4% data, highlighting its huge potentials on fast pure shift NMR spectroscopy. As a result, this study affords a promising paradigm for the AI-assisted NMR protocols toward broader applications in chemistry, biology, materials, and life sciences, and among others.

Synthesis of Ordered Mesoporous Silica with Nonionic Surfactant/Anionic Polyelectrolyte as Template under Near-Neutral pH Conditions.

Ordered mesoporous silica is widely used in catalysis, adsorption, and biomedicine, among which SBA-15 (Santa Barbara Amorphous-15) is one of the most widely studied. However, the synthesis of SBA-15 often requires strong acid (hydrochloric acid or sulfuric acid), which will not only corrode industrial equipment but also pollute the environment with the wastewater containing strong acid and halogen (sulfur). Here, we demonstrate a green synthetic strategy for SBA-15 under weakly acidic conditions through an anionic assembly route. With the assistance of poly(acrylic acid) (PAA) and 3-aminopropyltrimethoxysilane (APMS), the pH value of the synthesis system can be increased to 4-5, which is a mild near-neutral condition. In addition, halogen-free synthesis using organic acids is also achieved. The powder X-ray diffraction (XRD), transmission electron microscopy (TEM), and N2 sorption characterizations show that the obtained SBA-15 has good texture properties, with a specific surface area of 430-500 m2/g and ordered 6-8 nm mesopores, which is similar to SBA-15 synthesized in traditional strong acid. This strategy provides a facile and environmentally friendly route for the large-scale production of ordered mesoporous materials.

Cranial bone thickness and density anomalies quantified from CT images can identify chronic increased intracranial pressure.

PURPOSE: The diagnosis of chronic increased intracranial pressure (IIP)is often based on subjective evaluation or clinical metrics with low predictive value. We aimed to quantify cranial bone changes associated with pediatric IIP using CT images and to identify patients at risk. METHODS: We retrospectively quantified local cranial bone thickness and mineral density from the CT images of children with chronic IIP and compared their statistical differences to normative children without IIP adjusting for age, sex and image resolution. Subsequently, we developed a classifier to identify IIP based on these measurements. Finally, we demonstrated our methods to explore signs of IIP in patients with non-syndromic sagittal craniosynostosis (NSSC). RESULTS: We quantified a significant decrease of bone density in 48 patients with IIP compared to 1,018 normative subjects (P < .001), but no differences in bone thickness (P = .56 and P = .89 for age groups 0-2 and 2-10 years, respectively). Our classifier demonstrated 83.33% (95% CI: 69.24%, 92.03%) sensitivity and 87.13% (95% CI: 84.88%, 89.10%) specificity in identifying patients with IIP. Compared to normative subjects, 242 patients with NSSC presented significantly lower cranial bone density (P < .001), but no differences were found compared to patients with IIP (P = .57). Of patients with NSSC, 36.78% (95% CI: 30.76%, 43.22%) presented signs of IIP. CONCLUSION: Cranial bone changes associated with pediatric IIP can be quantified from CT images to support earlier diagnoses of IIP, and to study the presence of IIP secondary to cranial pathology such as non-syndromic sagittal craniosynostosis.

All-in-one strategy to develop a near-infrared triggered multifunctional bioactive magnesium phosphate bone cement for bone repair.

Bone cement is widely used in clinical with optimistic filling and mechanical properties. However, the setting time of bone cement is difficult to accurately control, and the existing bone cements exhibit limited therapeutic functionalities. In response to these challenges, we designed and synthesized Nd-doped whitlockite (Nd-WH), endowing bone cement with photothermal-responsive and fluorescence imaging capabilities. The doping amount and photothermal properties of Nd-doped whitlockite were studied, and the composite bone cement was prepared. The results showed that the setting time of bone cement could be regulated by near infrared irradiation, and the multiple functions of promoting osteogenic differentiation, antibacterial and anti-tumor could be realized by adjusting the power and irradiation time of near infrared. By incorporating Nd-doped whitlockite and bone cement, we developed an all-in-one strategy to achieve setting time control, enhanced osteogenic ability, tumor cell clearance, bacterial clearance, and bone tissue regeneration. The optimized physical and mechanical properties of composite bone cement ensure adaptability and plasticity. In vitro and in vivo experiments validated the effectiveness of this bone cement platform for bone repair, tumor cell clearance and bacterial clearance. The universal methods to regulate the setting time and function of bone cement by photothermal effect has potential in orthopedic surgery and is expected to be a breakthrough in the field of bone defect repair. Further research and clinical validation are needed to ensure its safety, efficacy and sustainability. STATEMENT OF SIGNIFICANCE: Bone cement is a valuable clinical material. However, the setting time of bone cement is difficult to control, and the therapeutic function of existing bone cement is limited. Various studies have shown that the bone repair capacity of bone cements can be enhanced by synergistic stimulatory effects in vivo and ex vivo. Unfortunately, most of the existing photothermal conversion materials are non-degradable and poorly biocompatible. This study provides a bone-like photothermal conversion material with photothermal response and fluorescence imaging properties, and constructed a platform for integrated regulation of the setting time of bone cement and diversification of its functions. Therefore, it helps to design multi-functional bone repair materials that are more convenient and effective in clinical operation.

Compound heterozygous ABCA12 variants identified in a Chinese patient with congenital ichthyosiform erythroderma: Advancing genotype-phenotype correlations and literature review.

BACKGROUND: Ichthyosis is a common keratotic skin disease with high clinical, etiological and genetic heterogeneity. There are four types of non-syndromic hereditary ichthyoses, among which autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of recessive Mendelian disorders. ARCI present with different phenotypes and ABCA12 pathogenic variants have been shown to cause complex ARCI phenotypes, including harlequin ichthyosis (HI), lamellar ichthyosis (LI) and congenital ichthyosiform erythroderma (CIE). METHODS: A sporadic male patient, clinically diagnosed with CIE, was enrolled in this study. Exome sequencing was combined with Sanger sequencing to confirm the diagnosis and identify the pathogenic variants. In silico predictions were made using multiple software programs, and the identified variants were interpreted using the ACMG guidelines. A review of all literature reported ABCA12 variants was performed to explore genotype-phenotype correlations. RESULTS: Compound heterozygous ABCA12 variants [c.5381+1G>A and c.5485G>C (p.Asp1829His)] (NM_173076) were identified. The two variants were not detected in the public database. c.5381+1G>A is predicted to affect ABCA12 mRNA splicing and Asp1829 is highly conserved among various species. In silico analysis suggested that these two variants were responsible for the phenotype of the patient. Genotype-phenotype correlation analysis showed that biallelic truncation variants and/or exon/amino acid deletions in ABCA12 are the most common causes of HI. Biallelic missense variants are most common in LI and CIE. CONCLUSIONS: The compound heterozygous ABCA12 variants caused the CIE phenotype observed in the patient. The spectrum of ABCA12 pathogenic variants were broaden. Genotype-phenotype correlation analysis provided detailed evidence which can be used in future prenatal diagnosis and can inform the need for genetic counselling for patients with ABCA12-related ARCIs.