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In this study, an effective composite material, manganese-modified magnetic dual-sludge biochar (Mn@MDSBC), was developed for the adsorption of ciprofloxacin hydrochloride (CIP). This composite was prepared by means of a simple one-pot method, which involved the pyrolysis of iron-based waterworks sludge (IBWS) and paper mill sludge (PMS) loaded with manganese (Mn) under controlled conditions in a nitrogen atmosphere. The synthesized Mn@MDSBC was subjected to a comprehensive suite of characterization approaches, which included N2 adsorption–desorption, X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS). Subsequently, static adsorption tests were conducted to investigate how different factors, including the initial solution pH, reaction time and temperature, CIP concentration, and ionic strength influence the adsorption of CIP by Mn@MDSBC. Mn@MDSBC had the maximum CIP adsorption capacity of 75.86 mg/g at pH 5, among the pH values ranging from 3 to 9. The pseudo-second order model provided the best description of the adsorption process, while the experimental data aligned more closely with the Langmuir equation than with the Freundlich model, indicating monolayer adsorption. The adsorption process was found to be non-spontaneous and exothermic according to thermodynamic analysis. The presence of Cl− and SO42− enhanced CIP adsorption, while PO43− weakened it. After five cycles of reuse, Mn@MDSBC experienced a 17.17% loss in CIP adsorption capacity. The primary mechanisms for CIP removal by Mn@MDSBC were identified as physical and chemical adsorption, hydrogen bonding, and π-π stacking interactions. In summary, the study underscores the high efficiency of Mn@MDSBC as a composite material for CIP adsorption, highlighting its potential for application in wastewater treatment processes.

Objective This study aimed to comprehensively analyze the detection capacity of non-invasive prenatal testing (NIPT) for chromosomal abnormalities of all 24 chromosomes, as well as high-risk indications for pregnancy and the fetal fraction, in a large cohort. Methods We retrospectively enrolled 118,969 pregnant women who underwent NIPT at Sichuan Provincial Maternity and Child Health Care Hospital from March 2019 to June 2022. The sensitivity, specificity, positive predictive value, negative predictive value, and positive chromosomal abnormality rate were calculated. The fetal fraction based on gestational age, maternal body mass index, and number was examined. Results NIPT demonstrated > 99% sensitivity and specificity for almost all of the common trisomies (T21, T18, and T13), sex chromosomal aneuploidies, rare autosomal trisomies, and microdeletion/microduplication syndromes. Positive predictive values varied from 12.0% to 89.6%. Advanced maternal age was associated with an increased risk of three major aneuploidies. The fetal fraction was positively correlated with gestational age and negatively correlated with the maternal body mass index. Conclusions NIPT can be used to effectively screen for chromosomal abnormalities across all 24 chromosomes. Advanced maternal age is a risk factor for high-risk pregnancy, and careful consideration of the fetal fraction is essential during NIPT.

In this study, activated carbon, iron-based waterwork sludge, and polyethyleneimine (PEI) were employed as the primary raw materials to synthesize the composite PEI@MMI(800) under the optimized conditions identified through experimental investigations. The resulting composite was employed as an adsorbent for static Cr(VI) adsorption tests. The results demonstrated that increasing the pH from 2 to 9 significantly decreased the Cr(VI) adsorption capacity from 41.09 mg/g to 15.75 mg/g. The adsorption process was well described by both the pseudo-second-order kinetic model and the Langmuir isotherm model. Thermodynamic analysis revealed that the adsorption process was spontaneous and endothermic in nature. The presence of anions (Cl−, SO42−, and PO43−) negatively impacted Cr(VI) adsorption, with their inhibitory effects following the order Cl− < SO42− < PO43−. Moreover, higher concentrations of these anions led to reduced Cr(VI) adsorption efficiency. After six cycles of use, PEI@MMI(800) retained 79.80% of its initial Cr(VI) adsorption capacity, indicating a loss of 20.20%. Based on the comprehensive characterization of the adsorbent and the results of the Cr(VI) adsorption tests, it was concluded that the removal of Cr(VI) by PEI@MMI(800) involved a combination of electrostatic adsorption, chelation of Cr(VI) by PEI, and reduction of Cr(VI) to Cr(III).

Background Few co-occurrence cases of mosaic aneuploidy and uniparental disomy (UPD) chromosomes have been reported in prenatal periods. It is a big challenge for us to predict fetal clinical outcomes with these chromosome abnormalities because of their highly heterogeneous clinical manifestations and limited phenotype attainable by ultrasound. Methods Amniotic fluid samples were collected from four cases. Karyotype, chromosome microarray analysis, short tandem repeats, and whole exome sequencing were adopted to analyze fetal chromosomal aneuploidy, UPD, and gene variation. Meanwhile, CNVseq analysis proceeded for cultured and uncultured amniocytes in case 2 and case 4 and MS-MLPA for chr11 and chr15 in case 3. Results All four fetuses showed mosaic chromosomal aneuploidy and UPD simultaneously. The results were: Case 1: T2(7%) and UPD(2)mat(12%). Case 2: T15(60%) and UPD(15)mat(40%). Case 3: 45,X(13%) and genome-wide paternal UPD(20%). Case 4: <10% of T20 and > 90% UPD(20)mat in uncultured amniocyte. By analyzing their formation mechanism of mosaic chromosomal aneuploidy and UPD, at least two adverse genetic events happened during their meiosis and mitosis. The fetus of case 1 presented a benign with a normal intrauterine phenotype, consistent with a low proportion of trisomy cells. However, the other three fetuses had adverse pregnancy outcomes, resulting from the UPD chromosomes with imprinted regions involved or a higher level of mosaic aneuploidy. Conclusion UPD is often present with mosaic aneuploidy. It is necessary to analyze them simultaneously using a whole battery of analyses for these cases when their chromosomes with imprinted regions are involved or known carriers of a recessive allele. Fetal clinical outcomes were related to the affected chromosomes aneuploidy and UPD, mosaic levels and tissues, methylation status, and homozygous variation of recessive genes on the UPD chromosome. Genetic counseling for pregnant women with such fetuses is crucial to make informed choices.

Background High sequence homology between CYP21A2 and CYP21A1P poses challenges to genetic diagnosis of congenital adrenal hyperplasia (CAH) due to 21‐hydroxylase deficiency (21‐OHD). Traditional genetic testing is unable to provide an accurate diagnosis due to the genetic complexity of CAH. Methods Deletions, duplications, and recombination breakpoints were precisely identified by long‐read sequencing (LRS). Results This study presented a pregnant woman, a 21‐OHD carrier detected by MLPA, and her husband, a normal subject also detected by MLPA. The fetus was suspected of having 21‐OHD based on clinical presentations such as enlarged adrenal glands, atypical external genitalia and karyotyping of 46, XX. LRS further identified the fetus as having the most severe salt‐wasting (SW) form of 21‐OHD with a compound heterozygote genotype. One allele was TNXA/TNXB CH‐2, while the other allele was CYP21A1P/CYP21A2 CH‐8. LRS precisely determined the genotypes of the fetus's father and grandmother with duplications, which misdiagnosed by MLPA. The multidisciplinary team recommended immediate glucocorticoid and mineralocorticoid treatment for the child after birth to prevent life‐threatening adrenal crisis. Conclusions LRS provides precise diagnosis for family members with CYP21A2 deletion or duplication, improving disease management and preventing potential adrenal crises. When used in pre‐pregnancy genetic testing, LRS can indicate high genetic risk and guide the appropriate therapy during pregnancy and immediately after birth. Long‐read sequencing (LRS) based on the long‐rang PCR identified the genetic complexities such as the deletion chimeras and duplicated CYP21A2 in congenital adrenal hyperplasia, enabling the precise diagnosis for the family pedigree.

In the digital economy era, the value of data elements has grown significantly, especially in the transportation sector, which boasts an extensive repository of transportation data assets. This study proposes a Stackelberg game-theoretic pricing model to optimize the utilization of these data elements. The model delves into the complexities of trading transportation data assets, exploring unique market trading strategies and pricing mechanisms. Focusing on a marketplace with a single seller and multiple buyers, the seller preprocesses data for platform distribution while devising strategic actions, simultaneously aligning with buyers' acquisition strategies. Leveraging the interplay between buyers and sellers, the model employs backward induction to demonstrate the existence and uniqueness of the game solution, followed by a comprehensive numerical analysis. The results indicate that data quality and market risks significantly influence unit pricing, transaction volumes, and the profits of all stakeholders. This method seeks to improve the accuracy of transportation data asset valuation by integrating essential data elements pertinent to trading entities. It provides a robust theoretical foundation for the management and decision-making processes related to transportation data assets.

Background: Tandem repeats (TRs) are highly prone to variation in copy numbers due to their repetitive and unstable nature, which makes them a major source of genomic variation between individuals. However, population variation of TRs has not been widely explored due to the limitations of existing approaches, which are either low-throughput or restricted to a small subset of TRs. Here, we demonstrate a targeted sequencing approach combined with Nanopore sequencing to overcome these limitations. Methods: We selected 142 TR targets and enriched these regions using Agilent SureSelect target enrichment approach with only 200 ng of input DNA. We barcoded the enriched products and sequenced on Oxford Nanopore MinION sequencer. We used VNTRTyper and Tandem-genotypes to genotype TRs from long-read sequencing data. Gold standard PCR sizing analysis was used to validate genotyping results from targeted sequencing data.  Results: We achieved an average of 3062-fold target enrichment on a panel of 142 TR loci, generating an average of 97X coverage per sample with 200 ng of input DNA per sample. We successfully genotyped an average of 75% targets and genotyping rate increased to 91% for the highest-coverage sample for targets with length less than 2 kb, and GC content greater than 25%. Alleles estimated from targeted long-read sequencing were concordant with gold standard PCR sizing analysis and highly correlated with alleles estimated from whole genome long-read sequencing. Conclusions: We demonstrate a targeted long-read sequencing approach that enables simultaneous analysis of hundreds of TRs and accuracy is comparable to PCR sizing analysis. Our approach is feasible to scale for more targets and more samples facilitating large-scale analysis of TRs.

Background: Tandem repeats (TRs) are highly prone to variation in copy numbers due to their repetitive and unstable nature, which makes them a major source of genomic variation between individuals. However, TRs are not been explored in the context of genomic variation, due to the limitations of existing tools, which are either low-throughput or restricted to a small subset of TRs. Here, we report a targeted sequencing approach combined with long-read sequencing technologies to overcome these limitations. Our approach described here presents an accurate and cost-effective method to explore TRs at the population level. Results: We report targeted enrichment of 142 TR loci using sequence capture combined with Nanopore and PacBio sequencing. We achieved 50-60% on-target sequence reads and an average of 100X sequence coverage per sample with Nanopore sequencing using 200ng of input DNA. Genotyping estimates from targeted long-read sequencing were equivalent to the accuracy of gold standard PCR sizing analysis with correlation greater than 0.98 for both Nanopore and PacBio sequencing. Genotyping estimates from targeted long-read sequencing were determined using two different methods (VNTRTyper and Tandem-genotypes) and results were comparable. Furthermore, genotyping estimates from targeted long-read sequencing were highly correlated with genotyping estimates from whole genome long-read sequencing. Conclusions: We demonstrate a targeted long-read sequencing approach that enables simultaneous analysis of hundreds of TRs and accuracy is comparable to PCR sizing analysis. Our approach is feasible to scale for more targets and more samples facilitating large-scale analysis of TRs.

Address Space Layout Randomization (ASLR) is one of the most prominently deployed mitigations against memory corruption attacks. ASLR randomly shuffles program virtual addresses to prevent attackers from knowing the location of program contents in memory. Microarchitectural side channels have been shown to defeat ASLR through various hardware mechanisms. We systematically analyze existing microarchitectural attacks and identify multiple leakage paths. Given the vast attack surface exposed by ASLR, it is challenging to effectively prevent leaking the ASLR secret against microarchitectural attacks. Motivated by this, we present Oreo, a software-hardware co-design mitigation that strengthens ASLR against these attacks. Oreo uses a new memory mapping interface to remove secret randomized bits in virtual addresses before translating them to their corresponding physical addresses. This extra step hides randomized virtual addresses from microarchitecture structures, preventing side channels from leaking ASLR secrets. Oreo is transparent to user programs and incurs low overhead. We prototyped and evaluated our design on Linux using the hardware simulator gem5.

Trusted I/O (TIO) is an appealing solution to improve I/O performance for confidential VMs (CVMs), with the potential to eliminate broad sources of I/O overhead. However, this paper emphasizes that not all types of I/O can derive substantial benefits from TIO, particularly network I/O. Given the obligatory use of encryption protocols for network traffic in CVM's threat model, TIO's approach of I/O encryption over the PCIe bus becomes redundant. Furthermore, TIO solutions need to expand the Trusted Computing Base (TCB) to include TIO devices and are commercially unavailable. Motivated by these insights, the goal of this paper is to propose a software solution that helps CVMs immediately benefit from high-performance networks, while confining trust only to the on-chip CVM. We present FOLIO, a software solution crafted from a secure and efficient Data Plane Development Kit (DPDK) extension compatible with the latest version of AMD Secure Encrypted Virtualization (SEV), a.k.a., Secure Nested Paging (SNP). Our design is informed by a thorough analysis of all possible factors that impact SNP VM's network performance. By extensively removing overhead sources, we arrive at a design that approaches the efficiency of an optimal TIO-based configuration. Evaluation shows that FOLIO has a performance dip less than 6% relative to the optimal TIO configuration, while only relying on off-the-shelf CPUs.