Zn Single-Atom Catalysts Enable the Catalytic Transfer Hydrogenation of α,ß-Unsaturated Aldehydes.

Highly active nonprecious-metal single-atom catalysts (SACs) toward catalytic transfer hydrogenation (CTH) of α,ß-unsaturated aldehydes are of great significance but still are deficient. Herein, we report that Zn-N-C SACs containing Zn-N3 moieties can catalyze the conversion of cinnamaldehyde to cinnamyl alcohol with a conversion of 95.5% and selectivity of 95.4% under a mild temperature and atmospheric pressure, which is the first case of Zn-species-based heterogeneous catalysts for the CTH reaction. Isotopic labeling, in situ FT-IR spectroscopy, and DFT calculations indicate that reactants, coabsorbed at the Zn sites, proceed CTH via a "Meerwein-Ponndorf-Verley" mechanism. DFT calculations also reveal that the high activity over Zn-N3 moieties stems from the suitable adsorption energy and favorable reaction energy of the rate-determining step at the Zn active sites. Our findings demonstrate that Zn-N-C SACs hold extraordinary activity toward CTH reactions and thus provide a promising approach to explore the advanced SACs for high-value-added chemicals.

Energizing Co Active Sites via d-Band Center Engineering in CeO2-Co3O4 Heterostructures: Interfacial Charge Transfer Enabling Efficient Nitrate Electrosynthesis.

The electrochemical nitrogen oxidation reaction (NOR) holds significant potential to revolutionize the traditional nitrate synthesis processes. However, the progression in NOR has been notably stymied due to the sluggish kinetics of initial N2 adsorption and activation processes. Herein, the research embarks on the development of a CeO2-Co3O4 heterostructure, strategically engineered to facilitate the electron transfer from CeO2 to Co3O4. This orchestrated transfer operates to amplify the d-band center of the Co active sites, thereby enhancing N2 adsorption and activation dynamics by strengthening the Co─N bond and diminishing the resilience of the N≡N bond. The synthesized CeO2-Co3O4 manifests promising prospects, showcasing a significant HNO3 yield of 37.96 µg h-1 mgcat -1 and an elevated Faradaic efficiency (FE) of 29.30% in a 0.1 m Na2SO4 solution at 1.81 V versus RHE. Further substantiating these findings, an array of in situ methodologies coupled with DFT calculations vividly illustrate the augmented adsorption and activation of N2 on the surface of CeO2-Co3O4 heterostructure, resulting in a substantial reduction in the energy barrier pertinent to the rate-determining step within the NOR pathway. This research carves a promising pathway to amplify N2 adsorption throughout the electrochemical NOR operations and delineates a blueprint for crafting highly efficient NOR electrocatalysts.

Electronegative Phosphorus-Integrated Co2+ Active Sites for Enhanced Electrocatalytic Nitrogen Reduction.

In the quest for proficient electrocatalysts for ammonia's electrocatalytic nitrogen reduction, cobalt oxides, endowed with a rich d-electron reservoir, have emerged as frontrunners. Despite the previously evidenced prowess of CoO in this realm, its ammonia yield witnesses a pronounced decline as the reaction unfolds, a phenomenon linked to the electron attrition from its Co2+ active sites during electrocatalytic nitrogen reduction reaction (ENRR). To counteract this vulnerability, we harnessed electron-laden phosphorus (P) elements as dopants, aiming to recalibrate the electronic equilibrium of the pivotal Co active site, thereby bolstering both its catalytic performance and stability. Our empirical endeavors showcased the doped P-CoO's superior credentials: it delivered an impressive ammonia yield of 49.6 and, notably, a Faradaic efficiency (FE) of 9.6% at -0.2 V versus RHE, markedly eclipsing its undoped counterpart. Probing deeper, a suite of ex-situ techniques, complemented by rigorous theoretical evaluations, was deployed. This dual-pronged analysis unequivocally revealed CoO's propensity for an electron-driven valence metamorphosis to Co3+ post-ENRR. In stark contrast, P-CoO, fortified by P doping, exhibits a discernibly augmented ammonia yield. Crucially, P's intrinsic ability to staunch electron leakage from the active locus during ENRR ensures the preservation of the valence state, culminating in enhanced catalytic dynamism and fortitude. This investigation not only illuminates the intricacies of active site electronic modulation in ENRR but also charts a navigational beacon for further enhancements in this domain.

Machine Learning for Sequence and Structure-Based Protein-Ligand Interaction Prediction.

Developing new drugs is too expensive and time -consuming. Accurately predicting the interaction between drugs and targets will likely change how the drug is discovered. Machine learning-based protein-ligand interaction prediction has demonstrated significant potential. In this paper, computational methods, focusing on sequence and structure to study protein-ligand interactions, are examined. Therefore, this paper starts by presenting an overview of the data sets applied in this area, as well as the various approaches applied for representing proteins and ligands. Then, sequence-based and structure-based classification criteria are subsequently utilized to categorize and summarize both the classical machine learning models and deep learning models employed in protein-ligand interaction studies. Moreover, the evaluation methods and interpretability of these models are proposed. Furthermore, delving into the diverse applications of protein-ligand interaction models in drug research is presented. Lastly, the current challenges and future directions in this field are addressed.

Associations between exposure to pesticides mixture and semen quality among the non-occupationally exposed males: Four statistical models.

Most epidemiological studies on the associations between pesticides exposure and semen quality have been based on a single pesticide, with inconsistent major results. In contrast, there was limited human evidence on the potential effect of pesticides mixture on semen quality. Our study aimed to investigate the relationship of pesticide profiles with semen quality parameters among 299 non-occupationally exposed males aged 25-50 without any clinical abnormalities. Serum concentrations of 21 pesticides were quantified by gas chromatography-tandem mass spectrometry (GC-MS/MS). Semen quality parameters were abstracted from medical records. Generalized linear regression models (GLMs) and three mixture approaches, including weighted quantile sum regression (WQS), elastic net regression (ENR) and Bayesian kernel machine regression (BKMR), were applied to explore the single and mixed effects of pesticide exposure on semen quality. In GLMs, as the serum levels of Bendiocarb, ß-BHC, Clomazone, Dicrotophos, Dimethenamid, Paclobutrazole, Pentachloroaniline and Pyrimethanil increased, the straight-line velocity (VSL), linearity (LIN) and straightness (STR) decreased. This negative association also occurred between the concentration of ß-BHC, Pentachloroaniline, Pyrimethanil and progressive motility, total motility. In the WQS models, pesticides mixture was negatively associated with total motility and several sperm motility parameters (ß: -3.07∼-1.02 per decile, FDR-P<0.05). After screening the important pesticides derived from the mixture by ENR model, the BKMR models showed that the decreased qualities for VSL, LIN, and STR were also observed when pesticide mixtures were at ≥ 70th percentiles. Clomazone, Dimethenamid, and Pyrimethanil (Posterior inclusion probability, PIP: 0.2850-0.8900) were identified as relatively important contributors. The study provides evidence that exposure to single or mixed pesticide was associated with impaired semen quality.

Functional differentiation of olive PLP_deC genes: insights into metabolite biosynthesis and genetic improvement at the whole-genome level.

KEY MESSAGE: This study identified 16 pyridoxal phosphate-dependent decarboxylases in olive at the whole-genome level, conducted analyses on their physicochemical properties, evolutionary relationships and characterized their activity. Group II pyridoxal phosphate-dependent decarboxylases (PLP_deC II) mediate the biosynthesis of characteristic olive metabolites, such as oleuropein and hydroxytyrosol. However, there have been no report on the functional differentiation of this gene family at the whole-genome level. This study conducted an exploration of the family members of PLP_deC II at the whole-genome level, identified 16 PLP_deC II genes, and analyzed their gene structure, physicochemical properties, cis-acting elements, phylogenetic evolution, and gene expression patterns. Prokaryotic expression and enzyme activity assays revealed that OeAAD2 and OeAAD4 could catalyze the decarboxylation reaction of tyrosine and dopa, resulting in the formation of their respective amine compounds, but it did not catalyze phenylalanine and tryptophan. Which is an important step in the synthetic pathway of hydroxytyrosol and oleuropein. This finding established the foundational data at the molecular level for studying the functional aspects of the olive PLP_deC II gene family and provided essential gene information for genetic improvement of olive.

Concurrent of compound heterozygous variant of a novel in-frame deletion and the common hypomorphic haplotype in TBX6 and inherited 17q12 microdeletion in a fetus.

BACKGROUND: TBX6, a member of the T-box gene family, encodes the transcription factor box 6 that is critical for somite segmentation in vertebrates. It is known that the compound heterozygosity of disruptive variants in trans with a common hypomorphic risk haplotype (T-C-A) in the TBX6 gene contribute to 10% of congenital scoliosis (CS) cases. The deletion of chromosome 17q12 is a rare cytogenetic abnormality, which often leads to renal cysts and diabetes mellitus. However, the affected individuals often exhibit clinical heterogeneity and incomplete penetrance. METHODS: We here present a Chinese fetus who was shown to have CS by ultrasound examination at 17 weeks of gestation. Trio whole-exome sequencing (WES) was performed to investigate the underlying genetic defects of the fetus. In vitro functional experiments, including western-blotting and luciferase transactivation assay, were performed to determine the pathogenicity of the novel variant of TBX6. RESULTS: WES revealed the fetus harbored a compound heterozygous variant of c.338_340del (p.Ile113del) and the common hypomorphic risk haplotype of the TBX6 gene. In vitro functional study showed the p.Ile113del variant had no impact on TBX6 expression, but almost led to complete loss of its transcriptional activity. In addition, we identified a 1.85 Mb deletion on 17q12 region in the fetus and the mother. Though there is currently no clinical phenotype associated with this copy number variation in the fetus, it can explain multiple renal cysts in the pregnant woman. CONCLUSIONS: This study is the first to report a Chinese fetus with a single amino acid deletion variant and a T-C-A haplotype of TBX6. The clinical heterogeneity of 17q12 microdeletion poses significant challenges for prenatal genetic counseling. Our results once again suggest the complexity of prenatal genetic diagnosis.

Managing the Severe Cavus Foot Deformity in Global Humanitarian Programs.

The cavus foot represents a complex spectrum of deformity ranging from the subtle idiopathic to the severe sensorimotor neuropathy and other neuromuscular deformities. The successful surgical treatment of the cavus foot depends on a fundamental understanding of the underlying multiplanar deformity, inherent muscle balance, and the rigidity of the hindfoot. The location of the deformity is described and understood according to its multiple apices. These deformities are addressed with osteotomies or arthrodesis directed at the apices of deformity. Simultaneously, correction of muscular imbalances with appropriate tendon transfers must also be performed to prevent recurrent deformity. With these principles in mind, the surgical correction of the cavus foot becomes simplified and algorithmically driven.

Global Research Trends and Focuses on Pierre Robin Sequence From 1992 to 2023: A Bibliometric Analysis of the Past 3 Decades.

There is currently a lack of scientific bibliometric analyses in the field of Pierre Robin sequence (PRS). Pierre Robin sequence is known for its clinical triad of micrognathia, glossoptosis, airway obstruction, and possible secondary cleft palate. These defects can lead to upper airway obstruction, sleep apnea, feeding difficulties, affect an individual's growth and development, education level, and in severe cases can be life-threatening. Through analysis of literature retrieved from the Web of Science Core Collection (WoSCC) database using Results Analysis and Citation Report and Citespace software, 933 original articles and reviews were included after manual screening. The overall trend for the number of annual publications and citations was increasing. On the basis of the analysis, airway evaluation and treatment, mandibular distraction osteogenesis (MDO), as well as descriptions of PRS characteristics have been the focus of research in this field. In addition, with advances in new technologies such as gene sequencing and expanding understanding of diseases among researchers, research on genetics and etiology related to PRS has become a growing trend.

ß-Sheet Assembly Translates Conservative Single-Site Mutation into a Perturbation in Macroscopic Structure.

Transferring structural information from amino acid sequence to macroscale assembly is a challenging approach for designing protein quaternary structure. However, the pathway by which the slight variations in sequence result in a global perturbation effect on the assembled structure is unknown. Herein, we design two synthetic peptides, QNL-His and QNL-Arg, with one amino acid substitution and use scanning tunneling microscopy (STM) to image individual peptides in the assembled state. The submolecular resolution of STM enables us to determine the folding structure and ß-sheet supramolecular organization of peptides. QNL-His and QNL-Arg differ in their ß-strand length distribution in pleated ß-sheet association. These structural variations lead to distinguishable outcomes in their ß-sheet assembled fibrils and phase transitions. The comparison of QNL-His versus QNL-Arg structures and macroscopic properties unveils the role of assembly to amplify the structural variations associated with a single-site mutation from a single-molecule scale to a macroscopic scale.

An Effective and Universal Long-Read Sequencing-Based Approach for SMN1 2 + 0 Carrier Screening through Family Trio Analysis.

BACKGROUND: Population-wide carrier screening for spinal muscular atrophy (SMA) is recommended by professional organizations to facilitate informed reproductive options. However, genetic screening for SMN1 2 + 0 carriers, accounting for 3%-8% of all SMA carriers, has been challenging due to the large gene size and long distance between the 2 SMN genes. METHODS: Here we repurposed a previously developed long-read sequencing-based approach, termed comprehensive analysis of SMA (CASMA), to identify SMN1 2 + 0 carriers through haplotype analysis in family trios (CASMA-trio). Bioinformatics pipelines were developed for accurate haplotype analysis and SMN1 2 + 0 deduction. Seventy-nine subjects from 24 families composed of, at the minimum, 3 were enrolled, and CASMA-trio was employed to determine whether an index subject with 2 SMN1 copies was a 2 + 0 carrier in these families. For the proof-of-principle, SMN2 2 + 0 was also analyzed. RESULTS: Among the 16 subjects with 2 SMN1 copies, CASMA-trio identified 5 subjects from 4 families as SMN1 2 + 0 carriers, which was consistent with pedigree analysis involving an affected proband. CASMA-trio also identified SMN2 2 + 0 in six out of 43 subjects with 2 SMN2 copies. Additionally, CASMA-trio successfully determined the distribution pattern of SMN1 and SMN2 genes on 2 alleles in all 79 subjects. CONCLUSIONS: CASMA-trio represents an effective and universal approach for SMN1 2 + 0 carriers screening, as it does not reply on the presence of an affected proband, certain single-nucleotide polymorphisms, ethnicity-specific haplotypes, or complicated single-nucleotide polymorphism analysis across 3 generations. Incorporating CASMA-trio into existing SMA carrier screening programs will greatly reduce residual risk ratio.

Extracting the Synthetic Route of Pd-Based Catalysts in Methanol Steam Reforming from the Scientific Literature.

The structured material synthesis route is crucial for chemists in performing experiments and modern applications such as machine learning material design. With the exponential growth of the chemical literature in recent years, manual extraction from the published literature is time-consuming and labor-intensive. This study focuses on developing an automated method for extracting Pd-based catalyst synthesis routes from the chemical literature. First, a paragraph classification model based on regular expressions is employed to identify paragraphs that contain material synthesis processes. The identified paragraphs are verified using machine learning techniques. Second, natural language processing techniques are applied to automatically parse the material synthesis routes from the identified paragraphs, generate regularized flowcharts, and output structured data. Lastly, we utilized the structured data of the synthesis routes to train machine learning models and predict the performance of the materials. The extracted material entities include the product, preparation method, precursor, support, loading, synthesis operation, and operation condition. This method avoids extensive manual data annotation and improves the scientific literature information acquisition efficiency. The accuracy of the 11 material entities exceeds 80%, and the accuracy of the method, support, precursor, drying time, and reduction time exceeds 90%.

BNM-CDGNN: Batch Normalization Multilayer Perceptron Crystal Distance Graph Neural Network for Excellent-Performance Crystal Property Prediction.

Recently, in the field of crystal property prediction, the graph neural network (GNN) model has made rapid progress. The GNN model can effectively capture high-dimensional crystal features from the crystal structure, thereby achieving optimal performance in property prediction. However, the existing GNN model faces limitations in handling the hidden layer after the pooling layer, which restricts the training performance of the model. In the present research, we propose a novel GNN model called the batch normalization multilayer perceptron crystal distance graph neural network (BNM-CDGNN). BNM-CDGNN encodes the crystal's geometry structure only based on the distance vector between atoms. The graph convolutional layer utilizes the radial basis function as the attention mask, ensuring the crystal's rotation invariance and adding the geometric information on the crystal. Subsequently, the average pooling layer is connected after the convolutional layer to enhance the model's ability to learn precise information. BNM-CDGNN connects multiple hidden layers after the average pooling layers, and these layers are processed by the batch normalization layer. Finally, the fully connected layer maps the results to the target property. BNM-CDGNN significantly enhances the accuracy of crystal property prediction compared with previous baseline models such as SchNet, MPNN, CGCNN, MEGNet, and GATGNN.

A systematic review and meta-analysis of glucocorticoids treatment in severe COVID-19: methylprednisolone versus dexamethasone.

OBJECTIVE: The preferred agent of glucocorticoids in the treatment of patients with severe COVID-19 is still controversial. This study aimed to compare the efficacy and safety of methylprednisolone and dexamethasone in the treatment of patients with severe COVID-19. METHODS: By searching the electronic literature database including PubMed, Cochrane Central Register of Controlled Trials, and Web of Science, the clinical studies comparing methylprednisolone and dexamethasone in the treatment of severe COVID-19 were selected according to the inclusion criteria and exclusion criteria. Relevant data were extracted and literature quality was assessed. The primary outcome was short-term mortality. The secondary outcomes were the rates of ICU admission and mechanical ventilation, PaO2/FiO2 ratio, plasma levels of C-reactive protein (CRP), ferritin, and neutrophil/lymphocyte ratio, hospital stay, and the incidence of severe adverse events. Statistical pooling applied the fixed or random effects model and reported as risk ratio (RR) or mean difference (MD) with the corresponding 95% confidence interval (CI). Meta-analysis was performed using Review Manager 5.1.0. RESULTS: Twelve clinical studies were eligible, including three randomized controlled trials (RCTs) and nine non-RCTs. A total of 2506 patients with COVID-19 were analyzed, of which 1242 (49.6%) received methylprednisolone and 1264 (50.4%) received dexamethasone treatment. In general, the heterogeneity across studies was significant, and the equivalent doses of methylprednisolone were higher than that of dexamethasone. Our meta-analysis showed that methylprednisolone treatment in severe COVID-19 patients was related to significantly reduced plasma ferritin and neutrophil/lymphocyte ratio compared with dexamethasone, and that no significant difference in other clinical outcomes between the two groups was found. However, subgroup analyses of RCTs demonstrated that methylprednisolone treatment was associated with reduced short-term mortality, and decreased CRP level compared with dexamethasone. Moreover, subgroup analyses observed that severe COVID-19 patients treated with a moderate dose (2 mg/kg/day) of methylprednisolone were related to a better prognosis than those treated with dexamethasone. CONCLUSIONS: This study showed that compared with dexamethasone, methylprednisolone could reduce the systemic inflammatory response in severe COVID-19, and its effect was equivalent to that of dexamethasone on other clinical outcomes. It should be noted that the equivalent dose of methylprednisolone used was higher. Based on the evidence of subgroup analyses of RCTs, methylprednisolone, preferably at a moderate dose, has an advantage over dexamethasone in the treatment of patients with severe COVID-19.

The impact of primary tumor resection for asymptomatic colorectal cancer patients with unresectable metastases: a systematic review and meta-analysis.

BACKGROUND: Whether patients with asymptomatic primary tumors and unresectable metastases of colorectal cancer (CRC) should undergo primary tumor resection (PTR) remains controversial. This study aims to determine the appropriateness of PTR for these individuals by evaluating a number of outcome measures. METHODS: A systematic literature search was performed. Outcome measures included overall survival, emergency surgery rates, incidence of postoperative complications, time to initiate chemotherapy, conversion rates, and chemotherapy-related toxicities. RESULTS: Patients who received PTR in addition to chemotherapy had a better overall survival rate than those who only received chemotherapy (HR = 0.62, 95%CI, 0.50-0.78, I2 = 84%, p < 0.00001). In the RCT subgroup, there were no significant differences with a HR of 0.72 (95%CI, 0.45-1.13, I2 = 17%, p = 0.15). More patients in the chemotherapy alone group could be converted to resectable status (OR = 0.47, 95%CI, 0.27-0.82, I2 = 0%, p = 0.008), but the incidence of emergency surgery was 23% (95%CI, 17-29%, I2 = 14%). The risk of chemotherapy-related toxicity was not significantly higher in the PTR group (OR = 1.5, 95%CI, 0.94-2.43, p = 0.09, I2 = 0%), with a 7% incidence of postoperative complications (95%CI, 0-14%, p = 0.05, I2 = 0%). The time to initiate chemotherapy after PTR was approximately 33.06 days (95%CI, 25.55-40.58, I2 = 0%). CONCLUSION: PTR plus chemotherapy may be associated with improved survival in asymptomatic CRC patients with unresectable metastases. However, PTR did not provide a significant survival benefit in the subgroup of RCTs. Additionally, PTR did not result in a significantly increased risk of chemotherapy-related toxicity, with a postoperative complication rate of approximately 7%, and chemotherapy could be initiated at approximately 33.06 days after PTR. Compared with the PTR plus chemotherapy, chemotherapy alone could result in a significantly higher conversion rate. However, about 23% of patients receiving chemotherapy alone required emergency surgery for primary tumor-related symptoms. The above results needed to be validated in future larger prospective randomized trials.

Mining Prognostic Biomarkers of Thyroid Cancer Patients Based on the Immune-Related Genes and Development of a Reliable Prognostic Risk Model.

Purpose: Tumor immunity serves an essential role in the occurrence and development of thyroid cancer (THCA). The aim of this study is to establish an immune-related prognostic model for THCA patients by using immune-related genes (IRGs). Methods: Wilcox test was used to screen the differentially expressed immune-related genes (DEIRGs) in THCA and normal tissues, then the DEIRGs related to prognosis were identified using univariate Cox regression analysis. According to The Cancer Genome Atlas (TCGA) cohort, we developed a least absolute shrinkage and selection operator (LASSO) regression prognostic model and performed validation analyses regard to the predictive value of the model in internal (TCGA) and external (International Cancer Genome Consortium) cohorts respectively. Finally, we analyzed the correlation among the prognostic model, clinical variables, and immune cell infiltration. Results: Eighty-two of 2,498 IRGs were differentially expressed between THCA and normal tissues, and 18 of them were related to prognosis. LASSO Cox regression analysis identified seven DEIRGs with the greatest prognostic value to construct the prognostic model. The risk model showed high predictive value for the survival of THCA in two independent cohorts. The risk score according to the risk model was positively associated with poor survival and the infiltration levels of immune cells, it can evaluate the prognosis of THCA patients independent of any other clinicopathologic feature. The prognostic value and genetic alternations of seven risk genes were evaluated separately. Conclusion: Our study established and verified a dependable prognostic model associated with immune for THCA, both the identified IRGs and immune-related risk model were clinically significant, which is conducive to promoting individualized immunotherapy against THCA.

SNHG1/miR-21 axis mediates the cardioprotective role of aloin in sepsis through modulating cardiac cell viability and inflammatory responses.

BACKGROUND: Aloin has cardioprotective effects, however, its cardioprotective role in sepsis remains unclear. This study aimed to analyze whether aloin could prevent sepsis-related myocardial damage and explore the underlying mechanisms by examining the expression of long-noncoding RNA (lncRNA) SNHG1 and microRNA-21 (miR-21). METHODS: The interaction of SNHG1 with miR-21 was identified by dual-luciferase reporter assay. The levels of SNHG1 and miR-21 were measured by real-time quantitative PCR. The cardioprotective function of aloin was assessed in a sepsis animal model, which was induced by cecal ligation and puncture, and in a myocardial injury cell model in H9C2 cells stimulated by lipopolysaccharide. Myocardial injury biomarker levels and hemodynamic indicators in mice model were measured to evaluate cardiac function. The viability of H9C2 cells was assessed by cell counting kit-8 assay. Inflammatory cytokine levels were examined by an ELISA method. RESULTS: Decreased SNHG1 and increased miR-21 were found in sepsis patients with cardiac dysfunction, and they were negatively correlated. Aloin significantly attenuated myocardial damage and inflammatory responses of mice model, and increased the viability and suppressed inflammation in H9C2 cell model. In addition, SNHG1 expression was upregulated and miR-21 expression was downregulated by aloin in both mice and cell models. Moreover, in mice and cell models, SNHG1/miR-21 axis affected sepsis-related myocardial damage, and mediated the cardioprotective effects of aloin. CONCLUSION: Our findings indicated that aloin exerts protective effects in sepsis-related myocardial damage through regulating cardiac cell viability and inflammatory responses via regulating the SNHG1/miR-21 axis.

Carrier burden of over 300 diseases in Han Chinese identified by expanded carrier testing of 300 couples using assisted reproductive technology.

BACKGROUND: Expanded carrier screening (ECS) has become a common practice for identifying carriers of monogenic diseases. However, existing large gene panels are not well-tailored to Chinese populations. In this study, ECS testing for pathogenic variants of both single-nucleotide variants (SNVs) and copy number variants (CNVs) in 330 genes implicated in 342 autosomal recessive (AR) or X-linked diseases was carried out. We assessed the differences in allele frequencies specific to the Chinese population who have used assisted reproductive technology (ART) and the important genes to screen for in this population. METHODOLOGY: A total of 300 heterosexual couples were screened by our ECS panel using next-generation sequencing. A customed bioinformatic algorithm was used to analyze SNVs and CNVs. Guidelines from the American College of Medical Genetics and Genomics and the Association for Molecular Pathology were adapted for variant interpretation. Pathogenic or likely pathogenic (P/LP) SNVs located in high homology regions/deletions and duplications of one or more exons in length were independently verified with other methods. RESULTS: 64.83% of the patients were identified to be carriers of at least one of 342 hereditary conditions. We identified 622 P/LP variants, 4.18% of which were flagged as CNVs. The rate of at-risk couples was 3%. A total of 149 AR diseases accounted for 64.05% of the cumulative carrier rate, and 48 diseases had a carrier rate above 1/200 in the test. CONCLUSION: An expanded screening of inherited diseases by incorporating different variant types, especially CNVs, has the potential to reduce the occurrence of severe monogenic diseases in the offspring of patients using ART in China.

Study on acoustic radiation force of a rigid sphere arbitrarily positioned in a zero-order Mathieu beam.

The expressions of the axial and transverse acoustic radiation forces of a rigid sphere arbitrarily positioned in a zero-order Mathieu beam are derived in this paper. The expansion coefficients of the off-axis zero-order Mathieu beam are obtained using the addition theorem of the Bessel functions, and numerical experiments are conducted to verify the theory. The three-dimensional acoustic radiation forces on a rigid sphere are studied when the beam is set at different ellipticity parameters, half-cone angles, and offsets of the incident wave relative to the particle center. Simulation results show that the axial acoustic radiation forces of the rigid sphere are always positive, but the transverse forces vary with the positions of the particle and the beam parameters. Also, by changing the frequency, half-cone angle, and offset of the zero-order Mathieu beam, the value and direction of the transverse forces can be adjusted, which has applications in controlling the rigid sphere to be close to or away from the beam axis. Furthermore, the finite element model is set up to verify the theoretical model, and the results obtained by the two methods are in good agreement. This work may contribute to a better understanding of the underlying mechanisms of the particle manipulation with different acoustic beams.

Subchondral bone cysts remodel after correction of varus deformity in ankle arthritis.

BACKGROUND: Subchondral bone cysts (SBCs) of the talus are frequently observed in ankle osteoarthritis (OA). It is unclear whether the cysts need direct treatment after correction of the varus deformity in ankle OA. The purpose of this study is to investigate the incidence of SBCs and the change after supramalleolar osteotomy (SMOT). METHODS: Thirty-one patients treated by SMOT were retrospectively reviewed, and 11 ankles had cysts preoperatively. After SMOT without management of the cysts, the evolution of cysts was evaluated on weightbearing computerized tomography (WBCT). The American Orthopaedic Foot and Ankle Society (AOFAS) clinical ankle-hindfoot scale and a visual analog scale (VAS) were compared. RESULTS: At baseline, the average cyst volume was 65.86 ± 60.53 mm3. The number and volume of cysts were reduced dramatically (P＜.05), and the cysts vanished in 6 ankles after the SMOT. The VAS and AOFAS scores improved significantly after SMOT (P＜.001), there was no significant difference between ankles with cysts and without cysts. CONCLUSIONS: The SMOT alone without direct treatment of the SBCs led to a decrease in the number and volume of SBCs in varus ankle OA. LEVEL OF EVIDENCE: Level IV, case series.