Identification of two novel heterozygous variants of SMC3 with Cornelia de Lange syndrome.

BACKGROUND: Cornelia de Lange syndrome (CdLS) is a multisystem genetic disorder, and cases caused by variants in the structural maintenance of chromosomes protein 3 (SMC3) gene are uncommon. Here, we report two cases of CdLS associated with novel pathogenic variants in SMC3 from two Chinese families. METHODS: Clinical presentations of two patients with CdLS were evaluated, and specimens from the patients and other family members were collected for Trio-based whole-exome sequencing. Pyrosequencing, chip-based digital PCR, minigene splicing assay, and in silico analysis were carried out to elucidate the impact of novel variants. RESULTS: Novel heterozygous variants in SMC3 were identified in each proband. One harbored a novel splicing and mosaic variant (c.2535+1G>A) in SMC3. The mutated allele G>A conversion was approximately 23.1% by digital PCR, which indicated that 46.2% of peripheral blood cells had this variant. Additionally, in vitro minigene splicing analysis validated that the c.2535+1G>A variant led to an exon skipping in messenger RNA splicing. The other carried a heterozygous variant (c.435C>A), which was predicted to be pathogenic as well as significantly altered in local electrical potential. The former showed multiple abnormalities and marked clinical severity, and the latter mainly exhibited a speech developmental disorder and slightly facial anomalies. CONCLUSION: Both patients were clinically diagnosed with Cornelia de Lange syndrome 3 (CdLS3). The newly identified SMC3 gene variants can expand the understanding of CdLS3 and provide reliable evidence for genetic counseling to the affected family.

Nomogram to predict central lymph node metastasis in papillary thyroid carcinoma.

Central lymph node metastasis (CLNM) of papillary thyroid carcinoma (PTC) is common. In our study, we built a nomogram to predict CLNM. We retrospectively analyzed 1,392 PTC patients. This group of patients was divided into a training cohort (including 1,009 patients) and a validation cohort (including 383 patients). Analyses of the correlation between inflammatory indicators, ultrasonic characteristics, pathological characteristics and CLNM were conducted. In the training cohort and validation cohort, the metastatic rates of CLNM were 60.16% and 64.23%, respectively. Univariate and multivariate logistic regression analyses demonstrated that Hashimoto's thyroiditis (HT), calcification, multifocality, capsule invasion, PLR (platelet-lymphocyte ratio) ≤ 130.34, large tumors and middle and lower positions were independent risk factors for CLNM. Then, we constructed a nomogram. The nomogram had good discrimination regardless of whether there was CLNM, with a C-index of 0.809. The calibration curve indicated that the nomogram had good visual and quantitative consistency (p = 0.213). Decision curve analysis showed that the nomogram improved the net clinical benefit with a threshold probability of 0-82% in the training cohort and 0-71% in the validation cohort. We constructed a nomogram to predict CLNM in PTC and assist surgeons in making personalized clinical decisions for PTC.

Diagnostic performance of coronary computed tomography angiography stenosis score for coronary stenosis.

BACKGROUND: Coronary computed tomography angiography stenosis score (CCTA-SS) is a proposed diagnosis score that considers the plaque characteristics, myocardial function, and the diameter reduction rate of the lesions. This study aimed to evaluate the diagnostic performance of the CCTA-SS in seeking coronary artery disease (CAD). METHODS: The 228 patients with suspected CAD who underwent CCTA and invasive coronary angiography (ICA) procedures were under examination. The diagnostic performance was evaluated with the receiver operating curve (ROC) for CCTA-SS in detecting CAD (defined as a diameter reduction of ≥ 50%) and severe CAD (defined as a diameter reduction of ≥ 70%). RESULTS: The area under ROC (AUC) of CCTA-SS was 0.909 (95% CI: 0.864-0.943), which was significantly higher than that of CCTA (AUC: 0.826; 95% CI: 0.771-0.873; P = 0.0352) in diagnosing of CAD with a threshold of 50%. The optimal cutoff point of CCTA-SS was 51% with a sensitivity of 90.66%, specificity of 95.65%, positive predictive value of 98.80%, negative predictive value of 72.13%, and accuracy of 91.67%, whereas the optimal cutoff point of CCTA was 55%, and the corresponding values were 87.36%, 93.48%, 98.15%, 65.15%, and 88.60%, respectively. With a threshold of 70%, the performance of CCTA-SS with an AUC of 0.927 (95% CI: 0.885-0.957) was significantly higher than that of CCTA with an AUC of 0.521 (95% CI: 0.454-0.587) (P < 0.0001). CONCLUSIONS: CCTA-SS significantly improved the diagnostic accuracy of coronary stenosis, including CAD and severe CAD, compared with CCTA.

What can molecular assembly learn from catalysed assembly in living organisms?

Molecular assembly is the process of organizing individual molecules into larger structures and complex systems. The self-assembly approach is predominantly utilized in creating artificial molecular assemblies, and was believed to be the primary mode of molecular assembly in living organisms as well. However, it has been shown that the assembly of many biological complexes is "catalysed" by other molecules, rather than relying solely on self-assembly. In this review, we summarize these catalysed-assembly (catassembly) phenomena in living organisms and systematically analyse their mechanisms. We then expand on these phenomena and discuss related concepts, including catalysed-disassembly and catalysed-reassembly. Catassembly proves to be an efficient and highly selective strategy for synergistically controlling and manipulating various noncovalent interactions, especially in hierarchical molecular assemblies. Overreliance on self-assembly may, to some extent, hinder the advancement of artificial molecular assembly with powerful features. Furthermore, inspired by the biological catassembly phenomena, we propose guidelines for designing artificial catassembly systems and developing characterization and theoretical methods, and review pioneering works along this new direction. Overall, this approach may broaden and deepen our understanding of molecular assembly, enabling the construction and control of intelligent assembly systems with advanced functionality.

Analysis on Foodborne Pathogen Contamination of Food Samples in Longnan City from 2013 to 2022.

The objective was to determine the prevalence of foodborne pathogens in food in Longnan City, Gansu Province, China. In this research, we conducted tests on baked foods, catering foods, meat, and fruits and vegetables sold in supermarkets, farmers' markets, restaurants, retail stores, street stalls, and school canteens from 2013 to 2022. We analyzed the variety of foodborne pathogens (Salmonella, Staphylococcus aureus, Listeria monocytogenes, Bacillus cereus, and diarrheagenic Escherichia coli) in different sites and food types. Once foodborne pathogens were detected in the sample, it was deemed unqualified. The total detection rates of foodborne pathogens were 1.559%, 3.349%, 1.980%, 1.040%, 3.383%, and 1.303% in food from supermarkets, farmers' markets, restaurants, retail stores, street stalls, and school canteens, respectively. No pathogenic bacteria were detected in baked foods. Salmonella, S. aureus, L. monocytogenes, B. cereus, and diarrheagenic E. coli were detected in catering foods, among which B. cereus had the highest detection rate. Salmonella was the most common pathogenic bacteria detected in meat, while the detection rate of pathogenic bacteria in fruits and vegetables was low, with only one positive sample for diarrheagenic E. coli. Among the six sites, street stalls (3.382%) and farmers' markets (3.349%) had higher detection rates of pathogens. In general, the detection rate of pathogens from 2013 to 2022 was not high, but there were also some hidden dangers. Catering food is vulnerable to pathogen contamination, and street stalls and farmers' markets are the main sites of pollution. According to the above findings, the regulatory authorities should continue to strengthen supervision, guarantee food safety through early warning, and reduce the risk of food contamination.

[Analysis of CLCN4 gene variant in a child with Raynaud-Claes syndrome].

OBJECTIVE: To analyze the clinical phenotype and genetic variant in a child with Raynaud-Claes syndrome (RCS). METHODS: A child who was diagnosed with RCS at the Children's Hospital Affiliated to Zhengzhou University for delayed language and motor development in August 2022 was selected as the study subject. Clinical data of the child were collected, and potential genetic variant was detected by next-generation sequencing and Sanger sequencing. The pathogenicity of the candidate variant was analyzed. RESULTS: The child, a 4-year-and-4-month-old male, has manifested global developmental delay, speech disorders, special facial features and behavioral abnormalities. Genetic testing revealed that he has harbored a hemizygous c.1174C>T (p.Gln392Ter) variant of the CLCN4 gene, which was not detected in either of his parents. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic (PVS1+PS2+PM2_Supporting). CONCLUSION: The c.1174C>T (p.Gln392Ter) variant of the CLCN4 gene probably underlay the PCS in this child. Above finding has expanded the mutational spectrum of the CLCN4 gene and enabled genetic counseling and prenatal diagnosis for his family.

Electrochemical Promoted Three-Component Trifluoromethylation/Spirocyclization Reaction of N-Arylsulfonylacrylamides to 4-Azaspiro[4.5]decanes.

An electrochemical facilitated three-component trifluoromethylation/spirocyclization reaction of N-(arylsulfonyl)acrylamides, CF3SO2Na, and H2O has been developed. Without the requirement of chemical oxidants, a number of unexplored trifluoromethylated 4-azaspiro[4.5]decanes were obtained in satisfactory yields under mild conditions. This work provides a new synthetic strategy for fluorine-containing spirocyclic compounds and shows a new perspective for the reactivity study of N-(arylsulfonyl)acrylamides.

An aminocaproic acid-grafted chitosan derivative with superior antibacterial and hemostatic properties for the prevention of secondary bleeding.

Uncontrolled bleeding is one of the leading causes of human mortality. Existing hemostatic materials or techniques cannot meet the clinical requirements for safe and effective hemostasis. The development of novel hemostatic materials has always been of great interest. Chitosan hydrochloride (CSH), a derivative of chitin, is extensively used on wounds as an antibacterial and hemostatic agent. However, the formation of intra- or intermolecular hydrogen bonds between hydroxyl and amino groups limits its water solubility and dissolution rate and affects its effectiveness in promoting coagulation. Herein, we covalently grafted aminocaproic acid (AA) to the hydroxyl and amino groups of CSH via ester and amide bonds, respectively. The solubility of CSH in water (25 °C) was 11.39 ± 0.98 % (w/v), whereas the AA-grafted CSH (CSH-AA) reached 32.34 ± 1.23 % (w/v). Moreover, the dissolution rate of CSH-AA in water was 6.46 times higher than that of CSH. Subsequent studies proved that CSH-AA is non-toxic, biodegradable, and has superior antibacterial and hemostatic properties to CSH. Additionally, anti-plasmin activity can be exerted by the dissociated AA from the CSH-AA backbone, which can help to lessen secondary bleeding.

High inhabitation activity of CMCS/Phytic acid/Zn2+ nanoparticles via flash nanoprecipitation (FNP) for bacterial and fungal infections.

Plant diseases prompted by fungi and bacteria are one of the most serious threats to global crop production and food security. The destruction of these infections posed a major challenge to plant protection by chemical control. Herein, we develop CMCS/PA/Zn2+ nanoparticles (NPs) using carboxymethyl chitosan (CMCS), phytic acid (PA) and metal ions (Zn2+) via flash nanoprecipitation (FNP) strategy. Metal complexes of PA with specified antibacterial and antifungal activities are expected to hold the potential and play a significant role in antimicrobial treatment. The size and size distribution of NPs was confirmed through Dynamic and Static Light Scatterer (DSLS). In acidic-infection microenvironment, the CMCS/PA/Zn2+ NPs can disintegrate and release Zn2+ in situ thus stimulated the corresponding antimicrobial activity. These CMCS/PA/Zn2+ NPs showed outstanding antibacterial efficacy (98 %) against S. aureus and E. coli bacteria in vitro, as well as an impressive antifungal efficacy of 98 % and 81 % against R. solani and B. cinerea at 50 µg/mL respectively. This study contributes a prospective idea to the development of organic-inorganic hybrid NPs as environmentally-friendly and safe agricultural antimicrobials.

Evaluation and Use of Organs from Donors Poisoned by Organophosphorus Pesticide.

BACKGROUND The aim of this study was to explore the evaluation and use of donor organs from donors with brain death caused by acute severe organophosphorus pesticides and provide a basis for the use of such donor organs. MATERIAL AND METHODS Seven cases of brain dead donors caused by acute organophosphorus pesticide poisoning from January 2014 to December 2018 in the hospital were collected, and a retrospective analysis was made of the donors' age, race, physiological and pathological changes, donor organ function changes and the organ use, liver or kidney function recovery, and complications of the recipients. The 18 recipients were followed up until June 31, 2022. RESULTS We found that 71.42% of organ donors were male, and 71.42% of organ donors were under 50 years old. The main cause of death was respiratory failure caused by organophosphorus pesticide poisoning. The liver and kidney functions of 7 donors were damaged, and 3 livers could not be used due to severe functional damage, but the liver or kidney function of 18 recipients gradually recovered after transplantation. Delayed recovery of graft function occurred after transplantation accounted for 21.43%, and the grafts had good short-term to medium-term performance. CONCLUSIONS Although the function of organs from donor with brain death due to acute severe organophosphorus pesticide poisoning is seriously damaged, most of the organs can still be used for transplantation. Individualized functional maintenance according to the situation of donors is conducive to improving the quality of organs.

Histone tyrosine sulfation by SULT1B1 regulates H4R3me2a and gene transcription.

Tyrosine sulfation is a common posttranslational modification in mammals. To date, it has been thought to be limited to secreted and transmembrane proteins, but little is known about tyrosine sulfation on nuclear proteins. Here we report that SULT1B1 is a histone sulfotransferase that can sulfate the tyrosine 99 residue of nascent histone H3 in cytosol. The sulfated histone H3 can be transported into the nucleus and majorly deposited in the promoter regions of genes in chromatin. While the H3Y99 residue is buried inside octameric nucleosome, dynamically regulated subnucleosomal structures provide chromatin-H3Y99sulf the opportunity of being recognized and bound by PRMT1, which deposits H4R3me2a in chromatin. Disruption of H3Y99sulf reduces PRMT1 binding to chromatin, H4R3me2a level and gene transcription. These findings reveal the mechanisms underlying H3Y99 sulfation and its cross-talk with H4R3me2a to regulate gene transcription. This study extends the spectrum of tyrosine sulfation on nuclear proteins and the repertoire of histone modifications regulating chromatin functions.

A rare coronary anomaly: The single left coronary artery with coronary artery fistula draining into the right ventricular outflow tract.

A previously healthy 9-year-old girl was referred to us for the evaluation of a murmur on a routine clinical examination. Routine electrocardiogram and chest x-ray were normal. The cardiac enzymes were normal. Combining ultrasound and CCTA, it was confirmed that the hemodynamics of the heart was a left-to-right shunt and that RVOT stole blood from the left ventricle through the single coronary artery (SCA).

Gastric cancer incidence trends in China and Japan from 1990 to 2019: Disentangling age-period-cohort patterns.

BACKGROUND: Recent data have shown divergent trends in gastric cancer (GC) incidence between China and Japan; however, the cause for has not been explored. METHODS: We retrieved GC incidence data from 1990 to 2019 from the Global Burden of Disease study, stratified by sex for both countries. We analyzed annual average percentage change (AAPC) via a joinpoint regression model and estimated the effects of age, period, and cohort via the age-period-cohort model. RESULTS: The age-standardized incidence rate trends for GC decreased in both countries and both sexes, but the reduction was more pronounced in Japan because the AAPC for Japanese males (AAPC = -2.65%; 95% CI, -2.98 to -2.32) was eight times greater than that of Chinese males (AAPC = -0.30%; 95% CI, -0.5 to -0.09). The age and cohort effects on the trend are similar in both countries: the risk of GC incidence increased with age among the Chinese and the Japanese but was lower among younger birth cohorts. The two countries showed contrasting trends over the study period; although the risk of GC rapidly decreased for Japanese males and females, it increased by twofold among Chinese males. CONCLUSIONS: The period effect is the main reason for the divergent trends in age-standardized incidence rate for GC in China and Japan. By comparing national cancer control programs in both countries, we concluded that countries with a high prevalence of GC, such as China, can learn from Japan's experience in controlling GC by actively conducting national population screening, which is expected to facilitate both prevention and treatment of GC. LAY SUMMARY: More than one-half of all new gastric cancer (GC) worldwide occur in China and Japan, but the reasons for the different incidence trends have not been thoroughly analyzed. Analysis using the age-period-cohort model confirmed that the cohort effect was the main reason for the decline in age-standardized incidence rate (ASIR) for GC and that the period effect may be the main reason for the divergent trends in gastric cancer ASIR in China and Japan.

Vasectomy reversal in China during the recent decade: insights from a multicenter retrospective investigation / 亚洲男科学杂志(英文版)

To date, there is little information about the demography of vasectomy reversal (VR) patients or the factors currently influencing VR effectiveness in China, especially after the universal two-child policy was released in 2015. In this research, demographic data and perioperative medical records of VR patients were extracted from seven major hospitals in different provinces or municipalities of China. Meanwhile, a telephone survey of the patients was conducted to collect follow-up information. Eventually, 448 VR cases from the past 13 years were included. The results were analyzed by stratified comparison to investigate factors that can influence postoperative vas deferens patency and pregnancy rate. Appropriately statistical methods were used, and all of the protocols were approved by the Ethics Committees of the institutes in this research. The results showed that the annual operation volume of VR quadrupled after the two-child policy was implemented. Nonmicrosurgery and a long duration of vasectomy were significantly associated with a lower patency rate. A follow-up survey showed that the general postoperative pregnancy rate was 27.2%. For female partners over the age of 35 years, the postoperative pregnancy rate showed a more severe decline, but only 35.5% of them had been given a fertility examination before their husbands' VR surgery. Our work revealed that more patients in China have been demanding VR in recent years. High-quality microsurgery and a short duration of vasectomy are crucial for restoring patency by VR. Clinical andrologists should perform a preoperative fertility evaluation of the patients' female partners.

Clinical features and microsurgical reconstruction of congenital unilateral absence of the vas deferens with obstructive azoospermia: a tertiary care center experience / 亚洲男科学杂志(英文版)

Patients with congenital unilateral absence of the vas deferens (CUAVD) manifest diverse symptoms from normospermia to azoospermia. Treatment for CUAVD patients with obstructive azoospermia (OA) is complicated, and there is a lack of relevant reports. In this study, we describe the clinical features and evaluate the treatments and outcomes of CUAVD patients with OA. From December 2015 to December 2020, 33 patients were diagnosed as CUAVD with OA in Shanghai General Hospital (Shanghai, China). Patient information, ultrasound findings, semen analysis, hormone profiles, and treatment information were collected, and the clinical outcomes were evaluated. Of 33 patients, 29 patients were retrospectively analyzed. Vasoepididymostomy (VE) or cross VE was performed in 12 patients, the patency rate was 41.7% (5/12), and natural pregnancy was achieved in one of the patients. The other 17 patients underwent testicular sperm extraction as the distal vas deferens (contralateral side) was obstructed. These findings showed that VE or cross VE remains an alternative treatment for CUAVD patients with OA, even with a relatively low rate of patency and natural pregnancy.

HPDL mutations identified by exome sequencing are associated with infant neurodevelopmental disorders.

BACKGROUND: Recent research found that biallelic HPDL variants can cause neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (NEDSWMA), with only a few reports. Clinical phenotypic information on individuals with damaging HPDL variants may also be incomplete. The phenotype of NEDSWMA is characterized by severe neurodevelopmental delay, brain atrophy, and spasticity in infancy. METHODS: Exome sequencing was used in the proband and his parents to identify the underlying genetic cause. Candidate mutations were validated by classic Sanger sequencing. The clinical presentation of the infant who carried HPDL variants was summarized. RESULTS: We identified a novel compound heterozygous variants in HPDL, c.995delC (p.T332Mfs) and c.1051C>T (p.Q351*) in the patient a 6-month-old boy presenting with global developmental delay, seizures, hypertonia, and limb spasticity. Brain magnetic resonance imaging (MRI) showed thin corpus callosum, ventriculomegaly, white matter volume reduction, bilateral frontotemporal subarachnoid widening, and sulcus deeping. CONCLUSION: Our results provided important information for the associations of variants in HPDL with the neurodevelopmental disorder in infants, and broaden the genetic spectrum of HPDL-related disease. This is the second report of the HPDL mutation causing infant neurodevelopmental disorders in a Chinese population.

Synthesis and Bioactivity of Novel Sulfonate Scaffold-Containing Pyrazolecarbamide Derivatives as Antifungal and Antiviral Agents.

Novel pyrazolecarbamide derivatives bearing a sulfonate fragment were synthesized to identify potential antifungal and antiviral agents. All the structures of the key intermediates and target compounds were confirmed by nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS). The single-crystal X-ray diffraction of the compound T22 showed that pyrazole carbamide is a sulfonate. The in vitro antifungal activities of the target compounds against Colletotrichum camelliae, Pestalotiopsis theae, Gibberella zeae, and Rhizoctonia solani were evaluated at 50 µg/ml. Among the four pathogens, the target compounds exhibited the highest antifungal activity against Rhizoctonia solani. The compound T24 (EC50 = 0.45 mg/L) had higher antifungal activity than the commercial fungicide hymexazol (EC50 = 10.49 mg/L) against R. solani, almost similar to bixafen (EC50 = 0.25 mg/L). Additionally, the target compounds exhibited protective effects in vivo against TMV. Thus, this study reveals that pyrazolecarbamide derivatives bearing a sulfonate fragment exhibit potential antifungal and antiviral activities.

In situ lattice tuning of quasi-single-crystal surfaces for continuous electrochemical modulation.

The ability to control the atomic-level structure of a solid represents a straightforward strategy for fabricating high-performance catalysts and semiconductor materials. Herein we explore the capability of the mechanically controllable surface strain method in adjusting the surface structure of a gold film. Underpotential deposition measurements provide a quantitative and ultrasensitive approach for monitoring the evolution of surface structures. The electrochemical activities of the quasi-single-crystalline gold films are enhanced productively by controlling the surface tension, resulting in a more positive potential for copper deposition. Our method provides an effective way to tune the atom arrangement of solid surfaces with sub-angstrom precision and to achieve a reduction in power consumption, which has vast applications in electrocatalysis, molecular electronics, and materials science.

A Visualized Dynamic Prediction Model for Lymphatic Metastasis in Ewing's Sarcoma for Smart Medical Services.

Background: This study aims to predict the lymphatic metastasis in Ewing's sarcoma (ES) patients by nomogram. The risk of lymphatic metastasis in patients with ES was predicted by the built model, which provided guidance for the clinical diagnosis and treatment planning. Methods: A total of 929 patients diagnosed with ES were enrolled from the year of 2010 to 2016 in the Surveillance, Epidemiology, and End Results (SEER) database. The nomogram was established to determine predictive factors of lymphatic metastasis according to univariate and multivariate logistic regression analysis. The validation of the model performed using multicenter data (n = 51). Receiver operating characteristics (ROC) curves and calibration plots were used to evaluate the prediction accuracy of the nomogram. Decision curve analysis (DCA) was implemented to illustrate the practicability of the nomogram clinical application. Based on the nomogram, we established a web calculator to visualize the risk of lymphatic metastases. We further plotted Kaplan-Meier overall survival (OS) curves to compare the survival time of patients with and without lymphatic metastasis. Results: In this study, the nomogram was established based on six significant factors (survival time, race, T stage, M stage, surgery, and lung metastasis), which were identified for lymphatic metastasis in ES patients. The model showed significant diagnostic accuracy with the value of the area under the curve (AUC) was 0.743 (95%CI: 0.714-0.771) for SEER internal validation and 0.763 (95%CI: 0.623-0.871) for multicenter data external validation. The calibration plot and DCA indicated that the model had vital clinical application value. Conclusion: In this study, we constructed and developed a nomogram with risk factors to predict lymphatic metastasis in ES patients and validated accuracy of itself. We found T stage (Tx OR = 2.540, 95%CI = 1.433-4.503, P < 0.01), M stage (M1, OR = 2.061, 95%CI = 1.189-3.573, P < 0.05) and survival time (OR = 0.982, 95%CI = 0.972-0.992, P < 0.001) were important independent factors for lymphatic metastasis in ES patients. Furthermore, survival time in patients with lymphatic metastasis or unclear situation (P < 0.0001) was significantly lower. It can help clinicians make better decisions to provide more accurate prognosis and treatment for ES patients.