Knowledge, attitudes, and practices of human papillomavirus and self-sampling among adult women: a cross-sectional study.

Background: This study aimed to investigate the knowledge, attitude, and practice (KAP) of human papillomavirus (HPV) and self-sampling among adult women. Methods: The cross-sectional, questionnaire-based study included adult women at Shanghai Pudong Hospital from October 14, 2022, to March 31, 2023. The questionnaire contained demographic information, knowledge, attitude and practice dimensions. Factors associated with KAP and self-sampling were identified by multivariate logistic regression. Results: A total of 1843 valid questionnaires were collected. The average knowledge, attitude, and practice score was 10.09 ± 5.60, 26.76 ± 3.80, and 6.24 ± 2.20, respectively. Urban residents (estimate = 0.705, p < 0.001), suburban residents (estimate = 0.512, p < 0.001), as well as individuals with undergraduate degrees and higher (estimate = 0.535, p < 0.001), were associated with good knowledge, while individuals lacking a history of HPV infection (estimate = -0.461, p < 0.001) and married individuals (estimate = -0.185, p < 0.001) were less likely to have good knowledge. Higher knowledge scores (estimate = 0.087, p < 0.001) and individuals with undergraduate education and above (estimate = 1.570, p < 0.001) were associated with a positive attitude. Being married (estimate = 0.291, p = 0.049) was associated with good practice, whereas not engaging in sexual activity (estimate = -0.959, p < 0.001) or lacking a history of HPV infection (estimate = -0.499, p = 0.011) were associated with unfavorable practices. Minorities (OR = 2.787, p = 0.038) and individuals with multiple sexual partners (OR = 2.297 for two partners, OR = 2.767 for three or more partners, p = 0.020 and p = 0.022) were positively associated with self-sampling. However, higher knowledge (OR = 0.952, p = 0.026) and attitude scores (OR = 0.929, p = 0.015) were negatively associated with self-sampling. Conclusion: Demographic and behavioral factors significantly influenced KAP scores and self-sampling behaviors regarding HPV. Urban residency, higher education levels, positive attitudes, and minority status correlated with favorable outcomes, while factors like marriage and lack of sexual activity were associated with less favorable practices.

Analysis of alterations in serum vitamins and correlations with gut microbiome, microbial metabolomics in patients with sepsis.

BACKGROUND: Vitamins are essential micronutrients that play key roles in many biological pathways associated with sepsis. The gut microbiome plays a pivotal role in the progression of sepsis and may contribute to the onset of multi-organ dysfunction syndrome (MODS). The aim of this study was to investigate the changes in serum vitamins, and their correlation with intestinal flora and metabolomic profiles in patients with sepsis. METHODS: The serum levels of vitamins were determined by Ultra Performance Liquid Chromatography (UPLC). 16S rRNA gene sequencing and Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS) targeted metabolomics were used for microbiome and metabolome analysis. RESULTS: In the training cohort: After univariate, multivariate (OPLS-DA) and Spearman analyses, it was concluded that vitamin levels of 25 (OH) VD3 and (VD2 + VD3), as well as vitamins A and B9, differed significantly among healthy controls (HC), non-septic critical patients (NS), and sepsis patients (SS) (P < 0.05). The validation cohort confirmed the differential vitamin findings from the training cohort. Moreover, analyses of gut flora and metabolites in septic patients and healthy individuals revealed differential flora, metabolites, and metabolic pathways that were linked to alterations in serum vitamin levels. We found for the first time that vitamin B9 was negatively correlated with g_Sellimonas. CONCLUSION: Sepsis patients exhibited significantly lower levels of 25 (OH) VD3 and (VD2 + VD3), vitamins A and B9, which hold potential as predictive markers for sepsis prognosis. The changes in these vitamins may be associated with inflammatory factors, oxidative stress, and changes in gut flora.

Comprehensive Pan-cancer Analysis of CMPK2 as Biomarker and Prognostic Indicator for Immunotherapy.

INTRODUCTION: UMP-CMP kinase 2 (CMPK2) is involved in mitochondrial DNA synthesis which can be oxidized and released into the cytoplasm in innate immunity. It initiates the assembly of NLRP3 inflammasomes and mediates various pathological processes such as human immunodeficiency virus infection and systemic lupus erythematosus. However the role of CMPK2 in tumor progression and tumor immunity remains unclear. METHOD: In this study we conducted a systematical analysis of CMPK2 across 33 different cancers based on datasets such as Genotype Tissue-Expression (GTEx) The Cancer Genome Atlas (TCGA) the Cancer Cell Line Encyclopedia (CCLE) and Tumor Immune Syngeneic Mouse (TISMO). Our focus encompassed the characterization of CMPK2 expression patternsclinical significance potential regulatory mechanisms and its relationship with the tumor immune profile including responsiveness to immune checkpoint inhibitor treatment. CMPK2 expression was elevated in 23 cancers and decreased in two cancers. Receiver operating characteristic curve analysis indicated that CMPK2 expression had a high diagnostic value for 16 cancers. Kaplan-Meier survival analysis showed that high CMPK2 expression was associated with Lower Overall Survival (OS)Disease- Specific Survival (DSS) and Progression-Free Interval (PFI) in Kidney Cutaneous Chromophobe (KICH) Uterine Corpus Endometrial Carcinoma (UCEC) and Uveal Melanoma (UVM) and the opposite was true in Skin Cutaneous Melanoma (SKCM). Immune microenvironment-related analysis revealed strong associations between CMPK2 expression and immune cell infiltration as well as immune checkpoint expression across various tumors. RESULT: Notably in four mouse immunotherapy cohorts CMPK2 expression in treated mouse tumors was post-treatment. In five clinical immunotherapy cohorts patients with high CMPK2 expression show better responses to immunotherapy. Furthermore the methylation level of the CMPK2 gene was closely correlated to its expression and tumor prognosis. Among these cancers the clinical and immunological indications of SKCM are particularly closely related to CMPK2 expression. CONCLUSION: Our analysis preliminarily describes the complex function of CMPK2 in cancer progression and immune microenvironment highlighting its potential as a diagnostic and therapeutic target for immunotherapy.

Research on risk factor filtering and rating of cold chain logistics from the perspective of root-state risk identification.

The natural attributes of perishable and vulnerable cold chain products make the cold chain have more risks than the general supply chain. The attribute characteristics and internal relations of various risks increase the complexity of risk analysis. The purpose of this paper is to study the horizontal and vertical assessment of various risk factors. The multi-dimensional risk measurement model is used to integrate the assessment of multiple risk factors of human, machine, environment, and management, and the cold chain risk management is discussed from the perspective of risk factor classification. The root-state risk identification (RSRI) method was used to identify potential risks. Based on the double standard filtering and multiple criteria, the filtering of irrelevant risks and screening of uncontrollable risks were evaluated, and the triangular fuzzy number method was used to quantitatively evaluate the controllable risk factors. A total of 223 potential risks, 18 important risks, and 6 key risks were identified, followed by inspection and quarantine reports, pesticide residues, improper loading and unloading operations, unqualified centralized environment, unqualified pre-cooling technology of carriages, and unreasonable storage temperature. According to the analysis results, targeted control measures are proposed to better prevent risks and reduce the probability of cold chain accidents. The traditional risk assessment method can only assess the impact of a single risk factor on the system. This assessment method overcomes this limitation and provides a new perspective for cold chain risk management. PRACTICAL APPLICATION: This study laid the foundation for further risk safety management of cold chain logistics.

Baseline 18F-FDG PET/CT radiomics for prognosis prediction in diffuse large B cell lymphoma.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma in adults. Standard treatment includes chemoimmunotherapy with R-CHOP or similar regimens. Despite treatment advancements, many patients with DLBCL experience refractory disease or relapse. While baseline 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) parameters have shown promise in predicting survival, they may not fully capture lesion heterogeneity. This study aimed to assess the prognostic value of baseline 18F-FDG PET radiomics features in comparison with clinical factors and metabolic parameters for assessing 2-year progression-free survival (PFS) and 5-year overall survival (OS) in patients with DLBCL. RESULTS: A total of 201 patients with DLBCL were enrolled in this study, and 1328 radiomics features were extracted. The radiomics signatures, clinical factors, and metabolic parameters showed significant prognostic value for individualized prognosis prediction in patients with DLBCL. Radiomics signatures showed the lowest Akaike information criterion (AIC) value and highest Harrell's concordance index (C-index) value in comparison with clinical factors and metabolic parameters for both PFS (AIC: 571.688 vs. 596.040 vs. 576.481; C-index: 0.732 vs. 0.658 vs. 0.702, respectively) and OS (AIC: 339.843 vs. 363.671 vs. 358.412; C-index: 0.759 vs. 0.667 vs. 0.659, respectively). Statistically significant differences were observed in the area under the curve (AUC) values between the radiomics signatures and clinical factors for both PFS (AUC: 0.768 vs. 0.681, P = 0.017) and OS (AUC: 0.767 vs. 0.667, P = 0.023). For OS, the AUC of the radiomics signatures were significantly higher than those of metabolic parameters (AUC: 0.767 vs. 0.688, P = 0.007). However, for PFS, no significant difference was observed between the radiomics signatures and metabolic parameters (AUC: 0.768 vs. 0.756, P = 0.654). The combined model and the best-performing individual model (radiomics signatures) alone showed no significant difference for both PFS (AUC: 0.784 vs. 0.768, P = 0.163) or OS (AUC: 0.772 vs. 0.767, P = 0.403). CONCLUSIONS: Radiomics signatures derived from PET images showed the high predictive power for progression in patients with DLBCL. The combination of radiomics signatures, clinical factors, and metabolic parameters may not significantly improve predictive value beyond that of radiomics signatures alone.

Understanding professional development challenges of Chinese public health professionals: association and prediction analyses with data validity screening.

Background: Little is known about the public health professionals engaged in educating and training new or future researchers in public health. Research in this direction identifies their issues, concerns, challenges, and needs. This study focused on the professional development challenges of Chinese public health professionals. Methods: Snowball sampling was utilized. A total of 265 public health professionals participated. An instrument of 6 dimensions (burnout, sleep issue, mood issue, friends' support, exercise, and challenges) was developed, revised, and administered online. Two different approaches, the conventional and data screening approaches, were applied. The former started with item quality analyses, whereas the latter began with data quality checks. The chi-square tests of associations and logistic regressions were performed on both approaches. Results and discussion: 19.25% of the participants were detected and deleted as careless respondents. Using both approaches, six professional development challenges except one ("Multidisciplinary learning") were significantly associated with various demographic features. The two approaches produced different models though they converged sometimes. The latent variables of exercise predicted professional development challenges more frequently than other latent variables. Regarding correct classification rates, results from the data screening approach were comparable to those from the conventional approach. Conclusion: The latent variables of exercise, such as "Exercise effects," "Expectations of exercise," and "Belief in exercise," might be understudied. More research is necessary for professional development challenges using exercise as a multidimensional construct. Based on the current study, screening and deleting careless responses in survey research is necessary.

Targeted metabolomics analysis of nucleosides and the identification of biomarkers for colorectal adenomas and colorectal cancer.

The morbidity and mortality of colorectal cancer (CRC) have been increasing in recent years, and early detection of CRC can improve the survival rate of patients. RNA methylation plays crucial roles in many biological processes and has been implicated in the initiation of various diseases, including cancer. Serum contains a variety of biomolecules and is an important clinical sample for biomarker discovery. In this study, we developed a targeted metabolomics method for the quantitative analysis of nucleosides in human serum samples by using liquid chromatography with tandem mass spectrometry (LC-MS/MS). We successfully quantified the concentrations of nucleosides in serum samples from 51 healthy controls, 37 patients with colorectal adenomas, and 55 patients with CRC. The results showed that the concentrations of N 6-methyladenosine (m6A), N 1-methyladenosine (m1A), and 3-methyluridine (m3U) were increased in patients with CRC, whereas the concentrations of N 2-methylguanosine (m2G), 2'-O-methyluridine (Um), and 2'-O-methylguanosine (Gm) were decreased in patients with CRC, compared with the healthy controls and patients with colorectal adenomas. Moreover, the levels of 2'-O-methyluridine and 2'-O-methylguanosine were lower in patients with colorectal adenomas than those in healthy controls. Interestingly, the levels of Um and Gm gradually decreased in the following order: healthy controls to colorectal adenoma patients to CRC patients. These results revealed that the aberrations of these nucleosides were tightly correlated to colorectal adenomas and CRC. In addition, the present work will stimulate future investigations about the regulatory roles of these nucleosides in the initiation and development of CRC.

Laser Direct Writing of Sol-Gel-Derived Vacancy-Rich Functional Oxide Semiconductors.

Fabricating micro/nanostructures of oxide semiconductors with oxygen vacancies (OVs) is crucial for advancing miniaturized functional devices. However, traditional methods for the synthesis of semiconductor metal oxides (SMOs) with OVs usually involve thermal treatment, such as annealing or sintering, under anaerobic conditions. Herein, a multiphoton-induced femtosecond laser (fs) additive manufacturing method is reported for directly writing micropatterns with high resolution (∼1 µm) and abundant OVs in an atmospheric environment at room temperature (25 °C). The interdigitated functional devices fabricated by these micropatterns exhibit both photosensitivity and gas sensitivity. Additionally, this method can be applied to flexible and rigid substrates. The proposed method realizes the high-precision fabrication of SMOs with OVs, enabling the future heterogeneous integration of oxide semiconductors on various substrates, especially flexible substrates, for various device applications, such as soft and wearable electronics/optoelectronics.

Identification of potential biomarkers and pathways for sepsis using RNA sequencing technology and bioinformatic analysis.

Long non-coding RNAs (lncRNAs) has been proven by many to play a crucial part in the process of sepsis. To obtain a better understanding of sepsis, the molecular biomarkers associated with it, and its possible pathogenesis, we obtained data from RNA-sequencing analysis using serum from three sepsis patients and three healthy controls (HCs). Using edgeR (one of the Bioconductor software package), we identified 1118 differentially expressed mRNAs (DEmRNAs) and 1394 differentially expressed long noncoding RNAs (DElncRNAs) between sepsis patients and HCs. We identified the biological functions of these disordered genes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analyses. The GO analysis showed that the homophilic cell adhesion via plasma membrane adhesion molecules was the most significantly enriched category. The KEGG signaling pathway analysis indicated that the differentially expressed genes (DEGs) were most significantly enriched in retrograde endocannabinoid signaling. Using STRING, a protein-protein interaction network was also created, and Cytohubba was used to determine the top 10 hub genes. To examine the relationship between the hub genes and sepsis, we examined three datasets relevant to sepsis that were found in the gene expression omnibus (GEO) database. PTEN and HIST2H2BE were recognized as hub gene in both GSE4607, GSE26378, and GSE9692 datasets. The receiver operating characteristic (ROC) curves indicate that PTEN and HIST2H2BE have good diagnostic value for sepsis. In conclusion, this two hub genes may be biomarkers for the early diagnosis of sepsis, our findings should deepen our understanding of the pathogenesis of sepsis.

Measurement and Simulation of Risk Coupling in Port Hazardous Chemical Logistics.

Hazardous chemical logistics and transportation accidents are the main type of port safety accidents. Correctly and objectively analyzing the causes of port hazardous chemical logistics safety accidents and the coupling mechanisms of risk generation are very important for reducing the occurrence of port hazardous chemical safety accidents. Based on the causal mechanism and coupling principle, in this paper, we construct a risk coupling system for port hazardous chemical logistics and analyze the coupling effects in the risk system. More specifically, a personnel-ship-environment-management system is established and the coupling between the four systems is explored. Taking Tianjin Port as an example, the risk coupling factors are analyzed in combination with system dynamics simulation. Under dynamic changes in coupling coefficients, the change of coupling effects are explored more intuitively, the logical relationships between logistics risks are analyzed and deduced, a comprehensive view of the coupling effects and their evolution process in accidents is provided, and the key causes of accidents and their coupling risk effects are identified. For port hazardous chemicals logistics safety accidents, the presented results not only allow for effective analysis of the causes of safety accidents, but also provide reference for the formulation of prevention strategies.

Psychological factors increase the risk of ovarian cancer.

This study evaluated whether psychological stress increases the incidence of ovarian cancer. A literature search of the electronic databases PubMed and Web of Science from the date of inception to August 2022 was undertaken. Studies with data on psychosocial factors associated with ovarian cancer incidence were included in this study. A random-effect model meta-analysis was undertaken to estimate these data. We used subgroup analysis to adjust for heterogeneity. A total of 4 articles, 10 sets of data, 8 cohort studies, and 2 case-control studies from 682 records were included in this review. Meta-analyses of the included cohort study subgroups suggested that psychological factors increase the risk of ovarian cancer (effect size = 1.37, 95% CI: 1.20-1.53); the subgroup of case-control studies suggested that psychological factors did not increase ovarian cancer risk (effect size = 0.84, 95% CI: 0.70-0.98). These findings indicate that psychological stress is a possible new risk factor for ovarian cancer.Prospero registration number: CRD42022357983IMPACT STATEMENTWhat is already known on this subject? Psychological stress has been shown to increase the risk of many diseases. The relationship between psychological stress and the incidence of ovarian cancer has not been confirmed.What do the results of this study add? The effect of psychological stress on the risk of ovarian cancer was estimated using meta-analysis as an overall ratio.What are the implications of these findings for clinical practice and/or further research? Relaxing psychological stress and appropriate psychotherapy in clinical settings can help reduce the risk of ovarian cancer.

Value of pre-treatment 18F-FDG PET/CT radiomics in predicting the prognosis of stage III-IV colorectal cancer.

Background and purpose: To investigate the value of radiomics features extracted from pre-treatment 18F-FDG PET/CT in predicting the outcomes of stage III-IV colorectal cancer (CRC), which may assist in clinical management strategies and precise treatment of stage III-IV CRC. Materials and methods: 124 patients with pathologically confirmed stage III-IV CRC who underwent pre-treatment 18F-FDG PET/CT scans were enrolled in this study. The least absolute shrinkage and selection operator Cox regression (LASSO-Cox) was used to select radiomics features, and the radiomics scores (Rad-scores) were calculated to build radiomics models. The performance of radiomics models was represented by the concordance index (C-index) and compared with clinical models and complex model. The bootstrap resampling method was used to create validation sets. Additionally, nomograms were developed based on complex models. Results: The C-indices of the radiomics model for predicting PFS and OS were 0.712 (95%CI: 0.680-0.744) and 0.758 (0.728-0.789), respectively. In the clinical model, these values were 0.690 (0.664-0.0.717) and 0.738 (0.709-0.767), respectively. However, in the complex model were 0.734 (0.705-0.762) and 0.780 (0.754-0.807), respectively. The Kaplan-Meier curves demonstrated that the radiomics model could effectively separate patients with stage III-IV stage CRC into high- and low-risk groups (p < 0.001). Multivariate Cox regression analysis confirmed the independent prognostic value of Rad-scores. Conclusion: Pre-treatment 18F-FDG PET/CT radiomics features can stratify the risk of patients with stage III-IV CRC and accurately predict their outcomes. These findings could be clinically valuable for precision treatment and management decisions in stage III-IV CRC.

Evolutionary Game Research on Green Construction Considering Consumers' Preference under Government Supervision.

Construction is closely related to people's lives and public activities. With regard to issues of energy conservation, emission reduction, and sustainable development put forth, the word "green" is increasingly used in the construction industry. Green construction is an inevitable requirement for the sustainable development of the construction industry. In addition, the government regulation mechanism is also the key to the establishment and development of green construction. Thus, on the basis of evolutionary game theory, this paper constructs an evolutionary game model of developers, general contractors, and the government. Then, the evolutionary stability strategies under different conditions are discussed. Lastly, the evolution mechanism in the game process of the green construction system and the influence of relevant parameters on the evolution path of the game model are analyzed through numerical simulation. The results show that (1) when consumer preferences change, the evolutionary stability strategies also change. Consumer preference plays a positive role in the establishment and development of green construction, but a certain increase in consumer preference will lead to free-rider behavior. (2) The government's control mechanism can not only effectively mobilize the enthusiasm of enterprises to participate but also effectively inhibit the free-rider behavior of enterprises; however, it cannot completely prevent the occurrence of free-rider behavior. (3) On the one hand, the government can advocate green consumption to promote the improvement of consumers' green preferences; on the other hand, enterprises actively carry out technological innovation and equipment advances to enhance the likelihood that consumers will embrace green preferences to achieve the optimal ESS. This study not only provides good guidance for developers and general contractors to make optimal strategic choices under different consumers' green preferences, but also provides a reference for the government to formulate reasonable regulatory policies. At the same time, it promotes the development of green construction and further promotes environmental protection.

High-Responsivity Multiband and Polarization-Sensitive Photodetector Based on the TiS3/MoS2 Heterojunction.

Two-dimensional (2D) material photodetectors have received considerable attention in optoelectronics as a result of their extraordinary properties, such as passivated surfaces, strong light-matter interactions, and broad spectral responses. However, single 2D material photodetectors still suffer from low responsivity, large dark current, and long response time as a result of their atomic-level thickness, large binding energy, and susceptibility to defects. Here, a transition metal trichalcogenide TiS3 with excellent photoelectric characteristics, including a direct bandgap (1.1 eV), high mobility, high air stability, and anisotropy, is selected to construct a type-II heterojunction with few-layer MoS2, aiming to improve the performance of 2D photodetectors. An ultrahigh photoresponsivity of the TiS3/MoS2 heterojunction of 48 666 A/W at 365 nm, 20 000 A/W at 625 nm, and 251 A/W at 850 nm is achieved under light-emitting diode illumination. The response time and dark current are 2 and 3 orders of magnitude lower than those of the current TiS3 photodetector with the highest photoresponsivity (2500 A/W), respectively. Furthermore, polarized four-wave mixing spectroscopy and polarized photocurrent measurements verify its polarization-sensitive characteristics. This work confirms the excellent potential of TiS3/MoS2 heterojunctions for air-stable, high-performance, polarization-sensitive, and multiband photodetectors, and the excellent type-II TiS3/MoS2 heterojunction system may accelerate the design and fabrication of other 2D functional devices.

Freeze-Dissolving Method: A Fast Green Technology for Producing Nanoparticles and Ultrafine Powder.

A new technology, a freeze-dissolving method, has been developed to isolate nanoparticles or ultrafine powder and is a more efficient and sustainable method than the traditional freeze-drying method. In this work, frozen spherical ice particles were produced with an aqueous solution of sodium bicarbonate or ammonium dihydrogen phosphate at various concentrations to generate nanoparticles of NaHCO3 or (NH4)(H2PO4). The freeze-drying method sublimates ice, and nanoparticles of NaHCO3 or (NH4)(H2PO4) in the ice templates remain. The freeze-dissolving method dissolves ice particles in a low freezing point solvent at temperatures below 0 °C, and then, nanoparticles of NaHCO3 or (NH4)(H2PO4) can be isolated after filtration. The freeze-dissolving method is 100 times faster with about 100 times less energy consumption than the freeze-drying method as demonstrated in this work with a much smaller facility footprint and produces the same quantity of nanoparticles with a more uniform size distribution.

Mechanobiologically optimized Ti-35Nb-2Ta-3Zr improves load transduction and enhances bone remodeling in tilted dental implant therapy.

The tilted implant with immediate function is increasingly used in clinical dental therapy for edentulous and partially edentulous patients with excessive bone resorption and the anatomic limitations in the alveolar ridge. However, peri-implant cervical bone loss can be caused by the stress shielding effect. Herein, inspired by the concept of "materiobiology", the mechanical characteristics of materials were considered along with bone biology for tilted implant design. In this study, a novel Ti-35Nb-2Ta-3Zr alloy (TNTZ) implant with low elastic modulus, high strength and favorable biocompatibility was developed. Then the human alveolar bone environment was mimicked in goat and finite element (FE) models to investigate the mechanical property and the related peri-implant bone remodeling of TNTZ compared to commonly used Ti-6Al-4V (TC4) in tilted implantation under loading condition. Next, a layer-by-layer quantitative correlation of the FE and X-ray Microscopy (XRM) analysis suggested that the TNTZ implant present better mechanobiological characteristics including improved load transduction and increased bone area in the tilted implantation model compared to TC4 implant, especially in the upper 1/3 region of peri-implant bone that is "lower stress". Finally, combining the static and dynamic parameters of bone, it was further verified that TNTZ enhanced bone remodeling in "lower stress" upper 1/3 region. This study demonstrates that TNTZ is a mechanobiological optimized tilted implant material that enhances load transduction and bone remodeling.

Rapid In-Situ Synthesis and Patterning of Edge-Unsaturated MoS2 by Femtosecond Laser-Induced Photo-Chemical Reaction.

Molybdenum disulfide (MoS2) is a representative transition metal sulfide that is widely used in gas and biological detection, energy storage, and integrated electronic devices due to its unique optoelectrical and chemical characteristics. To advance toward the miniaturization and on-chip integration of functional devices, it is strategically important to develop a high-precision and cost-effective method for the synthesis and integration of MoS2 patterns and functional devices. Traditional methods require multiple steps and time-consuming processes such as material synthesis, transfer, and photolithography to fabricate MoS2 patterns at the desired region on the substrate, significantly increasing the difficulty of manufacturing micro/nanodevices. In this work, we propose a single-step femtosecond laser-induced photochemical method which can realize the fabrication of arbitrary two-dimensional edge-unsaturated MoS2 patterns with high efficiency in microscale. Based on this method, MoS2 can be synthesized at a rate of 150 µm/s, 2 orders of magnitude faster than existing laser-based thermal decomposition methods without sacrificing the resolution and quality. The morphology and roughness of the MoS2 pattern can be controlled by adjusting the laser parameters. Furthermore, the femtosecond laser direct writing (FLDW) method was used to fabricate microscale MoS2-based gas detectors that can detect a variety of toxic gases with high sensitivity up to 0.5 ppm at room temperature. This FLDW method is not only applicable to the fabrication of high-precision MoS2 patterns and integrated functional devices, it also provides an effective route for the development of other micro/nanodevices based on a broad range of transition metal sulfides and other functional materials.

Whole exome sequencing identified a rare WT1 loss-of-function variant in a non-syndromic POI patient.

BACKGROUND: Premature ovarian insufficiency (POI) is a highly heterogeneous disease, and up to 25% of cases can be explained by genetic causes. The transcription factor WT1 has long been reported to play a crucial role in ovary function. Wt1-mutated female mice exhibited POI-like phenotypes. METHODS AND RESULTS: In this study, whole exome sequencing (WES) was applied to find the cause of POI in Han Chinese women. A nonsense variant in the WT1 gene: NM_024426.6:c.1387C>T(p.R463*) was identified in a non-syndromic POI woman. The variant is a heterozygous de novo mutation that is very rare in the human population. The son of the patient inherited the mutation and developed Wilms' tumor and urethral malformation at the age of 7. According to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) guidelines, the novel variant is categorized as pathogenic. Western blot analysis further demonstrated that the WT1 variant could produce a truncated WT1 isoform in vitro. CONCLUSIONS: A rare heterozygous nonsense WT1 mutant is associated with non-syndromic POI and Wilms' tumor. Our finding characterized another pathogenic WT1 variant, providing insight into genetic counseling.

Haploinsufficiency in non-homologous end joining factor 1 induces ovarian dysfunction in humans and mice.

BACKGROUND: Premature ovarian insufficiency (POI) is a common disease in women that leads to a reduced reproductive lifespan. The aetiology of POI is genetically heterogeneous, with certain double-strand break (DSB) repair genes being implicated in POI. Although non-homologous end joining (NHEJ) is an efficient DSB repair pathway, the functional relationship between this pathway and POI remains unknown. METHODS AND RESULTS: We conducted whole-exome sequencing in a Chinese family and identified a rare heterozygous loss-of-function variant in non-homologous end joining factor 1 (NHEJ1): c.532C>T (p.R178*), which co-segregated with POI and irregular menstruation. The amount of NHEJ1 protein in the proband was half of the normal level, indicating a link between NHEJ1 haploinsufficiency and POI. Furthermore, another rare heterozygous NHEJ1 variant c.500A>G (p.Y167C) was identified in one of 100 sporadic POI cases. Both variants were predicted to be deleterious by multiple in silico tools. In vitro assays showed that knock-down of NHEJ1 in human KGN ovarian cells impaired DNA repair capacity. We also generated a knock-in mouse model with a heterozygous Nhej1 variant equivalent to NHEJ1 p.R178* in familial patients. Compared with wild-type mice, heterozygous Nhej1-mutated female mice required a longer time to first birth, and displayed reduced numbers of primordial and growing follicles. Moreover, these mice exhibited higher sensitivity to DSB-inducing drugs. All these phenotypes are analogous to the progressive loss of ovarian function observed in POI. CONCLUSIONS: Our observations in both humans and mice suggest that NHEJ1 haploinsufficiency is associated with non-syndromic POI, providing novel insights into genetic counselling and clinical prevention of POI.