Enhancing waste sludge solubilization through radio frequency treatment perforating bacterial cells.

Sludge solubilization is known as a rate-limiting step of anaerobic digestion. Although radio frequency (RF) has been applied for sludge pretreatment due to its similar thermal effect as microwave, the potential non-thermal effects of RF treatment remain controversial. In this study, we demonstrate that RF pretreatment enhances the solubilization and lysis of sludge by 8.02%-19.69% through both thermal and non-thermal mechanisms with less energy input. Scanning electron microscope images provide direct evidence that RF-induced microcurrents penetrated bacterial cells, leading to the release of intracellular substances through formed pores. Additionally, the non-thermal effect of RF treatment which could weaken the cell protection and accelerate the lysis rate involves the disruption of binding forces between extracellular polymeric substances and microbial cells. On average, the utilization of RF at a frequency of 27.12 MHz demonstrates its efficacy as a sludge pretreatment technique, as evidenced by a 13.39% reduction in energy consumption and a 16.9% improvement in treatment performance compared to conductive heating (CH). The findings of this study elucidate the possible mechanism of RF treatment of sludge and could establish a theoretical basis for the practical application of RF treatment in sludge management.

Revealing disparities in different types of park visits based on cellphone signaling data in Guangzhou, China.

Urban parks play a crucial role in promoting the urban ecological environment and the health and well-being of dwellers. However, existing research on park visits and drivers has largely ignored the classification of parks. Using the four-level park system in Guangzhou as a case, this study first measured park visits based on cellphone signaling data. Then, the independent and interactive influences of driving factors on the visits of four types of parks were investigated and compared comprehensively based on the geographical detector model. The factor detector model preliminarily distinguished the functional and role differences of various park types. Nature and urban parks are more functional, and community and pocket parks mainly provide nearby residents with convenient relaxation spaces. The interaction detector further revealed the disparities in park visit drivers between four types of parks. The most significant finding is that nearby recreational facility is the key to the use of natural and urban parks, while the determining factor for the visits of community and pocket parks is the surrounding population. Based on these findings, the study recommends tailored strategies for each type of park, to promote effective management and increased utilization. In particular, the study highlights the importance of understanding the differences between park types and developing customized strategies to maximize the benefits of urban parks and foster a healthy and sustainable urban environment.

Spatially explicit carbon emissions by remote sensing and social sensing.

Scientific simulation of carbon emissions is an important prerequisite for achieving low-carbon green development and carbon peak and carbon neutralization. This study proposed a carbon emissions spatialization method based on nighttime light (NTL) remote sensing and municipal electricity social sensing. First, the economics-energy comprehensive index (EECI) was proposed by integrating the NTL and municipal electricity consumption (EC) data. Second, the carbon emissions were spatialized at a fine scale based on NTL, EC, and EECI, respectively. Finally, the geographical detector model was applied to quantify the influencing factors on carbon emissions from the perspectives of individuals and interactions. Results show that combining remote sensing and social sensing data helps depict carbon emissions accurately. The factor analysis found that GDP and population were the basis of carbon emissions, while the secondary industry and urbanization rate were the direct factors. This study is expected to provide constructive suggestions and methods for emission reduction, carbon peak, and carbon neutrality in high-density cities in China.

Giant axonal neuropathy (GAN) in an 8-year-old girl caused by a homozygous pathogenic splicing variant in GAN gene.

Giant axonal neuropathy (GAN) is a progressive disease that involves the peripheral and central nervous systems. This neurodegenerative disease is caused by variants in the GAN gene encoding gigaxonin, and is inherited in an autosomal recessive manner. Herein, we performed whole-exome sequencing on a 8-year-old child with dense, curly hair, weakness in both lower limbs, and abnormal MRI. The child was born to consanguineous parents. Our results revealed that the child carried the c.1373+1G>A homozygous pathogenic variant of the GAN gene, while both parents were heterozygous carriers. According to the validation at the cDNA levels, the splicing variant led to the skipping of exon 8 and affected the Kelch domain's formation. Unlike the previously reported cases of GAN, the child's clinical manifestations revealed peripheral nervous system involvement, no vertebral signs, cerebellar signs, and spasticity, but only MRI abnormalities. These results suggested that the patient's central nervous system was mildly involved, which may be related to the genotype. In order to further clarify the correlation between GAN genotype and phenotype, combined with this patient, 54 cases of reported homozygous variants of the GAN gene were merged for the analysis of genotype and phenotype. The results revealed a certain correlation between the GAN gene variant domain and the patient's clinical phenotype, such as central nervous system involvement and age of onset.

Elevated AST/ALT ratio is associated with all-cause mortality and cancer incident.

BACKGROUND: The aspartate transaminase (AST)-to-alanine aminotransferase (ALT) ratio, which is used to measure liver injury, has been found to be associated with some chronic diseases and mortality. However, its relevance to cancer incidence resulting from population-based prospective studies has rarely been reported. In this study, we investigated the correlation of the AST/ALT ratio as a possible predictor of mortality and cancer incidence. METHODS: A total of 9,946 participants fulfilled the inclusion criteria for a basic public health service project of the Health Checkup Program conducted by the BaiYun Community Health Service Center, Taizhou. Deceased participants and cancer incident cases were from The Taizhou Chronic Disease Information Management System. Odds ratios (ORs) and interval of quartile range (IQR) computed by logistic regression analysis and cumulative incidence rate were calculated by the Kaplan-Meier survival method and compared with log-rank test statistics. RESULTS: Serum ALT and AST levels were both increased in patients with chronic diseases, but the ratio of AST/ALT was generally decreased. The cancer incident cases (488 new cases) had a greater baseline ratio (median =1.23, IQR: 0.96-1.54) than noncancer cases (median =1.15, IQR: 0.91-1.44). Compared to the first quartile of the AST/ALT ratio, the population in the top quartile had a higher cumulative cancer incidence rate (7.54% vs. 4.44%) during follow-up period. Furthermore, an elevated AST/ALT ratio increased the risk of all-cause mortality. CONCLUSIONS: The ratio of AST/ALT is a potential biomarker to assess healthy conditions and long-term mortality. Especially for cancer, the AST/ALT ratio not only increases at baseline but also predicts the future development of cancer. The clinical value and potential mechanism deserve further research.

Clinical and genetic analysis of a case with centronuclear myopathy caused by SPEG gene mutation: a case report and literature review.

BACKGROUND: Centronuclear myopathy (CNM), a subtype of congenital myopathy (CM), is a group of clinical and genetically heterogeneous muscle disorders. Since the discovery of the SPEG gene and disease-causing variants, only a few additional patients have been reported. CASE PRESENTATION: The child, a 13-year-old female, had delayed motor development since childhood, weakness of both lower extremities for 10 years, gait swinging, and a positive Gower sign. Her distal muscle strength of both lower extremities was grade IV. The electromyography showed myogenic damage and electromyographic changes. Her 11-year-old sister had a similar muscle weakness phenotype. Gene sequencing revealed that both sisters had SPEG compound heterozygous mutations, and the mutation sites were c.3715 + 4C > T and c.3588delC, which were derived from their parents. These variant sites have not been reported before. The muscle biopsy showed the nucleic (> 20% of fibers) were located in the center of the cell, the average diameter of type I myofibers was slightly smaller than that of type II myofibers, and the pathology of type I myofibers was dominant, which agreed with the pathological changes of centronuclear myopathy. CONCLUSIONS: The clinical phenotypes of CNM patients caused by mutations at different sites of the SPEG gene are also different. In this case, there was no cardiomyopathy. This study expanded the number of CNM cases and the mutation spectrum of the SPEG gene to provide references for prenatal diagnosis and genetic counseling.

[A case of 16p13.11 microdeletion syndrome with febrile convulsion as the main manifestation].

OBJECTIVE: To explore the genetic basis for a girl with febrile convulsion as the main manifestation. METHODS: The child was subjected to whole exome sequencing (WES) and copy number variation sequencing(CNV-seq). Fluorescence quantitative PCR was carried out to validate the microdeletion in her family. RESULTS: The 7-year-old girl was diagnosed with febrile convulsion (complex type) for having fever for 3 days, mild cough and low thermal convulsion once. Her father, mother and aunt also had a history of febrile convulsion. A heterozygous deletion with a size of approximately 1.5 Mb was detected in the 16p13.11 region by WES and CNV-seq. The deletion has derived from her father and was confirmed by fluorescence quantitative PCR. CONCLUSION: 16p13.11 microdeletion syndrome has significant clinical heterogeneity. Different from those with epilepsy, mental retardation, autism, multiple malformations, carriers of 16p13.11 deletion may only manifest with febrile convulsion. Deletion of certain gene(s) from the region may be related to febrile convulsion and underlay the symptom of this child.

[Diagnosis of a case of 2q37 deletion syndrome by whole exome sequencing combined with whole genome low-coverage sequencing method].

OBJECTIVE: To analyze the clinical and genetic characteristics in a girl with 2q37 deletion syndrome. METHODS: Genomic DNA was extracted from peripheral blood samples taken from the patient and her parents, and was subjected to whole exome sequencing (WES) and low-coverage massively parallel copy number variation sequencing (CNV-seq). Candidate CNVs were verified by chromosomal karyotyping analysis and fluorescence quantitative PCR. RESULTS: The child was found to harbor a 6 Mb heterozygous deletion in 2q37 by WES and CNV-seq. The deletion has encompassed 98 genes with a range from GBX2 to LINC01881, and was de novo in origin. The result of fluorescence quantitative PCR was consistent with that of WES and CNV-seq. However, karyotyping analysis has failed to detect the deletion. CONCLUSION: The patient was diagnosed with 2q37 deletion syndrome. Combined WES and CNV-seq method features high resolution, high throughput, and high sensitivity, which can significant raise the diagnostic rate for patients with mental disorder, multiple malformations and unknown syndromes.

Incidence and mortality of cervical cancer in China, 2013.

OBJECTIVE: Estimating the incidence and mortality rate of cervical cancer became necessary to establish prevention measures and healthy policies. The aim of this study was to estimate the updated incidence and mortality rate of cervical cancer in 2013 in China. METHODS: According to the evaluation criteria developed by the National Central Cancer Registry of China, the data submitted from 255 cancer registries met the required standards in 2013. Cervical cancer cases were retrieved from the national database and combined with the 2013 national population data. The age-standardized incidence and mortality rates were based on the demographic structure of the national census 2000 and Segi's world population. RESULTS: In 2013, the estimated number of new cases and deaths from cervical cancer were 100,700 and 26,400, respectively. The crude incidence of cervical cancer was 15.17/100,000. The age-standardized incidence rates based on the Chinese standard population (ASIRC) and the world standard population (ASIRW) were 11.30/100,000 and 10.30/100,000, respectively. The incidence of cervical cancer in urban areas was 15.62/100,000 and the ASIRC was 11.12/100,000. The incidence of cervical cancer in rural areas was 14.65/100,000 and the ASIRC was 11.47/100,000. The mortality rate of cervical cancer was 3.98/100,000. The age-standardized mortality rates based on the Chinese (ASMRC) and world standard populations (ASMRW) were 2.76/100,000 and 2.62/100,000, respectively. The mortality rate of cervical cancer in urban areas was 3.85/100,000 and in rural areas was 4.14/100,000. Cervical cancer incidence and mortality increased with age. Urban areas had a higher incidence of cervical cancer and lower mortality rates when compared with rural areas. CONCLUSIONS: Dynamic monitoring of cervical cancer incidence and mortality is the fundamental work of cervical cancer prevention and control. Cervical cancer is a serious issue in women's health, and prevention strategies need to be enhanced, such as human papilloma virus (HPV) vaccination and screening programs.

Coupling of biocarriers and dynamic membrane for an enhanced volatile fatty acids production from sludge anaerobic fermentation.

Efficiently and economically recovering volatile fatty acids (VFAs) from sludge anaerobic fermentation (AF) poses a significant challenge. This study discovered a synergistic enhancement effect on VFAs production and membrane fouling control by combining Polyethylene (PE) biocarriers and dynamic membrane technology (DM) in an anaerobic bioreactor. The reduced sludge particle size and enhanced hydrolysis efficiency led to a VFAs yield of 1200 mg/L, which is 2.4 times higher than that of traditional AF processes and 1.7 times greater than using the DM module alone. The introduction of PE promoted the enrichment of hydrolytic bacteria, particularly the Christensenellaceae_R-7_group, and facilitated the biotransformation of organic matter. The frictional properties of PE significantly reduced DM fouling, maintaining the transmembrane pressure drop below 30 kPa throughout operation without the need for DM module replacement or cleaning. This study presents a novel approach for resource recovery from sludge through AF, offering new opportunities in the field.

Combining radio frequency heating and alkaline treatment for enhancement of sludge disintegration and volatile fatty acids production from anaerobic fermentation.

Sludge pretreatment plays a crucial role in solubilizing particulate matters to release organic matter for subsequent anaerobic fermentation (AF). This study innovatively combines radio frequency (RF) heating and alkaline treatment, and finds that the combined pretreatment achieved a sludge disintegration rate of 35.11 %, which is 15.19 % and 8.48 % higher than single RF or alkaline pretreatment. The dissociated ions from the alkali are conducive to RF action on sludge. Furthermore, the combined pretreatment significantly benefits the subsequent AF experiments, resulting in a 9-fold increase in volatile fatty acids production. Considering cost-effectiveness, the optimal operating condition is a 10-minute RF treatment at pH 10 with a total cost of 4.35 × 10-3 dollars per kg soluble chemical oxygen demand (SCOD) increased. These findings provide a foundational basis for the development of a novel technology for sludge pretreatment.

Cucurbitacin C as an effective anti-cancer agent: unveiling its potential role against cholangiocarcinoma and mechanistic insights.

BACKGROUND: Cholangiocarcinoma (CCA) is a malignant epithelial tumor characterized by a dismal prognosis. Given the lack of therapeutic strategies and durable treatment options currently available, identifying innovative treatments for CCA is an urgent unmet clinical need. Cucurbitacin C (CuC) is a distinct variant of the cucurbitacin family, displaying promising anti-cancer activity against various tumor types. The primary objective of our research is to elucidate the promising effects of CuC on CCA. METHODS: The impact of CuC on CCA cell lines was assessed by cell count kit-8 assay, EdU staining assay, colony formation assay, wound-healing assay, and Transwell assay. Flow cytometric analysis was conducted to explore the function of CuC treatments on cell-cycle distribution and apoptosis in CCA cells. Computational biology and network pharmacology approaches were utilized to predict potential targets of CuC. Furthermore, a tumor xenograft mouse model was established using CCA cells to explore the anti-cancer effects of CuC in vivo. RESULTS: Our research findings revealed that CuC exerted a suppressive effect on CCA cell progression. Cell viability assays, EdU staining assays, and colony formation assays demonstrated that CuC effectively suppressed viability and proliferation of CCA cells. Wound-healing assays and Transwell assays indicated that CuC effectively inhibits the migratory and invasive capabilities of CCA cells. Flow cytometry analysis elucidated that CuC played its anti-proliferative role in CCA cells by arresting G0/G1 phase and increasing apoptosis. Through bioinformatics and network pharmacology analysis, in conjunction with western blot analysis, we demonstrated CuC mediated the inhibition of CCA cell progression through modulation of JAK2/STAT3 pathway. Additionally, the CCA xenograft tumor model was established, and the results supported the inhibition of CuC treatment against CCA progression in vivo. CONCLUSION: Our study demonstrates that CuC possesses notable capabilities to suppress cell proliferation, migration, and invasion in CCA. Importantly, the inhibitory effects of CuC on CCA progression are attributed to its modulation of the JAK2/STAT3 signaling pathway. Altogether, our study demonstrated that CuC holds promise as a prospective therapeutic agent for treating CCA.

Unraveling the heterogeneity of cholangiocarcinoma and identifying biomarkers and therapeutic strategies with single-cell sequencing technology.

Cholangiocarcinoma (CCA) is a common malignant tumor of the biliary tract that carries a high burden of morbidity and a poor prognosis. Due to the lack of precise diagnostic methods, many patients are often diagnosed at advanced stages of the disease. The current treatment options available are of varying efficacy, underscoring the urgency for the discovery of more effective biomarkers for early diagnosis and improved treatment. Recently, single-cell sequencing (SCS) technology has gained popularity in cancer research. This technology has the ability to analyze tumor tissues at the single-cell level, thus providing insights into the genomics and epigenetics of tumor cells. It also serves as a practical approach to study the mechanisms of cancer progression and to explore therapeutic strategies. In this review, we aim to assess the heterogeneity of CCA using single-cell sequencing technology, with the ultimate goal of identifying possible biomarkers and potential treatment targets.

Exploring spatiotemporal pattern and agglomeration of road CO2 emissions in Guangdong, China.

Road transport is a prominent source of carbon emissions. However, fine-grained regional estimations on road carbon dioxide (CO2) emissions are still lacking. This study estimates road CO2 emissions in Guangdong Province, China, at high spatiotemporal resolution, with a bottom-up framework leveraging massive vehicle trajectory data. We unveil the spatiotemporal pattern of regional road CO2 emissions and highlight the contrasts among cities. The Greater Bay Area (GBA) is found to produce 76 % of the total emissions, wherein Guangzhou emits the most while Shenzhen has the highest emission intensity. Emission agglomeration is still an under-explored field, which we advance in this paper. We propose Quantile-based Hierarchical DBSCAN (QH-DBSCAN) to explore road CO2 emission agglomeration in GBA. Our method is the first one to identify the specific location and scope of emission hotspots. Emission hotspots exhibit significant concentration on major urban centers. Considering emission characteristics from multiple perspectives, we derive six emission categories, including four emission zones and two emission connectors. The density-based property of our method results in spatially contiguous regions with similar emission patterns. Accordingly, we divide policy zones and propose targeted strategies for road carbon reduction. The study provides new technologies and insights to achieve regional sustainable development.

Cucurbitacin I inhibits the proliferation of pancreatic cancer through the JAK2/STAT3 signalling pathway in vivo and in vitro.

Pancreatic cancer is one of the most aggressive solid malignancies, as it has a 5-year survival rate of less than 10%. The growth and invasion of pancreatic cancer cells into normal tissues and organs make resection and treatment difficult. Finding an effective chemotherapy drug for this disease is crucial. In this study, we selected the tetracyclic triterpenoid compound cucurbitacin I, which may be used as a potential therapeutic drug for treating pancreatic cancer. First, we found that cucurbitacin I inhibited pancreatic cancer proliferation in a dose-time dependent manner. Further studies have shown that cucurbitacin I blocks the cell cycle of pancreatic cancer in the G2/M phase and induces cell apoptosis. In addition, under the action of the compound, the invasion ability of cells was greatly reduced and markedly impaired the growth of pancreatic tumour xenografts in nude mice. Furthermore, the decrease in pancreatic cancer cell proliferation caused by cucurbitacin I appeared to involve JAK2/STAT3 signalling pathway inhibition, and the use of JAK2/STAT3 activators effectively restored the inhibition. In conclusion, our research may provide a basis for the further development of pancreatic cancer treatment drugs.

Linderalactone Suppresses Pancreatic Cancer Development In Vitro and In Vivo via Negatively Regulating PI3K/AKT Signaling Pathway.

Linderalactone is one of the main extracts of Linderae Radix, which is widely used in traditional Chinese medicine. There have been few studies on the antitumor effect of linderalactone in the past. In this study, we explored the anti-pancreatic cancer activity of linderalactone in vitro and in vivo. The results showed that linderalactone inhibited the proliferation of pancreatic cancer cells in a time- and dose-dependent manner. Cell migration and invasion were significantly inhibited by linderalactone. The cell cycle was arrested in the G2/M phase, and the expression levels of cell cycle-associated proteins changed significantly with linderalactone treatment. In addition, linderalactone induced cell apoptosis and altered the expression of apoptotic markers, such as caspase 3 and PARP1. Mechanistically, linderalactone suppressed the PI3K/AKT signaling pathway by downregulating the phosphorylation of PI3K and AKT. The xenograft study results were consistent with the in vitro results, and there was no obvious chemical toxicity. Thus, our research demonstrated that linderalactone exhibits antitumor activity against pancreatic cancer and may be developed as a potential anti-pancreatic cancer agent in the future.

Evidence on the association between NQO1 Pro187Ser polymorphism and breast cancer risk in the current studies: a meta-analysis.

Several molecular epidemiological studies were conducted in recent years to evaluate the association between NQO1 Pro187Ser polymorphism and breast cancer risk in diverse populations. However, the results remain conflicting rather than conclusive. This meta-analysis on 3177 cases with breast cancer and 4038 controls from seven published case-control studies showed that the 187Ser allele was not associated with a significantly increased risk of breast cancer (Ser versus Pro: P = 0.33, OR = 1.08, 95% CI = 0.92-1.28; Ser/Ser versus Pro/Pro: P = 0.58, OR = 1.16, 95% CI = 0.68-2.00; Ser/Ser versus Pro/Ser + Pro/Pro: P = 0.62, OR = 1.14, 95% CI = 0.68-1.90; Ser/Ser + Pro/Ser versus Pro/Pro: P = 0.30, OR = 1.07, 95% CI = 0.94-1.22). In the stratified analysis by ethnicity, we found that the Pro187Ser polymorphism was associated with increased breast cancer risk in Caucasians in the additive genetic model and dominant genetic model (P = 0.03, OR = 1.13, 95% CI = 1.01-1.26; P = 0.03, OR = 1.15, 95% CI = 1.01-1.30, respectively), whereas no significant in Asians (P = 0.44, OR = 0.94, 95% CI = 0.80-1.10) and postmenopausal women (P = 0.99, OR = 1.00, 95% CI = 0.84-1.19). The results suggest that NQO1 Pro187Ser polymorphism may contribute to breast cancer development in Caucasians.

Emerging role of microRNAs in major depressive disorder and its implication on diagnosis and therapeutic response.

BACKGROUND: Major depressive disorder (MDD) is a serious and common psychiatric disorder with a high prevalence in the population. Although great advances have been made, its pathogenesis is still unclear and a validated biomarker for diagnosis or therapeutic response remains unidentified. This review aims at summarizing the functional role of miRNAs in MDD pathogenesis and their potential as biomarkers for MDD diagnosis and antidepressant response. METHODS: We performed a bibliographic research on the main databases (PubMed, Google Scholar and Web of Science) using the terms "microRNAs", "major depressive disorder", "synaptic plasticity", "biomarker", "antidepressant treatment", in order to find studies that propose the role of microRNAs in MDD pathogenesis and their potential as biomarkers for MDD diagnosis and antidepressant response. RESULTS: microRNAs (miRNAs), a class of small noncoding RNAs, act as key regulators of synaptic plasticity in MDD pathogenesis. Growing researches provide the evidence for peripheral miRNAs as potential biomarkers for MDD diagnosis and antidepressant response. These results suggest that targeting miRNAs directly could be therapeutically beneficial for MDD and miRNAs are potential biomarkers of MDD and its treatment. LIMITATIONS: The role of miRNAs in MDD pathogenesis needs further investigation. Whether miRNAs in peripheral tissues truly represent brain-derived miRNAs is still unclear at the present time. Moreover, only a few blood miRNAs alterations are consistent across studies. CONCLUSIONS: Overall, miRNAs act key regulators of synaptic plasticity in MDD pathogenesis and hold significant promise as biomarkers or therapeutic targets for MDD, but further research is still needed.

The population characteristics of the main leukocyte subsets and their association with chronic diseases in a community-dwelling population: a cross-sectional study.

AIM: To analyse the characteristics of the main leukocyte subsets and elucidate their distributions amongst the natural population. We wanted to determine whether leukocyte subsets are potential biomarkers to evaluate the risk of common chronic diseases. BACKGROUND: The peripheral blood leukocyte count is a routine exam performed to detect pathogen infections. Recently, subsets of white blood cells and their homeostasis have shown strong associations with some chronic diseases. Therefore, studies aiming to discover whether the distribution of leukocyte counts and its subsets are useful for predicting health conditions are worthwhile. METHODS: This cross-sectional study analysed 10 564 residents from the basic public health service project of the Health Checkup Program performed by the BaiYun Community Health Service Center. Data on demographic information, physical measurements, medical history, and routine blood examination parameters were collected using questionnaires and health check-ups. Restricted cubic spline incorporated into logistic regression analysis was performed to evaluate the association between subsets of leukocytes and common chronic diseases. FINDINGS: The counts of leukocytes and their subsets in males were higher than those in females amongst all age groups, yet the percentages of lymphocytes and neutrophils did not present sex-specific differences. A low lymphocyte count and percentage were associated with old age. The neutrophil-to-lymphocyte ratio (NLR) in patients with hypertension was higher than that in the non-hypertensive population. The risk of NLR in the top quartiles was 1.17-fold higher than that in people in the lowest quartiles. CONCLUSIONS: The distributions of the white blood cell count and percentage were associated with age, sex, and body mass index (BMI). In addition to the immune barrier for pathogens, the NLR or monocyte-to-lymphocyte ratio (MLR) may be potentially used to indicate the risk of some chronic non-communicable diseases. Homeostasis of subsets of leukocytes may be an important biomarker for body health conditions.

Non-classic splicing mutation in the CPLANE1 (C5orf42) gene cause Joubert syndrome in a fetus with severe craniocerebral dysplasia.

BACKGROUD: Joubert syndrome is a rare neurodevelopmental disorder characterized by clinical and genetic heterogeneity. The characteristic molar tooth sign, which resulted from cerebellar vermis hypoplasia and midbrain anomalies, is expected to be the key diagnostic feature for this disease. However, it is not easy to make a definite diagnosis in prenatal only based on the imageology due to its clinical heterogeneity. CASE REPORT: We report on a fetus who was detected cerebellum dysplasia and encephalocele by ultrasound at 19 and 23 gestational weeks and confirmed by MRI examination. The pregnancy was terminated at 23 weeks of gestation. Postaxial polydactyly and deficiency in occipital bone and skin were identified in the induced fetus. RESULTS: The whole exome sequencing identified a novel compound heterozygous variation in the CPLANE1 gene related with Joubert syndrome, including a 2-bp insertion, NM_023073.3:c.1383_1384dup; p.(Gly462Glufs*3) and a non-classic splicing variation, NC_000005.10(NM_023073.3):c.7691-5_7691-4del. The pathogenicity of the non-classic splicing variation was further confirmed by cDNA level sequencing, which showed a exon 39 skipping that would introduce a premature termination. The novel compound heterozygous variation caused a complete function loss of the CPLANE1 gene. CONCLUSION: The cerebellum dysplasia fetus without obvious molar tooth sign was finally diagnosed as Joubert syndrome, combined with genetic detecting and the postnatal clinical symptoms. We also highlight the clinical heterogeneity of encephalodysplasia in Joubert syndrome, which increases the clinical diagnosis difficulty, especially for prenatal diagnosis. Our findings provided a new perspective for the prenatal diagnosis of Joubert syndrome with severe craniocerebral dysplasia and expanded the variation spectrum of the CPLANE1 gene.