Reaction mechanisms of chlorinated disinfection byproducts formed from nitrophenol compounds with different structures during chlor(am)ination and UV/post-chlor(am)ination.

Nitrophenol compounds (NCs) have high formation potentials of disinfection byproducts (DBPs) in water disinfection processes, however, the reaction mechanisms of DBPs formed from different NCs are not elucidated clearly. Herein, nitrobenzene, phenol, and six representative NCs were used to explore the formation mechanisms of chlorinated DBPs (Cl-DBPs) during chlor(am)ination and UV/post-chlor(am)ination. Consequently, the coexistence of nitro and hydroxy groups in NCs facilitated the electrophilic substitution to produce intermediates of Cl-DBPs, and the different positions of nitro and hydroxy groups also induced different yields and formation mechanisms of Cl-DBPs during the chlorination and UV/post-chlorination processes. Besides, the amino, chlorine, and methyl groups significantly influenced the formation mechanisms of Cl-DBPs during the chlorination and UV/post-chlorination processes. Furthermore, the total Cl-DBPs yields from the six NCs followed a decreasing order of 2-chloro-3-nitrophenol, 3-nitrophenol, 2-methyl-3-nitrophenol, 2-amino-4-nitrophenol, 2-nitrophenol, and 4-nitrophenol during chlorination and UV/post-chlorination. However, the total Cl-DBPs yields from the six NCs during chloramination and UV/post-chloramination followed a quite different order, which might be caused by additional reaction mechanisms, e.g., nucleophilic substitution or addition might occur to NCs in the presence of monochloramine (NH2Cl). This work can offer deep insights into the reaction mechanisms of Cl-DBPs from NCs during the chlor(am)ination and UV/post-chlor(am)ination processes.

Formation and toxicity alteration of halonitromethanes from Chlorella vulgaris during UV/chloramination process involving bromide ion.

Frequent algal blooms cause algal cells and their algal organic matter (AOM) to become critical precursors of disinfection by-products (DBPs) during water treatment. The presence of bromide ion (Br-) in water has been demonstrated to affect the formation laws and species distribution of DBPs. However, few researchers have addressed the formation and toxicity alteration of halonitromethanes (HNMs) from algae during disinfection in the presence of Br-. Therefore, in this work, Chlorella vulgaris was selected as a representative algal precursor to investigate the formation and toxicity alteration of HNMs during UV/chloramination involving Br-. The results showed that the formation concentration of HNMs increased and then decreased during UV/chloramination. The intracellular organic matter of Chlorella vulgaris was more susceptible to form HNMs than the extracellular organic matter. When the Br-: Cl2 mass ratio was raised from 0.004 to 0.08, the peak of HNMs total concentration increased 33.99%, and the cytotoxicity index and genotoxicity index of HNMs increased 67.94% and 22.80%. Besides, the formation concentration and toxicity of HNMs increased with increasing Chlorella vulgaris concentration but decreased with increasing solution pH. Possible formation pathways of HNMs from Chlorella vulgaris during UV/chloramination involving Br- were proposed based on the alteration of nitrogen species and fluorescence spectrum analysis. Furthermore, the formation laws of HNMs from Chlorella vulgaris in real water samples were similar to those in deionized water samples. This study contributes to a better comprehension of HNMs formation from Chlorella vulgaris and provides valuable information for water managers to reduce hazards associated with the formation of HNMs.

Interrelationships among abnormal P-wave axis, metabolic syndrome and its components, and mortality in US adults.

BACKGROUND: Metabolic syndrome (MetS) is associated with increased rates of cardiovascular disease and mortality and is linked to abnormal electrocardiogram (ECG) parameters. We aimed to explore the relationships and interactions among MetS and its components, abnormal P-wave axis (aPWA), and mortality rates. METHODS: We analyzed data from 7526 adult participants with sinus rhythm recruited from the National Health and Nutrition Examination Survey III. MetS was classified based on the NCEP ATP III-2005 definition. aPWA included all P-wave axis outside 0-75°. The National Death Index was utilized to identify survival status. Hazard ratios (HRs) and 95% confidence intervals (CIs) categorized by aPWA, MetS, and their components were analyzed using Cox proportional hazards models to investigate all-cause and cardiovascular mortalities. RESULTS: Within a median follow-up period of 20.76 years, 4686 deaths were recorded, of which 1414 were attributable to cardiovascular disease. Participants with both MetS and aPWA had higher all-cause (HR: 1.45, 95% CI: 1.29-1.64, interaction P = 0.043) and cardiovascular (HR: 1.36, 95% CI: 1.02-1.79, interaction P-value = 0.058) mortality rates than participants without MetS and with a normal P-wave axis. Participants with the greatest number of MetS components and aPWA had a higher risk of all-cause mortality (HR: 1.70, 95% CI: 1.13-2.55, P = 0.011). CONCLUSIONS: Individuals with both aPWA and MetS have a higher risk of mortality, and those with a greater number of MetS components and aPWA have a higher risk of all-cause mortality. These findings highlight the significance of integrating ECG characteristics with metabolic health status in clinical assessment.

Effects of cupric ions on the formation of chlorinated disinfection byproducts from nitrophenol compounds during UV/post-chlorination.

Cupric ions (Cu2+) are ubiquitous in surface waters and can influence disinfection byproducts (DBPs) formation in water disinfection processes. This work explored the effects of Cu2+ on chlorinated DBPs (Cl-DBPs) formation from six representative nitrophenol compounds (NCs) during UV irradiation followed by a subsequent chlorination (i.e., UV/post-chlorination), and the results showed Cu2+ enhanced chlorinated halonitromethane (Cl-HNMs) formation from five NCs (besides 2-methyl-3-nitrophenol) and dichloroacetonitrile (DCAN) and trichloromethane (TCM) formation from six NCs. Nevertheless, excessive Cu2+ might reduce Cl-DBPs formation. Increasing UV fluences displayed different influences on total Cl-DBPs formation from different NCs, and increasing chlorine dosages and NCs concentrations enhanced that. Moreover, a relatively low pH (5.8) or high pH (7.8) might control the yields of total Cl-DBPs produced from different NCs. Notably, Cu2+ enhanced Cl-DBPs formation from NCs during UV/post-chlorination mainly through the catalytic effect on nitro-benzoquinone production and the conversion of Cl-DBPs from nitro-benzoquinone. Additionally, Cu2+ could increase the toxicity of total Cl-DBPs produced from five NCs besides 2-methyl-3-nitrophenol. Finally, the impacts of Cu2+ on Cl-DBPs formation and toxicity in real waters were quite different from those in simulated waters. This study is conducive to further understanding how Cu2+ affected Cl-DBPs formation and toxicity in chlorine disinfection processes and controlling Cl-DBPs formation in copper containing water.

Comparative analysis of chlorinated disinfection byproducts formation from 4-nitrophenol and 2-amino-4-nitrophenol during UV/post-chlorination.

Nitrophenol compounds (NCs) are widely distributed in water environments and regarded as important precursors of disinfection byproducts (DBPs). Herein, 4-nitrophenol and 2-amino-4-nitrophenol were selected as representative NCs to explore chlorinated DBPs (Cl-DBPs) formation during UV/post-chlorination. Dichloronitromethane (DCNM), trichloronitromethane (TCNM), dichloroacetonitrile (DCAN), and trichloromethane (TCM) were formed from 4-nitrophenol and 2-amino-4-nitrophenol during UV/post-chlorination, and the yields of individual Cl-DBPs from 2-amino-4-nitrophenol were higher than those from 4-nitrophenol. Meantime, increasing chlorine contact time, UV fluence, and free chlorine dose could enhance Cl-DBPs formation, while much higher values of the three factors might decrease the yields of Cl-DBPs. Besides, alkaline pH could decrease the yields of halonitromethane (HNMs) and DCAN but increase the yields of TCM. Also, higher concentrations of 4-nitrophenol and 2-amino-4-nitrophenol would induce more Cl-DBPs formation. Subsequently, the possible formation pathways of DCNM, TCNM, DCAN, and TCM form 4-nitrophenol and 2-amino-4-nitrophenol during UV/post-chlorination were proposed according to transformation products (TPs) and density functional theory (DFT) calculation. Notably, Cl-DBPs formed from 2-amino-4-nitrophenol presented higher toxicity than those from 4-nitrophenol. Among these generated Cl-DBPs, DCAN and TCNM posed higher cytotoxicity and genotoxicity, respectively. Furthermore, 4-nitrophenol, 2-amino-4-nitrophenol, and their TPs exhibited ecotoxicity. Finally, 4-nitrophenol and 2-amino-4-nitrophenol presented a high potential to produce DCNM, TCNM, DCAN, and TCM in actual waters during UV/post-chlorination, but the Cl-DBPs yields were markedly different from those in simulated waters. This work can help better understand Cl-DBPs formation from different NCs during UV/post-chlorination and is conducive to controlling Cl-DBPs formation.

Biogenesis of Rab14-positive endosome buds at Golgi-endosome contacts by the RhoBTB3-SHIP164-Vps26B complex.

Early endosomes (EEs) are crucial in cargo sorting within vesicular trafficking. While cargoes destined for degradation are retained in EEs and eventually transported to lysosomes, recycled cargoes for the plasma membrane (PM) or the Golgi undergo segregation into specialized membrane structures known as EE buds during cargo sorting. Despite this significance, the molecular basis of the membrane expansion during EE bud formation has been poorly understood. In this study, we identify a protein complex comprising SHIP164, an ATPase RhoBTB3, and a retromer subunit Vps26B, which promotes the formation of EE buds at Golgi-EE contacts. Our findings reveal that Vps26B acts as a novel Rab14 effector, and Rab14 activity regulates the association of SHIP164 with EEs. Depletion of SHIP164 leads to enlarged Rab14+ EEs without buds, a phenotype rescued by wild-type SHIP164 but not the lipid transfer-defective mutants. Suppression of RhoBTB3 or Vps26B mirrors the effects of SHIP164 depletion. Together, we propose a lipid transport-dependent pathway mediated by the RhoBTB3-SHIP164-Vps26B complex at Golgi-EE contacts, which is essential for EE budding.

Effects of Ultrasonic Treatment on Physical Stability of Lily Juice: Rheological Behavior, Particle Size, and Microstructure.

The aim of this study was to investigate the rheological properties, particle size distribution, color change, and stability of lily juice under different ultrasonic treatment conditions (152 W, 304 W, 456 W, 608 W, and 760 W). The results showed that the lily juice exhibited non-Newtonian shear thinning behavior, and the viscosity decreased with the increase in ultrasonic power. Under ultrasonic treatment conditions, there was no significant change in the pH value and zeta potential value of the samples. The content of cloudy value and total soluble solids (TSS) increased gradually. However, both the sedimentation components and centrifugal sedimentation rate showed a downward trend and an asymptotic behavior. In addition, high-power ultrasound changed the color index (L* value decreased, a* value increased), tissue structure, and particle distribution of the sample, and small particles increased significantly. To sum up, ultrasonic treatment has great potential in improving the physical properties and suspension stability of lily juice.

Moderate oxidation of algae-laden water: Principals and challenges.

The occurrence of seasonal algae blooms represents a huge dilemma for water resource management and has garnered widespread attention. Therefore, finding methods to control algae pollution and improve water quality is urgently needed. Moderate oxidation has emerged as a feasible way of algae-laden water treatment and is an economical and prospective strategy for controlling algae and endogenous and exogenous pollutants. Despite this, a comprehensive understanding of algae-laden water treatment by moderate oxidation, particularly principles and summary of advanced strategies, as well as challenges in moderate oxidation application, is still lacking. This review outlines the properties and characterization of algae-laden water, which serve as a prerequisite for assessing the treatment efficiency of moderate oxidation. Biomass, cell viability, and organic matter are key components to assessing moderate oxidation performance. More importantly, the recent advancements in employing moderate oxidation as a treatment or pretreatment procedure were examined, and the suitability of different techniques was evaluated. Generally, moderate oxidation is more promising for improving the solid-liquid separation process by the reduction of cell surface charge (stability) and removal/degradation of the soluble algae secretions. Furthermore, this review presents an outlook on future research directions aimed at overcoming the challenges encountered by existing moderate oxidation technologies. This comprehensive examination aims to provide new and valuable insights into the moderate oxidation process.

[Mutation spectrum analysis of 23-site chip neonatal deafness genetic screening].

Objective:To analyze the mutation spectrum of 23-site chip newborn deafness genetic screening in Beijing, and to provide basis for genetic counseling and clinical diagnosis and treatment. Methods:The study included 21 006 babies born in Beijing from December 2022 to June 2023. All subjects underwent newborn deafness genetic screening in Beijing Tongren Hospital, covering 23 variants in 4 genes, the GJB2 gene（c.35delG, c.176_191del16, c.235delC, c.299_300delAT, c.109G>A, c.257C>G, c.512insAACG, c.427C>T, c.35insG）, SLC26A4 gene（c.919-2A>G, c.2168A>G, c.1174A>T, c.1226G>A, c.1229C>T, c.1975G>C, c.2027T>A, c.589G>A, c.1707+5G>A, c.917insG, c.281C>T）, Mt12SrRNA（m.1555A>G, m.1494C>T） and GJB3 gene（c.538C>T）. The mutation detection rate and allele frequency were analyzed. Results:The overall mutation detection rate was 11.516%（2 419/21 006）, with the GJB2 gene being the most frequently involved at 9.097%（1 911/21 006）, followed by the SLC26A4 gene at 2.123%（446/21 006）, the GJB3 gene at 0.362%（76/21 006） and Mt12SrRNA at 0.176%（37/21 006）. Among the GJB2 genes, c.109G>A and c.235delC mutation detection rates were the highest, with 6.579%（1 382/21 006） and 1.795%（377/21 006）, respectively. Of the SLC26A4 genes, c.919-2A>G and c.2168A>G had the highest mutation rates of 1.423%（299/21 006） and 0.233%（49/21 106）, respectively. Regarding the allele frequency, GJB2 c.109G>A was the most common variant with an allele frequency of 3.359%（1 411/42 012）, followed by the GJB2 c.235delC at 0.897%（377/42 012） and the SLC26A4 c.919-2A>G at 0.719%（302/42 012）. Conclusion:23-site chip newborn deafness genetic screening in Beijing showed that GJB2 c.109G>A mutation detection rate and allele frequency were the highest. This study has enriched the epidemiological data of 23-site chip genetic screening mutation profiles for neonatal deafness, which can provide evidence for clinical practice.

High-frequency hearing vulnerability associated with the different supporting potential of Hensen's cells: SMART-Seq2 RNA sequencing.

Hearing loss is the third most prevalent physical condition affecting communication, well-being, and healthcare costs. Sensorineural hearing loss often occurs first in the high-frequency region (basal turn), then towards the low-frequency region (apical turn). However, the mechanism is still unclear. Supporting cells play a critical role in the maintenance of normal cochlear function. The function and supporting capacity of these cells may be different from different frequency regions. Hensen's cells are one of the unique supporting cell types characterized by lipid droplets (LDs) in the cytoplasm. Here, we investigated the morphological and gene expression differences of Hensen's cells along the cochlear axis. We observed a gradient change in the morphological characteristics of Hensen's cells along the cochlear tonotopic axis, with larger and more abundant LDs observed in apical Hensen's cells. Smart-seq2 RNA-seq revealed differentially expressed genes (DEGs) between apical and basal Hensen's cells that clustered in several pathways, including unsaturated fatty acid biosynthesis, cholesterol metabolism, and fatty acid catabolism, which are associated with different energy storage capacities and metabolic potential. These findings suggest potential differences in lipid metabolism and oxidative energy supply between apical and basal Hensen's cells, which is consistent with the morphological differences of Hensen's cells. We also found differential expression patterns of candidate genes associated with hereditary hearing loss (HHL), noise-induced hearing loss (NIHL), and age-related hearing loss (ARHL). These findings indicate functional heterogeneity of SCs along the cochlear axis, contribute to our understanding of cochlear physiology and provide molecular basis evidence for future studies of hearing loss.

A straightforward approach for the rapid detection of red Noctiluca scintillans blooms from satellite imagery.

Red Noctiluca scintillans (RNS), a prominent species of dinoflagellate known for its conspicuous size and ability to form blooms, exhibits heterotrophic behavior and functions as a microzooplankton grazer within the marine food web. In this study, a straightforward technique referred to as the blue-green index (BGI) has been introduced for the purpose of distinguishing and discerning RNS from neighboring waters, owing to its pronounced absorption in the blue-green spectral range. This method has been applied across a range of satellite imagery, encompassing both multi-spectral and hyperspectral sensors. The study delved into three instances of bloom occurrences caused by RNS: firstly, in November 2014 and April 2022 off the western coast of Guangdong, and secondly, in February 2021 within the Beibu Gulf. The notable bloom event in the Beibu Gulf during February 2021 extended across an expansive area totaling 6933.5 km2. The motion speed and direction of the RNS bloom patches were also derived from successive satellite images. The recently introduced BGI method demonstrates insensitivity to suspended sediment, though its successful application necessitates accurate atmospheric correction. Subsequent efforts will involve the quantification of RNS blooms in a more precise manner, utilizing hyperspectral satellite data grounded in optimized band configurations.

The effect of dexmedetomidine on the postoperative recovery of patients with severe traumatic brain injury undergoing craniotomy treatment: a retrospective study.

BACKGROUND: Traumatic brain injury (TBI) has been a worldwide problem for neurosurgeons. Patients with severe TBI may undergo craniotomy. These patients often require sedation after craniotomy. Dexmedetomidine (DEX) has been used in patients receiving anesthesia and in intensive care units. Not much is known about the postoperative effect of DEX in patients with severe TBIs undergoing craniotomy. The purpose of this study was to explore the effects of postoperative DEX administration on severe TBI patients who underwent craniotomy. METHODS: Patients who underwent craniectomy for severe TBI at our hospital between January 2019 and February 2022 were included in this study. The patients were admitted to the intensive care unit (ICU) after surgery to receive sedative medication. The patients were then divided into DEX and control groups. We analyzed the sedation, hemodynamics, and other conditions of the patients (hypoxemia, duration of ventilation during endotracheal intubation, whether tracheotomy was performed, and the duration in the ICU) during their ICU stay. Other conditions, such as delirium after the patients were transferred to the general ward, were also analyzed. RESULTS: A total of 122 patients were included in this study. Among them, 53 patients received DEX, and the remaining 69 did not. The incidence of delirium in the general ward in the DEX group was significantly lower than that in the control group (P < 0.05). The incidence of bradycardia in the control group was significantly lower than that in the DEX group (P < 0.05). Other data from the DEX group and the control group (hypotension, hypoxemia, etc.) were not significantly different (P > 0.05). CONCLUSION: The use of DEX in the ICU can effectively reduce the incidence of delirium in patients who return to the general ward after craniotomy. DEX had no adverse effect on the prognosis of patients other than causing bradycardia.

MnFe layered double hydroxides confined MnOx for peroxymonosulfate activation: A novel manner for the selective production of singlet oxygen.

Singlet oxygen (1O2) is a reactive species for the selective degradation of stubborn organic pollutants. Given its resistance to harsh water environment, the effective and exclusive generation of 1O2 is acknowledged as a key strategy to mitigate water production costs and ensure water supply safety. Herein, we synthesized MnOx intercalated MnFe layered double hydroxides (MF-MnOx) to selectively produce 1O2 through the activation of PMS. The distinctive confined structure endowed MF-MnOx with a special pathway for the PMS activation. The direct oxidation of BPA on the intercalated MnOx induced the charge imbalance in the MnFe-LDH layer, resulting in the selective generation of 1O2. Moreover, acceptable activity deterioration of MF-MnOx was observed in a 10 h continuous degradation test in actual water, substantiating the application potential of MF-MnOx. This work presents a novel catalyst for the selective production of 1O2, and evaluates its prospects in the remediation of micro-polluted water.

Regulator of Ribosome Synthesis 1 (RRS1) Stabilizes GRP78 and Promotes Breast Cancer Progression.

Regulator of ribosome synthesis 1 (RRS1), a crucial regulatory factor in ribosome biogenesis, exerts a remarkable impact on the progression of breast cancer (BC). However, the exact mechanisms and pathways have not yet been fully elucidated. To investigate the impact of RRS1 on BC growth and metastasis, along with its underlying mechanisms. We discovered that RRS1 is overexpressed in BC tissues and cell lines. This study aims to regulate the level of RRS1 through lentiviral transfection technology to explore its potential function in BC cells. Knockdown of RRS1 resulted in the inhibition of cell proliferation, invasion, and migration, whereas overexpression had the opposite effects. We firstly identified the interaction between RRS1 and Glucose-Regulated Protein 78 (GRP78) using Co-immunoprecipitation (Co-IP) combined with mass spectrometry analysis, providing evidences of co-localization and positive regulation between RRS1 and GRP78. We observed that RRS1 inhibited the degradation of GRP78 through the ubiquitin-proteasome pathway, resulting in the stabilization of GRP78. In addition, our findings suggested that RRS1 promoted BC progression by activating the GRP78-mediated phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. In conclusion, this newly discovered RRS1/GRP78 signaling axis provides a molecular and theoretical basis for further exploring the mechanisms of breast cancer invasion and metastasis.

Comparative transcriptomic analysis reveals the molecular mechanism underlying seedling heterosis and its relationship with hybrid contemporary seeds DNA methylation in soybean.

Heterosis is widely used in crop production, but phenotypic dominance and its underlying causes in soybeans, a significant grain and oil crop, remain a crucial yet unexplored issue. Here, the phenotypes and transcriptome profiles of three inbred lines and their resulting F1 seedlings were analyzed. The results suggest that F1 seedlings with superior heterosis in leaf size and biomass exhibited a more extensive recompilation in their transcriptional network and activated a greater number of genes compared to the parental lines. Furthermore, the transcriptional reprogramming observed in the four hybrid combinations was primarily non-additive, with dominant effects being more prevalent. Enrichment analysis of sets of differentially expressed genes, coupled with a weighted gene co-expression network analysis, has shown that the emergence of heterosis in seedlings can be attributed to genes related to circadian rhythms, photosynthesis, and starch synthesis. In addition, we combined DNA methylation data from previous immature seeds and observed similar recompilation patterns between DNA methylation and gene expression. We also found significant correlations between methylation levels of gene region and gene expression levels, as well as the discovery of 12 hub genes that shared or conflicted with their remodeling patterns. This suggests that DNA methylation in contemporary hybrid seeds have an impact on both the F1 seedling phenotype and gene expression to some extent. In conclusion, our study provides valuable insights into the molecular mechanisms of heterosis in soybean seedlings and its practical implications for selecting superior soybean varieties.

STNet: A Time-Frequency Analysis-Based Intrusion Detection Network for Distributed Optical Fiber Acoustic Sensing Systems.

Distributed optical fiber acoustic sensing (DAS) is promising for long-distance intrusion-anomaly detection tasks. However, realistic settings suffer from high-intensity interference noise, compromising the detection performance of DAS systems. To address this issue, we propose STNet, an intrusion detection network based on the Stockwell transform (S-transform), for DAS systems, considering the advantages of the S-transform in terms of noise resistance and ability to detect disturbances. Specifically, the signal detected by a DAS system is divided into space-time data matrices using a sliding window. Subsequently, the S-transform extracts the time-frequency features channel by channel. The extracted features are combined into a multi-channel time-frequency feature matrix and presented to STNet. Finally, a non-maximum suppression algorithm (NMS), suitable for locating intrusions, is used for the post-processing of the detection results. To evaluate the effectiveness of the proposed method, experiments were conducted using a realistic high-speed railway environment with high-intensity noise. The experimental results validated the satisfactory performance of the proposed method. Thus, the proposed method offers an effective solution for achieving high intrusion detection rates and low false alarm rates in complex environments.

A de novo PKD1 mutation in a Chinese family with autosomal dominant polycystic kidney disease.

BACKGROUND: PKD1, which has a relatively high mutation rate, is highly polymorphic, and the role of PKD1 is incompletely defined. In the current study, in order to determine the molecular etiology of a family with autosomal dominant polycystic kidney disease, the pathogenicity of an frameshift mutation in the PKD1 gene, c.9484delC, was evaluated. METHODS: The family clinical data were collected. Whole exome sequencing analysis determined the level of this mutation in the proband's PKD1, and Sanger sequencing and bioinformatics analysis were performed. SIFT, Polyphen2, and MutationTaster were used to evaluate the conservation of the gene and pathogenicity of the identified mutations. SWISS-MODEL was used to predict and map the protein structure of PKD1 and mutant neonate proteins. RESULTS: A novel c.9484delC (p.Arg3162Alafs*154) mutation of the PKD1 gene was identified by whole exome sequencing in the proband, which was confirmed by Sanger sequencing in his sister (II7). The same mutation was not detected in the healthy pedigree members. Random screening of 100 normal and end-stage renal disease patients did not identify the c.9484delC mutation. Bioinformatics analysis suggested that the mutation caused the 3162 nd amino acid substitution of arginine by alanine and a shift in the termination codon. As a result, the protein sequence was shortened from 4302 amino acids to 3314 amino acids, the protein structure was greatly changed, and the PLAT/LH2 domain was destroyed. Clustal analysis indicated that the altered amino acids were highly conserved in mammals. CONCLUSION: A novel mutation in the PKD1 gene has been identified in an affected Chinese family. The mutation is probably responsible for a range of clinical manifestations for which reliable prenatal diagnosis and genetic counseling may be provided.

shinyTempSignal: an R shiny application for exploring temporal and other phylogenetic signals.

The molecular clock model is fundamental for inferring species divergence times from molecular sequences. However, its direct application may introduce significant biases due to sequencing errors, recombination events, and inaccurately labeled sampling times. Improving accuracy necessitates rigorous quality control measures to identify and remove potentially erroneous sequences. Furthermore, while not all branches of a phylogenetic tree may exhibit a clear temporal signal, specific branches may still adhere to the assumptions, with varying evolutionary rates. Supporting a relaxed molecular clock model better aligns with the complexities of evolution. The root-to-tip regression method has been widely used to analyze the temporal signal in phylogenetic studies and can be generalized for detecting other phylogenetic signals. Despite its utility, there remains a lack of corresponding software implementations for broader applications. To address this gap, we present shinyTempSignal, an interactive web application implemented with the shiny framework, available as an R package and publicly accessible at https://github.com/YuLab-SMU/shinyTempSignal. This tool facilitates the analysis of temporal and other phylogenetic signals under both strict and relaxed models. By extending the root-to-tip regression method to diverse signals, shinyTempSignal helps in the detection of evolving features or traits, thereby laying the foundation for deeper insights and subsequent analyses.

A distinct class of pan-cancer susceptibility genes revealed by an alternative polyadenylation transcriptome-wide association study.

Alternative polyadenylation plays an important role in cancer initiation and progression; however, current transcriptome-wide association studies mostly ignore alternative polyadenylation when identifying putative cancer susceptibility genes. Here, we perform a pan-cancer 3' untranslated region alternative polyadenylation transcriptome-wide association analysis by integrating 55 well-powered (n > 50,000) genome-wide association studies datasets across 22 major cancer types with alternative polyadenylation quantification from 23,955 RNA sequencing samples across 7,574 individuals. We find that genetic variants associated with alternative polyadenylation are co-localized with 28.57% of cancer loci and contribute a significant portion of cancer heritability. We further identify 642 significant cancer susceptibility genes predicted to modulate cancer risk via alternative polyadenylation, 62.46% of which have been overlooked by traditional expression- and splicing- studies. As proof of principle validation, we show that alternative alleles facilitate 3' untranslated region lengthening of CRLS1 gene leading to increased protein abundance and promoted proliferation of breast cancer cells. Together, our study highlights the significant role of alternative polyadenylation in discovering new cancer susceptibility genes and provides a strong foundational framework for enhancing our understanding of the etiology underlying human cancers.

Formation of halonitromethanes from benzylamine during UV/chlorination: Impact factors, toxicity alteration, and pathways.

Halonitromethanes (HNMs), a representative nitrogen-containing disinfection byproduct, have gained significant concerns due to their higher cytotoxicity and genotoxicity. UV/chlorination is considered a promising alternative disinfection technology for chlorination. This study aimed to investigate the HNMs formation from benzylamine (BZA) during UV/chlorination. The experimental results revealed that the yields of HNMs initially raised to a peak then dropped over time. Higher chlorine dosage and BZA concentration promoted the formation of HNMs, whereas alkaline pH inhibited their formation. The presence of bromine ion (Br-) not only converted chlorinated-HNMs (Cl-HNMs) to brominated (chlorinated)-HNMs Br (Cl)-HNMs) and brominated-HNMs (Br-HNMs) but also enhanced the total concentration of HNMs. Besides, the calculated cytotoxicity index (CTI) and genotoxicity index (GTI) of HNMs were elevated by 68.97% and 60.66% as Br- concentration raised from 2 to 6 µM. The possible formation pathways of HNMs from BZA were proposed based on the intermediates identified by a gas chromatography/mass spectrometry (GC/MS). In addition, the formation rules of HNMs in actual water verified the results in deionized water during UV/chlorination. The results of this study provide basic data and a theoretical basis for the formation and control of HNMs, which is conducive to applying UV/chlorination.