Microplastic Contamination of Non-Mulched Agricultural Soils in Bangladesh: Detection, Characterization, Source Apportionment and Probabilistic Health Risk Assessment.

Microplastic contamination in agricultural soil is an emerging problem worldwide as it contaminates the food chain. Therefore, this research investigated the distribution of microplastics (MPs) in agricultural soils without mulch at various depths (0-5, 5-10, and 10-15 cm) across different zones: rural, local market, industrial, coastal, and research areas. The detection of MP types and morphology was conducted using FTIR and fluorescence microscopy, respectively. Eight types of MPs were identified, including high-density polyethylene (HDPE), low-density polyethylene (LDPE), polypropylene (PP), polyethylene terephthalate (PET), polyvinyl chloride (PVC), polyvinyl fluoride (PVF), polyvinyl alcohol (PVA), and polytetrafluoroethylene (PTFE), with concentrations ranging from 0.6 ± 0.21 to 3.71 ± 2.36 MPs/g of soil. The study found no significant trends in MP concentration, with ranges of 0-2.1 ± 0.38, 0-2.87 ± 0.55, and 0-2.0 ± 0.34 MPs/g of soil at depths of 0-5 cm, 5-10 cm, and 10-15 cm, respectively. The highest MP quantity was recorded at 8.67 in coastal area, while the lowest was 6.44 in the local market area. Various MP shapes, e.g., fiber, film, pellet, fragment, and irregular, were observed across all layers. PCA suggested irrigation and organic manure as potential sources of MPs. The estimated concentrations of MPs possessed low non-carcinogenic and carcinogenic risks to the farming community of Bangladesh.

Characterization of Microplastics and Adsorbed/Dissolved Polycyclic Aromatic Hydrocarbons in the Biggest River System in Saitama and Tokyo, Japan.

This study presents a comprehensive characterization of microplastics (MPs) and adsorbed/dissolved polycyclic aromatic hydrocarbons (PAHs) in the Arakawa River, the largest river system in Saitama and Tokyo, Japan. The MPs were sampled at various points along the river, revealing an average number density of 2.21 ± 1.48 pieces/m3, with a predominant size range of 0.5-1 mm. Polymer analysis indicated that polyethylene (PE) comprised the highest proportion of MPs (55.9%), followed by polypropylene (PP) (22.4%) and polystyrene (PS) (21.7%). Seasonal fluctuations in MPs concentration were observed, with the highest values in winter and the lowest in summer. An analysis of adsorbed PAHs revealed a median partition coefficient (Kd) value of 3.58 × 104 L/kg for MPs, indicating their affinity for PAHs. Further PAHs analysis revealed that the PAHs with the highest mean values were bicyclic naphthalene, pyrene, and fluoranthene. A comparison with coastal MPs showed differences in PAH composition, with higher proportions of high-ring PAHs observed in coastal samples. The study also investigated the distribution of PAHs in the dissolved and suspended states in the river, finding that similar PAHs were distributed in both states, with the PAHs present in MPs being about 1/10,000 of those in the dissolved and suspended states. The study underscores the importance of the continued monitoring and management of MPs and associated pollutants in river ecosystems.

Physicochemical Characterization and Oxidative Potential of Iron-Containing Particles Emitted from Xuanwei Coal Combustion.

Respiratory diseases have been proven to be directly related to air pollutants. Xuanwei, located in South China, has been known to have the highest mortality rate for lung cancer in China because of the air pollutants emitted through local coal combustion. However, the mechanism of lung cancer induced by air pollutants is not clear. Based on the fact that a large number of iron-bearing mineral particles was found in Xuanwei coal combustion particles, the iron-containing particles were hypothesized to play important roles in the pathogenesis of the high incidence rate of lung cancer in this area. In this study, raw coal samples were collected from a coal mine in the Xuanwei area. Size-resolved particles emitted from the raw coal samples were collected using an Anderson high-volume sampler. Mineralogical characterization and an assessment of the oxidative potential of the iron-containing particles were conducted using cutting-edge technologies, and the biological activity of the particles were evaluated via DTT assay. Our data showed that the iron-containing minerals accounted for more than 10% of the measured particles emitted from Xuanwei coal combustion samples. The content analysis of ·OH generated from Xuanwei coal combustion particles showed that ·OH content was dependent on the size of particles in the surrogated lung fluid. The concentration of ·OH increased as the particle size decreased. The DTT assay data further demonstrated that when the mass concentration of dissolved irons increased, the oxidation potential of the particles increased. The highest proportion of divalent iron in the total dissolved iron was found in the submicron particles in low pH solution(pH = 1), which indicated that the oxidative potential induced by submicron particles was stronger than that induced by coarse particles and fine particles. Armed with the above data, the toxicological mechanism of the iron-containing mineral particles can be investigated further.

Examining the impact of nanoplastics and PFAS exposure on immune functions through inhibition of secretory immunoglobin A in human breast milk.

Emerging contaminants such as nanoplastics (NPs) and per- and polyfluoroalkyl substances (PFAS), have been detected in the environment and breast milk, thus exposing infants to potentially harmful chemicals during breastfeeding. Breast milk contains secretory immunoglobulin A (SIgA), an antibody that plays a vital role in disease protection and the development of the infant's immune system. This study employed molecular simulation and fractional factorial designs to assess the toxicity of NPs and PFAS on breast milk and their influence on infant immunity by inhibiting SIgA. The research found that NPs and PFAS have higher binding affinities to SIgA compared to the control compound. Polycarbonate (-10.7 kcal/mol) had the highest binding affinity among plastics, while Perfluorodecanoic acid (PFDA, - 8.0 kcal/mol) had the highest binding affinity among PFAS. The relative toxic index was higher for PFAS (2.4) than for plastics (1.9), suggesting that PFAS may pose a higher overall toxicity burden on the protein. The presence of specific combinations of NPs and PFAS in breast milk may potentially harm breastfeeding infants, although additional experimental studies are required to validate these findings. These results underscore the potential risks associated with these emerging contaminants in breast milk and their impact on infant immunity.

Comparison of the heterogeneous reaction of NO2 on the surface of clay minerals and desert dust particles.

Mineral particles in air could provide atmospheric chemical reaction interface for gaseous substances and participate in atmospheric chemical reaction process, and affecting the status and levels of gaseous pollutants in air. However, differences of the heterogenous reaction on the surface minerals particles are not very clear. Considering main mineral composition of ambient particles was from dust emission, therefore, typical clay minerals (chlorite, illite) and desert particles (Taklimakan Desert) were selected to analysize chemical reaction of NO2, one of major gaseous pollutants, on mineral particles by using of In-situ DRIFTS (diffuse reflectance infrared Fourier transform spectroscopy) under different condition. And In situ near-ambient pressure X-ray photoelectron spectroscopy (In situ NAP-XPS) was employed to investigate iron (one of the major metals) species variation on the surface of mineral dust particles during the heterogeneous reactions. Our data show that humidity controlled by deuterium oxide (D2O) has a greater effect on chemical reactions compared to light and temperature. Under dry conditions, the amount of heterogeneous reaction products of NO2 on the particles shows Xiaotang dust > chlorite > illite > Tazhong dust regardless of dark or light conditions. In contrast, under humidity conditions, the order of nitrate product quantity under moderate conditions was chlorite > illite > Xiaotang dust > Tazhong dust. In situ NAP-XPS results demonstrate that specie variation of the Fe could promote the heterogenous reactions. These data could provide useful information for understanding the formation mechanism of nitrate aerosols and removal of nitrogen oxides in the atmosphere.

[Anti-fatigue effect of Lubian on kidney Yin deficiency and kidney Yang deficiency mice and mechanism based on PI3K-Akt pathway].

This study aimed to investigate the anti-fatigue effect and mechanism of Lubian(Cervi Penis et Testis) on kidney Yin deficiency and kidney Yang deficiency mice. After one week of adaptive feeding, 88 healthy male Kunming mice were randomly divided into a blank group, a kidney Yin deficiency model group, a kidney Yin deficiency-Panacis Quinquefolii Radix(PQR) group, kidney Yin deficiency-Lubian treatment groups, a kidney Yang deficiency model group, a kidney Yang deficiency-Ginseng Radix et Rhizoma(GR) group, and kidney Yang deficiency-Lubian treatment groups, with eight mice in each group. The kidney Yin deficiency model and kidney Yang deficiency model were prepared by daily regular oral administration of dexamethasone acetate and hydrocortisone, respectively, and meanwhile, corresponding drugs were provided. The mice in the blank group received blank reagent. The treatment lasted 14 days. The exhaustive swimming time was measured 30 min after drug administration on the 14th day. On the 15th day, blood was collected from eyeballs and the serum was separated to determine the content of lactic acid(LD), blood urea nitrogen(BUN), lactate dehydrogenase(LDH), cyclic adenosine monophosphate(cAMP), and cyclic guanosine monophosphate(cGMP). The liver was dissected to determine the content of liver glycogen and the protein expression of phosphoinositide 3-kinase(PI3K) and protein kinase B(Akt). Compared with the kidney Yang deficiency model group, the kidney Yang deficiency-Lubian treatment groups showed increased body weight(P<0.05), relieved symptoms of Yang deficiency, decreased cGMP content(P<0.01), increased cAMP/cGMP(P<0.01), prolonged exhausted swimming time(P<0.01), reduced LD(P<0.01), elevated BUN content(P<0.01), increased liver glycogen content(P<0.01), and increased protein expression of PI3K and Akt in the liver(P<0.05). Compared with the kidney Yin deficiency model group, the kidney Yin deficiency-Lubian treatment groups showed increased body weight(P<0.01), relieved symptoms of Yin deficiency, increased content of cGMP(P<0.01), decreased cAMP/cGMP(P<0.01), prolonged exhausted swimming time(P<0.01), decreased LD(P<0.01), decreased BUN content(P<0.01), increased liver glycogen content(P<0.01), and increased protein expression of PI3K(P<0.05) and Akt in the liver(P<0.05). To sum up, Lubian can regulate Yin deficiency and Yang deficiency and increase glycogen synthesis by affecting the PI3K-Akt pathway, thereby exerting an anti-fatigue role.

Species difference in toxicokinetics and safety assessment of senecionine N-oxide in a UDP-glucuronosyltransferase 1A4 humanized mouse model.

Pyrrolizidine alkaloids (PAs) are naturally occurring hepatotoxins, and herbs containing PAs are of high concern. PAs are normally found in tertiary amines and N-oxide forms (PA N-oxides), yet the latter are less evaluated for their toxicokinetics. As a continuation of our investigation into the safety assessment of PA-containing herbal medicines, the toxicity and toxicokinetic characteristics of senecionine N-oxide (a representative toxic PA N-oxide) were investigated by using the UDP-glucuronosyltransferase 1A4 humanized mouse model (hUGT1A4 mouse model) and compared with those in wild-type mice simultaneously. Results show that the toxicity caused by senecionine N-oxide exposure was evidently decreased in hUGT1A4 mice as approved by pathology and biochemistry assays. In addition, a N-glucuronidation conjugate was exclusively found in hUGT1A4 mice but not in wild-type (WT) mice. In vitro studies proved that senecionine N-oxide initially reduced to the corresponding tertiary amine alkaloid (senecionine) and then underwent N-glucuronidation via human UGT1A4. The variation in toxicokinetic characteristics was also observed between hUGT1A4 mice and WT mice with a notably enhanced clearance of senecionine N-oxide and senecionine, and accordingly less formation of pyrrole-protein adducts in hUGT1A4 mice, which finally led to the detoxification of senecionine N-oxide exposure in hUGT1A4 mice. Our results provided the first in vivo toxicity data and toxicokinetic characteristics of senecionine N-oxide in a humanized animal model and revealed that human UGT1A4 plays an important role in the detoxification of senecionine N-oxide.

Freshwater species diversity loss embodied in interprovincial hydroelectricity transmission with ecological network analysis.

A major strategy for addressing the imbalance in source-network-load distribution is interprovincial electricity transmission; however, this process also causes various environmental effects. Previous studies have mainly examined thermal power transmission, and few insights have been gained into the challenges hydroelectricity transmission poses for biodiversity conservation. Here, we innovatively incorporated the freshwater species diversity footprint into a hydropower environmental impact assessment, calculating the interprovincial transfer of freshwater species diversity embodied in hydroelectricity transmission. We proposed an evaluation model of an interprovincial hydroelectricity transmission network using freshwater species diversity as the ecological element and creatively identified significant nodes and paths of the network. Up to 28% of the transfer of freshwater species diversity was related to the demand for hydroelectricity consumption in Shanghai. 64% of the relationships in the hydroelectricity transmission network were implemented at the expense of ecological losses on one side. Shanghai and Sichuan provinces and some transmission lines related to them were significant nodes and paths for improving the overall status of the network. This research can help policymakers comprehend the challenges to freshwater species presented by interprovincial hydroelectricity transmission and serve as a reference for ecological compensation for hydropower development.

Pollution levels and health risk assessment of potentially toxic metals of size-segregated particulate matter in rural residential areas of high lung cancer incidence in Fuyuan, China.

The highest incidence and mortality rate of lung cancer in rural area of Fuyuan has been a research hotspot, and the pathogenesis is still unclear. Therefore, atmospheric particulate matters (APMs) samples were collected between 18 February and 01 March 2017, exploring water-soluble potentially toxic metals (WSPTMs) and water-soluble inorganic ionic species (WSIIs) levels, size distribution, sources, acidity and alkalinity, and potential carcinogenic and non-carcinogenic risks, hoping to provide scientific basic data to solve this problem. In our study, the average ratio of nitrate ion (NO3-)/sulfate ion (SO42-) within PM1.1, PM1.1-2.0, PM2.0-3.3, PM3.3-7.0, and PM>7.0 were 0.22, 0.18, 0.15, 0.34 and 0.36, respectively, that revealed that combustion sources contributed to PM were more significant. The anions in equilibrium (ANE) / cations in equilibrium (CAE) < 1 for all samples within PM1.1, PM2.0-3.3, PM3.3-7.0 indicate that the APMs were alkaline, but PM1.1-2.0 particulate matter shows weak acidity. SO42- prefers to combine with NH4+ to form (NH4)2SO4, which hinders the formation of NH4NO3, the remaining SO42- and NO3- to neutralize the K+, KNO3 was formed at all particulate, however, K2SO4 can only be formed in PM<3.3. Arsenic (As) and Selenium (Se) were identified as the most enriched WSPTMs in all PM sizes, predominantly from anthropogenic emissions, were suggested that coal combustion is a significant source of PM-bound WSPTMs. Total WSPTMs exhibited high total carcinogenic risks (TCR) values (9.98 × 10-6, 1.06 × 10-5, and 1.19 × 10-5 for girls, boys and adults, respectively) in the smaller particles (< 1.1 µm). Se was considered as the major contributor (63.60%) to carcinogenic risk (CR) in PM2.0 and had an inverse relationship with PM size that should be of prime concern.

Pollution characteristics and risk assessment of potentially toxic elements of fine street dust during COVID-19 lockdown in Bangladesh.

Due to the COVID-19 pandemic, Bangladesh government took the measure like partial lockdown (PL) and complete lockdown (CL) to curb the spread. These measures gave a chance for environmental restoration. In this study, street dust samples were collected during PL and CL from four main urban land use categories in Dhaka city, such as industrial area (IA), commercial area (CA), public facilities area (PFA), and residential area (RA). Ten potentially toxic elements (Cr, Mn, Zn, Fe, Pb, Cu, Co, Ni, As, and Cd) in fine street dust particles (diameter < 20 µm) were determined following aqua-regia digestion and measured by inductively coupled plasma mass spectrometry (ICP-MS) to evaluate distribution, pollution sources, and potential risks to ecological systems and human health. Results showed that during PL, the concentrations of toxic elements in the dust were higher than that of CL. Cd and Fe were lowest and highest in concentration with 1.56 to 41,970 µg/g and 0.82 to 39,330 µg/g in partial and complete lockdown period respectively. All toxic elements were detected at high levels above background values where Fe with the highest and Cd with lowest concentrations, respectively. By land use, the levels of toxic elements pollution followed IA > PFA > RA > CA. Correlation analysis (CA), principal component analysis (PCA), and hierarchal cluster analysis (HCA) revealed that the sources of these analyzed toxic elements were mainly from anthropogenic which are related to industrial and vehicular or traffic emissions. Enrichment factor (EF), geoaccumulation index (Igeo), contamination factor (CF), and pollution load index (PLI) also suggested that the dust was more polluted during PL. Exposure of toxic elements to human was mainly via skin contact followed by ingestion and inhalation. Hazard quotient (HQ) values were < 1 except for Mn through dermal contact at all sites during partial and complete lockdown, similar to hazard index (HI), while Cr further showed high non-carcinogenic risks to children. Generally, children HI values were about 5-6 times higher than those of adults, suggesting a greater vulnerability of children to the health concerns caused by toxic elements in street dust. Carcinogenic risk (CR) values via ingestion pathway indicated all elements (except Pb) had significant health effect, while CR value by inhalation results showed no significant health effect. Cumulative carcinogenic risk (CCR) value had significant health effect except Pb in all land use categories. CCR values decreased during CL and reached at acceptable limit for most of the cases. This research provides a message to the local governments and environmental authorities to have a complete assessment of toxic elements in the street dust of Dhaka megacity in order to assuring public health safety and ecological sustainability.

Screening and characterization of inhibitory vNAR targeting nanodisc-assembled influenza M2 proteins.

Influenza A virus poses a constant challenge to human health. The highly conserved influenza matrix-2 (M2) protein is an attractive target for the development of a universal antibody-based drug. However, screening using antigens with subphysiological conformation in a nonmembrane environment significantly reduces the generation of efficient antibodies. Here, M2(1-46) was incorporated into nanodiscs (M2-nanodiscs) with M2 in a membrane-embedded tetrameric conformation, closely resembling its natural physiological state in the influenza viral envelope. M2-nanodisc generation, an antigen, was followed by Chiloscyllium plagiosum immunization. The functional vNARs were selected by phage display panning strategy from the shark immune library. One of the isolated vNARs, AM2H10, could specifically bind to tetrameric M2 instead of monomeric M2e (the ectodomain of M2 protein). Furthermore, AM2H10 blocked ion influx through amantadine-sensitive and resistant M2 channels. Our findings indicated the possibility of developing functional shark nanobodies against various influenza viruses by targeting the M2 protein.

A newborn male with Myhre syndrome, hearing loss, and complete syndactyly of fingers 3-4.

BACKGROUND: Myhre syndrome is a rare multisystem genetic disorder that is caused by de novo heterozygous gain-of-function variants in SMAD4. Patients with Myhre syndrome exhibit several phenotypes at different ages such as small size, autism, developmental delay, left-sided heart defects, and hearing loss and often have a characteristic facial appearance. The early clinical diagnosis of Myhre syndrome remains a major challenge, particularly in the first year of life. METHODS: A Chinese male infant with syndactyly of fingers, hypertelorism, short palpebral fissures, and short philtrum was enrolled into the ENT department of the Chinese PLA General Hospital. Whole exome sequencing analysis was used to detect the disease-causing variant. A literature review of Myhre syndrome was also performed. RESULTS: A recurrent de novo missense variant c.1498A > G p.I500V(p. Ile500Val) in SMAD4 was detected confirming the clinical diagnosis of Myhre syndrome at the age of 38 days. The infant appears to be the youngest reported case of Myhre syndrome. At 23-month follow-up, the affected infant has dysmorphic facial features, growth retardation, and previously undescribed complete syndactyly. Review the literatures noted several common features in Myhre syndrome patients including hearing loss (72.7%), characteristic facial features (26.0%-54.5%), finger and toe abnormalities (3.9%-48.1%), short stature (45.5%), and respiratory (30.0%) and cardiovascular problems (65.0%). CONCLUSIONS: Clinicians should have a low threshold to perform genetic testing on patients with features suggesting Myhre syndrome even in the first year of life. Although some individuals with Myhre syndrome have normal hearing, early onset or progressive hearing loss usually occur in one or both ears in most patients, with remarkable phenotypic heterogeneity. Syndactyly may be minor such as typical 2-3 toe involvement, or more complicated as was observed in our patient.

Addition of an affected family member to a previously ascertained autosomal recessive nonsyndromic hearing loss pedigree and systematic phenotype-genotype analysis of splice-site variants in MYO15A.

Pathogenic variants in MYO15A are known to cause autosomal recessive nonsyndromic hearing loss (ARNSHL), DFNB3. We have previously reported on one ARNSHL family including two affected siblings and identified MYO15A c.5964+3G > A and c.8375 T > C (p.Val2792Ala) as the possible deafness-causing variants. Eight year follow up identified one new affected individual in this family, who also showed congenital, severe to profound sensorineural hearing loss. By whole exome sequencing, we identified a new splice-site variant c.5531+1G > C (maternal allele), in a compound heterozygote with previously identified missense variant c.8375 T > C (p.Val2792Ala) (paternal allele) in MYO15A as the disease-causing variants. The new affected individual underwent unilateral cochlear implantation at the age of 1 year, and 5 year follow-up showed satisfactory speech and language outcomes. Our results further indicate that MYO15A-associated hearing loss is good candidates for cochlear implantation, which is in accordance with previous report. In light of our findings and review of the literatures, 58 splice-site variants in MYO15A are correlated with a severe deafness phenotype, composed of 46 canonical splice-site variants and 12 non-canonical splice-site variants.

Novel Approaches for Inhibiting the Indoor Allergen Der f 2 Excreted from House Dust Mites by Todomatsu Oil Produced from Woodland Residues.

House dust mite (HDM) is a globally ubiquitous domestic cause of allergic diseases. There is a pressing demand to discover efficient, harmless, and eco-friendly natural extracts to inhibit HDM allergens that are more likely to trigger allergies and challenging to be prevented entirely. This study, therefore, is aimed at assessing the inhibition of the allergenicity of major HDM allergen Der f 2 by todomatsu oil extracted from residues of Abies Sachalinensis. The inhibition was investigated experimentally (using enzyme-linked immunosorbent assay (ELISA), surface plasmon resonance (SPR), and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE)) and in silico using molecular docking. The results showed that todomatsu oil inhibits the allergenicity of Der f 2 by reducing its amount instead of the IgG binding capacity of a single protein. Moreover, the compounds in todomatsu oil bind to Der f 2 via alkyl hydrophobic interactions. Notably, most compounds interact with the hydrophobic amino acids of Der f 2, and seven substances interact with CYS27. Contrarily, the principal compounds fail to attach to the amino acids forming the IgG epitope in Der f 2. Interestingly, chemical components with the lowest relative percentages in todomatsu oil show high-affinity values on Der f 2, especially ß-maaliene (-8.0 kcal/mol). In conclusion, todomatsu oil has been proven in vitro as a potential effective public health strategy to inhibit the allergenicity of Der f 2.

Lung Cancer Stage Prediction Using Multi-Omics Data.

Lung cancer is one of the leading causes of cancer death. Patients with early-stage lung cancer can be treated by surgery, while patients in the middle and late stages need chemotherapy or radiotherapy. Therefore, accurate staging of lung cancer is crucial for doctors to formulate accurate treatment plans for patients. In this paper, the random forest algorithm is used as the lung cancer stage prediction model, and the accuracy of lung cancer stage prediction is discussed in the microbiome, transcriptome, microbe, and transcriptome fusion groups, and the accuracy of the model is measured by indicators such as ACC, recall, and precision. The results showed that the prediction accuracy of microbial combinatorial transcriptome fusion analysis was the highest, reaching 0.809. The study reveals the role of multimodal data and fusion algorithm in accurately diagnosing lung cancer stage, which could aid doctors in clinics.

Explore the attitudes of children and adolescent parents towards the vaccination of COVID-19 in China.

BACKGROUND: With the increasing incidence of asymptomatic carriers or milder symptoms, children and adolescents are likely to become a silent source of infection. In view of the efficacy and safety of vaccines in the treatment of novel Coronavirus pneumonia, population-wide vaccination will be an inevitable trend to control the spread of COVID-19. However, there is no survey on the attitudes of Chinese parents of children and adolescents towards their children's COVID-19 vaccination. METHODS: We used online questionnaires to find out the attitudes of Chinese parents toward their children's immunization against COVID-19. Logistic regression was used to explore the influencing factors. RESULTS: A total of 2019 parents participated in the survey. Overall, 74.38% parents said they would actively get vaccinated, 8.90% refused to get vaccinated, 4.60% said they would delay vaccination and 12.12% were still undecided. CONCLUSIONS: In general, Chinese parents have a high desire to be vaccinated against COVID-19, and most parents have a positive attitude towards their children's vaccination. However, many people still hesitate or even refuse to be vaccinated. Education background, attitudes towards children's vaccination, children's age, recent illness and other factors have a certain impact on Chinese parents of children and adolescents towards their children's COVID-19 vaccination.

Genetic Analysis of the LOXHD1 Gene in Chinese Patients With Non-Syndromic Hearing Loss.

Non-syndromic hearing loss (NSHL) is a common neurosensory disease with an extreme genetic heterogeneity which has been linked to variants in over 120 genes. The LOXHD1 gene (DFNB77), encoding lipoxygenase homology domain 1, is a rare hearing loss gene found in several populations. To evaluate the importance of LOXHD1 variants in Chinese patients with NSHL, we performed genetic analysis on LOXHD1 in 2,901 sporadic Chinese patients to identify the aspect and frequency of LOXHD1 causative variants. Next-generation sequencing using a custom gene panel of HL was conducted on 2,641 unrelated patients and whole-exome sequencing on the remaining 260 patients. A total of 33 likely causative variants were identified in 21 patients, including 20 novel variants and 13 previously reported pathogenic variants. Each of the 20 novel variants was evaluated according to ACMG criteria. These findings showed that causative variants in LOXHD1 were found in about 0.72% (21/2,901) of Chinese NSHL patients. This study is by far the largest number of novel variants identified in this gene expanding the range of pathogenic variants in LOXHD1, and suggests that variants in this gene occur relatively commonly in Chinese NSHL patients. This extensive investigation of LOXHD1 in Chinese NSHL patients proposed six recurrent LOXHD1 variants. These findings may assist in both molecular diagnosis and genetic counseling.

Firm evidence for the detoxification of senecionine-induced hepatotoxicity via N-glucuronidation in UGT1A4-humanized transgenic mice.

Uridine diphosphate glucuronosyltransferase (UGT)1A4 is responsible for N-glucuronidation of tertiary amines but is a pseudogene in commonly used rodent models in toxicity and safety assessment. As a continuation of our investigation into the toxicity and safety assessment of pyrrolizidine alkaloid (PA)-containing herbs, we generated a UGT1A4-humanized (hUGT1A4) transgenic mouse model to systematically study the toxicity, metabolism network, and toxicokinetic characteristics of senecionine (a representative toxic PA) and compared with that in the wide-type controls in parallel. As results, senecionine-induced toxicity was significantly decreased as approved by mortality, pathology, and biochemistry assays in hUGT1A4 mice and cultured primary hepatocytes. More importantly N-glucuronidation adduct was exclusively identified in all the hUGT1A4 mice, liver microsomes, and cultured primary hepatocytes, yet absent in the wide-type controls. The variation in toxicokinetic characters was also observed between hUGT1A4 mice and the wide-type controls with a notably inhibition of the toxification metabolites, i.e., pyrrole-protein adducts, in hUGT1A4 mice. Conclusively, UGT1A4 plays an important role in detoxification of senecionine and the hUGT1A4 mouse model is promising for the pre-clinical evaluation of the efficacy and toxicity of tertiary amine agents in drug development and safety assessment.

Analysis of the trade-off between hydroelectricity generation and ecological protection from the perspective of eco-efficiency in Southwest China.

Driven by the global net-zero carbon emission goal, even though the impact of hydropower on river ecosystems cannot be ignored, hydropower scale and intensity will be expanded in Southwest China (SC). Therefore, the trade-off between hydroelectricity generation and ecological protection remains an issue requiring urgent attention at the moment. This paper proposes an eco-efficiency (EE) indicator system of hydropower adopting the water consumption of hydropower product (PWC), labor, and capital as inputs and the power generation, ecological flow deviation (EFD) as outputs and then explores the factors influencing the EE value of hydropower in SC. The results indicate that (1) The EE incorporates the impact of each plant on fish, provides decision support for hydropower development planning and serves as the foundation for eco-dispatch operations. (2) Hydropower generation affects fish reproduction in SC, and the EE value of the Wu River is relatively low. (3) The scale of power generation and degree of fish protection are two significant factors that can increase the EE value of hydropower. To compensate for plant inadequacies in these two aspects, equivalent changes in hydropower planning and eco-dispatch operations should be implemented.