Association of dietary inflammation with tooth loss and cognitive decline in older adults from cross-sectional data: The moderated role of albumin.

OBJECTIVE: Growing evidence suggests a potential connection between tooth loss and cognitive function in recent years. Increasing studies have focused on their inter-relationship, however, the underlying mechanism has yet to be fully elucidated. Few studies have considered the role of dietary inflammation and serum albumin in the association between tooth loss and cognitive function. Therefore, the aim of this study was to explore the role of dietary inflammation and serum albumin in the association between tooth loss and cognitive impairment. METHODS: A sample of 1,009 US adults from the National Health and Nutrition Examination Survey (NHANES) provided data on oral condition, cognitive function, dietary intake, and serum tests. The association between tooth loss (exposure variable) and cognitive function (outcome variable) was assessed by linear regression. Furthermore, a moderated mediation model was established to examine the influence of dietary inflammation on the association between tooth loss and cognitive tests, and the visualization of the moderating effect of serum albumin concentration was displayed through the Johnson-Neyman curve. RESULTS: Participants with impaired dentition had worse cognitive function and a higher Dietary Inflammation Index (DII). DII was highly correlated with Immediate Recall Test (IR), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST), which mediated 16.46 %, 14.41 % and 11.28 % of the effect between tooth loss and cognitive functions. Additionally, the relationship between DII and DSST was moderated by serum albumin concentration. CONCLUSION: Tooth loss was associated with cognitive function which was affected by pro-inflammatory dietary patterns and serum albumin level. CLINICAL SIGNIFICANCE: This study presents evidence for dentists that dietary pattern change due to tooth loss plays a role in cognitive deterioration, which can also be moderated by serum albumin level. Therefore, the preservation of natural teeth is important for cognitive function, especially in an immunocompromised population with decreased serum albumin concentrations.

Human-virus protein-protein interactions maps assist in revealing the pathogenesis of viral infection.

Many significant viral infections have been recorded in human history, which have caused enormous negative impacts worldwide. Human-virus protein-protein interactions (PPIs) mediate viral infection and immune processes in the host. The identification, quantification, localization, and construction of human-virus PPIs maps are critical prerequisites for understanding the biophysical basis of the viral invasion process and characterising the framework for all protein functions. With the technological revolution and the introduction of artificial intelligence, the human-virus PPIs maps have been expanded rapidly in the past decade and shed light on solving complicated biomedical problems. However, there is still a lack of prospective insight into the field. In this work, we comprehensively review and compare the effectiveness, potential, and limitations of diverse approaches for constructing large-scale PPIs maps in human-virus, including experimental methods based on biophysics and biochemistry, databases of human-virus PPIs, computational methods based on artificial intelligence, and tools for visualising PPIs maps. The work aims to provide a toolbox for researchers, hoping to better assist in deciphering the relationship between humans and viruses.

Personalized radiomics signature to screen for KIT-11 mutation genotypes among patients with gastrointestinal stromal tumors: a retrospective multicenter study.

OBJECTIVES: Gastrointestinal stromal tumors (GISTs) carrying different KIT exon 11 (KIT-11) mutations exhibit varying prognoses and responses to Imatinib. Herein, we aimed to determine whether computed tomography (CT) radiomics can accurately stratify KIT-11 mutation genotypes to benefit Imatinib therapy and GISTs monitoring. METHODS: Overall, 1143 GISTs from 3 independent centers were separated into a training cohort (TC) or validation cohort (VC). In addition, the KIT-11 mutation genotype was classified into 4 categories: no KIT-11 mutation (K11-NM), point mutations or duplications (K11-PM/D), KIT-11 557/558 deletions (K11-557/558D), and KIT-11 deletion without codons 557/558 involvement (K11-D). Subsequently, radiomic signatures (RS) were generated based on the arterial phase of contrast CT, which were then developed as KIT-11 mutation predictors using 1408 quantitative image features and LASSO regression analysis, with further evaluation of its predictive capability. RESULTS: The TC AUCs for K11-NM, K11-PM/D, K11-557/558D, and K11-D ranged from 0.848 (95% CI 0.812-0.884), 0.759 (95% CI 0.722-0.797), 0.956 (95% CI 0.938-0.974), and 0.876 (95% CI 0.844-0.908), whereas the VC AUCs ranged from 0.723 (95% CI 0.660-0.786), 0.688 (95% CI 0.643-0.732), 0.870 (95% CI 0.824-0.918), and 0.830 (95% CI 0.780-0.878). Macro-weighted AUCs for the KIT-11 mutant genotype ranged from 0.838 (95% CI 0.820-0.855) in the TC to 0.758 (95% CI 0.758-0.784) in VC. TC had an overall accuracy of 0.694 (95%CI 0.660-0.729) for RS-based predictions of the KIT-11 mutant genotype, whereas VC had an accuracy of 0.637 (95%CI 0.595-0.679). CONCLUSIONS: CT radiomics signature exhibited good predictive performance in estimating the KIT-11 mutation genotype, especially in prediction of K11-557/558D genotype. RS-based classification of K11-NM, K11-557/558D, and K11-D patients may be an indication for choice of Imatinib therapy.

Sirolimus can promote the disappearance of renal angiomyolipoma associated with tuberous sclerosis complex: a prospective cohort study.

BACKGROUND: Renal angiomyolipoma (RAML) is the most common kidney lesion in patients with tuberous sclerosis complex (TSC), affecting about 80% of patients. It is a benign tumor that grows over time, usually bilaterally, and can easily lead to kidney complications such as acute hemorrhage. Herein, we investigated the efficacy and safety of sirolimus in children with TSC-associated RAML and explored the factors affecting tumor disappearance under sirolimus treatment through subgroup analysis. METHODS: A prospective cohort study was conducted. Sirolimus was initiated at 1 mg/(m2 × day), and dose adjustments were made by a 2-week titration period to attain a trough blood concentration of 5-10 ng/mL. The disappearance of RAML in children after sirolimus treatment was observed, and Cox regression was used to screen the factors affecting tumor disappearance. RESULTS: One hundred and twenty-six patients who met the criteria were analyzed. After 3 months, 6 months, 12 months, and 24 months of follow-up, tumors disappeared in 18 (14.3%), 30 (23.8%), 39 (31.0%), and 42 (33.3%) children, respectively. Tumors disappeared in 50 (39.7%) children by the last visit of each individual, and 30 (60%) of them occurred within 6 months. The multivariate Cox regression analysis showed that patients with a smaller maximum tumor diameter at baseline had a higher tumor disappearance rate. Thirty-six (29%) patients had stomatitis during the entire treatment period, and no serious adverse reactions were observed. CONCLUSIONS: Sirolimus could promote the disappearance of TSC-related RAML. The disappearance rate was correlated with the maximum diameter at baseline, and the smaller the tumor was, the higher the disappearance rate. It is well tolerated in the treatment of RAML associated with TSC.

Challenges in the Management of Children and Adolescents With Epilepsy in China During the COVID-19 Pandemic: An Online Survey-Based Study.

INTRODUCTION: To investigate the challenges in the management of children and adolescents with epilepsy in China during the coronavirus disease (COVID-19) pandemic. METHODS: We conducted a cross-sectional survey among 845 patients with epilepsy using an online-based questionnaire. The questionnaire focused on sociodemographic characteristics, epilepsy-related conditions, health care access, COVID-19 vaccination, and the mental health of caregivers. Depression was assessed using Patient Health Questionnaire-9. RESULTS: During the pandemic, 24.73% of the patients had increased seizures. The majority of patients (68.89%) experienced difficulty obtaining antiseizure medications. In addition, 94.79% of the patients had difficulty consulting a doctor. A total of 52.78% of the patients selected telemedicine services, and most found these services to be helpful. Moreover, 76.11% of the patients failed to complete the COVID-19 vaccination. More than half of the caregivers had anxiety and depressive symptoms. The risk factors for depression comprised irregularity in taking antiseizure medications, difficulty in obtaining antiseizure medications, and failure to consult a doctor on time. CONCLUSIONS: The COVID-19 pandemic presented a great challenge in the management of children and adolescents with epilepsy in China. The findings highlight the importance of improving health care systems and medication management and the mental health of their caregivers.

Noninvasive predictive models based on lifestyle analysis and risk factors for early-onset colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) incidence has increased among patients aged <50 years. Exploring high-risk factors and screening high-risk populations may help lower early-onset CRC (EO-CRC) incidence. We developed noninvasive predictive models for EO-CRC and investigated its risk factors. METHODS: This retrospective multicenter study collected information on 1756 patients (811 patients with EO-CRC and 945 healthy controls) from two medical centers in China. Sociodemographic features, clinical symptoms, medical and family history, lifestyle, and dietary factors were measured. Patients from one cohort were randomly assigned (8:2) to two groups for model establishment and internal validation, and another independent cohort was used for external validation. Multivariable logistic regression, random forest, and eXtreme Gradient Boosting (XGBoost) were performed to establish noninvasive predictive models for EO-CRC. Some variables in the model influenced EO-CRC occurrence and were further analyzed. Multivariable logistic regression analysis yielded adjusted odd ratios (ORs) and 95% confidence intervals (CIs). RESULTS: All three models showed good performance, with areas under the receiver operator characteristic curves (AUCs) of 0.82, 0.84, and 0.82 in the internal and 0.78, 0.79, and 0.78 in the external validation cohorts, respectively. Consumption of sweet (OR 2.70, 95% CI 1.89-3.86, P < 0.001) and fried (OR 2.16, 95% CI 1.29-3.62, P < 0.001) foods ≥3 times per week was significantly associated with EO-CRC occurrence. CONCLUSION: We established noninvasive predictive models for EO-CRC and identified multiple nongenetic risk factors, especially sweet and fried foods. The model has good performance and can help predict the occurrence of EO-CRC in the Chinese population.

5'tiRNA-Pro-TGG, a novel tRNA halve, promotes oncogenesis in sessile serrated lesions and serrated pathway of colorectal cancer.

BACKGROUND: Transfer RNA (tRNA)-derived small RNAs (tsRNAs) are small fragments that form when tRNAs severe. tRNA halves (tiRNAs), a subcategory of tsRNA, are involved in the oncogenic processes of many tumors. However, their specific role in sessile serrated lesions (SSLs), a precancerous lesion often observed in the colon, has not yet been elucidated. AIM: To identify SSL-related tiRNAs and their potential role in the development of SSLs and serrated pathway of colorectal cancer (CRC). METHODS: Small-RNA sequencing was conducted in paired SSLs and their adjacent normal control (NC) tissues. The expression levels of five SSL-related tiRNAs were validated by q-polymerase chain reaction. Cell counting kit-8 and wound healing assays were performed to detect cell proliferation and migration. The target genes and sites of tiRNA-1:33-Pro-TGG-1 (5'tiRNA-Pro-TGG) were predicted by TargetScan and miRanda algorithms. Metabolism-associated and immune-related pathways were analyzed by single-sample gene set enrichment analysis. Functional analyses were performed to establish the roles of 5'tiRNA-Pro-TGG based on the target genes. RESULTS: In total, we found 52 upregulated tsRNAs and 28 downregulated tsRNAs in SSLs compared to NC. The expression levels of tiRNA-1:33-Gly-CCC-2, tiRNA-1:33-Pro-TGG-1, and tiRNA-1:34-Thr-TGT-4-M2 5'tiRNAs were higher in SSLs than those in NC, while that of 5'tiRNA-Pro-TGG was associated with the size of SSLs. It was demonstrated that 5'tiRNA-Pro-TGG promoted cell proliferation and migration of RKO cell in vitro. Then, heparanase 2 (HPSE2) was identified as a potential target gene of 5'tiRNA-Pro-TGG. Its lower expression was associated with a worse prognosis in CRC. Further, lower expression of HPSE2 was observed in SSLs compared to normal controls or conventional adenomas and in BRAF-mutant CRC compared to BRAF-wild CRC. Bioinformatics analyses revealed that its low expression was associated with a low interferon γ response and also with many metabolic pathways such as riboflavin, retinol, and cytochrome p450 drug metabolism pathways. CONCLUSION: tiRNAs may profoundly impact the development of SSLs. 5'tiRNA-Pro-TGG potentially promotes the progression of serrated pathway CRC through metabolic and immune pathways by interacting with HPSE2 and regulating its expression in SSLs and BRAF-mutant CRC. In the future, it may be possible to use tiRNAs as novel biomarkers for early diagnosis of SSLs and as potential therapeutic targets in serrated pathway of CRC.

The association between tooth loss and cognitive decline in the aged population: The mediating role of HDL-cholesterol.

OBJECTIVE: Tooth loss and its impact on cognitive impairment have become a heated topic over the past decade as the global population continues to age. Despite the proliferation of research in this area, the underlying mechanism linking tooth loss and cognitive decline remains poorly understood. Limited investigation has been conducted to explore the potential role of lipid metabolism and its impact on the association between tooth loss and cognitive function. This study endeavored to identify the role of high-density lipoprotein cholesterol (HDL-C) concentration among older adults and its contribution to the link between tooth loss and cognitive impairment. METHODS: Data were retrieved from a public database, namely, the National Health and Nutrition Examination Survey (NHANES). Among 1,124 included participants who were aged above 60 years old, linear regression was performed to determine the association between tooth loss (moderate and severe tooth loss) and cognitive function [Consortium to Establish a Registry for Alzheimer's Disease-Immediate Recall (CERAD-IR), Delayed Recall (CERAD-DR), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST)]. Mediation analysis was used to test the effect of HDL-C on the association of tooth numbers and four cognitive tests. RESULTS: Participants with moderate and severe tooth loss had lower scores on cognitive performance (p<0.001) and lower levels of HDL-C (p<0.05). The HDL-C levels were highly correlated with CERAD-IR and DSST, which mediated 2.11% to 5.24% of the total effect between tooth numbers and cognitive function. CONCLUSION: Tooth loss was negatively associated with cognitive function which was mediated by serum HDL-C levels. CLINICAL SIGNIFICANCE: Dentists should realize that the potential broader implications of tooth loss on overall well-being, including cognitive performance. The preservation of natural dentition might serve as a preventive measure against cognitive impairment, possibly mediated by abnormal lipid metabolism.

Microbiota-derived tryptophan catabolites mediate the chemopreventive effects of statins on colorectal cancer.

Epidemiological studies have indicated an association between statin use and reduced incidence of colorectal cancer (CRC), and work in preclinical models has demonstrated a potential chemopreventive effect. Statins are also associated with reduced dysbiosis in the gut microbiome, yet the role of the gut microbiome in the protective effect of statins in CRC is unclear. Here we validated the chemopreventive role of statins by retrospectively analysing a cohort of patients who underwent colonoscopies. This was confirmed in preclinical models and patient cohorts, and we found that reduced tumour burden was partly due to statin modulation of the gut microbiota. Specifically, the gut commensal Lactobacillus reuteri was increased as a result of increased microbial tryptophan availability in the gut after atorvastatin treatment. Our in vivo studies further revealed that L. reuteri administration suppressed colorectal tumorigenesis via the tryptophan catabolite, indole-3-lactic acid (ILA). ILA exerted anti-tumorigenic effects by downregulating the IL-17 signalling pathway. This microbial metabolite inhibited T helper 17 cell differentiation by targeting the nuclear receptor, RAR-related orphan receptor γt (RORγt). Together, our study provides insights into an anti-cancer mechanism driven by statin use and suggests that interventions with L. reuteri or ILA could complement chemoprevention strategies for CRC.

Metformin abrogates Fusobacterium nucleatum-induced chemoresistance in colorectal cancer by inhibiting miR-361-5p/sonic hedgehog signaling-regulated stemness.

BACKGROUND: Chemotherapy resistance is the major cause of recurrence in patients with colorectal cancer (CRC). A previous study found that Fusobacterium (F.) nucleatum promoted CRC chemoresistance. Additionally, metformin rescued F. nucleatum-induced tumorigenicity of CRC. Here, we aimed to investigate whether metformin could revert F. nucleatum-induced chemoresistance and explore the mechanism. METHODS: The role of metformin in F. nucleatum-infected CRC cells was confirmed using cell counting kit 8 assays and CRC xenograft mice. Stemness was identified by tumorsphere formation. Bioinformatic analyses were used to explore the regulatory molecules involved in metformin and F. nucleatum-mediated regulation of the sonic hedgehog pathway. RESULTS: We found that metformin abrogated F. nucleatum-promoted CRC resistance to chemotherapy. Furthermore, metformin attenuated F. nucleatum-stimulated stemness by inhibiting sonic hedgehog signaling. Mechanistically, metformin diminished sonic hedgehog signaling proteins by targeting the MYC/miR-361-5p cascade to reverse F. nucleatum-induced stemness, thereby rescuing F. nucleatum-triggered chemoresistance in CRC. CONCLUSIONS: Metformin acts on F. nucleatum-infected CRC via the MYC/miR-361-5p/sonic hedgehog pathway cascade, subsequently reversing stemness and abolishing F. nucleatum-triggered chemoresistance. Our results identified metformin intervention as a potential clinical treatment for patients with chemoresistant CRC with high amounts of F. nucleatum.

Conversion of drylands to paddy fields on former wetlands restores soil organic carbon by accumulating labile carbon fractions in the Sanjiang Plain, northeast China.

BACKGROUND: Since the 1990s, drylands have been extensively converted to rice paddy fields on the former wetlands in the Sanjiang Plain of northeast China. However, the influence of this successiveland-use change from native wetlands to drylands to rice paddy fields on soil organic carbon (C) dynamics remains unexplored. Here, we compared the difference in soil organic C stock among native wetlands, drylands, and paddy fields, and then used a two-step acid hydrolysis approach to examine the effect of this land-use change on labile C I (LPI-C), labile C II (LPII-C), and recalcitrant C (RP-C) fractions at depths of 0-15 cm, 15-30 cm, and 30-50 cm. RESULTS: Soil organic C stock at a depth of 0-50 cm was reduced by 79% after the conversion of wetlands to drylands but increased by 24% when drylands were converted to paddy fields. Compared with wetlands, paddy fields had 74% lower soil organic C stock at a depth of 0-50 cm. The conversion of wetlands to drylands reduced the concentrations of LPI-C, LPII-C, and RP-C fractions at each soil depth. However, land-use change from drylands to paddy fields only increased the concentrations of LPI-C and LPII-C fractions at the 0-15 cm and 30-50 cm depths. CONCLUSION: The conversion of drylands to paddy lands on former wetlands enhances the soil organic C stock by promoting labile C fraction accumulation, and labile C fractions are more sensitive to this successive land-use change than recalcitrant C fractions in the Sanjiang Plain of northeast China. © 2022 Society of Chemical Industry.

A rise in saliva and urine pH in children with SCN1A-related epilepsy: An exploratory prospective controlled study.

Objective: SCN1A, encoding the alpha 1 subunit of the sodium channel, is associated with a range of related epilepsy. This study aims to assess saliva and urine pH in children with SCN1A-related epilepsy. Methods: A prospective controlled observational study with a 1:1 ratio was conducted on seven patients with SCN1A-related epilepsy and seven healthy children of the same family, gender, and age but without a history of seizures. The pH of saliva and urine was measured by pH test paper. Parents of patients with epilepsy recorded seizures to compare the relationship between pH and seizures. Results: The fourteen participants were all males, aged 1 to 14 years. Seven patients had different pathogenic SCN1A variants. The pH of saliva and urine was monitored for 21-95 days. The pH of saliva and urine was higher in patients with SCN1A-related epilepsy than in the healthy group. The urine pH in Dravet syndrome patients was high compared with other epilepsy patients. The urine pH in patients with seizures was higher than that in patients without seizures, which occurred during the study. Conclusions: The pH of saliva and urine was chronically high in patients with SCN1A-related epilepsy, and urine pH was higher in patients with seizures and with Dravet syndrome.

Endoscopic, clinicopathological, and growth characteristics of minute gastric cancer.

OBJECTIVE: To clarify the endoscopic, clinicopathological, and growth characteristics of minute gastric cancer (MGC) and to improve its detection rate. METHODS: Patients with early gastric cancer who underwent endoscopic submucosal dissection from July 2012 to September 2021 were retrospectively reviewed. MGC was defined as gastric cancer of 5 mm or less in size. Preoperative and postoperative endoscopic and pathological data were collected and analyzed. Follow-up information was collected until 9 April 2022. RESULTS: Eighty patients were enrolled, with 82 lesions observed under endoscopy and 87 diagnosed histopathologically. All patients received en bloc and curative resection. Compared with the time point when the last endoscopic examiniation prior to lesion deteciton was performed (t0), 64.29% of patients with MGC had disease progression at lesion detection (t1). However, 21.43% showed normal or only atrophic changes under white-light endoscopy, and their lesions were diagnosed accidentally by random biopsy. The majority of MGC lesions presented as type IIc and reddish, and 95.00% of cases had well-differentiated tubular adenocarcinoma. The mean growth rate of MGC was 0.0071 mm/day, and it took an average of 3.42 years to grow to 5 mm. There was no significant difference in the depth of invasion between the low cellular atypia group and the high cellular atypia group. CONCLUSIONS: Type IIc and reddish appearance are main endoscopic features of MGC. For cases with no obvious endoscopic changes, multipoint biopsy is helpful. MGC is mostly well differentiated and grows relatively slowly; therefore, MGC can still have a chance to be identified and resected curatively if it is missed diagnosed.

Non-enzymatic role of SOD1 in intestinal stem cell growth.

Superoxide dismutase 1 (SOD1) modulates intestinal barrier integrity and intestinal homeostasis as an antioxidant enzyme. Intestinal homeostasis is maintained by the intestinal stem cells (ISCs). However, whether and how SOD1 regulates ISCs is unknown. In this study, we established intestinal organoids from tamoxifen-inducible intestinal epithelial cell-specific Sod1 knockout (Sod1f/f; Vil-creERT2) mice. We found that loss of Sod1 in organoids suppressed the proliferation and survival of cells and Lgr5 gene expression. SOD1 is known for nearly half a century for its canonical role as an antioxidant enzyme. We identified its enzyme-independent function in ISC: inhibition of SOD1 enzymatic activity had no impact on organoid growth, and enzymatically inactive Sod1 mutants could completely rescue the growth defects of Sod1 deficient organoids, suggesting that SOD1-mediated ISC growth is independent of its enzymatic activity. Moreover, Sod1 deficiency did not affect the ROS levels of the organoid, but induced the elevated WNT signaling and excessive Paneth cell differentiation, which mediates the occurrence of growth defects in Sod1 deficient organoids. In vivo, epithelial Sod1 loss induced a higher incidence of apoptosis in the stem cell regions and increased Paneth cell numbers, accompanied by enhanced expression of EGFR ligand Epiregulin (EREG) in the stromal tissue, which may compensate for Sod1 loss and maintain intestinal structure in vivo. Totally, our results show a novel enzyme-independent function of SOD1 in ISC growth under homeostasis.

[Emission of Nitrous Oxide (N2O) from Lake Taihu and the Corresponding Potential Driving Factors].

Nitrous oxide (N2O) is one of the six greenhouse gases stipulated in the Kyoto Protocol. Its greenhouse potential over the past century was 298 times that of CO2, and the concentration of atmospheric N2O has been continuously and rapidly increasing during the past hundred years. Shallow lakes are an important source of atmospheric N2O. In order to explore the temporal and spatial changes and potential driving factors of N2O emissions from eutrophic water, we conducted field observations in February (winter) and August (summer) in Lake Taihu. We used the coefficient of diffusion-headspace bottle method to trace the variability in the N2O concentration[c(N2O)] and efflux[F(N2O)] from surface water bodies and explored the potential driving factors of N2O emissions. The optical measurements of dissolved organic matter (DOM) are an effective approach for tracing the source and composition of dissolved organic carbon (DOC) and dissolved organic nitrogen (DON). The migration and transformation processes of DOM also release a large amount of inorganic nitrogen, which changes the redox potential of the water column and thereby affects N2O emissions. Our results showed that the variability in c(N2O) and F(N2O) in the surface waters of Lake Taihu were strongly affected by water temperature and nutrient levels. The average c(N2O) of the surface waters was (19.7±2.7) nmol·L-1, corresponding to a mean F(N2O) of (41.1±1.8) µmol·(m2·d)-1, and the means of both c(N2O) and F(N2O) were higher in summer than those in winter (t-test, P<0.01). The input and accumulation of DOM could increase the production and emission potential of N2O in water bodies, as supported by both c(N2O) and F(N2O) significantly increasing with increasing level of terrestrial humic-like C1. The integration ratio of peak C to peak T IC:IT of DOM and the spectral slope S275-295 results indicated that there were high inputs of terrestrial DOM in the northwestern inflowing river mouths, concurring with the high production and emission of N2O found there. This suggested that the accumulation and degradation of terrestrial DOM potentially fueled the emission of N2O. Our results showed that water temperature, DOM composition, and nutrient level were all important factors affecting N2O emission from Lake Taihu. Long-term continuous observation can be applied to better evaluate the impact of various environmental factors on the production and emission of N2O in water bodies and to help with providing scientific emission reduction plans.

Alder encroachment alters subsoil organic carbon pool and chemical structure in a boreal peatland of Northeast China.

Boreal peatlands have been experiencing increased abundances of symbiotic dinitrogen-fixing woody plants (mainly alder species). However, how alder encroachment alters soil organic carbon (C) pool and stability is unclear. To examine the effects of alder encroachment on soil organic C, we measured soil organic C pool, phenol oxidase (POX) activity, organic C mineralization rate, and organic C chemical structure (alkyl C, O-alkyl C, aromatic C, and carbonyl C) using solid-state 13C nuclear magnetic resonance spectroscopy in the 0-10 cm, 10-20 cm, and 20-40 cm depths in the Alnus sibirica islands and adjacent open peatlands in the north of Da'xingan Mountain, Northeast China. A. sibirica islands had 28 %, 25 %, and 30 % greater POX activity and 36 %, 31 %, and 100 % higher organic C mineralization than open peatlands in the 0-10 cm, 10-20 cm, and 20-40 cm soil depths, respectively. Despite no significant changes in the 0-10 cm and 10-20 cm depths, alder encroachment reduced soil organic C pool in the 20-40 cm depth. Soil organic C pool in the 0-40 cm depth was lower in A. sibirica islands (298 Mg ha-1) than in the open peatlands (315 Mg ha-1). Moreover, alder encroachment increased alkyl (7 %) and carbonyl (57 %) C fractions but reduced O-alkyl C fraction (16 %) in the 20-40 cm depth, resulting in increased aliphaticity and recalcitrance indices. These findings suggest that alder encroachment will reduce soil organic C accumulation by accelerating microbial decomposition, and highlight that increased biochemical stabilization would attenuate soil organic C loss after alder expansion in boreal peatlands. Our results will help assess and project future C budgets in boreal peatlands.

Pesticide Informatics Platform (PIP): An International Platform for Pesticide Discovery, Residue, and Risk Evaluation.

Pesticides are widely used agrochemicals for crop protection. The need for novel pesticides becomes urgent as a result of the emergence of resistance and environmental toxicity. Pesticide informatics has been applied in different phase processes of pesticide target identification, active ingredient design, and impact evaluation. However, these valuable resources are scattered over the literature and web, limiting their availability. Here, we summarize and connect research on pesticide informatics resources. A pesticide informatics platform (PIP) was constructed to share these tools. We finally discuss the future direction of pesticide informatics, including pesticide contamination. We expect to share the pesticide informatics approaches and stimulate further research.

[Optical Composition and Potential Driving Factors of Chromophoric Dissolved Organic Matter in Large Lakes and Reservoirs in the Eastern Region of China].

Intensified urbanization has been occurring in the eastern region of China in recent decades, and excessive industrial and household sewage has been discharged into lakes and reservoirs, which has directly lowered water quality and destructed the functions of aquatic ecosystems. Lakes and reservoirs are typically drinking water sources supplying water for metropolitan areas as well as large- and medium-sized cities. Chromophoric dissolved organic matter (CDOM) is the colored fraction of DOM, and its source and optical composition strongly affect water supply safety and the health of surrounding citizens. In April 2021, we collected 68 samples from Reservoir Changtan (n=11), Lake Taihu (n=25), Lake Hongze (n=18), and Lake Gaoyou (n=14), and we further carried out 28 days of laboratory bio-incubation, together with optical measurements and parallel factor analysis (EEMs-PARAFAC) to analyze the bio-degradability ω(BDOC), sources, and optical composition of CDOM in these waters. The results showed that after 28 days of laboratory bio-incubation, the bioavailability of dissolved organic carbon (BDOC) of the four lakes and reservoirs were all higher than 50%. PARAFAC results showed that CDOM collected from the four lakes was composed of four fluorescent components, including a terrestrial humic-like C1, a tryptophan-like C2, and tyrosine-like C3 and C4. Protein-like components (C2, C3, and C4) contributed importantly to the CDOM pool in the four waterbodies, and in Lake Hongze the contribution of C2-C4 was as high as (90.0±2.2)%. In Lake Hongze, total phosphorus (TP) correlated closely with C1-C3, indicating that those components can be used to trace the variability of TP. Among the four waterbodies, a254 was positively correlated with DOC (R2=0.96, P<0.01), indicating that a254 can be used to estimate the dynamics of DOC in these waters. In Lake Taihu, we found a low level of humification index (HIX) and a high level of biological index (BIX), indicating that autochthonous substances contributed importantly to the CDOM pool in this lake. In comparison, allochthonous sources contributed importantly to the CDOM pool in the remaining three waters. The enhanced monitoring of the discharge of industrial and agricultural effluents in the upstream watersheds of the four waters can help to protect the water quality and maintain healthy aquatic ecosystems.

[Emission of Methane from a Key Lake in the Eastern Route of the South-to-North Water Transfer Project and the Corresponding Driving Factors].

Lakes play an important role in the biogeochemical cycling of dissolved organic matter (DOM) and the emission of methane (CH4). We investigated the concentration and effluxes of CH4 and then analyzed the corresponding driving factors in Lake Luoma, a key lake along the South-to-North Water Transfer Project. Our results indicated that Lake Luoma was a hotspot of CH4 emissions with an annual mean concentration and efflux of (0.12±0.09) µmol·L-1 and (21.0±18.5) mmol·(m2·d)-1, respectively. We found higher mean CH4 levels in the wet season than those in the dry season and further higher levels than those in the wet-to-dry transition season. Spatially, the CH4 efflux was higher in the northwest inflowing regions and lower in the southeast outflow regions. The variability in annual CH4 efflux was affected by a combination of water temperature and hydrological conditions. Terrestrial input of dissolved organic carbon (DOC) and chromophoric DOM (CDOM) had fueled the production of CH4 by providing necessary carbon substrates, and four PARAFAC DOM components were identified including a microbial humic-like C1, a tryptophan-like C2, a terrestrial humic-like C3, and a tyrosine-like C4. The CH4 efflux from the lake was significantly promoted by the input and accumulation of terrestrial humic-like components, and Chl-a had no correlation with CH4 efflux, suggesting that algal degradation was not directly fueling the emission of CH4. Lake Luoma had been significantly disturbed by human activities, and terrestrial input of nutrient loading (TN and TP) into the lake not only improved the productivity and trophic level of the water body but also enhanced the production and release of CH4 from the surface water. We concluded that the CH4 emissions in Lake Luoma can be influenced by the combination of environmental factors, CDOM composition, and nutrient level. Long-term observation is needed for better evaluation of the driving factors in fueling the emission of CH4 so as to effectively reduce the emissions of CH4 and other greenhouse gases by taking corresponding countermeasures.

Sirolimus treatment for tuberous sclerosis complex prior to epilepsy: Evidence from a registry-based real-world study.

OBJECTIVE: To evaluate whether sirolimus treatment could relieve the later burden of new-onset seizures in patients with tuberous sclerosis complex (TSC) prior to epilepsy. METHODS: A real-world matched case-control study was nested in another registry cohort study. Infants with TSC (<12 months old) without seizures whose parents agreed on sirolimus treatment for other symptoms were eligible for inclusion to the early sirolimus (ES) group. These patients were enrolled from 2015 to 2018. Controls in the late sirolimus (LS) group were matched from the registry cohort database for 2015-2018. Age and genotype were used as the initial stratifying criteria and other symptoms as the greedy matching criteria at a matching ratio of 1:4. None of the preventive drugs were introduced before seizure onset or before 2 years of age in the LS group. Both groups were followed up until June 2020. The primary objective was a comparison of the characteristics of the first seizure between the two groups. The secondary objective was the assessment of the final seizure status at the endpoint. RESULTS: There were 42 and 168 patients with TSC in the ES and LS groups, respectively. Early sirolimus treatment significantly reduced the seizure onset, especially in the patients aged <6 months. The mean onset-age was significantly delayed by sirolimus treatment (11.34±7.93 months vs. 6.94±6.03 months, P<0.001). The subtype of seizures that benefited the most was spastic (onset) seizures (all were infantile spasms) [5/42 (11.90%) vs. 73/168 (43.45%), P<0.001]; these seizures were either eliminated or alleviated. The sirolimus treatment addition prior to seizures was more effective than its addition after seizures in reducing drug-resistant epilepsy [10/42 (23.81%) vs. 70/147 (47.62%), P=0.004]. CONCLUSION: Early sirolimus treatment for TSC effectively modified the disease by preventing infantile spasms, delaying seizure onset, and relieving its severity. The anti-epileptogenic effect of sirolimus may be time- and dose-dependent.