Targeting ferroptosis regulators by natural products in colorectal cancer.

Colorectal cancer (CRC) poses a significant global health challenge, ranking as the third most diagnosed cancer and the second leading cause of cancer-related deaths. Despite advancements in treatment, challenges such as delayed diagnosis, multidrug resistance, and limited therapeutic effectiveness persist, emphasizing the need for innovative approaches. This review explores the potential of natural products, nutraceuticals, and phytochemicals for targeting ferroptosis-related regulators as a novel strategy in CRC. Ferroptosis, a form of regulated cell death characterized by iron-dependent lethal lipid peroxide accumulation, holds substantial importance in CRC progression and therapy resistance. Natural products, known for their diverse bioactive effects and favorable safety profiles, emerge as promising candidates to induce ferroptosis in CRC cells. Exploring amino acid, iron, lipid metabolism regulators, and oxidative stress regulators reveals promising avenues for inducing cell death in CRC. This comprehensive review provides insights into the multifaceted effects of natural products on proteins integral to ferroptosis regulation, including GPX4, SLC7A11, ACSL4, NCOA4, and HO-1. By elucidating the intricate mechanisms through which natural products modulate these proteins, this review lays the foundation for a promising therapeutic strategy in CRC.

Research on nowcasting prediction technology for flooding scenarios based on data-driven and real-time monitoring.

With the impact of global climate change and the urbanization process, the risk of urban flooding has increased rapidly, especially in developing countries. Real-time monitoring and prediction of flooding extent and drainage system are the foundation of effective urban flood emergency management. Therefore, this paper presents a rapid nowcasting prediction method of urban flooding based on data-driven and real-time monitoring. The proposed method firstly adopts a small number of monitoring points to deduce the urban global real-time water level based on a machine learning algorithm. Then, a data-driven method is developed to achieve dynamic urban flooding nowcasting prediction with real-time monitoring data and high-accuracy precipitation prediction. The results show that the average MAE and RMSE of the urban flooding and conduit system in the deduction method for water level are 0.101 and 0.144, 0.124 and 0.162, respectively, while the flooding depth deduction is more stable compared to the conduit system by probabilistic statistical analysis. Moreover, the urban flooding nowcasting method can accurately predict the flooding depth, and the R2 are as high as 0.973 and 0.962 of testing. The urban flooding nowcasting prediction method provides technical support for emergency flood risk management.

Final analysis of camrelizumab plus chemotherapy for untreated advanced or metastatic esophageal squamous cell carcinoma: The ESCORT-1st trial.

BACKGROUND: The interim analysis of the randomized phase 3 ESCORT-1st study demonstrated significantly longer overall survival (OS) and progression-free survival (PFS) for camrelizumab-chemotherapy than placebo-chemotherapy in untreated advanced/metastatic esophageal squamous cell carcinoma (ESCC). Here, we present the final analysis of this study and investigate potential indicators associated with OS. METHODS: Patients were randomized 1:1 to receive camrelizumab (200 mg) or placebo, both in combination with up to six cycles of paclitaxel (175 mg/m2) and cisplatin (75 mg/m2). All treatments were administered intravenously every 3 weeks. The co-primary endpoints were OS and PFS assessed by the independent review committee. FINDINGS: As of April 30, 2022, the median OS was significantly longer in the camrelizumab-chemotherapy group compared to the placebo-chemotherapy group (15.6 [95% confidence interval (CI): 14.0-18.4] vs. 12.6 months [95% CI 11.2-13.8]; hazard ratio [HR]: 0.70 [95% CI 0.58-0.84]; one-sided p < 0.0001), with 3-year OS rates of 25.6% and 12.8% in the two groups, respectively. The 2-year PFS rates were 20.4% in the camrelizumab-chemotherapy group and 3.4% in the placebo-chemotherapy group. Adverse events were consistent with those reported in the interim analysis. Higher PD-L1 expression correlated with extended OS, and multivariate analysis identified sex and prior history of radiotherapy as independent indicators of OS. CONCLUSIONS: The sustained and significant improvement in efficacy with camrelizumab-chemotherapy compared to placebo-chemotherapy, along with the absence of accumulating or delayed toxicities, supports the long-term use of camrelizumab-chemotherapy as a standard therapy in untreated advanced/metastatic ESCC. FUNDING: This study was funded by Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Garsorasib in patients with KRASG12C-mutated non-small-cell lung cancer in China: an open-label, multicentre, single-arm, phase 2 trial.

BACKGROUND: Garsorasib (D-1553; InventisBio, Shangai, China), a potent KRASG12C inhibitor, has shown promising antitumour activity in patients with KRASG12C-mutated (ie, Gly12Cys) non-small-cell lung cancer (NSCLC) in a phase 1 study. We report results from a phase 2 study conducted to evaluate the efficacy and safety of garsorasib in patients with locally advanced or metastatic KRASG12C-mutated NSCLC. METHODS: This open-label, multicentre, single-arm, phase 2 trial enrolled adult patients with KRASG12C-mutated NSCLC who had previously been treated with platinum-based chemotherapy and immune checkpoint inhibitors from 43 hospitals in China. Participants received 600 mg garsorasib orally twice per day. Tumour assessments were performed at baseline, at the end of every two cycles (of 21 days) for the first eight cycles, and at the end of every three cycles thereafter. The primary endpoint was objective response rate (ORR) as assessed by an independent review committee (IRC) following the guidelines in Response Evaluation Criteria in Solid Tumours, version 1.1. Efficacy and safety were assessed in all patients who received at least one dose of garsorasib. This trial is registered at ClinicalTrials.gov, NCT05383898, and is active but no longer recruiting. FINDINGS: From June 17, 2022, to May 17, 2023, of 225 patients screened for eligibility, 123 patients were enrolled and treated with garsorasib. Of these 123 participants, the median age was 64 years (IQR 59-68), 108 (88%) were male and 15 (12%) were female. At data cutoff (Nov 17, 2023), the median follow-up duration was 7·9 months (IQR 6·3-10·4), and 82 (67%) of 123 patients had discontinued treatment. The IRC-confirmed ORR was 50% (61 of 123 patients; 95% CI 41-59). 117 (95%) of 123 patients reported treatment-related adverse events, with 61 (50%) experiencing grade 3 or higher events. The most common types of adverse events of grade 3 or higher associated with garsorasib were hepatic and gastrointestinal events, including increased liver enzymes, such as aspartate aminotransferase (21 [17%] of 123 participants), alanine aminotransferase (19 [15%] of 123 participants), and gamma-glutamyltransferase (28 [23%] of 123 participants); nausea (2 [2%] of 123 participants); and vomiting (2 [2%] of 123 participants). No new safety signals were identified, and most of the adverse events were well managed. INTERPRETATION: The results show that garsorasib has a high response rate, long duration of response, and an acceptable and manageable safety profile in patients with previously treated KRASG12C-mutated NSCLC. Garsorasib potentially provides a promising treatment option for this patient population. FUNDING: InventisBio.

Comparative analysis of machine learning methods for prediction of chlorophyll-a in a river with different hydrology characteristics: A case study in Fuchun River, China.

Eutrophication is a serious threat to water quality and human health, and chlorophyll-a (Chla) is a key indicator to represent eutrophication in rivers or lakes. Understanding the spatial-temporal distribution of Chla and its accurate prediction are significant for water system management. In this study, spatial-temporal analysis and correlation analysis were applied to reveal Chla concentration pattern in the Fuchun River, China. Then four exogenous variables (wind speed, water temperature, dissolved oxygen and turbidity) were used for predicting Chla concentrations by six models (3 traditional machine learning models and 3 deep learning models) and compare the performance in a river with different hydrology characteristics. Statistical analysis shown that the Chla concentration in the reservoir river segment was higher than in the natural river segment during August and September, while the dominant algae gradually changed from Cyanophyta to Cryptophyta. Moreover, air temperature, water temperature and dissolved oxygen had high correlations with Chla concentrations among environment factors. The results of the prediction models demonstrate that extreme gradient boosting (XGBoost) and long short-term memory neural network (LSTM) were the best performance model in the reservoir river segment (NSE = 0.93; RMSE = 4.67) and natural river segment (NSE = 0.94; RMSE = 1.84), respectively. This study provides a reference for further understanding eutrophication and early warning of algal blooms in different type of rivers.

Interpregnancy Interval After Healthy Live Birth and Subsequent Spontaneous Abortion.

Importance: Many studies have reported that the interpregnancy interval (IPI) is a potential modifiable risk factor for adverse perinatal outcomes. However, the association between IPI after live birth and subsequent spontaneous abortion (SA) is unclear. Objective: To investigate the association of IPI after a healthy live birth and subsequent SA. Design, Setting, and Participants: This prospective cohort study used data from 180 921 women aged 20 to 49 years who had a single healthy live birth and planned for another pregnancy and who participated in the Chinese National Free Prepregnancy Checkups Project from January 1, 2010, to December 31, 2020. Statistical analysis was conducted from June 20 to October 5, 2023. Exposure: Interpregnancy interval, defined as the interval between the delivery date and conception of the subsequent pregnancy, was categorized as follows: less than 18 months, 18 to 23 months, 24 to 35 months, 36 to 59 months, and 60 months or longer. Main Outcomes and Measures: The main outcome was SA. Multivariable-adjusted odds ratios (ORs) were calculated by logistic regression models to examine the association between IPI and the risk of SA. Dose-response associations were evaluated by restricted cubic splines. Results: The analyses included 180 921 multiparous women (mean [SD] age at current pregnancy, 26.3 [2.8] years); 4380 SA events (2.4% of all participants) were recorded. A J-shaped association between IPI levels and SA was identified. In the fully adjusted model, compared with IPIs of 18 to 23 months, both short (<18 months) and long (≥36 months) IPIs showed an increased risk of SA (IPIs of <18 months: OR, 1.15 [95% CI, 1.04-1.27]; IPIs of 36-59 months: OR, 1.28 [95% CI, 1.15-1.43]; IPIs of ≥60 months: OR, 2.13 [95% CI, 1.78-2.56]). Results of the subgroup analysis by mode of previous delivery were consistent with the main analysis. Conclusions and Relevance: This cohort study of multiparous women suggests that an IPI of shorter than 18 months or an IPI of 36 months or longer after a healthy live birth was associated with an increased risk of subsequent SA. The findings are valuable to make a rational prepregnancy plan and may facilitate the prevention of SA and improvement in neonatal outcomes.

Long-Term Exposure to Fine Particulate Matter and Fasting Blood Glucose and Diabetes in 20 Million Chinese Women of Reproductive Age.

OBJECTIVE: Evidence of the associations between fine particulate matter (PM2.5) and diabetes risk from women of reproductive age, in whom diabetes may have adverse long-term health effects for both themselves and future generations, remains scarce. We therefore examined the associations of long-term PM2.5 exposure with fasting blood glucose (FBG) level and diabetes risk in women of reproductive age in China. RESEARCH DESIGN AND METHODS: This study included 20,076,032 women age 20-49 years participating in the National Free Preconception Health Examination Project in China between 2010 and 2015. PM2.5 was estimated using a satellite-based model. Multivariate linear and logistic regression models were used to examine the associations of PM2.5 exposure with FBG level and diabetes risk, respectively. Diabetes burden attributable to PM2.5 was estimated using attributable fraction (AF) and attributable number. RESULTS: PM2.5 showed monotonic relationships with elevated FBG level and diabetes risk. Each interquartile range (27 µg/m3) increase in 3-year average PM2.5 concentration was associated with a 0.078-mmol/L (95% CI 0.077, 0.079) increase in FBG and 18% (95% CI 16%, 19%) higher risk of diabetes. The AF attributed to PM2.5 exposure exceeding 5 µg/m3 was 29.0% (95% CI 27.5%, 30.5%), corresponding to an additional 78.6 thousand (95% CI 74.5, 82.6) diabetes cases. Subgroup analyses showed more pronounced diabetes risks in those who were overweight or obese, age >35 years, less educated, of minority ethnicity, registered as a rural household, and residing in western China. CONCLUSIONS: We found long-term PM2.5 exposure was associated with higher diabetes risk in women of reproductive age in China.

IMpower210: A phase III study of second-line atezolizumab vs. docetaxel in East Asian patients with non-small cell lung cancer.

Objective: IMpower210 (NCT02813785) explored the efficacy and safety of single-agent atezolizumab vs. docetaxel as second-line treatment for advanced non-small cell lung cancer (NSCLC) in East Asian patients. Methods: Key eligibility criteria for this phase III, open-label, randomized study included age ≥18 years; histologically documented advanced NSCLC per the Union for International Cancer Control/American Joint Committee on Cancer staging system (7th edition); Eastern Cooperative Oncology Group performance status of 0 or 1; and disease progression following platinum-based chemotherapy for advanced or metastatic NSCLC. Patients were randomized 2:1 to receive either atezolizumab (1,200 mg) or docetaxel (75 mg/m2). The primary study endpoint was overall survival (OS) in the intention-to-treat (ITT) population with wild-type epidermal growth factor receptor expression (ITT EGFR-WT) and in the overall ITT population. Results: Median OS in the ITT EGFR-WT population (n=467) was 12.3 [95% confidence interval (95% CI), 10.3-13.8] months in the atezolizumab arm (n=312) and 9.9 (95% CI, 7.8-13.9) months in the docetaxel arm [n=155; stratified hazard ratio (HR), 0.82; 95% CI, 0.66-1.03]. Median OS in the overall ITT population was 12.5 (95% CI, 10.8-13.8) months with atezolizumab treatment and 11.1 (95% CI, 8.4-14.2) months (n=377) with docetaxel treatment (n=188; stratified HR, 0.87; 95% CI, 0.71-1.08). Grade 3/4 treatment-related adverse events (TRAEs) occurred in 18.4% of patients in the atezolizumab arm and 50.0% of patients in the docetaxel arm. Conclusions: IMpower210 did not meet its primary efficacy endpoint of OS in the ITT EGFR-WT or overall ITT populations. Atezolizumab was comparatively more tolerable than docetaxel, with a lower incidence of grade 3/4 TRAEs.

Association between fine particulate matter and fecundability in Henan, China: A prospective cohort study.

OBJECTIVE: To investigate the relationship between ambient fine particulate matter (PM2.5) exposure and fecundability. METHODS: This study included 751,270 female residents from Henan Province who participated in the National Free Pre-conception Check-up Projects during 2015-2017. Ambient cycle-specific PM2.5 exposure was assessed at the county level for each participant using satellite-based PM2.5 concentration data at 1-km resolution. Cox proportional hazards models with time-varying exposure were used to estimate the association between fecundability and PM2.5 exposure, adjusted for potential individual risk factors. RESULTS: During the study period, 568,713 participants were pregnant, monthly mean PM2.5 concentrations varied from 25.5 to 114.0 µg/m3 across study areas. For each 10 µg/m3 increase in cycle-specific PM2.5, the hazard ratio for fecundability was 0.951 (95 % confidence interval: 0.950-0.953). The association was more pronounced in women who were older, with urban household registration, history of pregnancy, higher body mass index (BMI), hypertension, without exposure to tobacco, or whose male partners were older, with higher BMI, or hypertension. CONCLUSION: In this population-based prospective cohort, ambient cycle-specific PM2.5 exposure was associated with reduced fecundability. These findings may support the adverse implications of severe air pollution on reproductive health.

A document-level information extraction pipeline for layered cathode materials for sodium-ion batteries.

Natural language processing techniques enable extraction of valuable information from large amounts of published literature for the application of data science and technology, i.e. machine learning in the field of materials science. Nevertheless, the automated extraction of data from full-text documents remains a complex task. We propose a document-level natural language processing pipeline for literature extraction of comprehensive information on layered cathode materials for sodium-ion batteries. The pipeline enhances entity recognition with contextual supplementary information while capturing the article structure. Finally, a heuristic multi-level relationship extraction algorithm is employed in relation extraction to extract experimental parameters and complex performance relationships respectively. We successfully extracted a comprehensive dataset containing 5265 records from 1747 documents, encompassing essential information such as chemical composition, synthesis parameters, and electrochemical properties. By implementing our pipeline, we have made significant progress in overcoming the challenges associated with data scarcity in battery informatics. The extracted datasets provide a valuable resource for further research and development in the field of layered cathode materials.

Application of Rice Straw Inhibits Clubroot Disease by Regulating the Microbial Community in Soil.

Straw return is an effective agricultural management practice for alleviating soil sickness, but only a few studies have focused on the incorporation of straw with deep plowing and rotary tillage practices in vegetable production. To determine the effects of rice straw return on Chinese cabbage clubroot, a field experiment for three consecutive years in the same area was performed. Soil microbial high-throughput sequencing, quantitative real-time polymerase chain reaction (PCR) and other methods were used to detect Chinese cabbage plant growth, clubroot occurrence, soil chemical properties and soil microbial diversity and abundance. The results showed that straw addition could significantly reduce the clubroot disease incidence. Through Illumina Miseq sequencing, the diversity of the fungi decreased obviously. The relative abundance of the phyla Proteobacteria and Firmicutes was strikingly reduced, while that of Chloroflexi was significantly increased. Redundancy analysis suggests that soil properties may also affect the soil microbial composition; changes in the microbial structure of bacteria and fungi were associated with the available phosphorus. In conclusion, the continuous addition of rice straw can promote the growth and control the occurrence of clubroot, which is closely related to the microbial composition, and the inhibition effect is proportional to the age of addition.

Machine Alarm Fatigue among Hemodialysis Nurses in 29 Tertiary Hospitals.

Objectives To understand the status quo and related influencing factors of machine alarm fatigue of hemodialysis nurses in tertiary hospitals in XXX. Methods This cross-sectional study employed convenience sampling to select 460 nurses from 29 tertiary hospitals in XXX, who are involved in hemodialysis care. Surveys were conducted using General Information Questionnaire, Alarm Fatigue Scale, National Aeronautics and Space Administration Task Load Index(NASA-TLX) and Maslach Burnout Inventory Scale (MBI). Results The overall machine alarm fatigue score for 460 hemodialysis nurses from 29 tertiary hospitals in XXX was (16.43±6.44), indicating a moderate level. The multiple linear regression analysis shows that years of experience in hemodialysis nursing, the number of patients managed per shift, whether specialized nursing training has been received, self-reported health status, emotional exhaustion, and workload have statistically significant associations with alarm fatigue among hemodialysis nurses (P < 0.05). Among them, years of experience in hemodialysis nursing, the number of patients managed per shift, and workload are positively correlated with alarm fatigue among hemodialysis nurses. Conclusion This study indicates that certain demographic factors, workload, and occupational burnout are associated with machine alarm fatigue among hemodialysis nurses. Therefore, hemodialysis-related managers should establish a Machine Alarm Management System, implement Personalized Thresholds and Delayed Alarms, ensure reasonable staffing arrangements, improve compassion fatigue, and enhance anticipatory care. These measures aim to improve the health and psychological well-being of hemodialysis nurses, provide a conducive environment for professional training in hemodialysis, and ultimately address the current situation of machine alarm fatigue among hemodialysis nurses.

An Effective Method to Prepare Curcumin-Loaded Soy Protein Isolate Nanoparticles Co-Stabilized by Carrageenan and Fucoidan.

In this study, a novel and simple strategy is proposed based on 3D network formed by easily blending polysaccharide carrageenan (Car) and fucoidan (Fuc) without a crosslinker. The Fuc/Car dual coating effectively assists the self-assembly of soy protein-isolated (SPI)/curcumin (Cur, C) composite microcapsules (SPI/C) and achieves an excellent curcumin encapsulation efficiency (EE) up to 95.28% with a 4.16% loading capacity (LC) under optimal conditions. The resulting nanocomposites achieved a satisfying redispersibility in aqueous solution and enhanced the water solubility with a lower size dispersity index (PDI) of 0.12 and a larger zeta potential of -29.67 mV. The Fuc/Car double-layer network not only dramatically improved its thermal stability and photostability, but also provided controlled release and enhanced antioxidant activity in in vitro conditions. The underlying mechanism of the self-assembly of the curcumin-loaded nanoparticles was also addressed. The results proved the feasibility of the encapsulation of unstable hydrophobic bioactive substances (curcumin) with the dual anionic polysaccharide Fuc/Car co-stabilized SPI nanoparticles. This study paves the way for an alternative way of developing novel curcumin delivery systems and will have broad prospects in the pharmaceutical industries.

Identification of sensitive endpoints for the assessment of phthalates-induced reproductive and developmental toxicity: A literature mining study.

Dibutyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP), two common types of phthalates, are known to cause reproductive and developmental toxicity in animals and humans. The reference doses (RfD) of DBP and DEHP should be determined by sensitive endpoints. We here aimed to identify sensitive endpoints for DBP- and DEHP-induced such toxicity using published literatures. By examining the impacts of maternal exposure to DBP or DEHP on anogenital distance (AGD) and semen quality of offspring, we discovered that DBP or DEHP caused AGD decline in boys but increase in girls with DBP being more potent and the first 14weeks of pregnancy being more susceptible, suggesting a chemical- and time-dependent phenomenon. We also identified AGD shortening and total sperm count reduction as two sensitive endpoints for DBP- or DEHP-induced reproductive and developmental toxicity, respectively. Based upon these two endpoints and the employment of the Bayesian benchmark dose approach with an uncertainty factor of 3,000, we estimated the RfD values of DBP and DEHP were 15 µg/kg/day and 36 µg/kg/day, respectively. Thus, we uncover previously unrecognized phenomena of DBP- or DEHP-induced reproductive and developmental toxicity and establish new and comparable or more conservative RfDs for the risk assessment of phthalates exposure in humans.

Ferroptosis implication in environmental-induced neurotoxicity.

Neurotoxicity, stemming from exposure to various chemical, biological, and physical agents, poses a substantial threat to the intricate network of the human nervous system. This article explores the implications of ferroptosis, a regulated form of programmed cell death characterized by iron-dependent lipid peroxidation, in environmental-induced neurotoxicity. While apoptosis has historically been recognized as a primary mechanism in neurotoxic events, recent evidence suggests the involvement of additional pathways, including ferroptosis. The study aims to conduct a comprehensive review of the existing literature on ferroptosis induced by environmental neurotoxicity across diverse agents such as natural toxins, insecticides, particulate matter, acrylamide, nanoparticles, plastic materials, metal overload, viral infections, anesthetics, chemotherapy, and radiation. The primary objective is to elucidate the diverse mechanisms through which these agents trigger ferroptosis, leading to neuronal cell death. Furthermore, the article explores potential preventive or therapeutic strategies that could mitigate ferroptosis, offering insights into protective measures against neurological damage induced by environmental stressors. This comprehensive review contributes to our evolving understanding of neurotoxicological processes, highlighting ferroptosis as a significant contributor to neuronal cell demise induced by environmental exposures. The insights gained from this study may pave the way for the development of targeted interventions to protect against ferroptosis-mediated neurotoxicity and ultimately safeguard public health.

Development and Application of a Duplex RT-RPA Assay for the Simultaneous Detection of Cymbidium mosaic virus and Odontoglossum ringspot virus.

Cymbidium mosaic virus (CymMV) and Odontoglossum ringspot virus (ORSV) are among the world's most serious and widespread orchid viruses; they often infect orchids, causing devastating losses to the orchid industry. Therefore, it is critical to establish a method that can rapidly and accurately detect viruses in the field using simple instruments, which will largely reduce the further spread of viruses and improve the quality of the orchid industry and is suitable for mass promotion and application at grassroots agrotechnical service points. In this investigation, we established a rapid amplification method for virus detection at 39 °C for 35 min to detect the presence of CymMV and ORSV simultaneously, sensitively, and specifically in orchids. Primers for the capsid protein (CP)-encoding genes of both viruses were designed and screened, and the reaction conditions were optimized. The experimental amplification process was completed in just 35 min at 39 °C. There were no instances of nonspecific amplification observed when nine other viruses were present. The RPA approach had detection limits of 104 and 103 copies for pMD19T-CymMV and pMD19T-ORSV, respectively. Moreover, the duplex RT-RPA investigation confirmed sensitivity and accuracy via a comparison of detection results from 20 field samples with those of a gene chip. This study presents a precise and reliable detection method for CymMV and ORSV using RT-RPA. The results demonstrate the potential of this method for rapid virus detection. It is evident that this method could have practical applications in virus detection processes.

Biodiversity mitigates drought effects in the decomposer system across biomes.

Multiple facets of global change affect the earth system interactively, with complex consequences for ecosystem functioning and stability. Simultaneous climate and biodiversity change are of particular concern, because biodiversity may contribute to ecosystem resistance and resilience and may mitigate climate change impacts. Yet, the extent and generality of how climate and biodiversity change interact remain insufficiently understood, especially for the decomposition of organic matter, a major determinant of the biosphere-atmosphere carbon feedbacks. With an inter-biome field experiment using large rainfall exclusion facilities, we tested how drought, a common prediction of climate change models for many parts of the world, and biodiversity in the decomposer system drive decomposition in forest ecosystems interactively. Decomposing leaf litter lost less carbon (C) and especially nitrogen (N) in five different forest biomes following partial rainfall exclusion compared to conditions without rainfall exclusion. An increasing complexity of the decomposer community alleviated drought effects, with full compensation when large-bodied invertebrates were present. Leaf litter mixing increased diversity effects, with increasing litter species richness, which contributed to counteracting drought effects on C and N loss, although to a much smaller degree than decomposer community complexity. Our results show at a relevant spatial scale covering distinct climate zones that both, the diversity of decomposer communities and plant litter in forest floors have a strong potential to mitigate drought effects on C and N dynamics during decomposition. Preserving biodiversity at multiple trophic levels contributes to ecosystem resistance and appears critical to maintain ecosystem processes under ongoing climate change.

Microencapsulation of Lactobacillus plantarum with Improved Survivability Using Pufferfish Skin Gelatin-Based Wall Materials.

To improve the survivability of probiotics, Lactobacillus plantarum was microencapsulated using pufferfish skin gelatin (PSG)-based wall materials by spray-drying. This work investigated the protective effect of three different pH-dependent proteins (sodium caseinate (SC), soy protein isolate (SPI), and whey protein isolate (WPI)) combined with PSG on L. plantarum. The experimental results of spray-drying with an inlet temperature of 120 °C and an outlet temperature of 80 °C, storage at 4 °C for 6 months, simulated digestion, and turbidity indicated that PSG/SC had better stability and encapsulation effects and was more suitable to encapsulate L. plantarum than PSG/SPI and PSG/WPI. The optimum preparation conditions for L. plantarum microcapsules were a PSG/SC mass ratio of 2:1, an SC concentration of 20 g/L, and a cell concentration of 10 g/L. The encapsulation efficiency of the obtained microcapsules was 95.0%, and the survival rate was 94.2% in simulated gastric fluid for 2 h and 98.0% in simulated intestinal fluid for 2 h. Amino acid composition analysis exhibited that the imino acid and aspartic acid contents of PSG were 27.98 and 26.16 g/100 g protein, respectively, which was much higher than commercial bovine gelatin. This characteristic was favorable to the high encapsulation efficiency and stability of microcapsules. In vitro release experiments showed that the PSG/SC microcapsules did not disintegrate in simulated gastric fluid for 2 h but could completely release in simulated intestinal fluid for 2 h, which can maintain the high survivability of L. plantarum in simulated digestion. In general, this study demonstrated that microcapsules using PSG/SC as wall materials can effectively improve the survivability of probiotics and have great potential for application in probiotic products.

Retinal vascular density as a potential biomarker of diabetic cerebral small vessel disease.

AIM: The retina and brain share similar anatomical and physiological features. Thus, retinal imaging by optical coherence tomography angiography (OCTA) might be a potential tool for the early diagnosis of diabetic cerebral small vessel disease (CSVD). In this study, we aimed to evaluate retinal vascular density (VD) in diabetic CSVD by OCTA imaging and explore the associations between retinal VD and cerebral magnetic resonance imaging (MRI) markers and cognitive function. METHODS: In total, 131 patients were enrolled, including CSVD (n = 43) and non-CSVD groups (n = 88). The VD and foveal avascular zone of the retinal capillary plexus were measured with OCTA. A brain MRI was performed. RESULTS: MRI imaging showed that in the diabetic CSVD group, white matter hyperintensities (WMHs), particularly deep WMHs (58.82%), are the most common MRI marker, followed by cerebral microbleeds in the subtentorial and cortical areas (34.78%). The CSVD group showed increases in the prevalence of cognitive dysfunction (p = .034) and depression (p = .033) and decreases in visuospatial/executive ability and delayed recall ability. In the CSVD group, VDs of the macular superficial vascular plexus (32.93 ± 7.15% vs. 36.97 ± 6.59%, p = .002), intermediate capillary plexus (20.87 ± 4.30% vs. 23.08 ± 4.30%, p = .005) and deep capillary plexus (23.54 ± 5.00% vs. 26.05 ± 4.20%, p = .003) were lower than those of the non-CSVD group. Multiple linear regression analysis showed that VD of the macular superficial vascular plexus was independently associated with cerebral microbleeds. Meanwhile, VD of the macular intermediate capillary plexus was associated with white matter lacunar infarcts after adjustment. CONCLUSIONS: Diabetic CSVDs are characterized by MRI markers, including deep WMHs and cerebral microbleeds, and showed impaired cognition with decreased visuospatial/executive ability and delayed recall ability. OCTA imaging revealed a significant decrease in retinal microvascular perfusion in diabetic CSVD, which was related to MRI markers and cognitive function. OCTA might be a valuable potential measurement for the early diagnosis of CSVD.

Resistance role of Lactobacillus sp. and Lactococcus sp. to copper ions in healthy children's intestinal microorganisms.

Heavy metal exposure is closely associated with gut microbe function and tolerance. However, intestinal microbe responses in children to different copper ion (Cu2+) concentrations have not yet been clarified. Here, in vitro cultivation systems were established for fecal microbe control and Cu2+-treated groups in healthy children. 16S rDNA high-throughput sequencing, meta-transcriptomics and metabolomics were used here to identify toxicity resistance mechanisms at microbiome levels. The results showed that Lactobacillus sp. and Lactococcus sp. exerted protective effects against Cu2+ toxicity, but these effects were limited by Cu2+ concentration. When the Cu2+ concentration was ≥ 4 mg/L, the abundance of Lactobacillus sp. and Lactococcus sp. significantly decreased, and the pathways of antioxidant activity and detoxification processes were enriched at 2 mg/L Cu2+, and beneficial metabolites accumulated. However, at high concentrations of Cu2+ (≥4 mg/L), the abundance of potential pathogen increased, and was accompanied by a downregulation of genes in metabolism and detoxification pathways, which meant that the balance of gut microbiota was disrupted and toxicity resistance decreased. From these observations, we identified some probiotics that are tolerant to heavy metal Cu2+, and warn that only when the concentration limit of Cu2+ in food is 2 mg/L, then a balanced gut microbiota can be guaranteed in children, thereby providing protection for their health.