The Use of Real-World Evidence for Regulatory Decisions in China.

There is a growing demand for the use of high-quality real-world evidence (RWE) to support regulatory decision-making worldwide and in China, which highlights the need for conducting literature reviews to evaluate the available data and evidence. This study aims to review the use of RWE in Chinese regulatory decisions and to summarize relevant regulatory and methodological considerations to inform the future use of RWE in China. We identified policy documents, technical guidance documents, and cases on official Chinese government websites and extracted their contents separately. We consulted experts from the National Medical Products Administration (NMPA) and academic institutes and searched case-related articles for enrichment. We also searched and included articles related to the use of RWE/Real-world data in Chinese regulatory decisions. Six trial versions of technical guidance documents, 7 case studies, and 40 articles related to the Chinese regulatory decisions were included in this study. Based on the technical guidance, data quality, and appropriate study design and statistical analysis are the main concerns for RWE generation. The cases and articles related to regulatory decisions revealed 9 main concerns, including data sources and applicability, data quality, strength of existing evidence, appropriate study design and statistical analysis, regulated and transparent process for analysis and evidence generation, product safety and efficacy, product characteristics and clinical needs, ethical considerations and data security, and communicate adequately with regulatory authorities. Among these concerns, data issues are central. Preliminary attempts have been made by the NMPA to promote the use of RWE, but substantial challenges still remain.

Pooled and global burdens and trends of five common cancers attributable to diet in 204 countries and territories from 1990 to 2019: an analysis of the Global Burden of Disease Study.

OBJECTIVE: Increasing evidence has shown that dietary behaviors are closely correlated with the carcinogenesis and progression of many types of cancer. However, few studies have assessed the global diet-related burden of cancer. This study aimed to estimate the pooled burdens and trends of five types of cancers attributable to dietary behaviors. METHODS: Data regarding cancer attributable to dietary behaviors were extracted from the Global Burden of Disease study 2019, including the death cases and age-standardized death rates, and disability-adjusted life years (DALYs) estimated according to diseases, age, sex, the socio-demographic index (SDI) and location. RESULTS: According to the Global Burden of Disease study 2019, five types of cancer were affected by dietary behaviors: colon and rectum cancer; tracheal, bronchus and lung cancer; stomach cancer; esophageal cancer and breast cancer. Unhealthy dietary behaviors for cancer caused a total of 605.4 thousand deaths and 13951.3 thousand DALYs globally. The burden of cancer attributable to dietary risks was higher for men than for women. The highest age-standardized death rates in 2019 were observed in southern Latin America, and the lowest rates were observed in North Africa and the Middle East. The greatest increases in the age-standardized death rates, from 1990 to 2019, were found in Western Sub-Saharan Africa, with the greatest decreases in Central Asia. The highest attributable proportions of death or DALYs were colon and rectum cancer. The greatest diet-related cancer burden was observed in regions with a high-middle SDI. CONCLUSION: Global age-standardized deaths and DALYs rates attributable to diet-related cancer are considerable and cause a substantial burden. Successful population-wide initiatives targeting unhealthy dietary behaviors would reduce this burden.

Foxq1 Promotes Alveolar Epithelial Cell Death through Tle1-mediated Inhibition of the NFκB Signaling Pathway.

Acute lung injury is a common respiratory disease characterized by diffuse alveolar injury and interstitial edema, as well as a hyperinflammatory response, lung cell damage and oxidative stress. Foxq1, a member of the FOX family of transcription factors, is expressed in various tissues, such as the lungs, liver, and kidneys, and contributes to various biological processes, such as stress, metabolism, cell cycle arrest, and aging-related apoptosis. However, the role of Foxq1 in acute lung injury is unknown. We constructed ex vivo and in vivo acute lung injury models by lipopolysaccharide tracheal perfusion of ICR mice and conditioned medium stimulation of injured MLE-12 cells. Foxq1 expression was increased, and its localization was altered in our acute lung injury model. In normal or injured MLE-12 cells, knockdown of Foxq1 promoted cell survival, and overexpression had the opposite effect. This regulatory effect was likely mediated by Tle1 and the NFκB/Bcl2/Bax signaling pathway. These data suggest a potential link between Foxq1 and acute lung injury, indicating that Foxq1 can be used as a biomarker for the diagnosis of acute lung injury. Targeted inhibition of Foxq1 expression could promote alveolar epithelial cell survival and may provide a strategy for mitigating acute lung injury.

Cumulative inequality in social determinants of health in relation to depression symptom: An analysis of nationwide cross-sectional data from U.S. NHANES 2005-2018.

Social determinants of health (SDoH) have been linked to a higher likelihood of experiencing mental health problems. This study aimed to investigate whether the accumulation of unfavorable SDoH is associated with depression symptom. Data was gathered from a representative population participating in the U.S. National Health and Nutrition Examination Survey spanning from 2005 to 2018. Self-reported SDoH were operationalized according to the criteria outlined in Healthy People 2030, with a cumulative measure of unfavorable SDoH calculated for analysis. The presence of depression symptom was identified using the Patient Health Questionnaire in a representative sample of 30,762 participants (49.2 % males) representing 1,392 million non-institutionalized U.S. adults, with 2,675 (8.7 %) participants showing depression symptom. Unfavorable SDoH were found to be significantly and independently associated with depression symptom. Individuals facing multiple unfavorable SDoHs were more likely to experience depression symptom (P for trend < 0.001). For instance, a positive association was observed in participants exposed to six or more unfavorable SDoHs with depression symptom (AOR = 3.537, 95 % CI: 1.781, 7.075, P-value < 0.001). The findings emphasize that the likelihood of developing depression symptom significantly increases when multiple SDoHs are present, compared to just a single SDoH.

A novel method-based reinforcement learning with deep temporal difference network for flexible double shop scheduling problem.

This paper studies the flexible double shop scheduling problem (FDSSP) that considers simultaneously job shop and assembly shop. It brings about the problem of scheduling association of the related tasks. To this end, a reinforcement learning algorithm with a deep temporal difference network is proposed to minimize the makespan. Firstly, the FDSSP is defined as the mathematical model of the flexible job-shop scheduling problem joined to the assembly constraint level. It is translated into a Markov decision process that directly selects behavioral strategies according to historical machining state data. Secondly, the proposed ten generic state features are input into the deep neural network model to fit the state value function. Similarly, eight simple constructive heuristics are used as candidate actions for scheduling decisions. From the greedy mechanism, optimally combined actions of all machines are obtained for each decision step. Finally, a deep temporal difference reinforcement learning framework is established, and a large number of comparative experiments are designed to analyze the basic performance of this algorithm. The results showed that the proposed algorithm was better than most other methods, which contributed to solving the practical production problem of the manufacturing industry.

Simultaneous EEG-fMRI Investigation of Rhythm-Dependent Thalamo-Cortical Circuits Alteration in Schizophrenia.

Schizophrenia is accompanied by aberrant interactions of intrinsic brain networks. However, the modulatory effect of electroencephalography (EEG) rhythms on the functional connectivity (FC) in schizophrenia remains unclear. This study aims to provide new insight into network communication in schizophrenia by integrating FC and EEG rhythm information. After collecting simultaneous resting-state EEG-functional magnetic resonance imaging data, the effect of rhythm modulations on FC was explored using what we term "dynamic rhythm information." We also investigated the synergistic relationships among three networks under rhythm modulation conditions, where this relationship presents the coupling between two brain networks with other networks as the center by the rhythm modulation. This study found FC between the thalamus and cortical network regions was rhythm-specific. Further, the effects of the thalamus on the default mode network (DMN) and salience network (SN) were less similar under alpha rhythm modulation in schizophrenia patients than in controls ([Formula: see text]). However, the similarity between the effects of the central executive network (CEN) on the DMN and SN under gamma modulation was greater ([Formula: see text]), and the degree of coupling was negatively correlated with the duration of disease ([Formula: see text], [Formula: see text]). Moreover, schizophrenia patients exhibited less coupling with the thalamus as the center and greater coupling with the CEN as the center. These results indicate that modulations in dynamic rhythms might contribute to the disordered functional interactions seen in schizophrenia.

Application of furazolidone in Helicobacter pylori infection eradication.

Increasing antibiotic resistance is the primary reason for treatment failure of Helicobacter pylori (H. pylori) infection. To enhance the eradication rate, minimize the development of secondary resistance, and alleviate the socioeconomic burden, it is crucial to select H. pylori-sensitive antibiotics carefully. Furazolidone has been used for H. pylori eradication in developing countries for decades due to its affordability and low resistance rate. Numerous studies have demonstrated that furazolidone-containing regimens are more efficacious than those containing other antibiotics, as both first- and second-line therapies, and are also well tolerated. However, utility of furazolidone is restricted or not optimal in certain countries due to its infrequent but potentially severe adverse effects. The decision to discontinue usage of furazolidone because of concerns regarding adverse effects may be misguided. Here we comprehensively reviewed the studies on furazolidone at different dosages and treatment durations for H. pylori eradication. Further research on the mechanisms of action and clinical trials of furazolidone are of great practical importance.

The activation of HAMP promotes colorectal cancer cell proliferation through zinc-mediated upregulation of SMAD4 expression.

Background: Colorectal cancer (CRC) poses a significant challenge in digestive system diseases, and emerging evidence underscores the critical role of zinc metabolism in its progression. This study aimed to investigate the clinical implications of genes at the intersection of zinc metabolism and CRC. Methods: We downloaded CRC prognosis-related genes and zinc metabolism-related genes from public databases. Then, the overlapping genes were screened out, and bioinformatics analysis was performed to obtain the hub gene associated with CRC prognosis. Subsequently, in vitro assays were carried out to investigate the expression of this hub gene and its exact mechanism between zinc metabolism and CRC. Results: HAMP was identified as the hub CRC prognostic gene from overlapping zinc metabolism-related and CRC prognostic genes. In vitro analysis showed HAMP was over-expressed in CRC, and its knockdown inhibited RKO and HCT-116 cell invasion and migration significantly. ZnSO4 induced HAMP up-regulation to promote cell proliferation, while TPEN decreased HAMP expression to inhibit cell proliferation. Importantly, we further found that ZnSO4 enhanced SMAD4 expression to augment HAMP promoter activity and promote cell proliferation in CRC. Conclusions: HAMP stands out as an independent prognostic factor in CRC, representing a potential therapeutic target. Its intricate regulation by zinc, particularly through the modulation of SMAD4, unveils a novel avenue for understanding CRC biology. This study provides valuable insights into the interplay between zinc metabolism, HAMP, and CRC, offering promising clinical indicators for CRC patients. The findings present a compelling case for further exploration and development of targeted therapeutic strategies in CRC management.

Diagnostic, monitoring, and prognostic value of combined detection of cerebrospinal fluid heparin-binding protein, interleukin-6, interleukin-10, and procalcitonin for post-neurosurgical intracranial infection.

OBJECTIVE: Intracranial infection is a common complication after neurosurgery and can increase the length of hospital stay, affect patient prognosis, and increase mortality. We aimed to investigate the value of the combined detection of cerebrospinal fluid (CSF) heparin-binding protein (HBP), interleukin-6 (IL-6), interleukin-10 (IL-10), and procalcitonin (PCT) for post-neurosurgical intracranial infection. METHODS: This study assessed the diagnostic values of CSF HBP, IL-6, IL-10, PCT levels, and combined assays for post-neurosurgical intracranial infection with the area under the receiver operating characteristic (ROC) curve by retrospectively analysing biomarkers of post-neurosurgical patients. RESULTS: The CSF HBP, IL-6, IL-10, and PCT levels were significantly higher in the infected group than the uninfected group and the control group (P < 0.001). The indicators in the groups with severe intracranial infections were significantly higher than those in the groups with mild intracranial infections (P < 0.001), and the groups with poor prognoses had significantly higher indexes than the groups with good prognoses. According to the ROC curve display, the AUC values of CSF HBP, IL-6, IL-10, and PCT were 0.977 (95 % CI 0.952-1.000), 0.973 (95 % CI 0.949-0.998), 0.884 (95 % CI 0.823-0.946), and 0.819 (95 % CI 0.733-0.904), respectively. The AUC of the combined test was 0.996 (95 % CI 0.989-1.000), which was higher than those of the four indicators alone. CONCLUSION: The combined detection can be an important indicator for the diagnosis and disease monitoring of post-neurosurgical intracranial infection.

The crucial relationship between miRNA-27 and CSE/H2S, and the mechanism of action of GLP-1 in myocardial hypertrophy.

Cardiac hypertrophy is the most prevalent compensatory heart disease that ultimately leads to spontaneous heart failure. Mounting evidence suggests that microRNAs (miRs) and endogenous hydrogen sulfide (H2S) play a crucial role in the regulation of cardiac hypertrophy. In this study, we aimed to investigate whether inhibition of miR-27a could protect against cardiac hypertrophy by modulating H2S signaling. We established a model of cardiac hypertrophy by obtaining hypertrophic tissue from mice subjected to transverse aortic constriction (TAC) and from cells treated with angiotensin-II. Molecular alterations in the myocardium were quantified using quantitative real time PCR (qRT-PCR), Western blotting, and ELISA. Morphological changes were characterized by hematoxylin and eosin (HE) staining and Masson's trichrome staining. Functional myocardial changes were assessed using echocardiography. Our results demonstrated that miR-27a levels were elevated, while H2S levels were reduced in TAC mice and myocardial hypertrophy. Further luciferase and target scan assays confirmed that cystathionine-γ-lyase (CSE) was a direct target of miR-27a and was negatively regulated by it. Notably, enhancement of H2S expression in the heart was observed in mice injected with recombinant adeno-associated virus vector 9 (rAAV9)-anti-miR-27a and in cells transfected with a miR-27a inhibitor during cardiac hypertrophy. However, this effect was abolished by co-transfection with CSE siRNA and the miR-27a inhibitor. Conversely, injecting rAAV9-miR-27a yielded opposite results. Interestingly, our findings demonstrated that glucagon-like peptide-1 (GLP-1) agonists could mitigate myocardial damage by down-regulating miR-27a and up-regulating CSE. In summary, our study suggests that inhibition of miR-27a holds therapeutic promise for the treatment of cardiac hypertrophy by increasing H2S levels. Furthermore, our findings unveil a novel mechanism of GLP-1 agonists involving the miR-27a/H2S pathway in the management of cardiac hypertrophy.

Potential global distribution of Setaria italica, an important species for dryland agriculture in the context of climate change.

Setaria italica (S. italica, Linnaeus, 1753) is a drought-resistant, barren-tolerant, and widely adapted C-4 crop that plays a vital role in maintaining agricultural and economic stability in arid and barren regions of the world. However, the potential habitat of S. italica under current and future climate scenarios remains to be explored. Predicting the potential global geographic distribution of S. italica and clarifying its ecological requirements can help promote sustainable agriculture, which is crucial for addressing the global food crisis. In this study, we predicted the potential global geographic distribution of S. italica based on 3,154 global distribution records using the Maxent model and ArcGIS software. We assessed the constraints on its potential distribution based on the contribution of environmental factors variables. The predictive accuracy of the Maxent model was evaluated using AUC values, TSS values, and Kappa statistics, respectively. The results showed that the Maxent model had a high prediction accuracy, and the simulation results were also reliable; the total suitable habitats of S. italica is 5.54×107 km2, which mainly included the United States (North America), Brazil (South America), Australia (Oceania), China, India (Asia), and the Russian Federation (Europe). The most suitable habitat of S. italica was 0.52×107 km2, accounting for 9.44% of the total areas, mainly in the United States, India, the Russian Federation, and China. Soil and precipitation (driest monthly precipitation, hottest seasonal precipitation) are the most critical factors limiting the potential distribution of S. italica. Compared with the modern potential distribution, we predict that the four future climate change scenarios will result in varying reductions in the possible geographic ranges of S. italica. Overall, climate change may significantly affect the global distribution of S. italica, altering its worldwide production and trade patterns.

Ti3C2Tx/laser-induced graphene-based micro-droplet electrochemical sensing platform for rapid and sensitive detection of benomyl.

The design and fabrication of high-performance electrode devices are highly important for the practical application of electrochemical sensors. In this study, flexible three-dimensional porous graphene electrode devices were first facilely fabricated using common laser ablation technique at room temperature. After then, hydrophilic two-dimensional MXene (Ti3C2Tx) nanosheet was decorated on the surface of the laser-induced graphene (LIG), resulting in disposable Ti3C2Tx/LIG electrode devices. After introducing Ti3C2Tx nanosheet, the electrochemical active area, electron transfer ability of LIG electrode device and its adsorption efficiency toward organic pesticide benomyl was significantly boosted. As a result, the fabricated Ti3C2Tx/LIG electrode device exhibited significantly enhanced electrocatalytic activity toward benomyl oxidation. Based on this, a novel and ultra-sensitive electrochemical platform for micro-droplet detection of benomyl was achieved in the range of 10 nM-6000 nM with detection sensitivity of 169.9 µA µM-1 cm-2 and detection limit of 5.8 nM. Considering the low-cost Ti3C2Tx/LIG electrode devices are rarely used for electrochemical analysis, we believed this research work will contribute to exploring the broader application of MXene/LIG electrode devices in the field of electrochemical sensing.

SLC7A11-ROS/αKG-AMPK axis regulates liver inflammation through mitophagy and impairs liver fibrosis and NASH progression.

The changes of inflammation and metabolism are two features in nonalcoholic steatohepatitis (NASH). However, how they interact to regulate NASH progression remains largely unknown. Our works have demonstrated the importance of solute carrier family 7 member 11 (SLC7A11) in inflammation and metabolism. Nevertheless, whether SLC7A11 regulates NASH progression through mediating inflammation and metabolism is unclear. In this study, we found that SLC7A11 expression was increased in liver samples from patients with NASH. Upregulated SLC7A11 level was also detected in two murine NASH models. Functional studies showed that SLC7A11 knockdown or knockout had augmented steatohepatitis with suppression of inflammatory markers in mice. However, overexpression of SLC7A11 dramatically alleviated diet-induced NASH pathogenesis. Mechanically, SLC7A11 decreased reactive oxygen species (ROS) level and promoted α-ketoglutarate (αKG)/prolyl hydroxylase (PHD) activity, which activated AMPK pathway. Furthermore, SLC7A11 impaired expression of NLRP3 inflammasome components through AMPK-mitophagy axis. IL-1ß release through NLRP3 inflammasome recruited myeloid cells and promoted hepatic stellate cells (HSCs) activation, which contributed to the progression of liver injury and fibrosis. Anti-IL-1ß and anakinra might attenuate the hepatic inflammatory response evoked by SLC7A11 knockdown. Moreover, the upregulation of SLC7A11 in NASH was contributed by lipid overload-induced JNK-c-Jun pathway. In conclusions, SLC7A11 acts as a protective factor in controlling the development of NASH. Upregulation of SLC7A11 is protective by regulating oxidation, αKG and energy metabolism, decreasing inflammation and fibrosis.

In Situ Cell-Scale probing nucleation, growth and evolution of CsPbBr3 nanowires by optical absorption spectroscopy.

The growth kinetics of colloidal lead halide perovskite (LHP) nanomaterials are an integral part of their applications, remains poorly understood due to complex nucleation processes and lack of in-situ size monitoring method. Here we demonstrated that absorption spectra can be used to observe in-situ growth processes of ultrathin CsPbBr3 nanowires in solution with reference to the effective mass infinite deep square potential well model. By means of this method, we have found that the ultrathin nanowires, fabricated by hot injection method, were firstly formed within one minute. Subsequently, they merge with each other into a thicker structure with increasing reaction time. We revealed that the nucleation, growth, and merging of the CsPbBr3 nanowire is determined by the acid concentration and ligand chain length. At lower acidity, the critical nucleation size of the nanowire is smaller, while the shorter the ligand chain length, the faster the merging among the nanowires. Moreover, the merging mode between nanowires changed with their nucleation size. This growth kinetics of CsPbBr3 nanowires provides a reference for optimizing the synthesis conditions to obtain the one-dimensional(1D) CsPbBr3 with desired size, thus enabling accurate control of the nanowire shape.

Prevalence of diverse colorectal polyps and risk factors for colorectal carcinoma in situ and neoplastic polyps.

BACKGROUND: Most colorectal cancers originate from precancerous polyps. This study aimed to determine the prevalence of colorectal polyps with diverse pathological morphologies and to explore the risk factors for colorectal carcinoma in situ (CCS) and neoplastic polyps. METHODS: Inpatients admitted from January 2018 to May 2023 were screened through the hospital information system. Polyps were classified according to pathological morphology. The prevalence of polyps was described by frequency and 95% confidence interval. Univariate and multivariate logistic regression analyses were used to explore the risk factors for CCS and neoplastic polyps. RESULTS: In total, 2329 individuals with 3550 polyps were recruited. Among all patients, 76.99% had neoplastic polyps and 44.31% had advanced adenomas. Tubular adenoma had the highest prevalence at 60.15%, and the prevalence of CCS was 3.86%. Patients with a colorectal polyp diameter ≥ 1.0 cm or number ≥ 3 were 8.07 times or 1.98 times more likely to develop CCS than were those with a diameter < 1.0 cm or number < 3, respectively (OR 8.07, 95%CI 4.48-14.55, p < 0.0001; and OR 1.98, 95%CI 1.27-3.09, p = 0.002). The risk of CCS with schistosome egg deposition was also significantly increased (OR 2.70, 95%CI 1.05-6.98). The higher the levels of carbohydrate antigen (CA) 724 (OR 1.01, 95%CI 1.00-1.02) and CA211 (OR 1.16, 95%CI 1.03-1.32) in patients with colorectal polyps were, the greater the risk of CCS. When colorectal neoplastic polyps were analyzed, we discovered that for each 1-year increase in age, the risk of neoplastic polyps increased by 3% (OR 1.03, 95%CI 1.02-1.04), p < 0.0001. Patients with a polyp diameter ≥ 1.0 cm had a 2.11-fold greater risk of neoplastic polyps compared to diameter < 1.0 cm patients (OR 3.11, 95%CI 2.48-3.92), p < 0.0001. In addition, multiple polyps and CA199 levels are risk factors for neoplastic polyps. CONCLUSION: More than 3/4 of colorectal polyp patients have neoplastic polyps. Patients are more inclined to develop CCS and neoplastic polyps if they have large polyps (> 1.0 cm) or multifocal polyps. The levels of the tumor markers CA724 and CA211 show some potential usefulness for predicting CCS and may be exploited for early identification of high-risk populations.

Secular trends in the prevalence of meeting 24-hour movement guidelines among U.S. adolescents: evidence from NHANES 2007-2016.

Background: The 24-Hour Movement Guidelines (24-HMG) recommend a balanced combination of physical activity (PA), sedentary behavior (SB) and sleep (SLP) for optimal health. However, there is limited understanding of how well U.S. adolescents adhere to these guidelines. This study aims to analyze the prevalence trends of meeting the 24-HMG among a nationally representative sample of U.S. general adolescents. Methods: The study included 2,273 adolescents (55.3% boys) aged 16-19 who participated in the National Health and Nutrition Examination Surveys (NHANES) from 2007 to 2016. The researchers categorized the adolescents based on whether they met various PA, SB, and SLP recommendations, as well as different combinations of these recommendations, separately for boys and girls. The prevalence rate, weighted by survey data, was calculated along with a 95% confidence interval (CI) to assess the changes in meeting the 24-HMG among U.S. adolescents across different survey years and sociodemographic subgroups. Results: In the 2015-2016 cycle, approximately 6.3% of adolescents did not meet any of the three recommendations, while only 19.2% of adolescents achieved all three guidelines. Compliance with PA and SB recommendations among adolescents has decreased over time, from 72.5% (65.9% to 79.2%) to 64.2% (57.4% to 70.9%) for PA, and from 59.0% (49.6% to 68.4%) to 46.6% (37.8% to 55.5%) for SB, respectively, from 2007-2008 cycle to 2015-2016 cycle. Boys exhibited more favorable patterns in meeting different sets of recommendations compared to girls (p-value <0.001). This includes meeting both PA and SB guidelines (15.5% for boys and 11.1% for girls) and meeting both PA and SLP guidelines (19.5% for boys and 15.7% for girls). The level of parental education was found to have effect on meeting all three guidelines (Ptrend < 0.05). Conclusion: We analyzed ten consecutive years of representative NHANES data to evaluate the prevalence meeting 24-HMG and found that the proportion of adolescents aged 16-19 in the U.S. who adhered to all three movement guidelines simultaneously has consistently remained low throughout each survey cycle. Notably, there has been a significant decline in the proportion of adolescents meeting the SB guideline.

Adult hair follicle stem cells differentiate into neuronal cells in explanted rat intestinal tissue.

Hair follicle stem cells (HFSCs) are adult stem cells located in the outer root sheath of the follicle bulge with high neural plasticity, which promise a potential for the stem cell therapy for neurological diseases. Hirschsprung's disease (HD) is characterized by the absence of ganglia in the distant bowel. In this study, we elucidated the capacity of HFSCs to differentiate into neuronal cells in the aganglionic colon from embryonic rat. HFSCs were isolated from adult Sprague-Dawley (SD) rats and formed spheres that could be passaged. The cultured HFSCs expressed neural crest stem cells (NCSCs) markers such as SOX10, CD34, and nestin, which indicated their neural crest lineage. Subsequent differentiation assays demonstrated that these cells could give rise to neural progeny that expressed neuronal or glial markers. The aganglionic colon from the embryonic intestine was applied as in vitro explant to test the capacity of proliferation and differentiation of HFSCs. The HFSCs expressing GFP or RFP integrated in intestinal explants and maintained proliferative capacity. Moreover, the HFSCs differentiated into Tuj1- or S100ß-positive cells in the cultured intestinal explants. The results proposed that the HFSCs might be an alternative source of neural stem cells for the HD therapy.

Outdoor gardening activity with different frequency and duration may be associated with reduction of total and cause-specific mortality risk for general U.S. adults: Findings from the NHANES.

BACKGROUND AND AIMS: Engaging in recommended levels of physical activity (PA) is associated with reduced overall and cause-specific mortality rates. Our study aims to examine the relationship between gardening-specific PA and all-cause and cause-specific mortality based on representative U.S. adults. METHODS AND RESULTS: A total of 13,812 adults representing 663.5 million non-institutionalized U.S. adults were included in the National Health and Nutrition Examination Survey. Self-reported gardening activity (GA) was assessed by a validated questionnaire, and outcomes of interest were all-cause mortality and mortality specific to certain causes. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using survey-multivariable Cox proportional hazards models. During a median follow-up period of 16.8 years (Interquartile range = 14.8-18.7), there were 3,476 deaths. After adjusting for potential covariates, we found that participants exposed to GA were more likely to have a lower risk of total mortality [HR (95% CI): 0.76 (0.68, 0.85), P-value < 0.001], cancer-specific mortality [HR (95% CI): 0.81 (0.67, 0.99), P-value < 0.05], cardiovascular disease mortality [HR (95% CI): 0.65 (0.53, 0.80), P-value < 0.001], and respiratory disease mortality [HR (95% CI): 0.66 (0.45, 0.98), P-value < 0.05], compared to those without GA exposure. Furthermore, engaging in GA more frequently and for longer durations was significantly associated with a lower total mortality risk. CONCLUSION: Our study provides evidence that engaging in GA is associated with a decreased risk of overall and cause-specific mortality. However, further longitudinal or interventional studies are needed to investigate the potential benefits of GA.

Nitrogen Forms Regulate the Response of Microcystis aeruginosa to Nanoplastics at Environmentally Relevant Nitrogen Concentrations.

As essential primary producers, cyanobacteria play a major role in global carbon and nitrogen cycles. Though the influence of nanoplastics on the carbon metabolism of cyanobacteria is well-studied, little is known about how nanoplastics affect their nitrogen metabolism, especially under environmentally relevant nitrogen concentrations. Here, we show that nitrogen forms regulated growth inhibition, nitrogen consumption, and the synthesis and release of microcystin (MC) in Microcystis aeruginosa exposed to 10 µg/mL amino-modified polystyrene nanoplastics (PS-NH2) with a particle size of 50 nm under environmentally relevant nitrogen concentrations of nitrate, ammonium, and urea. We demonstrate that PS-NH2 inhibit M. aeruginosa differently in nitrate, urea, and ammonium, with inhibition rates of 51.87, 39.70, and 36.69%, respectively. It is caused through the differences in impairing cell membrane integrity, disrupting redox homeostasis, and varying nitrogen transport pathways under different nitrogen forms. M. aeruginosa respond to exposure of PS-NH2 by utilizing additional nitrogen to boost the production of amino acids, thereby enhancing the synthesis of MC, extracellular polymeric substances, and membrane phospholipids. Our results found that the threat of nanoplastics on primary producers can be regulated by the nitrogen forms in freshwater ecosystems, contributing to a better understanding of nanoplastic risks under environmentally relevant conditions.

Expression profiling of ALOG family genes during inflorescence development and abiotic stress responses in rice (Oryza sativa L.).

The ALOG (Arabidopsis LSH1 and Oryza G1) family proteins, namely, DUF640 domain-containing proteins, have been reported to function as transcription factors in various plants. However, the understanding of the response and function of ALOG family genes during reproductive development and under abiotic stress is still largely limited. In this study, we comprehensively analyzed the structural characteristics of ALOG family proteins and their expression profiles during inflorescence development and under abiotic stress in rice. The results showed that OsG1/OsG1L1/2/3/4/5/6/7/8/9 all had four conserved helical structures and an inserted Zinc-Ribbon (ZnR), the other four proteins OsG1L10/11/12/13 lacked complete Helix-1 and Helix-2. In the ALOG gene promoters, there were abundant cis-acting elements, including ABA, MeJA, and drought-responsive elements. Most ALOG genes show a decrease in expression levels within 24 h under ABA and drought treatments, while OsG1L2 expression levels show an upregulated trend under ABA and drought treatments. The expression analysis at different stages of inflorescence development indicated that OsG1L1/2/3/8/11 were mainly expressed in the P1 stage; in the P4 stage, OsG1/OsG1L4/5/9/12 had a higher expression level. These results lay a good foundation for further studying the expression of rice ALOG family genes under abiotic stresses, and provide important experimental support for their functional research.