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Integrated biochemical and biophysical signals regulate embryonic development. Correct neural tube formation is critical for the development of central nervous system. However, the role of microgravity in neurodevelopment and its underlying molecular mechanisms remain unclear. In this study, the effects of stimulated microgravity (SMG) on the development of human brain organoids are investigated. SMG impairs N-cadherin-based adherens junction formation, leading to neural tube defects associated with dysregulated self-renewal capacity and neuroepithelial disorganization in human brain organoids. Bulk gene expression analyses reveal that SMG alters Hippo and BMP signaling in brain organoids. The neuropathological deficits in SMG-treated organoids can be rescued by regulating YAP/BMP/ID1 axis. Furthermore, sing-cell RNA sequencing data show that SMG results in perturbations in the number and function of neural stem and progenitor cell subpopulations. One of these subpopulations senses SMG cues and transmits BMP signals to the subpopulation responsible for tube morphogenesis, ultimately affecting the proliferating cell population. Finally, SMG intervention leads to persistent neurologic damage even after returning to normal gravity conditions. Collectively, this study reveals molecular and cellular abnormalities associated with SMG during human brain development, providing opportunities for countermeasures to maintain normal neurodevelopment in space., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Objective: This study evaluates the utility of serum s-αKlotho levels as a quantifiable biomarker for overwork., Methods: Frontline medical workers aged 20-55 from Yiling People's Hospital of Yichang were recruited. Criteria included non-smokers, non-heavy drinkers, no chronic medication use, and no acute illnesses recently. Participants worked over 10 hours per day, 60 hours weekly, and had at least 3 years of experience. A control group was matched except for work conditions. Data were collected through surveys, and serum levels were measured., Results: Significant differences in serum Klotho were found between overwork and control groups. The overwork group had higher median s-αKlotho levels (49.99 pg/mL) compared to controls (27.88 pg/mL)., Conclusion: Overworked medical workers exhibited elevated serum s-αKlotho, suggesting s-αKlotho as a potential biomarker for overwork. Future research should use multicenter designs with larger samples to validate findings., Competing Interests: Conflict of Interest: NONE DECLARED, (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Occupational and Environmental Medicine.)

The reconstruction of damaged neural circuits is critical for neurological repair after brain injury. Classical brain-computer interfaces (BCIs) allow direct communication between the brain and external controllers to compensate for lost functions. Importantly, there is increasing potential for generalized BCIs to input information into the brains to restore damage, but their effectiveness is limited when a large injured cavity is caused. Notably, it might be overcome by transplantation of brain organoids into the damaged region. Here, we construct innovative BCIs mediated by implantable organoids, coined as organoid-brain-computer interfaces (OBCIs). We assess the prolonged safety and feasibility of the OBCIs, and explore neuroregulatory strategies. OBCI stimulation promotes progressive differentiation of grafts and enhances structural-functional connections within organoids and the host brain, promising to repair the damaged brain via regenerating and regulating, potentially directing neurons to preselected targets and recovering functional neural networks in the future., (© 2024. The Author(s).)

Introduction: Brain organoids are believed to be able to regenerate impaired neural circuits and reinstate brain functionality. The neuronal activity of organoids is considered a crucial factor for restoring host function after implantation. However, the optimal stage of brain organoid post-transplantation has not yet been established. External electrical signal plays a crucial role in the physiology and development of a majority of human tissues. However, whether electrical input modulates the development of brain organoids, making them ideal transplant donors, is elusive., Methods: Bioelectricity was input into cortical organoids by electrical stimulation (ES) with a multi-electrode array (MEA) to obtain a better-transplanted candidate with better viability and maturity, realizing structural-functional integration with the host brain., Results: We found that electrical stimulation facilitated the differentiation and maturation of organoids, displaying well-defined cortical plates and robust functional electrophysiology, which was probably mediated via the pathway of calcium-calmodulin (CaM) dependent protein kinase II (CAMK II)-protein kinase A (PKA)-cyclic-AMP response binding protein (pCREB). The ES-pretreated D40 organoids displayed superior cell viability and higher cell maturity, and were selected to transplant into the damaged primary sensory cortex (S1) of host. The enhanced maturation was exhibited within grafts after transplantation, including synapses and complex functional activities. Moreover, structural-functional integration between grafts and host was observed, conducive to strengthening functional connectivity and restoring the function of the host injury., Conclusion: Our findings supported that electrical stimulation could promote the development of cortical organoids. ES-pretreated organoids were better-transplanted donors for strengthening connectivity between grafts and host. Our work presented a new physical approach to regulating organoids, potentially providing a novel translational strategy for functional recovery after brain injury. In the future, the development of 3D flexible electrodes is anticipated to overcome the drawbacks of 2D planar MEA, promisingly achieving multimodal stimulation and long-term recordings of brain organoids., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Production and hosting by Elsevier B.V.)

Post-translational modification (PTM) refers to the covalent attachment of functional groups to protein substrates, resulting in structural and functional changes. PTMs not only regulate the development and progression of liver cancer, but also play a crucial role in the immune response against cancer. Cancer immunity encompasses the combined efforts of innate and adaptive immune surveillance against tumor antigens, tumor cells, and tumorigenic microenvironments. Increasing evidence suggests that immunotherapies, which harness the immune system's potential to combat cancer, can effectively improve cancer patient prognosis and prolong the survival. This review presents a comprehensive summary of the current understanding of key PTMs such as phosphorylation, ubiquitination, SUMOylation, and glycosylation in the context of immune cancer surveillance against liver cancer. Additionally, it highlights potential targets associated with these modifications to enhance the response to immunotherapies in the treatment of liver cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Zuo, Chen and Li.)

In brown-red soil, the effect of phosphorus and citric acid co-existence on the adsorption of cadmium was studied using indoor experiments and isothermal equilibrium adsorption analysis. After treatment with different doses of phosphorus and citric acid, the fractions of cadmium were altered by varying dry and wet conditions. The results showed that:① Soil treated with 10 mg·L -1 of CdCl 2 solution showed no notable effect on cadmium adsorption when a low concentration of phosphorus was added (40 mg·L -1 ); however, higher a concentration of added phosphorus (80 mg·L -1 ) significantly increased cadmium adsorption (an increase of 78 g·kg -1 and 7.89% compared to the control treatment); ② Using a 40 mg·L -1 phosphorus solution, the addition of citric acid proportionally reduced cadmium adsorption. This inhibition effect was more notable for the soil treated with low-dose phosphorus (40 mg·L -1 ) than the high-dose treatment with 1 mmol·L -1 and 5 mmol·L -1 citric acid (cadmium adsorption decreased by 30.89% and 40.97%, respectively). The effect of citric acid was not significant, however, at higher concentrations of phosphorus. When the concentration of citric acid reached 5 mmol·L -1 , cadmium adsorption was only 1% lower than without citric acid treatment; ③ Periodic dry-wet alternation significantly promoted the transformation of cadmium from a weak acid extractable and reducible state to an oxidizable and residual state in the soil. That is, the availability of cadmium in soil subjected to the combined action of phosphorus and citric acid decreased with an increase in wet and dry alternations.

[This corrects the article DOI: 10.18632/oncotarget.18138.].

The development of agriculture in the red soil sloping uplands has been increasingly restricted by low water availability, high temperatures, and low fertilizer use efficiency. Subsurface flow has a significant influence on runoff generation, nutrient loss, and soil erosion. The rainfall-runoff process makes it easy for nutrients on the sloping land to enter water bodies through subsurface flow mainly in the liquid phase, which may lead to environmental problems such as eutrophication and groundwater pollution. Phosphorus as one of the common nutrients causing eutrophication is immobile in the soil because it is easily absorbed and fixed by soil particles. Thus, the principal pathway of phosphorus release from the soil is the surface flow. In some regions, sufficient and concentrated rainfall results in the surface-subsurface flow that enhances phosphorus migration. Recently, researchers have studied the migration patterns of red soil phosphorus through surface flow and the impact factors arising from these migrations, as well as the generation of subsurface flow and its influence on phosphorus outputs. However, there are relatively few investigations that have comprehensively considered the influence of both surface flow and subsurface flow on the migration of red soil phosphorus. In order to investigate the characteristics of phosphorus loss through runoff under natural rainfall, a large-scale field lysimeter experiment was conducted with three treatments i.e., grass cover (GC), litter mulch (LM), and bare land (BL) on a red soil slope land in southeast China. Phosphorus loss through surface flow, interflow at different soil layers (30 cm and 60 cm), and groundwater flow (at 105 cm depth) was observed under each natural precipitation event over a one-year period. The results showed that:① The concentrations of total P (TP) and dissoluble P (DP) in surface flow were slightly higher than those in interflow and groundwater flow; the concentrations of TP and DP showed a gradual downward trend with the increase in soil depth. The total amount of TP runoff loss was ordered as BL (1.61 kg·hm -2 ) > LM (1.33 kg·hm -2 ) > GC(0.82 kg·hm -2 ). ② Surface flow, interflow, and groundwater contributed to 57%, 6%, and 37%, respectively, of the phosphorus runoff loss on BL plot; surface runoff was the main pathway of phosphorus loss. Groundwater flow was the crucial route of phosphorus runoff loss once a vegetation cover was in place; groundwater flow contributed to more than 71% of the phosphorus runoff loss while the surface flow contributed less than 14%. ③ Particulate phosphorus was the primary pattern of phosphorus transport which accounted for 64%-97% of the total amount of phosphorus runoff loss. The effect of phosphorus loss through groundwater flow cannot be neglected on the red soil slope land. The loss load of phosphorus through runoff can be controlled by grass cover and litter mulch treatments, whereas the concentrations of phosphorus in runoff do not significantly reduce.

Long non-coding RNAs (lncRNAs) play an important role in epigenetic regulation, and abnormalities may lead to male infertility. To investigate whether lncRNAs are involved in intergenerational inheritance of obesity and obesity-induced decline in fertility, we divided mice into obesity (F0 mice fed a high-fat diet, F0-HFD) and non-obese (F0 mice fed normal chow, F0-NC) model groups and their male offspring (F1-HFD and F1-NC, respectively). We examined the differences in the expression levels of lncRNAs and mRNAs in the F0-HFD/F0-NC and F1-HFD/F1-NC groups. The results revealed similar expression patterns in the F1-HFD/F0-HFD groups at both the lncRNA and mRNA levels. The maximum difference in the lncRNA expression was observed between the F0-HFD and F0-NC groups. The differentially expressed lncRNA targets and mRNAs identified in our study are mainly involved in GnRH signalling pathway, metabolic process, and Hippo signalling pathway; similarly expressed lncRNAs and mRNAs in F1-HFD/F0-HFD are closely linked with G-protein coupled receptor signalling pathway, pancreatic polypeptide receptor activity, and lysine biosynthesis, which may play an important role in the molecular mechanism of intergenerational inheritance of obesity. Furthermore, potential genes that might play important roles in the pathogenesis of obesity-related low fertility were revealed by lncRNA-and mRNA-interaction studies based on the microarray expression profiles. In conclusion, we found that lncRNA could be involved in obesity-induced infertility by expressing abnormalities, which could act as genetic vectors of paternal inheritance of obesity.

In the present study, the hypoglycemic, hypolipidemic, and antioxidative effects of metformin (MET) combined with Jiang Tang Xiao Ke (JTXK) granule derived from the "Di Huang Tang" were evaluated in mice with type 2 diabetes mellitus (DM) induced by high-fat diet/streptozotocin. DM mice were orally treated with MET (0.19 g/kg) either alone or combined with different doses (1.75, 3.5, or 7 g/kg) of JTXK for 4 weeks. Results showed that the serum and hepatic glucose, lipids, and oxidative stress levels were elevated in DM mice, when compared with the normal mice. MET treatment decreased FBG and serum glucagon levels of DM mice. Combination treatment with MET and JTXK 3.5 g/kg increased the hypoglycemia and insulin sensitivity at 4 weeks when compared with the DM mice treated with MET alone. However, neither MET nor MET/JTXK treatment could completely reverse the hyperglycemia in DM mice. JTXK enhanced the serum triglyceride (TG) and hepatic lipid-lowering effect of MET in a dose-dependent manner in DM mice. JTXK 1.75 and 3.5 g/kg improved the hepatoprotective effect of MET in DM mice. Synergistic effect of combination treatment with MET and JTXK on antioxidant stress was also found in DM mice compared with MET alone.

Organic acids can improve the phosphorus availability, influence the immobilization of heavy metals in soil, and has very complicated function in phosphorus activation and heavy metal passivation. This research took simulated Pb contaminated soil as material, phosphate and citric acid as remediation matter, adopted BCR continuous extraction, 0.01 mol · L(-1) CaCl2 and toxicity characteristic leaching procedure (TCLP) to evaluate the remediation effect. Besides, malic acid and NaNO3 were taken as desorption reagents to discuss the stability of the phosphorus-citric acid-Pb system. The results showed that: in the absence of citric acid, the amount of acid extracted Pb decreased along with the increase of P concentration; when the P concentration was 100 and 400 mg · kg(-1), acid extractable Pb increased with the increasing of citric acid concentration. However, residual Pb changed in the opposite direction from acid extractable Pb. The phenomenon showed that P improved the bioavailability of Pb, while citric acid had the opposite effect. With a certain organic acid concentration, extractable Pb contents extracted by 0.01 mol · L(-1) CaCl2 and TCLP both decreased with the increasing P concentration, therefore, P had immobilization effect on Pb in contaminated soil. But at a fixed P concentration, extractable Pb contents by 0.01 mol · L(-1) CaCl2 and TCLP changed in the opposite trend with the increasing citric acid concentration. The desorption rate of Pb in soil increased with the increasing malic acid concentration, the decreasing pH and the increasing ionic strength. The desorption extent of Pb in soil with P only was lower than that with both P and citric acid. But the stability of Pb passivated by the former was higher.

Two novel adsorbents to remove excess arsenate and arsenite in the drinking water were prepared for the first time by grafting monoamine and diamine, respectively, and then coordinating Fe(3+) on silica gel that was obtained using sol-gel method with two-step acid-base catalysis. It was found that both adsorbents had mesoporous structure, large specific surface, and high amino and iron content according to N(2) adsorption isotherms, FTIR, XPS, and NMR analysis. The removal ability and adsorption rate of the adsorbents were very high for both As(V) and As(III). Langmuir and Freundlich models were used to fit the adsorption isotherm and investigate the adsorption mechanism. The effects of chloride and sulfate anion on the removal of arsenate and arsenite for the two adsorbents were also studied., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objective: To investigate the proliferation and cytokine expression of Auricularia auricula polysaccharide (AAP) on peripheral blood monnuclear cells (PBMCs) in vitro., Methods: AAP was obtained by water extraction and alcohol precipitation, and purified by DEAE-cellulose chromatogram. PBMCs were treated with AAP at different levels. The Cell Counting Kit-8 (CCK-8) was used to determine the proliferation of PBMCs. The concentration of TNF-alpha and TFN-gamma in supernatant were investigated by ELISA., Results: The three fractions of AAP could stimulate PBMCs proliferation at the range of 100--800 microg/ml, and AAP2 enhanced significantly the level of TNF-alpha and IFN-gamma in supernatant of PBMCs (P < 0.05, P < 0.01)., Conclusion: AAP is an immunomodulator and can enhance the immunomodulatory activity through TNF-alpha and TFN-gamma.