GLT-1 downregulation in hippocampal astrocytes induced by type 2 diabetes contributes to postoperative cognitive dysfunction in adult mice.

AIMS: Type 2 diabetes mellitus (T2DM) is related to an increased risk of postoperative cognitive dysfunction (POCD), which may be caused by neuronal hyperexcitability. Astrocyte glutamate transporter 1 (GLT-1) plays a crucial role in regulating neuron excitability. We investigated if T2DM would magnify the increased neuronal excitability induced by anesthesia/surgery (A/S) and lead to POCD in young adult mice, and if so, determined whether these effects were associated with GLT-1 expression. METHODS: T2DM model was induced by high fat diet (HFD) and injecting STZ. Then, we evaluated the spatial learning and memory of T2DM mice after A/S with the novel object recognition test (NORT) and object location test (OLT). Western blotting and immunofluorescence were used to analyze the expression levels of GLT-1 and neuronal excitability. Oxidative stress reaction and neuronal apoptosis were detected with SOD2 expression, MMP level, and Tunel staining. Hippocampal functional synaptic plasticity was assessed with long-term potentiation (LTP). In the intervention study, we overexpressed hippocampal astrocyte GLT-1 in GFAP-Cre mice. Besides, AAV-Camkllα-hM4Di-mCherry was injected to inhibit neuronal hyperexcitability in CA1 region. RESULTS: Our study found T2DM but not A/S reduced GLT-1 expression in hippocampal astrocytes. Interestingly, GLT-1 deficiency alone couldn't lead to cognitive decline, but the downregulation of GLT-1 in T2DM mice obviously enhanced increased hippocampal glutamatergic neuron excitability induced by A/S. The hyperexcitability caused neuronal apoptosis and cognitive impairment. Overexpression of GLT-1 rescued postoperative cognitive dysfunction, glutamatergic neuron hyperexcitability, oxidative stress reaction, and apoptosis in hippocampus. Moreover, chemogenetic inhibition of hippocampal glutamatergic neurons reduced oxidative stress and apoptosis and alleviated postoperative cognitive dysfunction. CONCLUSIONS: These findings suggest that the adult mice with type 2 diabetes are at an increased risk of developing POCD, perhaps due to the downregulation of GLT-1 in hippocampal astrocytes, which enhances increased glutamatergic neuron excitability induced by A/S and leads to oxidative stress reaction, and neuronal apoptosis.

Effects of ECM protein-coated surfaces on the generation of retinal pigment epithelium cells differentiated from human pluripotent stem cells.

Retinal degeneration diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP), initially manifest as dysfunction or death of the retinal pigment epithelium (RPE). Subretinal transplantation of human pluripotent stem cell (hPSC)-derived RPE cells has emerged as a potential therapy for retinal degeneration. However, RPE cells differentiated from hPSCs using current protocols are xeno-containing and are rarely applied in clinical trials. The development of hPSC-derived RPE cell differentiation protocols using xeno-free biomaterials is urgently needed for clinical applications. In this study, two protocols (the activin A and NIC84 protocols) were selected for modification and use in the differentiation of hiPSCs into RPE cells; the chetomin concentration was gradually increased to achieve high differentiation efficiency of RPE cells. The xeno-free extracellular matrix (ECM) proteins, laminin-511, laminin-521 and recombinant vitronectin, were selected as plate-coating substrates, and a Matrigel (xeno-containing ECM)-coated surface was used as a positive control. Healthy, mature hPSC-derived RPE cells were transplanted into 21-day-old Royal College of Surgeons (RCS) rats, a model of retinal degeneration disease. The visual function of RCS rats was evaluated by optomotor response (qOMR) and electroretinography after transplantation of hPSC-derived RPE cells. Our study demonstrated that hPSCs can be efficiently differentiated into RPE cells on LN521-coated dishes using the NIC84 protocol, and that subretinal transplantation of the cell suspensions can delay the progression of vision loss in RCS rats.

Evaluation of the quality and readability of ChatGPT responses to frequently asked questions about myopia in traditional Chinese language.

Introduction: ChatGPT can serve as an adjunct informational tool for ophthalmologists and their patients. However, the reliability and readability of its responses to myopia-related queries in the Chinese language remain underexplored. Purpose: This study aimed to evaluate the ability of ChatGPT to address frequently asked questions (FAQs) about myopia by parents and caregivers. Method: Myopia-related FAQs were input three times into fresh ChatGPT sessions, and the responses were evaluated by 10 ophthalmologists using a Likert scale for appropriateness, usability, and clarity. The Chinese Readability Index Explorer (CRIE) was used to evaluate the readability of each response. Inter-rater reliability among the reviewers was examined using Cohen's kappa coefficient, and Spearman's rank correlation analysis and one-way analysis of variance were used to investigate the relationship between CRIE scores and each criterion. Results: Forty-five percent of the responses of ChatGPT in Chinese language were appropriate and usable and only 35% met all the set criteria. The CRIE scores for 20 ChatGPT responses ranged from 7.29 to 12.09, indicating that the readability level was equivalent to a middle-to-high school level. Responses about the treatment efficacy and side effects were deficient for all three criteria. Conclusions: The performance of ChatGPT in addressing pediatric myopia-related questions is currently suboptimal. As parents increasingly utilize digital resources to obtain health information, it has become crucial for eye care professionals to familiarize themselves with artificial intelligence-driven information on pediatric myopia.

Selection strategy for endoscopic necrosectomy approaches of infected walled-off pancreatic necrosis: Analysis of 101 patients from a single center with long-term follow-up.

OBJECTIVES: Endoscopic necrosectomy (EN) is a promising minimally invasive approach for treating infected walled-off pancreatic necrosis (WOPN). Multiple EN approaches are currently available, though criteria for selecting the optimal approaches are lacking. We aimed to propose a rational selection strategy of EN and to retrospectively evaluate its safety and effectiveness. METHODS: Altogether 101 patients who underwent EN for infected WOPN at a tertiary hospital between June 2009 and February 2023 were retrospectively included for analysis. Demographic characteristics, details of the EN procedures, procedure-related adverse events, and clinical outcomes were investigated. RESULTS: Among these 101 patients with WOPN, 56 (55.4%) underwent transluminal EN, 38 (37.6%) underwent percutaneous EN, and seven (6.9%) underwent combined approach, respectively. Clinical success was achieved in 94 (93.1%) patients. Seven (6.9%) experienced procedure-related adverse events, and seven (6.9%) died during the treatment period. During a median follow-up of 50 months, 5 (5.3%) of the 94 patients had disease recurrence, 17.0% (16/94) had new-onset diabetes mellitus, and 6.4% (6/94) needed oral pancreatic enzyme supplementation. The clinical success rate, procedure-related adverse event rate, and long-term follow-up outcomes were not significantly different among the three groups. High APACHE-II scores (≥15) and organ failure were identified as factors related to treatment failure. CONCLUSIONS: A selection strategy for EN approaches, based on the extent of necrosis and its distance from the gastrointestinal lumen (using a threshold of 15 mm), is safe and effective for treating infected WOPN in both short-term and long-term outcomes.

[Effects of Sophora japonica extract on alveolar bone mass in ovariectomized osteoporosis mice].

PURPOSE: To investigate the effect of Sophora japonica extract on alveolar bone mass in ovariectomized osteoporosis mice. METHODS: Six-week-old female non-pregnant wild-type C57BL/6J mice were randomly divided into sham operation group, ovariectomy(OVX) group and OVX+Sophora japonica extract group. Ovaries of the mice in the OVX group and the OVX+Sophora japonica extract group were removed, and the mice in the OVX+Sophora japonica extract group were treated by Sophora japonica extract at a dose of 150 mg/kg, three times a week for 4 weeks; while mice of the other two groups were given an equal volume of normal saline at the same time. Body weight was measured 3 times a week, and the micro-parameters of alveolar bone were detected by Micro-CT after 4 weeks. The data were analyzed by GraphPad Prism 9 software. RESULTS: Compared with the sham-operated group, the trabecular bone parameters of the alveolar bone in the OVX group were significantly decreased 1 month after operation (P＜0.05). One month after intervention with Sophora japonica extract, alveolar bone mineral density (BMD), trabecular number (Tb.N) and trabecular separation(Tb.Sp) in OVX mice was significantly rescued, with no significant difference compared to the sham surgery group(P＞0.05); but bone volume fraction(BV/TV) and trabecular thickness (Tb.Th) had not completely recovered to the levels of the sham-operated group(P＜0.05). CONCLUSIONS: Sophora japonica extract can effectively increase the alveolar bone mass reduced by estrogen deficiency and may be used as one of the potential drugs for the treatment of menopausal alveolar bone osteoporosis.

Minimally invasive soft tissue repair using shrunken scaffolds.

The minimally invasive injection of tissue engineering scaffolds is of interest as it requires a smaller incision and quickens recovery. However, the engineering of scaffolds capable of injection remains a challenge. Here, we report on a shrunken scaffold inspired by the shrinking of puffed food in a humid environment. A scaffold is freeze-dried to remove water then placed in a humid atmosphere. The humidity causes the dry scaffold to shrink by up to 90%. In addition, the humidity treatment reduces the scaffolds modulus minimizing the foreign body response after implantation. The scaffolds can rapidly swell into their original size and shape after application. A tool for the delivery of the minimally invasive scaffolds is developed and we demonstrate the potential for minimally invasive delivery using this shrinking technique.

Critical Care Experience Shapes Respiratory Therapists' Attitudes toward Death: A Survey Study.

Respiratory therapists (RTs) frequently encounter death in their work with critically ill patients. Healthcare providers' attitudes toward death significantly affect their approach to caring for dying patients; however, there is a lack of knowledge on RTs' attitudes toward death. This study examines how the work environment and personal characteristics of RTs influence their attitudes toward death. Utilizing the Death Attitude Profile-Revised-Chinese questionnaire, a cross-sectional survey compared non-critical care RTs (non-CCRTs, N = 86) to critical care RTs (CCRTs, N = 85). Non-CCRTs displayed significantly lower scores in overall acceptance of death compared to CCRTs (p = 0.015) and a tendency to actively avoid thoughts about death (p = 0.005). CCRTs scored higher in "neutral acceptance" (p = 0.015), and non-CCRTs exhibited higher scores on items reflecting a negative attitude toward death. RTs with shorter professional tenures showed heightened fear of death and avoidance tendencies. Perception of life and death education correlated with higher "fear of death" and "death avoidance" scores (p = 0.001). The findings indicate that CCRTs demonstrate a more neutral acceptance of death. Additionally, experience, sex, mental health status, and life-death education exposure significantly influence RTs' attitudes toward death.

RAS-Selective Lethal 3-Induced Ferroptosis Promotes the Antitumor Efficiency of Anti-Programmed Cell Death Protein 1 Treatment in Colorectal Cancer.

BACKGROUND/AIMS:  Anti-programmed cell death protein 1 (PD-1) treatment has exhibited clinical benefits in colorectal cancer (CRC). However, the low response rate of CRC to immunotherapy is an urgent problem that needs to be solved. MATERIALS AND METHODS:  MC-38 tumor cells was challenged subcutaneously in the flank of 7-week-old male C57BL/6 mice. The mice were randomly divided into 3 groups, and 200µg/mouse anti-PD-1 antibody and 100 mg/kg RAS-Seletive Lethal 3 (RSL) or phosphate buffer saline (PBS) were intraperitoneally injected every 2 days. The expression of oxidative stress and ferroptosis-related genes was measured by Western blotting, real-time reverse transcription-polymerase chain reaction, Prussian blue staining, and enzyme-linked immunosorbent assay. RESULTS:  Anti-PD-1 treatment-unresponsive tumors showed stronger immunosuppression than responsive tumors. Notably, the responsive tumors showed higher levels of H2O2 and reactive oxygen species, both of which could impair the antitumor effect of cytotoxic CD8+ T cells. The anti-PD-1 treatment-responsive tumors showed a higher expression of pro-ferroptosis genes and Fe2+ accumulation than those of anti-PD-1 nonresponsive tumors, indicating the potential role of ferroptosis in the efficacy of anti-PD-1 treatment. In MC-38 syngeneic tumor model, (1S, 3R)-RSL3 (RSL), a glutathione peroxidase 4 inhibitor, effectively promoted the antitumor effect of anti-PD-1 treatment in vivo. However, anti-PD-1 treatment did not affect the levels of ferroptosis-related genes in tumor model. Mechanistically, RSL treatment significantly upregulated the frequency of proliferating (ki67+) and cytotoxic (GZMB+) CD8+ T cells. Furthermore, the frequency of tumor neoantigen-specific interferon (IFN)-γ CD8+ T cells showed a significant increase after RSL plus anti-PD-1 treatment. CONCLUSION:  RSL may be a promising drug for potentiating the antitumor efficiency of anti-PD-1 treatment in CRC.

A structured biomimetic nanoparticle as inflammatory factor sponge and autophagy-regulatory agent against intervertebral disc degeneration and discogenic pain.

Lower back pain (LBP) is a common condition closely associated with intervertebral disc degeneration (IDD), causing a significant socioeconomic burden. Inflammatory activation in degenerated discs involves pro-inflammatory cytokines, dysregulated regulatory cytokines, and increased levels of nerve growth factor (NGF), leading to further intervertebral disc destruction and pain sensitization. Macrophage polarization is closely related to autophagy. Based on these pathological features, a structured biomimetic nanoparticle coated with TrkA-overexpressing macrophage membranes (TMNP@SR) with a rapamycin-loaded mesoporous silica core is developed. TMNP@SR acted like sponges to adsorbe inflammatory cytokines and NGF and delivers the autophagy regulator rapamycin (RAPA) into macrophages through homologous targeting effects of the outer engineered cell membrane. By regulating autophagy activation, TMNP@SR promoted the M1-to-M2 switch of macrophages to avoid continuous activation of inflammation within the degenerated disc, which prevented the apoptosis of nucleus pulposus cells. In addition, TMNP@SR relieved mechanical and thermal hyperalgesia, reduced calcitonin gene-related peptide (CGRP) and substance P (SP) expression in the dorsal root ganglion, and downregulated GFAP and c-FOS signaling in the spinal cord in the rat IDD model. In summary, TMNP@SR spontaneously inhibits the aggravation of disc inflammation to alleviate disc degeneration and reduce the ingress of sensory nerves, presenting a promising treatment strategy for LBP induced by disc degeneration.

Evaluating the performance of ChatGPT-3.5 and ChatGPT-4 on the Taiwan plastic surgery board examination.

Background: Chat Generative Pre-Trained Transformer (ChatGPT) is a state-of-the-art large language model that has been evaluated across various medical fields, with mixed performance on licensing examinations. This study aimed to assess the performance of ChatGPT-3.5 and ChatGPT-4 in answering questions from the Taiwan Plastic Surgery Board Examination. Methods: The study evaluated the performance of ChatGPT-3.5 and ChatGPT-4 on 1375 questions from the past 8 years of the Taiwan Plastic Surgery Board Examination, including 985 single-choice and 390 multiple-choice questions. We obtained the responses between June and July 2023, launching a new chat session for each question to eliminate memory retention bias. Results: Overall, ChatGPT-4 outperformed ChatGPT-3.5, achieving a 59 % correct answer rate compared to 41 % for ChatGPT-3.5. ChatGPT-4 passed five out of eight yearly exams, whereas ChatGPT-3.5 failed all. On single-choice questions, ChatGPT-4 scored 66 % correct, compared to 48 % for ChatGPT-3.5. On multiple-choice, ChatGPT-4 achieved a 43 % correct rate, nearly double the 23 % of ChatGPT-3.5. Conclusion: As ChatGPT evolves, its performance on the Taiwan Plastic Surgery Board Examination is expected to improve further. The study suggests potential reforms, such as incorporating more problem-based scenarios, leveraging ChatGPT to refine exam questions, and integrating AI-assisted learning into candidate preparation. These advancements could enhance the assessment of candidates' critical thinking and problem-solving abilities in the field of plastic surgery.

Cluster effect for SNP-SNP interaction pairs for predicting complex traits.

Single nucleotide polymorphism (SNP) interactions are the key to improving polygenic risk scores. Previous studies reported several significant SNP-SNP interaction pairs that shared a common SNP to form a cluster, but some identified pairs might be false positives. This study aims to identify factors associated with the cluster effect of false positivity and develop strategies to enhance the accuracy of SNP-SNP interactions. The results showed the cluster effect is a major cause of false-positive findings of SNP-SNP interactions. This cluster effect is due to high correlations between a causal pair and null pairs in a cluster. The clusters with a hub SNP with a significant main effect and a large minor allele frequency (MAF) tended to have a higher false-positive rate. In addition, peripheral null SNPs in a cluster with a small MAF tended to enhance false positivity. We also demonstrated that using the modified significance criterion based on the 3 p-value rules and the bootstrap approach (3pRule + bootstrap) can reduce false positivity and maintain high true positivity. In addition, our results also showed that a pair without a significant main effect tends to have weak or no interaction. This study identified the cluster effect and suggested using the 3pRule + bootstrap approach to enhance SNP-SNP interaction detection accuracy.

Unraveling non-radiative decay channels of exciplexes to construct efficient red emitters for organic light-emitting diodes.

Exciplex emitters naturally have thermally activated delayed fluorescence characteristics due to their spatially separated molecular orbitals. However, the intermolecular charge transfer potentially induces diverse non-radiative decay channels, severely hindering the construction of efficient red exciplexes. Thus, a thorough comprehension of this energy loss is of paramount importance. Herein, different factors, including molecular rigidity, donor-acceptor interactions and donor-donor/acceptor-acceptor interactions, that impact the non-radiative decay were systematically investigated using contrasting exciplex emitters. The exciplex with rigid components and intermolecular hydrogen bonds showed a photoluminescence quantum yield of 84.1% and a singlet non-radiative decay rate of 1.98 × 106 s-1 at an optimized mixing ratio, respectively, achieving a 3.3-fold increase and a 70% decrease compared to the comparison group. In the electroluminescent device, a maximum external quantum efficiency of 23.8% was achieved with an emission peak of 608 nm, which represents the state-of-the-art organic light-emitting diodes using exciplex emitters. Accordingly, a new strategy is finally proposed, exploiting system rigidification to construct efficient red exciplex emitters that suppress non-radiative decay.

C188-9 reduces patient-specific primary breast cancer cells proliferation at the low, clinic-relevant concentration.

OBJECTIVES: STAT3 is a transcriptional activator of breast cancer oncogenes, suggesting that it could be a potential therapeutic target for breast cancer. Therefore, this study investigated the potential application of C188-9, a STAT3 signal pathway inhibitor, in the treatment of breast cancer through a novel pre-clinical platform with patient-specific primary cells (PSPCs). METHODS: PSPCs were isolated from breast cancer samples obtained via biopsy or surgery from fifteen patient donors with their full acknowledgements. PSPCs were treated with C188-9 or other chemotherapeutic agents, and then analyzed with cell viability assay. Western blot assay and real-time quantitative PCR were also used to determine the expression and activity of STAT3 signaling pathway of corresponding PSPCs. RESULTS: C188-9 treatment at normal (experimental) concentration had valid inhibition on PSPCs proliferation. Meanwhile, treatment at a low (clinic-relevant) concentration of C188-9 for an extended period reduced cell viability of PSPCs still more than some of other traditional chemotherapy drugs. In addition, C188-9 decreased expression level of pSTAT3 in PSPCs from some, but not all patient samples. The treatment of C188-9 reduced cell viability of the breast cancer samples through inhibiting the STAT3 to C-myc signaling pathway. CONCLUSIONS: In this study, we tested a novel drug C188-9 at a low, clinic-relevant concentration, together with several traditional chemotherapy agents. PSPCs from ten out of fifteen patient donors were sensitive to C188-9, while some of traditional chemotherapy agents failed. This finding suggested that C188-9 could have treatment effects only on those ten PSPC patient donors, indicating the future personalized utilization of PSPCs.

Imidazolium-decorated Bis-cyanostilbene Macrocycle: An Effect Fluorescence Sensor for Pesticide Starane.

Fluorescence sensors for complicated molecules such as pesticides were paid much attention lately due to the merits of simple operation, high sensitivity and selectivity, and in-situ detection. In this work, a novel fluorescent sensor for pesticide starane was prepared based on imidazolium-decorated bis-cyanostilbene macrocycle (IBM). IBM exhibited the obvious "turn-on" fluorescence change from dark blue-green to bright blue after sensing starane with the high sensing selectivity among 28 kinds of guests. The detecting limitation was as low as 0.011 µM, which was the lowest one in literatures. The sensing mechanism was confirmed as that starane was located in cavity of IBM based on the molecular interaction of multiple hydrogen bonds, π-π stacking and hydrophobic interaction. The application experiments suggested that starane was examined well on test paper with good selectivity and was quantitatively detected in water samples, implying the good real-time and in-situ application potential for IBM on sensing starane in real environment and daily life.

Fractionation, spatial distribution, ecological and health risk assessment of cobalt and nickel in surface sediment of a bay along the southeast coast of China.

The fractionation and distribution of two potentially toxic elements (Co and Ni) were investigated in surface sediments to explore the pollution in Xiamen Bay, a special zone experiencing rapid economic growth and enormous environmental pressure. Relatively high concentrations were observed in nearshore areas with frequent human activities. The dominant fractions for Co and Ni were found to be residual, followed by exchangeable phase. Spatial differences in mobility and bioavailability inferred from chemical fractionations were more pronounced for Ni. Multiple evaluation methods including geo-accumulation index, risk assessment code, modified potential ecological risk index, etc., consistently indicated that pollution levels and ecological risks in the entire bay were generally classified as medium-low. However, non-carcinogenic risks of Co for children and carcinogenic risks of Ni for adults exceeded safety thresholds. Terrestrial weathering processes and industrial activities primarily contributed to the presence of these elements, while their distributions were mainly influenced by organic matter.

FGFR1 governs iron homeostasis via regulating intracellular protein degradation pathways of IRP2 in prostate cancer cells.

The acquisition of ectopic fibroblast growth factor receptor 1 (FGFR1) expression is well documented in prostate cancer (PCa) progression, notably in conferring tumor growth advantage and facilitating metastasis. However, how FGFR1 contributes to PCa progression is not fully revealed. Here we report that ectopic FGFR1 in PCa cells promotes transferrin receptor 1 (TFR1) expression and expands the labile iron pool (LIP), and vice versa. We further demonstrate that FGFR1 stabilizes iron regulatory proteins 2 (IRP2) and therefore, upregulates TFR1 via promoting IRP2 binding to the IRE of TFR1. Deletion of FGFR1 in DU145 cells decreases the LIP, which potentiates the anticancer efficacy of iron chelator. Intriguingly, forced expression of IRP2 in FGFR1 depleted cells reinstates TFR1 expression and LIP, subsequently restoring the tumorigenicity of the cells. Together, our results here unravel a new mechanism by which FGFR1 drives PCa progression and suggest a potential novel target for PCa therapy.

Efficient 2,3-Butanediol Production from Ethanol by a Modified Four-Enzyme Synthetic Biosystem.

2,3-butanediol (2,3-BD) is a versatile bio-based platform chemical. An artificial four-enzyme synthetic biosystem composed of ethanol dehydrogenase, NADH oxidase, formolase and 2,3-butanediol dehydrogenase was designed for upgrading ethanol to 2,3-BD in our previous study. However, a key challenge in developing in vitro enzymatic systems for 2,3-BD synthesis is the relatively sluggish catalytic efficiency of formolase, which catalyzes the rate-limiting step in such systems. Herein, this study reports how engineering the tunnel and substrate binding pocket of FLS improved its catalytic performance. A series of single-point and combinatorial variants were successfully obtained which displayed both higher catalytic efficiency and better substrate tolerance than wild-type FLS. Subsequently, a cell-free biosystem based on the FLS:I28V/L482E enzyme was implemented for upgrading ethanol to 2,3-BD. Ultimately, this system achieved efficient production of 2,3-BD from ethanol by the fed-batch method, reaching a concentration of 1.39 M (124.83 g/L) of the product and providing both excellent productivity and yield values of 5.94 g/L/h and 92.7%, respectively. Taken together, this modified enzymatic catalysis system provides a highly promising alternative approach for sustainable and cost-competitive production of 2,3-BD.

Seawater barium and sulfide removal improved marine habitability for the Cambrian Explosion of early animals.

An increase in atmospheric pO2 has been proposed as a trigger for the Cambrian Explosion at ∼539-514 Ma but the mechanistic linkage remains unclear. To gain insights into marine habitability for the Cambrian Explosion, we analysed excess Ba contents (Baexcess) and isotope compositions (δ138Baexcess) of ∼521-Myr-old metalliferous black shales in South China. The δ138Baexcess values vary within a large range and show a negative logarithmic correlation with Baexcess, suggesting a major (>99%) drawdown of oceanic Ba inventory via barite precipitation. Spatial variations in Baexcess and δ138Baexcess indicate that Ba removal was driven by sulfate availability that was ultimately derived from the upwelling of deep seawaters. Global oceanic oxygenation across the Ediacaran-Cambrian transition may have increased the sulfate reservoir via oxidation of sulfide and concurrently decreased the Ba reservoir by barite precipitation. The removal of both H2S and Ba that are deleterious to animals could have improved marine habitability for early animals.