Vanadium pentoxide interfacial layer enables high performance all-solid-state thin film batteries.

Lithium cobalt oxide (LiCoO2) is considered as one of the promising building blocks that can be used to fabricate all-solid-state thin film batteries (TFBs) because of its easy accessibility, high working voltage, and high energy density. However, the slow interfacial dynamics between LiCoO2 and LiPON in these TFBs results in undesirable side reactions and severe degradation of cycling and rate performance. Herein, amorphous vanadium pentoxide (V2O5) film was employed as the interfacial layer of a cathode-electrolyte solid-solid interface to fabricate all-solid-state TFBs using a magnetron sputtering method. The V2O5 thin film layer assisted in the construction of an ion transport network at the cathode/electrolyte interface, thus reducing the electrochemical redox polarization potential. The V2O5 interfacial layer also effectively suppressed the side reactions between LiCoO2 and LiPON. In addition, the interfacial resistance of TFBs was significantly decreased by optimizing the thickness of the interfacial modification layer. Compared to TFBs without the V2O5 layer, TFBs based on LiCoO2/V2O5/LiPON/Li with a 5 nm thin V2O5 interface modification layer exhibited a much smaller charge transfer impedance (Rct) value, significantly improved discharge specific capacity, and superior cycling and rate performance. The discharge capacity remained at 75.6% of its initial value after 1000 cycles at a current density of 100 µA cm-2. This was mainly attributed to the enhanced lithium ion transport kinetics and the suppression of severe side reactions at the cathode-electrolyte interface in TFBs based on LiCoO2/V2O5/LiPON/Li with a 5 nm V2O5 thin layer.

The Importance of Sintering-Induced Grain Boundaries in Copper Catalysis to Improve Carbon-Carbon Coupling.

Syngas conversion serves as a gas-to-liquid technology to produce liquid fuels and valuable chemicals from coal, natural gas, or biomass. During syngas conversion, sintering is known to deactivate the catalyst owing to the loss of active surface area. However, the growth of nanoparticles might induce the formation of new active sites such as grain boundaries (GBs) which perform differently from the original nanoparticles. Herein, we reported a unique Cu-based catalyst, Cu nanoparticles with in situ generated GBs confined in zeolite Y (denoted as activated Cu/Y), which exhibited a high selectivity for C5+ hydrocarbons (65.3 C%) during syngas conversion. Such high selectivity for long-chain products distinguished activated Cu/Y from typical copper-based catalysts which mainly catalyze methanol synthesis. This unique performance was attributed to the GBs, while the zeolite assisted the stabilization through spatial confinement. Specifically, the GBs enabled H-assisted dissociation of CO and subsequent hydrogenation into CHx*. CHx* species not only serve as the initiator but also directly polymerize on Cu GBs, known as the carbide mechanism. Meanwhile, the synergy of GBs and their vicinal low-index facets led to the CO insertion where non-dissociative adsorbed CO on low-index facets migrated to GBs and inserted into the metal-alkyl bond for the chain growth.

Age Gelation in Direct Steam Infusion Ultra-High-Temperature Milk: Different Heat Treatments Produce Different Gels.

To investigate the gelation process of direct ultra-high-temperature (UHT) milk, a pilot-scale steam infusion heat treatment was used to process milk samples over a wide temperature of 142-157 °C for 0.116-6 s, followed by storage at 4 °C, 25 °C, and 37 °C. The results of the physicochemical properties of milk showed that the particle sizes and plasmin activities of all milk samples increased during storage at 25 °C, but age gelation only occurred in three treated samples, 147 °C/6 s, 142 °C/6 s, and 142 °C/3 s, which all had lower plasmin activities. Furthermore, the properties of formed gels were further compared and analyzed by the measures of structure and intermolecular interaction. The results showed that the gel formed in the 147 °C/6 s-treated milk with a higher C* value had a denser network structure and higher gel strength, while the 142 °C/6 s-treated milk had the highest porosity. Furthermore, disulfide bonds were the largest contributor to the gel structure, and there were significant differences in disulfide bonds, hydrophobic interaction forces, hydrogen bonds, and electrostatic force among the gels. Our results showed that the occurrence of gel was not related to the thermal load, and the different direct UHT treatments produced different age gels in the milk.

The antidiabetic drug ipragliflozin induces vasorelaxation of rabbit femoral artery by activating a Kv channel, the SERCA pump, and the PKA signaling pathway.

We explored the vasorelaxant effects of ipragliflozin, a sodium-glucose cotransporter-2 inhibitor, on rabbit femoral arterial rings. Ipragliflozin relaxed phenylephrine-induced pre-contracted rings in a dose-dependent manner. Pre-treatment with the ATP-sensitive K+ channel inhibitor glibenclamide (10 µM), the inwardly rectifying K+ channel inhibitor Ba2+ (50 µM), or the Ca2+-sensitive K+ channel inhibitor paxilline (10 µM) did not influence the vasorelaxant effect. However, the voltage-dependent K+ (Kv) channel inhibitor 4-aminopyridine (3 mM) reduced the vasorelaxant effect. Specifically, the vasorelaxant response to ipragliflozin was significantly attenuated by pretreatment with the Kv7.X channel inhibitors linopirdine (10 µM) and XE991 (10 µM), the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) pump inhibitors thapsigargin (1 µM) and cyclopiazonic acid (10 µM), and the cAMP/protein kinase A (PKA)-associated signaling pathway inhibitors SQ22536 (50 µM) and KT5720 (1 µM). Neither the cGMP/protein kinase G (PKG)-associated signaling pathway nor the endothelium was involved in ipragliflozin-induced vasorelaxation. We conclude that ipragliflozin induced vasorelaxation of rabbit femoral arteries by activating Kv channels (principally the Kv7.X channel), the SERCA pump, and the cAMP/PKA-associated signaling pathway independent of other K+ (ATP-sensitive K+, inwardly rectifying K+, and Ca2+-sensitive K+) channels, cGMP/PKG-associated signaling, and the endothelium.

Design, Synthesis, Formulation, and Bioevaluation of Trisubstituted Triazines as Highly Selective mTOR Inhibitors for the Treatment of Human Breast Cancer.

The aberrant activation of the PI3K/mTOR signaling pathway is implicated in various human cancers. Thus, the development of inhibitors targeting mTOR has attracted considerable attention. In this study, we used a structure-based drug design strategy to discover a highly potent and kinase-selective mTOR inhibitor 24 (PT-88), which demonstrated an mTOR inhibitory IC50 value of 1.2 nM without obvious inhibition against another 195 kinases from the kinase profiling screening. PT-88 displayed selective inhibition against MCF-7 cells (IC50: 0.74 µM) with high biosafety against normal cells, in which autophagy induced by mTOR inhibition was implicated. After successful encapsulation in a lipodisc formulation, PT-88 demonstrated favorable pharmacokinetic and biosafety profiles and exerted a large antitumor effect in an MCF-7 subcutaneous bearing nude mice model. Our study shows the discovery of a highly selective mTOR inhibitor using a structure-based drug discovery strategy and provides a promising antitumor candidate for future study and development.

Prokaryotic community assembly patterns and nitrogen metabolic potential in oxygen minimum zone of Yangtze Estuary water column.

It is predicted that oxygen minimum zones (OMZs) in the ocean will expand as a consequence of global warming and environmental pollution. This will affect the overall microbial ecology and microbial nitrogen cycle. As one of the world's largest alluvial estuaries, the Yangtze Estuary has exhibited a seasonal OMZ since the 1980s. In this study, we have uncovered the microbial composition, the patterns of community assembly and the potential for microbial nitrogen cycling within the water column of the Yangtze Estuary, with a particular focus on OMZ. Based on the 16 S rRNA gene sequencing, a specific spatial variation in the composition of prokaryotic communities was observed for each water layer, with the Proteobacteria (46.1%), Bacteroidetes (20.3%), and Cyanobacteria (10.3%) dominant. Stochastic and deterministic processes together shaped the community assembly in the water column. Further, pH was the most important environmental factor influencing prokaryotic composition in the surface water, followed by silicate, PO43-, and distance offshore (p < 0.05). Water depth, NH4+, and PO43- were the main factors in the bottom water (p < 0.05). At last, species analysis and marker gene annotation revealed candidate nitrogen cycling performers, and a rich array of nitrogen cycling potential in the bottom water of the Yangtze Estuary. The determined physiochemical parameters and potential for nitrogen respiration suggested that organic nitrogen and NO3- (or NO2-) are the preferred nitrogen sources for microorganisms in the Yangtze Estuary OMZ. These findings are expected to advance research on the ecological responses of estuarine oxygen minimum zones (OMZs) to future global climate perturbations.

Recycling Valuable Alkylbenzenes from Polystyrene through Methanol-Assisted Depolymerization.

The vast bulk of polystyrene (PS), a major type of plastic polymers, ends up in landfills, which takes up to thousands of years to decompose in nature. Chemical recycling promises to enable lower-energy pathways and minimal environmental impacts compared with traditional incineration and mechanical recycling. Herein, we demonstrated that methanol as a hydrogen supplier assisted the depolymerization of PS (denoted as PS-MAD) into alkylbenzenes over a heterogeneous catalyst composed of Ru nanoparticles on SiO2. PS-MAD achieved a high yield of liquid products which accounted for 93.2 wt % of virgin PS at 280 °C for 6 h with the production rate of 118.1 mmolcarbon gcatal. -1 h-1. The major components were valuable alkylbenzenes (monocyclic aromatics and diphenyl alkanes), the sum of which occupied 84.3 wt % of liquid products. According to mechanistic studies, methanol decomposition dominates the hydrogen supply during PS-MAD, thereby restraining PS aromatization which generates by-products of fused polycyclic arenes and polyphenylenes.

Spatial decoupling of bromide-mediated process boosts propylene oxide electrosynthesis.

The electrochemical synthesis of propylene oxide is far from practical application due to the limited performance (including activity, stability, and selectivity). In this work, we spatially decouple the bromide-mediated process to avoid direct contact between the anode and propylene, where bromine is generated at the anode and then transferred into an independent reactor to react with propylene. This strategy effectively prevents the side reactions and eliminates the interference to stability caused by massive alkene input and vigorously stirred electrolytes. As expected, the selectivity for propylene oxide reaches above 99.9% with a remarkable Faradaic efficiency of 91% and stability of 750-h (>30 days). When the electrode area is scaled up to 25 cm2, 262 g of pure propylene oxide is obtained after 50-h continuous electrolysis at 6.25 A. These findings demonstrate that the electrochemical bromohydrin route represents a viable alternative for the manufacture of epoxides.

CO-Assisted Methane Oxidation into Oxygenates over Surface Platinum-Titanium Alloyed Layers.

Methane oxidation using molecular oxygen remains a grand challenge in which the obstacle is not only the activation of methane but also the reaction with oxygen, considering the mismatch of the ground spin states. Herein, we report TiO2-supported Pt nanocrystals (Pt/TiO2) with surface Pt-Ti alloyed layers that directly convert methane into oxygenates by using O2 as the oxidant with the assistance of CO. The oxygenate yield reached 749.8 mmol gPt-1 in a H2O aqueous solution over 0.1% Pt/TiO2 under 31 bar of mixed gas (20:5:6 CH4:CO:O2) at 150 °C for 3 h, while the CH3OH selectivity was 62.3%. On the basis of the control experiments and spectroscopic results, we identified the surface Pt-Ti alloy as the active sites. Moreover, CO promoted the dissociation of O2 on the surface of Pt-Ti alloyed layers and the subsequent activation of CH4 to form oxygenated products.

Comparison of different organic selenium supplementations on selenium status and serum biomarkers in dairy cows.

The objective of this study was to investigate the effects of two different organic selenium (Se) supplements, selenomethionine (Se-Met) and selenohomolanthionine (Se-Hlan), on the serum biochemical parameters and Se status of dairy cows. Different dietary Se supplementation treatments were set as follows: a control group (CON, adding sodium selenite at 0.3 mg Se/kg dry matter [DM]), 0.3 and 0.5 Se-Met (adding Se-Met at 0.3 and 0.5 mg Se/kg DM, respectively), as well as 0.3 and 0.5 Se-Hlan (adding Se-Hlan at 0.3 and 0.5 mg Se/kg DM, respectively). The experiment lasted 8 weeks. The serum measurements showed that both organic Se treatments resulted in higher uric acid than CON. Se-Met produced higher aspartate aminotransferase, glucose, urea, low-density lipoprotein cholesterol, and lactate dehydrogenase than Se-Hlan. Regarding the Se status, the highest milk Se values appeared in 0.5 Se-Met, with intermediate values in 0.3 Se-Met and 0.5 Se-Hlan, whereas the highest and lowest serum Se levels were presented in 0.5 Se-Met and 0.3 Se-Hlan, respectively. Our results suggest that Se-Hlan was not as efficient in boosting serum or milk Se as Se-Met and differences in serum biomarkers between Se-Met and Se-Hlan may be associated with distinct metabolic pathways for different forms of organic Se.

Rujifang inhibits triple-negative breast cancer growth via the PI3K/AKT pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Rujifang (RJF) constitutes a traditional Chinese medicinal compound extensively employed in the management of triple-negative breast cancer (TNBC). However, information regarding its potential active ingredients, antitumor effects, safety, and mechanism of action remains unreported. AIM OF THE STUDY: To investigate the efficacy and safety of RJF in the context of TNBC. MATERIALS AND METHODS: We employed the ultra high-performance liquid chromatography-electrospray four-pole time-of-flight mass spectrometry technique (UPLC/Q-TOF-MS/MS) to scrutinize the chemical constituents of RJF. Subcutaneously transplanted tumor models were utilized to assess the impact of RJF on TNBC in vivo. Thirty female BLAB/c mice were randomly divided into five groups: the model group, cyclophosphamide group, and RJF high-dose, medium-dose, and low-dose groups. A total of 1 × 106 4T1 cells were subcutaneously injected into the right shoulder of mice, and they were administered treatments for a span of 28 days. We conducted evaluations on blood parameters, encompassing white blood cell count (WBC), red blood cell count (RBC), hemoglobin (HGB), platelet count (PLT), neutrophils, lymphocytes, and monocytes, as well as hepatorenal indicators including alkaline phosphatase (ALP), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), albumin, and creatinine (CRE) to gauge the safety of RJF. Ki67 and TUNEL were detected via immunohistochemistry and immunofluorescence, respectively. We prepared RJF drug-containing serum for TNBC cell lines and assessed the in vitro inhibitory effect of RJF on tumor cell growth through the CCK8 assay and cell cycle analysis. RT-PCR was employed to detect the mRNA expression of cyclin-dependent kinase and cyclin-dependent kinase inhibitors in tumor tissues, and Western blot was carried out to ascertain the expression of cyclin and pathway-related proteins. RESULTS: 100 compounds were identified in RJF, which consisted of 3 flavonoids, 24 glycosides, 18 alkaloids, 3 amino acids, 8 phenylpropanoids, 6 terpenes, 20 organic acids, and 18 other compounds. In animal experiments, both CTX and RJF exhibited substantial antitumor effects. RJF led to an increase in the number of neutrophils in peripheral blood, with no significant impact on other hematological indices. In contrast, CTX reduced red blood cell count, hemoglobin levels, and white blood cell count, while increasing platelet count. RJF exhibited no discernible influence on hepatorenal function, whereas Cyclophosphamide (CTX) decreased ALP, GOT, and GPT levels. Both CTX and RJF reduced the expression of Ki67 and heightened the occurrence of apoptosis in tumor tissue. RJF drug-containing serum hindered the viability of 4T1 and MD-MBA-231 cells in a time and concentration-dependent manner. In cell cycle experiments, RJF diminished the proportion of G2 phase cells and arrested the cell cycle at the S phase. RT-PCR analysis indicated that RJF down-regulated the mRNA expression of CDK2 and CDK4, while up-regulating that of P21 and P27 in tumor tissue. The trends in CDKs and CDKIs protein expression mirrored those of mRNA expression. Moreover, the PI3K/AKT pathway displayed downregulation in the tumor tissue of mice treated with RJF. CONCLUSION: RJF demonstrates effectiveness and safety in the context of TNBC. It exerts anti-tumor effects by arresting the cell cycle at the S phase through the PI3K-AKT pathway.

The Effects of Combined Use of Linaclotide and Polyethylene Glycol Electrolyte Powder in Colonoscopy Preparation for Patients With Chronic Constipation.

OBJECTIVE: The purpose of this study is to evaluate the safety and efficacy of linaclotide and polyethylene glycol (PEG) electrolyte powder in patients with chronic constipation undergoing colonoscopy preparation. PATIENTS AND METHODS: We included 260 patients with chronic constipation who were scheduled to undergo a colonoscopy. They were equally divided into 4 groups using a random number table: 4L PEG, 3L PEG, 3L PEG+L, and 2L PEG+L. The 4 groups were compared based on their scores on the Boston Bowel Preparation Scale (BBPS) and Ottawa Bowel Preparation Quality Scale (OBPQS), adverse reactions during the bowel preparation procedure, colonoscope insertion time, colonoscope withdrawal time, detection rate of adenomas, and their willingness to repeat bowel preparation. RESULTS: In terms of the score of the right half of the colon, the score of the transverse colon, the total score using BBPS, and the total score using OBPQS, the 3L PEG (polyethylene glycol)+L group was superior to groups 3L PEG and 2L PEG+L ( P <0.05), but comparable to the 4L PEG group ( P >0.05). The incidence rate of vomiting was higher in the 4L PEG group than in the 2L PEG+L group ( P <0.05). There was no statistically significant difference in the insertion time of the colonoscope between the 4 groups. The colonoscope withdrawal time in the 3L PEG+L group was shorter than in groups 4L PEG and 3L PEG ( P <0.05) and comparable to that in the 4L PEG group ( P >0.05). There was no statistically significant difference in the rate of adenoma detection among the 4 groups ( P >0.05). The 4L PEG group was the least willing of the 4 groups to undergo repeated bowel preparation ( P <0.05). CONCLUSION: The 3L PEG+L is optimal among the 4 procedures. It can facilitate high-quality bowel preparation, reduce the incidence of nausea during the bowel preparation procedure, and encourage patients to undertake repeated bowel preparation.

Effects of Dietary Colostrum Basic Protein on Bone Growth and Calcium Absorption in Mice.

Colostrum basic protein (CBP) is a trace protein extracted from bovine colostrum. Previous studies have shown that CBP can promote bone cell differentiation and increase bone density. However, the mechanism by which CBP promotes bone activity remains unclear. This study investigated the mechanism of the effect of CBP on bone growth in mice following dietary supplementation of CBP at doses that included 0.015%, 0.15%, 1.5%, and 5%. Compared with mice fed a normal diet, feeding 5% CBP significantly enhanced bone rigidity and improved the microstructure of bone trabeculae. Five-percent CBP intake triggered significant positive regulation of calcium metabolism in the direction of bone calcium accumulation. The expression levels of paracellular calcium transport proteins CLDN2 and CLDN12 were upregulated nearly 1.5-fold by 5% CBP. We conclude that CBP promotes calcium absorption in mice by upregulating the expression of the calcium-transporting paracellular proteins CLND2 and CLND12, thereby increasing bone density and promoting bone growth. Overall, CBP contributes to bone growth by affecting calcium metabolism.

Universal Design Strategy for Air-Stable Layered Na-Ion Cathodes toward Sustainable Energy Storage.

Na-ion batteries (NIBs) are sustainable alternatives to Li-ion technologies due to the abundant and widely-distributed resources. However, the most promising cathode materials of NIBs so far, O3 layered oxides, suffer from serious air instability issues, which significantly increases the manufactural cost and carbon footprint because of the long-term use of dry rooms. While some feasible strategies are proposed via case studies, universal design strategies for air-stable cathodes are yet to be established. Herein, the air degradation mechanisms of O3 cathodes are investigated via combined first-principles and experimental approaches, with bond dissociation energy proposed as an effective descriptor for predicting air stability. Experimental validations in various unary, binary, and ternary O3 cathodes confirm that the air stability can indeed be effectively improved via simple compositional design. Guided by the predictive model, the designed material can sustain 30-day air-storage without structural or electrochemical degradation. It is calculated that such air-stable cathodes can significantly reduce both energy consumption (≈4 100 000 kWh) and carbon footprint (≈2200-ton CO2) annually for a 2 GWh NIBs manufactory. Therefore, the fundamental understandings and universal design strategy presented open an avenue for rational materials design of NIBs toward both elemental and manufactural sustainability.

Element-dependent effects of alkali cations on nitrate reduction to ammonia.

Catalytic conversion of nitrate (NO3-) pollutants into ammonia (NH3) offers a sustainable and promising route for both wastewater treatment and NH3 synthesis. Alkali cations are prevalent in nitrate solutions, but their roles beyond charge balance in catalytic NO3- conversion have been generally ignored. Herein, we report the promotion effect of K+ cations in KNO3 solution for NO3- reduction over a TiO2-supported Ni single-atom catalyst (Ni1/TiO2). For photocatalytic NO3- reduction reaction, Ni1/TiO2 exhibited a 1.9-fold NH3 yield rate with nearly 100% selectivity in KNO3 solution relative to that in NaNO3 solution. Mechanistic studies reveal that the K+ cations from KNO3 gradually bonded with the surface of Ni1/TiO2, in situ forming a K-O-Ni moiety during reaction, whereas the Na+ ions were unable to interact with the catalyst in NaNO3 solution. The charge accumulation on the Ni sites induced by the incorporation of K atom promoted the adsorption and activation of NO3-. Furthermore, the K-O-Ni moiety facilitated the multiple proton-electron coupling of NO3- into NH3 by stabilizing the intermediates.

Corrigendum: Comparison of cerebrospinal fluid space between probable normal pressure hydrocephalus and Alzheimer's disease.

[This corrects the article DOI: 10.3389/fnagi.2023.1241237.].

Multispecies transcriptomics identifies SIKE as a MAPK repressor that prevents NASH progression.

Nonalcoholic fatty liver (NAFL) remains relatively benign, but high-risk to end-stage liver diseases become highly prevalent when it progresses into nonalcoholic steatohepatitis (NASH). Our current understanding of the development of NAFL to NASH remains insufficient. In this study, we revealed MAP kinase (MAPK) activation as the most notable molecular signature associated with NASH progression across multiple species. Furthermore, we identified suppressor of IKKε (SIKE) as a conserved and potent negative controller of MAPK activation. Hepatocyte-specific overexpression of Sike prevented NASH progression in diet- and toxin-induced mouse NASH models. Mechanistically, SIKE directly interacted with TGF-ß-activated kinase 1 (TAK1) and TAK1-binding protein 2 (TAB2) to interrupt their binding and subsequent TAK1-MAPK signaling activation. We found that indobufen markedly up-regulated SIKE expression and effectively improved NASH features in mice and macaques. These findings identify SIKE as a MAPK suppressor that prevents NASH progression and provide proof-of-concept evidence for targeting the SIKE-TAK1 axis as a potential NASH therapy.

Gene inversion led to the emergence of brackish archaeal heterotrophs in the aftermath of the Cryogenian Snowball Earth.

Land-ocean interactions greatly impact the evolution of coastal life on earth. However, the ancient geological forces and genetic mechanisms that shaped evolutionary adaptations and allowed microorganisms to inhabit coastal brackish waters remain largely unexplored. In this study, we infer the evolutionary trajectory of the ubiquitous heterotrophic archaea Poseidoniales (Marine Group II archaea) presently occurring across global aquatic habitats. Our results show that their brackish subgroups had a single origination, dated to over 600 million years ago, through the inversion of the magnesium transport gene corA that conferred osmotic-stress tolerance. The subsequent loss and gain of corA were followed by genome-wide adjustment, characterized by a general two-step mode of selection in microbial speciation. The coastal family of Poseidoniales showed a rapid increase in the evolutionary rate during and in the aftermath of the Cryogenian Snowball Earth (∼700 million years ago), possibly in response to the enhanced phosphorus supply and the rise of algae. Our study highlights the close interplay between genetic changes and ecosystem evolution that boosted microbial diversification in the Neoproterozoic continental margins, where the Cambrian explosion of animals soon followed.

Ecosystem dynamics and hypoxia control in the East China Sea: A bottom-up and top-down perspective.

Decades of overfishing have greatly altered the community structure in the East China Sea (ECS). The decrease of top predators in the food web has weakened the control exerted from higher trophic levels. As a result, the biomass of benthic crustaceans, representing the third trophic level, has increased. This has probably led to a restriction of the second trophic level, diminishing its ability to control primary producer biomass. Consequently, the ecological pyramid of trophic levels in the ECS has been altered, reducing the top-down control on the first trophic level. This has made algal blooms more susceptible to occur under nutrient loads, temperate temperatures, and light availability. The reduced abundance of the fourth trophic levels has caused a larger portion of primary productivity to sink directly to the benthic community, bypassing the food web. This influx of sinking organic matter has resulted in organic enrichment in the bottom waters, impacting the biomass and diversity of benthic organisms. Furthermore, it has intensified anthropogenic carbon storage in the sediment. Subsequently, intense decomposition processes occur, leading to the development of anoxia and even hypoxia. The seasonal hypoxia off the Changjiang Estuary can be attributed to the combined influence of top-down control and bottom-up control related to nutrient loading, and terrestrial inputs. In order to mitigate extreme hypoxia events, it is necessary to implement comprehensive fisheries policies that prioritize the maintenance of a healthy and functional ecosystem. This approach should go beyond relying solely on watershed management strategies to regulate riverine inputs. PLAIN LANGUAGE SUMMARY: Decades of overfishing changed the food web in the East China Sea and weaken the resistance of ecosystem to hypoxia. Commercial fishing on top predators decreases the fourth trophic level while relatively increases the third trophic represented by crab and shrimp, which enhances grazing on the zooplankton. The decrease of the second trophic level fails to control the biomass of phytoplankton, thus more primary productivities directly sink to the benthic community and cause organic enrichment. The elevated flux of organic matters to the bottom waters causes the thrive of the carbs and shrimps, as well as more remineralization processes and eventually low oxygen level. Unlike the bottom-up perspective of hypoxia mechanism off the Changjiang Estuary, which is from the nutrient load, phytoplankton bloom, quick sink, effective decomposition and eventually hypoxia, the top-down control focuses on the changes of ecosystem structure and thus derived hindered energy transfer, changed community structure, enhanced carbon sink, elevated remineralization and ultimately hypoxia. These two mechanisms combine with each other and control the seasonal hypoxia off the Changjiang Estuary and even other coastal regions around the world.