Establishing reaction networks in the 16-electron sulfur reduction reaction.

The sulfur reduction reaction (SRR) plays a central role in high-capacity lithium sulfur (Li-S) batteries. The SRR involves an intricate, 16-electron conversion process featuring multiple lithium polysulfide intermediates and reaction branches1-3. Establishing the complex reaction network is essential for rational tailoring of the SRR for improved Li-S batteries, but represents a daunting challenge4-6. Herein we systematically investigate the electrocatalytic SRR to decipher its network using the nitrogen, sulfur, dual-doped holey graphene framework as a model electrode to understand the role of electrocatalysts in acceleration of conversion kinetics. Combining cyclic voltammetry, in situ Raman spectroscopy and density functional theory calculations, we identify and directly profile the key intermediates (S8, Li2S8, Li2S6, Li2S4 and Li2S) at varying potentials and elucidate their conversion pathways. Li2S4 and Li2S6 were predominantly observed, in which Li2S4 represents the key electrochemical intermediate dictating the overall SRR kinetics. Li2S6, generated (consumed) through a comproportionation (disproportionation) reaction, does not directly participate in electrochemical reactions but significantly contributes to the polysulfide shuttling process. We found that the nitrogen, sulfur dual-doped holey graphene framework catalyst could help accelerate polysulfide conversion kinetics, leading to faster depletion of soluble lithium polysulfides at higher potential and hence mitigating the polysulfide shuttling effect and boosting output potential. These results highlight the electrocatalytic approach as a promising strategy for tackling the fundamental challenges regarding Li-S batteries.

Neoadjuvant chemotherapy is noninferior to chemoradiotherapy for early-onset locally advanced rectal cancer in the FOWARC trial.

BACKGROUND: The early-onset rectal cancer with rapidly increasing incidence is considered to have distinct clinicopathological and molecular profiles with high-risk features. This leads to challenges in developing specific treatment strategies for early-onset rectal cancer patients and questions of whether early-onset locally advanced rectal cancer (LARC) needs aggressive neoadjuvant treatment. METHODS: In this post hoc analysis of FOWARC trial, we investigated the role of preoperative radiation in early-onset LARC by comparing the clinicopathological profiles and short-term and long-term outcomes between the early-onset and late-onset LARCs. RESULTS: We revealed an inter-tumor heterogeneity of clinical profiles and treatment outcomes between the early-onset and late-onset LARCs. The high-risk features were more prevalent in early-onset LARC. The neoadjuvant radiation brought less benefits of tumor response and more risk of complications in early-onset group (pCR: OR = 3.75, 95% CI = 1.37-10.27; complications: HR = 11.35, 95% CI = 1.46-88.31) compared with late-onset group (pCR: OR = 5.33, 95% CI = 1.83-15.58; complications: HR = 5.80, 95% CI = 2.32-14.49). Furthermore, the addition of radiation to neoadjuvant chemotherapy didn't improve long-term OS (HR = 1.37, 95% CI = 0.49-3.87) and DFS (HR = 1.05, 95% CI = 0.58-1.90) for early-onset patients. CONCLUSION: Preoperative radiation plus chemotherapy may not be superior to the chemotherapy alone in the early-onset LARC. Our findings provide insight into the treatment of early-onset LARC by interrogating the aggressive treatment and alternative regimens.

Lamin A/C mediates microglial activation by modulating cell proliferation and immune response.

Lamin A/C is involved in macrophage activation and premature aging, also known as progeria. As the resident macrophage in brain, overactivation of microglia causes brain inflammation, promoting aging and brain disease. In this study, we investigated the role of Lamin A/C in microglial activation and its impact on progeria using Lmna-/- mice, primary microglia, Lmna knockout (Lmna-KO) and Lmna-knockdown (Lmna-KD) BV2 cell lines. We found that the microglial activation signatures, including cell proliferation, morphology changes, and proinflammatory cytokine secretion (IL-1ß, IL-6, and TNF-α), were significantly suppressed in all Lamin A/C-deficient models when stimulated with LPS. TMT-based quantitative proteomic and bioinformatic analysis were further applied to explore the mechanism of Lamin A/C-regulated microglia activation from the proteome level. The results revealed that immune response and phagocytosis were impaired in Lmna-/- microglia. Stat1 was identified as the hub protein in the mechanism by which Lamin A/C regulates microglial activation. Additionally, DNA replication, chromatin organization, and mRNA processing were also altered by Lamin A/C, with Ki67 fulfilling the main hub function. Lamin A/C is a mechanosensitive protein and, the immune- and proliferation-related biological processes are also regulated by mechanotransduction. We speculate that Lamin A/C-mediated mechanotransduction is required for microglial activation. Our study proposes a novel mechanism for microglial activation mediated by Lamin A/C.

Vectorial holography over a multimode fiber.

Vectorial holography through a strongly scattering medium can facilitate various applications in optics and photonics. However, the realization of vectorial holography with arbitrary distribution of optical intensity is still limited because of experimental noise during the calibration of vectorial transmission matrix (TM) and reconstruction noise during the retrieval of input wavefront for a given holographic target. Herein, we propose and experimentally demonstrate the vectorial holography with arbitrary distribution of optical intensity over a multimode fiber (MMF) using the Tikhonov regularization. By optimizing the noise factor, the performance of vectorial holography over an MMF is improved compared with the conjugate transpose and inverse TM methods. Our results might shed new light on the optical communication and detection mediated by MMFs.

Quantum-Geometry-Induced Anomalous Hall Effect in Nonunitary Superconductors and Application to Sr_{2}RuO_{4}.

The polar Kerr effect and the closely related anomalous charge Hall effect are among the most distinguishing signatures of the superconducting state in Sr_{2}RuO_{4}, as well as in several other compounds. These effects are often thought to be derived from chiral superconducting pairing, and different mechanisms have been invoked for the explanation. However, the intrinsic mechanisms proposed previously often involve unrealistically strong interband Cooper pairing. We show in this Letter that, even without interband pairing, nonunitary superconducting states can support the intrinsic anomalous charge Hall effect, thanks to the quantum geometric properties of the Bloch electrons. The key here is to have a normal-state spin Hall effect, for which a nonzero spin-orbit coupling is essential. A finite charge Hall effect then naturally arises at the onset of a spin-polarized nonunitary superconducting pairing. It depends on both the spin polarization and the normal-state electron Berry curvature, the latter of which is the imaginary part of the quantum geometric tensor of the Bloch states. Applying our results to the weakly paired Sr_{2}RuO_{4} we conclude that, if the reported Kerr effect is of intrinsic origin, the superconducting state is most likely nonunitary and has odd parity. Our theory may be generalized to other superconductors that exhibit the polar Kerr effect.

Anti-phasic oscillatory development for speech and noise processing in cochlear implanted toddlers.

Human brain demonstrates amazing readiness for speech and language learning at birth, but the auditory development preceding such readiness remains unknown. Cochlear implanted (CI) children (n = 67; mean age 2.77 year ± 1.31 SD; 28 females) with prelingual deafness provide a unique opportunity to study this stage. Using functional near-infrared spectroscopy, it was revealed that the brain of CI children was irresponsive to sounds at CI hearing onset. With increasing CI experiences up to 32 months, the brain demonstrated function, region and hemisphere specific development. Most strikingly, the left anterior temporal lobe showed an oscillatory trajectory, changing in opposite phases for speech and noise. The study provides the first longitudinal brain imaging evidence for early auditory development preceding speech acquisition.

The roles of 5-HT in orofacial pain.

OBJECTIVES: Acute and chronic orofacial pain are very common and remain a vexing health problem that has a negative effect on the quality of life. Serotonin (5-HydroxyTryptamine, 5-HT) is a kind of monoamine neurotransmitter that is involved in many physiological and pathological processes. However, its role in orofacial pain remains inconclusive. Therefore, this review aims to summarize the recent advances in understanding the effect exerted by 5-HT on the modulation of orofacial pain. SUBJECTS AND METHODS: An extensive search was conducted on PubMed and Web of Science for pertinent studies focusing on the effects of 5-HT on the modulation of orofacial pain. RESULTS: In this review, we concisely review how 5-HT mediates orofacial pain, how 5-HT is regulated and how we can translate these findings into clinical applications for the prevention and/or treatment of orofacial pain. CONCLUSIONS: 5-HT plays a key role in the modulation of orofacial pain, implying that 5-HT modulators may serve as effective treatment for orofacial pain. However, further research on the precise mechanisms underlying the modulation of orofacial pain is still warranted.

Psychosocial Factors Associated With Long-Term Cognitive Impairment Among COVID-19 Survivors: A Cross-Sectional Study.

ABSTRACT: COVID-19 survivors complained of the experience of cognitive impairments, which also called "brain fog" even recovered. The study aimed to describe long-term cognitive change and determine psychosocial factors in COVID-19 survivors. A cross-sectional study was recruited 285 participants from February 2020 to April 2020 in 17 hospitals in Sichuan Province. Cognitive function, variables indicative of the virus infection itself, and psychosocial variables were collected by telephone interview. Univariate logistic regression and Lasso logistic regression models were used for variable selection which plugged into a multiple logistics model. Overall prevalence of moderate or severe cognitive impairment was 6.3%. Logistic regression showed that sex, religion, smoking status, occupation, self-perceived severity of illness, sleep quality, perceived mental distress after COVID-19, perceived discrimination from relatives and friends, and suffered abuse were associated with cognitive impairment. The long-term consequences of cognitive function are related to multiple domains, in which psychosocial factors should be taken into consideration.

Nanoscale Pickering emulsion food preservative films/coatings: Compositions, preparations, influencing factors, and applications.

Pickering emulsion (PE) technology effectively addresses the issues of poor compatibility and low retention of hydrophobic active ingredients in food packaging. Nonetheless, it is important to recognize that each stage of the preparation process for PE films/coatings (PEFCs) can significantly influence their functional properties. With the fundamental considerations of environmental friendliness and human safety, this review extensively explores the potential of raw materials for PEFC and introduces the preparation methods of nanoparticles, emulsification technology, and film-forming techniques. The critical factors that impact the performance of PEFC during the preparation process are analyzed to enhance food preservation effectiveness. Moreover, the latest advancements in PE packaging across diverse food applications are summarized, along with prospects for innovative food packaging materials. Finally, the preservation mechanism and application safety have been systematically elucidated. The study revealed that the PEFCs provide structural flexibility, where designable nanoparticles offer unique functional properties for intelligent control over active ingredient release. The selection of the dispersed and continuous phases, along with component proportions, can be customized for specific food characteristics and storage conditions. By employing suitable preparation and emulsification techniques, the stability of the emulsion can be improved, thereby enhancing the effectiveness of the films/coatings in preserving food. Including additional substances broadens the functionality of degradable materials. The PE packaging technology provides a safe and innovative solution for extending the shelf life and enhancing the quality of food products by protecting and releasing active components.

Efficacy and safety of chloral hydrate in auditory brainstem response test: A systematic review and single-arm meta-analysis.

OBJECTIVES: To evaluate the safety and efficacy of chloral hydrate in auditory brainstem response (ABR) tests. SETTING AND DESIGN: In this study, the authors systematically searched both English (Embase, PubMed, and Web of Science) and Chinese (Chinese National Knowledge Infrastructure, Wanfang Data, and VIP Chinese Science) databases. Two authors independently performed data extraction and quality assessment. The pooled sedation failure rate and the pooled incidence of adverse events were calculated via a random-effects model. Sensitivity and subgroup analyses were performed to explore the sources of heterogeneity, and the PRISMA guideline was followed. PARTICIPANTS: Patients with ABR tests receiving chloral hydrate sedation. MAIN OUTCOME MEASURES: The pooled sedation failure rate and the pooled incidence of adverse events. RESULTS: A total of 23 clinical studies were included in the final analysis. The pooled sedation failure rate of patients who received chloral hydrate sedation before ABR examination was 10.0% [95% confidence interval (CI) (6.7%, 15.0%), I2 = 95%, p < .01]. There were significant differences in the prevalence of sedation failure between sample sizes greater than 200 and those less than or equal to 200 (5.6% vs. 19.6%, p < .01) and between the studies that reported sleep deprivation and those that did not report sleep deprivation (7.1% vs. 18.9%, p < .01). The pooled incidence of adverse events was 10.32% [95% CI (5.83%, 14.82%), I2 = 98.1%, p < .01]. CONCLUSIONS: Chloral hydrate has a high rate of sedation failure, adverse events, and potential carcinogenicity. Therefore, replacing its use in ABR tests with safer and more effective sedatives is warranted.

Defect-Engineered ZIF-Derived Non-Pt Cathode Catalyst at 1.5 mg cm-2 Loading for Proton Exchange Membrane Fuel Cells.

Due to the sluggish kinetics of the oxygen reduction reaction (ORR) by non-Pt based catalyst, high loading of catalyst is required to achieve satisfactory fuel cell performance, which inevitably leads to the increase of the catalyst layer thickness with serious mass transport resistance. Herein, a defective zeolitic imidazolate framework (ZIF) derived Co/Fe-N-C catalyst with small mesopores (2-4 nm) and high density of CoFe atomic active sites are prepared by regulating the Fe dosage and pyrolysis temperature. Molecular dynamics simulation and electrochemical tests indicate that > 2 nm mesopores show insignificant influence on the diffusion process of O2 and H2 O molecules, leading to the high utilization of active sites and low mass transport resistance. The proton exchange membrane fuel cell (PEMFC) shows a high-power density of 755 mW cm-2 with only 1.5 mg cm-2 of non-Pt catalyst in the cathode. No apparent performance loss caused by concentration difference can be observed, in particular in the high current density region (1 A cm-2 ). This work emphasizes the importance of small mesopore design in the Co/Fe-N-C catalyst, which is anticipated to provide essential guidance for the application of non-Pt catalysts.

Quantum Simulation of Topological Zero Modes on a 41-Qubit Superconducting Processor.

Quantum simulation of different exotic topological phases of quantum matter on a noisy intermediate-scale quantum (NISQ) processor is attracting growing interest. Here, we develop a one-dimensional 43-qubit superconducting quantum processor, named Chuang-tzu, to simulate and characterize emergent topological states. By engineering diagonal Aubry-André-Harper (AAH) models, we experimentally demonstrate the Hofstadter butterfly energy spectrum. Using Floquet engineering, we verify the existence of the topological zero modes in the commensurate off-diagonal AAH models, which have never been experimentally realized before. Remarkably, the qubit number over 40 in our quantum processor is large enough to capture the substantial topological features of a quantum system from its complex band structure, including Dirac points, the energy gap's closing, the difference between even and odd number of sites, and the distinction between edge and bulk states. Our results establish a versatile hybrid quantum simulation approach to exploring quantum topological systems in the NISQ era.

Cochlear Reimplantation Rate and Cause: a 22-Year, Single-Center Experience, and a Meta-Analysis and Systematic Review.

OBJECTIVES: In terms of cochlear reimplantation, there is no consensus on the definition, range, or calculation formulation for the reimplantation rate. This study aims to put forward a relatively standardized and more explicit definition based on a literature review, calculate the rate of cochlear reimplantation, and examine the classification and distribution of the reimplantation causes. DESIGN: A systematic review and retrospective study. A relatively clearer definition was used in this study: cochlear reimplantation is the implantation of new electrodes to reconstruct the auditory path, necessitated by the failure or abandonment of the initial implant. Seven English and Chinese databases were systematically searched for studies published before July 23, 2021 regarding patients who accepted cochlear reimplantation. Two researchers independently applied the inclusion and exclusion criteria to select studies and complete data extraction. As the effect size, the reimplantation rate was extracted and synthesized using a random-effects model, and subgroup and sensitivity analyses were performed to reduce heterogeneity. In addition, a retrospective study analyzed data on cochlear reimplantation in a tertiary hospital from April 1999 to August 2021. Kaplan-Meier survival analysis and the log-rank test were adopted to analyze the survival times of cochlear implants and compare them among different subgroups. RESULTS: A total of 144 articles were included, with 85,851 initial cochlear implantations and 4276 cochlear reimplantations. The pooled rate of cochlear reimplantation was 4.7% [95% CI (4.2% to 5.1%)] in 1989 to 2021, 6.8% [95% CI (4.5% to 9.2%)] before 2000, and 3.2% [95% CI (2.7% to 3.7%)] after 2000 ( P =0.003). Device failures accounted for the largest proportion of reimplantation (67.6% [95% CI (64.0% to 71.3%)], followed by medical reasons (28.9% [95% CI (25.7% to 32.0%)]). From April 1999 to August 2021, 1775 cochlear implants were performed in West China Hospital (1718 initial implantations and 57 reimplantations; reimplantation rate 3.3%). In total, 45 reimplantations (78.9%) were caused by device failure, 10 (17.5%) due to medical reasons, and 2 (3.5%) from unknown reasons. There was no difference in the survival time of implants between adults and children ( P = 0.558), while there existed a significant difference between patients receiving implants from different manufacturers ( P < 0.001). CONCLUSIONS: The cochlear reimplantation rate was relatively high, and more attention should be paid to formulating a standard definition, calculation formula, and effect assessment of cochlear reimplantation. It is necessary to establish a sound mechanism for long-term follow-up and rigorously conduct longitudinal cohort studies.

Differential auditory cortical development in left and right cochlear implanted children.

Unilateral aural stimulation has been shown to cause massive cortical reorganization in brain with congenital deafness, particularly during the sensitive period of brain development. However, it is unclear which side of stimulation provides most advantages for auditory development. The left hemisphere dominance of speech and linguistic processing in normal hearing adult brain has led to the assumption of functional and developmental advantages of right over left implantation, but existing evidence is controversial. To test this assumption and provide evidence for clinical choice, we examined 34 prelingually deaf children with unilateral cochlear implants using near-infrared spectroscopy. While controlling for age of implantation, residual hearing, and dominant hand, cortical processing of speech showed neither developmental progress nor influence of implantation side weeks to months after implant activation. In sharp contrast, for nonspeech (music signal vs. noise) processing, left implantation showed functional advantages over right implantation that were not yet discernable using clinical, questionnaire-based outcome measures. These findings support the notion that the right hemisphere develops earlier and is better preserved from adverse environmental influences than its left counterpart. This study thus provides, to our knowledge, the first evidence for differential influences of left and right auditory peripheral stimulation on early cortical development of the human brain.

Role of bZIP Transcription Factors in Plant Salt Stress.

Soil salinity has become an increasingly serious problem worldwide, greatly limiting crop development and yield, and posing a major challenge to plant breeding. Basic leucine zipper (bZIP) transcription factors are the most widely distributed and conserved transcription factors and are the main regulators controlling various plant response processes against external stimuli. The bZIP protein contains two domains: a highly conserved, DNA-binding alkaline region, and a diverse leucine zipper, which is one of the largest transcription factor families in plants. Plant bZIP is involved in many biological processes, such as flower development, seed maturation, dormancy, and senescence, and plays an important role in abiotic stresses such as salt damage, drought, cold damage, osmotic stress, mechanical damage, and ABA signal response. In addition, bZIP is involved in the regulation of plant response to biological stresses such as insect pests and pathogen infection through salicylic acid, jasmonic acid, and ABA signal transduction pathways. This review summarizes and discusses the structural characteristics and functional characterization of the bZIP transcription factor group, the bZIP transcription factor complex and its molecular regulation mechanisms related to salt stress resistance, and the regulation of transcription factors in plant salt stress resistance. This review provides a theoretical basis and research ideas for further exploration of the salt stress-related functions of bZIP transcription factors. It also provides a theoretical basis for crop genetic improvement and green production in agriculture.

Fast Current-Driven Synthesis of ZIF-Derived Catalyst Layers for High-Performance Zn-Air Battery.

As a core component, the catalyst layer (CL) is widely used in fuel cell, metal-air battery, and other energy conversion devices. Herein, a highly efficient method for CL preparation via fast current-driven synthesis followed by pyrolysis is proposed. Compared with previously reported fabrication procedures of zeolite imidazolate frameworks (ZIF)-based CLs, this method directly deposits the ZIF precursor onto the conductive substrate in a very short time (≤15 min). The self-supporting CL, converted from ZIF membrane by simple single-step pyrolysis, is assembled with the gas diffusion layer to obtain cathode. Electrochemical tests exhibit a small potential gap (0.83 V) between the oxygen reduction and evolution reactions, as well as high performance and excellent stability for Zn-air battery (241 mW cm-2 at 390 mA cm-2 ), due to the unique design of a bi-continuous framework (interconnected pores and long carbon nanotubes) and Co-based active sites. This work may provide new directions for the fast fabrication of non-platinum group metal CLs for metal-air batteries or fuel cell applications.

Realizing the imaging simulation of reflective polarization volume gratings.

Near-eye holographic waveguide display system using novel reflective polarized volume gratings (RPVG) have lately gotten a lot of interest. However, from polarization characteristics to imaging simulation, there is no systematic approach based on RPVG. Here, a full methodology for solving this problem using the rigorous coupled wave analysis (RCWA) model is presented. This self-built RCWA model is used to examine the optical behavior of RPVG. This excellent portability of the RCWA model makes it possible for RPVG as a diffractive optical element, which is integrated into the commercial optical software Zemax via a self-compiled dynamic link library (DLL), and a full-color imaging simulation of the based-RPVG waveguide display system is obtained. Our work provides an instructive imaging analysis method using the RPVG for holographic waveguide display.

Insights into the flavor perception and enhancement of sodium-reduced fermented foods: A review.

Salt (sodium chloride, NaCl) is a vital ingredient in fermented foods, which affects their safety, texture, and flavor characteristics. Recently, the demand for reduced-sodium fermented foods has increased, as consumers have become more health-conscious. However, reducing sodium content in fermented foods may negatively affect flavor perception, which is a critical quality attribute of fermented foods for both the food industry and consumers. This review summarizes the role of salt in the human body and foods and its role in the flavor perception of fermented foods. Current sodium reduction strategies used in the food industry mainly include the direct stealth reduction of NaCl, substituting NaCl with other chloride salts, and structure modification of NaCl. The odor-induced saltiness enhancement, application of starter cultures, flavor enhancers, and non-thermal processing technology are potential strategies for flavor compensation of sodium-reduced fermented foods. However, reducing sodium in fermented food is challenging due to its specific role in flavor perception (e.g., promoting saltiness and volatile compound release from food matrices, inhibiting bitterness, and changing microflora structure). Therefore, multiple challenges must be addressed in order to improve the flavor of low-sodium fermented foods. Future studies should thus focus on the combination of several strategies to compensate for the deficiencies in flavor resulting from sodium reduction.

Global cognitive function is associated with sex, educational level, occupation type, and speech recognition rate in older Chinese adults: a single-center, prospective, cross-sectional study.

BACKGROUND: The development of cognitive impairment may be delayed if its risk factors are identified and detected, if its developmental trend can be predicted, and if early intervention can be performed. This study primarily aimed to investigate the association between global cognitive function and hearing loss, educational level, and occupation type and to determine any differences in such associations according to sex among older Chinese adults. METHODS: In this cross-sectional study, we prospectively recruited 219 individuals above 55 years old in an otolaryngology outpatient clinic who could write independently and had no severe vision impairment. Audiometric examinations included otoscopy, acoustic immittance, pure-tone audiometry, and speech audiometry for each ear. Cognitive function was evaluated by using the Chinese version of the Mini-Mental State Examination (MMSE). Multivariable linear regression analyses were performed to evaluate the relationship between variables and MMSE scores after adjusting for independent variables that were statistically significant in the univariable analyses. RESULTS: We enrolled 219 individuals: 98 men (mean ± standard deviation age, 63.08 ± 6.64 years) and 121 women (62.64 ± 7.17 years). The overall MMSE scores of the normal hearing group and the mild, moderate, and severe-to-profound hearing loss groups were 24.00 (5.00), 24.00 (5.00), 23.00 (5.00), and 23.00 (13.00), respectively. MMSE scores were higher among participants with higher educational levels (p < 0.001) and were significantly correlated with occupation type (p < 0.001). MMSE scores were significantly higher in men than in women (p < 0.001). However, after the analysis of the five subdomains, significant differences were only observed for attention and calculation (p < 0.001) and language (p = 0.011). We further compared the distribution of educational levels between men and women by using the chi-square test; there was no significant difference in educational level between the sexes (p = 0.070). CONCLUSIONS: We reported statistically significant relationships between global cognitive function and sex, educational level, and occupation type. Sex-specific strategies may be required to improve healthcare policies.

Exploring links between 2-oxoglutarate-dependent oxygenases and Alzheimer's disease.

Hypoxia, that is, an inadequate oxygen supply, is linked to neurodegeneration and patients with cardiovascular disease are prone to Alzheimer's disease (AD). 2-Oxoglutarate and ferrous iron-dependent oxygenases (2OGDD) play a key role in the regulation of oxygen homeostasis by acting as hypoxia sensors. 2OGDD also have roles in collagen biosynthesis, lipid metabolism, nucleic acid repair, and the regulation of transcription and translation. Many biological processes in which the >60 human 2OGDD are involved are altered in AD patient brains, raising the question as to whether 2OGDD are involved in the transition from normal aging to AD. Here we give an overview of human 2OGDD and critically discuss their potential roles in AD, highlighting possible relationships with synapse dysfunction/loss. 2OGDD may regulate neuronal/glial differentiation through enzyme activity-dependent mechanisms and modulation of their activity has potential to protect against synapse loss. Work linking 2OGDD and AD is at an early stage, especially from a therapeutic perspective; we suggest integrated pathology and in vitro discovery research to explore their roles in AD is merited. We hope to help enable long-term research on the roles of 2OGDD and, more generally, oxygen/hypoxia in AD. We also suggest shorter term empirically guided clinical studies concerning the exploration of 2OGDD/oxygen modulators to help maintain synaptic viability are of interest for AD treatment.