Inhibition of MMP8 effectively alleviates manic-like behavior and reduces neuroinflammation by modulating astrocytic CEBPD.

There is an intrinsic relationship between psychiatric disorders and neuroinflammation, including bipolar disorder. Ouabain, an inhibitor of Na+/K+-ATPase, has been implicated in the mouse model with manic-like behavior. However, the molecular mechanisms linking neuroinflammation and manic-like behavior require further investigation. CCAAT/Enhancer-Binding Protein Delta (CEBPD) is an inflammatory transcription factor that contributes to neurological disease progression. In this study, we demonstrated that the expression of CEBPD in astrocytes was increased in ouabain-treated mice. Furthermore, we observed an increase in the expression and transcript levels of CEBPD in human primary astrocytes following ouabain treatment. Transcriptome analysis revealed high MMP8 expression in human primary astrocytes following CEBPD overexpression and ouabain treatment. We confirmed that MMP8 is a CEBPD-regulated gene that mediates ouabain-induced neuroinflammation. In our animal model, treatment of ouabain-injected mice with M8I (an inhibitor of MMP8) resulted in the inhibition of manic-like behavior compared to ouabain-injected mice that were not treated with M8I. Additionally, the reduction in the activation of astrocytes and microglia was observed, particularly in the hippocampal CA1 region. Excessive reactive oxygen species formation was observed in ouabain-injected mice, and treating these mice with M8I resulted in the reduction of oxidative stress, as indicated by nitrotyrosine staining. These findings suggest that MMP8 inhibitors may serve as therapeutic agents in mitigating manic symptoms in bipolar disorder.

A unique hub-and-spoke model to optimize patient management in lymphoma using novel chimeric antigen receptor-T cell therapy in Southeast and South Asia.

Novel therapeutic options for cancer offer hope for patients and their families, particularly when the cancer has not responded to established treatment regimens. The chimeric antigen receptor (CAR)-T cell therapeutic approach has changed the treatment paradigm for relapsed or refractory lymphoma, extending the capacity of the patient's own T cells to detect and eliminate cancer cells through genetic modification of T-cell surface receptors. The process of establishing treatment centers and developing clinical expertize in this novel treatment strategy is complex. Time, resources, and a commitment to focusing health budgets on a new area are required. Currently, Singapore is the only country in southeast and south Asia with market authorization of the CAR-T product, tisagenlecleucel. Availability of CAR-T treatment across international borders provides patients in neighboring countries with choice in therapeutic options. This paper describes the unique hub-and-spoke cross-border collaboration developed between Singapore and its neighbors to provide access to CAR-T cell therapy for patients with relapsed or refractory lymphoma. To date in 2022, four patients have been included in the CAR-T treatment cross-border collaboration. Their stay in Singapore has been about 2 months' duration, including the pre-treatment evaluation, apheresis, CAR-T cell infusion and post-treatment monitoring. Patient support from referring and treating physicians, critical to the success of the undertaking, is characterized by early communication, patient selection, multi-disciplinary care, post-treatment monitoring, and attention to detail. The patient journey and the development and implementation of this unique collaboration are discussed.

A unique hub-and-spoke model to optimize patient management in lymphoma using novel CAR-T cell therapy in Southeast and South Asia.

Novel therapeutic options for cancer offer hope for patients and their families, particularly when the cancer has not responded to established treatment regimens. The CAR-T cell therapeutic approach has changed the treatment paradigm for relapsed or refractory lymphoma, extending the capacity of the patient's own T cells to detect and eliminate cancer cells through genetic modification of T-cell surface receptors. The process of establishing treatment centers and developing clinical expertize in this novel treatment strategy is complex. Time, resources, and a commitment to focusing health budgets on a new area are required. Currently, Singapore is the only country in southeast and south Asia with market authorization of the CAR-T product, tisagenlecleucel. Availability of CAR-T treatment across international borders provides patients in neighboring countries with choice in therapeutic options. This paper describes the unique hub-and-spoke cross-border collaboration developed between Singapore and its neighbors to provide access to CAR-T cell therapy for patients with relapsed or refractory lymphoma. To date in 2022, four patients have been included in the CAR-T treatment cross-border collaboration. Their stay in Singapore has been at least 2 months' duration, including the pre-treatment evaluation, apheresis, CAR-T cell infusion and post-treatment monitoring. Patient support from referring and treating physicians, critical to the success of the undertaking, is characterized by early communication, patient selection, multi-disciplinary care, post-treatment monitoring, and attention to detail. The patient journey and the development and implementation of this unique collaboration are discussed.

Mild cognitive impairment in novel SPG11 mutation-related sporadic hereditary spastic paraplegia with thin corpus callosum: case series.

BACKGROUND: SPG11 mutation-related autosomal recessive hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) is the most common cause in complicated forms of HSP, usually presenting comprehensive mental retardation on early-onset stage preceding spastic paraplegias in childhood. However, there are many instances of sporadic late-onset HSP-TCC cases with a negative family history, and potential mild cognitive deficits in multiple domains may be easily neglected and inaccurately described. METHODS: In this study, we performed next generation sequencing in four sporadic late-onset patients with HSP-TCC, and combined Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) to evaluate cognition of the patients. RESULTS: By evolutionary conservation and structural modeling analysis, we have revealed 4 novel pathogenic SPG11 mutations, and firstly confirmed mild cognitive impairment (MCI) with normal MMSE scores (≥27) and decreased MoCA scores (< 26) in these SPG11 mutation-related HSP-TCC patients, predominantly presenting impairment of executive function, delayed recall, abstraction and language. CONCLUSIONS: The results expand the mutational spectrum of SPG11-associated HSP-TCC from sporadic cases, and confirm MCI with combination of decreased MoCA and normal MMSE assessment, suggesting that clinicians should consider doing a MoCA to detect MCI in patients with HSP, particularly those with HSP-TCC.

C-4 sterol demethylation enzymes distinguish bacterial and eukaryotic sterol synthesis.

Sterols are essential eukaryotic lipids that are required for a variety of physiological roles. The diagenetic products of sterol lipids, sterane hydrocarbons, are preserved in ancient sedimentary rocks and are utilized as geological biomarkers, indicating the presence of both eukaryotes and oxic environments throughout Earth's history. However, a few bacterial species are also known to produce sterols, bringing into question the significance of bacterial sterol synthesis for our interpretation of sterane biomarkers. Recent studies suggest that bacterial sterol synthesis may be distinct from what is observed in eukaryotes. In particular, phylogenomic analyses of sterol-producing bacteria have failed to identify homologs of several key eukaryotic sterol synthesis enzymes, most notably those required for demethylation at the C-4 position. In this study, we identified two genes of previously unknown function in the aerobic methanotrophic γ-Proteobacterium Methylococcus capsulatus that encode sterol demethylase proteins (Sdm). We show that a Rieske-type oxygenase (SdmA) and an NAD(P)-dependent reductase (SdmB) are responsible for converting 4,4-dimethylsterols to 4α-methylsterols. Identification of intermediate products synthesized during heterologous expression of SdmA-SdmB along with 13C-labeling studies support a sterol C-4 demethylation mechanism distinct from that of eukaryotes. SdmA-SdmB homologs were identified in several other sterol-producing bacterial genomes but not in any eukaryotic genomes, indicating that these proteins are unrelated to the eukaryotic C-4 sterol demethylase enzymes. These findings reveal a separate pathway for sterol synthesis exclusive to bacteria and show that demethylation of sterols evolved at least twice-once in bacteria and once in eukaryotes.

Early Treatment in Acute Severe Encephalopathy Caused by ATP1A2 Mutation of Familial Hemiplegic Migraine Type 2: Case Report and Literature Review.

Familial hemiplegic migraine type 2 (FHM2) is an autosomal dominant inheritance disorder caused by ATP1A2 mutation, and the clinical spectrum is heterogeneous even with acute severe encephalopathy. However, up to now, early treatments against acute and severe attacks in FHM2 are still insufficient. Here, we report a 15-year-old female with intellectual disability due to FHM2 caused by a pathogenic ATP1A2 gene mutation, presenting mild-to-moderate headache at the onset, followed by confusion, complete right hemiparalysis, epileptic partial seizures, and conscious disturbance with rapid progression in acute attack. Brain magnetic resonance imaging (MRI) and magnetic resonance spectroscopy have revealed left extensive cerebral cortex edema, slightly decreased N-acetylaspartate for neuronal damage, and mildly increased lactate acid for mitochondrial dysfunction throughout the hemispheric swollen cortex. The patient is diagnosed as severe encephalopathy caused by FHM2. Based on literature review about pathophysiologic mechanism described in FHM2 recently, we use early treatments including prevention of glutamatergic excitotoxicity and protection of mitochondria function, as well as traditional antimigraine drug. The symptoms are all greatly improved and recovered within a short time, and follow-up MRI also shows complete disappearance of edema throughout the left hemispheric cortex. Altogether, the approach in our case may reduce the severity and duration of encephalopathy effectively, expend therapeutic options, and provide helpful references for acute severe encephalopathy in FHM2.

GGP modified daunorubicin plus dioscin liposomes inhibit breast cancer by suppressing epithelial-mesenchymal transition.

Tumor invasion and metastasis are the nodus of anti-tumor. Epithelial cell-mesenchymal transition is widely regarded as one of the key steps in the invasion and metastasis of breast cancer. In this study, GGP modified daunorubicin plus dioscin liposomes are constructed and characterized. GGP modified daunorubicin plus dioscin liposome has suitable particle size, narrow PDI, zeta potential of about -5 mV, long cycle effect, and enhanced cell uptake due to surface modification of GGP making the liposome could enter the inside of the tumor to fully exert its anti-tumor effect. The results of in vitro experiments show that the liposome has superior killing effect on tumor cells and invasion. In vivo results indicate that the liposome prolongs the drug's prolonged time in the body and accumulates at the tumor site with little systemic toxicity. In short, the targeted liposome can effectively inhibit tumor invasion and may provide a new strategy for the treatment of invasive breast cancer.

Clinical study of different doses of atorvastatin combined with febuxostat in patients with gout and carotid atherosclerosis.

OBJECTIVE: To evaluate the efficacy of atorvastatin combined with febuxostat in the treatment of gout patients with carotid atherosclerosis and to observe the effects on serum tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and C-reactive protein (CRP) levels, carotid plaques, and the adverse reactions. METHODS: Seventy patients with gout and carotid atherosclerosis admitted to Affiliated Hospital of Hebei University from January 2014 to June 2017 were randomly divided into a treatment group and a control group. The treatment group received oral febuxostat 40 mg/day combined with atorvastatin 40 mg/day. The control group was given 40 mg/day febuxostat combined with 20 mg/day atorvastatin for 90 days. The effects of treatment on TNF-α, IL-1ß, and CRP levels and carotid plaques of the patients were observed. RESULTS: After 90 days of treatment, serum TNF-α, IL-1ß, and CRP levels, as well as HUA and total cholesterol (TC), decreased in both groups after treatment. There were significant differences observed (p < 0.05). The carotid artery plaques in the two groups were significantly smaller after treatment (P<0.05). There was no significant difference in adverse reactions between the two groups (P > 0.05). CONCLUSION: Double doses of atorvastatin combined with febuxostat can effectively reduce uric acid to improve the inflammatory state in patients and reduce carotid plaques without increasing the incidence of adverse reactions.

Study on the evaluation of rheumatoid arthritis via doppler ultrasonography and anti-cyclic citrullinated peptide antibody analysis.

OBJECTIVE: This study aims to discuss the value of ultrasonic analysis and anti-cyclic citrullinated peptide (CCP) antibody analysis in evaluating the state of rheumatoid arthritis (RA). METHODS: This study was conducted during March 2016 to December 2016. Total 82 patients with RA who sought treatment in the Affiliated Hospital of Hebei University were included in this study. Data on ultrasonic and anti-CCP antibody, ESR, and RF were collected and compared. The RA patients were divided into two groups of mild disease activity (DAS28 ≤ 3.2) and moderate-severe disease activity (DAS28 > 3.2) to compare the changes in synovial thickness of joints. The changes of joint ultrasonography were also compared between positive and negative anti-CCP antibodies group. RESULTS: It is found that the number of patients suffering from joint involvement in the negative anti-CCP antibody group was larger than that of the anti-CCP positive antibody group (P <0.05); the thickness of the synovium of joints of patients in the group with moderate-severe disease activity evaluated via ultrasonography was significantly larger than that of the group with mild disease activity (P <0.05). CONCLUSION: It is possible to observe the degree of disease activity dynamically by combining ultrasonography with anti-CCP antibody and make a better assessment of patients to facilitate treatment.

Development and characterization of octreotide-modified curcumin plus docetaxel micelles for potential treatment of non-small-cell lung cancer.

We prepared octreotide (OCT)-modified curcumin plus docetaxel micelles to enhance active targeting and inhibit tumor metastasis by destroying vasculogenic mimicry (VM) channels. Soluplus was applied as an amphiphilic material to form micelles via film dispersion. The cytotoxic effects, active cellular targeting, and inhibitory effects on metastasis were systematically evaluated in vitro using A549 cells, and in vivo antitumor effects were evaluated using xenograft tumor-bearing mice. In vitro assays indicated that the OCT-modified curcumin plus docetaxel micelles showed robust cytotoxicity on A549 cells and effectively inhibited VM channels and tumor metastasis. Studying the mechanism of action indicated that OCT-modified curcumin plus docetaxel micelles downregulated MMP-2 and HIF-1α. In vivo assays indicated that OCT-modified curcumin plus docetaxel micelles increased drug accumulation at tumor sites and showed obvious antitumor efficacy. The developed OCT-modified curcumin plus docetaxel micelles may offer a promising treatment strategy for non-small-cell lung cancer.

The Ordering of Shannon Entropies for the Multivariate Distributions and Distributions of Eigenvalues.

In this paper, we prove the Shannon entropy inequalities for the multivariate distributions via the notion of convex ordering of two multivariate distributions. We further characterize the multivariate totally positive of order 2 ( M T P 2 ) property of the distribution functions of eigenvalues of both central Wishart and central MANOVA models, and of both noncentral Wishart and noncentral MANOVA models under the general population covariance matrix set-up. These results can be directly applied to both the comparisons of two Shannon entropy measures and the power monotonicity problem for the MANOVA problem.

The Arabidopsis UDP-glycosyltransferases UGT79B2 and UGT79B3, contribute to cold, salt and drought stress tolerance via modulating anthocyanin accumulation.

The plant family 1 UDP-glycosyltransferases (UGTs) are the biggest GT family in plants, which are responsible for transferring sugar moieties onto a variety of small molecules, and control many metabolic processes; however, their physiological significance in planta is largely unknown. Here, we revealed that two Arabidopsis glycosyltransferase genes, UGT79B2 and UGT79B3, could be strongly induced by various abiotic stresses, including cold, salt and drought stresses. Overexpression of UGT79B2/B3 significantly enhanced plant tolerance to low temperatures as well as drought and salt stresses, whereas the ugt79b2/b3 double mutants generated by RNAi (RNA interference) and CRISPR-Cas9 strategies were more susceptible to adverse conditions. Interestingly, the expression of UGT79B2 and UGT79B3 is directly controlled by CBF1 (CRT/DRE-binding factor 1, also named DREB1B) in response to low temperatures. Furthermore, we identified the enzyme activities of UGT79B2/B3 in adding UDP-rhamnose to cyanidin and cyanidin 3-O-glucoside. Ectopic expression of UGT79B2/B3 significantly increased the anthocyanin accumulation, and enhanced the antioxidant activity in coping with abiotic stresses, whereas the ugt79b2/b3 double mutants showed reduced anthocyanin levels. When overexpressing UGT79B2/B3 in tt18 (transparent testa 18), a mutant that cannot synthesize anthocyanins, both genes fail to improve plant adaptation to stress. Taken together, we demonstrate that UGT79B2 and UGT79B3, identified as anthocyanin rhamnosyltransferases, are regulated by CBF1 and confer abiotic stress tolerance via modulating anthocyanin accumulation.

The maize secondary metabolism glycosyltransferase UFGT2 modifies flavonols and contributes to plant acclimation to abiotic stresses.

Background and Aims: Nowadays, the plant family 1 glycosyltransferases (UGTs) are attracting more and more attention since members of this family can improve the properties of secondary metabolites and have significantly enriched the chemical species in plants. Over the past decade, most studies on UGTs have been conducted in Arabidopsis thaliana and they were proved to play diverse roles during the plant life cycle. The Zea mays (maize) GT1 family comprises a large number of UDP-glycosyltransferase (UGT) members. However, their enzyme activities and the biological functions are rarely revealed. In this study, a maize flavonol glycosyltransferase, UFGT2, is identified and its biological role is characterized in detail. Methods: The UFGT2 enzyme activity, the flavonol and glycoside levels in planta were examined by high- performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS). The functions of UFGT2 in modifying flavonols, mediating flavonol accumulation and improving stress tolerance were analysed using two ufgt2 mutants and transgenic arabidopsis plants. Key Results: By in vitro enzyme assay, the maize UFGT2 was found to show strong activity towards two flavonols: kaemferol and quercetin. Two ufgt2 knockout mutants, Mu689 and Mu943, exhibited obvious sensitivity to salt and drought stresses. The endogenous quercetin and kaempferol glycosides, as well as the total flavonol levels were found to be substantially decreased in the two ufgt2 mutants, with declined H2O2-scavenging capacity. In contrast, ectopic expression of UFGT2 in arabidopsis led to increased flavonol contents and enhanced oxidative tolerance. Moreover, expression of typical stress-related genes in arabidopsis and maize were affected in UFGT2 overexpression plants or knockout mutants in response to abiotic stresses. UFGT2 was also transferred into the arabidopsis ugt78d2 mutant and it was found to recover the deficient flavonol glycoside pattern in the ugt78d2 mutant, which confirmed its catalysing activity in planta. Conclusion: It is demonstrated in our study that a maize glycosyltransferase, UFGT2, involved in modifying flavonols, contributes to improving plant tolerance to abiotic stresses.

Optogenetic activation of cholinergic neurons in the PPT or LDT induces REM sleep.

Rapid eye movement (REM) sleep is an important component of the natural sleep/wake cycle, yet the mechanisms that regulate REM sleep remain incompletely understood. Cholinergic neurons in the mesopontine tegmentum have been implicated in REM sleep regulation, but lesions of this area have had varying effects on REM sleep. Therefore, this study aimed to clarify the role of cholinergic neurons in the pedunculopontine tegmentum (PPT) and laterodorsal tegmentum (LDT) in REM sleep generation. Selective optogenetic activation of cholinergic neurons in the PPT or LDT during non-REM (NREM) sleep increased the number of REM sleep episodes and did not change REM sleep episode duration. Activation of cholinergic neurons in the PPT or LDT during NREM sleep was sufficient to induce REM sleep.

Stereochemical investigations of the Tetrahymena cyclase, a model system for euphane/tirucallane biosynthesis.

The squalene cyclase of Tetrahymena pyriformis cyclizes 2,3-dihydrosqualene to euph-7-ene. This was used as a model for euphane biosynthesis. D-ring formation was demonstrated to involve pre-chair folding through an experiment with 2,3-dihydro-5-oxasqualene. This requires that a non-least motion rotation (120°) of the C17-20 bond in the intermediate deoxydammaranyl cation occurs before the first 1,2-hydride shift. Truncated substrates relieved the hindrance associated with this rotation and permitted a least motion pathway. Several triterpenes were found to be minor products of the Tetrahymena cyclase.

Effect of uncorrection versus full correction on myopia progression in 12-year-old children.

PURPOSE: To investigate the effects of no correction versus full correction on myopia progression in Chinese children over a period of 2 years. METHODS: Myopia was defined as cycloplegic spherical equivalent (SE) of ≤ -0.50 D. Uncorrection was defined as no spectacles worn, and full correction was defined as when the value of SE subtracted from the dioptric power of the child's current spectacles was less than 0.5 D. Ocular examinations included visual acuity, cycloplegic autorefraction, axial length and vertometer measurements. Questionnaires were completed by parents on behalf of the children. RESULTS: A total of 121 myopic children, with a median age of 12.7 years, were screened from the Anyang Childhood Eye Study, with 65 in the uncorrected group and 56 in the full correction group. At 2-year follow-up, children with no correction had slower myopia progression (-0.75 ± 0.49 D vs. -1.04 ± 0.49 D, P < 0.01) and less axial elongation (0.45 ± 0.18 mm vs. 0.53 ± 0.17 mm, P = 0.02) than children with full correction. In multivariate modeling, adjusting for baseline SE or axial length, age, gender, height, number of myopic parents, age at myopia onset, and time spent in near work and outdoors, children with no correction still had slower myopia progression (-0.76 ± 0.07 vs. -1.03 ± 0.08 D, P < 0.01) and less axial elongation (0.47 ± 0.03 mm vs. 0.51 ± 0.03 mm, P < 0.01). Myopia progression decreased significantly with an increasing amount of undercorrection in all children (r = 0.22, b = 0.16, P = 0.01). CONCLUSION: Our findings suggest that myopic defocus slows the progression of myopia in already myopic children, supporting previous findings from animal studies.

Pharmacologic Management for Heart Failure and Emerging Therapies.

PURPOSE OF REVIEW: This review aims to summarize the growing body of literature of HF with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF) with a focus on recent pharmacologics. RECENT FINDINGS: HFrEF continues to be more widely investigated than HFpEF. Ivabradine and combinatorial treatment with sacubitril and valsartan are promising newly approved therapies. Other experimental therapies have emerged, which include Serelaxin, Empagliflozin, Neuregulin, and Omecamtive mecarbil, among others. These drugs need to continue to be investigated for safety and efficacy. We predict ivabradine and combinatorial treatment with sacubitril-valsartan to develop as a widespread therapy. New therapies should be aimed at treating HFpEF or target the cardiomyocyte itself.

Liberal versus restrictive fluid management in abdominal surgery: a meta-analysis.

PURPOSE: This study compared perioperative restrictive fluid therapy to liberal (conventional) fluid therapy in patients undergoing major abdominal surgery and investigated the rate of post-operative morbidity (complication rates), recovery (time to flatus), and the length of hospital stay. METHODS: The Medline, PubMed, Cochrane, and EMBASE databases were searched until June 18, 2015. Randomized controlled trials, two-arm prospective studies, and retrospective studies were included in our analyses. A sensitivity analysis, publication bias assessment, and quality assessment were performed. RESULTS: The effects of the two therapies were similar in the subgroup analysis of patients who underwent hepato-gastroenterological surgery (P = 0.287). However, in a subgroup of patients who underwent vascular abdominal surgery, the restricted fluid treatment regimen was associated with a lower risk of complications in comparison with the conventional regimen (pooled OR = 0.12, 95 % CI 0.03-0.47, P = 0.002). There was no difference between the two regimens with respect to the incidence of cardiopulmonary complications (P = 0.733). However, the patients who received the restricted fluid treatment regimen had a shorter time to flatus (P = 0.031) and a shorter hospital stay (P = 0.033) than the patients who received the conventional regimen. CONCLUSIONS: Restrictive fluid therapy and liberal conventional therapy were associated with similar rates of overall and cardiopulmonary complications; however, restrictive fluid therapy was associated with a more rapid recovery and a shorter length of hospital stay.

NMR Tube Degradation Method for Sugar Analysis of Glycosides.

The sugar subunits of natural glycosides can be conveniently determined by acid hydrolysis and (1)H NMR spectroscopy without isolation or derivatization. The chemical shifts, coupling constants, and integral ratios of the anomeric signals allow each monosaccharide to be identified and its molar ratio to other monosaccharides to be quantified. The NMR data for the anomeric signals of 28 monosaccharides and three disaccharides are reported. Application of the method is demonstrated with the flavonoid glycoside naringin (1), the aminoglycoside antibiotics kanamycin (2) and tobramycin (3), and the saponin digitonin (4).

Following the transient reactions in lithium-sulfur batteries using an in situ nuclear magnetic resonance technique.

A fundamental understanding of electrochemical reaction pathways is critical to improving the performance of Li-S batteries, but few techniques can be used to directly identify and quantify the reaction species during disharge/charge cycling processes in real time. Here, an in situ (7)Li NMR technique employing a specially designed cylindrical microbattery was used to probe the transient electrochemical and chemical reactions occurring during the cycling of a Li-S system. In situ NMR provides real time, semiquantitative information related to the temporal evolution of lithium polysulfide allotropes during both discharge/charge processes. This technique uniquely reveals that the polysulfide redox reactions involve charged free radicals as intermediate species that are difficult to detect in ex situ NMR studies. Additionally, it also uncovers vital information about the (7)Li chemical environments during the electrochemical and parasitic reactions on the Li metal anode. These new molecular-level insights about transient species and the associated anode failure mechanism are crucial to delineating effective strategies to accelerate the development of Li-S battery technologies.